EMBO/sd-character-level-ner huggingface dataset:
F. Representative images for co-localization between POLD3 (red) and RAP1 (green). White arrows indicate co-localization events. Quantification of co-localization events between POLD3 and RAP1 is shown on the right. A total of 190-230 nuclei were scored from three independent experiments. Data information: All scale bars: 5 μm. Data are shown as mean ± SD. F: the red line marks the mean value. Statistical analyses were performed with Student's two-tailed unpaired t-tests with Welch's correction for normality of distribution, unless specified otherwise.
F. MMP detection with down- or up-regulation of lnc-AP/pep-AP in two groups of CRC cells. Scale bar, 10 µm.
(E) Schematic depicting key host proteins that control transport pathways associated with the TGN-RE-plasma membrane compartment. Protein colors depict their compartmentalized functions.
HCoVs.a to h. Inhibitory activity of EK1C4 in cell-cell fusion mediated by the S proteins of HCoV-OC43 (c)
C T1-weighted MRI axial images at thigh and calf levels show that the fatty degeneration is more prominent in thigh muscles, equally affecting posterior and anterior compartment, with relative sparing of the rectus femoris, sartorius and gracilismuscles until late stages (4, 10 and 11, respectively). Strikingly, the fatty tissue is located in the internal parts of almost all the affected muscles in thigh (1, 2, 3, 5-9), while the external regions are spared. At calf level, only the gastrocnemius medialis muscle (12) shows this pattern, while the soleus (13) is diffusely involved. Patient II.2 (PII.2) shows late-stage thigh muscles with an unusual involvement of the tibialis posteriormuscle (14) in the lower leg.
E, F. (E) qPCR analysis of gene expression in the KAP114 knockout strains (green bars) compared to wild type (black bars) under regular conditions. (F) qPCR analysis of gene expression in the KAP114 knockout strain (green bars) compared to wild type (black bars) grown in high salt conditions. qPCR fold-changes in mRNA expression are relative to control (YPD media, black bars). Actin was used as the internal control.
B U2OS wild‐type (WT) and USP45 knockout (KO) cells were irradiated with UV‐C (20 J/m2). At the indicated post‐irradiation times, genomic DNA was extracted and subjected to Southern dot blot analysis using antibodies recognising CPD and dsDNA total antibody. Data are shown from a triplicate experiment in which each blot is derived from independent cells.
FACS analysis of DQ-BSA (C) dye fluorescence in RCS treated with the indicated FGF ligands (50 ng/mL) for 16h. Concanamycin A was used at 100 nM for 1h to inhibit lysosomal function. Fluorescence intensities were expressed as % relative to vehicle (5% ABS). Mean +/- standard error of the mean (sem) of N=3 biological replicates/treatment. Analysis of variance one way (ANOVA) =0.005 (C); Tukey's post hoc test ***p<0.0005.
I. Permeability assay using vibratome section showing the leakage of retro-orbital injected cadaverine dye (red) in the brain of WT (top panel) and Glut1iECKO (bottom panel) mice. Note that cadaverine is retained in the intravascular area of WT mice (upper panel), but extravasated and accumulated in the brain parenchyma (white arrowheads) of Glut1iECKO (bottom panel) mice.
(A) NLRP3+/+ and NLRP3-/- THP-1 cells were incubated with SARS-CoV-2 at an MOI of 1 for 1 h, followed by washing away extracellular viruses and further culture for 3 h. Otherwise, cells were stimulated with 10 μM nigericin for 30 min following pretreatment with 1 μg/ml LPS for 3 h. Cell pellets were collected and immunoblotted with antibodies against the indicated proteins. Treatment with 1 μg/ml LPS for 3 h served as a control.
(b) Live Nile red quantification of wild-type and lipl-1lipl-3 double mutant worms shows that lipl-1 and lipl-3 contribute to the clearance of lipids from the endocytic pathway. Mean+s.e.m. signal intensity is shown as percentage relative to wild type; significant differences are indicated; n = 4 independent experiments.
