EMBO/sd-character-level-ner huggingface dataset:
Ex vivo proliferation assay with mature B cells from Tam‐treated mb1‐CreERT2 (upper row) or Tam‐treated mb1‐CreERT2;Sykfl/flmice (lower row). The cells were incubated with the indicated stimuli for 90 h.
Proliferation of mESCs expressing WT, Mettl14 KO, KO+WT, and KO+RK METTL14 over a 5-day period. Each point represents the average of three independent replicates and error bars represent standard deviation (SD). data from three independent replicates were analyzed by Student's t-test and shown as mean ± SD. *, p < 0.05; **, p < 0.01, ***, p < 0.001.
Bi-ii. Lateral view of the adult fly head. Scale bar: 100 μm.i. Rac1 overexpression with removing one copy of dlrrk (dlrrke03680/longGMR-GAL4,UAS-Rac1W), results in smaller eyes where most ommatidia are fused together.ii. Removing one copy of dlrrke03680 in GMR-GAL4 background, as control has no effect on eye morphology (GMR-GAL4/+;dlrrke03680/+).
COVID-19 caused dysregulation in lipoprotein metabolism, glycolysis and TCA cycle. The three boxes from left to right are control, mild and severe, in which gray means normal, blue means decrease, red means increase. CS: Citrate synthase; IDH: Isocitrate dehydrogenase; ACO2: Aconitase; OGDH: α-ketoglutarate dehydrogenase; DLD: Dihydrolipoyl dehydrogenase; SDH: Succinic dehydrogenase; MDH: Malate dehydrogenase; PDH: Pyruvate dehydrogenase; PDK: Pyruvate dehydrogenase kinase; ACLY: ATP citrate lyase; ACAC: Acetyl coenzyme A carboxylase; FASN: Fatty acid synthetase; LDH: Lactate dehydrogenase.
(C) Mitochondrial O2 consumption rates in SN were measured by high-resolution respirometry in the presence of following respiratory substrates: malate, pyruvate, and glutamate for Complexes I-IV, succinate for Complexes II-IV, glycerol 3-phosphate for mGpDH-IV and ascorbate and TMPD for complex IV, and normalized to protein content. Fmr1 KO mitochondria show elevated levels of respiration in the presence of succinate as well as ascorbate and TMPD (*p=0.0483 and *p=0.0360 respectively, n=9 per genotype, paired two-tailed t-test). Data are presented as a box-and-whiskers graph (the box extends from 25th to 75th percentiles, central horizontal line is plotted at the median, whiskers show 5th - 95th percentile).
I) Insulin levels were measured in plasma from control and Mfn2KO old mice subjected to GTT (n=6 mice per group).
(C) Representative pictures of the AGD of 13-week-old WT male (upper left), WT female (lower left), ARLmon/Y (upper right) and AR-/Y (lower right) mice.
Multiple sequence alignment of different HOIP orthologues illustrating the position K735 and K784 according to the ClustalX colour scheme. Sequences were retrieved from the NCBI protein database with the following accessions: Homo sapiens (NP_060469.4), Canis lupus (XP_005623312.1), Mus musculus (NP_919327.2), Monodelphis domestica (XP_007479924.1), Xenopus laevis (NP_001090429.1), Alligator mississippiensis (XP_006259801.1), Takifugu rubripes (XP_003968217.2) and Drosophila melanogaster (NP_723214.2).
Human bronchial epithelial BEAS-2B cells were infected with A/Scotland/20/74 (H3N2) virus (IAV) at MOI=1. After 4 h, cells were treated or not with succinate (Suc; 4 mg/ml) up to 20 h. Human alveolar epithelial A549 cells were infected with the recombinant influenza A/WSN/33 virus expressing a fusion NS1-eGFP protein at MOI= 0.5 for 4 h, then treated with 4 mg/mL of succinate. A549 cells were monitored for 24 h using a BioStation IM-Q device. (e) Single-cell dynamics of cell death as assessed by morphological analysis. Data are represented as the mean ± SEM of 3 independent experiments with 3 technical replicates each Statistical analysis was performed using the Mann-Whitney test (*P < 0.05).
