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0.43807 | e7dd33546a8f4bae808a7aeff8439cbf | Pathological phenotypes in muscle of individuals with TOP3A‐related mitochondrial disease
ASequential COX‐SDH histochemical staining in muscle biopsies of Pa2, Pa3‐1, Pa4 and Pa6 (as indicated), indicating a mosaic pattern of COX deficiency. Scale bar represents 100 μm.BQuadruple immunofluorescence assay to detect deficiency in complex I (NDUFB8) and complex IV (COXI) in Pa3‐1 (left) and Pa6 (right).CLong‐range PCR assay to detect mtDNA deletions in TOP3A patient muscle (lanes 2–5). Samples from unaffected individuals (lanes 6 and 7) and a single‐deletion mitochondrial disease patient (lane 8) are used as negative and positive controls respectively. “M” indicates marker.D–GMapping of mtDNA rearrangements in TOP3A mitochondrial disease patients. Total DNA samples from Pa2 (D), Pa3‐1 (E), Pa4 (F) and Pa5 (G) were analysed by whole‐genome sequencing, and the data were processed using the MitoSAlt pipeline. Deleted regions are shown as blue bars and predicted duplicated regions as red bars. The intensity of the colour corresponds to the abundance of the rearrangement.
Source data are available online for this figure.
| PMC10165364 | EMMM-15-e16775-g007.jpg |
0.427101 | 9e27a3d94c28474392acccf3f8780c93 | Effects of pathological TOP3A variants upon mtDNA structure and copy number
A, BAnalysis of mtDNA structure in muscle from individuals with TOP3A‐related mitochondrial disease using Southern blotting following restriction with BamHI (A) or PvuII (B). The black bar indicates the probe (nt. 16262‐128).C–FmtDNA phenotypes in U2OS Flp‐In cells treated with TOP3A siRNA, rescued using variant‐containing siRNA‐resistant forms of TOP3A. (C) Western blot of TOP3A protein expression. Cells were untransfected (lane 1) or transfected with TOP3A siRNA (lanes 2–11), then induced to express WT TOP3A (lane 3) or pathological variants of TOP3A (lanes 4–11). Note that TOP3A Ser810* does not carry a C‐terminal HA tag. β‐actin is used as a loading control. (D) mtDNA copy number for TOP3A rescue cells as in (C) determined using qPCR. Error bars represent SEM, n = 3 (Ala95Val) or n = 4 (all other samples), where each data point represents the mean of three technical triplicates. Significance values are shown for one‐way ANOVA compared to untreated wild‐type cells, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. (E) Southern blot of mtDNA structure from cells as in (C). The probe (black bar, nt. 16262‐128) detects both full‐length (FL) mtDNA and 7S DNA. The presence of hemicatenated mtDNAs is indicated. (F) Southern blot of uncut mtDNA to visualise different topological forms, from cells as in (C). Control DNA treated with BamHI (lane 1) or E. coli topoisomerase I (lane 2) acts as markers for linear and relaxed monomeric mtDNA respectively. Diagrams indicate the migration of different mtDNA forms.
Source data are available online for this figure.
| PMC10165364 | EMMM-15-e16775-g009.jpg |
0.449492 | b5cf326e97914e919a4bb18b30383e8b | ssDNA catenane substrate construction and validation
Synthesis of Lk1 ssDNA catenanes. Linear and circular R1 and R2 oligos are shown for size comparison (lanes 1–4). Products resulting from synthesis reactions omitting R2 (lane 5) or R1 (lane 6) are shown, as well as a complete synthesis reaction (lane 7). The migration of Lk1 ssDNA catenanes and circular and linear R1 and R2 oligos is indicated to the right of figure.Verification of Lk1 ssDNA catenanes. Linear and circular R1 and R2 oligos are shown for size comparison (lanes 1–4). The treatment of linear R1 oligo with ExoI (lane 5) is shown as a positive control for ExoI activity. Lk1 ssDNA catenanes were treated with ExoI (lane 6), S1 nuclease (lane 7) or CviKI‐1 (lane 8). The migration of Lk1 ssDNA catenanes and circular and linear R1 and R2 oligos is indicated to the right of the figure.
