EMBO/sd-character-level-ner huggingface dataset:
D S. cerevisisae wt, ubr1Δ san1Δ, and ubr1Δ san1Δ btn2Δ cells expressing tGnd1‐GFP (green) were grown at 30°C. DNA and nuclear envelopes were visualized by coexpressing Htb1‐mCherry or Nic96‐mCherry, respectively (red). The fraction of cells showing specific tGnd1‐GFP foci numbers per cell was determined. INQ formation in cells containing tGnd1‐GFP foci was determined (% cells with INQ) based on close vicinity of tGnd1‐GFP foci to Htb1‐mCherry or localization inside Nic96‐mCherry signals, yielding comparable results. Scale bars, 2 μm.
G - J: mEPSC frequency was increased in superficial CA1 pyramidal neurons of adult (4 months) NexCre cTKO versus littermate controls (G, **p = 0.0052). mEPSC amplitude was not altered (H, p = 0.1579). mIPSC frequencies were not different in superficial CA1 pyramidal neurons of adult (4 months) NexCre cTKO versus littermate controls (I, p = 0.3831) and mIPSC amplitude was not altered in superficial CA1 pyramidal cells of NexCre cTKO mice compared to cells of LM (J, p = 0.3712).
(d) Anti-Ape1 western blot of atg19Δ cells transformed with the indicated expression constructs. The lower Ape1 band indicates prApe1 processing and thus its delivery into the vacuole. Supplementary Fig. 6 shows the expression of the Myc-tagged proteins and a quantification of the assay.
Schematic of strategy used to generate the Her6::Venus knock-in; left arm LA, right arm RA.
g, Park2−/− BMDMs were transduced with lentivirus expressing BFP (−), wild-type parkin, or two separate mutant parkin alleles (T240R, P437L). Cells were infected with M. tuberculosis for 4 h and ubiquitin and M. tuberculosis co-localization was quantified and expressed relative to control BMDMs. Results are means ± s.e.m. of three independent experiments (**P  0.005, paired Student's t-test). h, The parkin and actin expression in cells from g was determined by western blotting.
(a) Experimental testing of the predicted SR (DU) rescuers of DNMT1 via drug combination experiments in 18 NSCLC cell lines insensitive to Decitabine. The matrix displays drug interactions between Decitabine, a DNMT1 inhibitor, and inhibitors of its predicted rescuer genes (X-axis) across 18 NSCLC cell lines (Y-axis) that are insensitive to Decitabine. Row labels present rescuer genes and their inhibitors. Colors in the matrix show whether the interactions found are significantly synergistic (red), antagonistic (green) or non-significant (in gray). Values in the matrix show average synergism (<1 synergism and >1 antagonism Thirteen predicted DU-SR rescuers (red lines), two predicted DD SR rescuers (green lines) of DNMT1 and one random control (JAK3i) were tested.
(E) IL-15 mRNA levels in small intestine homogenates from CftrWT mice or CftrF508del/F508del or TG-/-/CftrF508del/F508del or TG-/- mice (n= 10 per group). Mean ± SD of triplicates of independent pooled samples. ***p<0.001 vs CftrWT, °°p<0.01, ##p<0.01 vs CftrF508del/F508del (ANOVA, Bonferroni post hoc test).
B. FPKM of the 7 LncRNAs identified in the RNA-seq with high expression in PGCs. The solid lines at each end of the box plot represent the maximum and minimum values, respectively. The three dotted lines in the middle of the violin diagram represent the 75% percentile, the mean, and the 25% percentile in turn.
mRNA expression analysis (RTqPCR) of p53 target genes normalized to β-actin; n=3.
(b) Electron micrographs of livers from 18Q-htt and 111Q-htt mice. Right: number of lipid droplets (LD) per cell profile (prof.), mean area of LDs and percentage of cellular area occupied by LDs. Mean + s.d.; n = 3.
Brain cortical tissue obtained from Nrf2 (−/−) (6 months old, one male and two female) or wild-type (11 months old, two male and one female) mice were separated into sarkosyl-soluble (SS) and insoluble (SI) fractions as described in the Methods. The level of total tau was analysed by immunoblotting using a monoclonal antibody to total tau (Tau5). The relative molecular masses (kDa) are indicated to the left of each blot. Bar graph represents the relative optical density of sarkosyl-insoluble tau normalized with that of sarkosyl-soluble tau. n=3. Data shown are mean±s.e. and were analysed using Student's t-test. (*P0.05).
