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B Seedlings were grown for 7 days in W at either 22ºC, 2 days at 22ºC then transferred to 28ºC for additional 5 days (22ºC > 28ºC) or for 7 days at 28ºC, as represented in the panel. | [
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(D) Histogram of spatial initiation probabilities of DDB on static GMPCPP-microtubules. 294 initiation positions were detemined (from three experiments). Concentrations of DDB components as in B. | [
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D Schematic illustration of the proposed 'Cristae fission and fusion' (CriFF) as a working model and its link to CJ dynamics. | [
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B. Testes from Gemc1-/- mice have strongly reduced cellularity compared to Gemc1+/+ or Gemc1+/- animals, as measured by disaggregation of the tissue and cell counting with a Neubauer Chamber (n=3). Mean and standard deviation are indicated. | [
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A. Age-dependent reduction of lamin B1 in the SGZ. As early as 5.5 months of age, the levels of lamin B1 in the SGZ were markedly reduced. Insets show higher magnification images in the SGZ. | [
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C, Normalized spectra of livers and kidneys from a control (healthy) and a subject with hepatic steatosis. Each spectrum is from the same animal. Data information: In the figure, A.U. = arbitrary units | [
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Eight-week-old male WT and DOCK5-/- mice were fed a SD or HFD for 3 months. Experimental procedure for lipid infusion and the hyperinsulinemic-euglycemic clamp (HEC). | [
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Volcano plot depicting differentially expressed RNA-seq genes at 10% FDR after 12 weeks of treatment. Significantly different mammalian mitochondrial genes (MitoCarta 2.0) are annotated. | [
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(D) Cyclin A2dd cells with inducible CycB1-YFP (B1-WT) and CycB1-YFP-NLS (B1-NLS) were analysed for DIA induced cyclin B1 expression / cyclin A2 depletion. Samples were collected at indicated time points and probed by immunoblotting with cyclin B1 and cyclin A2 antibodies | [
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(F) ELISA of IL-1β in the supernatant of WT, NLRP3 KO or AIM2 KO THP-1 cells with ZIKV (MR766 or GZ01) (MOI=1) or DENV-2 (MOI=1) infection for 36 hrs. | [
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Tetraploid cells expressing Cap1-mNeonGreen were grown on PRE-SPO medium supplemented with 20 mM ascorbic acid, 1 mM DTT, or 1 mM glutathione for 24 h at 37°C. Cell images were analyzed to determine the percentage of viable cells with activated Cap1. | [
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K, L Immortalized and RAS-transformed MEFs were treated with either 10 μM metformin (K) or different concentrations of glucose (L) for 7 days. Individual proteins were detected by immunoblotting. | [
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F. GSEA plots of DEGs for early-fetal gene sets. G. GSEA plots of DEGs for late-fetal gene sets. Data information: *p<0.05, ** p<0.01, ***p<0.001, determined by nominal GSEA p-value. NES, normalized enrichment score. | [
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Caspase inhibitor QVD prevents caspase-3 activation/PARP cleavage by GPRC5A depletion in hypoxia. | [
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B, C Histology sections of mammary glands from a 5‐day‐old (B; n = 7) and a 10‐day‐old (C; n = 5) Wnt4::Cre; mT/mG female stained by double immunofluorescence microscopy for EGFP (green) and PR (magenta, not detected), counterstained with DAPI (blue). Scale bar: 50 mm. | [
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Tumor infiltrating immune cells were isolated from the either CT26 or MCA205 tumor bearing model and analyzed for the expression of BODIPY in CD206+ (black) and CD206- (grey) cells. | [
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C, Western blot analysis of DRP1, GAPDH (cytosolic marker) and TOM20 (mitochondrial marker) protein in cytosolic and mitochondrial fractions treated or not, with 2µM Mito-C as indicated. D, Quantification of western blots showed in C and expressed as a distribution of DRP1 in the cytosolic and mitochondrial fractions. Errors bars show the standard deviation (SD) of 5 independent experiments. E | [
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B. UMAP plots colored according to cell type identified by transcriptional signatures using the Immgen database as a reference. | [
