EMBO/sd-character-level-ner huggingface dataset:
I: Close-up view of the structure near the conventional FFAT of ORP1 as described in (PDBID: 1Z9O highlighting critical residues of rat VAP-A involved in the interaction. The nomenclature for rat VAP-A residues is based on the Uniprot sequence (Q9Z270) and not on the PDB file 1Z9O. Data information: Phosphorous, nitrogen, oxygen, and sulfur atoms are colored in orange, blue, red, and yellow, respectively. Carbon atoms are shown in green and grey/pink in the MSP domain and the FFAT motif, respectively. The numbers of the peptide residues are noted in subscript.
C Flow cytometric measurements of GFP levels in cells containing the transcriptional UPR reporter. WT cells containing the UPR reporter (SSY2306), cells additionally harboring an estradiol-inducible GAL promoter (SSY2307) and cells additionally harboring the system for estradiol-inducible expression of ino2* under the GAL promoter (SSY2308) were untreated, treated with 800 nM estradiol for 6 h, or treated with 8 mM DTT for 1 h. Data were normalized to untreated WT cells. Bars represent the mean of three biological replicates (n = 3), error bars are the standard error of the mean (s.e.m.). Asterisks indicate statistical significance compared with the corresponding untreated sample, as judged by a two-tailed Student's t-test assuming equal variance. Exceptions were the tests against the normalized value for wild-type cells, for which a two-tailed Student's t-test with unequal variance was applied. *, P < 0.05; n.s., not significant. WT, wild-type.
G - Heatmaps of relative expression levels of DEGs related to apoptosis (top) and proliferation (bottom). Rows correspond to independent biological replicates. Indicated are some example genes.
(D) Temporal bone CT-scan from patient II.7 (left column) and a control (right column) showing malformation of the semicircular canal. The left ear is shown on the upper panels while de right ear on the lower panels.
Detection of the newly synthesized proteins in mascRNA overexpressing cells transiently transfected with PQCXIP vector (PQ), QARS expressing (QARS) or GARS expressing (GARS) plasmid. Left, biotin detection of the labeled nascent proteins; right, coomassie staining of total proteins.   Quantification of the labeled nascent protein levels in Panel E.
C HeLa cells were transfected with USP19-specific siRNA and plasmid encoding Flag-Beclin-1, plus K11-linked-Ub. Protein was harvested after MG132 (10 μM) treatment for 3 h and immunoprecipitated with anti-Flag and immunoblotted with anti-HA.
Cells in the posterior compartment (blue) produce the short-range morphogen Hedgehog, which is received by cells immediately anterior to the compartment boundary, in the anterior compartment (dark green). Hh signal releases Ptc-mediated inhibition of Smo, allowing for the stabilization of the transcriptional co-effector Ci, and increased expression of the ENaC channel Rpk, which depolarizes cells immediately anterior to the compartment boundary. Depolarization results in increased membrane abundance of the Hh activator Smo, and increased transduction of Hh signal. This, in turn, increases expression of Rpk, reinforcing high levels of Hh signal transduction in the region immediately anterior to the compartment boundary.
esgts midguts expressing GFP alone (control), or expressing OvoB, and carrying a Dl-lacZ transgene that marks ISCs. Samples were stained for GFP (green) and ß-Gal (red); the graph shows quantification of ß-Gal-positive cells (ISCs).
Bar plots showing RT-qPCR data (mean mRNA fold-change ±S.D., from two biological replicates) for selected genes in HMGB1-overexpressing compared to control IMR90. The mean fold-change for each mRNA from HMGB1-knockdown RNA-seq data is also shown for comparison (magenta bars). *: P<0.01; unpaired two-tailed Student's t-test.
