EMBO/sd-character-level-ner huggingface dataset:
Perinatal lethality in Fus∆NLS/∆NLS mice.Figure 2(A) Photographs of Fus+/+ and FusΔNLS/ΔNLS pups immediately after birth (P0 animals).(B-C) FusΔNLS/ΔNLS mice showed significantly reduced body weight (B) and length (C). Weight and length values normalized to wild type (Fus+/+) are presented. N=11 Fus+/+, N=26 FusΔNLS/+ and N=14 FusΔNLS/ΔNLS; (*) p<0.05 (**) p<0.01 vs Fus+/+, (#) p<0.05 vs Fus∆NLS/+; One way ANOVA followed by Tukey post hoc test. (D) Representative haematoxylin and eosin stainings of lungs of Fus+/+ and FusΔNLS/ΔNLS at birth.
ATP level and mitochondrial membrane potential during amino‐acid starvation.Figure 3(A, B) Wild‐type, rho0, and Δatg7 cells were exposed to amino‐acid starvation medium supplemented with acetate (A) or galactose (B). When indicated, wild‐type cells were exposed to antimycin A (AA) or oligomycin (O) during the amino‐acid starvation period. ATP and protein from total cells (upper panels) or isolated mitochondria (lower panels) were determined at indicated time points. (C) Wild‐type and Δatg7 cells were exposed to amino‐acid starvation medium supplemented with acetate or galactose for 3 h. Wild‐type cells were exposed to antimycin A (AA), oligomycin (O), or CCCP (50 μM) during the amino‐acid starvation period when indicated. Cells were treated with the mitochondrial membrane potential‐dependent dye DiOC6(3) and examined by fluorescence microscopy. Average pixel intensities for at least 10 mitochondrial tubules (n=10) in 5 representative cells were determined for each condition. Values for wild‐type mitochondria in the presence of acetate were defined as 100% and relative values were calculated accordingly. The means and s.d. are shown.
Figure 8A. Experimental scheme for B-F. Whole-cell patch-clamp recordings were made from nearby pairs of uninfected and infected neurons expressing EGFP-GSK3α in CA1 of organotypic hippocampal slices from C57 wt and tauKO mice. EPSCs were elicited with CA3 Schaffer collateral stimulation. B. Representative traces for C-F, showing evoked AMPAR- and NMDAR-mediated EPSCs (collected at −60 mV and +40 mV, respectively) in paired uninfected (black traces) and EGFP-GSK3α-expressing neurons (green traces) in C57 wt or tauKO slices. C-F. Scatter plots showing individual recordings of pairs of uninfected and infected neurons at −60 mV (AMPAR-mediated EPSCs) in C57 wt (C) or tauKO slices (D), or at +40 mV (NMDAR-mediated EPSCs) in wt (E) or tauKO slices (F). Red circles represent the averages of all pairs in a given plot, and n denotes the number of cell pairs. In all cases, error bars represent SEM and statistical significance was calculated according to the Mann-Whitney U test.
Figure 3(A) Morphological phenotypes of the WT, chr11/17, pie1, swc2, and rin2 mutant plants. Shown are 24-day-old plants. The top panel shows the phenotypes of plants in the soil; the bottom panel shows the phenotypes of plants on the black cloth. (B) Shown are rosette leaves of the WT, pie1, swc2, and rin2 mutant plants. Rosette leaves were cut from bolting plants. (C) The early-flowering phenotype of the mbd9-1, mbd9-3, mbd9-4 and hta9-1/11-1 mutants compared to the WT. 24-day-old plants in soil are shown. (D) Numbers of rosette leaves of the WT and mutant plants shortly after bolting. Rosette leaves from at least 20 plants were counted for each genotype. Values are mean ± SD. ** P<0.01, student's t test. (E) Determination of the effect of the arp4-1, arp6 and swc6-1 mutations on flowering time. The top panel shows the number of rosette leaves in the WT, arp4-1, arp6, and swc6-1 mutant plants; the bottom panel shows a photograph of the plants. Rosette leaves from at least 20 plants were counted for each genotype. Values are mean ± SD. ** P<0.01, student's t test. (F) Determination of the effect of the tra1a and tra1b mutations on flowering time. The top panel shows numbers of rosette leaves of the WT, tra1a-1, tra1a-2, and tra1b mutant plants; the bottom panel shows a photograph of the plants. Rosette leaves from at least 20 null were counted for each genotype. Values are mean ± SD. ** P<0.01, student's t test.
