EMBO/sd-character-level-ner huggingface dataset:
C Hemizygous K18-hACE2 mice were treated intranasally with 20 µg of NM1251 (n = 8), NM1267 (n = 9) or NM1268 (n = 9) seven hours prior to infection with 3*103 PFU SARS-CoV-2 B.1.617.2 (Delta). survival were monitored for 14 days. ***P < 0.001 in orange between NM1251 and NM1267 and ****P < 0.0001 in purple between NM1251 and NM1268, by log-rank test
F, G DoT scores calculated using genes differentially expressed after Hoxb8 or Ikzf1 loss in Hoxb8-FL cells in the context of the human BMMC landscape. Arrows indicate the HSCs and megakaryocytic trajectories.
A-I Staining of small intestinal tissue sections of 12‐ to 16‐month‐old G3 mTerc−/− mice and age‐matched mTerc+/+ mice (n = 4-5 mice per group). Representative pictures of (A, B) H&amp;amp;E staining, (C, F, I) Quantification of the absolute numbers of ISPCs at the indicated positions in the crypt base per 50 crypts as determined by counting of (C) spindle‐shaped cells in between and adjacent to the Paneth cells. Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test.
(e) Images show 1.5-nm tomographic slices of the boxed region in c, and depict the IM (black arrow), whose edge (red arrowhead) is connected to the associated ER (black arrowhead). Numbers indicate the depth of the tomographic slices. Scale bars, 200 nm in a, 100 nm in b and c, and 50 nm in d and e.
(c) 293T cells were transfected with the indicated plasmids for 24 h and subjected to immunoprecipitation with anti-Flag monoclonal antibodies. The resulting immune complexes and TCL were analysed by immunoblotting with anti-Myc and anti-Flag polyclonal antibodies. Uncropped images of the immunoblots in c are shown in the Supplementary Information, Fig. S5.
(A) Predicted binding sites for miR-483-3p/-5p on the 3'UTR of mRNAs as indicated.
(C) WT and EGFR KO HeLa cells were infected with HSV1, RNA was extracted at 4 h.p.i. and IFNα mRNA induction was measured (n=3).
(D) Western blot analysis also confirmed that ADAR2 can be negatively regulated by AR at the protein level.
A. Wild type and GAL-Mia40 cells, and cells expressing a cytosolic version of Mia40 under GAL1 control were dropped on the indicated plates; ev, empty vector. Note, that the mitochondrial version of Mia40 suppressed polyQ toxicity, whereas the cytosolic version did not.
A Representative fluorescence confocal images of live HeLa cells expressing Fluc-EGFP and FlucR188Q-EGFP maintained in SF compared to SF+q. Scale bars, 10 μm. Data information: SF (serum free medium), q (queuine)
(F) Venn diagram showing the overlap between YAP signature 2 and the genes upregulated by more than 1.5 fold in BCC compared to IFE [28]
(c) USP33 regulates RALB binding to EXO84. Flag-tagged RALB was immunoprecipitated using anti-Flag (M2) agarose from HEK293T cells expressing the indicated constructs. The presence of EXO84 in RALB complexes was analysed by immunoblotting using anti-HA or anti-EXO84 antibody.
B Two-dimensional cell-cycle analysis (BrdU/PI) of cells described in (A). Sub G1 and G2/M fractions of cells were quantified and averaged with two additional, independent experiments (n=3, ± SD; WT: **, P = 0.0016; ***, P = 0.0004; Mcl1-/-: ***, P = 0.0003; **, P = 0.0017; cIap2-/-: **, P = 0.0043, Student's t test). Black bars exemplify shRNA Ctrl, white bars shRNA Usp9X samples.
The spine density deficit of Venus injected cDKOs mice (11% in basal and 18% in midapical dendrites) is rescued by APPsα to LM control levels. Images are maximum projections of deconvolved z-stacks. Scale bar: 5 µm. Spine density was normalized to LM control levels. n=number of neurons (from 5 animals per condition).
Schematic of the experiment. K and KM animals were set on doxycycline food until mammary tumours developed. Primary tumours were collected and single cells injected into Rag2-/- animals to recapitulate the tumours followed by either no treatment, drug treatment or switched to a normal diet.
