EMBO/sd-character-level-ner huggingface dataset:
Lost preference for the novel object (nov) comparing to the familiar object (fam) in AP-2µ KO mice tested 24h after training in NOR Representative heatmaps are shown in (G).
(F) Increased bacterial growth of Pst DC3000 hrcC in ddl-6. Leaves of four-week-old plants were inoculated with Pst DC3000 hrcC at OD600=5x10-4.
(b) Overlay of 2D-[15N, 1H]-TROSY spectra of BakΔTM with (red) and without (blue) nanodiscs.
(B) Comparison of cell-type composition between control and EML1-heKO. Numbers indicate percentage of total cells belonging to the respective cell-type. Data information: RG1: radial glia1, RG to bRG: radial glia to basal radial glia, RG2: radial glia to young neurons, IP: intermediate progenitors, YN: young neurons, MLC: mesenchymal-like cells.
A. Actively proliferating hTERT-RPE1 cells were transfected with scrambled or KV10.1 siRNA, and cell cycle distribution was determined using acridine orange staining. Knockdown of KV10.1 induces an increase in cells with DNA/RNA content compatible with G0 (rectangle). However, the quantitative increase (to approximately 10%) was insufficient to explain the abundance of ciliated cells (over 40%)
B Table summaries of the microscale thermophoresis binding assay The sequence of the respective synthetic peptides is indicated.
(B) Separation of IDH-wildtype GBM samples between those displaying high mTOR and microglia enrichment (+ve correlation, group 1 in orange) and those without this signature (group 2 in green).
D. Comparison of the average cell length of 178 strains obtained from two independent 96-well cultures of the 176 most phenotypically remarkable Keio strains and 2 WT replicates.
D. Representative P0 superior colliculus stratum griseum superficiale (SGS) (sagittal sectioning of P0 brains along the dashed red line in the schematic, maximal projection of 5 µm depth). Note the presence of Dicer within the SGS marked with neurofilament. n=3 independent experiments. Abbreviations: WT, wild type; P0, postnatal day 0. Scale bars: 30µm.
B, Venn diagrams illustrating the overlap of genome binding sites between (top) BRPF3, HBO1 and ORC1, and (bottom) BRPF3, BRPF1/2 and ORC1 in human cells.
G) Gene set enrichment analysis (GSEA) using specific secretory and enterocytic transcriptional signatures with respect to the list of up-regulated genes in Eed-/- crypts.
B. Representative images of S2 cells expressing GFP fusions (green) of the MDI proteins diagramed in (A). Staining with MitoTracker Red (red) to label mitochondria shows an overlapping signal (yellow), indicating proper localization to mitochondria for all fusion proteins except MDIΔMTS.
(C) Chromatin states at bidirectionally transcribed predicted enhancers loci. All Bidi loci identified in NBC samples (n = 961) and CLL samples (n = 8530) are shown. The Bidi loci show an enrichment of the states "Active 2 (predicted active enhancer)" and "Active 1 (predicted transcription start sites)"
GRVillinKO mice were treated with PBS (n=9) or 10 mg/kg DEX (n=10) before 5 mg/kg LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.
K. Representative WB of Skm OXPHOS and related system proteins. Two samples per condition are shown. Each sample contains extracts from 3 mice. Histograms represent quantification (wt, n= 6; LowOXPHOS, n= 6). NDUFA9 (CI), SDHA and B (CII), ETF subunits A and B, ETFDH, CoreII (CIII), subunit 1 (CIV), βF1(CV) and hATPIF1 immunoblots are shown. Tubulin is presented as a loading control. Data information: Bars are the mean ± s.e.m. of the indicated (n) mice/genotype. *p <0.05 when compared to wt by Student's t-test.
(A) The expression of NLRP3 protein in non treated and LPS/ATP treated wild type and Becn1+/- microglia was determined by Western blot and normalised to ACTIN. Reduction of BECN1 significantly enhanced expression of NLRP3; mean ± SEM, wild type n = 4, wild type LPS/ATP n = 9, Becn1+/- n = 4, Becn1+/- LPS/ATP n = 23; ANOVA with Tukey´s post hoc test *: p < 0.05.
