EMBO/sd-character-level-ner huggingface dataset:
(A Representative confocal images of HeLa and TRIM16KO cells treated with (A) MG132 (20 µM, 2h), scale bar: 7.5 µm. and the samples were processed for IF analysis with Ub and p62 antibody. (B Representative confocal images of control siRNA and TRIM16 siRNA transfected cells treated with (B) MG132 (20 µM, 2h), where IF analysis was conducted with Ub and p62 antibodies. (C The graph shows the the percentage of cells with Ub-p62 co-localized dots. Data from ≥10 fields (40X), n=3, Mean ±SD, **p < 0.0003, *p < 0.002 (Student's unpaired t-test). Data information: Unless otherwise stated, scale bar: 10 µm.
(C) Venn diagram comparison of putative Tyr-Asp interactors identified in the AP experiments using different sources of starting material.
(c) The measured average cell volume in the synchronized cell population (red; mean and s.d. of n=3; in Equation 6), the deconvoluted signal (in case of no synchronization loss; green; in Equation 6), and the simulated average cell volume considering the loss in synchronization (black; matching the measured concentration data; Equation 6).
(E) The secreted cytokine IL-10 was analyzed via ELISA. Data shown are the mean ± SEM (n=6 per group) and an unpaired t-test was performed; ***P<0.001.
D. Deletion of PUF3 in ρ0 cells downregulates mitochondrial proteins. SILAC analysis of mitochondrial fractions from ρ0 and ρ0 puf3∆ cells are shown. Equal amount of ρ0 cells labeled with heavy amino acids and unlabeled ρ0 puf3∆ cells were mixed to extract mitochondrial fraction for mass-spectrometry analysis. Three biological replicates were prepared for each pair of strains (Dataset EV5). Mitochondrial proteins encoded by Puf3-associated mRNAs are highlighted in red. Mia40 substrates are highlighted in green (gene list in Table EV1E). Mia40 substrates encoded by Puf3 associated transcripts are highlighted in green with red circle. The significantly changed proteins (P value < 0.05; fold change > 1.5 or < 0.67) are highlighted with dashed lines; numbers of significantly changed proteins are indicated.
J: BM, NexCre cTKO animals failed reduce their number of errors during training. [geno F(1,16) = 2.316 ns; day F(4,64) = 2.991, p = 0.0251; day × geno F(4,64) = 6.341, p = 0.0002].
(A, B) Plasma P-tau217 partly mediated the effect of Aβ PET on tau PET, when using tau PET quantified in Braak stages I-VI (A, "Tau PET global", 66% of the direct effect of Aβ PET on tau PET was explained by plasma P-tau217) or in the medial temporal lobe (B, MTL, entorhinal cortex and hippocampus, 29%). The P-values are from linear regression models used to estimate the mediation effects.
(A, B). Tables summarising the number and the sex of the pups recovered at weaning from Rif1+/- x Rif1+/- mice inter-crosses, either in a C57BL/6J (A) or in a mixed C57BL/6J-129/SvJ genetic background (B). The observed number of mice is compared to the expected number, based on the Mendelian ratio. p calculated by χ2.
A. Top, WB of ULK1-complex components in wt and KO-OFD1 cells assessed in FM (-) or STV (2,4h). Bands at same exposure, noncontiguous on the same gel. Bottom, ACTIN-normalized protein levels are expressed as fold increase compared with wt cells, represented by the dashed line (mean ± SEM); n=5 independent experiments. FM=full medium, STV=HBSS starvation.
(F) Western blot analysis of p62 expression, the autophagy-associated factor, in HCV-infected cells. WCL extracted from HCV-infected cells were analyzed by immunoblotting with anti-p62 antibody. β-actin was used as an internal loading control. (E and F) The relative intensity of Mfn2, VDAC1, and p62 expression normalized to β-actin was analyzed by ImageJ.
