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d, UMAP visualisation of 19,285 stromal and immune cells aligned and visualised as represented in b. | [
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(E, F) c-Maf quantification by qPCR (E) and cytokine concentration (F) in the supernatants of adult and cord blood ILC2s unstimulated, stimulated for 3h with PMA-Ionomycin (3h stim) and stimulated for an overnight with IL-33 and then 3h with PMA-Ionomycin (o.n. stim). ILC2s were sorted from 3 different donors. (E) Multiple T tests, unstimulated: p=0.000101; 3h stim: p=0.0036. (F) Multiple T tests, IL-13: p=0.022; IL-5: p=0.015 (*p<0.05). Bars represent mean ± SEM. | [
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B) Protein structure of MKKK7 and mutated versions of MKKK7 with the protein kinase domain shown in yellow and an ARM/HEAT repeat domain shown in blue. The position of the phosphorylated Serine residues is indicated with triangles and bold S below the protein structure. The red triangles indicate phosphorylated Serines that were targeted for mutagenesis or the corresponding phospho-mimic Aspartic acid. Blue triangles indicate the substitution with the non-phosphorylatable amino acid Alanine. Amino acid substitute versions of MKKK7 are shown below the wild-type. S, Serine; A, Alanine; D, Aspartic acid. | [
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(D) Mms4-Flag10 phosphorylation analyzed by immunoblot in wild type cells exposed to CPT. Wild-type cells were synchronized in G1 with α-factor, treated with DMSO or 50 µM CPT, let in G1 for 1 h, and released into S phase. Cells were collected at the indicated time points and Mms4 was immunodetected with anti-Flag antibodies. Clb2 immunodetection serves as a marker for G2 phase entry. FACS profiles corresponding the experimental setup are also shown. Two biological replicates have been performed. | [
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(G) Hematoxylin and eosin (HE)‐stained gastrocnemius (GA) sections from 6‐mo‐old Con and KO mice. Myofiber cross‐sectional area (μm2) is shown (n=3). | [
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Comparison of NUP58 mRNA abundance between late (P19) and early (P1) passage in wild-type cells (WT, top) and clone C5 (bottom). mRNA was quantified using qPCR and five independent probe sets amplifying different regions of NUP58 mRNA. Annealing of the probe sets is indicated at the bottom of the NUP58 structure. Relative mRNA abundance between P19 and P1 is color-coded for each exon analysed (according to the color bar shown below). Red triangles highlight the position of the identified mutations in C5. | [
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In vivo effect 24 h after hydrodynamic injection of B mice with plasmids expressing anti-miR-511 (n = 9), anti-miR-CTR (n = 9) or PBS (n = 10). TNFR1 protein levels in the liver were measured by ELISA 24 h after hydrodynamic injection (left panel). Survival of B mice injected with 20 μg TNF, 24 h after hydrodynamic injection (middle panel). Mice pretreated with anti-miR-511 (grey, n = 10) were significantly sensitized for TNF-induced SIRS compared to control groups and had the largest drop in body temperature (right panel) 12 h after injection of 25 μg TNF. | [
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(G) Strong immunoreactivity of the PBX1 direct target, NFE2L1, was also detected as very well defined nuclear punctuate structures in NM+cells of the SN in control samples (arrowheads), but were dramatically reduced in PD patients. Yellow asterisks indicate the nucleoli. (H) Percentage of NM+ neurons showing nuclear NFE2L1 staining in the SN of control donors and PD patients. (I) Graphical representation of all individual controls and PD patients analyzed, showing that NM+neurons with NFE2L1+nuclei in the SN of PD patients are less than 10% or are totally absent. | [
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H. Western blot analysis of input lysates and anti-BRD9 immunoprecipitations (IPs) from cells described in (G) expressing wt BRD9 or the chimeric BRD7DUF. The indicated proteins were detected with specific antibodies. Data are representative of two biological replicates. | [
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N, O Expression pattern of J2341 in WT (N) and seu-3 (O) seedlings at 5 DAG. P, Q Expression pattern of CS9227 in WT (P) and seu-3 (Q) seedlings at 5 DAG. In white arrows indicate the CSCs. Scale bars: 20 μm. | [
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Mice were injected with Ctrl MC38 cells or Ifn-DKO cells and treated with 5-FU or PBS. (G) Tumor volumes were quantified at the indicated days post cancer cell injection. N=5. | [
