EMBO/sd-character-level-ner huggingface dataset:
G. Box plots (the minimum, first quartile, median, third quartile, and maximum are shown, with data >1.5 interquartile ranges denoted with circles) for relative reporter activity (LUC/REN) in plants expressing different reportors and effectors. The relative LUC activities normalized to the REN activity are shown. The LUC/REN in plants expressing ProFT alone is set to 1.0. Data information: data are presented as mean ± SD, n=4. The letters "a" to "g" indicate statistically significant differences determined by Tukey's HSD test (P≤0.05). Two biological replicates were performed.
The ratio of HIF-1α to HIF-2α ChIP-seq signal for all canonical HIF-binding sites at (I) 16 hours hypoxia and at (J) 48 hours hypoxia was plotted against that at 6 hours hypoxia. Strong correlation in the HIF-1α to HIF-2α ratio was observed between the various timepoints
(I) Venn diagram showing the overlap between MCF7 DVL3 ChIP-seq peaks and H4K8ac ChIP-Seq.
PC9 cells (3X106/mouse) were subcutaneously implanted in the flanks of CD1-nu/nu mice. When tumors became palpable, mice were randomized in groups of 5-9 animals and treated for 90 days (grey areas) with 2XmAbs (cetuximab plus trastuzumab, 0.2 mg/mouse/injection), once every three days, or with erlotinib (50 mg/kg/day), once per day. Alternatively, mice were treated with combinations of erlotinib (50, 20, 10, 5 or 1 mg/kg) and the two monoclonal antibodies. Following 60 days of treatment reduced the frequency of erlotinib administration to once every other day (underneath dotted line). Tumor volumes (A) are shown. Mice were euthanized when tumor size reached 1,500 mm3.
(C) qRT-PCR analysis for Islr in CD45+, CD45-Epcam+, CD45-Epcam-CD90+ and CD45-Epcam-CD90- cells sorted from intestinal tissues. n = 3 technical replicates.
Human peripheral blood mononuclear cells (PBMCs) were cultivated for 48h in RPMI containing 80mg/dl glucose (NC) and supplemented with 10mM beta-hydroxybutyrate (BHB). T cell stimulation was performed through CD3/CD28 Dynabeads at a bead:cell ratio of 1:8. Human pan T cell RNA was isolated and cell culture supernatant was sampled. C Th1/Th2 cell transcription factors Tbet and GATA3 quantified via RT-qPCR and flow cytometric ratio of Th1/Th2 cells following differentiation, n=6/6/4 biological replicates. Data information: Data depicted as mean ± SEM (protein data) and box plots with median, twenty-fifth and seventy-fifth percentiles and range (all other). Dots indicating individual values. *p<0.05, **p<0.01, ***p<0.001, paired t-test/ Wilcoxon matched-pairs signed rank test, as appropriate.
F. Time-lapse imaging of transfected HEK293 YFP-EML4-ALK V3 WT to observe the movement of cytoplasmic foci. Representative still images are shown of an area of cytoplasm containing YFP-EML4-ALK V1 WT and V3 WT foci at the times indicated. Scale bar, 1 μm.
Percentage (%) of γ-H2AX positive cells in HeLa and CCNF K/O after transfection of the indicated siRNAs treated with Chk1i for 20 hours. Percent of γ-H2Ax positive cells were plotted as Mean % ± SD. Percentage (%) of hyper-RPA positive cells in HeLa and CCNF K/O after transfection of the indicated siRNAs treated with Chk1i for 20 hours. Percent of hyper RPA positive cells were plotted as Mean % ± SD.
A Diagram for three constructs expressing MAVS-Region III C-terminally tagged with GCN4-derived peptides, whose sequences are presented in bold.
(A) Simulations predict that after a break in stress, on reapplication of stress all cells turn on σV immediately and homogeneously (N=99).
Locomotor activity was assessed in the same experimental set as in the open-field test. After acclimation for 120 min, mice (n = 10-12/group) were injected (arrows) with MK-801 (0.2 mg/kg, B) and their locomotor activity was monitored. In the right panels, cumulative values for pre- and post-injection times are also shown.
