EMBO/sd-character-level-ner huggingface dataset:
A-GAfter iPSC‐based reprogramming of fibroblasts, we generated DAn from PD patients (n = 10) and gender‐ and age‐matched healthy controls (n = 4) using a 30‐day differentiation protocol. Blind to researcher, resulting iPSC‐derived DAn showed similar properties and maturation state in PD and controls. Specifically, studied iPSC‐derived DAn encompassed 30‐day ventromedial (vm)‐DAn‐enriched cultures of morphologically mature DAn showing typical bipolar morphology, lacking PD neural phenotypes, mostly of the A9 subtype, and showing properties of tyrosine hydroxylase (TH)+ mature neurons. Representative immunocytochemistry analyses of vmDAn from PD patients and controls showed that (D) The 1‐week neural progenitor cells (NPCs) from which iPSC‐derived DAn were generated strongly expressed DAn progenitor markers such as the nuclear‐related receptor 1 NURR1 (Scale bar, 12.5 μm).
(1) Under predivision conditions, SlmA·SBS may partially recruit FtsZ forming FtsZ·SlmA·SBS condensates, which may accumulate in transient microenvironments. Condensation into liquid droplets may aid in FtsZ·SlmA·SBS localization nearby the membrane. (2) Under division conditions, the amount of SlmA at midcell decreases and other elements would compete for the interaction with FtsZ, that would leave the condensates and, (3) in the presence of GTP, form a membrane anchored FtsZ ring. In non-central regions, FtsZ would still be under the control of SlmA, which protects the chromosomes from scission by aberrant division ring formation.
Time-lapse confocal images of tPH-CynA-KikGR expressing Dictyostelium AX3 cells. Below are zoomed in images from images above. Yellow arrows point to small satellite vesicles.
C: histochemical staining of skeletal muscle from II-2. Combined COX/SDH staining shows scattered COX negative (blue) fibres (arrows). The black bar corresponds to 100 µm.
F. Western blot analysis of CTRL#1 or BRD9-KO#1 lysates from cells treated or not for 16h with 1000 IU/mL of IFN-α2. The indicated proteins were detected with specific antibodies. Data are representative of at least two biological replicates.
(F) mRNA levels of Pou5f1, Nanog, Sox2, and Esrrb upon KO of Yap1. Data are represented as mean SD.
(A) Volcano curve analysis of dysregulated genes in miR-574-/- versus WT heart. The Padj is the P-values adjusted for multiple testing with correction using the Benjamini-Hochberg procedure. The dots above the dashed line show Padj<0.05.
(A) Immunofluorescence staining of FTCD and GM130, a Golgi marker. HepG2 cells were fixed, permeabilized, stained with a monoclonal antibody to FTCD, a polyclonal antibody to GM130 and DAPI, and observed by confocal microscopy. Scale bar = 10 μm.
(D) Tumor weight of each group subjected to in vivo limiting dilution assay (n = 6 biological replicates; mean ± SEM; ***P < 0.0001, *P = 0.0285, *P = 0.0162, *P = 0.0498, and *P = 0.0049; two-tailed unpaired Student's t-test).
(a) WT and dnm1Δ cells expressing Vph1-RFP and Idp1-GFP were grown in minimal synthetic dextrose medium and transferred to lactate medium at an initial density of OD600 0.08. The cells were then sampled daily and analysed by fluorescence microscopy (× 100 objective) during stationary phase mitophagy in lactate medium. Scale bar, 5 μm.
B-F: TEM images of control HeLa cell (B: HeLa -silenced HeLa cells. An interpretation scheme representing contacts between organelles is shown on the right; the ER, endosomes and ILV are in dark, light and medium gray, respectively. Mitochondria and Golgi are in pink and light green, respectively. Scale bars: 500 µm
(d) The levels of NCOA4 and p62 in ATG7 wild-type (+/+), heterozygous (+/−) or homozygous knockout (−/−) DLD1 clones 1 and 2 were determined
(F) Resting (R) or store-depleted cells (S) HEK cells transfected with STIM1-YFP and myc-STIM1 and with or without ANO8 or treated with siANO8, were used to immunoprecipitate (IP) STIM1-YFP and blot (B) for mys-STIM1. The inputs (In) are with anti-myc, anti-YFP or anti-ANO8. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.
