EMBO/sd-character-level-ner huggingface dataset:
(A) Transcriptional and protein abundance changes between inducing (+) and depleting (-) conditions (48h and 72h of depletion for Lon and FtsH, respectively) in ΔIndLon and ΔIndFtsH mutant strains. Differentially expressed (DE) Lon/FtsH candidate substrates were identified as proteins with a significant increase in abundance upon protease depletion that could not be attributed to an increase in mRNA levels, i.e. log2(protein_FC/mRNA_FC) ≥ 1 (upper dashed line). Differentially detected (DD) candidates were identified as proteins not detected in the induced condition and detected in the depleted condition, and whose mRNA level did not increase more than 2-fold (vertical dashed line).
D As compared with control siRNA (siCont) where ISCU1/2 expression was decreased after exposure to Hyp + SU5416 (white bars), lung delivery of siRNA specific for ISCU1/2 (siISCU) via Staramine-mPEG nanocomplexes (Polach et al, 2012) down-regulated ISCU1/2 in < 100-μm pulmonary vessels in Norm + SU5416 and Hyp + SU5416 (N = 5/group, ***P = 0.0006, **P = 0.0019 for Hyp + SU5416, **P = 0.0029 for siCont).
NE activates mTORC2 in vitro via cAMP, PI3K and Epac1. (A) Immunoblot analysis of BAT cells stimulated with norepinephrine (NE) for the indicated proteins.
(C) EBNA2 co-precipitates were submitted to kinase reactions in the absence (control) or the presence of the PLK1 inhibitor Volasertib (40 nM).
miR160 northern analysis in Meselect-separated leaf vasculature and epidermis in WT versus hst-1 plants, in three biological replicates (rep.). U6: as in (A). Relative U6-normalized band-intensity quantifications are indicated.
Flow cytometry analysis of mimic-nucleofected B lymphocytes. Dot-plots show B220+ IgG1+ B cells 48h after mimic nucleofection from at least 4 independent experiments and bar charts show mean values ± SEM of 4 independent experiments.
(C) Relative mRNA levels of FX in liver B220+CD11c+NK1.1+cells stimulated with various factors. Shown are averages (N = 4) with SEM and one-way ANOVA
b The c-Fos immunoreactivity was specifically increased in the hypothalamus (VMH), the inferior colliculus (IC), and periaqueductal gray (PAG) but not in the hippocampus (HPC) of a resuscitated Grin2aS/S mouse 90 min after AGS when compared to tone-exposed Grin2a+/+ littermates.
B Differential exon usage of the CD44 gene. C. Differential exon usage of the RPL17 gene.
PLS regression analysis of codon usage of HTE (n=100) versus LTE (n=100) proteins a G) TP 4 ( Visualized by X, Y correlation loadings. Outer and inner ellipses indicate 100% and 50% explained variance respectively. Percentages of observed variances explained by the PC-1 and PC-2 are indicated in parentheses along their respective axes
A. Schematic diagram representing the domains and constructs of human (h) and zebrafish (z) Nup358 used in this study. TPR, tetratricopeptide repeat; LRR, leucine rich region; R1-R4, RanGTP binding domain; ZnF, zinc finger domains; IR, internal repeats; CHD, cyclophilin-homology domain. Dotted line indicates the deleted region in the indicated construct. FG and FxFG sequence positions are represented as short and long black lines, respectively. Amino acid positions are indicated in numbers. FL, full-length; N, amino-terminal region; M, middle region; C, carboxy-terminal region.
(D) Schematic representation of a fluorescence-2-hybrid assay using mCherry-tagged, forced cytosolic chaperone
C Mice were infected with Ad‐FXR‐WT or the K217Q mutant and treated with GW4064, and SUMO2‐FXR levels were detected by IP/IB (n = 3 mice).
Sanger-sequencing chromatograms showing the target region of sgPik3caE542K, sgPik3caE545K and sgPik3caE453K in 3 independent tumors from WB1P-BE3 females injected with the corresponding Lenti-sgPik3ca-Myc vectors. Arrowheads highlight cytosines of the protospacer that show base editing. EditR was used to calculate the average frequency (%) of C-to-T conversion at the indicated target cytosines of the protospacers in tumors from WB1P-BE3 females injected with Lenti-sgNT-Myc or Lenti-sgPik3caE542K-Myc, Lenti-sgPik3caE545K-Myc and Lenti-sgPik3caE453K-Myc.
