EMBO/sd-character-level-ner huggingface dataset:
(B) BMDMs were treated with PA (500 µM) and 4µ8c (100 µM) or vehicle for 9 hours. RNA lysates were analyzed by qRT-PCR for miR-2137 expression (n=3 biological replicates). (C) BMDM cells were treated with tunicamycin (Tun; 5 µg/ml) and 4µ8c (100 µM) or vehicle (DMSO) for 9 hours. RNA lysates were analyzed by qRT-PCR for miR-2137 expression (n=3 biological replicates).
(K) Western blot analysis for phospho-TBK1 (Ser172) in WT and MAVS-knockdown BMMs treated for 4 hr with EVs from uninfected or M.tb-infected macrophages. β-actin served as a loading control. Densitometry of the western blots for (K) are shown.
G. Uptake assay for fluorescent myelin in WT hiMGL. Phagocytosis of myelin significantly decreased upon treatment with TREM2 antagonistic antibodies Ab1 and Ab2 (n=4, biological replicates).
(E) unc‐104 mutant animals are more resistant to hypoxic death induced by sodium azide.
I H&E staining of interscapular BAT from mice in (A) at 10 weeks of HFD (cohort 1). Representative images from n=3 mice for both groups. Scale Bar, 50µm.
C The self-renewal of CSCs in the indicated stable cell lines was analysed using a tumorsphere-formation assay. The number of tumorsphere cells (> 100 μm in diameter) was counted after 3, 5, and 7 days. Data represent the mean ± s.d. (n = 3). P-value was calculated based on a two-tailed Student's t-test (ZR-75-30 and HCC-1419 cells) or ANOVA with a post-hoc LSD test (BT474 and HCC-1954 cells). cell line information was indicated as follows: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; R, trastuzumab-resistant; PR, trastuzumab-partial responsive; S, trastuzumab-sensitive.
(C) Semi-thin sections of P28 retinae revealed degeneration of photoreceptor cells in the outer nuclear layer and outer and inner segment of Clcn3unc/unc/Clcn4-/-, but not of Clcn3unc/unc or Clcn4-/- mice (scale bar: 50 µm). RPE, retinal pigment epithelium; OS, photoreceptor outer segments; IS, photoreceptor inner segments; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer.
c, Wild-type (squares) and Δapg12 (circles) were cultured in nitrogen-starvation medium and their viability was determined by phloxine B staining.
Low expression of LRRC8D but not LRRC8A correlates with shorter survival of high grade serous ovarian cancer patients treated with platinum‐based drugsA-DDifferential survival based on LRRC8A (A, C) or LRRC8D (B, D) gene expression as extracted from the TCGA database (http://cancergenome.nih.gov/) (A, B) or using the data from Patch et al (2015) (C, D). As cutoff the lower tertile of LRRC8A or LRRC8D gene expression was used. P‐values were determined using the log‐rank test.
(j) Cyclin D1 (black) and isolectinB4 (white) staining of P5 retinas from Pald1+/+ and Pald1-/-pups. Scale bar: 100 µm.
(A) All analyzed 318 siRNA target genes were categorized into phosphatase families and marked according to the ability of their corresponding siRNAs to regulate EGFP-LC3 accumulation. PIP, phosphatidylinositol phosphatase; PTP, phosphotyrosine phosphatase; DUSP, dual-specificity phosphatase; PPP, (Ser/Thr) phosphoprotein phosphatase.
F, G DNA repair-related proteins (ATR and XRCC4), DDX3, and actin were assessed by immunoblotting in A549 (F) and H1299 (G) cells. Cells were pretreated for 4 h with vehicle control or 6 μM RK-33 and then radiated with 0 or 5 Gy. Outlined boxes indicate spliced lanes.
(I) Wound area measurements in WT and Col1α1cKO mice. WT, N=7; Col1α1cKO, N=5 biological replicates. Data are from two independent experiments. Two-way ANOVA performed comparing WT and Col1α1cKO mice.
