EMBO/sd-character-level-ner huggingface dataset:
(E) Box plot of tRNA levels for codons with strong (red, 20 codons), neutral (light gray, 18 codons), and weak (blue, 20 codons) destabilizing effects based on PACE. Data information: the box represents the interquartile range (IQR), with the median indicated as a black horizontal line in the box. The whiskers represent the variation within 1.5 IQR outside the upper and lower quartiles. Outliers are shown as dots.
Wild-type mice have small defined crypts in the small intestine with little nuclearβ-catenin at the bottom of the crypt. The small intestine of AhCreERAPCfl/fl, AhCreERCatnblox(ex3)/lox(ex3) (day 5) or AhCreERGsk3alphafl/fl betafl/fl (day 6) show the crypt-progenitor cell (CPC) phenotype with increased crypt size (red bar) and nuclearβ-catenin (arrows) along the crypt-villus axis. Scale bar, 100 μm.
D Immuno-histochemical detection of placensin in human placental villi obtained from women at 9 and 38 weeks of pregnancy. During early pregnancy, placensin immunostaining was found in cytotrophoblasts (c), whereas syncytiotrophoblasts (s) showed weak staining. At 38 weeks of pregnancy, strong placensin signals were detected in both syncytiotrophoblasts and cytotrophoblasts (arrows). Staining using E-cadherin antibodies confirmed the identity of cytotrophoblasts (Inset showing higher magnification E-cadherin (E-Cad) staining). Lower panels depict sections stained with nonimmune IgG as negative controls. Scale bars, 100 μm.
(B, C) Quantification of average number of LC3β dots per cell (B) and the percentage of LC3β dots that co‐localized with EEA1 per cell (C) (n=3 experiments/group; 25-30 cells/experiment).
(C) Proposed model for ROS regulation during loss of Dnmt3a. Loss of DNMT3A increases ALDH1L1 expression, thus leading to the increase in NADPH levels and increased activity of NADPH oxidase, leading to increased ROS levels. The increased oxidative stress contributes to mitochondrial dysfunction and muscle fatigue.
(Above) RNA-sequencing of purified CMs from 4 mice per age group reveal age-dependent increased expression of 3 secreted proteins Edn3, Tgfb2, and Gdf15; the colour intensity represents column Z-score, where red indicates highly and blue lowly expressed. (Below) mRNA expression of Edn3, Tgfb2, and Gdf15 was independently validated by RT-PCR in young and old isolated adult CMs. Data are mean ±S.E.M of n=8 mice per group.
Representative micrographs depicting (B) γH2A.X staining on the ventricle sections for the indicated cohorts.
B Boxplot showing expression changes of 1101 genes that were annotated in the 1447 peak regions defined in (A). Two-tailed unpaired Student's t-test was used to analyze statistical significance; P < 0.001.
(C) Quantification of cell surface area of isolated neonatal mouse cardiomyocyte of Tip30 Het and WT mice treated with endothelin-1 (ET-1) and Narciclasine (Narci) or without stimulation as indicated (N=6 samples/group).
(A) UMAP plot of snRNA-seq data from 64,381 combined neural cells from GW7 to GW23. Cell cluster phenotypes are labelled and the red arrow indicates the EGFR-expressing glial cluster (left). Selected UMAP plots from different development stages (GW7, GW11, GW18, and GW23) represent the neural development trend (right). Gray represents non-specific cell types.
(N) ish with ddc probe on wild-type and opn4 dko larvae sampled on the 6th dpf represents ddc expression in pineals. Biological replicates indicated with BR. Scale bar: 0.05 mm (O) Quantification of the adjusted intensity in the pineals from larvae presented in N, implies a significant higher ddc transcript level in the opn4 dko pineal. Data information: boxplot divides the data in quartiles: the box indicates the interquartile range, with the horizontal line in the box denoting the median of the data set, the whiskers extend to the minimum and maximum, and meet the box at the median of the lower (quartile 1) and median of the upper (quartile 3) half of the dataset. Black dots indicate biological replicates O: n=8), the red dot indicates the mean, red error bars indicate the confidence interval (95%), asterisks indicate significance (0.01<p(✱)<0.05, 0.001<p(✱✱)<0.01, p(✱✱✱)<0.001, ns = not significant).
