EMBO/sd-character-level-ner huggingface dataset:
Levels of BiP protein in wild type or ERp18 KO cells before and after ER stress induction with thapsigargin (TG). Panel 1 compares wild type and ERp18 KO cells as indicated. Panel 2 compares ERp18 KO cells to ERp18 KO cells that have been transfected with ERp18 (RV).
D Chromatin immunoprecipitation using anti-RUNX1 antibody. Immunoprecipitated DNA fragments were measured by real-time PCR using HEL cells expressing shRUNX1 and control (n=4, means ± SD).
Brain homogenates were fractionated by sucrose density centrifugation and immunoblotted for BACE1, rab5, or rab9. EE, early endosome; LE, late endosome. Signal intensities were quantified and are shown in the right graphs.
N,n': The binned distribution of Neun intensity is plotted as both frequency distribution graphs, in panel N, and cumulative probability plot in panel n'. The null neurons distribution is significantly shifted towards low levels of Neun intensity, Kolmogorov-Smirnov test **: p-value<0.01. Each value in panel N is represented as mean ± SEM obtained by measuring 900 cells from n ≥10 wells derived from two different preparations.
b) LEFT. Auto-ubiquitination assays were performed with wild-type HHARIRBR or an active site-dead mutant (C357A- HHARIRBR). Products were visualized by western blotting against GST. The zero time point was taken immediately prior to ATP addition, all other times are post-ATP addition. RIGHT. Identical assays as shown on left were performed with the UBR-hybrid. The active site-dead mutant (C357A) retains substantial auto-ubiquitination activity signifying that UbcH5~Ub is able to transfer Ub directly onto the GST-UBR-hybrid construct, bypassing the RING2 active site Cys.
A) Caco-2 cysts expressing an empty vector (pLKO) or shROCK1 (#02) or shROCK2 (#36) after 2 days of invasion were fixed and stained for E-cadherin, F-actin (Phalloidin) and nuclei (DAPI). Boxed regions i, ii and iii are shown at high magnifications. Arrowheads point to non-protruding cells. Arrow points to protruding cells. White stars show nuclei that engage in protrusions. Scale bars: 20μm. B) The number of protrusive Caco-2 cyst was quantified in each of the mentioned conditions and represented in a bar graph as percentage of total cysts (Means ± SEM of at least 3 independent experiments, paired t-test, ***p<0.001, *p<0.05 n.s: non significant).
G Expression of p73 in (F) was determined by immunoblotting with anti-p73 antibody. RFP was used as a control.
Average cellular compositions of tissues highlighted in panel (B) showing that the molecular similarities in their transcriptomes and proteomes are driven by similarities in cell types.
Panels (A and C): the pre-host attachment state. Panel (B): the post attachment state. The atomic structure of the conserved tube-baseplate core complex (derived from the T4 tube-baseplate complex) in the pre- and post-attachment states is fitted into the cryoEM maps. The color scheme is the same as in Figure 2. BW3 gp104 and its ortholog T4 gp7 are colored magenta. The putative chain of gp104 crossing three gp105 dimers is shown as a thick coil. (C) A thin slice through the pre-attachment state cryoEM map is shown. The plane of the baseplate is about 8° out of the plane of the paper. The distal part of the A511 tail fiber is formed by the gp108 trimer, whose structure is modeled with homologous domains that are fitted into the pre-attachment baseplate cryoEM map. The structures are shown as ribbon diagrams and colored in a rainbow pattern with N-terminus in blue and C-terminus in red. The numbers indicate the N- and C-terminal residues of the gp108 sequence that match the start and end of the homologous structures. The smaller insets show cross-sections whose positions are indicted with thicker black lines.
(J) Serum alanine aminotransferase (ALT) (left) and aspartate aminotransferase (AST) activities (right) from sepsisBIM mice pre-treated for 4 consecutive days with vehicle or 500 mpk TUDCA (10 mice per group). The bar graphs show means ± SD (standard deviations). Student's t-test was used to assess statistical significance, *P < 0.05.
