EMBO/sd-character-level-ner huggingface dataset:
Representative karyotypes of late passage, large T antigen immortalized MEFs after exposure to Cre recombinase and serially sorted for control (hCD2 plus) and ICL (hCD2 Minus) cells for chromosome lines (A) Ch12 Boxed panels denote targeted chromosome loss; arrows and asterisks denote shared and unshared, non-targeted chromosomal copy number variations respectively.
TseL secretion depends on VgrG-1. Western blot analysis of pellet (P) and supernatant (S) samples of the indicated strains. Samples were immunoblotted with antisera against TseL and Hcp and purified antibodies against DnaK. The unspecific band detected by rabbit serum is marked with an asterisk. One representative of three experiments is shown.
J Quantification of the percentage of weight loss at advanced stages of local relapse (week 5 post-surgery). Values were obtained relative to the mean weight for each group at day 19, which corresponds to the highest weight value before any decrease could be detected. Values are shown as mean ± s.e.m. (n=4 surgery + vehicle and n=6 surgery + DEBIO-0932 treated mice, 1 experiment). P value was calculated using two-tailed t-test.
Comparison of E) KRT20, F) MUC2, G) CHGA, H) LGR5 mRNA expression in organoids grown in FM or in basic medium and either untreated or treated with IFN-γ (n=3). Data are presented as mean +/- SD ,*: p≤0.05, **: p≤0.001, ***: p≤0.0001, as determined by one-way ANOVA, followed by Tukey's multiple comparisons test
D Mean intracellular calcium concentration in speed‐fluctuating (ΔV/V0 > 0.3; ΔV/V0 relative speed variation divided by the global median velocity) and non‐speed‐fluctuating (ΔV/V0 0.3) immature DCs (n = 187 cells from more than three independent experiments). P‐values were calculated using a Mann-Whitney test.
(A) Scoring loss of mitochondrial membrane potential (ΔΨm). 293 cells expressing luciferase (black), DRP-1 Δ73 (pink), DAPk ΔCaM (purple), and Bax (green) were assayed for loss of mitochondrial membrane potential 24 h after transfection using flow cytometric analysis of TMRM fluorescence. The fraction of TMRM-negative cells calculated from three experiments is shown in the graph below. The small increase in TMRM fluorescence in the kinase-transfected cells is not statistically significant.
E, Mean (+/- s.d.) expression fold-changes of the corresponding proteins (if detected in the proteomics data) in the two mutant cell lines (W1A, n=2; W6A, n=1) compared to Control (n=2). Multiple-testing-corrected P-values for unpaired two-tailed t-tests (proteomics) comparing fold-changes with respect to control are depicted above each bar (* P < 0.05, ** P < 0.01, *** P < 0.001).
(A) Confocal microscopy using Zeiss Airyscan microscope and Zeiss-blue3.1 software was used to visualize PIN2 in Arabidopsis roots. "e" denotes epidermis and "c" cortex. Scale bar = 20 µm. (B-D) Tuckey box plots show PIN2-GFP fluorescence intensity quantification (number of roots analyzed per experimental conditions = 8-10; arbitrary units, a.u.) at the total cell membrane in roots (B), and from epidermal (C) and cortex (D) plasma membrane in the different genotypes. The box plot shows the data within the interquartile range (25th and 75th percentiles) and a solid black line represents the median. Whiskers show maximum and minimum values no further than 1.5x IQR (interquartile range). Outlier data are plotted individually. Letters denote statistically significant difference between means as determined by one-way ANOVA analysis followed by Tukey HSD post hoc test (p < 0.05).
(G) The response of mitochondrial matrix-localized (left panel) and cytosolic (right panel) roGFP2-Tsa2ΔCR probes expressed in BY4742 wild-type and Δtsa1Δtsa2 cells, to the addition of exogenous H2O2 at the indicated concentrations. Cells were grown to exponential phase in SGal (-Leu) medium. The lighter colored curves are controls, showing the probe response upon the addition of water.