A. Fluorescence microscopy analysis of extracellular tachyzoites expressing GFP-TgAtg8 or its glycine mutant version, before or after induction of autophagy for 8 hours in HBSS. Autophagosomes are labelled by GFP-TgAtg8 in control parasites (arrowheads), but not by the glycine mutant version of the protein. B. Extracellular tachyzoites expressing GFP-TgAtg8 or its glycine mutant version were put to starve in HBSS medium for increased lengths of time and the proportions of cells displaying punctate or cytosolic GFP signals were assessed. Data are mean from n = 4 independent experiments ±SEM.
B, Normalized spectra of control and steatotic liver 10 and 120 min after ICG injection. Each line represents data from one animal. Each data point is from a single measurement of each animal at each time point. Data information: In the figure, A.U. = arbitrary units
I Plasma bile acids in (H). n=7 for all groups. ***P<0.001 PLTP relative to GFP and PLTPM159E by ANOVA one-way followed by Tukey's test.
A: Ambroxol treatment scheme. Mice were treated with ambroxol or vehicle and underwent a sham operation (laparotomy) or intestinal manipulation (IM). Small bowel muscularis externa (ME) was isolated and analyzed 3h or 24h after surgery.
J Representative images of ALP, ARS and Van Gieson's staining of primary calvarial osteoblasts
B. Parkin fails to ubiquitinate the FKBP38 K271/273R mutant. HeLa cells were transfected with the indicated vectors and treated with CCCP (10 µM) for 30 h. MG132 (30 μM) was added 5 h after CCCP treatment. Lysates of cells were subjected to an IP-IB assay with the indicated antibodies and compared ubiquitination levels of WT, K271R, K273R, and K271/273R FLAG-FKBP38.
(A, B) Overexpression of wildtype full-length human tau (hTau, also termed tau441 or tau40 or tau2N4R) induced significant alterations of 9 transcription factors screened by using Transcription Factors Activation Profiling Plate Array II, in which 96 transcription factors (Appendix Table S1 and S2) were monitored. The empty vector was transfected as a control (Ctrl).
(E) The phosphorylation state of RZZ and SpindlyF was monitored by ProQ Diamond after SDS-PAGE separation of reactions. Data information: Two technical replicates for panels , E
A model describing the role of a unique function for PAX6D isoform in regulating retinal specification. retinal fate choice versus forebrain is controlled by PAX6D by regulating a set of neural genes and retinal genes.
(C) Min6 cells were incubated with medium containing low glucose (LG, 0.5 mM) and high glucose (HG, 25 mM) in the absence or presence of 28 μM GHTT (HG+GHTT) and then stained with MitoSOX or CellROX for an additional 30 min. Signal from CellROX (right) and MitoSOX (left) was quantified and re-plotted into histograms. Data information: Data from 3 experiments are presented as the mean ± SD. one-way ANOVA test were used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.
(C) Quantification of actin intensity at the poles of cells at 6 mins post anaphase onset, before furrow formation under different conditions as in (A). Actin fails to be cleared from the poles upon Aurora B kinase inhibition during mitotic exit and is stronger when both centralspindlin and Aurora B kinase activity are affected, while it is cleared upon RACGAP1 depletion. Data represented as mean±SD for treatments - siControl- 0.98±0.05, siRACGAP1 - 0.99±0.04, ZM - 1±0.039, siRACGAP1+ZM - 1±0.037. Ordinary one-way ANOVA with multiple comparison- siControl vs siRACGAP1 - n.s., p=0.896, siControl vs ZM - **p=0.0018, siControl vs siRACGAP1+ZM - ****p<0.0001 and ZM vs siRACGAP1+ZM - p=0.1528.
(I) The percentage of lever presses during the light on and light off periods for WT and HET mice was also different, because the WT group pressed the lever preferentially during the light period. Data were averaged from the 9th and 10th sessions. For statistical significance (*P<0.05; **P<0.01; ***P<0.001).
