EMBO/sd-character-level-ner huggingface dataset:
(H) Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (CTRL vs. BAM15: P=0.0259, CTRL vs. CR: P=0.040) after 2-weeks of treatment in CTRL, BAM15, and CR treated animals (CTRL N=7, BAM15 and CR N=8).
Boxplots (plotted as in Fig 3B) of gene expression of ELP3, ALKBH8 and CTU2 upon treatment with 17β-E2 and/or ICI-182780 in MCF7 cells (extracted from (Wardell et al, 2012; Data Ref: McDonnell et al, 2012)). Wilcoxon-Mann-Whitney tests (two-sided) were used to assess differences between conditions (n = 10) and a global Bonferroni adjustment was applied on p-values.
Luciferase activity driven by the NF-κB (D) promoter in HEK293T cells transfected with Flag-RNF34 or its E3 ligase-dead mutant H342A followed by VSV infection for the indicated times. Luciferase assays were performed 24 hrs after transfection, and luciferase activity was reported as the fold induction. The luciferase reporter data are presented as means ± SEM. Two-tailed Student's t-test was used for statistical analyses: *, P < 0.05; **, P < 0.01; and ***, P < 0.001.
Figure 5. Differential lysine acetylation and protein expression in hda14 vs. wild-type leaves in isolated thylakoids (B, E) Volcano plots depict protein ratios (D-F, bottom row) for mutant vs. control, with p-values determined using the LIMMA package. Orange, protein with nuclear localization; Green, protein with plastidial localization; purple triangles, proteins of the Calvin-Benson (CB) cycle; blue diamonds (top row), proteins of the light reaction; localization information according to SUBA4 database. Blue circles (bottom row), proteins with lysine acetylation sites identified. Dashed lines indicate significance thresholds of either uncorrected p-values < 5% or Benjamini-Hochberg corrected FDR < 5%. A missing FDR line indicates that the 5% threshold was not reached by any of the data points.
Western-blot analysis of p-ULK1, p-AKT, p-S6, and p-p70S6K in GSC#9 treated for 1 hour with MPZ (20 μM) or rapamycin (RAPA, 50 nM). Total ULK, AKT, S6, and p70S6K served as loading controls. DMSO was used as a vehicle.
B. Schematic of the system for stimulating CAR T cells and imaging CAR dynamics. Supported lipid bilayers (SLBs) were coated with the extracellular domain of CD19 and an integrin ligand ICAM-1.
Western blotting analysis of the vacuolar delivery of the free YFP protein in the plants as shown in panel A. YFP-ATG8e/Col-0 plants were treated with N starvation as a positive control of autophagy induction. Total proteins were analyzed with GFP antibodies. Actin served as loading controls.
D-E: AAVS1KO and TLR7KO pDCs were either mock treated (mock) or exposed to SARS-CoV-2 (SARS-2, 1 MOI), supernatants were collected at indicated time points and analyzed for type I IFNα (D) and CXCL10 (E) proteins. Data information: Bars represent mean values and equal symbols represent the donors used throughout the experiments (n=4). Statistical significance was determined using the ratio paired student T test for agonist or virus treated cells and compared to their respective mock treated conditions, or by unpaired non-parametric T test when comparing matched conditions between different KOs. *TLR7-KO data had no variance and values of 0.
Saline and 2G8-treated MiaPaca-2 and Colo375 xenografts were subjected to RNA-seq analysis for mouse gene expression changes. Molecules most significantly by 2G8 treatment. Y-axis values shown are log10(FPKM+1) of the transcript levels (D-F).
C, Pearson and Spearman coefficients (rp and rs, respectively) of co-localization (PSC) of RFP-TSN2 with individual GFP-tagged TSN-interacting proteins listed in A and with both negative and positive control proteins (denoted by red arrowheads) under HS. Data represent means ± SD of at least 5 replicate measurements from three independent experiments.
Female and male gametocytes formation in mouse. Gametocytes were counted via Giemsa staining of thin blood smears. Gametocytemia was calculated as the ratio of male or female gametocytes over parasitized erythrocytes.
