EMBO/sd-character-level-ner huggingface dataset:
(G) FACS analysis of Gag positive cells from donor 2 in different conditions. Red: uninfected cells. Blue: untreated infected cells at 7 d p.i. as in B. Orange: cells were treated with NVP for 7 d as in C. Green: infected cells were exposed to NVP for 3 d, then NVP was washed out and cells were cultured for another 4 d as in D. Median of fluorescence intensities (MFI) for each sample are shown in the table.
SARS-CoV-2 complete genome sequence was used to design eight overlapping subgenomic viral fragments covering the complete genome. Positions on the genome (in nucleotide) are indicated in bold red.
(F) The boxed scheme describes the mitochondrial calcium overload hypothesis. Lactic acidosis forces the Na+/H+ exchanger (NHX) to import Na+, resulting in cytosolic Na+ overload. Subsequently, the Na+/Ca2+ exchanger (NCX) is forced into reverse mode to dispose of excess Na+, resulting in cytosolic calcium overload. This Ca2+ is then taken up by mitochondria, resulting in mitochondrial calcium overload. 2-DG (2-deoxyglucose; 50 mmol/L) blocks glycolysis through competitive hexokinase inhibition, whereas oligomycin (10 µmol/L) inhibits mitochondrial ATP synthase. G-6-P: glucose-6-phosphate.
Spearman correlation of relative SAMHD1 protein abundance and synergy delta scores for ara-C versus HU or dF-dC in a panel (n = 9) of haematological cancer cell lines. Error bars indicate s.e.m. Each data point corresponds to SAMHD1 protein levels determined by immunoblot analysis (n = 4 for each cell line, representative blot shown in Appendix Fig S2) and an average delta score from repeated dose-response matrix experiments each performed in triplicate: THP-1, n =4; HuT-78, n = 2; HL-60/iva, n = 1; KBM-7, n = 2 (HU) and 3 (dF-dC); K562, n = 3 (HU) and 4 (dF-dC); CCRF-CEM, n =3 (HU) and 4 (dF-dC); MV-4-11, n = 2 (HU) and 3 (dF-dC); Jurkat, n = 2 (HU) and 3 (dF-dC); MOLT-4, n = 2 (HU) an 3 (dF-dC).
(F) Pax7 (green) and Ki67 (red) staining was performed on the above single EDL myofibers. Scale bar = 50 µm. Quantifications of the numbers of each population, Pax7+Ki67-, Pax7-Ki67+, or Pax7+Ki67+, are shown on the right (n= 3 mice, each).
C-F. Immunofluorescence images of esg-GFP and Delta (Dl) staining with the midgut section from the R4 region of 14-day Drosophila (C), 26-day Drosophila (D), 40-day Drosophila (E), and 40-day Drosophila in response to 0.5 mM ALA administration, which started at day 26 after eclosion (F). esg-GFP (green) identifies ISCs and their differentiating cells. Dl staining (red) was used to visualize ISCs. Data information: DAPI stained nuclei are shown in blue.
ELISA for CCL2 performed on total back skin treated with IMQ. (n= 5-14; 2 independent experiments). Data information: Data are shown as mean ± SEM. P‐values were calculated by multiple t-test with Tukey (D multiple comparison test. Statistical significance: ns > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001. See Appendix Table S3 for exact P‐values.
O-Q) Representaitve pictures showing that adult pros clonal growth was not significantly altered on -his diet compared to CDD (after 7 days), quantified in (Q) (n = 12, 23,16). Scale bar = 75μm. R-T) Representaitve pictures showing that larval pros clonal growth was not significantly altered by dietary histidine reduction (25% his) compared to CDD (after 6 days), quantified in (T) (n=19,13). Scale bar = 50 μm.
B Western blot showing levels of Gli2a-FL and Gli2a-R forms in 20hpf wild type and MZgrk2 embryos injected with mRNA encoding Shh, dnPKA or mSmoA1-GFP, respectively. γ-tubulin was used as loading control. Three biological replicates of this analysis were performed.