(D) PRR7 distribution across subcellular fractions (TOT = whole lysate, Syn = synaptosomes, Nuc = nuclei) isolated from rat hippocampal tissue. Fib (Fibrillarin), SNAP25 and PSD95 were used as nuclear, presynaptic and postsynaptic markers, respectively.
C) Bar plot showing the percentage of differentially spliced introns among all expressed introns. Major and minor introns are displayed separately. More than 30 % of minor introns are differentially spliced under FUS knockout, whereas only a small subset of the major introns is affected.
Immunofluorescence (IF) of NSMCE2 and SCP3 on isolated mouse spermatocytes. Threads of NSMCE2 can be detected on regions of weak SCP3 signal, indicative of asynapsis (arrowheads). Scale bar, 2.5 μm.
(A) Strategy to generate WASH‐knockout (WASH−/−) mice. The coding exons of mWASH gene were shown as white boxes. The target vector with exon3 of mWASH gene was flanked with two loxP sites (arrow) and one neomycin resistance gene. The primers used for genotyping were KO primers for deficient genotypes, loxP primers for loxP site identification, and Southern blot probe for floxed mWASH gene. KO, knockout, m, mouse.
C. Western blot of protein lysates from untreated, Ad-null, TFEB, and TFEBmt-treated myotubes with anti-caspase-3 antibody. No activated (cleaved) products are detected in any condition. α-Tubulin was used as a loading control.
Correlation analysis of mRNA expression for, (d) ISX and BRD4, in 157 lung cancer samples.
(A-B) Macroscopic evaluation (A) and tumor volume (mock, n = 7 biological replicates; OTUD1, n = 9 biological replicates; OTUD1C320S, n = 9 biological replicates; mean ± s.e.m., ***P < 0.001, two-tailed unpaired Student's t-test) (B) of mock, OTUD1 and OTUD1C320S expressing CT26 tumors in BALB/c mice.
Confocal microscopy reveals typical "class B" pattern of βarr1 recruitment for V2R and B2R as reflected by first the localization at the plasma membrane and subsequently, internalization in endosomal vesicles upon agonist-stimulation. HEK-293 cells expressing V2R/B2R and βarr1-mCherry were stimulated with agonist (AVP; 100nM and Bradykinin; 100nM) and the localization of βarr1 was visualized using confocal microscopy. Representative images from three independent experiments are shown here, and the scale bar is 10μm. Visual scoring of images from three independent experiments revealed agonist-induced βarr1 recruitment (i.e. membrane and endosomal localization) in approximately 77% of the cells for V2R (221 cells) and 75% of the cells for B2R (662 cells).
A | hFwe-Lose biomarker expression is more abundant in nasopharyngeal swab probes from older adults. hFwe-Lose expression was analyzed by RT-qPCR in 283 nasopharyngeal swab samples taken from patients with age between 1 and 96 years, taken at the very beginning of the disease (the earliest contact with physician, before the disease progression). The vertical axis represents relative hFwe-Lose expression normalized to the mean of non-hospitalized patients. Colors depict the outcome groups: non-hospitalized (gray, n = 85), hospitalized (blue, n = 177) and deceased (red, n = 21). The shape of data points reflects the cohorts: circles for the training cohort (n = 203) and triangles for the validation cohort (n = 80). The lines show the fitted curves of an asymptotic model with the same asymptotic value but different rate constants per group (see Materials and Methods). Due to the comparatively low number of deceased patients in the dataset (n = 21), the curve for this group reflects the asymptotic value. Hospitalized and deceased patients show a positive correlation of hFwe-Lose expression and age with a larger rate constant for the hospitalized patients. (R2= 0.65) The p-value (< 0.001) indicates that the blue curve (for hospitalized patients) grows faster with age, compared to the gray curve for non-hospitalized patients).
(F) Purified His6-AMPKα1/β1/γ1 fusion proteins (250 ng) were mixed with purified His6-tagged ULK1 (1 µg) or Bcl-XL (200 ng) proteins in 1% Triton X-100 lysis buffer containing protease inhibitors and subjected to immunoprecipitation with anti-ULK1 antibody. The resulting protein complexes and 10% of the input proteins were analyzed by immunoblotting with anti-His-Tag polyclonal antibody.
