EMBO/sd-character-level-ner huggingface dataset:
(D) Network plot showing top UPR gene pairs with reduced, preserved or augmented co-expression. Each node represents a UPR gene and each edge represents a co-expression relationship between a gene pair. Red double line edges depict increased co-expression in SCNAhigh tumors compared to SCNAlow. Solid lines depict preserved co-expression between gene pairs and blue dotted lines depict reduced co-expression between gene pairs. Node colors represent the UPR branch pathway membership of genes, with green representing the IRE1 pathway, blue representing the PERK pathway, orange representing the ATF6 pathway and purple representing membership in more than one branch pathway.
G. Genes that were downregulated in Kdm6apKO pancreas (KDM6A-dependent genes) showed greatest changes in histone marks. Box plots show fold-changes of H3K27me3 (left) and H3K27ac (right) signals in Kdm6apKO compared to control. Signals were analyzed in KDM6A bound regions in promoters and enhancers of genes that were KDM6A dependent (grey; n=420 regions) and independent (white; n=8035 regions). The signals are average values from ChIP-seq experiments in two biological replicates. The horizontal central line marks the median. Box limits indicate the first and third quartiles and whiskers extend to highest and lowest data points within 1.5 x IQR outside box limits. P-values were determined by two-tailed Mann-Whitney U test.
B In the ZP-C domain of the precursor form of UMOD (left panel, teal), the polymerization-blocking EHP β-strand interacts hydrophobically with a short α-helix (αEF) encompassing the FXF motif. Hepsin-mediated cleavage of the CCS of this molecule (chain B/UMOD 2) triggers release of its EHP, which is replaced by α1β from the interdomain linker of a second UMOD subunit (chain A/UMOD 3) already incorporated at the end of a growing filament (right panel). This allows the FXF motif of molecule B to form an intermolecular β-sheet (αEFβ/βF'; upper dashed box) with the ZP-N fg loop of a third, incoming subunit (chain C/UMOD 4, magenta). Another result of the CCS cleavage is that the C-terminus of mature UMOD 2 is freed for interaction with the D8C domain of the same molecule (not shown). Elements are shown as in panel A, with disulfide bonds and glycan residues represented by thick dark grey and thin black sticks, respectively; β-strands are labelled as in the UMOD precursor (Bokhove et al, 2016a). C Hidden Markov model logos, highlighting the conservation of selected residues shown in panels B, D and E.
The green points were acquired during growth of WT, W133V and I91L+W133V mutants in the presence of different concentrations of thymidine, which follow the red curve. The inset plot shows the same graph with selected datapoints for I91L+W133V mutant. The cyan circle shows I91L+W133V mutant in the absence of any metabolite supplementation, while red and black points indicate metabolite levels following thymidine and dTMP supplementation respectively.
qRT-PCR for mDia1, mDia3, Fmn1 and Fmn2 and several CAF genes relative to Rps29 using RNA from control (sh-EV) and mDia2 knock-down (sh-mDia2) fibroblasts. N=3.
(C) Bar charts show the average frequency (left) and absolute number (right) ± SEM of the indicated populations, analyzed from 2 femurs and 2 tibias per mouse (n=10 mice analyzed for each genotype). All data are presented as mean±SEM. *p<0.05; **p<0.01, and ***p<0.001 by with one-way ANOVAs with two-tailed Student's unpaired t-test analysis for comparison of WT to PKCδ KO mice.
A. H&amp;amp;E staining of the nasal mucosa of E17.5 embryos of the indicated genotype. Normal respiratory pseudostratified columnar ciliated epithelium is shown in Gemc1+/+ embryos compared to the attenuated, flat columnar to squamous epithelium of Gemc1-/- embryos. Scale bars = 20 µm.
Immunoprecipitation was performed with GFP-binding protein immobilized on magnetic beads using extracts of Arabidopsis seedlings, expressing either YFP-MKKK7 or Lti6B. Seedlings were treated with 1 μM flg22 for the indicated time. YFP-MKKK7 and Lti6B-GFP were detected with an anti-GFP antibody while FLS2 was detected with an FLS-specific antibody. Upper panel shows (co)-immunoprecipated proteins, lower panel shows input levels of protein. Arrowheads indicate the position of proteins of interest.