Gene set enrichment analysis of genes with maximal expression above 1e-5 normalized UMI counts. Centrally (cv) enriched sets are marked with blue dots, portally (pn) enriched sets are marked with red dots. Green fonts denote pathways that are concordantly zonated in mouse, black fonts denote pathways that are not zonated in mouse and red fonts denote pathways that are inversely zonated in mouse. 'K' denotes gene sets obtained from KEGG database, 'H' denotes gene sets obtained from Hallmarks database.
Immunoblot analysis of mouse intestinal crypts treated with Wnt3a (60 ng/mL) for indicated time. The relative protein level was quantified and shown under each band.
A schematic illustration showing that accelerated RNAPII tends to evade from RNAPII stalling near gene poly-(A) sites (PAS). This leads to less efficient transcription termination and extended transcription read-through, reflected by the absence of RNAPII signal peaks downstream of PAS and elevated signal downstream of PAS stalling region by plaNET-seq.
(B) Decreased cell viability upon CCT depletion and A3A expression. CCT4 (left) and CCT7 (right) subunits were depleted by siRNA transfection in U2OS cells with dox-inducible A3A transgenes. Immunoblot analysis of cell lysates showed decreased expression of targeted CCT subunit, but no alteration in A3A expression. Scr indicates non-targeted siRNA, used as control. Ku-86 is a loading control. Following siRNA transfection to deplete CCT subunits, U2OS-A3A cells were treated with dox. Viability was determined by colorimetric change after addition of a water-soluble tetrazolium salt. Percent viability was normalized to untreated controls. Statistical analysis was performed using a paired two-tailed t-test, n=3 biological replicates; error bars, SEM.
(B) For RNAseq analyses, PC9 cells (3X106/mouse) were subcutaneously injected in the flanks of 13 CD1-nu/nu mice. When tumors reached 500 mm3, mice were treated daily with erlotinib (50 mg/kg). Once tumors that initially responded to erlotinib monotherapy started relapsing and reached 800 mm3, we switched to a combination of 2XmAbs plus erlotinib (50 mg/kg). The respective tumor volumes were sacrificed when tumor volumes reached approximately 500 mm3 Mice responding to erlotinib (N=3) were sacrificed after one week of treatment Mice resistant to erlotinib (N=3) were sacrificed when tumor volumes reached 800 mm3 whereas mice responding to erlotinib+2XmAbs (N=2) were sacrificed after one week of treatment RNA was extracted from all 13 tumors and utilized for RNA-seq analysis. Differentially expressed (DE) genes in the Erlotinib (Er)+2XmAbs arm compared to the Control group are presented in the heatmap.
Primary human alveolar macrophages from BALF of five pediatric patients (patients are color coded) were infected with the human H3N2 strain (Wyo) Wt and ΔF2 for 16 h at MOI 1. (K) Levels of IL-1β were measured by ELISA from the supernatants. The mean ± standard deviation is shown.
RT-qPCR analysis of SUL mRNA levels in WT and hst-1 rootstocks grafted onto WT or amiR scion. Error-bars: SD. Tukey's multiple comparisons test p-values are indicated. n=4.
(E) Alignment showing the introduction of RxL motif determinants to Far1 NLxxxL motif in mutants analyzed in time-lapse microscopy in panels 'G-H'.
(A-C) SHM analysis of the variable (V) region of the human BL2 cell line expressing an AID C-terminal mutant (JP8Bdel) fused to ER. Scheme shows the time points of siRNA transfection, the activation of JP8Bdel-ER by OHT, and the genomic DNA isolation for mutation analysis (A). Mutation frequency at the V region after 48 h of AID (JP8Bdel) activation; plot represents the summary of three independent experiments (B). The values are presented as mean ± sd (n=3). Statistical significance was assessed by two tailed unpaired Student's t-test (*** p ≤ 0.001). Western blot shows the knockdown efficiency by individual siRNAs (C).