(D) EphrinB2 is detected in cell lysates of 4T1, LLC1 and HUVEC, but not in B16F10 cells; representative of 3 immunoblotting.
E - Cells were infected with C. trachomatis L2 (MOI=1) for 24 or 46 h. Where indicated, 40 μM CP4d was added 2 hpi. tgm2 transcripts were measured by real-time RT-PCR and normalized to actin transcripts following the ∆∆Ct method. The data are presented as relative mRNA levels compared to uninfected cells and shown as the mean ± SD. Each experiment was performed in duplicate and repeated at least four times. P-values of Student's ratio-paired t-test <0.05 are shown.
E, F Single-labeling immunostaining showed NB-3 expression in the sham-operated (E) and injured (F) spinal cords from adult NB-3+/+mice.
Schematic diagram of the method in which PS exposure was detected in vivo using secreted Annexin V (secA5) fused with mCherry (red). Representative confocal z-stack images of secA5-mCherry (red) expression in the brains of wild-type mice using AAV9-GFAP-secA5-mCherry injection. The white circles indicate PS exposure detected by secA5. Scale bar, 10 μm.
(d) Stably transfected CN1.4 cortical cells were maintained in the presence of Dox (1 μg ml−1) to induce the expression of tau for 24 h, and subsequently treated with SFN (10 μM) for 12 h. The culture medium was exchanged for fresh media containing Dox (1 μg ml−1) but no SFN after washing with PBS. The cells were then incubated for an additional 18 h in the absence or presence of CQ (50 μM). The levels of tau phosphorylated at Ser262/Ser356 and Ser396/Ser404 were analysed by immunoblotting using the 12E8 and PHF1 antibodies, respectively. Tau, beclin-1 and LC3 were detected with the appropriate polyclonal antibodies. The relative molecular masses (kDa) are indicated to the left of each blot. (e) Bar graphs represent the relative optical density of phosphorylated tau, tau or LC3-II normalized with that of actin. n=4. Data shown are mean±s.e. and were analysed using Student's t-test. (*P0.05; **P0.01).
A. Timeline for injection of mice with Stx2a and OSMI-1. Mice were pre-treated with OSMI-1 or vehicle alone beginning 1 day before injection of Stx2a. Body weight changes and mortality were monitored every day for 1 week to determine the survival rate. Blood and tissue samples were collected at day 3 after Stx2a challenge.
RT-qPCR for pluripotency and mitochondrial ribosome subunit genes as in (E) (mean values ± SD). n = 3 biological replicates.
D) KLF5 expression in primary human samples of ADM and PanIN. One representative patient out of nine is shown.
(E) Experimental scheme of pulse-labelling of DNA fibers in shWRNIP1 cells. Cells were transfected with control siRNA (shWRNIP1siCtrl) or FBH1 siRNA (shWRNIP1siFBH1), and 48 h thereafter labelled with IdU, then treated or not with 4 mM HU.(F) Representative IdU tract length distributions in shWRNIP1siCtrl or shWRNIP1siFBH1 cells with or without HU treatment. Representative DNA fiber images are reported. Scale bars, 10 µm. Western blot shows FBH1 depletion in the cells. The membrane was probed with an anti-FBH1. GAPDH was used as a loading control. Median tract lengths are given in parentheses. See Tables S1 and S2 for details on the data sets and statistical test.
(e) Box-whisker plots show percentages of inhibition on immune cells chemotaxis by treatment with anti-CXCL12 IgG (CXCL12 neutralizing antibody). Box-whisker plots indicate median (middle line), 25th, 75th percentile (box) and the lowest/ highest data points (whiskers). ns, non-significant (t-test). Sample sizes are n = 5 NAFLD and n = 3 healthy, with 3-4 technical replicates per donor.