(A) Chromatin features mapped here displayed differences between CLL (patient CLL1) and an NBC donor (H7) as shown for the TCF4 locus, which encodes for a transcription factor from the E protein family. Based on the increased H3K4me1, H3K27ac and ATAC signal, two predicted enhancer loci were marked that became active in CLL. Note that the y-axis for RNA-seq is scaled differently for CLL (8000) and NBCs (100) to visualize that the TCF4 gene was not completely silenced but lowly expressed also in NBCs as evident also from the H3K36me3 mark. Light grey depicts active chromatin region and dark grey the confined enhancer locus coinciding with an open chromatin region.
(b) Renilla luciferase expression controlled by let-7 in HeLa cells depleted of NDP52 or ATG5 with siRNA (black and grey bars are independent siRNAs). Results are normalized to firefly luciferase and a version of the Renilla luciferase construct with mutated let-7 binding sites. n = 3 independent experiments. The asterisks denote mutations in the let-7 target sites of the reporter.
(A) Model of ArfGAP function in vesicle trafficking through the Golgi in yeast. Gcs1 and Glo3 function in trafficking from the cis-Golgi to the ER, whereas Age2 and Gcs1 may function at or beyond the TGN
Ldb2 KO mice (red, n = 10-11) were compared to control (blue, n = 10-11) in Y-maze test (F).
(G) H460 cells were transfected with wild type, Δ37, or Δ63 CSAG2 for 48 hr. Cells were then treated with the indicated concentrations of H2O2 for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).
Modeling predicts that increasing the ribosome synthesis rate leads to shorter recovery times in response to equal amounts of total antibiotic exposure. Here, we use and for slow and fast ribosome synthesis, respectively.
(G) Adipocyte sizes of iWAT from Ftoflox/flox and FtoAKO mice fed a HFD were estimated from the H&E staining results in (F) using ImageJ. The percentage of cells with the indicated sizes is shown. Data information: The data were presented as the mean ± SD (n = 6). Statistical analyses were performed using Student t‐test. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
(e) Transmission electron micrographs of EJ cells with stable shCont. or shROCK1#1 knockdown, cultured in control or HBSS medium for 16 h. Arrow bars indicate autophagic vacuoles. Scale bar, 500 nm.
(C) Flow cytometry analysis of transfected cells in (B) immunostained with anti-FLAG M2 antibody. Corresponding mean flourescence intensity values are shown.
Total intracellular glutathione (GSH + GSSG per 106 cells) in HCT116 WT cells as shown by GR re-cycling assay 48h post transfection of siRNA. Indicated values are means from four MRP1 siRNAs (n = 3), two xCT siRNA (n = 2-3) and two control siRNA (n = 2-3).
A BL-E5(+) cells were individually transduced with shRNA-directed against TET1 (TET1-sh1 and TET1-sh3), TET2 (TET2-sh4) or control shRNA. Knockdown efficiency was assessed through qRT-PCR relative to expression of the housekeeping gene RPS16.
(C) Phylogenetic representation of the Importin-β family from humans adapted from (O'Reilly et al., 2011). For further details see the main text. Members found to bind to either H3.1 or H4 in this study are coloured red. An asterisk indicates structural information regarding interaction with H3 (see Figure EV4)
C Sequences of synthetic PrP alleles differing in the octarepeat region of mousePrP. Conserved histidines in octarepeats 2-5 are coloured blue and missense mutations are shown in red. Overproduction of C2 fragment is indicated by ++ signs to the right of the panel.
(C Venn plot of RNA-sequencing datasets of treated cells at 8 dpt (n=3 independent samples, sequenced together) (C). for doxorubicin- or abemaciclib-treated groups (8 dpt) relative to vehicle-treated group from the RNA-sequencing datasets (p-value<0.01 was regarded as significant).
A-D J-Lat 8.4 cell line was mock-treated or treated with 5-AzadC and/or SAHA for different periods of time as indicated. Samples were harvested at indicated times. metabolic activity was assessed by a WST-1 assay (C, D). Means and standard errors of the means from three independent biological duplicates (n=6) are indicated. The result obtained with mock-treated cells was arbitrarily set at a value of 100% (C, D).
