EMBO/sd-character-level-ner huggingface dataset:
G,H Time-lapse images recorded by confocal microscopy in "line scanning mode", showing Ca2+ sparks and waves in cardiomyocytes at rest, extracted from mdx and mdx/CD38-/- mice; scale bars: 10 µM (horizontal), 500 ms (vertical). Bar graphs showing the averaged Ca2+ sparks (G) and waves (H) frequencies in cardiomyocytes isolated from WT (n=21 cells), mdx (n=28 cells) and mdx/CD38-/- (n=32 cells) mice. Data information: experiments performed in 3 mice of each group. After normality and variance comparison tests, significance was assessed using Kruskal-Wallis followed by Dunn's test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.
(F) Quantification of the mean (±SEM) number of DVGlut+ boutons per muscle 4 NMJ in each genotype. [UAS-RFP n = 23, UAS-dNmnat n = 21, UAS-Wnd n= 20 NMJs. 1-way ANOVA w/Tukey's multiple comparisons, DF=63, F=68.31, p < 0.0001. UAS-RFP vs UAS-dNmnat p=0.9818 (NS), UAS-RFP vs UAS-Wnd p < 0.0001(****)].
(A) Overview of yeast phospholipid biosynthesis in the endomembrane system and mitochondria, highlighting the enzymes most relevant to this study. Dashed arrows indicate multistep reactions; blue arrows indicate lipid flow into and from mitochondria, with thickness reflecting the estimated flux. CL, cardiolipin; DAG, diacylglycerol; PA, phosphatidic acid; etn-P, phosphoethanolamine; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; PS, phosphatidylserine; SL, sphingolipids.
Gene expression analysis by qRT-PCR of stem cell markers in Lgr5-DTReGFP ileums (n= 3 WT, 6 HE, 6 KO).
b, FRAP recovery curves for PhNT-connected cells (green, n = 42, R2 = 0.99), clustered cells (black, n = 16, R2 = 0.94) and single cells (red, n = 46, R2 = 0.97); Mann-Whitney analysis of fit for curves.
F Immunostaining of Sca-1 on femur sections of 8-week-old Lepr-Cre; tdTomato mice. Arrows indicated Sca-1+ tdTomato+ cells inside cortical bones of the femur diaphysis. Arrowheads indicated Sca-1+ tdTomato+ cells in the femur periosteum. B: Bone. BM: Bone marrow. Peri: Periosteum. Scale bars were 100 µm.
D Haplotypes of SlHAK20 among tomato natural variations. The distribution of Na+/K+ ratio in each haplotype group is exhibited by a box plot. The n indicates the number of accessions belonging to each haplotype. In the box plots, the middle line indicates the median, the box indicates the range of the percentiles of the total data using Turkey method, the whiskers indicate the interquartile range and the outer dots are outliers. Significant difference was determined by Student's t-test.
Retrotransposon transcription in WT (Hu303), fft2Δ (Hu1955), fft3Δ (Hu1867), and fft2Δfft3Δ (Hu2000). E) 5'RACE products run on a 1.5% agarose gel.
c-f, Expression of Ambra1 in the mouse embryonic nervous system. β-gal-staining on whole-mount Ambra1+/gt mouseembryos at E8.5 (c), E11.5 (d) and on a cross-section of E11.5spinal cord (e) is shown. Fb, forebrain; Hb, hindbrain; Mb, midbrain. f, Matching expression of the endogenous gene was revealed by whole-mount Ambra1 mRNA in situ hybridization analysis in E11.5 wild-type embryos.
(F) Confocal microscopy of THP-1 cells treated with LPS and LLOMe, and stained for TRIM16 and galectin-8. Line tracings correspond to arrowed dashed lines. Pearson correlation coefficient was calculated using SlideBook as described previously. Scale bars, 5 μm.
(C) TEM of OPA1 depleted Mic10-KO cells. Left: Representative TEM recordings showing CJs marked by arrows in a control cell and a similar view for an OPA1-KD cell. The CMs are colored in green and the OM and IBM together in magenta. Right: Quantification of mitochondria containing CJs or septa junctions. Sections that contained CJ-like structures were analyzed. Of these, the number of sections exhibiting septa or cristae structures (other) was quantified.
