EMBO/sd-character-level-ner huggingface dataset:
B Illustration depicts generation of the animal model with SARS-CoV-2 spike RBD-induced intestinal inflammation. Mice were fasted for 24 hours before acetic acid clysis. 16 hours after acid challenge, mice were given Control-Fc or Spike RBD-Fc intraperitoneally. Six hours later, TRITC-dextran or Evans Blue dye was injected intravenously for evaluation of permeability.
E) IHC on selected showing TF staining in G1 and G3 areas from human PDACs. The areas in the insets are shown at 4x higher magnification in the panels below. Data from one representative patient out of nine tested are shown.
(H) Quantification of pH3 positive cardiomyocytes and cardiomyocyte (CM) cytokinesis in mice 7 days after cryoinjury; *p=0.0264, ***p=0.0006.
(E) A cumulative distribution in control and hnRNPA1 depleted cells of the stability levels for mRNA transcripts with 3' UTR hnRNPA1 CLIP binding (Huelga et al., 2012). Transfection of tRFTyrGUA led to a significant right-shift in the expression levels of 3' UTR bound hnRNPA1 transcripts. Statistical significance was measured using the Kolmogorov-Smirnov test. (F) Cumulative distribution as in (E). Transfection of locked nucleic acid against tRFTyrGUA and treatment with 200µM H2O2 led to a significant left-shift in mRNA stability of 3'UTR bound hnRNPA1 transcripts. Statistical significance was assessed using the Kolmogorov-Smirnov test.
(H) Representative pictures of cardiac explants like in (G), stained for pH3 in addition. The quantification is shown on the right. Scale bar: 50µm. *p=0.0215.
Analysis of hippocampal neurons (DIV14) immunostained for ChgB as DCV marker and ß3-tubulin as morphological marker. ChgB puncta per μm neurite.
H. Boxplots showing H3K4me1 and H3K27ac content of BAZ2A-bound regions and loci not bound by BAZ2A at far-cis contacts in ESC+2i. Data from regions with lowest 10% and top 10% contact strength are shown. Box plots depict the minimum and maximum values. The mean is represented by a horizontal line within the boxes.
A. Analysis of the NP137 antibody (anti-netrin-1) epitope across netrin family members.
A comparative study of INCISOR's performance (red bars) in predicting patients drug response (TCGA) compared to ISLE and CFE based approaches (other colors). The Area under the curve (Y-axis) displays the predictive performance of different methods for 22 FDA approved drugs in TCGA. Predictions of CFE (cancer functional events) identified by Iorio et al. are displayed separately for CFEs inferred from mutation, methylation, and SCNA data.
(G) RZZ and RZZS complexes were reconstituted with the ZwilchE422A/D426A mutant and tested for filamentation at 20ºC in presence of MPS1 or upon mildly heating to 30ºC. Data information: Scale bars in panels G = 5 µm. Two technical replicates for panels G were performed.
F Representative FACS plots of MitoT on CD45+CD3+ T cells at increasing amounts of UC-MSC.
D, In ALN-induced neurons, confocal analysis is demonstrating a co-localization of GFP and glutamic acid decarboxylase (Gad65/67), a marker specific for GABAergic neurons. E, Quantification of GAD6567+/GFP+ cells with neuronal morphology shows that the majority of ALN-induced neurons are colocalizing with this GABAergic marker both in the AAV-dCAS as well as in the dCAM setting. Data information: Scale bars indicate 20 µm. Error bars represent mean ± SD. n= 6-8 mice (e) per condition. Tukey's multiple comparisons test * P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.
D. NLK deficiency reduces YAP S128 phosphorylation. Two CRISPR/CAS9 gRNA plasmids targeting different sites of NLK were transfected into HEK293A. WT cells and two pools of NLK CRISPR/CAS9 transfected cells were treated with 0.2 M sorbitol for the indicated time points. Data are presented as mean ± SEM. *p < 0.05 (two tailed student's t-test, n = 4).