Figure 4. Mmi1 drives Rrp6-dependent heterochromatin gene silencing at pericentromeric regions. (E) RNA-IPs showing that Rrp6-Myc13 binds to nam5/6/7 lncRNAs in a Mmi1-dependent manner. Average fold enrichment is shown with error bars that indicate mean average deviations (n=3) for (D, E). P value was calculated using a two-tailed Student's t-test.
BLI sensorgrams of high-affinity VHHs B Nanobody-loaded sensors were dipped into wells containing RBD at the indicated concentrations for 600 s, and then incubated with assay buffer for 1 h. The response curves (black) were fitted using a mass transport model. Fitted curves are shown in red.
(D) Analysis of LC3 processing by autophagy in the presence or absence of lysosomal protease inhibitors pepstatin A (10 μg/ml) and E64D (10 μg/ml) after doxorubicin (1 μg/ml) treatment for 12 h. *P0.05 compared with control shRNA group.
Cells isolated from the peritoneal cavity (peritoneum), spleen, or blood were evaluated by flow cytometry for the percentages of human CD19+ cells within the fraction of human CD45+ cells. Representative density plots are shown for the peritoneal cells.
(C) p62 immunostaining of tibialis anterior (TA) or quadriceps (Quad) muscle from 9-mo-old control, VCP-WT, or one of two VCP-RH transgenic lines (RH9 or RH12). Note accumulations of p62 in the middle of myofibers or along subsarcolemmal regions.
(C) Western blot analysis of LC3-I and LC3-II in the spinal cord lysates from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. n=3. Data presented as mean ± SEM. One-way ANOVA tests with Bonferroni's multiple comparisons: ****, p<0.0001.
G) Glucose-6-phosphate dehydrogenase activity was measured in ES (blue), Zscan4+ (red) and 2-cell-like cell (green) lysates using a fluorometric assay. Measurements were obtained from 3 independent biological replicates, performed in 3 technical replicates each. n.s. - not significant; one-way ANOVA. Data information: In panels A-C and G, boxes indicate the range between the first and third quantile, the band depicts the median and the whiskers extend no further than 1.5-times the interquartile range. Individual dots indicate the measurements obtained in each individual technical replicate.
Western blot of PMN treated with 1 µM PPP or 50 ng/ml IGF1 for 60 min. Cells were lysed and the extracts assessed for expression levels of dynein adaptor proteins, all proteins were assessed from the same blot. Hook3 expression didn't change after treatment with PPP or IGF1 compared to controls (DMSO, 100%; PPP, 102.16 ± 4.3%, P=0.67, Student's T-test, N=3 independent experiments; water, 100%; IGF1, 93.48 ± 4.2%, P=0.26, N=3 independent experiments, data shown are mean ± SEM). However, BICD1 expression was significantly increased in PMN treated with PPP compared to control (DMSO, 100%; PPP, 137.1 ± 7.3%, **P=0.002, Student's T-test, N=7 independent experiments). In contrast, IGF1R stimulation by IGF1 had no effect on BICD1 expression (water, 100%; IGF1, 88.1 ± 14.0%, P=0.49, Student's T-test, N=3 independent experiments, data shown are mean ± SEM). BICD2 expression didn't change after treatment with PPP or IGF1 compared to controls (DMSO, 100%; PPP, 104.44 ± 6.5%, P=0.51, N=3 independent experiments: water, 100%; IGF1, 106 ± 7.5%, P=0.51, Student's T-test, N=3 independent experiments, data shown are mean ± SEM).
Overview of the mammalian 40S in complex with IAPV-IRES. Left, cryo-EM final post-processed map of class 1 with 40S colored yellow and IAPV- IRES maroon. Right, corresponding final refined model with IAPV-IRES colored according to figure 1A.
E Quantification of ATG9 and LAMP1 co−localization in cells stably depleted for TBC1D5 (shRNA#1) or VPS29 (shRNA#2), transiently transfected with myc−TBC1D5 plasmid resistant to TBC1D5 shRNA#1. Cells were treated with KU0063794 (6 h), 20 h post−transfection, fixed, and immunostained with anti−LAMP1 and anti−myc antibodies.
(E) Expression of Mettl14 and p63 in WT and KO cells was determined by immunoblots with respective antibodies. Immunoblot for GAPDH was used as loading control.
