EMBO/sd-character-level-ner huggingface dataset:
(c) FLAG-eIF4A and TSC2-V5 co-immunoprecipitate in Kc167 cells in the absence of chemical cross-linker. Cells were transfected with FLAG-eIF4A and TSC2-V5 expression vectors and treated with media containing or lacking amino acids for indicated timepoints prior to lysis and anti-FLAG immunoprecipitation. The experiment was performed in absence of the chemical cross-linker DSP. Representative of 3 biological replicates.
(D) Genome browser view of CMS-IP data showing CMS (5hmC) distribution at Il2ra and Foxp3 locus for CD4+ naïve T cells and WT Treg cells. Hydroxymethylated regions (hmRs) and DhmRs are shown on the top; conservation (cons) is shown at the bottom.
(c) Knockdown of STUB1 represses Δ133p53α. MRC-5 fibroblasts (30 PDLs) were transfected with two siRNAs against STUB1 (no. 1 and no. 2) and control siRNA. At 4 days after transfection, immunoblots were performed using anti-STUB1, anti-Δ133p53α, DO-1 (detecting full-length p53), CM1 (detecting both Δ133p53α and full-length p53), anti-p62/SQSTM1 and anti-β-actin antibodies.
C. Schematic showing the functional and molecular mechanisms of Mettl3 and Mettl14 in antitumor immunotherapy.
C. Model of the role of MDI and Larp in mitochondrial biogenesis. MDI (green rectangle) localizes at the mitochondrial outer membrane, and recruits Larp (blue rectangle) to the mitochondrial surface. Larp interacts with polysome (blobs) and translation stimulators, and stimulate the translation of a subset of nuclear-encoded mRNAs. Proteins synthesized on the mitochondrial surface are in close vicinity of the Tom-Tim mitochondrial transporter complexes, which would facilitate their rapid transport into the matrix. The targets of MDI-Larp complexes include most nuclear-encoded ETC subunits, mitochondrial ribosomal proteins, TFAM, and mtDNA polymerase (Tamas) (collectively represented in red). Mitochondrial ribosomes are required for the biogenesis of proteins encoded by mtDNA, all of which are ETC subunits. Thus MDI-Larp complexes seem to coordinate the expression of both nuclear and mitochondrial genome to promote the biogenesis of ETC complexes.
(A) Representative pictures of the expression of NEDD4L, GP130 and p-STAT3 in the epidermis of a normal skin section (same specimen) and sections from psoriasis patients. Isotype are IgG antibodies from same species served as negative control. (B) Semiquantitative scoring of NEDD4L, GP130 and p-STAT3 in the epidermis detected by IHC. Data information: Each symbol represents one patient Scale bar, 200 μm (100×) or 50 μm (400×). All data are shown as the mean ± s.e.m., and significant differences were analyzed using two-tailed Student's t test (normal, n=15, psoriasis, n=36). * P＜0.05, ** P＜0.01, *** P＜0.001.
E) Plot representing the average value for all the target regions around the TSS obtained by ATAC seq after Control, H2A.Z.1 or H2A.Z.2 siRNAi.
(A) Schematic representation of M45 truncation mutants used in this and a previous [36] study. The C-terminal RNR R1 homology domain is shown in white, the unique N terminus in grey. The RHIM is marked black.
(C) Cellular and EV-associated miRNA levels were measured in Huh7 cells either expressing the pCIneo or HA-HuR expressing vectors by qRT-PCR (mean+/- s.e.m., n=5). Cellular miRNA levels were normalized against U6 snRNA.
F LNCaP cells were transfected with either control or two independent STAMP2-specific siRNAs, ST2-1 and ST2-2. Three days after transfection, cells were treated in the same way as in (D). Whole-cell lysates were prepared and subjected to Western blot analysis with the indicated antisera.
Schematics of the D-loop formation assay, including pre-incubation of template dsDNA with cGAS-cat (i), or with cGAS-cat being added after RAD51 was bound to dsDNA (ii).
SCR transcript levels in Col and hag1-6 hypocotyl (F) and cotyledon (G) explants at indicated days on CIM.
