EMBO/sd-character-level-ner huggingface dataset:
Oncosphere formation in SUM159-LM1 cells following treatment with JNKi or vehicle control. Values are mean from 10 wells per condition ± SD. Representative images of spheres
(A) A431 WT and SKO cells -/+ GFP-fused WT or A212P-seipin were delipidated, treated with OA for 1 h, fixed and stained with LD540. Maximum intensity projections of deconvolved confocal z-stacks. Dashed lines indicate cell boundaries. (B) Analysis of LD areas of cells treated as in (A) and imaged with widefield microscopy. Bars: % of LDs/cell in indicated size category, mean ± SEM, n=57-61 cells/genotype, 2 experiments, p**< 0.005 (unpaired T-test).
E. Traces showing average changes (mean±s.e.m.) in intracellular Ca2+ (Fura 2 ratio) in primary astrocytes after transfection with non-silencing (siCTL, black trace, n=216) or exonA-specific siRNA (siS1A, red trace, n=263). Data information: Data were obtained from three biological replicates (e.g. transfections) with each three measured dishes (technical replicates) with multiple cells each (yielding a total number n) and is shown as mean±s.e.m.
A-E The top 30 Age-TFs regulating the ageing-induced transcriptomic changes control a substantial part of Age-DEGs and Age-BPs in analysed tissues. Only the core Age-TFs targets (leading-edge targets), which accounts for the gene sets enrichment signal, were analysed for the Age-DEGs and Age-BPs regulated by corresponding Age-TFs. Hypergeometric test.
(c) Immunostainings of well-fed or 6 or 12 h fasted MXL-3::GFP young adults are presented. Quantification of GFP-positive nuclei relative to total intestinal nuclei (4,6-diamidino-2-phenylindole, DAPI) of two independent experiments shows that MXL-3 transiently delocalizes from the intestinal nuclei during fasting.
F. Number of filopodia detected in co-cultured HUVECs within 12 µm intervals relative to cell distal tip (n=30 cells; **P<0.01, P***<0.001, ns: not significant; one-way ANOVA with Bonferroni's correction)
C) Examples of different hepatic lipids within one class that are regulated in different directions in HF/HS fed as compared chow fed mice.
(a Immunostaining of heart sections for PCNA and MEF2 in 5 dpci pkma2+/-; pkmb+/- and pkma2-/-; pkmb+/- animals; magnified view of area in white boxes shown below; arrowheads point to PCNA+ CMs; white dashed lines mark the wound border; percentage of PCNA+ CMs in the border zone shown on the right (n = 4-6 ventricles of each genotype).
D. RNAchIP read density per kb on the indicated introns for input and IP in samples from both untreated and PMA stimulated cells, n=6 biological replicates, or 3-times randomized intervals, n=18 samples. Dots represent individual data points. HP1γ/KO introns are all 272 intronic intervals between exon junctions differentially detected in HP1γ and KO. Random introns are a matching library of random intronic intervals. E. RNAchIP read density per kb on the genes corresponding to the introns tested in (D), and analyzed as in (D), n=6 biological replicates, or 3-times randomized intervals, n=18 samples. Data information: All graphes represent mean and s.d. (** P < 0.005, ***P < 0.001; two-tailed Student's t-test).
HEK293 cells were transfected with siCTL, siDDX5, or siXRN2. The gene location and qPCR amplification region are shown at the top of each panel. The identified R-loop peaks were extracted from R-loop database (R-loop DB) for each gene region. R-loop: DRIP denotes anti-S9.6 DRIP-qPCR and Pol II ChIP denotes RNA pol II ChIP. The bar graphs show the average and S.E.M. from at least three independent experiments. Statistical significance was assessed using Student's t-test. *: p < 0.05; **: p < 0.01 and ****: p < 0.0001. B, E, H, S and X denote the location of the BsrGI, EcoRI, HindIII, SspI, and XbaI.
J Representative images showing the relative size of tumors derived from ME180 cervical cancer cells transfected with control shRNA (left, shCtrl) or YAP shRNA#1 (right, shYAP#1) (n = 6).