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qRT-PCR showing the expression levels of EMX2 and HOXB9 in the indicated cells treated with EZH2i or a DMSO control for 12 days. Values represent mean ± SEM from three biological replicates. Two asterisks indicate p-value < 0.01 (one-tailed unpaired Student's t-test). UT: untransformed, TR: transformed. | [
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(c) HCT116 cells (107) or stable FoxO1-knockdown HCT116 cells (107) were injected into the left or right hind legs of three nude mice. Six weeks later the mice were killed and the tumours were weighed and analysed (bottom graph). Tumour weights were 0.08 ± 0.10 g (without FoxO1 RNAi) and 0.48 ± 0.06 g (with FoxO1 RNAi), P = 0.020. Data are means ± sd. n = 3. | [
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A t-SNE map of combined scRNA-seq transcriptomes of total tissue cells from 13 reduction mammoplasties. Cell colors correspond to tissue specimens. B Same t-SNE map as (A) but colored by cell cluster (with cluster resolution 0.05). C Ternary plot positioning each cell according the proportion of basal, LP or ML signature genes expressed by that cell. The plot shows the same cells and cell colors as for (B). | [
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(b) Confocal images of the 150Q Neuro2a cells transfected with R, RH, RS, RHS, RQ and RHQ. Molecules containing QBP1 co-localized with the tNHTT-150Q-EGFP inclusions (bar, 5 μm). Cells with inclusions were chosen to illustrate the co-localization of QBP1-containing molecules with tNHTT-150Q-EGFP. | [
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E. Nucleation of the first cofilin domain onto 5 µm-long actin segments. Filaments are exposed to 20 nM mCherry-cofilin-1 from time t=0 onwards. N = 60 filaments, from 1 experiment for each condition. P-value = 4.10-15 (log-rank test). Data information: Thick solid and dashed lines are survival fractions calculated from the experimental data. Thin grey lines are single exponential fits. 95% confidence intervals are shown as shaded surfaces. | [
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Nascent RNA profile of AT5G41750. Nascent RNA RT-qPCR assay measuring RNAPII signal at 3 positions (dark red bars: probe 1, 2 and 3) on the gene upon flagellin 22 treatment in a 0 minute, 2 minutes, 3 minutes and 4 minutes time course. Nascent RNA signal values were normalized to reference gene ACT2. Error bars represent SEM from 3 independent replicates. The statistical significance of differences between NRPB2Y732F and NRPB2WT at the same time point were assessed by the two-sided Student's t-test. n.s. denotes not significant; * denotes p<0.05 and ** denotes p<0.01. Scale bar (black) represent 0.5 kb. | [
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Immunofluorescence staining for Collagen I and P4HA2 and quantification (right graph) in HeLa cells after siRNA against RASSF1A. Scale bars 20µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test (2-tailed) of n=3 experiments and error bars represent the mean ± S.E.M. | [
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(C) Rate constants of SERCA-, NCX- and slow mechanisms-based [Ca2+]i decay in hiPSC-CMs. (D) Relative contribution of SERCA, NCX and slow mechanisms to [Ca2+]i extrusion in hiPSC-CMs. | [
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(H and I) High magnification of autophagic elements in unstarved Epg5−/− MEFs. (H) The red arrow indicates a complex autophagic vacuole containing multilayered membrane structures (white arrowheads) and a lipid-like region (L). (I) The red arrow indicates an autophagosome containing cytoplasm and ribosomes. The red arrowhead points to an autophagosome containing a mitochondrion and cytoplasmic material with membranous structures. The white arrow shows an aAV-III vacuole. | [
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A Immunofluorescence analysis of kidney sections from diabetic nephropathy subjects and non-diabetic controls stained with KDM6A, KLF10, nephrin and WT-1. Scale bars, 50 μm. *P < 0.05 by Wilcoxon two-sample test (n = 6 for each group). | [
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(C) The bar graph depicts ethidine fluorescence density in arbitrary units of aged and fresh SNOC treated neurons at 2.5 h. | [
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C) Western blot analysis of H3122 parental and isogenic drug-resistant cell lines for the indicated proteins. | [
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(A) ATX serum protein levels were measured in blood serum samples from IBD patients and healthy controls using ELISA: active UC (n=26), active CD (n=34), control (Con) (n=26). | [
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(C) Immunofluorescence images and fluorescence intensity profiles of ENKD1 and Ninein in serum-starved RPE1 cells. The arrow marks the centriole subjected to the line scan. Scale bar, 2 µm. | [
