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D. Western blot of Atg13 in Ofd1fl/y;creKsp and control kidneys at pre-cystic (P8, left) and cystic (P22, right) stages. Gapdh was used as loading control. Atg13 protein levels are expressed as fold change compared with control mice; n=7 mutant/5 control mice at P8, n= 4mice/group at P22. | [
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(a-c) HeLa cells transfected with ARL8B or KIF2 siRNA, or with ARL8B overexpression construct (non-targeting siRNA and empty pcDNA vector used as transfection controls), were either left untreated, serum/amino-acid starved for 5 h, or starved and then recovered in amino-acid- and FBS-containing medium for 30 min. Cells were immunostained using LAMP1 antibody (a) and the percentage of cells with predominantly peripheral localization of LAMP1-positive vesicles was quantified (b) or subjected to immunoblotting (c) using antibodies as shown. Quantification of phospho-S6K levels relative to the total S6K is shown in (c). Values are means ± s.e.m. of three independent experiments carried out in triplicate. All comparisons are with the control within each treatment condition, *P0.05, **P0.01, ***P0.005 Student's t-test; n.s. not significant. Uncropped images of blots are shown in Supplementary Fig. S7. | [
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Total protein lysates (input) from GSC#9 treated with vehicle (-, DMSO) or MPZ (+, 20 μM, 1 hour) or with vehicle (-, H2O) or Z-VRPR-FMK (+, 75 μM, 4 hours), were processed for control immunoglobulins (Ig) or anti-QKI antibodies immunoprecipitation (IP). Western-blots were performed with indicated antibodies. Western-blots were performed with indicated antibodies. | [
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B, C. Expression analysis of miR-34/449 by in situ hybridization using locked nucleic acid (LNA) probes in wild type cortices at E14. Mature miR-449, miR-34b and miR-34c are preferentially expressed in the subventricular (SVZ) and ventricular (VZ) zones of the neocortex. Scale bar, 50 μm (B), 10 μm (C). | [
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G. Newly synthesised R-loops in BU-1 during S phase in wild type (black) and primpol (red). Error bars represent 1SD of three biological repeats of the experiment. *** p ≤ 0.001, * p ≤ 0.05; unpaired t-test | [
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A. HeLa cells treated with non-targeting (Ctrl) or C9orf72 siRNA were immunostained for endogenous p62. Accumulation of p62 was quantified by counting p62 positive puncta per cell from 3 independent experiments (Mean ± SEM; unpaired t-test, **** P ≤ 0.0001); N (cells) = Ctrl: 74, C9orf72: 55). C9orf72 knockdown was confirmed by RT-qPCR (Appendix Fig S2). Scale bar = 10 µm. | [
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F. Quantification of rescued ovaries harboring at least one stage 9 egg chamber in genotypes numbered from 1 to 11 after one day or several days on yeast. Grey bars (1-4) are control flies. n= number of ovaries. | [
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B. Top panel; depiction of amino acid sequence corresponding to the SIMs in the indicated proteins used in this study. Hydrophobic residues involved in SUMO binding are indicated in red. Bottom panel; constructs expressing GFP-control or GFP-fused SIMs of indicated proteins were co-transfected with HA-AGO2 in HEK293T cells and IP and WB were performed to determine the extent of interaction. | [
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(E) Images were captured of the hair coats of Sirt7+/+ and Sirt7-/- mice at 15 months. The yellow dashed lines indicate hair thinning or hair loss. | [
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C HeLa cells stably expressing SEPT6-GFP were harvested, and then tested with Co-IP. HeLa cells expressing GFP were used in parallel as control. GFP-trap magnetic agarose beads were used to isolate SEPT6-GFP from cells, and extracts were immunoblotted for Drp1, SEPT2, SEPT7, or GFP. The lysates were immunoblotted for GAPDH as control for cellular protein levels. | [
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A Schematic representation of the exon/intron organization of Celf2 genomic locus. Arrows indicate TSS sites. | [
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(C) Immunofluorescent microscopy staining of Fstl1 (green) and S100a4 (red) in the ischemic area. Arrows indicate Fstl1 and S100a4 double positive cells. Scale bar indicates 20μm. | [
