EMBO/sd-character-level-ner huggingface dataset:
C. Upon completion of the chronic feeding study, an insulin tolerance test was performed on mice with single treatment of 0.75 U/kg insulin (n = 4 per group). * P = 0.0246 and * P = 0.0305 using unpaired 2-tailed Student's t tests.
A, B, C, D, E The effect of the individual and the combination of two TFs on the expression of target genes ERF11 (A) The relative luminescence was calculated relative to the control, 35S::GUS (n = 4 biological repeats). Green represents activation, red repression and gray absence of regulation. Data information: Data are presented as mean ± SEM, n = 3 independent experiments.
Q, Representative image of hearts from 7 dpi tcf21:nucGFP transgenic fish treated by PBS liposome, Clodronate liposome and Dex, respectively. The red boxes mark the peripheral area, and the white boxes mark the injury area and are shown in their respective zoom-in images to the right.. White dashed lines indicate approximate resection plane.
A) Superposition of the 20 lowest energy solution structures of the NDP52 domain
(D) BI‐1 WT MEFs were stably transduced with lentiviral expression vectors to deliver an shRNA against bi‐1 mRNA or control mRNA (luciferase shRNA). Cell survival was measured after treatment of cells as described in (B). Mean and standard deviation of an experiment made by triplicate, representative of two independent experiments.
Schematic diagram describing the generation of mixed bone marrow chimeras. Lineage-depleted bone marrow of B cell-deficient JHT Prdm1+/+ mice was mixed at ratio of 1:15 with lineage-depleted bone marrow of T-cell deficient Eβ-/- Prdm1ihCd2/+ or control Eβ-/- Prdm1+/+ mice prior to injection into lethally irradiated Rag2-/- recipient mice and subsequent analysis 4 months after transplantation
B) Cells generated in (A) were differentiated using PMA and transfected with a control siRNA (siCtrl) or an ADAR1-targeting siRNA (siADAR1). The type I IFN response was monitored 56h post-transfection by RT-qPCR analysis to determine IFN-β and IFIT1 transcript expression, normalized to a housekeeping gene (ACTB). ADAR1 knockdown efficiency was monitored by ADAR1 p110 expression, normalized to ACTB and displayed relative to siCtrl. Data are means ± s.d. from a representative of three biological replicate experiments.
A) Michaelis-Menten kinetic parameters of purified PP2A-B56α and PP2A-B55α holoenzymes were determined against the indicated phospho-peptides. Mean and standard deviation shown in plots as black bars (n=3 independent experiments)
(C) Western blot analysis of EVs isolated by UC from HCT116 cells cultured in glutamine-replete and -depleted medium for 24 h, following transduction with a Rab11a or control non-targeting (NT) shRNA knockdown construct over previous two days. Bar chart shows change in putative exosome proteins in EVs secreted from Rab11a knockdown cells relative to NT-treated cells in glutamine-depleted conditions, following initial normalisation to cell lysate protein. (C') Growth curves are for HCT116 recipient cells pre-treated with EVs isolated as in (C) or with vehicle (PBS). ****P colour denotes significant increase relative to EVs from glutamine-replete cells (black) and Rab11a knockdown cells (red).
C Detection of the C-circles co-immunoprecipitated with Ada2-Myc in type II survivors. The DNA co-immunoprecipitated with Ada2-Myc was amplified by RCA, loaded on a dot blot and detected with a telomeric TG1-3 probe. The numbers above the blot refer to clones in (A) and correspond to type II survivors produced in independent cultures. The lower panel shows the efficiency of Ada2-Myc IP analyzed by western blot with anti-Myc antibody.
D Tumor growth curves alongside images of dissected tumors collected on day 28. Note the partial inhibition of growth in CDDP and CDDP+PFT- α-treated mice.H Tumor growth curves alongside images of dissected tumors collected on day 35. Note the complete disappearance of tumors at day 35 and the significantly reduced tumor regrowth up to day 70 in CDDP+PFT- α-treated mice.
