EMBO/sd-character-level-ner huggingface dataset:
Figure 3A. Confocal microscopy shows that active Akt (phospho-S473Akt) is localized in the basal body of primary cilia (right side panels show higher magnification).B. INVS is localized in the proximal region of the INVS compartment in primary cilia (INVS compartment, right side panels show higher magnification).C. INVS co-localizes with γ-tubulin, a centrosome marker.D. Anti-phospho-Akt substrates stain positively at the basal region of the primary cilia (arrows), as determined by anti-acetylated tubulin (right side panels show higher magnification). E. Silver-intensified immunogold electron microscopy shows that both phospho-Akt (left side panels) and INVS (right side panels) were localized to the ciliary pocket of primary cilia in the presence of PDGF-AA (white arrow). F. Schematic representation of the view from an electron microscope.
Figure 3A) Cell numbers in nests (blue - left scale) and LECs territories (red - right scale) (profiles are averaged from three segmented movies). B) Mean cell area evolution of histoblasts (blue - left scale) and LECs (red - right scale). Note the progressive increase in mean histoblast area (profiles are average from three segmented movies). C) Net change rate in cell number variation for nests (red line) versus nests growth (black line). Note the temporal correlation in phases, but the reduced magnitude in cell numbers (profiles are collected from single nests and normalized; control black lines are retrieved from Figure 1). D) Net change rate in cell number variation for LECs (blue line) versus tissue growth (black line). Note the full pattern correlation and the oscillations in LECs net rate numbers (profiles are collected from single nests and normalized; control black lines are retrieved from Figure 1). E) Evolution of the net change rate of histoblasts MCA (red line) versus net change rate of nest growth (black line). Note the delay in reaching the sustained growth phase and the reduced magnitude of the MCA rate (profiles are collected from single nests and normalized; control black lines are retrieved from Figure 1). F) Evolution of the net change rate of LECs MCA (blue line) versus net change rate of LECs tissue growth (black line). Note the oscillatory MCA rate around 0 and the tendency toward negative values (MCA decrease) (profiles are collected from single nests and normalized; control black lines are retrieved from Figure 1).
Figure 4A-F. Primary colonization of SPF mice with N2 WT, T6SS mutant (ΔtssC) and complemented (ΔtssC pTssC) followed by secondary challenge with N1 WT (A and B, n=5 mice) N2 WT (C and D, n=5) or E1 WT (E and F, n=4) was performed.A, C and E. FecalCFU for primary and secondary strains was determined for four weeks post-secondary challenge.B, D and F. Selected time points were tested for statistical difference of secondary challenge between groups. This includes four weeks post-secondary challenge (B) and three days post-challenge (D and F).
Quantitative scanning of C99-Bpa substrate interaction sites with γ-secretase.Figure 3Quantitative crosslinking analysis revealed V44, L49, M51 and L52 as major interactions sites of C99 with γ-secretase with high crosslinking efficiencies ranging from ~2-8% of input. While the PS1 NTF was bound by C99 over nearly the whole range of residues, only very few residues bound to PS1 CTF. Several residues in the substrate N-terminal extracellular domain bound to NCT. PEN-2-binding residues clustered in the membrane-flanking extracellular and intracellular domains of C99.
