EMBO/sd-character-level-ner huggingface dataset:
(I) Quantification of apoptotic cells using Incucyte ZOOM (Caspase-3/7- positive cells) in lung-resident fibroblasts isolated from IPF and TGFα mice on Dox for 6 wks and treated with control or AURKB siRNA for 72h. **P < 0.005, ****P < 0.00005, 2-way ANOVA, (n=4).
Growth curves of hOSE cells at the 4th passage with or without ectopic expression of LATS2.
A Deletion of NUP2 and MLP1/2 reduced HXT2 mRNA enrichment in the bud. FISH under glucose shift conditions with strains in which different NPC components were deleted. B Quantification of (A).
A. Schematic representation of the experimental protocol. Abbreviations: LCM, laser capture microdissection. B, C. RT-PCR performed on RNA extracted from axons collected by LCM (Ax) or from eyes. (B) β-Actin mRNA is present both in eyes and axons, while MAP2 and H4 are present only in the eye sample, suggesting the absence of contamination from cell bodies or other cells in LCM axonal samples (Bellon et al, 2017). Abbreviations: Ax, axonal sample; Eye, stage 37/38 eye; LCM, laser capture microdissection; -, PCR no template control; NT, RT no template control.
Representative IF images showing the expressions of nuclear YAP, DATP cell marker CLDN4, and AT1 cell marker AQP5 in the airways of normal background (top) and BO (bottom) human lungs. CLDN4 (white), AQP5 (red), YAP (green), and DAPI (blue). Of note, a flattened airway layer in BO lungs. Scale bars, 100μm.
G, H. Representative z-projected fluorescence images and statistics showing the large dextran uptake in Syt11 KD and control DRG neurons. Neurons were loaded with 50 μM tetramethylrhodamine-dextran (40 kD) by 2-min exposure to 100 mM KCl. Scale bars, 10 μm.
(d) Representative ultrastructural images show late endosome/lysosome-like structures that are labelled with anti-GFP gold particles (panels 3, 4) in HEK 293T cells transiently transfected with Rubicon-EGFP. These structures are enwrapped by double membranes (panel 4 inset) and co-labelled by anti-GFP (developed by DAB) and anti-Lamp1 (gold enhanced) (panels 5-7) antibodies. Note that mitochondria are mostly negative for Rubicon-EGFP (panel 4). The negative controls are without antibody (panels 1-2). M, mitochondria. Scale bars, 200 nm.
WT or Sirt5-deficient MEF cells (Sirt5 +/+ or Sirt5 -/-) were infected with or without VSV-GFP viruses for 12 h, and viral infectivity was detected by flow cytometry analysis (n = 3) (R). Data information: All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).
E) Western blot analysis of protein phosphorylation in HEL, K562Mpl‐mKO2 and K562Mpl‐mOrange2 cells after Tpo stimulation (50 ng/mL Tpo, 10 min).
I, J (I) (vehicle) and (J) (144DG11) show 7 month old Gbeys/ys mice following 3 months under the respective treatments. Note unkempt fur in vehicle treated animal, which was improved by 144DG11.
(E) Representative images of western blot for an α-tubulin antibody. GAPDH was used as a loading control. (F) Quantitative analysis of intensity of α-tubulin in (E). Number of mice, (Control: n=4, S311A: n=5). *, P<0.05 versus Control.
(d) LC3 levels in infected MDCK cells. MDCK cells were infected with wild-type or ΔactA2 bacteria for the indicated times. EBSS (Earle's balanced salt solution, a starvation medium) and rapamycin (100 μg ml−1) were used as controls.
(C) The nucleotide sequences showing the -1348/-948 region in the human UHMK1 gene. The red text indicates the candidate ATF4 binding sites.
G,H Phenotypic analyses showing that PIF4-induced hypocotyl elongation is partially. dependent on the function of BIC1 and BIC2. The Col-0, bic1bic2, PIF4-MYC and PIF4-MYC/bic1bic2 plants were grown for 5 days under long-day conditions. Images of the representative seedlings are shown in (G) and the hypocotyl lengths of indicated genotypes were measured and are shown in (H). Data are means ± SD (n>20). **p < 0.01, as determined by Student's t-test. Scale bar, 2 mm.