Genetic design of the PK-LacZ construct. Expanded sequence shows the PK secondary structure with the slippery site underlined, as well as the two genes (gene10 and lacZ) in differing reading frames.
3D reconstruction from serial sectioning reveals that growing α1-tubulin(-) 'sporozoites' lack apical polarity and fail to pull in nuclei. Microtubuli: green; rootlet fiber (connecting apical pole to centriolar plaque): red; rhoptries: purple; endomembraneous vesicles (Golgi, premicronemes): brown; nucleus: cyan; sporozoite plasma membrane and inner membrane complex: blue; dotted lines show location of sporoblast membrane. 17 and 10 sections of 100 nm and 300 nm thickness were processed for the tomograms in WT and α1-tubulin(-) parasites, respectively. Scale bar: 1 µm.
The mRNA expression in the BAT of male OXGR1KO mice after 14-day resistance exercise (n = 4 per group).
I. Cell proliferation is not affected in BAZ2A-KO ESC+serum. Data represent relative cell numbers 2 days culture starting with the same number of cells. Average values of four independent experiments. Error bars represent s.d. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (ns, non-significant).
A Overexpression of MOAP-1 downregulates levels of p62 bodies in the ATG5-depleted cells. HepG2 cells were infected with lentivirus encoding short hairpin RNA for ATG5 (shATG5) or scramble control (shCtrl) for 48 hours before being transfected with Myc-MOAP-1 or empty vector (EV) control for 24 hours and subjected to IF analysis using anti-p62 (in red) and anti-Myc (in green) antibodies. Cells expressing Myc-MOAP-1 were marked by dashed lines.
A-C DAPI-staining visualization of sperm formation in wild-type male (A), Mpfgmyb [X] (B), and Mpfgmyb [Y] (C) plants. Note that background DAPI staining visualizes flagella (arrows) in addition to nuclei (arrowheads). (B′) is an enlarged image of the boxed region in (B), visualizing an incompletely condensed nucleus. Scale bars, 5 µm.
EDL myofibers isolated from WT and Myf6-KO mice fixed at time T=0 and stained with PAX7, MYOD and DAPI. Scale bar=30μm L Quantification of the percentage of MYOD+/PAX7+ satellite cells per fiber in Myf6-KO (n= 88 myofibers) vs WT (n= 86 myofibers) myofibers. Two-tailed t-test, error bars = +/- SD M Quantification of the average percentage of MYOD+/PAX7+ satellite cells per mouse in Myf6-KO and WT myofibers (n=3 mice). Two-tailed t-test, error bars = +/- SD
H. Survival graph of Casp8WT and Casp8ECko mice after Enbrel® treatment (n=7 WT, 5 ECko + IgG, 8 ECko + Enbrel; Log-Rank test).
(F) Consensus model of periodicities in centriolar cartwheel along the proximal-distal axis. Surface representation of offset double rings tightly superimposed with ~3.2 nm periodicity, in register with the next such offset double ring located ~5.2 nm away, thus amounting to an overall periodicity of ~8.4 nm. Note that these values are based on the T. mirabilis 36% class, which has the most clearly resolved periodicities, yet does not have a CID as shown in this composite model, with related values in other species; see text for details. The CID exhibits a related ~8.4 nm mean periodicity in the two Trichonympha species. Two spoke periodicities are observed: close to the hub, pairs of spokes are ~8.4 nm apart, whereas spoke pairs merge towards the periphery, where their periodicity is hence ~16.8 nm, matching that of the pinhead and connected microtubules. spoke angles are merely illustrative and limited by the resolution of the available STA maps. alternative modes of spoke merging may be revealed by analyzing much larger sub-volumes and be present in other species
H) Analysis of the area under the curve (mean +SEM of biological replicates with n=12 for wt, n=5 for PD-1-/-, n=12 for APP/PS1, and n=8 for APP/PS1 PD-1-/-, ANOVA (DF=3, F=6.98, p=0.001), * p<0.05, ** p<0.01).