LRRC8 subunit‐ and osmolarity‐dependent caspase induction in HCT116 cellsA, BCisplatin‐induced caspase activity in the continuous presence of 200 μM cisplatin under isotonic conditions (A), or after 1 h exposure to 200 μM cisplatin under iso‐ and hypotonic conditions (B), was followed over time in WT, HAP1−/−, LRRC8D−/−, and LRRC8 −/−HCT116 cells. Results from HAP1−/− and LRRC8D−/− were obtained with two different clonal cell lines each and averaged.CCaspase activation after 1‐h exposure to 4 μM staurosporine under iso‐ or hypotonic conditions of WT, HAP1−/−, LRRC8D−/−, and LRRC8 −/−HCT116 cells.Data information: Data are presented as mean ± SEM, n = 3-6. *P < 0.05; **P < 0.01; and ***P < 0.001. Similar results were obtained in three independent experiments. Fold change in (A) refers to t = 0. Control experiments indicated that hypotonicity per se had no effect (Appendix Fig S4).
A-I Glucose metabolic parameters were assessed following 5 days of treatment of DIO male mice with vehicle (white), liraglutide (10 nmol/kg) (gray), RM-493 (3.6 μmol/kg) (black), or liraglutide (10 nmol/kg) and RM-493 (3.6 μmol/kg) (checkered). (G) HOMA-IR. Data represent means ± SEM;n = 8 in (A-H); *P < 0.05, **P < 0.01, ***P < 0.001.
LSM images of cross-sections through the jugular lymph sac / primordial thoracic duct (jls/pTD) of an E13.5 control embryo stained for surface VEGFR3 and β1 integrin. Scale bar: 10 µm
Viability of indicated strains (mean ± SD; n = 3). Data information: Welch's unpaired t-test was used to determine the p-value
j, Enteritis histology score of specific pathogen-free (SPF) and germ free (GF) housed mice (n = 10/9/7/7; median shown; Kruskal-Wallis with post-hoc Holm's-corrected Mann-Whitney U-test). k, Representative images of p-IκBα immunoreactivity under conditions as in j (n = 4). Scale bars, 20 µm. Results represent four (f), three (c) or two (a, b) independent experiments. *P  0.05, **P  0.01, ***P  0.001.
(D) Super resolution images of immunofluorescence staining for LC3 (red), FTMT (green) and Tom20 (blue) in FTMT knockdown-Huh7 cells transfected with FTMT-GFP or FTMT siRNA-resistant FTMT-GFP before and after DFP (1.0 mM) treatment. White arrows indicate colocalization of LC3, FTMT, and Tom20.
E Activities of Wnt/β-catenin and MAPK target genes in organoid single cell transcriptomes, ordered along latent time.
D) Histological analysis of representative PDAC-PDX (HuPa4, HuPa8 and HuPa11). Hematoxylin-eosin, anti-TIMP1, anti-MMP7, anti-TSP2 and anti-CCN2 staining of PDAC-PDX tumors (200X, scale bars: 100μm)
A. Schematic representation of the wing imaginal disc and its relationship to the adult wing. The cell fate map of the wing disc is adapted from (Bryant, 1975).
Immunofluorescent images of liver and kidney 24h after sham (with or without starvation) or CLP (n= 6-7/group, combined data of 2 independent experiments). White scale bar = 20µm. The amount of lipid droplets (LDs)/cell and average size of LDs (represented by voxel counts) were calculated for each Z-stack. Averages of the amount and size of LDs were converged for each mouse and biological replicates are depicted in the table as mean ± SEM.
(g) After being transduced with control or BZLF1-expressing lentivirus for 48 h, EBV-WT- and EBV-ΔBRLF1 infected Ramos cells were stained with PI and measured using fluorescent flow cytometry. Representative images of pyroptotic cells are shown and the percentages of pyroptotic cells were calculated in duplicate.
B. Microglia from Plcg2P522 (blue: P522) mice and Plcg2R522 mice (red: R522) from neonate cortex (solid colour) or hippocampus (striped) were loaded with Fluo-8 Ca2+ indicator. These cells were then examined for peak changes in fluoresce after exposure to LPS (50 ng/ml) or Aβ1-42 oligomers (0.5 µM). Data information: Data shown as the mean±SD of 3 independent experiments. The data were analysed by two-way ANOVA with Sidak's post-tests (*=p<0.05, **=p<0.01, ***=p<0.001).
D. Deconvolved fluorescence micrograph showing the lack of colocalization of Chm7-GFP and clustered Nup170-mCherry in a nup133Δ strain. Scale bar is 1 μm.