Immunofluorescent staining of CD3, CD8 and CD45 (red) counterstained with DAPI for DNA (blue) using control or shVgll4 LLC tumors from C57BL/6 mice. Statistical analysis of the percentage of CD3, CD8 and CD45 positive cells in the tumors is shown in the right panel respectively. n=3 tumors for each group
Genetic design of the LacZ reporter construct whose expression is activated by the inducer IPTG.
RT-PCR of major (U2-type) AT-AC introns in SYCP2 (intron 5) and TAF2 (intron 1), and minor (U12-type) AT-AC intron in IPO5 (intron 21) on RNA extracted from HeLaEGFP-AID-CENATAC cells depleted of GAPDH or CENATAC. Schematic representations of unspliced/spliced PCR products are depicted on the right.
(E) Blockade of the fission machinery by d.n.DRP1 or Bnip3 inhibition by RNAi reduces FoxO3‐mediated autophagosome formation. Animals were transfected with YFP‐LC3, c.a.FoxO3 in presence or absence of d.n.DRP1 or shRNAs against Bnip3. Twelve days later, muscles were collected and analysed for fluorescent vesicles formation (*P0.001) n=450.
Strategy for computing interaction scores for each tumor. A score is computed as the sum of the products of all ligands and matching receptors of the recurring interaction network. These are compared to the average score obtained when randomizing the real interaction network in a manner that preserves the number of outgoing and incoming interactions of each ligand and receptor (Scorerand). The ratio of the real and randomized scores constitutes a network score.
(I) Pearson correlation analysis of ISLR and CTGF (P < 0.001; R = 0.69), ISLR and FSTL1 (P < 0.001; R = 0.81), as well as ISLR and CYR61 (P < 0.001; R = 0.65) in human colorectal cancer based on TCGA RNA-seq database.
A Flow chart of human tissue homogenization and subsequent fractionation into cytosolic (C) and mitochondria-containing heavy membrane (HM) fraction. With authorization by the local ethics committee, human tissue samples were obtained from the Institute of Pathology, University Hospitals of Basel.
L6 myoblasts were transfected with the genetic cytosolic Ca2+ sensor GCaMP6s. Cells were also transfected with non-targeted siRNA (Control) or siRNA directed at endogenous STIM1 (siSTIM1). Some cells with endogenous STIM1 knockdown were also transfected with full-length wild type (WT) or mutant (S257A, S257E or L251S) STIM1-mRuby3. Ca2+ levels over time (fold of 0 mM Ca2+ + EGTA basal) and (C) quantification of SOCE in in L6 myoblasts incubated in buffer containing 1 or 0 mM Ca2+ and treated with 2 µM thapsigargin during the indicated times.
C. BASCs emerge at early postnatal stages and contribute to epithelial turnover throughout life. β-galactosidase staining of lung sections derived from BASC v-race animals collected at indicated time points. Arrow highlights β-gal+ cell at P6. Scale bar: 200 µm.
Schematic showing the generation of a translocation intermediate with SecA dN20::H6 (purple) recruited to SecYEG liposomes containing Ni-modified lipids (cyan circles). Addition of imidazole dissociates SecA dN20::H6, which can then be replaced by WT or mutant SecA (tan).
A-C Immunofluorescence against HSP90 in mouse brains with established metastases. (A) HSP90 positive structures in areas not affected by the metastasis includes the medial habenula, where neurons co-localize with the chaperone. Scale bars: 100 µm (low magnification), 50 µm (medial habenula nucleus), 12 µm (high magnification neurons). (B) Established metastases from different primary origins and oncogenomic profiles stained with HSP90. Dotted lines delineate the metastasis (cc: cancer cells). Scale bars: 75 µm. (C) Iba1 colocalizes with HSP90 within areas affected by metastases. BB: bisbenzamide. Scale bar: 75 µm (low magnification), 12 µm (high magnification).
Refined atomic model of the TRAPPIII complex shown as it likely interacts with membranes. The arrow points to the location of the unmodeled conserved region.
A and B. Cytoplasmic (A) or mitochondrial (B) Ca2+ flux was measured in N2a-IP3R3 cells treated with PRE-084 (5 µM) or NE-100 (5 µM) for 1 h prior to fluorescent imaging. Cytoplasmic and mitochondrialCa2+ flux were detected by fluo-4 and Case12-mito, respectively. The fluorescent intensity was normalized by the resting state at 0 s, and plotted as mean ± SD. n = 10 each. **: p < 0.01, *: p < 0.05. Two-way ANOVA with subsequent post hoc Tukey's test.