Scatterplot of log2 fold accessibility changes in d2_SLRA Dax1-/- cells and of log2 fold H3K27ac ChIP signal changes in d2_SL Hdac3-/- cells relative to WT controls at Hdac3- and/or Dax1-bound regions. Regions colored in red are associated with Gata6.
Distribution of center-to-center distances in cells released for 45 minutes into S phase.
G) ErbB4 enrichment in synapses formed in hippocampal cultures after infection with either the SypCFP/Nrg3 or the SypCFP/Nrg3∆EGF virus. We compared neuronal cultures of different genotypes (Nrg3-/- and wildtype cultures indicated by N3- and wt, respectively). ErbB4 enrichment was calculated as the level of ErbB4 in synapses formed by infected neurons (vGlut1/2+/SypCFP+ boutons) divided by the level of ErbB4 in synapses formed by uninfected neurons (vGlut1/2+/SypCFP- boutons). The dashed line indicates a ratio of 1 at which SypCFP positive and negative boutons would behave identical H) Quantification of the preference for neurons expressing SypCFP/Nrg3 or SypCFP/Nrg3∆EGF to form synapses on ErbB4+ neurons. The synapse preference was calculated as the proportion of vGlut1/2 boutons containing SypCFP that were present on ErbB4-positive neurons divided by the proportion of such boutons present on ErbB4-negative neurons. I) Quantification of SypCFP enrichment in excitatory synapses on ErbB4+ neurons. Enrichment was determined as the ratio between SypCFP levels in SypCFP+/vGlut1/2 boutons on ErbB4-positive and -negative neurons
(H) The qRT-PCR analysis with cytosolic DNA (minus mitochondria) isolated from control or IRGM shRNA or EtBr treated IRGM shRNA HT-29 (Rho0) cells.
b. Heatmap depicting mean expression of the top 20 upregulated genes of fibroblast isolated from wound-induced tumours (Pap) compared to fibroblasts from wild-type (WT) and inflamed (InvEE) back skin (n=3 per condition). PRSS35 is indicated in red as a top upregulated gene in CAFs.
(A) Experimental setup used for cell synchronization, auxin and EdU treatment of Cdca5 Δ/Δ sor-LAP-AID F-box mouse embryonic fibroblasts.
(K) Quantification of γH2A.X+ cardiomyocyte nuclei is on the right. Scale bar = 50 µm.
(B) CohesinHalo488 loaded onto DNA in the presence of Scc2-Scc4 was incubated in the buffer with or without TEV protease. After high-salt washing, CohesinHalo488 intensities on DNA were measured. Red bars denote the median, lower, and upper quartile values (n ≥ 98; *p < 0.0001, two-tailed Mann-Whitney test).
(D) RPA1 is required for the accumulation of SLFN11 at laser-induced DNA damage tracks. A SF268 cell line stably expressing wild-type RPA1 under the control of a tetracycline-inducible promoter was generated. The resulting cell line infected with RPA1-specific lentiviral shRNA targeting the 3'-UTR of RPA1 transcript was induced by doxycycline addition for 48 hr and then laser-microirradiated. Thirty minutes later, cells were fixed and stained with anti-RPA2 and anti-SLFN11 antibodies. Scale bar, 10 µm.
CRISPR-deletion of 18qp53-binding site reveals local changes in transcription and γH2AX formation in response to DNA damage. (A) Schematic showing the deletion of ~70 bp region covering non-canonical p53 binding site and adjacent (TG) n repeat in chromosome18q.
(F) HEK293 cells were co‐transfected with GFP or GFP‐GABARAP along with either wild‐type HA‐ULK1 or the DFP mutant. GFP and GFP‐GABARAP were immobilized on GFP‐Trap resin and HA‐ULK1 binding was analysed by western blotting. Figure source data can be found with the Supplementary data.
Infarct volume of animals injected with MTMyc or MTFL457 expressed as a percentage of the hemisphere volume. Means ± SEM are given. Differences were analyzed by Student's t-test (***p = 0.00008; n = 14). Results for MTFL457 are also expressed as percentage of the infarct volume in animals injected with MTMyc.