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L IFA of DHHC2 and ISP1 in zygotes of dhhc2kd parasites complemented with 4Myc tagged WT PyDHHC2 of P. yoelii, PfDHHC2 of P. falciparum, or PyDHHC2 with PAT catalytic deficient mutation C128A. Scale bar = 5 μm. | [
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Representative skin phenotypes of Foxn1nu/nu (Nude), or KRT14-cre; Aff4flox/flox (Aff4 cko) mice are shown macroscopically or histologically after hematoxylin and eosin staining (H-N). The phenotypes compared are as follows: hair coats, 4-month-old adults; (E-G) vibrissae, P7; (H) hair follicles with growing hairs, juveniles; (I-K) regressing hair follicles, juveniles; (L-N) epidermis, P9. In panel H, micrographs from left to right are WT, Nude, and Aff4 cko. In panels I-K, HF marks examples of hair follicles. In panels L-M, arrowheads indicate the dermal/epidermal border; arrows mark examples of bent hair shafts. Scale bars: H, L-N, 20 µm; I-K, 40 µm. | [
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C Hematoxylin-eosin staining in scWAT showing multilocular adipocytes in Cdk4-/- (scale bar 50 μm). | [
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Representative multicolour flow cytometry analysis of 2 independent experiments showing TMEM119 and P2RY12 expression levels in CD11b+CD45int microglia of saline or LPS-injected mouse brains. For the unconjugated TMEM119 antibody, negative stands for primary antibody without secondary antibody. For P2RY12 antibody, negative represents isotype PE control. | [
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E. Proportions (Y-axis) and numbers (within bars) of cells arising from the different fusion ages are listed for each cluster. Numbers are down-sampled to 1221 cells in the smallest age group for proper representation. UMAP depicting the fusion age at which the cells were isolated. | [
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(A) Expression in E. coli and purification of human GS (hGS). Protein was separated by SDS-PAGE and stained with Coomassie Blue dye. M: marker Precision Plus Protein Dual Color Standard (Biorad). From right Lanes 1-4: E. coli Bl21(DE3) cells containing the expression vector without (lanes 1 and 2) and with (lanes 3 and 4) the coding sequence of hGS. Samples were taken immediately before (lanes 1 and 3) and 3,5 h later (lanes 2 and 4) the induction of expression with isopropil-β-D-1-tiogalattopiranoside (IPTG) 0.7mM. The same number of bacteria was analyzed in each sample. Lane 5: isolated and purified inclusion bodies (4 μg). Adiacent boxed lane: Western Blotting analysis of GS. | [
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(B) Visualization of major classes of spinal cord cells by integrated UMAP plots of cell clusters. Cell types are labelled and circled with dotted lines (top). Violin plots show the most distinct and commonly used marker genes for each cell cluster (bottom). Cell-type annotations are listed on the right and shown in varying colours. | [
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(E) No evidence for an epigenetic function of Pax5-Jak2 in early B cell development. The genome-wide distribution of the histone marks H3K4me3, H3K27ac and H3K27me3 in in vitro cultured Pax5Jak2/- and Pax5Prd/- progenitor cells was determined by ChIP-seq analysis The average density of the three histone marks in these progenitor cells was determined for a region from -2.5 kb to +2.5 kb from the summit of the Pax5-Jak2 peaks identified in Pax5Jak2/+ B-ALL cells The results of two different ChIP-seq experiments per cell type are shown. | [
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Heat-map indicating DEG patterns comparing SC-conv and SC-naïve macrophages stimulated with the S-protein. Z-score is indicated in a color score. | [
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(A) Total cell lysates prepared from the indicated HCT116 cell lines were analyzed by immunoblotting. For comparison, different amounts of proteins (1:3 ratio) were applied. An asterisk indicated non-specific crossreactive bands. | [
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Quantification of ABCA1 immunoblots from primary BMMs infected as in (A). Representative immunoblot is shown in Supplementary Fig S7E. LXR ligand stimulation with 1 μM T0901317 or vehicle control was performed for 8 h or 30 h. Error bars represent ± SEM for n = 2 (**P = 0.007). | [
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Venn diagrams showing the overlap between H3K27me3-associated EZH2 binding sites detected at each stage of de novo transformation. | [