(F) Proteolysis of a pool of 3[H]labeled cytosolic proteins by intact (left) or disrupted (right) lysosomes isolated from untransfected mouse fibroblasts (none) or fibroblasts transfected with wild‐type (WT) or the indicated mutant forms of hLAMP‐2A. Values are the mean+s.e. of two experiments with triplicate samples.
C. Docking model of the STIM1 CAD domain to ORAI at the beginning (red) and at the end (green) of a 50ns MD simulation.
(A Immunostaining of GFAP with LAMP1 and Cath D in the spinal cord sections from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. Scale bar = 5 µm.
A. A549 cells were transfected with 2 μg of poly(I:C) for 6 hrs and then infected with ZIKV (MOI=3) for 18 hrs (Pre-treatment) or infected with ZIKV first for 6 hrs and then transfected with poly(I:C) for 12 hrs (Post-treatment). Levels of ZIKVgenomic RNA were determined by qRT-PCR. Values are expressed as mean ± standard error. ***P<0.001 (Student's t-test), N=3
A. SecB fails to restore proOmpA translocation ATPase activity stimulation of SecA(noC-tail) in the presence of TF. proOmpA translocation ATPase activity stimulation (as in Fig. 1C; SecB molar excess over proOmpA indicated). T/M ratio of SecA(noC-tail) in the absence of TF or SecB= 100%; lane 1; all other values were expressed as a % of this value. n= 4 biological replicates; mean values ± SEM. Unpaired parametric t-test, 95% confidence interval: **: p= 0.0048; ****: p < 0.0001.
mRNA expression levels of JUN family transcription factors. Normalised TPM is shown for TB IL-2, TB IL2nil, TB+ IL-2 and TB+ IL-2nil. Standard deviation is shown for 3 replicates.
E. WB confirmation of the interaction between pep-AP-Flag and TALDO1 in HEK293T, HCT116/L-OHP and SW480/L-OHP cells.
(C) Single cells were grouped into 60 clusters according to their expression of genes encoding homeodomain proteins (Fig 2A) and arranged along the inferred AP position (Fig 1D, 1E). For each cluster, the mean expression of Ig encoding genes was computed. Heatmap depicts Ig encoding genes in columns and clusters in rows; mean expression is color-coded and median expression level is visualized by circle size. Gene families are highlighted in color codes. The colored bars highlight the Ig genes expressed in anterior MNs (MN2c, MN2a, MN4, MN3).
Analysis of FAO levels in 1205Lu cells exposed to 3T3-F442A EV and treated, or not, with cycloheximide (CHX) (n=5).
Primary ILC3 cells were sorted from LPs and were stimulated with (IL-7 group) or without IL-7 (None group). mRNA expressions of relative genes were detected by qPCR.
A Monomerisation does not result in large conformational changes in FICD. Shown is the alignment, from residues 213-407, of FICD molecules in the asymmetric unit. Monomeric FICDL258D and dimeric wild-type FICD ± ATP, are coloured as indicated. Glu234, ATP (and Mg, where applicable), are shown as sticks (or green spheres). The inhibitory alpha helix (αinh) and gross domain architecture is annotated. Note the only significant deviation in tertiary structure is the flipping of the TPR domain in the FICDL258D:ATP structure. The FICD:Apo structure is from PDB: 4U0U.
(D) Tumor growth curves for the 7 tumors arising from the CRISPR-SAM-engineered cells xenografted in nude mice
(E) AsiSI endonuclease-integrated U2OS cells were transfected with siControl and siEWS. Cells were incubated with doxycycline for 4 hours to induce DSBs. With or without changing the Dox-added media to fresh media for 2 hours (for release samples), the amount of chromatin-associated PARP1 was measured using ChIP assay. (N.T: Non-treat, T: AsiSI treat, Release: Damage released samples). Data represented as mean ±SEMs, and technical repeats (n=3), significance determined by two-way ANOVA, ***P< 0.001.
B. Niaspan treatment of Vim-/- mice does not affect mouse growth, as the growth rate in WT (n=8, saline; n=6 Niaspan) and Vim-/- (n=10 saline and n=10 Niaspan) mice either saline or Niaspan-treated is not significantly different, Linear Mixed Effect (LME) models.