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Control and si-IRGM transfected HT-29 cells uninfected or infected with CHIKV and qRT-PCR analysis were performed with (E) SAMHD1 | [
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(B-C'') Immunostaining of mosaic germaria with anti-GFP (green), to identify clonal cells by the lack of GFP, and either 8C4 (B-B'') or 10F1 (C-C'') monoclonal anti-Cbl (red). DAPI was used to visualize DNA. White arrowheads indicate aubHN2/+ control GSCs; yellow arrowheads indicate clonal mutant aubHN2 GSCs. Scale bar: 10 μm. | [
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(F) In vitro kinase assay of RSK3 with N-terminal (F1), middle (F2), and C-terminal fragment (F3) of ATXN1. | [
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I-J, Kaplan-Meier recurrence-free (I) and overall (J) survival analysis of PCa patients stratified according to median THEM6 expression. Data information: Statistical analysis: logrank test. Data reproducibility: n = 35 tumours for THEM6 low and n = 34 tumours for THEM6 high. | [
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(B) Two-colour SIM images in control and myosin VI-depleted cells illustrating the localisation and distribution of the distal appendage markers Cep164 and ODF2 at the centrioles, stained with anti-acetylated tubulin antibody. Representative images are shown; scale bar, 500 nm. | [
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(G) IDH1 K224 deacetylation regulated cellular NADPH/NADP+ redox in cells. In HCT116 stable cells with IDH1 knockout and re-expressing the indicated proteins, the ratio of NADPH/NADP+ in cells was measured as followed by manufacture's instruction. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For , G statistical significance was assessed with the one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01. n.s. = not significant. | [
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Heat map diagram of DEGs in LV during late Telogen compared to mid Telogen, relative to biological processes, analyzed using the Enrichr platform (Chen et al., 2013; Kuleshov et al., 2016). Data shown represent the log2 (FPKM+1). | [
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(B) Immunoprecipitates of anti‐Beclin antibodies prepared as described in (A) were assayed for PI 3‐kinase activity in the presence of wortmannin at concentrations of 0 nM (lane 1), 1 nM (lane 2), 10 nM (lane 3), 100 nM (lane 4). The labeled lipids were extracted and separated by thin layer chromatography, followed by detection by autoradiography using a bioimaging analyzer BAS2000 (Fuji Film). | [
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C. Phosphorylation status of Ser127 or Ser128 determines interaction between 14-3-3 and YAP. Lysates from HEK293T cells transfected with plasmids indicated in the figure were immunoprecipitated with anti-Flag antibody and immunoblotted with anti-HA antibodies (top two panels). Lysates were immunoblotted with anti-HA or anti-Flag antibodies (bottom two panels). "n.s." arrow indicates a non-specific band also visible in the non-transfected lane. | [
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A) Schematic illustration of Suv39h1 protein. ΔN-Suv39h1 lacks the 41 N-terminal amino acids but contains a chromodomain. | [
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Membrane lipid class composition of classes contributing at least 1% of total membrane lipids, the inset shows CDP-DAG and the separate lyso(L)-phospholipids (lyso-PL); Data information: All data were obtained by mass spectrometry and are presented as mean ±SD (n=3 biological replicates); * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, unpaired two-tailed t-test of the indicated bar compared to the cho2opi3 parent unless indicated otherwise. | [
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D) Trajectory plots comparing the trajectories of Chordc1 and Psat1 in WT and mdx mice. | [
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A. Ectopic expression of NLK attenuates interaction between YAP and 14-3-3. Lysates from HEK293T cells transfected with plasmids indicated in the figure were immunoprecipitated with anti-HA antibody and immunoblotted with anti-GFP antibody (top two panels). Whole cell lysates (WCL) were immunoblotted with antibodies shown in the figure (bottom three panels). | [
