EMBO/sd-character-level-ner huggingface dataset:
Figure 1Polygon distribution of biological tissues compared with Voronoi diagrams. A) Segmentation of a Drosophila prepupa wing imaginal disc epithelium (dWP). B) Adult Biceps (BCA) biopsy stained with anti-collagen VI (green) and anti-Myosin Heavy Chain (red) antibodies. C) Segmentation of the image showed in (B). D) Segmented image from a chicken embryo neural tube epithelium (cNT). E) Polygon distribution of the different biological tissues analysed. Two types of distribution can be distinguished: The Poisson Voronoi polygon distribution for Diagram 1 (D1) and cNT, and the conserved polygon distribution for the rest of image categories. F) Diagram with Voronoi seed distributed randomly in the plane. G) Poisson-Voronoi tessellation of the seed showed in (F). H) Resulting Voronoi diagram after performing four Lloyd´s algorithm iterations to the Diagram 1 (Diagram 5, D5). In all figures data are represented as mean ± SEM. Scale bar, 10 m in (A) and (D); 150 mm in (B).
Figure 5. A) Diagram resulting from a vertex model simulation that includes cell proliferation. B) Diagram resulting from a vertex model simulation that includes cell proliferation and heterogeneous reduction of line tension among the tissuecells. C) Diagram resulting from a vertex model simulation with heterogeneous reduction of line tension and an impairment of the cell division when tension value is under the 30 percent of the initial value D) Similar simulation than in (C) with a threshold of 40 percent. E-H) Density plot showing the frequency of a value for four, five, seven and eight sided cells respectively, depending of the percentage of hexagons (P6) in the CVT diagrams. The values for the individual myosin mutant images (violet) and the individual diagrams of the four simulations (light grey, grey, light pink and pink) are shown in each plot. The average value for each simulation is shown with a black circumference.
Figure 1A BreastMark microarray platform; Kaplan-Meier curves of overall survival (OS), demonstrating that high expression of ESRP1 (red line) is associated with poor prognosis in ER+ breast cancer. A log rank test was used to calculate P=2.8 e-07 (n= 934, number of events= 216). B BreastMark microarray platform; Kaplan-Meier curves of overall survival (OS) of ER- breast cancer. A log rank test was used to calculate P=0.4481 (n= 322, number of events= 130). C BreastMark microarray platform; correlation of ESRP1 expression with overall survival in tamoxifen-treated patients. A log rank test was used to calculate P=1.218, e-06 (n= 210, number of events= 49). D BreastMark microarray platform; correlation of ESRP1 expression with overall survival in chemotherapy-treated patients. A log rank test was used to calculate the P=0.28 (n= 129, number of events= 21) E The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) RNA-seq dataset; Kaplan-Meier curves of overall survival (OS) in ER+ breast cancer, demonstrating that high expression of ESRP1 (red line) is associated with poor prognosis in ER+. A log rank test was used to calculate P=0.00011 (n= 656, number of events= 62). F The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) RNA-seq dataset; Kaplan-Meier curves of overall survival (OS) in ER- breast cancer. Red-high ESRP1 expression; Black-low ESRP1 expression. A log rank test was used to calculate P=0.19 (n=100, number of events=17).
Figure 2A-B Clonogenic survival of METTL3-knockdown (A) and METTL3-overexpression (B) in normal liver cell line WRL68 cells for 7 days in normoxia condition (21% O2) and quantification of clusters in A-1 and B-1, respectively. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments. C-D The IC50 of METTL3-knockdown SMMC-7721 cells (C) and Bel-7402 cells (D) after treated with sorafenib for 24h under hypoxia condition (1%O2). Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments. E Overexpression of wild type METTL3 or catalytic mutant METTL3 in sorafenib-resistant HepG-2 cells. F The global RNA m6A level in sorafenib-resistant HepG-2 cells with wild type METTL3-overexpression or catalytic mutant METTL3-overexpression by dot-blotting assay. G-I Rescue of shRNA-resistant wild type METTL3 but not catalytic mutant METTL3 sensitized METTL3-knockdown SMMC-7721 cells (G), Bel-7402 cells (H) and sorafenib-resistant HepG-2 cells (I) to sorafenib treatment. The IC50 of the cells was measured after treated with sorafenib for 24h under hypoxia condition (1%O2). Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments. J Cell survival assay of sorafenib-resistant HepG-2 cells with wild type METTL3 overexpression or catalytic mutant METTL3 overexpression after treated with sorafenib for 24h under hypoxia condition (1%O2). Scale bar, 1mm. K Capillary-like structures in HUVECs treated with the tumor-conditioned medium (TCM) from control HCCs and METTL3-knockdown HCCs cultured under hypoxic conditions for 48 h. Quantification of the number of tubes with image J in K-1. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments. L-M The relative mRNA expression levels of angiogenesis genes were detected in SMMC-7721 cells (L) and Bel-7402 cells (M) with METTL3-knockdown by RT-PCR assay. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments. N The protein levels of VEGF-A in METTL3-knockdown HCCs. O The protein levels of PDGF-B in METTL3-knockdown HCCs.
