EMBO/sd-character-level-ner huggingface dataset:
Figure 4A, B HeLa cells and the Sgo1-K492A mutant cells were immunostained with the indicated antibodies. Example images are shown (A). The immunofluorescence intensity ratio of centromeric INCENP/ACA was determined on around 250 chromosomes in 10 cells (B). Data information: Means and error bars representing S.D. are shown ; unpaired t-test). Scale bars, 10 μm. C, D HeLa and the Sgo1-K492A cells were exposed to nocodazole for 4 hr. Mitotic cells were cytospun onto coverslips and fixed for immunostaining. Example images are shown (C). The immunofluorescence intensity ratio of centromeric TOP2A/arm TOP2A was determined on around 150 chromosomes in 10 cells (D). Data information: Means and error bars representing S.D. are shown unpaired t-test). Scale bars, 10 μm. E, F HeLa and the Sgo1-K492A cells were transfected with siRNA, and immunostained with the indicated antibodies. Example images are shown (E). The immunofluorescence intensity ratio of centromeric Aurora B/ACA was determined on around 250 chromosomes in 10 cells (F). Data information: Means and error bars representing S.D. are shown unpaired t-test). Scale bars, 10 μm. G, H HeLa and the Sgo1-K492A cells were transfected with siRNA, and treated with nocodazole for 5 hr. Mitotic cells were cytospun onto coverslips and fixed for immunostaining. Example images are shown (G). The immunofluorescence intensity ratio of centromeric TOP2A/arm TOP2A was determined on around 280 chromosomes in 10 cells (H). Data information: Means and error bars representing S.D. are shown unpaired t-test). Scale bars, 10 μm.
Figure 3(A) scRNA-seq profiling of SCG cultures using 10X Genomics Chromium Single-Cell v3 Reagent Kits enabled the detection of viral RNAs in a small neuronal subpopulation (cyan) during reactivation (B) Differential gene expression analysis of cellular transcripts showed a significant upregulation of at least 19 viral transcript units (TU) and a subset of cellular genes in neurons undergoing reactivation Three host transcripts were also downregulated. Gadd45b is highlighted with a green asterisk. Vertical hashed blue lines indicate Log2 fold changes >1.5 and < -1.5, while the horizontal hashed blue line indicates an adjusted p-value of 0.01. Significantly regulated genes are named and shown as magenta circles. (C) Heatmap showing the relative levels of selected cellular and viral transcripts in neuronal subpopulations containing either minimal HSV-1 mRNAs, indicative of latent or uninfected neurons, or with abundant HSV-1 mRNA, indicating reactivation
Figure 4(A) The islets of WT, Pdia4-/- (KO) and Pdia4tg/tg (TG) BKS mice were isolated and grown in complete DMEM medium containing 3.3 mM (LG) and 30 mM glucose (HG) for 12 h. The islets stained with propidium iodide (PI), photographed, and quantified. Scale bar = 50 μm. Data information: Data from 3 experiments are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant. (B) The islets from the mice (A) were treated with 3.3 mM (LG) or 30 mM glucose (HG). After lysis, the lysates underwent immunoblotting analysis using the antibody against Beclin 1, LC3 , p62 and actin. The islets from the mice (A) were incubated with MitoGreen plus MitoSOX in the presence of glucose at 3.3 mM (LG) and 16.7 mM (HG). Mitochondrial ROS in the islets were visualized and quantified. Scale bar = 100 μm. Data information: Data from 3 experiments are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant. The islets from the mice (A) were incubated with Hoechst 33342 (Ho) plus CM-H2DCFDA in the presence of glucose at 3.3 mM (LG) and 16.7 mM (HG). cytosolic ROS in the islets were visualized and quantified. Scale bar = 100 μm. Data information: Data from 3 experiments are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant. (E) Mitochondria isolated from the mouse islets (A) were measured for the activity of ETC CI (left), CII/III (middle) and CIV (right) using MitoCheck assays. Data information: Data from 3 experiments are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant. (F) The membrane fraction of the pancreas from the mice (A) was measured for Nox activity using luminometric assays. Data information: Data from 3 experiments are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.