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(A) Gene ontology enrichment of stress- and Cdc55-dependent phosphorylation sites using DAVID v6.8. (Huang et al., 2009). Sets were defined according to phosphorylation site fold-changes in setup SR igo1∆igo2∆ (see Figure 2F). GO levels (of the category "GOTERM_BP_DIRECT") were required to be between level 3 and level 6, and GO terms should have at least two counts in the given set. The heat-map illustrates the respective fold enrichments for the resulting GO-terms in each set. The heat-map was sorted according to the enrichment values in Set1, and secondly according to the sum of the enrichment values in Set2 and all quantified phosphorylation sites in SR igo1∆igo2∆. | [
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F, SMMC cells were treated with 100 μM etoposide (+) or untreated (-) for 24 h, and Western blot analysis was performed. | [
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a) UnaG-based hypoxia sensing is applicable in vivo as shown here using the human Gli36 glioblastoma model. 500 Gli36 glioblastoma cells, constitutively expressing mCherry and stably transfected with the HRE-dUnaG sensor construct, were stereotactically transplanted into the cortex of a SCIDmouse. Shown is a 30 µm cryosection of a growing tumor 10 days after transplantation. Tumor cells are distinguished from the surrounding cortex by mCherry expression. Blood vessels were contrasted by immunostaining against PECAM-1. Expression of dUnaG was visualized by its green fluorescence and predominates in areas with reduced vascular density (outlined by white line in the composite panel (bottom right).b) Representative area from the tumor shown in a), which is located outside the viewfield in a) positioned more closely to the tumor border. Also at the tumor border UnaG-expressing cells are preferentially observed at a distance to PECAM-1+ vessels. | [
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A. Overview of biological material used for generating the liver proteome atlas. (hHSC: hepatic stellate cell, hHEP: hepatocyte, hKC: Kupffer cell, hLSEC: liver sinusoidal endothelial cell; TWNT4 and LX2: immortalized human hepatic stellate cell line, SK-Hep-1: human hepatic adenocarcinoma cell line, HepG2: human liver cancer cell line). Number of biological replicates is n=6 for bulk liver, hepatic artery and portal vein; n=3 for hHEP, hLSEC, hHSC, hKC and n=1 for HepG2, SK-Hep1, LX2 and TWNT4. No additional replications of the experiment was done in laboratory. | [
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E) Graph showing the relative expression of Cdkn1a in WY, WO, WG, YC and OC FAPs and MuSCs, measured by qPCR | [
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Representative H&E (top) and IF images (bottom) of control, dKO, and qKO airways at day 21 post tamoxifen treatment. Tomato (for Scgb1a1 lineage, red), CC10 (green), AQP5 (white), and DAPI (blue). Quantification of Scgb1a1 lineage-labeled tdTomato+CC10+ secretory cells in (G). Data are presented as mean ± SEM (n=3 mice for each genotype). | [
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F A schematic model for PABPN1L Function during the MZT. During oocyte maturation and fertilization, PABPN1L recruits BTG4 and CCR4-NOT deadenylase to the poly(A) tails of maternal transcripts and mediates cytoplasmic mRNA decay. At the molecular level, PABPN1L-Cter and BTG4-Cter2 mediate the BTG4-PABPN1L interaction, and arginine-171 determines the poly(A)-binding ability of PABPN1L. Furthermore, PABPN1L protects BTG4 from being polyubiquitinated by SCFβTrCP1 and degraded to create an expression window of BTG4 to mediate maternal mRNA decay. These events are prerequisites for ZGA. The gradient ribbons represent the indicated protein level and activity. Deep color represents a high level and activity. The functional domains of PABPN1L and BTG4 proteins are illustrated. | [
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C: Higher magnification showing LAMP1+ vacuoles (arrowheads) in prion-infected COCS. | [
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E, F Immunofluorescent analysis (E) and statistical quantifications (F) of the cell proliferation marker Ki67 in xenografts derived from T387 GSCs expressing shUSP33 or shNT. Disruption of USP33 in GSCs reduced cell proliferation in GBM xenografts. Scale bar, 80 μm. (n = 5 tumors for each group; ***, p < 0.001; mean ± s.e.m.; two tailed unpaired t-test). | [
