EMBO/sd-character-level-ner huggingface dataset:
A) Schematic representation of the Y48G1C.1 / pid-2 gene and its mutant alleles (xf23 and tm1614). The line plot displays the predicted disorder of the Y48G1C.1 / PID-2 protein, as obtained from PONDR, using the algorithms VL3 and VL-XT.
MITOL deletion resulted in hyper-activation of IRE1α RNase in ER stress. WT or MITOLnestin mice were injected with Tu for 24 hours and spinal cord was analyzed by qRT-PCR.
DCs were sorted from spleens of WT or Nlrc3-/- mice. Purified DCs were treated for 48 hours with LPS (100 ng/ml) in the presence or absence of the p38 inhibitor SB203580 (10 μM or indicated concentrations). CFSE proliferation assay (D) among naive 2D2 CD4+ T cells stimulated with MOG(35-55) plus DCs. NC: negative control.
B. A heatmap showing experimental validation of model-predicted inhibitor response. All inhibitors were tested at 500nM. Green text indicates an FDA-approved drug. Our model predicted Axitinib to be ineffective, therefore, used as a negative control.
C) Western blot documenting comparable expression levels of the MS2-FUS constructs. Cell extracts were subjected to SDS-PAGE and western blotting followed by detection of the MS2 fusion proteins by anti-MS2 antibodies (green). Tyrosine tubulin (red) served as loading control.
(a-d) Levels of mitochondria-shaping proteins during starvation. Protein samples (20 μg) from MEFs of the indicated genotype were separated by SDS-PAGE and immunoblotted with the indicated antibodies. Cells were starved for the indicated times.
Figure 7: Transient binding of HSFA2 governs sustained H3K4 methylation after HS.Top panel: Transient binding of HSFA2 after HS induces sustained induction of H3K4me2 (light blue) and H3K4me3 (dark blue) through direct or indirect recruitment of chromatin modifying factors. H3K4me3 and H3K4me2 levels remain elevated after H3K9ac (orange) and HSFA2 binding (red) have decreased and hence mark recent transcriptional activity of the locus, leading to sustained induction and transcriptional memory upon recurring stress. Bottom panel: In hsfa2, H3K4me2 and H3K4me3 remain low while the H3K9ac levels are only slightly changed compared to wild type. Profiles were drawn based on the data obtained for the APX2 locus.
Incidence of spontaneous colitis observed in wild-type (WT) and CD4+ cell-specific Adar1 knockout (Cd4cre A1fl/fl) mice (n = 11 for each group;
A-B: pDCs were either mock treated or exposed to the SARS-CoV-2 FR2020 early Wuhan-like strain or the SARS-CoV-2 alpha variant B.1.1.7 (0.1 MOI). Supernatants were collected at indicated time points and the production of type I IFNα (A) and CXCL10 (B) was quantified. Data information: Bars represent mean values with standard error of the mean and symbols represent individual pDC donors (n=3-4). Equal symbols represent equal donors Statistical significance was determined using the ratio paired student T test and compared the treated condition with the time point-matched mock condition *
Network summarizing liver-enhanced expressed proteins and signaling cascades significantly altered in COVID-19 patients (Lipid metabolism).
Chromatin accessibility ratio of SHOH vs SLOL cells in loci overlapping ES cell super-enhancer regions or not.
L, M IF of β-catenin at E60 and E90; The yellow arrows indicate the localization of β-catenin in the nucleus. Data information: Scale bars = 50 µm.
(F) Mean ± SEM body weight of ASMko and wt mice treated or not with PLX at the indicated time during long-term treatment (n= 7 mice per group, Two-way Anova, Bonferroni post hoc).
(C) bi‐1+/+ and bi‐1−/− mice were injected with 50 ng/ml of tunicamycin by intraperitoneal injection (N=3) and then LC3 levels were monitored in liver protein extracts by western blot analysis. Right panel: quantification of relative LC3‐II levels, **P0.005.
