EMBO/sd-character-level-ner huggingface dataset:
Top panel, analysis of clonogenic growth of HOP62 cells assessed 14 days after transfection with various siRNA duplexes as indicated. Bottom panel, images of HOP62 clones taken at the day of clonogenic growth assessment. Data are means of 4 independent experiments ±SEM. All values were normalized, colony area of averaged (avrg) siCTRL#1 and #2-transfected cells was set as 1. The Mann-Whitney U test; **p<0.01.
F Expression patterns of representative MAPKKK5-dependent genes. qRT-PCR analysis of defense-related genes in 8-day-old seedlings exposed to 40μM (GlcNAc)7 for 3h. Data are shown as the average of three independent biological replicates ± SD. The asterisks indicate statistically significant differences from the WT controls by Student's t-test (P < 0.05).
(J) L929 cells stably transfected with control shRNA or ZDHHC18 shRNA were transfected with HT-DNA (2 μg/mL) for the indicated times before immunoblotting analysis with the indicated antibodies. Data information: HT-DNA: herring testis DNA; NC: negative control.
(A, B, C, D, E) Dot and box-plot comparing each of the p-tau biomarker between the Aβ-negative (A-; blue; n = 250) and the Aβ-positive (A+; red; n =131) groups. Aβ positivity was defined as CSF Aβ42/40 ratio < 0.071.
(Left) Mean number of both TAF and non-TAF in troponin I-positive mouse embryonic cardiomyocytes at days 0, 3, 5 and 10 following 10Gy X-irradiation. Data are mean ±S.E.M of n=3 independent experiments; 30-50 troponin positive cardiomyocytes were analysed per experiment. (Right) Mean percentage of γH2AX foci co-localising with telomeres (% TAF) in troponin C-positive mouse embryonic cardiomyocytes at days 0, 3, 5 and 10 following 10Gy X-irradiation. Statistical analysis performed using one-way ANOVA (Holm-Sidak method); * P<0.05. Significant differences were found for mean number of non-TAF, but not for mean number of TAF.
g, Intracellular ATP concentrations in cells as in f. Results represent means ± s.d. (n = 5 each). *P<0.05.
(J) High magnification images and their 3D rendered replicates from cerebellar wt and ASMko microglia identified by Iba-1 and of the myelin marker MBP. Scale bars, 10 μm.
Left: Normalized peptide abundance for collagens from hCAFs (each CAF duplicate is represented, CAF1 in blue, 2 in red and 3 in black) treated or not with FAK inhibitor. Right: Heatmap of the collagen modifications in the 3 hCAFs upon FAK inhibition in hCAFs. The value of log2 fold-change between FAK inhibitor treated CAFs and non-treated CAFs for each protein was indicated by the colored scale, with red indicating increased expression while blue implies decreased expression. For each CAFs and each protein, log2 fold-change was calculated based on 2 technical replicates per condition
We confirmed that 2-DG suppressed TGFβ1-induced proteins of αSMA and ColA1 in COUP-TFII OE cells without change the protein of COUP-TFII by western blot (n=3). **p<0.01 by one-way ANOVA.
Linear ubiquitin accumulates at disease-associated protein aggregates under endogenous LUBAC expression. M1-linked ubiquitin (red) and disease-associated proteins (green) were analyzed by immunocytochemistry in SH-SY5Y cells using the 1E3 antibody (Millipore) (B) DAPI (blue). Scale bar, 20 µm.
Upper: A diagram of the domain structure of full length CIP2A protein. Red: RIP=Required for Interaction with PPP2R5C; Orange: RH=Required for Homodimerization; Blue, CC=Coiled coil. Lower: Co-immunoprecipitation coupled western blot analysis assays revealed the interaction of CIP2A-BP with CIP2A via the N-terminus domain of CIP2A. Upper: A diagram of the domain structure of CIP2A protein fragment (1-245). Red: RIP=Required for Interaction with PPP2R5C. Lower: Co-immunoprecipitation coupled western blot analysis assays revealed the interaction of CIP2A-BP with CIP2A via the N-terminus domain of CIP2A (amino acid 159-245).
