EMBO/sd-character-level-ner huggingface dataset:
Waterfall plot of change in lesion size in patients with measurable disease classified as having a G1 (blue) or G2 (red) profile. Dotted lines represents the limit to define significant progression (upper line) or significant regression (lower line).
Pearson correlation coefficients between eWAT weight and cell numbers of MHCIIlow, MHCIIhi, CD11c+ ATMs, Ly6ChiMHCII-, Ly6ChiMHCII+, Ly6C-MHCII+, and Ly6G+ neutrophils. Significance was determined using the Pearson correlation test.
G, WB analysis demonstrating suppression of CGAS-STING signaling by the SGK1 inhibitor in VM-glial cultures. Representative blots are shown on the left. The levels of the active forms of CGAS-STING signaling molecules are quantified from 5-10 independent blots (right). Data are represented as mean ± SEM. One-way ANOVA. Significantly different at p=0.001#, 0.014* (CGAS), 0.00004#, 0.0002* (STING), 0.017#, 0.037* (pTBK1), 0.009#, 0.045* (pIRF3), 0.012#, 0.036* (pP65) in graph G.
Escape latency of mice in Morris water maze task. *WT+Vehicle mice vs. Tg+Vehicle mice, #Tg+5104434 mice vs. Tg+Vehicle mice. Statistical analysis by two-way ANOVA with Bonferroni's multiple comparisons. #P < 0.05, ***P ≤ 0.001 and ****/####P ≤ 0.0001 Data information: N = 12 mice per group All data are presented as mean ± SEM, **** p < 0.0001 by multiple comparison.
(C) Superimposing the CA7 α-helix-6 (CA7 in blue, areas where mutations1-3 are located is in yellow, and the putative actin interacting CA7 helix in red) on the Twf-C/G-actin structure (grey) shows a sterically compatible structure.
BATs were isolated from cold-exposed mice (4℃, 72 h) or control mice (30℃, 72 h), then lysed and subjected to western blotting for analysis of the indicated proteins (A). Relative protein expression levels, normalized to Actin, are shown in (B).
(A) The response of a mitochondrial matrix-localized Grx1-roGFP2 sensor expressed in wild-type, Δtsa1Δtsa2, Δpor1, Δtrr2, Δtrx3 or Δprx1 cells to a bolus of exogenous H2O2 at the indicated concentrations. Cells were grown in SGal (-Leu) medium and harvested at early exponential phase.
Differential interaction heatmap for 16-19Mbp of chr3L shown in log2 fold change. TADs defined using Hi-C interactions of EGFP-KD (control, upper right) or Piwi-KD (lower left) OSCs are overlaid on the heatmap.
I: PSB-1011 (20μM) treatment inhibited ATP-triggered calcium responses in HEK cells transfected with P2X2. Data are represented as ΔF/F0 +SEM; n=102 HEK cells. J: The P2X2 receptor antagonist PSB-0711 (20μM) nearly abolished the ATP-triggered calcium response in HEK cells transfected with P2X2. n=219 HEK cells.
(D) HFF2/T cells stably overexpressing HA-GRWD1 were established by retroviral infection. Cells were cultured in the presence or absence of actinomycin D (5 nM) for 12h and then treated with or without MG132 (20uM) for 6 h as indicated. Whole cell extracts were analyzed as above.
(I) qRT-PCR analysis for TFEB target genes (TRPML1, BECLIN, MAPLC3B and LAMP1) was performed on ARPE-19 cells treated with DMSO or NSC668394. Bar graphs represent mean values ± s.e.m. of at least 3 independent experiments. Mann and Whitney *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.005.
A. Enzymatic activity of respiratory complex CII in Skm isolated mitochondria from wt and LowOXPHOS mice fed with chow or HFD (wt, n= 4; LowOXPHOS, n= 4; wt + HFD, n= 4; LowOXPHOS + HFD, n= 4).
MoLC were transfected with siCTR or siS100A9 and infected with HIV-GFP vectors for 24h. DNA was extracted and copies of late reverse transcripts were quantified by qPCR. Shown data were collected from experimental triplicates ± SD of four different donors (n=4).
IdU track lengths from U2OS cells. 200 DNA fibers obtained from 2 independent experiments were measured for each condition.