(D, E) Percentage of cells infected with either WT or TKO Listeria strains displaying one or several LAMP2+ (D) or NDP52+ (E) Listeria vesicles. Values are means±s.e.m. n=3. *P0.05; **P0.01. Scale bars: 10 μm.Source data for this figure is available on the online supplementary information page.
A, B Intersection of the top 200 differentially expressed genes (sorted by statistical significance) in tumourspheres and tumours (Nfib high-expression vs. the respective controls) and putative transcriptional targets of Nfib determined by ChIP-seq in mammary gland (Shin et al, 2016) (A) and epithelial-melanocyte stem cells (Chang et al, 2013) (B) (association rule: Basal+extension: 5000 bp upstream, 1000 bp downstream, 10000 bp max extension, curated regulatory domains included).
B AGO6 dysfunction decreases Pol V occupancy at chromatin of loci where Pol V transcript levels are affected by AGO6. Anti‐NRPE1 antibody was used for ChIP assays. Means ± SD are shown, n = 3.
C Luminex assay showing cytokine levels in the supernatant from the coculture of survivin-specific TC and either CCR9hi MCF7 (transfected with CCR9-specific siRNA) or CCR9lo MCF7 (transfected with control siRNA) cells.
(A) A γδ TnpR recombinase (green) was induced from a cumate-inducible promoter. TnpR recombines two res site (blue and red arrows) that flank a tet resistance cassette (orange arrows) to excise the intervening DNA. Recombination requires supercoiling-dependent juxtaposition of res sites.
D. Representative images of soft agar assay results using cells in (A). Scale bar, 1 mm.
C Motility Assay as a measure for transgene toxicity. Displayed is the mean number of body bends per 30 s ± SEM (N = 3). Statistical analysis was done using two-way ANOVA with Dunnett's multiple comparison test. ** p ≤ 0.01, *** p ≤ 0.001.
(d) ROCK1-deficient hearts or control hearts from animals fed or starved for 16 h were subjected to electron microscopy to identify autophagosome structures. Arrows indicate autophagic vacuoles. Scale bar, 500 nm.
I IHC staining of cleaved caspase 3 in liver sections of starved Li-CluhWT and Li-CluhKO mice. Arrows point to positive apoptotic foci. Scale bar, 200 µm.
C. Co-IP assays of HA-tagged MFN1 with various FLAG-tagged wild-type GASZ, its domain deletion mutants, or GASZ with MLS mutations in 293T cells.
(A) Plot of the slope of inactivation as a function of current density in the presence (red) and absence of ANO8 (black). Increasing current density was obtained by varying external Ca2+ between 2-50 mM. The results are mean±s.e.m and difference were analyzed by unpaired t test. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.
B. Individual tumor growth in GSK-LSD1 (n = 9) or vehicle-treated (n = 8) mice. Red arrow: start of therapy, day 22
(A) Representative images of control cells (upper panel) or cells treated with α-synucleinfibrilsATTO-550 (bottom panel) for 16 hours; in red: α-synucleinfibrils and in green: WGAAlexa-488 (plasma membrane dye marker), blue: DAPI. Scale bar represents 10 μm (n = 3 independent experiments).(B) Relative percentage of TNT-connected cells after α-synucleinfibrils treatment as in A shows an increase in TNT number upon fibrils treatment. Data are mean ± s.e.m (***, p < 0.001 by paired, two-tailed Student's t-test).