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(A) Experimental setup to measure single-molecule FRET in translocation complexes immobilized on a surface. | [
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A) Vacuolar membranes of wildtype (BY4741), nyv1∆ vam3∆, ypt7∆ or vma16F190Y cells were labeled with the vital dye FM4-64. A vacuole that was in a sufficiently peripheral location to be selectively photobleached was exposed to a laser pulse (white arrows indicate the bleaching area). Recovery of fluorescence in this area was assayed 10 seconds later by spinning disc confocal microscopy. Scale bar: 2 µm. B) Kinetics of FM4-64 recovery in (A). Means and s.d. are shown for 20 vacuole clusters from 3 independent experiments. | [
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(f) SH-SY5Y cells were treated with SFN for 12 h, and cell lysates were used for the ChIP assay using anti-Nrf2 antibody as described in the Methods. Data shown are mean±s.e. and were analysed using Student's t-test. (*P0.05; **P0.01; ***P0.001). | [
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C. Fold enrichment of WT HA-IN1 over input at all the genes where HA-IN1 has been detected by ChIP-seq analysis. Each dot represents a gene. Grey, tDNAs ; Red, other Pol III-transcribed genes ; Blue, Pol II-transcribed genes. The dashed line indicates the separation between Pol II and Pol III-transcribed genes. | [
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IL-1β ELISA of supernatants collected from Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS and either vehicle control (Vh, DMSO) or 10 µM MCC950 for 24 h (n=5). Data shown in (H) are pooled from 5 independent replicates. | [
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(E) Immunoblot analysis from the same samples as in (A), for expression of SLC25A46, regulators of the cell cycle and markers of senescence. SDHA was used as a loading control. | [
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(a) MCF7 cells stably expressing Myc-TEV-Flag-Beclin 1 (MEF-Beclin 1) and parental controls were lysed and subjected to MEF-tag-based purification. Proteins bound to MEF-Beclin 1 were isolated and detected by SDS-PAGE and silver staining. Seven bands specific for MEF-Beclin 1 are numbered. (b) Six bands were identified by nanoflow LC-MS/MS and MASCOT software. | [
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A. Representative images of brainstem cryosections stained by triple immunofluorescence labeling for vGluT1 (green), CaV2.1-type Ca2+-channels (red), and the active zone protein Bassoon (purple). Cryosections were obtained from littermate control and Nrxn123 TKO mice at P12-14. Scale bar, 10 μm. | [
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(A) Validation of anti-phasic Rac1 expression in mouse (mRac1, red) and human enteroids (hRac1, black) by qRT-PCR. (B) Quantitative analysis of fluorescent intensity from SYTOX orange in Rac1-KD bHIEs. | [
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Mapping of open chromatin as well as active and repressive histone modifications at upstream regulatory regions of the Prdm1 locus in pro-B cells and plasmablasts. Open chromatin was determined by ATAC-seq (Buenrostro et al., 2013), and active (H3K4me2, H3K4me3, H3K9ac) and repressive (H3K27me3) histone marks were mapped by ChIP-seq analysis in ex vivo sorted pro-B cells (ATAC-seq and H3K27me3, this study), short-term in vitro cultured pro-B cells (H3K4me2, H3K4me3, H3K9ac) (Revilla-i-Domingo et al., 2012) and in vitro LPS-induced plasmablasts (Minnich et al., 2016) (Table EV4). The indicated upstream regions were previously shown by 3C-analysis to interact with the Prdm1 promoter (Wöhner et al., 2016). The mm9 genomic coordinates of mouse chromosome 10 and the respective positions of two human SNPs (rs658431 and rs548234) are indicated. RPM, reads per million mapped sequence reads | [
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E) Differential expression of ARM vs HM.1 microglia for APPtg and TAUtg mice separately. Genes with a positive log(fold change) (LFC) are higher expressed in ARMs compared to HM.1 microglia. As can be seen which genes are more highly expressed in ARMs vs HM.1 cells are highly similar among APPtg and TAUtg mice (Spearman correlation r=0.91, p=2.2e-16). LFC > |0.2| with padj<0.05 are considered significant. | [