SASP heatmap: Pearson correlation clustered heatmap showing a curated list of known SASP genes (top panel) or a selection of secreted SASP proteins (bottom panel) in young (3 months) and old (20 months) mouse CMs (n=5 per age group). The colour intensity represents column Z-score, where red indicates highly and blue lowly expressed.
(h) Δ133p53α rescues STUB1 knockdown-induced senescence. MRC-5 fibroblasts were transfected with STUB1 siRNA (no. 1) as in e. At the next day after the second transfection (on day 5), the cells were transduced with a lentiviral vector driving Δ133p53α or its vector control. At 5 days after the lentiviral transduction, the cells were stained for SA-β-Gal activity. Representative pictures (left) and quantitative data (right) are shown. Percentages of SA-β-Gal-positive cells were from triplicate experiments (mean±s.d.). **P0.001 (Student's t-test).
A-H. SEM images of an opened embryo (A), the ExE cavity wall (B) where blood islands are indicated by white arrow, the allantois surface (C-C'), an opened allantois (D) and its zooms (E-E') where filaments are indicated by white arrows, the epiblast-derived side of the amnion (F), the mesoderm-derived side of the amnion (G) and its zoom (G').
C Hemizygous K18-hACE2 mice were treated intranasally with 20 µg of NM1251 (n = 15) or NM1267 (n = 12) seven hours prior to infection with 3*103 PFU SARS-CoV-2 B.1. survival were monitored for 14 days. , ****P < 0.0001, by log-rank test
(a) GFP-LC3 dots in S2 cells expressing GFP-LC3 alone or PGRP-LE and GFP-LC3, treated for 2 h with TCT (100 nM), highly purified DAP-type PGN from L. plantarum (DAP; 100 μg/ml) or lysine-type PGN from S. epidermidis (Lys).
Similarity plot of the near full-length genome sequence (A) and S gene sequence (B) of Pangolin-CoV to sequences of 2019-nCoV_WIV02, Bat-CoV RaTG13, Bat-CoV ZC45 and Bat-CoV ZXC21. While Pangolin-CoV has a high sequence identity to 2019-nCoV and Bat-CoV-RaTG13 in most regions of the S gene, it is more similar to Bat SARSr-CoV ZXC21 and Bat SARSr-CoV ZC45 at the 5′ end (B). More importantly, Pangolin-CoV is highly similar to 2019-nCoV in the functional RBD region of the S protein, with only one amino difference (insert in B). Because of the presence of genetic recombination, there is a discrepancy in cluster formation among the outcomes of phylogenetic analyses of different regions of the S gene (C).
(E) Venn diagram showing overlapping between DVL3-bound genes and DVL3 transcriptional targets in MCF7 cells. A total of 3% of differentially expressed genes identified by RNA-seq comparing NTC and shB DVL3 were also DVL3 direct targets identified by ChIP-seq. From these, 87.5% were up-regulated and 12.5% down-regulated. A total of 5.6% of differentially expressed genes identified by RNA-seq comparing EV and DVL3-WT were also DVL3 direct targets identified by ChIP-seq. From these, 56.5% were up-regulated and 43.5% down-regulated.
Clustering of metabolome data in patients and controls; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites in blood of PEO (C) Data information: Colours in VIP score and volcano plots indicate the same most relevant and/or significantly changed metabolites among all patients groups. C3, component 3; CDCA, chenodeoxycholic acid; GABA, γ-aminobutyric acid; OH-Kyn, 3-hydroxy-DL-kynurenine
(f) NRK cells stably expressing LAMP1-Cherry; clathrin-GFP were starved for 4 h and time-lapse images were acquired by spinning-disc microscopy. Scale bar, 500 nm. The white arrows indicate a clathrin punctum moving along a LAMP1-positive structure.