B. Quantification of Sec24C redistribution to SGs over time after SA treatment (the ratio between Sec24C (mean fluorescence intensity) in SG puncta and cytosolic Sec24C). Mean ± s.e.m. n = 50 cells per experiment, N = 3.
G. Quantification of images shown in (F). Each dot represents the number of 53BP1 foci per nucleus. A total of 114-140 nuclei were scored from two independent experiments. Statistical analyses were performed using two-way ANOVA Mixed effect model. Data information: All scale bars: 5 μm. Data are shown as mean ± SD, with the red line marking the mean value.
(B) AhR activation by exogenous and endogenous ligands promotes SMAD3 induction. 501Mel cells AhR wild-type or knock-out have been exposed to exogenous and endogenous AhR ligands; TCDD (5nM) or ITE (10µM) or the solvent (DMSO) during 10 days. n=5 biologically independent experiments for AhR WT cells and n=3 for AhR KO cells. Each histogram represents the mean + s.d. (C) AhR activation by exogenous and endogenous AhR ligands promotes TIPARP induction. 501Mel cells have been treated as described in B. n=5 biologically independent experiments for AhR WT cells and n=3 for AhR KO cells. Each histogram represents the mean + s.d.;
(A) An equal number of FACS-isolated SCs from C57 mice were cultured for 24 hrs and treated with 0, 1, 10, or 20mM 2-DG (glycolytic inhibitor) or NaN3 (respiration inhibitor) for 3 hrs before measurement of ATP production. The relative ATP levels normalized to the 0 mM values are plotted. N=3 mice.
(D) Quantitative analysis of poly-GA aggregates in the spinal cord using immunohistochemistry. Images from complete spinal cord sections at 1 mm intervals. One-way ANOVA, Tukey's post hoc test, F(5,12)=1.625, p=0.2270. *** p<0.001, ns not significant. TG-Ova-(GA)10 vs. TG-PBS p<0.0001; TG-(GA)15 vs. TG-PBS p=0.2460. Scale bar indicates 100 μm.
b, The number of vacuoles per cell was quantified for the experiment in a. 150 cells from three independent experiments were counted for each condition. Values represent the mean, error bars the SEM.
A-I. Dye release time courses from liposomes as a percentage of maximal release. B. Five different reactions, where 130 nM of GSDMD and 400μM 6-carboxifluorescein-loaded liposomes prepared with E. Coli extract polar lipid were incubated with caspase-1 concentration of (nM): 15, 8, 5, 2.5, 1.2 (colored dark to light blue). The time point of 20 min is highlighted by a vertical dashed line.
(B) Half maximum inhibitory concentration (IC50) of pooled sera collected on 90 dpv were characterized in HEK293T cells infected with WT-CHIKV (MOI 5). Sera were serially diluted at 1:625000, 1:125000, 1:25000, 1:16000, 1:8000, 1:5000, 1:4000, 1:2000, 1:1000, 1:500, 1:250. Sera dilution to obtain IC50 are shown in parenthesis.
H. Cells were treated as in (G) and immunostained for TRAPPC2 and eIF3. Scale bar, 10 µm. The graph shows the quantification of TRAPPC2 localization in SG puncta (mean intensity). Data are mean ± s.e.m. expressed as a percentage of TRAPPC2 signal in SGs after Flavopiridol, SNS-032 or Dinaciclib treatment compared to the control (cells treated with SA alone). N=3, three independent experiments, n=60-80 cells per experiment. ****p<0.0001, One-way ANOVA with Dunnett's multiple comparison test.
(B) Western blot data (n=1) with quantification demonstrated reduced α-Dystroglycan (α-DG) in P1's muscle compared to control. (C) Western blot data with quantification demonstrated reduced α-Dystroglycan in fibroblasts from P1 and P2 compared to control (c), although not to the extent of the reduction observed in fibroblasts from a patient with a confirmed α-dystroglycanopathy (α-DG pt) due to biallelic pathogenic variants in LARGE (n=1).
(f) Sld3 recruitment reaction performed as in (a). Sld7 was omitted from this experiment.
M238P cells were transduced with a miR-143/-145 construct and selected for stable expression of the cluster or transduced with a control vector, followed by RNA-seq analysis (dataset 2, n = 2). (E) Venn diagram summarizing the comparison of the best-predicted targets following the 2 gain-of-function approaches. Subsets of miR-143-3p and miR-145-5p predicted targets downregulated by both mimics and stable lentivirus expression are shown (red boxes).
