EMBO/sd-character-level-ner huggingface dataset:
Figure 1(A) A schematic view of the lncPSCA and PSCA loci. The risk-associated SNP rs2978980 is shown as the red vertical line. Data from the UCSC Genome Browser, including epigenetic marks for histone H3 lysine 27 acetylation (H3K27ac) are shown. (B) Abolishment of a RORA binding site in the lncPSCA intronic enhancer by the rs2978980 T>G SNP. The risk allele G of rs2978980 disrupts a RORA binding motif.  (C) Electrophoretic mobility-shift assay (EMSA) with biotin-labeled RORA consensus, rs2978980T or rs2978980G probes and HGC-27 or MGC80-3 nuclear extracts. HGC-27 or MGC80-3 left panel: EMSA with RORA consensus or rs2978980T probes. Lane 1-8: from the first lane at the left side to the right side. Lanes 4 and 8, probe only; lanes 2 and 6, probe and nuclear extracts; lanes 1, 3, 5 and 7, probe and nuclear extracts plus 100× unlabeled rs2978980T (lanes 1 and 5) or RORA consensus probes (lanes 3 and 7). HGC-27 or MGC80-3 right panel: EMSA with rs2978980T or rs2978980G probes. Lanes 1 and 6, probe only; lanes 2 and 7, probe and nuclear extracts; lanes 3-5 and 8-10, probe and nuclear extracts plus 100× unlabeled rs2978980T (lanes 5 and 8), rs2978980G (lanes 3 and 10) or RORA consensus probes (lanes 4 and 9). (D) Sanger sequencing chromatograms of the SNP region indicated that the MGC80-3 cell line carries the TG genotype and HGC-27 has the GG genotype. (E) ChIP-qPCR assays using MGC80-3 cells carrying the rs2978980TG genotype. The presence of RORA-binding lncPSCA enhancer region was verified by qPCR with NPAS2 as the positive control. Region a and b: the negative control regions of lncPSCA promoter and intron 1; region c: the lncPSCA enhancer region around rs2978980 SNP; region d: the positive control NPAS2 promoter region. Left subpanel: RORA ChIP-qPCR fragments on lncPSCA (a, b and c) and NPAS2 (d) genes; right subpanel: RORA ChIP-qPCR results of lncPSCA (a, b and c) and NPAS2 (d) genes. Data show one representative example of three biological replicates. (F) Suppression of RORA using siRNAs (siRORA-1 and siRORA-2) could markedly down-regulate lncPSCA expression in MGC80-3 cells but not in HGC-27 cells. In detail, MGC80-3 and HGC-27 cells were transfected with siRORA-1 and siRORA-2, lncPSCA and RORA expression levels were measured by RT-qPCR and Western Blot. (G) In gastric cancer or normal tissues of Discovery cohort (n = 96) and Validation cohort (n = 30), there were significantly positive expression correlations between RORA and lncPSCA. (H) Expression levels of lncPSCA were quantified using RT-qPCR in tumor-normal pairs of both cohorts, respectively. All data of lncPSCA expression were normalized to GAPDH expression levels.
Figure 7(A-B) Confocal sections of wild-type and Snap29 mutant eye-antennal imaginal discs (eye disc portion to the left) of L3 larvae. Discs were labeled with phalloidin and DAPI to visualize the subcortical f-actin cytoskeleton and nuclei, respectively. Arrowheads in B point to actin-rich unpolarized cells in apical, medial and basal sections of the same disc. (C) High magnification of a single confocal cross-section of wild-type and Snap29 mutant eye disc tissues. Two facing folds of the tissue are separated by the apical lumen. aPKC and Dlg mark the apical and lateral plasma membrane domains, respectively. In Snap29 mutant tissue the apical-basal polarity is disrupted. (D) Single confocal cross-sections of wild-type and Snap29 eye-antennal discs, expressing Puckered-LacZ (Puc-lacZ), a reporter of JNK signaling activation. (E-H) Single confocal cross-sections of wild-type and Snap29 eye-antennal discs (E-F), and of otherwise wild-type and Snap29 eye-antennal discs expressing the bacterial apoptosis inhibitor p35 (G-H). Anti-activated-Caspase 3 (Casp3) marks apoptotic cells.