C. Activation of FOXJ1 by GEMC1 is inhibited by the co-expression of Geminin (compare 3rd and 4th lanes). Example Western blot is shown below. Results graphed are the mean and standard deviation of 3 individual experiments in HEK293T cells.
(B) Overview of GNATs substrate specificities. The number of NTAed subtrates with each of the 6 major active GNATs is displayed in a pie chart according to the N-terminal pattern retrieved. The dataset is identical to that of panel A. N-terminal residues of proteins starting with Met is displayed in dark and light orange while all the other likely resulting from NME are colored with a blue pallet. Very similar pictures are obtained if only N-termini with NTA yields over 50% are figured. The starting, acetylated amino acid is indicated and labeled with the cytosolic Nat-type substrate specificity (i.e., NatA-F) according to the classic distribution
Endogenous METTL14 interacts with PRMT1. The reciprocal endogenous co-immunoprecipitation (IP) assays were performed using the METTL14 antibody for IP and the PRMT1 antibody for Western blot detection (left panel) and using the PRMT1 antibody for IP and the METTL14 antibody for Western blot detection (right panel).
Analysis of shScramble (gray)‐, shIP3R(1,3) A (blue)‐, shIP3R(2,3) B (red)‐, and shIP3R(1,3) C (green)‐expressing DCs migrating in micro‐channels (n > 100 cells per condition from 3 independent experiments for shIP3R(1,3) A and shIP3R(1,3) C and two independent experiments for shIP3R(2,3) B).C Inverted sequential epifluorescence images (20×) of a representative control DC (left) and an immature shIP3R(1,3) C‐silenced DC (right) migrating in micro‐channels. DCs were differentiated from LifeAct‐GFP transgenic mice and imaged every 2.2 min.
Effect of TFL457, TFL482 and TFL541 on neuronal viability after chronic excitotoxicity. Cultures were preincubated with peptides and treated with NMDA for 0-6 h as before. Values for each time point were represented relative to those of neurons incubated with the same peptide but no NMDA. Mean ± SEM of eleven (TFL457), three (TFL482) and seven (TFL541) independent experiments is given.
D Cell lysates of LNCaP cells stably expressing an empty vector (Vector) or a vector expressing ATF4 (ATF4) were prepared and subjected to Western blot analysis with the indicated antisera.
D, HeLa cells transfected with siRNA to reduce expression of MitoNEET (CISD1), NAF-1 (CISD2) or MiNT (CISD3) and immunostained with anti TOM20 antibody. Arrowheads indicate fragmented mitochondria.
(B) WASH KO MEFs were treated with or without EBSS at 37°C for EBSS followed by kinase assays. Cells were lysed and incubated with anti‐Beclin 1 antibody to precipitate the autophagy‐related Vps34. Immunoprecipitates were separated into two equal parts, one for kinase assays and the other for input detection. RLU, relative light unit.
(g) Immunoblot of Atg14 IP in WT or Atg5−/− MEFs maintained in the presence of serum.
D. Lysates of Elp4-FLAG-containing yeast expressing the Elp2 loop mutants were incubated with α-FLAG resin and eluted with 3xFLAG peptides then analyzed by Western Blot using α-HA and α-FLAG antibody
E. The expression levels of mRNA related to energy metabolism in iBAT from WT and TRPV2KO mice. mRNA expression levels of Ucp1, Pgc1a, Ppary, Adrb3, cytochrome c oxidase subunit 4 isoform 1 (Cox4i1), PR domain containing 16 (Prdm16), Ucp2, lipoprotein lipase (Lpl) and cluster of differentiation 36 (Cd36) were examined and normalized to the levels of 36B4. Data are presented as mean ± SEM, n = 15; * P < 0.05 vs. WT group; ** P < 0.01 vs. WT group. Unpaired Student's t-test.
A) Confocal microscopy images show a tubule (upper panel) labeled with UIS4 and IBIS1 (white arrowheads), an elongated membrane cluster (middle panel) in which both proteins are present, and vesicles (bottom panel) that are often labeled with both UIS4 and IBIS1 (yellow arrow) and frequently labeled with only one protein (yellow arrowheads).