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B. Plasmid-barcode based mapping of enriched variants across all targeted genes under AEC selection. The innermost circle represents the ORFs in the E. coli genome, with the green bars highlighting regions that were zoomed 50X. Positive log2 enrichment scores of variants under increasing selective pressures are plotted as orange bars facing outward. Not enriched variants are plotted in gray bars facing inward. Two distinct biological replicates are combined in this plot, using a weighted enrichment score (described in the methods section) | [
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total eFluor780+ events in the BAL of adult Csf2ra-/- recipients 1 year (F, G) after neonatal transfer of cells described in A (n = 7 mice). Age-matched Csf2ra-/- (KO) (n = 5 mice) and WT (n = 4 mice) were included as negative and positive controls. | [
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(E-F) miR-515-5p directly interacts with NRAS, MARK4 and PI3KC2B's 3'UTR. Relative luciferase activity levels were measured 24 h after co-transfection of MCF-7 (E) and MDA-MB-231 (F) with 3'UTR-luciferase reporter constructs and either with miR-515-5p or miR NC. Data shown are normalised mean of three independent experiments ± SEM. (B-F) P values were calculated by t-test between miRNA conditions and their respective NC conditions (*, P<0.05; **, P<0.01; ***, P<0.001). | [
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Effect of calpain inhibition on mitochondrial Ca2+ levels recorded with GCAMP6f (H) in cells treated with cl-HK2pep . Data information: Experiments throughout the Figure are carried out on HeLa cells; cl-SCRpep, negative control of cl-HK2pep (2 μM each); where indicated calpain inhibitor PD150606 (50 µM each) are pre-incubated 1 h before peptide treatment. | [
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D. Representative immunoblot of MMP10 and caveolin in ultracentrifuge-enriched microvesicle proteins from cell-conditioned media following treatment with vehicle (-) or 1 µM 4HT for 24 h as well as MMP10, caveolin and GAPDH in cell lysates (top left). Absolute arbitrary unit values for MMP10 levels in western blots of ultracentrifugation-enriched microvesicle proteins (bottom left). Means ± SEM (n=4), p value by ratio paired t test. Ratios of MMP10 to caveolin (bottom center) or to total microvesicle proteins (bottom right). Means ± SEM (n=4), p value by ratio paired t test. | [
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(C) Lysosomal pH values in WT and NDST3 KO RPE1 cells calculated from the fluorescence ratio of LysoSensor Yellow/Blue dextran staining against the pH calibration curve in (B) (n = 3 independent cultures, *P = 0.0242). (D) Lysosomal pH values measured for WT and NDST3 KO RPE1 cells after the treatment with Baf A1 (100 nM, 1h) (n = 3 independent cultures, *P = 0.0305). Data information: Error bars represent ± standard deviation. Scale bar, 10 μm. | [
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D Results of blind histopathological evaluation of Tsc2-deficient 105K tumors treated with vehicle or drugs, in monotherapy or in combination with rapamycin. The histograms show the proportion of defined phenotypic scores: 1+, < 5% of the tumor; 2+, 5-50% of the tumor; and 3+, > 50% of the tumor. Cytological atypia was graded as mild (1+), moderate (2+), or severe (3+). Significant differences relative to rapamycin were determined using Fisher's exact test (epithelioid ***P = 9x10-4 and *P = 0.025; fibrosis, clorgyline and loratadine *P = 0.015, and rasagiline *P = 0.032; glandular, clorgyline *P = 0.030 and rasagiline *P = 0.045; and atypia, loratadine P = 0.010). | [
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(A) AUT2 is identical to YNL223w. Genomic fragments of complementing plasmids and constructed subclones are illustrated. X, XbaI; B, BclI; N, NruI; H, HindIII. | [
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(a) Histological section to demonstrate the individual cell layers of the zebrafish retina. The photoreceptor layer (PR, comprising rod and cone photoreceptors) lies immediately adjacent to the retinal pigment epithelium (RPE) at the outermost surface of the eye. Thioflavin-S labelling of retinal sections was used to identify neurofibrillary tangles in the photoreceptor layer (marked with yellow dotted lines). No labelling was observed in the retina of rho::GFP at 8 d.p.f., whereas distinct thioflavin-S-positive tangles (arrows) were observed in the photoreceptor layer of rho::GFP-tau fish. Note, the RPE is highly autofluorescent due to the presence of silver pigment. High power regions are shown in the top right of each panel. | [
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In situ hybridization of Mettl5 transcript at different embryonic stages. The central nervous system (CNS) is highlighted in the schematics. Data retrieved from FlyExpress 7. (http://www.flyexpress.net/search.php?type=image&search=FBgn0036856). | [
