EMBO/sd-character-level-ner huggingface dataset:
DU145 cells were supplemented with cell-permeable aspartate (6mM, esterified) or glutamate (3mM, esterified) following ASNase treatment, with esterified leucine (6mM or 3mM) as control.
Representative FACS plots showing aNSCs (GFP+EGFR+), qNSCs (GFP+EGFR-) and C cells (GFP-EGFR+) in the adult V-SVZ.
C, D Following transfection with AMPKα1/2-targeting siRNAs for 2 days, WM115 cells were treated with 10 μM metformin for 3 days. HSP mRNA levels were quantitated by qRT-PCR (mean ± SD, n = 6, Student's t-test, n.s., not significant, *P < 0.05, **P < 0.01).
Quantification of (E) in which large budded cells were classified according to their Mtw1-GFP signal into the three indicated groups. Scale bar represents 5 µm. A total of 100 cells was quantified for every strain. Mean values of the three indicated groups were calculated and plotted in a bar chart. Error bars indicate the SEM of 3 independent experiments.
(C) Ratio of IL-12- or TNF-producing cells in 5.2+ vs 5.1+ pDC of indicated MCMV-infected MBMC mice
B. Replication fork degradation (IdU/CldU ratio) in U2OS cells transfected with indicated siRNAs and processed as in (A) (bars, mean; n=200 fibers, pooled from two independent experiments, per condition).
Spearman correlation between APA Shannon index and APA variability between replicates for each gene group in different tissues. An empty square indicates P value of the correlation is larger than 0.01.
(c) The lipidation reaction is largely insensitive to PE concentrations when run on highly curved liposomes. Coupling of GL1 and LC3 to PE was assessed on liposomes of two sizes (400 nm, black squares; sonicated, red circles) and varying molar percentage of DOPE. The extent of lipidation is determined as in Fig. 2. (n = 2 for 30 and 55% PE, n = 4 for all the other points, and error bars represent standard deviation.) P values were determined by comparing sonicated with 400 nm samples at each PE concentration. **P 0.1; *P 0.01. Uncropped versions of all gels are included in Supplementary Fig. 7.
(A) Linearised versions of the indicated plasmids were transformed into SPT5-9MYC budding yeast cells and integrated at the ura3 locus. For each transformation, four colonies were analysed by immunoblotting and DNA sequencing as shown. Colonies transformed with plasmid expressing Spt5-3A either lost the plasmid (1), contained the SPT5-3A DNA but failed to express Spt5-3A protein (2+4) or experienced a gene conversion and thus expressed wild type Spt5 from the integrated plasmid DNA (3).
(B) Left Panel: Quantified fusion of the Alpha + E484K variant S protein normalized to D614G S. Right Panel: Representative images of fusion at 20h. Scale bar: 200 µm. Top and bottom are the same images with and without Hoechst channel.
D. Gene lists near the 37 hypo-methylated genomic regions with REST/NRSF binding confirmed using the ChIP-Atlas database. Blue highlights indicate DMRs in the intron of overlap genes. Magenta highlights indicate DMRs in intergenic regions between upstream and downstream genes. Gray highlights indicate DMRs with the REST/NRSF binding motif. The black circle indicates ASD-related genes (SFARI genes), and the black triangle indicates schizophrenia-related genes (SZ genes).
A. Transferrin (Tf, red) uptake in Syt11 KD (GFP-positive) and control neurons. Quantitative data are on the right. Scale bars, 20 μm.
E Cells were treated with different methionine concentrations as indicated. Apoptotic rates were detected by flow cytometry and normalized to those of the untreated cells (n=4). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, ***P ≤ 0.001.
D PAM50 classifier results showing probabilities of the non-adherent and adherent CTC-ITB-01 fractions matching molecular subtypes. Selected bars are not visible due to extremely low probability (close to zero). Both fractions show greatest alignment with a luminal B subtype. Starting from lowest probability, the adherent fraction of CTC-ITB-01 was classified as 0% (±0%) normal-like, 6.22% (±9.0%) Basal-like, 17.85% (±8.6%) ERBB2-positive, 0% (s=0%) luminal A, and 75.92% (s=0.7%) luminal B breast cancer subtype. The suspension cell fraction of CTC-ITB-01 was classified as 2.04% (s=3.5%) normal-like, 0% (s=0%) Basal-like, 17.32% (s=9.7%) ERBB2-positive, 33.5% (s=23.8%) luminal A, and 68.67% (s=18.6%) luminal B breast cancer subtype, respectively. Data was generated from n=3 replicates.
