EMBO/sd-character-level-ner huggingface dataset:
(A) MSA180 architecture. Predicted signal peptide (black), conserved regions (hatched; see Appendix Fig S2 for sequence alignments), likely boundaries of the SERA6-interacting regions (double-headed arrows; fragments I and J from Fig 1B) and predicted molecular mass of each species based on its amino acid composition (in parentheses) are indicated. A semi-tryptic MSA180-derived peptide (filled block arrowhead) was detected from fragment I and is likely a result of SUB1 cleavage (see Fig EV4).
B. T6SS secretion assay of A. tumefaciens C58 Δtap-1Δatu3641 containing an empty pTrc200 vector (V) or its derivatives expressing tap-1, atu3641, tde1-tdi1, or tde2-tdi2.
B) Vinculin immunofluorescence staining of whole mount wild type, Tek-Cre::Lama5-/- and Lama4-/- mice mesenteric resistance arteries reveal smaller adhesion complexes in Tek-Cre::Lama5-/- (arrow heads) and larger adhesion complexes in Lama4-/- vessels (arrow heads). Scale bar is 10 µm. Correpsonding quantification of sizes (C) and frequency distribution (D) of adhesion complexes per endothelial cell. Data are means ± s.e.m from 300 cells from 9 wild type and 9 KO arteries isolated from 3 mice/genotype. ***P<0.001, ****P<0.0001, unpaired t-test.
(A) Immunocytochemistry of patient-derived cystinotic tubuloids (CNTSPatient-1 and CTNSPatient-2) and healthy kidney tissue-derived control tubuloids (CNTSWT-1 and CTNSWT-2) for PAX8, TP63 and F-actin. Scale bar = 100 µm.
c) Skinbowmice were induced at a time were the back skin contained both areas of anagen and telogen and samples collected for evaluation at 7 days. Histogram charts represent the relative frequency of clone size from clones attached (top row) or not (bottom row) to HF in anagen and telogen phase at induction. Even at a rate of one cell division per 24h, 7 cycles of divisions results in 128 cells. Therefore the findings reported are not incompatible with our claims as suggested. Observation of spontaneous recombinations if they exist are therefore a very rare event that we have never been able to observe. Such rare event is unlikely to influence our analysis based on sizes of hundreds of clones. Chi square test, *** p=0.001; ** p=0.01.
A) MhsT is shown in a ribbon representation (scaffold helices in blue, bundle helices in red, and TM5 in dark grey, sodium ions shown as purple spheres, L-4-Fluoro-phenylalanine, bound between unwound region of TM1 and TM6, shown as green spheres.
MISTRG mice were reconstituted or not at birth with human CD34+ cord blood HSPCs, and intravenously injected with 10x106 U-2932 or RC-K8 cells at six weeks of age. the occurrence of clinical symptoms (weight loss, hind leg paralysis) was recorded for each mouse (J).
D. Average expression level of the genes used as known markers to assign each epithelial cluster in the reference atlas dataset. ﻿Cells colored by the expression of nub, wg, zfh2, Sox15, grn, bnl, eyg, Ance, Idg4 and drm.
(E) Working model of cartwheel stacking, with alternation of two modes of SAS-6 ring stacking: pairs of rings are tightly superimposed with a rotational offset (dashed line) and such offset double rings are then stacked in register (solid line); the offset direction is consistent in T. spp., T. agilis and T. mirabilis, yet may be different in other species, as suggested in Paramecium (Klena et al). Surface representation of SAS-6 rings in different shades for clarity; homodimers highlighted by black contour.
Stem-loop RT-qPCR-based analysis of epidermis/vasculature ratio of miR160 levels (top) and RT-qPCR analysis of ARF17miR160 mRNA levels (bottom) in the samples in (C). Error bars: SD. t-test (top) and Tukey's multiple comparisons test (bottom) p-values are indicated. n=3.
B16F10 melanoma cells with or without mTRF2 overexpression were inoculated into the backs of immunocompetent mice and treated with anti-GR1 antibody or isotypic control (200µg/IP). The tumor volume was determined every 2 days using hemi-ellipsoid formula (B). Tumor volume are presented in mm3 along the time in days. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.
a HEK cells transfected with a luminescent cAMP sensor were incubated with 10 nM CXCL12 alone and in the presence of 10 nM Gal-3 CRD followed by stimulation with forskolin, an activator of adenylate cyclase. Results are shown as luminescence relative to baseline (RLU, example of n = 3).