Figure 5A Lysates of H1299 cells expressing Flag-MICAL2PV were immunoprecipitated using an anti-Flag antibody, and immunoprecipitated proteins were analyzed by Western blotting using different antibodies as indicated. B H1299 cells were co-transfected with different combinations of plasmids as indicated. The cell lysates were immunoprecipitated using an anti-Myc antibody. Immunoprecipitated proteins were analyzed by Western blotting using different antibodies as indicated. C The monooxygenase (MO) domain of MICAL2PV interacts with Miro2. A schematic representation of protein domain organization in MICAL2PV and its truncation mutants was shown in (panel a). H1299 cells were co-transfected with Myc-Miro2 and different HA-tagged MICAL2PV mutants. Following transfection, cells were lysed and immunoprecipitated using an anti-HA antibody and subjected to Western blotting with different antibodies (panel b). D MICAL2PV interacts with N-GTPase, EF hand and C-terminal domains of Miro2, but not with the C-GTPase domain. A schematic representation of protein domain organization in Miro2 and its truncation mutants was shown in (panel a). H1299 cells were co-transfected with Flag-MICAL2PV and different Myc-tagged Miro2 mutants. Transfected cells were lysed, and immunoprecipitation was performed using an anti-Myc antibody and subjected to Western blotting with different antibodies as indicated (panel b). It should be noted that the upper band (marked by "*") migrating closely above the Flag-M2 band in the top section of panel b is a non-specific species because it is present in anti-Myc immunoprecipitates of cells only expressing the vector control, not expressing any Myc-Miro2 (lane 1). E MICAL2PV interacts with the C-terminal domain of Miro2 containing the transmembrane region. H1299 cells were co-transfected with plasmids encoding Flag-MICAL2PV and Myc-tagged Miro2 mutants as indicated. Following transfection, cells were lysed for immunoprecipitation using the anti-Flag antibody and Western blotting. Please note the Myc-Miro2 (410-618) protein band in lane 4 migrated as a faint band, slightly faster than the IgG light chain. F MICAL2PV inhibits the mitochondrial localization of Miro2 and mitochondrial infiltration. H1299 cells were co-transfected with Myc-tagged Miro2 and GFP-tagged MCAL2PV (GFP-M2) or control vector. Following transfection, cells were fixed and stained with anti-Tom20 (red) and anti-Myc antibodies (magenta). Confocal microscopic images were taken under the same objective and the same microscope settings. In cells co-expressing the GFP vector and Myc-Miro2 (upper panels), most of Miro2 signals (magenta) are co-colocalized with mitochondria (red Tom20 signals). However, a significant fraction of Miro2 signals is not colocalized with mitochondria in cells co-expressing GFP-M2 and Myc-Miro2 (marked by the yellow arrowheads). Mitochondria in cells expressing GFP-M2 show the perinuclear distribution pattern, whereas mitochondria in cells transfected by Myc-Miro2 without GFP-M2 (marked by the yellow stars) exhibit an infiltration pattern into the cortical cytoplasm. Scale bar: 20 μm.
Fig.Figure 9Temporal inactivation of a specific E1 and E2 pool by disulfide bond formation leads to local deSUMOylation of one or several unknown SUMO targets. This in turn is required to maintain ATM activity, which is required for DNA damage response and cell survival.