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Overview of all identified vemurafenib resistance mechanisms in patient and PDX samplesResistance mechanisms discovered in each of the lesions have been identified: a) in patients samples by WES (BRAFV600E amplification in M032R1, R2 and R5; MEK1T55delinsRT in M032R4 and M032) and immunoblotting (of alternative form of BRAF in M032R3); and b) in PDX by IHC and qPCR (BRAFV600E amplification in M032R2 and R5) and PCR analysis (MEK1T55delinsRT in M032R1 and R4). Gray arrows indicate that the lesion was at the back side. ampl., amplification; alt., alternative. | [
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b, Analysis of HeLa cells treated with the indicated siRNAs and stained with NDP52 antiserum. NDP52-positive bacteria were counted by microscopy 1 h after infection with S. Typhimurium. siRNAs are further characterized in Supplementary Fig. 2. | [
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Mice were analysed 2 days after TAC (a-e). a, Electron microscopic analysis. Images of mitochondria at higher magnification are shown in subsets. Scale bar, 1 µm. b, Autolysosome after incubation with anti-DNA antibody and 10 nm gold staining. Scale bar, 200 nm. Arrows indicate labelled DNA. | [
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Gene ontology enrichment analysis of the upregulated genes indicates male-specific or preferential biological processes. | [
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Erlotinib IC50 values were quantified in RHOB-overexpressing or RHOB-depleted (D) HCC827 cells, (E) HCC2935 cells and (F) H3255 cells, as determined by an MTS assay after 72 h treatment. RHOB overexpression or inhibition was monitored by western blotting for each condition. | [
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Sublingual C. albicans infection of WT and Stim1fl/flCd4Cre mice as described in Figure 5. (C) Macroscopic images of the C. albicans-infected tongues of mice at day 7 p.i. | [
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Intracellular un-esterified cholesterol distribution as detected by filipin staining in Npc2+/hypo IMCs cultured with or without 50 μg/ml bNPC2 for 48 h. Scale bars, 25 μm. Quantitative data in the bar graph were obtained by analysing 265 bNPC2-untreated (-bNPC2) and 252 bNPC2-treated (+bNPC2) cells from three independent cultures using the method described in (A). | [
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A. The interaction partners of YTHDF1 were identified by pull-down assays and mass spectrometry. The Flag-YTHDF1 pull-down assay was performed in CNE2EBV cells transfected with a plasmid encoding Flag-tagged YTHDF1. The proteins in the differentially abundant bands were identified by mass spectrometry. | [
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ciPSCs have developmental potentials to form teratomas containing tissues from all three germ layers. Scale bar, 100 μm. Chimeric mice were generated from ciPSCs. | [
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D: GST-tagged full length ORF (aa 1-132) and deletion constructs (aa 1-64, aa 65-132 and aa 31-132) of p14ARF as well as GST alone were subjected to in vitro-MT assays in the presence of GST-PRMT1 as described in (B). Methylation activities were detected by autoradiography (upper panel). Asterisks indicate methylated p14ARF proteins, whereas the arrowhead marks p14ARF-unrelated background signals (likely deriving from PRMT1 automethylation). Amounts of p14ARF proteins and GST alone were visualized by immunoblotting using α-GST antibody (lower panel). Asterisks highlight the expected size and location of the different proteins. Size markers (in kDa) are shown on the left. | [
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(E) Immunohistochemistry (IHC) of pS6 (Ser235/236) on skin sections from HS and Rosacea. Higher magnified images of boxed areas are shown at the bottom right of lower magnified images for each group. Epi, epidermis; Der, dermis. Scale bar: 50 μm. | [
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Quantitation of cells shown in A-C. Number of cells counted/condition: 712 - 1343 in three independent experiments; statistical significance via One-way ANOVA; p < 10-5, ± s.e.m. | [
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(B) The cell lysates from HeLa cells were collected and analyzed after GS for indicated time (lane 1~5), or GS for 2 h followed by 2 h chase in NM (lane 6). The cell lysates were subjected to Phos-tag gel and regular SDS PAGE respectively. | [