RNA-seq analysis of CD4+ T cells isolated from 3 WT and 3 Stim1fl/flCd4Cre mice that were differentiated into pathogenic Th17 cells (pTh17: IL-1β, IL-6, IL-23) and non-pathogenic Th17 cells (npTh17: IL-6, TGFβ1). (A) Differentially expressed genes (DEG) in WT and STIM1-deficient npTh17 and pTh17 cells. P (adj.) < 0.10.
E WT and C2βD1212A/D1212A mice were subjected to thromboembolic stroke model. Representatives T2-weighted MRI of coronal section taken 24 hours after the onset of in situ clot formation by α-thrombin were shown. Graph quantification of infarct volume measurements. Data represent mean ± SEM (n=23-25 mice per group; **p<0.01, Unpaired t-test).
(C) Endolysosomal membranes from MSD, MPS‐IIIA and WT MEFs were stained with C‐laurdan and subsequently analysed by fluorescence spectrophotometry to calculate the GP value (see Materials and methods section for details). Distribution of cholesterol was also measured throughout the gradient ad expressed as percentage of total cholesterol in raft (DRMs) and soluble fractions.
(d) RALB ubiquitylation at Lys 47 affects activation of TBK1 and IRF3. At 48 h after transfection with empty vector (V), Flag-RALB-G23V and Flag-RALB-G23V-K47R, 293-hTLR3 cells were treated with 10 μg ml−1 of poly(I:C) for 6 h. Immunoblot analysis was performed using the indicated antibodies. Uncropped images of blots are shown in Supplementary Fig. S7.
(E) A20 mRNA quantified via qPCR (mean of three independent experiments ± standard deviation; two-tailed Student's t-test *P<0.05).
A-E) Overall survival of patients with tumors containing mutations in pathways A) WNT signaling, B) Hedgehog signaling, C) NOTCH2 signaling, D) p53 independent DNA damage repair, E) TGFβ signaling, stratified by groups receiving no systemic treatment (n=336), endocrine therapy only (Endo only; n=1,579), endocrine and chemo therapy (Endo + Chemo ± any; n=914), as well as HER2 treatment with any other treatment or none (HER2 ± any; n=348). Specific treatments in these groups are detailed in Table EV4. In each Kaplan-Meier plot, wildtype (wt) cases are plotted in blue, mutated (mut) cases are plotted in red, the log-rank P value is given, and the hazard ratio (HR) for mutation is given with a 95% CI and after uni-variable and multi-variable (MV) Cox regression adjustment. Covariables included in the MV analysis were age at diagnosis, lymph node status, tumor size, and the variables denoted by the following symbols: ¶, ER, PgR, HER2, and NHG; ¤, ER, PgR, and NHG; $, HER2 and NHG. Abbreviations: ER, estrogen receptor; PgR, progesterone receptor; HER2, human epidermal growth factor receptor 2; NHG, Nottingham histological grade.
(d) FACS blots to detect CD25+FoxP3+ Treg cells in lungs 2 weeks after AdCre inhalation. Cells were gated on CD4+ populations. Numbers indicate percentages among total CD4+ cells in the lungs.
(A-C) Time and concentration dependent clustering of Fib-Tau in primary neurons. Representative images are shown for certain conditions to illustrate Fib-Tau clustering time dependence (A, top-row) and concentration dependence (A, bottom-row). Quantification of the number of Fib-Tau clusters per µm2 (B) or fluorescence intensity of clusters At low concentrations (up to 0.72nM) the density of clusters increased with time (between 10 and 60 min) but the increase in intensity was small. At high concentrations of Fib-Tau (≥1.8nM), both density and size increased with increasing time. Box-plot represents: median, interquartile range and 10-90% distribution; One-way ANOVA with Dunnett post-hoc test, number of images analysed from 3 cultures (from left to right: 25, 25, 25, 25, 70, 45, 45, 45, 45, 45, 30, 40, 40, 40, 40 and 40 images). Data information: *p<0.05; **p<0.01; ***p<0.001; ns= not significant. Scale bar 2µm
In the absence of a ΔpH, the time course of pyruvate homo-exchange was similar for the Mpc1/Mpc3 proteoliposomes and the empty liposomes (n=4).
