EMBO/sd-character-level-ner huggingface dataset:
(C) Collagen gel contraction assays were used to determine the contractile ability of control or FRS2 knockdown HASMCs (*p<0.05 compared to control; unpaired two-tailed Student's t test. N=3).
(G Lactate production assay in control and MIG-6 knockdown BT549 cells with or without GLUT1 overexpression.
D: FACS analysis of ESC-derived cells confirming that D20LS, D20LK, and D20LSK cell populations express the early hematopoietic marker CD41 and the pan-hematopoietic marker CD45.
b, Reduced Nestin/Pax-6-positive progenitors and increased TUJ1-positive neurons in Seckel organoids. In ventricular zones of WT organoids, there are significantly more Pax6 positive cells than TUJ1 positive cells, which is not the case in Seckel organoids (*p<0.05). TUJ1/Pax6 ratio in graph on the right shows significantly more TUJ1 positive cells vs. Pax6 cells in Seckel organoid ventricular zones (* p<0.05). Error bars are s. e. m. Ordinary Two-way ANOVA followed by Sidak's multiple comparisons test. n = 10 WT organoids (2520 cells). Seckeln = 10 organoids (2024 cells). Scale bar 20 μm.
Prevalence of individual RKPT residues and prevalence of carbonylated form in experimentally measured peptides combining all 3 biological replicates of both conditions for each organism. Ratios are given above each pair of bars. All proportions are significantly different between each RKPT and their respective carbonylation state by two-tailed z-test of two proportions (p-values < 0.01; see Materials and Methods), meaning carbonylated proportions are not determined simply by relative prevalence of RKPT. See also Appendix Fig S1.
(d) Length of resected DNA at Sμ-Sα junctions obtained from the joining of DSBs with blunt ends. Statistical significance as evaluated by two-tailed unpaired Student's t-test is shown. (e) Summary of the characteristics of Sμ-Sα recombination junctions resulting from the joining of DSBs with blunt ends.
(E) Representative immunoblots depicting the changes in the α-SNAP protein levels at various time points after DHPG treatment in cortical synaptoneurosomes in the presence or absence of anisomycin.
D) Primary neurons of tamoxifen-inducible Mfn2 KO mice were transfected at DIV3 with ER-GFP, mt-RFP plus the indicated plasmids. Tamoxifen-treated (for 72 h) and vehicle-treated neurons (WT; red dashed line) were fixed and mitochondria-ER co-localization was analyzed using Mander's coefficient (n= 15 neurons analyzed in 3 independent experiments). Data are presented as mean ± SEM. Data information: *p<0.05 versus WT; #p<0.05 versus Mfn2 KO neurons, one-way ANOVA followed by Tukey's post-hoc test. Scale bar: 500 μm.
A: Squares indicate male family members, circles female family members. Black symbols represent clinically affected, gray represent unknown phenotype, clear symbols represent unaffected individuals. The arrow with 'P' indicates the proband in each family and 'us' indicates un-sequenced due to lack of DNA from that individual. The mutation in each family is given next to the family number; a horizontal black line above an individual's symbol indicates they are heterozygous for that mutation as identified by either whole exome sequencing (family 3 and 4) or Fluidigm array (family 1, 2, 5 and 6), and verified by Sanger sequencing.
Time course of subepidermal blister healing in control (A) and SC-depleted epidermal defects (C).
C. Quantification of Sec24C localization at SGs over time (the ratio between Sec24C (mean fluorescence intensity) in SG puncta and cytosolic Sec24C). Mean ± SD. n = 60-80 cells per experiment, N = 3.
B Position of the identified UQCRH deletion in the two affected patients. Empty bars, untranslated region (UTR); Filled bars, translated sequence; thin blue lines, intron; red line underline the two deleted exons.
F. Structural rearrangements of the AAA-ATPase dependent heterohexameric ring throughout four states for the RPT6 and RPT1 mapped to the 4 states described by Wehmer et al.
The level of phosphorylated Smad2 (P-Smad2) and total Smad2 (Smad2) was assessed by immunoblotting and β-actin was used as a loading control. Lower bar graphs show WB quantification of P-Smad2 (P-S2) normalized to β-actin. (A) Activation of the pathway was assessed in non-Group 3 (blue) and Group 3 (yellow) MB cell lines in response to TGFβ or ActivinB stimulation for 1h.