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C. Representative western blot showing changes in various ER stress markers and O-GlcNAcylation-related protein expression in THP-1 cells treated with Stx2a (10 ng/mL) for 3 h in the presence or absence of O-linked N-acetylglucosamine transferase (OGT) inhibitor OSMI-1 (10 µM final) or serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 a (IRE1a) inhibitor MKC-3946 (10 µM final). D. Quantification of the band intensities in (C). Data are presented as mean ± S.E.M. (n = 3 biological replicates) normalized against β-actin, which was used as a loading control. Data information: Statistical analysis was performed using two-tailed Student's t-test. *P < 0.05; **P < 0.01; and ***P < 0.001. | [
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(A) Scheme of individual actin filaments polymerizing on functionalized glass surfaces from profilin-actin in solution. (B) Time-lapse TIRF microscopy of single filament growth from Alexa488phalloidin-stabilized seeds (green) in the presence of 5μM profilin-actin. | [
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(d) Immunoblots for indicated proteins in isolated fractions from starved mouse liver. Hom, homogenate; LE, late endosomes; Cyt, cytosol; APG, autophagosomes; APL, autophagolysosomes. | [
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(E) Representative pictures of ZEB1 and MITF immunostainings, before and after vemurafenib treatment, in the tumor from patient 1, exhibiting primary resistance to BRAFi. Scale bar = 80 µm. Right: Magnification of MITFhigh and MITFlow clones in the resistant tumor under treatment. Arrows indicate endothelial and stromal cells that also show positive staining for ZEB1, besides tumor cells. | [
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ELISA analysis of IL-1β secretion from HMDMs transduced with lentiviruses expressing shCon or shABRO1 prior to stimulation with control medium (Con), LPS or LPS plus ATP. Cell lysates were immunoblotted with anti-ABRO1 and anti-GAPDH antibodies. | [
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E, Time lapse video-microscopy snapshot on HeLa cells transfected with NAF-1-mRFP (red) and treated with fluoMito-C (green). The distance/intensity fluorescence quantification graph illustrates the codistribution of fluoMito-C and NAF-1-mRFP. | [
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(C, D) THP1 cells were infected with HSV-1 KOS, ΔICP27 or HSV-1 ΔNLS. The localization of the major NLS is illustrated in panel C. Supernatants were harvested 18 hpi for measurement of type I IFN bioactivity. | [
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Western blot analysis performed with lysates of (N) Irgm1+/+ and Irgm1-/- mouse brain to determine levels of STAT proteins (n=3 mice). | [
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(d) The effects of induction of wild-type CerS1 and C18-ceramide and catalytically inactive mutant CerS1 (+ tet) in the regulation of mitochondrial function were assessed by measuring OCR using the SeaHorse and compared to roles of noninduced controls (− tet). | [
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B. Representative traces of the forward DNA unzipping in the presence of dSaCas9/sgRNA showing the force versus the number of unzipped base pairs. The naked DNA unzipping signatures are also presented for comparison (gray). Insets: zoomed-in view of the regions with increases in force. The dashed lines illustrate the interaction sites between dSaCas9 and the DNA. Black arrows indicate the force peaks of the pre-PAM interaction. | [
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(A) Schematic diagram of affected proteins and the locations of the point mutations identified in: EARS2 p.Gly110Ser, p.Gly224Ser, p.Arg516Gln, p.Arg120Trp, p.Gln199Arg and p.Ala88Glu mutations-catalytic and anticodon binding domain of the protein; TRMU p.Tyr301Cys and p.Ala10Ser- amino terminal catalytic and carboxy terminal β-barrel domain; QRSL1 p.Val229Gly -amidase signature domain; GOT2 p.Gly188Ser and p.Lys364Glu located in the large catalytic and small catalytic domains and GLS p.Ala432Ser found in the central glutaminase domain. Multiple sequence alignment of the above mentioned proteins shows the conservation of the affected amino acids across species using Jalview software. Analysis was performed using protein sequences from human (Q5JPH6, O75648, Q9H0R6, P00505, O94925), mouse (Q9CXJ1, Q9DAR5, Q9CZN8, P05202, D3Z7P3), zebrafish (Q0P499, Q503J2, F1QAJ4, Q7SYK7, Q8JFS4), frog (Q66JG3, F6TJB0, Q0VFI5, Q28F67, F7B417) and chicken (Q5ZJ66, Q5ZKW0, F1NLA0, P00508, A0A1D5PNV1). | [