D. Detection of secreted InlK in the supernatant of ΔsrtA mutants over-expressing InlK. Western blotting was carried out on trichloroacetic acid precipitates of ΔsrtA and ΔsrtA+pPRT-inlK culture (OD600 = 1) supernatants using the rabbit polyclonal anti-InlK antibody.
(D) Quantification of total lung hydroxyproline levels in mice treated with vehicle or barasertib. *P< 0.05, ***P < 0.0005, 1-way ANOVA, (n=8-10 mice/group).
Top: Schematic representation of WT (orange) and dpr12 RNAi-expressing (green) single γ-KC axons. Bottom: Measurements of the relative location to which WT (I) and dpr12 RNAi (L) axons grow across the entire length of the adult γ lobe, alongside the relative position of the proximal border of the γ4 zone (see O, as well as Figure EV2).
A The average distribution of nucleosomes centred on the RE1 site (n=871), spanning 2 Kb of flanking genomic sequence.
E) Comparison of pTDP-43 score to neoaggregate formation per patient showed positive correlation for FTLD-TDP-A and no correlation for FTLD-TDP-C. Trendline is shown per subtype. Best-fit value of linear regression model: FTLD-TDP-A (y=1.286x+1.123, R2=0.6099, p=0.0667), FTLD-TDP-C (y=-0.2655x+2.805, R2=0.03133, p=0.7758).
F Activities of TFF3, FABP1, MKI67 and MMP7 in organoid single cell transcriptomes, ordered along latent time.
The role of cristae structure as well as CJ formation and sealing on the generation of the difference in ΔΨm between cristae and IBM were studied by disrupting cristae using Mic10- and Mic60-deficient cells. Mic60 support cristae formation. Mic10 is essential for CJ formation, and, in its absence, cristae tend to remain as vesicles detached from IBM. Live-cell Airyscan imaging of TMRE was used in all figure panels and models. Representative images of Hap1 control (top row) vs. Mic60 KO (middle row) and Mic10 KO (bottom row); Mic60-KO mitochondria show very few cristae structures. TMRE staining along the IMM is relatively homogeneous, indicating decreased ΔΨCr-IBM. In general, Mic10 KO in Hap1 cells results in decreased TMRE signal intensity at cristae relative to IBM (arrowheads) as compared to control cells. Deletion of Mic10 induces detachment of cristae from IBM (see Figure 8). Except for the detached cristae vesicles, the TMRE staining is homogeneously distributed n Mic10-KO cells, indicating decreased ΔΨCr-IBM. Scale bar = 500 nm. N = 3 independent experiments. Quantification of C, showing Mic60 KO in Hap1 cells results in significant decrease in ΔΨCr-IBM. While Mic60-KO cells show a marked loss of normal cristae structures, depletion of cristae does not appear absolute, making it possible to compare TMRE FI at cristae relative to IBM. N = 3 independent experiments. Quantification of C, showing Mic10 KO in Hap1 cells results in a significant decrease in ΔΨCr-IBM. Note: quantification of ΔΨm at cristae relative to IBM was performed only on cristae structures that appeared to maintain attachment to IBM. N = 3 independent experiments.
E. Immunoblot analysis of U2OS/GFP-FAM111B cell lines treated or not with DOX in the absence or presence of Z-VAD-FMK.
D Structures of the dp5 and dp6 domains in CbpFR6. The side chains of D167-D168 are shown.
qRT-PCR analysis of cell lysates from control, YAP-5SA or YAP-S94A expressing A549 cells treated with IFNγ for the indicated times
C. Schematic illustration of the regulatory features of the ALK kinase domain and the effects of mutations. The side chains of key residues are shown as sticks. The αC-helix of inactive ALK interacts with the JM domain through hydrophobic contacts and the αAL-helix through polar contacts. The interactions between αC-helix, the JM domain and the A-loop are destabilised by mutations such as F1174L, R1275Q that drive the activation of ALK. The Lys-Glu salt-bridge can be disrupted by an inactivating mutation (K1150M).