H Dependency of SRSF9 on the interaction of CLK1∆C (H) with HSATIII. HSATIII-ChIRP was performed using control and SRSF9-depleted cells expressing FLAG-CLK1 proteins (42°C for 2 h and recovery for 1 h at 37°C). Input: 1%. Graphs represent coprecipitation ratios of FLAG-CLK1 proteins to HSATIII in the control and SRSF9-depleted cells.
Signr3+/+ (WT) or Signr3−/− (KO) mice were orally gavaged with NCK56, NCK2187, or SlpA on days −1 and −3, and 3% DSS was given in the drinking water. Mice were gavaged with bacteria or purified SlpA every other day for an additional three times, and immunity was analyzed by flow cytometry at day 10.B, C Colonic DCs and macrophages (MΦs) were analyzed by flow cytometry for the production of IL‐1β (B), and colonic FoxP3+ Tregs were evaluated for co‐expression of RORγt+ (C). n = 5 mice/group. Gray tinted line = isotype control; black = untreated; purple = DSS; red = DSS + NCK56; green = DSS + NCK2187; blue = DSS + SlpA.
H. Genes that were co-bound by KDM6A and HNF1A showed greatest downregulation in Kdm6apKO pancreas, compared with KDM6A-bound genes that were not bound by HNF1A. Box plots show median and IQR of Log2 TPM fold-changes and whiskers extend to highest and lowest data points within 1.5 x IQR outside box limits. P-values were determined by two-tailed Student's t tests and n=4 replicates per condition.
Example FRAP image series for cytosol and the different Tau accumulation types in HEK sensor cells treated with AD brain lysate (pre-bleach=-2s, immediately after bleaching=0s, after recovery=40s). Arrows indicate position of bleached ROIs. Scale bars=5 or 10 μm as indicated.
C. Na+ binding isotherms of EAAT1CRYST at pH 7.4 in the presence (pink) and absence (blue) of UPCH101. Mutation D400380N at Na3 strongly impairs Na+ binding (green). Solid lines represent fits of Hill equation.
E. Mutant forms of YAP which have different phosphorylation status of Ser127 or S128 differentially rescue retarded wound healing caused by NLK knockout. HEK293 wild type or HEK293 NLK knockout cells were transfected with indicated plasmids ("EV" stands for "empty vector"), and the wounded areas after 0 and 24 hr were measured by using the TScratch program (left panel). Graphs show percentage of unfilled areas at 24 hr compared to 0 hr, and average values from a representative of multiple experiments performed in triplicate (right-top panel).
D. Schematic representation of the experimental paradigm. Concentrations used: 0.5μg/μL pCS2-mCherry or pCS2-eGFP plasmids; 250μM miR-181-MO or control MO cocktail; 50μM miR-181 or control mimics (top). Representative images of RGC axons within the optic tectum. White arrows indicate axons targeted both by MO (green) and miRNA mimics (red) (bottom). Abbreviations: co-MO, control morpholino. Scale bars: 20µm. E. Quantification of misprojecting axons. The number reported on the bars are the total number of co-electroporated axons. Note how miR-181 mimics rescued aberrant misprojection of morphant axons in vivo. Each data point corresponds to one independent experiment. Total number of axons and brains analyzed: 96 axons, 4 brains (co-MO+ctrl mimics), 101 axons, 4 brains (miR-181-MO + ctrl mimics), 134 axons, 4 brains (miR-181-MO+miR-181 mimics). n=4 independent experiments. Values are mean ± SEM. Abbreviations: co-MO, control morpholino; ns, not significant.
(A) Shank2-/- dams failed to nurture their pups. Pups nurtured by Shank2+/+ mice display milk in their stomach (arrowheads, upper left panel), while milk was absent in the stomach of Shank2-/- pups (arrowhead, lower left panel). Pups of Shank2+/+ mice gradually gained weight (black circles) whereas no weight gain was observed in pups delivered by Shank2-/- mothers (blue circles), two-way mixed ANOVA, effect of genotype: ***P<0.001, effect of day: P=0.962, day x genotype interaction: ***P<0.001, Shank2+/+ n = 12, Shank2-/- n = 9.
RT-qPCR of Dgcr8 exon 3 in Dgcr8Δ/Δ GPCs 5-7 days following tamoxifen treatment (n = 3). Samples were normalized to actin, and data are presented relative to untreated Dgcr8flox/Δ GPCs.
