EMBO/sd-character-level-ner huggingface dataset:
F, Western blot of BT308NS showing caspase 3 activation (cleaved casp-3), at the indicated time points after IR in the absence (-) or in the presence (+) of JNJ38877605. Vinculin was used as loading control.
E-H EN immunohistochemistry staining of human normal liver (E), fibrotic liver (F), and cirrhotic liver (G, H). Weak EN expression in portal tracts of normal liver (E). Abundant EN expression detected in activated HSC in fibrous septa of fibrotic (F), active cirrhotic (G), and inactive cirrhotic liver (H). Scale bars: 500 μm.I-N Higher magnification of EN-stained normal liver (I), fibrotic liver (K), and (active) cirrhotic liver (M) compared to alpha-smooth muscle actin (αSMA) immunohistochemistry on serial slides (J, L and N). Scale bars: 100 μm.
A Co-staining of SNX10-Flag and LPS in Caco-2 cells transfected with SNX10-Flag after treatment with OMVs (100 μg/mL) for 24 h. Scale bar: 20 μm.
(D) Representative images of chromosome spreads from the indicated conditions. Scale bar, 5μm. (E) Quantification of (D). The distance between the two peak intensities of CREST was measured for 5 kinetochore pairs and averaged for a single cell and plotted. The data are from 4 independent experiments and the mean and SD are indicated.
C Mlkl-/- MDFs and Ripk3-/-Mlkl-/- MDFs stably transfected with constructs encoding MLKL, USP21, USP21C221R, MLKL-USP21 and MLKL-USP21C221R were treated with doxycycline, TSI or in combination. Propidium iodide positive cells were quantified in real time by IncuCyte live cell imaging. Data are plotted as mean ± SEM of three independent experiments.
G qPCR analysis of IFNB mRNA levels in WT and G3BP1-/- U937 cells transfected with dsDNA as indicated. n = 3 technical replicates. Data information: Error bars, mean with s.d. , **P < 0.01, two-tailed t-test.
Puf3-15A mutation downregulates Puf3-associated mitochondrial transcripts in ρ0 cells. ρ0 and ρ0 puf3-15A cells were cultured to log phase. RNAseq was performed with three biological replicates per genotype (Dataset EV7). All the transcripts and the Puf3-associated transcripts encoding mitochondrial proteins (gene lists in Table EV1D) are shown. The significantly changed transcripts (P value < 0.05; fold change > 1.5 or < 0.67) are highlighted with dashed lines; numbers of significantly changed transcripts are indicated.
B Observed dsDNA processing pattern of Sgs1 in the presence of RPA including an overview over successive bursts and pauses (upper panel) and detailed views of single bursts (lower panels). Unwinding events are always followed by slow rewinding events (orange sections).
Representative Western blotting showing the MeCP2 expression in CTRL and silenced hTERT-RPE-1 cells, with respect to GAPDH, used as loading control.
iPS cells were treated for 3 hours with 150 nM of LY411575, 1 µM of MLN4924, 10 µM of Roscovitine, 10 µM DRB or 10 µM XAV939. DMSO has been used as vehicle control. Western blot analysis reveals that NICD levels were increased upon treatment with Roscovitine, DRB, XAV939, or MLN4924. NICD is undetectable following LY411575 treatment. NICD antibody detects a doublet following Inhibitor treatment and the top band disappears following λ phosphatase treatment indicative that this top band is a phosphorylated isoform. β-Actin served as loading control.   Quantification of the density of western blot bands in (C) using ImageJ software. Data are expressed as fold changes compared to DMSO treatment. All data represent the mean ± SEM from three independent experiments. One-way ANOVA analysis, followed by Dunnett test, was performed with *p≤0.05, **p≤0.01, ***p≤0.001 and ns= not significant.
Coherent feed-forward networks coordinate the regulation of FT by the circadian clockAs highlighted in the discussion, the flowering system is based on a combination of coherent feed-forward pathways, allowing a single component to play multiple reinforcing roles in the system (Mangan Alon,2003). This is highlighted here in the case of the EC and the PRRs.The EC can repress FT expression through at least three partially redundant pathways, involving coordinated control of CDF1, FKF1 and GI levels.Similarly, the PRRs can activate FT expression through at least three pathways. Rectangles denote protein species, and parallelograms denote transcript species. Solid and dashed lines indicate direct and indirect forms of regulation, respectively.
