EMBO/sd-character-level-ner huggingface dataset:
G Flow cytometric measurements of GFP levels of WT and Δhac1 cells containing the UPR reporter (SSY2306, 2314) and overexpressing ICE2 from plasmid pSS761 where indicated. Data were normalized to untreated WT cells. Mean + s.e.m., n = 3 biological replicates. Asterisks indicate statistical significance compared with the corresponding untreated sample, as judged by a two-tailed Student's t-test assuming equal variance. Exception was the test against the normalized value for wild-type cells, for which a two-tailed Student's t-test with unequal variance was applied. n.s., not significant..
GO terms retrieved by GREAT analysis associated with distal FOXA2 peaks specific of CFPAC1 (left) or PANC1 (right). Terms are ranked by the negative log10 p-value from binomial correct test.
(H) Radiant flux of individual µLEDs as a function of driving current. The thick line indicates the mean, error bars the standard deviation of the mean. Non-functional µLEDs (which did not emit light, 158 out of 560 µLEDs) have been excluded.
H. Heatmap of expression level for highlighted genes and core enriched genes in EMT gene set.
D Single‐cell transcriptomics was used to validate the above proteome data by clustering mRNA transcripts encoding proteins that underpin vesicular release processes (red color labels highest mRNA abundance, whereas dark blue color indicates the lack of mRNA expression).
(c,d) Fbxo7 expression restores elevated Mfn steady-state levels in parkin (c) but not PINK1 (d) mutant Drosophila. Histograms show mean ± s.e.m. of densitometry analysis of Mfn immunoblots above, normalized to complex Vα (CxVα). Control genotypes are park25/+; da-GAL4/+ (c) and PINK1B9/+; da-GAL4/+ (d).
A, B Analysis of AID mutagenic activity in Elastase1 (A) and Elastase2a (B) by next-generation sequencing. Pancreatic DNA was isolated from pools of R26AID+/KIp48CRE+/KI and control R26AID+/+p48CRE+/KI 20-week-old mice, and then PCR-amplified with specific primers and sequenced as previously described (Perez-Duran et al, 2012). Graphs show cytosine mutation frequency overall (total) or at AGCT hotspots. n = 2. *P-value: Elastase1: 0.0382; Elastase2a: 0.009.
Maximum projection of z-stack sections of hTERT-RPE1 cells expressing MCHR1-GFP (blue), DsRed2-PACT (red) and ECFP-SKL (green) 48 h after serum starvation. The ECFP-SKL-positive cell with primary cilia, indicated by the red box, was analyzed by FIB-SEM. Top, differential interference contrast (DIC); bottom, merged image. Scale bar, 10 µm.
B. Glucose starvation decreases R388 methylation of SIRT7 in a time-dependent manner. MEF cells stably expressing Flag-SIRT7 were cultured in glucose-free media as indicated. R388 methylation level of immunopurified SIRT7 was determined by western blot
(B) Adult TA muscles were transfected with Bnip3 together with d.n.AMPK or mock vector and cross‐sectional area was measured (*P0.001) n=480.
(G) 3*103 mouse dermal fibroblasts (MDFs) of the indicated genotypes were re-plated after vehicle or abemaciclib treatment (4 μM for 8 times 24 hours) and stained with 0.2% crystal violet 8 dpt (n=3 independent experiments). (H) 8 dpt, treated MDFs were incubated with EdU for 20 hours and stained (n=9 samples from 3 independent experiments). ( Data information: Data are means ±SD. Unpaired student t-test *p<0.05, **p<0.01, ***p<0.001.
higher time resolution of the indicated section of the Day +1 in (B), representing a hippocampal paroxysmal discharge (HPD).
A. DRG neurons expressing Myc-Syt11 were immunostained for Myc-Syt11, dynamin (Dyn), AP-2, clathrin (CL), TGN46, synaptobrevin 2 (Syb2), and LAMP1. For dynamin, the box along the plasma membrane was straightened, enlarged, and is shown in the upper right panels with arrows indicating co-localized puncta. An enlarged inset of the inside of the cell (box) is shown in the lower panel. For localization of the transferrin receptor, EGFP-transferrin receptor (TfR) was expressed in DRG neurons. Scale bars, 10 μm.