F. ELISAs were used to analyze the inhibitory effect of OSMI-1 on IL-8 and CCL-2 production from 3D cultures of human mini-kidneys exposed to Stx2a (10 ng/mL) for 72 h (n = 3 biological replicates). The effects of OSMI-1 were compared with those of the vehicle (DMSO) controls. Data information: Error bars for bar graphs are presented as mean ± S.E.M. Statistical analysis was performed using two-tailed Student's t-test. *P < 0.05; **P < 0.01; and ***P < 0.001.
A, B mRNA expression of COUP-TFI and COUP-TFII following shRNA-mediated knockdown of (A) COUP-TFI or (B) COUP-TFII in hESC-atrial cardiomyocytes (AM) at day 30.
GDH (L), enzyme activity after exercise. Male C57BL/6 mice (10 weeks) fed with normal chow were divided into three groups receiving non-exercise, running wheel free access for 1day or resistance exercise for 40 min (n = 8-9 per group).
ABE purifications from HeLa cells treated with 10nM non-targeting siRNA (nt siRNA) or DHHC5 siRNA were immunoblotted for Dsg2. Loss of the band in the +HA pull-down in the DHHC5 siRNA condition shows that Dsg2 palmitoylation is dependent on DHHC5.
(h) Oil Red O staining of striatal tissue from brain of two different unaffected control individuals (top) and two individuals with HD (bottom). Nuclei are highlighted with hematoxylin. Lipid droplets are visible as red puncta. Subject identifiers are shown in each panel.
(B) Percent colocalization of L. pneumophila with p62. Hundred bacteria were scored from each coverslips. Images were captured with the 60× objective and magnified 3×, scale bar = 10 μm.
Figure 5: Anti-VEGF therapy led to decreased infiltration of CD68+ macrophages in human GBM. Anti-CD68 (A), anti-CSFR1 (B) and anti-CD206 (C) immunohistochemistry of patient samples derived from treatment-naive GBM (n=24), post-radiochemotherapy (S/RTx/CTx) (n=7) and post-radiochemotherapy + bevacizumab (S/RTx/CTx/Bev) (n=29) therapy is shown.
Western blot analyses of Fgf21 expression in 9-week-old livers (n=3-6 per group, 3 independent repeats). α-tubulin, loading control for Western blot analysis.
F. Differentiation of wild type (WT), Sp1+/-, Nr5a2-/- and Fos-/-Jun-/- mESCs in the 3KI background to definitive endoderm.
IKBKE gene (encoding for IKKε) was deleted in MCF10A cells via CRISPR-Cas9 technology. 3 knockout clones were combined for each cell line. IKKε CRISPR-Cas9 knockout MCF10A cells form less colonies when grown in soft agar with macrophage-conditioned medium for 5 weeks compared to CRISPR-Cas9 control (nontargeting crRNA) cells. Colonies ≥ 50 μm were counted. Error bars represent mean ± SEM from 3 independent experiments (n=3 per condition). Media from two macrophage donors were combined in 1:1 ratio in each experiment. Macrophage donors are indicated as M1A - M1 activated, M2A - M2 activated macrophages.
Flow cytometric analysis of lymph node γδ T cells in RORγtCRE-STAT3F/F (Cre+) and littermate control mice (Cre−). In graphs, each symbol represents a mouse or experiment and line the median. Representative dot plots showing IL-17A (A) or IL-17F (D) and IFNγ production in γδ T cells before (steady-state) and after IMQ-induced psoriasis. Numbers in gate indicate % positive cells; numbers outside the gate indicate mean fluorescence intensity of IL-17A or IL-17F. (B, E) Frequency of IL-17A+ (B) and IL-17F+ (E) γδ T cells before (steady-state) and after (IMQ) IMQ-induced psoriasis. (C, F) Quantification of mean fluorescence intensity (MFI) of IL-17A (C) and IL-17F (F) staining in γδ T cells after IMQ-induced psoriasis (each color represents a different experiment).
(A) SUMOplot (Abgent) predicts that HTT is SUMOylated downstream of HTTex1p lysines. SUMOplot analysis predicts two high-probability SUMO sites (red) and three low-probability SUMO sites (blue) identified downstream of HTT exon 1. Greater than 13 overlapping noncovalent SIMs are observed within this fragment (yellow).
