EMBO/sd-character-level-ner huggingface dataset:
(A) Picrosirius red (PSR) staining of collagens (red) in PDAC tissue following surgical resection. Scale bar represents 200 µm. (B) Quantification of PSR in low-grade (1-2) and high-grade (3) tumors indicated in panel A as percentage of area. n=15 primary PDAC samples. Data information: data are represented as mean±SD, Student's t-test.
Representative western blot images and quantification of phospho-IRS1 (Y612) and phospho-AKT (T308) over GAPDH with insulin stimulation (10 nM or 100 nM, 5 min) after iron treatment (250 µM, 24 h).
(D-G) Cortical neurons around the lesion in MCL‐1Δ/Δ animals are positive for the autophagic marker LC3. Brain sections from animals with the indicated genotypes (P14 for E, G; P7 for H) were stained for LC3 (Green) and the neuronal marker NeuN (in H, red), along with the nuclear stain Hoechst (Blue). Confocal images were taken using × 10 (E) or × 63 (G, H) objectives. Scale bars=200 μm (E); 50 μm (G, H). Quantification of the LC3 staining is shown in D. The total number of cells was determined by counting the Hoechst‐positive nuclei. Data are expressed as percent of LC3‐positive cells in at least three animals per genotype±s.d. *P0.01. (F) Quantification of the total surface area occupied by autophagosomes. Data are expressed as percent of total cortical area covered by autophagosomes in at least 16 EM images per genotype±s.d. P0.005 (I) Representative EM images from MCL‐1+/Δ and MCL‐1Δ/ΔP14mice. N, nucleus; *, autophagosomal structures; arrowheads, double membrane; arrow, mitochondrion inside a vesicle.
Parental and TGF-β isogenic cell lines were treated with 50nM volasertib for 72 hours. Cells were then harvested, and lysates were immunoblotted for cleaved PARP and γH2AX proteins were subsequently quantitated and normalized with β-actin (B).
(c) The heatmap shows the correlation coefficients between proteins (rows) and clinical parameters (columns).
Figure 4. Dynamic reorganization of chromosomes during mitosis.. (F) Bottom left: log-ratio between cdc20 and cdc15 arrested cells. Upper right: log-ratio of cdc15-arrested and cdc15 -released 40 min cells. Blue to red color scales reflect the enrichment in contacts in one population with respect to the other (log2). Yellow arrowheads: inter-centromere contacts. Pink arrowheads point at the right arm anaphase loop.
As in Figure 2B, normalized counts of processed fragments mapping to the right arm of Alu RNAs that are differentially processed (rows) between AD and no AD for each MAP patient (columns) (Dataset EV2). Red corresponds to higher normalized counts of processed Alu RNA fragments.
HEK293T cells transfected with GST-tagged empty vector, NEMO-WT, or NEMO-K326R, with or without Strep-tagged MARCH2 were infected with VSV-GFP. (D-F) Viral replication was determined by fluorescence microscopy (D)
D) he effect of the pie1 and mbd9-1 mutations on the formation of the SWR1 complex as determined by IP-MS. Transgenic plants expressing Flag-tagged MBD9, PIE1, and CHR11 in the WT and mutant backgrounds were subjected to the IP-MS experiment with anti-Flag agarose.
(E) SGC7901 cells were incubated with chlorpromazine (CPZ, 50 μM), genistein (GEN, 200 μM), 5-(n-ethyl-n-isopropyl)-amiloride (EIPA, 100 μM), or methyl-β-cyclodextrin (MβCD, 10 mM), following by the incubation of Cy3-CRNDE-EXO. Confocal microscopy was used to detect the Cy3-labelled CRNDE in SGC7901 cells. The nuclei were stained with DAPI. Right: Flow cytometry was performed to quantitate the Cy3-positive cells. Data information: The results shown are from three biological replicates. Data are expressed as mean ± SD. one-way ANOVA.
C) Representative confocal microscopy images of calcein green labelled FIS organoids of a healthy individual and a CF patient, before and 60 min after stimulation with Fsk (5 uM). Scale bar, 200 μm.
(D-E) Scatterplot displaying the up (red) or down (blue) regulation of probes (log2 fold change >= 2) identified by sequential pairwise comparisons across either αβ (D) or γδ (E) development.