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F,G, Western blots of lysates from HEK293T cells transfected with the indicated constructs. The asterisk marks an unspecific band. Representative blots from at least three independent experiments are shown. | [
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A Differences in sensitivity to increasing IMT1 doses between RKO cells and resistant RKO cells. The graph shows mean values ± SEM of n=3 independent experiments. | [
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(A) Superimposition of camrelizumab/PD-1 with PD-1/PD-L1 complex structure (PDB code: 4ZQK). PD-1 is shown as surface format in light blue, while PD-L1 is shown as deep teal cartoon and camrelizumab-scFv is depicted as cartoon. VL of camrelizumab-scFv is colored in yellow and VH in deep salmon. | [
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(C) Dose-response curves of two drugs for which high MERTK (left panels) or ACVR2A (right panels) expression was predicted to confer drug resistance. For each drug, three cell lines predicted to be sensitive (dark blue) and three cell lines predicted to be resistant (yellow) were assayed for viability. The experimental data validated that cell lines predicted to be more sensitive to a drug indeed showed this phenotype (data represents the average of three technical replicates; see Appendix for details). | [
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S100A9 expression was analysed by (A) immunoblotting or (B) flow cytometry in stably transduced HEK293T cells using anti-myc and anti-S100A9 as indicated. Immunoblot loading controls were done with anti-actin. Flow cytometry negative and positive controls were done with non-transduced parental cells (in grey) and HEK293T cells stably expressing the red emitting fluorescent protein E2C (E2C-Far Red), respectively. Experiments shown are representative of three (n=3). | [
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H) Larval brains at various time points from grh-Gal4; UAS-CD8-GFP were labeled with Msps, Dpn, and GFP. | [
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(C) Close-up of OTULINC129A and its interaction with the proximal ubiquitin (Ub). M86, Y91, E95, and R122 of OTULIN and their interaction with each other and with the F4 patch of the proximal Ub are depicted. Interactions (dotted red lines) and water molecules (light blue) < 5 Å are shown. Residues of the catalytic triad (A129, H339, N341) in pale cyan. | [
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E. Jurkat cells were transfected with mtYFP and treated as indicated. 32h after AICD induction cells were fixed and immunostained with an anti-cytochrome c antibody. Cytochrome c localization index was calculated from 30 randomly selected images per condition. Data represent mean ± SE of four independent experiments. | [
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Successful injections represented as a percentage of total for a novice user on the manual microinjection system, an experienced user on the manual microinjection system, and the Autoinjector. | [
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MCF10A WT or two independent clones for MDA5 KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later E) cells were harvested for real-time quantitative PCR instead of immunoblotting. IFNB1 mRNA level was measured by real-time quantitative PCR. Data are presented as mean + standard error of the mean of three biological replicates. | [
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H. Same as (E) except images are TIRF footprints of tsA201 cells treated either with vehicle (control) or with U18. | [
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(D, E) Inhibition of the interaction between endogenous BCN1, TAB2 and TAB3 by a BCN1 fragment corresponding to the TBD. HeLa cells were transfected with pcDNA3.1 (empty vector) or with plasmids encoding the TBD or a His-tagged Beclin 1 variant lacking the TBD (His-BCN1ΔTBD), followed by co‐immunoprecipitation of endogenous TAB2 (D) or TAB3 (E) and detection of BCN1. | [
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(A) Principal component analysis (PCA) plot of the first two components of the analyzed samples showing separation between the three treatments: far-red illuminated wild-type, far-red illuminated pXccBphP (XccBphP overexpressing) and dark wild-type Xcc treatments. | [
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G. IHC for expression of active β-catenin in colon or wild-type and Angptl2-/- mice. Scale bar = 50 μm. | [