(a-c) MEFs of the indicated genotype were treated as indicated, counted and 2.7×105 cells were lysed. Lysates were separated by SDS-PAGE and immunoblotted using the indicated antibodies. (d) Ratio between the densitometric levels of cyclophilin D and those of PMP70 in MEFs of the indicated genotype. One representative experiment of five independent repetitions performed as in a-c is shown.
(e) ITT was performed after 18 weeks of HFD (left), and KITT calculated (right). *P0.05; Student's t-test (left) and one-way ANOVA (right).
A, B, C, D Based on a threshold of log2[fold change (FC)] > 1, the 20 TFs were categorized into four groups. the second group reached the threshold after 1 h (B) The arrow indicates the initial upregulation of every group. Data information: Data are presented as mean ± SEM. n = 4 independent experiments. FDR values are available in Table EV1.
B) Western blot immunovisualization of subunits of the respiratory complexes. Note the increased protein levels in Cox15sm/sm vs. WT samples, which are reduced to normal levels upon rapamycin treatment. Additional samples were run on a separate gel (not shown)
B Bar plot showing the percentage of cells in the G0/G1 (red bars), S (blue bars) and G2/M (green bars) phases of the cell cycle among each of the 7 sorted cell subsets of Dataset 3.
(F) U2OS (EGFP-Flex1-STGC-1541) cells were infected by retroviruses expressing RAS or empty vector, and the percentage of EGFP positive cells was assayed by FACS 5 days following infection (left). U2OS (EGFP-Flex1-STGC-1541) cells expressing shRNAs for RAD51, POLD3 and PIF1 shRNAs or shRNA vector were infected by retroviruses expressing RAS, and the percentage of EGFP positive cells was assayed by FACS 5 days after infection (middle). Expression level of RAD51 and POLD3 is shown by Western blot analysis (right). Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Signiﬁcance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01 and n.s. (not significant) P>0.05.
E) Representative immunohistological analysis of CD163 (scavenger receptor present in macrophages), AGR2, and TMED2 in non-inflamed colonic biopsies from healthy controls and patients with active or quiescent CD.
D. Representative bioluminescence images of brains with indicated 528 GSC tumor xenografts expressing shC, shL115-1, or shL115-2 at 45 days after implantation. Images represent results of 5 mice per group of 2 independent experiments. E. Quantification of the bioluminescence activity in D.
HT-29 cells were transfected with a nonspecific (NS) siRNA or with the indicated siRNAs for 72 hours. Cells were pre-treated with 10 μM QVD-OPh (Q) plus 5 μM Birinapant (S), and exposed to 10 ng.mL-1 of TNFα (T). G Small EVs fractions were purified from the culture medium by ultracentrifugation. Shown is a representative diagram of particle count obtained with tunable resistive pulse sensing analysis (TRPS, qNano, IZON).
(B) In vitro deadenylation activity assay using protein extracts from HT1080 (WT) and HT1080PARN KO (PARN KO) cells.
F Representative images of ALP and ARS staining. Mouse MSCs were treated with Smurf1 or control siRNAs, and cultured in osteogenic medium for 5 and 10 days, respectively
F Oxygen consumption in isolated BAT from 10-week-old male WT and FADD-D mice on a SD (n = 4 for each genotype). Data are expressed as mean ± SEM. *P = 0.0025, **P = 0.0006 (Student's t-test).
d, Labelling density of cathepsin-D as estimated in two independent experiments. e, Labelling density of LAMP-1.
D Effects of inhibitors (n=6 biological replicates) and mimics (n=4 biological replicates) of piRs-3-I2 and piRs-3-I3 on food intake.
Western blot analysis of Parkin and Parkin aggregation in human Healthy Control (HC) (n=3) and Diabetic Mellitus (DM) (n=12) platelets. Graphical representation and statistical analysis of HC (n=3) and DM (n=12) individuals. (modified parkin *p=0.035 vs. HC). Actin served as the loading control.