Figure 6A. Scheme of the minigene constructs containing the Prl exon and surrounding introns (blue) between human beta globin exons (dark grey), and containing CACACA motifs (red boxes; Prl3 wt) or mutant versions (light grey boxes; Prl3 CAmut). Orange arrowheads, position of the primers used in the assay performed in B. B. RT-PCR analysis of the RNAs produced in the splicing assay with the Prl3 wt or Prl3 CAmut constructs as depicted in A transfected into HP1γ or KO cell lines. The top 210bp and bottom 120bp amplicons correspond to the included form (beta globin with Prl exon, more included in lane1, blue arrow, compared to lane 2), and the skipped form (beta globin exons only) of RNA, respectively. Orange arrowheads, position of the HBGEX-F and HBGEX-R primers used in PCR analysis. C. Histogram showing the loss of inclusion of the Prl3 exon upon depletion of HP1γ (in KO) relative to inclusion in the presence of HP1γ with the Prl3 wt (red) or Prl3 CA mut (grey) reporters. Based on the quantitation of 4 experiments as the one depicted in B. Values represent the fold change relative to HP1γ as a reference (dashed line). Graph represents mean and s.d. (*** P < 0.001; two-tailed Student's t-test; n=4). D. Model of HP1γ-dependent impact on splicing events via its binding to repeated intronic hexameric motifs (red arrows).
Figure 6qRT-PCR assays showed expression of ASS1 in Caco-2, SW620, SW480, HCT116 and SW-1116 cells. Western blotting assays showed the expression of ASS1 in Caco-2, SW620, SW480, HCT116 and SW-1116 cells. qRT-PCR and western blotting assays showed stable expression or depletion of ASS1 in SW-1116 and Caco-2. NC, Negative control. Depletion of ASS1 decreased cell migration in SW-1116 cells. Scale bar represents 100 μM. qRT-PCR assays showed stable expression of LOC113230 in Caco-2. Western blotting assays showed stable expression of ASS1WT and ASS1 K234R via an viral infections into Caco-2 or Caco-2 LOC113230 FL cells, respectively . Transwell assays showed the effect of ASS1WT and ASS1K234R on Caco-2-Vector or Caco-2-LOC113323 cell migration. Scale bar represents 100 μM.. The expression of ASS1 in 65 paired CRC samples were analyzed by qRT-PCR. Representative immunostaining images of ASS1 levels in CRC samples on TMA chip. Scale bar represents 50 μM. Summary of ASS1 expression on TMA chips. P<0.01. P-value of the IHC scoring results on TMA chips was analyzed by the McNemar test and Pearson's chi-square test. (N) Kaplan-Meier analysis for overall survival of patients with high or low expression of ASS1. P < 0.001. P-value for Kaplan-Meier curves was determined using log-rank test. Pearson's correlation analysis showed that a significant negative correlation between the level of ASS1 and LOC113230 in CRC samples. R2=-0.53. P < 0.05. The LOC113230 and ASS1 expression levels were normalized to the GAPDH level, respectively.
TC randomization does not decrease gut microbial diversity in infants or mothers.Figure 3Fig 3: TC randomization does not decrease gut microbial diversity in infants or mothers. Shannon diversity measures are plotted as the interquartile range with median for each TC exposure class and time point grouping for infants and mothers.