C) Western blot analysis for protein levels in Raji cells that expressed NTC or YTHDF3 shRNAs and knocked down MYC or not (C). HPRT1 and β-actin serve as negative and loading controls, respectively. Data are representative of at least three independent experiments.
(E) Surface representation of the crystal structure (PDB: 5IGQ) of the COP1 WD40 domain colored according to electrostatic surface potential, calculated by APBS (Baker et al, 2001), in complex with the TRIB1 tail (cyan). Inset shows zoomed view of TRIB1 Q356 inserting its sidechain into the central channel of the COP1 WD40 domain.
(E) Determination of the effect of the arp4-1, arp6 and swc6-1 mutations on flowering time. The top panel shows the number of rosette leaves in the WT, arp4-1, arp6, and swc6-1 mutant plants; the bottom panel shows a photograph of the plants. Rosette leaves from at least 20 plants were counted for each genotype. Values are mean ± SD. ** P<0.01, student's t test.
A. In each experiment, one transcriptional regulator with an inducible promoter is rapidly overexpressed in response to 1 µM β-estradiol.
(C) Determination of cellular ROS in Pacs1+/+ and Pacs1-/- FOB cells with CellRox Green. Quantification shows the mean fluorescence intensity (MFI) from three separate pairs of Pacs1+/+ and Pacs1−/− mice. Two-tailed paired t test, **P < 0.01.
(C) RT-qPCR analysis of the mRNA levels of methyltransferases and demethylases in P493-6 cells treated with Tet for 0h or 24h. Data were presented as mean (±SD), n = 3 biological replicates. * P<0.05 relative to corresponding -Tet group (Student's t‐test).
Western blots show that the degree of Ago3 phosphorylation was reduced upon Siwi KA mutant as well as Siwi WT and DDH mutant expression.
A Expression of phosphorylated and total STAT3 and NF-κB p65 in the colon of wildtype and Vil-Ogt KO mice
A-C. Analysis of (A) IL-17A expression by wild type CD4T cells, followed with the analysis of (B) GM-CSF and (C) GM-CSF and IFNγ co-expression by Th17 cells.
(H) Measurement of serum fluorescein isothiocyanate (FITC)-dextran to evaluate the permeability of the intestines. Data are mean ± SEM from five biological replicates per group. *P<0.05, **P<0.01 using one-way ANOVA.
C Firefly luciferase expression of constructs that contain distal and proximal enhancers of OCT4 after transfection of pRh6 and 2a2iL-RH6. The ratio of firefly luciferase expression to Renilla luciferase expression (expressed from co-transfected plasmid) measured 48 h after transfection showed proximal enhancer activity in pRH6 and distal enhancer activation in 2a2iL-RH6. OCT4 PE-Luc ***P<0.001, OCT4 DE-Luc *P<0.05 (t-test). Data presented as mean ± SD (n=3).
(A−I) Induction of GOMED in Atg5 KO MEFs by CBM treatment. (C-F) Involvement of Golgi membranes in the generation of AL-like structures. (C) CLEM analysis of mCherry-syntaxin 6-expressing Atg5 KO MEFs. Cells were treated with CBM (2 mM) for 24 hr and observed using fluorescence and electron microscopy. mCherry-syntaxin 6puncta merged with the AL-like structures. Scale bar = 5 µm. "N" indicates nucleus. A magnified image of the dashed square is shown in the inset. Scale bars = 2 µm.
B) lexatumumab treated OVCAR3 lysates for indicated early time points were analyzed for caspase-3, ROCK1, pMLC, PARP, PD-L1 and CMTM6 etc. as indicated.