Numbers of ASCL1+ cells in V-SVZ coronal sections 2 days after TAM treatment. n=3, **p= 0.0087. V-SVZ coronal sections stained for ASCL1 (red) and nuclei (blue). Scale bar: 50 μm.
B Upper panel. SDS-PAGE stained with Coomassie blue in which Bem1 is indicated. Lower panel. The liposomes were composed of 100% phosphatidylcholine (PC), 80% PC and 20% phosphatidylethanolamine (PE), 95% PC and 5% phosphatidic acid (PA), 95% PC and 5% phosphoatidylinositol (PI), 95% PC and 5% PI(4,5) P2 (PI(4,5) P2), 95% PC and 5% PI4P (PI4P), 80% PC and 20% phosphatidylserine (PS) or 75% PC 20% PS 5% PI4P (PS+PI4P). (S) supernatant, (P) pellet.
AP staining of WT and 11 RBP-KO ES cell lines after LIF withdrawal. Scale bar, 200μm.
, E) HH/SMO reduces Smaug levels and its overall negative effect on reporter expression. Mean values of the relative levels of reporter expression (determined as above) (D) or of λN-SNAP-Smaug (ratio λN-SNAP-Smaug/GFP-SNAP) (E) in the absence of SMO constructs (red) or in the presence of SMOWT-HA (green), SMOPKA-SD-HA (blue) or SMO∆958-HA (yellow), without HH (plain boxes) or in presence of HH (striped boxes). N=6 (independent biological replicates), except for "no SMO, no HH" and "SMOWT with HH" conditions where n=10 (independent biological replicates). A representative gel is shown in Fig EV3D. Note that SMOWT-HA or HH alone had reproducible weak effects that were observed in two independent biological triplicates but were not statistically significant. See also Fig EV3E-F.
C. Scatter plot showing the number of animals which displayed the hemorrhage phenotype across the progeny derived from an outcross of veal2gib005Δ8/+ zebrafish injected with IVTs of different veal2 variants. Control indicates veal2gib005Δ8/+ zebrafish without complementation. Data from three different experiments plotted as individual values; the middle bar represents mean percentage and the error bar represents ± standard deviation.
A Cell lysate from COI12KO cells at 3 hpm was incubated with radiolabeled double‐stranded 27‐nt RNAs and the different truncated mutants of Coi12p (schematically shown on the top). The Twi1p‐containing complex was immunoprecipitated with an anti‐Twi1p antibody, co‐precipitated RNAs were separated on a denaturing gel, and 27‐nt RNAs were detected by autoradiography. The intensities of the bands in the different conditions relative to the wild‐type (WT) sample (2nd column) are shown on the top. A representative experiment is shown on the bottom.
The Ca2+ signal elicited by frustrated phagocytosis was significantly reduced in Ned-19 (10 μM)-treated WT and in all TPC-KO BMDMs; maximum Ca2+ amplitude, expressed as a percentage of WT control (n = 314-641 cells). Phagocytosis of opsonized 3-µm (B and C) and 6-μm (D) beads was inhibited by Ned-19 (B) and in BMDMs from Tpcn-/- mice compared to WT (n = 134-280 cells).
E. Time-lapse imaging of transfected HEK293 YFP-EML4-ALK V1 WT to observe the movement of cytoplasmic foci. Representative still images are shown of an area of cytoplasm containing YFP-EML4-ALK V1 WT and V3 WT foci at the times indicated. Scale bar, 1 μm.
(A) Depletion of Gadd45b expression using lentiviral-transduced shRNAs in latently-infected SCG neurons case cause HSV-1 reactivation. HSV1-GFP-Us11 latently-infected cultures were infected with lentiviruses expressing either two different shRNAs against Gadd45b mRNA or a non-silencing shRNA (NS). Reactivation was quantified by scoring the percentage of wells expressing GFP after 5 days. Knockdown efficiencies for individual shRNAs in latently-infected SCG neurons were confirmed by RT-qPCR using RNA collected in parallel. Reactivation rates were quantified from 30 wells for each condition, 3 biological replicates. RT-qPCR were quantified from 3 biological replicates. The bars and error bars are mean ± SD. Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (*, p<0.05; ***, p<0.001; ****, p<0.0001). P values are calculated using two-tailed unpaired Student's t test. P values > 0.05 were not significant (ns).