Model for the NCOA5‐mediated repression of Abca1 expressionIn response to sterol ligand treatment, LXR-RXR heterodimers initially induce the transcription of Abca1 through recruitment and activation of RNAPII (left). Following prolonged sterol ligand treatment, the NCOA5 repressor directly interacts with LXR at the Abca1 promoter. This repressor complex inhibits the recruitment and function of RNAPII resulting in attenuated expression of Abca1 (right). We hypothesize that prolonged sterol ligand treatment induces a regulatory modification on NCOA5 (shown in green), such as phosphorylation, which facilitates its recruitment to LXR.Crosstalk between pro‐inflammatory TLR3 and anti‐inflammatory LXR pathways promotes the association of NCOA5 with LXR, resulting in the inhibition of RNAPII recruitment and function, and repression of Abca1 gene expression. The regulatory modification of NCOA5 following activation of these two pathways may be similar or distinct to that in (A). We also cannot discount the contribution of additional constituents of this transcriptional complex to the recruitment of NCOA5.
D) Representative flow cytometry graphs for CD25 and CD54 staining in IL-2 and IL-15 NK cells in the presence or absence of PGE2.
B, C. HME cells expressing wild-type, T387A, or T387D STAT2 were seeded in 96-well plates at 8000 cells/well. On the second day, the cells were treated with IFN-β (10 IU/ml) for 2 h. The cells were then exposed to different multiplicities of infection of VSV for 2 h, followed by fresh media containing 10 IU/ml of IFN-β. The cells were analyzed by staining with crystal violet (B) after 48 h.
The release of fully processed, mature Dyn B under different stimulation conditions was analyzed in microdialysates collected from the hippocampus of pDyn-deficient (KO) animals two weeks after injection of AAV-pDyn. Three baseline samples (BL; 25 min each) were collected. This was followed by 25 min low-frequency stimulation (LF), 25 min baseline, and 25 min high-frequency stimulation (HF; I).
(E) Plaque formation dynamic of SPP1 was monitored by automated scanning Levin-Reisman et al., 2010() on a lawn of infected (10-6 PFU/ml) PY79 (WT) or ET41 (ΔdltA) cells grown on an MB agar plate. Shown are average values and SD from kinetics random plaques for each strain (n ≥ 10).
E HeLa cells were treated with control (CTRL) or SEPT7 siRNA for 72 h, labelled with MitoTracker Red CMXRos, then fixed and labelled for endogenous P-Drp1 for quantitative confocal microscopy. Representative images shown here. The scale bar represents 1 μm. The recruitment of P-Drp1 to mitochondria was significantly decreased as compared to control cells as measured by Pearson's correlation coefficient from at least 5 independent experiments (mean ± SEM, analysis of at least 250 cells per biological replicate). Student's t-test, * = p<0.05.
E. Quantitative TMT-based proteomic analysis of wild-type and Fbxl4 knock-out liver tissue protein extracts. Proteins from three control and three Fbxl4 knock-out liver protein extracts were TMT-labelled, quantified and analyzed separately as described in Materials and Methods; the data from control and knock-out animals were averaged after the analysis and presented as -log10 of the adjusted p-value vs log2-fold change (logFC). Mitochondrial proteins were selected according to mouse MitoCarta 2.0(Calvo et al, 2016) and highlighted in red; lysosomal proteins were selected according to hLGDB database(Brozzi et al, 2013) and highlighted in yellow.
Deterministic modeling of responses to multi‐pulse EGF/NGF stimulation at different dosages.
D Number of screened presynaptic proteins manually annotated according to their function and localization in the presynaptic terminal. Number of proteins identified with wild-type (wt) CSPα-mCit-PA or its mutant variants (ΔL116 and L115R) are indicated.
(C) MKH2/MK ratios were measured in cells grown under the same conditions as for biofilm formation. Data are expressed as average ± SD of three independent experiments. * Denotes p < 0.05 compared to WT via one-way ANOVA with Dunnett's posttest.
(B) Representative MRI pictures of untreated and irradiated mice at d0 and d14 after treatment start.
A. Superposition of the β5i/β6 active sites of genuine mouse iCP and the hβ5i/hβ6 human/yeast chimera illustrates that Met45 adopts the same 'open' conformation in both structures. Amino acid side chains important for substrate binding are depicted as sticks. The catalytic Thr1 is colored in black. Met31, the single amino acid difference between mouse and human β5i active sites, is highlighted in green.