Cartoon illustrating at which levels GPR56 may enhance canonical Wnt signaling (turquoise dashed arrows): at the level of ligand-receptor/co-receptor interaction, β-catenin, downstream of β-catenin, indirectly via activation of Rho/SRF through Gɑ12/13. CHIR99021 is a GSK3 inhibitor that prevents degradation of β-catenin thus enhancing Wnt signaling. MAL/MKL1 (Megakaryocytic Acute Leukemia) is a strong activator of the Rho/SRF 3DA Luc reporter.
C) Confocal live cell (upper panel), or fixed cells (lower left panel), imaging of K562 cells expressing MpleGFP or MplmKO2 treated with NT or anti‐JAK2 siRNA showing a difference of distribution of intracellular Mpl in the siRNA treated cells compare to the control cells. After treatment with anti‐JAK2 siRNA, Mpl strongly colocalizes with the ER marker, calnexin. This colocalization in treated vs non‐treated cells is quantified and shown in Figure C lower right panel. Nuclei are labeled with Hoechst and scale bars = 5 µm.
IL-10 (B) and IL-1β (C) ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS, beraprost (1 and 10 µM), cicaprost (1 and 10 µM), Iloprost (1 or 10 nM) or vehicle control (Vh, DMSO). Data shown are representative of at least 3 independent experiments.
A Detailed image of the neurosurgery procedure that visualizes the GFP+ brain tumor (high magnification) with a 480nm light source and goggles equipped with emission filters. The asterisk in the low magnification labels the field of view for the surgeon, which is amplified in the high magnification through the emission filter equipped in the goggles. The arrow in the high magnification points to the GFP+ tumor as seen by the surgeon.
D) Thermal stability profile for all unmodified SAFB peptides (green) and the phosphorylated S604 (pS604) (purple) in HeLa cells. Data from (Potel et al, 2020).
Severity scores were calculated at different time points (P55, P70, P80 in D). Sample size for D n=10 wt treated with vehicle and n= 20 ko (9 treated with vehicle and 11 treated with CX546). Data are represented as mean ± SEM.
(D) WASH deficiency increases K63‐linked ubiquitination of Beclin 1. WASH+/+ and WASH−/− MEFs were treated with EBSS at 37°C for 1 h and lysed for immunoprecipitation (IP) with anti‐Beclin 1 antibody and probed with antibody against K63‐linked poly‐ubiquitin.
USP36 interacts with snoRNP proteins in the nucleolus. The nucleoli purified from H1299 cells transfected with empty vector or Flag-USP36 plasmid were assayed by co-IP with anti-Flag antibody, followed by IB to detect the indicated proteins.
RNA-seq analysis of WT and Dppa4 (E) KO mESC clones. The dot plot displays the average gene expression of three independent clones from each cell type; n = 3.
e-g, Representative 3D deconvolved MIP images from live imaging of Nrl.Gfp+/+ (green) P8 photoreceptors at DIV1-3 labelled with SiR-tubulin (red) (N = 7 independent cultures). Photoreceptors exhibit a variety of processes, including nascent inner segment-like protrusions (yellow arrows), neurites (blue arrows) and rare tubulin+ve PhNTs (magenta arrows); Scale bar = 5 µm;
Primary hippocampal neurons were transduced with GFP or GA175-GFP after 4 days in vitro, incubated for 7 days (DIV 4+7), and treated with vehicle (DMSO), MG132 (10µM) or rolipram (30 µM) for 16h. Filter trap assay with quantification of SDS-insoluble aggregated GA175-GFP. n=5 biological replicates. Scatter plot with mean ± SD. One-way ANOVA with Tukey's multiple comparisons test.
C Western blot analysis of Bak in the heavy membrane (HM) fraction of human heart, cerebral cortex (CNS GM), kidney, brain white matter (CNS WM), lung, liver, and skeletal muscle tissue. The cytosol fraction obtained from CNS cortex (C), LDH, and Tom20 serve as fractionation and loading controls. n = 3.