(A) Atg16L1 KO MEFs stably expressing either full‐length Atg16L1(1-588), Atg16L1(1-230) or Atg16L1Δ(230-300) were cultured in regular DMEM or starvation medium for 1 h. Cells were fixed and subjected to immunofluorescence microscopy using anti‐Atg16L1 antibody. Note that full‐length Atg16L1 and Atg16L1(1-230), but not Atg16L1Δ(230-300), showed punctate structures under starvation conditions (inset).
More young HO-1-/- LT-HSCs are in G1 and S/G2/M cell cycle phases. The presented cell cycle analysis is from two independent experiments. Young HO-1-/- MPPs do not differ in cell cycling from young HO-1+/+ MPPs. The presented cell cycle analysis is from two independent experiments. More old HO-1-/- LT-HSCs are in G1 phase in comparison to old HO-1+/+ LT-HSCs, but not in S/G2/M phase. The presented cell cycle analysis is from two independent experiments. Old MPPs do not differ in cell cycling between genotypes. The presented cell cycle analysis is from two independent experiments.
(b) STUB1 mRNA is downregulated at replicative senescence. The same set of cells as in a were examined by qRT-PCR. Data were from triplicate experiments (mean±s.d.). *P0.01; **P0.001 (Student's t-test).
(D) FACS analyses of p75 cell surface expression upon ZEB1 overexpression. Bar chart representing the mean percentage of p75-high, int, low and negative cells from 2 independent experiments (Fisher's exact test).
B) Representative images of Western-blots of immunoprecipitated fractions from S. cerevisiae extracts with Okp1-6×flag and Ctf19-4×myc; fl: Okp1_fl; cmΔ: Okp1 variant without the Ctf19-Mcm21 binding motif (Okp1_cmΔ); IP: immunoprecipitated samples. Protein G: beads coated with Protein G only (used as control); positions of molecular masses of standards are indicated; uncropped images are in Appendix Fig S8B,C.
Albumin-cre mice were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10 knockout mice (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice and KLF10flox/flox were treated with WD/CCl4 for 12 weeks. KLF10flox/flox mice were used as the control (Ctrl). n=5 per group. (A-B) Protein levels of KLF10, zDHHC7 and TNF-α (A), and their normalization to β-actin (B). Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test
A-C. 2ac clones established after transfection with an empty vector (empty) or plasmids expressing wild type Jmjd2c (2c wt) or a catalytic mutant (2c mut) were exposed to OHT as indicated and subsequently used for (A) WB.
Immunoblots showing the levels of CBF1-myc proteins after exposure to FR (H), R (I) or B (J) light. CBF1-myc seedlings were first grown at 22°C for 4 d in D, and then transferred to continuous FR, R or B light for the indicated time periods ranging from 1 h to 24 h. anti-HSP was used as a sample loading control. Numbers below the immunoblots indicate the relative band intensities of CBF1 or CBF1-myc normalized to those of loading control, respectively. The ratio of the first clear band was set to 100 for each blot.
(A) Gene expression analysis of PBMCs isolated from healthy individuals after infection or stimulation with Borrelia burgdorferi (Bor), MDP, or Pam3Cys (Pam). Heatmap shows log2 (fold change) relative to mock-treated control.
(C) Numbers of unambiguous unique differential O-glycosites identified with the two different approaches. The stacked bar graph differentiates between glycosites identified on peptides with single and multiple HexNAc/HexHexNAc modifications.
(G) Gefitinib did not block, but prolonged STING-EGFR interaction. Raw 264.7 cells were pre-treated with gefitinib or DMSO for 1 hour before cGAMP stimulation. Cell lysates were prepared at indicated time points, immuno-precipitated with anti-STING antibody and subjected to Western blot.
(A) Red1 signals disappeared at early in meiosis and then reappear in spores. Representative deconvolved images of a strain expressing both Red1‐tdTomato and CFP‐Mmi1 during meiosis are shown. DNA was stained with DAPI. Bars, 2 μm.