B. One-carbon folate metabolism in P. falciparum. The parasite encodes all the enzymes necessary for a complete cytosolic pathway but only appears to possess a single enzyme-serine hydroxymethyltransferase-in the mitochondrion. Highlighted in white are the conventional enzymes and reactions of one-carbon metabolism in the mitochondria of other eukaryotes.
Voltage responses from P22 Clrn2clarinet/+ (G) and Clrn2clarinet/clarinet (H,I) IHCs. Note that Ca2+-dependent action potentials could be induced in mature IHCs (I).
(H) Correlation between clinical metastatic staging and SOX9 protein across the TMA of 142 cases of human medulloblastoma. The SOX9 protein levels were determined by IHC in Figure 3F. Tumors with SOX9 protein level frequently presented (p=0.038, Fisher's exact test,) with the M3 metastatic staging, spread to the spinal cord (red bars). Analysis was carried out by comparing patients with high SOX9 protein rank (Rank 5-7) versus patients with low SOX9 protein rank (Rank 1-3).
A) Manhattan plot of genome-wide association for expression of Ifi203 in liver. Red line shows Bonferroni-corrected threshold and blue shows an FDR =0.01 pvalue of significance calculated based on FaST-LMM pvalues.
The first five modes of correlated movements. Direction of motion is indicated by the arrows. Informativity of the respective modes measured as variance of the corresponding mode divided by variance of the first mode. Scale bars: 10 nm.
Semi-thin cross sections of femoral quadriceps nerves stained with alkaline methylene blue. Note the smaller size of Ccp1-/- and Ccp1-/-Ttll7-/- nerves (A).
B. Lifespan analyses of chd-7(gk290) mutants (n=339; red) compared to WT (n=444; black). Log-rank test was performed for statistical analyses. ***p < 0.001.
Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on cryofixed samples ( (J) There is no change in the number of docked SVs per AZ length (M18WT: 14.36 ± 0.32 docked SVs/pm AZ; M18Y473D: 14.34 ± 0.32 docked SVs/pm AZ, multilevel analysis, p = 0.969). (G-J) M18WT : N=3 independent cultures, n=159 synapses; M18Y473D: N=3 independent cultures, n=156 synapses.
(D) Heat map of the row-wise z-scores of 16 EMT hallmark genes in SOX9-WT and -T236/T240A samples. Heat map was generated using the GenePattern software (Reich et al., 2006).
Type VII collagen (COL7) labeling in WT dorsal skin sections (P1). Scale bar: 200 μm.
D Expression of Prox1a and Engrailed proteins (Eng) in somites of wild-type, MZgrk2 and grk2-GFP mRNA injected MZgrk2 embryos at 30hpf. Each panel shows Prox1a in green, Eng in red and the merge images with DAPI staining in blue. (n=10 for each sample). Scale bar, 50μm.
RIP assays were employed to validate the association of ASS1 with LOC113230 in SW-1116 cells. Antibodies against HuR, GAPDH or control IgG were served as controls.
A. A model illustrating the Drosophila "esg>luciferase" reporter system of chemical administration. The chemicals were fed to Drosophila with esg-GAL4-driven luciferase expression on the 26th day after eclosion. After administration for 14 days, Drosophila were dissected, and the activity of luciferase in their midguts was measured.
D). Avascular area in choroid in sodium iodate model was determined and quantified using Image J. E). Thickness of retina in H&E staining was quantified and bar graph was shown using ImageJ. Data information: Bars and error bars represent mean ± SEM. All experiments were carried out in three independent studies. Two-way ANOVA was used as statistical test.
(b) Estimation of gene editing at the Trim28 loci using NGS-sequencing of amplicons. Black bars indicate % of frameshift indels. Columns show an average of two biological replicates per guide RNA and error bars show mean ± SD.
D Pull-down assay of the interactions between SUFC and apo- or iron-bound form of DJA6. GST-tagged mature iron-bound or apo-DJA6 was used as the bait, MBP and MBP-tagged mature SUFC were used as the prey. The bound proteins were eluted and analyzed by staining and immunoblotting.