Exocet quantification assay of EVs particle numbers. Each bar represents a mean of n=3 technical replicates, vertical lines indicate SD. *, p < 0.05; ***, p < 0.001; n.s. not significant (two-tailed t-test).
C. Changes in the expression of cytokines in THP1 macrophages upon treatment with different domains of S1 subunit at 1 µg/ml for 24 hr. Data information, data are shown as the mean of three technical replicates; in (D), data are shown as the mean of 20 individual donors. Error bars denote SEM. ∗p < 0.05, ∗∗p < 0.01, Multiple t-test.
E. SDS-PAGE analysis of the GST-pull down assay where wt and dimer disrupting mutants of hsMis18α77-187 and hsMis18β56-183 were co-expressed as His- and GST-tagged proteins, respectively in E. coli. While wt GST-hsMis18β56-183 showed interaction with wt His-hsMis18α77-187, hsMis18 proteins harbouring dimer-disrupting mutations, GST-hsMis18β56-183 V77E/Y172D and His-hsMis18α77-187 V82E/Y176D did not show noticeable interaction. The corresponding Ni-NTA pull downs showing the expression of His-tagged proteins are shown in Fig EV2D.
NLRP3 ubiquitination analysed by western blot. LPS-primed (1 μg/mL, 4 hrs.) murine BMDMs pre-incubated with either 0.1% DMSO or P22077 (at the indicated concentrations) for 15 mins. before treatment with ATP (5 mM, 30 mins.). Endogenous NLRP3 was immunoprecipitated (IP) with anti-NLRP3 and probed with either anti-ubiquitin (Poly-Ub), anti-K63-ubiquitin (Poly-K63-Ub) or anti-NLRP3. As a negative control, cell lysate made from LPS-primed and 10 μM P22077 treated cells was immunoprecipitated with a nonspecific IgG. Total levels of NLRP3 in cell lysates (input) were also probed. Western blots of supernatants and cell lysates for IL-1β are also shown as a control for P22077 inhibition. Bands in the figure represent: Pro-IL-1β (31 kDa); mature IL-1β (mIL-1β, 17 kDa) and NLRP3 (120kDa). β-actin is shown as a loading control. Blots are representative of 2 independent murine donors for 2.5µM P22077 and 4 independent murine donors for 10 µM.
(a) RT-PCR analysis of LC3, IL-8, CHOP and GADD34 in U2OS cells subjected to glutamine deprivation (−Q) or exposed to TPG (1 μM). (
wild-type (WT) (n=6) or Stat4 knockout(Stat4-KO) (n=6) mice receiving intraperitoneal injection of PBS or LIF during challenge with 3% DSS. DAI (stool consistency and bleeding score) of colitis mice treated
Retina vessel density in the retinal front. Quantification of the vessel area in the outer 20% of the vasculature (pink in D) (vessel area normalized to vascularized area). P, postnatal day; error bars: SD; 2-way ANOVA p=0.0054; Bonferroni's multiple comparison test, *p<0.05, ** p <0.01. P4 n=3-5 retinas, one retina/mouse, P5 n=4-6, P6 n=3-5, P7 n=4-5.
C) The length of both CldU labels surrounding IdU tracks (newly fired origins) was measured before calculating a ratio representing symmetry around new origins. Quantification of the average positive ratio in the Mybl2+/+ and Mybl2Δ/Δ ESCs. Y-axis was cut to change scale and display large values. Statistical analysis was performed using the Mann Whitney U test. 55 and 75 ratios were recorded in the Mybl2+/+ and Mybl2Δ/Δ respectively from 3 replicates ( **** p< 0.0001).
B Composite map of the complete human 43S PIC after focused and multi-body refinements on individual sub-complexes, filtered at local resolution.
B. Deletion of the domain of KV10.1 responsible for interaction with cortactin abolished the effects of KV10.1 overexpression on the abundance of cilia.