Recruitment assays. GFP-VAP-A (C ; green) were left untransfected (C) and labelled using anti-Flag (magenta) antibodies. The subpanels on the right are higher magnification (3.5×) images of the area outlined in white. The Overlay panel shows merged green and magenta images. The Coloc panel displays a colocalization mask on which pixels where the green and the magenta channels co-localize are shown in white. Scale bars: 10 µm. Inset scale bars: 2 µm.
A Representative immunoblots of the expression of PGC1-1α in DC cells treated with vehicle or 3 mM NR. Quantification of the indicated proteins is from three immunoblots.
D. Same type of data as in (A) for the CENP-A nucleosome assembled with tailless H2A (H2A, 1-109) alone (pink) and in complex with CENP-CCR (light blue).
Violin plot representing % rescued morphology of Mitome siRNAs. The siRNA able to rescue mitochondrial fragmentation were selected with a univariate 3-components statistical model programmed in R using the following ground truths for morphology: fragmented (NT siRNA, n=30), rescued (DNM1L siRNA, n=30), and hyperfragmented (OPA1 siRNA, n=30). The defined threshold for positive rescued hits (thick dotted line inset) was 49.81% (solid dash on the Y axis and thin dotted line in the inset) and identified 91 candidate genes from one experiment.
Control or CEP41 siRNA-transfected HUVECs cultivated under either static or shear stress states and examined in a wound healing assay in (A). Scale bars, 600 μm. Quantification of the extent of wound closure in (A) displayed graphically by measuring the distance between the lines at the indicated time points in (B). Data are presented as mean ± SD of three independent experiments (n ≥ 3 scratches per experimental condition). Statistical significance was determined using the two-way ANOVA followed by Tukey's post hoc test (***P < 0.01, ns: non-significant).
Domain architecture of PTPIP51 and overall structure of PTPIP51_TPR. The transmembrane (TM), coiled-coil (CC), and tetratricopeptide repeat (TPR) domains are presented. Each TPR pair is marked with a different color: red, TPR1 (α1 and α2); orange, TPR2 (α3 and α4); yellow, TPR3 (α5 and α6); green, TPR4 (α7 and α9); blue, TPR5 (α10 and α11). Two α-helices that are not involved in a TPR (α8 and α12) are highlighted in light blue. The lower panel shows helical wheel projections for the PTPIP51_TPR structure showing one of the features typical of a multi-TPR protein: TPR pairs forming a superhelical twist. The diagram was drawn using NetWheels (http://lbqp.unb.br/NetWheels).
E, F. Representative confocal images of mitochondrial fusion in WT 293T polykaryons in cultures subjected to the PEG-based fusion assay in the presence or absence of endogenous hFis1. Both WT 293T cells stably expressing mitoGFP or mitoRFP were transfected with scrambled siRNA (control siRNA) or hFis1-siRNA as indicated and then co-cultured and fused using PEG treatment. Left panel: control siRNA transfected; right panel: hFis1-siRNA transfected (E). Quantitative analysis of the mitochondrial fusion in individual hybrid cells was performed by the Pearson's correlation coefficient in three independent experiments and data summarized in (F).
Co-IP analysis showing the amounts of bindings between ErbB receptors. Cell lysates from CDK12-overexpressing ZR-75-30 cells were immunoprecipitated with anti-HER2 antibody and immunoblotted using the indicated antibodies. IgG, negative control. Cell line information: ; n/a, CDK12 non-amplified/HER2-amplified cells S, trastuzumab-sensitive.
Gadd45a mRNA level in the hippocampus of Gadd45a-overexpressing mice (red, n=7) was significantly increased (t10=4.189) as compared to Gadd45a-WT (n=5). Values shown are mean ± SEM; unpaired t-test: ** = p<0.01.
C-D. Enrichment of plasma-cell signature genes in KO as compared to WT activated B cells (C) and Enrichment of MYC-target genes in WT as compared to KO activated B cells (D). Enrichment of gene sets is depicted by a BARCODE plot; P-value calculated via FRY test show the statistical significance of enrichment of each gene set. A p-value of less than 0.05 was considered as significant.