TLN accumulations are distinct from lysosomes. A TLN (15-nm gold)-containing structure as obtained by the conventional cryosectioning technique double labeled with Lamp-1 (10-nm gold). The TLN-positive compartment is clearly distinct in size and from lysosomes (L) and lacks Lamp-1. P, plasma membrane. Bar, 200 nm.
C, IHC staining of THEM6 expression in CWR22res and 22rv1 orthografts. Scale bar represents 100 µm. Data information: Data reproducibility: representative image from 3 independent biological experiments.
(A) Exemplar image of EB3-tdTomatoHeLa cell used for kymograph analyses. To assess astral MT number and dynamics a line (blue) was added to images from the pole to the cortex.
(C) mRNA expression of Vim on indicated days of WT EB and Tnfaip2-/- EB differentiation (n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by multiple t-tests with Holm-Sidak correction for multiple testing).
D. Short telomeres in Rb∆K4 mice. Images of splenocyte metaphase spreads hybridized with the telomere repeat probe (pink). Note shorter telomeres in Rb∆K4 splenocytes (arrows). Bottom, quantitative analysis of 10 splenocyte metaphases from one pair of Rb∆K4 and control littermate; (P<0.001 by two-tailed Mann-Whitney-Wilcoxon test).
Bioluminescent images and the corresponding quantification of tumours in mice implanted with GBM#P3 cells at days 7 (n = 5 per group, P = 0.58) and 21 (n = 5 per group, P = 0.005). Statistical significance was determined by two-sided Student's t‐test. Body weight of tumour-bearing mice after 3 weeks of EFV or PBS treatment. Data are shown as the mean ± SEM. Statistical significance was determined by two-sided Student's t‐test.
C. Immunofluorescence quantifications (C) of relative Cyclin B1 and MAD1 levels at unattached and attached kinetochores in cells arrested in STLC. Each dot represents a kinetochore, data is from 40 kinetochore pairs (13 cells, max 5 kinetochore pairs/cell).
(D) Co-IP analysis of the interaction between KEAP1 and p62 in absence and presence of TRIM16.
E. Paired goodness-of-fit values for Per2::Luciferase oscillations of baseline, single-transfection and double-transfection SCN (p=0.02, Prok2.Cre before and after, ns. p=0.17; ProkR2.Cre before and after, ns. p=0.99; both Prok2.Cre and ProkR2.Cre applied before and after ****p<0.0001).
(c) Immunoblot for ubiquitin in homogenates (Homog), cytosol and the autophagic fractions described in a, using 6% (top) and 16% (bottom) gels. Dotted line separates stacking and running parts of gel.
Antibodies against Siglec‐5 and Siglec‐14 neutralized the interaction between Siglec‐14 Fc to Hsp70, as determined by ELISA.
(I) Western blot analysis of QKI-5 protein levels in BEAS-2B, A549 and H1299 cells. β-actin was used as an internal control.
A Montage of class averages and 3D volumes of humanTFG (amino acids 1‐193; EMDataBank accession code EMD‐6076). Two sets of 2D class averages and 3D volumes are shown with the left columns showing the class averages generated by reference‐free alignment and classification and the right columns showing 3D RCT volumes corresponding to the class average to the left. Scale bars, 50 Å.
D The fraction α of the A blocks in the shell versus the length of the A blocks (represented by the number of segments) of spherical paraspeckles in the steady state. The parameters used for the calculations are shown in the Materials and Methods.
(A) Lysates from HCT116 cells were immunoprecipitated separately with anti‐XIAP antibody and an isotype‐matched control IgG. Immunoprecipitates and input were analysed by western blotting. The data are representative of two biological replicates.
(D) Top GO terms obtained using DAVID Functional Annotation Bioinformatics Microarray 6.7 for first and second phase genes and genes activated upon NFKBIA knockdown, as in (C), as indicated.
(B) (left) Representative images of anti-IBA1 immunostaining in dentate gyrus and amygdala from AppNL-G-F mice receiving either AAV-VHH-B9 or AAV-GFP; (right) quantification of the IBA1+ cell number in the indicated brain regions across experimental cohorts.
(D) Meta-gene alignment of BRD4 signals on BRD4 ranked SEs. Pol II and H3K27ac ChIP-seq reads were aligned centering on BRD4 SEs of LPS treated WT macrophages.