E. Spectral images at high magnification of ExE region from fixed K8-eYFP LB/NP embryos (n=20). E: lateral view where white arrows point to allantois edge and red arrows to amnion. E': lateral view where blue arrow shows Anterior Separation Point and red arrow the amnion. E'': posterior view focused on allantois where yellow arrow indicates allantois cortex and magenta arrow the mesenchyme. K8-eYFP appears in yellow and DAPI in cyan. F. Immunostaining on sagittal section (anterior to the left) of a LB K8-eYFP embryo (n=20) with anti-eGFP antibody (yellow) focusing on ExE region (F); higher magnification images of allantois edge (F', yellow arrow) and base (F'', magenta arrow). G-G'. Immunostaining on sagittal section of a LB wild-type embryo (n=32) with anti-Krt8 antibody (white) (G); higher magnification acquisition centred on allantois (G') where yellow arrows indicate allantois cortex and magenta arrows point to allantois mesenchyme. Da
(D) Still images of representative Hela cells expressing Lifeact-GFP and H2B-mCherry captured at early anaphase under different conditions i.e. Control siRNA, knock-down of centralspindlin protein RACGAP1, in the presence and absence of Aurora B kinase inhibitor (2µM ZM). Scale bar - 10 µm (E) Quantification of aspect ratio of cells treated with different conditions as in (D) at 6 mins after anaphase onset, before furrow formation. Aurora B inhibition and siRACGAP1 individually have a moderate effect on aspect ratio, while together have a stronger impact during mitotic exit. In combined treatment, mitotic cells hardly undergo any elongation and remain spherical before re-spreading. Ordinary one-way ANOVA with multiple comparison. Each treatment is compared with siControl, ****p<0.0001 for all comparisons. Data represented as box-whisker plot, with box showing 25th-75th percentile values, whiskers-min to max value and line representing median. Mean±SD for different treatments- siControl (n=38) - 1.455±0.19, ZM (n=32) - 1.219±0.16, siRACGAP1 (n=25) -1.144±0.078 and siRACGAP1+ZM (n=16) - 1.013±0.03. Cells for different treatment pooled from n>3 independent experiments.
(B) t-SNE plot of the thyrocyte cluster with expression of tg, pax2a and ctsba. The color scale represents the normalized expression counts for each gene ranging from lowest (yellow) to highest (red). (B') Histogram overlaid with density plots depicting the distribution of normalized gene expression for tg, pax2a and ctsba.
(C) proteins and His-tagged CARS protein purified from E. coli. The segments of AMPKγ2 are shown in the bar graph above (C). The red arrows indicate the target bands.
Western blots for exercise-associated phosphorylated proteins in (top) contracted (+) or sham (-) rat muscle and (bottom) muscle from mice that underwent a treadmill running protocol (+) or remained at rest (-). Total AMPK and 14-3-3 were used as loading controls.
H, I Western blot analysis (H) and quantification (I) of CHL1 expression in sensorimotor cortices of NB-3+/+ and NB-3−/− mice after SCI. *p < 0.05; one-way ANOVA followed by Bonferroni post-test. Data were analyzed from 3 independent experiments each including 3 mice per group.
G. Cross section signal intensity of the immunostained endogenous PRC1 (magenta line) from a HeLa cell expressing tubulin-GFP and immunostained for PRC1. Area under the peak is defined as Icross, measured at the position of the blue line as in scheme. Horizontal lines mark the background signal (black line), vertical lines delimit the area (grey) where the signal was measured.
(A) Scanning electron micrographs of cochlear tissue from P19 animals indicate no HC loss in the absence of Elp3 but illustrate some defects of polarity, as misaligned HCs and dysmorphic stereociliary bundles are visible (red arrows and white arrowheads, respectively). Scale bars=5µ
Expression of shRNA-resistant LINC00115 WT but not mutant or empty vector (EV) rescued LINC00115 shRNA-inhibited ZNF596 mRNA (A) expression in 1123 GSCs.
(B, E) Representative images of a hippocampal cell transfected at DIV10 with RFP (to visualize transfected cells), pSUPER (control) or DCLK1 shRNA, fixed at DIV14 and stained for EB3. Black lines indicate the neuronal soma outline. Scale bars = 10 µm.