Pantothenate is metabolized into dephospho-CoA through a series of enzymes within the cytosol (PanK1/2, PPCS1/2, PPCDC, and PPAT). The final step involves the generation of CoA by DPCK and is believed to occur within the apicoplast. Within the apicoplast, CoA is used to generate acetyl-CoA and malonyl-CoA and is used by ACPS to carry out the 4-phosphopantetheine modification of ACP to generate holo-ACP. The CoA produced within the apicoplast is also believed to be exported into the cytosol for utilization throughout the parasite cell. PanK1/2: pantothenate kinase 1 or 2; PPCS1/2: phosphopantothenoylcysteine synthase 1 or 2; PPCDC: phosphopantothenoylcysteine decarboxylase; PPAT: phosphopantetheine adenylyltransferase; DPCK: dephospho-CoA kinase; ACP: acyl carrier protein; ACPS: acyl carrier protein synthase; ACC: acetyl-CoA carboxylase; PDH: pyruvate dehydrogenase.
(f) In cultured neurons, viability was tested by MTT after siRNA for Atg7 and OGD/R (n=7 per condition; ***P0.001, with ANOVAs followed by the Bonferroni/Dunn post hoc test).
A Normal human fibroblasts and HGPS fibroblasts were serum-starved for 48 h and stained for progerin (red), acetylated tubulin (green) and DNA (blue). The representative images show that the cell with high progerin (inset 2), but not low progerin (inset 1), displays defective cilia formation. Scale bars, 20 μm or 2 μm (in the magnified images).
(E) Reducing reagents disrupt the interaction between wild-type/C106 HMGB1 and Beclin1. As a control, before IP, samples were incubated with 50 mM DTT (+DTT) and assayed for protein expression levels as indicated by IP or Western blotting. Blots are representative of two independent experiments with similar results.
Lysates from HEK293 cells transiently transfected with murine SPPL2c-myc (isoform A) were treated with the glycosidases PNGase F or Endo H as indicated prior to Western blot analysis with anti-SPPL2c (C-term). Deglycosylation of endogenously expressed LIMP2 was analysed as control.
D CTCF-ChIP in naïve and activated T cells and relative qPCR for CD45 DNA. Rabbit IgG ChIP served as control.
(B) Quantification of the surface area of α-Actinin-positive NRVMs with or without knockdown of NCoR1 and/or MEF2a. A total of 15-20 NRVMs was randomly chosen from 3 replicate coverslips for each group and used for statistical analysis.
Blood was drawn from treated and untreated tumor-bearing mice at the time of tumor resection and plated in culture dishes. The formation of tumor cell colonies was traced over time. Graph shows the number of GFP+ tumor cell colonies (n=8) (L).
(D-E) The qRT-PCR results using mouse tumor tissues revealed that circFNTA expression was significantly reduced (D), and the expression of its host gene FNTA was correspondently decreased in the shcircFNTA group as compared to the PLKO group (E).
B-C Rectal temperature was measured at 24°C (B), and rectal temperature was monitored during acute cold exposure at 4°C for 6 hours (C) in Cdk4flox/flox (n=15) and Cdk4flox/flox Sf1-Cre mice (n=15).
F Representative gel showing levels of spliced and unspliced XBP-1 in liver tissue from control and CCl4-induced cirrhotic mice and the effect of 4μ8C treatment.
A summary of the changes in clinical variables, plasma metabolomics, inflammatory proteomics and oral/gut microbiome after CMA treatment in NAFLD patients
(N, O) C2C12 cells were transfected for 48 h with GFP, GFP‐Jumpy (Jumpy), GFP‐MTM1 (MTM1) or GFP‐MTMR2 (MTMR2), lysed, analysed for p62, GFP and actin by immunoblotting (N) and percentage of p62 were quantitated (mean±s.e.m., n=3) (O).
F-H, RNAseq measurement of mRNA for (F) Fxr1, (G) Fxr2, (H) Fmr1 during SD. n=3 in each condition, Student's T-test *p<0.05.
Toxicity of CY190602 in patients harboring deletion of chromosome 17p (including p53 locus) compared to patients without del17p. Viability of samples was normalized to background apoptosis for individual patient samples. For all experiments, cell viability was determined after 72 h of drug treatment. Data represent mean ± SD.