Polarised light image of Picrosirius red stained back skin section shown as binary image at indicated time points after wounding.
B. Isosurface views as in A of the 14-PF MT decorated with NN. α-tubulin, light grey; β-tubulin, dark grey; NDC, blue. The valley between PFs 1 and 14 represents MT seam, where NN does not bind.
(a) Wild-type yeast cultured in S(-NC) for 4 h. PtdIns(3) P was labelled intensely in the EF of autophagosomal membranes. A lower but still significant amount of labelling was also seen in the PF of autophagosome membranes as well as in the EF of the vacuolar membrane. Scale bar, 0.5 μm.
Live imaging of adult PDGFRαH2BEGFP back skin during wound healing. Representative time-lapse images of adult wound bed at PW4, where Z-directional movement is visualized by pseudo colouring the fibroblast nuclei (red, movement towards the basement membrane; blue, movement away from the basement membrane).
(e) Detrended spatial profile of Venus::HES5 (black) and NGN2::mScarlet-I (red) intensity from the same transverse slice of E10.5 spinal cord in ventral-dorsal direction.
Under conditions of ER-stress the dimeric form FICD is favoured (right hand side). Dimeric FICD cannot bind ATP in an AMPylation competent mode but can efficiently catalyse deAMPylation of BiP-AMP (thereby remobilising BiP back into the chaperone cycle). A decrease in unfolded protein load in the ER, possibly associated with a decreased ER ADP/ATP ratio, shifts the FICD monomer-dimer equilibrium towards monomeric FICD. Monomeric FICD can bind MgATP in an AMPylation competent conformation and, as such, AMPylate and inactivate surplus BiP.
(C) Representative images and quantification results for a colony formation assay in BT549 cells with GFP or MIG-6 knockdown.
Isolation of dermal EC subtypes from the ear skin of 5 weeks old Prox1-GFP mice using multicolor flow cytometry. Whole-mount immunofluorescence for LYVE1 (on the left) defines three Prox1-GFP+ lymphatic vessels subtypes that are sorted using the indicated gating scheme (on the right): LYVE1low/- collecting vessel (green arrow, col); LYVE1intermed pre-collecting vessel (grey arrow, pre-col); LYVE1high lymphatic capillary (magenta arrow, cap).
G. Genomic position of a B4 SINE repeat and CACACA consensus motifs at the location of the RNAchIP peak
D. Relative values of plasma purine and pyrimidine degradation pathway intermediates, compared to controls on ND. Right: illustration of major metabolites and synthesis of pyrimidine and purines.
SPP1 and TNC expression in the indicated breast cancer cells treated with increasing concentrations of JNKi.
C Neutralization of SARS-CoV-2 by the indicated VHH antibodies. The neutralization experiment was performed Note the gain in neutralization efficacy when a VHH is trimerized. Re6B06, for example, is 30 000-fold more potent when symmetry-matched with the virus Spike.
(a) Detrended spatial profile of NGN2::mScarlet-I intensity from transverse slice of E10.5 spinal cord from heterozygous knock-in mouse in ventral-dorsal direction;red indicates motorneuron (MN) domain, blue interneuron domain (IN).
(Left) The 25-kDa neddylated species induced by oxidative stress increases with time in WT U2OS cells. U2OS WT or NEDP1 KO cells were treated with 600 μM H2O2 for the indicated time and then lysed in LDS sample loading buffer and processed for Western blot analysis. (Right) The same 25 kDa NEDD8 species, which is strongly induced in WT cells, is present in untreated NEDP1 KO cells and does not further increase after oxidative stress induced by H2O2 (as indicated by the arrow).
Quantitative real-time PCR analysis of HOXA4, YAP, CTGF, and CYR61 in HEK 293T cells with overexpression of HOXA4 and/or constitutive active form of YAP (YAP -5SA). *P<0.05, **P<0.01 vs YAP-5SA with LacZ, by ANOVA with Sidak's correction.
Heatmap of enrichment scores (-log10(P-value)) for KEGG pathways significantly enriched for LMS and HMS protein-coding genes (DAVID, P-value < 0.05).