Fig.Figure 1(A) N-glycan. Glucoses, blue; mannoses, green; N-acetylglucosamines, black. GI removes glucose 1. GII removes glucoses 2 and 3. UGGT1 adds-back glucose 3. UGGT1 can only modify the terminal mannose on branch A (black circle). αMI and EDEM1, EDEM2 and EDEM3 remove light green, α1,2-bonded, mannose residues. CST inhibits GI and GII. KIF inhibits α1,2mannosidases. (B) AATNNN and ATZNNN. N-glycans in red. The E342K mutation of ATZNNN is in blue. (C) Control of polymerization propensity for the Halo-tagged versions of AAT (lanes 1 and 4) and of ATZ (lanes 2 and 5). Polymers and monomers corresponding to (Miranda et al., 2010; Ronzoni et al., 2021) are seen with anti-Halo (lanes 1-3) or with the polymer-specific 2C1 antibody (lanes 4-6). Synthesis control in SDS-polyacrylamide gel by visualization of tetramethylrhodamine (TMR) ligand-labeled Halo-AATNNN and Halo-ATZNNN (lanes 7-9). (D) HaloTag pulse-chase analysis in WT MEF monitoring fluorescent Halo-AATNNN during up to 6 h of chase in the presence of BafA1. The fluorescent JF646-Halo ligand and the polymer-specific 2C1 antibody stains are shown. (E) Same as (D) for fluorescent Halo-ATZNNN. (F) Quantification of accumulation of fluorescent Halo-AATNNN and Halo-ATZNNN within LAMP1-positive endolysosomes. Mean ± SEM, n=20, 11, 10, 13 for Halo-AATNNN, n= 18, 12, 12, 13 for Halo-ATZNNN. Two-way ANOVA and Sidak's multiple comparison test, ns P>0.05, *** P<0.001.
TCHP regulates PCM1 and GABARAP stability A, B (A) Control or TCHP knock-down HUVECs were subjected to cycloheximide (CHX) and MG132 treatments for the indicated number of hours before immunoblotting.Figure 2Control or TCHP knock-down HUVECs were subjected to cycloheximide (CHX) and MG132 treatments for the indicated number of hours before immunoblotting. PCM1 levels were analysed in the insoluble fraction. Laminin has been used as a loading control. Below panel: Quantification of PCM1 degradation. (one-way ANOVA; *p=0.0180 vs control time 0). Control or TCHP knock-down HUVECs were subjected to cycloheximide (CHX) and MG132 treatments for the indicated number of hours before immunoblotting. Condition as in (A), Western blot for anti-GABARAP and anti-ACTIN antibodies. Below panel: Quantification of GABARAP degradation. (one-way ANOVA; *p =0.0215 vs control time 0). Control or TCHP overexpressing HUVECs were subjected to CHX treatment for the indicated number of hours prior to immunoblotting. Western blot was probed for anti-PCM1 and anti-V5 antibodies. Laminin has been used as a loading control. Control or TCHP overexpressing HUVECs were subjected to CHX treatment for the indicated number of hours prior to immunoblotting. Western blot was probed for anti-V5, anti-GABARAP and anti-ACTIN antibodies. Below panels: Quantification of C (one-way ANOVA; **p<0.0001 vs control time 0; ##p=0.0003 vs control CHX) and D (one-way ANOVA; **p<0.0001 vs control time 0; ##p=0.0056 vs control CHX).
Transcriptional regulation of p62 in SIVE monkey brains, and its presence in human and monkey neurons associated with ubiquitin.Figure 7(A) Relative values (RV) of p62 mRNA level in frontal lobe of SIVE versus SIV and uninfected (UN) monkeys, n = 7 for SIVE, n = 12 for SIV and n = 9 for UN, P<0.05. B) RV of p62 mRNA level in frontal cortex of HAD versus non neurological diseased subjects (NNDS), n = 8 for HAD and n = 10 for NNDS, P<0.0001. (C) p62 and ubiquitin immunoreactivity on serial sections in SIVE monkeys, as well as those with HAD in brain sections from hippocampus. p62 has a diffuse immunoreactivity in UN monkeys and in human NNDS and a dot profile structures in SIVE and HAD brain tissues. Higher magnification views are shown in green insets. Black arrows indicate p62- or ubiquitin-immunoreactive structures within the neuronal cell body or proximal processes, and red arrowheads indicate a dot-like immunoreactivity in the neuropil. Scale bar, 20 µm.