(H) Representative images of E16.5 coronal brain sections were immunostained for PAX6. The GFP plasmid was electroporated into WT and KO mice brains at E13.5, and the mice were sacrificed at E16.5. Scale bar represents 50 μm. (I) Quantification of GFP and Pax6 double positive cells in the VZ/SVZ. n=6 mice, independent replicates. Date information: Representative images from at least three independent experiments. Error bars represent the means ± S.E.M.; Two-tailed unpaired t-test, P < 0.05(*), P < 0.01(**) or P < 0.001(***). n.s., not significant.
(A) The highest number of exophers is produced during the hermaphrodite reproductive period and in aging animals. Males do not produce exophers during the first days of adulthood and begin to generate a small number of exophers later in life. Starting n = 90 hermaphrodites and 150 males; N = 3.
Combination of YAP/TAZ deficiency and Sorafenib treatment suppressed tumor growth in a HCC xenograft model. SNU398-shLuc or SNU398-shYAP/TAZ (shY/T) cells were transplanted into the flanks of immunodeficient NSG mice. Once the tumors were palpable, mice were treated with 20mg/kg Sorafenib or vehicle control, and tumor sizes were measured twice a week (b). Tumor weights were also recorded after sacrifice of the mice Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using two-way ANOVA analysis. Mouse numbers of shLuc + Vehicle, shY/T + Vechicle and shY/T + Srf were 4 per cohort, mouse numbers of shLuc + Srf were 3 per cohort.
(G) Measurements of the dissociation of mant-ADP for 80 s (left panel) and the enlarged view for the first 8 s (right panel). KIF1A(WT) and KIF1A(E239K) (final concentrations 50 µM) preloaded with mant-ADP were mixed into an excess of unlabeled ATP (5 mM) with or without taxol-microtubule. Fluorescence decreases were observed upon the dissociation of mant-ADP.
f, Expression of the transcription factors Xbp1 (by RT-PCR (PCR with reverse transcription; top); note that the lower band reflects the UPR-related splice form), ATF4, CHOP, phospho-Jun N-terminal kinase (JNK-P-Thr183/Thr185) and total JNK(by immunoblot analysis, with a-tubulin as a loading control; bottom) in lymphoma cells as indicated (n = 3 each, gels were cropped to ease presentation; full-length blots are provided in Supplementary Fig. 16).
(i) Left panel, representative TEM micrographs of purified autolysosomes from starved clathrin-GFP-expressing cells. Scale bar, 250 nm. Right panel, SIM image of purified autolysosomes stained with GFP and LAMP1 from the same experiment. Scale bar, 5 μm.
No direct physical interaction between kugeln (BLECs - black arrowheads; kugeln - white arrowheads) and BLECs was observed (n=21 4dpf embryos; 3 experimental repeats). Depth-coded MIPs showed that BLECs and kugeln are present on different anatomical planes (depths; purple ventral (v), white dorsal (d); BLECs - black arrowheads; kugeln - white arrowheads).
B Hair cell viability in larval zebrafish pre-treated with control-, tlr4ba- and/or tlr4bb-targeting morpholino oligonucleotides (MO) and subsequently treated with 15 μM cisplatin. Data information: In both panels each data point represents a score of hair cell integrity in an individual animal (taken from multiple samples per animal) with lines representing mean and standard deviation. Statistical comparisons to control morpholino (B, except as indicated in blue) were assessed by one-way ANOVA. *, P<.05; **, P<.01; ****, P<.0001 (Tukey test).
F. Quantification of Golgi mCherry-P4M intensity relative to cytoplasm. Control: n=11; NPC1I1061T: n=14; Control + ACBD3: n=12.
(A, B) Detection of autophagic vacuoles by LC3‐GFP and their modulation by ABT737 and by Beclin‐1‐specific siRNAs. HeLa cells were transfected with control or Beclin‐1‐specific siRNAs, 24 h later re‐transfected with LC3‐GFP, cultured in complete medium (CM) for 24 h, and finally kept 12 h either in CM or in nutrient‐free (NF) conditions, in the presence or absence of 1 μM ABT737. Representative microphotographs of cells cultured in NF medium are shown in (A) and the percentage (means±s.d., n=3 separate experiments) of LC3‐GFP‐transfected cells bearing LC3‐GFP aggregates in the cytoplasm (LC3‐GFPvac) are quantified in (B). The insert in (B) demonstrates the efficiency of the Beclin‐1‐specific siRNAs, as quantified by immunoblot.
