EMBO/sd-character-level-ner huggingface dataset:
C In vitro RNA processing assay with nuage-nuclear fraction from testicular lysates of Miwi knockout (-/-), heterozygous (+/-), and slicer activity-deficient (-/ADH) mutants, and 5'-end radioactively labelled RNA targets corresponding to approximately one and two repeats of major and minor satellite sequences (see panel A for details). Transcripts corresponding to 162, 300, and 542 nt of the 18S rRNA sequence served as controls. Arrow indicates the cleavage products of In vitro transcribed sense major satellite RNAs after reactions.
H. Images of representative TH-Cre and TH-Cre;fl/fl striatal sections immunostained with the TH antibody. Scale bar = 1 mm.
Measurement of cytokines present in cell culture supernatants of T cells co-cultured with either tumor-derived neutrophils (T + Ne; n=3) or with tumor-derived monocytes (T + Mo; n=3). Cytokines with a log2 fold change >0.6 or <-0.4 were considered as differentially present in supernatants. Shown is a heatmap of scaled cytokines levels (z-score) differentially present in T + Ne compared to T + Mo. Adjusted p-values were calculated by moderated t-test (limma) and Benjamini post test and were <0.05 only for MMP9 and RELMβ. Supernatants of T cells alone (T only; n=2) served as internal control. T cells cultured with monocytes did not have differential presence of cytokines compared to T cells alone.
(J) Analysis of chromosome spreads after Smc3 or Cdca5 deletion and nocodazole treatment. Representative images from every category are shown; size bar, 10 µm; error bars denote s.e.m.; n > 500 per genotype.
Fold change of all RP transcripts (grey) in Th1 cells compared to naïve CD4+ T cells. Data taken from RNA sequencing experiments described in reference 24. Fold changes in IL-10 (red) and IFNγ (blue) indicated for comparison. The statistical significance of the observed up-regulation of RP transcripts in Th1 cells is determined by Chi-squared test.
Chart illustrates the changes of EphA2-pS897 and EphA2-pY588 by BI-D1870 alone and with cisplatin in mesothelial cells. Upon combination with 10 µM cisplatin for 72 h, 10 µM BI-D1870 decreased EphA2-pS897 and EphA2-pY588. See Appendix Fig S7J for immunoblot.
(H) Expression of the Ptprc (CD45) gene from exon 3 to exon 8, as determined by RNA-seq of Pax5Jak2/+ and Pax5+/- Cdkn2ab+/- B-ALL cells. The alternatively spliced exons 4 (A), 5 (B) and 6 (C) are indicated in orange in the respective exon-intron structure of the Ptprc gene. Ptprc transcripts of B220+ Pax5+/- Cdkn2ab+/- B-ALL cells contain all three exons, thus giving rise to expression of the CD45 isoform RABC (known as B220). In contrast, reads at exon 4 are barely detectable and reads at exon 6 are strongly reduced in the mRNA of Pax5Jak2/+ B-ALL cells, which likely gives rise to the CD45 isoforms RBC and RB
Representative pictures of double immunostaining with VEcad (red) and KLF4 (green) on diaphragm sections of mdx-Control and mdx-CriptoMy-LOF Data information: Nuclei were counterstained with DAPI (blue).
C Model prediction for the basal expression level of the dual specific phosphatase (DUSP). DUSP abundance ratio between BaF3-EpoR and mCFU-E cells was identified by the mathematical model. The solid line indicates the profile likelihood. The dashed red line indicates the threshold to assess point-wise 95% confidence interval. The asterisk indicates the optimal parameter value.
c, Fluorescence microscopy of HeLa cells infected with indicated Shigella mutant strains. Scale bar, 10 µm.
a, Maximal treadmill running distance for mice of indicated genotype. Data represent mean ± s.e.m. of 5 mice per group.
D: The cell lines were STLC-synchronised and mitotic cells (M) isolated by shake off. Asynchronous (AS) cells were included as a control. Cells were lysed and subjected to GFP TRAP immunoprecipitation (IP) and subsequent immunoblotting (IB) with the indicated antibodies. Data information: All blots are representative of at least 3 independent experiments.