MRE11 degradation analysis. 5' Cy3-labeled substrates (80 nM) were pre-incubated with indicated concentrations of CST wild-type (i) or ∆700N mutant variant (ii) at 37°C for 5 min. Reactions were completed by adding MRE11 (200 nM) for an additional 20 min incubation and then stopped by SDS and proteinase K. Samples were resolved in 27% denatured polyacrylamide gel. The results are graphed and error bars represent the standard deviation (± SD) calculated from at least three independent experiments.
Figure 8, A role for CD22 dynamics and organization in restraining BCR signaling in naïve B cells.(A) In the steady-state, CD22 dynamics and nanoclustering are regulated by CD45. Sialylated CD45 works as a spacer between mobile molecules of CD22 displaying high amount of sialic acid. This organization limits the extent of active CD22 (red tails, side view) and restrains the proximity of CD22 to the BCR (long arrow, side view). This equilibrium allows a low level of basal signalling required for B cell survival.(B) When CD45 is absent, the tendency of CD22 to form self-interactions via sialic-acid binding increases together with CD22 nanocluster size and inhibitory activity. Bigger clusters of hyperactive CD22, no longer trapped by CD45, can access the BCR more easily (short arrow, side view) restraining the signalling.(C) The inability of CD22 to bind the sialic acid (Cd22R130E) on either CD45 or neighboring CD22 molecules decreases the size of CD22 nanoclusters with a concomitant increase of CD22 lateral mobility (dashed arrows, side view and top view) and phosphorylation. In this situation CD22 is able to explore larger area and access more BCRs (short arrow, side view) thus leading to a higher signal inhibition.
C. All primary colonization and secondary challenge pairs were tested with 3 NTBF and 2 ETBF strains. Stable colonization of the secondary challenge strain significantly above the limit of detection is denoted as a '+' while non-significance is denoted as a '−' (n=4 mice per group). The diagonal gray bar indicates self secondary challenge, the horizontal red bars show strains that provide broad colonization resistance against non-self strains and the vertical dashed box indicates a strain that has an enhanced secondary colonization phenotype.
(G) Micrographs of transmission electron microscopy imaged extracellular vesicles (EVs) isolated from sham treated (upper row) and GW4869 treated animals (lower row). (G'' and G''') are magnifications of boxed areas in overview images to the left. (H) Dot plot depicting miR-204 levels in the CSF isolated 2 h after the ventricular injection of GW4869 inhibitor.
A) Schematic illustration of iAID-conditioned Cdc55 depletion system: Cdc55 is fused with an AID (Auxin-inducible degron) tag rendering the protein sensitive to auxin (Morawska and Ulrich, 2013; Nishimura et al., 2009). Expression of AID-Cdc55 is controlled by a TetOff promoter and is repressed in the presence of doxycycline. Upon addition of auxin Cdc55 is rapidly depleted.
Mean ± SEM SM levels, expressed as percentage of vehicle values, in cerebellar extracts from WT and ASM-KO mice after two months of vehicle or PF treatment (***PWTVeh Vs KO Veh <0.0001, *PKO Veh Vs KO PF = 0.0465), n = 4 mice per group, one - way ANOVA, Bonferroni post hoc).
(A) The consequence of miR-155 and miR-181b mimics on cell viability, 5 days post transfection, relative to a negative control miRNA mimic is shown across a panel of normal and ovarian cancer cell lines as indicated. Each data point is the mean of n=3/cell line. In the screen, miR-155 was found to reduce cell viability (Z-score < -2) in one cell line, and TCGA expression data revealed no significant change in expression of this miRNA in ovarian tumors. miR-181 was found to reduce viability (Z-score < -2) in 2 cell lines, and TCGA expression data revealed no significant change in expression of this miRNA in ovarian tumors. N, normal cell lines (IHH, HOSE, HBEC3, HBEC13, HBEC30, and HBEC34), EOC, epithelial ovarian cancer cell lines. miR-155 data points for each cell line are shown in black while miR-181b data points are displayed in red.