B. Significantly altered metabolites (FDR<0.2; P<0.05, n=5/group) in liver tissue of GRAC (red) and GROX (green) mice Bar graph represent mean±S Statistics for graph one-way ANOVA followed by Tukey"s
Protein-protein interaction assays. Myc-Egg WT, Myc-SV40-NLS-Egg WT, and Myc-SV40-NLS-Egg K1085R mutant were expressed with Flag-Wde in OSCs. Immunoprecipitation was conducted using anti-Flag antibody while anti-Myc (upper) and anti-Flag (lower) antibodies were used for western blotting.
C External validation of the LC score. Left, the log2-trasnformed Em/Ad expression ratios of GATA6 and NKX2-1 detected in an independent set of blinded collected EBCs were plotted as in (B). The SVM based classifier confirmed its discriminatory power between control and LC samples. Right, box plot of the LC score on the validation set of EBCs.
B Pull down assay indicates that recombinant purified GFP-myoVa and untagged caldendrin (cald wt) directly bind to each other in a Ca2+-dependent manner. Note that there is no binding observed for a Ca2+-binding mutant of caldendrin (cald mut / Left panel). Right panel: neither wt nor mut caldendrin bind to GFP-coupled beads.
I, Adult-born neurons of KO mice exhibit reduced numbers of dendritic spines in the outer molecular layer (n = 32 neurons from 3 mice, WT; n = 46 neurons from 4 mice, KO). Depicted are individual data points for every neuron with genotype means ± SEM (p-value from unpaired t-test). J, Mean spine size per animal was reduced in KO mice (n = 50 spines per mouse). K, Mean percentage of mushroom spines (diameter of spine head ≥ 0.45 µm) per animal was lower in KO mice compared to WT mice. L, Representative fluorescence image of dendritic spines in WT and KO mice. Scale bar: 5 µm.
D ChIP experiments performed using anti-myc antibodies and extracts from cells as in (A) followed by qPCR using tiTEL specific oligonucleotides. Values correspond to fraction of input DNA expressed as fold increase over THI+ TSA-. Unt: untagged strain (CAF545). Bars and error bars are averages and SD from at least three independent experiments. * P < 0.05, ** P < 0.01 (relative to THI+ TSA-; two-tailed Student's t test).
HEK293 cells were transfected with α11.2 with the K1647E mutation, α2δ-1, and β2A plus α-actinin-1 WT or E847K/E851K before cell attached patch recording. Representative single CaV1.2 channel recordings of CaV1.2 K1647E with WT or E847K/E851K α-actinin-1. Mean assemble averages for all experiments for both combinations. Dot plots and means + SEM for availability (c), NPo (d), Po (e), unitary current amplitude i (f), and mean of the current of a single channel calculated from the ensemble averages of each experiment (g) (**p<0.01; unpaired t-test; n = 16 to 30; see Suppl. Fig. 8 and Table 6 for more details).
Relative enrichment of indicated proteins in MTA pulldowns from wild type (WT) or Mbd3-null (Mbd3KO) ES cells, normalised to 2x MTA proteins. NuRD components comprising the remodelling subunit are labelled in blue, those comprising the deacetylase subunit in red. As MTA proteins are the bait in these experiments, they may be isolated more efficiently than their interaction partners. Error bars represent standard deviation from three (Mta1 and Mta2) or six (Mta3) replicate pulldowns.
f, Initiation and duration of translocation of PX-mCherry to phagosomes (yellow bar), GFP-BECN1 translocation (blue bar), GFP-LC3 translocation (green bar) and Lysotracker recruitment (acidification) were determined during the first 2 h after internalization (10 cells per group, error bars indicate s.d.)
(F) Immunoblot analysis of conditioned medium (LAP peptide) and cell extracts (hepsin and vinculin) from control (DOX) or hepsin overexpressing (DOX+) MCF10A pIND20-HPN supplemented with 100ng/ml latent-TGFβ (Small Latent Complex). Ponceau was used as a loading control for the cell culture medium.