(a) Equivalent time points in the four different mutants at which the microarray analysis was performed (R, approximately halfway through the major phase of rod death; C0, onset of cone death; C1 and C2, first and second time point during cone death, respectively). Time is indicated in postnatal days weeks. Cartoons depicting the progression of cone death are shown below the corresponding time points.
The viability of Y. pseudotuberculosis YPIII expressing the indicated CNFY derivatives was assessed in equalized bacterial cultures using the BacTiter-Glo Microbial Cell Viability Assay kit (Promega). The data represent the mean ± SD of three independent experiments, carried out in triplicates.
g, Shifts in phase durations for RPE cells treated with 2 μM CVT-313. A boxplot representing the distributions of durations in untreated cells is underlaid for comparison. *, P < 1 × 10-5, 2-sided Kolmogorov-Smirnov test. (n = 117 cells).
F Total RNA was extracted from wild‐type and COI12 KO cells at the indicated time points of conjugation, separated on a denaturing gel, and visualized by nucleic acid staining (GelRed). Bands corresponding to rRNAs, tRNAs, and scnRNAs are marked with an arrowhead.
C Western blotting analysis of metabolic enzymes in WT and Dgcr8−/−ESCs. Actin serves as a loading control.
(A, B) Pml+/+ and Pml-/- BMDMs were treated with zVAD + AT406 (zA) (A) or TNF + zVAD (Tz) (B), as in Fig. 1, for the indicated times. Contents of RIPK1, p-RIPK1[S166], RIPK3, p-RIPK3, MLKL, and p-MLKL in cell lysates was analysed by immunoblots. Bottom panels, quantitation of p-RIPK1[S166] from three biological replicates using normalized intensity of p-RIPK1[S166] in WT cells at 4 h as 1. Data show mean ± SD.
A. Flow cytometry of cells isolated from heart tissue when scaled against TMRM staining and also FSC and SSC parameters of flow cytometry.
(B) Murine embryonic fibroblasts (MEFs) from WT or ATG16L1‐deficient (ATG16L1 KO) mice infected with Listeria WT for 4 h were analysed by IF using an antibody against ubiquitinated proteins (Ubi).
G-H, Quantification of THEM6 expression in PCa tissue samples according to Gleason score (G) and metastatic status (H) in the patients analysed in F. Data information: Centre line corresponds to median of data, top and bottom of box correspond to 90th and 10th percentile, respectively. Whiskers extend to adjacent values (minimum and maximum data points not considered outliers). Statistical analysis: two-tailed Mann-Whitney U test. Data reproducibility: G: n = 99 tumours for Gleason score ≤ 7 and n = 63 tumours for Gleason score > 7. Panel H: n = 151 tumours for non-metastatic patients and n = 76 tumours for metastatic patients.
D In vitro ubiquitin conjugation assay of UbcH7 catalyzed by GST-tagged PknG or its mutants at 37°C for 30 min. Reaction products were immunoblotted with antibodies against UbcH7 (top panel), Ub (middle panel), and the GST tag on PknG (bottom panel).
Immunofluorescent staining of cGAS (red) in THP-1 cells treated with FITC-ecGAMP (5 μg/ml) (green) or FITC-icGAMP (0.1 μg/ml) (green) for 4 h, nucleus in blue (DAPI). Scale bar, 10 μm.
B Wright-Giemsa staining of untreated and b-estradiol-treated (48 hours) WT clone 1 (WT1) as well as double-mutant clone 1 (int1/8 Mut1).
(B) Levels of β-lactamase (Bla) and β-lactamase-Im7 L53A I54A were detected by Western blotting using a polyclonal antibody recognizing β-lactamase in the WT strain MG1655 and in isogenic strains containing insertions in the pstSCA genes (CL248 (pstS::Tn5), CL249 (pstC::Tn5), CL250 (pstA::Tn5)). Maltose binding protein (MBP) was used as a control.
CH12F3-2 cells stably expressing the indicated shRNAs were stimulated with a cocktail of cytokines (CIT) to induce class switching to IgA. The percentage of IgA+ cells was monitored 24 and 48h post-stimulation by staining with an anti-IgA antibody followed by flow cytometry analysis.