Persistence of neocortex expansion and increased cortical neuron numbers in adult 11B mouse brain at P56.Figure 3A Dorsal view of adult wildtype (WT) and 11B mouse brain at P56. Orange lines illustrate the measurements of neocortex width and length; red lines illustrate the measurements of neocortex area. B, C Quantification of neocortex width, length and area. D Data information: Scale bar, 1 mm Data are the mean of 8 (WT) and 8 (11B) adult littermate mice. Error bars indicate SD, two-tailed unpaired Student's t-test , * P < 0.05, ** P < 0.01, **** P < 0.0001. P < 0.0001 (B, neocortex width); P < 0.0001 (C) D Representative DAPI staining (white) of P56 adult WT and 11B mouse neocortex illustrating the measurements of cortical perimeter (blue) and thickness (red). E, F Quantification of cortical perimeter (E) and thickness (F) in the rostral part of P56 adult WT and 11B mouse brain. G Data information: Images are single optical sections Scale bar, 1 mm Data are the mean of 8 (WT) and 8 (11B) adult littermate mice. Error bars indicate SD, two-tailed unpaired Student's t-test , * P < 0.05, ** P < 0.01, **** P < 0.0001. P = 0.0297 (E); P = 0.0092 (F) G, H Representative immunofluorescence for Ctip2 (magenta), Satb2 (green) and Brn2 (yellow), combined with DAPI staining (white), of P56 adult WT and 11B mouse neocortex at the position where cortical thickness was measured (D, red lines). Data information: Images are single optical sections Scale bar, 20 µm I, J Quantification of zone thickness (I) and layer thickness (J) of P56 adult WT and 11B mouse neocortex at the position where cortical thickness was measured (D, red lines). Data information: Data are the mean of 8 (WT) and 8 (11B) adult littermate mice. Error bars indicate SD, two-tailed unpaired Student's t-test , * P < 0.05, ** P < 0.01, **** P < 0.0001. P = 0.0227 (I, CP); P = 0.0308 (J, layer II+III) K-M Quantification of Satb2+ (K), Brn2+ (L) and Ctip2+ (M) neurons in a 200 µm-wide field of P56 adult WT and 11B mouse neocortex. Data information: Data are the mean of 8 (WT) and 8 (11B) adult littermate mice. Error bars indicate SD, two-tailed unpaired Student's t-test , * P < 0.05, ** P < 0.01, **** P < 0.0001. ; P = 0.0278 (K); P = 0.0133 (L).
– Tau protein is necessary for the stress-induced death of newborn granule neurons.Figure 4A Representative image of a mouse subjected to forced swimming in the Porsolt test. B Schematic diagram of the experimental design. C Representative images of 1-week-old newborn granule neurons labeled with CldU (green) belonging to WT CNP, WT P, Tau-/- CNP, and Tau-/- P mice. Cell nuclei were labeled with DAPI (blue). Scale bar 50 µm.D-E Quantification of the number of 1-week-old CldU+ cells (D) and apoptotic fractin+ cells (E) in each experimental group.
Fig.Figure 3A. Scatter plots correlating the variations in Myc share at promoters (averaged between the 2, 4 and 8h time points) and in RNA synthesis (at 8h), relative to untreated cells, for Myc-dependent and independent genes. The Spearman correlation between the two parameters is reported. B. The ability of the Myc share in predicting the transcriptional outcome can be represented in terms of a Receiver operating characteristic (ROC) curve, which represents the Sensitivity (true positive rate) and Specificity (true negative rate) of a predictor (i.e. Myc share) in discriminating between two classes (i.e. up- and down-regulated genes), using different thresholds. The largest the area under the curve (AUC), the largest is the predictive power, in a scale from 0.5 (random classification: grey line) to 1 (perfect predictor). For each system, the dot corresponds to the variation of Myc at which promoters begin increasing their share of Myc binding. C. Fold-change in Myc levels at each bound promoter (at 4h LPS, relative to time zero) as a function of the initial binding intensity at time zero (expressed as log2 of the coverage in a 200 bp window around the summit of the peak). Peaks containing a canonical E-box are highlighted in black. D. Percentage of Myc-bound promoters within the indicated transcriptionally regulatory categories that contains a canonical or variant E-box. The overall chi-square is 207.7 with a p-value <0.00001. The contribution to the chi-square of each category is reported above the corresponding bar in the plot.
