EMBO/sd-character-level-ner huggingface dataset:
A: Cartoon representation of SARS-CoV-2 N-CTD. Ribbon representation of SARS-CoV-2 N-CTD showing the separated monomer and dimer. One monomer is coloured in pink, and the other is coloured in yellow. B: Rotation of (A) along the x-axis by 90° to show the top view.
Mean tumor-to-background ratio (TBR) for [18F]FDG (left) and for [68Ga]Pentixafor (right) in MM.1S and OPM-2 xenograft-bearing NOD SCID mice. Shown is the mean ± SEM, n = 8 tumors (4 mice); *P = 0.0111 for [18F]FDG and *P = 0.0113 for [68Ga]Pentixafor (Student's t-test). One-way ANOVA revealed significant differences between the groups; P < 0.0001 (not graphically shown).
(B) Real-time PCR analysis of RNA expression of NAD-synthesizing enzymes in the 6 months old WT and p32cKO hearts. Error bars are presented as mean ± SD. Student's t-test was performed on WT mice vs p32cKO mice (n = 6), ***p < 0.005, *p < 0.05. The right panel shows the NAD synthesis pathway and mRNA expression levels are indicated by red arrows. NAM: nicotinamide, NA: nicotinic acid, QA: quinolic acid, NMN: nicotinamide mononucleotide.
(C) Delay in neuronal migration by CAMDI deletion. Coronal sections through the somatosensory cortex of P21 WT and CAMDI-KO mice were analyzed following in utero electroporation of EGFP plasmid at E14.5. Scale bar, 100 μm.(D) Quantification of the number of EGFP-positive neurons. Note the abnormal distribution of neurons in lower cortical layers of CAMDI-KO mice. n = 3 for WT mice (546 cells), n = 4 for KO mice (680 cells). *, p<0.05, ***, p<0.001. Two-way ANOVA followed by Scheffe's post-hoc test. Data are presented as mean ± SEM.
(f) Expression of Beclin 1 in MCF7 cells restores the survival advantage conferred by p53 depletion. MCF7 cells that carry a tetracycline-repressible Beclin 1 expression construct were cultured to avoid Beclin 1 expression or to induce it, transfected with a control siRNA or a p53-specific siRNA, subjected to metabolic stress, and finally stained with DiOC6(3)/PI.
(I) FAM134B WT or knockout (KO) U2OS cells were treated with CAMK2 activator Ionomycin (Iono), EB1089 or inhibitor KN93 for 24 hours, Western-blot was performed to analyze the proteins as indicated.
C Quantitative RT-PCR of the samples from (B). For RSRC2 and SRSF2 the ratio of NMD isoform to canonical isoform was calculated. Data points and means are plotted as log2 fold change (log2FC) (n=3).
(F) Time course of H3.1-EGFP release from its mitochondrial tether after co-transfection with mCherry-IPO4
(A) Asynchronously growing HeLa CCL2 cells were immunostained with the indicated antibodies, and early telophase cells were observed using a super-resolution confocal laser scanning microscope (LSM-880 with Airyscan) (left panel). Scale bars, 10 μm. Linear signal profiles of β-catenin/Plk1/β-catenin p-S60/F-actin in the contractile ring region from the XY plane of immunostained early telophase cells (right panel). All immunofluorescence images and linear signal profiles show representative data of more than 50 telophase cells obtained from three independent experiments. The value of the relative neck thickness is shown in the lower left corner of the merged images (A).
C | An age- and sex-adjusted statistical model suggests hypertension, diabetes and chronic kidney disease to have the highest impact on hFwe-Lose expression. A linear regression model was created to account the patient's age upon analysis of hFwe-Lose expression in relation to comorbidity status. "Other comorbidity" refers to a cumulative effect of diseases or conditions, not directly associated with COVID-19 (cancer, Down syndrome, solid organ transplant, sickle cell disease, bone marrow transplant). The plot illustrates the effect of selected comorbidities (horizontal axis) on relative hFwe-Lose expression (vertical axis). The p-values of the respective linear models for all significant comorbidities are presented on the plot. The error bars represent the 95% confidence interval.