I Graph shows qPCR analysis of Pdgfa, Pdgfb, Igf1, Igf2, Cxcl12, Hgf and Kitl expression (normalized to Actb) in purified CD31+ Emcnhi ECs compared to CD31+ Emcnlo ECs.
H GB glioblastima neurospheres [5 × 104 cells (indicated by the dashed line)] were infected with the indicated lentiviruses. After 96 h, the number of viable cells was counted. Bars indicate mean ± s.d. (n = 4).
(D) Densitometric analysis of the Western blots shown in panel C. The graph represents the relative amount of VP30 present in the eluates compared to the input. The data represent the mean ± S.D. from two independent experiments (n=2). Statistical significance was calculated using ANOVA with Tukey's multiple comparisons test. **p<0.005.
a, t-SNE representation of the four subclasses of cancer-associated fibroblasts (CAFs) and perivascular-like cells (PVL), named myofibroblast-like CAFs (myCAFs; 280 cells), inflammatory-like CAFs (iCAFs; 1,129 cells), differentiated-PVL cells (dPVL cells; 122 cells) and immature-PVL cells (imPVL cells; 198 cells).
G. Decreased PKCδ expression using shRNA counteracts prazosin-induced GIC death. Viability analysis of GICs transduced with scrambled or PKCδ shRNA and treated with prazosin for 72 h. *P < 0.005 by two-tailed unpaired Student's t-test, n=4.
(A) Western blotting analysis of NCoR1 in neonatal rat ventricular myocytes (NRVMs) transfected with siControl or siNCoR1 for 3 days. siControl indicates control siRNA; siNCoR1, NCoR1 siRNA.
(F, G) Submitochondrial localization of SLP2. (F) Mitochondria were isolated from MEFs and fractionated in the presence or absence of proteinase K as indicated. Fractions were analyzed by SDS-PAGE and immunoblotting. MFN2 served as OM marker, TIMM23, SMAC/DIABLO, and YME1L as IMS markers, and AFG3L1 and AFG3L2 as matrix marker proteins.
(c) Western blot analysis showing levels of LC3-I and LC3-II in control- and FIPI-treated CHO cells grown in normal medium (Nm), after nutrient starvation (St) or after nutrient starvation in the presence of 50 nM bafilomycin (St+B). Treatments were for 3 h. Right panel: quantification of protein signal intensities showing LC3-II protein levels in extracts from nutrient-starved and bafilomycin-treated CHO cells following FIPI treatment. Black bars, DMSO (vehicle); grey bars, FIPI treatment. Values denote means±s.e.m. (n=4).
(C) Co-immunoprecipitation between VP30 and the indicated PPxPxY containing host factors. Empty expression plasmid (Vector) or FLAG-tagged host protein expression plasmids were co-transfected with an HA-VP30 expression plasmid in HEK293T cells. An anti-FLAG immunoprecipitation (IP: Anti-FLAG) was performed. Western blots of IP and whole cell lysates (WCL) are shown. Anti-β-tubulin was used as a loading control for the WCLs.
(D-E) Venn diagrams showing the overlap of the genes differentially upregulated and down regulated following knockdown of the three factors mentioned in (A).
Venn Diagram representing all preys detected in less than 5 and more than 1 KZFPs interactomes. In blue, are shown the preys that only appear in interactomes alongside KAP1, in red the preys that only appear in interactomes devoid of KAP1 and in purple the preys that are in both types of interactomes.
Representative immunofluorescence of normal and HD patient-derived fibroblasts stained for GAPDH and mitochondrial ROS with Mitosox. Three independent images per condition were analyzed to calculate Mitosox intensity and the Pearson's correlation coefficient for quantification of colocalization between GAPDH and mitochondrial ROS. #P = 0.03; ##P = 0.02; *P = 0.006; **P = 0.005. Images were acquired at 63× magnification, and brightness and contrast of images were adjusted by 50%.
Colony forming assay for GBM cells infected with lenti-Ctrl or lenti-CYP46A1. Shown are means and SEM (n = 3). LN229: *P = 0.013; GBM#P3: *P = 0.012. Statistical significance was determined by two-sided Student's t‐test.