(B) Scheme of the Vps41 primary sequence with indicated motifs. The Vps41 protein harbours two motifs in its N-terminal region that have been shown to affect Apl5 binding, a PEST motif as well as an amphipathic lipid packaging sequence (ALPS) motif Furthermore, phosphorylation sites at residues S367, S368, S371 and S372 are shown, which are mutated in a phosphomimetic mutant (SD).
(H) U2OS (EGFP-Flex1-STGC-1541) cells expressing FLAG-PIF1 WT or mutants with endogenous PIF1 was depleted by shRNA, were treated with 2 mM HU for 24 hr. The percentage of EGFP positive cells after HU treatment was quantified by FACS analysis 3 days after HU removal. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Signiﬁcance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01 and n.s. (not significant) P>0.05.
(C) SGA and flow cytometry analysis in budding yeast. The array involves the crossing of MATα query strain harboring the FPR construct with the MATa non-essential gene deletion mutant library. The systematic selection as described in Baryshnikova et al, 2010 results in haploids containing the gene deletion and FPR. Quantification of the resultant haploids by high-throughput flow cytometry records fluorescent signals in up to 50,000 cells for each gene deletion mutant.
(H) 786-0 or 769-P cells (WT or stably expressing shGDH1) were transfected with siNC or siRNF213 for 48 hours and then were treated with or without aa starvation for the indicated times. Cell viability was determined. Unpaired t-test was used with ***p < 0.001.
Quantification of cell death with a 7-AAD assay (E), N=7 samples/group in NRCM transduced with Ad.Con or Ad.TIP30 and stimulated as indicated. PE: phenylephrine.
(C) Schematic depicts the overlap of tRNAs in (A) that decreased over time with tRFs from (B) that were induced.
Pedigrees of the two families, indicating autosomal recessive inheritance. The genotype of the VPS16 c.2272-18 position is indicated. ?, not available for testing. (A) Family of patient A. The three sisters are healthy, but an older brother had previously died at 11 months from suspected heart failure after showing signs of developmental delay from an age of 3 months of age. (B) Family of patient B. The mother previously had two spontaneous miscarriages but the two sisters are healthy.
(E-F) Representative (E) Seahorse experiment and statistical analysis of (F) basal OCR and maximal respiration of 5-day-old gas-1; cest-2.2 O/E mutant C. elegans fed with control and cest-2.2 RNAi since hatching (ordinary one-way ANOVA with Tukey's multiple comparisons test, n=7-9 biological replicates, from 3 independent experiments). Data information: , points represent mean± SEM bars represent mean± SEM Across experiments, p value summary is ns= not significant, *p<0.05, **p < 0.01; ***p < 0.001, ****p<0.0001.
B. Expression and localization of concavinC7A-GFP in blood stage parasites. Scale bar 5 µm.
E. Fluorescence amplitude difference between rAβ1-42 alone (rAβ1-42 = 0) and in the presence of the peptides (Statistics: Brown-Forsythe and Welch Anova tests with Dunnett T3 multiple comparisons correction, n=2 independent experiments with 4 repeats). Graph: Mean difference and 95%CI. * P ≤0.05, *** P≤0.001, **** P≤0.0001.
ChIP-qPCR results show the association of Flag-tagged HP1c with Notch target genes. The amount of immunoprecipitated DNA in each sample is represented as signal relative to the total amount of input chromatin (equivalent to 1). HA antibody is used as a control. Error bars indicate SEM. n=3 technical replicates. Data are evaluated with two-tailed Student's t-test (*p < 0.05, **p < 0.01, ***p < 0.001).
(C) Zoomed view displaying periodic repeats of the central hub (CH) and several cartwheel inner densities (CIDs) in P. tetraurelia. CIDs, red arrowheads and red plot profile; CH, blue arrowheads and blue plot profile. Overlay between CID and CH peaks is plotted on the right in red and blue. Mean distance between CID peaks, red 8.6 +/- .8 (n= 5). Distances between CH peaks split into two distinct populations: smaller (within a ring-pair), green 3.1 +/- 1.3 (n= 6); larger (between ring-pairs), blue 5.5 +/- .7 (n= 5); average periodicity, black 4.2 +/- 1.3 (n= 11).