F) Immunocytochemical analysis of a mixed culture containing neurons from wildtype and Nrg3-/-; Gad1/Gad67-GFP animals triple-stained against ErbB4, GFP and Nrg3. To improve visibility, ErbB4 and Nrg3 signals are also shown separately (F', F''). ErbB4+ interneurons from Nrg3-/- animals are GFP-positive and are indicated by open arrowheads; ErbB4+ interneurons from wildtype animals are GFP-negative and are indicated by filled arrowheads
(D) Representative immunoblots of laminin-binding analysis using FKRP- and corrected-NSCs treated with 4BPPNit and DMSO only controls. (E) Quantification of laminin-binding activities, compared with DMSO only controls. Data information: Intensities of laminin-binding activity are normalized to GAPDH protein expression. Note that the left and right panels of the immunoblots are not equivalent exposure time. Values indicate mean ± s.d. (n= 3 or 4 biological replicates; One-way ANOVA; NS, not significant; * p<0.05; ** p<0.01).
E. In vitro phosphorylation by Plx1. Apc3-loop fragment, α-Casein, N-terminus of Cdc20 (N159) or MBP protein was incubated with purified Plx1 in the presence of [γ32P]-ATP at 23˚C for indicated times, separated by SDS-PAGE and detected by autoradiography and Coomassie brilliant blue (CBB) staining.
B, enrichment of five subsets of the DET signatures for CHIKV infection phase and viral titer among each of the 92 coEMs (X axis), showing the fractional overlap of the module with the DET signature (Y axis). Negative log10-scaled q values (Benjamini-Hochberg adjusted P values; Fisher's exact test) are depicted as red asterisks on the secondary Y axis (right hand side), clipped to a maximum of 10. The only modules with overlaps in any of the subsets that exceed FDR < 0.05 are turquoise and sienna. The horizontal line indicates a threshold of FDR < 0.05. The three highlighted coEMs from A are again labeled.
(B) Structure modelling of HIV-1 capsid hexamers with focus on MHR alongside C-terminus of EB1 in red boxes. Identical residues are indicated in red and similar residues are indicated in dark orange. UCSF Chimera 1.12 software was used for structure modelling of NL4-3 hexamer (PDB 3J3Q) and EB1 (PDB 2HKQ).
F) High magnification of boxed region from (D). The top (i) and the bottom (ii) side of the Boyden chamber membrane were stained for F-actin, E-cadherin, ZO-1, Ezrin and Hoechst. Arrow points to the protrusive cells of an invasive cyst and the white stars show the nuclei that engage in the protrusion. Scale bars: 40 μm.
Effects of DC and Beva treatments on Ren13, Ren86, Ren28 and Ren50-PDOX. Quantification of tumor weight in control and treated tumors from 4-5 samples/tumor/treatment group by Mann Whitney test. Box plots indicate median, Q1/Q3 and max/min value whiskers.
C: Kaplan-Meier survival curves indicating extended survival for mice bearing established G401 xenografts treated with the 3-day continuous infusions of EC8042 in (B). The shaded box indicates the duration of treatment. Asterisk indicate an animal sacrificed due to unknown causes not related to tumor progression or drug toxicity (see text).
A Real-time PCR analysis for pro-inflammatory cytokines and neurotrophic factors. BV2 microglia and primarily cultured astrocytes were transduced with C, N, F, and NF. Real-time PCR analyses were carried out 12 h after LPS (100 ng/ml, for pro-inflammatory cytokine expressions), IL-4 (10 ng/ml, other M2 markers), or without the treatment (neurotrophic factors). Significantly different from the control (C)*, N#, F‡ at P < 0.05, n = 3-6 PCRs; one-way ANOVA followed by Bonferroni post hoc test.