Drp1S616 phosphorylation in dermal fibroblasts derived from sporadic PD patients. A quantitative analysis of phospho-Drp1S616 (pS616/Drp1) in sporadic cases is shown (j). Student's test. *p<0.05. Data was presented as mean ± SEM of three independent experiments.
Representative images of gross specimens of primary cecal tumors (top) and liver metastatic lesions (bottom) in mice orthotopically (cecal) injected with CALIC knockdown HCT116 cells. Tumors are marked with yellow arrows. (Right) Percentage of mice with primary tumors and liver metastases.
Quantification of non-esterified cholesterol content by means of filipin staining in hearts of mice on HFD for 17 weeks followed by treatment for 1 week with 2H10 antibody (n=5) compared to control antibody treated mice (n=5). Data presented as box-and-whisker plots. Boxes represents lower/upper quartiles with the median values indicated with a horizontal line. Whiskers represent min-max values.Statistical evaluation using t-test, p-value: ** <0.01.
B COG map detailing significantly enriched or scarce functional categories expressed in vitro and in vivo during the presence of corticosteroids.
(d) Comparison of somatic mutation rate (mutations / Mb) between human tumours carrying HUWE1 mutations or not grouped according to MLH1 status. Note that the increased mutation rate is found primarily in tumours where MLH1 is not silenced indicating increased mutation rate (and HUWE1 mutation itself) is not due to silencing of MLH1 (Mann-Whitney, p = 0.0007, n ≥ 11).
a, Percentage of ciliated cells in control (Ctrl) and IFT20− MEFs (*P = 0.030, n = 3) and wild-type (WT) and Ift88−/− KECs (**P = 0.003, 25 cells each, n = 3) after 24 h of serum removal. Arrows, cilia.
(F) B6J or STING-/- mice were depleted of NK cells via treatment with anti-NK1.1 (right panel) or left untreated (left panel). One day after NK cell depletion, B6J or STING-/- mice were i.v. infected with 4 x 105 PFU parental MCMV or MCMV m152stop. 16 hpi, RNA was extracted from spleen homogenates and MCMV E1 transcript levels were determined by qRT-PCR. Data were normalized to 107 cellular β-actin transcripts (D-F).
C. UMAPs depicting the relative expression of migration genes CXCR4 and EPHA5. Visualization of the gene expression of migration genes CXCR4 and EPHA5 along the pseudotime axis. D. UMAPs depicting their relative expression of neurotransmitter genes GRIA4 and GRIA2 along with visualization of their gene expression along the pseudotime axis.
D Percentage of GFP+ cells within T cell subpopulations 17 days after CD40LG editing of healthy male donor (HD; n=11) or patient (Pt; n=1) derived CD4+ T cells, measured by FACS analysis. Median ± IQR.
D, E Hypocotyl lengths of seedlings grown under continuous white light at 20 °C for 7 days or at 20 °C for 4 days followed by 3 days at 28 °C. Representative seedlings are shown in (D). Numbers indicate the ratio of hypocotyl lengths (28 °C/20 °C). Different letters above each box indicate statistically significant differences (ANOVA and Tukey's HSD; P < 0.05; n > 15). In the box plots, the thick lines indicate median values, the lower and upper ends of the boxes represent the 25th and 75th percentiles, and the ends of the whiskers are set at 1.5 times the interquartile range.
Human Aβ exhibits a biphasic profile in CSF of APP transgenic miceA, B Aβ40 and Aβ42 concentrations in CSF of male APP23 mice (heterozygous; 3 (n = 14), 6 (n = 12), 8 (n = 10), 12 (n = 11), 19 (n = 9), and 25 (n = 6) months of age). CSF Aβ40 (F(1, 56) = 22.351, P < 0.001) as well as CSFAβ42 (F(1, 56) = 38.597, P < 0.001) followed a significant quadratic trend.