(E) Changes in the protein to mRNA fold changes ratio, log2(protein_FC/mRNA_FC), in the double mutant strain ΔIndLon_FtsH as compared to the predicted ratio, computed as the sum of the log2 ratios of both individual mutants. Proteins that showed a significant change in protein level in at least one of the individual mutants are shown (374 proteins). Proteins whose ratio deviated significantly from the predicted one (upper and lower dashed diagonal lines) reveal epistasis effects.
H) Cortex glial (NP2222-GAL4>) overexpression of Hh.N.EGFP significantly reduces NB EdU incorporation (n= 13,12 brain lobes).
(A) Oxygen consumption rate (OCR) measured by SeaHorse Extracellular Flux assay of Stat3+/+ and Stat3-/- cells maintained in 2i condition in the presence of LIF. 200nM FCCP treatment, a mitochondria uncoupler, resulted in higher OCR increase in Stat3+/+ compared to Stat3-/- cells, showing a higher level of maximal mitochondrial electron transport chain (ETC) activity in Stat3+/+ cells. Injection of 200nM Antimycin shows similar non-mitochondrial respiration rates for both Stat3+/+ and Stat3-/- cells. Mean and s.e.m. of 5 technical replicates is shown.
Mean REV-ERBα per AC16 cell nuclear and cytoplasmic area across all images for each condition from quantification of the RNA-FISH data. AC16 cells (REV-ERBα): 37°C (65), 18°C 5h (30), 18°C 5h then 37°C 2h (21), 18°C 24h (63), 18°C 24h then 37°C 2h (64)
A Representative 3D images with Insulin and Caveolin-1 immunostaining in pancreatic islets from young mice. Combined box and whiskers, and scatter plots show the vessel density analysis in the pancreatic islets and non-islet areas from young and aged mice. Data information: The white and dashed lines in panel A, B, D, F, H and I represent the outlines of pancreatic islets. (n=5), P-values, and two-tailed unpaired t-tests in panel (A, E and I) and one-way ANOVA tests with Tukey's multiple comparisons tests in panel (G and H). *: P < 0.05; **: P < 0.01; ***: P < 0.001; ****: P < 0.0001. Nuclei: TO-PRO-3. Is: pancreatic islet. f.u: fluorescence unit.
Z-projection of centrosomes isolated from cells expressing GFP-centrin1 during prometaphase arrest and forced exit, which were immunostained with p34-Arc. N=2 independent experiments. Scale bar = 2µm.
(A) The autophagy was detected by immunofluorescence assay of LC3B in the cells 48 hours after different treatment.
IF stainings of the apical marker CD13 on liver tissue sections from livers at 1 d post sham OP or BDL. Shown are maximum projections of 50 µm z-stacks in the CV (left, orange) and PV (right, blue) region. Images in (a) and (f) are background-subtracted. Scale bars, 50 µm (a), 1 µm (c), 5 µm (f).
(A) Kaplan-Meier curve representing distal metastasis-free survival of a cohort of breast cancer patients (N = 1609) as a function of their primary tumor's CFL1 expression levels (Data from KMPlot (Gyorffy et al., 2010)). Patients' primary tumors' CFL1 expression levels were classified as low (blue) or high (red) expression.
F Western blot of HA from Pah1 phosphorylation reaction that contained hypophosphorylated Pah1-HA from ∆ice2 cells (SSY3096) and microsomes from ∆nem1 cells (SSY3075). Phosphorylated Pah1 from ∆nem1 cells (SSY3065) and hypophosphorylated Pah1 from ∆ice2 cells are shown for reference.
Asynchronously growing human U-2 OS cells were treated with 0.5 Gy of IR, allowed to recover for the indicated time periods, and stained for 53BP1 and DNA content for cell cycle resolved quantification of 53BP1 foci in individual cells by QIBC.
(A) HT29 cells were infected with Shigella WT, S325, or ospD deletion mutants, and incubated for 8 h. Aliquots of cellular supernatants were subjected to cytotoxicity assays. *P<0.05 (one-way ANOVA).
