EMBO/sd-character-level-ner huggingface dataset:
Evoked and spontaneous release in autaptic munc18-1 null hippocampal neurons expressing M18Y473D, M18Y473D/P335A or wild-type Munc18-1 as control.(D) Depression of EPSC amplitude during a 10 Hz train. Inset shows first 4 pulses normalized to the first EPSC.
(B) UBA enrichment of ubiquitinated proteins from HeLa+HA-Parkin cells, BAX-/- BAK-/- (DKO) HeLa cells or wild-type (WT) HeLa cells expressing HA-Parkin in response to 1 µM of each of ABT-737 and S63485 for 3 h (BH3) in the presence of QVD.oph (10 μM). Representative of three independent experiments.
(A) rBCV biogenesis in BMMs infected with either wild type (2308), VirB-deficient (ΔvirB11), ΔbspF, or complemented ∆bspF (ΔbspF::bspF) bacteria, measured as the percentage of LAMP1-positive BCVs over time. Data are means ± SD of n=3 independent experiments. Asterisks indicate statistically significant differences (P<0.05, two-way ANOVA followed by Dunnett's multiple comparisons test) compared to control (2308).
E) Sen1 Nter interacts with the C-terminal domain (Cter) of Sen1 both in the presence and in the absence of the NIM in vitro. Pull-down experiments using either a wt or a ∆NIM version of recombinant Sen1 Cter immobilized on glutathione-sepharose beads and a TAP-tagged version of Sen1 Nter expressed in yeast. Representative gel of one out of three independent experiments.
(E) Volcano plot of the differential gene expression analysis of n=318 SPF and 510 GF cells based on Wilcoxon Rank Sum tests. The shown genes are filtered based on an average log2 fold change (avg. log2FC) > 0.2 and adjusted p-value < 0.05.
A. UMAP embedding of human ileum-derived organoids colored by the expression of HAstV1.
(B) BAX/BAK-deficient HeLa cells reconstituted with BAX and where indicated HA-Parkin were treated with antimycin A and oligomycin (AO) for 2 h and then 1 µM of each of the BH3 mimetics ABT-737 and S63485 for 6 h. Cell death was assessed at the indicated times by LDH assay. Data is mean +/- SD of four independent experiments.
E) Representative fluorescence images of EdU and pH3/cleaved caspase 3 staining in paclitaxel-only and palbociclib plus paclitaxel dual treated HFs following drug washout. Where DNA synthesis has resumed following reversal of the G1 arrest, paclitaxel cytotoxicity is emergent. HS - hair shaft; "wo" - washout. 20 µm scale.
(D) MIR376A blocked starvation induced SQSTM1 degradation in MCF-7 cells. ACTB was used as a loading control. SQSTM1/ACTIN densitometric ratios were marked.
C. IFA was performed on parasites expressing WT EK-GFP or its S37A mutant 6-12h post-invasion to detect (i) RAP1, which is transferred to PV post invasion, and (ii) MSP1 which is located at the PVM. Parasite expressing WT EK-GFP exhibited typical round ring like shape. In contrast, several parasites expressing the S37A mutant exhibited irregular morphology with much smaller vacuolar space and in some parasites RAP1 was found outside the PV (Scale bar-1 μm).
C GPX1 protein level was plotted using the immunohistochemical scores as described in methods. (left) representative images from immunohistochemistry staining for GPX1 in tissues from patients who suffered acute myocardial infarctions. (right) plot of GPX1 scores in each BZ and DZ (n = 9 patients). DZ, distant area; BZ, border zone. Scale bars, 250 μm (left). * p = 0.0039.
(B) Sirt5 deficiency suppresses GSH production in MEFs. The ratio of [GSH/GSSG] was determined in cell extracts as described in 'Materials and Methods'. The results are average ± SD of 3 independent experiments *p<0.05 (two-tailed unpaired t-test).
qPCR measurements of RNA levels (n=3) for the three isoforms of JARID2 in HaCaT cells. The RNA levels are plotted relative to 18S rRNA. Level of JARID2 isoform-1 is significantly higher than that of isoform-2 (***P<0.001) and isoform-3 (****P<0.0001).