(G) A proposed model for a role of SIRT5 in mediating oxidative stress to increase IDH2 and G6PD activities, NADPH production, and cellular protection. SIRT5 is activated by oxidative stress by a yet unknown mechanism. The active SIRT5 stimulates IDH2 and G6PD by desuccinylation and deglutarylation, respectively, thereby increasing NADPH production and protecting cells from ROS damage.
(A) Percentage of single LT-HSCs from septin 7fl/fl of septin 7∆/∆ mice that completed first and second division up to 48 hours post initiation of culture. (192 sorted HSCs cells were analysed, error bars indicate mean±SD).
(A) Schematic drawing depicts the step-wise development of the nervous system in Drosophila, starting during embryogenesis, progressing through three larval stages and metamorphosing during pupal stage into the adult nervous system. The first connections in the neuromuscular system are formed between MNs and muscles in late Drosophila embryos (stage 16). MNs at this stage expressing UAS-RFP under the control of the motoneuronal driver OK371-GAL4 (OK371>RFP) are color-coded along the ventral nerve cord according to different patterns of Hox gene expression. OK371-RFP positive MNs were FACS sorted and single cells were sequenced by targeted Smart-Seq2 to enrich for Hox gene representation (HoxSeq) as spatial markers (see also Materials and Methods).
B, Measurement of TOC1-GFP protein turn-over in TOC1, 5X, T135A, S175A native promoter lines by cycloheximide (CHX) treatment. 10-d-old seedlings grown in 12h/12h light/dark cycles were subject to cycloheximide (CHX) or ethanol (Mock) treatment for indicated time length. Data from 3 independent trials were fitted to non-linear Weibull regression curves. Data information: TOC1 protein was detected by α-GFP, ADK was used as loading control. TOC1/ADK ratio was calculated by the intensities of TOC1-GFP bands normalized by the intensities of ADK bands using ImageJ.
D: Relation between signal duration and response amplitude for IEGs and ILGs derived from qPCR validation data. Median amplitude is based on six qPCR-validated ILGs and six qPCR-validated IEGs.
A, Schematic of the CHOP locus. Black boxes indicate amplicons for subsequent ChIP-qPCR analysis.
Figure 2. Mmi1 binding to nam1 lncRNA controls MAPK-mediated entry into sexual differentiation. (B) Mating assay showing the percentage of zygotes forming over time in the same cells as in (A).
A). Recombinant human LIF inhibited growth of BAE cells in a dose-dependent manner. BAE cells were cultured in the presence of vehicle and indicated concentrations of recombinant human LIF (rhLIF). Cell proliferation was analyzed after 6 days, n=3. Data information: Bars and error bars represent mean±SD. All experiments were carried out in three independent studies. siNegative, negative control siRNA not targeting any known genes. Two-way ANOVA was used as statistical test.
E Molecular details of the RBD⋅Re5D06 interaction. Left: overview of the RBD⋅Re5D06 complex, with the RBD shown as a green ribbon overlayed with its semitransparent surface. Re5D06 is shown as a ribbon (in magenta) with orange CDR loops. Right: Details of the RBD⋅Re5D06 interaction interface. RBD and Re5D06 are shown as transparent ribbons colored as on the left, with selected interface side chains depicted in green (RBD) or magenta (Re5D06). Blue marks nitrogen, oxygen is shown in red. A water molecule is shown as a yellow sphere. Dashed lines link interacting atoms (distance ≤ 4 Å). Lines pointing onto backbones indicate contacts to carbonyl-carbons or amide groups.
Core genome phylogeny of part of the Saccharomyces Genome Resequencing Project (SGRP) yeast isolates; coloured dots indicate the four strains whose KOs library was screened in this study.