Cynomolgus monkeys were administered 24F4A (10 or 1 mg/kg) or vehicle (n = 3 for each dose group) intravenously. Cynomolgus monkeys were bled at various time points, and flow cytometry was used to measure BDCA2 expression and receptor occupancy. PDCs were defined as CD20−, CD14−, CD123+, and HLADR+.E Whole blood from vehicle- or 1 mg/kg 24F4A-treated monkeys was stimulated with CpG-A, and induction of IFN-I was measured by MxA bioassay at various time points pre- and post-treatment. Horizontal black lines represent the model-based estimates of the geometric mean of IFN-I in pre- and post-dose samples. Duplicate symbols represent independent replicates of the MxA bioassay for that time point. Statistical analysis was performed using a two-way mixed-effects analysis of variance (ANOVA).
Antioxidant treatment rescues cells from death caused by TSC1 knockdown. Relative viable cell number counts of P493-6 (-Tet) cells expressing scrambled control shRNA or TSC1-specific sh-RNA 3 days after seeding equal number of viable cells (Trypan blue exclusion), in the presence of 10 μM of the antioxidant BHA where indicated (mean ± st.dev., n=3 biological replicates).
(B) A 10-fold dilution series of cells from exponential SC cultures of the indicated strains were spotted on SC +/- the indicated dose of genotoxic agents.
(A) 293A cells were transfected with plasmids expressing HA-tagged M45 or an unrelated MCMV control protein (m143) and Flag-tagged IKK subunits. Lysates were subjected to immunoprecipitation (IP) using an anti-HA antibody. Immunoprecipitates were analyzed by immunoblotting (IB) using anti-Flag antibody. Whole cell lysates (WCL) were immunoblotted using Flag-, HA-, and actin-specific antibodies, respectively.
(G) The transcription levels of the atrophy-related genes were up-regulated in gastrocnemius muscles of Epg5−/−mice.
MDA-MB-231 derivatives were plated on coverslips pre-coated with a fluorescent gelatin. Two hours later, cells were probed for actin and TKS5. The number of cells with invadopodia were quantified in three experiments. Shown are means ± SD. Each determination included 80 cells. Scale bar, 10 μm.
F. Summary of the Upf1 domains interaction with Upf1-23 and Upf1-decapping components, based on the data presented in this work
2 μM of GST-TRF1 and 0.1 μM of human b-Raf kinase were incubated in the presence of the bRaf inhibitors dabrafenib and vemurafenib.
Abundance of indicated metabolites in NIH-3T3 cells treated with TGFβ or mock for 48h, relative to mock-treated cells. Metabolites were measured by GC-MS.
(C, D) The increased STAT1 and pY-STAT1 in hippocampal total extracts and the nuclear fraction of 12-month-old hTau transgenic mice measured by Western blotting (n=4, Mann-Whitney test). Data information: Data were presented as mean ± SD. *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP, wt or Ctrl.
C. Heatmap showing the mean growth rate value for data binned by both mean cell area and mean nucleoid area. The cell and nucleoid areas are strongly correlated (ρ = 0.84, 95% CI [0.83, 0.85]). The median value of αmax per bin is color-coded according to the color scale. The inset highlights the linearity of the relationship between mean cell area and mean nucleoid area. The orange dots and error bars represent the binned data, with the black line showing the best linear fit to the binned data.
Agarose gel electrophoresis (1%) analysis of RT-PCR products using indicated primer pairs and cDNA made of mRNA isolated from NVH 0075-95 after 4 and 16 hours growth in liquid cultures or genomic DNA as control.
(C) NIH3T3 cells stably expressing GFP-tagged Ub, LC3, Atg5, WIPI-1, Atg14L1, Atg9L1, or ULK1 were transfected with Effectene-coated beads for 3 h in the presence or absence (mock) of 30 µM UBEI-41 (a ubiquitin E1-specific inhibitor) and subjected to immunocytochemistry for galectin3. The percentages of GFP-positive per galectin3-positive beads were enumerated. At least 30 beads were counted (n = 3). The values are the mean ± SD. Statistical analysis was performed by Student's unpaired t test. *, P < 0.05.