(c) SLC7A11 protein levels were upregulated by the exposure to Sorafenib, yet downregulated by siRNA-mediated depletion of YAP/TAZ. HLE cells were transfected with siCtrl or siY/T and cultured with DMSO or 6μM Sorafenib for 18 hours before harvest, followed by immunoblotting for YAP/TAZ and SLC7A1. GAPDH served as loading control. Results represent three independent experiments.
Quantification of IL-1β concentration (pg/ml) in the supernatant of primary macrophage cultures from COVID-19 patients (n = 44; red bars) or SC-naïve individuals (n = 24; blue bars) stimulated with LPS or S-protein (0.1 µg/ml). To activate IL-1β secretion nigericin was added for 2h. For statistical analysis, two-way ANOVA with tukey post hoc test was used. TNF-α (pg/ml) secreted from macrophages derived from SC-naïve and COVID-19 patients as described above. Cells were stimulated with LPS (SC-naïve/COVID-19 n = 4), LPS with nigericin (SC-naïve n = 4; COVID-19 n = 6), S-protein (SC-naïve n = 5; COVID-19 n = 4), S-protein with nigericin (SC-naïve n = 3; COVID-19 n = 4) or left unstimulated (SC-naïve n = 3; COVID-19 n = 4). Significances shown in the figure are always in comparison to the unstimulated control.
Western blot analysis of UCP1 and GAPDH in BAT lysates from WT and KO female mice at 4 and 12 mo old (n = 3 per group). Protein levels were normalized to that of GAPDH. RT-qPCR analysis of Ucp1 mRNA level in BAT collected from (B) relative to Gapdh mRNA level
C Immuno-blots for the detection of PAP8 in total protein extracts (Col-0 Tot) the nuclear fraction (N) and the plastidic fractions (EP, etioplast; CP, chloroplast) of etiolated (Dark) or photomorphogenic (Light) Arabidopsis seedlings by immuno-Western blotting using a PAP8 antiserum (PAP8). As control, a mixture of antisera raised against Histone 3 (H3) and the large subunit of ribulose 1, 5-bisphosphate carboxylase/oxygenase (RbcL) was used to evaluate reciprocal contaminations. The lanes are extracted from the same blots provided in the Source Data file.
(A) BI‐1 KO MEFs were stably transduced with lentiviral vectors expressing an shRNA against beclin‐1 (shBeclin‐1) or ire1α (shIRE1α) mRNA or luciferase (shLuc) as control. The levels of LC3, Beclin‐1, IRE1α and Hsp90 were monitored by western blot.
Immunolabeling of muHTT aggregates (red) in R6/2 ACSF and R6/2 chol-high mice (N=3/group). Zoom of representative confocal images of immunostaining against muHTT aggregates (red) showing muHTT aggregates positive for EM48 antibody in the infused and contralateral striatum (A) and relative quantification of number (B) and size (C) of aggregates. Hoechst (Ho, blue) was used to counterstain nuclei. 18 images/animal were analyzed from 9 sections throughout the entire striatum. The data are shown as scatterplots with means±standard error. Each dot corresponds to aggregates counted in all the images from 3 animals. Scale bars: 10 µm (A) Statistics: one‐way ANOVA followed by Newman-Keuls multiple comparison tests (*p<0.05; **p<0.01; ****p<0.0001).
(C) A549 cells were treated for 24 hours with 100 µM of the ADPRT activity inhibitor MIBG and then left uninfected (NI) or infected with P. aeruginosa containing ExoS with ADPRT activity only (SG-A+). Cell lysates were evaluated by immunoblotting.
Result of co-immunoprecipitation experiments demonstrating the interaction of Dicer protein with Ago1 and Ago1x in HeLa cells.