(E-G) Flow cytometric CD11b+Ly6C+Ly6G- monocyte quantifications in (E) spleen, (F) liver and (G) kidney from 6-day old indicated mice. Data information: Statistics were analyzed by student t-test , E, F, G Dots represent individual biological replicates. Error bars represent means ± SD. ns not significant; * p<0.05; ** p<0.01.
C Treg induction by CLys and CSN in presence of monocyte/non-monocyte fractions and naïve CD4+CD45RA+CD45RO- T cells.
Quantification of data shown in G. Anaphases were scored from 4 independent experiments (mock), or 3 independent experiments (remaining conditions). Anaphases were considered positive for UFB if there was PICH staining between DAPI bodies. Single knockdown conditions had >50 anaphases scored. Combined knockdown conditions had >88 anaphases scored. Values shown are mean±sd. Conditions were compared using one-way ANOVA followed by Dunnett's multiple comparison test. Quantification of data shown in G. Number of PICH stained UFBs counted per anaphase. Values shown are total counts over 3 independent experiments, shown mean±sem. Total number of anaphases per condition were as follows: Mock n=134, siBLM/siSLX4 n=90, siRAD54/siSLX4 n=96, siRAD54/siBLM/siSLX4 n=88. Conditions were compared using Kruskal-Wallis test followed by Dunn's multiple comparison test.
I-L. Hep2 (I), Huh-7 (J), MRC-5 (K), and undifferentiated HTBE (L) were treated and infected with VSV-GFP Data information: Total Integrated Green Fluorescent Intensities were determined using the Incucyte live-cell analysis system after 24h Data represent means and standard deviations from n=3 biological experiments (individual data points shown). Statistical significance was determined by 1-way ANOVA on log-transformed intensity values (*p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001). , dotted lines are a visual guide for maximum and minimum virus replication in control cells in the absence and presence of IFN-α2, respectively. Numbers above IFN-α2-treated bars indicate their approximate difference to the respective untreated conditions.
A, B Left, confocal images of LimE (top) and kymographs of cortical LimE (bottom) in single cells with PKBA (A) or RacGEF1ΔN (B) steadily recruited (scale bars, 10 μm). Right, color coded overlays of LimE in single cells.
C Phage production during a one‐step phage growth curve experiment with wild‐type (black) and BREX‐containing (red) strains of B. subtilis BEST7003 infected with Φ3T. Error bars represent SD. Y‐axis represents relative phage concentrations normalized to the value at the beginning of the infection.
B) 22G RNA coverage of the 21U sensor(RNAe) in the indicated genetic backgrounds.
(f-g) Average levels of (f) mRNA quantified by RNAseq (blue) or qRT-PCR (grey) or (g) protein quantified by mass spectrometry (dark green) or western blot (grey) for select p53 target genes under rising p53. Data information: n=2 biological replicates, error bars represent std dev.
(B) Growth curves of the AOXHA expressing cell lines and their corresponding EV controls. Cell growth was monitored every six hours after substituting the medium in two replicate 24-well plates, one plate with medium without uridine (Uridine-), and the second plate with medium supplemented with 50 µg/ml uridine (Uridine+). The graphs show the average confluence ± SD at each time point (n=6 wells per cell line).
(F) Areas below the curves calculated from the time of rapamycin addition for each of the three separate experiments (means ± S.E.M., n=3). One-way ANOVA with Dunnett's multiple comparisons was used for statistical analysis (* P = 0.0478 and 0.0287 for #20 and #26 clones, respectively).
Selection of enriched functional GO categories by DAVID analysis in differentially expressed genes between human sh-TFEB and scr-shRNA ECs. GO analyses were performed individually on down‐ or up‐regulated genes using DAVID tool (biological process). GO terms are ranked by P‐value corrected by Benjamini Hockberg method, and the number of genes is indicated.
(B) Early to late effects on progenitor and neuron behavior upon Nr2f1 deficiency. Early in development (E10.5-E12-5), Nr2f1 loss causes cell cycle acceleration, increased NP self-renewal and sustained Pax6 expression. Neurogenesis (as well as the expression of neurogenetic factors such as Tbr2 and P21) is delayed, thus allowing amplification of the progenitor pool and lateral expansion of the posterior hemispheres. At later stages (E13.5-E14.5), neurogenesis comes into play and neurons are produced at high rate. Persistent Pax6 expression in the expanded NP population leads to abundant basal RG production at late time points (E16.5-E18.5). High neuronal output results in radial expansion and generation of a thick posterior cortex.