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A. Quantification of mRNA expression by RT-qPCR of candidate miR-34/449 targets that might regulate spindle orientation in E14 cortex samples from miR-34/449 KO mice compared with littermate controls (Het). Expression was normlaized (norm.) to Phosphoglycerate kinase (PGK) mRNA levels. Significance was tested by Welch's t test: p = 0.009756 (JAM-A (Het) vs. JAM-A (KO)), all the rest Het vs. KO comparisons p=n.s. (n = 4 cortices per genotype group, 2 independent litters). All subfigures were statistically tested as in A. * indicates p ≤ 0.05, ** indicates p ≤ 0.01, *** indicates p ≤ 0.001. Red bar indicates median. | [
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(E,F) HeLa cells were co-transfected with the indicated GFP-TDP NLS reporters and iRFP or GA175-iRFP. Cell lysates were immunoprecipitated with anti-GFP and immunoblotted with indicated antibodies to detect co-immunoprecipitation of the TDP-43 NLS with importin-α5/KPNA1 nuclear import receptor. (F) Quantification of KPNA1 levels normalized to total GFP-NLSTDP reporter levels in anti-GFP immunoprecipitates. n=3 biological replicates. Scatter plot with mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. *** denotes p<0.001. See also Figure EV4. Red dashed line indicates the control's expression level. | [
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D. RNaseII/R enzymes act as conserved molecular 'readers' of destabilizing post-transcriptional modifications. In prokaryotes, e.g. E. coli, structured RNA is marked by a polyA-polymerase (PAPase) for subsequent degradation by RNaseR, 3′-to-5′ exoribonuclease with intrinsic preference for 3′ adenylated RNA. In eukaryotes, e.g. flies or mammals, structured RNA undergoes 3′ terminal uridylation by a terminal uridylyltransferase (TUTase) for subsequent degradation by Dis3l2, a 3′-to-5′ exoribonuclease with intrinsic preference for 3′ uridylated RNA. | [
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B. U2OS/GFP-FAM111A WT cells treated or not with DOX were subjected to GFP IP followed by immunoblotting with indicated antibodies. C. As in (B), using U2OS/GFP-FAM111B WT cells. | [
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Schematic representation of immunoprecipitation of protein-RNA complexes engaged to RNAPII shown in (B). With UV-crosslinking of protein-RNA interactions (UV+) or without (UV-), the chromatin fraction is isolated from the cells and treated with (Pre-RNase+) or without RNase A (Pre-RNase-). RNAPII, shown in gray, is 1st immunoprecipitated. The immunoprecipitants are treated with RNase A to release a protein, shown in green, from the protein-RNA-RNAPII complex. | [
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O. Quantification of Pbk expression positive beta cells. Four mice for each group, 10 islet images per mouse were analyzed. ns, not statistically significant difference (unpaired two-tailed student's t-test). | [
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D. Zebrafish embryos at one-cell stage were microinjected with plasmids as indicated followed by extraction of embryonic proteins at the 96-hpf stage. Protein levels of CHOP, p-eIF2α, total eIF2α, Endou-Flag, and its variants were detected using Western blot analysis. GAPDH served as an internal control. E. HEK 293T cells were transfected with indicated plasmids followed by analysis of the protein levels of CHOP, p-eIF2α, total eIF2α, Endou-Flag, and its variants using Western blot . Here, α-tubulin served as an internal control. Protein levels relative to each internal control were presented in each lane. | [
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(A) Analysis of Sμ-Sα recombination junctions in the genomic DNA isolated from siControl- and siPhf5a-transfected CH12F3-2A cells stimulated by CIT for 48 h. The values are presented as mean ± sd (n=3), Statistical significance was evaluated in reference to siControl by two-tailed unpaired Student's t-test (*p ≤ 0.05, ** p ≤0.01, *** p ≤0.001). | [
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Quantification of mean fluorescence intensity (MFI) of MitoTracker green staining in iNKT cell subsets; | [
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Co-immunoprecipitation analyses of the interactions between SGS3, SGS3ΔCC, or SGS3CC and VISP1 or VISP1mARM. N. benthamiana leaves were agroinfiltrated with constructs as indicated and treated with 2 mM 3-MA at 48 hpi, and collected for IP with anti-Flag beads 12 h later. | [
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The relative frequency of Gly at the C-termini of indicated proteomes, i.e. mouse (Mus musculus), fly (Drosophila melanogaster), nematode (Caenorhabditis elegans), plant (Arabidopsis thaliana), yeast (Saccharomyces cerevisiae), and bacteria (Escherichia coli). | [