G Left: Representative pictures of lung tissue sections stained immunohistochemically with a rabbit primary antibody (upper left: negative sample; lower left: positive sample). Brown areas represent intra-alveolar aggregates of P. murina organisms. Right: Representative pictures of P. murina organisms detected by immunofluorescence in lungs homogenate (upper right: negative sample; lower right: positive sample).
A. Experimental design. Thirty days after the last pIpC injection, PKCδfl/fl and PKCδ cKO mice were treated with a single dose of 5-FU (150mg/kg, i.p.) and analyzed subsequently by FACS and BrdU incorporation studies.
(C) Subcellular fractions of a discontinuous sucrose gradient collected from top to bottom, separated by SDS-PAGE, and immunoblotted for LAMP1, EEA1, Rab11, Rab8, PMP70, GM130, and Na+/K+ ATPase.
(C) Model for the relationship between Atro, Ft/Hippo and neuronal homeostasis. Atro wt overexpression, and more effectively polyQ Atro overexpression, causes a downregulation of ft transcription and of other genes important for photoreceptor neuron function and homeostasis. This results in downregulation of Ft/Hippo signalling, which affects neurodegeneration. Healthy Ft/Hippo signalling contributes to neuronal homeostasis through effective autophagy. Atro may also exert Ft‐independent effects through other factors (like Tetraspanins) and polyQ Atro also affects neurons through polyQ‐specific factors (like misfolding and aggregation), which put additional pressure on the autophagic system. Other polyQ proteins may not feed into the Ft/Hippo pathway, as in the case of Htt‐ex1‐93Q in flies.
F. Representative images of WIPI2 staining in wt HK2 cells transiently expressing eGFP-OFD1 (HBSS,90min). Green, eGFP-OFD1, red, WIPI2; blue, Hoechst labels nuclei. On the right, quantification of WIPI2 puncta in eGFP-OFD1 transfected cells compared with non-transfected cells (Ctrl) is shown. Scale bar=10μm. n≥90 cells analyzed/sample, n=3 independent experiments.
(D) Representative western blot of DLL4 levels in scr and circHIPK3 stable TREx cells at 0 and 24 hours post induction with GAPDH as a loading control. Densitometry analysis of n=3. Data information: data are presented as mean ± SD. *P<0.05, **P<0.01, ***P<0.001 (Unpaired Student's t-test). All repeats are biological.
Hematoxylin and eosin labeling and Oct4 immunohistochemical staining of teratomas derived from WT and hnRNPLL-KO ES cells (left). Representative Oct4-positive regions are shown. The percentage of Oct4 positive region (%) is plotted (right). The data represent the means ± SD, (n=3, from biological repeats). *P＜0.05; ***P＜0.001, T-test was used to determine the significance. Scale bar, 100 μm.
K Schematic representation of the role of SEU in SCR-mediated activation of WOX5 expression. In WT roots, SEU is recruited to the promoter of WOX5 through the SEU-SCR interaction. SEU interacts with SDG4, which promotes H3K4me3 deposition in the WOX5 promoter. The SCR-SEU-SDG4 ternary complex plays an essential role in activating WOX5 expression and QC specification. Mutation of SEU impairs the formation of the SCR-SEU-SDG4 complex, which leads to dramatically reduced WOX5 expression and defective QC identity.
E. Metascape analysis of upregulated genes for enriched pathway terms in genes identified after 6h of 4SU-labeling. Major pathway clusters are labelled.
Scatter plots representing the association of CSF PGRN with different cognitive tests. Only the subjects of the Alzheimer's continuum group (n = 474) were included. In all tests studied, higher levels of CSF PGRN were associated with worse cognitive performance (namely, lower scores in ADNI-Mem, ADNI-EF and MMSE and higher scores in ADAS-Cog11, ADAS-Cog13 and CDR-SB). The analysis and the graphs are excluding PGRN outliers; including them rendered similar results (Appendix Table S6). Abbreviations: ADAS-Cog, Alzheimer's disease Assessment Scale - cognitive subscale; ADNI-Mem: ADNI memory composite score; ADNI-EF: ADNI executive function composite score; CDR-SB: clinical dementia rating Sum of Boxes; MMSE, Mini-Mental State Examination.