Source data are available online for this figure.
| PMC10165364 | EMMM-15-e16775-g010.jpg |
0.485685 | a7bc0cac048040bca9c2c68e37a231c2 | mtDNA rearrangements in patient muscle
Enlargement of the NCR region in whole‐genome sequence data of Pa2, indicating the locations of small mtDNA rearrangements. The locations of mtDNA cis‐elements in this region are indicated (LSP, light‐strand promoter; HSP, heavy‐strand promoter; OriH, origin of heavy‐strand replication; CSBs, conserved sequence blocks).Mitochondrial DNA rearrangements from Pa1 (Nicholls et al, 2018). Whole‐genome sequencing data were analysed using the same version of the MitoSAlt pipeline as for newly reported individuals (Fig 2) to permit comparison of breakpoint mapping datasets. Deleted regions are shown as blue bars and predicted duplicated regions as red bars. The intensity of the colour corresponds to the abundance of the rearrangement.Analysis of mtDNA rearrangements in Pa2 and Pa5‐1 using Southern blotting. Total muscle DNA (250 ng) was restricted with BamHI, and then left further untreated or incubated with 1 U of T7 endonuclease I, separated on agarose and Southern blotted using probe A (indicated with a black bar). Diagrams indicate the structures visible.
Source data are available online for this figure.
| PMC10165364 | EMMM-15-e16775-g011.jpg |
0.452858 | 997543c70d3b4f69a22e8f52cca32cb8 | Location and modelling of pathological TOP3A variants
Pedigrees and segregation of TOP3A variants in mitochondrial disease patients described in this study. Affected individuals are shown as filled shapes. Males are represented as squares, females are represented as circles and deceased individuals are indicated with diagonal lines. Arrows indicate the probands.Domain structure of the TOP3A protein. Domains are assigned according to Bocquet et al (2014). The locations of truncating variants in TOP3A are indicated above the diagram and missense variants are below the diagram. Variants found in mitochondrial disease patients are shown in blue, and variants found in Bloom syndrome that are included in this study are shown in orange.Sequence conservation of pathological TOP3A variants. Affected residues are highlighted in yellow, and sequence homology is indicated below the sequences.Location of pathological variants within the structure of TOP3A (PDB: 4CGY). Domains are coloured according to the assignments in (B). Affected residues are shown in red. The location of the catalytic tyrosine residue (Tyr362) and magnesium ion cofactor (Mg2+) are also indicated. RMI1 is not shown.Enlarged images of affected residues as in (D). Interactions involving the side chains of these residues are depicted as black lines.
| PMC10165364 | EMMM-15-e16775-g013.jpg |
0.413939 | b3d3ca661ed34bebb364295ab2ffdafc | Experimental approach for frankenbacteriosisThe experimental approach combines metaproteomics with validation analyses in tick and human cells and in blood-feeding ticks for the identification and characterization of tick midgut commensal bacteria involved in interactions with tick-borne pathogens. Sphingomonas were selected for frankenbacteriosis to interfere with tick infection by A. phagocytophilum, the causative agent of HGA. Molecular and metabolic engineering produce FrankenSphigomonas-MSP4 producing on cell membrane the A. phagocytophilum MSP4 antigen involved in receptor-mediated pathogen infection. Transovarial and transstadial transmission of FrankenSphigomonas-MSP4 by I. scapularis tick vectors of A. phagocytophilum with reduction in pathogen infection was shown in vivo. The results may translate into a lower risk of pathogen transmission and caused disease HGA. | PMC10165458 | gr1.jpg |
