EMBO/sd-character-level-ner huggingface dataset:
(B) (Left) Microphotographs of aortas (en face) from Apoe-/- and Frs2SMCKO/Apoe-/- mice after 16 weeks of high fat diet after staining with Oil Red O. (Right) Lesion area quantification. All data shown as mean ± SD. (***p<0.001 compared to Apoe-/-; unpaired two-tailed Student's t test). 12 mice per group.
Q) GlyS or Atg1 knockdown significantly improved the crawling time of larvae treated with CQ and starved for 6 h. SEM is indicated for n = 10 larvae. The p values were calculated relative to white RNAi control larvae (*p<.05, **p<.01).
G Left ventricle myocardial fibrosis was tested by Masson staining in WT and Cuedc2-/- mice. The represent results were shown in (G) and the quantitative analysis of myocardial fibrosis was shown in (H). *p = 0.0177, n = 5 in each group.
The human rDNA promoter region contains one ARRE2-like sequence. The red letters in gray shaded area indicate the probe sequences used in panel D. Gray shaded area indicates the upstream control element. Blue color indicates the core promoter region.
(A) Immunoblot of patient fibroblast cell lines (P1 and P2) and three independent controls (C1-3). Immunoblots were probed with the indicated primary antibodies. Quantification of BET1 protein levels normalized to GAPDH. Data represented are mean ± SD of three independent biological experiments. Significant differences of P1 BET1-levels were checked compared to each control (***=p<0.001, one-way-ANOVA followed by Tukey`s post-hoc test).
C. Frequency of specific isoform name for 2,487 multi-isoform UniProtKB canonical proteins.
(a) A schematic of the workflow for Trim28-KO in mouse NPC cultures. Scale bars: embryo 1 mm, NPCs 20 μm.
G, H Representative images showing expression of YAP (in red) in normal (G) and HPV16-containing humanforeskinkeratinocyte raft cultures (n = 5 each) (H). Scale bars: 100 μm.I, J High-resolution images showing the expression and cellular location of YAP in normal (I) and HPV16-containing humanforeskinkeratinocytes raft cultures (J). Scale bars: 20 μm.
G and H Cholesterol levels, protein expression (G) and cell growth (H) of SK-HEP-1 cells stably expressing control shRNA or p53 shRNA in LPDS medium in presence or absence of 5μg cholesterol.
(B) Size of mutant nsun strains at young adult and egg-laying stages. Approximately 100 synchronised young adults of each strain were measured. Images were processed using custom algorithms to recognize C. elegans and measure their cross-sectional area.
C, Average Ca2+ response following stimulation in terminals with or without a mitochondrion (average of ΔF measurement taken for a t=20-30s of B), ΔF/F0 = 1.9 0.3 with and 3.5 0.4 without mitochondria, paired t-test, ***p<0.0001.
WT and Mfn1/2 double KO were transfected with: E) GFP and the indicated plasmid. After 48 h, the effect of caffeine-induced (20 mM) ER Ca2+ release on mitochondrial Ca2+ was measured (n= 25 cells from 3 independent experiments). Data are presented as mean ± SEM.
J-L Quantification of Ki67 (K), LC3-B (K), and VEGF-A (L) expression in immunohistochemical images by Image Pro Plus (IPP) analysis. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD.
(P) EM of muscle from Dmef2-Gal4/UAS-GlySi animal starved on low-nutrient food +CQ. Note that the intermyofibril spaces (red asterisk) and sarcomere structure are not distorted.
C Re5D06 produced in the indicated expression host was analyzed by differential scanning fluorimetry (DSF) with a temperature range from 20 to 95ºC (in the presence of SYBR Orange). Unfolding is measured as an increase in fluorescence (caused by the exposure of hydrophobic residues that bind the dye). Melting temperatures are defined as the inflection point of the melting curve before reaching the first melting peak. Stable proteins produce no melting peak.