Pulsing experiment was repeated in the presence of protease inhibitor (PI) that reduced the lag time for a given TI feedrate (f = 0.28 mmol/g/h). The TI feedrate is abbreviated as f (units: mmol glucose/g dry cell weight/hour). Wild-type lag (from Figure 2A empirical fit) is indicated by the dotted grey line
C. Western blot analysis of CD133 protein expression level in MDA-MB-231 cells treated with siNT or siRASSF1.
(a) Schematic of extracting kymograph information from tissue data by averaging Venus::HES5 intensities observed in E10.5 heterozygous spinal cord slices to generate one intensity profile in the dorsal-ventral axis per timepoint (see Materials and Methods). (b) Representative kymograph data showing spatiotemporal Venus::HES5 expression profile along ventral-dorsal direction in a 15μm wide apical region and observed over 14h; local bands of 20μm width in D-V; region of interest markers indicate: *low to high, **high to low and ***re-occurring high/low activity in the same area.
(F) Growth curve of 1603MED cells after transfection with either siCTRL (blue) or siINHBB (red). The p-values were determined by unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001.
D Tyrosine phosphatase activity in anti-IDO1 immunoprecipitates from P1.HTR cells transfected with IDO1.WT cells and treated with PI3K catalytic inhibitors (indicated) or medium alone (ctrl). Data represent the mean ± SD (n = 3 technical replicates).
RNAPII CRAC were performed in the presence of the indicated versions of SEN1 expressed from its own promoter in a centromeric plasmid, upon depletion of the chromosomally-encoded version of Sen1 in a Sen1-AID strain. E) Metagene analyses of transcribing RNAPII at CUTs performed as for mRNAs but using the annotated transcription termination site (TTS) as the reference point. F) Analysis of termination defects in the different mutants at CUTs. Box-plots performed as in (B). The RT index is calculated as the average signal over a window of 400 nt downstream of the TTS, divided by the average signal over a window of 100 nt downstream from the TSS (CUT100). For each CUT (n=329), the values correspond to the average of two independent biological replicates. P-values < 0.001 are indicated by three asterisks.
F. Human intestinal organoids were incubated with media (mock) or infected with HAstV1. At 24 hpi the presence of IFNλ in the media was tested by ELISA. Dotted line indicates detection limit of the assay.
G. Top: graphical representation of the functional (invasion) assay performed using MDA‑MB‑231 derived EVs on MCF7 recipient cells. Bottom: Boyden chamber invasion assay in 3D matrigel of EVs isolated from different steps of ultracentrifugation. EVs were collected from conditional medium produced by MDA-MB-231 expressing Control (pcDNA3) or FLAG-RASSF1C. The 2K (large EVs), 10K (medium EVs or MVs) and 100K (small EVs, including exosomes) pellets were collected and equal amount of EVs (normalized according to protein content) were incubated with MCF7 cells. MCF7 were evaluated for invasion after 24 hours. Data information: All data are from n=3 independent experiments. Data are analyzed by Student T-test and represented as mean ± SEM.* p ≤ 0.05, ** p ≤ 0.01, **** p ≤ 0.0001.
H Zebrafish larvae were overexpressed the indicated protein for 48 hours and challenged with VSV for another 6 hours, then the mRNA levels of ifn1 in zebrafish larvae were measured by qRT-PCR (left panel). Every dot represents three zebrafish embryos. Horizontal square bracket shows the statistical analysis of the comparison with 'PBS mock', the rest shows the comparison with 'PBS VSV'. PBS mock, n=5; PBS VSV, n=13; AKT2 VSV, n=7; AKT2-T309A/S474A VSV, n=9. H&E staining (middle panel) and survival rates (Kaplan-Meier curve) (right panel) were collected from zebrafish larvae after VSV micro-injection for 18 hours or longer. The arrows indicated the VSV-infected eye and skeletal muscle in zebrafish larvae. Bars, 100 μm. Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using a one-way ANOVA test or log-rank (Mantel-Cox) test Data are from three independent biological replicates Error bars mean ± SD).