0.450927 | 5fd4a266439e4541901d7dbd5427d761 | Changes in I. scapularis tick microbiota composition in response to A. phagocytophilum infection(A) Representation heatmap profile in response to A. phagocytophilum infection of bacteria identified by metaproteomics analysis in the microbiota in the midgut (MG) of uninfected and infected ticks. The peptides with hits matching to specific bacteria were confirmed and assigned to the corresponding species, genus or family (Data S1). The remaining peptides matching to multiple families were assigned to unidentifiable bacteria. Bacterial assignments were grouped and the total number of PSM for each classification category were normalized against the total number of PSM to compare results between midgut from A. phagocytophilum-infected and uninfected ticks by Chi2-test (p < 0.01; N = 2 biological replicates) (Data S1). Sphingomonadaceae were identified with ATP synthase subunit b (red arrow) and selected for further analysis.(B) Rickettsia and Sphingomonas spp. DNA levels in A. phagocytophilum-infected and uninfected adult female ticks. The 16S rDNA and spt DNA levels were determined by qPCR, normalized against tick 16S rDNA and rpS4 genes and normalized Ct values were compared between infected and uninfected ticks by Student’s t-test with unequal variance (p ≤ 0.01; N = 13 biological replicates).(C) Representative confocal microscopy images of MG tissue sections from uninfected and A. phagocytophilum-infected I. scapularis female ticks. Red arrows point at the localization of Sphingomonas spp. (Green). Blue, nuclear DAPI dye. Scale bar (a)-(f), 20μm at 40x optical magnification. Scale bar (g)-(h), 60μm at 120x optical magnification.(D) Sphingomonas spp. DNA levels in unfed and fed larvae (N = 5), A. phagocytophilum-infected and uninfected nymphs (N = 4) and unfed uninfected adult females and males (N = 5). The spt DNA levels were determined by qPCR, normalized against tick 16S rDNA and rpS4 genes and normalized Ct values were compared between infected and uninfected nymphs by Student’s t-test with unequal variance (p > 0.05; N = 4–5 biological replicates).(E–H) IAFGP but not P2 peptide binds to SpAR92 peptidoglycan but do not inhibit biofilm formation. Streptavidin-coated magnetic beads were incubated with 0.1 mg/ml of (E) biotinylated proteins (b-IAFGP-GST and b-GST) or (F) biotinylated peptide (b-P2 and scramble peptide b-sP1) and peptidoglycan isolated from SpAR92 and E. coli cultures. Bound and unbound fractions were collected and spotted onto nitrocellulose membrane. Biotin was detected using monoclonal anti-biotin antibody. Bacterium peptidoglycan was detected using a polyclonal goat wheat germ agglutinin antibody (WGA). Bacterium peptidoglycan incubated with magnetic beads alone was used as negative control. (G) SpAR92-associated biofilm formation was determined after static incubation at 30 °C for 24 h in media alone (R2AG) or supplemented with 0.1 mg/mL of sP1 control scrambled peptide, P2, GST, GST-tagged IAFGP (IAFGP) or an equal amount of PBS. Representative images of biofilm formation in 96-well plates and dissolved stains for quantitative analysis are shown above the graph. (H) Bacterial growth was measured at 0 h, 8 h, 21 h and 24 hat 600 nm during the static biofilm assay. Medium represents the uninfected control sample. Results were pooled from 3 independent experiments with 3–4 technical replicates each. Data represent mean ± SEM. Statistical significance was calculate using One-Way Anova followed by Tukey post-hoc test (p < 0.05; N = 3 biological replicates). | PMC10165458 | gr2.jpg |
0.400543 | 37de39d3bb8d47219d0ca816db379c9d | Effect of SpAR92 on the viability of uninfected and A. phagocytophilum-infected ISE6 tick cellsExperiments were conducted with ISE6 tick cells uninfected and infected with A. phagocytophilum NY18 isolate and cultured in L-15B300:R2A (1:1) medium with SpAR92. Uninfected ISE6 cells were cultured in L-15B300:R2A (1:1) medium with and without SpAR92 and samples collected at different time points.(A) Typical growth of ApAR92 and ISE6 cells cultured in L-15B300:R2A (1:1) medium at 31°C.(B) Cell viability (proportion of live/viable, necrotic, dead/late apoptotic and apoptotic cells) was measured by flow cytometry using the FITC apoptosis detection kit. The percentage of apoptotic, dead, necrotic and live cells was compared between ISE6 and ISE6 + SpAR95 cells at each time point by Student’s t-test with unequal variance (p = 0.05; N = 3 biological replicates).