(B) The APOBEC3 mutational signature is enriched in tumors with CCT gene mutations. Single base substitution (SBS) patterns, as defined by COSMIC Mutational Signatures v2, were evaluated in CCT-mutated and CCT non-mutated cancer genome sequences. Depicted are the mutational signatures attributable to APOBEC3 activity (SBS 2 and SBS 13). Denoted p-values determined by Wilcoxon rank sum test.
Expression of , PID-4::mTagRFP-T (B) in perinuclear granules in the germline. DEPS-1::GFP (B mark P granules. The indicated dashed boxes reflect zoom-ins on specific nuclei to better visualize the granules, and their overlaps. One L4 gonad is shown for each animal. Note that most of the L4 gonad is in pachytene stage. Arrow heads indicate individual condensates. Scale bar: 25 µm.
F. Growth rate of single cofilin domains, normalized by the cofilin concentration. N = 50 (from 3 independent experiments) and 20 (1 experiment) domains on non-oxidized and oxidized filaments, respectively. Measurements were obtained using 20 and 100 nM cofilin (non-oxidized actin) and 10 nM cofilin (oxidized actin). Note that this normalized growth rate does not depend on the cofilin concentration (Appendix Fig S4A). Bars: mean and S.D. P-value = 7.10-8 (t-test).
D. Sequencing of MUT DIS3L2-bound tRNAVal and tRNALeu confirmed the uridylation status of the tRNA fragments identified by CLIP-seq. Genomic sequence for each tRNA is indicated on top with the 3' trailer region separated by a vertical line. Non-templated uridine residues are in red.
(B) Wild-type primary B cells were treated with vehicle control (-), 5 μg/mL anti-kappa antibody or 1 µM LatA for the indicated time. Cells were lysed and analysed by SDS-PAGE followed by immunoblotting with phospho-Lyn (Y507) and actin as loading control. The intensity of phosphorylated proteins, normalized to actin, was referred to the respective unstimulated sample, set as 1.
(B) α-Synuclein fibrils were introduced into HEK293 cells, followed by addition of DMSO, 100 nM bafilomycin (BafA1), or 200 nM rapamycin (Rapa). Cells were stained by anti-phosphorylated α-synuclein antibody (green) and DAPI (blue) 1 h (left panels) or 24 h (right panels) after introduction.
(B) A fragment encompassing amino acids 432-520 of Atg13 (wt) or the corresponding FV mutant (FV) was expressed in E. coli and incubated in excess with an immobilized GST‐tagged fragment of Atg1 (amino acids 501-897) purified from E. coli (GST‐Atg1). Input (5.5%) and bound proteins were analysed by coomassie blue staining, which stains proteins proportional to their size. The size of marker proteins (in kDa) is indicated on the left.
H The immobility time in the FST with intra-hippocampal infusion of ARL67156 after CSDS (n = 21, 12, 23, 19 mice. Treatment F 3, 71 = 12.94, P < 0.0001; CSDS - ACSF vs Ctrl - ACSF, P = 0.0036; Ctrl - ARL67156 vs Ctrl - ACSF, P = 0.0428; CSDS - ARL67156 vs CSDS - ACSF, P < 0.0001. One-way ANOVA with Fisher's LSD test).Data information: data are expressed as the means ± SEM. NS P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001. Ctrl, control.
hCDC14A, not the inactive hCDC14AC278S, dephosphorylates the serine residue 142 of DBN1 in vivo. RPE1 cells expressing GFP, hCDC14A-GFP, and hCDC14AC278S-GFP under TetON promoter were serum starved in presence or absence of Dox for 48 h prior to fixation for immunofluorescence. DBN1pS142 was detected with a phospho-specific antibody. DNA was stained with DAPI. Scale Bar = 10 μm
E Cohesin loading complex is required for completion of chromosome replication after MMS treatment. Intact chromosomes were isolated from wild type (Y39) and scc2-4 (Y4366) cells cultivated at permissive temperature (25°C) and processed for PFGE. M, MMS
F) Immunoblot showing the levels of CDC7 and actin in the Mybl2+/+ and Mybl2Δ/Δ ESCs. Bar graph (lower panel) represents average band density of CDC7 in Mybl2Δ/Δ ESCs relative to actin and relative to Mybl2+/+ ESCs from three independent repeats. Error bars represent SD. Statistical analysis was carried out using a two-tailed unpaired t-test (ns=no significant).