Mitochondrial Bax is activated apoptosis stimulus-independent.Figure 5A Caspase 3/7 activity measured in HCT116 Bax/Bak DKO cells overexpressing Bax, BaxTBak, Bak or BakTBax with or without Bcl-xL overexpression in the absence of apoptosis stimuli. Caspase activity is displayed in relative fluorescence units (RFU). pcDNA3.1-transfected cells served as control. Data represent averages ± SEM. n ≥ 3. p-values according to One Way ANOVA are displayed.B Staurosporine (STS, 1 µM)-induced caspase 3/7 activity of Bax/Bak DKO cells overexpressing Bax, BaxTBak, Bak or BakTBax with or without Bcl-xL overexpression displayed in relative fluorescence units (RFU). Data represent averages ± SEM. n ≥ 3. p-values according to One Way ANOVA. BaxTBak activities with and without Bcl-xL expression revealed no significant difference (n.s.), while in the presence of Bcl-xL overexpression BaxTBak activity is significantly higher than Bax, Bak or BakTBax activities (p < 0.001). C Analysis of the active Bax conformation in HCT116 Bax/Bak DKO cells expressing wild-type Bax or BaxTBak with (dark grey bars) or without Bcl-xL overexpression (light grey bars) by the monoclonal antibody 6A7 (Sigma) detecting the active Bax protein fold by fluorescence imaging. Cells were analyzed prior or after treatment with 1 µM STS in the presence of the pan-caspase inhibitor qVD. Data are represented as % of the expressing cell population ± SEM. n = 4. D HCT116 Bax/Bak DKO cells ectopically expressing wild-type Bax or BaxTBak with (dark grey bars) or without Bcl-xL (light grey bars) were analyzed in the presence or the absence of 1 µM STS and qVD for retained mitochondrial cyt c. Data are represented as % of the expressing cell population ± SEM. n = 4. E Flow cytometry analysis of Annexin V-staining of Bax/Bak DKO cells expressing Bax, BaxTBak, Bak or BakTBax in the absence (red line) or the presence of Bcl-xL overexpression (black line), following STS-treatment. The percentage of gated cells is displayed in the color of the corresponding graph. Data represent averages ± SD. n = 4. F Colony formation of Bax/Bak DKO cells transfected with pcDNA, Bax, BaxTBak, Bak or BakTBax with or without Bcl-xL overexpression. STS (1 µM) was added for 24 hrs before cells were replated and colonies were stained with methylene blue typically 14 days after treatment. G Quantification of colony formation of Bax/Bak DKO cells expressing Bax, BaxTBak, Bak or BakTBax with or without Bcl-xL overexpression after STS treatment (Fig. 5F). Data represent averages ± SEM. n = 4. p-values according to One Way ANOVA. BaxTBak expressing cells with or without Bcl-xL expression showed no significant difference (n.s.).H Quantification of the colony formation of Bax/Bak DKO cells expressing Bax, BaxTBak, Bak or BakTBax in presence of Bcl-xL overexpression without apoptosis stimulation. Data represent averages ± SEM. n = 5. p-values according to One Way ANOVA.
Figure 6F. Groups of BALB/c female mice (n = 5) were inoculated twice with 10 µg of the proteins indicated at the top of each panel, folded in either the prefusion conformation for hRSV F, F-410 and F-411 or in the postfusion conformation for hMPV F. One week after the last dose, mice were sacrificed and their blood collected. A) Each mouse serum was tested in ELISA for antibody binding to the F proteins indicated at the bottom of each panel. *P = 0.00046 and **P = 0.02459. Groups of BALB/c female mice (n = 5) were inoculated twice with 10 µg of the proteins indicated at the top of each panel, folded in either the prefusion conformation for hRSV F, F-410 and F-411 or in the postfusion conformation for hMPV F. One week after the last dose, mice were sacrificed and their blood collected. B) Mouse sera were also tested in microneutralization assays with hRSV and hMPV, indicated at the bottom. *P = 0.04138, **P = 0.04831 and ***P = 0.00339. The results in A and B are presented as in Fig. 3.
Identification of MALAT1-hi and MALAT1-lo subpopulations of rod photoreceptors.Figure 2A) Feature expression heatmap of a panel of known marker genes for rod photoreceptors across the identified 16 retinal cell clusters. Brown colour indicates ≥100 nTrans (number of transcripts). B) Representation of the three donor retina samples in the six rod photoreceptor clusters. C) Violin plot showing high or low expression levels of MALAT1 in rod photoreceptor clusters. D) Distribution of rod photoreceptor populations with high MALAT1 expression (MALAT1-hi) or low MALAT1 expression (MALAT1-lo) in three donor retina samples. E) Fluorescent in situ hybridization analysis of human peripheral retina showing heterogeneous levels of MALAT1 expression in the rod photoreceptors located in the outer nuclear layer (ONL). INL: inner nuclear layer; OPL: outer plexiform layer. Scale bar = 20µm.
Figure 6A) 3D reconstruction of wing disc immuno-labelled for endogenous Ptc and dorsally over-expressing the Tsp96F-HA construct, keeping the ventral side of the disc in wild type condition as internal control. the dorsal accumulation of Ptc in very large punctae across the apico-basal axis, but mainly at the basal side of the epithelium. On the right, graphs represent fluorescence values from apical to basal, comparing dorsal and ventral sides and showing a shift of the highest values towards the basal side after Tsp96-HA expression. B) Confocal image of a wing disc with a clone expressing Tsp96F-HA and immuno-labelled with anti-Ptc and anti-HA antibodies, which co-localize in the large basolateral punctae (yellow arrows). C) Electron microscopy image from immunolabelled (anti-GFP) Hh-receiving cells of a wing disc expressing Ptc-GFP and Tsp96F-HA. The detailed image shows large sac structures that accumulate several dense MVBs positive labelled for Ptc.