(f) IL-17A increases resistance to nitrogen starvation. Cells were first grown in YPD medium overnight and then switched to nitrogen-free SLAD medium in the presence of 10 ng ml−1 IL-17A. Viability, expressed as a percentage of colony-forming units at zero time, was measured over a 15-day period. Cells were exposed to 0.1 (black circle), 1 (black triangle) or 10 ng ml−1 (black square) IL-17A or drug vehicle (open circle) at the beginning of the cultures or, in the case of 1 ng ml−1 (open triangle), also added every two other days. Data are mean±s.d. P-values ranged from 0.05 to 0.001 for all samples treated with 10 ng IL-17A; P0.05, on days 3 and 5 for samples treated 1 ng IL-17A every two other days (one-way analysis of variance Bonferroni post-test) (n=3).
Uc.291 predicted binding region to interact with ACTL6A (nucleotide 1763-1912) by Global Score (score of 0.59). Dotted line define the CROSS score threshold [43].
B, Sequence alignment of Scaf1 protein in mouse and zebrafish. Structural and functional regions previously described in mouse are indicated in shaded grey boxes. Thick blue line indicates the proteolytic processing site in the mouse sequence.
A-B Pths increases the translation of RNAs involved in (A) mitochondrial function and (B) metabolic pathways, along with transcription, translation, signal transduction, immune responses as well as redox processes
USP36 promotes the binding of Nop58 to box C/D snoRNAs. H1299 cells transfected with Flag-Nop58 and V5-USP36 individually or together were assayed by RNA-IP with anti-Flag or control mouse IgG, followed by RT-qPCR detection of the indicated box C/D snoRNAs (A). Shown is one representative experiment of three independent experiments. Data were presented as mean ± SD, n=3 technical replicates. *P<0.05, compared to Nop58 alone (Student's t-test).
(B) Depicted are phosphopeptides that responded to NCS treatment in A-T cells. No significant elevation was observed in these phosphorylations in A-T cells following continuous inhibition of DNA-PK. Box plots depict 71 phosphopeptides measured in two independent biological replicates. The box indicates the range from first to third quartiles, and the central band represents the median. Upper and lower whiskers extend from the box to the maximum and minimum values which are not farther than 1.5 time the interquartile range (IQR).
A. Schematic drawing of the mdi genomic locus showing the CG3249 (mdi) transcript (gray box) and coding region (black box), and the location of the gfp insertion generated by CRISPR/ Cas9-mediated recombination with 2 guide RNAs (arrows). The resulting fusion protein is referred to as MDI-GFP. The mdi1 mutation is a 2.4 kb deletion that removes most of the mdi coding region.
A. Immunofluorescence of collagen matrix sections co-stained for cleaved collagen neo-epitope Col1 3/4C and DAPI (left panels). Second harmonic generation (SHG) images of collagen fibers within 3-dimensional collagen matrices at 15 µm and 45 µm below the cell surface (middle panels). Scale bar = 20 µm. Graphs indicate the mean ± SEM fibrillary collagen areas at 2.5 µm increments below the cell/collagen interface (n=5). SHG fibrillar collagen (red); cells (green).B, C. Grey level correlation matrix (GLCM) texture analysis of SHG correlation (n=6) and contrast (n=5). Mean ± SEM at each distance.
Osmotic minipumps containing saline or Ly6G antibody were implanted subcutaneously in Lyzs-Cre and p38γ/δLyzs-KO mice. These animals were fed a ND or MCD for 3 weeks. (A) Neutrophils and monocytes as a percentage of circulating leukocytes, measured in total blood.
C57BL/6J male mice were injected with asparaginase (ASNase) or PBS every three days for 2 weeks. Mice were exposed to 4˚C for 6 h before sacrifice for gene expression analysis.
Kaplan-Meier survival curves of wild-type (WT) an glp4(bn2) (E), strains fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1
Mice were immunized with MOG35-55 peptide and were monitored daily for clinical symptoms of EAE. Mice were treated intermittently with three times a week (s.c.) schedule with LU-001i (15 mg/kg), PRN1126 (40 mg/kg), PRN1126+ LU-001i (40 mg/kg+15 mg/kg), or vehicle starting from the start of the experiment. Data points represent the means of the clinical scores ± SEM of 12 mice pooled from two independent experiments. All data were statistically compared to the vehicle treated group.