(C) The percent of apoptotic ISE6 cells was compared between groups by two-way ANOVA test (∗p < 0.03; N = 3 biological replicates). Representative images of Giemsa-stained cells at 72 h are shown.(D) Tick cell viability after incubation with SpAR92 at different time points. Cell viability was measured by flow cytometry using the Annexin V-fluorescein isothiocyanate (FITC) apoptosis detection kit. The percentage of apoptotic, dead/late apoptotic, necrotic and viable/live cells was compared between infected and uninfected cells by Student’s t-test with unequal variance (p < 0.05; N = 3 biological replicates). Values in red and blue are significantly higher and lower when compared to uninfected ISE6 cells, respectively.(E) Selected samples of ISE6 tick cells infected with A. phagocytophilum NY18 isolate and cultured in L-15B300:R2A (1:1) medium with SpAR92×were examined by microscopy (Zeiss, 10× objective) at 12, 24, 36, 48 and 72 h after treatment in cultures with 1:1, 1:10 and 1:100 dilutions of the SpAR92 inoculum. Red arrows point at the localization of ISE6 cell nuclei. Green arrows point at SpAR92. Black arrows point at lysing ISE6 cells mixed with SpAR92. Bars, 10 μm.(F) Competition between A. phagocytophilum and SpAR92 in ISE6 tick cells. Bacterial growth profile of A. phagocytophilum (Ap) and SpAR92 (Sp) cultured alone (Ap and Sp) or combined (Ap + Sp or Sp + Ap). The ISE6 tick cells were incubated at 31°C with 100 μL/mL of SpAR92 suspension or culture medium alone in 24-well plates for 12 h before infection with 100 μL of semi-purified A. phagocytophilum or culture medium alone and incubated for additional 84 h. Samples (3 wells per time point) were collected every 12 h after A. phagocytophilum infection. A. phagocytophilum DNA levels were determined by msp2 qPCR and normalized against tick 16S rDNA and rpS4 genes. Normalized A. phagocytophilum msp2 Ct-values and SpAR92 CFU/ml were compared by two-way ANOVA test between Ap/Ap + Sp (blue and red lines; ∗∗p < 0.05; N = 3 biological replicates) and Sp/Sp + Ap (green and yellow lines; ∗p < 0.05; N = 3 biological replicates). | PMC10165458 | gr3.jpg |
0.387172 | 9371f633094f471ca4abcd4774a55a80 | Infection of I. scapularis female ticks with A. phagocytophilum and SpAR92 and competition between both bacteria(A) Tick injection.(B) Tick capillary feeding.(C) Tick artificial feeding. Experiments were conducted with A. phagocytophilum Norway isolate and SpAR92 in I. scapularis female ticks. Groups of 10 ticks each (5 ticks only for artificial feeding) were untreated or treated with A. phagocytophilum (Ap) and Ap + SpAR92 (Sp). All ticks survived after each treatment. Groups of 5 ticks were collected and dissected at 24 and 72 h post treatment (72 h only for artificial feeding). An independent experiment was conducted with tick injection containing SpAR92 alone to evaluate bacterial levels in the midgut of untreated ticks at 24 and 72 h after treatment. Salivary glands and/or midgut were extracted from dissected ticks. A. phagocytophilum and SpAR92/indigenous Sphingomonas spp. DNA levels were determined by qPCR targeting msp2 and spt, respectively and normalized against tick 16S rDNA and rpS4 genes. Normalized Ct-values were compared by Student’s t-test with unequal variance (p < 0.05; N = 5 biological replicates) for Sphingomonas between untreated and treated groups (upper graph with red bars in tick injection), for A. phagocytophilum between Ap-treated groups at 24 and 72 h and between Ap-treated and Ap/Sp-treated groups at 72 h, and between Sphingomonas and A. phagocytophilum in Ap/Sp-treated group at 72 h.(D) Tick injection.(E) Tick capillary feeding.(F) Tick artificial feeding. Tendency lines with significant differences between untreated and treated groups at 72 h are shown in blue for A. phagocytophilum (Ap) and in red for SpAR92. A. phagocytophilum and SpAR92 DNA levels were determined by qPCR targeting msp2 and spt, respectively and normalized against tick 16S rDNA and rpS4 genes. Normalized Ct-values were compared between 24 and 72 h or between untreated and treated groups by Student’s t-test with unequal variance (∗p < 0.05; N = 5 biological replicates).(G) Proposed mechanism for competition between Sphingomonas spp. in I. scapularis tick microbiota and A. phagocytophilum. | PMC10165458 | gr4.jpg |