(A) Schematic representation of wild-type (wt), targeted (flx) and deleted (Δ) Cdca5 alleles (left) and Southern blot of mouse genomic DNA (right). Red triangles, loxP sites.
F. Genes related to major ZGA initiation, like Hsc70, Hsp70, Erv4, Eif1a, and Zscan4, are expressed normally in LincGET depleted L2C embryos compared to that in Control embryos. Embryos injected with LNA were collected at phCG 48 hours at the late 2-cell stage for TM-qPCR analysis. The error bars represent s.e.m. About 100 embryos were used for each group and three experimental replicates were performed. n.s., p > 0.05.
6-week-old male CD36 knockout mice were administered with AAV-TBG-wildtype-CD36, wildtype-CD36 plus KLF10, palmitoylation site mutant CD36, mutant-CD36 plus KLF10 through tail vein injection, and then kept on WD/CCl4 for 12 weeks. n=5 per group. (C) Body weights and liver/body weight ratio. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA
PI staining of pKNOLLE:FLAG-PI4Kβ1 expressed in the pi4kβ1 pi4kβ2 double mutant background indicates rescue of cytokinetic defects. Arrowhead, cell wall stub in the pi4kβ1 pi4kβ2 double mutant. Scale bars, 50 µm.
(C) TFR1 mRNA levels in muscle biopsies from cancer-patients of late stage cachexia (19 healthy subjects, 17 cachectic patients with at least 10% total body weight loss) Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
(d) HCT116 cells were labelled with [3H]leucine for 48 h, washed and incubated for 24 h, before being subjected to serum starvation for 24 h or 0.5 mM H2O2 for 12 h in the presence or absence of 3-MA. At 12 or 24 h after treatment, the relative degradation of long-lived proteins was measured by counting radioactivity. Data in d are means ± s.d. (n = 3). Two asterisks, P 0.01; asterisk, P 0.05; NS, not significant, P > 0.05; Student's t-test.
G. A schematic model for the induction of DDR, senescence and diabetes in Rb∆K7 mice and the effect of vitamin C diet. Normal pancreatic β-cells can re-enter the cell cycle in response to mitogenic signals. In contrast, Rb∆K7 β-cells display a repressive chromatin and stable differentiation state, which, in response to mitogenic signals, elicits a DDR, cellular senescence and SASP, leading to gradual islet degeneration. We propose that the epigenetic modifier, vitamin C, prevents the establishment of a stable repressive state during differentiation of Rb∆K7 β-cells, thus reduces DDR and senescence in response to mitogens, facilitating cell cycle re-entry/regeneration and alleviating diabetes in Rb∆K7 mice. SC denotes senescent cell.
(D) Senescence-associated β-gal assay (SA-β-gal) of cells treated as in C. Scale bar, 100 μm.
(e) ACE2+PCSK+ dual positive cells across lung cell types. Fraction (y axis) of different ACE2+PCSK+ or ACE2+TMPRSS2+ dual positive cells across lung cell types (x axis). Dots: different individuals, line: median.
(A) Primary root length of Col-0 wild type plants or eir1-1 mutant plants was measured using the ImageJ program 3 days after 5 mM KNO3 or KCl treatments. Tukey box plot show results from 3 independent biological replicates per experimental condition (n = 10-15 roots each replicate). The box plot shows the data within the interquartile range (25th and 75th percentiles) and a solid black line represents the median. Whiskers show maximum and minimum values no further than 1.5x IQR (interquartile range). Outlier data are plotted individually. Asterisk indicates statistically significant difference between analyzed by unpaired, two-tailed and assuming equal variance t-test (** p < 0.01).
H A two-dimensional snapshot of a propagating wave (direction of propagation indicated with the dashed arrow). A line scan corresponding to the STEN-CEN profile is shown on the right.
Co-immunoprecipitation from whole-cell lysate of OSCs before (control) and after (Zuc KD) Zuc depletion and subsequent western blotting show that the levels of Piwi and Armi in the Flag-Gasz (F-Gasz) complex increased upon Zuc depletion (Zuc KD).
A, Quantification of Nox4 mRNA levels (A) in cultured rat cardiomyocytes after increasing degrees of serum starvation as compared to serum-replete cells (15% serum). n=4 cell preparations/group.
