EMBO/sd-character-level-ner huggingface dataset:
F Cideb deficiency alleviates the whole body inflammation response. Serum TNFα, MCP1 and IL6 levels of WT and Cideb-/- mice under chow diet and HFLF diet (n = 8 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.
ECE2 expression on protein level. Immunohistochemistry (IHC) for ECE2 in 50d old COs shows accumulation in the CP' and at the apical surface (Scalebar=50µm). Ventricle-like lumen in COs is marked as V'.
B. Quantification of the impact of stable end-on KT-MT attachments on MT-flux in NDC80-depleted cells under indicated conditions and in early prometaphase cells with and without the CENP-E inhibitor GSK923295. MT-flux values are plotted with mean ± SD. N (number of cells, number of independent experiments): siControl (49, 5), siNDC80 (59, 6), siNDC80 + siKIF4A (41, 3), siNDC80 + STLC (bipol.) (28, 3), siNDC80 + siKIF15 (36, 4), siNDC80 + siCLASPs (33, 3), siNDC80 + siKIF2A (38, 4), siNDC80 + GSK923295 (38, 3), early prometaphase (23, 3), early prometaphase + GSK923295 (28, 3).
A. The structure of the sE-linker* trimer is displayed as ribbons colored by domains as in Figure 1. The previously determined structure of the TBEV sE401v trimer (PDB 1URZ, [15]) is superposed in light grey with fusion loops (FL) in orange, highlighting the disordered domain II tip in the new structure. The two subdomains of domain II, base and tip, are indicated. Disulfide bonds are shown as dark grey sticks. The residues of the stem are displayed as sticks color-coded according to atom type, with carbon atoms green. B. Close-up view of the sE-linker* trimer with one subunit colored as in (A) and the others in grey. The segment connecting helix αA to the η3 3/10 helical turn (see Appendix Fig S1) of the adjacent subunit is shown as sticks colored according to atom-type with carbon atoms light grey. Broken lines mark polar interactions of the stem with surrounding residues (with distances ranging between 2.7Å and 3.4Å). An open arrow marks the C-terminal end of the sE401v trimer structure reported previously (PDB 1URZ). C. For comparison, the same region of the stem is represented for the DENV-1 sE structure (PDB 4GSX, [19]), using the same color scheme.
E Immunoblotting of TLR7 in the endosome isolated from HEK293T cells that were transfected with GFP-TLR7 or GFP-TLR7 mutant vectors.
(D) Gross images and H&E staining of lung and liver from TFAM+/LKO or TFAMLKO mice injected with Akt/β-catenin. Different time points were shown. Liver/body weight ratio and percentage of microscopic tumor area was used as the measurements of the tumor burden. Scale bars, 1mm (lung); 50μm (liver). Data information: Sample sizes of about 30 mice per group is shown when calculating the metastasis rate or tumor burden.
The frequency of (F) CD163+ MQs and (G) CD163- MQs in BM of HO-1-/- mice is altered.
J Left, the putative complex of FADD (yellow) and PPAR-α (colorful) by molecular modeling is portrayed in ribbon representation. Middle, the residue S194 of FADD and PPAR-α residue K448 are shown in sphere representation, which is immediately proximal and capable of hydrogen bonding interactions. Right, the key residue D194 of FADD-D and PPAR-α residue Q445, K448, K449, R465 are shown in sphere representation, which is immediately proximal and capable of salt bridging interactions.
Back skin sections of P49 mouse skin immunostained for LYVE1 (red), CD34 (green) and counterstained with DAPI (blue). n= 3 - 4 skin samples per mouse, n= 3 - 4 mice. Scale bar, 100 μm. epi, epidermis; der, dermis. White arrowheads denote the proximity of lymphatic capillaries to HFSC.
5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. once with AAV8-shCrebh or control AAV8-shLuc. Western blot analysis of hepatic Sel1L and Crebh 5 weeks post injection (n=3 mice each, 2 independent repeats). Hsp90, loading control for Western blot analysis.
Graph of the number of degradation events scored as in D. A degradation event was counted if electron dense-cargo or organelles were surrounded by a single membrane (lysosome) or double membrane (autophagosome). Red line indicates mean across all the mice.