B-D) Allelic variation plots showing the peak SNP for Ifi203 expression (rs31614030) at the CC or TT allele (x-axis) plotted against expression of Ifi203 (B), levels of hepatic PC(38:3) (C), and plasma insulin levels (D). Red line shows Bonferroni-corrected threshold and blue shows an FDR =0.01 pvalue of significance calculated based on FaST-LMM pvalues.
(b-e) Representative confocal images of muscle and adipose tissue of larvae carrying RasV12; ctrl, RasV12; scrib-/- and RasV12; scrib-/-, atg13-/-//atg13-/- showing glycogen levels (white) at day 6 and day 8.
(B, C) The ratio (GFP/mCherry) of selected proteins is indicated for (B) proteins relevant for flagellum formation and (C) cell division proteins and a T4SS substrate. The ratio of the mean intensities from 3 independent proteomics experiments is shown.
Cellular growth measured as the ratio of nucleolus /nuclear volume was significantly reduced in larval nerfin-1 NBs after 6 days his dietary reduction (25% his compared to CDD, n=14,6) quantified in (N).
(a) A schematic of the workflow for the single nuclei RNA-seq of cortical tissue from Emx1-Cre/Trim28-KO animals and their littermates.
F,G qRT-PCR for mRNA expression of the quiescence-related markers Bmp6 (F) and Fgf18 (G) in epidermis of control (Ctr) and Bcl-2EOE mice (P27), (n=4 biological replicates; mean ± standard error of mean (SEM); * p<0.05, *** p<0.001, two-tailed unpaired Student's t-test).
(c) Hierarchical clustering of apical Venus::HE5 expression from one representative experiment showing behaviour in the same area over time; columns represent fluctuations in Venus::HES5 intensity in small local areas (bands) obtained by dividing the spatial signal into non-overlapping 20μm regions and normalizing to the mean and standard deviation of each region over time (z-scoring); data has been subject to a Gaussian blur pre-processing step (see Appendix Figure S2b and Methods).
B-C Human mo-DCs pre-treated with JNKi (SP600125, 25µM) (B) or AP-1 Inhibitor (T-5224, 20 µM) (C) for 1h were stimulated with R848 (10 µg/ml). CCL2 and IL-23 were analyzed by ELISA. (n = 5-11; 2-3 independent experiments). Data information: Data are shown as mean ± SEM. P‐values were calculated by paired, two-tailed t-test (B, C, Statistical significance: ns > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001. See Appendix Table S3 for exact P‐values.
E Relative mRNA expression levels of the specified genes in HCT116 cells, treated as indicated for 16h (NEN (N) 1.2 µM, Domperidone (D) 30 µM, Cyclodextrin (CyD) 0.75%). F Immunoblot analysis of HCT116 whole cell lysates using antibodies against gammaH2AX and treated as indicated for 16h (NEN 1.2 µM, Domperidone (Domp) 30 µM, Cyclodextrin (CD) 0.75%). Data information: data are presented as mean (SD) (N=3) and were analyzed by a one-way ANOVA with Tukey post-hoc test * p< 0.05; ** p< 0.01;*** p< 0.001; **** p < 0.0001.
Amino acid sequences of the designed peptides EK1 and EK1C. The dotted lines represent E-K salt-bridge with i to i + 3, or i + 4 arrangement.
(B) SOFG staining of spinal entheseal tissue and Immunohistochemical analysis of CaSR+ and Runx2+ cells in human spinal tissue. The bottom panels show higher magnification of the boxed area in the top panels. Data information: SP: spinous process; IL: interspinous ligament; SL: supraspinous ligament; UIL: uncalcified interspinous ligament; TZ: transitional zone. Data shown as mean ± SD.. ** P < 0.01 compared between groups. Scale bar: 100μm
(G) Distribution of distance to nucleus, normalized on cell size, quantified by image (as in e) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of LAMP-1+ endosomes. Results are from three independent experiments for a total of 432 late endosomes in 12 untreated (UT) cells (36 ± 9 endosomes per cell) and 1184 late endosomes in 18 CilioD cells (66 ± 9 endosomes per cell) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***.
(G, H) Western blot analysis of lysosomal proteins in the spinal cord lysates from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. Asterisk indicates non-specific bands. n=3.
