EMBO/sd-character-level-ner huggingface dataset:
(A) Per2 is known to act as an intermediary between the light detector and the melatonin synthesis pathway. Box plot shows per2 mRNA levels measured by qPCR in 6 dpf larvae placed under a low (light blue box) or medium intensity (dark blue box) LD regime. Under low intensity light a significant reduction in the per2 transcript levels is detected in the light phase. Bar under the chart indicates the 12:12 hour LD interval. (B) Box plot as in A shows mRNA levels of arntl1b, which is in part regulated by per2. Under low intensity light a significant reduction in the arntl1b transcript level is detected at ZT3 and an increase at ZT21. (C) Plot as in A shows mRNA levels of per1a, which is regulated by the Arntl-Clk heterodimer. Under low intensity light a significant reduction in the per1a transcript level is detected at ZT21 and an increase at ZT9. (D) Box plot shows similar per2 mRNA levels between wild-type (blue box) and opn4 dko (grey box) under a medium intensity LD regime at 6th dpf. (E) Box plot as in D, shows similar arntl1b mRNA levels. (F) Box plot as in D, shows similar per1a mRNA levels. (G) Box plot as in D, shows similar clk1a mRNA levels. (H) Box plot as in A shows ddc mRNA levels. Similar levels were detected between wild-type larvae under a low or medium intensity LD regime. (I) Box plot as in A shows asmt mRNA levels. Under a low intensity LD regime a significant increase in the asmt transcript level is detected at ZT3. Data information: boxplot divides the data in quartiles: the box indicates the interquartile range, with the horizontal line in the box denoting the median of the data set, the whiskers extend to the minimum and maximum, and meet the box at the median of the lower (quartile 1) and median of the upper (quartile 3) half of the dataset. Black dots indicate biological replicates (n=12), the red dot indicates the mean, red error bars indicate the 95% confidence interval and asterisks indicate significance (0.01<p(✱)<0.05, 0.001<p(✱✱)<0.01, p(✱✱✱)<0.001, ns = not significant). Expanded
B Western blot analysis for Hwa performed with lysates from embryos treated as indicated in (A). 1cs, 1-cell stage; 2cs, 2-cell stage; st6, 32-cell stage; st8.5, blastula stage. Blots are representative of 3 independent experiments. C Densitometry analysis of Hwa bands from the western blot in (B) for corresponding lanes normalized to α-tubulin. n = 3 independent experiments, mean ± SEM, *p < 0.05, **p < 0.01 by unpaired t test.
(a) Immunoblot analysis of lysates of human monocytes-macrophages primed with LPS (10 ng) and then transfected with poly(dA:dT) (1.5 μg/ml) or treated with nigericin (4 μM) for 6 h (numbers below lanes as in Fig. 1d).
Cells were infected with a moi 10 of influenza (Flu) (A) or SFV (B) for 4, 8 or 24h. Levels of EGOT (A-E) were calculated by qRT-PCR in RNA isolated from the control, treated or infected HuH7 cells. GAPDH expression was also evaluated in all cases and used as a reference to calculate the relative levels of each transcript. The experiment was performed twice in triplicate (n=6). Each value shows the average and error bars indicate standard deviations. Asterisks mark significant differences (ns, non-significant; * denotes p<0.05, ** p<0.01) obtained with a two-tailed non-parametric Mann-Whitney U-test.
Representative images of the hippocampus and cortex (layers II-V) from control and treated mice stained with anti-mouse glial fibrillary acidic protein (GFAP; red)/DAPI (nuclear, blue) to identify activated astrocytes, 20x, scale bar: 50μm Representative images of the hippocampus and cortex (layers II-V) from control and treated mice stained with isolectin B4 (ILB4) to identify activated microglia, 20x, scale bar: 50μ
O, P NF-AAV-mediated mDA neuroprotective effects were further assessed with the experimental schedule (O), in which AAV injections were subjected after three consecutive MPTP injections. Shown in (P) is TH+cell counts of the left and right sides of the midbrains. *P = 0.000012 (D14), 0.000036 (1M), 0.000027 (2M), n = 6-7, paired Student's t-test.