Percentage of acceptor neurons containing α-syn puncta for each of the indicated treatments.
(B) Serum from WT and Tg rats (n = 6) were collected. MiR-483-3p and -5p associated with CD144 were enriched by immunoprecipitation with anti-CD144. Levels of miR-483-3p/-5p were measured by qPCR. Data information: Values are expressed as mean ± SEM.
E. HeLa cells were infected with lentiviruses expressing control shRNA, lncRNA-MIF shRNA-1, -2 or -3. Forty-eight hours after infection, total RNA was subjected to real-time RT-PCR analysis. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).
(C) Plot from flow cytometry analysis of CD38+ and Egr2+ macrophages in forepaw skin from 10-wk-old WT and RDEB mice. (D) Bar graph of flow cytometry analyses as in C of inflammatory macrophages (CD38+Egr2-) or tissue-repair macrophages (CD38-Egr2+) macrophages in forepaw skin of newborn, 4-wk-old and 10-wk-old WT and RDEB mice. Plotted as fold increase compared to mean of age-matched WT paws; replicates per age; n = 5-6 (CD38+Egr2-); n = 4-5 (CD38-Egr2+). ( Data information: Individual data points, mean ± S.E.M are shown. The data were analyzed by one-way ANOVA with Tukey's correction P values < 0.05 are considered significant.
Figure 4 - Oligomerization interfaces.A Cartoon illustrating the arrangement of the two layers of the yNap1c2-H2A-H2B oligomer.B A ribbon view of the protomers B and C comprising the IF1 interface.C Close-up view of interactions in the IF1 oligomerization interface.D Ribbon view of protomers A and A' comprising the inter-layer oligomerization interface IF2.E Close-up view of interactions in the IF2 interface.F Crystal packing interactions. To illustrate packing, the two layers were moved apart. Packing of the two layers in the crystallographic asymmetric unit is stabilized by two inter-layer IF2 interfaces (indicated by two arrows facing each other) between protomers A-A' and B-B'. The IF2 interface between protomers C provides for packing to the neighboring unit cells. H2A is colored in red, H2B in blue and yNap1 in green and yellow. See also Fig EV3.
(B) Brightfield image of the retinal explant showing the macula (yellow pigmented) with the approximate location of the multi-electrode array chip indicated.
(A) The indicated strains were infected with SPP1 (10-6 PFU/ml), spread over MB plates, and plaque diameter was monitored after 20 hrs of incubation. Shown is average plaque diameter and SD for each strain (n ≥ 54).
(C) Phosphorylation at Serine 1176 of eNOS was reduced in the aortas of mice lacking EC cilia. Aortas from control and mutant mice were stained for eNOS, p-eNOS-S1176, acetylated α-Tubulin, and Hoechst to label DNA.
(A,B) (A) Transient expression of PAP8NLSm5-GFP mutated in the NLS as described in Fig. EV4A. The circle marks the position of the nucleus (N) as observed with DIC in (B); yellow arrowheads show stromules (str). Scale bars equal 20 µm.
Control or Myc-CSAG2 expressing HCT116 p53 -/- cells were treated with the indicated concentrations of doxorubicin (J) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).
A Mechanism of the nucleophilic substitution reaction between BrEtY and Cys. The product is a thioether, which is stable in reducing SDS-PAGE.
(E) Depletion of TMEM59 reduces recovery of SA from infected cells. HeLa cells were transfected with the indicated siRNAs, infected with SA 96 h later (5 h, moi=0.1) and lysed for CFU evaluation. The experiment was carried out three independent times. The graph displays average CFU counts obtained for the 10−1 dilution of the relevant extracts, ±s.d. of the three data sets. Asterisks indicate significant differences (P<0.01, paired Student's t‐test).