B) Pattern 3 Protein network based on global pattern analysis: Node size and color is based on betweenness centrality score of each node in the network. Top 10% of the most central nodes are indicated
(C) Venn diagram showing the overlap between YAP Signature 1 and the genes upregulated by more than 1.5 fold in BCC compared to IFE[28
Metabolite levels of reduced NADH were measured in Rv, Rv∆aosR, and Rv∆aosR::aosR in normal and CHP stressed cells using LC-MRM MS/MS analysis. The absolute values obtained under normal conditions were normalized to 100% for each strain and the relative values were calculated for samples processed from CHP treated cells. The data indicates relative levels of metabolites (mean percent ± SD) of four replicates (n=4).
tRNA modifications orchestrate parasite development at a translational level in a collective model whereby: (1) High levels of Am and s2U at ring stage stabilize the "hypomodified" tRNA molecules or serve as a precursor for the subsequent modifications; (2) a synchronous increase in 22 of the 28 modifications serves to signify tRNA maturation. This parallels up-regulation of translational and metabolic activities through the ring-to-trophozoite transition depicted by the graphs showing peaks of synthesis of DNA, RNA and protein (adapted from (de Rojas & Wasserman, 1985)); (3) Increase in the levels of particular wobble modifications enhance the recognition to specific codon(s) out of other synonymous codons. This results in selective translation of codon-biased transcripts which manifests in the codon usages of the late trophozoite and schizont proteomes
(a) Phenotypes of SA187-colonized or non-colonized wild type Col-0, hsfa2, hsfa1q and ein3-1 mutant plants upon long-term aquired thermotolerance treatment (LAT): 9 d old plants without and with SA187 (LAT, LAT+187) were treated at 37°C for 3 h, then returned to 22°C for 2 d. At d 11, plants were heat stressed at 44°C for 30 min and incubated for recovery at 22°C; or direct heat stress treatment (HS): 11 d old plants without and with SA187 (HS, HS+187) were treated at 44°C for 30 min and incubated for recovery at 22°C.
Fractions of orthologous genes in different groups exhibiting different subcellular localizations of mRNA isoforms in rat neurons. Same: isoforms enriched in same cellular location. Diff: isoforms enriched in different cellular locations, i.e. one isoform in neuropil and another one in soma. (Fisher exact test: *P < 0.05; **P < 0.01; ***P < 0.001).
E: Suppression of EZH2 expression and activity antagonizes mithramycin activity in BT12 rhabdoid tumor cells. Data represents dose response curves of mithramycin in BT12 cells following a 48h exposure in the presence of siRNA silencing of the PRC2 subunit EZH2 or treatment with the EZH2 inhibitor EPZ-6438 relative to mithramycin alone (media) or a non-targeting siRNA (siNeg). Data represents mean with standard deviation derived from three independent experiments.
Morphology of four-week-old soil-grown plants of Col-0, sniper1-1, sniper2-1, eds1-2, SNIPER1H129Y, SNIPER1H129Y eds1-2, sniper1-1 sniper2-1 eds1-2 and sniper1-c1 sniper2-1 eds1-2. sniper1-1 is an exonic T-DNA insertional mutant. sniper1-c1 is a SNIPER1 knockout mutant containing 807bp deletion that was generated by CRISPR-Cas9 system. Scale bar = 1 cm.
E EGFR, ZEB1, and GAPDHimmunoblots in uninduced U87FO cells (-) and in cells transfected with LNA oligos targeting miR-200a-200b-429 (LNA 200) and miR-146b (LNA 146b), or with a non-targeting LNA (C), and induced with Dox for 48 h (+Dox). Representative images are shown.
A. The results of IHC examining using anti-DDX4 antibody shows that the overexpression of LncBMP4 increases the number of PGCs in the genital ridge, and interference with LncBMP4 reduces the number of PGCs in the genital ridge. The number of PGCs was counted through the Segmentation module of Image J software. Scale bars:200 μm (top row),40 μm (bottom row) (Data are shown as mean ± SEM, n = 3 independent experiments, * p < 0.05, ** p < 0.01, **** p < 0.0001, one-way ANOVA).
METTL14 is arginine methylated in vitro. In vitro methylation assays were performed by incubating recombinant PRMTs (1-8) with purified GST-tagged METTL14. Ponceau staining shows the loading of the recombinant proteins. The black dots indicate PRMT enzymes; black triangles indicate arginine methylated-METTL14; open triangles indicate recombinant METTL14 proteins.