J, K Representative pictures of Olfm4 in situ hybridization on small intestinal sections of 9‐month‐old G3 mTerc−/− mice (K) and age‐matched mTerc+/+ (J) mice. Arrowheads point to positive cells. Dashed lines outline the crypts. Note that the remaining ISPCs in G3 mTerc−/− mice were mostly located in position 4 above the Paneth cells. Scale bar: 20 μm.
(K) IDH1 K224 deacetylation was dependent on SIRT2 catalytic activity. SIRT2 H187Y was a catalytically inactive mutant.
(G) Similar transfection as in (F) was performed. The cells were treated with ActD for indicated times, and then were processed for qRT-PCR analysis. The level of raptor mRNA was quantified and normalized relative to GAPDH mRNA. Data from three independent experiments represented as means ± S.E.M., *, p<0.05; **, p<0.01, one-way ANOVA.
(A) Measurement of PMO uptake in dystrophic muscle cells (H2K mdx cells) in the presence of MOTS-c (scale bar: 10 μm) (n=6; **p<0.001). PMO-M refers to PMO and MOTS-c (the same is for the rest unless otherwise specified).
(D) OMA1 mediates accelerated processing of L-OPA1 in Slp2-/- MEFs. Processing of OPA1 and PGAM5 was monitored in Slp2-/-, Oma1-/-, and Slp2-/-Oma1-/- cells by immunoblotting after inhibition of cytosolic protein synthesis with cycloheximide (CHX).
E MRI of body fat content: standard non-fat-suppressed (left), fat-suppressed (middle) and fat-only (right). Representative images of three independent experiments (n = 6 total for each genotype) showing similar results are shown.
E) the recurrence of HCC patients stratified by TFAM expression. G) the recurrence of HCC patients stratified by nuclear F-actin positive rates.
C U2OS cells treated with the indicated siRNAs were stained with anti-α-tubulin antibodies and Hoechst 33258. Histograms represent frequency of mitotic cells with the multipolar spindle in the indicated conditions. Values are mean percentages ± SEM from three independent experiments (n = 30 for each condition). *P < 0.05 (one-tailed t-test).
Cell surface phenotype and numbers of alveolar (C; digested lung) and peritoneal (D) macrophages in WT and DKO mice. Additional gating for CD11b+ cells was applied for peritoneal macrophages as indicated. Levels of CD11b expression on WT and DKO AMs are shown, and median fluorescent intensity for CD11b expression was quantified (C, bottom left; 3 mice per genotype). Absolute numbers of CD11chiCD11bloSiglecFhi alveolar macrophages from digested lungs (C) and CD11b+F4/80hi peritoneal macrophages (D) from WT and DKO mice are shown (bottom; 4 mice per genotype).
(E) In vitro colony-forming capacity of progenitor cells. Sorted KSL cells were cultured in semisolid medium. Counting and classification of colonies were performed in independent littermate pairs (n = 3 mice per group). GEMM, Colony-forming unit-granulocyte, erythroid, macrophage, and megakaryocyte; GM, Colony-forming unit-granulocyte and macrophage; M, Colony-forming unit-macrophage; E, Burst-forming unit-erythroid.
IF staining and confocal analysis of p63 in the organotypic human epidermis obtained as described in (C). Dotted lines represent the insert border. One representative experiment of three is shown. Scale bars: 50μm Box plot showing quantification of p63 positive nuclei on total nuclei. Each central line represents the median; each box represents Q1 (quartile 1, below the median) and Q3 (quartile 3, above the median); the whiskers represents minimum (Q1-1,5*IQR) and maximum (Q3+1,5*IQR). IQR=interquartile range; 16, 15, and 19 images were analysed for SCR, si-uc.291 (1), and si-uc.291 (2) respectively; *p<0.05; ** p<0.01, Student's t-test.
(N extension reflex as a function of time after treating Gbeys/ys mice with vehicle (n=8) or 144DG11 (n=9) at 6 months of age (at onset). Data information: Two way ANOVA with repeated measures show that, throughout the period, treatment values were higher than vehicle (p<0.07) Significant difference (p<0.05, two-tailed t-tests) at specific time points is denoted by *. All error bars represent s.d.