Addition of 1 ng rhTNF to fracture supernatant increased CCL2 protein levels in the air pouch. "Neat" indicates level of CCL2 in fracture supernatant before injection into air pouch. Data are presented as mean ± SEM. FS versus FS + TNF **P = 0.0020 by one-way ANOVA with Bonferroni's multiple comparisons test.
Representative picture of Nsmce2+/+ and Nsmce2lox/lox animals fed for 40 weeks with a 4‐OHT‐containing diet (see also Movies EV1 and EV2).
C) Enrichment of transcription factor targets among the 'top 18' genes (red bars) and the GWAS genes with p<0.001 (green bars), using i-CisTarget (Imrichová et al, 2015). Data information: Significant enrichment : ***: p< 0.001; *: p<0.05. P-values are empirical and Bonferroni-adjusted in (C).
a, REST-deficient cortical neurons cultured from REST cKO mouse embryos show increased vulnerability to H2O2 and oligomeric Aβ42 toxicity. Cell viability is expressed as percentage of the value in untreated cultures. Values represent the mean ± s.e.m., n = 6-8. *P  0.05, **P  0.01 by Student's unpaired t-test.
Frequencies of ommatidia with different numbers of rhabdomeres are shown at 3 days after eclosion in progeny of flies expressing mutant huntingtin exon 1 (gmrQ120) crossed to either a control stock (w1118; W) or to Dhc64C (dynein heavy chain mutant; Dhc; a) or Roblk (dynein light chain mutant; Robl; b) flies. P ≤ 0.0001 (Mann-Whitney U test).
A. Survival curves of A53T α-synuclein TG mice, with LAG3 knockout, heterozygous LAG3 expression, or LAG3 WT. Median survival was shortest for α-synuclein TG LAG3‑/‑ at 239 d, followed by α-synuclein TG LAG3+/- at 260 d and α-synuclein TG LAG3+/+ at 268 d. The survivals of ASYNA53T LAG3‑/‑, LAG3+/- and LAG3+/+ mice were similar (Mantel-Cox log-rank test, p-value = 0.165). Mice were euthanized and dissected in the late-stage symptomatic phase, which would inevitably result in death within a week. None of the control LAG3‑/‑ α-synuclein WT mice died over the course of the experiment.
Flow cytometric analysi in Prdm1ihCd2/+ (red) and wild-type (gray) mice (at the age of 2 months) at day 14 after NP-KLH immunization Flow cytometric analysis of splenic TFH cell histograms display cell surface expression of hCD2 and intracellular staining of Bcl6 (H) in hCD2lo (black) and hCD2hi (blue) Prdm1ihCd2/+ as well as wild-type (gray) TFH cells
(E) Stable HeLa cells expressing pIRES-empty vector, IRF2BP1 WT or IRF2BP1 K579R were treated with siRNA against endogenous IRF2BP1 or non-targeting (nt) siRNA. Exogenous siRNA-resistant IRF2BP1 was expressed at low levels similar to endogenous IRF2BP1. * refers to an unspecific band.
F, G Analysis of enzymatic activity of the succinate dehydrogenase related to the malate dehydrogenase activity in mitochondria isolated from kidney (F) and liver (G). Values of 3 animals per genotype are plotted as percent of wild-type. sh, shTAZ.
(A) qRT-PCR analysis of SUMO-modifying proteins and enzymes in cortex and striata of WT mice at 12 weeks. Relative expression for all the SUMO enzymes is normalized to mouse β-actin.
(D) Co-localization between ODF2 and PIDD1 (n = 11), FBF1 and PIDD1 (n = 21), and ANKRD26 and PIDD1 (n = 17) assessed on images The value represents the fraction PIDD1 objects touching either ODF2, FBF1 or ANKRD26 objects.
Conversion of the mmi-1 Model reaction network into influence diagrams based on two assumptions of kinetics. Left: symmetrical inhibition governed by balanced degradation rate constants in the complex. Right: asymmetrical and unidirectional inhibition governed by unbalanced degradation rate constants between mRNA and miRNA in the complex. Red: mRNA; Green: miRNA. Weights of the orange arrows describe the magnitudes of the degradation rate constants.