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D Western blot for adiponectin (ADPOQ) released into the media during differentiation by 3T3-L1 adipocytes transfected with the indicated si-RNAs. Ponceau stained image provides loading control. | [
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Nuc/Cyto ratios in MCF-7 cells (ENCODE data) for genes bound by hnRNPK (from (B)) and other genes. Enrichment ratios and boxplots are as in C, P-value computed using two-sided Wilcoxon rank-sum test. | [
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(c) The Ulk1 S317/777A mutant is defective in autophagosome formation. The indicated MEFs were starved of glucose (4 h) and the formation of GFP-LC3-positive autophagosomes was examined by confocal microscopy. GFP-LC3; green and DAPI; blue. Scale bar, 20 μm. | [
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survival rate (B) of the egr2-3 mutant and egr2/EGR2:EGR2-Myc complementation lines under non-acclimated (NA) and acclimated (CA; 4 d at 4°C) conditions. Two-week-old seedlings grown on MS medium containing 0.8% agar were treated at −5°C for 0.5 h (NA) or −8°C for 0.5 h (CA). Data information each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test). | [
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B) Conceptual mathematical modeling schematics depict TNF-induced necroptosis signaling via RIPK1/3 (RIP) and phosphorylation of MLKL (pMLKL). RIP is counteracted by a putative (B) stimulus-induced, NFκB-dependent survival factor X. | [
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DNA and crRNA sequence used for experiments of a single target and multiple PAMs. DNA sequence is shown for the single-target single-PAM construct and schematic representation is shown for multiple-PAM containing constructs. | [
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An equivalent experiment was setup as in (A) but now 2 μM dimerizer was added after 60 seconds. Conjugated cells were maintained in the dark to maintain OptoCAR signaling. Bounded line shows mean ± SEM (n=3). | [
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scRNAseq was performed on sorted CD45+, Annexin V-, BM cells from a pool of two control mice and two IFNγ-treated mice at day 12, and on a pool of two control and two pools of two IFNγ-treated mice on day 17 (blue and yellow dots in Fig. 1B indicate the individual mice from the CTRL and IFNγ groups, respectively). (E) Heatmap showing top marker genes (obtained from unsupervised clustering) used for custom classification of cells that belong to the lymphoid compartment. | [
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(B) cis-eQTLs and the associated genes identified in females, males, and in both sexes (FDR < 20%). | [
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D The mRNA levels of VSV and RBM47 in blood samples of IFNAR1 deficient (IFNAR1-/-) mice (n = 6 per group) infected with VSV. Mice were infected with shmRBM47 or control lentivirus for 7 days and then challenged with VSV for another 24 h. Each dot represents one mouse. The PCR results are represented as the means ± SD of n = 6 biological replicates. Data information: The data shown are representative of n = 3 independent experiments. NS, non-significant; **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test). | [
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F Quantification of 18F-FDG uptake in indicated tissues from mice in (E). After the 18F-FDG PET/CT imaging, indicated tissues were harvested and the radioactivity was measured by scintillation counter. n=5 for both groups. *P<0.05 relative to GFP by Student's t-test. N.S., not significant. | [
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(A) Percentage of regenerating axons after laser axotomy of DIV 14-17 rat cortical neurons expressing either GFP (control) or GFP and p110δ in the presence of the indicated inhibitors, 14h after laser injury. Numbers on bars are injured axons per group. | [
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C. Average dynamics of nucleoid separation and cell constriction for WT and the ΔmatP mutant strain. The cumulative distributions of the fraction of cells with two nucleoids (blue) and of the fraction of cells with a constriction degree above 0.15 (red) were plotted against cell age. Cell age was calculated according to the rank of each cell based on their cell length with the formula $\text{age}_{i}\left( F \right) = \ - \frac{ln(1 - \frac{F}{2})}{ln(2)}$, where F represents the fraction of cells with a cell length equal or below the length of cell i (Wold et al, 1994). D. Same plots as in C for three strains clustering in island 8 with the ΔmatP strain. The WT curves shown in C were plotted in gray for comparison. E. Same plots as in C for two island-8 strains, ΔycjV and ΔhslU, and the ΔhslV strain, which does not partition in island 8. | [