CV protrusions (arrowheads) and vascular loops (asterisks) were observed in zebrafish at 35 hpf. The images within the dotted rectangles are magnified in the right panels. A, anterior; P, posterior; CA, caudal artery; CV, caudal vein. Scale bars, 40 μm. Quantification of the length of the CV protrusions in (G) presented graphically by measuring them in equivalent fields of view (within five somites).
A, Immunoblot analysis of protein lysates from HeLa cells treated with EBSS for 1 h and then incubated with complete medium (refeed) for the indicated times. Samples were run under non-reducing conditions. B, Quantification of immunoblot data shown in (A). Data are presented as mean ± SD using one-way ANOVA (*)p<0.05, and (***)p<0.001 from three independent experiments. C, Quantification of immunoblot data shown in (A). Data are presented as mean ± SD using one-way ANOVA (*)p<0.05, and (***)p<0.001 from three independent experiments.
c, An ML1-/- skin fibroblast cell showed autofluorescence in LAMP1-positive compartments. Autofluorescence (green) was detected within a range of excitation wavelengths (shown with excitation at 480 nm). No significant autofluorescence was observed for a ML1+/+ cell. Lysosomes were stained with a LAMP1 antibody (red). Differential interference contrast (DIC) images are shown for comparison.
(A) Gene expression analysis of WT and Clec12a−/− BMDMs infected with Listeria for the indicated times. Heatmap shows log2 (fold change) relative to uninfected WT BMDMs at indicated time points. Shown are the top ten most-significant upregulated and downregulated genes in Clec12a−/− BMDMs compared to WT BMDMs.
Re-introduction of Cideb rescues SREBP processing in Cideb-/- liver. WT and Cideb-/- mice were injected with AAV-GFP or AAV-Cideb, and sacrificed for IB with the indicated antibodies 20 days after the injection.
(F) Patient-derived and control B cells were cultivated for 24 hours and TNF was determined by ELISA. Data are presented as mean ± SD of 3 individual experiments performed in two technical replicates; *, P = 0.028; unpaired t-test.
A Recombinant Gadd45a protein and its G39A mutant were added to the histones-oligo DNA mixture. The mixtures were separated by 4% non-denaturing PAGE and stained with ethidium bromide (EB). The oligo DNA probes were amplified from the Oct4 promoter.
A. Jurkat cells were treated with 100 µg/ml CHX for 0, 0.5, 1.5, 4, 8, 12 or 24 hours. Protein degradation was monitored by Western blotting and stabilities of several short-lived endogenous proteins were confirmed using antibodies (including lamin B, securin, β-catenin, GCIP interacting protein p29) and compared to stable proteins (such as GAPDH and actin). Proteoform-specific bands were used to calculate protein half-lives which were in a good agreement with turnover times obtained from pSILAC
MECP2-silenced or control hTERT-RPE-1 cells were starved for 48 h before treatment with 200 nM and 500 nM SAG for 24 h. Cells were stained with anti-Smo and anti-acetylated α-tubulin antibodies. The percentages of Smo-positive cilia were calculated. The graph shows the average of three independent experiments (mean ± S.E., *** p<0.001, by two-way ANOVA followed by Bonferroni post hoc test). Two-way ANOVA demonstrated a significant silencing effect (F (1, 12) = 160; p<0.0001), a significant SAG treatment (F (2, 12) = 259.4; p<0.0001) and a significant interaction (F (2, 12) = 36.85; p<0.0001).
A. Fear-conditioning test. Freezing (%) was monitored in the cued (top) and contextual (bottom) tests before (pre) and after (post) administration of clozapine (left) or haloperidol (right). Data are presented as means ± S.E.M. (n = 7-9/group). *, p < 0.05; ***, p < 0.001 (Tukey test); #, p < 0.05 (t-test, KO/saline vs. KO/clozapine).
Mutations in the α-helices of hinge 2 prevent 30S binding while the Y592A/Y593A (C-terminus) and L353Y (A-loop in NBSII) exchanges do not influence ribosome binding.