(A-B) Overall survival of ER-negative metastatic breast cancer (n=226) (A) and lung adenocarcinoma (n=719) (B) patients according to MARK4 mRNA levels found in their tumors was represented using the Kaplan Meier-plotter [25].
D Immunofluorescence microscopy images of the localisation of FAK and zyxin in HeLa cells expressing GFP‐KSHV‐TK‐DEAD (white arrowheads).
J. The representative image of co-staining of Pbk and BrdU in pancreatic sections. Islet area was circled with white dashed line. Pbk and BrdU co-staining are denoted by white arrows. Scale bar: 50 μm. K. Quantification of the percentage with pbk and BrdU co-staining cells among total Pbk positive cells in HFD-fed mouse islets. The mean value of four mice from 5 sections for each mouse were presented.
E) Overnight treatment with hyaluronidase destroys PNN as shown by immunofluorescence for aggrecan (red), DAPI (cyan) and βIII-tubulin (green) and confocal analysis. Scale bar: 20µm
Figure 7. Working model for Tel1 function at replication forks in CPT. CPT-induced Top1 trapping on DNA results in the accumulation of DNA supercoiling ahead of an incoming replication fork. In the presence of this torsional stress Mrc1 promotes fork reversal. Reversed forks can be targeted by nucleases, mainly MRX-Sae2, which nucleolitically process the regressed arm. Tel1 counteracts the action of MRX-Sae2 either directly or through a still unknown factor (X), thus preventing unscheduled fork degradation. Reversed forks stabilization by Tel1 can support the completion of DNA replication after the repair of CPT-induced damage by either reversed fork reactivation or fusion with an incoming fork. Expanded view Figure and Table legends
(A) Occurrence of CID or fCID in species analyzed in this study (T. spp., T. agilis and T. mirabilis, blue background), and in select other organisms, not to scale, mapped on a taxonomic tree generated using phyloTv2 based on NCBI taxonomy - https://phylot.biobyte.de/. See Discussion in main text for references.
Sorted CD4+CD25hiCD127- Tregs were stimulated with anti-CD3, anti-CD28 and IL-2 in the presence or absence of IL-12. a. Tregs were stimulated for 50 minutes with IL-12 or vehicle. Histograms show a representative example of n=8 independent experiments performed of the expression of phosphorylated molecules at 30 minutes after stimulation for pAKT and pFoxo1, and at 40 minutes for pFoxo3 in vehicle- (grey open histogram) or IL-12-treated (dark open histogram) Tregs. Grey histograms represent the isotype. The time points selected were based on kinetic experiments performed for a total of 50 minutes
A. Immunofluorescence images of MAD1 and MAD1-pT716 kinetochore levels in nocodazole-arrested RPE1 cells treated with or without AZ-3146. Scale bars = 5µM.
Recombination frequencies using the direct‐repeat chromosomal system leu2‐k::ADE2‐URA3::leu2‐k in WT and RNAPII mutants. Deletion events were detected and quantified in media containing 5‐fluorotic acid (FOA) and could be directly visualized as red sectors.
(f) Effects of DSS colitis injury on RNA expression levels of stem (Lgr5 and Krt19) and progenitor (Atoh1 and Notch1) cell markers. Lgr5 mRNA expression is significantly decreased after exposure to DSS (N=6-7 per condition). Data are represented as mean ± SEM analyzed using Student's t-test. *P≤0.05, ** P≤0.01.
HepG2 cells were transfected with lentivirus vectors expressing shRNA targeting KLF10 or negative control (Ctrl). n=3. Results represent three independent experiments. (A) Protein level of KLF10, and its normalization to β-actin.
(H, I) Simultaneous measurements of ER Ca2+ with ER-GECO1 and PI(4,5) P2 hydrolysis with PHPLCδ-GFP in response to cell stimulation of M3 receptors. Traces are shown in (h) and the average slopes are in (i). Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.