a) Expression of GCaMP3.figf3(a) Expression of GCaMP3.0 in the mushroom body of an individual fly, focused on the horizontal lobes. The red line indicates a region of interest used to determine changes in fluorescence emission. Scale bar represents 50 μm. (b) False color-coded image of Ca2+ activity in the horizontal mushroom body lobes shown in a. Warm colors indicate high levels, cold colors indicate low levels or no Ca2+ activity. The numbers indicate changes in fluorescence ΔF (%). (c,d) Time course of Ca2+ increase in horizontal mushroom body lobes of 3-d-old and 30-d-old Spd− flies evoked by the odors 4-methyl-cyclohexanol (MCH) or 3-octanol (OCT) in comparison with the diluent, mineral oil (n = 5 flies, non-parametric Mann-Whitney U test found no substantial difference between the Ca2+ increase of 3-d-old and 30-d-old Spd− flies evoked by the odors). The gray bars indicate the duration of the odor stimuli. Data are presented as mean ± s.e.m.
Figure 8MQ can bind both high molecular weight (HMW) targets such as mutant p53 and low molecular weight (LMW) targets e.g. GSH and Cysteine. MQ conjugation to GSH (GS-MQ) is reversible, indicating that MQ can transfer between multiple HMW and LMW cellular targets. Thus, GS-MQ serves as an intracellular drug reservoir. MRP1 regulates GSH and oxidized GSH (GSSG) content and exports GS-MQ. Therefore, MRP1 inhibition potentiates the effect of APR-246/MQ through a dual mechanism: 1) inhibition of GS-MQ efflux and 2) disruption of the intracellular thiol balance sensitizing cells to oxidative stress. We postulate that a MQ reservoir is similarly formed by conjugation to other thiols (R-SH) targets, e.g. Cys. Furthermore, xCT and MRP1 collectively regulate LMW target availability and thus the intracellular reservoir of MQ, thereby governing sensitivity to APR-246.
Figure 3a-c Jurkat T cells migrated in the presence of 10 nM CXCL12 with increasing concentrations of (a) Gal-3, (b) Gal-3 CRD, and (c) Gal-1 (A-C: n = 4). D Human CD4+ T cells migrated in the presence of 10 nM CXCL12 alone and with 10 nM Gal-3 (dark green), Gal-3 CRD (light green), and Gal-1 (blue, n = 3). E-F (E) Jurkat T cells migrated to increasing concentrations of CXCL12 alone (black) and CXCL12 in the presence of 0.1 nM of Gal-3 CRD (light green). (F) The inhibitory effect of Gal-3 CRD is shown as percentage of the chemotactic effect of CXCL12 (E-F: n = 3). G Jurkat T cells were allowed to migrate in the presence of CXCL12 at increasing concentrations alone and with 0.1 nM Gal-1 or 100 nM Gal-1 (n=3). H Jurkat T cells did not migrate in the sole presence of 1 nM to 1 µM Gal-3, Gal-3 CRD (both n = 5), or Gal-1 (n = 4). I The viability of Jurkat T cells was assessed after incubation with 1 µM CXCL12 alone and in the presence of Gal-3, Gal-3 CRD and Gal-1 (n = 2). (J) THP-1 cells migrated in the presence of 10 nM CXCL12 alone and with 10 nM Gal-3, Gal-3 CRD and Gal-1 (K) neutrophils migrated in the presence of 10 nM CXCL12 alone and with 10 nM Gal-3, Gal-3 CRD and Gal-1 L Human eosinophils migrated in the presence of 10 nM CCL26 alone and with 10 nM Gal-3, Gal-3 CRD, and Gal-1 (n = 3). M CD4+ T cells migrated in the presence of 1 nM CCL17 alone and with equimolar concentrations of Gal-3, Gal-3 CRD, and Gal-1 (n = 4).