D. Differentially expressed genes in long-lived mitochondrial mutants show significant overlap with genetic targets of the p38-mediated innate immune signaling pathway. Significantly modulated genes in long-lived mitochondrial mutants nuo-6 and isp-1 (six biological replicates per strain) were compared to genes that are modulated in response to exposure to the bacterial pathogen P. aeruginosa strain PA14 in a PMK-1- and ATF-7-dependent manner There is a highly significant degree of overlap between genes upregulated by activation of the p38-mediated innate immune pathway and genes upregulated in nuo-6 and isp-1 mutants. Similarly, there is a highly significantly degree of overlap between genes downregulated by activation of the p38-mediated innate immune pathway and genes downregulated in nuo-6 and isp-1 mutants. The p-values indicate the significance of the difference between the observed number of overlapping genes between the two gene sets and the expected number of overlapping genes if the genes were picked at random.
Images and comparisons of number of Prox1+ LECs within initial 100 μm portion (upper) and VEGFR3 expression (lower, presented as relative fluorescent intensity (FI)) in CD31+/LYVE-1+ lacteals of jejunum from WT and DTR mice. Each dot indicates mean value of 5-10 villi in a mouse (n = 6 mice/group). AU, arbitrary unit. Scale bars, 100 μm.
Structure of the relevant (Siglec-like sialic acid-binding) domain of the highest-scoring template 5KIQ (SrpA binding region), and predicted three-dimensional model of the IgSF domain from the β protein, constructed from the Hhpred alignment using MODELLER.(Webb & Sali, 2016)
(E, F) Kaplan-Meier survival curves of indicated MLL-ENL transduced cells transplanted into primary recipient (solid lines) and secondary recipient mice (dotted lines).N=15 mice were used for Ctnnb1fl/fl (blue solid line) and n=10 mice were used for Ctnnb1del/del (green solid line) in (F). For all secondary transplants (dotted lines) n=5 mice were used per group.
GFP-ORAI1 expressing HEK293 cells were transfected with mCherry-STIM1 (WT or L374P) and left unstimulated or stimulated with 1 μM TG in Ca2+-free Ringer's solution. (D,E) Representative TIRF microscopy images from one of two repeat experiments. Scale bars, 10 μm.
(D) This increase in total NeoR protein in 3‐MA‐treated cells is associated with an increase in cytoplasmic, and a decrease in endosomal/lysosomal NeoR protein levels.
F. Clonogenic survival of 5-azadC-treated HeLa cells transfected with indicated siRNAs (mean±SEM; n=2 independent experiments).
A Bisulfite DNA methylation sequencing of the Athila6ATE transcriptional start site (TSS) in genotypes with silenced TEs (left of the dashed line) or transcriptionally active TEs (right of the dashed line). Methylation in the CG (red), CHG (blue) and CHH (green) sequence contexts are shown (H = C, T, or A). Error bars represent Wilson score interval 95% confidence limits. For multiple statistical tests, one‐way ANOVA was performed using Tukey's multiple comparison test. ns, not significant.
D The immunoprecipitation analysis. HA-CXCR4DD-DsRed co-precipitated with ENTREP when co-transfected with either ITCH C830A or delWW12. Data shown are representative of at least two independent experiments.
786-0 or 769-P cells were supplemented with methylated αKG (500 μM), 2HG (500 μM) or αKG (500 μM) +2HG (500 μM) for 36 hours under aa starvation conditions. the mRNA levels of the indicated RP genes were tested using qPCR (I).
D Averages for CD spectroscopic thermal denaturation of recombinant PDIA1WT and mutants.
Macrophages produce little to no inflammatory cytokines when incubated with either (a) whole iRBC for 24 h. One-way ANOVA with Tukey test for multiple comparisons was performed to determine statistical significance Each symbol represents the value obtained for cells from an independent donor in an independent experiment. (a) n=4; Asterisks indicate significance (*p<0.05, **p<0.01 and ***p<0.001) when values were compared with RBC
A549 cells were transfected for 48h with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool). Immunoblots (up) and quantification (down) of YAP levels in confluent (E) A549 UBTD1 depleted cells treated or not with cycloheximide (CHX) for 2h. Immunoblot of UBTD1 shows the level of siRNA-mediated depletion. Actin was used as a loading control.