(C)-A deconvolved image of L2 dendritic trees for which the perimeter was measured during analyses.
(A) Fraction of polysomal ribosomes quantified from polysome profiles in the wild type and noNSUN strains subject to a 4 h heat shock at 27°C. ns = non-significant. Data information: In (A , n = 3 biological replicates. In (A), data are presented as mean ± SEM, unpaired two-tailed Student's t-test.
(A) Cell proliferation and immunoblotting assays in BT549 cells with Luciferase or MIG-6 knockdown.
C. Quantification of OCR (basal respiration) with full media (5mM glucose, 0.5mM pyruvate and 0.5mM glutamine) showing the effect of lactate treatment (2mM) in HBVPs. (n=7 from independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.)
Ara-C EC50 values plotted as a function of RNRi concentration in SAMHD1+/+, -/- and rescue (WT, H233A) THP-1 cell line pairs. EC50 values in the absence of RNRi are indicated by the black and red dotted line. Error bars indicate s.e.m. of two (HU and dF-dC) or three (3-AP) independent experiments, each performed in duplicate.
B. Blow up of the ESI-mass spectrum of the TF:proOmpA:SecB4 super-complex from A (complete dataset in Fig. EV3). Left: charge state distributions, at the indicated m/z range. Right: masses deconvoluted from the mass spectra (as in Fig. 2B). Inset cartoon depicts stoichiometry. Representative spectrum shown; n=2 biological replicates.
(E) Representative Western Blot analysis of mCherry-p150Glued WT co-immunoprecipitated with GFP-STIM1 WT, NN, ΔCC1-3/WT (ΔCC/WT) or ΔCC1-3/NN (ΔCC/NN) in co-transfected HEK 293T cells. Negative control (CTL) was performed incubating cell lysate from HEK 293T co-transfected with an empty GFP vector together with mCherry-P150Glued WT with pre-cleared protein A or G-Sepharose and the rabbit GFP antibody. Below, its quantification by normalized densitometry. Results are the average ± SD of three independent assays. The value of P150Glued co-immunoprecipitated with GFP-STIM1 WT from each biological replicate was normalized on itself and so those immunoprecipitated with GFP-STIM1 NN, ΔCC/WT or ΔCC/NN. Results were analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for STIM1 WT and NN p> 0.05 not significant (ns), for STIM1 WT and ΔCC/WT p> 0.05 not significant (ns) and for STIM1 WT and ΔCC/NN p≤ 0,05 *.
Detailed view of the Sir4 H‑BRCT-Esc1pS1450 peptide interaction. Sir4 H‑BRCT is displayed as orange model with residues involved in peptide binding shown as sticks (orange, atom colors). The Esc1pS1450 peptide is presented as sticks in grey (atom colors). Electrostatic interactions are highlighted with green dotted lines while main hydrophobic contacts are shown as dotted lines in black. Detailed view of the Sir4 H‑BRCT-Ty5pS1095 peptide interaction. Sir4 H‑BRCT is displayed as in (C) while the Ty5pS1095 peptide is presented as sticks in blue (atom colors). Protein-peptide interactions are labeled as in (C). Detailed view of the Sir4 H‑BRCT-Ubp10pT123 peptide interaction. Sir4 H‑BRCT is displayed as in (C) while the Ubp10pT123 peptide is presented as sticks in green (atom colors). Protein-peptide interactions are labeled as in (C).
(A) The enrichment of HIF1α, SNAI2, TWIST1/2, and ZEB1 binding sites on the promoters of Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5 was determined by Pscan Zambelli et al, 2009(). The resulted Z-scores were listed. "Max. M" suggested the maximum Z-score generated with SNAI2, TWIST1/2, and ZEB1 binding sites on one indicated promoter. "Average" suggested the average Z-score of all transcriptional factors tested in the Pscan software on one indicated promoter.