3D organoids were generated from WT and mutant p53 cells expressing non-targeting control (NT) or Rab11-FIP1 shRNAs (sh1 and sh2). D. Percent of WT p53 and mutant organoids exhibiting a basaloid-like morphology (n>50 organoids generated from three different cell passages quantified). Bar graph represents mean diameter ± SEM. n.s. WT p53 non-targeting control vs Rab11-FIP1 shRNAs, *p=0.046 mutant p53 non-targeting control vs Rab11-FIP1 shRNA1, ***p=0.0002 mutant p53 non-targeting control vs Rab11-FIP1 shRNA2 (One-way Anova).
(C) ABR thresholds (10, 20, 40 kHz) in control and Dia1-/-mice at 5 weeks of age (dB SPL, mean SE). No hearing loss was observed in Dia1-/-mice (n = 8) compared with control mice (n = 4).
(A) Two-way unsupervised hierarchical cluster of Z-score distributions by Euclidian distance. Any miRNA mimic with a z-score ≤ -2 in at least one cell line was included. Seed sequences of each miRNA mimic are on the right. Bars correspond to arbitrary cluster boundaries. Seeds in red correspond to miRNAs with decreased expression in serous, clear cell, or endometrioid ovarian cancer relative to normal tissue (Iorio et al, 2007).
BDNF stimulation causes a decrease in the TRBP-Dicer interaction. Young cortical neurons were treated with BDNF or vehicle control and co-immunoprecipitations (co-IPs) were performed using 2μg control IgG or polyclonal anti-TRBP antibodies. Dicer binding in co-IP was normalized to inputs in each experiment (p=0.001, t-test type 2, n=3, error bars represent s.d.).
16-days old MCF10A spheroids grown in matrigel/collagen mix were stimulated for 24h with either macrophage-conditioned or control medium. Representative images of Ki67 positive nuclei of MCF10A cells. Spheroids stained for DNA (Hoechst 33342 in blue), F-actin (Phalloidin in red) and Ki67 (green).
E, F. HeLa cells were cotransfected with either miR-449a mimic or a negative control mimic, together with JAM-A-GFP fusion protein and GFP. Whole cell extracts were subjected to immunoblot analysis to detect GFP. GFP was used to normalize (norm.) by transfection efficiency as loading control. p = 0.001176 (JAM-A WT Neg. ctrol. vs. miR-449a mimic) (n = 9 independent wells, 4 independent transfections).
Quantification of the expression of the six key altered genes in cultured PDKN2 cells (passaged for 14 population doublings) vs. their respective original patient tumor samples using qPCR. For bar charts, data presented as means with error bars representing standard deviations (SDs).
(B) Sequence logos of all unique lysine acetylation sites after GNAT expression in E.coli. Uniprot E.coli protein sequences were used as background population (sequence logos were generated using iceLogo
(F) Left, representative images of 22Rv1-P cells in the transwell invasion assay. Right, statistic data of invasive ability of ESM1 expressing cells. Scale bar: 100 μm.
(J) The transfection efficacy of oecircFNTA WT and oecircFNTA Mut was tested by qRT-PCR.
[c] Summary of mean ± SEM cumulative SLE counts. The number of replicates was the same as in (b). At the recording endpoint, the total SLE count in Xrcc1Nes-Cre is significantly higher than both WT and Parp1-/- Xrcc1Nes-Cre (Kruskal-Wallis ANOVA, p < 0.0017, * indicates significance with Dunn's post-hoc comparisons).
A, B. The protein level of STAT1 was negatively correlated with METTL3 and METTL14 in human pMMR-MSI-L CRC colon tissue (r2=-3.2477 for METTL3, r2=-2.7491 for METTL14). Each dot represents one tumor tissue.
A volcano plot of proteins that showed significant up- or downregulation of pTyr levels (absolute fold change > 1.5, p < 0.05) in the whole brain of Ptprd-/- mice (P21). Note that IL1RAPL1 is the protein with the strongest decrease in pTyr levels. (n = 3 for WT and 3 for KO). See Dataset EV1, 'Phosphoscan Results' tab for a full list of significantly changed proteins.