A, CRISPR-modified cells (Brightfield, left) that express GFP-nesprin-2 (middle) and mCh-LAC (right) show nesprin (orange arrow) but not lamin accumulation at the front of the nucleus as it is deformed through a narrow constriction. B, Quantification of intensity of GFP-nesprin-2 and mCh-LAC, normalized to the intensity at the sides. Error bars correspond to the standard deviation. Constriction: n=19 cells over 5 biological replicates, 15 µm: n= 27 over 6 biological replicates. A Wilcoxon signed-rank test is used to compare matched samples, stars (*P < 0.05, **P < 0.01) denote comparisons to the measurement at the side, and pounds (#P < 0.05, ##P < 0.01) denote a comparison to the "before" time point.
B HOPS was pivotal for apoptosis induction. Hops+/+ and Hops−/− MEFs were subjected to etoposide (Eto) and apoptosis was analysed by flow cytometry (left) and showed as a graph (right). Data information: the experiments were performed three times in primary cells from three different mice per condition. The experiments in MEFs were performed three times. Representative panels are shown. In data are presented as mean ±SD. * P < 0.05; ** P < 0.01; *** P < 0.001, by two tailed Student's t-test.
The number of molecules per cell for STAT1, STAT2, IRF9 and USP18 were simulated by the mathematical model for untreated Huh7.5 and HepG2-hNTCP cells as well as for cells stimulated with 1.2 pM and 608 pM Roferon for 24 hours.
Lysates from CD1a+ and CD1a- cells from human skin dermis or epidermis (Epi) were subjected to immunoblotting for the expression of S100A9 proteins. Loading control was done with anti-actin (n=2).
(E). Percentage change in parasitemia following neutrophil challenge of RBCs infected by different parasite lines (NF54, Dd2, SL, PfEMP1-KO).
A Purified TAP-tagged Rik1-containing complexes analyzed by SDS-PAGE and silver staining. mock: a mock purification from an untagged strain. Proteins identified by LC-MS/MS are indicated at right, with the number of identified unique peptides in parentheses.
GSEAs showing upregulation of genes belonging to the K-Ras, Angiogenesis and mTORC1 gene sets in (WT) compared to VEGFR2 Y1212F isolated ECs. K-Ras and Angiogenesis gene sets derived from C57Bl/6 iECs kept in basal condition; mTORC1 gene set derived from C57Bl/6 iECs treated with VEGFA for 3h. See Supplementary Table 2. Enrichment score (ES), normalized ES (NES) are shown. P-values <0.05 were regarded as significant. Heat maps displaying gene regulation in gene sets shown in A. The color in the heatmap shows the gene expression value, expressed as a z-score across animals. Red color represents relative higher expression and blue color represents relative lower expression value. The z-score is calculated by (x-x')/s where x is individual gene expression, x' is the mean of the gene expression across samples and s is standard deviation of the gene expression across samples.
E. Immunoblot of phospho-S622 Drp1 in cortices and brainstem of 3-month-old Ifnb+/+ and Ifnb-/- mice and quantification.
G Examples of RNA-seq read maps of HSATIII target RNAs. Affected introns and exons are indicated by blue (down-regulated upon HSATIII knockdown) and magenta (up-regulated) boxes.
Schematic designs for metabolic energy measurements at different temperatures and after i.p. injection of CL316243 (CL). Changes between 2 temperatures occurred linearly at 2 h
Proliferation of melanoma cells over indicated times after treatment with siASNS, HA-GSK3-β (S9A), or both (H).
(C) Chemical structures of selected drugs displayed in panels A and B; see all tested drugs in Appendix Figure S4.
(H) β-Catenin is directly phosphorylated by Plk1. Bacterially purified full-length GST-β-catenin was incubated with either HA-Plk1 wild type (WT) or HA-Plk1 kinase defective mutant K82M (KM) purified from insect cells in the presence of [γ-32P] ATP. Incorporation of γ-32P into GST-β-catenin was confirmed by SDS-PAGE followed by autoradiography analysis.