IB analyses to determine the interaction between β-catenin and BBR peptide by in vitro pull-down assays using purified His-β-catenin and GST-BBR proteins
G. Genes that loose KDM6A binding in Hnf1a-mutant pancreas are predominantly downregulated in Hnf1aaKO pancreas and are direct HNF1A target genes (red dots).
A, B, C Transmission electron microscopy image analysis was used to quantify mitochondrial size, circularity and roundness in DX/REL neuroblastoma pairs (mean +/- SD shown). Data information: , n=137-241 mitochondria per cell line statistical analyses were performed using a two-tailed Mann-Whitney U test, with significance p<0.05 (trend p<0.10).
D. Detection of Ty5, Ty5ΔTD5+bNLS or Ty1 de novo integration events at HMR and HML loci, SCR1 and upstream of all glycine tDNAs, by PCR using a primer in HIS3 and a primer in the locus of interest. Retrotransposition was induced in cells transformed with WT or mutated pGAL1-Ty5his3AI (Ty5 or Ty5ΔTD5+bNLS) and pGAL1-Ty1his3AI (Ty1). Total genomic DNA was extracted from His+ cells obtained from independent cultures. Nucleosome position (green circles) is indicated on the right of the panels (Brogaard et al, 2012).
E. Upf1 interaction with a 30-mer 3' biotinylated RNA fragment was tested by mixing purified Upf1 helicase domain with Nmd4 and testing the fraction of recovered protein on streptavidin beads after washes with 150 mM and 300 mM NaCl containing buffer solution
IL-1β ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS, 10 ng.ml-1 IL-10, 10 µM beraprost or vehicle control (Vh). Data shown are representative of at least 3 independent experiments.
(D) Viral loads in spleen of infected humanized mice at the day of sacrifice. Error bars indicate mean ± SEM. Number of biological replicates per group: EBNA2 WT EBV: n = 13; EBNA2 S379A EBV: n = 11; EBNA2 S457A T465V EBV: n = 9.
in vitro angiogenesis assay was performed in static or shear stress-exposed HUVECs transfected with the indicated siRNAs for 18 h in (C). Scale bars, 600 μm. Quantification of tube node number in (D) and tube length in (E) from data examined within equivalent fields of view at each time point using the ImageJ angiogenesis analyzer. Data are shown as mean ± SD of five independent experiments with ≥ 5 tubulogenesis regions per condition.
(A) Co-Immunoprecipitations (Co-IPs) of PRR7 with GluN1, PSD95 and GluN2B from rat brain lysates. FT = flowthrough, IgG = normal IgGs.
(A) The interaction of WASH with Beclin 1 was validated by yeast two‐hybrid assays. Yeast strain AH109 was co‐transfected with Gal4 DNA‐binding domain (BD) fused WASH and Gal4 activating domain (AD) fused Beclin 1. p53 and large T antigen or a known WASH interactor Bloc1s2 was introduced as positive controls.
Immunoblotting of His-GID1 proteins using constructs shown in (D). Proteins were separated by SDS-PAGE, followed by immunoblotting with anti-His-tag antibodies. The PA binding activity of different truncation mutations were analyzed by fat-immunoblotting. The red arrowheads indicate truncated proteins with different molecular weights.
(A) HeLa cells were treated with control or indicated siRNA for 72 hours and SL biosynthesis measured by [3H] - sphingosine pulse-chase assay. GSL levels are expressed as fold changes with respect to control. CERT and FAPP2 knockdowns (blue bars) were used as controls.
Widefield images of Rad51-ssDNA molecules (unlabeled) in the presence of GFP-Rdh54 (green; 1, 3, 10 and 30 nM).
J Immunoblot analysis of NLRP3 in CCDC50-WT and CCDC50-KO THP-1 cells stimulated with LPS in combination with ATP. Data information: actin was used as a loading control. All the experiments were repeated at least once.
Flow cytometry analysis of tumours collected on Day 10 following treatment (n = 3 animals per group). ILP with TNF/Mel/SM significantly increased infiltration by CD3+ lymphocytes (B) and CD3-CD161+ NK cells (C).