A Time course expression profiles of CASPLs in response to Pst DC3000 (AvrRpm1) treatment. Analysis was based on the Genevestigator database (http://www.genevestigator.ethz.ch/). The darker color corresponds to stronger expression. ND, not determined.
RAD21 and EMT-related molecules in parent MDA-MB-453 breast cancer cells (P) and the corresponding CSLCs (indicated by CSC or CSLC) sorted according to the CD44+ cancer stem cell markers were observed by (B) Western blot analysis. Data are presented as the mean ± S.D. for three independent experiments. *P < 0.01. Statistical significance was validated by Student's t-tests.
(B) HeLa cells expressing mycBioID alone and HA-Parkin were used to confirm the specificity of the Tollip-Parkin interaction.
(A-B) Human fibroblasts (BJ) were treated with vehicle (water for 8 times 24 hours) or abemaciclib (1 μM for 8 times 24 hours). The population doubling over the 8 days treatment is plotted (A). 1 or 8 dpt, cells were incubated with EdU for 20 hours and stained and quantified (n=9 samples from 3 independent experiments; scale bar, 150 μm) (B). Data information: Data are means ±SD. Unpaired student t-test *p<0.05, **p<0.01, ***p<0.001. dpt, days post treatment.
(D-E) Representative MA currents recorded at -60 mV in large DRG neurons in response to repetitive mechanical stimulation with a blunt glass probe displaced 2-6 µm in 0.4 µm increments every 15 s (step protocol) before (black) and after (red) exposure to 25 µM Baclofen. Not every trace is shown for clarity. Inset above the current traces show the mechanical step protocol indicating the displacement of the mechanical probe.
B. Ectoderm differentiation of the 3KI mESC line (marked by the expression of Sox1::GFP). C. Mesendoderm differentiation of the 3KI mESC line (marked by the expression of T::3xTagBFP).
E. Quantification of mTREM2 expression levels in lysates of cultured human macrophages isolated from GRN-FTLD patients (data shown in D). mTREM2 levels were normalized to HC (n=4). Data points indicate individual patients. Data information: Data represent mean ± SEM. For statistical analysis of patient samples in comparison to HC, the unpaired, two-tailed student`s t-test was performed. Statistical significance was set at *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001; ns, not significant
B. Association of Rif1-∆C594 at replication origins is enhanced in HU block. ChIP enrichment of Rif1 and Rif1-∆C594 around early origin ARS1426 (left) and late origin ARS1412 (right)
Spearman correlation between tissue APA differences and APA variability between replicates in each tissue pair.
H Quantification analysis of changes in histone Kcr at Mir-203 proximal regions by ChIP-qPCR among different groups of NSPCs. The amplified genomic regions of two pairs of primers (P1 and P2) are shown in (G). Data are presented as mean ± SEM of three independent biological replicates, n = 3. Two-tailed unpaired Student's t-test was used to analyze statistical significance; P < 0.05, P < 0.01.
Same as (E) with amiRhen1-14 scions and non-transgenic WT or hen1-14 rootstocks. Average relative U6-normalized band-intensity quantifications from two biological replicates are indicated.
(E) Representative cells showing release of H4-EGFP and H3.1-EGFP. Scale bar represents 5 μm
A: Immunohistochemistry analysis recapitulates the biochemistry described in vitro for mithramycin. G401 tumor sections at 20X magnification stained with H&E, cleaved caspase 3 (CC3; apoptosis) or H3K27me3. A marked increase in CC3 that correlates with H3K27me3 staining is seen only in mice treated with the continuous infusion schedule but not vehicle. Scale bar (lower left): 50μm.
(g-i) Atg8 was co-incubated with the indicated Atg19 domains at 40 μM and run on a size exclusion column. Individual elution profiles are shown above; Coomassie stained SDS-PAGE gels below. Columns: (a-f,i) S200 3.2/30; (g,h) S75 3.2/30. M: size marker. All experiments shown have been carried out twice.
(C) Average barbed end growth velocities of actin polymerization on WAVE1-immobilized surfaces. At least 40 filaments were analyzed per condition.