Cell fractionation upon inhibition of DPP9 activity. HeLa cells were incubated for 4 days with the DPP9 inhibitor 1G244 or as control with DMSO. Cells were subjected to fractionation into 'cytosol' (supernatant) and 'mitochondria' (pellet) by differential digitonin lysis and centrifugation. The IMS marker proteins CPOX and cytochrome c were exclusively localized to the pellet fraction at one specific digitonin concentration (lanes 2,5,8,11) irrespective of 1G244 treatment. Likewise, the cytosolic marker protein LDH localized under all conditions to the same fractions. Conversely, endogenous AK2 appeared at this digitonin concentration in the 'cytosol' fraction but only upon 1G244 treatment (compare lanes 2 and 5). Thus, inhibition of DPP9 results in appearance of AK2 in the cytosol. Quantification shows loading-control adjusted AK2-signals of 1G244-treated 'cytosol' fraction (lane 5) over DMSO-treated 'cytosol' fraction (lane 2). White arrow head indicates the endogenous AK2 appearing in the cytosolic fraction upon 1G244 treatment. Reported values are the mean of 3 independent experiments; error bars represent ±SD. Student's t-test was performed.
B. Cortical and cerebellar lysates from NEX-Cre, NEX-Cre;fl/+ or NEX-Cre;fl/fl mice were immunoblotted with the FBXO7 or γ-tubulin antibody. The latter served as loading control.
Western blot detection of FLAG-tagged ARS proteins in mascRNA overexpressing cells transiently transfected with PQCXIP vector (PQ), QARS expressing (QARS) or GARS expressing (GARS) plasmid. β-Tubulin was used as a loading control.
(A, Representative FACS plots of the EGFP+ CD4+ T cell proliferation in the different experimental groups (right) and indicated experimental conditions (top) using the Cell Trace Violet detection method. In A, grey shaded histograms represent the fluorescence obtained from nonstimulated CD4+ T cells before stimulation and retroviral transduction. n = 3 independent experiments.
(H) 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 PTPRN2 and PLCB1 expression levels (Data from KMPlot (Gyorffy et al., 2010)). Patients' primary tumors' PTPRN2 and PLCB1 expression levels were classified as low (blue) or high (red) expression.
(A) Triplicate samples of H1-Hela cells were infected with PV at an MOI of 0.1 pfu/cell, and cell-associated virus was collected at the indicated times post-infection. NH4Cl (20 mM) was added to the media at the time of infection (solid line). Virus titers were then determined by plaque assay. (B) Infection as in (A), carried out to 16 h to represent a multiple-cycle infection.
D Oxygen consumption measurements in control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in glucose or galactose. Values of basal and maximal respiration along with ATP-production dependent, proton leak respiration and spare capacity are shown. Data are shown as mean ± SD, n = 4 biological replicates; ∗p < 0.05, ∗∗p < 0.01, ∗*∗p < 0.001.
Maximum projection (2 z-slices) of HeLa cells immunostained for F-actin (Phalloidin), Tubulin, Pericentrin and DAPI at metaphase and early anaphase showing actin accumulation around centrosomes in early anaphase. Scale bar- 10µm Quantification of F-actin (Phalloidin) intensity around pericentrin positive centrosomes in HeLa cells immunostained as in (A), showing the increase in F-actin around centrosomes at early anaphase. Mean actin metaphase = 1 ± 0.03996, n=92, mean actin anaphase = 1.875 ± 0.08895, n=121, Student t-test, ****p<0.0001;
B. Protein abundance profile over time for axon-related proteins Trim46 and Tau in control neurons and neurons treated with Centrinone-B (+C).