C. Left: representative traces of AMPA mEPSCs recorded in layer V pyramidal neurons are illustrated. Right: the histograms represent means ± S.E.M. of AMPA mEPSC frequency and amplitude measured during the last minute of recording, n = neurons from 3 to 5 mice per group. The mEPSC frequency is: 4.7 ± 0.4 Hz for Vehicle (n=9 from N= 7) and 6.8 ± 0.4 Hz for THC (n=9 from N= 5) conditions, respectively, p < 0.01and 5.3 ± 0.5 Hz and 4.6 ± 0,3 Hz for THC+SB258585 (n=10 from N= 6) and THC+Rapa (n=9 from N= 5) conditions, respectively, p < 0.05 and p < 0.01 vs. THC-injected mice. In B and C, * p < 0.05; ** p < 0.01; *** p < 0.001, one-way ANOVA followed by Newman-Keuls test.
(C - F) Quantification of the QR.ap migration angle (C D), distance (E) and speed (F) in mig-2S139A/E mutant animals. Each line in (C  E) represents the measurement from one movie of QR.ap migration. Error bars indicate SD. N = 12 -17. **, P 0.01; ***, P  0.001 by Student's t tests.
(C) TUNEL (green) staining in shScr, sh1 and sh2 at day 5 of neuroectodermal differentiation. Nuclei were counterstained with DAPI. Scale bar, 20 µM.
(A) The intraerythrocytic state of P. falciparum illustrating the localization of PfFNT within the parasite's plasma membrane.
(A) WT and atg1Δ cells expressing mitochondria targeted mCherry cultured in SD-N +50 mM MES-KOH (pH 6.2) medium for 120 hours were observed by fluorescent microscopy. Mitochondrial DNA was stained with SYBR green I, and mitochondria were visualized by mitochondria targeted mCherry. Scale bar, 2 µm.
C Growth of p53+/+ and p53-/- HepG2 cells transfected with and without exogenous SQLE (HA-SQLE) in LPDS medium. Protein expression is assayed after transfection 24 hours.
E. Analysis of TRAPPC2 localization at SGs upon CLIC1, CRYAB and ENO1 depletion. Mean ± s.e.m. n>100. ****p<0.0001; ns: not significant, One-way ANOVA with Dunnett's multiple comparison test.
A, B Representative images of tumorxenografts of ME180-MXIV (MX, right flank), ME180-YAP (A) (YAP, left flank), and ME180-YAPS127A (B) (YAPS127A, left flank) cells implanted in athymic nude mice. Red lines indicate the edge of tumors.C The growth curve of humantumorxenografts derived from control (ME-MX) and YAP-overexpressing ME180cervical cancer cell lines (ME-YAP, ME-YAPS127A) implanted in the athymic nude mice. Each point represents mean ± SEM of six tumors (control n = 10).
(A) Representative confocal images of stage 17 embryonic heads highlighting the expression of Dfd (purple), Myosin in muscles (blue) and FasII in axonal projections (green) in control (elav>RFP) animals and in animals with reduced Dfd expression in neurons (elav>DfdRNAi) or in muscles (Mef2>DfdRNAi) or both in both tissues (elav;Mef2>DfdRNAi). The single channels for the projections (FasII staining) of MN2a and/or MN3 to the MHE, MHD or LR muscles of an early stage 17 Drosophila embryo are shown. Asterisks highlight the location of MN2a and MN3, respectively. MN2a is identified by the FasII expressing axonal projection emerging from a Dfd expressing MN, which normally innervates the Dfd expressing MHE muscle (as shown in the elav>RFP control), while MN3 is identified as the MN underneath MN2a, which normally innervates the MHD muscle (as shown in the elav>RFP control). The panel on the right side represents a schematic drawing of the confocal image shown on the left side, summarizing the innervation of the anterior muscles (LR, MHE, MHD) by projections emerging from MN2a (magenta) or MN3 (cyan) in control and perturbation conditions.
(f) Peak to peak distance in auto-correlation from detrended Venus::HES5 signal collected in apical regions of spinal cord between E9.5-E11.5; bars indicate mean and SD of individual slices from 3 independent experiments; Kruskal-Wallis test not significant, p=0.44.
(F) FoxM1 luciferase activity determination for young adult mouse colonocytes (YAMCs) treated with DMSO or 10 nM TCDD for 1 d, n=3 per group.
(B) Seven ub-HSs show strong correlation between ubiquitin binding and Slx8 enrichment (Slx8-9myc ChIP). 16-kb-windows of the indicated regions centered around the ub-HSs are depicted for ubiquitin and Slx8 binding profiles. Ubiquitin (FK2) data for WT and cdc48-6 are from the same experiment as depicted in (A). Data represent means from two independent replicates.