(B) The indicated myc-SNX18 PX-BAR constructs were transfected into HeLa cells, and their tubulation efficiency was measured by scoring the percentage of cells displaying more than three elongated structures longer than 5 µm (n = 300). The graph shows the mean of two independent experiments ± range (error bars). Bars, 10 µm.
(a) Diagram of pup ultrasonic vocalization at the frequency level after Fourier transforms (b-d) (b) Total call durations, (c) Call durations and (d) Call numbers of WT, HET, and KO mouse pups. nWT=13 mice, nHET=16 mice, and nKO=18 mice. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**), p<0.001(***).
(B-E) In the eye, representative results were gained from 2 WT and 2 USH1C pigs at 12 months of age. For the limited number of animals, no statistical evaluation was performed. (B) A retinal dysfunction is evident in the multifocal electroretinogram (mfERG) of the visual streak in USH1C pigs to WT. Yellow/red colors indicate higher response amplitudes (1-1.5 µV), while blue/green colors indicate lower response amplitudes (0-1 µV) reflecting cone photoreceptor activity in the tested area. (C) Upper Panel: The average sum potential from the tested area highlights a delayed and lower peak amplitude in the visual streak in USH1C vs WT pigs. Traces indicate the average of all 61 hexagonal segments of single mfERG recordings. Lower Panel: Localization of the mfERG recordings. (D) Ganzfeld (gf) ERG recordings in USH1C pigs vs WT demonstrate a significant reduction in the scotopic standard flash responses and responses after photopic standard flash stimuli. Left panel (top to bottom): Dark adapted single flash recordings following a low light (0.03cd*s/m2, rod only) or a brighter (3cd*s/m2, rod and cone) stimulus. The oscillatory potentials shown at the bottom are extracted from the above standard flash recording. Right panel (top to bottom): Response after a light adapted single flash at 3cd*s/m2 intensity and responses following a light adapted flicker (same intensity) at 30Hz. (E) The retinal architecture as demonstrated by optical coherence tomography remained fairly intact, indicating a large therapeutic window.
TIGAR expression modulates autophagy in response to nutrient starvation or metabolic stress.(B) (Left panel) Confocal microscopy images of the fluorescence in U2OS cells stably expressing GFP-LC3 and transfected with scrambled or TIGAR siRNAs. After 48 h transfection, cells were then left untreated, exposed to nutrient starvation for 5 h or to metabolic stress for 18 h. (Right panel) Quantitation of the percentage of GFP-LC3-positive cells displaying GFP puncta from three independent experiments. The mean values with standard deviation are presented.
(G, H) Intradermal tumorigenicity assays with SCC13 cells overexpressing HSD17B7 (HSD17B7-oe) versus control (Ctrl). Mice were sacrificed 15 days after injection. Shown are representative images and quantification of tumor cells density, assessed by immunohistochemical staining with anti-pan keratin antibodies (G) as well as % of Ki67 positive cells in pan-keratin positive areas (H). For (G), n(tumors per condition) = 4; for (H), n(3-5 fields per tumor, 4 tumors per condition) 15, 19. *p<0.05; Horizontal line: median. One-tailed paired t-test. Scale bar in (G, H): 100μm.
(D) Immunoblot analysis of endogenous SALL4 or PLZF protein levels in HuH7 cells treated with DMSO, thalidomide or 5-hydroxythalidomide for 24 h. (E) Immunoblot analysis of endogenous PLZF or IKZF1 protein levels in THP-1 cells treated with DMSO, thalidomide or 5-hydroxythalidomide for 24 h. Data information: Data in bar graphs in (D) and (E) were calculated as relative PLZF band intensity with PLZF band intensity of DMSO as 100. Error bars donated ± standard deviation (n = 3) and P-values were calculated by one-way ANOVA with Tukey's post-hoc test (NS = Not Significant, *P < 0.05, **P < 0.01 and ***P < 0.001).