E. NHBE cells from five donors were infected with GFP-expressing SARS-CoV-2. Infection of cells was monitored microscopically as green fluorescence through live-cell imaging at 72 hours post-infection (hpi) and is shown as the mean of the GFP-positive area relative to the whole area covered by cells in the same well. NHBE cells were were treated in (E) with the indicated drugs 4 hours after infection. Data are normalized to the DMSO control (N = 5). Two-sided independent Student's t-test with Benjamini-Hochberg FDR correction. Data information: Data are represented as means ± 95% CI from at least five/ten biological replicates *p < 0.05, **p < 0.01, ***p < 0.001.
Huh7.5 cells were transfected with the control vector or the Flag-tagged Rubicon expression plasmid for 24 hours followed by infection with HCV. (C) RFP and GFP puncta in cells with the over-expression of Rubicon at different time points after HCV infection. Merged images are shown to the right. (D) Percentages of RFP puncta that were also positive for GFP in Huh7.5 cells transfected with either the control vector or the Rubicon expression plasmid. The results represent the average of >50 cells.
Scatter plots showing correlation between RNA-seq (transcription) and Ribo-seq (translation; log2) in proliferating and senescent IMR90. Pearson's correlation values (ρ) and the number of genes in each plot (N) are also shown.   As in panel F, but correlating RNA-seq and whole-cell proteome changes.
(f) ACE2-protease co-expression analysis for the 20 most significant human proteases in AT2 cells. Significance (dot size, -log10(adjusted P value)) and effect size (color) for co-expression of ACE2 with different proteases (columns) across cell types (rows).
B LINC00941 knockdown on day 3 in calcium-induced keratinocyte differentiation cultures results in increased expression of SPRR5 (FC = fold change) (n = 3 biological replicates/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).
Double-immunolabeling of Sororin (green) and SYCP3 (red), and counterstaining of the chromatin with DAPI (blue) on spread Sgo2-/- spermatocytes at (A) pachytene (Pac.), (B) diplotene (Dip.), (C) metaphase I (M I), and (D) metaphase II-like (M II-like). The sex bivalent (XY) is indicated. Arrowheads indicate round bodies. Arrows in (A) indicate the pseudoautomal region in the sex bivalent, and the centriolar area at cell poles in (C,D). Scale bar: 10 µm.
A No differences of Vdac1/VDAC1 expression between MEF cell lines (replicates/condition n = 3 and independent experiments n = 2). The graph shows fold change expression (mean ± SEM) in Tsc2-deficient relative to wild-type MEFs.
(H,I) MFI levels of pSTAT3 in TAM-MG (CD45+ P2RY12+ CD49d-) (H) and p-NF-κB (p-P65) in TAM-BMDM (CD45+ P2RY12- CD49d+) (I) from Rheb1fl/fl (fl/fl, blue, n=4) and Cx3cr1-Rheb1Δ/Δ (Δ/Δ, red, n=5) GL261 tumours. Representative FACS plots are displayed for each cell type (mean ±SEM, Two-Way ANOVA Tukey test).
Detection of pS357-PDI in HepG2 cells treated with 2.5 μg/ml Tm (F) for indicated times.
(G) miR-10b overexpression does not increase mammosphere formation in PTEN-depleted cells. MCF-7-miR-Scr-OE cells (left panels) and MCF-7-miR-10b-OE (right panels) were transfected with a Dicer-substrate RNA directed toward PTEN, and after 24 h, quantitative RT-PCR assays for PTEN, SOX2, OCT4, SNAIL and Vimentin were performed. Additionally, the same cells were analyzed for mammosphere formation. The graph shows the mean and standard error of the relative increase of each marker or number of mammospheres in PTEN-depleted cells (black bars) and in cells transfected with a scrambled control (white bars) in three independent biological experiments performed by triplicate.
LC3 (C), colocalization with M.tb were analyzed. Data shown are representative of three independent infections. The results are the mean ± SD of three independent experiments. n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).