Figure 6A Position of TGF-β family members in the volcano plot of differentially expressed genes in 2a2iL- and primed hPSCs. X-axis shows log2 fold-change and y-axis shows negative log10 adjusted P-value <0.05 (Adjusted P-value was obtained using the Benjamini and Hochberg correction to determine the false discovery rate). Red and blue points represent up-regulated genes in 2a2iL- and primed hPSCs, respectively. Genes with no significant expression change are shown in gray. B qRT-PCR analysis of several TGF-β-related genes in pRH6 and 2a2iL-RH6. **P<0.01, ***P<0.001 (t-test). Data presented as mean ± SD (n=3). C Inhibition of the TGF-β pathway by two small molecules, SB43 and A83. Left panel: morphology of naïve-like cells three days after treatment. Right panel: morphology of treated cells after passaging. Scale bar: 100 µm. D Heatmap shows expression of putative LRH-1 target genes in this study's transcriptome profiles. Colors indicate log2 fold change of marker genes in the naïve versus primed hPSCs, with a range from dark blue for lower expression to dark red for higher expression. E Heatmap shows expression of putative RARγ target genes in this study's transcriptome profiles. Colors indicate log2 fold change of marker genes in the naïve versus primed hPSCs, with a range from dark blue for lower expression to dark red for higher expression. F KEGG analysis of putative LRH-1 and RARγ target genes are up-regulated in 2a2iL-hPSCs. Adjusted P<0.05 (adjusted P-value was obtained using the Benjamini and Hochberg correction to determine the false discovery rate with a log2 fold-change >1).
Analysis of nCoV-2019 receptor usage.Fig. 4usage.Determination of virus infectivity in HeLa cells with or without the expression of ACE2. h, human; b, Rhinolophus sinicus bat; c, civet; s, swine (pig); m, mouse. ACE2 protein (green), viral protein (red) and nuclei (blue) was shown. Scale bar=10 um.
Beclin‐1 interacts directly with Zwint‐1 and localizes to the mitotic apparatus.Figure 5(A) Immunoprecipitation of endogenous Zwint‐1 in HeLa cell extracts expressing HA‐Beclin‐1 or HA‐GFP. Input is 3.5% of the immunoprecipitated material. (B) GST‐Zwint‐1 or GST‐beads were used to pull down recombinant purified His6‐Beclin‐1. (Left) Coomassie‐blue‐stained gel of the purified recombinant proteins (1 μg). (Right) A western blot of GST proteins and His6‐Beclin‐1 in the input and bound fractions. His6‐Beclin‐1 in the input represents 4% of the amount used for the pull‐down. (C) Zwint‐1 levels do not change in Beclin‐1‐depleted cells. Cells were treated with nocodazole before fixation. On the right, magnified individual kinetochore pairs stained for Zwint‐1 (red) and CREST (green), and quantification of Zwint‐1 levels normalized to CREST signal from three independent experiments (error bars=s.d.). (D) Beclin‐1 is associated with both the centrosome and the mitotic spindle during mitosis. HeLa cells were permeabilized before fixation and immunostained for Beclin‐1 (green), α‐tubulin (red) and DNA (DAPI, blue). (E) Beclin‐1 is retained on the k‐fibres. HeLa cells were cooled on ice before permeabilization and fixation, and stained with anti‐α‐tubulin (red) and anti‐Beclin‐1 (green) antibodies. (F) Beclin‐1 forms discrete foci in the vicinity of the outer kinetochore in a microtubule‐dependent manner. Untreated cells (left) and nocodazole‐treated cells (right) were pre‐extracted and fixed before labelling with Beclin‐1 (green) and Zwint‐1 (red) antibodies. (G) The fluorescent‐tagged Cherry‐Beclin‐1 forms foci in the vicinity of the outer kinetochore. HeLa cells transfected with indicated constructs were pre‐extracted and fixed before labelling with Zwint‐1 (green) antibody. Magnified areas are shown on the right. (H) Beclin‐1 localization close to the kinetochore does not depend on the ZW10 protein. Cells treated with Control, Beclin‐1 and ZW10 siRNA were pre‐extracted and fixed before labelling with Beclin‐1 (green), CREST (blue) and ZW10 (red) antibodies. DNA was visualized with DAPI. (C-H) Scale bar, 10 μm. DAPI, 4′,6‐diamidino‐2‐phenylindole; DNA, deoxyribonucleic acid; GFP, green fluorescent protein; GST, glutathione S‐transferase; HA, haemagglutinin.