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(B, C) RNA isolated from untreated or MG132-treated (20 µM, 2h) control or NRF2 siRNA transfected cells were subjected to qRT-PCR with primers of genes as indicated. The fold induction in MG132 treated samples is calculated relative to untreated samples. Mean ±SD, n=3, *p < 0.05 (Student's unpaired t-test). Data information: Unless otherwise stated, scale bar: 10 µm. | [
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Control cell line (Tgfbr2wt) (A) and two Tgfbr2-mutant cell lines (Tgfbr2mut1 and Tgfbr2mut2) (B-C) were treated with TGFβ at different time points, and cell growth (MTT) assays were performed. P value by t test is shown. NS, not significant. | [
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During ESC differentiation towards meiotic germ cells in vitro (X-axis), the X-chromosome inactivation status (Y-axis) differs between cell populations and is associated with distinct meiotic germ cell potential in PGCLCs. While somatic cells go through the most complete X-inactivation (red line), EpiLCs and subsequently PGCLCs reach moderate X-inactivation levels (PGCLC XGFP-), or escape X-inactivation entirely (PGCLC XGFP+). XGFP- PGCLCs, which have undergone moderate X-inactivation followed by gradual X-reactivation (green arrow, orange and red cells) are most efficient in differentiating into meiotic germ cells and can develop into oocytes and primary follicles. On the other hand, XGFP+ PGCLCs, which have never gone through X-inactivation and stayed constitutively active (light green cells), or XGFP- PGCLCs, which have reactivated too rapidly (dark green cells), do not show efficient entry into meiosis and mostly display an abnormal mitotic character. | [
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E,F, Co-immunoprecipitation experiments in HEK293T cells transfected with the constructs shown in (A). In (F) cells were co-transfected with DVL2 as indicated. Unspecific bands resulting from antibody cross-reaction are marked with asterisks. Representative blots of n ≥ 3 independent experiments are shown. | [
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(A-A''') Immunostaining of Smo protein (red) and full-length Ci (light blue) in discs expressing en-Venus. Smo is expressed at higher levels in the P compartment and in a stripe 5-10 cells wide just anterior to the A-P compartment boundary. White arrowhead indicates cells just anterior to the A-P compartment boundary. | [
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G,I Up, Representative γ-H2AX immunofluorescence (green) in wt and junD-/- fibroblasts before (-) or after γ-irradiation (2Gy, 45 min) (G). Blue signal corresponds to DAPI staining. Down, box-plots of large γ-H2AX foci per nuclei (diameter > 0.8 μm). At least 50 nuclei per genotype have been used for quantification. | [
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Calculation of active mitochondria using the JC-1 assay by genotype in control and PKAN lymphoblasts. | [
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(C) Kymographs showing fluorescently-tagged Klp5/Klp6 (Kinesin) co-imaged with fluorescently-tagged microtubules (MT) in the presence (top panels) and absence (bottom panels) of Mcp1. Banding on MT, caused by unequal incorporation of fluorescence, illustrates the force exerted on the MT by continued growth into the cell cortex. Dashed yellow line indicates the cell end | [
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(a) Intracellular ATP in fresh lysates of Atg5f/f and Atg5f/fCD19-Cre splenic B cells activated for 3 d with LPS (3) or left untreated (0). | [
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(E) DA level (pictograms per head) in the head of males of the indicated genotypes. n = 4 (100 heads per genotype). | [
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(A) Effect of HDAC6 over-expression or CAMDI co-expression on the level of acetylated α-tubulin in the centrosome. HeLa cells co-transfected with Centrin2-EGFP with/without HDAC6-HA and FLAG-CAMDI were immunostained with anti-EGFP (green) and anti-acetylated α-tubulin antibodies (red). Scale bar, 1 μm.(B) Quantification of intensity of acetylated α-tubulin at centrosome. n = 25, 30, 30 cells. *, p<0.05, One-way ANOVA with Bonferroni's post hoc test. Data are presented as mean ± SEM. | [
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F. Kaplan-Meier survival analysis of Kaplan-Meier plotter (http://kmplot.com/analysis/) for the relationship between the relapse-free survival (RFS) or overall survival time (OS) of breast cancer patients (BRCA, n=349 (low)/205 (high)), liver cancer patients (LIHC, n=270 (low)/100 (high)), patients with kidney renal clear cell carcinoma (KRIC, n=156 (low)/374 (high)), and patients with kidney renal papillary cell carcinoma (KIRP, n=208 (low)/79 (high)) and their expression of hTrmt13. | [