(H) HEK-293T cells expressing active (RagBGTP/RagDGDP) or inactive (RagBGDP/RagDGTP) Rag heterodimers were pulled down using glutathione-Sepharose beads and immunoblotted with antibodies against GST and MITF (used to detect Rag proteins and endogenous MITF, respectively). IP, immunoprecipitation.
Accumulation of Ub in autophagy-deficient brain. Ub profile from the 1% Triton X-100-soluble and -insoluble fraction of autophagy-deficient brain homogenates captured with P2UBA resin. (B) Control Atg5 littermates (Atg5flox/+;nestin-Cre; denoted +) at 16 (open circles; n = 4) and 26 wk (open diamonds; n = 3) or Atg5 KO (Atg5flox/flox;nestin-Cre; denoted −) at 16 (closed circles; n = 4) and 26 wk (closed diamonds; n = 3) are shown. Each symbol represents one animal. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.005.
(C) The first instar TBPH-/- larvae were selected to standard food containing with Rapamycin and PA. Quantitative developmental viability analysis of W1118, TBPH-/- and TBPH-/- treated with Rapamycin and PA. The data from three independent experiments indicated the means ± S.E.M., **, p<0.01, one-way ANOVA.
(C) Wild-type and FIP200−/− MEFs were transfected with retroviral vectors encoding GFP-Atg5 or GFP-LC3. Resulting cells were cultured in the starvation medium for 120 min. The cells were fixed and examined by fluorescence microscopy. Bar, 20 μm.
(b) Quantitative PCR analysis of Lamp2a, Lamp2b and Lamp2c mRNA in T cells from L2A-cKO mice (right); results are presented relative to those of their control littermates (left), set as 1.
(F) mRNA expression of Tnfaip2 measured by RT-qPCR in ESCs on the indicated days of differentiation induction of WT EBs [n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test), the P value for the upregulation of Tnfaip2 on consecutive time points (day-0, -2 and -3) was calculated starting with the probability of maximum rank-based difference, i.e. having two groups of three data points perfectly separating, p1,b = 0.1 (bidirectional) and P1,u = 0.05 (unidirectional); the probability of finding a triple series of max. difference starting at some timepoint is Ptriple,tp = p1,b · p1,u · p1,u, and finding such a triple somewhere across the 4-step time series is Ptriple = Ptriple,tp + (1- p1,u) · Ptriple,tp = 0.0005.
A Representative western blot of primary hepatocytes starved in HBSS for the indicated time points and probed with indicated antibodies. Pan-actin was used as loading control. B, C Quantification of western blots as shown in (A). Antibody signal was normalized to pan-actin signal and signal of phospho-protein was normalized to signal of total protein (n=4 independent experiments). Data information: In (B, C), data shows the mean ± SEM. **, P≤0.01 for genotype and ***, P≤0.001 for time (Two-way ANOVA). Error bars show minimum and maximum values.
SNX10 conditional knockout (SNX10 cKO) mice with or without IL-10 KO background and littermate wild type (WT) mice with or without IL-10 KO background were compared (n = 6 animals, each group). D Clinical score was evaluated every two weeks from the 4th week to 16th week. Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. ***p < 0.001 vs WT group; ###p < 0.001 vs IL-10 KO group.
C. In vivo evaluation of different shRNA and TuD combinations after packaging into double-stranded AAV8 vectors and intravenous (i.v.) injection of 1x1011 particles into HBV-transgenic mice (HBV1.3.32). Anti-HBV activity was determined by measuring HBsAg and HBeAg levels in the serum of treated animals at the indicated time points post-AAV injection.
Body weight gain over a 24-week period of high-fat feeding (n = 13-14 animals per group). Panel shows experimental design for Figures 4-6.