A. Jurkat T cells were transfected with the indicated combinations and relative doses of expression constructs encoding MYC-FOXP3, FLAG-USP44 along with an IL-2 promoter-driven firefly luciferase reporter. After 8 hours stimulation with PMA/Inomycin, cells were lysed and luciferase activity, which was observed and normalized to renilla luciferase activity.
5 ng/ml TGF-β and DMSO were applied to stimulate SW-1116 -Vector or SW-1116 -LOC113230 cells for 24 and 48 hrs, respectively. Cell migration was detected by transwell assays. Scale bar represents 100 μM.
G-I Rescue of shRNA-resistant wild type METTL3 but not catalytic mutant METTL3 sensitized METTL3-knockdown SMMC-7721 cells (G), Bel-7402 cells (H) and sorafenib-resistant HepG-2 cells (I) to sorafenib treatment. The IC50 of the cells was measured after treated with sorafenib for 24h under hypoxia condition (1%O2). 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.
(G)-The sleep metrics of flies with silenced expression of the Atg5 gene in per-positive cells.
(B) Immunofluorescence staining of D324MED medulloblastoma cells showing nuclear co-localization of HA-SOX9 WT (AlexaFluor 568; Red) and FLAG-FBW7α (AlexaFluor 488; Green). The cell nuclei were counter-stained with DAPI (blue). Image set is representative for multiple image fields taken at 40x objective magnification. Scale bar indicate 20 µm.
Left panel: Early developmental programs pattern single cells according to their position in the embryo. Morphogenic gradients establish specific homeodomain protein expression patterns along embryonic body axes (i.e. dorsal ventral axis = DV axis, anteroposterior axis = AP axis). Left middle panel: After neuroblasts have undergone several divisions, neurons terminally differentiate and establish unique identities depending on their homeodomain TF expression (color code). Right middle panel: A unique homeodomain TF expression specifies Ig domain receptor expression in matching synaptic partners, resulting in differential affinities of Ig domain proteins promoting selective synaptic target choice. Right panel: Common homeo-signatures regulate interaction partners within individual neuro-muscular circuits.
(G) Effect of NAT on growth of HCT116 colon cancer cells in mice (BALB/cSlc-nu/nu, 6 wks old, female) (data are means ± SEM; n=5). *P<0.05, **P<0.01 vs. without NAT. Test mice began to freely drink 5 mg/ml NAT solution for 7 d before transplantation of the tumor cells on day 0: the average amount of NAT consumed by each mouse was about 8.8 mg/day (0.4 - 0.5 g/kg weight/day). HCT116 cells (5.0 x 106 cells) were transplanted into each test mouse using a 1 ml syringe with a 27G needle.
E. EATR assay in chondrocytes with indicated genotypes (ctrl=wild type) showing % of cells with acidified ER measured by FACS. FGF18 was used at 50 ng/mL overnight. Mean +/- standard error of the mean (sem) of N=4 biological replicates. Analysis of variance one way (ANOVA) p<0.0001: Tukey's post hoc test ***p<0.0005; *p<0.05; NS not significant.
C. qRT-PCR analysis of Fam134b and Lamp1 from medaka fish embryos treated with FGF18 (50 ng/mL) for 24h. Values were normalized to Hprt gene and expressed as fold change relative to untreated fish. N= 5 biological replicates. Mean +/- standard error of the mean (sem). Paired Student's T-test **p<0.005; *p<0.05.
Densitometry analysis of p65/RelA phosphorylation as presented in (A) from three independent experiments.
Localization of RACK1 (E) in mock, TRAPPC3-KD and TRAPPC2-KD HeLa cells treated with SA. G3BP was used to stain SGs. Scale bar, 10 µm. Each graph shows the quantification (mean intensity) of the respective protein in SG spots expressed as a percentage of the mock (TRL). Mean ± S.D. independent replicates. , *p<0.05; ****p<0.0001 in (E), One-way ANOVA with Dunnett's multiple comparison test.