C, HCT116 cells were transfected with either a NT siRNA or a siRNA against RPL11 for 24 hrs and were pretreated for 30 mins in the absence (-) or the presence (+) of the combination of 10 µM of the ATR inhibitor VE-821 (ATRi) and 10 µM the ATM inhibitor KU-55933 (ATMi), followed by addition of the vehicle alone (-) or MPA 10 µM for additional 24 hrs. The levels of p53 were analyzed on Western blots. GAPDH was used as a loading control. Quantification of band intensity of p53 of at least two independent experiments is shown (right panel). Data information: All data are presented as Mean ± SD, relative to control. *p<0.05, **p<0.01, ***p<0.001, by two tail T-Student's test.
RPE-specific overexpression of VEGF-A in VMD2Cre+/WTROSA-STOPfl/fl-VEGF-A164mice (VEGF-ARPEmice) results in CNV at sites of VEGF-A overexpression (Cre+ patches (white nuclei); red arrow), while Cre- areas with normal VEGF-A expression show no CNV (white arrow). Neovessels are CD31+ (red). VEGF-A-induced CNV lesions and RPE barrier breakdown in VMD2Cre+/WT ROSA-STOPfl/fl-VEGF-A164mice resemble those seen in VEGF-Ahypermice (B.-C., arrows; phalloidin staining in green). Scale bars 100 μm.
(I, J) Representative confocal micrographs and quantification of DQ-BSA and BSA in CTNSWT, CTNS-/-, and CTNSPatient cells, respectively (n = 7-14 quantified images). Scale bars are 20 µm.
C Immunolocalization of SIRT7 and ATPase in the kidneys of C57BL6 mice with metabolic acidosis (SIRT7, red; ATPase, green; DAPI, Blue). Scale bar: 20 μm. Controls of the specificity of antibodies using kidney of SIRT7-deficient mice are provided in Appendix Fig S4.
D. Ovaries were dissected, lysed and protein extracts analyzed by Western Blot using anti-Rpp30, anti- GFP or anti-tubulin antibodies. Orange arrows indicate overexpressed and endogenous Rpp30 signals. Genotypes are numbered as 1,2,3.
b, Interaction between Apg8 and Apg3. Lysates of Δapg3 cells expressing APG3 and/or Myc-APG8 from 2µ plasmids were immunoprecipitated with anti-Apg3 antibody, and immunoblotted with anti-Apg3 and anti-Myc antibody.
A. Schematic of WDTC1 knockdown-rescue lentiviral vector (top). 3T3-L1preadipocytes were lentivirally transduced to generate stable cells expressing a non-specific (NS) shRNA control, shWDTC1 targeting endogenous Wdtc1mRNA, or cells simultaneously expressing shWDTC1 and shRNA-resistant WDTC1; bottom, confirmation of knockdown and WDTC1 ectopic expression.
D) Venn diagrams showing the overlap between the genes showing significant up or downregulation in nuclear or cytoplasmic RNA levels in AC16 cells exposed to the different cold temperatures.
B) Representative zygotene-like Stag3 mutant univalents. Nuclear spreads were immunostained for SYCP3, ACA and: SYCE1, SYCE2 and TEX12. Filled arrowheads indicate SC assembly between sites of LSAEs. Bars, 1 μm
(I) K437R‐Beclin 1 mutant suppresses autophagosome formation. Beclin 1‐knockdown HeLa cells expressing WT‐Beclin 1 or K437R‐Beclin 1 were infected with lentivirus encoding GFP‐LC3, and stimulated with EBSS for 1 h in the presence or absence of 20 nM BafA1. GFP‐LC3 dots were visualized by confocal microscopy. Scale bar, 10 μm. Data are shown as means±s.d. **P0.01 and ***P0.001. All the above experiments were repeated for at least three times with similar results.Source data for this figure is available on the online supplementary information page.
C. The most downregulated genes in Kdm6apKO pancreas are shown ranked by q-value, and are almost invariably bound by HNF1A and down regulated in Hnf1aaKO pancreas, or known to be direct HNF1A-dependent target genes from other studies (red and purple, respectively).