Under normal conditions in WT mice, both glucose and lipids enter the cell and are used as cellular fuels. In this situation, both pathways are used and are driven by PDK4 according to needs and fuel availability.In the case of ALS, metabolic flexibility is lost because of chronically increased PDK4 and subsequent inhibition of PDH and PFK1 leading to glycogen accumulation. Increased lipid use through β-oxidation that can only function under aerobic conditions may underlie the greater endurance capacity in SOD1G86Rmice. With time, the cell produces more reactive oxygen species, thereby inducing cellular damage.Data information: CD36, CD36 antigen/fatty acid translocase, CPT1, carnitine palmitoyl transferase 1, FAs, fatty acids, FA-CoA, acyl-fatty acids, GLUT4, glucose transporter 4, LPL, lipoprotein lipase, PDH, pyruvate dehydrogenase complex, PDK4, pyruvate dehydrogenase kinase 4, PFK1, phosphofructokinase 1, ROS, reactive oxygen species. Drawing was performed with the website Somersault1824 (http://www.somersault1824.com).
A. KT299 (MATa hkr1Δ msb2Δ ssk2/22Δ) was exposed to the indicated concentrations of α-factor for 15 min in the absence of osmostress. Phosphorylation of Fus3 and Kss1 was detected by immunoblotting.
(A) Red1 possesses a putative zinc‐finger domain. A BLAST search reveals homology between Red1 and a conserved domain termed pfam10650, a CCCH‐type zinc‐finger that has the CX8CX4C3H motif as a consensus sequence. The arrow indicates the conserved histidine residue, which is substituted for isoleucine.
Western blot analysis of Collagen Ⅰ and Ⅲ expression in liver tissues from control and F-CRTH2 KO mice 4 weeks after CCl4 challenge.
B.) Genotyping PCR confirming the deletion of the endogenous DPCK (Δdpck) using primer pairs
(D) HE staining of lesional skin sections from WT and Raptor cKO mice injected with LL37 or control vehicle (n=6 for each group). Scale bar: 50 μm. (E) Dermal infiltrating cells were quantified (n = 6 for each group) for each high power field (HPF).
In vitro modelling. WT or MPSIIIA GAG (0.8 μg/ml HS) was applied to WT mixed glial cultures for 24 hours before harvesting the media or cell extract and measuring levels of IL-1β.
E) Curve of correlation between chymotrypsin-like activity and Ub-K48 linked proteins in the intestine, where variability between mice is observed.
(D) Graph showing the expression levels of miR-206-3p and miR-145-5p in FAPs treated or not with TSA after antagomiR treatment (n=3, biological replicates). Star (*) indicates statistical analysis by t-test relative to FAPs -; *p<0.05, **p<0.01
Ctcflos tr1 KD (ASO 1) and Ctcflos tr 3 and 4 KD (ASO 2) with their respective controls and (M-O) Ctcflos tr1 KD (ASO 1) and its control in UCP1 wildtype (WT) and UCP1 knockout (KO) cells, measured by microplate-based respirometry (Seahorse XF96 Analyzer). Oxygen consumption is recorded under basal conditions and in response to successive injection of oligomycin (5µM), isoproterenol (1.5µM), FCCP (1µM) and antimycin A (5µM) to determine basal leak, UCP1 dependent uncoupled, maximal and non-mitochondrial respiration, respectively. Data are expressed after deduction of non-mitochondrial respiration. Mean values ± SD, n=4-5 (biological replicates). Quantification of isoproterenol-stimulated UCP1-mediated uncoupled respiration, expressed as fold of basal leak respiration. Mean and single values, (K n=4 (biological replicates), paired t test *p<0.05, (L) n=5 (biological replicates), paired t test *p<0.05, (N, O) n=7 (technical replicates), unpaired t test, n.s. p>0.05, ****p<0.0001.
(f) Myotubes immunofluorescence of cells in proliferation medium (P.M.) and after 2, 4 and 6 days of myogenic differentiation in serum free medium. Control (untreated), shCD20-treated C2C12 cells, C2C12 and HSkM myoblasts pre-treated with anti-IGF2R for 24 hours were stained. Desmin-positive myotubes are shown in green. Scale bars=75 μm.
ELISA detection of IFNβ release from mBMDMs stimulated with ecGAMP and icGAMP at indicated concentrations for 4 h.
(D) Autocorrelation of GAL10. The fit of 2 linear lines reveals a burst duration of 152.4 ± 2.3s. n = 19 traces. Shaded area and errors indicate SEM.