A. Expression of FoxM1 and ICAT was examined via IHC staining in 30 GBM and paired adjacent normal tissues. Representative ICAT and FoxM1 expressions are shown in a section of a GBM tumor with adjacent normal brain. Scale bar: 50 µmB. ICAT stainings were scored as 1-12 according to the intensity and percentage in the 30 GBM and paired adjacent normal tissues. Boxes indicate interquartile range. Bars from each box extend to largest and smallest observations.C. FoxM1 stainings were scored as 1-12 according to the intensity and percentage in the 30 GBM and paired adjacent normal tissues. Boxes indicate interquartile range. Bars from each box extend to largest and smallest observations.
(B) FLAG-tagged tandem ubiquitin binding entity (TUBE) assay was performed to pull down linear ubiquitin linkages in patient-derived and control fibroblasts and B cells. One representative out of three independent experiments is shown.
Percentage of multiple-tethered MP-SVs per ribbon of the total MP-SV pool show more multiple-tethered SVs in OtofPga/Pga IHCs. Percentage of docked MP-SVs per ribbon of the total MP-pool. The number of docked SVs is significantly increased at OtofPga/Pga inhibited and specifically at stimulated AZs. P-values for (I) and (J) are calculated by Fisher's exact Chi-square test, wild-type: inhib, n = 102 SVs; rest, n = 82 SVs; stim, n = 99 SVs; OtofPga/Pga: inhib, n = 123 SVs; rest, n = 96 SVs; stim, n = 111 SVs; ns p > 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001
(B) Immunoblotting of CD4 T cells and MDMs treated with Pam3CSK4 for 6 hours. * indicates an unspecific band. One representative experiment out of three is shown.
(B) Gross appearance of E14.5 embryos of indicated genotype. Scale bars, 2.5 mm.
(F, G) HeLa cells were transfected with the indicated siRNAs. After 48 h, the cells were transfected with LAMP1-RFP (red), with or without myc-Dynactin 1 for 30 h. And then the cells were incubated with Earle's Balanced Salt Solution (starvation) for 2 h. The cells were stained with anti-LC3 (green) antibody. Cells were visualized using microscope IX71. Regions within the dotted boxes are magnified in the insets. Scale bar, 5μm. The quantification data of the colocalization of LC3 and LAMP1 is shown in Figure 7G. Data from three independent experiments represented as means ± S.E.M., **, p<0.01, one-way ANOVA.
C Phenotypes of vector control, pER8::CDF4, pER8::CDF4-RNAi and pER8::amiCDF4 plants, after treatment with 20 µM estradiol for seven days at 18-days-old. Scale bars indicate 1.5 cm.
K: Representative immunostaining of Neun (green) and Tuj1 (red) positive neurons at DIV14. Scale bars: 15 µm.
D, E. Mice were infected with PR8 and treated with equivalent doses of IFNα or IFNλ or Veh Ctrl at days 2, 4 and 5 post infection; viral load assessed at 4dpi (E) (data representative of two independent experiments, n=3-5).
smd1b mutant displays similar AS events as observed in RNAi-ASCO. Quantification of SR34 isoforms splicing index by RT-qPCR.
B LNCaP cells were transfected with either control or ATF4 siRNA and were cultured for 2 weeks. The colonies formed were stained and photographed.C The area covered by the colonies on each plate in (B) was quantified and represented as percentage of the total area of the plate. *P = 0.0023.
(A) Venn diagram of STK38 partners identified in both starvation and suspension conditions by proximity biotinylation assay coupled to mass spectrometry identification (B) Heatmap representation of common STK38 interactors identified in both starvation and suspension conditions according to their dynamic of association with STK38 (with a minimal fold increase of 1.38 ± 0.06). Unsupervised hierarchical clustering was generated based on their association fold using Pearson correlation. (C) Representation of the 10 most cellular component enriched terms of the two clusters (assessed by using the Gene Ontology (GO) database
(B) MCF-7, SKBR-3 and T47-D breast cancer cells were transfected with gain- or loss-of-function constructs/shRNAs and their respective controls (a miR-10b-OE plasmid or anti-miR-10b). MREs of the validated target HOXD10 and of the putative targets PTEN and PIK3CA were cloned into pMIR-Report, and dual luciferase reporter assays were performed. A mutated control miR-10b (MRE MUT PTEN) was also included. Bars show the mean ± SEM from 6 independent transfections.