Genotypes are indicated as WT for S100a4cre-/- x Fstl1flox+/flox+ mice and cfKO for S100a4cre+/- x Fstl1flox+/flox+. (C) Western blot analysis of Fstl1 protein expression in ischemic and sham-operated hearts at day 7 after the surgery. Quantified values of Fstl1 protein in WT and cfKO mouse hearts normalized by GAPDH band intensity are shown. Statistical analysis was performed by two-way ANOVA. Post Hoc test was performed by Tukey test. Error bars represent mean ± SEM (n=5 for each sham group and n=6 for each MI group).
c, Recombinant PCAF acetylates His6-BRD4 at lysine residue 332. Acetylated BRD4 was detected by anti-acetyl Lysine antibody. Data information: Each experiment was repeated at least three times.
(D) Top: Representative images of In situ PLA performed between BRCA2 and DDX5 antibodies in cells bearing BRCA2 (WT) or BRCA2-T207A (T207A), as indicated. Cells were fixed directly or 4h post-irradiation (6Gy). Single antibody controls in non-irradiated BRCA2 WT cells are shown. Scale bar indicates 10 µm. Bottom: Quantification of the number of PLA spots per nucleus. At least 750 cells were counted per condition from three independent experiments. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test and the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single PLA spot.
Heat map showing the correlations between expression levels of genes in the molecular signature of MPNSTs.
H,I: Close-up view of the hydrophobic pockets interacting with the 2nd residue (F207) (H) and the 9th residue (F214) (I) of the Phospho-FFAT of STARD3; residues of MOSPD2 constituting the pockets are indicated. Data information: Phosphorous, nitrogen, and oxygen atoms are colored in orange, blue, and red, respectively. Carbon atoms are shown in slate blue, grey and rose in the MSP domain, the classic FFAT motif, and the Phospho-FFAT motif, respectively. the protein surface is colored according to the YRB scheme, showing hydrophobic, negatively and positively charged atoms in yellow, red and blue, respectively; the other atoms are in white
D) Single cell trajectory reconstructed with monocle 2 on the NI dataset. The first panel shows the overlap of all clusters and subsequent panels show restricted number of clusters for which the RNA velocity analysis suggested a filiation.
B-D BSP amyloid aggregation in vitro is pH-dependent in 10 mM EDTA (B), protein concentration-dependent in 10 mM EDTA and at pH 4.5 (C) and strongly inhibited by millimolar Ca2+ at various protein concentrations (D).
E. mRNA levels of indicated proliferation and ISC markers in isolated crypts from wild-type (n=4) and Angptl2-/- (n=4) mice based on qRT-PCR analysis.
A. MITOL interacts with Parkin under CCCP treatment. HeLa cells or HeLa cells stably expressing HA-Parkin were transfected with the indicated vectors and treated with DMSO or CCCP (10 µM) for 4 h. Lysates of cells were subjected to an IP assay with anti-myc antibody and IB assay with the indicated antibodies.
I TEER value of Caco-2 cell monolayers incubated with or without OMVs (100 μg/mL) for 24 h was analyzed (n = 9 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001.
C, Cell viability of BT308NS, irradiated in the absence (5 Gy) or in the presence (5 Gy + JNJ) of the MET inhibitor JNJ38877605 (500 nM), and analyzed at the indicated time points. Vehicle: non-irradiated cells (fold vs. vehicle-treated cells at time 0, mock). *: t-test, p<0.01.
D) The LS‐TVN detectable in primary hepatocytes infected with UIS4‐mCherry‐expressing P. berghei also consists of elongated membrane clusters (yellow arrowhead), vesicles (white arrow) and tubules (yellow arrow). Infected cell 18 h post‐infection.
EAE was induced by immunization of naive B6 mice with MOG (35-55), and the mice were randomly divided into five groups. BMDCs transduced with either lentiviral vector encoding GFP and NLRC3 (LV-NLRC3) or only GFP (LV-Ctrl) were administered i.v. 4 times, once every 4 days, starting at day 10 after EAE induction. Recall proliferative to MOG (35-55) in splenocytes taken from DCs-treated mice 26 days after EAE induction.