Figure 1Phloroglucinol staining of wild-type seedlings inoculated with PTI-inducing Pst DC3000 hrcC-, virulent Pst DC3000, and avirulent Pst DC3000 (AvrRpm1) and Pst DC3000 (AvrRpt2). Data information: Twelve-day-old seedlings were flood-inoculated with P. syringae at 108 cfu/ml in (A hrcC-, Pst DC3000 hrcC-; DC3000, Pst DC3000; AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation B Phloroglucinol staining of wild-type adult leaves inoculated with PTI-inducing Pst DC3000 hrcC-, virulent Pst DC3000, and avirulent Pst DC3000 (AvrRpm1) and Pst DC3000 (AvrRpt2). The upper images are enlarged ones of the lower boxes at 2 dpi. Scale bars, 100 μm. Data information Six-week-old leaves were syringe-infiltrated with P. syringae at 108 cfu/ml in (B hrcC-, Pst DC3000 hrcC-; DC3000, Pst DC3000; AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation; IS, infected site; UIS, uninfected site. C Quantification of lignin content in pathogen-treated seedlings Data are shown as means ± SD (n = 4; 20-30 seedlings each). Data information: Twelve-day-old seedlings were flood-inoculated with P. syringae at 108 cfu/ml Significant differences are indicated by different letters (Tukey's HSD test; P < 0.05) Experiments were repeated 3 times with similar results. hrcC-, Pst DC3000 hrcC-; DC3000, Pst DC3000; AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation D Quantification of lignin content in pathogen-treated wild-type leaves Data are shown as means ± SD (n = 4; 3-9 leaves each). Data information: Six-week-old leaves were syringe-infiltrated with P. syringae at 108 cfu/ml Significant differences are indicated by different letters (Tukey's HSD test; P < 0.05) Experiments were repeated 3 times with similar results. hrcC-, Pst DC3000 hrcC-; DC3000, Pst DC3000; AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation E Quantification of lignin content in wild-type leaves treated with different titers of Pst DC3000 (AvrRpm1). Data are shown as means ± SD (n = 4; 3-9 leaves each). Six-week-old leaves were syringe-infiltrated with P. syringae at the indicated titers in (E). Significant differences are indicated by asterisks (t test; *P < 0.05; **P < 0.01; ***P < 0.001). Experiments were repeated 3 times with similar results. dpi, days post-inoculation F Quantification of lignin content in wild-type and rpm1-3 rps2-101c leaves treated with avirulent bacteria. Data are shown as means ± SD (n = 4; 3-9 leaves each). Six-week-old leaves were syringe-infiltrated with P. syringae at 108 cfu/ml Significant differences are indicated by asterisks (t test; *P < 0.05; **P < 0.01; ***P < 0.001). Experiments were repeated 3 times with similar results. AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation
Loss of the piRNA pathway reduces food intake and body weight.Figure 3A Body weight measurements of dsPiwi1-treated locusts and dsGFP-treated control locusts (dsGFP-treated, n=17 locusts, dsPiwi1-treated, n=20 locusts; dsGFP-treated, n=45 locusts, dsAgo3-treated, n=26 locusts). ***P<0.001 (Student's t-test). ns: not significant (Student's t-test). The center line of the boxplots represents median value, the bounds of the box represent 75th and 25th percentile, and the whiskers represent maximum and minimum value. Data information: All assays were performed on fourth-instar locusts. B Responses of locust nymphs in a dual-choice test in a Y-tube olfactometer after Piwi1 knockdown (n=46 locusts), ns: not significant (chi-square test). Data information: All assays were performed on fourth-instar locusts. C Analysis of the behavioral phenotypes of locusts in an arena after Piwi1 knockdown (n=18 locusts), ns: not significant (Student's t-test). TDM, total distance moved. Data information: All assays were performed on fourth-instar locusts. D, E Analysis of the exoskeleton traits of locusts (n=36 locusts), ns: not significant (Student's t-test). Data information: All assays were performed on fourth-instar locusts. F Analysis of the exoskeleton traits of locusts (n=36 locusts), ns: not significant (Student's t-test). Data information: All assays were performed on fourth-instar locusts. G Food intake by dsPiwi1-treated locusts and dsGFP-treated control locusts within 1 h (n=5 biological replicates) , ***P<0.001 (Student's t-test). Data information: All assays were performed on fourth-instar locusts.