E Surface representation of the central cavity of the β subunit showing a tunnel formed near the active site. The Cys195-linked farnesyl moiety is anchored into the hydrophobic tunnel.
(B) Steps in the route to T-blast cell transformation and re-activation. Purified CD4+ or CD8+ T cells were activated with 2 µg/ml ConA for 40 hours and then maintained in IL-2 as TB. Cells were re-stimulated with 20 ng/ml PMA and 2 µM Calcium Ionophore (PMA/I).
Fluorescence anisotropy was used to measure the binding affinity of Timeless-Tipin for the indicated DNA sequences. B. Binding affinity of Timeless-Tipin for a range of G4 DNA sequences Single-stranded (ss20: 5′-6FAM-ATAAGAGTGGTTAGAGTGTA) and double-stranded (ds20: ss20 annealed to complementary sequence) DNA were also tested as controls.
(D) GmLMM1 interacts with NbRXEG1 in N. benthamiana plants. Data information: The experiments were performed three times as biological replicates, with similar results.
(D) CRISPRa induction of promoters with varying basal expression levels. CRISPRa-, basal expression of the promoter; CRISPRa+, expression activated by dCas9-AsiA-m2.1 and associated gRNA-H4.
C. Quantification of EYFP-Parkin signal heterogeneity in PC6 cells demonstrates that Miro1 overexpression induces Parkin translocation from the cytosol to mitochondria, which is significantly weaker than PINK1 overexpression- or A&O (3 h)-induced translocation. **P < 0.01 and ****P < 0.0001 vs control group, n = 18-32 cells from 3 dishes per group, Kruskal-Wallis test
(H) pho8Δ60pho13Δatg13Δ cells expressing wild‐type Atg13 (wt), the Atg13‐FV mutant (FV) or an empty plasmid were grown to mid log phase and starved for 4 h in SD‐N medium. Pho8Δ60‐specific alkaline phosphatase (ALP) activity (nmol/min/mg) was measured in three independent experiments as described in 'Materials and methods', and plotted as relative ALP activity with standard deviation (s.d.) compared to the wild‐type controls.
(F-G) Single confocal sections of S2 cells at the indicated mitotic stages stained to detect Snap29, nuclear pores (WGA), and CyclinB (F), or Snap29, Spc105R, and the nuclear lamina (LaminA) (G). Note the transient perinuclear enrichment of Snap29 in early prophase. WGA stains also cytoplasmic speckles in hemocyte-derived S2 cells (Rizki Rizki, 1983). High magnification of the insets in C-G shows localization of Snap29 relative to the indicated markers.
(E) Neutrophils induced by low dose treatment in PB (section i) and BM (section ii).
(A) Left panel: BI‐1 WT and KO MEFs cells were incubated in EBSS, and then cell viability was monitored using the MTS assay. Right panel: a similar experiment was performed after treating cells with the indicated concentration of tunicamycin for 24 h. Mean and standard deviation are presented of triplicates representative of three independent experiments.
E. HeLa cells transfected with RNF4 siRNA were synchronized in early S phase by double thymidine block. Six h after release from the block, cells were pulse-labeled with 5-azadC for 30 min. Mitotic cells were isolated by shake-off 8 h later, washed and incubated or not with MPS1 inhibitor (MPS1i) and collected at the indicated times. Cells were then processed for immunoblotting with indicated antibodies.
D Specific H‐bond interactions between K350 of Gli1ZF and Gli1 binding site consensus, as predicted by MD.
A IF for PRMT5 (green) and OCT4+PGCs (arrows) at E10.5, and MVH+PGCs (arrows) at E11.5 (red).
G, Percentage of new-born neurons (BrdU/NeuN-positive) that expressed c-Fos after ENR (n = 5 mice, WT; n = 5 mice, KO). H, Representative fluorescent image of c-Fos expression in BrdU/NeuN-positive cells in the DG. Scale bar: 25 µm.