Immunofluorescence labeling of GLUT1 (white), early endosomes (EEA1, green) and nuclei (blue) in HUVECs treated with VEGF-B186 for 10 min, 30 min or 2 h. Scale bar, 10 µm.
A, B Single-molecule FISH (smFISH) on mouse hippocampal neurons. (A) Representative pictures of smFISH on BDNF-treated WT (top) and KO (bottom) mouse hippocampal neurons (DIV6) using a probe directed against the Mirg transcript (green). (Middle) Hoechst (blue). (Right) MAP2 immunostaining (red). Pictures show a zoom-in on the cell body, since the signal detected in WT neurons was restricted to the nuclei (scale bar: 5μm). (B) Representative pictures of smFISH on mouse wild type hippocampal neuron cultures (DIV6; basal) using a probe specific for the Mirg transcript (green). (Middle) Hoechst (blue). (Right) MAP2 immunostaining (red). Top: overview, scale bar: 10μm; bottom: zoom-in, scale bar: 5μm.
(e) NRK cells were transiently transfected with adenovirus expressing GFP-Atg14L or GFP-Atg14L4C4A and fixed under nutrient-rich conditions. The cells were stained with anticalnexin antibody as an ER membrane marker. Higher magnification of the boxed areas is shown below. Bars, 10 µm.
Correlation between predicted and measured transcription levels for each bacterial species with various proportions of data for model training. Data were randomly split for the training and test sets, respectively, and Pearson correlation between predicted and observed transcription levels was computed for 10 times for each proportion. Box plots are displaying the interquartile range (IQR) with median values (black line) and whiskers extending to the highest and lowest points within 1.5x of the IQR.
(a) Prediction of drug response in terms of survival: The Y-axis displays the hazard ratio of patients as a function of upregulation of predicted rescuers
(B-C) Indices of (B) normalized basal OCR and (C) maximal respiration of wt, gas-1(fc21) and gas-1(fc21); cest-2.2 O/E mutant nematodes across (n=9, one-way ANOVA with Tukey's multiple comparison test, n=9 biological replicates, from 3 independent experiments). Data information: bars represent mean± SEM Across experiments, p value summary is ns= not significant, *p<0.05, **p < 0.01; ***p < 0.001, ****p<0.0001.
(D) HeLa CCL2 cells transfected with HA-Ect2 were infected with sh-control luciferase (shGL) or shPlk1 lentiviruses. The resulting cells were used for immunoprecipitation analysis using anti-HA antibody, and immunoprecipitates were separated by 10% SDS-PAGE followed by immunoblot analysis with the indicated antibodies.
CD31+ tumor vessel area (B) and of αSMA+pericyte-covered vessels over the total number of CD31+ vessels (with representative images) (C) in vehicle and glufosinate (20mg/kg) treated mice (n=6). Six images per tumor were analysed. Scale bar: 50µm.
A,B) Real-time qPCR analysis of ANG-2 levels in retina and RPE/choroid complexes of JR5558 and C57Bl/6J (C57) mice. A) Relative expression levels of ANG-2 were significantly increased in the RPE/choroid complexes of JR5558mice in comparison to C57, at 50 and 62 days old (P = 0.022 at D50 and P = 0.042 and at D62). B) By contrast, retina levels of ANG-2 were not significantly different between C57 and JR5558mice, indicating neovascularization is driven locally by ANG-2. SEM is shown as error bar with n = 4 animals per group. *Denotes statistical significance of JR5558mice compared to wild type C57bl6 using unpaired T-test for each time point analyzed separately.
(D) Ratio of SLC3A2 integrated densities to GAPDH; SEM, n=3 independent experiments. Statistical tests used: (D) One sample T-tests All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats.
(F) BMDMs were transfected with siRNAs targeting UBQLN1 or siCON and infected with live/dead Mtb strain. IFN-γ was added 1d prior to infection if indicated. %Viable bacteria were quantified 24 and 48 hpi. Data are from 2 independent experiments. *P<0.05; ***P<0.001, Fisher's exact test, comparing the proportion of viable and non-viable bacteria in indicated samples.