Immunofluorescence analysis of viral antigens in lungs of SARS-CoV-2-infected hACE2 mice.Figure 3. Immunofluorescence analysis of viral antigens in lungs of SARS-CoV-2-infected hACE2 mice.Co-localization of SARS-CoV-2 S protein and hACE2 receptor in hACE2 mouse lungs, the sections were incubated with anti-SARS-CoV-2 S protein antibody, anti-human ACE2 antibody, and DAPI. The lung sections of ACE2-Mock mice (a-d). The lung sections of ACE2-HB-01 mice (e-h). The white arrows showed the viral S protein (f) and hACE2 (g), respectively, the yellow arrow showed the merge of viral S protein and hACE2 (h). White bar=25 µm.
Figure 5A) Ubiquitination of endogenous RB in C33 cells synchronised in the G1 or G2/M cell cycle phases under stress conditions. B) In vitro RB ubiquitination by MDM2 wild type and the phosphomimetic mutant MDM2(S395D). C) In vitro RB ubiquitination by MDM2(S395D) in presence or absence of RB mRNA. D) A representative clonogenic assay. Increasing concentrations of MDM2 were transfected in H1299-RBKO stable transfected with RB-HA or RB+5´UTR. The cells were treated with doxorubicin to induce genotoxic stress conditions. Data are means ± s.d. of three independent experiments, student t test was used to calculate statistical significance (*p <0.05). E) Evaluation of cyclin E mRNA levels in an MDM2 dose-dependent manner. The H1299 cells were treated with doxorubicin during 16 h to induce genotoxic stress. Data are means ± s.d. of three independent experiments, student t test was used to calculate statistical significance (*p <0.05, ***p< 0.001). F) Working model of the MDM2 mechanism of RB regulation. Under genotoxic stress conditions MDM2 induce the G1 cell cycle phase via RB tumour suppressor. In the G1 cell cycle phase MDM2 increases the synthesis of RB, allowing the RB-E2F1 binding, promoting in this way the G1 cell cycle arrest. During G2/M, MDM2 ubiquitinate and degrades RB promoting the cell cycle progression.
Figure 8A) Laser microsurgery was performed at the different sides of the ventral nests during phase 2 (300 minutes) in parallel cuts [in the LEC tissue at 40 µm of the nests/LEC border (cyan) and within the nests at 10 µm (red) and 40 µm (green) of the edge]. Myo-GFP transgenic pupae were used to visualize the cortex displacements. This example illustrates at the anterior edge the laser cuts positions. Scale bar = 15 µm. B) Cortex recoil velocity (pixels per second) at different time points after laser cutting (+ 10 sec) for a single experiment. Note the exponentially decaying speed. C) Inferred stress differences (brown) and mean recoil velocities (blue) as measured by PIV and in the LECs (cyan - n = 18)), 10 µm (red - n = 16) and 40 µm within the nest (green - n = 20). Error bars represent Standard Deviations. D) Snapshots of a laser cut in the nest area. PIV arrows are shown in red. Scale bar = 5 µm. E) Comparison of the mean laser recoil velocities in phase 3 for Dacapo overexpressing nests (green) with wild type (blue) at different distances (-40 - n = 16, -10 - n =22, +40 - n = 14) Error bars represent Standard Deviations. F) Comparison of the mean laser recoil velocities in phase 3 for P35 overexpressing nests (green) with wild type (blue) at different distances (-40 - n = 17, -10 - n = 20, +40 - n = 15) Error bars represent Standard Deviations.