(E) mRNA relative expression level of Il-6, Il-12 and Il-23 from XBP1fl/flIRE1fl/fl, XBP1ΔDC IRE1truncDC and XBP1ΔDC BMDCs infected with Pru parasites for 16 h compared to non-infected (NI) conditions. Results are normalized to the housekeeping gene Gapdh. Two-way ANOVA Tukey's multiple comparisons, ns: p>0.05; *: p<0.05; **: p<0.01; ***: p<0.001; ****: p<0.0001; mean ± S.E.M (n=3-5 mice pooled from 2 independent experiments).
(a) Quantification of numbers of hyperplastic lesions/per lung (mean values±s.e.m.) in KRas;Atg5fl/+ and KRas;Atg5fl/fl mice2 weeks after AdCre inhalation treated either with an isotype control Ab or a depleting anti-CD25 Ab. n=4 per group. **P0.01 (χ2-test assessing the genotype effect in a generalized linear model with log link). (b) Histological lung sections of KRas;Atg5fl/+ and KRas;Atg5fl/fl littermate mice treated with an isotype control Ab or anti-CD25-immunodepleting Abs. Mice were killed 2 weeks after AdCre inhalation and their lungs were processed for histopathology. Representative lung images (haematoxylin and eosin (HE) staining) are shown for each genotype and treatment. Scale bars, 2 mm.
Western blot analysis of unsynchronized HeLa-H2B/tub cells was carried out to monitor expression of p(S10)-H3, total H3 and TIAR in control and TIAR-depleted cells (mean ± SD; n = 3). Data information: Statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.
Longitudinal associations between CSF T-tau, Ng and NFL and other AD traits. Data are estimates (-coefficients) from linear mixed effects models, with 95 % confidence intervals. The estimates are the effect of time plus the biomarker by time interactions, capturing the longitudinal effects of the biomarkers. For each model, the "average" effect of time is also shown for comparison. Effects were significant (*), meaning that biomarker levels affected the slopes of the outcome, for FDG-PET: T-tau (p=.00038) and Ng (p=.0019) in A-positive. Biomarkers and outcomes were standardized to z-scores. Note also that the range of the y-axes differs for the different outcomes, for visualization purposes. Models were adjusted for age and sex, and education (for cognitive measures), and intracranial volume (for MRI measures). Aβ42 and T-tau were measured using the the INNOBIA AlzBio3 kit (Fujirebio, Ghent, Belgium), Ng was measured using an in-house immunoassay for Ng (Portelius et al, 2015) and NFL was measured using the NF-light® ELISA kit (Uman Diagnostics, Umeå, Sweden).
(C, D) Quantification (C) and images (D) of hACE2 protein expression level by Western blot from the lungs of the same mice as in panels A and B, presented in the same order.
(E) Relative expression of in vitro transcribed CGG-nLuc reporter in HEK293T cells pre-treated with DMSO and SRPIN340. Error bars represent mean +/- SD (n=9 biological replicates). Data information: Statistical analysis was performed using Student's t test with Welch's correction. ∗p < 0.05; ∗∗p < 0.01
(D) Representative confocal micrographs (as maximum intensity projections) of wild-type K562 cells and indicated deletion isolates expressing tf-NBR1. Selected regions (white box) of micrographs are shown as single and merged channels from fluorescence microscopy. Red fluorescent protein (RFP), magenta; Green fluorescent protein (GFP), green; Hoechst, blue. Scale bars: large panels, 5 µm; small panels, 1 µm. All images scaled equally.
G. P493-6 cells were co-transfected with the indicated reporter constructs and Renilla luciferase plasmid. Twenty-four hours after trasfection, cells were treated with doxycycline for 0 hour and 12 hours respectively. Then reporter activity was measured and plotted after normalizing with respect to Renilla luciferase activity. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).
B S1 and S3 alleles, by virtue of limited geometries (modified from Chattopadhyay et al, 2005), may have access to distinct subsets of the full range of biological activities of WT PrP, which has access to interchangeable component 1, 2 and 3 geometries.
G Representative images of ALP, ARS and Van Gieson's staining of MSCs obtained from Sp7-Cre;Usp34f/f and littermate control mice
(d) Left panel: Flow cytometry characterization of BOECs for endothelial, leukocyte and progenitor cell markers (grey - isotype control; red/blue/green/purple - cell lineage marker staining). HUVEC and monocytic THP-1 cells were used as positive controls for endothelial and leukocytic markers respectively. Right panel: Percentages of positively expressing cells. Sample sizes are n = 4-6 healthy, n = 2-7 NAFLD.