(H) Statistical analysis of the Y‐Maze test. S, O, and N represent the start arm, old arm, and new arm. The percent of time that mice stayed in each arm was recorded and analyzed. Whiskers represent the minimum to maximum value; central lines represent median values; boxes represent the values between upper quartile and lower quartile. Compared with those of WT mice, the entries of KO mice into new arms were decreased, while the entries into old arms were increased.
Figure 5. Differential lysine acetylation and protein expression in hda14 vs. wild-type leaves under low light conditions (C,F). Volcano plots depict lysine acetylation site ratios (A-C, top row) for mutant vs. control, with p-values determined using the LIMMA package. Orange, protein with nuclear localization; Green, protein with plastidial localization; purple triangles, proteins of the Calvin-Benson (CB) cycle; blue diamonds (top row), proteins of the light reaction; localization information according to SUBA4 database. Blue circles (bottom row), proteins with lysine acetylation sites identified. Dashed lines indicate significance thresholds of either uncorrected p-values < 5% or Benjamini-Hochberg corrected FDR < 5%. A missing FDR line indicates that the 5% threshold was not reached by any of the data points.
(F) AR16 (PrrnE-gfp) (WT, cyan) and ET411 (Pveg-mCherry, ∆dltA) (∆dltA, purple) cells were mixed, infected with low concentrations (10-8 PFU/ml) of SPP1, placed on an agarose pad, and plaque formation was followed by time lapse confocal microscopy. Shown are overlay images from GFP (cyan) and mCherry (purple) signals of the bacterial lawn captured at the indicated time points (hrs). The plaque is seen as a hole formed on the bacterial lawn. Scale bar 150 µm.
I: Apoptosis was analyzed by flow cytometry (I) using FITC-labeled AnnexinV and propidium iodide (PI). The increase in the apoptotic cell fraction upon gemcitabine and/or MS023 was quantified for four independent experiments (mean ± SD, ***: p-value ≤ 0.001, *: p-value ≤ 0.05 using Welch´s t-test).
(A) Schematic diagram of the reporter construct for analyzing the DNA DSB repair by NHEJ. Incompatible DNA ends produced by I-SceI-induced DNA cleavage are repaired by NHEJ, which removes the intervening TK, resulting in GFP expression. Triangles indicate the positions of primers used to amplify a fragment encompassing the repaired junction after I-SceI cleavage.
F) Barplot comparing the logFC of the genes associated with steroid treatment estimated in this study to the estimates of Liu et al. (2012).
B UMOD sheet model, generated by antiparallel juxtaposition of multiple copies of the UMODfl composite map, according to the 2D information shown in panel A. Due to lack of information in the direction perpendicular to the plane of the sheets, the exact position of adjacent filaments relative to this plane is unknown; for simplicity, the depicted model has been generated by assuming that the cores of the filaments making up the sheet lie on the same plane. Individual filaments are alternately colored light and dark grey, with N-terminal protein regions highlighted in pink and magenta, respectively. The zig-zag view of two adjacent filaments in the sheet resembles the projection of a double helix (see inset of Fig 1A) and the regular presentation of UMOD branches generates a molecular Velcro surface for the capture of UPEC.
E Comparison of the reprogramming efficiencies of SKO-MEFs and SKOM-MEFs overexpressing wild-type or mutant Gadd45a proteins. The reprogramming efficiencies were compared with SKO or SKOM, respectively. (**p≤0.01, ***p≤0.001; n=3)
C RBM47-deficient or control IFNAR1+/+ and IFNAR1-/- MEFs were infected with VSV or HSV-1. The cells were harvested at 12 hpi. (VSV) or 24 hpi. (HSV-1), and viral RNA levels were analyzed using qRT-PCR.The PCR results are represented as the means ± SD of n = 3 biological replicates. Data information: The data shown are representative of n = 3 independent experiments. NS, non-significant; **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test).
D Human PBMCs were transfected with USP19-specific or scramble siRNA and treated with rapamycin (250 nM) for 18 h. The extracts were analyzed by immunoblot with indicated antibodies.