Sublingual C. albicans infection of WT and Stim1fl/flCd4Cre mice as described in Figure 5. (D) Histological images of H&E (left) and PAS-stained (right) tongue tissue at day 7 p.i. Scale bars 100 μm. Arrows point to clusters of polymorphonuclear (PMN) cell (neutrophil) infiltrates.
(d) The cycle threshold (x-axis) vs. the coverage of the genome (y-axis and color depth) for the total RNA-seq.
(A) Schematic depicts the molecular mechanism by which S. flexneri co-opts the host actin polymerization machinery: the bacterial autotransporter IcsA localizes to one bacterial pole where it recruits and activates host actin nucleation promoting factor N-WASP. N-WASP then recruits and activates the host actin nucleator Arp2/3 complex to initiate actin polymerization.
Flow cytometry analysis of PD-L1 after gemcitabine and RT (as described above) in KPC (E) and Pan02 (F) following Stat1 downregulation by siRNA (mean ± SD, n=3, Student's t-test). MFI, mean fluorescence index;
(A) Equilibrium binding of OTUD1 C320A and C320R to K63-linked diubiquitin was measured by fluorescence polarization using FlAsH tagged K63-linked diubiquitin in which the proximal ubiquitin was fluorescently-labeled. Error bars indicate s.d. and are based on three measurements per data point. One representative experiment of two is shown.
Abro1+/+ and Abro1−/− mice were intraperitoneally injected with Alum (1 mg per mouse) or vehicle (PBS) for 6 h. flow cytometric analysis of peritoneal cell exudates (E). n = 6 for PBS groups and n = 12 for Alum groups.
Length distribution of BrdU tracks measured at that time for wild type, rad9∆, rad53-11 and rad53-11 rad9∆ cells. Median lengths are indicated in red. For each sample, at least 200 tracks were measured from two biological replicates.
Ellipsoid body knock down of Octβ2R results in no significant change of stx. Data represent mean±SEM: 1.012±0.006, 0.635±0.027, 1.323±0.136; 0.839±0.055, 1.201±0.072, 0.790±0.052. N=3.
Representative time-lapse images of H9C2 rat cardiomyoblasts expressing AcGFP-53BP1 from 3 days after 10Gy irradiation at the indicated times (mins). Images are maximum intensity projections with a 6.7µm focal depth.
24OHC levels in spent media from LN229 (left) and GBM#P3 (right) cells transduced with lenti-Ctrl or lenti-CYP46A1 measured using targeted LC-MS/MS
B) Association analysis of gene expression levels with TBV measures in ASD and control toddlers. See permutation analysis in Appendix Table S6. ** p<0.001
Averaged protein stability was calculated from the data for total mutant protein levels and mutant C. elegans heat shock paralysis (Fig S2, 3 and 8). Averaged mutant Munc18-1 function was obtained from the data for MEA plate assay, antibody uptake, and synaptopHluorin release (Fig S4 and Fig 5-7). See Materials and Methods for details.
A Lipidomics-based quantification of indicated lipid species in mice that received tail-vein injection of adenovirus expressing PLTP or GFP (control). Blood and tissues were harvested after 10 weeks of HFD. n=4 for GFP and n=5 for PLTP in mice on HFD. LPC = (lyso) phosphatidylcholine, LPE = (lyso) phosphatidylethalonamine, PA = phosphatidic acid, SM = sphingomyelin, TAG = triglycerides, FFA = free fatty acid. Statistical analysis is demonstrated (P value) relative to GFP by Student's t-test.
E Cell surface expression of CD11b was assessed on unstimulated or IL-33 (50 ng/ml) treated Dusp5+/+ (red) or Dusp5-/- (blue) BM-derived eosinophils for 20 hours (left). Percentage of CD11bhi surface expression of representative FACS analysis (left) was quantitated (right) from a total of three independent samples.F Cell surface expression of CD69 was assessed on unstimulated or IL-33 (50 ng/ml) treated Dusp5+/+ (red) or Dusp5-/- (blue) BM-derived eosinophils for 20 hours (left). Quantitation of CD69 surface expression of representative FACS analysis (left) was quantitated (right) from three independent samples.