K Bar graphs show time-course analyses of IMR90 cells transduced with lentiviral sgRosa, sgA#10 or sgA#19. Data are expressed as means ± s.d., * denotes ns (not significant); **, p < 0.01; ***, p < 0.001. N = 3, unpaired t test.
B-G Model calibration with time-resolved quantitative immunoblot data of mCFU-E cells in blue and BaF3-EpoR cells in black. Growth-factor deprived mCFU-E cells (5x106 cells per condition) and BaF3-EpoR cells (1x107 cells per condition) were stimulated with different Epo doses and absolute concentrations were determined for pEpoR (B), pAKT (C), ppERK (D). The scale for pS6 (E) was estimated in arbitrary units.
(B) Human BJ fibroblasts, hTERT-RPE1 epithelial cells and lung mesenchymal stem cells were treated with vehicle (DMSO for 8 times 24 hours) or doxorubicin (250 nM for 24 hours) or paclitaxel (50 nM for 24 hours) or palbociclib (1 μM for 8 times 24 hours) or abemaciclib (1 μM for 8 times 24 hours). At 8 dpt, RNA was isolated and mRNA for the indicated p53-associated SASP genes quantified by qRT-PCR relative to tubulin (n=3 independent experiments). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001.
F, G. Wild type (WT, CD45.1+) or TGFbR2fl/fl dLck-Cre OT-I cells (KO, CD45.1+) were adoptively transferred from young donors into young or aged hosts (CD45.2+) one day prior to PR8-OVA infection. F. Resident OT-I cells were enumerated in the lung of young or aged mice at 50 d.p.i.
B ChIP-qPCR analysis showing the association of BIC1 with the promoter regions of BZR1/PIF4 target genes. The 6-d-old Col-0 and 35S:BIC1-Flag seedlings were used for ChIP assays.
(J) Summary table of eQTLs with statistically significant association with HSD17B7 expression in experimentally determined HKC transcription profiles (52 strains) and differential distribution in Black versus White populations by analysis of 1000 Genomes Phase I May 2011 (AFRICA (N=246), EUROPE (N=380)) with Fixation index (Fst ) value >0.3. The effect of the genotype was modeled as additive linear and tested for its significance (p-values) using t-statistic.
WB showing ΔNp63α, Klf4, K10 and Loricrin (Lor) protein levels in HEKn transfected cells as described in (A). β-actin was shown as loading control. One representative experiment of three is shown.
A Single plane confocal microscope image during germband entry from control or atosPBG embryos, or those expressing pths, GR/HPR, and LKR/SDH in macrophages (mac>). Embryos were stained for antibodies against S293-phosphorylated inactivated Pyruvate Dehydrogenase (pPDH, green) or total PDH (magenta) in macrophages (red). Higher pPDH/PDH ratios are consistent with higher ATP/ADP levels. Data information: Scale bars: 10µm
M. Proliferation of melanoma cells over indicated times after treatment with siASNS, siSLC3A2, or both.
(A) Schematic representation of the shRNA screening aimed to identify genes whose knock-down enhanced the anti-proliferative effects of AZD8186 (PI3Kβi), GDC0941 (pan-PI3Ki) or MK2206 (AKTi) on the PTEN-null cell line MDA-MB-468. The shRNAs directed against the transcripts of three genes are shown in three different colours. shRNAs against gene 1 are depleted in the vehicle-treated condition compared to time 0 and they most likely target an essential gene. shRNAs against the transcripts of gene 2 are unchanged in all conditions, while shRNAs silencing gene 3 are selectively depleted in the AZD8186-selected cells compared to vehicle and their abundance is not affected by the 2-weeks long culture with vehicle. Gene 3 is a good candidate for inhibition in combination with AZD8186.
Raw264.7 cells (B) were stimulated with LPS (20 ng/mL, 20 min) in the presence/absence of ATX inhibitor (50 μM, 30 min) or vehicle (Veh, DMSO 0.1%). Cell lysates were subjected to co-immunoprecipitation (IP) with CD14 antibody, followed by immunoblotting (IB) with TLR4 antibody.
B, C Jejunal spheroids were cultured as indicated. (C) Representative images of spheroids stained for Ace2 (green) and β-catenin (red). Nuclei are visualized with bisbenzimide (blue). Scale bars, 20 µm.