(A) Proteins and metabolites differentially accumulating in response to the Tyr-Asp feeding were delineated using two-way ANOVA embedded in MeV software Howe et al., 2011(), followed by False Discovery Rate (FDR) correction. Heat map representation of the respectively, 212 and three differential (two-way ANOVA; FDR corrected p≤0.05) proteins and metabolites across five time-points. Data is presented as log2 fold change between control and treatment. Red indicates down- whilst blue up-regulation. 1: log2 fold change (FC) 15 min; 2: log2 FC 30 min; 3: log2 FC 1 h; 4: log2 FC 6 h; 5: log2 FC 24 h; M: median log2 FC of all time points.
(B) Quantification of ATPase activity of DDX43 variants. The graph on the right indicates the ratio of the hydrolyzed ATP produced by DDX43 mutants to that of the WT DDX43. Data represent the mean+/- standard deviations. n=3 independent experiments. *p < 0.002 as determined with the t-test.
(b) Some SR interactions of DNMT1 occur between genes proximally located on the signaling pathway. DU rescuer genes of DNMT1 are colored blue.
I, Heatmaps representing the methylation levels at the top Differentially Methylated Regions (DMRs; n=100; upper panel) or the Imprinting Control Regions (ICRs; n=103 different imprinting loci; lower panel) in the indicated samples (referred to panels A,B). Color code and scale of DNA methylation, from 0.0 (red) to 1.0 (green) is applicable to both heatmaps.
A Family pedigrees of Subjects 1, 2 and 3 show segregation of identified homozygous NDUFC2 variants within each family.
D, E Representative images (D) and quantification (E) of Nile red staining of fat body lipid droplets in dsNPF1-treated locusts and dsGFP-treated controls (n=5 biological replicates). The scale bars represent 50 µm, the data are shown as the mean ± SEM (Student's t-test, **P<0.01).
Blood samples were collected from healthy volunteers and septic patients (n= 13 septic patients, = 15 healthy controls). Plasma was prepared and (A) FFA and (B) glycerol concentrations were determined as described in the methods. P-values were calculated with two-way Student t-tests.
B Pie chart depicting Bayesian fine-mapping results for an AS-associated locus on 2p15 (left panel). MPRA results in stimulated T cells (right panel) showing that rs6759298 has a significant expression-modulating effect (the strongest of any variant at this locus) while the other candidate SNPs have negligible effects.
dN/dS ratio comparison between genes with different major PAS locations (Mann-Whitney U test, *P < 0.05; **P < 0.01; ***P < 0.001).
(C) HeLa cells were transfected with Effectene-coated latex beads for 3 h and subjected to immunocytochemistry for LC3 and Ub (top) or LC3 and p62 (bottom). Bar, 5 µm. The percentages of LC3- or p62-positive beads per Ub-positive (Ub+) or Ub-negative (Ub−) beads were enumerated. Statistical analysis was performed by Student's unpaired t test. *, P < 0.01.
A) Flow cytometry of CD83 on MoDCs after incubation of TLR4 ligand (E. coli LPS) and TLR1 and 2 ligand (Pam3csk4) for 4 hour.
Effects of PG treatments on the viral production. PG-containing medium (2% or 4.7% PG), or standard cell culture medium, were applied to RV-infected cells (MOI of 10) 2 HPI (1 hour after virus absorption). (e) Effects of PG treatments on virus production at different infection points. 4.7% (v/v) PG was applied between 2-7 HPI ('early infection'), and then diluted to 2% between 7-11 HPI, or 4.7% PG was applied between 7-11 HPI ('late infection'), and diluted prior to harvesting the virus. Each group was compared to the control group (10 h treatment with 2% PG). Each group was compared to the control group (10 h treatment with 2% PG). Application of 4.7% PG for 5 h significantly reduced virus replication (P = 0.0016) between 2-7 HPI compared to the control group. PG treatment between 7-12 HPI did not significantly reduce the viral titre compared to the control group (P = 0.1141). Infectious titres represent mean±SD values estimated for four independent biological replicates. Statistical analyses were performed using a Kruskal-Wallis test, followed by uncorrected Dunn's multiple comparisons test (**P < 0.002).