MC38 colon carcinoma, B16F10 melanoma cell lines were s.c. injected into the shaved flanks of Usp44fl/flFoxp3Cre+ mice and their wild type (Usp44fl/flFoxp3Cre-) littermates (1x105 cells/mouse; n=5-9 mice/group). Tumor dimensions were measured every 2 days, and changes in the mean tumor volume over time were observed (lower panels). Upper panels depict representative photographs of excised tumors.
Expression of pTGIF1 and Twist1 in human tissue microarrays of human PDAC samples was analyzed by immunohistochemistry. Representative pictures at different stages (40x) are shown.
F. Single-cell suspensions of tumor tissues from MC38 tumor-bearing C57BL/6 mice treated with vehicle or TP-16 for 2 weeks were analyzed for immune cell infiltration by flow cytometry analysis. Representative flow cytometry and dot plots of intratumoral frequencies of CD8+ T cells (n = 5).
D The left two panels show surface representations of Re5D06 (magenta) and the thermostable variant R28 (yellow). The ribbon diagram (right) depicts an overlay of both nanobodies with changed hydrophobic core side chains shown as sticks. Note that these mutations close a large cavity originally present in Re5D06.
(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. (B) Typical confocal images of neurons stained for MAP2, Synaptobrevin /VAMP2 and Munc18-1. Scale bar = 50πm.
A-I. Dye release time courses from liposomes as a percentage of maximal release. C. Three different reactions, where 5 nM caspase-1 and 400 μM 6-carboxifluorescein-loaded liposomes prepared with porcine brain total lipid extract were incubated with GSDMD concentrations of (nM): 520, 260,100 (colored dark to light green).
Pulse radiolabeling after re-expressing MITRAC15FLAG in MITRAC15-/- cells. Samples were analyzed by SDS-PAGE and digital autoradiography. Relative pulse signal intensity of ND2 was normalized to ATP6 (error bars indicate SEM from three biological replicates; *p < 0,05; **p < 0.01; unpaired t-test).
Figure 4. CI tree built on the whole datasetDecision tree for the 4-gene signature was built using ctree function from the party package in R. Significant predictor genes are displayed in oval nodes. Numbers between nodes indicate the inverse ∆Ct values for each split. Terminal nodes display the relative proportion of samples from TB (dark grey) and healthy controls (light grey).
D) Loss of C. elegans TDP-43 ortholog, tdp-1, rescues glutamatergic tail/phasmid neurodegeneration caused by hrpa-1HsLCD290V after 22 hours paraquat induced oxidative stress, but not hrpa-1(∆). N=4-12 animals/genotype/trial, significance from two tailed t-test; tdp-1∆=tdp-1(tgx58). E) Loss of C. elegans TDP-43 ortholog, tdp-1, rescues glutamatergic tail/phasmid neurodegeneration caused by hrpa-1HsLCD290V after 22 hours paraquat induced oxidative stress, but not hrpa-1(∆). N=4-12 animals/genotype/trial, significance from two tailed t-test; tdp-1∆=tdp-1(ok803).
G, H, Relative tumor volume (G) and weights (H) of the PDX (BE564T) after the treatment. *P<0.05 by unpaired two-tailed t-test. (H) Data are the mean of tumor weight of each group (5 mice/group); error bar: SD
D) Knockdown of STAT3 in BAE cells. BAE cells were transfected with siRNAs targeting STAT3. qRT-PCR was performed to examine STAT3 mRNA levels. STAT3 level in siNegative was set as 1. Data from three independent experiments were averaged and shown Data information: Bars and error bars represent mean±SD. All experiments were carried out in three independent studies. siNegative, negative control siRNA not targeting any known genes. Two-way ANOVA was used as statistical test.
α, β, indicate Atg16L1 isoform α, β; ∆CCD indicates Atg16L1∆CCD; asterisk indicates a non-specific band. Atg16L1∆/∆ indicates mice expressing ∆Atg16L1. The number of endogenous LC3 or GFP-Atg5 dots was counted (c, d). The results shown are mean + s.d. (n > 20).
D. Schematic diagram of two lnc-AP OE plasmids of sORF-Flag fusion and the corresponding initiation codon mutant.
C-E. Western blot analysis for CCNA, CCNB, Cdk1 and GAPDH (loading control) protein expression in lysates from control (si-GFP) and TAZ-depleted (si-TAZ) (E) MDA-MB-231 and CAL27 cell lines. Representative images are shown.