Figure 7(Top) The Cripavirus family of type IV IRESs is able to capture free 40S sub- units and engage them on a pre-translocation complex by recruiting 60S. This complex is extremely dynamic, with the 40S alternating between non-rotated and rotated configurations with respect to the 60S subunit. IRESs belonging to this family, exemplified by the CrPV-IRES, recruit elongation factors by mimicking a rotated stated of the ribosome with tRNAS. (Bottom), The Aparavirus family of IRESs follows a similar pathway in order to assemble a pre-translocation complex, however, specific structural components of this family allow for additional contacts with the 60S, limiting the rotational freedom of the 40S. Elongation factors engagement and thus effective ribosome hijacking is accomplished by mimicking a ribosome state with tRNAs in hybrid configurations.
Figure 3A. Quantification of oxygen consumption rate (OCR) showing the effect of lactate treatment on the respiration (induced) in various cells including HBVP, mBP, HASMC, BMEC and 3T3L1. The media was changed into glucose-, pyruvate- and glutamine-free media before OCR measurement and lactate (2mM) was added the media to measure induced OCR. (n=10 from independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.) B. Quantification of OCR showing the effect of lactate dose dependent treatment (0.5, 2 and 10mM) in HBVPs. (n=9 from independent experiments. Error bars indicate the standard error of the mean (SEM)) C. Quantification of OCR (basal respiration) with full media (5mM glucose, 0.5mM pyruvate and 0.5mM glutamine) showing the effect of lactate treatment (2mM) in HBVPs. (n=7 from independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.) D. Quantification of ATP using a LC-MS/MS spectrometry in control and lactate treated (2mM, 4hr) HBVPs. (n=3 from independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.)
Figure 5a) Clinical course of the disease. Normalized weight at day n was calculated as follows: % of initial weight of the animal at day n. b) Lung infectious titers (measured using a TCID50 assay) expressed in TCID50/g of lung. c) Lung viral RNA yields (measured using an RT-qPCR assay) expressed in virus genome copy/g of lung. d) Plasma viral RNA loads (measured using an RT-qPCR assay) expressed in viral genome copies/mL of plasma.
Figure 4Human, mouse and total tau protein levels in cortical TBS-extracts of rTg4510, rTg4510-Mapt0/0, and control mice: The amount of human tau (Tau13 antibody) was comparable in rTg4510 and rTg4510-Mapt0/0, moTau (Tau/5) was comparable in WT and rTg4510, and total tau levels (hu+moTau, DAKO antibody) were (expected) highest in rTg4510 mice. Mean±SEM, n=3 mice/group, non-significant. Whole brain weights of 9-month-old animals revealed pronounced brain matter loss in rTg4510 compared to WT mice (weight loss >16%), which was rescued in rTg4510-Mapt0/0 mice to >96%. Mean±SEM, n=5 mice/group. Cortical thickness measured adjacent to HPC, from CTX surface to corpus callosum, was decreased in rTg4510 mice by ≈25% compared to WT mice. rTg4510-Mapt0/0 showed no CTX thinning compared to Mapt0/0 or WT mcie. Mean±SEM, n=3 mice/group. The number of neurons (NeuN+ cells) in the cortex of rTg4510 mice was significantly reduced to ≈67% compared to both WT and rTg4510-Mapt0/0. Mean±SEM, n=3 mice/group. The volume of hippocampal region CA1, with CT the most effected regions in rTg4510 mice, was significantly reduced in rTg4510 by ~70% volume; rTg4510-Mapt0/0 had significantly larger CA1 volume left (reduced by only ~40%). Mean±SEM, n=3 mice/group. rTg4510 showed strong signs of neuroinflammation with extremely high numbers of activated astroglia (GFAP+, red) and microglia (Iba1+, white) in the CTX compared to WT mice. Both astro- and microgliosis was reduced by ~50% in rTg4510-Mapt0/0 mice. Mean±SEM, n=3 sections/mouse and 5 mice per/group. For all panels: two-tailed Student's T-test and one-way ANOVA with Bonferroni for multiple comparison, ns not significant, scale bars 100 µm.
Proposed model for the integration of NFAT and NF-κB signalling pathways.Figure 10Swollen AF conidia are taken up by macrophages. The AF-containing phagosome rapidly acidifies, resulting in the activation of endosomal PRRs such as TLR9. TLR9 signalling drives BTK activation, which in turn activates phospholipase Cγ (PLCγ) by phosphorylation. PLCγ activation initiates the calcium flux required for calcineurin-mediated NFAT translocation into the nucleus. Additionally, NF-κB translocation is activated from the cell surface and acts in synergy with NFAT for TNF-α production. TNF-α secretion results in neutrophil recruitment which is the cell type required for efficient fungal clearance.