B) Surface representation of the hRSV F structure stabilized in the prefusion conformation, as reported (McLellan et al., 2013a). One of the protomers is shown as a red ribbon. Antigenic site IV is magnified and colored as in (A) for the F-410 and F-411 chimeras.
(B,C) Quantification of the nuclear morphologies (B) or γH2AX-positive DNA damage foci (C) from different cancer lines, as indicated, treated continuously with palbociclib (1μM) for 0, 1, 2, or 3 weeks. Either 100 cells (nuclear morphology) or 50 cells (γH2AX) were scored per condition per experiment and bar graphs represent mean data + SEM from 3 experiments.
A. Lysates of HEK293T cells, transfected with empty control vector, myc-FBXO7 or myc-FBXO7 ΔF-box plasmids together with the FLAG-PSMA2 expression plasmid, were immunoblotted with the FLAG, myc or pan 14-3-3 antibody.
(d) Immunohistochemistry of brain tissue from individuals with grade III Huntington disease showed 4E-BP1 in intranuclear inclusions. No 4E-BP1-stained inclusions were seen in controls (data not shown). (
C Quantitation of signal intensities in B showing mSt-2xML1N colocalizing with LAMP1 (means ± s.d.; n > 100 cells from three independent experiments). **, P < 0.01; *, P < 0.05.
(B) Cartoon representation of the 7-bladed ROD β-propeller (indicated as blades 1-7) modelled with AF2. The positions of blade 2, blade 3, and an α-helical hairpin representing an insertion between strands β3c and β3d are indicated. The four strands of each blade are indicated as A-D, with A and D being the innermost and outermost strands. The circle represents the entry point of the farnesyl binding pocket.
(Q and R) SQST-1(del 26-181)::GFP is expressed at dramatically elevated levels and accumulates into a large number of aggregates in lgg-1 (Q) and epg-7 (R) mutants.
(A) Series of events in MPP-R and MPP-D (boxes with solid and dashed outline, respectively) preceding the outbreak in MPP-R. The encounter between MPP-R and MPP-D workers which may have initiated the outbreak in MPP-R is shown in the grey box to the right. * quarantine in MPP-D involved all positive cases(n=94) as well as those among the 185 workers with negative test results who had been directly employed in meat processing. Negatively tested employees with other roles (e.g., administrative or security staff) were not quarantined.
Immunoprecipitation analysis of the endogenous clathrin interaction with LRP6 signalosome components in BCL9 MF-overexpressing mitotic cells.
(A) IF analysis of c-Rel and RelA/p65 in P6 WT and IκBα KO intestines. Scale bars in 25 μm.
(B-D) IL-1β and IL-18 protein levels measured in (B) spleen, (C) liver and (D) kidney homogenates from 6- to 9-day old indicated mice. Data information: Statistics in (B-D) were analyzed by student t-test (IL-18 graphs in B, C, D and IL-1β graph in D) or Mann-Whitney test (IL-1β graphs in B and C). Dots represent individual biological replicates. Error bars represent means ± SD. ns not significant; * p<0.05.
Comparison of mRNA levels of VEGF-C in the whole tissue of jejunum and ileum from WT and DTR mice (n = 5 mice/group).
Model calibration with the amount of molecules per cell of STAT1, STAT2, IRF9 and USP18 determined 24 hours after prestimulation with 0, 2.8 pM, 28 pM or 1400 pM IFNα. Calibrator proteins were spiked into 10 µg of total protein lysate and subjected to quantitative immunoblotting. Immunoblot detection was performed by chemiluminescence using a CCD-camera-based device. Averaged values (N=4) are displayed with standard deviations. Green squares indicate amounts estimated by the mathematical model.
A Semiquantitative RT-PCR of UPF1SL or UPF1LL transcript levels following transfection of HEK-293 cells with the indicated siRNAs.
(D) PBX1 is also present in TH+ adult mDA neurons of the substantia nigra (SN) and ventral tegmental area (VTA).
H&E staining of native rat lung tissue and decellularized scaffold showed the absence of nuclei following decellularization. Scale bar, 40 μm.
A. Phagocytic uptake of fluorescently-labelled latex beads by WT and Tpl2[D270A] (Tpl2D270/D270A) BMDMs. Intracellular fluorescence was monitored following uptake of AF488 latex beads by BMDMs, (n = 4 wells). Data information: One representative experiment out of three shown. Error bars and shaded areas represent SEM. **** P < 0.0001.