B GSEA displaying correlations of the gene-expression profiles between control and CDK12-overexpressing cells based on RNA-seq results.
I, A proposed working model for the p53-USP7-H2Bub1 axis in the regulation of SLC7A11 expression.
B, H1299 cells treated were subjected to transmission electron microscopy. Representative images are shown. Arrow head indicates condensed and marginated chromatin.
(F) Immunoblot analysis of the NFATc1 expression level in human keratinocyte HaCaT cells treated with SIRT7 siRNAs.
Two top-ranked SplashRNA-designed shRNAmirs targeting human Nurd complex components and a control shRNAmir targeting human CD4 were cloned into both miR-AB and miR-E lentiviral vectors with Venus as reporter. The lentiviruses packaged by these constructs were used for transduction of multiple human cell lines. RNAi efficiency was determined by western blot (WB) analysis of target protein levels in the lysates of the transduced cells. -actin served as loading control.
Relative volume of tumours grown in 12 Rag2-/- animals after treatment with Tepotinib or vehicle control (3K and 3KM tumours for each condition). No statistical significance was found by One-way ANOVA. Mean +/- SEM.
D. Blood glucose levels for insulin tolerance test (ITT) of control (n=4) or RbpjiΔEC (n=3) mice kept on HFD. Data represent unpaired t-test, mean ± SEM. E. Quantification of AUC for ITT in D. Data represent mean ± SEM, unpaired t-test.
(A) Representative transmission electron microscope (TEM) image showing the presence of EVs in the CSF in two independent experiments.
(D) The frequency of contact-dependent assembly (left panel) and number of assemblies per cell per min (right panel) in cells from different strains as indicated on x-axis. Three biological replicates were performed for each strain. At least 500 cells were analyzed per replicate on 3D-SIM time-lapse imaging of sheath dynamics (TssB-sfGFP) in 3 min period. Bar graph (left panel) and scatter dot plot (right panel) show mean ± SD. Unpaired t-test was performed.
J Quantification of the concentration of DEBIO-0932 reached in animals harboring H2030-BrM established brain metastases 6h after oral administration of DEBIO-0932 at 160 mg/kg. The concentration was measured in both the plasma and the brain for each mouse. Values are shown as mean + s.e.m. (n=3 mice per experimental condition). P value was calculated using two-tailed t-test.
I) Effect of 24 h incubation with 250 ng/ml TRAIL on Nalm6 199R, Nalm6 199R BAK KO and Nalm6 199R BOK KO, measured as DRAQ7+ cells with respect of total cell surface and normalized to untreated conditions. Each dot corresponds to the average normalized value of 3-4 technical replicates in n=3 independent experiments.
(A-C) Three different mediation models are shown, testing plasma P-tau217 as a statistical mediator of plaque density on tangle density. Panel A shows the mediation of total tangle density (significant mediation, 60% of the direct effect of plaque density on tangle density was explained by plasma P-tau217). Panel B shows the mediation of medial temporal lobe (MTL, entorhinal cortex and hippocampus) tangle density (no mediation). Panel C shows the mediation of tangle density in all regions except the MTL (strongest mediation, 77%). The P-values are from linear regression models used to estimate the mediation effects.
Knockdown of Mfn2 inhibited IRE1α ubiquitylation by MITOL. HEK293 cells were transfected with either scramble RNA, siMfn2 and indicated vectors 24 hours prior to immunoprecipitation assay.
A Immortalized Brca1F/−MEFs were infected with retroviruses expressing the indicated shRNAs and/or Cre recombinase, followed by selection with puromycin for 72 h. Cells were arrested in mitosis with colcemid and mitotic chromosomes were processed for CO‐FISH analysis. Metaphase chromosome spreads were stained with Cy3‐conjugated leading strand telomeric PNA probe (red) and FITC‐conjugated lagging strand telomeric PNA probe (green). DNA was counter‐stained with DAPI (blue).B The frequency of chromosome‐type telomeric fusions in cells treated as in (A) was quantified as a percentage of total number of chromosomes (illustrated in Supplementary Fig S2A). A minimum of 2,000 chromosomes were scored for each treatment. Error bars represent SD of at least two independent experiments. P‐values were calculated using an unpaired two‐tailed t‐test. *P ≤ 0.05; **P ≤ 0.01; NS, P > 0.05.