A,B Representative bright-filed (A) and AP staining (B) images of the WT and Mettl5 KO mESCs cultured in 2i/Lif medium. Scale bars represent 100 μm and 50 μm, respectively.
A. hTR RNA, hTERT and NHP2 mRNA expression, normalized to ACTB mRNA and to 143B/TEL+ cells, in a series of TEL+ and ALT+ human cell lines as indicated (n=3). Data information: Data are presented as mean ± SD. Statistical analyses were performed using one-way ANOVA with post-hoc Tukey's test for multiple comparisons.
Plots and Pearson correlation analysis of reciprocals of EC50 vs. the force-dependent effective in-situ affinities AcKa at 15 pN (G).
(h) Luciferase activity levels showing the NFAT transcriptional activity in cardiomyocytes transfected with Scr Ctrl, pre-miR-132 or pre-miR-212 (n=5).
(D) Real-Time PCR analysis for HIF1α mRNA expression in BT549 cells with GFP or MIG-6 knockdown. The quantified results are presented as mean ± SD (n=4). ***p < 0.001, by Student's t-test.
Diagram of the gene conversion (GC) assay used in this study. Red line represents galactose-inducible HO endonuclease cut site.
A. Quantification of three categories of midguts treated with the pH indicator Bromophenol Blue in Drosophila of indicated genotypes. The numbers of quantified guts from left to right are 90, 90, 90, 90, and 90. Error bars show the SD of three independent experiments. Data information: Error bars represent SDs. p-values for lifespan curves (C) were calculated by the log-rank test. The statistical tests used in other panels were student's t-tests. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.
HF morphogenesis stages at P4 in lesional, nonlesional, and unaffected littermate control skin (n=5 biological replicates).
A Confocal immunofluorescence microscopy images of P1.HTR cells either untransfected (Untr) or transfected with IDO1.WT (WT) or vector alone (Mock) and stained with antibodies recognizing IDO1 (green). Nuclei were stained with DAPI (blue). Scale bar, 20 µm.
h-j, m-o, The numbers of autophagic vacuoles (h, m) and autophagic vacuoles containing mitochondria (i, n) and persisting mitochondria (j, o) in reticulocytes (h-j) and erythrocytes (m-o). Error bars indicate s.d. (*P  0.05; n = 55 cells).
(C) Average size, normalized on cell size, quantified by image (as in a) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes. Results are the average ± SEM of two independent experiments for a total 830 early endosomes in 13 shCTL/GFP cells (64 ± 6 endosomes per cell), 719 early endosomes in 10 shSTIM1/GFP cells (60 ± 6 endosomes per cell), 820 early endosomes in 12 shSTIM1/GFP-STIM1 WT cells (68 ± 6 endosomes per cell) and 400 early endosomes in 12 shSTIM1/GFP-STIM1 NN cells (33 ± 7 endosomes per cell) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for shCTL/GFP and shSTIM1/GFP p≤ 0,001 ***, for shCTL/GFP and shSTIM1/GFP-STIM1 WT p> 0.05 not significant (ns), for shSTIM1/GFP-STIM WT and shSTIM1/GFP-STIM1 NN p≤ 0,001 *** and for shSTIM1/GFP and shSTIM1/GFP-STIM1 NN p≤ 0,05 *.
(f) Cell-cell concentration differences in HES5 between neighbours, normalised to mean concentration of HES5 in that domain; grey data points represent normalised concentration difference between a pair of neighbours, bars shows mean and SD; 2 independent experiments; 2-tailed Mann-Whitney test with p-values ***p = 0.003, ****p<0.00001.
Plots and Pearson correlation analysis of reciprocals of EC50 vs. the force-dependent effective in-situ affinities AcKa at 5 pN (E), 10 pN (F)
(B) Representative Western Blot analysis of endogenous KIFC1 and STIM1 proteins (both normalized on total tubulin levels) in ECs silenced with a control siRNA (siCTL) or one targeting KIFC1 (siKIFC1) or two control siRNAs (siCTLsiCTL) or two targeting KIFC1 and STIM1 (siKIFC1siSTIM1). Results are the average ± SD of three independent experiments and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,01; Bonferroni for siCTL and siKIFC1, KIFC1 expression p≤ 0,001 ***, STIM1 expression p> 0.05 not significant (ns) and for siCTLsiCTL and siKIFC1siSTIM1, KIFC1 expression p≤ 0,01 **, STIM1 expression p≤ 0,05 *.