Molecular and clinical features of the cancer genome atlas (TCGA) pan-cancer MPM patients (n = 87) stratified by the presence of KRAS standalone (n = 10) and combined KRAS/TP53 (n = 7) alterations. Shown are unsupervised hierarchical clustering of n = 86 patients (gene expression data were not available for one patient) by 40 genes significantly overexpressed in KRAS/TP53-altered over KRAS-altered over KRAS/TP53-normal patients KRAS/TP53/NF2 co-mutation frequency
(B) An expression plasmid for RIG-I N (stimulated) or ev (unstimulated) was co-transfected with IFNβ-Luc, pRL-TK and the indicated expression plasmids in 293T cells and analyzed as in (A). Data information: (A-G) Data is combined from three independent experiments.
Western blot of Flag-tagged REV-ERBα levels (short and long exposure) in whole cell extracts from AC16 cells transferred from 37°C to 18°C for the time periods indicated and also returned after each of these time periods to 37°C for 2h. TP53 was used as a loading control as its transcript levels show minimal changes in response to 18°C exposure Ponceau stain is shown as an additional loading control.
Differentiation outcome for cells sorted in G1 phase differentiated in the presence of 3μM CHIR (n=7). p-values: two-sided t-test with unequal variance.
(C) Top-ranked enriched KEGG terms in genes that were differentially regulated respectively in the two comparisons (LL37 vs control, and LL37 vs LL37+RAPA) revealed by GSEA analysis. NF-κB signaling pathway was highlighted in red box.
C. PCH analysis is a reporter for the oligomerization state of fluorescence proteins. It reports the measured photon counts per molecule and the average number of molecules within the observation volume. Diagram illustrates potential oligomerization state of monomer (black), dimer (red), and trimer (blue) from PCH analysis.
(C) Super-enhancers are associated with the production of long eRNAs. Boxplots showing length of TT-seq-defined eRNAs originating from Med1-defined super-enhancers (n=552) or other enhancer regions (n=6,934). Median, hinges, whiskers and notches are shown as in (B). P-value by two-sided Mann-Whitney U-test.
Representative auto- (green and violet curves) and cross-correlation (CC, BAX-DRP1, grey curves) curves of DRP1-AF488 and BAX-AF633 measured by FCCS in solution (A) Dash gray line depict raw data and solid lines correspond to data fitting.
Primary VSMCs (left panel), A10 (middle panel), and HEK 293T cells (right panel) were transfected with siRNAs targeting ctnnb1 (β-catenin) or scrambled RNA. After 36 hr, the cells were pulsed with 0.5 µM puromycin for 15 min and then harvested. The puromycin incorporated peptides were detected by Western blot analysis with puromycin antibody. β-catenin blots indicated efficacy of siRNA and actin was used as a loading control. The average puromycin/actin ratio (n=3) is shown in the graphs to the right of each cell type and the error bars indicate standard deviation. A one-way ANOVA and Tukey post-hoc test was performed, with p-values indicated above the error bars
E. Relative transcripts (RT) of Il-15, Tnf, and Tgfb1 (left to right) from total lung samples obtained from aged and young animals at 60 d.p.i. was evaluated by qPCR.
J) Gene Ontology performed on cluster 1 (left panel) and cluster 2 (right panel) genes.
Western blot showing the protein level of CAMSAP2 in negative control and CAMSAP2 siRNA transfected hRPEs. GAPDH was used as loading control. Bar chart shows quantification of protein levels normalized to GAPDH in each condition.
LL37 and IRGM gene expression is upregulated following NOD2 activation (A‐D). Alveolar macrophages were incubated in the presence of 10 μg/mL of MDP or 100 ng/mL of LPS for 24 h. Upregulation of (A) LL37 and (D) IRGM gene expression was assessed after specific ligand recognition by quantitative PCR using the Taqman system and the ΔΔCT method for relative quantification. The fold change in gene expression relative to unstimulated cells is depicted. Data are representative of two independent experiments (n = 7-12). Bold lines indicate median values.