Mass spectrometry analysis of 6-keto-PGF1α, TXB2 and PGE2 content of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated for 3 h with 100 ng.ml-1 LPS. n = 6. Two-way ANOVA statistical analysis with Tukey's multiple comparison post-test was performed.
Interphase NPC insertion occurs via inside-out extrusion of the INM, followed by INM/ONM fission and fusion (Otsuka & Ellenberg, 2018). Nucleoporins are not depicted. The mature NPC, highlighting proteins examined in fat body cells. Green, cytosolic filaments; yellow, outer ring subcomplex; pale blue, inner ring subcomplex; brown, transmembrane nucleoporins; red, phenylalanine-glycine repeats (FG-Nups) that form the permeability barrier; white/blue, nuclear basket Nups.
Quantification of normalized MA Piezo2 currents in HEK293 cells transiently transfected with Piezo2+ GABAB1+ GABAB2 + GFP (A, n=12), treated with the PI3K inhibitor Wortmannin 50 nM (B, n=10) Cells were treated with wortmannin 30 min before the experiments, and were present throughout the measurements.
The average number of ILB4+ positive microglial cells over three fields of view per mouse of the hippocampus (C) and the cortex (D) were counted (n=4 mice per group, average of 3 fields of view per mouse). Data are expressed as mean ± STDEV and were tested by one-way ANOVA with Tukey's post-test; ***P<0.001. Symbols above bars are versus WT
C | Quantification of intracellular Ca2+ influx The median area under the curve of the Ca2+ influx kinetics was calculated, single dots represent data from individual mice, mean ±SD. Statistical significance was calculated by applying the Mann-Whitney-U test n. s. = not significant, ** p ≤ 0.01.
B) Single cell trajectory reconstructed with monocle 2 on the WI dataset. The panels show restricted number of clusters for which the RNA velocity analysis suggested a filiation.
(E-G) HeLa cells were transiently transfected with GRINA-Myc for 24 hr before fixing and staining. (E and F) GRINA-Myc colocalizes with both TGN46 and VPS35. In this example, GRINA-Myc expression (in the cell marked by an asterisk in E) reduced the cell's TGN46 expression compared to surrounding untransfected cells and caused enlargement of VPS35-positive endosomes. The area in (E) magnified in (F) is indicated by a dashed line. (G) GRINA-Myc expression also perturbs CIMPR localization. In this example, GRINA-Myc transfection (in the cell marked by an asterisk) caused CIMPR to localize to round vesicular structures positive for GRINA-Myc, some of which appeared larger than regular endosomes, whereas TGN46 staining was almost absent in the transfected cell.
(D) Schematic strategy of Npm1 conditional knockout. Excision of exons 1-6 from the Npm1 allele by Cre-recombinase produces an Npm1-knockout allele. Hypomorphic allele (top), NEO-free allele (middle, Flox) and excised allele are shown. The genomic sequence is depicted as a black line, with black boxes representing exons 1-11. Grey box, red triangles and arrows represent an Frt (blue)-flanked neomycin resistance cassette (NEO), the loxP site, and genotyping primers, respectively.
D Conditional overexpression of a dominant-negative DDmyc-PKArG321E-Ty that cannot bind cAMP leads a dramatic reduction in plaque formation while over-expression of DDmyc-PKArWT-Ty is well tolerated by the parasite.Scale bars = 3 mm (D)
C. TranDs from EAAT1WT (magenta) and EAAT1CRYST (orange) structures are overlapped using HP1 as reference.
F. Neutravidin precipitates (PD) from biotin-treated HeLa cells ectopically expressing GFP-TBC1D15 (GFP-1D15) together with BioID-SKIP or BioID-EV. Representative immunoblots against GFP, HA and VPS18 are shown, TL: total lysate. G. Quantification of GFP-TBC1D15 biotinylation by BioID-SKIP over BioID-EV in response to VPS18 depletion expressed as % of control (siC), n=4 independent experiments performed in HeLa or HEK293T cells. H. Quantification of VPS18 protein abundance from experiments in G, n=4.