D) Electrophysiological analysis scoring muscle strength recovery performed in vivo on ablated TA (control) and wet-spun implanted contralateral TA (graft) (n=3), statistical significance was analyzed by Anova test (P < 0.05 was considered significant: *55Hz=0,016830182; *75Hz=0,012686264; *100Hz=0,009143348; *150Hz=0,009327048).
A-F CoQ9 levels in tissue homogenates from brain (A), cerebellum (B), heart (C), kidney (D), extensor (E) and triceps surae (F) of male and female Coq9+/+ and Coq9Q95Xmice at 6 and 12 months of age. Data are expressed as mean ± SD. Statistical analysis was performed on 6-month-old Coq9+/+mice versus 6-month-old Coq9Q95Xmice and 12-month-old Coq9+/+mice versus 12-month-old Coq9Q95Xmice. **P < 0.01; ***P < 0.001. Student's t-test (n = 8 for each group).
APP/PS1 mice were systemically treated with SH-4-54 for 6 weeks and compared to age-matched APP/PS1 mice treated with vehicle. In the Morris Water Maze test, treatment with SH-4-54 led to significantly faster latencies to reach the hidden platform on the last training day (Two-way repeated-measures ANOVA followed by Bonferroni post-hoc test).
(C) PBX1 is first detected in the ventro-lateral part of the LMX1a+ domain at E10, preceding the birth of the first (TH+) mDA neurons at E10.5. At E12.5, PBX1 is present in all mDA neurons, but not all PBX1+ cells are TH+. White boxes indicate the area showed in higher magnification (right).
B, C LGR5hi and LGR5lo cells were freshly isolated from 3‐month‐old LGR5‐GFPki mice 6 h after 12 Gy γ‐irradiation (IR) or from non‐irradiated (NIR) mice (n = 3 mice per group). (B) qPCR analysis of relative mRNA expression of apoptosis‐related genes compared to GAPDH. Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test.
Representative images of γH2AX antibody staining on small intestine paraffin sections from WT, Gadd45a-/-, G3Terc-/-, and G3-dKO mice (7 months old). Arrows indicate γH2AX positive nuclei (C). Quantification of the percentage of γH2AX positive cells per small intestine crypt (n=4-6 mice per group) (D).
(C) A549 cells, stably expressing GFP-LC3, were infected with WT or P. aeruginosa mutants and evaluated by fluorescence microscopy, scale bars: 10 µm. GFP-LC3 puncta representing the autophagosomes was quantified and presented in the graph. Each bar represents mean value from three independent experiments and error bars represent standard deviation. Statistical significance between assays was determined using One-way ANOVA followed by Dunn's Multiple Comparison Test. *p ≤ 0.05; **p ≤ 0.01. P. aeruginosa mutant strains legend: ΔSTY (mutant deficient for the three cytotoxins), WT (contains all cytotoxin), ΔS (deficient for ExoS but still express ExoT and ExoY), ΔTY (express ExoS but deficient for ExoT and ExoY).
(C) Representative plot of cell cycle distribution at 48 hours post induction in scr, circHIPK3 and DLL4 KD cells, with G1 phase (blue), S phase (pink) and G2/M phase (green) highlighted.
C. Asynchronous Rev3l+/+ and Rev3l-/- MEFs were subjected to PLA as by using γH2AX and HP1β antibodies and processed as in (B). p-values were calculated by Mann-Whitney test ( *: p<0.05). Red lines indicate the mean values. Error bars: SEM. Controls with a single antibody are also shown. Three independent experiments were performed.
A. Example of littermate males of the indicated genotypes 26 days post partum. Additional examples are provided in Appendix Fig S2.
Impaired wound closure in αSMA-TK mice. (E) αSMA-TK mice and WT littermates were placed on GCV regimen three days prior to wounding (day -3). On day 21, GCV treatment was stopped and the mice monitored until day 39. WT, N=7; TK, N=9 biological replicates. Data are from two independent experiments. Two-way ANOVA and Sidak's multiple comparison test were performed comparing WT to TK mice.