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(G-I) Simultaneous expression of Y701F-STAT1 did not induced any further change on basal synaptic transmission (I/O curve) compared with expression of hTau alone, recorded in hippocampal CA3 (G). LTP magnitude was calculated as the average (normalized to baseline) of the responses recorded 40-60 min after conditioning stimulation. (I). (n=5 slices from 4 mice for each group). Data information: Data were presented as mean ± SD , two-way analysis of variance (ANOVA) followed by Bonferroni' s post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP or hTau; #, p<0.05, ##, p<0.01 vs hTau. | [
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C Numbers of T and B cells found in the blood of WT and Arhgap45-/- mice. Data information: In the results for each mouse are shown as a dot and correspond to three to four experiments involving a total of 12-25 mice. * P ≤ 0.033, ** P ≤ 0.002, *** P ≤ 0.001, **** P ≤ 0.0001; unpaired Student's t test. Mean and SEM are also shown. | [
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(A) Immunoblot analysis and quantification of pTFEB S211 in HeLa cells stably expressing TFEB-GFP. Data are presented as mean ± SD, ***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas ). GAPDH immunoblotting was performed as a loading control. | [
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A. Representative images of mouse hippocampal neurons transfected with either GFP-expressing control or Lrig1 shRNA vector at 9 DIV and maintained for 3 additional days in vitro (9+3 DIV). Scale bar, 15 m. Boxed area represents a higher-magnification image showing the profuse proximal dendritic arborization of Lrig1-shRNA transfected neurons.B. Sholl analysis of the dendritic arbor from hippocampal neurons transfected with either control or Lrig1 shRNA-GFP vector at 9 DIV and maintained for 3 additional days in vitro (9+3 DIV). Data are shown as mean SEM of n=3 independent experiments. *p<0.05 and **p<0.01 by two-way ANOVA followed by Bonferroni multiple comparisons test.C-G. Quantification of primary (C), and secondary (D) dendrites as well as total dendritic branching (E), terminal dendritic points (F), and total dendritic length (G) of hippocampal neurons transfected with either control or Lrig1 shRNA-GFP vector. The results are shown as mean SEM of n=3 independent experiments. *p<0.05 by Students t test. | [
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(F) HeLa cells infected with control or PAQR3-overexpressed lentivirus were treated with GS for 4 h. PI(3)P levels were determined as in Figure 2E(n = 5; **p < 0.01; ns, not significant). | [
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PC and PC biosynthesis have become obsolete (blurred). The inhibition of Acc1 (highlighted in red) is essential for shortening average acyl chain length, which in turn is required for maintaining the physical properties of membranes faced with excess PE. The decreased non-bilayer propensity of PE is indicated by its reduced conical shape. | [
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A 601-nucleosomal arrays were incubated in 0.5, 5 mM MgCl2, 5 mM MgCl2 + MNase, and analyzed by the differential centrifugation assay to determine the fraction oligomeric. The amounts of DNA in the supernatant fraction were measured. Note that for the MNase-digested oligomers the supernatant fraction also includes the digested free linker DNA. Each value is the mean of three measurements and the error bars represent the standard deviation. | [
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% of telomere FISH signal loss in 30 months old wild-type mice and late generation Terc-/- mice (6 months old) in comparison to 4 months old wild-type mice. Data are from n=3 mice. >100 CMs were analysed per mouse. | [
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E. Representative western blot of AKT phosphorylation in liver 7 minutes after intravenous injection of PBS or 1.5 U/kg insulin in control (n=3) and Rbpji∆EC (n=3) mice five weeks after recombination. F. Densitometric analysis of western blot in E. n=3, data represent mean ± SEM, unpaired t-test. | [
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(D) HeLa GFP-LC3 cells were transfected with the indicated myc-tagged SNX18 constructs for 16 h, starved for 2 h, and analyzed by confocal imaging. Bars, 10 µm. | [