(C) Experimental scheme of pulse-labelling of DNA fibers in wild-type cells (shWRNIP1WT) or WRNIP1-deficient cells (shWRNIP1). Cells were transfected with BRCA2 siRNA (siBRCA2), and 48 h thereafter labelled with IdU, then treated or not with 4 mM HU.(D) Representative IdU tract length distributions in shWRNIP1WT/siBRCA2 or shWRNIP1siBRCA2 cells treated or not with HU. Median tract lengths are given in parentheses. See Tables S1 and S2 for details on the data sets and statistical test. Representative DNA fiber images are reported. Scale bars, 10 µm. Western blot shows BRCA2 depletion in shWRNIP1WT and shWRNIP1 cells. The membrane was probed with an anti-BRCA2 or anti-WRNIP1. GAPDH was used as a loading control.
(L,M) Proportion of mice in the SHP099 and control groups with macroscopic (L) and microscopic (M) evidence of metastases; Fisher's exact test; ***P<0.001.
(C, D) Quantification of Ki67+/ERG+ cells in heart sections of mice kept on a ketogenic diet or control diet for four weeks or six weeks. Data are presented as mean ± SD. n≥3; *, p<0.05; **, p<0.01; ***, p<0.001 unpaired Student's t-test.
Ub and p62 accumulate in α- and β′-COP-depleted 293/GFP-LC3 cells. (A) 293/GFP-LC3 cells were treated with control or β′-COP siRNA for 48 h, then fixed and labeled with anti-p62 and anti-ubiquitin antibodies for colocalization with GFP-LC3.
A Exon-intron structures for human FBN1 and FBN2 genes. Conserved furin cut sites are indicated. Asprosin (Asp) is encoded by exons 65-66 of the FBN1 gene whereas a conserved Asp-like sequence is found in exons 64-65 of FBN2.
Chromosomal organization of the ena genes and primers used for transcript analysis (arrows).
G) Freshly isolated PBMC were placed in Boyden chambers towards media conditioned by cells silenced for TMED2 and incubated for 24 h. Migrating cells were then characterized and quantified (*): p=0.0149.
(C) NeoR‐ and NucNeoR‐transfected RCC1.24 cells were treated with 100 U/mL IFN‐γ for 48 h to induce MHC class II expression. Subsequently, the cells were washed and co‐cultured with the CD4 clone 20‐4/A4, which recognizes a peptide derived from NeoR on HLA‐DP3. GM‐CSF secretion by the T cells was measured 20 h later by ELISA. Both transfectants were recognized after IFN‐γ treatment, indicating that directing NeoR into the cell nucleus does not abrogate antigen presentation.
Oxygen consumption over a 90-hour period. Grays columns indicate dark phase (n = 6-8 mice per group). Average oxygen consumption specified for light phase, dark phase, and total (n = 6-8 animals per genotype).
D. Relationship between nucleotide and amino acid changes of the mESC-specific SATS isoforms as compared to corresponding common isoforms. Plus values represent nucleotide/amino acid expansions in the SATS isoforms, minus values represent nucleotide/amino acid deletions. The top and right boxplots are the quantile plots of nucleotide changes or amino acid changes, respectively. Black bars within the quantile box represent the median of changes.
(C) Dot blot analysis of telomere repeat or Alu repeat DNA from p53+/+ or p53-/- HCT116 cells treated with DMSO or etoposide (ETP) (as described in panel A), that were subject to ChIP with antibodies to IgG, p53, γH2AX, TRF2, or TRF1. Quantitation of three independent ChIP-assays for TRF1 and TRF2 is shown in the panel to the right. (
(C) ELISA of IL-1β in the supernatants of wild type (WT), NLRP3 knockout (KO) #1 or AIM2 KO#1 THP-1 cells left untreated (UT), or pretreated with LPS (500 ng/ml, 3 hrs) followed by ATP (5 mM, 6 hrs) stimulation, or stimulated with poly (dA:dT) (1mg/ml, 6 hrs), or infected with ZIKV (MOI=1, 36 hrs).