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Schematic drawing of S. cerevisiae RNAPII transcription active center. Trigger loop is shown in blue. TL-interacting Rpb2 domain is shown in beige. Proline 1018 (P1018, green) and gating tyrosine 769 (Y769, red) are highlighted. The schematic drawing is based on PDB: 2e2h [15]. | [
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C-F RT-qPCR analysis of mRNA from ribosomal protein fractions for control (black) and pths KD (gray) transcripts from S2R+ cells. RNA was isolated individually from fractions and pooled into five categories: RNP, 40S/60S, monosome, low polysome (di- and trisome), and high polysome (remaining fractions). The data were plotted relative to the amount present in the monosome fraction for each transcript. The mRNA levels of subunits of mitochondrial complexes (C) I, (D) III and (E) V were reduced in low and high polysome fractions in pths KD cells compared to the control cells, while (F) mRNA levels of GAPDH in the same fractions, used as an internal control, were not changed (n=3 independent biological replicates for control and pths KD). For (C,E-F) low polysome fraction for control vs. pths KD: (C) p=0.057, (D) p=0.0039, (E) p=0.09, (F) p=0.5. For (C,E-F) high polysome fraction for control vs. pths KD: (C) p=0.039, (D) p=0.046, (E) p=0.041, (F) p=0.66. G-I Western blots and their quantifications of protein extracts from control and pths KD S2R+ probed with (G) MT-ND1 (for mitochondrial complex I) n=4, p<0.0001), (H) ATPsynt-β (for mitochondrial complex V) n=3 p=0.034 and (I) tubulin β antibodies p=0.56) (n=3). Profilin serves as loading control. N=biological replicates. Data information: Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ****p<0.0001. Unpaired t-tests (C-F, G-I). | [
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(F , G) Representative FACS plot of single cells from Tg(tg:nls-mVenus-T2A-NTR) animals at 2 mpf (F) and 8 mpf (G). Calcein (Pacific Blue) labels live cells, while green fluorescence (FITC) labels thyrocytes. Percentage values represent proportion of calcein+ thyrocytes within total calcein+ cells. | [
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Effect of HK2 targeting on in vitro tumorigenicity. HK2-silencing with two different shRNAs (shHK2-1 and shHK2-2) in CT26 colon cancer cells inhibits growth in soft agar (B; colony area±SEM; n=6 replicates obtained from 3 independent experiments; Student's t test ***p<0.001; A.U., arbitrary units). Data information: Throughout the Figure, cl-SCRpep or SCRpep are used as peptide negative control. | [
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c, Immunoblot of LC3 and &amp;bgr;-actin in +/−KRas cells for two independent tumours. | [
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B Sedimentation assay to quantify condensation of unmodified TDP-43 versus in vitro phosphorylated TDP-43 (+CK1δ, +ATP) and controls (CK1δ or ATP only); TDP-43 detected by Western blot (rabbit anti-TDP-43 N-term). Due to incomplete TEV cleavage, some TDP-43-MBP-His6 remains present and co-fractionates with cleaved TDP-43, due to TDP-43 self-self interaction. C Quantification of band intensities of cleaved TDP-43 shown as means of Supernatant/(Supernatant+Condensate) [S/(S+C)] ratio of three independent experimental replicates (n=3) ± SD. ***p < 0.0002 by one-way ANOVA with Dunnett´s multiple comparison test to Wt. | [
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(A and B) HeLa cells expressing HA-Parkin and MITOL∆C8 (A) or MITOL∆C8 lacking E3 activity (B) were treated with 15 µM CCCP for 3 hours, and then subjected to immunocytochemistry with anti-Flag and anti-ubiquitin antibodies. Expanded peroxisomes were ubiquitylated upon E3 activity of MITOL. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm. | [
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Representative picture of a 4.5-month-old double knockout (Grn-/-/Tmem106b-/- ) mouse after manual flip. | [
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NPC2 immunoblots of cell lysates from primary IMCs cultured with or without 50 μg/ml bNPC2 for 48 h. | [
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Mimicking the unacetylated state of Cse4-K49 (cse4-K49R) partially suppressed the temperature-sensitivity of cbf1∆ cse4-R37A. cbf1∆ cse4∆ strains carrying the indicated cse4 alleles on a plasmid were spotted on full medium and grown | [