G. Distribution of final patterns in cells of the indicated widths as indicates, and lengths of 9-10 μm.
(D-E) Transmission electron microscopy of indicated H1299 cells cultured in glucose starvation (Glu-) medium or hypoxia. The yellow asterisks mark mitochondria. The red arrows indicate autophagic structures. All quantitative data are presented as mean ± s.e.m. from 3 independent experiments; ***P < 0.001 compared to shNC treated with H2O2 or hypoxia (Mann-Whitney test); Scale bar, 1 μm.
F. SIRT7 associates with PRMT6 in vitro. Recombinant GST-PRMT6 were incubated with HEK293T lysates. After GST pulldown, the interaction of recombinant protein with endogenous SIRT7 was analyzed by western blot. The arrows indicate GST and GST-PRMT6 protein, respectively
A. Confocal microscopy images of live fibres derived from 3 to 4 month-old GFP-LC3:WT (top left), untreated GFP-LC3:GAA−/− (bottom left) or TFEB-treated GFP-LC3:GAA−/− (right) mice. All fibres were transfected with mCherry-LAMP1 to visualize lysosomes (red). The effects of TFEB are clearly visible - overall reduction in lysosomal size, appearance of normal size lysosomes (similar to those in the WT), and lysosomal docking to the plasma membrane (inset). Bar: 10 µm.
K,L, Immunostaining for Tbr2 (red) and Ngn1 (green) in control (K) and Gpr124KO (L) cortices. M-O, Quantification of neurogenic (Ngn1+) RGs and BPs (M), newborn BPs (N) or expanding (Tbr2- Ngn1-) RGs (O) in control and Gpr124ECcKO cortices (mean±SEM; N=4; * p<0.05, ** p<0.01). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm
G. Representative images of astrocytes labeled with Aldh1l1-EGFP reporter in cortex and OB of Daam2 cHet and cKO mice at postnatal day 28 (P28). Scale bar: 50 μm. H-K. Overall complexity of astrocytes with Aldh1l1-EGFP reporter was measured by Sholl analysis (Two-way ANOVA) and total process length (Student's t-test). Data is presented as mean ± SEM. n= 6-10 cells from N=3-5 mice per genotype, *p<0.05, p****<0.0001
(B) Fraction of cytosolic lncRNAs with experimental evidence for ribosomal binding with (red) or without (blue) an overlapping conserved short open reading frame.
(b) Immunoblot analysis of unprocessed and processed caspase-1 and IL-1β in lysates and supernatants of differentiated THP-1 cells treated as in a.
(D) Immunoblots showing endogenous NFATc1 pull-down by GST-SIRT7 in HEK293T cells.
(B) Alignment of the receptor binding motif of SARS-S with corresponding sequences of bat-associated betacoronavirus S proteins that are able or unable to use ACE2 as cellular receptor reveals that 2019-nCoV possesses amino acid residues crucial for ACE2 binding.
(D-F) Spine enrichment and puncta size and intensity of PSD-95 were comparable under basal conditions for WT, E17R, and T19K PSD-95 (A.U., arbitrary unit).
(A) Representative time-lapse image illustrating CTL rounding upon target engagement. Scale bar, 5 µm. (B) Quantification of CTL shape (roundness coefficient) in unconjugated and conjugated CTLs. A circular shape corresponds to an index of 1. Each dot represents one CTL. Bars represent mean values. ( Data information: Data were pooled from three independent experiments. (***p<0.001, ns, not significant, unpaired t‑test).