(G) Genotypic ratio of Bbs4+/+, Bbs4GT/+ or Bbs4KO/+ (Het), and Bbs4GT/GT (GT) or Bbs4KO/KO (KO) offspring at weaning from mating of Bbs4GT/+ (n=145 pups) or Bbs4+/KO (n=168 pups) parents. Binomial test was used for statistical comparison of the observed distribution to the expected Mendelian ratio.
(G) Sera from wild-type (WT) BKS and Leprdb/db mice, aged 4, 8, and 18 weeks, B6 mice, fed with a normal diet (ND) and a high fat diet (HFD) for 4 weeks, and humans, healthy volunteers and diabetic patients (T2D), were quantified for Pdia4 level using an anti-Pdia4 ELISA kit. Data information: Data from 3 experiments more are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.
B RT-PCR analyses of indicated RNAs in control (WT), ∆44 and in GS∆44 myocytes collected after 9 days upon the induction of differentiation. GAPDH was used as control. Representative results are shown (n=3).
Wild type (WT) and TRIM21 knockout (KO) mice were infected with 0.5 x 10^5 FFU LCMV clone 13 (6 mice per group), and either received anti-N mAb KL53 (+) or control (-) intraperitoneally on days 1 and 3pi. Two mice were uninfected (UI). A) Weights were monitored throughout infection, with final day 8 weights of individual mice presented separately.
IL-1β (C) and TNF (D) ELISA of Gata6-WT and Gata6-KOmye pMɸ stimulated for 24 h with the indicated LPS concentrations. n=3, two-way ANOVA analysis with Sidak's multiple comparison post-test.
(A) Pex11-GFP pexophagy assayed by microscopy in pex3Δ cells and pex3Δatg1Δ cells transformed with plasmids containing either WT PEX3 or pex3‐177, or with an empty plasmid ycplac111. Cells were grown in glucose, transferred to oleate medium for 18 h and switched to SD‐N medium for 22 h.
(F) GFP-ATG8a cleavage immunoblot for given treatments. The ratio of free GFP to loading control, normalized to the 16h pre-treated sample (set to 1) is provided below each band.
G, WT and SNX10 KO Caco-2 cells were transfected with Ad-vector or Ad-SNX10, followed by treatment with or without OMVs (100 μg/mL) for 24h. Total cell lysates were subjected to immunoblots with the indicated antibodies (n = 3 independent experiments).
Neutrophil - T cell co-cultures treated with vehicle (T + Ne), 10µm of the MMP inhibitor GM6001 (T + Ne + MMPi) T cell proliferation after three days of indicated co-culture conditions. T cell proliferation index is numbers of proliferated T cells under indicated condition relative to the number of proliferated T cells when cultured alone.
cTAZ effectively repressed antiviral activity of IFN-α. Transfection and infection were performed Top: GFP intensity of cell lysates was measured by a fluorometer. Bottom: viral GFP and ectopic cTAZ protein levels were detected by IB.
Structure-based flow chart for the virtual screening of small molecules interacting with the LARP6-RRM domain.
(B) Immunoblotting analysis of Ub in XO8 GSCs and XO8 GSC-derived cells in the course of differentiation (P1-P7). (C) Similar to (B) except that XO6 GSCs were used.
, Effect of Bumetanide on Col1a2 and Col3a1 mRNA expression in MRC-5 cells. GAPDH was used as housekeeping gene. *P < 0.05 vs vehicle, #P < 0.05 vs Control (two-way ANOVA); n = 6 for all groups.
H. PBL34 rescues pbl34/35/36 triple mutant ROS burst in response to 3-OH-C10:0. Treatment was same as in (E). pPBL34:PBL34-HA was introduced to pbl34/35/36 triple mutant, and the homozygous transgenic line was used for ROS burst assays. Values are means ± SD (n=6 biological replicates). (ANOVA, P <0.01).
The effect of Atg14L localization on its function. (a) Atg14L knockout mouse ES cells were transfected with GFP, GFP-Atg14L, GFP-Atg14L4C4A, or GFP-ER-Atg14L4C4A of the pCAG vector and subjected to starvation. The cells were fixed and immunostained with anti-Atg16L or anti-LC3 antibodies. (b and c) The number of Atg16L-positive puncta (b) and LC3-positive puncta (c) per cell was counted in at least 10 GFP-positive cells, and mean ± SD values are presented. Bars, 10 µm.