(b) Knockdown of eIF4A, but not other translation initiation factors, blunts TORC1 inactivation upon amino acid withdrawal. Kc167 cells treated with indicated dsRNAs for 4 days and then incubated with complete Schneider's medium or Schneider's medium lacking the indicated amino acids for 30 minutes prior to lysis.
B. Huh-7 cells were treated with or without BFA for 6 hours before staining for Rab18 (red) and LD (green). Bar = 10 μm.
(C,D) Local structures of top and front views of RAG TCC (M848 configuration 1) near integration site, depicted as in Fig 3C, D.
O Expression of fst was detected by RT-qPCR in KM from WT sibling and Runx1-FLT3/ITD transgenic zebrafish at 18 months old. The RT-qPCR experiments were performed in triplicates and data were presented as mean ± SEM. **P<0.01.
D Sequence alignment of partial MAVS (1-30 amino acids) from human, macaque, cow, pig, dog, mouse and rat. The red box indicates a conserved lysine (K7).
C. Bright-field microscopy and fluorescence microscopy pictures of WT, TP53KO and onco-RNF43/TP53KO human colon organoid lines grown in two different media and transduced with the TOP-GFP reporter. Images were taken 6 days after splitting. Scale bars represent 1000 μm.
(D) Survival of WT, PI3Kγ null (left) and liver-specific PI3Kγ knockout mice (PI3Kγ floxtg/tg x AlbCre(tg)/tg, middle) or systemic application of the PI3Kγ inhibitor, AS605240 (right) in a model of polymicrobial sepsis induced by peritoneal contamination with a human stool suspension. Animal numbers: B6: 86 (%male: 52, %female: 48), B6-Pi3kcgko/ko: 59 (%male: 51, %female 49), B6-Pi3kcgflox/flox x AlbCre(tg)/tg: 25 (%male: 68, %female 32), FVB/N Vehicle: 25 (%male: 44, %female 56), FVB/N AS: 43 (%male: 44, %female 56)
(B) Immunoblot showing the degradation of MAVS in HEK293T cells infected with VSV (MOI = 1.0) for the indicated times in the presence or absence of NH4Cl (3 mM). α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.
(b) siHif1α effectively knockdowns expressed Hif1α cDNA WT, but not a Hif1α cDNA silent mutant form refractory to siHif1α (Hif1α cDNA REFR.) in mice MEF.
Armi-Flag (Armi-F) WT and the ∆N34 mutant were expressed in OSCs where endogenous Armi and Zuc had been depleted by RNAi (Zuc KD + Armi KD). Immunoprecipitation and subsequent western blotting show that Armi-F WT but not Armi ∆N34 mutant bound with Gasz in the cells. Both Armi WT and ∆N34 mutant interacted with Piwi to similar extents. Luciferase-Flag (Luc-F) was used as a negative control.
Mitochondrial membrane potential of control and p53EE expressing H1299 cells in the absence and presence of increasing concentrations of BID BH3 peptide. Treatment with the mitochondrial depolarizer CCCP is shown as a positive control; n=3.
C: U2OS cells were transfected with EGFP-tagged wild type (wt) or mutant (RK) p14ARF, either alone or in combination with Myc-tagged wild type PRMT1-containing plasmids. Cells with predominant nucleo-/cytoplasmic localization of p14ARF-EGFP (for both wt and RK) were quantified in the absence or presence of PRMT1 overexpression, i.e. in p14ARF-positive as well as p14ARF/Myc-PRMT1-double positive cells, by immunofluorescence staining and cell counting. Relocalization of p14ARF wt and RK into the nucleo/cytoplasm upon overexpression of PRMT1 was defined in percentage of cells for five independent experiments (mean ± SD).