F, G Effects of the mutation, K277R, on the interaction of FXR with the p65 subunit of NF‐κB (F) or SMRT (G) detected by CoIP.
Analysis of brain mRNA expression of 4.5-month-old mice (5 wild type 4 Tmem106b-/- mice) detected by the Neuroinflammation panel by NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for in all volcano plots. Gliosis related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (A) Comparison of differentially expressed mRNA of Tmem106b-/- mice in comparison to wild type mice. From 622 detected genes 21 are significantly upregulated, while 12 are significantly reduced.
Immunostaining of phospho-cMet in non-regressed tumours carrying or not the amplification in chromosome 6. Yellow numbers indicate the total number of cMet positive cells/total number of cells counted. Scale bar 100 µm.
(B) ChIP assays for HIF1α and its binding motif. Antibodies anti-IgG and anti- HIF1α were used in the ChIP assays. qRT-PCR was performed to quantify the binding activity. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For B , statistical significance was assessed with a two-tailed unpaired Student's t-test. *P<0.05 and **P<0.01. n.s. = not significant.
(D) Time traces of mean YFP fluorescence per cell. Each trace represents a single cell lineage's response to 1 µg/ml lysozyme. (109 traces from two independent experiments). Lysozyme added at the black dashed line.
Tfeb expression in the vasculature (mice n=10). Representative images of glomerular, arterial (scale bars: 10 µm) and interstitial vessels (scale bar: 50 µm) of kidney (p17) of Tfeb-EGFP mice stained with anti-CD31 (B) and anti-GFP
Frequency of colonies appearing at day 8 and day 12 from HSCs co-cultured with HO-1+/+ or HO-1-/- MSCs. *p< 0.05, ***p<0.001, Fisher exact test.
(L and M) BALB/c mice (n = 3 mice per group) were injected with 5x105 4T1 cells from WT or Il-17rbDel clone via tail-vein. Lung colonization was examined by lung morphology (L) and the numbers of tumor nodule (M) on day 21. Scale bar: 1 cm.
8-week-old male C57BL/6J mice were administered with AAV-GFP or AAV -Klf10 through tail vein injection, and then kept on WD/CCl4 for 12 weeks. n=5 per group. (B) Protein levels of KLF10 in the livers (left) and its expression was normalized to the β-actin (right). Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test
F. Fat body specific knockdown of ERK7 by RNAi (BDSC 56939) leads to an increase in larval weight at 72h AED (F, N=5 replicates of 15 larvae/replicate for each genotype).
(A) Overview of a cluster of MERS-CoV-induced membrane modifications in Huh7 cells prepared as described in Fig. 4. Some DMSs are boxed in orange while regions with CM are encircled in blue. In comparison with the densely-labelled surrounding DMVs, these regions are relatively devoid of autoradiography signal.
a, Quantification of ATG16L1 mean fluorescence intensity by image-based flow cytometry of 10,000 cells, n = 4 (wild-type, WT), 5 (T300A). Data represent 3 independent experiments. b, Quantification of caspase 3 activity upon glucose starvation of 2 × 104 cells, n = 5. Data represent 2 independent experiments. c, Quantification of mean LC3-II area of samples in a. Data represent 3 independent experiments.
G-J Double immunolabeling of PDS5B (green) and kinetochores (ACA, red), and staining of the chromatin (DAPI) in a metaphase II spermatocyte.
H. Scatter plot histogram analysis of the remyelination index in cerebellar explants at 6dpl after LPC exposure cultured in absence or in presence of 100 μΜ D-Asp. Data were normalized to vehicle control Data information: The values represent the means ± S.E.M. Level of significance was determined by using ); H, one-way ANOVA P<0.001 followed by Bonferroni post hoc test, *P<0.05 versus controls, ˄P< 0.05 versus LPC (n=4 animals, 3-4 slices per group)
(A) HeLa cells co-transfected with indicated HA tagged enzymes (GCS, LCS, GM3S and Gb3S) and GRASP55-GFP were lysed, immunoprecipitated with anti-GFP antibody or control IgG and were analysed by western blotting for interaction by immunoblotting (IB) with anti-HA antibody. I represents 5% on the input lysate, U 5% of the unbound fraction and IP the immunoprecipitate. Red asterisks indicate IgG bands and arrow heads indicates the expected position of HA-tagged enzymes
Survival probabilities of in which CheY was found to interact with FliM. Black line, a bi-exponential fit; dashed line, a fit of the fast decline process G, phosphorylated and acetylated CheY(I95V)-Atto647 (presence of acetate, 50 mM, pH 7.0; ΔcheZ background, strain EW669). 40 cells were recorded with a total of 2660 trajectories.