(B) ROC analysis comparing AUC values of CSF p-tau235, p-tau231 and p-tau217 discriminating A+T- from A-T-. Both CSF p-tau217 and p-tau231 a showed a statically higher accuracy discriminating A-T- from A+T- than CSF p-tau235
(B) Ultrastructure of HCV-infected cells showing perinuclear clustering of damaged mitochondria. Control naïve Huh7 cells (left) and stable cells harboring HCV full-length replicon FLR-JFH1 (right) were examined by electron microscopy. In the zoomed images, typical ultrastructure of mitochondria in naïve cells and ultrastructural abnormalities of mitochondria in HCV replicon cells are shown. Organelle mark: N, nucleus; M and white arrow, mitochondria. Scale bar = 1 µM. Fluorescent images (below) indicate the expression of HCV core protein in HCV replicon cells. Cells were immunostained with anti-HCV core antibody (red). Nuclei were stained with DAPI (blue).
D. Representative images showing morphological changes in spheroids from 3D cultures of human mini-kidneys following Stx2a (10 ng/mL) treatment for 72 h in the presence or absence OSMI-1 (10 µM, final). E. Quantification of estimated spheroid diameter in (D) [n = 11 independent spheroids (biological replicates)]. The effects of Stx2a in vehicle controls were compared with those of spheroids maintained in the absence of Stx2a, and OSMI-1 treatment was compared with that of the vehicle (DMSO) controls in the presence of Stx2a. Data information: Error bars for bar graphs are presented as mean ± S.E.M. Statistical analysis was performed using two-tailed Student's t-test. *P < 0.05; **P < 0.01; and ***P < 0.001.
(D) RNA samples from untreated, serum-starved primary keratinocytes from WT and Ifnar1-KO mice were analyzed by qRT-PCR for Irf7, Rsad2, Oasl2 and Ifnar1 relative to Rps29.
APOE (red staining) immunohistochemistry of control donor tissue (G) and adjacent to GA lesion (H).
(C) Western blotting for the indicated proteins on tissue lysates from forepaws from RDEB mice treated as in A. α-SMA, α-smooth muscle actin; Thbs-1, thrombospondin-1. Data information: β- actin or β-tubulin was used as loading control
(C-E) RT-qPCR for p21 (C), PARDG6 (D), or 18q subtelomeric RNA (E) in 18q WT or18q Δp53 treated with DMSO (black) or 50 μM etoposide (red) for 24 hr. (F) ChIP-qPCR assay for γH2AX at 18q subtelomere in 18q WT or 18q Δp53 treated as in panels B-E.
(A, B) Comparison of arbitrary translation efficiency (TE) values of (A) late trophozoite stage (TP 40) and (B) schizont stage (TP 46) proteins across all experimental time points. The arbitrary TE is defined here as the normalized protein abundance per mRNA abundance to mimic the translational output per mRNA copy in a biological system. The top 5% up-regulated proteins (n = 100) at (A) late trophozoite stage (TP 40) and (B) schizont stage (TP 46) were used for this analysis. Differences among all groups were first tested by one-way ANOVA analysis, followed by Dunnett's test as multiple comparison post-test to find significant differences between pairs of (A) TP 40 or (B) TP 46 and other time points. P<0.01 is denoted as **. P<0.0001 is denoted as ****. Scatterplots of mRNA and protein fold-changes (log-transformed) at time points (C) 40 h and (D) 46 h in the erythrocytic cycle. Quadrants are designated with roman numerals. Data points falling into quadrant I are designated as high translationally efficient (HTE) proteins while those falling into quadrant IV are designated low translationally efficient (LTE) proteins
(F) Quantification of Ki67+ endothelial cells in several organs of mice kept on a ketogenic diet or control diet for four weeks (gastrocnemius and soleus muscle) or two weeks (brain, lungs, subcutaneous adipose tissue, liver). Data are presented as mean ± SD. n≥3; *, p<0.05; **, p<0.01; ***, p<0.001 unpaired Student's t-test.