(F) Same analysis as in Figure 5G but old I90 cells transfected as in (A) were used. C, control; L, lactacystin, N, NH4Cl/Leu. Values are expressed as mean±s.e.m. *P0.05 versus nons control, or as indicated, n=3.
A. T6SS secretion assay of A. tumefaciens strains: wild type C58, ΔtssL, Δtap-1, and Δatu3641 harboring a pTrc200 vector (V) or derivatives pTap-1 (tap-1 expressed from pTrc200), or p3641 (atu3641 expressed from pTrc200).
Immunoblot analysis of IL-1β and active caspase-1 p20 in cell supernatants (Sup) and the indicated proteins in cell extracts (Cell ext) from WT and CYLD KO BMDMs, stimulated as in (A).
Supplementation of Pi to the nutrient-deficient plants (0.05 + Pi) significantly reduced hyper-accumulation of anthocyanin (C) triggered by GMVs. Data information: The boxplots show representative data from three independent experiments (n=12). Whiskers represent the min to max data range, the median is represented by the central horizontal line. The upper and lower limits of the box outline represent the first and third quartile. Different letters denote significantly different means at p < 0.05, Tukey's multiple comparison test within each group of the same DAT.
(C) Comparison of Ctcflos, Ucp1 and 45SrRNA transcript abundance in total RNA and poly A RNA fraction of primary differentiated brite adipocytes derived from 129S6 mice, assessed by qPCR, n=1.
(B) NO donors reduced Bcl-2 phosphorylation in HeLa cells, as analyzed by immunoblotting with anti-phospho-Bcl-2 antibody.
C: Recombinant MSP domains pulled down with peptides corresponding to the Phospho-FFAT motif of STARD3 (unphosphorylated; mono-phosphorylated on S209 or S213; bi-phosphorylated on S209 and S213), and with the control peptides were revealed by Coomassie blue staining. The recombinant proteins subjected to the assay are showed in the input fraction.
Intensity of nuclear YAP1 expression in liposarcoma patient samples. Immunoreactivity was assessed using a semi‑quantitative score (0, negative; 1, weak; 2, moderate; and 3, strong) defining the staining intensity in the positive control (hepatocellular carcinoma) as strong. Only tumors with at least moderate staining (semi‑quantitative score ≥2) and ≥30% YAP positive cells were considered positive for the purposes of the study.
c. Relative mRNA levels of PRSS35 in lysates from normal skin (WT, n=4 mice), inflamed skin (InvEE, n=4 mice), wounds (d14pw, n=4 mice) and wound-induced papillomas (Pap, n=5 mice). (* p=0.0159; Mann-Whitney test). Data represent means of three technical replicates ± S.E.M.
(C) Coomassie-stained SDS-PAGE gels showing GST-pulldown experiments between IFT88/52N-GST complex immobilized on GSH beads and various combinations of IFT-B2 proteins. The left gel shows the IFT-B2 input mixtures, the right gel shows the bound material after washing and elution from the beads. A pentameric IFT-B2 complex (IFT80/57/54/38/20) is efficiently pulled down by IFT88/52N-GST, but not by empty beads (compare lanes 1 and 2). Omission of IFT54/20 (lane 4), or IFT80 (lane 5) does not influence the binding of any of the other components, but a lack of IFT57/38 in the mixture abolishes detectable pull-downs of IFT54/20 and IFT80 (lane 4), indicating that IFT57/38 is the direct interaction partner of IFT88/52N. Indeed, IFT57/38 alone (lane 7), but not IFT54/20 (lane 6) or IFT80 (lane 8), is sufficient to be pulled down in this assay. Contaminating bands from the IFT88/52N sample are marked with asterisks.
(C, D) Bristles are pigmented and properly shaped when flies carry hs-GAL4 without a target gene (C) but are often white, bent, and shortened when hs-GAL4 drives expression of UAS-Foxn1 (D). Flies in panels C and D were raised at 25°C. Arrows denote examples of white bristles. Data information: Representative phenotypes are shown in all panels. Scale bars, 100 μm.