Confocal images of WT, akap KO, c5rap2 KO, pcnt KO, pc-ak-2KO and pc-c5-2KO cells stained for EB1 (green) EB1 comets around the centrosome
(H) Scheme summarizing the epistatic interdependencies between DAPs emerging from work displayed in this Figure.
A) UMAP clustering of sorted Cd11b+/Cd45+ myeloid cells from mouse hippocampus. ARM: activated response microglia; CAM: CNS-associated macrophages; CPM: cycling and proliferating microglia; HM.1: homeostatic microglia cluster 1; HM.2: homeostatic microglia cluster 2; IRM: interferon-response microglia; MHC.high: high MHC-expressing microglia; Mnc: monocytes; TRM: transitioning microglia.
C Scatter plot graphs showing the tumor weight upon treatment by the indicated mono- or combo-therapy. Error bars show mean ± SEM of tumor weight (n = 10 to 11 tumors from 6 mice per condition). ***P=0.0002, Kruskall-Wallis test followed by Dunn's multiple comparison test; ns, non significant.
(H) Immunofluorescence staining against F4/80 and CathB in Cb of Npc1nmf164 mice. Scale bar, 30 μm. The table shows mean ± SEM percentage of microglia presenting CathB staining in Npc1nmf164 and wt mice. Below, magnified images of the selected areas. Scale bar, 20 μm.
(D) Outline of the construction of donor vectors with TAP or GFP tags flanked by 1 kb of 5' and 3' homology sequences.
(C) Heat Maps of the PRBS associated to up- and down-regulated genes. The log2 normalized signal enrichment centered on PRBs (T0 and R5') located from −5 Kb upstream of the TSS to the TTS of up- and down-regulated genes is shown (upper panel). Lower panel: The Average profile of PRBs at R5' associated to up-, down- and non-regulated genes is depicted.
Western blot for p53 pS15, p53, and vinculin (vinc) in PHD1-silenced HCT116 upon treatment with 300 μM 5-FU for 8 h with or without 0.5 mM DMOG for 26 h. Vinculin (vinc) is used as a loading control.
Inhibitory effect of the indicated doses of BO-110 (in µg/ml) or vehicle (V) on MDK mRNA expression determined by qRT-PCR in SK-Mel-147 (16 h after treatment). Data correspond to average mRNA levels in three experiments with technical replicates normalized to vehicle control ± SD. Statistical significance was determined by ANOVA.   qRT-PCR analysis of relative mRNA levels of MDA5 16 h after treatment of SK-Mel-147 with the indicated doses of BO-110 (in µg/ml) (BO). Data correspond to the mean ± SD of three experiments with three technical replicates. Statistical significance was determined by ANOVA.
(C) Relative alkaline phosphatase (ALP) activity indicative of autophagy. n = 3.
Additional MR investigations of patient A at 28 months of age. (E) T1-weighed coronal images demonstrating thinning of the posterior corpus callosum and reduced volumes of the cerebellar hemispheres and vermis. (F) Magnetic resonance spectroscopy of the white matter showing a decreased N-acetylaspartate (NAA) peak at 2.02 ppm (arrow). (G) T1-weighed MRI of the spinal cord showing contrast enhancements around the conus medullaris (arrowheads). May-Grünwald-Giemsa-stained bone marrow smear from patient A with myelopoietic cells containing dense granules (arrowheads), suggestive of a lysosomal storage disorder.
B. Histone H3 was immunoprecipitated from HepG2 cells with or without endogenous HAT1 depletion (by knockout). The levels of succinylation, acetylation, histone H3, HAT1, and β-actin were analyzed by Western blot analysis in the cells.
(A) Heatmap of differentially expressed genes between IL-33KO (n=3) and WT (n=3) epidermis after topical treatment with DNFB. Representative genes in differentially affected biological pathways are listed on the heatmap (the full list of differentially expressed genes is shown in Appendix Table S1).
Cross-sectional area (CSA) of electroporated EmGFP-positive myofibers (250 fibers per sample) was analyzed 7 d after denervation. n = 5 for each group, mean ± SEM. **p < 0.01. n.s., not significant (unpaired two-tailed Student's t-test).