A. Co-immunoprecipitation of Larp with MDI-myc in transfected S2 cells. Tubulin was used as loading control.
(b-o) All panels show retinal flat mounts except for i and l. Green signal indicates PNA expression and red signal indicates red/green or blue opsin. The wild-type retina is shown at P35 in b-d. Red/green opsin (b) and PNA (c, d) expression were detected both dorsally and ventrally, whereas blue opsin (c,d) was detected only ventrally. The Pde6b−/− mouse is analyzed in e-g and j-o. A central to peripheral gradient of PNA and shortening of cone outer segments is shown in e-g. At P20, there were fewer elongated outer segments in the center (e) as compared with the periphery. Higher magnifications of a central or peripheral outer segment from e are shown in f and g, and a wild-type outer segment is shown in h (white line marks the outer segment). A quantification of outer segment length at 3 weeks is shown in i (error bars represent s.d. of 15 measurements each). With the shortening of outer segments during degeneration, red/green opsin was localized throughout the membrane of the cell body, and PNA, which detects an extracellular protein(s), was reduced to a small dot attached to the residual outer segment (j) (yellow shows red/green and PNA overlap, arrow). A higher magnification of a cone showing red/green at the membrane is displayed in k (arrow). A cross section showing red/green in cell body is shown in l (arrows) (P70; j-l). During degeneration, red/ green opsin was detected mainly dorsally (m), whereas PNA (m, n) or blue opsin (o) expression were not altered (m and n, P21; o, P49). GCL, ganglion cell layer; INL, inner nuclear layer.
A . MC3T3E1 cells were transfected with pTOPFLASH together with pCMV-β-gal. After 24 h, the cells were treated with DMSO, KY-02061 in DMSO, or 5 µM PolyR-DBM for 2 days. The luciferase activities of whole cell lysates were measured and normalized with β-galactosidase activities. [n=3]
B - Northern blot analysis of total RNA isolated from the same cultures at the same time point as used for flow cytometry, probed for OmrA (strains containing pOmrA) or OmrB (strains containing pOmrB). 5S rRNA was used as loading control.
L Diagram illustrating the biomechanical stress-associated downregulation of RUNX2-Wnt/β-catenin pathway in the mesenchyme, inducing upregulation of Wnt signaling in the epithelium, which triggers PT development.
D, E, Differences in mean fluorescence intensity of GFP and GNAT1 protein staining (D) and transcripts (E) between donor and acceptor photoreceptors. (GFP: wt recipients, n=9 images from 3 transplanted animals; Nrl-/- recipients n=8 images from 4 transplanted animals. GNAT1: Nrl-/- recipients, n=7 images from 3 transplanted animals).
B Immunohistochemical analysis of DDR1 and DDR2 levels on human melanoma tissue microarrays. Representative IHC images and quantification (right bar histograms) of DDR1 and DDR2 expression in normal skin, naevus, primary melanoma (PM) and lymph node melanoma metastases (MM). Scale bar, 100 µm. Histological scoring of the samples was performed in blinded fashion. Samples were scored as low, medium or high for DDR1 or DDR2 expression (naevus, n = 12; PM, n = 30; MM, n = 20).
(C and D) Poly(A) tail analysis of GAPDH and ACTB mRNAs from total RNA isolated from PABPDHFR cells described in (B) was determined by extension poly(A) tail (ePAT). PCR products were run on high-resolution agarose gels. 'A12' represents the size of ePAT RT-PCR amplicons derived from a mRNA with a fixed (A12)-tail.
F. Representative RABIF-GFP PLA images and quantitations from cells expressing GFP-RAB13(T22N) carrying wt or ∆PMO RAB13 3'UTR. N>70 cells. Bars: mean ± s.e.m.. Arrows indicate PLA signal at the cell periphery. Arrowheads indicate PLA signal within the cell body. Boxed regions are magnified in the insets. Scale bars: 10 μm; 4 μm in insets.
(A) 293T cells were cultured in complete medium made of dialyzed serum for 24 h which was then replaced with medium in which one amino acid was eliminated and cultured for 8 h. Then, WB was used to measure p-AMPK, p-ACC, p-Raptor and total AMPK, ACC, Raptor protein expression. "Nor" = normal medium. Actin served as the loading control. The red text "-Cys" indicates that cystine deficiency most significantly activates AMPK and its substrates.