D, Models of RMD mediated by SSA (RMD/SSA) or BIR (RMD/BIR). When a DSB is created in the middle of two repeats, the DNA ends of both sides are resected, generating 3' ssDNA overhangs, until the repeat sequences on opposite sides are both exposed. Then ssDNA of the repeat sequences anneal, resulting in a product with internal sequences deleted. When a DSB is generated close to one repeat, ssDNA formed in one repeat first can invade the other repeat still in duplex using BIR, which can also give rise to a deletion product identical to the SSA product after cleavage of D-loop. Pink arrow: putative structure-specific endonucleases to cleave non-homologous tails; blue arrow: putative structure-specific endonucleases to cleave the D-loop.
D. Naïve murine CD4+ T cells were isolated by FACS from lymph node and spleen cell suspension of USP44fl/fl CD4Cre+ mice and that of their wild type littermates (USP44fl/fl CD4Cre- mice; n=2-3/group/experiment). iTreg cells were generated from these mice as described for Fig. 1 before incubation on a microscope slide pre-coated with poly-L lysine for 1h. Adhered cells were then fixed by PFA for 0.5 followed by blocking with 1% BSA for 1h, then incubation with the specified antibodies. Representative confocal microscopy images (40X) were visualized for endogenous USP44 (red) and FOXP3 Baxter et al(). DAPI was used to visualize cell nuclei (blue); scale bar 50μm.
Immuno-FISH showing EC neurons having both misfolded somatic tau (Alz50, red) and human tau mRNA (green; white arrows) in rTg4510-Mapt0/0 but rarely in rTg4510 mice. n=3 sections, 2 mice/group. Scale bars 50 μm.
(G) SMAD3 depletion (siRNA#1 & #2) decreased cell density and increased BRAFi effect (vemurafenib) on BRAFi-resistant cells (SKMel28R). CTR for non-targeting siRNA. DMSO for dimethylsulfoxide (solvent of vemurafenib; BRAFi). n=3 biologically independent experiments. Each histogram represents the mean + s.d. (H) SMAD3 depletion (siRNA#1 & #2) decreased cell density and increased BRAFi effect (vemurafenib, BRAFi) on BRAFi-resistant cells (Me1402). CTR for non-targeting siRNA. DMSO for dimethylsulfoxide (solvent of vemurafenib). n=3 biologically independent experiments. Each histogram represents the mean + s.d.
B. Results of the sequential digestion workflow applied to a synthetic 7-protein mix, compared to using trypsin alone in four replicates and parallel digestion with trypsin, AspN, chymotrypsin and GluC. A trypsin four replicate experiment shows a large overlap of the four datasets with little gain. Parallel digestions with trypsin, AspN, chymotrypsin and GluC demonstrates high complementarity but moderate gains over trypsin. Sequential digestion shows low overlap between the four datasets and the largest gain in unique residue pairs. C. Gains of repeated analysis (trypsin only), parallel digestion and sequential digestion for the same data as shown in panel B.
E. Western blot analysis of LC3 and Lamp1 proteins from growth plate lysates of mice with indicated genotypes. β-actin was used as loading control. N=3 mice/genotype were analyzed. Bar graph shows quantification. Mean +/- standard error of the mean (sem). Student's un-paired T-test *p<0.05.
B. Cross-linking experiment of full-length and cleaved GSDMD. GSDMD at a concentration of 2 μM was incubated at room temperature with 5 nM caspase-1. After enzymatic cleavage, GSDMDNterm is highly cross-linked by DSS, resulting in the gel-impenetrating species highlighted by the arrow. GSDMDCterm is not cross-linked.
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 shCtrl, by ANOVA with Sidak's correction.
b, Cross-linking experiment with recombinant Atg18wt as in a, performed in the presence of increasing concentrations of liposomes containing 5% PI(3,5) P2.
(C) Quantification of the percentage of bacteria decorated with EPAC in cells infected with S. aureus. ** p<0.01 (paired Student's t-test, n = 20 cells/condition). These data are representative of three independent experiments.
(H) The expression of representative markers of 5C, naïve and primed states was summarized in E3.5, 4.5, 5.5 and 6.5 epiblast.