D, Chromatin Immunoprecipitation (ChIP) assay in LS174T cells. Top panel, PCR products cells exposed to vehicle or FKK6 and run on a 2% agarose gel. DNA 100 base pair marker; Vehicle,10% DMSO; FKK6 (10 μM); 1/10 Input - 0.2 million cells before IP; IgG - IP with polyclonal rabbit IgG; PXR - IP with PXR antibody. Bottom panel, quantitative PCR from the ChIP assay for compounds tested with the gene specific PCR amplicon normalized to GAPDH (fold expression). Dash line, 2-fold expression. The data is one representative experiment of two independent experiments (each n = 3 biological replicates, n = 4 technical replicates). Mean fold expression is expressed above each histogram (mean + SD).
Inhibition of microglial phagocytosis results in decreased microglial IL-1β expression. Eyes of rd10 animals were treated with intravitreal injections of cRGD at P20, and analyzed at P23 by immunohistochemistry for Iba1 (green) and IL-1β (red), and compared to uninjected eyes and with eyes injected with inactive analog, cRAD (n = 3 eyes in each category). Immunopositivity was high in infiltrating microglia (indicated by arrows) for untreated and cRAD-injected control eyes and significantly reduced in microglia in cRGD-injected eyes (upper panel), as demonstrated by the quantification of IL-1β expression (area of immunopositivity as a fraction of the ONL) (lower left panel). ONL thickness correlated negatively with the extent of IL-1β immunopositivity (lower right panel). Scale bar, 25 μm.
(H) Transgenic expression of EGFP-Vector (vector), EGFP-wild-type Spns1 (spns1 WT), or EGFP-mutant Spns1 (spns1 E153K) in [Tg(CMV:mCherry-LC3);spns1hi891/hi891] animals at 84 hpf. Scale bar, 10 µm. Quantification of data presented in H is shown for ratio of yolk opaqueness phenotype (n = 48), mCherry intensity (red) (n = 6), and merge intensity of EGFP and mCherry (yellow) (n = 6) in the right graphs; the number (n) of animals is for each genotype. Three independent areas (periderm or basal epidermal cells above the eye) were selected from individual animals. Error bars represent the mean ± standard deviation (S.D.), *p<0.005; ns, not significant.
A: Superposition of the SARS-CoV-2 N-NTD structure with other human-infecting CoV N-NTD structures. The ribbon representation of each structure is coloured separately (SARS-CoV, PDB: 2OFZ, cyan; HCoV-OC43, PDB: 4LI4, pink; MERS-CoV, PDB: 4UD1, orange; HCoV-NL63, PDB: 5N4K, blue) (Lin et al, 2014, Papageorgiou et al, 2016, Saikatendu et al, 2007, Szelazek et al, 2017). The loops that show significant differences are highlighted by dotted circles. The AMP ligand in the HCoV-OC43 N-NTD-AMP complex is shown as a stick structure. B: Structural superimposition of SARS-CoV-2, SARS-CoV and MERS-CoV N-NTDs with that of HCoV-OC43 bound to AMP to show the detailed interactions involved in AMP binding. C: Structural superimposition of HCoV-NL63 N-NTD with HCoV-OC43 N-NTD bound to AMP to show the detailed interactions involved in AMP binding.
A Schematic of genome-wide experiments performed on naïve and activated CD4+ T cells.
(e) COS-7 cells transfected with empty vector (pcDNA3.1) or wild-type PLC-ε for 4 h and treated with or without 50 μM calpeptin for 48 h post-transfection were assessed for the proportion of EGFP-positive cells with EGFP-HDQ74 aggregates. Error bars show 95% confidence interval. ***P 0.001; **P 0.01; *P 0.05; NS, nonsignificant.
Representative examples of maturing erythroblast series in wild type and Sl/Sl E12.5 FL, as identified by imaging flow cytometry. Scale bars: 10μm.
(D) Cholesterol rescues the level of accessible cholesterol on the plasma membrane of 25HC-treated cells. Calu-3 cells were pretreated with ethanol or 5 µM 25HC for 16h. Cells were washed and incubated with PBS or 20 µM cholesterol for 1 h. After further incubation with ALOD4, cells were washed with PBS twice and lysed. The amount of bound ALOD4 was examined by western blotting.