D. Models summarizing the domain structures of EML4 and EML4-ALK proteins consisting of a coiled-coil region (dark green) followed by basic region (black), 12N blade (orange), blades 1-4 (purple) and blade 5 (lilac). The ALK JM domain is coloured light blue and the kinase domain is coloured light green.
Respiration rate was measured, and breathing pattern was recorded, with irregular respiration patterns indicated in red (d).
G C.elegans wild-type (N2) and mutant strains for ubc-25(ok1732), for scav-3(qx193) or the ubc-25 and scav-3 double mutant (ok1732;qx193) carrying a EGFP-Gal3 transgene were imaged in adult worms (L4 + 24 h). 3D reconstructions of the hypodermis. Small and big units represent 1 and 5 µm, respectively.
(B) Schematic representation of plasmid constructs used for in utero lentiviral infection. Whole-mounts or sections of adult infected epidermis with empty vector (EV) or Gata6-ires-GFP (G6OE) lentivirus were stained for GFP and Fasn. In vivo overexpression of Gata6 leads to ectopic Fasn expression in the HF/SG unit. White dotted lines define SG, and yellow dotted lines define a cyst. Note that the cyst is mostly negative for Fasn in agreement with its SD-like phenotype. White arrows indicate GFP-positive infected cells. These cells are stained with Fasn only in G6OE condition. H&E-stained skin from G6OE mice shows a cyst with SG elements in the HF unit (black arrows). Staining for Gata6 (both endogenous and exogenous) shows that Gata6 expression occurs in a limited number of cells (representative image in upper right panel). Bottom left graph shows quantification of the percentage of clones labelled for both Fasn and GFP in the SG, HF and IFE compartments. Data are means ± SD and originate from 4 EV mice and 8 G6OE mice (average of 11 clones per mouse). (C) Whole-mounts adult infected epidermis with EV or G6OE lentivirus stained with LipidTOX. Ectopic Gata6 cells are not stained with LipidTOX indicating an incomplete sebaceous maturation. Data information: Scale bars: 50 μm.
(c) Degradation kinetics of wild-type Dvl2 and its variants under starvation conditions. Lower panel: quantification of the immunoblotting results.
The pentose phosphate pathway (PPP) of M. florum along with ribose import. The transaldolase (TALA) reaction (pink) was missing in the network. Structural similarity between two 2-deoxy-ribose-phosphate aldolases (Mfl121, red in left box; Mfl639, red in right box) to a known transaldolase from the PDB (light blue) served as basis for the addition of this gene-associated reaction in the model. The observed essentiality (Ess.) and expression (Exp.) of genes (see panels c and d) associated with each reaction of the PPP are indicated by green (essential or expressed) or red (non-essential or non-expressed) colored squares.
Cry2-mEGFP-53BP1 1203-1972 W1495A assembles into FokI-induced DNA repair compartments within seconds after light induction. FokI was induced for 1h where indicated before cells were light-activated and imaged at 15 seconds intervals. Red arrowheads mark the FokI-induced lesion with mCherry accumulation.
(D) Oxygen consumption in state 3 respiration in mitochondrial fractions from siRNA‐transfected cells. Antimycin A with NT siRNA was used as a control. A.U., arbitrary unit; CCCP, carbonyl cyanide m‐chlorophenyl hydrazone; MPP, mitochondrial processing peptidase; NT, non‐targeting; PARL, presenilin‐associated rhomboid‐like protease; siRNA, short interfering RNA.
C. Maximum intensity projection confocal image of a sodium arsenite treated HeLa cell immunostained for endogenous Nup358 (green), P bodies (red, Dcp1a as a marker) and SGs (blue, eIF3η as a marker) using specific antibodies. Scale bar, 10 μm. The histograms represent fluorescence intensity profile along the dotted arrows. Adjacent graph represents quantitative data showing percentage of P bodies (top) or SGs (bottom) associated with nuclear envelope (NE), Nup358 positive AL, with each other or unassociated with any of the other mentioned structures (others). Data are presented as mean SD (n = 3).