J. RAB13 PI plotted against respective GAPDH PI. The slope of the coloured lines represents the average RAB13/GAPDH PI ratio; the dashed grey line represents a 1:1 ratio (n=29 cells).
BrdU incorporation assays in VSMCs transduced with the indicated genes. The percentage of BrdU positive cells in each group is shown. Nine to twelve images were randomly acquired and analyzed. **P<0.01 vs LacZ, by ANOVA with Sidak's correction.
A representative example of a 7 days (7d) old adult female posterior midgut at low (A) and high magnification (B, Region 4-Region 5) showing the initiator caspase reporter DBS-S-QF (Red, immunostaining anti-HA). Flies were reared under experimental regime that protects the intestinal epithelial integrity (intestine reared in Oxford Medium and flies transferred every two days into vials with fresh food, see Figure EV1) at 25 Co. The image on the left was acquired at low magnification with the 10x objective, while the right panel was acquired using the 40x. The left and right images in all examples correspond to independent intestines of the same genotype and treatment. Genotype: y1 w1118 UAS-mCD8::GFP.L QUAS-mtdTomato-3xHA Act-DBS-S-QF (BL83131)
Example sites prone to carbonylation. (A) DRA0302_P252, (B) DR0099_P51, and (C) b0911_K411; and example robust site (D) b3313_P69. Data information: All atoms of central RKPT side chains are shown, with carbonylatable atomic site in red (predicted and measured carbonylated) or black (predicted and measured not oxidized) and labeled with the 1-letter code of the containing amino acid. Positive (blue) and negative (pink) charges within 8Å are labeled. Carbonylatable lysine sites (purple) within 8Å are labeled. Molecular surfaces within 5Å of the central CS are dark gray. See also Fig EV3.
C Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and nuclei (DAPI, blue), in control (NHDF) fibroblasts. D Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and nuclei (DAPI, blue), in patient fibroblasts. E Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and nuclei (DAPI, blue), in control (NHDF) fibroblasts transduced with wild-type UQCRH. F Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and nuclei (DAPI, blue), in patient fibroblasts transduced with wild-type (WT) UQCRH. G Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and nuclei (DAPI, blue), in control (NHDF) fibroblasts transduced with the pseudogene UQCRHL. H Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and nuclei (DAPI, blue), in patient fibroblasts transduced with the pseudogene UQCRHL. I Graph indicates the staining intensity of UQCRC2 in control (NHDF) fibroblasts (green) and patient fibroblasts (red), those respective cell lines transduced (T) with wild-type UQCRH (diagonal lines) and those cell lines transduced with the pseudogene UQCRHL (vertical lines) measured using Image J, Data are given as mean ± SEM. One-way ANOVA (Kruskal-Wallis test), * p < 0.05; n = 3 macroscopic field (10-14 cells for macroscopic field were measured).
A Western blot analysis of the different forms of Gli2a in MZgrk2 embryos compared to wild type, shh mRNA and dnPKA mRNA injected wild type and cyclopamine (Cyc(A)) treated wild type 20hpf embryos. Gli2a-FL levels are low relative to Gli2aR levels in wild type embryos, but are elevated in response to pathway activation (shh and dnPKA mRNA injected). Gli2aR levels are increased while Gli2a-FL is undetectable in CycA treated and MZgrk2 mutant embryos. Probing the same blot with rabbit anti-GRK3 (which recognizes the zebrafish Grk2 protein) reveals a complete loss of full length Grk2 in MZgrk2 embryos. Probing with anti-γ-tubulin was performed as a loading control. Three biological replicates of this analysis were performed.
(C) Average Δψm before (left, gray) and after fission (right, filled and empty circles denote depolarized and hyperpolarized mitochondria respectively). Only fission events where Δψm of both mitochondria could be continuously tracked are included (n=7).