F, Hierarchical tree showing the relationship between the MC subtypes and the myeloid cells from kidney marrow.
(B) Confirmation of ENSA/ARPP19 S67 phosphorylation in mitotic extracts from Ctr and DIA treated cells, before and after ENSA/ARPP19 siRNA depletion.
(V) Survival of hydrogen peroxide-treated animals. (In all three repeats, P = 0.000 for epg-7 vs. sqst-1;epg-7; P > 0.2 for wild type vs. sqst-1;epg-7; log-rank test).
MTT assays (E) indicated that treatment with Tipifarnib (farnesyltransferase inhibitor) can partly reverse oecircFNTA-increased invasion in J82 and UMUC3 cells. Scale bar, 100 μm.
(A) Schematic description of viral entry, endosomal maturation, replication, translation, and accompanying cell signaling and regulation or immune responses, described in the main text. Mainly, SARS-CoV-2 spike binds the host receptor ACE2 (Hoffmann et al., 2020a) complexed with the amino acid transporter B0AT1 (Yan et al., 2020) Proteolytic cleavages (e.g. by TMPRSS2) are essential to viral entry, including spike priming and membrane fusion, or lysosomal escape after endocytosis. PIKfyve is the main enzyme synthesizing PI(3,5) P2 in early endosome (de Lartigue et al., 2009), and PI(3,5) P2 regulates early to late endosome events.. TPC2 is a major downstream effector of PI(3,5) P2 (Li et al., 2019b). Dominant pathways in four modules involved in SARS-CoV-2 infection are listed in the upper right boxes (see also Table 2). The diagram also shows selected drugs that have been identified and experimentally validated to inhibit or reduce SARS-2-CoV-2 infection (mainly viral entry) in highlighted in boxes (with red fonts).
Total intensity profiles (Mean ±SEM) of tPH-CynA-KikGR on the membrane over time show different decay rates for less polarized (green, n = 5) and more polarized (red, n = 8) Dictyostelium cells. The dashed lines show the respective single exponential fit to the data. Mean half time for vegetative cells = 7.5 min; for developed cells = 55 min (from single exponential fit to the data).
A) Elevated Plus Maze. Percentage of time spent in open arms and number of entries in open, closed and total (open+closed) arms. (n = 12 for time in open arm, n=24 for arm entries).
B Trans-activation activity assays of CDF4 in Arabidopsis protoplasts. The full-length ORF of CDF4 and its four deletion constructs Dof (gray boxes) represent the DNA-binding domains of CDF4. Negative control was the effector vector without gene inserts. The effector vector used is shown in the left panel. The GAL4 transient expression assays were performed using Arabidopsis protoplasts, shown in the right panel. Deletion of the CDF4 N-terminal domain compromised the transcriptional repression by CDF4 in our assay. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t test.
Experiments were performed to address possible effects of the pi4kβ1 pi4kβ2 double mutant on endocytosis of markers relevant for cell plate formation. Panels a-f display data obtained using cytokinetic cells Enhanced accumulation of KNOLLE at the cell plate at the end of cytokinesis in the pi4kβ1 pi4kβ2 double mutant. Five-day-old seedlings were immunostained with anti-KNOLLE antibodies (green) and counterstained with DAPI (blue). Scale bars, 10 μm. Quantification of KNOLLE intensity at the cell plate from (C), normalized to the signal intensity of intracellular compartments. ***, a significant difference (p<0.0001) according to a two-tailed Mann-Whitney U-test (wild type, n = 26 cells, 20 roots; pi4kβ1 pi4kβ2, n = 41 cells, 37 roots).
(E) Distance of the tip of the tube, and the leading ER and Golgi accumulations from the cell junction that defines the base of the cell. Line and shading represent mean and 95% confidence interval, n=4.
(F) SAG12 expression level in rosette leaves at various development stages. Three independent experiments were conducted. Values are given as mean ± SD, n=4. *p<0.05 by Student's t-test.