E. HEK293 cells were treated for 2, 4 and 8 h with 20 μM neocarzinostatin (NCS). After treatment, cells were incubated with 2',7'-H2DCF-DA to cytofluorometrically assess the intracellular production of H2O2. Values are shown as units of DCF fluorescence relative to untreated cells. Values are shown as units of fluorescence relative to NCS-untreated cells (arbitrarily set as 1) and represent the means ± SD of n = 3 independent experiments. n.s., not significant.
qRT-PCR for PHD1, PHD2, and PHD3 in HCT116 silenced for PHD1 (*P = 0.0006 toward Scr), PHD2 (*P = 0.0004 toward Scr), or PHD3 (*P = 0.0075 toward Scr). A two-tailed unpaired t-test was performed with n = 3/group.
(Q) The qRT-PCR analysis with RNA isolated from untreated or Bafilomycin A1 (300 nM; 4 h, 8 h, and 12 h) treated control or Flag-IRGM expressing HT-29 stable cells as indicated.
D) Sequence alignment of Stn1 highlighting serine 74 identified in fission yeast as a phosphorylated residue.
G) Quantification graph showing Jupiter-GFP protein levels in qNSCs by normalizing to that in MB NSCs in (F). n=10 brain lobes (BL) for normal food condition; n=14 BL for NR food condition. ****p<0.0001.
A (Upper) Schematic representation of ER-located fluorogenic probe Halo-tag K73T/L172Q mutant (AgHaloER). SP: signal peptide. The carboxyl-terminal KDEL motif is the ER retention sequence. (Lower) Diagram of AgHaloER that detects ER proteostasis in live cells.
(C) qRT-PCR analysis of PR1 expression levels in Col-0, map4k4-1 and c867 after mock (MgCl2) or Pst DC3000 inoculation, values are the means ± SD, n = 3 (biological replicates), p < 0.01. Data information: Statistical analysis were performed using a one-way ANOVA with Newman-Keuls multiple comparison tests or t-tests. n.s. indicate non-significant.
F, PTPN3 and PTPN3 (D811A) abolish the interaction between TβRI and Smurf2 in HEK293T cells. HEK293T cells were co-transfected with plasmids as indicated. 20 h later, cells were treated with MG132 (20 μM) for 4 h, followed by IP and Western blotting.
A. Immunoblots showing the levels of MCM3 and PrimPol proteins in PRIMPOL WT and KO cells. MEK2 and Ponceau-S are shown as loading controls.
Serial dilutions of the indicated strains were spotted on complete medium and grown at 30°C or 20°C. Otrt1∆ and Otrt1∆cay1∆ are strains with circularized chromosomes lacking telomeric sequence (Supplementary Fig S7).
C Detection of MAPKKK5K375M -GFP and MAPKKK5K375M,6xA-GFP transiently expressed in Arabidopsis protoplasts.
C) Transmission electron microscopy (TEM) of autophagosome like structures within MoDCs infected with Pg381, Mfa1+Pg and FimA+Pg for 12 hours (upper, middle and lower panels, respectively). The right and left sections show the different magnifications of randomly selected sections. Pg381 and FimA+Pg strains are mostly enclosed in the characteristics double-membrane intracellular vesicles (Orange arrows). Contrary, Mfa1+Pg escaped these autophagic (double-membrane) vesicles and enclosed within single membrane structures or freely occupy the cytoplasm (Green arrows).
B. Normalized fitness functions of E. coli BW25113 in the absence of tet(B) and their corresponding model fits in the presence of varying concentrations of antibiotics TET, DOX, and MCN in the media ([S]M). Normalized quadruplicate data is shown for each antibiotic.
D: Gt1 cells transiently expressing PIKfyve-GFP or PIKfyveΔAcyl (24h) were subjected to a [35S]Met/Cys pulse (20 min, 37 °C) and immediately lysed or chased (60 min). Proteins were immunoprecipitated with anti-GFP antibody and subjected to SDS-PAGE and autoradiography. Lysates from cells treated with siRNA against PIKfyve were also pulsed and immunoprecipitated and subjected to autoradiography to ensure correct band is detected. Error bars represent s.e.m. (n=3 individual biological replicates).
D Comparison of the location of developmental stage‐specific Scl binding sites relative to TSS shows that Scl binding near TSS occurs more often in later hematopoietic development compared to mesoderm.