(G) ChIP-Seq genome-browser views showing co-localization of uSTAT5 binding with CTCF.
L) Scheme represents overall hypothesis: feedback loop between DDR, mTORC1 and mitochondrial biogenesis stabilize cellular senescence and are key factors for the development of the senescence-associated pro-oxidant and pro-inflammatory phenotypes.
Time-lapse images of agarose-embedded cells were taken at RT with supply of fresh PM Glc+ura medium throughout one budding cycle. Only (F) shows fixed cells immunostained for Sed5p. All cells produced the β'-COPVN•Dsl3pVC BiFC pair. Most strains contained plasmids encoding different organelle markers as indicated below. BiFC signals are pseudocolored green, organelle markers are pseudocolored red. Scale bar 5 µm.B. Sec13pRFP, ER exit sites marker
Total number of WT, heterozygous and homozygous embryos (E3.5 and slow (R749H) RNAPII mutation or repaired with the WT sequence (silent oligo). Repair oligos and the stage that embryos/mice were analyzed are indicated.
regular sucrose diet (RS) or high sucrose diet (HS) samples were subjected to immunoblotting and TDP-43 protein levels were examined.
(A) NPM1 expression in CD34+Lin- cells from myelodysplastic syndrome (MDS) patients compared to healthy volunteers (n = 29).
A Analysis of STAT2 nuclear translocation by immunofluorescence. Bone marrow derived macrophages (BMDMs) of wild type (WT), Stat1Y701F (YF), Stat1-/- (S1), Stat2-/- (S2) and IRF9-/- (IRF9) mice were seeded on cover slips and stimulated with 250 IU/mL of IFNβ for 30 min or 24 h. The cells were fixed and stained for STAT2 specific antibody followed by Alexafluor® 488 conjugated secondary antibody (green). Nuclei were stained with DAPI (blue). Studies are representative of more than three independent experiments. The scale bars represent 10 µm.B Quantitative evaluation of STAT2nuclear translocation. The intensity of STAT2-dependent immunofluorescence over DNA staining (DAPI) was quantified using ImageJ software in 20 cells from two independent experiments. Bars represent a mean with standard deviation (SD) and asterisks denote the level of statistical significance (***, p≤ 0.001); p-value was calculated using unpaired t-test.
B. Overview of the proximity labeling workflow: interactomes of T.I.-mCherry or T.I.-BRD9 were determined in the presence/absence of a 60min stimulation with 1000 IU/mL of IFN-α2 and 500μM biotin for 30min.
D. Volcano plot of transcripts containing a conserved miR-212/132-3p target site in in vitro polarised (Th1 condtions, 18h post stimulation) CD4+ T cells from WT or miR-132-/- mice.
(C) Averaged fluorescence intensity profiles of GFP-dynein at growing microtubule plus ends for the conditions as in B. Mean values from three separate experiments per condition (with a total of at least 69 kymographs) are shown; error bars are s. e. Experiments were performed at 30°C.
In healthy cells Stx17 facilitates normal division of mitochondria (Mt) by interacting with Drp1. Upon mitophagy stimulation, Stx17 dissociates from Drp1 and interacts with Atg14L for autophagosome formation. In the case of autophagy, mitochondria elongate due to inactivation of Drp1, whereas in mitophagy, FUNDC1 (FDC1) is dephosphorylated by cleaved PGAM5 (PGAM5*), which facilitates excessive division of mitochondria (Mt*) by interacting with Drp1. Stx17 supports this process by releasing PGAM5. Under normal division conditions, FUNDC1 associates with CNX through unknown protein(s).
(E) Tumor volume in mice treated or not with LPS, where indicated mice received anti-CD62L antibody 12h before LPS treatment.
E Quantification of WT and ∆ice2 cells with Rtn1-mCherry puncta after treatment with 8 mM DTT for the times indicated. Mean + s.e.m., n = 3 biological replicates. Asterisks indicate statistical significance compared with the corresponding value in WT cells, as judged by a two-tailed Student's t-test assuming equal variance. *, P < 0.05; **, P < 0.01; n.s., not significant.