B Density plots of changes in relative mRNA abundance as determined by RNA-seq following treatment of HEK-293 cells with 1 µM thapsigargin for 6hr (left) or 9hr (right). Genes were categorized as up-regulated by siUPF1total only or siUPF1LL only under basal conditions. Statistical significance was determined by K-W test, with Dunn's correction for multiple comparisons.
overall as well as disease-specific survival probability (B) of DLBCL patients pSTAT3 positivity was a strong negative prognostic factor in the entire cohort (B)
(C) PD experiments with GST-SUMO IκBα fusion protein and serial dilutions of histone-enriched HEK-293T lysates. Quantification of three independent replicates is shown.
H. Prmt6 depletion decreases R388 methylation of endogenous Sirt7. Scramble control cells (scr) or MEF cells stably expressing two different shRNAs (#1 and #2) against Prmt6 was established. R388 methylation of immunopurified endogenous Sirt7 was determined by western blot
C. Simulations analogous to the experiments shown in Fig. 1B, with the same cell dimensions as in Fig. 2B. The left-hand column depicts the spatially perturbed MinD attachment profile, showing gradients along the diagonal lines of the rectangles. With these attachment profiles, the Min distributions in the three cells quickly evolve into longitudinal, striped, and transverse patterns, respectively.
The ERMIT assay relies on the signaling properties of IRE1, one of the three ER stress sensors and reports for a dimerization event occurring in the lumen of the ER. The assay can be applied to heterodimerization or homodimerization events. Western blot showing the expression of AGR2 dimers (D) and monomers (M) in HEK293T subjected to DSP-mediated cross-linking and that were previously transfected with either a control siRNA (siCTL) or treated or not with tunicamycin (Tun) prior to cross-linking (D). Reduced or non-reduced samples were resolved by SDS-PAGE and immunoblotted using anti-AGR2 anti-calnexin (CANX) antibodies (for loading control).
b, AMBRA1-BECN1 interaction in mammalian cells. 2FTGH cells were co-infected with retroviral vectors encoding BECN1 and the indicated Myc-tagged AMBRA1 proteins, or Myc-tagged β-gal as a negative control. CT, C terminal; FL, full length; NT, N terminal. Protein extracts were immunoprecipitated using an anti-Myc-tagged antibody (IP Myc). Purified complexes and corresponding total extracts were analysed by western blot using anti-Myc (WB Myc, upper panels) or anti-BECN1 (WB BECN1, lower panels) antibodies. When multiple bands are present, the upper band has the expected molecular mass. A scheme of the various AMBRA1 mutants is reported.
(B-C) Cumulative distributions of (B) kcat values All distributions were significantly different with p < 0.05 using a non-parametric Wilcoxon Rank-Sum test (Appendix Table S4).
(B) Representative picture of telomeric signals used for Q-FISH analysis on metaphase spreads from SV40T-transfomed fibroblasts and Muntjac cells used to normalize the signals. (C) Individual and mean values of Q-FISH analyses for control and patients. Mean fluorescence intensity of Muntjac cells was set to 1. Error bars indicate s.d.. (D) Graphical representation of (C) showing the average of fluorescence ratios (relative to Muntjac). Error bars indicate s.e.m.. The non-parametric Kruskal-Wallis test was applied to compare relative fluorescence values between Ctl and P1, and Ctl and P2.
I. Percentage of LGALS1-positive puncta staining in the control (Scr) and MDGI-silenced (sh1) cells. In total 0.4-1.2x104 LGALS1-stained cells were analysed from 50 mm2 coverslip areas (n = 6). Data are represented as mean ± SD. **P < 0.01, two-tailed, nonparametric Mann-Whitney's U-test.
(G) Immunoblot analysis of EphA2 and IL-1β in lung homogenates were from wild-type (WT) and EphA2-kockout (KO) mice on day 1 and day 3 of intranasal infection with reovirus (4×104 PFU per mouse), β-actin served as a loading control throughout.
A A drop in PKAc1-Ty-iKD expression is detected as early as 24 hours upon ATc treatment with almost no protein detectable after 36 hours.