(E) SKO + WT-seipin-GFP cells were delipidated and treated with OA for 1h, fixed and stained with LipidTox Red. Single focal plane of a 3D-SIM z-stack. (F) Analysis of (E), bars: % of LDs/cell with the indicated number of WT-seipin-GFP punctae associated, mean ± SEM, n=12 cells (693 LDs), 2 experiments, p**< 0.005 (Tukey multiple comparisons test).
Quantification of mean fluorescence intensity of Sir4-GFP using >100 cells. Error bars show the SD from 3 independent experiments. Quantification of cells containing Sir4 clusters at the nuclear envelope (NE). Data are represented as mean ± SD from 3 independent experiments where >100 cells were counted.
E-H) Dissection of energetic components with increasing mainchain depths for each charged residue. Mean values are plotted, whiskers indicate edges of a 95 % confidence interval for the population mean based on a t-distribution. The number of replicates per group is indicated. The numbers of observations per group are the same as those indicated in panel D.
I-K p53+/+ and p53-/- HCT116 cells transfected with control or SQLE siRNA for 48 hours were injected into nude mice separately. (I) Tumor volume were recorded after inoculation (top). Western blot was performed using lysates of xenograft tumors (bottom). (J) Average tumor weights (top) and images (bottom) of xenograft tumors (3weeks, means ± SD, n=7) are shown. (K) Cholesterol concentrations of xenograft tumors were examined.
B Ribbon representation of the Re9F06⋅RBD⋅Re5D06 complex as in A, but with RBD-bound ACE2 shown as a semitransparent brown surface. Docking of ACE2 is based on the alignment of the RBD with the SARS-CoV-2 RBD⋅ACE2 complex (PDB ID 7KMS (Zhou et al., 2020b); RMSD=0.986 Å). Note the clash of ACE2 with Re5D06 and Re9F06.
Classification of genes differentially expressed in LXRα-Tg hearts (see Supplementary Fig S3).
(C) Scheme of the generation of transgenic Lgr5-GFPCreERT2 X Tomatof/f mice. eGFP and CreERT2 expression are controlled by the intestinal stem cell specific marker Lgr5 promoter, and the tdTomato reporter cassette is knocked into the Rosa26 locus. A floxed STOP cassette is upstream of the tdTomato gene, thus preventing tdTomato expression in the absence of tamoxifen. Upon tamoxifen exposure, CreERT2 recombinase will be translocated into the nucleus, and the STOP sequence between the loxP sites is excised and the tdTomato reporter is permanently and constitutively expressed in intestinal stem cells and their progeny.
(F) Hypothetical model for the distribution of LAMP‐2A in microdomains at the lysosomal membrane and its changes with CMA activity (see text for details).
Two types of 127-kb tandem MGE detected in multi-drug resistant S. suis ST7 isolates in lineage III. The 127-kb MGE encodes eight antibiotic resistance genes. The integrative and conjugative elements (ICE, in orange) and prophage (in purple), both of which are flanked by att sites, are tandemly arranged in two possible orders. The antibiotic-resistance genes are indicated in red. The chromosomal conserved genes around MGE are indicated in black.
YAP mRNA levels in HT3 cells treated with or without E6 (400 nM) for 48 h in McCoy's 5A with 1% serum. mRNA levels were measured with real-time PCR. Data were normalized with 18S mRNA. Each bar represents mean ± SEM (n = 5). Bars with same letters are not significantly different from each other (P > 0.05) (P = 0.3233).
Phagosomes from KO and induced cells were isolated as in (A). Permeabilized, unfixed phagosomes were incubated with 10 µM of the indicated peptides for 3 hours at 25oC in Perm buffer. Phagosomes were then washed and stained for H2-Ld. Shown are histograms of indicated stains. Flow cytometry plots of (D).