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C) STRING network of proteins enriched on H2AQ105me (highlighted in red are proteins involved in ribosome biogenesis). | [
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D). Western blot of LMF1-partners after pBPA photo-crosslinking and affinity tag purification. The DMSO panel does not include pBPA and serves as a negative control. Fractions were eluted with increasing concentrations of imidazole. An arrow points to LMF1 | [
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A. Autophagic vesicles marker GFP-TgAtg8 was found in the cytosol of tachyzoites and occasionally in punctate vesicles in recently egressed parasites. | [
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Western blot analysis of CTFβ (A) levels upon miR-132 down- (ant-132) (left panel) or upregulation (miR-132) (right panel) in APPPS1hippocampus at six and three months of age, respectively. Sample size, n=9 per group for miR-132 down regulation and n=6 per group for miR-132 overexpression. Values were normalized to respective control groups and presented as mean ± SEM. The Student's t-test was used. | [
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A) Pg381 and mutant strains count after 24 hr incubation with human MoDCs with/without Rapamycin treatment. The survived bacteria were measured after maintaining the lysed MoDCs suspension in anaerobic broth for 5 days. The plot represents the means ±standard deviation of CFU within MoDCs harvested from three healthy individuals (* P<0.001). The analysis of readings used One-way AVOVA analysis of different groups and Tukey's test for multiple comparisons. | [
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Schematic of the constructs used for conditional expression of AID in epithelial cells. An AID-IRES-GFP cassette preceded by a transcriptional STOP flanked by LoxP sites was introduced by homologous recombination within the endogenous Rosa26 locus (R26AID+/KI mice, top). R26AID+/KI mice were bred with Villin-CRE and p48-CRE mice to achieve specific AID expression in colon and pancreas, respectively (bottom). | [
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QPCR validation of transcripts involved in the stem cell signalling pathway that are upregulated upon 5'-tsRNA knockdowns using ASOs. (n =2) Error bars represent SEM, significance was calculated using unpaired t-test. | [
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(M and N) Expressing pseudo-phosphorylated Tau (TauS199E) further increased the K49-acetylation of β-catenin. N2a cells were transiently transfected with Vec, Tau40 or TauS199E for 48 h, levels of K49-acetylated β-cat, total β-cat and total Tau were detected by Western blotting (n=3 biological replicates each group). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Vec ; #, P<0.05, ##, P<0.01, ###, P<0.001 vs β-cat WT plus vs Tau (N) Data were analyzed by one-way ANOVA | [
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D Model showing the proposed membrane topology of Mpc1 and Mpc3. Whereas Mpc1 has only two transmembrane helices, Mpc3 has three. | [
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Peripheral mitochondria were quantified in WM3734 cells with stable knockdown of TMX1. A peripheral mask was applied based on the membrane staining (CellMask Green) and mitochondria covered area (MitoTracker DeepRed) was evaluated (see Fig. 9). Representative images (I) and quantification (J). In (J), data are presented as mean ± SEM (n values: control=163, TMX1 kds=116). | [
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D, E Analysis of shScramble (gray)‐ and shIP3R(1,3) C (green)‐expressing DCs migrating in micro‐channels in the presence of 20 μM ML7 (n > 70 cells per condition from 3 independent experiments). Velocity fluctuations (ΔV/V0) of immature DCs migrating in micro‐channels (D). Boxes illustrate 10-90 percentiles of values, and whiskers represent the range of values. P‐values were calculated using a Kruskal-Wallis test. Frequency of changes (E) in direction observed in DCs migrating in micro‐channels. Means plus SD are shown. A Kruskal-Wallis test was applied for statistical analysis. | [
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C Clustering of mitophagosomes (white arrows) co-labeled by antibodies against LC3 and Cyto c or p62 and HSP60 within swollen/dystrophic presynaptic terminals indicated by synaptophysin (SYP) surrounding amyloid plaques in AD mouse brains. | [
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E) Representative blots of Miro1, Miro2 and actin from whole cell lysates of wild-type and Miro1-floxed ERT Cre-recombinase MEFs treated with and without 4-OH tamoxifen for 48 hours. Lysates were taken one day after the end of treatment. | [