The S. typhimurium-induced macrophage death does not require caspase activity. BMDPM were infected with wild-type S. typhimurium or the TTSS-defective invG mutant in the presence or absence of 50 μM of the pan-caspase inhibitor Z-VAD, and cell death was measured as indicated in the legend to Fig. 1.
C, D. ETC-159 and olaparib synergistically inhibit the growth of ETC-159 resistant pancreatic cancer cell line PaTu8988T. (C) PaTu8988T cells were seeded in soft agar and treated with ETC-159, olaparib or the combination of the two inhibitors at an equivalent dose as described in Figure 1A. Representative image of soft agar colonies from PaTu8988T cells combination study in a 48-well plate is shown. (D) The Combination Index (CI) values of olaparib and ETC-159 calculated from two independent experiments using the Chou-Talalay CompuSyn software.
D, E Three‐month‐old mTerc+/+ mice were γ‐irradiated with 12 Gy. Small intestinal tissue was collected at 3 h after IR (n = 3 mice per group). (D) Representative picture of TUNEL staining. Arrowheads and numbers indicate ISPC positions in the crypts. Scale bar: 20 μm. (E) Percentage of TUNEL‐positive ISPCs at indicated positions in basal crypts. Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test.
B Western-blot of whole cell extracts for different components of the protein import machinery in control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in either glucose or galactose containing medium.
Purified NK cells were activated with IL-2 or IL-15 in the presence or absence of PGE2 (1µM) and tested for (C) Viability by flow cytometry using fixable live/dead staining after two days of culture (n=7, biological replicates).
(D) An overview of the timeline of the experiment. (A-D) Each colour corresponds to a donor; 6 different donors were analysed. The dashed line represents the detection limit. An ordinary one-way-ANOVA test was used for statistical analysis: ns, not significant; *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001.
Vegfc/LacZβ-Gal staining and LYVE1 peroxidase staining.Data information: Arrows indicate the VEGF-C expression in arterialSMC, arrowheads indicate the VEGF-C expression in SMCfibers in the villus, and asterisks highlight the VEGF-C expression in circular smooth muscle cell layer of the intestinal wall. Scale bars: 50 μm, except (C) inset 25 μm.
(F) Representative confocal images of the shift in the fluorescence emission of Keima from 458 to 561 nm. Scale bar, 10 μm.
(C) Left panel is the autoradiography results of a GST pull-down assay showing that radiolabeled human PIAS1 interacts with HTTex1p. Right panel is a phosphorimager analysis of GST pull-downs, performed in triplicate, showing the percentage of 35S-labeled PIAS protein that bound the GST proteins: GST alone, unexpanded HTT with and without the proline-rich region (20QP and 20Q), expanded HTT with and without the proline-rich region (51QP and 51Q), and the proline-rich region alone (Pro). Error bars were calculated as an estimate of SE = STDEV(n)/SQRT(n-1).
F X-Gal and H&amp;amp;E staining on artificial muscle section revealing vessel connection with host vasculature by Indian ink, injected into the femoral artery immediately before sacrifice. Scale bar: 20 μm.
(B) Upper panel: dissolved oxygen curve over 120 h time course showing controlled depletion (1), sustained hypoxia (2) and controlled reaeration (3). Points represent the average of three biological replicates and were measured via fiber optic technology that non-invasively probes oxygen levels in the culture (PreSens Precision Sensing GmbH). Lower panel: expression profiles (RNA-seq) of desA1 and desA2 over the time course and oxygen levels. Error bars show the standard deviation from three biological samples.
E. Surface plasmon resonance sensorgrams of Nec-1 targeting Aβ(1-42) aggregates (left), and the corresponding dissociation fitting curve from the saturated region (right) under various concentrations of Nec-1.
G Surface morphology of FI, CI, PI and PI+MVF on day 0 as visualized by scanning electron microscopy. Scale bar: 50 µm.
H. VEGF-A continues to be highly expressed in secondary nuclear fiber cells in the aged lens (shown is a lens of a 24-months old VEGF-Ahyper mouse; nuclear β-galactosidasestaining (arrow) reflects cellular VEGF-A expression). Cor: lenscortex; Cap: lens capsule. DAPI labels nuclei (blue). Scale bar 25 μm.