(B) Crystal structure of the HAT domain of Tetrahymena GCN5 bound with both peptide ligand and CoA (PDB code 1QSN). The absence of a β7 strand and the different C-terminus creates an accessible groove at the surface of the HAT protein promoting internal N-ε lysine acetylation of the substrate peptide. The main chain (top) and solvent accessibility (bottom) of both proteins are displayed as grey ribbon or grey surface, respectively). α1α2 loop, β4 strand, β5 strand are colored in red, yellow and pink. β6α4 loop in B are coloured in cyan. Peptides and the CoA moiety are displayed as green and orange sticks, respectively.
(A) Body temperature measurements in Fundc1fl/fl/Ucp1cre- (Cre-) and Fundc1fl/fl/Ucp1cre+ (Cre+) fasting male mice before and during cold exposure (4°C) for the indicated time. Body temperature (B) before and after 72 h cold exposure (4°C) of Cre- and Cre+ male mice.
In panels (A) violin plots show the variability in continuous leaf 16, ear phenotypes among the 60 individual plants used in downstream analyses. Data information: In all violin plots, the median is indicated by the white circle. The black box extends from the 25th to the 75th percentile, and black whiskers extend from each end of the box to the most extreme values within 1.5 times the interquartile range from the respective end. Data points beyond this range are shown as black dots. The red open circle indicates the mean of the distribution, with red whiskers extending to 1 standard deviation above and below the mean.
(B) Localization patterns of different ASY1:GFP variants together with ASY3:RFP (for staging of zygotene and pachytene) in a asy1 mutant background during prophase I. Bar: 5 μ
C A schematic model for SGTA action during membrane protein biogenesis. A signal sequence or the first TMD of a nascent chain is bound by SRP as it leaves the ribosomal exit tunnel. If the elongation arrest is inefficient or the distance between the first and second hydrophobic signals short, SGTA is recruited to the ribosome by a downstream signal located inside the ribosomal exit tunnel (route i). As translation continues SGTA binds directly to the exposed hydrophobic signal and can reduce co-translational ubiquitination of the nascent chain. Upon arrival to the ER membrane both SRP and SGTA dissociate from the nascent chain, which is inserted into the ER lipid bilayer. In this model inefficient recruitment of SGTA (route ii) might result in increased co-translational ubiquitination of nascent chains and possibly their proteasomal degradation.
(b) Immunoblot for the indicated proteins of homogenates (Hom), mitochondria (Mit) and lysosomal membranes and matrices isolated from cells stably expressing KFERQ-PS-CFP2 maintained for 16 h in media supplemented (+) or not (−) with serum. (c) Quantification of the amount of KFERQ-PS-CFP2 associated to lysosomes (matrix and membrane) performed in blots as the one shown in (b). Values are expressed as percentage of the total KFERQ-PS-CFP2 in the cell and are mean+s.e. of three different experiments. Difference in the lysosomal associated KFERQ-PS-CFP2 between serum+ and serum− condition (*) were significant for P=0.033 (t-test).
Graphs revealing that significantly upregulated cytokines in the proteome profiler in Casp8ECko mice are associated to the complement cascade (C) (n= 4 WT, 4 ECko, multiple t-test with Holm- Sidak method). Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001.
I. Detection of di-phosphorylated Pbs2. KT005 (ste11Δ pbs2Δ) transformed with YCplac22I'-Pbs2-HA was treated with the indicated concentrations of NaCl for 5 min. Pbs2-HA was immunoprecipitated from cell extracts, and subjected to Phos-tag SDS-PAGE. Blots of these gels were probed with (upper panel) anti-phospho-T518 or (lower panel) anti-HA. J. Same as in (I), except that the yeast strain KT003 (pbs2Δ) was used.
, Hydroxyproline content in lungs from control and F-CRTH2 KO mice treated with saline or bleomycin. *P < 0.05 vs control, #P < 0.05 vs saline group (two-way ANOVA); saline groups, n = 4 each, bleomycin groups, n = 8 each.
d, RT-PCR analysis of autoimmune regulator (Aire) and TRA expression in mTECs isolated from Atg5-/- to wild-type, or wild-type to wild-type grafts. Expression of β-actin (Actb), intestinal trefoil factor (Tff3), casein 2 (Csn2) and salivary protein 1 (Spt1) are also shown (5-fold serial dilutions). Data are representative of two experiments.