Figure 7Body weight gain in male WT littermates and OXGR1KO mice. At 8 weeks of age, male C57BL/6 WT control or OXGR1KO mice were switched to HFD. After 12 weeks of HFD feeding, mice were further divided into two groups, receiving non-exercise or resistance exercise for 14 days. (n = 8 per group). Exercise-induced body weight loss in male WT littermates and OXGR1KO mice. Body weights from exercise mice were subtracted by the average body weight of non-exercise control group for each genotype (n = 8 per group). Exercise-induced fat mass loss in male WT littermates and OXGR1KO mice. Fat mass from exercise mice were subtracted by the average fat mass of non-exercise control group for each genotype (n = 8 per group). Cumulative food intake of male WT littermates and OXGR1KO mice after 14-day resistance exercise (n = 8 per group). Weight index of gWAT (E) and iWAT (F) of male OXGR1KO mice after 14-days resistance exercise (n = 8 per group). Body composition of male OXGR1KO mice after 14-days resistance exercise (n = 8 per group). Serum AKG levels of male WT and OXGR1KO mice after resistance exercise. Male WT and OXGR1KO mice (10 weeks) fed with normal chow were receiving resistance exercise for 40 min (n = 8 per group). The serum AKG levels were tested before and immediately after exercise. Serum E level in male OXGR1KO mice after 14-day resistance exercise (n = 8 per group). The mRNA expression in the BAT of male OXGR1KO mice after 14-day resistance exercise (n = 4 per group). protein expression of UCP1 in the BAT of male OXGR1KO mice after 14-day resistance exercise (n = 4 per group). the mRNA expression of HSL and ATGL n the gWAT of male OXGR1KO mice after 14-day resistance exercise (n = 4 per group). Oxygen consumption in male OXGR1KO mice after 14-day resistance exercise (n = 8 per group). RER in male OXGR1KO mice after 14-day resistance exercise (n = 8 per group).
Model of LC3‐positive vacuoles that are associated with ROS generation by NADPH oxidases in goblet cells.Figure 8
Mothers and children harbor a large number of differentially methylated regions between smokers and non‐smokers at time of birth.Figure 2Circular representation of DNA methylation levels for mothers (outer circle) and children (inner circle). The height of each bar indicates the methylation change between the smoking and non‐smoking group (dark hue: hypermethylation, light hue: hypomethylation).
LAMP1 decreased within MoDCs infected with P.Fig 10A) Epifluorescence microscopy images of MoDCs infected with pre-labeled bacteria (green-CFSE). LAMP1 detected by transduction of red fluorescent protein (RFP) chimera using baculovirus transgenes to MoDCs. B) The mean of fluorescent intensities ±standard deviation of LAMP1 were quantified in three different experiments (* p<0.001). C) The upper scattered plot shows the co-localization of red and green signals in sections of MoDCs infected with Pg381 and mutants strains. The lower plot shows the average of Pearson's correlation measures of three randomly selected region of interest (ROI) within each field within 3 different experiments (* p<0.0001) (Table 4 and 5). All analysis of fluorescence intensity used One-way ANOVA analysis of different groups and Tukey's test for multiple comparisons.
Strategies for exclusive induction under particular p53 dynamics (a) Schematic of transcriptional and post-transcriptional cFFLs and iFFL.Figure 5(a) Schematic of transcriptional and post-transcriptional cFFLs and iFFL. (b) Examples of genes showing exclusive protein expression under rising p53 expression due to cFFL motifs at the transcriptional (RAD51C) or translational (SESN1) levels, and exclusive protein expression under oscillatory p53 expression due to iFFL motifs at the transcriptional level (HSPG2). (c) Four distinct strategies for exclusive protein induction.
Figure 6A The premature egress induced by PKA genetic inhibition is exacerbated when host cells are heavily infected (data is from three independent biological replicates). B Transferring supernatants of Shld-1 treated cultures from cells infected with DDmyc-PKArG321E-Typarasites at a MOI of 8 induces egress of parasites from cells infected at a MOI of 2 within three hours (data is from three independent biological replicates; statistical analysis was done by two-tailed t-test). C Acidification of the culture medium induces parasite egress in less than 10 minutes. The effect is inhibited in presence of compound 1 (data is from two independent biological replicates).  D Neutralisation of cultures with the weak base NH4Cl blocks premature egress induced by DDmyc-PKArG321E-Ty stabilisation. This block is circumvented by addition of the Ca2+ ionophore A23187 or the PDE inhibitor BIPPO (data is from three independent biological replicates). Data information: Data are presented as mean ± SD.