(C) Detailed interactions of N-glycans on N58 of PD-1 with camrelizumab-scFv. The observed glycans on N58 of PD-1 are highlighted in sticks and colored in green. Residues with hydrogen bond and van der Waals force interaction are shown as sticks and labeled while Hydrogen bond and van der Waals force interaction are shown as dashed red lines.
Left: NIH-3T3 cells expressing sgCtrl, sgSlc25a1-1 or sgSlc25a1-2 were treated with TGFβ or mock for 6h, and ROS levels were measured by flow cytometry for CM-H2DCFDA after incubation with CM-H2DCFDA for the last 30 min of the treatment. Values are relative to mock-treated sgCtrl expressing cells. Right: western blot of NIH-3T3 cells expressing sgCtrl, sgSlc25a1-1 or sgSlc25a1-2.
A Col-0 (WT) and dog1-3 mutant plants were either watered normally or subjected to water withdrawal for 5 days and then watered again and allowed to recover for 2 days. A picture of a representative experiment is shown. Scale bar, 2 cm.
E. Immunoblotting demonstrates depletion of all three RNase H2 protein subunits in Rnaseh2bA174T/A174T MEFs and RNASEH2BA177T/A177T LCLs. Representative of three independent experiments.
F. Osmotic stress does not disrupt the interaction between YAP and TEAD1. HEK293A cells were treated with 0.2 M sorbitol for 1 hr. Endogenous YAP was immunoprecipitated with YAP antibody, and TEAD1 and YAP were detected by Western blot. Cells were serum starved for 1 hr as indicated (- serum).
Figure 2. Increased ISG expression in tissues from Rnaseh2bA174T/A174T miceA. Transcript levels of multiple ISGs are significantly elevated in heart.B. Transcript levels of a subset of ISGs are significantly increased in kidney.C. No ISG upregulation is evident in the brain. ISG transcript levels determined by RT-qPCR normalised to transcript levels of the housekeeping gene HPRT (Oas1a was undetectable in brain). Each data point represents the mean of technical replicates of tissue RNA from a single mouse. n=9 nine-month old Rnaseh2bA174T/A174T mice, n=4 age-matched control wildtype C57BL/6Jmice. Horizontal line, mean; error bars, SEM. * = p<0.05, ** = p<0.01, two-tailed t-test.
G: Schematic representing the predicted effects of HMMR knockout on FAM83D-CK1α delivery to the mitotic spindle. In the absence of HMMR, no FAM83D and by extension no CK1α, can localise to the spindle.
(B, C) Functional classification and subcellular localization of identified lysine-acetylated proteins. Lysine-acetylated proteins identified over all experiments were classified according to MapMan categoriesOver- or underrepresentation of categories was determined using a Fisher's exact test with all proteins identified at 1% FDR as background population. Blue and red arrows mark categories significantly enriched at 5% FDR (Benjamini-Hochberg) and a 1.5-fold-change cut-off.
(E) Relative values of protein levels for LOX members in PDAC tumors assessed by proteomic analysis (6 mice per condition and samples were analysed in duplicates
(a) Fibroblasts of individuals with mucolipidosis II (I-cell disease; upper right panel) or Hurler syndrome (lower right panel) were compared with parental control cells (left panels). The alleles are indicated. Cells were fixed and stained with the indicated antibodies and DAPI to visualize DNA. Arrowheads point to the accumulated MRs. Scale bars are 20 μm. (b) Quantification of a (mean ± s.d. of three independent experiments; n, total number of cells; P, probability of a two-tailed paired t-test).