(C) UgpB expression is sufficient to lead to higher levels of Im7 L53A I54A protein. Im7 L53A I54A and UgpB were expressed in a ugpB mutant strain (CL543) from pCDFTrc and pTrc99a vectors, respectively, both of which have an IPTG-inducible promoter. Periplasmic fractions were isolated and examined by Western blotting. "-" indicates strains containing empty vector and "+" indicates strains containing a recombinant plasmid encoding either Im7 L53A I54A or UgpB. MBP was used as a loading control. Data information: These experiments were repeated twice with similar results and one representative is shown.
Time-lapse imaging of an embryo with transiently halted cardiac contraction (using Tricaine). Despite absent blood flow kugeln still changed shape (grey arrowhead), retained shape (white arrowhead) or protruded and retracted (black arrowhead; time post cessation of flow is indicated on micrographs; 3dpf; grey inverted LUT). Time-lapse of an embryo with transiently halted cardiac contraction as in (C) showed that kugel diameter still oscillates (time post cessation of flow).
A. Exponential cells of indicated strains (below the bars) were plated onto LB agar and either were, or were not UV-irradiated. After overnight incubation, CFU were counted. UV sensitivity of the mutant strains (KO) was then calculated as the ratio between irradiated vs non-irradiated cells and normalized to this ratio from the wt strain As a consequence, the wt ratio is 1. The experiment was conducted 4x (biological replicates) and the bars show the geometric mean. The p-values, shown above the bars, were computed using two-tailed unpaired t-test for logarithms of the ratios. The error bars show ±SEM (computed on the log scale).
Albumin-cre mice were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10 knockout mice (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice and KLF10flox/flox were treated with WD/CCl4 for 12 weeks. KLF10flox/flox mice were used as the control (Ctrl). n=5 per group. (L) CD36 protein expression in plasma membrane fractions from mouse livers, and its normalization to ATP1a1. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test
(D) Hoechst staining (4-6) of GFP-positive 293 cells (1-3) 60 h after cotransfection with GFP and DAPk ΔCaM (1 and 4), DRP-1 Δ73 (2 and 5), or p55/TNFR1 (3 and 6). Arrows point to condensed nuclei resulting from DRP-1 Δ73 or DAPk ΔCaM transfections (4 and 5).
(A) Schematic representation of the mintbody. H3K27me3-specific single-chain variable fragment (scFv) is genetically fused with a fluorescent protein (FP).
B-D Endogenous TMEM41B locus was tagged with C-terminal Myc using CRISPR-directed homologous recombination in HeLa cells. HeLa knock-in (KI) cells were compared to parental HeLa (-) and HeLa cells stably transduced with a TMEM41B-Myc over-expression (OE) construct. (B) Confocal micrographs of cells stained with antibodies against CANX and Myc confirming ER localization of both KI and OE TMEM41B-Myc. Scale bar represents 20 μm
(B) Phylogenetic tree constructed from an alignment of 93 fungal Hrr25 orthologs. Branches in green represent Hrr25proteins from Saccharomycotina yeast with the conserved central domain (see Figure EV1A for sequence alignment). Branches in blue represent Saccharomycotina Hrr25 proteins lacking this domain. Orange stars indicate the presence of a Mam1 ortholog in each species' genome. E. cymbalariae (white star) possesses an un-annotated Mam1 ortholog on chromosome VII (region ~313000-315000, 32% identity to S. cerevisiae Mam1 residues 83-242, identified by TBLASTN (NCBI)). Purple diamonds denote organisms in which point-centromere sequences have been identified (Meraldi et al, 2006; Gordon et al, 2011). Point-centromeres and Mam1 orthologs are both exclusive to the group of yeast whose Hrr25 orthologs possess the central domain.
(D) CysLT1 protein expression in CysLT1 knockdown HBMEC using shRNA (left panel) and relative invasion frequency of 8 GBS isolates in CysLT1 knockdown and control HBMEC. t-test. From left to right, p value of K79 is 0.0039, p value of K160 is 0.0082, p value of K161 is 0.00091, p value of K181 is 0.0087, p value of K226 is 0.00020, p value of K237 is 0.0039, p value of K238 is 0.00066, p value of P539 is 1.76E-05 (right panel).
Density representation of the p150-docked structure (solid blue in left inset, transparent in right) superposed over the high resolution pointed end map shows where the coiled coil sits.