G. Fibril length difference between Aβ alone and in presence of peptides (Statistics: Brown-Forsythe and Welch Anova test with Games-Howell multiple comparison correction). Graph: Mean difference and 99%CI. ** P≤0.01, **** P≤0.0001. At least 9 different positions on grid and at least 100 fibrils were counted for each condition (except Aβ+P23, Aβ+P24). Fibril length distribution in Appendix Figure S7.
GPRC5A depletion markedly increases caspase-3 activation/PARP cleavage during hypoxia.
From the results of RepeatMasker, percentage of the up-regulated dsRNA regions (928 regions highlighted in panel C) that contain or largely overlap with the Alu elements. For comparison, repeated for 10 times, the same number of intra-genic regions were randomly selected and the percentage of Alu was counted with RepeatMasker. The results, i.e., percentages of Alu in these 10 random sets, were summarized as the box plot. Percentage of the introns harboring the up-regulated dsRNA regions (698 introns in total, accounting for 864 of the 928 regions shown in panel C) that contain the previously identified HNRNPC binding regions. For comparison, 10 sets of randomly selected introns, which have the same length distributions as the 698 introns, were also queried. The results, i.e., percentages of the introns containing the HNRNPC binding regions in these 10 random sets, were summarized as the box plot.
Graph of fold-changes of proteins enriched (P-value < 0.05) in proteomics analysis of CENATAC vs. control co-immunoprecipitations of HeLaEGFP-CENATAC cells (three biological replicates). Splicing factors are depicted in orange. See also Appendix Figure S7.
(D) Graph represents the levels of Rod-GFP determined relative to CID-RFP measured at late congressing KTs (n≥15 neuroblasts for each condition, n≥3 independent experiments). Data information: Statistical analysis was calculated using an unpaired t-test (Mann-Whitney). p values: **, <0.01; ****, <0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.
Combined IF and DNA FISH analysis of RAD54 (IF), PML (IF) and telomeres (FISH) in ALT cell lines SaOS2 and HuO9. Scale bars = 10 µm
K, Fluorescent in situ hybridization for fosl1a at 7 dpi. The white boxed region is shown in a higher magnification image to the right for the injury area. cdh5 was used to label all EC cells and the red boxed region is shown in a higher magnification image to highlight a pan-EC cdh5 expression in green. White dashed lines outline the heart and the yellow dashed lines indicate approximate resection plane. Scale bar = 25 μm. A stands for arium, V stand for ventricle and OFT stands for outflow tract.
I In vitro ookinete differentiation of the complemented parasites. Values are means ± SEM (n=3 biological replicates), two-tailed t test, **, P<0.01, ***, P<0.001.
(A) The mutant chm allele we used removes the catalytic, histone acetyltransferase MYST domain. The chm mutants consistently display 50% mRNA reduction in young (7 days) and midlife (22 days) when compared to wild-type flies. N=5 young wt, 6 young chm mutants, 4 midlife wt and 6 midlife chm mutants.
A. Schematic of the Shld2 exon 4 showing the 3 sgRNAs used to produce a 251 base pair deletion in one founder line that leads to a frameshift and usage of a premature stop codon.
mRNA expression levels of the indicated genes were assayed by real-time PCR and normalized to Actb (C).
The SARS-CoV RBD is shown as a white molecular surface (PDB ID: 2AJF), with residues that vary in the 2019-nCoV RBD colored red. The ACE2 binding site is outlined with a black dotted line.
(h) Stripped autolysosomes were pretreated with GFP or PtdIns(4,5) P2 antibody and then incubated with rat brain cytosol. Autolysosomes were washed and then analysed by western blotting with antibodies against AP2α and LAMP2.
Immunofluorescence microscopy as described above except using control siRNA-treated (G and H) BMMs. quantitative analysis of M.tb colocalization with Lamp-1 in control siRNA-treated mouse BMMs Data shown are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. Scale bar, 5 μM n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by two-tailed Student's t-test.
D The amounts of intracellular HIV-1 RNAs of latently infected primary CD4+ T cells which were isolated from PBMCs of HIV-1-infected individuals. αCD3/αCD28/IL-2 treatment was performed as positive control. shCHAF1A lentiviruses were packaged to knock down endogenous CHAF1A. shluc lentiviruses treatment was performed as negative control. SAHA was added as LRA supplement.