(a-c). Drp1 is required for mitochondrial fission induced by PINK1. Drp1-null HeLa cells (Drp1KO) and their wildtype controls (Drp1WT) were co-transfected Δ110-PINK1-GFP-FKBP with FRB-MTS. Cells were induced with 250 nM rapalog for 2 hours to activate PINK1 kinase, followed by immunodetecting mitochondria (TOM20, red) and Δ110-PINK1-GFP-FKBP /FRB-MTS (Δ110-PINK1, green). Nuclei were labeled with DAPI (blue). Cells treated with solvent (DMSO) were used as a treatment control. Representative images were shown (a, upper panel, scale bar=25 μm). Higher magnification images are also included (a, lower panel, scale bar=10 μm). Mitochondrial morphology in different transfections was quantified. (b, c). Student's test. ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments. For each condition, >100 cells were analyzed.
(E) Cellular localization of TslA in A. baylyi cells. Cells of the strain (tssB-sfGFP) were fixed by 2% paraformaldehyde and treated with GTE buffer, then probed with anti-TslA antibodies, followed by incubation with secondary antibodies conjugated with Alexa Fluor Plus 594. Signals were detected using a widefield microscope. Phase contrast, GFP, RFP and merged images are shown (GFP: TssB; RFP: TslA). Data information: Scale bars and time intervals are indicated.
D. SEC-MALS analysis of His-GFP-spMis18C-term-α shows that it exists as a homotrimer with a measured molecular weight of 119.8 kDa. (Theoretically calculated MW of a monomer is 38.3 kDa).
C) Representative traces of IKr steady state activation in WT hiPSC-CMs in Tyrode (left), in the presence of 5 µM LUF7346 (middle) and after the application of 5 µM E4031 to selectively block IKr (right). Inset: voltage clamp protocol.
293T cells were cotransfected with plasmids encoding FLAG-Stx17 WT and the indicated PGAM5-GFP constructs, and analyzed
Protein fractions. Protein fractions were obtained by normalizing iBAQ values by the total sum of all values. The obtained protein fractions were then averaged over the biological replicates (n = 4) for visualization. The fractions glucose transport, glycolysis, arginine pathway and remaining fraction are significantly different between the two strains (p < 0.001, calculated with two-sided t-tests).
(c) Flag-Beclin1 Wt or T119A transfected HeLa cells were incubated in glucose-rich or nutrient-free (HBSS) media, in the presence or absence of ROCK1 inhibitor Y27632. Total cell extracts were used for IP using Flag agarose. Eluted protein was analysed by western blotting against Bcl-2 and Beclin1. Inputs and IP were run on separate gels and same exposure is shown.
(E) IHC for CDC50A and vGluT2 in the developmental dLGN at P14, P21 and P30. The left panels show the overview of immunostaining in the dLGN, scale bar = 200 µm. The right panels are the zoomed-in images, scale bar = 5 µm. Arrows indicate the colocalized CDC50A and vGluT2. (F) Quantification of the percentage of CDC50A+/vGlut2+ synapses. The result shows that a significantly higher percentage of CDC50A+/vGlut2+ synapses at P21 and P30 than P14. N = 6 for biological replicates.
Relative expression of indicated genes in Panc1 measured by qRT-PCR after treatment with different HDAC inhibitors. Note the downregulation of ZEB1 and upregulation of miR-203, miR-200, and E-cadherin by mocetinostat. n = 3, mean ± SEM; unpaired Student's t-test. For significance, see Supplementary Table S1.
siRNA knockdowns were performed in triplicate, and lipase secretion was quantified relative to NC siRNA. Error bars indicate the standard error. Quantification of the percent of each protein remaining from three independent experiments. Error bars indicate the standard error.
(D) Intracellular mycobacteria harvested and assayed for viability based on time to positivity (75 growth units) at day 0 and day 7 using the MGIT 960. All bar and line graphs are reported as mean ± s.e.m. of three independent experiments performed in triplicate. § P<0.05; * P<0.001.