Figure 6(A) At the Golgi, the recruitment of PI4KB can be controlled through the action of ACBD3. PI4KB can recruit c10orf76 to the Golgi, with this playing a role in the dynamics and localization of GBF1 and active Arf1-GTP and their downstream effectors (1). Active, membrane localized Arf1-GTP can activate PI4KB (2). (B) In a c10orf76-knockout cell, there is decreased recruitment of GBF1 and active Arf1, with this potentially describing the decreased levels of PI4P. (C) In enterovirus infected cells there are multiple mechanisms that can alter PI4P levels and Arf1 activation. The 3A proteins from different viruses can activate PI4KB, primarily through hijacking ACBD3 (i), as well as directly binding to GBF1 (ii). Viruses that require c10orf76 to replicate rely on the PI4KB-c10orf76 interface, emphasising the importance of manipulating PI4KB-c10orf76 and GBF1/Arf1-GTP dynamics to facilitate viral replication.
Figure 6(i) When Shigella invades and multiplies within epithelial cells, PAMPS and DAMPs are released. Host cells detect these PAMPs and DAMPs, and subsequently trigger apoptosis as host defense to clear bacterial infection. (ii) To counteract this, Shigella delivers OspC1 effector, and directly or indirectly prevents caspase-8 activation and apoptotic cell death. (iii) On the contrary, host cells detect bacterial disturbance of caspase-8 activation, resulting in induction of necroptosis as a backup host defense. (iv) Again, Shigella subsequently delivers OspD3 effector, which targets RIPK1 and RIPK3 for degradation via its protease activity to prevent necroptosis.
Figure 1The VPR and DPR (right) were dissected from E10.5 Pdx1-GFP embryos (left). Scale bar: 500 µm. DPR, dorsal Pdx1-expressing region; VPR, ventral Pdx1-expressing region; Duo, duodenum bud. FACS gating for sorting GFPlow and GFPhigh cells from the VPR and DPR. The ratios of GFPhigh cells to GFP+ cells in the VPR and DPR. The data show the mean ± SEM; n = number of independent biological replicates, unpaired t-test. ***p-value < 0.001. PCA plot of single-cell RNA-transcriptomes of GFP+ (circle), GFPlow (triangle) and GFPhigh (square) cells from the VPR (blue) and DPR (orange). Each point represents a single-cell. Three groups of cells are included in three colored circles. Hierarchical clustering of 815 genes correlating with the first two PCs identified three groups of cell types and four major distinct clusters (a-d) of genes (p < 1 ×10-9, cell cycle-related genes are excluded). Each column is a single-cell, and each row represents one gene. Cluster-specific TFs are listed on the right. The genes in bold are known to have roles in pancreatic development. L, GFPlow; H, GFPhigh. Selected GO categories enriched among the four clusters of genes in (E).
Secretagogin locus in the paraventricular nucleus of the hypothalamus A–A3 Secretagogin+ neurons populate the paraventricular, dorsolateral, ventromedial, periventricular and arcuate nuclei of the mouse hypothalamus (Paxinos & Franklin, ).Figure 1A-A3 Secretagogin+ neurons populate the paraventricular, dorsolateral, ventromedial, periventricular and arcuate nuclei of the mouse hypothalamus (Paxinos Franklin, ). Red circles denote the localization of neuronal perikarya and their relative densities. AHP, anterior hypothalamus; Arc, arcuate nucleus; DM, dorsomedial nucleus; ME, median eminence; Pe, periventricular nucleus; PVN, paraventricular nucleus, PVNm, magnocellular part; SON, supraoptic nucleus; VM, ventromedial nucleus. B-B2 Largely non‐overlapping distribution of AVP+, oxytocin+ and secretagogin+ (sgcn+) neurons in the magnocellular PVN. The mousesupraoptic nucleus (SON) harbored vasopressin+ and oxytocin+ but not secretagogin+neurons. Open arrowheads pinpoint single‐labeled neurons. Solid arrowhead denotes AVP/secretagogin dual‐labeling. lv, lateral ventricle; PVNm, magnocellular part of the paraventricular nucleus; scgn, secretagogin.B3, B4 Secretagogin+neurons had smaller somatic diameters than AVP+ or oxytocin+neurons yet without a difference in their diameter quotient, a measure of ovoid profiles (*P 0.05, Student's t‐test). C-D3 Terminal‐like profiles in the posterior pituitary (arrowheads in C) suggesting that secretagogin can co‐exist, even if infrequently with oxytocin. Solanum tuberosum lectin (Sol. tub) was used to identify blood vessels.