A Human SNCA gene contains six coding exons and two 5' non-coding exons. The exons are represented by vertical colored boxes. The region from exon 1a to exon 2 (~2.5 kb) is scaled up to show the distribution of histone PTMs. Distribution of the histone PTMs from the SN region of one donor brain sample is shown. Peaks of three different histone PTMs, H3K4me3 (green), H3K27ac (blue), and H3K27me3 (black), at the regulatory region of SNCA were adopted from Roadmap Epigenomics Database. For a detailed view, please see Appendix Figure S1 where screenshot of the original figure is shown. The TSS is indicated by a red vertical bar and distances of exon 1a and 1b from the TSS are indicated.
I Probable range of mechanical stress inside the mandible evaluated by multiple simulation tests in which serial stress and Young's modulus were inputted into the cup model; the cup was set with the outer surface fixed (left, dr = 0 denotes that radial deformation of the outer surface equals 0) or the outer surface free (right).
(B) Expression of SASP targets of NF-κB obtained from RNA-seq analysis (Dataset EV1B), was quantitated using RT-qPCR from the shRNA (RELA) stably expressing U2-OS cells. For knockdown efficiency see Appendix Fig S4A. Cells were treated with doxycycline (Dox) to induce knockdown of p65. Heatmap represents targets normalized to the untreated Scrambled control. Expression is shown as log2 change with p values < 0.05. Statistical analysis performed using ANOVA with Bonferroni correction for multiple testing. First-phase and second-phase samples were irradiated (20 Gy) 1.5h and 7 Days prior to harvest, respectively. Analysis based on n = 3 biological replicates.
Dose-dependent viability assays of BRCA1-proficient (+BRCA1) or -deficient (-BRCA1) TP53-deleted cells treated with drugs at the indicated concentrations for six days.
Representative maximum intensity z-stack-projected images of DAPI-stained (blue) AC16 exposed to 18°C and returned to 37°C for the time periods indicated, probed by RNA-FISH for CRY2 (B)
A PS1 FAD mutations display little or no effect on substrate interactions at the exosites. Asterisks indicate antibody crossreactivities to C99 monomer.
(C) Representative long axis four-chamber cardiac magnetic resonance images of CLIP-170 S311A TG mice and control mice over 1 year after tamoxifen induction. Left column showed systole images and right column represented diastole images. Three mice from each group were analyzed for cardiac MRI. The representative images were shown.
Asparagine content in BAT of mice in (B). n=5 mice each group. Data information: Data represent means±SEM. *P<0.05; **P<0.01; ***P<0.001; unpaired two-tailed Student's t test.
A MEF eEF2K WT, KO or KO reconstituted with human eEF2K (Flag-eEF2K) were analyzed for cell growth at indicated times. Fold change (means ± s.e.m of triplicate) of the cell number just before treatment are shown. Histogram shows percentage of growth inhibition after 72h of 10 μM NFR. P values are 1way ANOVA with Bonferroni posttest calculated from 3 independent experiments. *** P value ≤ 0.001.
Cartoon representation of CNFY, colored according to domain boundaries determined with PiSQRD (Aleksiev et al, 2009). Dark blue: domain D1, cyan: domain D2, dark green: domain D3, yellow: ADP-ribosyltransferase-like domain D4, pink: deamidase domain D5. Other colors indicate the position of sequence motifs that have been identified in E. coli CNF1, namely light blue: p37LRP/67LR receptor-binding motif, red: hydrophobic stretches predicted to form membrane-inserting α-helices, orange: cleavage site, magenta: main Lu/BCAM receptor-binding motif. The positions of N- and C-terminus are indicated by N and C, respectively. Surface representation of CNFY as seen from two different orientations with respect to B. Note that the cleavage site between D3 and D4 (orange) as well as the deamidase active site in D5 are partially blocked in the structure of full-length CNFY. The C-terminal domain D5 interacts mainly with D3 (610 Å­2), which partially hides the catalytic site of D5, but it interacts only weakly with D4 (380 Å2), which itself establishes an extensive interface with D1 (1390 Å2) by mainly hydrophilic interactions (17 hydrogen bonds and 6 salt bridges).