B Responses of locust nymphs in a dual-choice test in a Y-tube olfactometer after Piwi1 knockdown (n=46 locusts), ns: not significant (chi-square test). Data information: All assays were performed on fourth-instar locusts.
A. Representative electron micrographs of HRP uptake from standard (SE) or 100 mM K+ (100K) bath solution. Scale bar, 2 μm.
B Expression of PDI variants in zebrafish. Zebrafish embryos at 1-2 cell stage were injected with sense mRNA coding for the indicated PDIs (PDIA1WT, PDIA1D292N and PDIA1R300H: 200 pg/embryo; ERp57WT, ERp57D217N and ERp57Q481K: 80 pg/embryo). Protein expression was confirmed by Western blot analysis using anti-V5 antibody in total embryo extracts at 24 h post-fertilization (hpf). Actin was used as a loading control. In the left panel 80 µg protein and in the right panel 120 µg protein extract were used.
D-E. Respiration of isolated mitochondria from Ifnb+/+ and Ifnb-/- whole brains. OCR measurements under Complex 1 substrates (pyruvate/malate) were obtained at baseline (B) and on addition of ADP, oligomycin, FCCP and rotenone/antimycin A to capture S3, S4o, S3u, and nonmitochondrial respiration. N=3-4 mice per group; bar graphs show mean + SE.
D) Phylogenetic alignment of the NDP52 zinc finger. Zinc-coordinating residues in bold, conserved residues in the helix in red. The asterisk indicates D439, the residue mutated in subsequent experiments. Hs - Homo sapiens, Bt - Bos taurus, Gg - Gallus gallus and Xe - Xenopus laevis.
B Biochemical analysis of HOPS intracellular localization. RKO cells were transfected or not with HOPS and fractionated into nuclear and cytoplasmic component. Aliquots relative to the same cell number per fraction were immunoblotted using anti-p53 and anti-HOPS antibodies. GAPDH and Lamin B1 are purity controls of cytoplasmic and nuclear fraction respectively. Data information: all the experiments detailed above were performed three times, and representative panels are shown.
G Western blot analysis showing the equivalent expression of the λN-HA-AGO1proteins used in the tethering assays shown in panels (A,B,E,F).
WT Hoxb8-FL cells were treated with CHIR-124 in the presence or absence of the pan-caspase inhibitor QVD. Cell death was assessed after 24h using flow cytometry as in (A).
Representative immunoblot of M2 anti-FLAG immunopurification of media conditioned for 24 h on HEK293T cells co-overexpressing FTTTRA25T, ERdj3WT, ERdj3H53Q, and/or BiP, as indicated. Media inputs (1:400) are shown as a control. Lysates from these cells are also shown to confirm the increase of BiP afforded by overexpression.
F. Representative images (top) and quantification (bottom) of collagen gel-contraction ability of CAFs (monoculture) or CAFs co-cultured with siCNT (co-siCNT) or sihMENA(t) PANC-1 cells (co-sihMENA(t)). Dashed white circles illustrate the margins of the gel area. Data are presented as the mean ± SD of two biological replicates. Statistical analysis was performed with one-way ANOVA P=0.005, followed by Bonferroni's multiple comparison test ANOVA: *P<0.05, **P<0.01.
B, C Aβ40 and Aβ42 (pmol/g wet brain) in the FA-soluble brain extract from the same APP23mice showed a robust increase with age; ANOVA revealed a significant cubic trend (F(1, 56) = 221.114, P < 0.001 and F(1, 56) = 370.947, P < 0.001, respectively).
B. Representative western blot for PI4KIIα and PI4KIIIβ in control and U18-treated tsA201 cells. Protein levels were normalized to β-actin. Individual points (PI4KIIα: n=3; PI4KIIIβ: n=4) represent protein levels of each +U18 band normalized to control.
Variable selection and median canonical weight strength from bootstrap sCCA modeling in the CReATe PGB cohort. See Table EV1 for additional detail on genetic variants.