Figure 4(A) Schematic representation of microbiotal transfer experiments where recipient mice are gavaged with a suspension of fecal pellets in PBS from donor mice that are either fed a Regular-chow Diet (RD) or a high-fat diet (HFD). (B) Experimental timeline describing preparation of mice for microbiotal transfers where mice receive 5 days of antibiotics (Neomycin and Ampicillin) at 6 weeks of age. Starting at 7 weeks of life, RD x RDT- and HFD x RDT-mice receive weekly microbiotal transplants from RD donor mice and HFD x HFDT-mice receive weekly microbiotal transplants from HFD donor mice until sacrifice at week 13. At the age of 11 weeks, mice are subjected to 4 laser burns per eye. (C) Weight gain and (D) area under the curve of percentage weight gain of RD x RDT, HFD x RDT and HFD x HFDT mice; n= 13(RDxRDT), 12(HFDxHFDT), 14(HFDxRDT); CI 99%. (E) Representative circle charts of relative abundance of bacterial phyla in gut microbiota of RD-fed mice receiving a RD transfer and HFD-fed mice receiving a HFD or RD transfer (F) relative proportion per experimental group of different phyla; n= 5(RDxRDT), 5(HFDxHFDT), 4(HFDxRDT); Bacteroidetes; CI 99%, Firmicutes; CI 95%, Proteobacteria; CI 95%, Actinobacteria and Spirochaetes. (G) Compilation of compressed Z-stack confocal images of FITC-dextran-labeled CNV and single-plane confocal images of isolectin B4-stained choroidal flat mounts from RD x RDT, HFD x RDT and HFD x HFDT mice. (H) Quantification of area of FITC-dextran-labeled CNV over area of isolectin B4-stained laser impact area fold RD x RDT; n= 6(RDxRDT), 9(HFDxHFDT), 9(HFDxRDT), with 15(RDxRDT), 21(HFDxHFDT), 16(HFDxRDT) burns total; CI 95%. (I) Concentration of gut absorbed Evans Blue in serum 24 hours after oral administration in RD- and HFD-fed mice, after RD or HFD microbiotal transplant; n= 3(RDxRDT), 3(HFDxHFDT), 4(HFDxRDT); CI 95%. (J) mRNA expression of Il-1β; n= 5(RDxRDT), 4(HFDxHFDT), 5(HFDxRDT), Il-6; n= 5(RDxRDT), 4(HFDxHFDT), 4(HFDxRDT); CI 99%, Tnf-α; n= 5(RDxRDT), 4(HFDxHFDT), 4(HFDxRDT); CI 95% and Vegf-a; n= 5(RDxRDT), 4(HFDxHFDT), 5(HFDxRDT); CI 95% in choroids.
Snai1 does not regulate BH3‐only protein expression in the intestinal epithelium but regulates Serinc3 expression A–C Droplet digital PCR analysis of Bmf, Bbc3/Puma and Bcl2l 11/Bim after conditional Snai1 loss in in vitro organoid culture.Figure 8A-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). D qRT-PCR analysis of Serinc3 downregulation after conditional Snai1 loss in in vitro organoid culture. VillinCreERT2 Snai1+/+ (control) and VillinCreERT2 Snai1fl/fl SI organoids were treated for 24 (P = 0.0001) and 72 h (P = 0.006) with tamoxifen. Bars represent mean ± SD. n = 3 mice per group. E SW480 cells, which transiently express GFP‐SNAI1, were used to detect direct binding of SNAI1 to the promoters of known target genes CDH1, IL8 and a novel target SERINC3 revealed by microarray analysis. An unrelated DNA region was used as a negative control. Anti‐GFP antibody was used to immunoprecipitate GFP‐tagged SNAI1, while IgG control antibody was used as a negative control. The results are given as relative enrichment compared to input material and are representative of three independent experiments.