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Number of cells showing γH2AX foci in intestine and lung tumors samples of mice treated with vehicle or with ETP-47037 for 10 days. Representative images are shown to the right (n = 4). | [
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A Primary hippocampal neurons were stained for Actin and Ankyrin G. A comparison between PFA- and glyoxal-fixed samples shows that actin staining with phalloidin works as least as well in both, showing the prominent actin rings. Ankyrin G staining is brighter in PFA-fixed cells. | [
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Scheme showing an overview of Shp2‐dependent signaling systems and target genes, which are involved in senescence and cell cycle programs in PyMT tumorcells. | [
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C. Compared to mock organoids (i), SARS-CoV-2-exposed Day-15 organoids display SARS-CoV-2-positive cells (AB4, green) in their outer periphery, a region of the cortical plate (ii) that is specified by TUJ-1-positive neurons (magenta). L, the lumen of a VZ, the inner area of an organoid where NPCs are located, is free from SARS-CoV-2-positive cells. Magnified region (dotted while box) is given below. At least ten organoids from five different batches (n=5) are tested. Figures display scale bars. | [
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The Western blotting illustrates the overexpression of SRSF2 in sorted GFP+ cells on day 5 during differentiation, which were induced with DOX from day 2.5 to 5. GAPDH was used as the loading control. The bar graph presents the quantification of SRSF2 protein expression. The P-value was determined by an unpaired two-tailed Student's t-test. | [
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C. LAMP-1 immunofluorescence of HeLaWT and HeLaVPS41KO cells. Similar to patient derived fibroblasts more LAMP-1 positive compartments are seen in HeLaVPS41KO cells (quantified in C'). >10 cells per cell line per experiment were quantified (n=3). Scale bars, 10µm. | [
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Representative images of β-galactosidase staining in TOPGAL rMC (D) BALO cultures before (day 6, control) or 5 days after treatment with either 4 μM Scra or mo142-3p (day 11 of co-culture). BASC and rMC were isolated form the lung homogenate of TOPGAL mice. β-galactosidase+ rMC at day 11 of culture are indicated with arrows. | [
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SPEN and proteins of the m6A RNA methylation machinery interact with the A repeat to initiate X-linked gene silencing; PCGF3/5-PRC1 recruitment via hnRNPK interaction with the B and C repeats is responsible for the accumulation of H2AK119ub and concomitant enrichment of the PRC2-mark H3K27me3 over the entire X chromosome. In the absence of B and C repeats, there is no enrichment of PcG marks in intergenic regions, but a slight increase at silencing X-linked genes is seen; this could be caused by passive recruitment induced by gene silencing; nevertheless, recruitment of these marks are necessary to stabilize the initial silencing mediated by the A repeat interactors. | [
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Molecular structure of CEACAM1 (CC1)-N, in which each strand of the IgV structure is coloured differenty. | [
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B) Representative images of donor (upper panel) and acceptor cells (lower panel) after 24 h co-culture. Donor cells were loaded with α-synuclein fibrils prior to co-culture with GFP-transfected acceptor cells; in red: α-synuclein fibrils, in green: acceptor cells and in blue: nuclei. Scale bar represents 10 μm. (n = 3 independent experiments). A larger field where donor and acceptor cells are shown is presented in Figure EV 3A.(C) Percentage of donor and acceptor cells containing α-synuclein fibrils after co-culture as in B: all acceptor cells received α-synuclein fibrils.(D) Quantification of the number of α-synuclein fibrils in donor and acceptor cells after co-culture as in B. Donor cells contain around 70 α-synuclein fibrils puncta (median) while acceptor cells contain 38 α-synuclein fibrils puncta, respectively (****, p < 0.0001 by two-tailed Mann Whitney test).(E) Quantification of the average size of α-synuclein fibrillar foci in donor and acceptor cells after co-culture as in B. (****, p < 0.0001 by two-tailed Mann Whitney test). In Figure EV 3 is shown an example of α-synuclein fibrillar puncta detection in an acceptor cell. After detection, the number and the size of foci were determined using the ICY software. | [
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