C CTC-ITB-01 and MCF-7 cells were grown under the same culture conditions in the presence or absence of E2 as indicated. 24h after E2 deprivation or E2-treatment cells were harvested. Western blots of the protein lysates were probed with antibodies targeting ER-alpha, FOXM1, Bcl-2, PR-A, PR-B and ID1, actin was used as loading control, visualized at long exposure (l.e.) and/or short exposure (s.e.).
E Half-open siliques of a heterozygous plant showing the embryo greening; scale bar equals 250 µm. The given number is the position rank of the silique from top to bottom of the inflorescence presenting the segregation of homozygous and heterozygous seeds based on their ability to transiently develop chloroplasts.
A-C, Zoom-in analysis of fibroblasts identified in Fig 2. A, tSNE plot colored by FB subpopulations. B, Dot plot showing expression of ECM genes in FB subpopulations. C, Bar plot showing relative proportion of FB subpopulations in FB at each time point.
(A) Mitochondrial (Mito, top left), ER (bottom left) and membrane (Mem, right) fractions of Min6 cells were precipitated with isotype (Iso) or anti-Pdia4 (Pdia4) antibody. The fractions and immunoprecipitates (IP) underwent immunoblotting analysis.
Analysis of mPAP (E) for the indicated groups (7 rats in each group). Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups
(C) Gene tracks of ChIP-seq signals for H3K9me2 and H3K27me3 around the VCAM1 locus in TNF-α (-) and TNF-α (+) ECs.
293T-FcR-Kb cells co-expressing empty vector or Rab mutants (Rab5ACA, Rab22ACA, Rab7ADN) individually, with either LacZ as a control or US6 were analyzed for cross-presentation of OVA using B3Z cells. The effects of US6 on cross-presentation were analyzed by plotting the mean percentage of IL-2 release by cells co-expressing US6 (A) with control vector or Rab mutants compared to cells co-expressing LacZ with control vector or Rab mutants, respectively.
(A) Immunoblot showing the degradation of MAVS in HEK293T cells subjected to VSV infection (MOI = 1.0) for the indicated times. α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.
16HBE cells were seeded sparsely, treated with DMSO, GSK1120212 (500nM), PD0325901 (500nM), or SCH772984 (1M), and incubated for 3 days. All data are representative of 3 independent experiments. (a) Cell lysates were analysed by western blotting for pERK, total ERK, p-p90RSK or total RSK1.
Representative images showing SA-β-gal staining in the hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells with or without RB1 or TP53 knockdown. Cells were collected at the 7th passage.
B. Fluorescence microscopy pictures of GFP-TgAtg8-expressing tachyzoites during their intracellular development and division. The arrowhead indicates the residual body made of maternal material left after endodyogeny.
(B) Quantification of telomere fusions in SMCHD1 wild-type or SMCHD1 knockout HeLa inducible shTRF2 cells treated with or without doxycycline for the indicated number of days (d7, d8, d11). Bars represent average number of fused chromosome ends. SDs were obtained from 3 independent experiments (>1,900 telomeres counted/condition/experiment). (***) P < 0.001, (**) P< 0.01; (*) P< 0.05; unpaired two-tailed Student's t-test.
B Proteins extracted from wild‐type cells at 2 hpm and from the COI12 KO cells at the indicated time of conjugation (hpm) were analyzed by Western blot as described in (A).
Position of a Bax (α2-α5) dimer structure in ribbon representation relative to the lipid bilayer of a bicelle. The protein structure is placed against the lipid bilayer with a 60° tilt angle between its longest axis (L) and the bilayer normal axis (N) as derived from the best sigmoidal fitting. The hydrophobic α4-α5 surface contacts the lipid bilayer. Amide protons are shown as spheres color-coded similarly as in panel B. The polar headgroup region and the nonpolar acyl tail region of the lipid bilayer are indicated by light blue and light orange colored strips, respectively. The estimated thickness for the DMPC lipid bilayer is indicated on the left side. The Bax (α2-α5) dimer structure on the left is rotated 180° to generate the structure on the right showing the nonpolar residues in the α4-α5 surface, most of which contact the nonpolar core of the lipid bilayer. Note that the two positively charged R89 residues on the boundary of the nonpolar surface are close to the polar lipid headgroups.