a) Atg7−/− livers display decreased ERK phosphorylation.f4(a) Atg7−/− livers display decreased ERK phosphorylation. Immunoblots for the indicated proteins in liver homogenate (Hom) and cytosolic (Cyt) fractions of control (Con) and liver-specific Atg7−/− mice are shown. The bars represent mean±s.e.m. *P0.05, **P0.01, ***P0.001 compared with Con; Student's t-test, n=4. (b) Atg7−/− livers display decreased ERK2 dimers. Immunoblots show the indicated proteins in Hom from Con and Atg7−/− livers. The bars represent mean±s.e.m. *P0.05, ***P0.001 compared to Con; Student's t-test, n=4-5. Arrows indicate p42 monomers and dimers. (c) Atg7−/− brown adipose tissues (BAT) display decreased ERK phosphorylation. Immunoblots for indicated proteins in Hom from Con and Atg7−/−BAT. The bars represent mean±s.e.m. **P0.01 compared with Con; Student's t-test, n=4-6. (d) Atg7−/− livers exhibit decreased nuclear ERK phosphorylation. Immunoblots show the indicated proteins in homogenate (Hom, lane 1) and nuclear fractions (lanes 2-5) from Con and Atg7−/− livers. The bars represent mean±s.e.m. ***P0.001 compared with Con; Student's t-test, n=4-5. (e) LC3 C terminus glycine-deleted (ΔG) mutants exhibit decreased ERK phosphorylation. Immunoblots for indicated proteins in total lysates from CFP-LC3- and CFP-LC3ΔG-transfected NIH/3T3 cells exposed or not to EGF (10 min). The bars represent mean±s.e.m. ***P0.001 compared with Con; Student's t-test, n=8.
Figure 1 [A] The same MVs from GB03 caused opposed impacts on plants grown in different medium. The petri dishes contain plastic partitions (red dotted lines) that separate different medium. 0.5 MS and 0.05 MS indicate 1/2-strength (nutrient-sufficient) and 1/20th-strength (nutrient-deficient) Murashige & Skoog medium. Images were taken at 11 days after treatments (DAT).  [B] Quantification of total leaf area per plant (square centimeter, cm2). Values correspond to the means ± SE of three biological replicates. Different letters denote significant differences at p < 0.05, Tukey's multiple comparison test within each group of the same DAT.  [C] Effective quantum yield of photosystem II in plants. n=3 biological replicates, mean± SE. Asterisks denote significant differences at * p < 0.05, ** p < 0.01 and *** p < 0.001, Dunnett's multiple comparison test (comparing with the control) within each group of the same DAT  [D] Cell death visualization by trypan blue staining of 11 DAT leaves. Bar= 1mm  [E] Gene Ontology (GO) comparative analysis of Arabidopsis genes that were induced at 5 DAT by nutrient deficiency alone (0.05C vs 0.5C) and that were induced by the nutrient deficiency plus GMVs (0.05T vs 0.5C). Diagrams are designed based on VirtualPlant platform. The size of circles represents the number of genes in each GO category. Scale color bar indicates the p-value cut-off of over-representation equal or less than the cutoff for each GO category. Darker color indicates higher possibility of each GO category.
a) Western blotting showing downregulation of lap (i) or increase in.f7(a) Western blotting showing downregulation of lap (i) or increase in Atg8a-II (ii) expression level in adult fly heads on lap downregulation using the UAS-RNAi lines lapGD12732 or lapKK105767, or the heterozygous allele lap1. Quantification of lap/actin and Atg8a-II/actin is shown. Genotypes: Control w; elav-GAL4/+; for the RNAi lines: w; elav-GAL4/ lapKK105767 and w; elav-GAL4/+; lapGD12732/+; for the lap1 allele: w; elav-GAL4/+; lap1/+. (b) Western blotting showing the accumulation of tau in Drosophila adult flyheads on lap downregulation using the UAS-RNAi lines lapGD12732 or lapKK105767, or the heterozygous allele lap1. Quantification of tau/lapGD12732 is shown. Genotypes: Control w; elav-GAL4/+; for tau-WT: w; elav-GAL4/+; UAS-tau-WT/+; for RNAi lines: w; elav-GAL4/ lapKK105767; UAS-tau-WT/+ and w; elav-GAL4/+; lapGD12732/tau-WT; for the lap1 allele: w; elav-GAL4/+; lap1/+ or w; elav-GAL4/+; lap1/UAS-tau-WT.