A) Epifluorescence microscopy images of MoDCs infected with pre-labeled bacteria (green-CFSE). LAMP1 detected by transduction of red fluorescent protein (RFP) chimera using baculovirus transgenes to MoDCs.
(c) MN-1 cells were immunoblotted for LC3 in the presence or absence of ammonium chloride to evaluate autophagic flux. A representative LC3 western blot is shown. All ratios were normalized to MN-1 WT cells at baseline, which was set to 1. (d) The ratio of LC3-II:actin for c determined by densitometry analysis using ImageJ. n = 3 independent experiments, F = 0.4501, one-way ANOVA with post hoc Tukey test. *P 0.05.
(C) The 38 upregulated genes identified (>2 fold where padj=<0.05) were converted to DAVID IDs and used for gene ontology analysis. 3 gene clusters were significantly enriched (p-value = <0.05, drawn on the plot as a dotted line) in the data set: zinc finger proteins (p=2.2 x 10-7), negative regulators of metabolic processes (p=0.0036) and angiogenesis (p=0.011). Venn diagrams on the right show numbers of upregulated genes, ZNFs and KZNFs and the overlap.
Liquid chromatography-mass spectrometry (LC-MS/MS) analysis was performed to determine different metabolites of RK-33.
Kaplan-Meier analysis of tumor formation in control (blue, n = 8) and GS493‐pretreated (red, n = 8) MLN4924;MMTV‐Cre;Shp2fl/flmice. The bar indicates the duration of treatment.
(B) LC-MS/MS spectra of the N-terminal part of the GFP-immunoprecipitated and LysC digested polyGA protein expressed as in (A).
(a) Levels of dark, dronc, drice and rpr transcripts were measured from third instar larvae (L3), 6 h and 14 h RPF salivary glands from control (blue) and dUTX1 (red) by qPCR and expressed relative to the internal control gene rp49.
(C) Comparisons of the flap domain of PPM1H with PPM1A (left) and the tudor domain (right). Apart from a conserved loop (dotted circle) which forms an interface with the catalytic domain, the sequences and structures of flaps are diverse among the PPM family.
Incubation of human melanoma with human platelets or ASM for 5 min triggers co-clustering of ceramide and activated β1 integrin on the surface of the tumor cells. Cells were stained with FITC-coupled anti-active β1 integrin (HUTS-4) antibodies and Cy3-coupled anti-ceramide antibodies. Shown are representative stainings from each four independent experiments.
B. Red and green pixels overlap fraction (above, left) representing the co-localization of FGFR2 with EGFR; red and far red pixels overlap fraction (above, right) representing the co-localization of FGFR2 with the recycling marker Tf; far red and green pixels overlap fraction (below, left) representing the co-localization of EGFR with the recycling marker Tf; green, red and far red pixels overlap fraction (below, right) representing the co-localization of FGFR2, EGFR, and the recycling marker Tf in T47D stimulated for 40 min. Values represent the median ± SD of at least 3 independent experiments. Representative pictures are shown in A and Appendix Figure S6A. *, p value<0.005 (Student's t-test).
(U) Representative image of Western blotting analysis of HIF1α, REDD1, 4E-BP1, S6 and P70S6K (in their phosphorylated and unphosphorilated form) to test mTOR activation in normoxic (NRX) and hypoxic (HYP) IL10 macrophages treated with glufosinate (20µM), rapamycin (20nM) and a combination of both (n=3).
Activity profiles (Tx) of regulatory sequences from donor phyla Proteobacteria and Firmicutes in 10 bacterial species. GC contents of regulatory sequences from the phylogenetic groups are shown on right. 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 the IQR. For normalization, transcription levels in log10 scale were transformed to Z-scores. All measurements are based on two biological replicates.
I-K Anti-miR-210 delivery (N = 10/group) ameliorated the elevation of RVSP, **P = 0.0031 (i) and vascular remodeling, as reflected by increased percent of muscularized arterioles (N = 8/group, **P = 0.0091) (J) and increased medial thickness relative to vessel diameter in < 100-μm pulmonary vessels (N = 6/group, **P = 0.0021) (K).