B and C, The effects of RAD52, POLD3, ATM and H2AX inactivation on BIR/RMD with cleavage at L17/D10k. The frequency of BIR/RMD in mES cells carrying the RMD-GFP reporter was determined using the sgRNAs/Cas9 at L17/D10k in RAD52 KO cells or after POLD3 depletion by siRNA (B), or after treatment with ATM inhibitor (ku55933, 15mM) or H2AX depletion by siRNA (C).
Insulin partially rescues MAGE-A3/6 protein levels upon nutrient deprivation. HeLa cells were treated for the indicated times with EBSS alone or EBSS containing NEAA (10 mM) or insulin (10 µg/mL). Quantitation represents average of n=3 with standard deviation shown.
(c) Representative 3D rendering of RasV12; scrib-/- tumors (red) and central nervous system (yellow), over time.
(D-F) Upper panels: Immunoblots of smooth muscle markers, phosphorylated Smad2 (p-Smad2), and TGFR1 expression in control and FRS2 knockdown HASMCs treated with SB431542 (10 m), TGFR2 or Smad2 shRNA lentiviruses. Blots are representative of three independent experiments. Bottom panels: Band intensities of SM-calponin and p-Smad2 were normalized to -tubulin, HSP90, or Smad2 and expressed as a fraction of a control value.
A: Developmental stages of ESC differentiation to HSPCs, showing the populations isolated on days 6 and 20.
Quantitative real-time PCR analysis of differentiated VSMC marker genes in primary human VSMCs with PDGF-BB stimulation for 24 hours. *P<0.05, **P<0.01, by unpaired two-tailed Student's t-test.
(A) Box plots show the GLUT1 (SLC2A1) gene expression in different breast tumor subtypes in the Servant dataset of 343 primary breast cancer carcinomas, analyzed using Illumina HumanWG-6_v3 Arrays. The gene expression levels are determined using the R2 platform. In the box plot, error bars are the 95% confidence interval, the bottom and top of the box are the 25th and 75th percentiles, the line inside the box is the 50th percentile (median), and any outliers are shown as open circles. **p < 0.01, by Student's t-test..
(a) Schematic representation of the IgH locus of WT and of 8X-LexA binding element (LexA-BE) knocked-in CH12F3-2A cells. The a, b and c bars indicate the position of primers used for ChIP-qPCR in Fig. 1b. A protein in which the DNA-binding domain (DB) of LexA was tagged with 3X-FLAG and a nuclear localization signal (NLS) (FNLDD) was expressed in WT (FNLDD alone) and Sα-engineered (FNLDD- Sα-LexA) CH12F3-2A cells.
(D) Euc1 Slx5-binding mutants (SBM1, SBM2) affect Euc1-Slx5 interaction in Y2H assays. AD-Euc181-183 constructs harboring mutations in the region required for Slx5 binding were probed for interaction with BD-Slx5 constructs as described in Fig. 4A. Mutations: SBM1: aa 139-143 ENQKK>ANAAA, SBM2: aa 162-165 KEVF>AAAA. Serial dilutions were spotted and cells were grown at 30°C for 2 days. See Appendix Fig. S6A for expression levels.
Pom1 gradients decay length decreases with the amplitude at the pole. Each dot corresponds to one average profile as in (C). The trans-phosphorylation model predicts a slope of -1/2 in log-log space (red line), close to the observed linear regression of -0.52 (black line) and well within the two SE confidence interval (shaded area). Each data point is weighted by its inverse variance of the mean in the linear regression.
A CD8+T cells from OT‐I Rag2−/−mice expressing wild‐type (LCK) or LCKS59A proteins were stimulated with H‐2Kb‐positive antigen‐presenting cells pulsed with serial dilutions of the OVA (257-264) peptide, the OVA peptide variants Q4 and T4, and VSV, a peptide that is not recognized by the OT‐I TCR. CD69 up‐regulation (left) and TCR down‐regulation (right) were analysed. Data are representative of three independent experiments.
A. UMAP of scRNA-Seq data from human ileum-derived organoids (n=16,682 cells); dots corresponding to cells are colored by the cell type.
Transmission electron microscopy analysis of mitochondrial morphology in the epiblast of E4.5, diapause and E5.5 embryo. Mitochondria analysed, E4.5 (n mitochondria = 55), diapause (n mitochondria = 62), E5.5 (n mitochondria = 65).