RNA-seq analysis was conducted on Tnfaip2-/- EBs vs. WT EBs on day-3 of differentiation induction of EBs (n=3 biological replicates). The heat maps depict the intersection of DEGs with the following gene (D) "ectoderm development" Tnfaip2 and 5 other stem cell-related genes (Tfcp2l1, Dppa3, Fbxo15, Zfp42 and Klf2) were additionally incorporated based on literature searches. The color scale represents the gene-wise z-score calculated from normalized gene expression levels. The asterisk refers to the gene identified in this study.
A. Overview of the lysine metabolism in E. coli. The arrows are color coded according to the different metabolic categories, as defined in the figure legend. Genes targeted in the library are highlighted in green. The insets represent examples of library designs for two targeted proteins, with the targeted residues included inside the gray surface representation
Linear model of α-actinin domains (CH, calponin homology domains; SR, spectrin repeats; EF, EF hands). Bars and numbers on top of the model depict the segments used in this work.
F Comparison of TAZ gene expression, normalized to S12, in heart, liver, and kidney, analyzed in triplicates by quantitative PCR. n= 5 per genotype.G TAZ gene expression in percent. Wild-type is set to 100%.
Representative cortical images of MXO4 staining for APP and APP/Nlrp3-/- 15 months old mice. Scale bar: 50µm.
(A) Western-blot analysis of Huh7 cells transfected with the expression plasmids of HA-tagged GST and various HCV nonstructural proteins. Cells were lysed 48 hours after transfection for analysis. The localizations of molecular weight markers are indicated. The asterisk denotes a nonspecific protein band.
(B) MEFs transiently expressing Myc‐PAT4 were immunostained with the antibodies indicated. Scale bars, 20 μm.
D) Scatter dot plot represents number of vesicles per cell in SBP-GFP-GluK2 RUSH experiment with SEZ6∆cytoER-HA (control) or SEZ6FL-HA co-transfection. Vesicle counts from 15 to 28 cells per timepoint from 2 independent experiments with mean number of vesicles and error bars (SD) are shown. Mann-Whitney test was used to compare HA-tagged SEZ6FL and SEZ6∆cytoER at each time point. At 20 min ***p-value=0.0007, at 40 min ****p-value<0.0001.
(E) F4/80+ cells in 10 randomly selected high-powered fields (HPF) per liver section were counted to calculate average F4/80+ cells per HPF. Mean ± SD. Two experiments, n=2-4 mice per group. One-way ANOVA with Bonferroni's multiple comparisons test; ****P < 0.0001
(F) TH staining by immunohistochemistry (Scale bar, 2000µm) in the SN (left) and striatum (right) of WT and SNCA Tg mice, 6 days after treatment.
Figure 6c. For down-regulated genes with differentially used exons, exons close to the 5´ and 3´end tend to be up- and down-regulated, respectively. Box plots show the log2 fold-change in exon usage after CDK12 inhibition determined by DEXSeq. Exons were grouped into deciles according to their relative exon position. n=3 replicates.
Real-time PCR analysis of cxcr4 transcript expression levels in HeLa (negative control) and in MM cell lines MM.1S and OPM-2. Shown is the mean relative expression ± SEM (n = 3 independent experiments). Values are normalized to the expression of ubiquitin (Ub). The asterisk indicates statistically significant differences (HeLa vs MM.1S: P < 0.001; HeLa vs OPM-2: P < 0.0001; Student's t-test).
Circular representation of DNA methylation levels for mothers (outer circle) and children (inner circle). The height of each bar indicates the methylation change between the smoking and non‐smoking group (dark hue: hypermethylation, light hue: hypomethylation).
OptoCAR‑T cells were loaded with a ratiometric Ca2+indicator (Indo-1) before conjugation with ligand-presenting cells. Conjugated cells were gated on by flow cytometry and the Indo-1 ratio, as a readout of intracellular [Ca2+] was measured over time. Vehicle addition after 60 seconds caused no detectable change in this ratio. Bounded line shows mean ± SEM (n=5).