I Mitochondrial cytochrome c release in response to tBid and BimBH3 peptide in CHLA15-Ctrl, CHLA15-shMFN2 and CHLA15-shPACS2 cells. Data information: , data points are mean of duplicate wells (SD<0.05 at all points) in a representative experiment from at least two biological replicates
D Immunohistochemistry against HSP90 was performed in human brain metastases (n=60) from lung (40 cases) and breast cancer (20 cases).
C. Top. IN1 is recruited at Pol I-transcribed genes. ChIP‐qPCR analysis as described for panel 3B. Data represent means ± SD (n = 3). Bottom. Schematic representation of the RDN1 locus with DNA amplicon positions.
B, immunofluorescence analysis of NRF2 in Du145TXR or MCF-7ADR cells treated with indicated agents for 12 hours. Scale bar, 10 μm. Data information: Results are representative of three independent experiments.
Figure 1. Identification of non-canonical p53 binding sites in human subtelomeres. (A and B) ChIP-seq tracks for p53 in camptothecin (CPT) treated or untreated HCT116 cells were aligned with RNAPII, CTCF, RAD21, and SMC1 for human chromosome18q (A) or 13q (B) subtelomeres. Position relative to the centromeric end of the terminal TTAGGG repeat tract are indicated in bp at the top. Subtelomeric DNA paralogy segment tracks, internal telomere-like sequence tracks (red CCCTAA), and annotated RefSeq gene tracks are indicated above the ChIP-seq tracks. (C) Alignment of human subtelomeric elements containing non-canonical p53 recognition sequences. The position of the RepeatMasker-defined LTR10c element is shown; also note the (TG) n microsatellite repeat adjacent to the p53 binding site. (D) Schematic organization of non-canonical p53 binding sites found in human subtelomeres.
D. Averaged ΔCm traces induced by 200-ms depolarization in the presence and absence of dynole-34-2TM (Dynole). Cm traces and endocytic rate were measured as in (A) except that 10 μM dynole-34-2TM with 0.1% DMSO was dialyzed into patched cells.
B. AlphaLISA-mediated quantification of p-Syk in human macrophages with a dose titration treatment of Ab1 and Ab2 with or without liposomes for 5 min. IC50 and maximal inhibition (max) are indicated by a dotted line. Data represent the mean ± SEM (n=3 independent experiments). Data information: Data represent mean ± SEM. For statistical analysis of patient samples in comparison to HC, the unpaired, two-tailed student`s t-test was performed. Statistical significance was set at *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001; ns, not significant
Confocal images of DHHC5, Dsg2 and Golga7b in Golga7b depleted A431 cells three hours after calcium was reintroduced to the media in calcium switch experiments. See Appendix Figure S6 for quantification of data in panels B-D.
(F) Increased eggshell permeability caused by emb-27 knockdown elevates exopher production. n = 103 and 89; N = 3.
Mean ± SEM time spent in the open arms of the Elevated Plus Maze by WT and ASM-KO mice after two months of vehicle or PF treatment (*PWTVeh Vs KO Veh = 0.0342, n = 7 mice per group, two - way ANOVA, Bonferroni post hoc).
G-L Live confocal images of ddaC neurons visualized by ppk-Gal4 driven mCD8::GFP expression at WP or 16 h APF. Simultaneous knockdown klp10A and msps (H) almost fully rescued the dendrite morphological defects and the pruning defects compared with the msps, control RNAi neurons. Wild type larvae fed with colchicine (J) showed pruning defects in comparison with those feed with DMSO (I). ddaC neurons with Kat-60 overexpression (L) exhibited abnormal dendrite arborization and pruning defects. Red arrowheads point to the ddaC somas.
(G) Restored expression of wild-type or 3KR mutant in 786-0 cells lacking GDH1 followed by pretreatment of the cells with or without aa starvation for 24 hours. Cells were collected, and total RNA was extracted for further qPCR using primers against the mRNA of RP genes.
a. Incidence of wound-induced papilloma formation in InvEE PRSS35+/+ (WT; n=8) and InvEE PRSS35-/- (n=10) mice at site of wounding. (* p=0.0218; Gehan-Breslow-Wilcoxon test).