Network of putative interactors, ranked as described in the text, and relative GO analysis. Interactors expressed in the epidermis are shown
(C) Illustration of the experimental procedure for MNs in an MFC treated with the fluorescently tagged retrograde tracer CTX in the distal compartment. Neuronal cell bodies in the primary neuron whose axons have traversed into the distal compartment were also labeled by the retrograde tracer.
(G) The molecular basis of interaction between GRASP55 and ceramide glucosyltransferase C-terminal peptide is studied by building a model of GRASP55:GCS peptide structure in the absence of the complex crystal structure. The carboxylate group of Leu of 'LDV' motif retains conserved hydrogen bonds with the backbone of 95LLGV98motif of GRASP55. Gly97 residue, which crucial to GRASP:GCS interaction is highlighted (pink).
C Protein extracts of THP-1 cells infected with SeV for various time points (upper lanes) were subjected to immunoprecipitation with anti-Beclin-1 and immunoblot analysis with antibodies shown on the left.
B HeLa cells were infected with S. flexneri for 4 h 40 min, labelled with MitoTracker Red CMXRos, fixed and labelled with antibody for endogenous SEPT7 for quantitative confocal microscopy. The scale bar represents 1 μm.
(l,m) Confocal microscopy (l) and quantification of the colocalization of GFP-LC3 signals (green) with M90T and ΔIcsB (m) of wild-type and NEMO-deficient (Ikbkg−/−) GFP-LC3-expressing MEFs infected for 0.5 h with wild-type S. flexneri (M90T) or S. flexneri ΔIcsB and incubated for 1.5 h in the presence of gentamicin. Red, RFP. Arrows indicate colocalization of GFP-LC3 signals with S. flexneri. Scale bars, 10 μm. *P 0.05, and **P 0.01 (t-test). Data represent three independent experiments with at least 100 cells each (error bars, s.e.m.).
(E) Quantification of extracellular endogenous Aβ40, Aβ42 and of Aβ42/Aβ40 ratio by ELISA analysis of conditioned media of 9 DIV siBin1, siCD2AP or siControl neurons (n=6; *PAβ40=0.0270 siBin1 vs. siControl, *PAβ42/40=0.0378 siBin1 vs. siControl, *PAβ42/40=0.0463 siCD2AP vs. siControl, t-test, mean ± SEM).
E Carbonate extraction of the heavy membrane protein fraction of human brain white matter (CNS WM) and lung tissue analyzed for the presence of Bak by Western blot. Membrane-associated protein supernatant (S) and membrane-integral protein pellet (P) are displayed. Smac is released from the mitochondrial inter membrane space (IMS) during carbonate extraction and CoxIV remains in the pellet. n = 2.
(E) The COPI vesicle reconstitution system was performed as described above (in D), and then the fraction of LCS and GCS in COPI vesicles versus their total distribution (on Golgi membranes and in COPI vesicles) was calculated.
C | Quantification of surface IgD mean fluorescence intensity (MFI) in Ptenf/f x MD4-trangenic mice in presence (mb1-cre +/+) and absence (mb1-cre +/ki) of Pten. Single dots represent the average MFI of 4 independent measurements per mouse (n), mean ±SD. Statistical significance was calculated by using an unpaired two-tailed t-test.
B. List of sequences showing indels at the veal2 locus at somatic level in F0 zebrafish embryos injected with TALEN arms.
H HeLa cells with stable knockdown of RNF123 were generated by shRNA. Western blot was performed as described in Fig 2A.
Immunoblotting of protein extracts from CAFs treated (+) or not with SOM230 (10−7 M) for the indicated times, using anti-P-Akt, anti-P-S6 or anti-4E-BP1 antibody (representative of n = 3).
A. Total quantified proteins at day one, three and seven upon primary cell culture in hepatocytes (hHEP), hepatic stellate cells (hHSC) and liver sinusoidal endothelial cells (LSEC). In all cases, number of biological replicates is 3. Values are presented as mean ± s.d. No additional replications of the experiment was done in laboratory.
H-J, ASC expression in the SNs and SN microglia of SNCA-PD mice. n=5 mice per group. Data are represented as mean ± SEM. Significantly different at p=1.91E-09* in graph I and p=0.0079* in graph J.