(B and C) Total proteins or RNAs were prepared in MEFs or liver tissues from wild-type or JfkKO mice for western blotting analysis (B) or qPCR measurement (C), respectively. Error bars represent mean ± SEM (n = 6, *p < 0.05, paired two-tailed Student's t-test).
(J) IgA, IgG and IgM isotype distribution of single-cell-sorted HBHA-reactive memory cells. Mean and SEM are indicated.
(a) Ganglioside composition of human fibroblasts, iPSCs, differentiated iPSCs and enriched iPSC-derived neurons (after FACS) from control (line C1-1), GBA-PD (line PD1-1) and GD (line GD1-1) subjects. Cell lipids were metabolically labelled with [1-3H]sphingosine and visualized by digital autoradiography.
D) Representative images of SYTO 9 and propidium iodide (PI) double stained M. florum cells, harvested from an exponential or death-phase culture, observed by widefield fluorescence microscopy. The brightness of each channel was adjusted equally between conditions. Scale bar: 5 µm.
Macroscopic assessment of the gastrointestinal tract of Mex3a KO and WT mice. These images are representative of the phenotype observed in mutant animals euthanized at different postnatal days. Boxed areas depict the distal small intestinal section (ileum) used for subsequent immunohistochemical analyses.
total protein in the BAL of adult Csf2ra-/- recipients 8 weeks after transfer (n = 5 mice). Age-matched Csf2ra-/- (KO) (n = 3 mice) and WT (n = 3 mice) were included as negative and positive controls.
(E-I) Role of the dephosphorylation of Ulk1 at Ser637 on etoposide-induced Ulk1 puncta formation and Atg13 phosphorylation. Ulk1/Ulk2 DKO MEFs stably transfected with HA-Ulk1 or its mutants, S637D and S637A, were treated with etoposide (10 µM) for the indicated times. (E, F) Cells were immunostained with an anti-Ulk1 antibody (E), and the population of cells with Ulk1 puncta was calculated (n > 100 cells in each experiment) (F). Data are shown as the mean  ±  SD (n = 3 experiments). *p < 0.05, **p < 0.01.
G, Spike rate increases with rising stimulus intensity were significantly shallower in OtofI515T/I515T SGNs, both for repetitive stimulation with 50ms tone bursts (left, p=0.014, t-test) and for continuous stimulation with amplitude modulated tones (right, p<0.001, Mann-Whitney U test).
E) Sequence alignment of budding yeasts' Ctf19-Mcm21 binding motif of Okp1. Similar residues are coloured red; conserved residues are on red background. We show full alignment in Fig EV5.
Immunoblot analysis of YAP expression in WT or Stat4-KO IECs treated with LIF (20 ng/ml) for different durations; β-actin was used as a loading control (top). The statistical analysis of YAP protein intensity is shown in the bottom panel.
(C) Expression of MAKR5-GFP fusion protein under control of the MAKR5 promoter in 5-day-old Col-0 or bam3 roots.
(C) Summary of results mapping interaction region of SIRT1 recognized by CSAG2. HEK293FT cells stably expressing HA-CSAG2 were transfected with indicated Myc-SIRT1 constructs for 48 h before IP with anti-HA followed by SDS-PAGE and immunoblotting for anti-Myc.
D, E Model for Bax-mitochondrial association before (D) and after (E) PCD-inducing stress. In unstressed cells, Bax continuously samples the MOM but does not insert into the MOM and is removed by pro-survival proteins (Bcl-2, Bcl-XL) in a process termed retrotranslocation. In response to stress, cyclin C associates with Bax stabilizing its interaction with the MOM in a fission complex dependent manner. Increased dwell time makes Bax more efficiently targeted by BH-3 only proteins activated by stress. BH-3 only protein binding induces conformational changes promoting Bax MOM insertion, homodimer formation and oligomerization ultimately leading to PCD.
A Depleted CRISPR guides (negative hits) in IMT1-treated RKO cells plotted as log2 fold change (LFC) versus log10 of adjusted p-value.