(D) cytosolic FUS reduces the VAPB-PTPIP51 interaction more potently than wild type FUS. Cells were transfected with PTPIP51-HA and either EGFP control, EGFP-FUS or EGFP-FUSC. PTPIP51 was immunoprecipitated using the HA tag and bound endogenous VAPB detected by immunoblotting. Both inputs and immunoprecipitations (IP) are shown. FUS was detected using EGFP antibody. Bar chart shows relative levels of VAPB bound to PTPIP51 in the immunoprecipitations following quantification of signals from immunoblots. VAPB signals were normalized to immunoprecipitated PTPIP51-HA signals.
A Co-IP of V5-tagged Expanded with the FLAG-tagged N-terminal region of Karst/βH-Spectrin, but not other Karst truncation constructs.
(H) Luciferase activity in lysates of UC-MSCs transfected with luciferase reporter plasmids of pGL3-basic empty vector (basic), wild type ISLR promoter or mutant promoter with mutation of ETS1 binding sites under normal and ETS1 overexpression conditions. n = 3.
(C) T47D-MTVL cells were untreated or treated for 5 and 30 min with hormone and submitted to ChIP assays with anti-PRS294phos antibody or IgG as control. The histograms show the mean ± SD of 3 experiments performed in duplicate. * P-value < 0.05.
(l) [Ca2+]m efflux rate derived from j and k during the initial 60 s following Ru360 addition (NS; not significant; n = 3).
Mice, implanted with control cells (Ctrl) or myoblasts expressing low (V Low) or medium (V Med) VEGF levels, were treated with the anti-NRP1A antibody blocking Sema3A/NRP1 binding (AbαNRP1A) or with control IgG2a. Analyses were performed after 1 week.A, B Quantification of recruited NEM in sites of new angiogenesis by increasing VEGF doses, expressed as number of CD11b+ cells/mm2 of area (A) or /cm of vessel length (B). Data represent the mean ± SEM of individual images (n) acquired from three muscles/group. (A) Ctrl IgG2a, n = 11; Ctrl AbαNRP1A, n = 17; V Low IgG2a, n = 24; V Low AbαNRP1A, n = 28; V Med IgG2a, n = 25; V Med AbαNRP1A, n = 34; *P < 0.05, **P < 0.01 and ***P < 0.001 by Kruskal-Wallis analysis with Dunn's multiple comparisons test: V Low IgG2a versus Ctrl IgG2a P = 0.0068; V Low IgG2a versus V Low AbαNRP1A P = 0.0068; V Med IgG2a versus V Med AbαNRP1A P = 0.0460. (B) V Low IgG2a versus V Low AbαNRP1A P < 0.0001; V Low IgG2a versus V Med IgG2a P = 0.0193; V Med IgG2a versus V Med AbαNRP1A P = 0.0046.
B-F) NK cells were stimulated with IL-15 and purified as CD25+/CD54+ and CD25-/CD54- and co-cultures with K562 cells (5:1 ratio) for six hours and analyzed for the expression of B) CD107a, C) IFNγ, D) Perforin, E) TRAIL and F) Granzyme B were by flow cytometry (n=4, biological replicates).
e-f, Quantitative analysis of collagen abundance (e) and orientation (f) using second harmonic generation (SHG) from cellular derived matrices from stromal subsets and representative images multiphoton SHG images (n = 3 biological replicates). All SHG intensity values within each replicate were normalised to the SHG intensity of the myCAFs. Error bars represent standard deviation. Statistical significance for collagen abundance (e) was determined using unpaired two-tailed Student's t test with equal standard deviation with p‐values denoted by asterisks: *p < 0.05, **p < 0.01 and ***p < 0.001. After normalization of the orientation peak distributions (f), statistical significant was determined using a Kruskal-Wallis test with Dunn's post-hoc multiple comparisons test (p value < 0.0001).
D Kaplan-Meier (non-parametric) survival curve showing significantly extended tumor-free survival of KPC mice treated with LOX antibody (1 mg/kg i.p., twice weekly) + gemcitabine (100 mg/kg i.p., twice weekly) (green line, n = 17), compared with gemcitabine ± isotype control antibody-treated mice (blue line, n = 22, P = 0.014) or LOX antibody alone (red line, n = 9). Treatment was initiated when mice were 70 days old (randomization was not used when recruiting the mice) and the mice were treated twice weekly. Censored mice did not develop PDAC.