Figure 3A) Liquid droplets observed by brightfield and fluorescence microscopy when Oregon green labeled TDP-43 (4 μM, 10% labeled protein) was mixed with no RNA control or increasing A(GU)18 RNA concentration at 250 mM salt. Representative images from 3 biological replicates using 2 different protein preparations. Scale bars, 10 μm. B) Area of droplets plotted at different A(GU)18 concentrations. Mean and SD of >150 droplets from 3 biological replicates using 2 different protein preparations. C) TDP-43 concentration in the light phase measured as a function of A(GU)18 (blue) or A(CA)18 (red) concentration measured by Bradford protein assay. Mean and SD from >6 biological replicates using 2 different protein preparations. (250 mM NaCl, 4 µM TDP-43) D) Phase separation of TDP-43 (4 μM) at increasing salt concentration without RNA or in the presence of increasing A(GU)18 concentration. Scale bars, 10 μm. Inlay added to top right panel for increased visibility, scale bar 1 μm. E) Phase diagram derived from panel D, denoting either no droplets or droplet formation for each condition.
plt and wox5 mutants show more CSC differentiation and QC divisions.Figure 3A, Schematic representation of a longitudinal section of an Arabidopsis RM. QC cells are marked in red, CSCs are marked in dark blue, CCs in light blue. Combined mPSPI (grey) and EdU (red) staining for 24 hours (SCN staining) to analyse the CSC (A-I) and QC division phenotype (J-R) within the same roots are shown. B-H, Representative images of the SCN staining in Col, and the indicated single, double, and triple mutant roots. QC positions are marked by yellow arrowhead. I, Analyses of the SCN staining for CSC phenotypes. Frequencies of roots showing 0, 1, 2, or 3 CSC layers are plotted as bar graphs. J, Schematic representation of a transversal section of an Arabidopsis RM. QC cells are marked in red, CEI initials are marked in turquoise. K-Q, Representative images of transversal sections with QC cells outlined in yellow. R, Analyses of the SCN staining for QC division phenotypes. Frequencies of roots showing 0, 1, 2, 3 or ≥4 dividing QC cells are plotted as bar graphs. Number of analysed roots (n) (biological replicates) is indicated for each genotype and results from 2-5 technical replicates per genotype. QC = quiescent center, CSC = columella stem cell, CEI = cortex endodermis initial, SCN = stem cell niche, mPSPI = modified pseudo-Schiff propidium iodide, EdU = 5-ethynyl-2'-deoxyuridine, scale bars represent 5 µm.
TBC1D15 binds ATG8 family proteins.Figure 7.(A) The indicated cells transiently expressing YFP-GABARAPL1 (green) and mCherry-Parkin (red) were treated with valinomycin for 3 hr. Scale bars, 10 μm. (B) YFP-TBC1D15 overexpressed in HEK293 cells was subjected to binding assays with GST-fused proteins (GABA, L1, and L2 represent GABARAP, GABARAPL1, and GABARAPL2, respectively). 5% input and bound fractions were analyzed by immunoblotting with anti-GFP antibody (upper panel). Coomassie brilliant blue (CBB) staining shows GST-fusion proteins in bound fractions (lower panel). (C) Binding assay carried out as in (B) with GST-GABARAPL1 WT (GST-WT) or its Y49A/L50A mutant (GST-YL). Immunoblotting with anti-GFP antibody (upper panel) and CBB staining (lower panel) are shown. (D) Cell extracts from HEK293 overexpressed HA-TBC1D15 and YFP, YFP-GABARAPL1 (YFP-WT), or its Y49AL50A mutant (YFP-YL) were subjected to pull down assays with GFP-Trap. 5% input and bound fractions were analyzed by immunoblotting with anti-HA (upper panel) and anti-GFP (lower panel) antibodies. (E-H) The indicated YFP-tagged TBC1D15 full-length, truncated, or point-mutant protein or YFP-Fis1 overexpressed in HEK293 cells were subjected to binding assays with recombinant GST-GABARAPL1. 5% input and bound fractions were analyzed by immunoblotting with anti-GFP antibody (upper panel) and CBB staining (lower panel). (I) Summary of binding abilities of truncated or point-mutated TBC1D15 constructs. -, +, ++, and +++ indicates binding of recombinant GST-GABARAPL1 to less than 1%, 1-5%, 5-10%, and over 10%, respectively of the total YFP-TBC1D15 fragment. Yellow boxes indicate YFP tags. (J) LC3-LC3 and mCherry-Parkin stably expressing TBC1D15−/− cells in the presence of HA-tagged TBC1D15 WT or F280A mutant were treated with valinomycin for 3 hr. Cells were subjected to immunofluorescence microscopy with anti-HA antibody. Scale bars, 10 μm. (K) The YFP-LC3 morphology of cells in (J) was quantified. The error bars represent ±SD from three independent replicates. Over 50 cells were counted in each well.