E, F, Luciferase assay in rTg4510:Fluc-EGFP mice. E, Left, scheme of brain regions used for luciferase assay color-coded by their vulnerability to tau pathology. Right, specific luciferase activity measured in the indicated brain regions of 4-month-old and 16-month-old rTg4510:Fluc-EGFP mice normalized to control littermates. F, Fluc-EGFP protein quantity in the indicated brain regions of rTg4510:Fluc-EGFP mice measured by Western blot (for representative blots, see Fig. EV3B). Values are normalized to control littermates. N=6 rTg4510:Fluc-EGFP mice, 4 WT:Fluc-EGFP mice, 6 CaMKIIα-tTA:Fluc-EGFP mice and 1 tetO-tauP301L:Fluc-EGFP mouse at 4 months; 4-5 rTg4510:Fluc-EGFP mice, 5 WT:Fluc-EGFP mice, 3 CaMKIIα-tTA:Fluc-EGFP mice and 4 tetO-tauP301L:Fluc-EGFP mice at 16 months. WT:Fluc-EGFP, CaMKIIα-tTA:Fluc-EGFP and tetO-tauP301L:Fluc-EGFP littermates did not differ from each other and were pooled together as controls. Light-red and dark-red asterisks indicate comparisons to the corresponding littermate group (one-sample t-test), black asterisks indicate significant comparisons between corresponding brain regions of rTg4510:Fluc-EGFP mice at 4 vs. 16 months (two-tailed t-test).
(F) Phylogenetic characteristics of BetaCoV/Shenzhen/SZTH-003/2020, and this isolate was indicated with a triangle.
(D) EZH2 knockdown C4-2 cells were transfected with the bicistronic reporter vector in combination with empty vector, Myc-tagged EZH2 WT or deletion mutants followed by western blot analysis with indicated antibodies (bottom) and luciferase assay (top). Data shown as means±SD (n=3). * P<0.01.
(C) Pacs1-/- FOB cells were stimulated with 0.625 µM thapsigargin (black arrowhead) under Ca2+-free conditions to measure intracellular Ca2+ stores. Kinetic traces of four independent experiments are shown (Pacs1+/+ gray, Pacs1-/- pink) with the mean overlaid in bold (Pacs1+/+ black, Pacs1-/- red).
(c) Jurkat cells were transfected with 24K and 33K Atg5 using lentiviral gene transfer. Cell death was observed as a consequence of enforced expression of truncated Atg5 within two days. Morphological analysis (Diff-Quik) is also shown and revealed that the type of death was apoptosis (nuclear condensation, cell shrinkage).
H Confocal image of proliferating astrocytes at P10 (ACSBG1+, cyan; MCM2+, magenta) that did not express NESTIN (white). I, J Quantification of total proliferating astrocytes (ACSBG1+/KI67+ for P3/P7; ACSBG1+/MCM2+ for P10/P14) per area at distinct timepoints per total DG (I) or hilus, GZ and ML (J). Data information: All data are represented as mean ± SEM; number of experimental animals throughout figure: n = 5 (P3) and n = 6 (P7, P10, P14), I) indicated by red dots; scale bars ,H = 10 µm,
(E) Normalized expression levels of the native core promoters. Their activities spanned over a broad range of three orders of magnitude (promoter constructs contained block 1.11 and block 7.11 combination as nucleosomal sequences). Each color represents a different class of core promoter architecture. The middle hinge represents the median. The Interquartile range the difference between the 75th and 25th percentiles. Individual points represent values over 1.5 times the interquartile range. 3-4 biological replicate measurements. (including new cell transfection procedures and measurements of promoter activities).
(C) Immunoblot analyses performed using Abs raised to LC3 or β-actin. Experimental conditions were identical to those outlined in panel A. Gel images representative of three experiments are shown.
(F) α-Synuclein and CSPα were immunoblotted in WT and MPS-IIIA total brain lysates at indicated ages Total protein levels were quantified.
(A) Model of post-influenza bacterial infection illustrating infection with sub-lethal dose of influenza virus (25 pfu) followed by sub-lethal dose of secondary bacterial challenge (Streptococcus pneumoniae serotype 19F, 2x105 cfu) 7 days later. Where appropriate, mice lungs were analysed at days 0, 1 and 3 post-secondary bacterial infection, corresponding to days 7, 8 and 10 post-influenza virus infection, respectively
I, ROC of the diagnostic prediction model with plasma INSL5 level in individuals with VCA-IgA-negative plasma in all three cohorts.
A LC-ESI-MS/MS spectrum of Dnmt3a pulled down by Biotin-As in NIH3T3 cells. NIH3T3 cells were treated with 10 μg/mL Biotin-As for 2 hours, followed by pull-down assay and determination using LC-ESI-MS/MS.