C.- D. Kaplan-Meier plots showing time to biochemical recurrence in months for PDK4 in primary tumors (C) and in primary and metastatic tumors combined (D) in the MSKCC PCa GSE21032 data set. Groups were generated by a median split. P-values were estimated by Log-rank test (C-D) and adjusted with Benjamini-Hochberg method (D). + = censored.
Formalin-fixed paraffin-embedded (FFPE) sections from control or Tgif1KO mice were immunostained with anti-pSmad2 antibody and revealed by immunofluorescence (IF) and DAPI. Representative pictures at 40x are shown (n=30). Scale bars, 100 μM.
(D) Histochemistry and immunohistochemistry of quadriceps muscle from VCP-RH-expressing transgenic mice. Hematoxylin and eosin (H&amp;amp;E) staining of a 15-mo-old animal with an RV, p62 immunostaining of an RV from a 12-mo-old animal, LC3 immunostaining of an RV, and subsarcolemmal accumulations of LC3 from a 12-mo-old animal. The bracket highlights one LC3-positive myofiber. A single muscle fiber is outlined in white. (C and D) Arrows denote vacuoles or accumulations of p62 or LC3. Bars, 30 µm.
BMDCs generated from c-Junfl/fl or c-JunΔ/Δ Mx1-Cre BM were stimulated with IMQ for 12h. CCL2 protein was quantified by ELISA. (n= 7-10; 3 independent experiments). Data information: Data are shown as mean ± SEM. P‐values were calculated by multiple t-test with Kruskal- Wallis (E) multiple comparison test. Statistical significance: ns > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001. See Appendix Table S3 for exact P‐values.
BrdU labeling of Col17a1-/- skin at P2. Scale bar: 100 μm. (Bottom) Quantification of BrdU-positive cells in the epidermis surrounding blisters (n= 3 (control) and 4 (Col17a1-/-) biological replicates). The data are shown as the mean ± SE. Student's t-test. NS, no significance.
(b) The PF/EF ratio of the PtdIns(3) P labelling density in autophagosomal membrane (mean±s.e.m.). The ratio was small (that is, PF) in WT, but close to 1 (that is, PF≅EF) in ymr1Δsjl3Δ. The experiment was repeated three times and the number of colloidal goldparticles per μm2 was measured in more than ten randomly selected images.
(E) H&E, SOFG and Immunofluorescence analyses of the spine specimen of PGIS model compare to baseline. n=5 per group.
A, B. Constitutive and BR-responsive growth of bes1-DxhsfA1qM seedlings. Hypocotyl elongation of 7-day-old dark-grown (A) and light-grown (B) seedlings on medium containing either 1 μM epi-BL, 1 μM BRZ or DMSO as a control (c). Left: Mean and SD of 30 plants. Significant difference at P≤0.05 of results is indicated with different letters and was determined with a Student's t-test. Right: photos of representative plants.
(A) HeLa cells were transfected with EGFP-Nup50 and different truncations. After 24h cells were shortly pre-treated with 0.1% Triton X-100 in PBS, fixed with 4% PFA and analyzed by confocal microscopy (left panel). Scale Bar: 10 µm. The graph (right panel) shows the Nup50 domains (blue: Importin α interaction domain, green: NPC targeting domain and pink: Ran binding domain) and the truncation tested. Ability to bind the nuclear rim is indicated on the right.
Analysis of tumor initiation ability of vehicle- and JNKi-treated cells from experiment described in panel (K); n = 3 mice per group, two implantations per mouse.
C Yeast two‐hybrid (Y2H) assays were performed with a GAL4 DNA‐binding domain fusion and/or activation domain for each protein indicated in the table to detect interaction between these proteins. Cells grown on media lacking LEU, TRP and HIS (to select for bait and prey plasmids) or tested for lacZ reporter gene activity.
F and G p53+/+ and p53-/- HepG2 cells were cultured for 48 hours in medium containing fetal bovine serum (Serum) or lipoprotein-depleted FBS (LPDS). Protein expression was shown by western blotting (F). mRNA levels of SQLE were examined by qRT-PCR (G). P: premature SREBP2; M: mature SREBP2.