RNA-seq analysis was conducted on Tnfaip2-/- EBs vs. WT EBs on day-3 of differentiation induction of EBs (n=3 biological replicates). The heat maps depict the intersection of DEGs with the following gene sets ;, (C) "mesoderm development"
Human myoepithelial and luminal cells isolated from breast specimens were cultured in collagen gels for 14 days to reform ductal structures with luminal compartment. Reformed ducts were then cultured for 7 days in macrophage-conditioned or control medium in presence of amlexanox. Representative images showing the filling of the ductal lumen with cell nuclei. The ducts were stained for DNA (DAPI in blue) and F-actin (Phalloidin in red). Scale bar: 20 μm. Macrophage donors are indicated as M1A - M1 activated, M2A - M2 activated macrophages.
Detection of pS357-PDI in HepG2 cells treated with 1 mM DTT (G) for indicated times.
B. Comparative analysis of fragment S1, S2, and L production in SRS2 and srs2Δ cells during a time-course experiment (Combined data from Figs 4D and 5B). Blue two-ended arrow indicates a ~ 0.5 h time difference between the formation of fragments S2 and L in srs2Δ mutants. Since the distance between the BlgII site on the right and the EcoRI site is ~6 kb the rate of restoration of dsDNA in srs2Δ mutants can be roughly estimated at 12 kb/h. The rate of re-synthesis is much faster in wild-type cells as the difference between S2 and L is not even detectable at the 1 h time point. . Strains used: NK4691-4693; NK4805-4808.
Confocal images of ddaC neurons expressing UAS-mCD8::GFP, UAS-Nod-lacZ or UAS-Kin-lacZ and immunostained for β-galactosidase at wL3 stages. (A-C) Wild-type ddaC neurons (A) displayed normal distribution of Nod-lacZ signals in dendrites. In contrast, in msps810 mutants (B) and tacc59/tacc74 mutants (C), ddaC neurons exhibited altered Nod-lacZ distribution patterns, with highly enriched stainings in the somas and decreased signals in the dendrites.
Lung ECs isolated from miR-483-Tg rat and WT littermates were exposed to normoxia or hypoxia (0.2% O2) for 24 hr. Proliferation of ECs were measured by flow cytometry Data information: Values are expressed as mean ± SEM. Data are representative of three independent experiments Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups
(A) Structural alignment of the MSP domains of MOSPD2 (PDB ID: 1WIC; green) and VAP-A in complex with the FFAT motif of ORP1 (PDB ID: 1Z9O; orange). The FFAT peptide is in blue
A. Enhanced recruitment of DDX11 to chromatin associated PCNA following exposure to 4 µM PDS for 24 hours. PCNA was precipitated from cross-linked chromatin and the immunoprecipitate blotted for FLAG-DDX11.
e. Representative pictures of back skin of WT and PRSS35-/- mice at different days post-wounding (dpw). Scale bar: 1 cm.
Figure 4 - MAP2K1 is a predictive marker for inhibitors targeting EGFR Effect-size heat maps of six drugs (see titles of panels) targeting EGFR. It is evident that the different drugs showed different profiles but also that high MAP2K1 expression (blue/red gradient across cell lines) was consistently associated with drug resistance (dark blue/yellow gradient across cell lines; AUC: area under the curve; see main text and Appendix for details). See also Figure EV5.
(G-I) BALB/c mice (G) fed with a gluten-free diet for at least 3 generations, or (H) NOD or (I) NOD-DQ8 mice orally challenged with vehicle or gliadin for 4 weeks (5 mg/daily for one week and then 5 mg/daily thrice a week for 3 weeks). Representative traces of CFTR-dependent Cl- secretion measured by forskolin (Fsk)-induced increase of chloride current (Isc (μA/cm2)) in small intestines mounted in Ussing chambers; quantification of the peak CFTR inhibitor 172 (CFTRinh172)-sensitive Isc (∆Isc) in tissue samples (n=3 independent experiments). Mean±SD of samples assayed; **p<0.01, ***p<0.001 vs challenged with gliadin (Student's t test).