B, Both WOX5 (red) and PLT3 (green) are present homogenously within the nuclei of the QC cells. WOX5 can move to the CSCs and is recruited there by PLT3 to NBs (yellow), where interaction takes place and RNA is present (grey in magnification). This maintains the stem cell character of the CSCs (arrow) but already leads to a determination to subsequent CC fate. Gray dots represent starch granules.
Expression profiles of HuR, PP2A and miRNA let-7a are connected to IL-6 expression in RAW 264.7 cells. Data obtained from experiments described in previous figures are summed up to plot the changes in IL-6 mRNA levels against time of LPS treatment along with changes in PP2A, miRNA let-7a and HuR (D).
(H) EpiSC resetting in 2i+LIF measured by Oct4-GFP+ colony formation of Stat3 knockdown EpiSCs transiently transfected with Tfcp2l1, Gbx2 and Klf4. n=4 independent experiments: Student"s t-test, p-value indicated on plot. Box plots indicate min, median, max. See also Appendix Fi
A Top. Representative immunoblots from GluA2 coimmunoprecipitations probed for Sec23 and GluA2 after no treatment, 10 min DHPG, and 2APB/dantrolene followed by 10 min DHPG. Bottom. Quantification of Sec23 normalized to GluA2 under each of these conditions. For 10 min DHPG, n = 8; for 10 min DHPG + 2APB/dan, n = 6, p < 0.05, ANOVA.
A-B Time-controlled knock-down of ecd in the dorsal compartment of the wing discs (see Fig 1C for the expression pattern of apGalts). IF of control (A) and apGalts>ecdRNAi (B) wing discs, stained for Hh. Next to the images are quantifications of the respective staining in the dorsal versus ventral compartment of control (n=4) and apGalts>ecdRNAi (n=5) wing discs. Graphs show mean (thick line) ± SD (thin lines). Dashed yellow lines indicate the position of the A/P boundary. Statistical analysis (t-test) revealed no significant differences in Hh expression in the dorsal compartment between control and apGalts>ecdRNAi wing discs. Thus, loss of Ecd does not affect Hh production and spreading. Wing discs were analyzed 48 h after RNAi induction. Scale bars= 50 μm.
(C and D) RAW264.7 cells were infected with BCG at an MOI of 5 for the indicated time points (C) or at indicated MOIs for 24 h (D). The expression levels of miR-155 were examined by real-time PCR.
E. TLR4/LPS-stimulated mTORC1 signaling requires TBK1: TBK1+/+ and TBK1-/- MEFs were serum starved (20 hr.), pre-treated with amlexanox [50 μM] (2 hr.) or Torin1 [100 nM] (30 min), and stimulated -/+ LPS as in A.
C. U1-Orp1-roGFP2 cells were treated with Vs for 15 min, followed by exposure to H2O2 for 2 min, and ratiometric response was measured.
(B) HeLa cells were transfected with siRNAs and plasmids as indicated. Expression of the respective proteins was verified by western blotting. Detection of β‐tubulin served as loading control.
(B) U2OS (EGFP-Flex1-BIR-5086) cells were treated with or without 2 mM HU for 24 hr, and the percentage of EGFP positive cells was quantified by FACS analysis 3 days after HU removal. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Signiﬁcance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01.
E. Localization of β-gal+ cells in adult BASC viewer animals. BADJ-associated and "alveolar" β-gal+ cells are expressed as percentage of all lineage-labeled cells (means±SD n=3).
(D-F) Real-time PCR analysis of the expression of TRIM59 in SNU-4th (D), SNU719 (E) and YCCEL1 cells (F) transfected with the above different mimics.
Representative images of U2OS cells stably expressing GFP-SPRTN or GFP-ACRC that were transfected with control (CTRL) or UBC9 siRNAs, exposed to formaldehyde in the presence or absence of ubiquitin E1 enzyme (UBA1) inhibitor TAK-243 (Ub-E1i) as indicated and fixed one h later. Scale bar, 10 μm.
C. The interactions between YTHDF1 DDX17 (C) were measured by co-IP in 293T cells. The results were detected using specific antibodies.