B-G - Stains and quantifications of human cerebral organoids electroporated with the indicated construct combinations, to reveal the frequency of electroporated cells remaining as progenitors (%GFP+Ki67+/GFP+). Histograms represent mean ± SEM; symbols in plots indicate values for individual organoids; X2-test, *P < 0.05. N = 8-11 replicates per group. Dashed lines indicate ventricular surface, solid arrowheads indicate Ki67+/GFP+ cells, open arrowheads indicate Ki67-/GFP+ cells. Scale bars, 50 µm.
F. Levels of U3 snoRNA immunoprecipitated by the anti-m3G cap antibody in HeLa cells infected with an anti-DCP2 or a non-targeting shRNA and expressing GFP, PNRC1WT or PNRC1W300A transgenes. The average ± SD of 2 independent experiments with three technical replicates is reported.
L. The relative production of EBV virions in CNE2EBV cells transfected with YTHDF1-specific siRNAs (siY1-1 and siY1-2) or the siNC control following EBV reactivation, was measured by qPCR. After 24 h of siRNA transfection, CNE2EBV cells were treated with NaB (2 mM) for 24 h, and the DNA from the cell-free culture supernatant was harvested for qPCR. The number of EBV copies in the supernatant of the cells was quantified by qPCR using specific primers targeting BamHI-W fragment region of EBV. The mean value of EBV copies in the siNC cells was normalized to 1.
Effect of nucleoside (NS) cocktail treatment from 1-3 dpf on the incidence of cardiac edema in WT and yap-/- mutant larvae. Each point represents the percentage of affected embryos in each independent clutch. n>7, **p<0.01, two-sided Student's t-test; values represent the mean s.e.m
D. Velocity auto-correlation (VAC) over the delay in minutes (min) for all cell tracks in a cluster. The curves are color-coded to denote the corresponding cluster. For visualization purposes, the VAC is shown for a time delay corresponding to 24 hours of imaging. The dashed box depicts the VAC for each cluster for 4 hours of imaging to visualize the initial decay.
(B, C) Number of total ILC2s and percentage of c-Maf+ (T test, ***p<0.001) (B); activation status of ILC2s (2way ANOVA, interaction: F(3,24)=27.44, p<0.0001) (C) from lungs after acute or chronic papain-induced lung inflammation (*p<0.05, ***p<0.001, ****p<0.0001). Bars represent mean ± SEM. Data information: are representative of 2 independent experiments.
H Working model: HMGCL and βOHB promote tumor expansion and dissemination. PDA tumor cells expressed HMGCL (left panel). In this setting, PDA can use βOHB from direct source as tumor surrounding βOHB, mimicked in our study by direct injection of βOHB, and indirect source from degradation of various nutrients. βOHB and HMGCL contribute to tumor growth and metastases formation. In metastases, ketone bodies genes are upregulated. When HMGCL is knock-out (right panel), contribution of βOHB in TCA cycle is reduced and tumor growth as well as dissemination capacity of tumor cells are strongly disturbed.
(G) Membrane lipid density from CG MD simulations. The combined POPC and cholesterol lipid density was contoured at the bulk density to show the extent of interactions between NHE9 (shown as tubes) and lipids. (left) Top view (from extracellular side) (right). Side (in-membrane) view. The circular shape of the membrane patch is an artefact from the rotational superposition of the orthorhombic simulation system prior to density analysis and indicates that the protein was rotating freely in the membrane.
(A) α-Synuclein fibrils were introduced into HEK293 cells stably expressing both DsRed-LC3 and EGFP-parkin. After 24 h, the cells were immunostained with anti-phosphorylated α-synuclein (P-αSyn). There was no alteration in the localization of EGFP-parkin. The arrows indicate α-synuclein inclusion. Scale bar, 10 µm.
H. MCF-7 cells were co-transfected with Myc-TRIM46 and wild-type HDAC1 or indicated HDAC1 mutants for 48 h. Cellular proteins were extracted for western blotting analysis.
(d) Calpain-mediated, truncated ATG5 (tATG5), that is, the N-terminal part of ATG5, failed to bind survivin. The ATG5-K130R mutant was the control.