Example images showing the localization of SOX2-SNAP and OCT4-HALO by fluorescence microscopy of SBROS cells. Scale bar: 50µm.
C. Chemical and hematological analyses of blood pooled from three mice at day 3 after Stx2a challenge. Data are presented as mean ± S.E.M. (n = 3 biological replicates from nine mice, two-tailed Student's t-test). The effects of OSMI-1 (1000 µg/mouse) were compared with those of the vehicle control. *P < 0.05; **P < 0.01; and ***P < 0.001
(C) Proximities of mitochondria comparing the contralateral (red) and ischemic (black) hemispheres. Bar diagram shows percents of mitochondrial proximities found to be smaller or larger than 400 nm. The same data set is summarized as a contingency table on the right, (P0.001; two‐way Fisher's exact test).
Primary structure of Bub1 with sequence of CD1 shown and residues mutated in red. Schematic of fusion constructs used in panels (E and F).
C, D. Quantification of endosperm nuclei in cycb1 single (C) and double (D) mutants. Boxes and whiskers represent min to max values with the median indicated as a central horizontal line, n = 26-30 seeds per genotype. Asterisks show significant differences in the number of endosperm nuclei per seed in a Kruskal-Wallis test followed by Dunn's multiple comparisons test (**** P < 0.0001).
D Two step crosslinking method identified Gadd45a could interact with chromatin in the promoter regions of Oct4 and Nanog. Cells were crosslinked with DSG before ChIP-PCR analysis. (**p≤0.01; ***p≤0.001; n=3)
A Heat map from RNA-Seq data from FACS-isolated muscle stem cells and single myofibers showing relative expression of Pax7, Myf5, MyoD, Myog and Myf6.
C) Quantification (mean ± SD) of Goblet cells in crypts and villi from the same mice sown in A and B. More than 100 crypts and villi were scored for each condition after 15 days from the first β-naphthoflavone administration.
(A) Ribosome profiles from PABPDHFR cells grown in the presence or absence of TMP for 12 hours. Lysates were subsequently resolved by ultracentrifugation on 5-50% sucrose gradients and fraction were collected during which time UV absorbance at 254nm (Abs 254 nm) was monitored for tracing. 40S and 60S subunits, monosomes (80S) and polysomes positions are indicated above tracings. PABP-expressing and -depleted cells are denoted by a black and blue trace lines, respectively.
Figure 5. p53-dependent histone modification changes in response to DNA damage stress. HCT116p53-/- (left panels) or p53 +/+ (right panels) were treated with DMSO (black) or 50 µM etoposide (red) for 24 hrs and assayed by ChIP-qPCR at various locations relative to the TTAGGG repeats across the chromosome18qsubtelomere (panel A) or 13qsubtelomere (panel B) or for control regions (p21 promoter, GKN1/2, PARKIN) as indicated below. ChIP- for p53, H3K9Ac, H3K27Ac, γH2AX, or IgG control were quantified as % input. Error bars indicates SD and * indicates p value<.05 using student t-test comparing ChIP values in p53+/+ relative to p53-/- cells for specific primer pairs.
This table displays all the KZFPs associating with 3 or more unique interactors, the identity of these interactors as well as the features associated with them.
(C) The relative ZWF1 mRNA levels were measured by qPCR. Cells were grown into an exponential phase and treated by 200 mM HU for 0, 30, 60 min. mRNA were prepared just as described in Methods and Materials. The relative mRNA levels of ZWF1 to ACTIN1 were determined by qPCR analyses. The value of the untreated WT sample was normalized to 1. Error bars represent standard deviations (SD) from at least three biological repeats. Statistical significance was evaluated based on Student's t-test (*0.01< P-values <0.05).
(B) Rescue effect of Parkin knockdown on reduction of mitochondrial complex I enzyme activity caused by HCV infection. NT-KD and P-KD cells infected with HCVcc were harvested on day 3 post-infection and used for analysis of the activity of mitochondrial complex I enzyme (mean ± SD; n = 3; *p<0.05).
Immunofluorescence of Sall4 in WT cells and Nfatc1 knockdown cells on d12. n = 3. Scale bar, 100 μm. RT-qPCR analysis of pluripotent genes expression in cells treated with shNC and shNfatc1. n = 3.