B-C PBMC cells with shNC, shNF45 or shNF90 lentivirus infection were stimulated with P/I for 12h, then the freshly replaced medium without P/I after another 24 h culture was harvested for IL-2 and IFN-γ detections by ELISA.(n=3)
C The qRT-PCR analysis of Akt2 mRNA in PEMs stimulated with lipo-poly(I:C) (1 μg/mL), lipo-poly(A:T) (1 μg/mL), lipo-ISD (3 μg/mL) or HSV-1 (MOI, 1) for 6 hours. n=3, respectively. Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using one-way ANOVA test Data are from three independent biological replicates Error bars mean ± SEM).
In-gel proteasome assay following native gel electrophoresis (top) and immunoblotting of proteasome complexes (30S, 26S and 20S) (bottom) in young (5wph), adult (12 wph) and old (39 wph) killifish brains. For additional samples and low exposure pictures see Figure EV5B and EV5C.
G-I Gene set enrichment analysis (GSEA, broadinstitute.org) of microarray data from proliferating MuSCs. Comparison of linc-MYH-/- vs. WT proliferating MuSC transcriptomes shows enrichment of genes related to cell proliferation (G), enrichment of genes containing cis regulatory elements for YY1 (H) and p53 (I). Enrichments are highly significant using the most conservative familywise-error rate method (FWER). Enrichments were lost in linc-MYH-/- MuSCs after additional deletion of INO80 (dKOs) compared to Pax7-Crepos / INO80-/- MuSCs.
(C-F). Viral loads of throat (C) and anal (D) swab specimens collected from the inoculated macaques at day 3, 5 and 7 pi were monitored. Viral loads in various lobe of lung tissue from all the inoculated macaques at day 7 post infection were measured (E). RNA was extracted and viral load was determined by qRT-PCR. All data are presented as mean ± SEM.
D. Gene ontology enrichment analysis of up- and down-regulated genes, analyzed separately using Metascape (http://metascape.org). The top 10 significant GO terms (biological pathways and processes) associated with up- and down-regulated genes are shown. The y-axis represents the GO category (ribosomal biogenesis pathways/processes are highlighted in bold), and the x-axis represents the -Log10 (P-value) of GO terms.
F-H Overexpression of shRNA-resistant wild type METTL3 but not catalytic mutant METTL3 rescue autophagy phenotype in METTL3-knockdown SMMC-7721 cells (F), Bel-7402 cells (G) and sorafenib-resistant HepG2 cells (H) by representative immunostaining images of LC3 under hypoxia condition for 48h. Scale bar, 200μm. Quantification of the numbers of GFP-LC3 puncta/cell by Imaris in F-1, G-1 and H-1, respectively. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.
D. Quantification of CLIMP63 fluorescence intensity into TMEM192-HA decorated lysosomes. Mean +/- standard error of the mean (sem) of N=3 biological replicates/treatment/genotype (ctrl=wild type). n=10 cells/experiment were analyzed. Analysis of variance one way (ANOVA) p=1.55e-7; Tukey's post hoc test ***p<0.0005; NS not significant.
(A) Quantitation of mCherry-TDP-43 distribution (nuclear only or cytoplasmic) in control U20S, VCP-WT-, VCP-RH-, VCP-AE-, or VCP-EQ-expressing cells, or control U20S cells treated with 10 µM Baf or 50 µM chloroquine (Chlq) for 4 h from 10 different fields from two independent experiments. Error bars represent the standard error from 20 fields in two independent experiments. *, P < 0.02 when compared with VCP-WT-expressing cells. (B) Epifluorescent images for mCherry-TDP-43 (red) and DAPI (blue) in control U20S, VCP-WT-, VCP-RH-, or VCP-AE-expressing cells, or control U20S cells treated with Baf or chloroquine for 4 h. Arrows denote cytosolic TDP-43 and perinuclear TDP-43 inclusions.
Propagation of humantau protein to neurons in the DG (white arrows) in ECrTgTau-Mapt0/0 mice. Close-ups show DG neurons from three ECrTgTau-Mapt0/0 mice (DG I-III). Immuno-FISH proofs the absence of humantau expression in DG neurons, which have huTau protein but no humantau mRNA. Scale bars 50 μm.