A. Confocal images show Iba1-immunoreactive microglia and macrophages in RPE/choroid whole mount preparations 48 hours after laser coagulation and intravitreal application of low (0.2 µg) and high (3 µg) dose polySia avDP20 or PBS-vehicle. Laser spots of vehicle-injected SIGLEC11 transgenic (tg) and wild type control animals revealed strong accumulation of activated microglia and macrophages, which was effectively decreased in polySia avDP20-injected SIGLEC11 tg animals and to a lower extent in wild type controls. Representative images out of at least three independent experiments are shown. Scale bar: 50µm.B. Quantification of the average pixel intensity of Iba1-positive area in laser spots reflects accumulation of reactive microglia/macrophages on RPE/choroid whole mounts. In comparison to the accumulation of reactive microglia/macrophages in control animals, there is a reduced pixel intensity found in polySia avDP20-treated SIGLEC11 tg animals. Notably, treatment with a high polySia avDP20 dose (3 µg) also reduced accumulation of microglia/macrophages in laser spots of wild type animals. Data show mean +/- SD. * p< 0.05, ** p< 0.01, *** p< 0.001, One-way ANOVA followed by Fisher's LSD. WT PBS (n = 24 spots), WT 0.2 µg Sia (n = 37 spots), WT 3 µg Sia (n = 20 spots), SIGLEC11 tg PBS (n = 25 spots), SIGLEC11 tg 0.2 µg Sia (n = 35 spots), SIGLEC11 tg 3 µg Sia (n = 31 spots), WT PBS vs WT 3 µg Sia p = 0.0147, WT 0.2 µg Sia vs SIGLEC11 tg 0.2 µg Sia p = 0.0046, SIGLEC11 tg PBS vs SIGLEC11 tg 0.2 µg Sia p = 0.0071, SIGLEC11 tg PBS vs SIGLEC11 tg 3 µg Sia p < 0.0001.
(A-E) Wild-type and Cd22R130E primary B cells were labelled with Atto 633-conjugated Fab fragments against CD22 or IgM, settled onto nonstimulatory coverslips and imaged. Single particle trajectories were then analysed.(A) Trajectories of CD22 in Wild-type (left) and Cd22R130E cells (right) showing diffusion of single particles over 6 s.B) Diffusion coefficients of 300 representative CD22 and IgM particles. Bars and numbers indicate the median.(C) Confinement analysis. Bars and numbers indicate the median.(D and E) Two-population analysis of CD22 diffusion. Analysis of CD22 diffusion plotted on a logarithmic scale and fitted to two Gaussian-shaped curves to account for slower and faster diffusing populations.(D) Wild-type (blue line and circles) and Cd22R130E (blue dotted line and squares middle) primary B cells were compared in an overlay (left) and the proportions of the faster diffusing populations plotted (right).(E) Proportions of faster-diffusing populations.
F View focusing on the NBDs and the unassigned extra density (ED) reaching from the 40S via the HLH into NBSI. The ABCE1 map was low-pass filtered at 6 Å. Schematic representation highlighting the position of the ED with respect to the NBSs.
Healthy control (filled circles) or BLM-induced mice were treated with vehicle (filled squares), 1 nmol (empty circles), 3 nmol (empty squares), or 10 nmol (filled triangles) FA-TLR7-54 and then sacrificed on day 21 for analysis. (D) H&E staining and trichrome staining of lung tissue (scale bars, 200 μm).
(A-E) Horizontal sections of the adult head lamina cartridge. (A) In repo>GFP.nls flies, two lamina neurons L1, L2 axons (L) and R1-6 axons (blue area) were surrounded by the electron-dense cytoplasm of the epithelial glia (G). The section was examined at three different depths, and the size of a single cartridge is not significantly different at different depths. (B-D) repo>Shits1 adults maintained at 29°C for 4 days. Axons were enlarged but intact. A large number of small and medium vacuoles were identified in the epithelial glia. (C) Small vacuoles in the glia that contained a double-membrane structure (arrowhead). (C') Higher magnification of the boxed area in (C). (D) A double-membrane autophagosome-like structure (arrowhead) in the glialcytoplasm. (E) In repots>DERDN adults maintained at 29°C for 2 days, large vacuoles were identified in between the lamina cartridges. N: glialnuclei. (E') Higher magnification of the boxed area in (E), which shows autophagosome-like vesicles (arrowhead) in the gliacytoplasm.