(A) Lysates from siRNA-treated U20S cells (scramble control [Scr] or VCP siRNA KD) after autophagic induction via nutrient deprivation for 0, 2, or 4 h and immunoblotting for LC3 and α-tubulin. LC3II degrades over time in control but not in KD cells. One of two experiments is shown.
(G) Sorted CD14+ monocytes from donors were infected with SARS-CoV-2 at an MOI of 1 for 1h, followed by washing away extracellular viruses and further culture for 3 h. Cells were immunoblotted with antibodies against the indicated proteins. CD14+ monocytes from healthy donors were treated with 10 μM nigericin for 30 min following pretreatment with 1 μg/ml LPS for 3 h and served as a positive control. Data information: experiments were repeated for three time with similar results.
B. All m/z features detected from iRBC extracts plotted as the log2 ratio of their abundance detected in 13C-glucose versus 12C-glucose conditions. 859 m/z features (from a total 33,691 m/z features identified) were significantly altered in 13C versus 12C samples of iRBC. Highlighted in black is a single m/z feature (m/z 275.0167).
A) Volcano plot of the fold-change (x-axis) plotted against significance (y-axis) of lipids changing upon HF/HS feeding. Lipids are colored according to fold-change (log2, absolute) > 1 (orange), p-value <0.05 (red) or both (green). Pvalues calculated from differential expression using limma
(C, E) and HT-29 (D, F) cells were treated with the indicated concentrations of NaB for 24 h. C.D. The percentage of apoptotic cells in HCT-116 (C) and HT-29 (D) cells was quantified in three independent experiments using an annexinV/PI assay (annexinV+/PI-) by flow cytometry and expressed as mean ± SD. One-way ANOVA was used to compare between the control cells and NaB treatments. *p<0.05, ** p<0.01 compared to control. E.F. Representative Western blots of full-length and cleaved PARP products in HCT-116 (E) and HT-29 (F) cells.
b, c) Quantification of b) neutrophil infiltrates (NIMP positive) and c) mean number of TAF positive hepatocytes in liver of young (3 months) and old (24 months) mice. Data are mean±S.E.M. of 3-5 mice per group ; d) Quantification of mean number of TAF in hepatocytes as a function of the distance from a Ly6G labelled neutrophil. Data are from 5 mice aged 29 months of age, line indicates linear relationship between mean TAF and distance (linear regression and F test: R2=0.35; P<0.0001);
(B-G) Munc18-1 null hippocampal neurons were rescued with wildtype Munc18-1a or a Munc18-1 mutant, Y473A, in which Y473 was replaced with alanine.(C) Quantification of confocal images. Average synaptic Munc18-1 intensity (M18WT: 389 ± 85 a.u., n=21; M18Y473A: 321 ± 48 a.u., n=20, t-test with Welch correction, p = 0.4868), somatic Munc18-1 intensity (M18WT: 328 ± 49 a.u., n=21; M18Y473A: 245 ± 42 a.u., n=20, t-test, p = 0.2810), synapse number (M18WT: 129 ± 14, n=21; M18Y473A: 159 ± 16, n=20, t-test, p = 0.1548) and dendrite length (M18WT: 0.433 ± 0.028, n=21; M18Y473A: 0.461 ± 0.037, n=20, t-test, p = 0.5473).
F) Epidermal thickness of WT and Pvt1 KO skin grafts was quantified and presented as box and whisker plots. The plot indicates the mean (solid diamond within the box), 25th percentile (bottom line of the box), median (middle line of the box), 75th percentile (top line of the box), 5th and 95th percentile (whiskers), 1st and 99th percentile (solid triangles) and minimum and maximum measurements (solid squares). n=6 (biological repeats), P<0.05 (Student's t-test). n=18, P<0.01 (Student's t-test).
Localization of RACK1 (I) in untreated cells or cells pre-treated with the indicated CDK inhibitor (1 µM, 150 min) and then with SA (300 µM, 30 min). G3BP was used to stain SGs. Scale bar, 10 µm. Graphs show quantification of the localization of the respective protein with SGs, expressed as a percentage of the control. Mean ± s.e.m. of one representative experiment out of three independent replicates, n=60-80. ****p<0.0001, One-way ANOVA with Dunnett's multiple comparison test.