Figure 5LC3I and LC3II (A), p62 (B) and BNIP3 (C) protein expression was measured in gastrocnemius muscle from young and old control and Mfn2KO mice (n=4-6 mice per group). LC3II/LC3I ratio was also calculated. Data were normalized by tubulin and expressed as a fold change compared to young control mice. D) Autophagic flux was evaluated in gastrocnemius muscle by treating control and Mfn2KO young mice with chloroquine for five days. LC3, p62 and BNIP3 expression was measured (n=4-5 mice per group). E) Representative TEM images of quadriceps muscle from Mfn2KO young mice, control old mice and Mfn2KO old mice showing the presence of autophagosomes and mitophagosomes (n=3 mice per group) (Scale bar: 500 nm). F) Representative TEM images of control and Mfn2KD C2C12 myotubes showing the accumulation of autophagosomes upon Mfn2 deficiency (n=3 independent experiments) (Scale bar: 2 µm). G) Presence of autophagic proteins (BNIP3, LC3 and Parkin) on mitochondrial enriched fractions obtained from control and Mfn2KD C2C12 myotubes untreated or treated with CCCP (n=3 independent experiments). Data were normalized by TIM44 as a loading control and expressed as a fold change compared to young control mice and represent mean ± SEM. #p<0.05 Mfn2KO vs. control mice or Mfn2KD vs. control cells, *p<0.05 old vs. young mice or treated vs. untreated cells.
Figure 2A -C. Drug-resistant ABL1-T315I rescues dasatinib- and imatinib-induced cytotoxicity. Western blot analysis of (A) transient and (B) tetracycline-inducible overexpression of ABL1-T315I in H1915 cells treated with dasatinib or imatinib. C. CFA with dasatinib or imatinib for H1915 cells with or without tetracycline-inducible expression of ABL1-T315I. Error bars represent mean ±S.E.M., n=9, *P<0.001 by two-tailed unpaired Student's t-test (control, DMSO vs dasatinib P=4.3×10-12 vs imatinib P=6×10-6; dasatinib, control vs tetracycline, P=9×10-7; imatinib, control vs tetracycline P=9.7×10-5). D-F. Knockdown of mutated ABL1 reduces viability of lung cancer cells. Top, western blot analysis of ABL1 knockdown in (D) Beas-2B, (E) H1915 and (F) H2110 cells upon transfection with three ABL1 siRNAs, negative control (scrambled) and CyclophilinB positive control. Bottom, MTT assay showing viability of (D) Beas-2B, (E) H1915 and (F) H2110 cells in response to ABL1 knockdown. Error bars represent mean ±S.E.M, n=9, *P<0.005, **P<0.001 by two-tailed unpaired Student's t-test (Beas-2B, scrambled vs siABL1-3 P=0.002; H1915, scrambled vs siABL1-1 P=0.004, vs siABL1-2 P=0.001, vs siABL1-3 P=0.002; H2110 scrambled vs siABL1-1 P=5×10-6, vs siABL1-2 P=2×10-5, vs siABL1-3 P=4.2×10-6).