(d) Western blot analysis of GST-RILP pull down from UOK257 cells showing DENN domain dependent association of FLCN with RILP N-terminal, Rab binding domain (RBD) and C-terminal fragments.
F. Pathway enrichment analysis for the DEGs in the Mef2c-knockdown cells compared with control cells at day 5 of neural differentiation.
Figure 3. Differential lysine acetylation and protein expression in Arabidopsis leaves after inhibitor treatment. Vacuum-infiltration of leaf strips with solutions containing either of the two deacetylase inhibitors trichostatin A (B, D) versus a buffer control for 4 hours leads to differential accumulation of lysine acetylation sites. Volcano plots depict protein ratios (C, D) for inhibitor treatment vs. control, with p-values determined using the LIMMA package. Orange, protein with nuclear localization according to SUBA4 database. Blue, proteins with lysine acetylation sites identified. Dashed lines indicate significance thresholds of either uncorrected p-values < 5 % or Benjamini-Hochberg corrected FDR < 5 %. A missing line indicates that the significance threshold was not reached by any of the data points.
D Genomic feature distribution of H3K122succ peaks obtained with the three H3K122succ antibodies. The percentage of peaks in the 1st exon, remaining exons, intergenic regions, 1st intron, other introns, promoter/ TSS (≤ 1 kb from TSS), promoter (1-2 kb) and 3' UTR is displayed. A random distribution of peaks is shown for comparison
A. Volcano plot showing genes upregulated in symptomatic individuals that were significantly correlated with IgM+ activated MBCs. B. Volcano plot showing genes upregulated in symptomatic individuals that were significantly correlated with T-bet+ CD4+ T cells.
(D) CFSE-loaded T cells isolated from lymph nodes of Bbs4FL/FL OT-I Rag2KO/KO (OT-I) and CD4-Cre Bbs4FL/FL OT-I Rag2KO/KO (Bbs4 cKO, OT-I) littermates were incubated with DDAO-labeled WT splenocytes loaded with OVA peptide or with the indicated altered peptide ligands for 20 min. Percentage of T cells conjugated with the APCs was determined by flow cytometry. Four biological replicates were performed. Mean+SEM. Statistical significance was calculated using two-tailed Mann-Whitney test, p >0.05 for all peptides.
The structural change of the SARS-CoV-2 S1 RBD observed in the presence of heparin by circular dichroism (CD) spectroscopy.(A) CD spectra of 200 μg/mL spike 1 alone (purple) or with 30 μg heparin (orange) in phosphate buffered saline pH 7.4. Theoretical sum of spike 1 alone and 30 μg of heparin (control) if no interaction was observed (black). (B) Δ secondary structure (%) of (A). A 2.4% increase in helix and 2.2% decrease in antiparallel secondary structural features were calculated (BestSel) for the observed spectrum compared to that of the theoretical, summative spectrum of the SARS-CoV-2 S1 RBD in the presence of heparin.
G: Intracellular ROS production measurements of the specific ROS level calculated by total ROS/MTDR in control, WS5A and CP2A iPSC-derived NSCs using DCFDA and MTDR (n=6, technical replicates per clone for control; n=5, technical replicates per clone for WS5A; n=3, technical replicates per clone for CP2A).
(C) Boxplot showing antimycin A resistance for 154 strains grouped by the two alleles at the pyk1 locus. Strains carrying a C at this genomic locus (orange box) generally have higher antimycin resistance than strains carrying the reference allele T (blue box). As is standard, this boxplot and all other boxplots in this manuscript show the median of the data as central line, the quartiles as box and the extend of the rest of the distribution as whiskers. Points which are 1.5 times the inter-quartile range beyond the high and low quartiles are considered outliers and shown individually.
K Survival analysis of lung cancer patients in low and high DDX3 expressing tumors (Kaplan-Meier curve and log-rank test, P = 0.016).
D, Proliferation of CTL and THEM6 KO CRPC cells treated with tunicamycin (2.5 µg/ml) for 72 hours. Cell count is normalised to initial number of cells at T0. Data information: Data are presented as mean values +/- SD. Statistical analysis: 1-way ANOVA with a Dunnett's multiple comparisons test. Data reproducibility: n = 3 independent biological experiments.