A) Boxplots showing GK effect - the difference between TANGO score and PureTANGO score - per charged GK, and per position with reference to the APR. Negative numbers indicate N-terminal positions, positive numbers refer to C-terminal positions. The upper whiskers indicate the largest value no further than 1.5 times the Inter-Quartile Range (IQR) from the upper hinge, the lower whiskers show the smallest value at least 1.5 * IQR from the lower hinge. Notches extend 1.58 * IQR / sqrt(n) from either side of the median and represent a 95% confidence interval for the median value. Significance was determined through Kruskal-Wallis test with a post-hoc Wilcoxon analysis for pairwise testing and Bonferroni correction for multiple testing. Adjusted p-values are indicated for each comparison. The number of observations per group is indicated beneath each box.
G: Radar chart indicating the relative levels of pAKT (pink line), pEGFR (light blue line), or total EGFR levels (dark blue line), in autophagy-deficient cell lines relative to their control counterparts. The following knockouts were introduced: glial cells (sgAtg7), HT29 (crATG7), MCF-7 (sgATG5), A549 (sgATG5), U2OS (sgATG5), and MEFs (Atg16l1-/-).
H-K. Representative flow analysis and quantification of CD8+ T cell activation markers: Granzyme B (H), IFN-γ (I), TNF-α (J), and PD-1 (K) (n = 5).
C RGB‐line profile across the vesicle indicated with arrow in (B); red-AP2A1; green-ATG9A; blue-TBC1D5.
(F) Luciferase assay in HEK cells overexpressing miR-143 or miR-145 transfected with a plasmid harboring the WT or muted sequence of the miR-143 and miR-145 binding sites present in FSCN1 3'UTR. Each bar represents the mean ± SE of experiments performed at least in triplicate. ***P≤0.001, ****P≤0.0001. P-values were calculated using Paired Student t-test.
(D) Endogenous Co-IP of BET1 and ERGIC-53. Immunoblots of HEK 293T cell lysates (+ lysate) or lysis buffer (-lysate) incubated with (+) or without (-) BET-1 antibody followed by precipitation with protein A/G beads. ERGIC-53 signal was only present in samples with lysate and antibody. whereas * denotes unspecific signals from beads used for precipitation. As a positive control GOSR2 antibody was used.
NEDD8 trimers specifically bind to the second zinc finger of PARP-1. NEDP1 KO U2OS cells were transfected with GFP, GFP-PARP-1, or with GFP fused to the Zn1 domain (AA 1-96), the Zn2 domain (AA 97-215), the Zn3 domain (AA 216-336) or the Zn1+2 domains (AA 1-215) of PARP-1. 24 hours post transfection, cell lysates were collected and immunoprecipitation with GFP-Trap was performed. Bound proteins were eluted and resolved by SDS-PAGE analysis, followed by Western blot analysis with the indicated antibodies.
(A) The central channel in the PfFNT-MMV007839 protomer viewed from the parasite's membrane plane. The channel, calculated by HOLE (Smart et al., 1996), is indicated by blue dots. There is one constriction site (colored red) formed in the central channel. Residues forming the constriction are in green sticks. Residues that line the rest of the channel are in cyan sticks. (B) Representative figure of the calculated diameters of a PfFNT-MMV007839 protomer.
B) Solid phase transfection of nontargeting (scrambled) or CCNA2 targeting gRNAs into Cas9 expressing RPE-1TP53 -/- cells. Cells were fixed after 72 hours and imaged after DNA staining with Hoechst. C) Quantification of nuclear size measurements from Fig 2B. Data derived from 3 independent experiments. P value (scrambled vs CCNA2) < 2e-16, Kolmogorov-Smirnov test.
D Data points correspond to mean output of stochastic Monte Carlo simulation results for the average protein age as function of position, 2.5 hours after initiation Colored lines correspond to theoretical predictions for protein age in each model