Figure 7(a) The scatter plots show the positive correlation of CFHR1 in BALF (MS-intensity, x-axis) with meta lung function (y-axis). (b) The UMAPs show the subset of COL1A2+ mesenchymal cells in the integrated scRNAseq dataset, with the pericytes highlighted by the dotted line. From left to right, the colors represent the cell type identities, disease status, expression of the pericyte markers PDGFRB and CFHR1, respectively. (c) The volcano plot depicts the fold changes (x-axis) and the -log10 p-values (y-axis) derived from the differential gene expression analysis using diffxpy between ILD and controls within the subset of PDGFRB+ pericytes (outlier values truncated). (d) The bar graphs show the top regulated gene categories after enrichment analysis using GO terms and Uniprot keywords. (e) The heatmap shows the expression of genes most strongly associated with SSTR2 expression within the pericytes (left color bar indicates significant correlation or anti-correlation). (f) Immunofluorescence analysis of SSTR2, the pericyte cell type marker PDGFRB and a marker for smooth muscle cells DESMIN in IPF (n=3) and control samples (n=3). (g) Representative images of immunohistochemistry analysis of SSTR2 protein expression in tissue regions (n = 474) from ILD patients (n = 53) and control patients (n = 26). (h) Correlation of immunohistochemistry signal of SSTR2 with Ashcroft scores. (i) The bar graph shows the genes most strongly correlated with SSTR2 belonging to the GO category "transcription regulators". The dotted line marks a correlation coefficient of zero. (j) The bar graph shows the top correlated transcriptional regulators, predicted by ingenuity Pathway Analysis (IPA) for the SSTR2 gene-gene correlations. The dotted line marks a correlation coefficient of zero. (k) Diffusion map of pericytes colored by cell type and inferred pseudotime represents pericyte differentiation. (l) Diffusion map of pericytes colored by the gene expression of indicated genes. (m) The line plot illustrates smoothed expression levels of the indicated genes across the pericyte pseudotime differentiation trajectory.
Figure 7(A) Representative morphologies of smyhc1+/+, smyhc1R673H/+, and smyhc1R673H/R673H larvae at 2 dpf after 24 hour treatment with 0.25% DMSO (control) or 25 μM para-aminoblebbistatin. All larvae treated with para-aminoblebbistatin develop a slight dorsal tail curve and pericardial edema regardless of genotype. All para-aminoblebbistatin-treated smyhc1R673H/+ (n=9) and smyhc1R673H/R673H (n=3) larvae are indistinguishable from smyhc1+/+ unlike the untreated larvae which have markedly curved or distorted body axis. (B) Representative images of smyhc1+/+, smyhc1R673H/+, and smyhc1R673H/R673H larvae at 3dpf after 48 hour treatment with 0.25% DMSO (control) or 25 μM para-aminoblebbistatin. All larvae treated with para-aminoblebbistatin develop a slight dorsal tail curve and pericardial edema regardless of genotype. Para-aminoblebbistatin-treated smyhc1R673H/+ (n=9) and smyhc1R673H/R673H (n=3) larvae are indistinguishable from smyhc1+/+ unlike the untreated larvae which have markedly curved or distorted body axis.