F. Quantification of unperfused vessel segments. Anti-CSF1 antibody treatment induces a reduction in the number of unperfused vessel segments (asterisk). (n=5 mice per group) (300µm depth stack). Statistical analysis: A.F. t-test; Error bars: A-C-F: meanSD;
D, Quantification of the fraction of cells with EGFP foci among the cells with and without tau expression and p-tau pathology. N=4 rTg4510:Fluc-EGFP mice, 3 WT:Fluc-EGFP mice, 3 CaMKIIα-tTA:Fluc-EGFP mice and 3 tetO-tauP301L:Fluc-EGFP mice. WT:Fluc-EGFP, CaMKIIα-tTA:Fluc-EGFP and tetO-tauP301L:Fluc-EGFP littermates did not differ from each other and were pooled together as controls. One-way ANOVA with Tukey's multiple comparisons test. ANOVA: ****p < 0.0001. Pairwise comparisons between groups are indicated on the graph.
A, B Immunoblot analyses of the protein abundance of the METTL3/METTL14/WTAP heterotrimer in PBMCs (A) and BMDMs (B) upon challenge with VSV-eGFP, poly(I:C), HSV-1 or HSV60 at the indicated time points.
(d) Subculture day 3 representative GPA/CD43 plots and subculture day 6 CD45/CD43 plots are shown (n=6 and n=5 biological replicates
H Summary of the PPIs found in the high confidence CSK and CRKL first neighbors subnetwork (see C) that were validated by co-immunoprecipitation (see D to G). Interactions validated and non validated by co-immunoprecipitation are shown using red and blue edges, respectively. Interactions untractable by co-immunoprecipitation analysis due to the lack of specific antibodies are shown as gray edges.
Either young WT (A, B) or old APPPS1 (C-E) tissue was treated with clodronate (Clo) to remove CD68 positive cells or vehicle Ctr from 1 until 7 DIV. Treatment was stopped and subsequently old (A, B) or young (C-E) tissue was added to the culture as schematically indicated in A and C. and analyzed 14 days after. Removal of CD68 positive cells in either young WT or old APPPS1 tissue prevents amyloid plaque clearance in the co-culture model.(A) Immunofluorescence analysis of the old APPPS1 slice co-cultured with the young WT slice pre-treated with Clo and Ctr and immunostained with CD68 (red) and M3.2 (green). Scale bar: 50 µm.(B) Quantitative analysis of core-only plaques in the old APPPS1 tissue co-cultured with the young WT tissue pre-treated with Clo and Ctr as indicated in A reveals a decreased number of core-only plaques upon Clo treatment. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, including total of 6 independent slice culture dishes (***P < 0.001).(C) Immunofluorescence analysis of the old APPPS1 slice treated with Clo and Ctr and subsequently co-cultured with the young WT slice and immunostained with CD68 (red) and M3.2 (green). Scale bar: 50 µm.(D) Area of CD68 positive cells (CD68 coverage) in the old APPPS1 tissue treated with Clo and Ctr and subsequently co-cultured with the young WT tissue as indicated in C. CD68 coverage is reduced upon Clo treatment. The values are normalized to CD68 coverage of the Ctr and represent mean ± SEM from 3 independent experiments, including total of 6 independent slice culture dishes (***P < 0.001).(E) Quantitative analysis of core-only plaques in the old APPPS1 tissue treated with Clo and Ctr and subsequently co-cultured with the young WT tissue as indicated in C reveals a decreased number of core-only plaques upon Clo treatment. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, including total of 6 independent slice culture dishes (**P < 0.01).
C. Detected 13C6-labeled proteins were analyzed by IPA for prediction of functions associated with proteins decreased or increased by >2-fold in MDA-MB-231-EV-treated cells. Pie charts show the numbers of proteins categorized by subcellular localization.
(A) mtDNA NGS performed in 84 hiPSC clones distributed in non-mitochondrial disease group (n=43 hiPSCs derived from 16 individuals) and MELAS group (n=41 hiPSCs derived from 3 patients). See also Table S1 and Table S2.