A Immunohistochemistry (IHC) detection of AR in four malignant prostatetumors and two paired NATs. Representative microphotographs of HE staining showed normal prostatic gland (NATs) and poorly differentiated adenocarcinoma cells. IHC analysis indicated heterogeneous AR expression among patients. Magnification, 40×. N1a and M3a were collected from the same patient ((Supplementary Table S5). N2b and M4b were gathered from another patient ((Supplementary Table S5).
A Autophosphorylation as measured in a ELISA assay is shown for WT and interaction mutants in presence of control vesicles (PC; phosphatidylcholine) or PI(4,5) P2 containing vesicles. Plotted are mean values from two independent autophosphorylation reactions, each determined in duplicates (n=4). Mutant nomenclature is as shown in Table 2.
IF analysis of active Notch1 (ICN1) (C) in the indicated IκBα backgrounds at P6 intestines. Scale bars in 25 μm.
Littermate control and δWD mice were challenged intranasally with IAV strain X31 (103 pfu). (A) Mice were monitored for weight loss at indicated time-points. (n = 8).
G LNCaP cells were transfected with either control (Ctrl) or ASNS siRNA. The cells were then cultured for 2 weeks. The colonies formed were stained and photographed. Knockdown of ASNS was confirmed by Western blot analysis shown at the top.H Quantification of the data shown in (G). *P = 0.0087.
E. p4xDPCSUMO was incubated in NPE for 60 min and supplemented with buffer or recombinant RNF4 (WT or C130A). At the indicated time points following RNF4 addition, the DPC plasmid was recovered by DPC pull-down and immunoblotted against M.HpaII.
E) Weighted dot plot representing the enrichment (Log2 fold change) of the markers in hemocytes originating from the lymph gland (DotGFP-WI) compared to embryonic hemocytes (srpGFP-WI) from WI larva. The lymph gland hemocytes and embryonic hemocytes were traced using the lymph gland driver DotGal4 and the embryonic driver Srp(hemo)Gal4 respectively combined with a lineage tracing construct. The relative expression levels are indicated by the size of the dots and the pvalue of the log2 fold change with the gradient dark blue (not significant) to light blue (p<10-3). The p-value are estimated by bilateral student test and indicated as follow: ns = not-significant (>0.05), "*" = p[0.05 - 0.01[, "**" = p[0.01-0.001[, "***" = p <0.001].
(D) Mcp3 rescues loss of Mdm12. Wild-type (WT) or mdm12Δ cells transformed with the empty plasmid pYX142 () or mdm12Δ cells over-expressing either Mcp3 or Mdm12 (as a control) were analysed at 30°C or 37°C by drop dilution assay on rich medium containing glycerol (YPG).
E Percentage of the indicated bem1 constructs associated with liposomes containing 75% PC, 20% PS and 5% PI4P.
(d) Overexpression of EndoB1T145A inhibits MPP+-induced neuronal death. Data are means ± s.e.m.; n=5.
Relative mRNA expression profile in eWAT (WT n=7, TG n=8, TGxKO n=8). Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice.
(d) Mitochondrial ATP measured in situ by mitochondrially targeted luciferase in cells of the indicated genotype starved for the indicated times. Data represent mean ± s.e.m. of five independent experiments and are normalized to the initial value.
(D) Mitochondria isolated from control and patient fibroblast were solubilized in digitonin buffer and analyzed by 4-13 % gel BN-PAGE and Western blot. SC, supercomplexes.
C Transcript levels for genes involved in lipid metabolism and gluconeogenesis in livers of WT and KO mice after 25 weeks on NC or HFD. Stearoyl-Coenzyme A desaturase (Scd1), fatty acid transporter (CD36), glycerol-3-phosphate acyltransferase (Gpat), carnitine palmitoyltransferase I (Cpt1), peroxisome proliferator-activated gamma (PPARγ), pyruvate dehydrogenase acetyl-transferase (Pdk4), PPARγ coactivator 1 alpha (PGC1α), diacylglycerol O-acyltransferase (Dgat), and facilitated glucose transporter (Glut4). (males, n=4-5). Transcript levels were normalized to 18S. Data information: values shown are mean ±SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; **** = p < 0.0001 (two-way ANOVA with multiple comparisons).