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Wild type and rad9∆ cells were synchronized in G1 and released into S phase with the addition of pronase in medium containing IdU and 200 mM HU to activate the DRC. Then, DSBs were induced by the addition of 100 μg/ml Zeocin to activate the DDC. HU was washed away 45 minutes later to inactivate the DRC and cells were resuspended in fresh medium containing CldU and 100 μg/ml Zeocin, in order to keep the DDC active. Samples were collected at the indicated times. | [
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Tukey box plots of the mean cLuC ratios (C) obtained from PPI experiments with wild-type CSPα-mCit-PA and its mutant variants. | [
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MECP2-KO cortical organoids plated on MEA (K; left: schematic depicts process of plating organoids on MEA; right: top-down view of organoid on MEA; scale bar = 200 µm) showed decreased population spiking | [
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E. HeLa cells transfected with indicated siRNAs were treated with 5-azadC and/or SUMOi in late S phase as outlined in (A). Cells were then collected at the indicated times after 5-azadC withdrawal and analyzed by flow cytometry. Data are representative of three independent experiments. Proportion of cells with G2/M DNA content is indicated. | [
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h, Representative haematoxylin and eosin images of Xbp1Dgr;PC and wild-type mice scored in i. Scale bars, 50 µm. i, Enteritis scoring in Xbp1fl/fl (WTfl), Defa6-cre+ (WTcre) and Defa6-cre+;Xbp1fl/fl (Xbp1Dgr;PC) mice (n = 21/26/29; median shown; Kruskal-Wallis with post-hoc Holm's-corrected Mann-Whitney U-test). Results represent two (b, d) independent experiments. *P 0.05, **P 0.01, ***P 0.001. | [
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(I-J) ICP-MS quantification of total (I) and protein-bound (J) iron in mouse quadriceps (n=4-5). Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. | [
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(A, B) A free energy diagram of the transport cycle (black) and its modulation (colors) by positive or negative allosteric modulators, PAMs (A), or NAMs (B), respectively. Cartoon representations of the low-energy states are below the diagrams and are colored as in Figure 1. The barrier heights are not to scale to the measured rates. Substrate binding to the apo OFS precedes isomerization into the IFS via the highest-energy TS (‡) that structurally resembles the IFS. Substrate release and recycling into the OFS complete the cycle. PAMs, shown as squares in the cartoons of the states, bind with higher affinity to the IFS (dark cyan squares) than to the OFS (light cyan squares). Therefore, they stabilize all IFS-like states, including the TS, and smoothen the energy landscape (cyan line). PAMs that bind too tightly to the IFS may become inhibitory, as apo OFS becomes a high-energy state (dotted blue line). NAMs bind tighter to the OFS ((B), dark magenta squares) than to the IFS (light magenta squares), increase the ruggedness of the landscape (magenta line), and slow down transport. | [
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(E) HeLa cells expressing HA-Parkin with various pathogenic mutations were treated with CCCP, followed by immunocytochemistry. (A, D, and E) Higher magnification views of the boxed areas are shown in the insets. (F) Parkin colocalization with mitochondria was analyzed in >100 cells per mutation. Example figures indicative of robust colocalization (counted as 1), weak colocalization (counted as 0.5), and no colocalization (counted as 0) are shown. Error bars represent the mean ± SD values of at least three experiments. | [
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A Schematic diagram shows how the SunTag-JARID1A system is recruited at the SNCA promoter. The dCas9-5xGCN4, scFV-JARID1A, and sgRNA plasmids are co-overexpressed in the cells. The dCas9-5xGCN4 is recruited to the SNCA promoter as directed by the specific sgRNA. Five scFV-JARID1A molecules in turn recognize the GCN4 polypeptide sequences of dCas9. Upon recruitment of the entire system, SunTag-JARID1A demethylates H3K4me3 at the target region. | [
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A) ROC curve shows the capability of plasma oxLDL concentration in discriminating ACM vs. HC subjects (data as in Figure1A). The red dot shows the point where the difference between sensitivity and specificity is minimized; this value, corresponding to the oxLDL cut-off = 86 ng/ml, was used to part the whole ACM cohort in two subpopulations. | [