(E) OMA1 interacts with SLP2. OMA1-/-FITR293T cells ectopically expressing OMA1-myc were transfected with pcDNA5 (Control) or pcDNA5-SLP2-FLAG (FLAG). Isolated mitochondria were solubilized in digitonin and subjected to immunoprecipitation using FLAG-specific antibodies. Native eluates of the precipitate were analyzed by BN-PAGE and immunoblotting using SLP2-, YME1L-, PARL-, and myc-specific antibodies. In, input (8%); E, eluate (100%). Samples were analyzed by SDS-PAGE in parallel (lower panel).(F) Quantification of immunoprecipitation efficiencies in (E).
(F) Overview of electroporated areas of neocortices as revealed by mCherry fluorescence (magenta) showing the effects of Cas9 protein together with either control gRNA (top) or gGFP (bottom) on GFP expression (green, fluorescence). Dotted lines indicate the electroporated area of the VZ. Single optical sections; scale bars, 200 μm.
(E) The enrichment of the gene set "HALLMARK_OXIDATIVE_PHOSPHORYLATION" within differentially expressed genes between CD48- HSCs and CD48+ progenitor cells. NES and q values represent normalized enrichment scores and FDR, respectively.
Representative I-V curves of oocytes injected with the indicated RNAs in a bath solution containing 100 mM Na+ (G), , showing PC1-TLD/PC2_AA gave rise to current with similar properties as full-length PC1/PC2_AA channel.
Quantification of the plasma membrane signal of DHHC5 in (C and D), ****=p<0.001 t-test, control siRNA n=23, Golga7b siRNA n=23.
(a) Paramagnetic relaxation enhancement (PRE) with a free-radical-modified stearic fatty acid in DPC micelles. Low values indicate location inside whereas values close to one suggest a location outside the detergent micelle. Orange bars: TREM2-TMH wt, green bars: K186A variant. The N-terminal residues of TREM2-TMH-wt are located deeper inside the micelles as in the K186A case, whereas the C-terminal end is positioned at the outside for wild-type and inside for the K186A variant. Negative bars indicate missing assignments.
TUNEL assay performed in tumors described in C. On the left, typical immunofluorescence images (blue - nuclei, green - TUNEL). On the right, graph reports the percentage of TUNEL positive cells in tumors as described in C. Each dot represents a tumor. Data represent the mean (±SD) and two-way ANOVA with Sidak's multiple comparison test was used to verify the statistical significance.
B Bioinformatic analysis defined 16 secreted candidates (fold change ≥5) from brown compared to white adipocytes.
M: Paired-pulse stimulation revealed a significant defect of short-term plasticity at ISI 10 and 160 ms (unpaired Student's t-test, ∗p < 0.05).
(C) FYCO1-decorated vesicles move along the MT tracks. HeLa cells transfected with mCherry-FYCO1 and GFP-tubulin were live imaged by confocal microscopy 48 h after transfection. Movements of FYCO1-decorated structures were tracked with ImageJ MTrackJ plug-in (National Institutes of Health) and presented as 8-min-long tracks in the overlay image.
A Diagram of the dissected miniature pig mandible slice illustrating the deciduous (DC) and permanent (PC) canine and application of compression in vitro using Flexcell FX-5000 Compression System.
F. The percentage numbers of cells (Fig 7D) in G1, S or G2/M phase were analyzed by FlowJo 7.6 software. Data shown are mean ± SD (n = 3).
C 22Rv1 cells from Supplementary Fig S2 were subcutaneously implanted into both flanks of male nude mice (six mice per group). Tumor size was measured at the indicated time points. Student's t-test was performed to analyze the statistical significance, n = 10. *P = 0.037; **P = 0.039. Error bars indicate SEM.D Representative tumors from (C) right after resection at the final time point are shown.
(B) Islet graft survival of five groups of mice was assessed by monitoring blood glucose and calculated using the Kaplan-Meier method. Cumulative data from two independent experiments are shown. Statistical analysis was performed with a log-rank test. ***P<0.001.