B Functional classification of selected differentially expressed genes in sorted suprabasal BSC vs basal BSC after RNA-seq analysis (red: up-regulated genes, green: downregulated genes; fold change > 2, p < 0,05
Bar graph showing the relative levels of free/total cholesterol in HN31 cell extracts exposed to the indicated perturbagens Values represent mean±SEM. Data points represent values from biological replicates. Statistical tests employed were Student's t-test and ANOVA.
(D) The desuccinylase activity of SIRT5 is stimulated by oxidative stimuli. Flag-SIRT5 was ectopically expressed in HEK293T cells. The transfected cells were treated with increased concentrations of Paraquat or H2O2 for the indicated periods. Flag-SIRT5 was purified by immunoprecipitation with Flag beads, eluted with Flag peptide, and then subjected to the desuccinylase activity assay as described in 'Materials and Methods'. The SIRT5 desuccinylase activity was normalized against its protein level. The results are average ± SD of 3 independent experiments *p<0.05, ***p<0.001 (two-tailed unpaired t-test).
An equal number of Ctrl and YY1iKO cells were cultured for 36h; basal extracellular acidification rate (ECAR) level were measured and normalized with cell numbers. N=3 mice.
G. Average distribution profiles of sense SINE repeats on indicated exons and on ±0.7kb of surrounding introns.
DC3.2 Rab39a KO cells were transduced with dox inducible mcherry-tagged Rab39a. Cells were plated in 35 mm glass bottom dishes and induced with 1 µg/ml dox. The next day, 1 µm latex beads conjugated with Alexa 488-NHS (1 bead/cell) were added. After 2 hours at 37oC, cells were imaged under a Leica TCS SP5 confocal microscope. Green = Alexa 488 labeled beads. Magenta = mcherry-Rab39a. Arrows highlight internalized beads surrounded by Rab39a. Scale bar = 10 µm. Representative image of two independent experiments.
(f) Left: Scheme of long-range interactions between Sμ-Sα elements in the IgH locus before and after AID activation. Right: Representative gel picture of the 3C assay detecting the Sμ-Sα interaction in WT or Samhd1 KO CH12F3-2A cells with or without CIT stimulation for 24 h. Gapdh was amplified as a loading control.
Fibroblast activation during wound repair. quantification of α−sma fluorescence intensity in pixel per area inside the upper and lower wound bed (n= 4 PW0, PW2, PW7, PW21; n= 3 PW10, PW14; n= 2 PW4 biological replicates)
Swollen AF conidia are taken up by macrophages. The AF-containing phagosome rapidly acidifies, resulting in the activation of endosomal PRRs such as TLR9. TLR9 signalling drives BTK activation, which in turn activates phospholipase Cγ (PLCγ) by phosphorylation. PLCγ activation initiates the calcium flux required for calcineurin-mediated NFAT translocation into the nucleus. Additionally, NF-κB translocation is activated from the cell surface and acts in synergy with NFAT for TNF-α production. TNF-α secretion results in neutrophil recruitment which is the cell type required for efficient fungal clearance.
(J) Ratio of WT and Mettl14 KO cells with inducible expression of MYC in the co-culture model was quantified and shown as dot plots. n=8, P<0.01 (Student's t-test) for KO cells without Dox treatment (no MYC expression) compared with WT cells or KO cells with Dox stimulation (exogenous MYC expression) at both Day 7 and 14. Error bar represents S.D.
(B) After 48 h, the cells were fixed and the degree of colocalization between ER and mitochondria based on red and green fluorescent pixel overlap was analyzed using Mander's coefficient (n= 30 cells analyzed in 3 independent experiments). Data are presented as mean ± SEM. *p<0.05, two-tailed Student's t-test.
(E) Compiled percentages of CHIKV-infected (ZsGreen positive) leukocytes at 2 days post infection (dpi) for the respective groups (n=5 per group). Background ZsGreen signals are indicated by the dotted line.
Left - Quantification of percent Nanog-GFP positive colonies. Right - Total Nanog-GFP positive colonies obtained after ten days of AA+2i treatment in Tdg-depleted pre-iPSC (Tdg) or control (Empty).