Analysis of SPP1 and TNC mRNA levels in SUM159-LM1 cells grown as monolayer or spheres and treated with vehicle or JNKi. For panels A-D, values represent the mean of qPCR triplicates ± SD.
D Cartoon depicting sequestration of AMPylated BiP by a covalently linked, disulphide-stapled, S-SFICDA252C-H363A-C421S dimer (trap).
B, Metagene profiles for Pol II (upper panel) and Ub-H2B (middle panel) ChIP-seq for USP22-dependent, USP22-Bound genes. mRNA analyses of select Bound gene transcripts are presented (lower panel). Three independent experiments are represented as mean ± SEM, with significance measured by Student's t-test, *p<0.05, **p<0.01, ***p<0.005 C, Metagene profiles for Pol II (upper panel) and Ub-H2B (middle panel) ChIP-seq for USP22-dependent, SAGA-Unbound genes. Nonparametric Mann-Whitney analyses of 7 bins (grey shade) surrounding TSS (TSS) and the midpoint of the profiles (Body) in Thaps treated conditions are reported. mRNA analysis of select Unbound gene transcripts are presented (lower panel). Three independent experiments are represented as mean ± SEM, with significance measured by Student's t-test, **p<0.01, ***p<0.005.
D. Normalized gene expression for genes associated with differentiation of the goblet (top) and the enterocyte lineage (bottom)
(I) The percentages of three subsets of CD45+CD11c+ DCs (n = 8). (J-L) The percentages of (J) Foxp3+ Treg, (K) T-bet+ Th1 and (L) RORγt+ Th17 among CD3+CD4+ population in lamina propria were shown by flow cytometry (n = 8). Data information: Data were representative and were the median ± interquartile range from three independent experiments. P values were calculated by one-way ANOVA followed by Tukey's post hoc test for multiple comparisons.
C. List of proteins containing phosphorylation sites more abundant in cells expressing CDKL5NLS-WT versus KD, with phosphorylation sites having PTM score probabilities > 75% (peptides with a 100% PTM score probability are shaded in grey). Phosphorylation sites with a R-P-X-[S/T]-[A/G/P/S] motif are highlighted in red.
A: Live cell imaging results showing in vitro meiotic division of WT and Cnot6l-/- oocytes. Abbreviations: PM, prometaphase; MI, metaphase I; AI, anaphase I; TI, anaphase I-metaphase II transition; MII, metaphase II; PB1: polar body-1. Hours after released from GV arrest were indicated. Scale bar, 20 μm
A) Enrichment of the putative LRP6 binding sites bound to AGO2 in miR-cluster-Dox-MCF-10A cells after the miR-424/503 cluster is induced with 100ng/ml of dox for three days. A CDC25A-binding site is included as a positive control and a region of B2M and GAPDH are included as negative controls. The error bars show the standard deviation.
The plasmids encoding HA-TRAF2, HA-TRAF3, Flag-TRAF6, Flag-ASS1 or LOC113230 were co-transfected into SW-1116 cells and western blot assays were performed using antibodies against ASS1, HA, Flag or GAPDH.
Three-dimensional feature engineering from molecular properties. Initial properties that can be determined only with an atomic resolution structure, in the context of an amino acid sequence, or that depend only on amino acid identity are denoted at left. This property list is a non-redundant abbreviated set of all properties considered (see Appendix Table S4 and Materials and Methods for full detail). Columns of the feature matrix at right are alternating property sums and means at spatial scales denoted below matrix. p = a molecular property; i = RKPT residue; k = neighbor residues of i; r = radius length. See also Fig EV3.   Sequence-homology-based features for machine learning were derived by performing sequence alignments of all RKPT sites (+/- 10 residues) anchored at the central residue to compute alignment scores that were then reduced to a computationally manageable number of features by principal component analysis (PCA).
D) Solid phase transfection of nontargeting (scrambled), GOLGA2 targeting gRNA complexes into Cas9 expressing RPE-1TP53 -/- cells. Cells were fixed after 72 hours, stained with Golga2 antibody (red), and Hoechst (blue) to mark DNA and imaged. Scale bar, 50μm. E) Quantification of experiments in Fig 2D. Data derived from 3 independent experiments. P value (scrambled vs GOLGA2) < 2e-16, Mann-Whitney U test.