Figure 5Location of known Parkin ubiquitination sites within the Miro structure. MiroS is shown in a 180°‐rotated top view (relative to Fig 2). Four residues in dMiro correspond in sequence and structure to residues that are ubiquitinated by Parkin in human Miro1 (hMiro1) or human Miro2 (hMiro2) [22]. These are shown as spheres (K220, R240, K439 and K600; labelled with dMiro numbering). An alignment of a 10‐aa segment of dMiro, hMiro1 and hMiro2 flanking each ubiquitinated site is shown. The large blue 'K' within each sequence alignment indicates the ubiquitinated residue in hMiro1 or hMiro2, and a smaller, underlined K indicates that dMiro has a lysine in the same position. Residue S324, a candidate Pink1 phosphorylation site, is also shown in spheres. Note the side‐chain of K439 is disordered in the MiroS structure, so it is modelled as an alanine. dMiro/Dm Miro, Drosophila Miro; Hs Miro 1/2, human Miro1/2.
Sen1 is required for normal RNAP3 transcription.Figure 2(left) ChIP-qPCR analysis of Rpc37 in the presence or absence of Sen1 at the indicated loci in a population of cycling cells (mean ± standard deviation from 4 biological replicates). (right) Western blot analysis of Rpc37 protein levels in the presence or absence of Sen1. Tubulin was used as a loading control. (left) Total RNA from the indicated strains were separated on a 2,8% agarose gel. (right) Quantification of overall tRNA levels (mean ± standard deviation from 3 biological replicates). Strand-specific RT-qPCR was used to quantify the indicated RNAP3 transcripts. Transcript levels were normalized to act1 (mean ± standard deviation from 3 biological replicates).
Figure 5(A) Still images of the Movies EV3 (Control, upper panel) and EV4 (NEF, lower panel), obtained by intravital time lapse 2PM imaging of draining popliteal LNs 24hrs post immunization with HEL-OVA/CFA, following adoptive transfer of GFP BHEL cells (green) and mTomato CD4OT-II cells (red) expressing empty vector (Control; upper panel) or NEF WT (lower panel), respectively. High endothelial venules (HEVs) (white) were labeled by intravenous injection of Alexa660-labeled Meca-79 antibody and collagen (blue) is visualized by second harmonic generation (SHG). Yellow and orange arrows indicate stable and transient ISs, respectively. Numbering of ISs corresponds to that in the respective Supplemental movies. Scale bar 20µm. (B) Quantification of the duration of interactions as indicated by the arrows in A. Touching T and B cells were manually quantification using virtual reality (InViewR, Arivis). Each dot represents one T-B interaction pair. Red bar shows median. Data is derived from 5 to 6 movies, acquired from 4 mice in 2 independent experiments. Percentages on top indicate frequency of interactions that lasted 20min or longer. (C) Still images of the Movies EV5 (Control, upper panel) and EV6 (NEF, lower panel), obtained by intravital time lapse 2PM imaging of draining popliteal LNs 8d post immunization with HEL-OVA/CFA, following adoptive transfer of GFP BHEL cells (green) and mTomato CD4OT-II cells (red) expressing empty vector (Control; upper panel) or NEF WT (lower panel). Follicular dendritic cells (FDCs) (white) were labeled by subcutaneous injection of Alexa647-labeled anti-CD21/CD35 antibody and collagen (blue) is visualized by SHG. Yellow and orange arrows indicate stable and transient ISs, respectively. Numbering of ISs corresponds to that in the respective Supplemental movies. Scale bar 20µm. (D) Quantification of the duration of interactions as indicated by the arrows in C. Touching T and B cells were manually quantification using virtual reality (InViewR, Arivis). Each dot represents one T-B interaction pair. Red bar shows median. Shown is one representative dataset out of two, derived from 5 to 8 movies, acquired from 4 mice. Percentages on top indicate frequency of interactions that lasted 20min or longer.
Figure 5 Schematic describing the sequence space explored by the combined library (left). Table listing the top 10 most important features. The relative feature importance is given as relative percentages in the last four columns. The size of the circles is scaled per method (lasso, ridge, xgboost, stacked). The direction column denotes the direction of enrichment of the given feature for functional sequences compared to non-functional sequences (up, positive direction and down, negative direction)