(F) Stacked bar plot (Marimekko chart) color-coded for the relative contribution of cells derived from the respective anatomical regions. Ranges of p-values are provided for significantly enriched regions per cluster, based on hypergeometric tests. Benjamini-Hochberg correction was applied to correct for multiple testing (*P < 0.05; **P < 0.01; ***P < 0.001).
(B) The kinetics of PAR accumulation was analyzed by western blotting. WT and Ews-/- cells were treated with H2O2 (1 mM, 20 minutes), followed by incubation in fresh media for the indicated times to allow release of DNA damage
A The genomic structure of Gr28b. It is composed of five different forms by alternative splicing. The arrow head indicates the P-element insertion. White boxes indicate predicted untranslated regions in flybase. Arrows indicate primers for RT-PCR.
D458 cell lines were treated with PBS (vehicle, black) or with ActivinB (green). Growth curve experiments showing cell proliferation upon ActivinB treatment. The p-values were determined by unpaired t-test and two-way ANOVA *p < 0.05, **p < 0.01, ***p < 0.001.
(C) Visualization of the different MNs based on Dfd expression in MN2a and the MHE, which is innervated by a FasII positive axon emerging from MN2a (projection A), while the motoneuronal projections from MN3 (projection B) innervates the Dfd-negative MHD located just underneath the MHE (see also B). All MNs are highlighted by yellow circles.
A, Yeast two-hybrid (Y2H) assay of interactions between the Gal4 DNA binding domain BD-NF-YB2/3, BD-NF-YC3/4/9 and Gal4 activation domain AD-TOC1/5X fusions. Yeast growth shown on leucine-, tryptophan-deficient plate indicates successful plasmid transformation, and yeast growth shown on leucine-, tryptophan-, histidine-deficient and 3-AT plate indicates positive protein interactions.
(C) UMAP plots color-coded for the compartment that cells were isolated from. Parenchyma (dark orange); choroid plexus (dark cyan); perivascular space (pink); leptomeninges (violet).
J. Western blotting results of midguts indicate a decrease of LAS in the midguts of aged Drosophila. Loading controls, β-tubulin. K. Quantification of LAS band intensity as seen in experiments (J). Error bars indicate the SD of three independent experiments. L Data information: Error bars represent SDs. Student's t-tests, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.
(e) Effect of deoxyribonucleoside supplementation individually or in combination on the rate of IgM to IgA switching in CH12F3-2A cells. Data are presented as % IgA switching relative to the IgA switching in cells treated with an equivalent volume of the solvent in which the deoxyribonucleosides were dissolved (n=3; mean ± sd; two-tailed unpaired Student's t-test; ** = p ≤ 0.01; *** = p ≤ 0.001).
G Western blot showing YAP levels in non-targeting control siRNA (siCtrl)- and YAP siRNA (siYAP)-transfected HT3 cells.
(e,f) MBd enrichment in cancer cells leads to increased anchorage-independent growth. MKLP1-GFP-expressing HeLa cells are separated into 'MBd-high' and 'MBd-low' subpopulations. An increase in the 'MBd high' over 'MBd low' ratio is associated with an increase in soft-agar colony formation (e). No significant difference was observed when the enrichment of the MBd-high subpopulation was less than threefold. More soft-agar colonies are formed when MBds are enriched by NBR1 depletion (NBR1 shRNA) in HeLa (f, left; P=0.0012, n=3) and mouse 134-4 cells (f, right; P=0.0086, n=3); control, shNT. Data are mean±s.d., and the colony number (e,f) is the sum of INT-violet-stained colonies from ten random fields.
D Illustration of interbacterial competition mediated by VpT6SS1 when introduced into V. natriegens (yellow) on a plasmid (pT6SS1), as shown in C. Prey cells are denoted in blue.
B) Distribution of the difference in netcharge between orthologs from a Mycoplasma species devoid of DnaK (M. crocodyli, indicated as MYCCM), and its closest DnaK-expressing relative (M. synoviae, indicated as MYCS5).