A) Formation of GFP-LC3 autophagic puncta in TMED2 overexpressing HEK239T cells as monitored using confocal microscopy (right panel). DAPI was used for nuclear staining visualization. Percentage of GFP-LC3 puncta in control (CTL) and TMED2 overexpressing HEK293T cells as quantified from three independent experiments by counting 240 GFP-LC3 positive cells for each condition (left panel). (**): p=0.0032.
Numbers of EMP effectively transferred in neonates (white circle) and numbers of EMP-derived AM (red circles) in BAL and lung of adult Csf2ra-/- recipients 8 weeks after transfer (n = 5 mice).
G, H Histograms of instant eccentricities (left) and 2D plots of adherent surface versus speed (right) of Arghap45−/− naive T cells on 2D surface coated with ICAM-1 and CCL21. In the 2D plot, the single adherent (projected adherent area > 25 %) and slow (instant speed < 15 µm/min) cell population is highlighted. Data information: In (H), events which combined null motility and adherence over the recorded time have been excluded.
The CEP41-depleted HUVECs were transfected with expression vectors encoding nothing (MOCK), CEP41, or HIF1α and cultivated under hypoxia. Whole cell lysates were used for immunoblot assays for phospho-AURKA and AURKA, and the resulting data were compared to those of normoxic and hypoxic control cells. Protein levels were normalized against β-ACTIN in the same blots. NOR, normoxia; HYP, hypoxia.
Dual-Luciferase assay wih a construct bearing the 5'UTR of YTHDF1 in SW620 cells with or without APC overexpression. Data are represented as mean ± SEM. *p<0. 05, **p<0. 01 (3 biological replicates, t-test).
A) Schematic of the EMS mutagenesis screen carried out using the piRNA sensor and identification of a novel allele (mj261) of the rpb-9 gene.
Representative pictures of E13.5 and E18.5 embryos of the indicated genotypes. Scale bar E13.5 = 1 mm, E18.5 = 5 mm. Quantification of fetal liver cell number at E13.5. Bars represent means ± S.E.M. (N=4 for Chk1fl/+, N=3 for Chk1fl/+ Vav-Cre and N=4 for Chk1fl/- Vav-Cre).
E. KDM6A functions as a transcriptional activator of direct target genes in pancreatic cells. Left: Downregulated, but not upregulated, genes in Kdm6apKO pancreas were enriched for KDM6A binding. P-values and odds ratios (O.R.) were calculated by Fisher's exact test. Right: Venn diagrams showing overlap of down and upregulated genes with KDM6A binding.
Using FTAREA values, the number of days to flower was calculated and compared to data from Corbesier et al (1996) (see Supplementary Information). Error bars represent standard deviation. Simulated flowering: solid black line, filled squares; data: dashed black lines, empty squares.
Bar plots with dot density plots showing that apical areas of WT cells were significantly smaller than those of LUZP1 KO cells [118.34 ± 57.84 μm2 (WT) vs. 185.32 ± 76.69 μm2 (LUZP1 KO)]. n = 3. **p < 0.01 (Mann-Whitney U test). Bars and error bars represent the mean ± standard deviation (SD).
F. Expression pattern of LincGET and Dyei at different stages of preimplantation mouseembryos by TM-qPCR. The error bars represent s.e.m. About 50 embryos of each stage were used and three experimental replicates were performed.
Karyotypic analysis of later passage, control and ICL of a replicate (#1) of Ch9 (D) lines. All chromosomes are shown for 20 metaphases. Target chromosomes are boxed in red.
A qPCR of cDNA from L1236 and L428 HL cell RNA obtained 5 days post H2A.B knockdown. Amplification was performed using primers that anneal to the ETS and ITS spliced-out regions to detect nascent rRNA. ETS and ITS, external and internal transcribed regions, respectively. The relative levels of both ETS and ITS were normalised to the average expression levels of the B2M and HPRT1, and presented as mean ± SD for eight biological replicates. The significance of the difference was determined by student's t test and denoted as * p < 0.05; *** p < 0.001.