(F) Blood ammonia levels determined after 4 days under HPD (n=5 mice/group); ***p<0.001, **p<0.01, *p<0.05 (One-way ANOVA). Data information: Treatments Scavenger (Na-benzoate 250 mg/kg/day, i.p.) and L-arginine (L-Arg, 250 mg/kg/day, i.p.); TB-1 (15 mg/kg every 2 days, i.p). WT mice were age-, gender- and strain (C3H)-matched. All values are shown as averages ± S.E.M.
B Cytochrome c reductase activity, standardized to malate-dehydrogenase activity in cardiac mitochondria, were plotted as % of wild-type, n= 3 per genotype.
Relative number of beating EBs on D12 as in (L) (mean values ± SD). n = 3 biological replicates.
A) ATG9 positive membranes were immunoisolated from approximately 2 × 107 fed (F) or starved (S) HEK293A cells using a monoclonal hamster anti-ATG9 (ATG9) or control hamster IgM and immunoblotted for ATG9 using a rabbit polyclonal antibody, TRAPPC8, TRAPPC4 and actin.
E. Comparison of average transcript mRNA half-lives across their respective GC3- and GC-content ranges. Number of transcripts within each gene optimality range is indicated above their respective points. Data information: In (E), error bars represent the 95% confidence intervals.
D. Rapamycin suppresses TLR3-stimulated IRF3 nuclear translocation in RAW264.7 macrophages: Cells were pre-treated with rapamycin and stimulated -/+ poly (I:C) for 3 hr. as in A, fixed, and processed for confocal immunofluorescence microscopy using an anti-IRF3-Alexa 488 antibody and Dapi staining. The graph represents the mean +/- SD of at least 400 cells total from three independent experiments. *p=.002 relative to no Poly(I:C) by paired t-test (two-tailed); **p.003 relative to +Poly (I:C) by paired t-test (two-tailed). Scale bar = 10 μM.
Unsupervised learning by principal component analysis (PCA), circle - primary sample (PRI), triangle - PDX sample; each color corresponds to 1 patient
(E) A simple model incorporating mRNA, protein translation and PER2::LUC stability that were measured experimentally (inputs) shows that the observed oscillating stability of PER2 is sufficient to generate rhythmic PER2::LUC expression (output).
(H-J) Immuno-gold localization of Snap29 in cryo-sections of S2 cells in pro-metaphase. Pseudo-coloring in red identifies chromosomes (Ch), in yellow membrane organelles and in green MTs. The white arrows in H-I indicate examples of signal in the nucleoplasm that is not associated to membranes, but rather, to electron-dense material. MVB: multivesicular body; NE: nuclear envelope; PM: plasma membrane.
(B) Immunohistochemical costainings of TREM2 (magenta) and IBA1 (green) microglia in the cortex of isotype control and 4D9 injected WT and APP-NL-G-F mice. Side panel shows images from each staining at a larger magnification indicated by the dotted white boxes. Scale bar = 10µm; scale bar (inset) = 2.5µm.
(G) Quantification of the percentage of cells that constricted (to an area < 50%, yellow), cells that showed impaired constriction (to an area >50 and <100%, green) and cells that expanded (to an area >100%, blue) after 7 min in control embryos and in βH-spectrin knock-down embryos.
B Venn diagram showing overlaps between Scl, Hand1 and Gata4 (Oda et al, ) binding sites in Flk1+mesoderm documents that some of SclMES binding sites are also bound by cardiac TFs.
(A) Quantitative analysis of Rnf114 mRNA by realtime-PCR in various mouse tissues and organs shows that Rnf114 was predominately expressed in oocytes.
E. Enhanced microglial clustering around amyloid plaques in the absence of PGRN. Left: IBA1-stained microglia clustering around X-34-positive amyloid plaque cores in 4-month-old APPPS1/Grn+/+ mice. Right: Age-matched APPPS1/Grn-/- mice display microglial hyper-clustering around amyloid plaques compared to APPPS1/Grn+/+. Dotted white boxes indicate the area that is shown at higher magnification. Scale bars indicate 10µm and 3µm in inset. Immunohistochemical quantification of IBA1 positive microglial cell number per plaqu
(E) Clonogenic assays in the presence of 3 µM PLX4032, and with or without IPTG (200 µM) as indicated. The graphs represent the mean number of colonies in 3 independent experiments (Student's t-test).