F, G. Gene set enrichment analyses for assessing the enrichment of Tfcp2l1-activated genes (F) and -repressed genes (G) in 2i-ESCs and FBS-ESCs. The number of permutations is 1,000 times of phenotypes.
Whole mount (f) images of Atoh1 lineage labeled crypts. Data information: Nuclei are counterstained with Dapi (blue); white dashed lines indicate basement membrane. Scale bars =50μm
(A) Colony morphology and AP activity of Control and Yap1 KD ES cells upon differentiation. Morphology and AP staining pictures were taken 2 days after differentiation.
(d) Electron microscopy (left) of resting TH1 cells and TH1 cells activated for 24 h as in a,b (top row); below, enlargement of areas outlined above, showing individual lysosomes (arrows). Original magnification (top row), ×12,000; scale bars (bottom row), 1 μm. Right, morphometric analysis of cells as at left. *P = 0.037 and **P = 0.034 (t-test).
(a) ITT performed 2 h after IL-1β injection. Eight-week old male C57BL/6 mice were intraperitoneally injected with saline or mouse recombinant IL-1β (1 μg/kg).
J Cartoon depicting protocol of B-T cell co-culture used to assess functionality of corrected T cells. CD4+ T cells were stimulated with beads (B) or with PMA/Ionomycin (PI) or kept resting (R) prior to co-culture with allogeneic naive B cells (1:1 ratio). B cells cultured alone or in presence of soluble CD40L (sCD40L) were used as negative and positive controls, respectively.
(G-I) Cryo-EM structural characterization of the CGA-CGA stalled 80S RNC. (G) Schematic representation of the stalling situation (top) and molecular model of the CGA-CGA stalled RNC (bottom). (H) General overview of the A, P and E sites with P/P and E/E tRNAs and mRNA. (I) Detailed view of the mRNA in the A site as in (F). Downstream mRNA is indicated by the dotted line. Note the rotation of the C+4 base compared to the CGA-CCG mRNA.
d, TNF-α, IL-1β and IL-6 levels in culture media of WT and T316A macrophages infected with 20 m.o.i. Y. enterocolitica. Data represent 2 independent experiments, n = 4 mice.
A-F The indicated cells were transfected with siCon, siH19, empty vector, or pH19. RNA, cell viability (as indicated by viable cell numbers), and caspase activity (as a readout for apoptosis) were analyzed 48 h post-transfection. Combined results from two patient cells in each group are presented.
cse4-K49R suppressed the lethality of cse4-R37A with ctf19∆. Tetrad dissection of a ctf19∆ strain crossed with cse4-R37A (left) and cse4-R37A K49R (right). Representation
B) Viral titers (viral genome copy VG per cell) determined by qPCR in cortical, hippocampal and rest of brain areas of Fmr1-KO mice treated with saline solution (Vehicle), AAVPHP.eB-∆N-DGKk (PHP.eB), AAVRh10-∆N-DGKk (Rh10) 8 weeks after injections. Data are mean ± SEM. Each dot represents an individual mouse.
Generation and characterization of FLT3/ITD-transgenic zebrafish. GFP expression was detected by florescent microscopy (F-H) and in blood circulation and thymus by WISH (I and J, blue arrow) in WT sibling and Runx1-FLT3/ITD transgenic zebrafish (F1) embryos at 4 dpf. FLT3/ITD-positive zebrafish (F1) were confirmed by PCR genotyping of GFP and FLT3/ITD using genomic DNA from fin clip of WT siblings and Runx1-FLT3/ITD transgenic zebrafish (F1) at two months old. Fish 4, 5 and 6 showed germline transmission of FLT3/ITD transgene (K). Data information: Scale bar = 500 μm.
E, F HeLa cells transfected with siRNA and plasmids encoding the indicated proteins were treated and immunostained Example images are shown (E). The immunofluorescence intensity ratio of centromeric EGFP-TOP2A/arm EGFP-TOP2A was determined on around 300 chromosomes in 15 cells (F). Means and error bars representing S.D. are shown unpaired t test). Scale bars, 10 μm.