(B) Heavy/light ratio for approx. 500 proteins identified in the screen. SPATA2 stands out with a substantially elevated H/L ratio. Each dot represents a protein.
b, Percentages of autophagic vacuoles (AVs) containing only lipid, other cargo or mixed cargo calculated from samples processed as in Supplementary Fig. 16b (*P  0.001, **P  0.0001, n = 46). (Supplementary Figure 16 Effects of starvation on hepatic lipid droplets. a, Mouseliverelectron micrographs. Arrows: Lipid-containing double membrane vesicles. b, Electron micrographs of autophagic vacuoles (AVs) isolated from mice fed or starved for the indicated time periods. The percentages of double membrane vesicles containing lipid in isolated AVs from 3-4 mice per condition are shown (*P<0.01 as compared to fractions from fed animals). (*) indicate lipid)
(A) Proposed models for repair of DSBs generated at broken replication forks (see text for details). seDSB: single-ended DSB; deDSB: double-ended DSB. Pink arrows: endonucleases to remove Flex1 or other secondary structures at DSB ends or DNA tails at the fork junctions.
(B) A summary visualization of the metabolic pathway enrichment result for the top consistent DF reactions across the datasets, with more importance given to the various in vivo patient datasets (Methods). Y-axis represents the odds ratio of enrichment, the dot color corresponds to the adjusted P value from Fisher's exact tests, and dot size corresponds to the number of enriched reactions within each pathway. Half-dots plotted on the top border line correspond to infinity odds ratio values. The pathways on the X-axis are ordered by P value and only those with FDR<0.1 are shown.
(A) Mass spectroscopy analysis of levels of cholesterol and cholesteryl esters in purified islets from Abca12tm1d mice versus control animals at 16 weeks of age (mean±SEM, n=10, 4 and 5 mice per genotype respectively; COH=cholesterol, CE=cholesteryl ester).
A Schematic of the control of lipid synthesis by estradiol-inducible expression of ino2*.
Drawing of the TSC1 promoter and luciferase-reporter constructs with the predicted E-box (CACGTG, pos. -317/-322) indicated. Relative luciferase units (RLU) of co-transfection experiments using the indicated TSC1-promoter-reporters with MYC normalized to empty pcDNA3 expression vector in HeLa cells (mean ± st. dev., n=3). Immunoblot shows MYC overexpression and α-tubulin as loading control.
(D) Gastrocnemius weight in mice subjected to iron deprivation by feeding with an iron deficient diet (IDD) combined to a phlebotomy (PHL) (n=5-6); Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
Figure 4. Deletion of both β-catenin and Hoxa9 abrogates leukemia development in LSK-MLL-ENL cells. Keys and colour code in the left top corner indicate the origin and the β-catenin and Hoxa9 status of MLL-ENL transduced cells. (A) Colony numbers in serial replating assay of MLL-ENL transduced cells. Images of typical 4th round colonies shown above. Data are represented as mean ± SD.
(C) Scheme of ketone body oxidation and the tricarboxylic acid (TCA) cycle. MCEC were incubated with 1 mM 13C4-β-hydroxybutyrate or 1 mM 13C4-acetoacetate for 24 hours or the same concentration of unlabeled ketone bodies ([12C] isotope). The [13C]-labeled fractions of the TCA cycle intermediates citrate, α-ketoglutarate and malate (marked with blue star) were quantified with an untargeted metabolomics approach indicating that 13C carbon from ketone bodies was incorporated into TCA cycle intermediates.
F Images displaying the collagen (blue) revealed by Masson's trichrome staining in limb of WT, mdx, and mdx/CD38-/- mice. The dot plot shows the quantification of collagen staining area (% total area) in limb of WT (n=4), mdx (n=5) and mdx/CD38-/- (n=5) mice. Scale bars: 200 µm. Data information: Each dot of the graphs represents a mouse. in triplicate. After normality and variance comparison tests, significance was assessed using: : ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.