(a) Δ133p53α is colocalized with p62/SQSTM1 upon autophagy induction. MRC-5 fibroblasts expressing FLAG-Δ133p53α (wild-type) were cultured under amino-acid- and serum-starved conditions for 4 h, and co-immunostained with anti-FLAG antibody (Δ133p53α, green) and anti-p62/SQSTM1 antibody (red). Two representative sets of images, including nuclear staining with 4′,6-diamidino-2-phenylindole (DAPI) and merged images, are shown. Scale bars, 10 μm.
C. Top functional annotations for differentially expressed genes in Hnf1aaKO pancreas.
(F) Validation of siRNA knockdown efficiency for IP3R1 and IP3R3. HeLa cells transfected with siRNA targeting IP3R1 or IP3R3 were analyzed for IP3R1 and IP3R3 protein expression by immunoblotting.
K Intensity plots of GflB (blue) and RapGAP1 (orange) across the green dotted arrow in J.
IRE1α oligomers were stabilized by MITOL KO. MEFs transfected with IRE1α-GFP were treated with Tu. After 4 hours, these cells were washed with PBS and subsequently re-fed with fresh media for indicated periods. The right panels show 5-fold magnification images of the boxed regions. Percentages of cells with IRE1α-foci were calculated from 100 cells by visual inspection at indicated periods after wash out of Tu in each independent experiment. Scale bar represents 10 µm.
B. Multiple alignments of the N-terminal regions of the human and mouse LDB family. Please note that the N-terminal regions are highly diverged between LDB1/Ldb1 and LDB2/Ldb2. The bar indicated the position for the peptide for antibody production.
D-H Morphometric quantification of data shown in A. Synapses of VPS34IN1-treated stimulated neurons display reduced numbers of SVs/ bouton area in (D) and an accumulation of endocytic membrane invaginations (E), endosome like vacuoles (ELV) (F), clathrin-coated pits (CCP) (G), and clathrin-coated vesicles (CCV) (H). n = 100 (SV) and n = 200 (invagination, ELV, CCP, CCV) profiles per condition; Two-way ANOVA; Tukey's Multiple Comparison Test. Data information: Data presented as mean ± SEM n.s. not significant; ***p < 0.001; ****p < 0.0001
Graph of flow cytometry data shows the percentage of cells in given cell‐cycle phases 48h after transfection with plasmids encoding scrambled siRNA or siRNA specific for CDK2. Graph represents the mean of three independent experiments. All data represent the mean ± SEM from three independent experiments. Student's t-test analysis was performed, with **p≤0.01 (ns=not significant).
A: Conspicuous downregulation of PIKfyve, but not FIG4 or VAC14, in brain lysates of terminally sick mice intracerebrally inoculated with prions (RML). Control: mice inoculated with non-infectious brain homogenate (NBH). Right: Quantification of immunoblot. Each dot represents one mouse. ***: p<0.001; unpaired t-test. Error bars represent s.e.m
Western blot for p53, phosphorylated p53 at Ser15 (p53 pS15), and vinculin (vinc) in HCT116 treated with 300 μM 5-FU for 8 h and silenced for PHD1, PHD2, or PHD3.
(D) Raster Imaging Correlation Spectroscopy (RICS) analyses was performed for WT (left) or RagA/B KO (right) HAP1 cells expressing endogenously GFP-tagged Raptor (green curves) with either mCherry-tagged ArfGAP1 (blue curves) or RFP1 as a control (red curves). Auto-correlation (AC) or cross-correlation (CC) curves are shown for samples in conditions with amino acids (+AA, solid curve) or without amino acids (-AA, dashed curve).
16-days old MCF10A spheroids grown in matrigel/collagen mix were stimulated for 24h with either macrophage-conditioned or control medium. Macrophage-conditioned medium induces filling of the spheroid lumen with cell nuclei compared to control. Error bars represent mean ± SEM from 11 independent experiments (n=2 per condition; 50 spheroids each). Macrophage donors are indicated as D1-D16. M1D - M1 differentiated, M1A - M1 activated, M2D - M2 differentiated, M2A - M2 activated macrophages.
B. EYFP-Parkin translocation accelerates in the presence of the L-type Ca2+ channel agonist Bay K 8644 (5 μM; n = 19-21 cells; difference between the curves p < 0.0001, two-way ANOVA; lines show mean, dashed area shows SEM)
Histogram of transcriptional read-through length (nt) from PAS of protein-coding gene (plaNET-seq FPKM>5, n=9316) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red).