(C-D) Immunostaining of mosaic adult retinas with eyeless-Flippase-induced clones of cells homozygous for EMC3e02662, labelled by the absence of RFP (red), show loss of (C) TRP (Mab83F6, in blue) when UAS-HA-Xport-A is expressed. (D) Expression of TRP (Mab83F6, in blue) is observed in EMC3e02662 homozygous cells, when HA-Xport-A4L is expressed. The rhabdomeres are stained for actin (Phalloidin, in green). The UAS constructs were expressed under the control of Rh1-GAL4. Scale bars represent 10 μm.
Cell number of BALF samples were from wild-type (WT) and EphA2-kockout (KO) mice (n=3 per strain) on day 1 and day 3 after intranasal infection with reovirus (4×104 PFU per mouse). Shown is mean ± SD. Data information: Each symbol represents an independent experiment; small horizontal lines indicate the average of triplicates. *P<0.05, **P <0.01 and ***P<0.001 (unpaired t test). Data represent three independent biological replicates.
B. Pharmacokinetic measurements of serum levels of 4D7 in mice after intraperitoneal injection at 0, 1, 24, 48, 72 and 110 hours since administration.
(E) flg22-induced ROS in Col-0 and ddl-6. Leaf discs from four-week-old plants were assayed for ROS production upon 100 nM flg22 treatment over 30 min. The data are show as mean± SE (n=24).
Pairwise analysis comparing proportion of oscillators in CTRL versus MBSm embryos indicated as dots; paired t test with two tail significance p<0.01**.
Snapshot from luminescence movie of SNSF cells in differentiation. White arrowheads: cells starting to express SOX1-P2A-FLUC; Orange arrowheads: cells staying SOX1-negative throughout the experiment. Red: SOX2-NLUC, turquoise: Sox1-P2A-FLUC. Scale bar: 50µm.
A comparison of the SILAC-derived abundance as a function of time, for several proteins that either show differential behaviour between WT and the mutants (Idh2, Idp1 and Aco2) and proteins that behave similarly between all the genetic backgrounds tested (Hsp78). Shown are mean protein ratios (two replicates for mutants, three replicates for WT), error bars indicating peptide-based relative s.d.
(C) A20 and ABIN-1 inhibit CARD14-induced NF-kB activation. HEK293T cells were transfected with NF-kB reporter plasmid, A20 (3 ng) or ABIN1 (15ng) and the indicated concentrations of FLAG-tagged CARD14sh. Luciferase activity in cell lysates was measured 24 h later. Values are the mean of triplicates ± s.e. Protein expression of transfected plasmids was verified by western blot and is shown in the accompanying panels.
Pah1 converts phosphatidic acid (PA) into diacylglycerol (DAG) for lipid droplet biogenesis. Ice2 inhibits the Nem1-Spo7 complex and hence Pah1. Ice2 thereby increases PA availability and relieves repression of Ino2/4-driven lipid synthesis genes, thus promoting ER membrane biogenesis. These mechanisms coordinate the production of lipid metabolic precursors and lipid synthesis enzymes.
D) Frequency of new fired origins for Mybl2+/+ and Mybl2Δ/Δ ESCs with or without ATM inhibitor treatment. Error bars represent SEM. Statistical analysis was carried out using unpaired t-test. At least 500 replication structures were counted per treatment group from 4 separate repeats.
A. Confocal time-lapse live imaging was performed in Tg(c-myb:GFP;kdrl:mKate-CAAX) embryos from 28 to 42 hpf (Movie EV 1). Shown are three representative time-points in which the transformation from hemogenic endothelial cells to the hematopoietic fate is visible, indicated by the white arrowheads. For each time-point merged images are shown. White arrowheads denote double-positive cells.B. Cell counts of total numbers of kdrl+cmyb1+ cells "in view", dividing and respectively emerging HSPCs. n=10 movies from n=3 biological replicates were analyzed. A non-parametric Mann-Whitney test was used to test for statistical significance and error bars are shown as ± s.d.
B, Representative images showing the contribution of human control iPSCs or miiPSCs cells to mouse blastocysts. These structures were co-immunostained with (human) anti-OCT4 and anti-HuNu antibodies. Td-Tomato, red; Scale bars, 50 μm.