In vitro desuccinylation assay on H3K122succ peptides with recombinant SIRT7 (D) Unmodified H3K122 peptide was used as control (left dot). Peptides were probed with H3K122succ AB #2 after incubation with sirtuins.
(C,D) HeLa cells transiently transfected with empty pCDNA3 or DOR were incubated in DMEM (basal) or in HBSS (starvation). Cells were processed by transmission electron microscopy. Arrows indicate autophagosomes. Insets are autophagosomes (diameter, 407±63 nm). Scale bars, 1 μm. Autophagosomes were counted in 50 randomly chosen transfected cells. *Significant effects of starvation, P0.05; τsignificant effects of DOR overexpression, P0.05. DMEM; Dulbecco's modified Eagle medium; DOR, diabetes‐ and obesity‐regulated gene; GFP, green fluorescent protein; HBSS; Hank's balanced salt solution; LC3, microtubule‐associated protein 1A/1B‐light chain 3.
Primary astrocytes from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were stimulated with IFN-γ (10 ng/ml) for four hours. Thereafter, cells were treated with CHX (100 μg/ml) for indicated times. Whole cell lysates were analyzed by WB with indicated antibodies.
Brcc3 expression confirmed by western blotting [biological replicates (n=3) with three different cell lines (male: #A6, #A13, #A17; female: #A4, #A10, #A11)].
E. ER-localized MITOL is transported from the mitochondria, and is not newly synthesized protein. HeLa cells stably expressing HA-Parkin were co-transfected with vectors for MITOL-KikGR and FLAG-FKBP38. After ultraviolet light (365 nm) exposure to the whole plate, cells were incubated with or without CCCP (10 µM) for indicated time, and monitored for red and green KikGR fluorescence. Scale bar, 10 μm. Higher magnification images of the boxed regions are shown in the small panel. Right panel is schematic experimental model for KikGR in this study.
HWestern blot analysis of the kinetics of ULK1, FUNDC1, and the phosphorylated in MEFs treated with FCCP(20 μM) for the indicated times.actin
(d) Dvl2-LC3 interaction in vivo. IB, immunoblotting; IP, immunoprecipitation; S, starvation; WCL, whole-cell lysate; N, nutrient-rich.
A. Representative FACS plots of splenocytes from diseased secondary recipients that were transplanted with 104 to 105 flow-sorted myeloid leukemia blasts (ML: CD11b+Gr1+/CD3-CD4-CD8-) from sick primary Myc/Bcl2+LSK-, GMP- or DN2-transplanted mice. Cell percentages in indicated gates are shown.
(a) Expression of GCaMP3.0 in the mushroom body of an individual fly, focused on the horizontal lobes. The red line indicates a region of interest used to determine changes in fluorescence emission. Scale bar represents 50 μm. (b) False color-coded image of Ca2+ activity in the horizontal mushroom body lobes shown in a. Warm colors indicate high levels, cold colors indicate low levels or no Ca2+ activity. The numbers indicate changes in fluorescence ΔF (%).
(C-E) Bar plot showing mean mRNA levels of VCAM1, ICAM1, and SELE measured 4 hrs after stimulation of ECs with or without TNF-α ± (siKDM7A+siUTX). Data are shown as means ± SE (n=3). *P < 0.05 compared to TNF-α (-) siKDM7A+siUTX (-). † P < 0.05 compared to TNF-α (+) siKDM7A+siUTX (-). Statistical differences were analyzed by the Tukey-Kramer test.
E Consistently, higher experimentally measured PER2 levels in the SCN at the dosing time leads to a larger PF-670-induced phase delay which was also captured by the NHP model when 20 mpk dosing was used.
(B) Human embryonic kidney 293A (HEK293A) cells were co-transfected with HA-tagged ArfGAP1 or RFP1 (control), together with Myc-tagged S6K1. Cells were starved of amino acids for 1 hour (-AA), and then 1 mM of leucine (+Leu), glutamine (+Gln), or asparagine (+Asn) were added for 2 hours. Immunoprecipitates (IP) or whole cell lysate (WCL) samples were probed for HA, Myc, and phosphorylated S6K1 at Thr 389. Vinculin was a loading control.