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(B) The stiff or soft cells were isolated from ALDH- or ALDH+ 4T1 cells by microfluidic chip. Then, these cells were injected into the mammary fat pads of NSG or BALB/c mice mice (100 cells/mouse). Twelve weeks later, the tumor formation was recorded. n = 10. | [
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F) Expansion of a vacuolar fusion pore in real time. pmc1∆/vcx1Δ cells were labeled with FM4-64 and immobilized in a 50 µL flow chamber (Ibidi). The osmotic value of the medium was changed by perfusion with water, using a pump with a flow of 30 µL/s. A frame was acquired every 2 s for a total period of the 30 s, using the laser at minimal intensity. | [
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(D) Consequence of SIX4 depletion in PEO1 cells on E-cadherinplasma membrane accumulation 48 hours after transfection. Cells were counterstained with phalloidin and DAPI. | [
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D) UCSC genome browser shot of the human IL3/CSF2 locus showing DNase-Seq and ChIP-Seq in CD4 TN and TB with (red) and without stimulation (black) with PMA/I for 2 hours, plus the ENCODE Jurkat T cell DNase-Seq data (Thurman et al, 2012b). Black arrows represent stable DHSs and red arrows are inducible DHSs, with the distances in kilobases of the DHS from either the IL3 or CSF2 promoters. | [
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A Dose response curves of ID188 (p27-29) and ID211 (p26-28) organoids treated with FOLFIRINOX over three days. ATP was measured with CellTiter-Glo assays. Shown is the mean ± SD of three independent experiments. | [
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C Elongation response of seedlings of the indicated lines grown for 7 days in continuous W or 2 days in W then transferred for 5 days to W+FR (R:FR, 0.02). The mean hypocotyl length in W (HypW) and W+FR (HypW+FR) of at least four biological replicates was used to calculate HypW+FR-HypW. Error bars represent SE. Data information: Different letters denote significant differences (one-way ANOVA with Tukey test, p-value <0.05) among means. | [
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(A) NF-κB activation during MZT. Immunofluorescence staining of p65 shows nuclear translocation of p65 at the two-cell stage and thereafter. Scale bar = 25um. | [
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E HUVEC transduced with lacZ or with SHP2 were either untreated (-) or treated (+) with thrombin for 30 min followed by immunoblotting either VE-cadherin immunoprecipitates or cell lysates for the indicated antigens on the right. | [
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D-E WT donor derived Gr, B, CD4 T, and CD8 T cells in the peripheral blood Data information: Data are shown as percentages of the total number of white blood cells (WBCs). Data were collected at month 7 post transplantation for the uMT-/- group and month 8 post-transplantation for the NSG group, and presented as mean ± SEM. n=7 mice for the uMT-/- group and n=6 for the NSG group. *p<0.05, **p<0.01, ***p<0.001 (two-tailed and two-sample equal variance Student"s t-test) | [
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Quantification of actin levels from Westernblot of whole CO lysate reveals a reduction in ECE2 KO COs (n=4 independent batches of CTRL and ECE2 KO COs with 3 pooled COs each sample; *P = 0.021 in Kruskal-Wallis One Way Analysis of Variance on Ranks and Dunn's Pairwise Comparison). | [
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Ribbon diagram of the VgrG and Tle1 pseudoatomic structure, coloured according to the chain and in different orientations | [
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E Bioenergetic profiles measured with Seahorse flux analyzer showing the contribution of OCR and ECAR to cellular bioenergetics upon the aforementioned treatments. Data represent the mean ± SEM of n=3 independent experiments. | [
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D-F, Adipose tissue measurements on hematoxylin-eosin (H&E)-stained adult zebrafish sagittal sections. (D) Adipose tissue area per total section area (average of three sections/biological replicate) and (E) adipocyte size (average of 20-30 adipocytes of ventral adipose tissue per biological replicate) (Δ1 +/+ n=3, Δ2 n=8). scaf1Δ1 and scaf1Δ2 are represented with circles and squares, respectively. | [
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