(F) Sept2 immunoprecipitation from mock or Mdivi-1-treated HeLa cells probed for Drp1 and Sept2. (G) Quantification of two independent experiments showing decreased Drp1 co-immunoprecipitation with Sept2 upon Mdivi-1 treatment.
F Mean absolute number of IL-17+ CD4 T cells in the retina (upper panels) or mean percentages of IL-10+ LAG-3+ Foxp3- CD4 T cells in the spleens of of HEL-TCR transgenic mice with vasculitis (lower panels). Results are mean + SEM (n=3, 4 or 5). **p <0.01 and ***p <0.001 by one way ANOVA with Bonferroni post hoc test.
B HeLa cells stably expressing SEPT6-GFP were infected with S. flexneri AfaI for 4 h, harvested, and then tested with Co-IP. Empty vector and/or uninfected HeLa cells were used in parallel as control. GFP-trap magnetic agarose beads were used to isolate SEPT6-GFP from cells, and extracts were immunoblotted for SEPT6, GFP, SEPT7, or p62. The lysates were immunoblotted for GAPDH as control for cellular protein levels.
D. Detection of the levels of acetylated H3K18 at the 35S promoter and ACTIN 7 in the wild-type, idm1-14, idap1-2 and idap2-2 plants. ChIP was performed using an antibody against acetylated H3K18.
A Schematic of the liposome floatation assay. In the assay, liposomes of defined lipid composition were floated through a dense sucrose gradient by ultracentrifugation. Protein that associates with the liposomes are enriched in the supernatant.
Sequence logo representation of the top scoring 8-mers obtained by hybridization with the PIF4, BES1 and PIF4-BES1 proteins
(C) H&E staining of the skin in unshaved Sirt7−/− and Sirt7+/+ mice on P90 and P130.
C, The FERM domain of PTPN3 is necessary for its binding to TβRI. FLAG-TβRI and HA-PTPN3 (wildtype or truncations) were co-transfected into HEK293T cells. Cells were harvested after 24 h and subjected to IP by HA antibody. TβRI, PTPN3 and PTPN3 truncations were detected by Western blotting with appropriate antibodies.
O 3H-Glutamine uptake in MeWo cells transfected with si-GCN2 and treated 48 hr later with LDHAi for 6 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001
Longitudinal associations between CSF T-tau, Ng and NFL and other AD traits. Data are estimates (-coefficients) from linear mixed effects models, with 95 % confidence intervals. The estimates are the effect of time plus the biomarker by time interactions, capturing the longitudinal effects of the biomarkers. For each model, the "average" effect of time is also shown for comparison. Biomarkers and outcomes were standardized to z-scores. Note that the y-axes for WMH are flipped, so that the lower ranges constantly reflect "worse" outcomes. Note also that the range of the y-axes differs for the different outcomes, for visualization purposes. Models were adjusted for age and sex, and education (for cognitive measures), and intracranial volume (for MRI measures). Aβ42 and T-tau were measured using the the INNOBIA AlzBio3 kit (Fujirebio, Ghent, Belgium), Ng was measured using an in-house immunoassay for Ng (Portelius et al, 2015) and NFL was measured using the NF-light® ELISA kit (Uman Diagnostics, Umeå, Sweden).
G. 2D-TLC analysis of 32p-labeled mononucleotides derived from IVT or CDK9-bound 7SK RNA, with the first panel depicting a schematic migration pattern of the indicated 5'-phosphorylated mononucleotides.
(f) Binding of YAP and TAZ to a DNA fragment containing the TEAD binding motif in the SLC7A11 promoter. ChIP was performed on HLE cell lysate with antibodies against YAP and TAZ and rabbit IgG as control. DNA fragments were amplified using the primers specific for TEAD binding motif in the SLC7A11 promoter region shown in (e). The non-coding region NC10 served as negative control, and the bona fide TEAD target gene CYR61 served as positive control. Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using one-way ANOVA. Results represent three independent experiments.
G. Schematic of pICLpt illustrating the SapI site, which is regenerated upon replication-coupled repair (Knipscheer et al, 2009).
F CWR22 xenografts were grown in nude mice, and tumors were collected at different times after castration. The association between ATF4 and STAMP2 in the tumor samples was determined by Western blot analysis.