MS/MS spectrum of the K202-ε-GGH containing peptide from CtUba4C202K. A representative annotated fragmentation spectrum is shown with the b- and y-ions marked in red and blue, respectively. The precursor ion at m/z 591,98 is labelled in green. The peptide sequence is shown at the top with the collision-induced fragmentation pattern. The Urm1 conjugation site was identified by detection of the GGH remnant motif generated by chymotryptic digestion.
F Western blot analysis of lysates of cells treated As a positive control, cells were treated with the mTOR-inhibitor Torin1 (1 µM) for 2 h. GAPDH was probed as loading control.
F MedIP with antibody specific to 5caC followed by qPCR with the indicated CD45 primers in naïve and activated CD4+ T cells. Values represent means +/- SD from three independent IP experiments. p= two-tailed Student's t test comparing the indicated values.
(b) Aversive associative memory performance at 3 h after training (ITM), ARM and ASM of 3-d-old Spd1mM+ and Spd5mM+ compared with Spd− flies (n = 8-9 independent experiments; F = 2.05 for ITM, F = 0.02 for ARM, F = 1.74 for ASM; one-way ANOVA with Bonferroni correction).
G PCNA was increased in WT PH pulmonary vessels but was decreased in miR-210−/− tissue exposed to either condition (N = 5/group) (**P = 0.0096, *P = 0.0124, *P = 0.0263 for miR-210−/−).
(D) AEP activity assay with brain lysates from different brain hemispheres of single side pre-vagotomy DSS-treated 3xTg mice. Data represent the mean ± SEM; representative data of three samples; *P =0.0162 (*P < 0.05) compared with control, one-way ANOVA.
(D) qPCR levels of LOX family in PSCs, normalized to RPLP0 and relative to control
Quantification of human MT in sorted CD3+ MitoTneg and MitoTpos cells after mitoception with UC-MSCs, by transmission electron microscopy (n=25 independent cells analyzed per group). Graph shows mean ± SEM and statistical analysis by Student's t-test.
(A) Western blot detection of SMCHD1, ATMpS1981, CHK2 pT68, CHK1 pS345, RPA pS33, RPA pS4/8, γH2AX and Vinculin in wild-type or SMCHD1 KO HeLa cells γ-irradiated with 3Gy dose and harvested at the indicated times (1h, 12h, 24h) after the treatment.
MDM were treated with 5μM ETO for 18h, 3μg/ml cGAMP and 10ng/ml IFNβfor 18h. RNA was isolated and qPCR performed for selected genes using TaqMan assays. Expression levels of target genes were normalised to GAPDH. (n = 3, mean ± s.e.m.; *P‐value ≤ 0.05; (ns) non‐significant, paired t‐test).
The expression of LIMT is shown relative to (A) PAM50 subtypes (N=381 patients), (B) tumor grade (N=309), (C) HER2 status (N=309) and (D) ER status (N=381 patients). Expression of individual lncRNAs was determined in tumors from breast cancer patients of the Oslo2 study using Agilent arrays. Molecular subtypes of the corresponding tumors were determined by using the PAM50 classifier. The Student's t-test was applied to evaluate differences in lncRNA expression between two groups. To evaluate differences in expression among three or more groups, we applied one-way analysis of variance (ANOVA).
(B Four HUP serum samples giving discrepant results by PCR method were tested in the neutralization assay of pseudotyped lentivirus (Fig. 4A). Data represent the mean±SD of duplicates. *, p<0.05; **, p<0.005; ****, p<0.00005; (Paired two-tailed t-test comparing all serum dilutions to the pre-COVID sample)
(B) IHC images showed vGluT2+ signal was dramatically reduced in the outlined area of mice received Cdc50a shRNA viruses, but not in controls. Scale bar, 100 µm. d: dorsal, m: medial.
(G) Immunofluorescence of HA-(PR)20 (green) and the nucleolar factor UBF1 (red) in U2OS cells treated with 7.5 μM HA-(PR)20 alone or together with heparin (0.5 μM). Data information: Scale bar (white) indicates 2.5 μm. *, p<0.1; ***, p<0.001; t-test.