A. Hierarchical clustering of differentially regulated transcripts from RNA-seq between vehicle and TGFβ1-treated AECs in the co-culture (p-adj < 0.05, t-test with Benjamini-Hochberg Correction). Significantly regulated profibrotic genes (marked by asterisk) and histone/DNA methyltransferase encoded genes (marked in blue) are listed on the right side.
(B) Analysis and quantification of Xbp1 splicing in DLD1 and SKOV3 cells treated with varying concentrations of Reversine (Rv) for 12, 24, 48, and 72 hours. Thapsigargin (Tg) is shown as positive control.
B) Editing outcomes of hCD34+ cells nucleofected with POT1 sgRNA-1 before transplantation determined by NGS. Data information: The vertical dashed line shows the site of CAS9 cut and the base pairs noted in red show insertion. A dash inside a gray box indicates a deleted base pair.
(A-D) Compared with the control (A) flies, posterior midguts of Notch OE flies exhibit decreased ISCs and ee cells (B), while HP1c OE flies show increased ISCs and ee cells (C), and the phenotype of Notch OE can be rescued by HP1c OE (D). Arrows mark ISCs, arrowheads mark ee cells, circles mark ISC-ISC, ISC-EB or EB-EB nests. ISCs were visualized with esg-GFP alone, EBs were stained with both esg-GFP and Su(H)-lacZ, while ee cells were labeled by Pros and DNA was marked by DAPI. Scale bars, 30 μm.
(P-R) Co-IP analysis of the interaction between HA-p62 and (P) Flag-RIG-I, (Q) Flag-TLR3, (R) Flag-cGAS in the absence and presence of GFP or GFP-IRGM in HEK293T cell lysates.
D, Upper panel, while for stimuli up to 20ms exocytosis from OtofI515T/I515T (n=13) and Otof+/+ (n=11) IHCs was similar, sustained exocytosis, representing most likely the release of replenished vesicles, was significantly reduced in OtofI515T/I515T IHCs (t-test). Lower panel, Ca2+-current integrals were of similar size.
(C-D) Confocal images of HeLa cells transfected with EGFP-ORP5PH or EGFP-ORP5ORD (C) together with PTPIP51-HA and immunostained using HA antibody to detect PTPIP51. Scale bar, 10 μm.
J. LPS increases mTOR P-S2159 in vivo: Mice (C57BL6, 6 wks old) were injected intraperitoneally with PBS or LPS [1 mg/kg-BW] (2 hr.). mTOR was immunoprecipitated from spleen tissue, and IPs and WCL were immunoblotted as indicated. The graph depicts levels of mTOR P-S2159 relative to total mTOR in spleen tissue -/+ LPS. n=8 from 3 independent experiments +/- SD. *p=.004 relative to PBS treated control mice by paired t-test (two-tailed).
B, C. Representative Cm traces induced by 200-ms pulse depolarization (arrows) ib DRG neurons. DRG neurons were transfected with plasmids expressing shSyt11-2 (Syt11 KD, KD) or scrambled shRNA (Sc) and Cm recording was performed 5 days after transfection. Endo-5s represents the Cm decay 5 s after stimulation. Insets show Ca2+ currents recorded in the same neurons.
B Probability density plots of FOF1 a-mNG jump distances in E. coli WT and fabA(Ts) cells.
(A) 293T cells were transfected with Flag-ULK1 or control empty vector and subjected to immunoprecipitation with anti-Flag antibody, followed by immunoblot analysis with the indicated antibodies.
(b) Bath application of 100 μM TAT-GluN2Bct-CTM (36.54 ± 7.1% of control; n = 8; P = 0.001), but not TAT-GluN2Bct (89.13 ± 10.78%; n = 7; P = 0.311), 60 min before and during H2O2 treatment (300 μM; 30 min) knocked down DAPK1 at 2 h after washout, and this effect was rescued by NH4Cl (20 mM; n = 8; **P = 0.003 to control; P = 0.106 to H2O2-treated). One-way ANOVA, F(4,34) = 11.628, P 0.001. Bars represent DAPK1 levels relative to saline control group. β-actin was used as a loading control.