(E) Representative culture showing the X-activity reporter during PGCLC induction. Images for bright field (BF), XGFP, and XTomato were taken for ESCs, EpiLC d4 and PGCLC d5. Scale bar, 50 μm.
F Representative images of adipogenic, osteogenic and chondrogenic differentiation following shRNA knockdown in Lepr-Cre+ BMSCs. Scale bars were 100 µm.
(A) Flow cytometry dose response curve for cell binding of 4D9 mAb (EC50= 0.29nM), 4D9 Fab (EC50=0.17nM), and isotype to HEK cells stably overexpressing mouse TREM2. Data represent the mean ± SEM (n=2).
E. HumanHEK293T cells were transfected with plasmids expressing the indicated GFP-TatA-Flag substrates and different rhomboid proteases. Whole cell lysates were analyzed by western blot.
B. A close-up view of the interactions between Nec-1 and surrounding residues in RIPK1. Nec-1 is shown in green. The hydrophobic residues around Nec-1 in RIPK1 kinase domain are shown in sticks. Hydrogen bonds in this and all other figures are represented by yellow dashed lines. Docking score of Nec-1 in RIPK1 was -9.550.
Pyruvate kinase (PK) activity in FLAG immunoprecipitates from human endothelial cells expressing FLAG-tagged wild-type (WT), Y657F (YF) or Y657D (YD) eNOS; n=6 independent cell batches (1-way ANOVA and Tukey).
(A) Representative immunofluorescence staining of α-Actinin in NRVMs transfected with siRNA for 48h and then treated with vehicle (H2O) or PE for another 48h. Scale bar: 50μm. siMEF2a indicates MEF2a siRNA.
G Pol II-ChIP in the WT- and Mut-hmC clones, and a WT-C CHO clone generated with an unmethylated hCD45 minigene. qPCR for hCD45 DNA as indicated. ChIP values represent means +/- SD from three independent IP experiments. *p=0.013, **p=0.0089, two-tailed Student's t test comparing the Wt-hmC and Mut-hmC values.
(C) Images of TBK1 KD cells expressing mCherry-NDP52 or mCherry-OPTN under valinomycin treatment from Movie EV 5. Cyan, GFP-Parkin; magenta, mCherry-NDP52. Images are representative of two independent experiments. Scale bars, 10 µm
D, E IF of Lef1 in E60 mandible slices subjected to 3 or 0 kPa stress for two days. (D', E') are magnifications of boxed regions in the corresponding figure panels. Dashed lines mark the epithelium of PC. F Relative IF expression levels of Lef1 in the epithelium and mesenchyme after applying 3 and 0 kPa pressure. Data information: Data represent the means ± SEM. Scale bars = 100 µm. n = 3 for all experiments. Unpaired t-tests for , *P < .05, **P < .01, ***P < .001; NS. not significant.
Orthotopic xenograft MPNSTs derived from cell line S462 showed a number of differences in genomic alterations when compared to the S462 cell line itself. The outermost layer shows the full set of canonical human chromosomes. The next layers, from outside to inside, show the BAF of the S462 cell line (A), and its derived xenograft at passages 1 (B) and 4 (C). Copy number variations are represented by a colored line under each BAF (gray: 2n, red: > 2n (chromosomal gain); green: < 2n (chromosomal loss). LOH events are shown in blue. Pink highlights mark the differences between cell line and xenografts compatible with a selection process, while orange highlights mark the regions consistent with structural genomic changes due to engraftment process and passaging.
Representative images showing tumorigenesis (red circle area) of hOSE-YAPS127A cells with or without pRB knockdown or LATS2 deletion. Tumors formed by hOSE-YAPS127A cells with RB1 knockdown or LATS2 deletion are shown in red circle area. Right panel showing representative tumors formed by hOSE-YAPS127A-LATS2KO and hOSE-YAPS127A-shRB1 cells. Please note that no tumor xenografts formed in hOSE-YAPS127A alone group.
Cholesterol accumulation inhibits lysosomal fusion. Endolysosomal membrane cholesterol measurements and Filipin staining were carried out in either (A) WT MEFs loaded with cholesterol or in MSD
effect of in vivo TGFBRi and MMPi treatment of mice for two weeks on colon tumor formation. D, Experimental setup. Apcfl/fl-Cdx2CreERT2 mice were treated with Tamoxifen and, one day post treatment, injected with either MMPi (n=10) or the TGFBRi SB431542 (n=10) at 40mg/kg for two weeks with five injections per week. Vehicle treated mice: n=11.