B Western blot analysis of liver lysates (100 µg) shows that intein-mediated protein trans-splicing efficiently reconstitutes full-length eGFP. Single AAV: n=5; AAV-intein: n=5. Arrows indicate both full-length eGFP and excised inteins. C Quantification of eGFP protein bands. Values are reported as mean±SEM. Each dot represents the eGFP protein band quantification from animals injected with either single AAV n=5 or AAV intein n=5.
(D) Methylated RNA immunoprecipitation (MeRIP)-qPCR analysis of m6A levels of Hif1a mRNA in siCtrl and siFto 3T3-L1 cells. Data information: The data were presented as the mean ± SD of triplicate tests (n = 3). Statistical analyses were performed using Student t‐test.∗∗p < 0.01, ∗∗∗p < 0.001.
B Correlation plot for kidney mRNA expression of Sirt7 and Slc12a7 that codifies KCC4 in the mouse BxD genetic reference population (www.genenetwork.org).
Manual PAR scores were divided in to quartiles and then were compared to progression-free survival in the CRPC TMAs. *=p<0.05, ns=not statistically significant by Log-rank (Mantel-Cox)
Correlation between ChgB puncta per neuron and total neurite length (mm) for uninfected control (grey) and NPY-pHluorin infected (green) neurons. Linear regression, inset shows goodness of fit (r2) and significance (p-value) per group. Slopes are not significantly different, ANCOVA: p = 0.19.
(A) Representative western blot showing a mildly altered protein acetylation pattern (Anti AcK) between 1 week (young) and 4 week (midlife) old flies. Tubulin served as a loading control. N=4-5 per group. Tub, Tubulin.
(E) Confocal images of GFP‐S‐Ubqln1 WT in Hela cells transfected with RFP, RFP‐Ubqln4 or RFP‐Ubqln4 ΔUBL.
(G) IceLogo representation of the protein N-termini with modified NTA yield vs proteins with unmodified NTA yield. The color symbol associated to each residue is Black is aliphatic, green is small hydrophilic.
(B,C) Confocal images of HeLa cells transiently transfected with DOR or GFP‐LC3 and incubated with 50 nM Lysotracker in DMEM or HBSS. Scale bars, 10 μm.
D Heatmaps showing pairwise comparison of MPRA activity for all constructs (mRNA/DNA) between donors - left panel: resting CD4 T cells; right panel: stimulated CD4 T cells.
(B) Modelled structure of C. elegans UAF-2 binding to 5'-UAGGU-3'. The structure was modelled based on sequence homology to U2AF23 from S. pombe (Appendix Fig S9) and crystal structure of S. pombe U2AF23/U2AF59 complex bound to the RNA (Yoshida et al, 2020). N-terminal Zn finger 1 (ZnF1), U2AF homology motif (UHM) and C-terminal Zn finger 2 (ZnF2) domains are colored in blue, yellow and green, respectively. Red spheres indicate zinc ions. The position of the amino group methylated upon m6A modification (N6) is indicated with an arrowhead.
Mice were injected with Ctrl or STING-KO MC38 cells, and treated with PBS or 5-FU. (D) Pictures of tumors and spleens from a representative experiment. Image panels were cropped from the same picture.
(g) Midguts dissected from animals at puparium formation that contain Uba1H33 loss-of-function MARCM mutant cell clones (GFP-positive) that are stained with p62 antibody and analysed by fluorescence microscopy. Control wild-type and heterozygous cells have no GFP. Representative images are shown.
(d) Confocal image of a GFP-positive patched-expressing clone, with mCherry-Atg8a expressed in all cells. Fat body was dissected from well-fed larvae and imaged after formaldehyde fixation.
(C) The interaction between TRB1 and EPCR1. Arabidopsis plants carrying TRB1-Flag and/or EPCR1-Myc transgenes were used for co-IP.