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(C) Representative images of lung metastatic nodules developed in mice 8 weeks after injection of QKI-5-overexpressing A549 cells or control A549 cells. The surgically resected lungs were stained Red arrowheads indicate metastatic nodules established in lungs. Scale bar, 5 mm. (D) Comparison of the number of lung metastatic nodules between QKI-5-overexpressing group and vector group (n = 10 mice per group). Data are shown as the boxplot. Central band: median; Upper and lower line of boxes: upper and lower quartile; Upper and lower line of whiskers: maximum and minimum. | [
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C. Growth curve analysis of loop mutants in -Ura media with and without K. lactis toxin zymocin. Shaded regions correspond to the SEM at each time point. N=3. | [
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D. DNA unwinding by DnaB was initiated from the downstream side of the PAM after the association of the SaCas9 protein (n = 11). Representative traces show the number of unwound base pairs versus time under an assisting force of 12 pN. For clarity, the traces have been shifted along the time axis. The dotted lines indicate the expected SaCas9 binding positions. | [
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Scatterplot of DamID-seq signals (log2 ratio) for FlyBase genes (left) or genome integrated TEs (right) in EGFP-KD (control, x-axis) and Piwi-KD (y-axis) samples. Both x- and the y-axis is a log2 ratio. Gypsy signal with the greatest decrease upon Piwi-KD is indicated and shown in genome browser view in (B). | [
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(A) Representative images and percentage of HeLa cells with more than 5 H3S10-P foci after transfection with the indicated siRNAs and either pEGFP-C1 (RNH1-) or pEGFP-M27 (RNH1+). Mitotic cells were excluded for the analysis by DAPI staining. More than 300 total cells were considered. Data represent mean ± SEM from three independent experiments. *p<0.05, **p<0.01, ***p<0.001 (one-tailed paired t-test). Black stars denote significant increases whereas red stars denote significant decreases. | [
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A Comparison of the CD81 model (after 1 µs simulation; colored by structural elements) and the CD53 crystal structure (green). Compared to CD53, the conformation of CD81 EC2 protrudes higher from membrane plane owing to the longer EC1 and different helix A orientation in CD81. The transmembrane regions of CD53 and CD81 are essentially unchanged during the 1 µs simulation. The MD simulation is performed using GROMACS (Van Der Spoel et al., 2005) and CHARMM36m force field (Huang et al., 2017). | [
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(C) Quantification of total BM-MNCs in Ctrl mice and lethargic/dead Npm1 cKO mice (n = 4 mice per group). | [
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(F) Stills from time-lapse sequence of representative Hela cells expressing mNeon-Green Aurora B and Cell Mask to label cell membrane, exiting mitosis, showing the dynamic re-localization of Aurora B from DNA to the overlapping microtubules and cleavage furrow with control siRNA treatment (arrows top). With knock-down of RACGAP1, Aurora B still re-localises from the DNA to the microtubules and furrow in the midzone in early anaphase (arrows bottom), but the microtubule localization is lost at later stages (asterisk bottom). Scale bar - 10 µm. | [
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(D) Confocal images of HeLa cells transiently transfected with DOR and LAMP1‐GFP, or with YFP‐LC3 and LAMP1‐GFP. Scale bars, 10 μm. Contrast‐corrected merge RGB pictures and the Z‐projection of Product of the differences from the mean (PDM) images are shown in all panels. Colour scales of PDM images have different maximal values, so the different conditions are not comparable from these projections. Product of the differences from the mean (PDM) values closer to 1 show reliable colocalized pixels. DAPI, 4′,6‐diamidino‐2‐phenylindole; DMEM, Dulbecco's modified Eagle medium; DOR, diabetes‐ and obesity‐regulated gene; GFP, green fluorescent protein; HBSS, Hank's balanced salt solution; LAMP1, lysosomal‐associated membrane protein 1; LC3, microtubule‐associated protein 1A/1B‐light chain 3. | [
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A, B Jejunal spheroids were cultured in differentiation medium containing 10 µM of Forskolin or an equivalent volume of DMSO. (B) Quantification of the average expression ± s.e.m. of Cldn4 mRNA relative to the DMSO treatment group (n = 3 independent experiments). *p<0.05 compared to DMSO group by unpaired t test. | [
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MDA-MB-231 cell were treated with 10 μM of PDD0017273 for indicated times, cell lysates were analysed by Western blot (n=3). | [