Histograms of the pSTAT3 mean fluorescence intensity (MFI) of MSC2 cells when TRF2 was overexpressed and the target gene knocked down (G) Data information MFI of n=3 independent experiment is normalized to controls and represented as fold change of MFI (n = 3 independent experiments; *p < 0.05 and **p < 0.01; Student's t-test).
B Isotope profiling of [13C6,15N3]-labeled L-histidine measured by LC-MS/MS in Tsc2-deficient and wild-type MEFs grown in DMEM 10% FBS without unlabeled L-histidine. Labeled-measured metabolites are depicted in the X-axis. The significant differences correspond to two-sided t-test (*P = 0.032 and **P = 0.008; replicates/condition n = 5). Average values are indicated with lilac-colored lines.
(B) 3D reconstruction of the RZZ complex with densities corresponding to ROD-A, Zwilch-A, and ZW10-A colored in firebrick, yellow-orange, and deepblue, respectively. ROD-B, Zwilch-B, and ZW10-B are displayed in equivalent lighter colors as indicated.
B. Western blot for Ctrl and STING KO YUMM1.7 cells, assayed with STING and Gapdh antibodies.
G. Densely cultured RPE cells transduced with CRISPR-SAM targeting USP9X were fractionated into cytosolic and nuclear extracts, and analyzed by Western blotting for the indicated proteins.
E, F. Human apoptosis antibody array analysis of multiple proteins using pooled lysates from iPSC-derived human kidney organoids following Stx2a (10 ng/mL) treatment for 72 h in the presence or absence OSMI-1 (10 µM, final). (E) Antibody spots representing signal differences are indicated in red boxes. (F) The graph shows the average of relative spot intensities for each protein compared to those measured in the control in the absence of Stx2a exposure (n =2 biological replicates). Dashed line represents the reference point of the fold change. Data information: Error bars for bar graphs are presented as mean ± S.E.M. Statistical analysis was performed using two-tailed Student's t-test. *P < 0.05; **P < 0.01; and ***P < 0.001.
Distributions of FUS-tRIP reads (upper panel) and ContAb-tRIP reads (lower panel) mapped to the relative positions of all coding genes in mouse. The ngs.plot tool [58] was used to calculate the average RPM for a gene structure. The average RPM at each position was normalized based on the total RPM mapped to each gene. The standard error of normalized RPM is shown as a semi-transparent shade around the average curve. TSS, transcriptional start site; TTS, transcriptional termination site.
F Analysis of the exoskeleton traits of locusts (n=36 locusts), ns: not significant (Student's t-test). Data information: All assays were performed on fourth-instar locusts.
Ventro-dorsal and lateral radiographs were taken on clinical exam days and scored for the presence of pulmonary infiltrates by a clinical veterinarian according to a standard scoring system (0: normal; 1: mild interstitial pulmonary infiltrates; 2: moderate pulmonary infiltrates perhaps with partial cardiac border effacement and small areas of pulmonary consolidation; 3: severe interstitial infiltrates, large areas of pulmonary consolidation, alveolar patterns and air bronchograms). Individual lobes were scored and scores per animal per day were totaled and displayed (e). Grey: data derived from animals euthanized on 3 dpi; black: data derived from animals euthanized on 21 dpi. Identical symbols have been used to denote identical animals throughout the figures in this manuscript.
Analysis of shScramble (gray, n = 2,400 cells)‐, shIP3R(1,3) A (blue, n = 1,611 cells)‐, and shIP3R(1,3) C (green, n = 1,454 cells)‐expressing DCs migrating in the device described in Supplementary Fig S3I, stained with Hoechst and imaged every 2 min during 24 h at 10× magnification. Values were obtained from three independent experiments. Cell trajectories were obtained by tracking their nucleus.A Graph showing the DC mean instantaneous speed. P‐values were calculated with a t‐test analysis.B Mean instantaneous speed distribution of migrating DCs.
Body weight gain and cumulative food intake of male OXGR1 adrenal-specific reexpression mice (OXGR1REAG). Male OXGR1KO mice (8 weeks) were adrenal-specifically injected with control HBAAV2/9-GFP (OXGR1KO control) or HBAAV2/9-OXGR1 (OXGR1REAG). Two weeks after injections, mice were switched to HFD and further divided into two groups, receiving tap water or water supplemented with 2% AKG for 12 weeks (n = 8 per group).