C, D. ChIP-qPCR shows increased occupancy of (C) POL2-S5p at promoters of profibrotic genes in AECs subjected to TGFβ1 for 24 h, whereas no enrichment of (D) POL2-S2p at the gene bodies of these genes was detected. Negative IgG control is shown in Appendix Figure S5B (mean + s.d., n = 3 biological replicates). E, F. ChIP-qPCR shows increased occupancy of (E) POL2-S5p at promoters and (F) POL2-S2p at the gene bodies of profibrotic genes in AECs subjected to TGFβ1 for 48 h. Negative IgG control is shown in Appendix Figure S5C (mean + s.d., n = 3 biological replicates).
A, B. virus replication at 12 and 24 hpi, in HDAC6+/+ and HDAC6-/- BMDMs in response to VSV-GFP (MOI = 10) infection (A) and PR8-GFP (MOI = 5) infection (B).
(a) Alignment of the Beclin 1 CC domain sequences from various species. The coloured segments and the italic abcdefg on top of the sequence indicate the heptad repeats typical of CC structure. The coloured spheres below the sequence indicate the residues at a (orange) and d (blue) position of each heptad repeat.
H) Cell death induced by GFP-BAK and GFP-BAK R127H on HCT AKO, measured as DRAQ7+/GFP+ cells. Unpaired Student's t-test. *** p<0,001 with respect to GFP BAK wt.
G Venn diagram of genes that are upregulated (padj < 0.05 and log2FC > 1) after LINC00941 depletion (red) and downregulated (padj < 0.05 and -1 > log2FC) in SPRR5 deficient (yellow) organotypic epidermal tissue on day 3 (n = 3-5 epidermal tissue cultures/knockdown group).
Male C57BL/6J mice were fed with chow diet supplemented with 0 and1% SUC for 6 weeks. The enzymes activity of (F) SDH, (G) HK, and (H) LDH in gastrocnemius.
(A) Western blot analyses of the knockout efficiency of Cdc20 in Cdc20f/f and Sp7-Cre;Cdc20f/f BMSCs.
(C-F) Seahorse XF extracellular flux analysis performed on cells 24h after treatment. Sequential injections of oligomycin (Oligo.), FCCP, and a combination of rotenone and antimycin A (Rot. + AmA) were performed to assess mitochondrial fitness. Flux was normalized to relative protein units (RPU) measured after the run with an SRB assay. Data is representative of three independent experiment (n = 3). Error bars represent the standard deviation of biological replicates (SD). (C) Oxygen consumption rates (OCR) Data information: Significance between means was first determined using ANOVA. Significance p-values were calculated using Fisher"s LSD. *, p < 0.05; **, p < 0.01 from NT controls
Jurkat cells were exposed to either DMSO, or dieldrin in DMSO for 30 min. RNA-seq was then performed on cDNA libraries prepared after depletion of ribosomal RNAs. Schematic showing that only a fraction of the APEs (sites of divergent transcription activated 2-fold or more by dieldrin) match promoters and enhancers annotated as active in T cells (APETs). The remaining APEs are designated APEDs (specific to the dieldrin treatment).
(I, Examination of the neuronal activation pattern after pup presentation in Shank2+/+ and Shank2-/- mice using c-Fos immunocytochemistry. Schematic map of the neuronal pathway regulating social attachment behavior in mice.
A. Theoretical distribution of lengths of mature cells when NEZ correlates with 1/ln(rEZ) (as in panel C) and when it does not (as in panel D). In the correlated case, the values extracted for real wild type plants for l0EZ , rEZ and NEZ were used (n=122, all data in panel C). For the non-correlated case, the real values of rEZ and NEZ were randomly coupled in pairs and the l0EZ value for the associated rEZ was used.
(D) Western blot analysis of cross-linked ASC in the Triton X-insoluble pellet from LPS-primed BMDMs pre-treated with LicoB (20 μM) or vehicle and then stimulated with nigericin, ATP, poly(I:C), and MSU. Pam3CSK4-primed BMDMs were treated with LicoB (20 μM) and then stimulated with LPS.
Kaplan-Meier survival graph indicates prolonged life span of Wwox knockout mice injected with AAV9-hSynI-mWwox [total n=18, spontaneously dead n=6, mice taken out for electrophysiology/electron microscopy/analysis, are shown in yellow, n=12] compared to mice injected with AAV9-hSynI-GFP (n=6) or the non-injected (n=8 (P <0.0001, Log-rank Mantel-Cox test).