L. Pbk KD in INS-1 cells suppresses cell growth. Western blot data showed the decreased Pbk expression level in INS-1 cells with Pbk-targeted shRNA transduction. Cell growth curve was from three independent experimets (n=3). ***P < 0.0001 (Vector:shRNA-#1), *P = 0.0181 (Vector:shRNA-#5) , (Two way ANOVA). M. The role of ectopic expression of Pbk-WT and Pbk-Mut on INS-1 cell growth. Western blot data showed the overexpression of V5-flaged wild type and mutant Pbk in INS-1 cells. Cell growth curve was from three independent experimets (n=3). **P = 0.0069 (Two way ANOVA). ns, not statistically significant difference.
Sites that bound (B) canonical HIF-1 (i.e. identified in both HIF-1α and both HIF-1β ChIP-seq experiments) or (C) canonical HIF-2 (i.e. identified in both HIF-2α and both HIF-1β ChIP-seq experiments) were identified from ChIP-seq datasets in HepG2 and HKC-8 cells following 16 hours incubation in 0.5% oxygen and from normoxic RCC4 cells and compared with previously published data from MCF-7 cells. (D) The proportion of total HIF-1 or HIF-2 sites that were shared between 2, 3 or 4 cell lines is plotted. For sites that are shared between (E) HepG2 and HKC-8 cells, (F) HKC-8 and RCC4 cells, or (G) RCC4 and HepG2 cells, the ratio of HIF-1α/HIF-2α signal for one cell line was plotted against the other. The ratio of HIF-1α/HIF-2α in one cell line correlates well with that in the other. ChIP-seq signal is averaged across two independent experiments
(H) Immunoblot of SCOT, BDH1 and β-actin in immortalized murine cardiac endothelial cells (MCEC).
E Representative images of coronal sections showing synapse formation between the glutamatergic corticospinal terminals and spinal neurons in NB-3+/+ and NB-3−/−mice. Corticospinal axons, neurons, and glutamatergic terminals of corticospinal axons were labeled with BDA (red), Tuj1 (blue) and vGlut1/2 (green), respectively. Each group showed the data from the rostral and caudal spinal cord in the condition of sham-operated or 12 weeks post-injury. Scale bar, 20 μm.F Quantification of the number of glutamatergic corticospinal synapses per neuron in each group. n.s., not significant, **p < 0.01; two-way ANOVA followed by Fisher's LSD. n= 15 mice per group.
]. (E) Representative EPSP and mEPSP electrophysiological traces from larval NMJs at Muscle 6. Recordings were taken from WT control larvae (Elav-Gal4>UAS-RFP), hiw mutants driving a control transgene (hiwND8;Elav-Gal4 > UAS-RFP), and hiw mutants expressing an RNAi to knockdown NAD+syn (hiwND8;Elav-Gal4 > UAS-NAD+syn-RNAi).
(E) 8 dpt, qRT-PCR of indicated NF-κB associated SASP genes was performed using indicated treated BJ cells 8 dpt (n=3 independent experiments). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.= Not significant.
Successful targeting of DBN1 was confirmed by sequencing the PCR amplicons surrounding the locus. For example, in clone 3.3, there was a single base insertion in both DBN1 alleles (T in the one, G in the other) to cause disruption of protein expression through the introduction of a premature stop codon.
Ingenuity Pathway Analysis (IPA) of AKG-induced transcriptome signature in adrenal chromaffin cell treated with AKG. The mRAN was extracted from adrenal chromaffin cells after 3-hrs incubation of vehicle or AKG (100 μM). (n = 3 per group).
E. Confocal single plane images of third instar larval wing discs from Mef2>mCherry-RNAi, (left panel) and Mef2>chinmo[HM04048]-RNAi (right panel) stained with anti-Zfh1 (red) and DAPI (cyan). Scale bars: 50 μm. F. Quantification of phenotype displayed in (E). Stacked bars showing the percentage of wing discs scored as either normal or as abnormal. Data are expressed as mean ± sem, N = 32 discs per genotype, n = 3 independent experiments.
VPS4B copy number and dependency scores of selected cancer cell lines obtained in CRISPR/Cas9 and RNAi screens deposited in the DepMap portal (https://depmap.org/portal/).
(A) Levels of D-dimer, CRP, ferritin, white blood cells, and neutrophils are shown for all patients.