Three CLK-mouse lines were generated and subsequently immunized with eOD-GT8 60mer in adoptive transfer/immunization system (precursor frequency:1 in 104). eOD-GT8-specific splenic IgG1+ or IgM-IgD- B cells were single-cell sorted at day 36 post immunization for single-cell PCRs. (C) Hotspot analysis. The quality of mutations was assessed via hotspots analysis for both heavy (left) and light (right) antibody chains. Weblogos were generated via publicly available online tools
(A) Schematic of PP7-tagged RNA reporters and PCP-NLS-FLAG constructs used in this study.
B. Homology model of TetB using YajR (PDB 3wdo) built using Phyre2 where the periplasmic side is on top and the cytoplasmic side is on the bottom. The A-helices are shown in blue, B-helices are shown in green, C-helices are shown in grey and the interdomain loop is in cyan. Spheres indicating variant positions were made using PyMOL (L9- pink, V339- purple and G366- orange). Right image depicts the view through the central TetBpore from the periplasm into the cytoplasm.
(B) Ceftriaxone-resistance depends upon ycbB and relA' expression. The disk diffusion assay was performed with BW25113 ΔrelA ΔsltY harboring pKT2(ycbB) and pKT8(relA') or pKT8(relA') only. Induction was performed with 40 µM IPTG and 1% L-arabinose for ycbB and relA', respectively. Disks were loaded with 30 µg of ceftriaxone.
A, Quantitative data-independent scanning (DiS) mass spectrometry protein profiles for CI, CIII and CIV. Vertical numbers indicate the BNGE gel slices. Left and right profiles correspond to scaf1+/+ and scaf1Δ1/Δ1 animals, respectively. Red heatmap corresponds to the E-score from two proteotypic Scaf1-derived tryptic peptides spanning sequences ascribed to the CIII interacting site (in green) and to the CIV interacting site (in yellow). Thick blue line, marked with an asterisk, indicates the putative proteolytic site in Scaf1.
Deficiency of Rabin8, a GEF for Rab8a, enhanced the physical interaction between BAG6 and WT Rab8a proteins. Flag-tagged WT Rab8a was expressed in Rabin8 siRNA-treated cells, and Flag immunoprecipitates were probed with an anti-BAG6 antibody. Note that all cells used were treated with 10 μM MG-132 for 4 h.
Examples (D) and quantification (E) of Northern blot analyses of minor (U6atac, U4atac, U11, and U12) and major (U2, U1, U4, U5, and U6) spliceosome snRNAs in HeLaEGFP-AID-CENATAC cells (three biological replicates, normalized to the control). See also Appendix Figure S8.
(C) In vivo ubiquitination assay to detect MDM2 autoubiquitination in H1299 cells. Lysates were prepared from H1299 cells transfected with the indicated expression vectors (His-Xpress-MDM2, 2 ug; HA-Ub, 0.5 ug; RPL11-FLAG, 1 ug; HA-GRWD1-FLAG, 1.5 ug) for 48 h, treated with proteasome inhibitors for 6 h before harvest, and then immunoprecipitated with anti-MDM2 antibody. Immunoprecipitates (IPs) and inputs were immunoblotted with the indicated antibodies.
D Distributions of pairwise Ka/Ks (nonsynonymous to synonymous nucleotide substitution rates) ratios between PIWI duplicates in arthropods (n = 17 in Drosophila and n = 37 in others, Mann-Whitney U test, *P<0.05). The center line of the boxplots represents median value, the bounds of the box represent 75th and 25th percentile, and the whiskers represent maximum and minimum value.
Immunoblotting analysis of BCL9 and cell cycle protein expression in double thymidine synchronised cells; the black arrow indicates the delayed band of mitotic BCL9.
(D) Phase contrast images of WT and Gata6 iKO keratinocytes 3 days after induction with TM (n > 3 per genotype).
Scheme illustrating the Nsmce2‐mutant allele (Nsmce2SD) used in this study, which was generated through introducing the mutations on exon 6 (see ).
B CY exhibited enhanced activity against BCR-ABL Arf−/− murine ALL cells in vitro.
H. Relative shox mRNA expression normalized to reference genes eef1a and b-actin in zebrafishembryos treated with 100 nM ATRA (n = 4). Embryos were collected at 24 hpf and treated with mock control or ATRA. RNA was extracted from 10-15 embryos after 6 hours treatment.
Weight and representative images of WT and KO BAT. Three mice per group were analyzed