A role for CK1 and GSK3 in the cytoplasmic oscillator(A) Period (n=3, mean ±SEM) analyses of WT and CKO PER2::LUC cells in the presence or absence of CK1δ/ε inhibitor PF670462 (0.Figure 5(A) Period analyses of WT and CKO PER2::LUC cells in the presence or absence of CK1δ/ε inhibitor PF670462 (0.3 µM; PF). Period analyses of WT and CKO PER2::LUC cells in the presence or absence of GSK3 inhibitor CHIR99021 (5 µM; CHIR). Period analyses of WT and CKO PER2::LUC cells in the presence or absence of CRY inhibitor KL001 (1 µM). (D) Schematic model integrating CRY-independent timekeeping into the existing canonical model of the circadian clock. The CRY-dependent gene expression feedback loop (TTFL) is required for most circadian regulation of transcriptional clock controlled genes (CCGs) and therefore for robustness and behavioural and physiological rhythmicity. However, it is dispensable for circadian timekeeping per se, as reported by residual oscillations in PER2 protein levels, suggestive of the existence of a coupled underlying (cytosolic) timekeeping mechanism involving CK1 and GSK3 (cytoscillator).
Figure 6Venn diagram analysis of BCL9 mitotic phosphorylation sites in HeLa cells by mass spectrometry. Schematic diagram of the position of two phosphorylation sites on the BCL9 N-terminal domain, and protein alignment analysis of the sequence around T172 in different species from http://www.uniprot.org. In vitro CDK1/cyclin B1 kinase assay for immunoprecipitation-purified BCL9-Flag or T172A-Flag proteins. Immunoprecipitation analysis of transiently-expressed BCL9-MF or T172A-MF interactors in synchronised cells, from G1S to G2 M phase. The relative level of BCL9-MF or T172A-MF immunoprecipitation is determined; red numbers indicate up-regulation, and green numbers indicate down-regulation compared to the starting time point. Immunoprecipitation analysis of the transiently-expressed BCL9-MF interaction in mitotic cells treated with RO3306. Immunoprecipitation analysis of the interaction of the T172 inactive mutant T172A, the activation mutant T172D, and the double inactive mutant T172\T144 (2A) or activation mutant (2D) transiently-expressed in mitotic cells. Quantification for the inactive or activation mutant interactions indicated in Fig 6F. The wild type BCL9 interaction is normalised to 1, indicated by a green dashed line with an arrow. A schematic diagram of BCL9 phosphorylation regulation of its interactions.
Figure 6A, Immunoblot analysis of protein lysates from HeLa cells treated with EBSS for 1 h and then incubated with complete medium (refeed) for the indicated times. Samples were run under non-reducing conditions. B, Quantification of immunoblot data shown in (A). Data are presented as mean ± SD using one-way ANOVA (*)p<0.05, and (***)p<0.001 from three independent experiments. C, Quantification of immunoblot data shown in (A). Data are presented as mean ± SD using one-way ANOVA (*)p<0.05, and (***)p<0.001 from three independent experiments. D, Relative quantitative RT-PCR analysis of the mRNA expression of autophagy- (UVRAG), lysosome- (ATP6V1C1), oxidative stress response- (TXNRD1 and HMOX1), cell cycle control- (CDKN1a) and cytokine production (IL6) -related genes in TFEB/TFE3-double knockout MEFs cells stably expressing TFEB-FLAG-WT or TFEB-FLAG-C212A and treated with 5 μM arsenic trioxide (ATO) or 12.5 μM NaAsO2 for 12 h. Data are presented as mean ± SD using two-way ANOVA (*)p<0.05, (**)p<0.01, (***)p<0.001, and (****)p<0.0001 from three independent experiments. E, Schematic representation of TFEB/TFE3 redox regulation in response to chronic stress conditions.