B Effect of mycolactone on MM.1S BzR cell viability after 48 and 72 h of treatment, as measured by exposure of Annexin V and incorporation of PI. Data are Mean % of live, apoptotic and dead cells from technical duplicates, relative to total cells. Data information: , shown data are representative of 2 independent experiments with similar results.
(F) Bars represent mean blood lactate levels for 3-month and 15-month old male MCK-miR-499 and NTG mice following a 25 min run on a motorized treadmill. For 3-month blood lactate, NTG, n = 9; MCK-miR-499, n = 10. For 15-month blood lactate, NTG, n = 7; MCK-miR-499, n = 5. *p = 0.039 (3-month), *p = 0.018 (15-month).
(B) Intercentrosomal (centrosome-to-centrosome) linear signal profiles of β-catenin/Ect2 (upper panel) and β-catenin p-S60/Ect2 (lower panel) from the XY plane of the immunostained cells in (A). All immunofluorescence images and linear signal profiles show representative data of more than 50 telophase cells obtained from three independent experiments (A, B).
(E) CCM1 incompatibility probably occurred during the divergence between S. bayanus and the common ancestor of S. cerevisiae, S. paradoxus, S. mikatae and S. kudriavzevii. The endogenous CCM1 in S. cerevisiae was replaced with its orthologous alleles from other Saccharomyces sensu stricto yeasts. Only the strain carrying S. bayanus CCM1 displayed growth defects on glycerol-containing plates.
(H) Two-dimensional agarose gel analysis of telomeric DNA from HCT p53+/+ or or p53-/- treated with 50 µM etoposide for 24 hrs. Ethidium gel (top) and Southern blot probed with TelG probe (lower panel). Single stranded telomere DNA (red arrow) and recombination/ replication-associated structures (blue arrow) are indicated.
C. DNA methylation analysis in different mutant plants. Upper panel: heat map showing the methylation levels of IDM1 targeted hyper-DMRs in idap1-2, idap2-1, mbd7-1, idm1-1, and ros1-4 in three contexts. Light yellow indicates low methylation, and black indicates high methylation. Lower panel: box plots showing CG, CHG and CHH methylation levels at IDM1 targeted hyper-DMRs in the indicated mutants. Asterisks indicate significant differences between the wild-type and the indicated mutants (*p < 10-15, Mann-Whitney U test).
D) Aggregate Peak Analysis based on the K562 loops coordinates The heatmaps are centered on the loop positions +/- 250kb using 25kb resolution Hi-C data. There is a ~50% reduction of loop intensity as assessed by z-scores and log2 fold change.
(C, C') Amiloride incubation does not diminish Rpk expression. White arrowhead indicates approximate position of the A-P compartment boundary, yellow arrowhead indicates approximate position of the D-V compartment boundary.
D Backbone-RMSDs for AMSIN-1 and CBSIN-2, shown as a function of time (30 ns simulations). The box marks the time for extracting the snapshots from the trajectories (49.9-50 ns) in (E) and (H). A total of 11 snapshots were taken from an MD simulation.
Densitometry analysis of the abundance of the indicated proteins based on immunoblot images as shown in (A). Data are means of 10 (phospho-Rel and cleaved caspase 7), 9 (p52, caspase 8 and cleaved caspase 9), 7 (phosphorylated and total IκB) or 5 (cleaved caspase 3) independent experiments. Error bars are SEM. Statistical significance was assessed using the following tests: one-sample t-test (caspase 8, cleaved caspases 9, 7 and 3, total and phospho-IκBα) or Wilcoxon signed rank test (phospho-RelA and p52); *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.
(a) Immunofluorescent detection of endogenous LC3 (red) in liver sections from fed or starved Pld1 WT and KO mice. Sections were counterstained with DAPI. Scale bar, 5 μm. (b) Quantitative analysis of endogenous LC3 immunofluorescence in liver sections derived from fed or starved Pld1 WT and KO mice. Histograms show the average number, size and surface area of LC3-positive compartments. Values denote means±s.e.m. ((n=25-28), 4 mice per genotype). **P0.01.