(A) Flow cytometry analysis of surface PRPH expression. NSC-34 cells were infected with EV-A71 S41 at MOI 10 for 1h before staining with Viability Dye and anti-PRPH antibodies. Data are expressed as Mean Fluorescence Intensity.
Comparative analysis of the amount of LAMP2A in wild-type or Ctns−/−liverlysosomes was performed using two different anti-LAMP2A antibodies. 15 μg of lysosomal proteins were loaded in each lane. Ab1, anti-LAMP2A antibody raised against the twelve amino acids of the cytosolic region of ratLAMP2A largely validated to recognize mouseLAMP2A but not other LAMP2 isoforms (Cuervo Dice, 1996). Ab2, anti-LAMP2A Abcam Ab18528. Decreased lysosomalLAMP2A was evident using either antibody. LAMP1 was used as a loading control. Representative of two independent experiments with similar results.
B. Schematic of crystalized miRNA and target sequences. Vertical lines indicate base pairs observed in structure. miRNA colored red; target RNA colored dark blue (here and throughout manuscript).
G, H Confocal images of primary hepatocytes grown in HBSS and stained with anti-CLUH and anti-TIA-1 (G) or anti-G3BP1 (H) antibodies. Right panels show 5x magnified boxed areas. Scale bar, 10 μm.
FISH of CHX or VerruA-treated cells. Chloro: chloroform; solvent control for VerruA; NT: not treated; control for CHX.
(C) Mitochondria from siRNA‐transfected cells treated with 10 μM CCCP or dimethylsulphoxide were incubated with or without respiration substrate (Resp. mix) for 30 min at 37°C.al hour.
C) Cells transfected as in B were treated with IN1 for 18 hours as indicated, fixed and labelled for ubiquitin (green), FIP200 (red) and p62 (blue). FIP200-positive bodies were quantified from 4 independent experiments with mean +/- SEM plotted. Cells transfected with ATG14 siRNA generated significantly more FIP200 bodies per cell than all other conditions tested.
I Representative western blots using antibodies against p-p53 (serine 15), p53 and β-actin in control and 10 µM CDDP-exposed whole cochlear extracts.J-K Histograms representing the levels of total p53 protein (J) and p53 phosphorylation (K) in control (gray bars) and CDDP-exposed cochleae (green bars, n=6 cochleae per condition and per time point). Actin served as a loading control. Data are expressed as mean ± SEM. One-way ANOVA test followed by post hoc Tukey's test (J: *P ≤ 0.023; K: *P=0.032, **P=0.007, ***P ≤ 0.0008, cochleae at the different times after CDDP exposure vs. control 12h).
(F Double immunofluorescence for Cyclin D1 and β-catenin (F), in colon tumors from control (n=4) and cKO (n=4) mice. Scale bar: 100 μm.
Flow cytometric analysis of the tetraploid Gam-GFP reporter strain grown on SCD with or without PQT (600 μg/mL), H2O2 (2 mM), or PL (100 μg/mL) for 24 h at 37°C.
Heatmap representing expression z-score of the 98 significantly over-expressed genes in the TAU MOL vs. TAU VEH comparison, for all experimental conditions. Color-coding was performed according to the z-score of the normalized reads counts divided by gene length. Clustering was performed using the Unweighted Pair Group Method with Arithmetic mean method and the Pearson"s dis
(A) Cells in early G1 stably expressing nAC-mCherry and doxycycline-inducible ACTN4-SNAP were analyzed by time-lapse microscopy. ACTN4-SNAP was labeled by SNAP-Cell 647SiR dye (green). Different arrows mark dynamic ACTN4 clusters. The white square 1 is shown as a timeseries on the right. The white square 2 is shown as a magnification below. The white square 3 shows an actin filament decorated with ACTN4 that was analyzed by linescan in Fig 2B. Scale bar overview (nAC) represents 10 µm. Scale bar time series and magnification 5 µm.
(G) Immunoblots indicate that miR-517a suppresses expression of ARCN1 in multiple miR-517a sensitive cell lines.