(B) Mononuclear cells were isolated on day 30 of animals shown in (A) from the CNS of PBS- and DTX-treated CD11c-DTR/GFP→C57BL/6 that had been transferred with 2d2.tdRFP Th17. Flow cytometry was performed on surface stained cell samples. Cells were pre-gated on lymphocyte cells (FSC SSC gate) and PI-negative; pooled data of three animals; representative of two independent experiments.
(B) Chromatin transitions within differential active states between NBCs and CLL. Heatmap representation of the amount of chromatin (log2 Mb+1) transitioning from a particular state in NBC (rows) to CLL (columns). Transitions were considered for all recurrent active chromatin state regions (states 1, 8 ,9 and 11) present in a minimum of 3 samples even if the consensus state was not an active state. Accordingly, the matrix includes transitions between non-active states at low frequencies.
A. In Brachyury (T)-Cre; mTmG embryos, mesoderm-derived cells express membrane eGFP (mG, green) and the other cells membrane tdTomato (mT, grey).
(E) Level of eIF-2a and its phosphorylated form, estimated by western blot using specific antibodies, in siCon or siHuR treated and starved Huh7 cell extracts. Western blot data of HuR confirm reduction of this protein upon siRNA treatment. CAT-1 and Aldolase mRNA levels were estimated by real time quantification and normalized against GAPDH level. Values of siCon treated samples were taken as unit (mean+/- s.e.m., n=3). In the right panel the relative quantity of phosphorylated eIF-2a measured by densitometry were plotted. Levels of p38 and phosphor-p38 levels in siCon and siHuR treated Starved Huh7 cells were detected by western blot.
Immunoblot analysis of phosphorylated ULK1 (Ser 757), total ULK1, and actin in KRIT1 KO+KRIT1, and KRIT1 KO MEFs. Where indicated, cells were treated with 100 nM Torin1 for 4 h. The results are representative of three independent experiments.
Bar plots showing relative occurrence of differential-splicing events in IMR90 undergoing senescence (left), in HMGB1-knockdown IMR90 (middle) or in HMGB1-bound mRNAs (right). The number of bound mRNAs (N) analyzed is indicated below each bar.   Venn diagram showing differential-splicing events shared between conditions from panel F.
During cellular stress, Nox4 at the MAM augments the level of Akt activation secondary to redox inhibition of PP2a. Activated Akt in turn phosphorylates InsP3R and leads to an inhibition of calcium flux from ER to mitochondria. Mitochondrial calcium is maintained at a low level, the mitochondrial membrane potential (ΔΨm) is preserved, and cells remain viable. When Nox4 is deficient (bottom panel), high PP2a activity dephosphorylates Akt and leads to a reduced level of InsP3R phosphorylation. This removes the restraint on calcium transfer from ER to mitochondria resulting in increased mitochondrial calcium levels, triggering of the mPT, loss of ΔΨm and eventual cell death.
F. Western blot analyses of cortical and hippocampal lysates from APP/PS1mice for APP and sAPP expressions.
(A-D) Changes in mRNA transcript levels of a series of adhesion molecules (A), chemokines (B, C) and cytokine receptors (D) in injured retinas compared with contralateral noninjured retinas, assessed 1 day after GT intoxication. n = 6 per group.
F Violin plots of selected genes showing the comparison between control and MECP2-KO neurons from the single-cell analyses (log2(expression) values) that overlapped with the results obtained via RT-PCR array.
(C,D) In the SS of adult rhesus monkey, COX6A2 immunoreactivity is present exclusively in PV+ cells (n animals=1, 1-year-old, n sections=6). White arrowheads indicate PV/Cox6a2 double positive cells.
(E) Western blot of whole cells lysates stained with an α-HA antibody. Residues exchanged with BrEtY are indicated in the upper row, mutations at PTH1R are indicated on the left side. The red arrows indicate the two most prominent signals. Red squares indicate signals that vanish upon removal of specific Cys residues in PTH1R.