C. Using a fluorescent reporter strain for the innate immunity gene T24B8.5 confirms that innate immunity genes are upregulated in the long-lived mitochondrial mutants and that components of the p38-mediated innate immune signaling pathway are required for their upregulation. Scale bar indicates 250 µM. Three biological replicates per strain were quantified. Data information: Error bars indicate SEM. *p<0.05, **p<0.01, ***p<0.001. Statistical significance was determined using a two-way ANOVA with Bonferroni post-test
Analysis of the number of genes that are shared among the 100 most abundant transcripts and proteins. Regardless of the tissue, the fraction of shared genes rarely exceeds 20%.
Hematoxylin and eosin staining (H&E) and immunostaining for the proliferation marker protein Ki67 of representative tumor sections from all experimental groups, Scale bars, 200 μm for H&E and 100 μm for Ki67. T, tumor; B, brain. The low-magnification inserts represent negative controls with the secondary antibody alone on serial sections used for both Ki67 and caspase-3 immunostainings.
(A) It is unclear how genetic circuits (centre) tune phenotypic variability in a bacterial population in response to genetic perturbation, environmental stress and history (left) to modulate the fraction of cells that activate a given pathway (right).
A) GFP tagged Syb protein expressed in Hh-receiving cells co-localizes with endogenous immuno-labelled Ptc along the apico-basal axis (3D reconstruction). Vesicles containing Syb and Ptc are visualized at lateral and basal planes (arrows), and can be detected along cytonemes marked with Syb-GFP (arrowhead).
Confocal immunofluorescence analysis of Kitl-tdTomato expression in the E10.5 FL. A cryosection through a E10.5 (35-36sp) Kitl-tdTomato transgenic FL is shown. Arrowheads indicate Kitl-tdTomato+ CD31+ Kit- endothelial cells. Asterisks indicate Kitl-tdTomato+ CD31- Kit- mesenchymal cells or hepatoblasts. Note proximity of Kitl-tdTomato+ cells and Kit+ hematopoietic cells. Scale bars: 50μm (left panel), 25μm (magnified inset). N>5 embryos analyzed.
(F) qRT-PCR analysis showing the dynamic changes of Islr in colonic tissues from mice upon DSS treatment and after DSS removal. n = 4 at each time points.
Subcellular localization of β-catenin in the indicated stable cell lines were analysed by cellular fractionation (B)
C) Quantification of SOD1 at 130 days indicates that Parkin knockout does not affect the levels of transgenic mutant human SOD1 expressed in SOD1-G93A spinal cord. Results are expressed as mean ± SEM and as percent of Non Tg; n= 8 (4 males and 4 females); no statistically significant differences relative to SOD1 expression were found between G93A and PKO/G93A, p= 0.214, by paired Student's t test. Differences between Non Tg and G93A (by paired Friedman's test with Dunn's correction), *p= 0.020 and PKO and PKO/G93A (by paired one-way ANOVA with Tukey's correction), ***p= 0.0001.
(T) Representative immunoblots for HDAC6, Ac-α-tubulin and GAPDH in the NDST3 KO RPE1 cells over-expressing HDAC6 or EGFP.
Scatter plots comparing the estimated logFCs across mice groups. Panel H: mdx vs mdx++.
C-L Effects of N‐terminal substitutions on Noc localisation, in strains: DWA211 (F5E), 318 (F9E), 316 (K2E), 212 (R7E), 322 (F5A), 323 (F8A), 325 (F9A), 206 (WT), 328 (S4A) and 329 (S4L), as indicated. Insets show the corresponding phase contrast light microscopy images. Scale bar, 5 μm.
(D) Ten pM agrin was added to the medium. AChRs were visualized with Alexa594-conjugated α-bungarotoxin (red signals) in the infected myotube (green GFP signals). Ctgf knockdown decreased the number and length of AChR clusters. Scale bar = 10 µm.
Pairwise comparison of transcriptional profiles of 421 universally-active regulatory sequences between bacterial species. Example scatter plots with relatively high and low Pearson correlation in the heatmap (marked i and ii) are shown on left.
D: Upper panel: area (blue) and total traction force (red) as a function of time for the computational oscillatory cell. Lower panel: Corresponding correlation function between the area change rate and total force (dashed line), actin (red) and myosin (green).