B. Rif1-∆C594 retains function to control DNA replication. Growth of a cdc7-1 rif1-∆C594 mutant was compared with growth of cdc7-1 RIF1 and cdc7-1 rif1∆ strains at 23ºC (permissive temperature for cdc7-1 allele), 26ºC (mild restrictive temperature) and 30ºC (strict restrictive temperature)
D Box plots of Em/Ad of GATA6 (left) or NKX2-1 (right) in FFPE lung tissue sections from controls or LC patients. Samples were staged according to the TNM Classification (UICC, 7th edition).
LPS-primed Abro1+/+ and Abro1−/− BMDMs were treated with various doses of ATP. ELISA of IL-18 (B) in the culture supernatants.
(D) Cell proliferation of A2dd, CycB1dd and B1dd/B2ko following mock or DIA treatment. 1000 cells were plated in each well (diameter 3.5cm) and incubated for 10 days before methanol fixation and Crystal Violet staining.
Quantification of apoptotic corpse in wild-type (WT), brc-1(tm1145) and brd-1(gk297) strains fed as in (A) and left untreated (C Bar graphs are mean ± SEM. Data information Data are presented a mean ± SEM N= 8-10 worms per replicate and condition, * P < 0.05, *** P < 0.001 and **** P < 0.0001 vs untreated; ### P<0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey"s multiple comparison
Human bronchial epithelial BEAS-2B cells were infected with the influenza A/Scotland/20/74 (H3N2) virus (IAV) at MOI=1 for 4 h, and subsequently treated or not with 4 mg/mL of succinate (Suc) for 20 h. (g) Plaque-Forming Unit assays determined the production of infectious viral particles in cell supernatants. Data information: Data are represented as the mean ± SEM of 3 biological replicates with (g) 2 technical replicates each. Statistical analysis was performed using the paired t-test (g), (*P < 0.05).
(D) Representative immunoblotting of Y755-phosphorylated MuSK, total MuSK, and β-actin in the diaphragm at E18.5 of wild-type (WT), Ctgf-/-, and Ctgf+/- mice.
Four-day-old seedlings of 35S:ARR12:YFP, 35S:ARR12S323A:YFP, and 35S:ARR12S323D:YFP were transferred to 1/2 MS medium supplemented with or without 50 mM or 75 mM NaCl. After three days of salt treatment, plant phenotypes were determined.
Images of mESCs transduced with Rptor or Rictor shRNAs in SL. Scale bar, 400 µm.   Relative proliferation of mESCs as in (A) (mean values ± SD). n = 3 biological replicates.
A549 were transfected with control siRNA (siC) and AGR2-tergetd siRNA (siAGR2). After 24 hours, cells were transfected with p53-luciferase construct. Cells were then treated as in (C) and luciferase experiments were performed. n=4, biological replicates ﻿(mean ± SD. ﻿Differences were analyzed by Unpaired Student's t-test using Prism 9 (GraphPad), except when otherwise indicated.
Clonogenic survival assays of U2OS WT and PHF6 knockout cells that were depleted for luciferase or XRCC4 and treated with 2, 3 or 4 Gy IR. Shown is the relative survival as compared to the undamaged control. Error bars represent the SEM of three individual experiments.
F Analysis by mass spectrometry of immunoprecipitated proteins. ApCatSper 1‐4, β, γ, and δ were identified in the immunoprecipitates obtained with both the anti‐ApCatSper 2 and anti‐ApCatSper 3 antibodies. The number of tryptic peptides identified and the respective sequence coverage are given.
a, Representative flow-cytometry plots of CD44 and CD62L expression on total CD8 T cells of 45-wk-old Dj-1 KO and age- and sex-matched WT mice.
Detection of endogenous Ago1x by Western blot in HEK293 cells using anti-Ago1x antibody and pre-immune serum.
U2OS cells (D) and RPE1 hTert immortalized primary epithelial cells (E) were transfected with siRNA oligos targeting the hits in a similar setup as described in A), but now analyzed for mitotic entry by MPM2 and PI staining by flow cytometry. For normalization see materials and methods. Error bars represent the SEM of three independent experiments.