H) and I) Representative TEM images of control and Mfn2KD C2C12 myotubes untreated or treated with NSC-134754 showing the accumulation of autophagosomes (H) and the presence of mitochondrial alterations (I) in Mfn2KD or NSC-134754 treated cells (Scale bar: 2 µm).
(C) RNAi of Fis1 and Bnip3 significantly prevents MuRF‐1 and atrogin‐1 promoters activation during starvation. TA muscles were transfected with either 5 kb of the MuRF‐1 promoter (left panel) or 3.5 kb of atrogin‐1 promoter (right panel) with or without shRNAs vectors against Fis and Bnip3. In fasting experiments, after 7 days from transfection mice were starved for 24 h. A renilla‐luciferase construct (pRL‐TK) was co‐transfected to normalized for transfection efficiency. The activation of MuRF‐1 and atrogin‐1 promoters was determined by firefly activity and normalize for the renilla. Each condition represents the average of at least three independent experiments±s.e.m. (*P0.05).
A Hepsin cleaves the membrane-proximal CCS sequence of GPI-anchored UMOD homodimers, triggering the dissociation of the EHP from the corresponding ZP-C domain. Flor clarity, UMOD branch domains preceding EGF IV have been omitted. B EHP displacement activates ZP-C for polymerization by allowing it to form an intermolecular β-sheet with an incoming ZP-N domain from another homodimer. C Reorientation of the second ZP-C allows it to also be processed by hepsin, locally detaching the growing filament from the membrane. D The interdomain linker, whose ordered precursor structure is also perturbed upon EHP dissociation, undergoes a major rearrangement that both replaces the ZP-N/ZP-N interface of the UMOD precursor and compensates the loss of the EHP by DSE, completing filament formation.
Relative GSEC-APP/Aβn stabilities were assessed in cell-based GSEC thermoactivity assays, which evaluate changes in GSEC processivity (Aβ(38+40)/42 ratio) upon incubation at 42°C for 24h, relative to 37°C. Aβ peptides in the conditioned medium collected from the indicated MEF cell lines (transiently expressing APPC99) were quantified and the Aβ(38+40)/42 ratios determined. The data are shown as mean ± 95% CI, as % of the WT GSEC cell line incubated at 37°C for 24h, N = 6 independent experiments. One-way ANOVA followed by Dunnett's post-hoc test with comparison to WT was used to determine the statistical significance (F(DFn, DFd): F(6, 46) = 100); ****p > 0.0001 compared to WT at 37°C, #p > 0.05, ##p>0.01, ####p>0.0001 compared to WT at 42°C. Note: Aβ profiles (including Aβ43 levels) normalized to total Aβ quantified in the cell-based thermoactivity assays with the different mNCT WT/mutants are shown in Figure EV2.
(A) Serum-starved HaCaT cells were treated for 24 h with poly(I:C) (5 μg/ml) in the presence or absence of FGF7 (10 ng/ml). RNA samples were analyzed by qRT-PCR for IFNL1, IFNB, RSAD2, IRF1, IRF7, CGAS, TLR3 or DDX58, relative to RPLP0.
Representative images of liver sections stained with H&E (scale bar represents 100 µm)
B HEK293 cells were transfected with KCC4 together with SIRT7 with a scramble shRNA (-) or a shRNA against SIRT7 (+), and KCC4 activity and protein level were determined at the indicated pH. SIRT7 expression in these conditions is presented in C.
(c) Schematic representations of the domain structures of Atg14L and Rubicon. Atg14L contains two coiled-coil domains (CCD1 and CCD2), which are also homologous with the SMC domain (structural maintenance of chromosomes). Rubicon contains an N-terminal RUN (for RPIP8, UNC-14 and NESCA) domain, a C-terminal Cys-rich domain and a central CCD domain.
A Anti-SARS-CoV-2 neutralizing antibodies in plasma of vaccine breakthrough cases (n=54) and close contacts (n=86) were measured by surrogate virus neutralization test (sVNT). The percentage inhibition of ACE2 binding to RBD at plasma dilution of 1:800 is given. The wild type (Wuhan) strain or Delta (B.1.617.2) strain RBD was used respectively.