Phosphorylation of the PAT1 peptide SSFVSYPPPGSISPDQR, which include Ser208, in Col‐0 and mkk1/1‐summ2 before and after flg22 treatment. The phosphorylation stoichiometry is illustrated relative to Col PAT1 without flg22 treatment. The ratios were obtained using quantitative iTRAQ mass spectrometry.
Proliferation (48 h) of melanoma cell lines measured after transient knockdown of TMX1 or TMX3.
A. Pie charts representing, on a feature-by-feature basis, the relative distribution of COG categories among the gene deletion strains associated with s ≥ 3. The enriched COG categories are labeled and highlighted with an exploded pie sector. The under-represented COG categories are further highlighted by an asterisk. Enrichments and under-representations with an associated (FDR-corrected) q-value < 0.05 were considered significant. Only morphological and growth features with at least one enriched or under-represented COG category are represented. B. Same as A but for s ≤ -3.
H Schema of the experimental design. Fresh surgically-resected human brain metastases (n=19) from various primary origins were used to perform patient-derived organotypic cultures (BrM-PDOC) and treated with DEBIO-0932 at 10 µM and 1 µM for 3 days.
Figure 2. SPOP localizes to nuclear speckles or other nuclear bodies. Confocal microscopy images of fixed NIH 3T3 cells transiently expressing (A) full length HA-SPOP, (B) GFP-Gli31455, and (C) HA-SPOP+GFP-Gli31-455 are shown. DAPI was used to stain the nucleus, SPOP localization was identified using a anti-HA antibody, nuclear speckle localization was identified using a anti-SC-35 antibody, and Gli31-455 localization was identified via GFP fluorescence. SPOP co-localizes with a marker for nuclear speckles or with the substrate Gli31455. The areas with overlapping HA- and GFP signal contain 75% of the punctate HA signal, and 100% of the punctate GFP signal.
(C, D) Confocal z-projections of adult DIP-δT2A-Gal4/1-119 trans-heterozygous mutant (D) or DIP-δ1-119/+ heterozygous (C) brains, which express MiMIC mediated Dpr12GFSTF (Dpr12-GFP; green), in which DIP-δ-Gal4 either drives expression or UAS-DIP-α (D) or not (C). Grayscale panels represent single channels, as indicated. The γ-lobe is outlined in white.
C. Carfilzomib, Bortezomib and MLN9708 activate Il-1β-luciferase in M2 macrophages in a dose-dependent manner. BMDMs from Il-1β-luciferase transgenic mice were treated by IL-4 (20 ng/mL) for 24 hours, then treated by DMSO, Carfilzomib, Bortezomib or MLN9708 at indicated concentrations. Luciferase activity was monitored 12 hours later. Data from three experiments are presented as the mean ± SD.
D-F. Data are presented as in A-C for another cell that showed persistent oscillations along the horizontal axis throughout growth. The number of cells that fit this category was 28/97.
HEK293T were transfected with NF-kB luciferase reporter plasmid and FLAG-tagged full-length CARD14 (FL) or CARD14sh (short) at the indicated concentrations and analyzed 24 h later. (C) Immunoblotting for c-Jun, phospho-c-Jun, JNK, phospho-JNK, p38 and phospho-p38 as indicated. Actin was used as a loading control. Data are representative of two independent experiments.
D, Knockdown of PTPN3 blocks TGF-β-induced PAI-1 gene transcription. Experiment was done with qRT-PCR primers specific to PAI-1. Data are shown as mean ± SEM; n = 3. Statistical analysis was performed using two-tailed Student's t-test. ***P < 0.001.
Scatter plot of YTHDC1 KD up-regulated introns (logFC≧1, p<0.01). The X- and Y-axes show the GC contents and ∆LogFC (HSATIII KD-control) of each intron, respectively. Magenta lines indicate |∆LogFC|=0.5. Analysis was applied to 1742 introns (49 introns not applicable to the analysis were excluded from 1791 introns). 659 introns (∆LogFC≧0.5) were plotted above the upper magenta line.
Percentage of survival with respect to weeks of age in WT and ASM-KO mice treated with vehicle or PF (**P = 0.0031, n = 5 mice in WT vehicle, WT PF treated and KO vehicle, 6 mice in KO PF treated, Mantel-Cox)