(G) Confocal micrographs of the optic lobe (medulla region) of young flies expressing a mutated form of human tau protein exhibiting Ref(2) P- and tau-positive aggregates (arrows). Genotypes: (G) elav/+;UAS-E14/+.
Sensitivity of U2OS cells transduced with shRNA targeting Chk1 (shChk1) or non-targeting shRNA (shScr) and Lenti-GFP-Polη or Lenti-GFP (-). Cell number was determined 7 days after transduction (5 days after maximal downregulation). Data represent the mean (+SD) of 3 independent experiments.
(A) Immunoprecipitation assays testing the physical interaction between CHK2 and proteins encoded by autophagy-related genes in HCT116 cells. Lysates were extracted for immunoprecipitation with CHK2-specific antibody or control IgG, followed by probing with antibodies specific for Ulk1, Atg5, Beclin1, Atg7 or LC3.
A. Schematic representation of the wild type (WT) and knock-out (KO) GemC1 alleles. A lacZ-neo cassette has been inserted between exons 2 and 3 of the GemC1 gene. A splicing acceptor site (SA) upstream of lacZ ablates gene function (knock-out first allele, [38])
E Serum AST and ALT levels of WT and Cideb-/- mice under chow diet and HFLF diet (n = 8 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.
B) Projection images of three confocal sections (1 μm) from the apical side of the wing discs. Quantification of co-localization rates using apical projection images; central horizontal lines show median values of N=8-12 , box shows lower and upper quartiles and the whiskers show the maximum and minimum excluding outliers. Note that at the apical side no clear significant reduction in co-localization rates (1= total coverage of red by green) is observed after RNAi expression or in Tsp96F-HA over-expression.
(A) HeLa cells transfected with GFP-ATG16L1 for 24 hr were incubated for 15 min with 2.5 μg/ml with HRP-cholera toxin subunit B at 4°C and then for 10 min at 37°C. Cells were then fixed and treated for immunogold labeling on cryosections. ATG16L1 was detected with anti-ATG16L1 antibody (15 nm), and cholera toxin was detected using anti-HRP antibody. Scale bar, 150 nm.
ATP levels in HD patient-derived fibroblast cells. n = 2. *P = 0.003; **P = 0.004.
Heatmap showing fatty acid lipolysis- and uptake-related genes differentially expressed among the eWAT ATM subsets from HFD (16 weeks) treated mice. Each cluster has three biological replicates. The z-score of the gene expression profiles gives a scale to measure the differential expression. Gene set enrichment analysis (GSEA) identified significant transcriptional upregulation in oxidative phosphorylation and the TCA cycle/respiratory electron transport signaling pathway in CD11c+ ATMs when compared with MHCIIhi ATMs obtained from eWAT of HFD-treated (HFD 16 weeks) mice. Gene ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) with false discovery rate (FDR) <0.05.
(B) Two-fold dilutions of total nuclear protein extracts from the third instar larvae of the ash122/ash19011 mutants supplemented with various transgenic constructs and wild type flies were analyzed by western blot with anti-Ash1 antibodies. Arrowhead indicates the position of Ash1 protein. Note that transgenic proteins are expressed at comparable level.
C Prenylation status of Ykt6 in WT and PTAR1 KO cells. Recombinant Ykt6 samples and cell lysates of WT cells, PTAR1 KO cells, and PTAR1 KO cells stably expressing PTAR1 (KO + PTAR1) were separated by DOC-PAGE (upper) or SDS-PAGE (lower), and analyzed by immunoblotting with anti-Ykt6 antibody.
A-C ROC analysis was performed to test the accuracy to discriminate between Aβ-positive (A+) from Aβ-negative (A-) individuals. Aβ positivity was defined as CSF Aβ42/40 < 0.071 (A), Aβ PET positive visual read (B) or Aβ PET Centiloid (CL) > 12 (C). Abbreviations: CSF, cerebrospinal fluid; Mid, mid-region; NfL, neurofilament light; N, N-terminal; p-tau, phosphorylated tau; t-tau, total tau.