Representative electron micrographs of homofibrils formed by M451-90, RIPK1497‑583, His-Ub-RIPK3387‑518 or ZBP1170-355 individually, and heterofibrils formed by indicated mixtures.Samples prepared twice from independent protein preparations
A. Average 2D tSNE map of the 985 strains with at least one morphological or growth feature with a |s| > 3, plus the 240 independent WT replicates used as controls. Color-coded islands resulting from the dbscan algorithm (ε = 4.9, minPoints = 3) were defined by groups of strains clustering together with the same dbscan parameters in more than 90% of the generated tSNE maps. Dots in the scatter plot (left graph) represent strains color-coded based on their island affiliation (right graph). Light grey dots represent strains that were not consistently (less than 90% of the time) associated with one of the islands.
(C) IF for β1 integrin (red) and αSMA (green) on wound tissue sections at day 17 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar: 20 μm.
(D and E) WT mice fed the MCD diet were i.v. injected with a 1:1 mix of DiO-labeled Lyzs-Cre neutrophil and DiD-labeled p38γ/δLyzs-KO neutrophils (6x106 cells in total; n=10). One hour after injection, liver-infiltrating neutrophils were assessed by flow cytometry (D) and fluorescence micrography on liver sections (E).
(d) Immunoblot analysis (bottom) of LAMP-2A in total lysates of naive and memory CD4+ T cells obtained from 4- or 22-month-old mice and left resting (R) or activated for 24 h as in a (A); above, quantification from results below (n = 3 mice per group). *P = 0.009 (t-test).
Chemotaxis of N2, odr-3(n2150), odr-3(n2046), AWC(-), lim-4(ky403), lim-4(yz12), odr-7(ky4), AWA(-) and ASH(-) worms to 1-undecene at 1:10 dilution. n ≥ 3 assays. ns (not significant) P > 0.05, **** P ≤ 0.0001 as determined by one-way ANOVA, followed by Dunnett's multiple comparison test. Error bars indicate SEM.
D Representative Western blot analysis using antibodies against β-actin and cleaved caspase 3 in whole cochlear extracts.E Histogram representing the change in cleaved caspase 3 expression levels over time in control and CDDP group (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 (*P ≤ 0.028, **P=0.0007, cochleae at the different times after CDDP exposure vs. control 12h).
Space filling and cartoon representation of heterodimer structures in the Ca2+-free (A) and Ca2+-bound states (B). Both structures are built based on the MICU1 homodimer structure (PDB code: 4NSC) in the apo state. Ca2+-free and Ca2+-bound MICU1 were colored in wheat and gray, respectively. Ca2+-free and Ca2+-bound MICU2 were colored in purple and yellow, respectively. Calcium ions are shown as blue and red spheres in MICU1 and MICU2, respectively. Comparison of MICU1-MICU2 structures in the apo (wheat and purple) and Ca2+-bound states (gray and yellow). The conformational differences are highlighted by boxes (black dotted lines). The black arrows show the direction of the conformational change from apo to Ca2+-bound state. Proposed model for mitochondrial Ca2+ uptake regulated by MICU1-MICU2. In the apo state, MICU1-MICU2 form a loose complex which inhibits the uniporter. Upon Ca2+ binding, the conformational changes of the EF-hands promote a transition to a more compact state, which activates Ca2+ uptake.
KIC mice were treated for 4 weeks and KPC mice were treated for 55 days with Mac84 (control) or 2G8. The activation of SMAD2 (P-Ser465/467) (E and H-I), STAT3 (P-Tyr705) (F and J-K) and expression of IL-6R (G) was detected by immunohistochemistry (n = 4/group).