B MEFs/HA-Atg14 cells were infected with S. pneumoniae TIGR4 WT or ΔcbpC for 1, 2, or 3 h in the presence or absence of Bafilomycin A1 (BafA1). The lysates were subjected to SDS-PAGE and analyzed by immunoblotting with the indicated antibodies.
C) ykt6ts pho8∆60 cells containing an empty plasmid, 3HA-Ykt6 or 3HA-tagged Ykt6 mutant variants as indicated were analyzed as in A).
(E) 2 x 106 Control or ZEB1-shRNA A375 cells were injected subcutaneously into nude mice. The mean tumor volume for 5 mice is represented (± SEM). (Student's t-test).
(A) In vitro translation of a luciferase mRNA with or without of 0.5 μM (PR)20 and in the presence of increasing amounts of a 646 nt non-coding RNA (n=3). Data represent mean values ± SEM.
pat1 mutants have a serrated leaf, semi‐dwarf phenotypePlants photographed at 4 weeks of growth in short day conditions, genotypes as indicated. Col‐0 and eds1‐2 plants and pat1‐1 and pat1‐1/eds1‐2, respectively, were placed in the middle of the same pots before the pictures were taken.
C Heat map of the N protein HCIPs identified by SFB-tandem affinity purification. N protein HCIPs were compared among seven human coronaviruses using the preys' spectral counts. Three areas of the heat map are manually selected, enlarged and labeled as (1), (2), and (3), which are enriched by all N proteins of the seven human coronaviruses. Functional characterization for each protein is shown with the red circles below the enlarged images.
B. Change of RNA2/RNA1 ratios after carotid artery injection.The area around the arcuate nucleus was microdissected at the times indicated post injection. The ration of RNA1/RNA2 was determined using real-time PCR. Changes became apparent statistically significant after 4 and 8 hrs ( 2 hrs: p=0.3; 4 hrs: p=0.003, 8 hrs: p=0.0006, n=5)
(K) Kinetics of phosphorylation. Raw 264.7 cells were treated with cGAMP for the indicated time. Cell lysates were subjected to Western blot using the indicated antibodies.
A The model is represented as a process diagram and reactions are modulated by enzyme catalysis (circle-headed lines) or inhibition (bar-headed lines). Prefix 'p' represents phosphorylated species. Bold framed species were experimentally measured. White capsules represent inhibitors. Binding of the ligand Epo to its cognate receptor results in the phosphorylation of EpoR. Receptor and associated complexes are depicted in yellow, the AKT pathway is red, the ERK pathway is blue, and cell cycle genes and the S6 network is shown in green.
A, B. Identification of mitochondrial ribosomal proteins and pseudouridine synthase interacting proteins by sucrose gradient centrifugation in cells treated with siRNA (B). Individual fractions were separated by SDS-PAGE and immunoblotted with the indicated antibodies. The migration of the mt-SSU (28S), the mt-LSU (39S) and the mitochondrial monosome (55S) are shown.
(D) Endogenous transcript analysis by RT-qPCR in the mutants. The bars represent fold gene expression ratio of coding and divergent transcript normalized to the expression of the reference gene, UBC6.
Images from fixed GFP-Rab34 transfected cells showing contacts between GFP-Rab34 positive peri-nuclear membranes and lysosomes.(b) A projection of 4 planes from a structured illumination microscopy super-resolution Z-stack of the same cells.