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C Transcript levels (FPKM from RNA-seq data) in BT168FO cells of the genes shown in B. Data are means of 3 independent biological replicates. | [
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Flow cytometry of intracellular Foxp3 staining in CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding A-C/EBP or C/EBPζ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the left panel and pooled data with mean values fro E 7(F are shown on the right. Dot plots are gated for CD4+GFP+ and numbers indicate percent Foxp3+ cells in the gate | [
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E qPCR of selected transcripts in edited SU-DHL-6 cells (n = 4 independent experiments). Significance was determined as compared to control Data information: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. | [
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A) ykt6ts cells containing centromeric plasmids as indicated were grown at permissive temperature (23 ºC), shifted to the restrictive temperature at 37 ºC for 1 hour before starvation for 1 hour at 37 ºC. Cells were lysed and the total extract (T) separated into a cytoplasmic (S) and a 100'000x g membrane pellet (P) fraction. Fractions were analyzed by anti-HA, anti-Tom70 and anti-Pgk1 Western blotting. One representative experiment out of three biological replicates is shown. | [
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Quantitation of the BODIPY signal shown as (G) integrated total lipid, for the genotypes n=10 for each genotype. The box end points are the upper (75%) and lower (25%) quartiles, the whiskers define the maximum 95th percentile and minimum 5th percentile values respectively, the central band is the median, the square is the mean and the diamond an outlier. Data were quantified for significance using Student's t test. ***p<0.001, **p<0.01. | [
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Immunoblot analysis of indicated cell lines, starved for 6 hours (HBSS) as indicated, and treated with 25 μM MG132 or 200 ng/ml of bafilomycin A1 (Baf A1) for the indicated times. In E, endogenous CALCOCO1 is analysed and the bars represent the mean±sd of band intensities relative to the actin loading control, as quantified using ImageJ of three independent experiments. Statistical comparison was analyzed by one-way ANOVA followed by Tukey multiple comparison test and significance displayed as ***p ˂ 0.001, **p ˂ 0.005, *p ˂ 0.01; ns is not significant. | [
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(b) Colocalization of p62 with ΔactA2. MDCK/pGFP-LC3/pp62-3×Myc cells were stained with an anti-ubiquitin antibody (light blue), anti-Myc antibody (red), DAPI (white) and anti-GFP-LC3 (green). Scale bar, 10 μm. Arrowheads indicate GFP-LC3-, ubiquitin- or p62-positive bacteria. | [
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E) Cumulative frequency curve [%] of the observed coefficient of variation (CV) of proteins that were identified and quantified in at least three out of five replicates in each sample type. The resulting median and average CV for each sample type are shown. | [
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F) Relative importance of the statistics at each position for Gradient Boosting. | [
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(H) Tg(pcsk1:GFP) is expressed in regenerating β cells within the islet (arrowheads), but not outside the islet (arrow), at 6 dpf in larvae overexpressing igfbp1a. Scale bar: 15 μm. | [
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J Quantification of α- and β-Tubulins membrane association Values are means ± SEM from three independent repeats. | [
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(a) COS-7 cells transfected with EGFP-LC3 construct for 4 h were treated with DMSO (control), 0.2 μM rapamycin (positive control), 47 μM SMER10, 43 μM SMER18 or 47 μM SMER28 for 16 h, and analyzed by fluorescence microscopy. The effects of treatment on the percentage of EGFP-positive cells with >5 EGFP-LC3 vesicles are shown. Error bars denote s.e.m. P 0.0001 (all SMERs). | [
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(F) Venn diagrams showing genes nearest to H3K27ac SEs common in WT and KO macrophages (left), H3K27ac SE region from WT and KO macrophages (right). | [
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SKOV3-OPCML cells stimulated with Gas6 over a 12 hour time course and (A) stained with DAPI (cyan), Anti-OPCML (green) and Anti-AXL (red) antibodies (scale bar = 10μm) | [
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(B) A representative cryo-electron micrograph of paclitaxel-stabilized T. thermophila MTs. | [