D, E, There was no difference in hIGFREO and WT glucose tolerance (as measured by glucose tolerance test and area under the curve (AUC)) (n=7-9 mice per group).
A Autoradiography of in-organello mitochondrial translation products derived from HEK293 wild-type cells in the presence of tobramycin, incorporation of 35S-Met and 35S-Cys in MT-CO1 protein. Following in-organello translation proteins were immunoprecipitated and analyzed by autoradiography. Lane 1, 3: controls; lanes 2, 4: in-organello translation in the presence of 1000 µM tobramycin. MT-CO1 bands were quantified and ratio of 35S-Cys / 35S-Met calculated, the 35S-Cys / 35S-Met ratio in the absence of tobramycin was set as 1 (n=3), error bars indicate SEM.
Structural alignment of the core OTU folds (central β-sheet and two supporting α-helices) from CCHFV vOTU (blue, PDB 3PHW) and EschOTU (orange). Surrounding regions are less-well conserved and shown as semi-transparent.
Mitochondria isolated from the untransfected cells were resuspended in the cytosol isolated from the cells transfected with Ub-R-GFP and incubated at RT for I hour, the mitochondria were then isolated from the in vitro system, then treated with or without proteinase K and subjected to immunoblot analysis.
(C+D) T2-weighted magnetic resonance imaging (MRI) analysis of these brains confirmed that all mice developed tumors of similar size. T1-weighted MRI images showed decreased vessel permeability as measured by Gadovist extravasation in tumors expressing hE7 or mE7 (red arrows; n = 6; one-way ANOVA). Scale bar represents 2.5 mm
A, Immunostaining of cytokeratin 8 (CK8), a marker of epithelial cell lineage, showed that epithelial alignment is collapsed and the trophoblast invades the stroma at implantation sites in Rb1f/f mice, while epithelial alignment is persistent and trophoblast invasion into the stroma is compromised in Rb1d/d mice. Scale bar = 200μm; arrowhead, an embryo.
(C) Column graph showing changes in colon length. Data are mean ± SEM from seven biological replicates. **P<0.01, NS- non-significant using one-way ANOVA.
(D) The recruitment of Neil3 to the oxidative lesions is inhibited by olaparib treatment (1 µM, 1 hour). 0.1 % DMSO in medium for 1 hour as mock. Oxidative damage was induced by KillerRed (KR) system with the exposure to a 15-W SYLVANIA cool white fluorescent bulb for 10 minutes. Scale bar, 2 μm. The foci were indicated with white arrowheads. Right panel: the percentage of Neil3 foci co-localized with KR was quantified.
A PLX4032 dose-response curves of parental cells expressing wild-type YAP or YAP-5SA. Mock-transfected cells were used as a control.
Mice were treated by 2% dextran sodium sulfate (DSS) in drinking water for 7 days. (D) Survival curves of COPS8fl/fl and COPS8ΔIEC mice during DSS-induced colitis. Difference in survival was determined with Kaplan-Meier analysis, **P<0.01. Representative data from 20 biological replicates per genotype. (
CD4+ T cells were isolated from the spleens of WT, EGR1KO and EGR4KO mice by cell sorting. (J) Comparison of the number of Th1 polarized cells between WT, EGR1-/- and EGR4-/- CD4+ T cells.
Oxygen consumption rate (OCR) was measured in freshly isolated mitochondria from wild-type and mutant mouse cortex. Baseline OCR, effect of age (p<0.0001) and genotype (p<0.05).
, g, LC-MS analysis revealed increased glucose consumption from medium (f) and extracellular lactate accumulation (g) in Atg7-null cell lines. Values are the average of eight (Atg7+/+) and seven (Atg7−/−) biological replicates.
Figure 1. MGC show increased tyrosine nitration in response to mycobacteria and TLR2/MyD88 dependency. A Histological sections from biopsies of an osteolytic lesion of the calcaneus from a patient with M.xenopi infection, at onset of disease (1st) and 2 months later (2nd) were quantified by microscopy with hematoxylin/eosin staining and by liquid cultures (table). Image of immunohistochemistry for nitrotyrosine (red) and hematoxylin counterstaining of 2nd biopsy samples, dashed line indicating MGC; scale bar, 20µm.