Treatment of NPC fibroblasts and NPC null mice with thioperamide. Fibroblast lines obtained from patients with well-established heterozygote mutations in the NPC1 (GM17912 line: NPC1 P1007A / T1036M; GM17911 line: NPC1 I1061T / T1036M) or with a homozygote mutation in the NPC2 gene (GM17910 line: C93F / C93F) were treated or not for 72h with thioperamide 10µM, stained with filipin (cholesterol) and analysed by fluorescence automated microscopy.
293T cells transiently expressing FLAG-Stx17 wild type (WT) or the K254C mutant were incubated with ethanol (Vehicle) or 20 μM CCCP (+CCCP) for 2 h, lysed, immunoprecipitated with anti-FLAG M2 beads and then analyzed by IB using the indicated antibodies.
(C) From top to bottom: experimental design, fluorescence pictures of the SVZ of a 4D- (left) and 4D+ (right and insets magnified) mice and quantification of the proportion of BrdU+ among B1, C and A cells (identified as in B). Note that in 4D+ mice quantification was restricted to the RFP+ subpopulation (red bars).
(g) Expression analysis of PGC1α/PPARα target genes in liver from either fasted or fed mice with indicated genotypes. Bar graphs show mean ± s.d. for n = 4. *P≤0.05; **P≤0.01 compared with the respective controls (fed or fasted).
C Western blot analysis in the C57#1 DLP mouse prostate organoid line upon acute removal (24 hours) or long-term adaptation to A83-01 removal, in the presence or absence of Activin A (50 ng/mL, 24 hours).
Re-introduction of Cideb rescues the expression of SREBP target genes in Cideb-/- liver. Transcript levels of lipogenic genes determined by qPCR from WT and Cideb-/- liver. WT and Cideb-/- mice were injected with AAV-GFP or AAV-Cideb, and sacrificed for qPCR 20 days after the injection (n = 3 per group).
Confocal analysis of lysotracker staining (red) in GSC#9 treated for 16 hours with vehicle (DMSO) or MPZ (20 μM). Alternatively, GSC#9 were either treated for 16 hours with H2O or Z-VRPR-FMK (75 µM) (upper panel) or transfected with sic and siMALT1 (bottom panel). As indicated, number of lysotracker-positive puncta and lysotracker pixel intensity (arbitrary unit, AU) were quantified per cell. Data are presented as the mean + s.e.m. on 3 independent experiments. Each dot represents one cell. n>30. Nuclei (DAPI) are shown in blue. Scale bars: 10 μm.
(C) Genomic DNA was isolated from each transfectant and subjected to PCR using the primer pair indicated in A.
B) Crystal violet staining of viability assay on RPE-1 Parental cells and Taxol resistant clones obtained from A. For the clones' nomenclature, sg# represents the sgRNA from where they are derived and C# the clone number.
F. Boxplot showing changes in H3K27me3 in ESC+2i upon BAZ2A at BAZ2A-regulated and random genes. Mean of normalized H3K27me3 read counts in ESC+2i treated with siRNA-control or siRNA-Baz2a over TSSs (+/- 1kb) of upregulated, downregulated and random genes were calculated. Log2-fold changes of (siRNA-Baz2a/siRNA-control) are plotted. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (** < 0.01 and *** < 0.001). Box plots depict the minimum and maximum values. The mean is represented by a horizontal line within the boxes.
(C) TIRF microscopy of actin polymerization in- (blue arrows) and outside (red arrows) of WAVE1-micropatterns (magenta) in the presence of 1uM profilin-actin visualized by a filament-binding probe (5nM Alexa488-UTRNN).
Effects of ablation of Smo in CaMKIIα-positive neurons (G-I), on the progression of kindling including seizure class (A,D,G,J), evoked electrographic seizure duration (ESD) (B,E,H,K) and the number of stimulations required to reach equivalent seizure intensity (C,F,I,L). In G-I, Ctrl: Smofl/fl induced by tamoxifen; CaMK: Smofl/flCaMKIIα-CreERT2 induced by tamoxifen, n=14-20.
(I) Cyclin A2 siRNA depletion causes endoreplication. Following 72 hours of siRNA transfection MCF7 and MCF10A cells were analysed by PI staining and FACS. The histograms show the changes in DNA content (PI Int.) towards >4N following cyclin A2 depletion.