Sub-synaptic characterization of GABAAR and GlyR domains. (H-J) Detections of GABAARs but not GlyRs at the same SSDs were reduced after 4-AP treatment (KS, p < 0.0001 in H and J, p < 0.01 in I). Number of synapses: n = 439 in TTX, n = 531 in 4-AP condition, from three independent experiments.
A. In vivo genetic complementation of the E. coli MC4100 wild-type (WT) and secB or/and tig knock-out derivatives by either an empty vector or one carrying the secB or tig (encoding TF) genes or derivatives (see "Plasmid" table in Appendix), as indicated. Serial dilutions of a culture (OD600= 0.5) were spotted (12μl) on LB-Ampicillin plates containing or not anhydrotetracycline (AHT; 5 ng/ml) and grown at 16°C or 30°C (as indicated). n= 3-7 biological replicates.
(C) The frequency of CX3CR1+ macrophages in CD45+CD11b+ population and ALDH activity in CD45+CD11b+CX3CR1+ macrophages in lamina propria (n = 8). Data information: Data were representative and were the median ± interquartile range from three independent experiments. P values were calculated by one-way ANOVA followed by Tukey's post hoc test for multiple comparisons.
Protection (%) is percent survival minus percent survival of control condition. PC data calculated from panel B. FCCP final concentrations 0.001, 0.01, 0.1, 1 nM. One-way ANOVA with Tukey's post hoc test, PC vs. 0.001 nM FCCP, *p = 0.0012, 0.001 nM FCCP vs 0.01 FCCP, *p = 0.0142, n = 4,3,3,3,3 independent experiments each bar from left to right, each averaged from 3 technical replicates with at least 15 animals per replicate. Data show mean ± SEM.
(D) Lysates from C2C12 myoblasts (GM) were subjected to co-immunoprecipitation (Co-IP) assays with anti-YY1 or anti-IgG antibodies and blotted with anti-Hif1α or anti-YY1 antibodies.
Figure 8. Scheme of FGF-dependent regulation of TGF signaling in smooth muscle cells and endothelial cells.In both smooth muscle cells and endothelial cells, suppression of FGF signaling leads to reduction of let-7 miRNAs expression that, in turn, results in increased TGFβR1 expression and activation of TGFβ-dependent transcriptional program. In SMC (left panel), activation of TGFβ signaling promotes SMC conversion from proliferative to contractile phenotype thereby reducing the number of SMCs in the plaque and reducing plaque growth. In contrast, in EC activation of TGFβ signaling promotes endothelial-to-mesenchymal transition thus increasing the number of plaque SMCs and promoting plaque growth.
B) Size distribution of X-chromosomal MOF and H4K16ac regions, which are present in both early and late embryos. P-value (Wilcoxon rank sum test) is indicated. Total number of regions are 459, 443, 854 and 400, respectively.
C-D C2C12 myogenic cells showed a reduced level of glycosylated α-dystroglycan when the Notch signaling inhibitor DAPT or LY3039478 was added to the differentiation medium. This indicates that reducing Notch signaling can affect α-dystroglycan glycosylation in wild-type C2C12 myoblasts cells, which do not harbor any known mutations in α-dystroglycan glycosyltransferases or Poglut1.
(x,y) cross-section of the computational model simulation of the dermal maturation process at the indicated Monte Carlo Steps (MCS). Colour code indicates epidermis (green), proliferating fibroblasts (blue), quiescent fibroblasts (yellow), ECM (grey) and adipocytes (brown).
(A) Fed rat liver lysosomes were extracted with 1% of the indicated detergents and then subjected to sucrose gradient centrifugation. Aliquots collected from top to bottom were subjected to SDS-PAGE and immunoblotted for LAMP‐2A and flotillin‐1. Stars indicate the aliquots of the gradient of translucent appearance (highly enriched in lipids).
E. Gross appearance, hematoxylin and eosin as well as Ki67 stained sections of representative Th-MYCN and Alk-F1178S;Th-MYCN tumours. Scale bars indicate 250μm.