Ccq1 promotes nucleosome stability at native subtelomeres.Figure 2A Left: Schemes of CLRC and the shelterin complex. Middle and right: Scheme depicting the position of the ura4+ reporter gene and heterochromatin islands relative to telomeric repeats and TAS regions; note that the minichromosomesome Ch16 does not contain TAS. B-C ChIP-qPCR analyses of H3K9me2 (B) and H3 (C) in WT and ccq1Δ cells (n = 3 independent experiments. D Fold change of WT over ccq1Δ for H3K9me2 and H3 level Data information: In (B, C), data are normalized to input and to the average of three euchromatic loci (EC) as internal contro and represented as mean ± SEM
Figure 6Glucose administration leads to R388 hypermethylation of Sirt7 in mouse hepatocyte. After fasting for 16 hrs, mice were injected with glucose. Hepatic tissue was harvested in a time-dependent manner as indicated (n=3 for each time point). SIRT7 protein was immunoprecipitated from whole liver extracts. R388 methylation of Sirt7 was determined by western blot (A Scale bar in the upper panel, 500 µm; scale bar in the lower panel, 100 µm Glucose administration leads to R388 hypermethylation of Sirt7 in mouse hepatocyte. After fasting for 16 hrs, mice were injected with glucose. Hepatic tissue was harvested in a time-dependent manner as indicated (n=3 for each time point). SIRT7 protein was immunoprecipitated from whole liver extracts. R388 methylation of Sirt7 was determined b immunohistochemical staining (B). Scale bar in the upper panel, 500 µm; scale bar in the lower panel, 100 µm AICAR and PRMT6 inhibitor decrease R388 methylation and epigenetically downregulate SIRT7-target genes. MEF cells stably expressing Flag-SIRT7 were incubated with or without PRMT6i for 12 hrs, followed by treatment with 1 mM AICAR for 12 hrs. R388 methylation of SIRT7 was determined by western blot (C) (Data shown are mean±SD, n=3 experimental replicates, **p<0.01; ***p < 0.001, unpaired two-tailed t test AICAR and PRMT6 inhibitor decrease R388 methylation and epigenetically downregulate SIRT7-target genes. MEF cells stably expressing Flag-SIRT7 were incubated with or without PRMT6i for 12 hrs, followed by treatment with 1 mM AICAR for 12 hrs H3K18ac level at SIRT7-target gene promoters were determined by ChIP-qPCR. Normal rabbit IgG was used as a negative control (D) (Data shown are mean±SD, n=3 experimental replicates, **p<0.01; ***p < 0.001, unpaired two-tailed t test AICAR and PRMT6 inhibitor decrease R388 methylation and epigenetically downregulate SIRT7-target genes. MEF cells stably expressing Flag-SIRT7 were incubated with or without PRMT6i for 12 hrs, followed by treatment with 1 mM AICAR for 12 hrs mRNA expression was determined by qPCR analysis (E) (Data shown are mean±SD, n=3 experimental replicates, **p<0.01; ***p < 0.001, unpaired two-tailed t test AICAR and PRMT6 inhibitor decrease R388 methylation and epigenetically downregulate SIRT7-target genes. MEF cells stably expressing Flag-SIRT7 were incubated with or without PRMT6i for 12 hrs, followed by treatment with 1 mM AICAR for 12 hrs Mitochondria mass was determined by Mito Tracker Red staining (F). (Data shown are mean±SD, n=3 experimental replicates, **p<0.01; ***p < 0.001, unpaired two-tailed t test G. The model illustrating regulation of SIRT7 by arginine methylation. R388 methylation inhibits the H3K18 deacetylase activity of SIRT7 to maintain mitochondria homeostasis in an AMPK-dependent manner