Dexamethasone treatment accelerates increase in activity of sucrase maltase reaching adult organoid level ( ) at day 13 of the culture. Activity is given in µM glucose/µg protein·min-1 (n = 3 independent organoid cultures).
(A-B) Glycogen phosphorylase is not required for glycogen autophagy (antiglycogen, red; GFP, green; DAPI, blue). (A) UAS-GlyPi/+; Dmef2-Gal4, UAS-GFP-Atg8/+ larvae starved on low-nutrient food +2.5 mg/ml CQ for 6 h exhibited high levels of colocalization between GFP-Atg8 and glycogen.(B) Higher magnification of region outlined in (A)
B) Single point activity assays of USP1WT and deletion mutants on Ub-Rho show signifi­cantly increased activity in mutants where insert L1 and L3 are both deleted.
B Global O-GlcNAc protein expression with Western blot, GAPDH served as a control.
The average size of cells decreased after lag. Micrographs and cell length distributions (n > 400 per distribution) are shown for specific time points, with f = 0.6 mmol/g/h
(D) GST-GSDMD and its mutant lacking amino acids 265-284 were mixed with His-tagged nucleocapsid, followed by a GST-pulldown assay. Input and precipitates were immunoblotted with antibodies against the indicated protein tags. Data information: Experiments were repeated for three times with similar results.
A Venn diagram of the genes up- or down-regulated by ATRA in TN and Lum tumors is shown. The number of genes commonly or selectively regulated in TN and Lum tumors is indicated.
(H) Representative immunofluorescence images of Iba1 (green) and APOE (red) on cortical sections from SPF and GF mice. Nuclei were stained with DAPI (blue). Scale bar: 50 μm. White arrowheads indicate APOE+/Iba1+ microglia and arrows show APOE-/Iba1+ microglia. Quantification of APOE+/Iba1+ microglia. Each symbol represents one mouse. At least three slides were examined per individual mouse. Data are presented as mean ± s.e.m. Significant differences were determined by unpaired t-test and marked with asterisks (*P < 0.05). Data are representative of two independent experiments.
C. Light/heavy ratio of tau peptides in label-free mass spectroscopy of media from HEK293T cells overexpressing tau or tau and DnaJC5 compared to 100 ng 15N labelled recombinant tau. Light peptides represent endogenous tau peptides. Data are mean ± SEM, n=3 biological repeats, ***p<0.001.
(D) Distribution of distance to nucleus overtime, normalized on cell size, quantified by image (data correspond to movies EV1 and EV2) segmentation (see Material and Method, Live imaging experiments) of Rab5+ endosomes, appearing for 60 seconds. Results are from three independent experiments for a total of 903 early endosomes in 18 siCTL cells (50 ± 5 endosomes per cell) and 935 early endosomes in 20 siSTIM1 cells (47 ± 9 endosomes per cell). Data are analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,01 **.
Schematic diagram of the Spatc1l gene coding region and region deleted using CRISPR/Cas9. The start codon sequence is labeled in red. Blue arrows indicate the forward and reverse primers used for genotyping. The numbers in boxes indicate exons, and filled boxes show Spatc1l coding regions. The 178-bp sequence deleted in the targeted allele of a Spatc1l-/- mouse (red dots) is indicated in partial sequencing results, shown below.