I) Simultaneous 525nm and 405nm light prevents spike silencing J) Constant 405nm light (12.9 log photons) presented with 525nm light of decreasing intensity from 14.9 - 12.9log photons in 6 steps of 10s (left) or 20s (right). 525nm light antagonised the 405nm-driven hyperpolarisation for all intensities except 12.9log photons
J. Quantification of germinal centers identified in spleen sections as shown in I. Results represent the data from one experiment and numbers represent biological replicates for each group (WT; n = 6, KO; n = 6).
(B) Immunoblot analysis of PPCA in rat liver lysosomes, their membranes (MB) and matrices (MTX) (100 μg of protein) incubated alone (None) or with 5 mM MgCl2. Arrowheads indicate the precursor (54 kDa) and heavy chain (32 kDa) of the mature PPCA.
(A) The differences in cell-to-cell gene expression variability for the TATA and the paused effector gene groups were analyzed using the scRNA-seq data. The coefficient of variation (standard deviation/mean) of gene expression was calculated for all genes in the tissue with the highest expression for each gene. The median coefficient of variation was consistently lower for the paused genes compared to the TATA genes.
Dot plot reporting the correlation of EGFR and miR-9 expression in primary HNSCC samples evaluated by qRT-PCR. The number of analyzed samples (n), the Spearman correlation value (r) and its significance (p) are reported in the graph.
(E, F) qRT-PCR shows reduction of Wnt‐target gene expression (E) Axin2 (*P=0.017) and (F) Cyclin D1 (**P=0.0036) after 8 h starvation (mean±s.e.m., three (Axin2) or six (Cyclin D1) independent experiments performed in triplicate).
Percentage of polyploidy (>4N) following B12536 (5 nM) in control and CEP55 knockdown MDA-MB-231 cells. Graph represents the mean±SEM of three independent experiments.
C Projection of Hoxb8-FL transcriptome onto the LK/LSK mouse landscape. The projection score (based on nearest neighbours) reflects relative transcriptional similarity to the Hoxb8-FL state for each LK/LSK cell. For the majority of cells no neighbours are identified (grey), some cells exhibit low similarity (yellow) and a small set of cells exhibit high similarity (blue).
F. Loss of pancreatic islet area in Rb∆K7 mice correlates with reduced proliferation and H3K36me3 histone marks, but not with increased cell death. TUNEL analysis showing apoptosis in 10 day-old Rb∆K7 islets is even lower than in control littermates. Arrow points to a rare apoptotic cell in control islet. Serine800/804 phosphorylation of pRb in β-cells from 10 day-old control but not Rb∆K7 islets with a Ser-to-Ala substitution at this site. BrdU incorporation and PH3 staining showing reduced S-phase and mitotic cells, respectively, in 2- and 3-week old Rb∆K7 vs control islets. Reduced H3K36me3 staining in pancreatic islets from 3-week old Rb∆K7 mice compared to control littermates (n>3 for each experiment). Scale bar, 100 μm.
B Pearson correlation coefficient calculated Data were shown as mean ± SEM of N > 80 cells from four independent experiments. ***p < 0.001 (one-way ANOVA, the post hoc Tukey's HSD test).
Figure 5d Examples of genes whose transcription processivity and expression is dependent on the CDK12 kinase activity. Nuclear RNA-seq data on the respective strand and RNAPII, P-Ser2, P-Ser5 and SPT6 ChIP-seq data for MED13 genes from cells either treated (red) or not (blue, CTRL) with 3-MB-PP1 were visualized with Gviz. Read counts were normalized to the total number of mapped reads per sample and averaged between replicates. Blue and red boxes below the RNA-seq data indicate the 90% distance in control and CDK12 inhibited samples, respectively.
A GST-ISP1 pulls down endogenous β-Tubulin from cell lysate of WT ookinetes. Lower panel indicates the Coomassie blue stain of recombinant GST and GST-ISP1.