(G) Female athymic mice were injected subcutaneously with either CP20 GFP-miR-CTL or CP20- GFP-miR-195 or CP20- GFP-miR-195 + MICU1 cells and tumor volume was measured, values are mean ±SE, n=10. *P<0.05, Student's t-test.
f, Protein expression of ISX, ISX(69Kac) and Vimentin in tumor and normal parts from patients with NSCLC by western blotting. N, normal tissue; T, tumor mass; Arrow, target protein; *, unspecific band.
(C) Confocal microscopy images of zebrafish larvae (Ctrl mo or Gp96 mo) infected (low dose) in the tail muscle, with the GFP-expressing wt or Δhly Lm for 24 h, immunolabelled for KDEL-proteins (green), and stained with phalloidin (actin, red) and DAPI (white). Images show actin rich structures at the cell cortex (arrows) and ER-KDEL puncta (arrowheads) in larvae infected with wt strain.
f. Representative example of the proliferation of Tresp cells from HC (upper row) and RRMS patients (lower row) either alone (first column) or in co-culture with Tregs that had been previously incubated with either vehicle, LY294002 or MK2206 for one hour and washed to remove drug traces. g. Statistical analysis of the percentage of suppression as in h at different Treg:Tresp ratios of n=8 experiments performed. *p < 0.05, **p < 0.005, ***p < 0.0005.
DC(p38-KO) and DC(p38+NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Expression of Il12, Il6 and Il23 mRNA in DCs sorted from spleens of DC(WT), DC(NLRC3-KO), DC(p38-KO) and DC(p38+NLRC3-KO) mice 26 d after EAE induction, presented relative to that of Gapdh.
Model of aluRNA‐driven maintenance of the nucleolusThe knockdown of aluRNA or treatment with α‐amanitin induces the segregation of nucleolar compartments into smaller domains (dispersion process) as observed (Figs A and A, and Appendix Fig S2). With regard to rRNA production, those "droplets," which may vary in composition, are less efficient but some rRNAs are still produced albeit at low levels (Appendix Fig S1B and C and Fig C and D). Overexpression of aluRNA promotes assembly into larger nucleolar subcompartments, with enhanced Pol I activity (see Fig ). This model is in excellent agreement with the previously reported liquid‐like model of the nucleolus (Brangwynne et al, ; Weber Brangwynne, ) and suggests a RNA binding‐driven liquid‐like transition between dispersed nucleolar domains and intact and fully functional nucleoli.
J Production of Gr, B, CD4 T, and CD8 T cells by expanding clones that produce more than 0.1% of WBCs in each lineage Data information: Data were collected at month 4 after secondary transplantation and presented as mean ± SEM. n=7 mice for the primary control (WT+WT) and deficient co-transplantation (WT + uMT-/-) groups. n=4 mice for the secondary transplantation control group (WT + WT) and n=6 for the secondary deficient co-transplantation group (WT + uMT-/-). *p<0.05 and **p< 0.01 (two-tailed and two-sample equal variance Student"s t-test)
E Wild type and Traf3ip3-/- HEK293T cells were treated with or without VSV, SeV or poly (I:C) as indicated for twelve hours. IFNB induction was measured by qPCR.
B. Relative fold change in expression level of endocytic recycling genes in invasive vs. non-invasive cells, and in mutant vs. WT p53 cells based on microarray and RNA-seq analysis, respectively.
A,B Tumor growth curve (left) and summary of end-point tumor masses (right) of 6-8 week-old wildtype (WT) and Peli1-KO (KO) mice inoculated s.c. with B16F10 (A; WT, n=7; KO, n=6) or E.G7 (B; WT, n=5; KO, n=5) tumor cells.
Deletion of HSC82 selectively decreases ∆ψm in ρ0 puf3∆ cells. Cells were cultured to mid-log phase and stained with 125 nM TMRM for FACS analysis. The red ] highlight two cell lines for comparison.
DNA and crRNA sequences used for multiple PAM experiments with indicated labeling positions. Di-nucleotide GG PAMs are shown in boxes.