B. Deconvolved fluorescence micrographs of Chm7-GFP and truncations with Nup170-mCherry NE marker and merge of green and red channels. Scale bar is 5 μm.
A Reactome Pathway analysis for all 174 transcription factor genes with higher expression in DIE (upper) and all 205 genes higher in CTX GM (lower) astrocytes.
B HeLa cells were fixed and labelled with antibody against SEPT7 and secondary antibody coupled to HRP, and processed for TEM. The right image is enlarged from the boxed region in the TEM image, and shows a SEPT7 (S7) filament (labelled in black) intersecting with the mitochondrial (Mt) fission site. The scale bar represents 100 nm. See also Fig EV4.
I, Response of fliM∆N ∆cheA cells expressing FliMN-CheY (strain EW696) to acetate and benzoate (10 mM each; pH 7.0). FliMN-CheY expression was induced with 800 μM IPTG. Lines and shaded regions are the mean time spent in clockwise rotation ± SEM. The black arrow indicates the estimated time point at which the stimulus entered the flow chamber.
Morphological evaluation of IMCs cultured for 2 weeks without additional cytokines. The cells grown on culture plates were imaged by phase-contrast microscopy (left). Then, the cells were trypsinised and smeared on glass slides for Giemsa staining (right). These cells are intermediate to large sized, round or amoeboid cells with cytoplasmic vacuolation, consistent with a macrophage morphology. Scale bars, 50 μm.
K. Relative expression of veal2 across Fluorescence activated cell sorted (FACS) GFP(+) endothelial cells (EC) and GFP(-) non endothelial cells (NEC). fli1a and actb were taken as positive control and normalization control, respectively. Data from three different experiments represented as fold change relative to EC values ± standard deviation.
Quantitative PCR (qPCR) analysis of YAP/TAZ targets (Cyr61, Thbs1, Amotl2), ATF4 and the targets of ATF4 (Trib3, Slc7a5, Slc7a11).
(A) Workflow of the experiment presented in panel (C), depicting synaptoneurosomes (SN) isolation and in vitro stimulation in the presence of radioactive 35S-labelled methionine/cysteine mix.
A Schematic depiction of the growth assays. Cells expressing only one hexose transporter at a time were picked from a plate, serially diluted and plated on fresh YPD plates.
(F) Representative immunofluorescence images of Spindly phS499 levels at unaligned and aligned KTs in a PoloWT-EGFP expressing Drosophila S2 cell. Insets show magnifications of the outlined regions, which highlight either a unaligned (u) KT or an aligned (a) KT. CID was used as a KT reference. Plotted profiles of signal intensities of phS499 and CID are shown for the highlighted KTs. Data information: Data are shown as mean ± SD. Scale bar: 5 μm.
c. Statistical analysis of the frequency of IFN+Foxp3+ cells in Tregs stimulated as in c of n=8 experiments performed.
H) (top) 4 months old and 15 months old micelivers [control (-) or rapamycin (+)] stained with Sen--β-Gal solution (Sen--β-Gal activity is evidenced by blue staining). Data are from n=3 mice per group; (bottom) Representative image showing Sen--β-Gal staining (Sen--β-Gal activity is evidenced by blue staining) in hepatocytes and corresponding immuno-TeloFISH (arrows represent co-localizing foci); Asterisks denote statistical significant P<0.05 using One-way ANOVA.
A) Survival of P. gingivalis strains within MoDCs after 6, 12, 24 and 48 hours. Blue lines show P. gingivalis strains survival within MoDCs and their survival in anaerobic condition in the absence of DCs are showed in black lines.
C. The five contacting interfaces between MvcA(green surface) and ubiquitin(magenta), each is indicated by a dashed circle and a letter from A-E. The image on the right is obtained by a 180° rotation of the left structure around the indicated axis. The interaction patch involving the C-terminal tail of ubiquitin is indicated by dashed circle. CTC: carboxyl terminus contacts.