(A-C) Embryos co-expressing CIBN-PatJ::GFPpm, RhoGEF2-CRY2::mCherry and the membrane marker GAP43::mCherry were photo-activated at the cell base after cells had already apically constricted. (A) Prior to photo-activation, cells were apically constricted and elongated. (B) In the non-activated region, within 6 min cells expanded their base and shorten. (C) In the photo-activated region, cell shortening was inhibited. (D-F) Cellular features extracted from the reconstructed cell shapes displayed in boxplots (pre A: pre activation (npre A = 107), initial time point; NR: non-activated region (nNR = 10); AR: activated region (nAR = 37)). The central mark, bottom and top edges of each box indicate the median, 25th and 75th percentile, respectively. Whiskers extent to the most extreme data point and the '+' symbol indicates an outlier. Notches indicate comparison intervals. (D) The mean cell length at the initial time point was 45 µm (blue). 6 min after, the non-activated cells (green) shrank to about half of the size (26 µm), whereas photo-activated cells (red) only shrank to 39 µm. ANOVA result: F(2,151)=110.2, p=3e-30; Cohen's D: d > 1.5 for all comparisons. (E) The basal area in the pre-activation control of 30 µm enlarged to 60 µm in the non-photo-activated cells, but remained at 30 µm in the activated region. ANOVA result: F(2,151)=52.02, p=6.5e-18; Cohen's D: dpreA:NR, dAR:NR > 2, dpreA:AR < 0.5. Please note the logarithmic y-axis. (F) The cell volume did not change between the different conditions. There were no statistically significant differences between group means as determined by one-way ANOVA (F(2,151)=2.227, p=0.11). In all panels, **** indicates p ≤ 0.0001, and n.s. indicates no statistically significant differences according to two-sample t-Test.
(J) Quantification of myotube formation in the indicated myoblasts transduced with Ad.EV or Ad.NF-κB/HIF-1α and induced to differentiate in normoxia. Myotube counts are the mean of six fields (n = 3). Error bars represent SD.
System of partial differential equations describing the process of dermal wound healing.
Whole-mount immunofluorescence of ear skin, mesentery and flank, showing nuclear FOXP2 staining in collecting lymphatic vessels (arrows, col), but not in LYVE1+ lymphatic capillaries (cap) or blood vessels (bv).
(A) Substrates used for crystallization of the 8-oxo-dG:dATP insertion complex. The primer terminal base (ddC) is shown in cyan. The incoming dNTP (dATP) and corresponding templating 8-oxo-dG are shown in magenta and green, respectively.
C-D Clone 11 were treated with the indicated concentrations of PH02 (left panels) or PH02 in combination with 10 nM PEP005 (right panels) for 24 h and cells analysed by flow cytometry. Results presented as Δmean fluorescence intensity (ΔMFI) of DsRed expression and fold increase in DsRed expression for solo and combination treatments, respectively. Data Information: Mean and SE are determined from three biological replicates (n=3) and technical duplicates. Statistical significance, as determined by one-way ANOVA is indicated: ****, P<0.00005. The exact P-values are listed in the Appendix Table S1.
At early night, wild-type (A) and 5X (B) TOC1 are equally present and recruit transcriptional repressors NF-YB/C and HDA15 with PRR5 (not shown) to inhibit expression of PHGs. As night progresses, PIF3 levels rise, and the advanced phase of 5X, more rapid degradation and poorer PIF3 interaction result in lesser presence of 5X at target promoters, relative to wild-type TOC1, leading to attenuated inhibition of PHGs and enhanced hypocotyl growth. At late night, low TOC1 and PRR5 levels reduce NF-YB/C and HDA15 recruitment, resulting in PIF3 release to activate downstream PHGs that leads to maximal pre-dawn hypocotyl growth.
Mitochondria from wild type and MITRAC15-/- cells were isolated and analyzed by BN-PAGE. Triton X-100 (left site) or digitonin (right site) were used for solubilization. The amount of complex I was quantified utilizing the NDUFS1 signal and normalized against SDHA levels (error bars indicate SEM from three biological replicates).
A. Cartoon of in vivo experimental approach. MDA-MB-231CFP;Cre and reported T47DDsRed cells were co‑injected in one mammary gland of 10 mice per experiment.
Visualization of the H3K27ac, Lsd1 and H3K4me2 CUT & RUN and of RNA-seq tracks of the TGFB2 promoter region in Epi-CTR, -HOT, -HOTΔP and -HOTΔL cells.
(E) Cluster ID annotation with heatmap. Cluster IDs are indicated in rows, while surface marker expression levels are indicated by the columns. The color represents the relative mean fluorescence intensity (MFI) of a surface marker. Blue and red represents low and high MFI, respectively. Red square and ovals highlight differences of several PhenoGraph clusters in infected joints at 6 dpi.
(B) Isothermal titration calorimetry of purified recombinant YqgPNTD and selected divalent cations.