(D) PtenΔC/ΔC mice (2-4 months) treated with Slc6a20a-ASO display partially normalized levels of whole-brain glycine, as shown by the lack of difference between saline-treated WT and ASO-treated PtenΔC/ΔC mice. Note that the glycine levels observed here are ~4 times lower than those measured in Fig. 3A, which could be attributable to different mouse ages (P21 in Fig. 3A vs. 2-4 months in Fig. 5D), absence and presence of ASO injection, or lot-to-lot variation of the ELISA kits. (n = 8 mice for WT-saline, 5 for WT-ASO, 7 for ΔC-saline, and 8 for ΔC-ASO, **P < 0.01, ns, not significant, two-way ANOVA with Tukey's test). The error bars represent SEM.
(B) Attachment (left panel) and invasion (right panel) of wild-type F. nucleatum 12230 (Fn) to the non-cancerous SB cells, either untreated or transfected with antisense or sense ANXA1, and to the cancerous 10C cells, either untreated or transfected with control or ANXA1- or CDH1-specific siRNA or both (MOI 50:1). F. nucleatum attachment and invasion to the untreated SB cells were designated as 100%, respectively; all other values were expressed as relative to those obtained with untreated SB. Data are mean values ± SEM. The experiment was performed in triplicates and repeated four times. *p<0.05, **p<0.01 and ***p<0.001 (one-way ANOVA).
(A) FKRP-NSCs treated with 4BPPNit showed increased IIH6 reactivity, compared with untreated control cells. Note that the augmented IIH6 reactivity by 4BPPNit is much weaker than the that in CRISPR-corrected NSCs. Under the same exposure time, the signal intensity of IIH6 reactivity is saturated in corrected-NSCs. Data information: Intensities of glycosylation are normalized to GAPDH protein expression.
Cells transfected with the control siRNA (siNC), the Rubicon siRNA (siRb), the Rubicon expression plasmid (pRubicon) or the UVRAG expression plasmid (pUVRAG) were infected with HCV (m.o.i. = 1). The incubation media were harvested at 24 and 48 hours post-infection and used to infect naïve Huh7.5 cells. Cells were lysed for Western-blot analysis of the HCVcore protein (B) two days after infection. Actin served as the loading control in (B).
G) Double immunofluorescence for Ki67 and β-catenin (G) in colon tumors from control (n=4) and cKO (n=4) mice. Scale bar: 100 μm.
(A) Expression of indicated proteins was determined by western blot in patient-derived and control fibroblasts and B cells and A549 OTULIN WT and KO cells. One representative out of three independent experiments is shown.
(D) Schematic of proliferating RM1 cell isolation from bone and lung metastases following IC injection for preliminary RNA-seq and orthogonal validation by qRT-PCR.
A Wild type MEF cells were fixed before (control) and following S-HAD treatment (10 µM, 4 h) then nuclei (DAPI), cyclin C (indirect immunofluorescence) and mitochondria (MitoTracker Red) were visualized by fluorescence microscopy. Merge panels present DAPI staining (blue) only. Zoom panels (4X) are indicated by the boxes in the merge panels. Green arrows indicate cyclin C and mitochondrial co-localization. Bar indicates 10 µM.
B-D Jejunal spheroids were cultured in differentiation medium with DMSO only or with 1 µM dmPGE2 and pharmacological inhibitors of EP1 (EP1i, SC 51322), EP2 (EP2i, PF 04418948), EP3 (EP3i, L-798,106) or EP4 (EP4i, L-161,982) at a concentration of 10 µM or an equivalent volume of DMSO vehicle. **p<0.01, ***p<0.001, ****p<0.0001 compared to the DMSO only group by one-way ANOVA and Dunnett's post-test. (C) Quantification of average spheroid area ± s.e.m. relative to spheroids treated with DMSO alone (n = 4 images from two independent experiments).
(E) Comparable surface levels of CD16:7 constructs. Transfected 293 cells were processed for anti‐CD16 flow cytometry. The graph displays percentages of positive cells (left axis) and means of fluorescence of positive cells (MF, right axis) obtained from triplicates. Data are expressed as means ±s.d. of the triplicates.