(c) HeLa cells incubated in HBSS were collected and endogenous phosphorylation of MYPT1 was determined by western blotting. The same blot was then washed in TBST for 30 min, blocked in 5% milk and was analysed for total MYPT1 as a control. Extracts from this experiment were rerun on 7.5% gel and analysed for ROCK1 and β-actin.
(C) The localization of Eg5 in the spindle upon NuMA depletion. HCT116 TetOsTIR1 NuMA-mAID-mClover-FLAG cells with 2-centrosomes were treated with 1 μg/ml doxycycline Dox and 500 μM IAA. Gray, green, red, and blue represent α-tubulin, NuMA (mClover), Eg5 and DNA, respectively. Z-projections of 5 sections, every 0.3 μm. Scale bar, 5 μm.
g, Chart of selected genes for which mRNA is enriched in either ATG16L1-deficient Paneth cells (baseline is WT Paneth cells) or ATG16L1-deficient thymocytes (baseline is WT thymocytes). Only haemoglobin is in common in these two sets of analyses. NS, not significant. Scale bars: a, b, 10 µm; c, d, 500 nm.
RPE cells or RPE cells stably expressing indicated EGFP-FAM110A variants were transfected with control (siNC), FAM110A or CSNK1D siRNA and grown for 48 h. Alternatively, cells were incubated with PF670462 for the last 12 h. Cells were treated with MG132 for 30 min prior fixation. Impaired chromosomal alignment was scored in >30 metaphase cells per condition. Error bars indicate median ±SD. Statistical significance was determined by ANOVA (n=3) (**** p<0.0001, *** p<0.001).
C RT-PCR analyses for CELF2a and DUXAP8 expression in WT and GS∆44 myoblasts (GM) and myocytes (DM). GAPDH was used as control. Representative results are shown (n=3).
C WES data analysis pipeline. A total of 179,579 sequence variants in 20,800 genes were identified in 108 unrelated KS patients, and among of them nonsense, missense, frameshift, and essential splice-site variants were further investigated. These variants were divided into four subtypes (high, likely high, medium, low), and most of the medium to high variants were localized on the X chromosome. The genes on the X chromosome that contained more than two types of medium to high variants were selected. As the extra paternal-origin X chromosome in KS might be caused by impaired recombination between sex chromosomes during meiosis I, only the testis-specific genes ESX1, LOC101059915, and USP26 were further investigated. The variant frequencies of these three genes in the KS patients were compared to the variant frequencies of these three genes in the 1000 Genomes Project. The frequency of USP26 variants had the highest fold increase.
B (Left) Snapshots of representative actin networks assembled in the presence of 600 nM Alexa-488-labeled ADF/cofilin (replacement of unlabeled ADF/cofilin). (Right) Quantification of ADF/cofilin's fluorescence intensity relative to actin. Data are presented as mean +/- SD (n = 34 for Act_Sc branched, n = 28 for Act_N2 branched, n = 43 for Act_Ca branched, n = 24 for Act_Sc linear, n = 15 for Act_N2 linear and n = 27 for Act_Ca linear). ***P<0.001 (Kruskal-Wallis test, with multiple comparisons).
Overview of the PE‐QMS experimental strategy to identify LXR ligand‐stimulated and LXR binding‐dependent interactions with the Abca1 promoter. Nuclear extracts were prepared from RAW 264.7 macrophages treated with control or 1 μM T0901317 (depicted as a black circle) for 18 h. The Abca1 promoter region was used to isolate gene regulatory complexes under the indicated conditions. Immobilized templates were washed, and bound proteins eluted and digested. Peptides were purified, then identified, and quantified by mass spectrometry.
A Representative tile scan 3D images with α-SMA, Isolectin, FABP4 and Emcn in the pancreas from 17-weeks-old Gja1i∆EC mutant and control mice. Insets show higher magnifications of regions.
C. Dynamics of MavQ association with LCV. BMDMs were infected with the wild-type L. pneumophila strain at an MOI of 2 for the indicated experimental durations. At least 100 phagosomes (n≥100) were counted for each sample to obtain the percentage of MavQ-positive LCVs.