Yield reduction assay was performed to determine the inhibitory effects of ACE2-Fc on virus titers The culture medium and cell extracts were harvested 24 hours post-infection for real-time PCR (B)
Correlation of protein AD/non-AD fold changes in pairwise combinations of two cohorts each. Combinations are Sweden vs Berlin (D), and Magdeburg/Kiel vs Berlin (E). Proteins included differ significantly (p < 0.05) and consistently in abundance by AD status in both cohorts each.
Eight weeks female lincRNA-EPS-/- mice (n=5) and WT littermates (n=5) were injected (i.v.) with VSV (sub-lethal dose, 6×107 pfu/g) for 12 h, and negative control groups were injected with PBS (n=3). Pathological section of liver and lung were harvested by H&E staining (H).
(c) Vps34 kinase activity. HEK 293T cells were co-transfected with Myc-Vps34-Vps15 and Flag-Rubicon or Flag vector, either in the absence or in the presence of Beclin 1-EGFP. Myc-Vps34-Vps15 was immunoprecipitated by an anti-Myc antibody and used for the in vitro kinase assay. The resulting radioactive PI(3) P was separated by TLC, quantified and normalized against the amount of immunoprecipitated Myc-tagged Vps34, as measured by western blotting (upper panel). The quantified results (lower panel) show that overexpressing Rubicon significantly downregulated the Vps34 kinase activity to 0.58-fold, but only without Beclin 1 overexpression (*P = 0.04, one-tailed Student's t-test with unequal variances, n = 4).
E Summary of the predicted consequence of the isoform switch events as shown by the feature acquired by the upregulated isoform. ncRNA stands for noncoding RNA, and NMD stands for nonsense mediated decay.
(B) Quantification of freezing behavior in a fear conditioning test after intraperitoneally injecting TAT or TAT-pS3 peptides in Nedd4-2 WT mice (left) or Nedd4-2 cKO mice (right) (n = 8).
Fetal death due to infection with hyperhemolytic GBS ΔcovR and non-hemolytic ΔcovRΔcylE in WT C57BL6 and NLRP3 inflammasome-deficient mice; fetal death is represented by the number of dead fetuses/total number of fetuses obtained from 6 pregnant mice per group. 'n' indicates total number of pups (both live and dead); *P = 0.011, **P = 0.0015, ****P < 0.0001, Fisher's exact test. Fetal death due to ΔcovRΔcylE in WT C57BL6 and NLRP3KO mice was not significant and is indicated as NS; P = 0.31, Fisher's exact test.
(B) Western blot analysis of SARS-CoV-2 Spike 1-1273, 1-674, and 319-591 expression in HEK293T cells. The black arrows indicate the location of the induced target proteins.
(E&F) Gli1-tdTomato+ cells expanded primarily in the outer medullary region. In contrast, COUP-TFII+ cells are distributed both in cortex and medulla. A subset of COUP-TFII+ cells (green) overlap with genetically labeled Gli1+ pericyte/perivascular cells (red) in UUO injury model (n=3 animals per group). CTL: contralateral kidney. Quantification by confocal micrographs in 200x hpf.
Radiolabeled [35S]COA7 (F) precursors were imported into mitochondria that were isolated from HEK293 MIA40 WT/WT and WT/Del53-60 cells. The samples were analyzed by reducing SDS-PAGE and autoradiography. The results of three biological replicates were analyzed, quantified, and normalized to control mitochondria at 45 min. The data are expressed as a mean ± SEM (n=3). IAA, iodoacetamide.
(i) Quantification of tetramer-positive cells at day 30 after infection as in a. Horizontal dashed lines (g,h) indicate the limit of detection. *P ≤ 0.05, **P ≤ 0.005 and ***P ≤ 0.0005 (unpaired t-test). Data were pooled from two independent experiments (a) or at least two independent experiments (c-i) with three to seven mice per group (error bars, s.e.m.) or are from one experiment with samples obtained from two independent experiments (b).