A, B. Comparison of the mean miR expression level by in TCR-stimulated naive CD4 T cell small RNA-seq libraries from uninfected and HIV-1NL4-3 (A) or HIV-2ROD (B) infected samples (24h). Only miRNAs with a minimum of 10 normalized read counts. Library normalization was performed using the mean normalization method available in Deseq package of Bioconductor (Anders Huber, 2010). Lines indicate changes of +/- 1 log2 fold between samples (n=3, paired pools of three individual samples per library). miR-34c-5p is highlighted in black.
Distribution of S. indica apoplastic proteins identified by LC-MS/MS analysis from different symbiotic stages (5, 10 and 14 dpi) and in relation to proteins identified in CF of S. indica axenically grown in CM. In total, 102 S. indica proteins were identified in the APF of colonized barley roots. Of these, 33 proteins were present at all three time points. Twenty proteins were unique at 5 days post infection (dpi), 4 at 10 dpi and 21 at 14 dpi.
(C) Dual-color image of an infected cell with EdU (red) and immunolabeled lamin (grey). Curves to the right plot the intensity profile of EdU and lamin along the dashed blue line. The EdU intensity peaks do not coincide with lamin enrichment. See also Fig. EV1A,B.
Glial shNf-1/shTp53 sgAtg7 (A) cells were either left untreated (+serum) or serum starved (-serum) 4 hr then stimulated 2 ng/mL EGF for 15 min before analyses by western blotting.
Representative confocal images of NRP1 and IBA1-stained mononuclear phagocytes on choroidal flat mounts from LysM-Cre/Nrp1+/+ and LysM-Cre/Nrp1fl/fl mice at D3. Arrow heads indicate NRP1-positive mononuclear phagocytes. Scale bar: 20μm.
Synaptic transmission in autaptic excitatory munc18-1 neurons expressing M18WT or a non-phosphorylatable Munc18-1 variant, M18Y473F, was tested with whole-cell patch clamp electrophysiology.(F) The amount of DSE-triggered EPSC depression was quantified by the ratio of the average EPSC amplitude (taken over 4 pulses given at 0.2 Hz) before or immediately following 10 seconds depolarization to 0mV. Typical EPSCs before and following DSE induction are depicted on the left. Average DSE (M18WT: 0.57 ± 0.04 fold, n=20; M18Y473F: 0.53 ± 0.04 fold, n=16, t-test, p = 0.5227).
The expression of LOC113230 in SW-1116-Vector, SW-1116-Snail1, HCT116-Vector or HCT116-Snail cells examined by qRT-PCR assays.
Immunohistochemical staining of 40-µm coronal brain sections with anti-TMEM16A antibody. In the mHb, TMEM16A signals colocalize with the cholinergic marker ChAT (arrows). High magnifications of the indicated areas are shown in the merged panel.
B Western blot analysis was performed using JurkatTat LTR-DsRed, clone 11, to detect the expression of SP1, NFκB p65, IκBα, total H3K9-me3, and H3K9ac. The cells were treated for 24 h with PH02 and/or PEP005. Data information: The results are determined from three biological replicates (n=3). Statistical significance, as determined by ratio paired t test, is indicated as follows: ***, P<0.0005; ****, P<0.00005. The exact P-values are indicated in the Appendix Table S1. Source data is available for Figure 6B.
B Relative UPP1 mRNA expression levels in HCT116 cells treated as indicated (NEN (N) 1.2 µM, Domperidone (Domp, D) 30 µM, Imipramine (Imi), Desipramine (Desi), Amitriptyline (Ami) each 30 µM, Clomipramine (Clomi) 20 µM), determined by qPCR. Data information: data (N=3) are presented as mean (SD) and were analyzed by one-way ANOVA with Tukey post-hoc test In (B), right panel, significance is indicated for the comparison of combinatorial treatments (NEN+TCAs) to controls. ** p< 0.01;*** p< 0.001; **** p < 0.0001.
D) Paclitaxel treatment (100 nM, 24h) induces the formation of micronucleated bodies, as visualised by Hoechst 33342 staining (arrows), localising to the proliferative region of the hair matrix. i - 20 µm scale; ii - 10 µm scale.