Quantification of α-tubulin fluorescence intensity (as a measure of MT mass polymer, C), in control and centrinone-treated WT, akap KO, c5rap2 KO and pcnt KO cells. Non-centrinone treated double KO cells and centrinone-treated WT cells after washout were also included. Scatter plots show each individual data point and horizontal black lines bars represent the mean.
c, Typical original twitch recordings of developed force of heart muscles from control (thin line) and LAMP-2-deficient (thick line) mice. d, Average values of developed force. Preparations of LAMP-2 deficient mice had a significantly lower baseline developed force at a stimulation frequency of 4 Hz and 10 Hz; P  0.01.
a, WT and Park2-/- mice were infected with wild-type M. tuberculosis by aerosol and lung bacterial burdens were determined by plating (means ± s.d., n = 5 per group, *P < 0.02 by Student's t-test).
Bronchial epithelial (BEAS-2B) cells were challenged with PBS (as control) or with 2 µg/mL Poly(I:C) (PIC) or with influenza A/Scotland/20/74 (H3N2) virus (IAV) at MOI=1 for 4 h and treated or not with succinate (Suc) for 20 h. A neuraminidase (NA) activity test (b) were used to assess the production of physical (b viral particles in the supernatants of IAV-infected cells, treated or not with succinate. Data information: Data are represented as the mean ± SEM of 6 (b, c, e) independent experiments. Statistical analysis was performed using the Kruskal-Wallis test with Dunn's post-test (*P < 0.05).
C. Metaphase spreads stained with Leishman, obtained from control (-) or TMP-UVA-treated cells (2 µM TMP, 2 h followed by 5 s irradiation). Scale bar, 10 µm. Representative images of chromosomal breaks and fusions are shown at higher magnification.
I. Diagram of two transcripts that only differ in a single nucleotide (G in yellow) which creates a frame shift, making one transcript enriched in optimal codons, and the other in non-optimal codons. Time-coursenorthern blot shows that non-optimal transcripts decay faster than their optimal counterparts. The radioactive intensity is shown in italics and normalized to the 1hpi sample for each injection.
F GST‐tagged wild‐type Coi12p (GST‐Coi12p) or GST‐tagged Coi12p lacking the TPR domain (GST‐Coi12p‐∆TPR) was incubated with His‐tagged wild‐type Hsp82p (His‐Hsp82p) or His‐tagged Hsp82p lacking the C‐terminal MEDVD sequence (His‐Hsp82p‐∆C) and affinity‐purified with glutathione‐coupled beads. Proteins before (input) or after (GSTpull‐down) the purification were analyzed by Western blot using anti‐GST (top) and anti‐His (bottom) antibodies. The positions of GST‐Coi12p, GST‐Coi12p‐∆TPR, His‐Hsp82p, and His‐Coi12p‐∆C are marked with arrowheads.
A Caspase activation was measured by fluorescent cell analysis in wild-type MEF cells treated with S-HAD (10 µM, 24 h) or cisplatin (CP, 30 µM, 16 h). n = 3. Error bars indicate SD with * and ** indicate p <0.05 and p<0.01, respectively using Student's T test.
C Effect of pargyline hydrochloride, a pan-KDM inhibitor, on high glucose-mediated nephrin expression. Immortalized mouse podocytes were cultured in the indicated cultured media in the presence or absence of pargyline hydrochloride (1 μM) for 48 hours. Protein lysates from the treated podocytes were analyzed for nephrin expression by immunoblotting. *P < 0.05 versus normal controls, #P < 0.05 versus untreated HG-incubated cells (Wilcoxon two-sample test; n = 3).
LDH release assays from THP-1 cells left untreated or primed with IFNγ, transfected with siRNA against indicated GBPs or non-targeting control (CTRL) and infected with indicated strains of Tg for 24 h.
(F) The degradation of long-lived protein in HeLa cells transfected with myc-SNX18 or a myc control plasmid was quantified as in B (graph shows mean ± SEM [error bars], n = 4). *, P < 0.05; **, P < 0.01. See also Figs. S1 and S2.
(B) Gene ontology analysis for down-regulated genes based on RNA-seq data in E15 hFOXM1-cKI mice.
D) Gene Ontology (GO) enrichment for genes within the APPtg-Blue module. The x-axis depicts -log10(FDR-adjusted p-value) multiplied by the enrichment score (ES), where the red line represents an -log10(0.049)*(ES=1).