(C,D) MDA-MB-231 cells overexpressing PTPRN2, PLCβ1, or a control vector (C) or LM2 cells transfected with siRNA targeting PTPRN2, PLCβ1, or a control siRNA (D) were immunostained for PI(4,5) P2 levels and analyzed by fluorescence microscopy. Mean fluorescence intensity of plasma membrane levels of the lipid were quantified. N = 50 cells/group. Left, representative immunofluorescence images of cells stained with anti-PI(4,5) P2 antibody (red) and 4',6-diamidino-2-phenylindole (DAPI, blue). Scale bar, 10 μm.
(B) Graphic representation of the percent of specking cells over time. Maximal intensity projections from Z-stacks were generated for each image set before the number of cells and specks per field were calculated using CellProfiler. (A) represents images from one experiment out of three independent experiments of which percentage of specking cells data is represented in (B) with each line representing one field-of-view.
B. Reduced TLR4-induced mTORC1 signaling in mTORA/A primary macrophages: BMDMs were treated as in A except stimulated -/+ LPS [100 ng/mL] (30 min). The graph quantitates three independent experiments each with n=1 (n=3 total). The level of P-S6K1-T389 normalized to total protein in mTOR+/+ macrophages stimulated with LPS was set at 100%. *The confidence interval at 95% (58.6-71.2%) indicates statistical significance between mTOR+/+ vs. mTORA/A BMDMs.
A-C Droplet digital PCR analysis of Bmf, Bbc3/Puma and Bcl2l 11/Bim after conditional Snai1 loss in in vitro organoid culture. VillinCreERT2 Snai1+/+ (control) and VillinCreERT2 Snai1fl/fl SI organoids were treated for 24 h with tamoxifen. No differences in gene expression were observed (n = 3).
Abro1+/+ and Abro1−/− mice were intraperitoneally injected with Alum (1 mg per mouse) or vehicle (PBS) for 6 h. ELISA of IL-1β in the peritoneal lavage fluid (D) n = 6 for PBS groups and n = 12 for Alum groups.
H, I Quantification of immune cell and inflammatory markers (H) and PRRs (I) in adipose tissue of weight-matched HFD-fed WT-R (n = 5) and NOD2-R (n = 4) mice, *P = 0.01, **P = 0.001, and ***P = 0.0001.
Yeast complementation assays performed in a sensitized strain (BET3-GFP::HIS3, trs85∆::KANMX) to assess the functionality of Trs85 mutants within the region shown in E. Representative of n=3 independent experiments. (WT = wild-type, EV = empty vector)
C, D Immunoblotting analysis was performed to detect MARS protein levels in samples with 2 and 3-4 copies. Protein-level intensity shown in (D) was quantified using ImageJ and divided by the protein-level intensity of actin. The results were then graphed relative to samples with 2 copies. E, F MARS2 protein expression levels were detected (E) and quantified (F). Actin was used as a loading control. Data are presented as the mean ± SEM. *P ≤ 0.05, **P ≤ 0.01. Unpaired Student's t test was used
Evaluation of liver toxicity following glufosinate treatment. hepatotoxicity markers ALT (Alanine Aminotransferase) and AST (Aspartate aminotransferase) (D) in serum of vehicle and glufosinate (10 and 20 mg/kg) treated mice (n=8).
Population distribution of representative ERK activity trajectories in response to different GF dosages. Data representative of n = 3 experiments.
(c) Untransfected HeLa cells or cells stably expressing VPS29-GFP, GFP-VPS35 wild-type or GFP-VPS35 D620N were lysed and the lysates incubated with anti-VPS26 to IP the retromer CSC.
Histopathological (A-D) and virological (E) examinations of the lung tissues from an ill Malayan pangolin naturally infected with Pangolin-CoV (A and B, 200× and 400×, respectively) and an uninfected Malayan pangolin (C and D, 200× and 400×, respectively). Interstitial pneumonia with extensive infiltration of inflammatory cells is seen in the lung tissue from the infected pangolin. Viral particles are seen in double-membrane vesicles in the transmission electron microscopy image (small scale = 50 nm) taken from the Verno E6 cell culture inoculated with supernatant of homogenized lung (E), with morphology indicative of coronavirus (inserts at the upper right corner of E).