(C Atomic force microscopy analysis of E. coli BL21 and MG1655 immobilized using the Poly-L-Lysine protocol. (C) Entire bacteria and high-resolution comparisons of untreated and convertase-labeled E. coli BL21 exposed to C5-C9 (Conv-MAC) for 10 minutes. Scale bars: 800 nm (left) and 30 nm (right). Height Scales: 1.01 µm (left), 8 nm (top right), 22 nm (bottom right). Width of magnification boxes (left): 42 nm, height scales: 8 nm (top left) and 13 nm (bottom left). Arrows highlight E. coli porin structures, an asterisk highlights the C5b-7 stalk. Height profiles (bottom) are shown for the white dashed lines in the images.
D Experimental validation of basal DUSP expression in mCFU-E and BaF3-EpoR. Quantitative RT-PCR was performed with all samples on the same plate, allowing a direct comparison of mRNA levels between mCFU-E and BaF3-EpoR cells. Data is normalized to the Rpl32 gene. Ratios of expression in BaF3-EpoR cells compared to mCFU-E cells are shown as box plots. N=10. For details, see Appendix K.
(b) Immunofluorescence analysis of COS-7 cells expressing wild-type (Gln23; Q23) or mutant (Gln74; Q74) huntingtin with antibody to LC3 showed more autophagic vacuoles in cells expressing mutant huntingtin that had aggregates (arrow). COS-7 cells without the primary antibody (negative) and COS-7 cells without any treatment (untreated) stained for LC3 are also shown. The numbers of EGFP-positive cells expressing wild-type or mutant huntingtin with (+agg) and without (−agg) aggregates that had higher numbers of autophagic vacuoles (>15-20 vesicles per cell) is shown in the graph. COS-7 cells grown in starvation medium (starvation) or treated with rapamycin (Rap) for 4 h to induce autophagy had more autophagic vacuoles (arrows).
(B) Apoptosis in U2OS cells stably over-expressing Flag-tagged-TIGAR (clones TIGAR#5 and TIGAR#7) or control cells (clones Cont#1 and Cont#3), as measured by cells with a sub-G1 DNA content. Cells were transfected with either scrambled, TIGAR siRNA1 or TIGAR siRNA2. Cells were left untreated, exposed to nutrient starvation for 6 h or to metabolic stress for 24 h.
E. Mutation of the PIP-box in full-length HUWE1 also blocks PCNA interaction. Full-length Myc-tagged HUWE1 (wild-type or PIP-mutant) was transfected in 293T cells. Following Myc-immunoprecipitation, endogenous PCNA was detected in wild-type, but not PIP-box mutant (FF) complexes.
Immunoblots of WT and non-palmitoylatable mutant Golga7b from immunoprecipitations of WT DHHC5 and a pair of DHHC5 mutants (DHHS5 = catalytically inactive mutant where catalytic cysteine has been mutated to serine, C-terminal mutant = mutant where the 3 C-terminal palmitoylation sites of DHHC5 have been mutated to alanine residues.). WT and DHHS5 immunoprecipitates both WT and mutant Golga7b but the C-terminal mutant is unable to immunoprecipitate either form of Golga7b showing that the palmitoylation of the C-terminus of DHHC5 is essential for the stability of this interaction.
pi4kβ1 pi4kβ2 double mutant phenotype were recorded. Immunostaining of meristem cells of five-day-old plants using anti-tubulin (green) counterstained with DAPI (false colour red). Asterisks, multiple nuclei in one cell; arrowheads, multiple phragmoplasts in one cell. Dashed lines indicate the outlines of exemplary multinucleated cells. Scale bars, 10 µm.
A, B Interactions between Tap-1 and TseL (A) or VgrG-1 (B). Shown are immunoblots of lysates (total) and immunoprecipitates with anti-FLAG affinity beads (IP:FLAG) of V52Δtap-1 (A) or V52 vgrG-1::myc (B) transformed with empty vector or a plasmid encoding His-tagged or FLAG-tagged Tap-1.
Concentration of total cell-free DNA (cfDNA) in 13 CSF samples. Samples in which SCNAs were detected are shown in dark blue, and tended to have higher levels of total cfDNA
(D) The interaction of HDA9 with ARID2, ARID3, and ARID4. ARID2-Myc, ARID3-Myc, and ARID4-Myc transgenic plants were crossed to HDA9-Flag transgenic plants and their progeny were used for co-IP.