The thickness of the apical F-actin belt is increased in ECE2 KO COs. C, Example images of apical F-actin belt in 60d old CTRL and ECE2 KO COs with F-actin labeled by AlexaFluor594-conjugated Phalloidin (Scalebar=100 µm). D, Quantification of the thickness of apical F-actin belt in Fiji [86] by measuring the area of F-actin and dividing by the length of apical surface reveals significant increase in ECE2 KO COs (Box plots: mean=red line, median=black line, box represents 25th and 75th percentiles, whiskers extend to 10th and 90th percentiles, all outliers are shown; n=number of analysed ventricles in 2 batches; Kruskal-Wallis One Way ANOVA on Ranks and Dunn's Pariwise Multiple Comparison: ***P < 0.001).
(A) qRT-PCR analysis of defense-related genes in 10-day-old seedlings exposed to 0.5 µM Pep2 for 10 h. (*, p < 0.05 in two-tailed tests compared to the corresponding WT values. Relative Ct values of two independent experiments with three biological replicates each were combined for statistical analysis.)
H The effect of HSATIII knockdown on pooling of intron-retaining RNAs in control (CHO) and CHO (His9) cells (42°C for 2 h and recovery for 2 h at 37°C). Arrows indicate the positions of PCR primers.
Representative images of small intestine crypt sections stained with antibody against pATM (Ser-1981)(E). Quantification of frequencies of pATM (Ser-1981) positive crypt cells (n=4-6 of 7-month old mice per genotype) (F).
E-G GO analysis. GO enrichment was performed using Ingenuity Pathway Analysis. Protein localization (E), molecular function (F), and biological function (G) are plotted in a single panel.
(C) Phasor analysis was performed for the FLIM/FRET experiments described in (B) in WT (left) or RagA/B KO (right) HAP1 cells expressing mCherry-tagged ArfGAP1 and endogenously GFP-tagged Raptor. Cells either had amino acids (+AA) or were starved of amino acids (-AA). For each condition, the first panel shows the fluorescence signal of the green channel. The second panel shows the phasor distribution of GFP (black circle), GFP-tagged Raptor (green circle), and GFP-tagged Raptor plus mCherry-tagged ArfGAP1 (red circle). The green line indicates where the GFP phasor would fall when containing autofluorescence. The third panel shows spatial distribution of pixels associated with FRET. Scale bars: 9 μm for WT (left) and 5 μm for RagA/B KO (right) cells, respectively.
(b) THPN-induced cell death is prevented by the autophagic inhibitors wortmannin (100 nM) and chloroquine (20 μM) but not by the apoptotic inhibitor zVAD (20 μM) or the necrotic inhibitors butylated hydroxyanisole (100 μM) and necrostatin-1 (30 μM). The cells were pretreated with each inhibitor for 1 h separately before the THPN treatment (20 μM, 48 h). Ctrl, control.
BAT temperature of WT (n = 5) and Ucp1∆L (n = 6) male mice measured before and after i.p. injection of CL316243. *p < 0.05, repeated-measures two-way ANOVA
As in (A,B) but in mice maintained on the HFD for 10 weeks and then gavaged Mondays, Wednesdays, and Fridays for 3 weeks with vehicle or 120 mg/kg SH-BC-893; n=9. Rx, treatment number of a total of nine doses.
Representative images of U2OS cells expressing indicated GFP-ACRC alleles that were treated with 5-azadC in the presence or absence of SUMO inhibitor (SUMO-E1i), fixed 2 h later and immunostained with DNMT1 antibody. Scale bar, 10 μm.   Quantification of data in (G), showing proportion of cells displaying GFP-ACRC co-localization with DNMT1 foci (mean±SEM; at least 100 cells quantified per condition per experiment; n=3 independent experiments).
A. MCF-7 cells or MCF-10A cells were infected with lentiviruses carrying the indicated constructs. Cells were split into 96-well plates and then harvested at the indicated day. Cell growth curves were measured with MTS assays.
Left panels: Representative single-channel and merged images of HUVECs expressing GFP-LC3 and immunostained for STX17. Scale bars, 25 µm and 2 µm in the inset. Right panels: Quantification of LC3/STX17 positive cells in the presence or absence of BafA1 (one-way ANOVA; **p=0.0060 vs control; #p=0.0136 vs control BafA1) and quantification LC3/STX17 positive puncta per cells (n=50 cells; one-way ANOVA; **p<0.0001 vs shTCHP BafA1).