A Circular genome plot for Actinomyces sp. oral taxon 171 str. F0337 with genes encoding AITD-like peptides. In this GView image, red and blue tracks show genes on forward and reverse strands, respectively. AMSIN genes and their immediate upstream and downstream genes are shown. ABC, ATP binding cassette. HP, hypothetical protein. The BioProject database accession number for the genomes is PRJNA43131. The AMSIN gene cluster was verified by PCR amplification (inset) and DNA sequencing. Arrows in green mark binding positions of the two specific primers.
(C) Volcano plots of genes differentially expressed in tumor interstitial fluid (TIF) of mock and OTUD1 expressing CT26 tumors. Left, example of genes downregulated in OTUD1 overexpressing tumor interstitial fluid; right, example of genes upregulated in OTUD1 overexpressing tumor interstitial fluid.
A. A schematic diagram showing the strategy of generating Tfcp2l1 knockout (KO) mice. E2, exon 2 (purple box); triangle (red arrow), loxP site; HET, heterozygotes; KO, homozygotes.
(B) Average plots of Med8 cleavages around the TSSs of genes upregulated and downregulated ≥2 fold in SM (Saint et al., 2014) in WT and med15Δ. Control cleavages were subtracted from SM cleavages at each base position.
Quantification of telomere-induced foci (TIFs) by double immunofluorescence with anti-RAP1 and anti-γH2AX antibodies. Representative images are shown to the right. White arrowheads: colocalization of γH2AX and RAP1.
(B) Interaction between endogenous Ulk1 and recombinant PPM1D. Lysates from healthy PPM1D+/+ MEFs were incubated with GST-PPM1D or GST. Binding molecules were then analyzed by western blotting using anti-Ulk1 and anti-GST antibodies. "Total lysate" indicates 7% of the lysates that were incubated with GST fusion protein.
B Denature-IP analysis (with anti-Flag) of K63-linked polyubiquitination of NLRP3 in cotransfected HEK293 cells left untreated or treated with CQ for 6 h.
K. 3D reconstruction of a dividing radial glial progenitor at early anaphase. A coronal section of an E14 brain of a heterozygous control mouse was stained with anti-phospho-Vimentin antibody (red), anti-γ-tubulin antibody (green/yellow), phalloidin (magenta), and DAPI (blue) and imaged by 3D confocal microscopy. "s" indicates spindle axis, "α" indicates angle relative to ventricular surface plane, which was determined by a vector path as indicated by thin white lines located on the left side of the image. Yellow dots highlight the centrosomes of the spindle poles from the analyzed dividing cell. Scale bars: 5 μm.L. Quantification of spindle orientation in radial glial cells as in K for E14 brains of miR-34/449 KO and littermate controls (Het). Each dot represents a single dividing cell; p-value = 3.166e-05 (Het vs. KO) (n = 131 vs. 107 cells, n = 4 brains per genotype group, 2 independent litters).
B. Localization of Lrig1 (red) in coronal sections from P15 ratbrain by immunofluorescence. Anti-Lrig1ECD antibodies label dentate gyrus cells, CA1-CA3 hippocampalneurons and pyramidal corticalneurons (*). Scale bar, 400 m.
B) Protein expression levels of Jmjd1a/b in HP1-cTKO cells were monitored by immunoblotting. The intensities were quantified using ImageJ software and summarized on the right. The thin gray line and bold colored line show individual data and the mean of experimental replicates, respectively.
Representative immunofluorescence (IF) staining of Ki67 and TDP-43 in the regions of frontal cortices from 6-mon-old WT and FTLD-TDP Tg mice. Nuclei were stained with 4',6-diamidino-2-phenylindole (DAPI; upper panel in blue) or neural marker NeuN (lower panel in green). Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm.
(E-G) Immunofluorescence (IF) images depicting localization of Yap1 in J1 (D), CJ7 (E), and E14 (F) mouse ESC (top) and dESC (bottom). The white arrow indicates nucleolus. Bottom panels represent higher magnification of the above panels. Dashed circle indicates nucleus border.
H3K9me2 ChIP‐seq enrichment profiles for swi6+ and swi6∆ cells on the telomere of the right arm of chromosome 1. Two independent biological replicates for each genotype were performed (replicates 1 and 2).