(A) The AH109 strain was co‐transformed with pGBKT7 containing the C‐terminal (CT) domain of mAtg9 (bait) and pGADT7, or pACT2, containing the CT domain of p38IP (prey). The interaction was then visualized by growth of co‐transformed yeast on SD‐Trp/Leu/His plates for 3 days at 30°C.
(F) Cells were transfected by siRNAs as indicated, followed by incubation in serum-starvation media for 24 h, and immunostained for IFT20 (red) and γ-tubulin (green). Scale bar, 10 μm. (G) Quantification of the percentage of IFT20 fluorescent intensity at the centriole shown in (F). Data represent mean ± SD (n=3 experiments), 150 were scored per condition per experiment, *P < 0.05, Student's t-test.
Diagrams showing the domain organization of SUMO (Smt3), Siz2, Rfa1, Rfa2 and Rfa3. Orange circle indicates known (Rfa1 and Smt3) or predicted (Siz2) SUMO modification sites. Dash lines represent truncation mutants used in this study in addition to the full-length proteins.
(A) Heat map representation of the most 17 deregulated Panther identified immune related genes in TNC high (WT/shC) and TNC low (KO/shTNC) tumors (N = 2 tumors each).
Measurement of RelA and RelB protein levels in RELA RELB double KO single cell clones generated in RPE1-hTERT cells.
(A) A summary of significantly different plasma metabolites compared to time baseline in metabolic cofactor supplementation and control studies based on untargeted metabolomics measurements. Red and blue colors denote the increased and decreased plasma levels compared to baseline, respectively. * Denotes significance (one-way ANOVA; FDR <0 .05).
(B) Volcano plot showing genes more expressed in mILC2s purified from Id2-CreERT2-c-Maffl/fl mice (dark red), genes more expressed in mILC2s purified from Id2-CreERT2+c-Maffl/fl mice (dark blue), and genes not significantly differentially expressed (grey). The horizontal dashed line depicts the significance threshold at BH-adj. p-value=0.02, while the vertical dashed lines depict an absolute log2(fold change) threshold=1.
D. GSEA showed increased expression of indicated oncogenic pathway genes in Kdm6apKO pancreas.
G Wild type, Traf3ip3-/- and Mavs-/- mice (n=6 each) were injected with VSV via tail vein injection at 5×107 pfu per mouse, and the survival rates were monitored for 15 days. P values were determined by unpaired two-tailed Student's t-test. *P<0.05
Schematic representation of the multi-step filtering strategy employed to identify functionally important changes in EZH2 distribution induced by neoplastic transformation. Blue and red numbers represent the number of peaks/genes present after each filtering step in untransformed and transformed cells, respectively. UT: untransformed, TR: transformed.
Dot plot showing the correlation between the change in coverage of LADs for each TAD (x-axis), and changes in intra-TAD interactions upon Piwi-KD (y-axis). Trend lines are in red. Spearman's rank correlation rho is indicated along with the p-value (algorithm AS 89).
f, PA-TU-8988T cells stably expressing shGFP or shNCOA4-1 were treated with H2O2 and cell viability was measured at 72 h. Bars and error bars represent mean values and s.d., respectively, of technical triplicates. ***P 0.001 using a two-sided t-test.
Representative Coomassie-stained gel of size exclusion chromatography fractions after purification of recombinant wild-type TRAPPIII complex. Representative of n=3 independent experiments.   As in A, using a Trs85 truncation containing only the final 198 amino acids. NOTE: Trs85[501-698] is ~25kD in size and now migrates at the same size as some of the core subunits. The species migrating near 85kD are contaminants present due to the lower expression level of this mutant construct. Representative of n=3 independent experiments.   As in A/B, using a Trs85 mutant with a truncation of the loop from 575-603. Trs85[∆575-603] appears to dissociate from the core during chromatography, indicating a reduced affinity for the core subunits. Representative of n=3 independent experiments.
(E) Validation of the binding specificity for the Hippo WW domain-containing proteins. HEK293T cells were transfected with the indicated SFB-tagged constructs and subjected to the pulldown assay.