(b) HCT116 cells were serum-starved for 24 h and the cytosolic proteins were extracted for co-immunoprecipitation with anti-FoxO1 or anti-SIRT2, followed by probing with anti-SIRT2 or anti-FoxO1, respectively (top and middle panels). FoxO1(WT) was also transfected into H1299 cells and the cytosolic protein was extracted, followed by co-immunoprecipitation with anti-FoxO1 and probing with anti-SIRT2 (bottom panels).
B. Hemolytic activity of culture supernatants of GAS strain 188, 188SLO-, and 188SLO(Y255A). The amino acid substitution Y255A in SLO abrogates the ability of SLO to porate the host cell membrane, demonstrated by the failure of culture supernatants from 188SLO(Y255A) to lyse erythrocytes despite producing wild-type amounts of the variant SLO protein. Inset, corresponding Western blot for SLO in culture supernatants from these strains.
A-C. 2ac clones established after transfection with an empty vector (empty) or plasmids expressing wild type Jmjd2c (2c wt) or a catalytic mutant (2c mut) were exposed to OHT as indicated and subsequently used for (C) serial plating for the generation of growth curves.
(i) Relative number of P-bodies per cell (detected with 18033 serum-recognizing GW182) treated with indicated siRNAs. n=3, *P=0.0002 NDP52, P=0.004 ATG5.
Fig. 4. Spironolactone antagonizes ERBB4 phosphorylation both in in vitro and in vivo.(G) Spironolactone (applied as 10 µM) significantly increases frequencies (n=12; p=0.0454) and amplitudes (n=12, p=0.0478) of sIPSCs in pyramidal neurons of PFC. Representative traces of sIPSCs (upper) and a histogram of mean sIPSC (lower) are shown for both before and after addition of spironolactone.
(b) Electron micrographs of striatal neurons from wild-type (Ctr) and HD94 mice grown over a wild-type ratastrocyte monolayer. Arrows, abnormally short (black) or abnormally long (green) mitochondria. Right: number of mitochondria per cell profile. Mean + s.d. of ten cells per group in triplicates.
c, quantification of Iba1+ cells, Arg1+ cells and Iba1+Arg1+ cells in the lungs. mock_saline n=3 (males), mock_ivermectin n=4 (males), CoV_saline n=9 (6 males and 3 females), CoV_ivermectin n=6 (4 males and 2 females). Data information: M: male hamsters; F: female hamsters. Horizontal lines indicate medians. The p value is indicated in bold when significant at a 0.05 threshold. Mann-Whitney test
(D) Activity of TEAD-Luciferase reporter in primary intestinal epithelial cells upon mIslr, Yap1 or mIslr and Yap1. n=4.
Spleen, mLN or PP cells from Vα14 TN iNKT mice and PP cells from an IL-4-/- mouse were cocultured with anti-CD40 activated wild type or CD1d-/- B cells. 1μg α-GalCer was added to the cultures to specifically activate iNKT cells. Blocking antibodies to IL-4 or isotype were added as indicated. IgG1+ class switched B cells were enumerated by flow cytometry after 4 days of coculture
C. MEFs were transfected with FUNDC1-MYC. 24 h post-transfection, cells were fixed and immunostained by anti-MYC and anti-DRP1. Bar = 10 µm.
C Fe-S-dependent Complex I-specific activity was decreased in WT PH mice as compared with control (N = 7/group, left bars, ***P < 0.0001), but activity was preserved in the lungs of miR-210−/−mice in either condition (N = 8/group, right bars), NS P = 0.3693.
H. Heat map showing the enrichment of mRNA targets of the 7 microRNAs shown in (G) with a gene-set identified by GWAS studies linking genes to cognition in healthy humans (Davies G, 2018). Note that target genes of miR-181a-5p, miR-148a-3p and miR-146a-5p are significantly overlapped in a hypergeometric test (Fold enrichment > 1.5 and FDR<0.05). *P = 0.02, **P = 0.0008, ***P = 2.267e-05.