Figure 3(A) IF for pan-cadherin, combined with DNA staining, to quantify asymmetric vs. symmetric division in VZ APs. Dashed white lines denote the cleavage plane, and solid lines mark the "cadherin hole". Asterisks mark the apical-most basolateral membrane flanking the "cadherin hole". Cell divisions were scored as symmetric or asymmetric when the cleavage plane bisects (left) or bypasses (right) the cadherin hole, respectively. Scale bar 2 μm. (B) Quantification of symmetric vs. asymmetric AP division in E13.5 control and DKO neocortices, expressed as percentage of total AP divisions. Four independent embryos per genotype from three litters were analysed. A total of 110 and 99 cells were counted for controls and DKOs, respectively. Data are means ± SEM. (C) IF for alpha-tubulin to visualize mitotic spindle and astral microtubules in E13.5 control and DKO neocortices. Central and apical-basal astral microtubules denoted by white and purple arrows, respectively. Scale bar 2 μm. (D) Quantification of apical-basal, central and total (sum) number of astral microtubules in mitotic APs of control and DKO E13.5 neocortices. Data are means of microtubules per cell ± SEM (at least 10 cells counted per embryo)(n=3 embryos, 3 litters). (E, F) In utero electroporation (IUE) of plasmids expressing GFP plus shControl (Co) or shCcny/l1 into the lateral ventricles of E13.5 wildtype embryos, followed by analysis at E15.5 or E17.5. (E) IF for GFP and Tbr2 in the E15.5 neocortex. (F) IF for GFP and the deep- layer neuron marker CTIP2 in the E17.5 neocortex. (E, F) White arrowheads denote double-positive cells. Insets of magnified cells (indicated by blue arrowheads) depict representative GFP + Tbr2 (E) or GFP + Ctip2 (F) co-staining. Scale bars 20 μm. (G) Quantification of the percentage of GFP+ cells that are Tbr2+, in control and shCcny/l1 neocortices at E15.5 upon IUE at E13.5. Data are means ± SEM (n=3 embryos). (H) Quantification of the percentage of GFP+ cells that are Ctip2+, in control and shCcny/l1 neocortices at E17.5 upon IUE at E13.5. Data are means ± SEM (n=4 embryos). (I) IF for βIII-tubulin (Tuj1) of control (Ccny+/-; Ccnyl1-/-; shRNA Co) and mutant (Ccny+/-; Ccnyl1-/-; shRNA Ccny) NPC monolayer cultures grown in differentiation medium for seven days. Insets depict neurons with representative neurite morphology for controls and mutants. Scale bar 20 μm. (J) Quantification of the percentage of Tuj1+ cells from (I). Data are means ± SEM (experiment performed twice in triplicates, representative experiment shown). (K) Immunoblot analysis of protein lysates extracted from control and mutant NPCs prior to culture in differentiation medium, using an antibody against lysine 48-ubiquitin (K48-Ub) to label polyubiquitinated proteins targeted for proteasomal degradation. GAPDH, loading control. Two representative samples per genotype are shown.
Figure 2Surface H2-Kb levels of wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed by flow cytometry. Surface H2-Kb levels of wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed by flow cytometry. Surface H2-Kb levels of wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed by flow cytometry. Cross-presentation of OVA by wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed and IL-2 release is shown Cross-presentation of OVA by wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed and IL-2 release is shown Cross-presentation of OVA by wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed and IL-2 release is shown
Figure 3A Lysates from Caco-2 cells transfected with SNX10-Flag were subjected to pull down assay with anti-Flag antibody conjugated agarose, followed by immunoblots with the indicated antibodies. B Representative images of co-staining of SNX10-Flag and Lyn in Caco-2 cells expressing SNX10-Flag. Scale bar: 20 μm. C, D Levels of p-Lyn, Lyn, E-cadherin and SNX10 in WT and SNX10 KO Caco-2 cells treated with or without OMVs (100 μg/mL) for 24h were determined by immunoblots (C) and quantified by ImageJ software (D) (n = 3 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001. E, F Caco-2 cells were transfected with Ad-vector or Ad-SNX10, followed by treatment with or without OMVs (100 μg/mL) for 24h. Lysates were extracted and subjected to immunoblots with the indicated antibodies (E) and quantified by ImageJ software (F) (n = 3 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001. G, WT and SNX10 KO Caco-2 cells were transfected with Ad-vector or Ad-SNX10, followed by treatment with or without OMVs (100 μg/mL) for 24h. Total cell lysates were subjected to immunoblots with the indicated antibodies (n = 3 independent experiments). H WT and SNX10 KO Caco-2 cells were transfected with Ad-vector or Ad-SNX10, followed by treatment with or without OMVs (100 μg/mL) for 24h. quantified by ImageJ software (H) (n = 3 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001. I Cytoplasmic and nuclear proteins were extracted from WT and SNX10 KO Caco-2 cells treated with or without Tolimidone (10 μM), and the indicated proteins were analyzed by immunoblots. J TEER value of Caco-2 cell monolayers after incubation with or without Tolimidone (10 μM) for 24 h was analyzed (n = 9 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001. K Caco-2 cell monolayers on transwell membranes were treated with or without Tolimidone (10 μM) for 24h. FITC dextran was added to these cells (top of the membrane). After 2h, FITC-dextran levels in the bottom chamber wells were measured (n = 9 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001.