J Myocardial FDG uptake quantified as standard uptake value (SUV); n = 6/group. *P = 0.0001 versus WT sham, #P = 0.047.
Synaptic transmission was assessed during and immediately after sustained stimulation in autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473D. (A) Rundown of EPSC amplitude during 100 pulses at 10 Hz. Top: example traces of the current evoked by 40Hz stimulation.
Synaptic transmission was assessed during and immediately after sustained stimulation in autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473D.(B) EPSC charge during 100 pulses at 40 Hz. Top: example traces of the current evoked by 40Hz stimulation. Insert shows total charge transferred during entire train (M18WT: 2.63 ± 0.38 nC; M18Y473D: 1.48 ± 0.24 nC, t test with Welch correction, p = 0.0177).
(L) Schematic illustration of different pluripotent states and developmental stages.
(C) Timecourse monitoring fluorescence increase on liposomes following addition of 4 µM BID-BH3 peptide to 50 nM BAK or BAK-Ub in the presence or absence of 25 mM TCEP. Data is mean +/- SD of three independent experiments.
B, C. Scatter plots showing transcriptional changes between human GV and MII stage oocytes from unidentified control patients (B) and between control and MOSAsn95Lys MII oocytes (C), separately. Genes that were increased or decreased more than two-folds are indicated in red and blue, respectively. RPKM, reads per kilobase per million mapped reads.
(h) Peak:to:peak distance in auto-correlation plots of detrended Venus::HES5 spatial profile in DMSO and DBZ treated E10.5 Venus::HES5 spinal cord slices; gray dots represent significant mean peak-to-peak distance of DMSO (100) and DBZ (105) auto-correlation functions collected from 3 z-stacks per slice and 2 repeats (left and right of ventricle) with multiple timepoints; bars indicate median per experiments from DMSO (n=3) and DBZ (n=4) experiments; error bars indicate SD; 2 tailed Mann-Whitney test ****p<0.0001.
(C) Average number, normalized on cell size, quantified by image (as in a) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of LAMP-1+ endosomes. Results are the average ± SEM of three independent experiments for a total of 249 late endosomes in 15 siCTL cells (16 ± 2 endosomes per cell) and 441 late endosomes in 13 siSTIM1 cells (34 ± 3 endosomes per cell) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***.
Graphs showing the changes in the fura-2 ratio in cells of the indicated genotypes in response to ML-SA1 and GPN. Arrows serve as event markers that denote the points of time at which the drugs were added. Grey lines on top represent the time at which the bath Ca2+ was removed. All values represent mean±SEM from 3 biological replicates.
Western blot analysis of the indicated mitochondrial fission proteins in melanoma cells treated, or not, with EV from 3T3-F442A adipocytes (3T3-EV). Tubulin (TUB) is used as a loading control.
EMT and OGS were modulated with TGFβ (TGFβ1/2/3, 1ng/ml each), Repsox (1 μM), oligomycin (1 µM), and 2-DG (5 mM) at the late stage during reprogramming with 5C medium (I).
(B) Rad6 binds to DNA in the absence and presence of MMS. ChEC analysis of G1-synchronyzed cells released in the absence or the presence of 0.033% MMS for the indicated times. Data information: DNA gel electrophoresis, DNA content (cell sorting) and quantification of DNA digestion profiles are shown. The experiments were repeated twice with similar results.
(A) Systemic PKM2KO results in increased total plasma cholesterol and LDL-C levels in mice (n=8). Data information: Data are displayed as means ± SD. Statistical significance was assessed using a two-tailed Student's t-test, ∗p < 0.05, ∗∗p < 0.01 and ∗∗∗p < 0.001.
F. Dot blot of tau levels in media of M17 neuroblastoma cells treated with YM-01. Quantification of extracellular tau levels are mean ± SEM, n=6, *p<0.05 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis. Intracellular levels shown by Western blot. DnaJC5 was detected on Western blot by FLAG antibody.
F Analysis of proteomics indicates that MAGE-A1, MAGE-A4, MAGE-A10, and MAGE-A11 are not regulated by nutrient deprivation or DCAF12. Average (n=3) with standard deviation is shown with statistical analysis by student t-test. Asterisks *** indicate p<0.001 (student t-test).