Figure 3A. Isosurface top view of the whole 13-PF MT cylinder and a side view close-up on NN binding site at the vertex of 4 tubulin dimers, where NDC of NN decorates the MT lattice. α-tubulin, white; β-tubulin, grey; NDC, blue. The valley between PFs 1 and 13 represents MT seam, where NN does not bind. B. Isosurface views as in A of the 14-PF MT decorated with NN. α-tubulin, light grey; β-tubulin, dark grey; NDC, blue. The valley between PFs 1 and 14 represents MT seam, where NN does not bind. C. Relative extent of MT lattice decoration based on average intensities of layer lines representing NDC (8 nm periodicity) and tubulin (4 nm periodicity) in averaged Fourier transforms of WT-MT and NN-MT segments, as described in Appendix Fig S6 and in Materials and Methods. D. Comparison of the DCX binding clefts in the 13-PF and 14-PF MTs and mapping of the associated small (<0.8 Å) conformational adjustments in NDC. NN-MT lattice fragments were aligned on the indicated α2 and β2 tubulin subunits (ALIGNMENT). Deviations in tubulin are depicted with grey scale and in NDC with colour scale. Two perspectives are shown to cover all major MT-binding loops of NDC.
Figure 2(A) Schematic representation of the gating charge analysis. The gating charge Q was obtained by calculating the surface beneath the off-gating currents (enlarged in gray and denoted by "charge"). Relative gating charge amplitudes in (B) and (C) were obtained by dividing the gating charge Q by the ion current amplitude I ("Ampl.") at +165 mV. (B) Voltage dependence of the WT ClC-5 off-gating charge normalized to the ionic current at +165 mV in the absence or presence of adenine nucleotides (n=7-12). Error bars represent SEM. Red lines depict Boltzmann fits to the data; fit parameters are provided in Appendix Table S1. (C) Voltage dependence of the WT ClC-3 off-gating charge normalized to the ionic current at +165 mV in the absence or presence of adenine nucleotides (n=4-5, Error bars represent SEM.). Red lines represent Boltzmann fits to the data
Figure 3A Protein was extracted from the area at risk of left ventricle from wild-type or Cuedc2-/- mice with 30-minute ischemia followed by 30-minute reperfusion and subjected to immunoblot analysis. Representative results from 2 mice are shown, and each experiment was repeated for three times. B Neonatal mousecardiomyocytes were subjected to hypoxia for 6 hours, followed by the indicated times of reoxygenation, before protein was extracted and subjected to immunoblot analysis. C Luciferase assay of WT or Cuedc2-/- MEFs transiently transfected with an NF-κB-responsive luciferase reporter and then, 1 d later, treated for 6 h with TNF (10 ng/ml; TNF) or for H/R. * p = 0.0032, n = 3 per group, ** p = 0.013, n = 3 per group. D Wild-type and Cuedc2-/- mice were treated with a sham or I/R operation in vivo. Three hours after the onset of reperfusion, the mRNA levels of tumor necrosis factor α (TNFα), interleukin 6 (IL-6) and interleukin 23 (IL-23) were tested. * p = 0.0005, ** p = 0.0001, n = 3 per group.