Confocal micrographs of EphA2 (red) and GPRC5A (green) in primary OCKI_p06 patient cells cultured in 3D collagen for 4 d before 72 h treatment with or without 10 µM cisplatin. Scale bars: 20 μm.
B VP1389 interacts with VP1390. Co-immunoprecipitation of FLAG-tagged VP1390 or BC3020 using Myc-tagged VP1389 when co-expressed in V. parahaemolyticus Δvp1389 (input). Precipitated proteins (output) were detected by immunobotting using α-Myc and α-FLAG antibodies. Source data are available online for this figure.
(E) SH-SY5Y cells were transfected with GFP-labelled Tollip for 24 hours then treated with AO, AO/100 μM bafilomycin A1 (AO/BfnA1) or AA alone for 2 hours prior to fixation. Cells were then immunostained for GFP (green), PDH E2/E3bp (red) and TOM20 (blue) and imaged by widefield immunofluorescence microscopy. GFP-Tollip was observed on TOM20+ve/PDH-ve MDVs (arrowheads). Zoom insets represent 7x magnification.
B. Splenocytes were isolated from ATG7 fl/fl and wt C57/BL6mice. Activation of splenocytes and AICD were performed as previously described. At day 5 after activation, cells were infected with retroviral constructs expressing CRE recombinase. Where indicated, cells were pre-incubated with 100nM rapamycin for 24h before AICD induction. Apoptotic cells were detected 2h after AICD induction by flow cytometry as AnnexinV/PI double positive cells.
B. Cross-linking of engineered variants of the Smc5/6 hexamer. As in (a) using Smc5 and Smc6 cysteine mutants. Schemes indicate the location of engineered cysteines and their expected ability to cross-link in a rod-like and a ring-like conformation. High-molecular weight species were analysed by SDS-Page and Coomassie staining. Wild-type hexamer ('wt') is included as cross-linking control. Species occurring only in the presence of engineered cysteines are labelled by coloured arrowheads. Cross-linking efficiencies were calculated from the intensity of Coomassie-stained bands by comparing the band of the corresponding cross-linked species to the bands of unmodified Smc5 and Smc6. Numbers below the gel quantify the percentage of cross-linked protein species in the displayed gel. Comparable numbers were obtained in at least one additional independent experiment.
Wild type, rad9∆ and mrc1∆ cells were arrested in G1 with α-factor and were released synchronously into S-phase with the addition of pronase, in medium containing BrdU and 0.1% or 0.033% MMS. Cells were collected at the indicated time points.
C Cell death phenotypes of leaves inoculated with Pst DC3000 (AvrRpm1). Data information: AvrRpm1, Pst DC3000 (AvrRpm1) dpi, days post-inoculation.
Western blot for CSF-1R in untreated (Unt) BV2 microglia, or BV2 microglia transfected with non-targeting or Csf-1r targeting siRNA. Corresponding densitometry (below) representative of technical replicate of n = 3 blots (One-way ANOVA with Dunnett's multiple comparison, *** p = 0.0003, error bars indicate SEM).
A Representative images of ovules from wild-type (Col-0), herk1 anj, lre-5 and fer-4 20 hours after emasculation (HAE) displaying the mature female gametophyte structure. Images presented here are maximum intensity projections from confocal microscopy images across several z-planes of ovules stained as per [70]. Scale bars = 50 µm.
Live cell imaging of LysoTracker positive spots in WT, LRRK2 KO macrophages treated with 1 mM LLOMe, followed by lysosomal recovery after LLOMe wash-out. One representative experiment out of three shown. Differences between slopes in the LLOMe treatment window were estimated using linear regression.
(C) IHC staining of three representative TMAs from patients enrolled in the QUASAR 2 clinical trial and the corresponding quantification of the signal by pathologists.
B Quantification of Nox4 protein levels (B) in cultured rat cardiomyocytes after increasing degrees of serum starvation as compared to serum-replete cells (15% serum). n=4 cell preparations/group. A representative immunoblot for Nox4 and tubulin as a loading control is shown in panel B.