Left panel, indicated melanoma cells exposed to 3T3-F442A EV were fixed, stained with BODIPY and Phalloidin before observation by confocal microscopy. Right panel, quantification of the percentage of cells presenting lipid droplets (LD) within membrane protrusions (n=6).
(A, B) Demembranated sperm chromatin was preincubated in Xenopus egg extract, depleted for MEL28/ELYS or Nup50 (B) or control treated (Mock, A). After 10 min, membranes were added to the reaction. Reactions were stopped at the indicated time points by fixation and analyzed by confocal microscopy after immunostaining with α-MEL28/ELYS (A), α-Nup50 (B), and mAb414 (A, B). Chromatin was stained with DAPI (blue in the overlay). Scale bar: 10 μm.
KEGG pathways enriched among genes whose regulation is associated to mortality. Only pathways with FDR<0.05 are shown.
(A) Solution NMR structure of cytosolic N-terminal domain of YqgP (YqgPNTD, amino acids 1-177), showing ensemble of 30 structures with lowest energy, and the structure with minimum energy displayed as cartoon.
(A-C) Alignment of SSDs of pre-synaptic RIM1/2 and SSDs of post-synaptic gephyrin, GlyRs, and GABAARs, respectively. (A1-C1) Distances were measured between the intensity peaks of paired SSDs in rendered dual-color dSTORM images (yellow line, values given in mean ± SD). RIM1/2 was labelled with Alexa 647 and gephyrin (mAb7a) with Cy3B in (A1). RIM1/2 was labelled with Cy3B, while GlyRs or GABAARs were labelled with Alexa 647 in (B1) and (C1). (A2-C2) Trans-synaptic alignment of SSDs of gephyrin, GlyRs, GABAARs and RIM1/2. SSDs were segmented by H-watershed. Data are plotted as mean ± SD. Number of synapses: n = 48 (A1, A2) from three independent experiments (no treatment), n = 30 (B1, B2) from two experiments with TTX treatment, n = 16 (C1, C2) from two experiments with TTX. Only synapses with side view profiles were included. All images are adjusted to the same scale. Scale bar: 200 nm.
A. The Pearson correlation analysis of RNA-seq results of oocyte samples from unidentified control patients and MOSAsn95Lys patient 1.
H) Body fat % of both experimental cohorts prior to (week 0) or 8 weeks on a HF/HS diet.
(B) Representative time-course of 2 mmol/L phosphate on calcification of LmnaG609G/+ VSMCs (up). Calcification was visualized with Alizarin red. Representative microscopic images (10x; scale bar: 100 µm) showing calcification of treated and untreated LmnaG609G/+ VSMCs (down).
PMN treated with 0.5 µM E4 for 30 min showed a significant decrease in phospho-IGF1R levels compared to controls. Protein levels were normalised to β-actin (*** P< 0.001, Students t-test, N=3 independent experiments, data shown are mean ± SEM).
B. Western blot analysis of Fam134b isoforms in mock, TFEB S142A:S211A and TFE3 S246A:S312A over-expressing U2OS cells showing induction of FAM134B-2, but not of FAM134B-1 isoform by TFEB/TFE3. Filamin A was used as loading control. Blot is representative of N=3 independent experiments.
f, Seckel NPCs differentiated into TUJ1-positive neurons under non-differentiating conditions. Error bars show ±s. e. m. *** p<0.001, t-test. n = 3 independent experiments. 633 cells for WT and 275 cells for Seckel. Scale bar 5 μm.
BMDMs were stimulated with C.albicans for 24h and the supernatant was isolated and added to primary ILC3 cells. (1) Supernatant from BMDMs without stimulation. (2) Supernatant from BMDMs with stimulation of C.albicans. (3) Supernatant from BMDMs with stimulation of C.albicans and IL-7 antibody. Productions of IL-22 by ILC3 cells were detected by ELISA. mRNA expressions of Il-22 in ILC3 cells were detected by qPCR.
(A) Schematic of the workflow for the culture of primary hippocampal neurons and 48 hours of PTX-treatment.