Nup50 is crucial for NPC assembly (A) Western blot analysis of mock and Nup50 depleted Xenopus egg extracts, with or without addition of recombinant Xenopus Nup50.Figure 1(A) Western blot analysis of mock and Nup50 depleted Xenopus egg extracts, with or without addition of recombinant Xenopus Nup50. 1, 2, and 4 µl of extracts were analyzed with indicated antibodies. (B) Confocal microscopy images of fixed nuclei assembled for 120 min in mock depleted (mock) and Nup50 depleted (∆Nup50) Xenopus egg extracts supplemented with either buffer or recombinant Nup50. In the left column, membranes were pre-labelled with DiIC18 (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindocarbocyanine Perchlorate, red) and chromatin was stained with DAPI (4′,6-Diamidin-2-phenylindol, blue). Three right columns show the immunofluorescence staining for Nup50 (green) and, NPCs (mAB414, red) on the chromatin (DAPI). Scale bars: 10 µm. (C) The average percentage of closed nuclear envelopes (upper panel) as well as mAB414 positive nuclei (lower panel) for 100 randomly chosen chromatin substrates in each of 3 independent experiments is shown. Data points from individual experiments are indicated. (D) HeLa cells were transfected with 10 nM control (n=84) or Nup50 siRNA (n=171), 20 nM control (n=101) or Nup50 siRNA (n=157) and 40 nM control (n=86) or Nup50 siRNA (n=204). 72 h post transfection, cells were fixed with 4% PFA and stained with antibodies against Nup50 and mAB414, chromatin was labeled with DAPI. Scale bars: 50 µm. Quantitation of the mAB414 rim intensity at three different Nup50 RNAi and control oligo concentrations. The means are indicated as diamonds, error bars show the standard deviations. P-values have been calculated from a student t-test comparing the mean between the experimental conditions. (E) Western blot analysis of HeLa cells treated as in (D) 72 h post transfection.
RNA was extracted from young fertile adults fed ad libitum or fasted for 6 h.figf1RNA was extracted from young fertile adults fed ad libitum or fasted for 6 h. ddCts (delta delta cycle thresholds) were calculated normalizing to ama-1 and the efficiency of the primer sets as previously described. Means+s.e.m. are depicted. lipl-1 to lipl-5, n = 6 independent experiments. lipl-6 to lipl-8, n = 3independent experiments. Significant t-test derived P-values are indicated. WT, wild type.
GABAergic defects and behavioural anomalies are suppressed by ephedrine treatment in mut-chd7 C.Figure 6A. Movement scores of chd-7(gk290) mutants (red) compared to N2 wildtype (WT; black). Two-tailed T-test was performed for statistical analyses and movement score was considered different to WT (N=3, n=30; ****p < 0.0001, Student's t-test). B. Lifespan analyses of chd-7(gk290) mutants (n=339; red) compared to WT (n=444; black). Log-rank test was performed for statistical analyses. ***p < 0.001. C. WT and chd-7(gk290) animals with defects in the GABAergic (black) and cholinergic nervous system (grey) at the L4 stage (N=4, n=100; ****p<0.0001; Student's t-test). D-F. Example pictures of the GABAergic nervous system cell bodies, commissures, axonal gaps and axonal breaks larger than 50 µm per worm in chd-7(gk290) mutants expressing unc-47p::mCherry. G-I. GABAergic neurodevelopmental defects of WT (black) and chd-7(gk290) mutants (grey) at the L4 stage classified in axonal gaps per worm (G), number of GABAergic cell bodies (H) and number of commissures (I). N=4, n=100; ****p<0.0001, Student's t-test. J. Chemical libraries (3850 compounds) were first screen in chd-7(gk290) C. elegans mutants and positive hits were tested on chd7 zebrafish mutants. K. 49 compounds that improved motility phenotypes in chd-7(gk290) mutants were identified. These compounds were clustered in 6 main functional categories.  L. Movement scores of chd-7(gk290) mutants treated with ephedrine (blue) compared to the solvent DMSO (black). N=3, n>100; ****p<0.0001, Student's t-test. M. Defects of the GABAergic nervous system at the L4 stage in chd-7(gk290) mutants treated with ephedrine (grey) compared to DMSO (black) (N=3, n>100). ****p<0.0001, Student's t-test. N. Average activity per second is wild-type and mutants treated with ephedrine compared to non-treated mutant (wild-type treated with ephedrine is referred to as Control). Ephedrine suppresses hyperactivity in chd7 mutant fish. n=24; ****p<0.0001, one-way ANOVA. O. Representative images of GABAergic neurons and total number of GABAergic neurons (GFP+ cells) in the optic tectum (OT) and cerebellum (CB) regions of wild-type, chd7 mutant and ephedrine-treated fish (n=9; ****p<0.0001; One-way ANOVA). Treatment with ephedrine ameliorated the number of GABAergic neurons. P-Q. p-ERK is reduced in mutants following treatment with ephedrine as shown by Western blot quantification (N=4). ****p<0.0001, one-way ANOVA. R. qPCR analysis of paqr3b expression in chd7+/+ , chd7-/- and chd7-/- treated with ephedrine (N=4; ****p<0.0001; ns, not significant, one-way ANOVA.