C. Co-immunoprecipitation of GFP-DPR interacting proteins in cytoplasmic fraction using GFP-trap beads. Immunoprecipitants were served for immunoblot with anti-EXOSC10 antibody. The same membrane was reprobed with anti-GFP antibody. D. Quantification of the relative intensities of "EXOSC10 in co-IP fraction" / "EXOSC10 in input". E. Co-immunoprecipitation of GFP-DPR interacting proteins in nuclear fraction using GFP-trap beads followed by immunoblot using anti-EXOSC10 antibody. The same membrane was reprobed with anti-GFP antibody. F. Quantification of the relative intensities of "EXOSC10 in co-IP fraction" / "EXOSC10 in input".
F. Sequence alignment of proteins containing the PxVxL motif important for an interaction with HP1, with canonical residues shown in red.
C, D) Western blots (C) and quantification (D) of Mfn2 in spinal cord homogenates at disease end stage. Protein levels are normalized by β-actin. Results are expressed as mean ± SEM and as percent of Non Tg; n= 8 (4 males and 4 females) mice per group; No statistically significant differences were found between G93A and PKO/G93A (p=0.078 by paired Wilcoxon's test); ***p= 0.0007 by paired Friedman's test with Dunn's correction (for Non Tg vs. G93A) and *p= 0.037 by paired Friedman's test with Dunn's correction (for PKO vs. PKO/G93A). Parkin knockout increases the levels of Mfn2 in SOD1-G93A mice at disease end stage.
The tubular stress marker Lipocalin-2 (LCN2) is not expressed in early time points but increases in time course in late stages when fibrosis is more prominent, as seen on histological staining
(C) Representative immunoblots of selected kinases whose phosphorylation status was unaffected (PRKAA1, RPS6KB1, and acetyl-CoA carboxylase a [ACACA]) or affected by resveratrol or/and spermidine treatment (PTKB, AKT1, MAPK8, and CDKN1B), validating phosphoprotein array data.
CI-linked (I state 3 respiration in isolated heart, kidney and liver mitochondria (n=8/group) We used malate, pyruvate and glutamate to generate NADH for the cI Bar graphs represent mean±SD Statistics: one-way ANOVA followed by Tukey"s test. Significant differences between groups (p value) are indicated on g
(d) Beclin-1 Ser 14 is the main in vitro ULK1 phosphorylation site. Beclin-1 WT, and S4A and S14A mutants were subjected to an in vitro ULK1 kinase assay. The reaction was developed by autoradiography and stained for Beclin-1 input levels by Coomassie blue. Results are representative of two unique experiments.
Relative mRNA expression of ATGL in C2C12 cells transfected with Ago-183/96 and FoxO1 as indicated (n=5 per group for RT-PCR analysis).
Treatment of WT E. coli cells with sub-MIC concentration of Tmp (0.5μg/ml) leads to filamentation at 42°C when grown in amino acid supplemented medium. However, a recA knock-out strain under similar condition shows no elongation, indicating the role of SOS pathway in filamentation. A sulA knock-out continues to elongate, indicating the role of sulA-independent pathways. An E. coli strain deleted for the e14 prophage region however showed no filamentation upon Tmp treatment, indicating that sfiC gene in the e14 region might be one such sulA independent player. The central band in the box plots represents the median of the distribution, the box ends represent the 25th and 75th percentile, the whiskers represent the 10th and 90th percentile, while the dots represent the 5th and 95th percentile. Data was usually obtained from 2-3 biological replicates. The number of cells used to derive the boxplot distributions in the different panels range usually between 100 to 200 (please refer to Figure 3 source data for exact number of cells for each dataset).
(E) qRT-PCR analysis of Acta1 and Nppa in NRVMs. n=4. Data represent three independent experiments. Student's t test was used for statistical analysis.
(c-e) Neutral lipids in striatal cells from 7Q-htt and 111Q-httmice (c), grown on a monolayer of their own astrocytes
(B) High resolution imaging of the F-actin cortex, E-cadherin, and phospho-MyoII in a mitotically rounded follicle cell. Note maintenance of adherens junctions including both E-cad and the contractile actomyosin ring during mitotic rounding. Asterisks or pH3 staining indicate a single mitotic cell. Scale bar ~3µm. n > 4 independent biological replicates.