V. Relative kinase activity of human PRKCB2 under standard conditions and in the presence of various concentrations of the WT VEAL2 RNA and VEAL2-AS RNA. 52nM of the PRKCB2 protein was used per reaction. Data from three different experiments plotted as mean fold change values ± standard deviation.
(F) Filamentation assays with the indicated combinations of 8 µM mChRZZSF, MPS1 (1 µM), and lambda phosphatase (0.4 mg/ml) in presence of 10 µM reversine. Dephosphorylation reactions were carried out on already formed filaments (see Methods). Samples were imaged by confocal microscopy. Dephosphorylation does not dissolve already formed filaments. Data information: Scale bars in panels , F, 5 µm. Two technical replicates for panels , F, were performed.
G Percent of animals of the indicated genotype containing aggregates of Poly(Q)44::YFP at the indicated time (in days) after L4 stage. *P<0.001, Student t-test corrected for multiple comparisons at each time point using the Holm-Sidek method. N=3 trials, 50-80 animals per trial per day. Error bars indicate SEM.
A. Schematic representation of the AOM/DSS procedure. To develop colitis-associated cancer (CAC), WT (n=11) and OMA1-/- (n=12) mice were injected intraperitoneally with AOM (10 mg/kg) on day 0. Then, three cycles of feeding water with 1.5% DSS treatment were administered. Mice were euthanized on day 105 and all intestinal tissues, tumors, and serum were collected. After mice were euthanized, intestines were removed and flushed with cold PBS. All experiments were repeated with three independent biological replicates.
(d) Western blot analysis on total proteins extracted from hiwΔN, wild-type (C155-Gal4/+) and Rae1 expression (C155-Gal4/+; UAS-NTAP-Rae1/+) larval brains. Full-length blots are presented in Supplementary Figure 12. (e) Quantification of Hiw protein levels in the wild-type and the Rae1 expression larval brains (*P 0.001, based on seven independent experiments). Arrows indicate a 38-kDa endogenous Rae1 protein and the arrowheads indicate the 58-kDa transgenic NTAP-Rae1 protein. Error bars denote s.e.m.
C Knockdown of RNF123 potentiates the activation of the IFN-β promoter induced by RIG-I, RIG-I CARD, MDA5, and MDA5 CARD, but not that by VISA, TBK1, and cGAS/STING. 293T-GFPsh, shRNF123 #1, #3, and #4 stable cell pools (2×105) were transfected with the indicated plasmids. Luciferase assays were performed 24 h after transfection.
B Left, structural modules of complex I highlighted in colours based on mouse cryo-EM structure (PDB: 6g2j) (Agip et al., 2018). NDUFC2 is shown in black. Right, surface view indicates subunits interacting in a neighbourhood of less than 10 Å to NDUFC2. All other subunits not interacting on any part of the protein are in transparent cartoon view.
E. (top panels) Serial replating of Myc-Bcl2+DN2 cells in methylcellulose generated myeloid clones with stable genomic reassembly of the Dβ1 TCR locus in vitro (gel: left two lanes). Upon transplantation, the same clones induced myeloid leukemia that retained the initial rearrangement in vivo (gel: right two lanes) as assessed by nested PCR. GL = germline. (bottom panels) Methylcellulose-based replating of Myc-Bcl2+GMPs generated myeloid clones that exclusively displayed the TCRß locus in germline configuration.
H-I Co-immunoprecipitation analysis of HA-SIRT5 with Flag-MAVS-truncated mutants. HEK293T cells were co-transfected with the indicated plasmids. Anti-Flag antibody conjugated agarose beads were used for immunoprecipitation and the interaction was analyzed by immunoblotting with the indicated antibodies. Flag-MAVS fragments (WT: full length; ΔC1, 1-173 aa; ΔC2, 1-513 aa; ΔN1, 91-540 aa; ΔN2, 173-540 aa; ΔCARD, Δ10-77 aa; ΔPR, Δ103-173 aa; ΔTM, Δ514-535 aa). Data information: IP, immunoprecipitation; TCL, total cell lysates.