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A Cryo-EM density map of the H2A.B-NCP at 3.9 Å resolution: disc view (left) and gyre view (right). | [
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Blood vessel staining with CD31 (red). DAPI staining of the sections is shown in blue. Scale bar, 200 μm. 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. | [
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(B) Immunofluorescence of histone chaperones in fixed cells using the same antibodies used in (A). Cells are segregated into those undergoing replication and those that are not. Scale bar represents 5 μm | [
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(b) Bidimensional electrophoresis and Sypro Ruby staining of these fractions. Left, intact vacuoles; right, vacuole contents. Horizontal dimension, isoelectric point (pH); vertical, molecular mass (kDa). *P 0.05. | [
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(A) Interaction network of B56δ with its associated proteins identified in this study. Blue line indicates B56δ interaction with PPM1G. Red dashed line represent interaction with PP2A complex proteins. | [
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F Individual proteins were measured by immunoblotting using lysates of three tumors from each treatment group. | [
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TNF measurement in the serum of GRfl/fl and GRLysMKO (n=4). Mice were treated with PBS or a lethal dose of LPS (12.5 and 2.5 mg/kg for GRfl/fl and GRLysMKO mice respectively) , with or without pre-treatment with 10 mg/kg DEX and blood was drawn 2 hours later. TNF concentration was measured with ELISA. | [
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(A) LocScale cryo-EM density map of Ape4 dodecamer in complex with Nbr1-ZZ1. Twelve Ape4 subunits are colored differently and all Nbr1-ZZ1 molecules are colored in orange. (B) Ribbon representation of the Ape4-ZZ1 complex structure. | [
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BMDMs from wild type, Traf3ip3-/- and Mavs-/- mice were treated with or without VSV, SeV, poly (I:C) or HSV-1 respectively as indicated for six hours. Ifnb (A), Ifna4 (B), Il6 induction was measured respectively by qPCR. All data are presented as the mean values based on three independent experiments, and error bars indicate s.d. P values were determined by unpaired two-tailed Student's t-test. *P<0.05 and **P<0.01. NS indicates no statistically significant difference. | [
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A, MCF10A WT cells were pretreated with AZD6738(250 nM) and RO-3306 (9 μM) for 2 hours, and then irradiated with 20 Gy, 3 days later, cells were harvested for immunoblotting with indicated antibodies. | [
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(A) Serum samples collected from individual mouse (M 1-5) immunized with F 110-136 peptide were tested for antibody binding against F-p27 (110-136) peptide or F 1-34 peptide (control) in ELISA. | [
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(B) Clear cytoplasmic vacuolization (arrows) in cerebellar corticalPurkinje cells. HE, scale bar 100 μm. | [
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mRNA expression of PIK3CA in human patient samples; significant difference (P < 0.05) between tumor and normal tissue *P = 2.13 × 10−4 determined by paired two-tailed Student's t-test, n = 18 patients. | [
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F) Analysis of mtDNA amount (n=9/group). Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey's correction: **p=0.0020; *p=0.0296 | [
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METTL14 IDR arginine methylation occurs at multiple arginine residues within RGG/RG motifs. Mutation of five arginine sites identified from mass spectrometry reduces METTL14 arginine methylation, but only mutation of all arginine sites to lysine completed blocked METTL14 methylation. Ponceau S staining shows the loading of the recombinant proteins. The black triangles indicate arginine methylated-METTL14; open triangles indicate recombinant METTL14 proteins. | [
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E) Quantification of two STELA experiments, including that shown in (D). Indicated in red is the mean telomere length and the error bars indicate the standard deviation. | [
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Average daily distance run by HFD-fed mice treated with vehicle (n=8) or SH-BC-893 (120 mg/kg, n=6) on Mondays, Wednesdays, and Fridays over 4 weeks when housed with a running wheel. | [
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