(A) Overview of the quantitative proteomic approaches used to identify differentially phosphorylated peptides, either in crude extracts or in SAGA purifications. Cells were metabolically labeled using a SILAC procedure and grown either in rich medium or shifted to nutrient starvation conditions. Several independent experiments were carried out with forward and reverse labeling schemes (see methods for details).
i.t. administration of Tat-P4-(C5)2 (20 µM) at day 14 and 28 after injury in the maintenance phase of SNI model in mice shows significant increase in pain withdrawal threshold up to 3 hours with equal efficacy in male and female mice (compared to time 0 pre-injection, D14 n=8/group/gender, D28 n=6 male, n=7 female).
(C and F) Chromosome spreads exactly as described in B and E), except that spreads were additionally stained with an antibody against Rec8 (green). The CREST signal appears in red and DNA in blue. Rev: Reversine. Scale bar indicates 5 µm in (A and D), and 10 µm in (B, C, E and F). In all panels n indicates the number of oocytes with the shown phenotype and the total number of oocytes analyzed.
I Protein complexes involving aggregators. Heatmaps show the absolute difference in solubility change after heat shock between each complex member. Protein complexes with at least 75% of its members quantified and containing at least 60% of its members as aggregators are shown. 'DNA repair complex' = 'DNA repair complex NEIL2-PNK-Pol(beta)-LigIII(alpha)-XRCC1'.
B. Immunostaining of endogenous mTOR and LAMP1 in C2C12 cells under amino acids starvation (-AA), or in response to AA stimulation (+AA) in the presence or absence of LA-B (100 nM). Scale bar, 20 μm.
(E) At least one amplicon scored as a hit for each of the core autophagy genes tested, with the exception of Atg8, which is our marker for autophagy and is being overexpressed with Dmef2-Gal4, and Atg4.
(A) The CLIP-signature of ECHDC1 suggests that it was hypermethylated and down-expressed in all the breast cancer cell lines (n=24) in which it was identified as rCCS gene.
Inhibition of GSK3 stabilizes cMyc and βcatenin protein levels. cMyc and βcatenin decrease Tcf7l1 protein levels resulting in the de-repression of FoxA2, allowing responsiveness to endoderm inducers such as nodal/activin.
C Control larva in which a GFP-expressing cell was wounded. No GFP is induced in or taken up by the surrounding cells.
(b) HEK293 cells were transfected with TRAF6 RNAi oligonucleotide (TRAF6 siRNA) or unrelated oligonucleotides as a control (Ctrl siRNA). Then, cells were co-transfected with vectors encoding ULK1-HA and ULK1-Myc and protein complexes were immunoprecipitated using anti-Myc antibody. Protein extracts were analysed by western blotting using anti-HA, anti-Myc and anti-TRAF6 antibodies. Quantification of ULK1-HA relative to ULK1-Myc is reported on the right. n = 3 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.037.
Q Representative examples of field views captured within the hippocampal fissure (indicated by the abundant large vessels), the GZ with its densely packed granule neurons and the hilus containing much larger neuronal somata; expression of GCaMP7 virus (green), labelling of astrocytes by hGFAP-RFP (red). Data information: scale bars = 50 µm Q,
(c) Localization of MHC class II-eGFP (MHCII GFP) in phagosomes of primary macrophages from Slamf1+/+ or Slamf1−/− MHC class II-eGFP (B6) mice and 3-μm beads coated with E. coli outer membrane extract. (d) Entry of 3-μm beads coated with E. coli outer membrane extract into lysosomes loaded with Texas red-dextran. Right (c,d), quantification of fluorescence in the microscopy at left. Numbers in bottom right corners (a,c,d) indicate time (in min). Original magnification (a-c), ×60. DIC, differential interference contrast. Data are representative of three combined experiments (a) or at least three independent experiments (b-d) with at least 100 beads or 80 bacteria in each (error bars, s.d.).
Modulating KLF4 by knockdown or overexpression significantly affects synergism on Olaparib/Cisplatin in MCF7 Data are mean ± SEM; one-way ANOVA was used for the statistical analysis. The asterisk in the panels represents the significant difference (p<0.05). The exact p-Values were supplied in Appendix Table S4.