(A) Top bar: gradient of population admixture of the indicated HKC strains of Black versus White individuals, on the basis of the SNP genotype analysis shown in Figure 1B, with the simplest assumption of two ancestries (K = 2).Gradient ranges from black to white colors for Black and White individuals with no population admixture, respectively. Individuals with increasing proportions of White population admixture are represented with degrading shades of grey. Left: heat map of expression levels of the indicated genes from the OXPHOS gene signature of Fig 3C, in Black versus White HKC strains ordered according to genome admixture calculations and in three strains of White HKCs with HSD17B7 overexpression. Modified Z scores of the individual genes, as median-centered log2 Intensity values divided by standard deviation, are shown by color gradient variations. Right: heat map of expression levels of the same genes in three White HKC strains infected with a HSD17B7 overexpressing lentivirus versus empty vector control as in Fig 5A (strains: 260, 275, 249). Expression levels are derived from global transcriptomic analysis (Clariom D hybridization; GEO accession number GSE172288) and expressed as logFold Change values of treated vs control samples.
Representative plot (left) and quantification (right) of the reconstitution of the B cell and T cell compartments after adoptive transfer. The graph shows the mean percentage of CD19 and CD4 positive cells from n ≥ 5 reconstituted mice ± SEM.
D Quantification of FRET efficiency (percentage) in junctions of HUVEC expressing VE-cad FL or VE-cad FL-TS. Cells were either exposed to flow and PMNs or to flow alone, fixed using 4 % PFA and washed with PBS. FLIM measurements were performed at sites of transmigration (PMNs) or at junctions without PMNs (Flow).
A. Immunoblots show the levels of the indicated proteins in whole cell extracts (WCE), soluble and chromatin-enriched fractions. Tubulin and CTCF are shown as controls for soluble and chromatin-bound proteins, respectively. The position of the ubiquitylated form of FANCD2 (Ub-FANCD2) is indicated. Ponceau-S staining is shown as a loading control.
(B) Effect of FUEE-SBR on Smaug activity. The relative levels of reporter expression obtained in the same experiment as in (A-C) are represented as a function of the % of phosphorylated Smaug. Color of data points correspond to ng of transfected FUEE-SBR in A-C.
C ChIP-qPCR analysis showing that the association of BIC1 with the promoter regions of BZR1/PIF4 target genes is dependent on PIFs. The 6-d-old 35S:BIC1-Flag and 35S:BIC1-Flag/pifQ seedlings were used for ChIP assays.
(C) HEK-293E Cells were deprived of serum for 2 hr followed by insulin (100nM) stimulation for the indicated time. Lysates were analysed by Western blot for phosphorylation of RagC and proteins known to belong to the Akt and mTOR pathways. Graph shows mean of quantitative analyses of the Western blots after normalization for total protein or the loading controls.
D, Clockwise rotation of tethered fliM(E214W)∆N ΔcheZ cells (strain EW718) at various concentrations of FliMN-CheY. The concentrations shown are estimates based on the calibration curve , for which a similar CheY expression system was used. Each data point is the average of all measurements at similar FliMN-CheY concentrations, weighted by the sample number of each experiment.
Impact of BO-110 on tumor-bearing mice implanted with syngeneic B16R2L (5 x 105 cells). When tumors have an average size on 100 mm3, mice were randomized into two groups and treated with BO-110 (BO) or vehicle (V), every second day for 2 weeks. The arrow indicates the start of the treatment. Tumor size was measured with a caliper at the indicated time points. , N= 4 mice per condition. Statistical significance was determined by Two-Way-ANOVA.
E and F. RT-QPCR analysis of individual genes related to MCC formation in the oviduct (E) and trachea (F) of Gemc1-/- mice compared to wild type littermates, using 18S rRNA as a reference (n=2). Genes examined generally fall into 3 classes: centriole duplication (Cep152, Plk4, Cetn2), Deuterosome mediated centriole expansion (Deup1, Ccdc78, Ccno) and transcription of genes required for MCC differentiation (FoxJ1, Myb, Mcidas).
, red boold cells (RBCs) (n = 5 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), **P = 0.0049, two-tailed unpaired Student's t-test) in wild-type (WT) and Otud1─/─ mice with or without low-iron diets for indicated times.