0.425093 | 4f3a5acc72c3480e938ac0231847e80b | Characterization of Franken Sphingomonas(A) The expression of msp4 and hsp70 genes in Franken Sphingomonas were characterized by RT-PCR ΔRn at 30th Cq and compared between Franken Sphingomonas and control SpAR92 by Student’s t-test with unequal variance (p < 0.001; N = 10 biological replicates). Results are represented as ΔRn Franken Sphingomonas to SpAR92 ratio.(B) Flow cytometry showing the presence of MSP4 on the surface of FrankenSphingomonas-MSP4, SpAR92 and A. phagocytophilum (NY18). For flow cytometry, cells were stained with FITC-goat anti-rabbit IgG to visualize MSP4, and the viable cell population was gated according to forward-scatter and side-scatter parameters. The SpAR92 and A. phagocytophilum were included as negative and positive MSP4 controls, respectively. The MFI geometric mean determined by flow cytometry was compared between SpAR92 and A. phagocytophilum or FrankenSphingomonas-MSP4 by Student’s ttest with unequal variance (∗p < 0.001, N = 5 biological replicates).(C) A. phagocytophilum msp2 DNA levels at 72 h after co-infection of ISE6 tick cells with A. phagocytophilum and SpAR92, FrankenSp-MSP4 or FrankenSp-HSP70. DNA levels were normalized to rpS4 (∗∗p < 0.01, N = 4 biological replicates).(D) A. phagocytophilum msp2 DNA levels at 72 h after co-infection of HL60 human cells with A. phagocytophilum and SpAR92, FrankenSp-MSP4 or FrankenSp-HSP70. DNA levels were normalized to β-actin (∗p < 0.05, N = 4 biological replicates).(E) Representative images of immunofluorescence analysis of MSP4 in ISE6 tick cells at 72 h after infection with A. phagocytophilum alone and in combination with SpAR92, FrankenSp-MSP4 or FrankenSp-HSP70. Cytospin preparations were incubated with MSP4 primary antibody (green, conjugated with FITC) and mounted on ProLong Diamond Antifade Mountant with DAPI reagent (blue). The localization of MSP4 protein around tick cells is illustrated for FrankenSphingomonas-MSP4 in a red square. Bars, 10 μm. | PMC10165458 | gr5.jpg |
0.414347 | 1f45cb4629a84ffe97b97b390ca4ce77 | Infection of I. scapularis female ticks with Franken Sphingomonas and A. phagocytophilum(A) Adult female and male ticks were artificially fed with Franken Sphingomonas (producing A. phagocytophilum MSP4 or HSP70) or control blood and incubated for oviposition and hatching of larvae. After oviposition, egg masses were counted under microscopy and DNA extracted from individual egg masses and to identify Franken Sphingomonas by qPCR targeting spt and msp4 or hsp70. Analyzed eggs (laid by 10 different adults for each gene and control) and 100% of the analyzed larvae (N = 30, 10 larvae from 3 different adults for each gene) from adult ticks only artificially fed with Franken Sphingomonas were positive for both spt and msp4 or hsp70. A group of nymphs were incubated for molting to adults and 100% of the analyzed female adults (N = 20) only derived from nymphs with FrankenSphingomonas were positive for both spt and msp4.(B) Larvae of I. scapularis ticks with and without FrankenSphingomonas were fed on uninfected or A. phagocytophilum (NY18)-infected C3H/HeN mice. Eight groups of 5 mice each were inoculated with A. phagocytophilum-infected (N = 20) or uninfected (N = 20) HL-60 cultured cells. Franken Sphingomonas were identified in tick larvae by qPCR targeting spt and msp4 genes. Mice were infested with 30 I. scapularis larvae per mouse. The engorged larvae were held in a humidity chamber for 34 days until molting into nymphs. DNA was extracted from 10 nymphs from each experimental group. Individual nymphs were analyzed by msp2 qPCR for infection with A. phagocytophilum and by spt qPCR for detection of Franken Sphingomonas and indigenous Sphingomonas spp. DNA levels were normalized against tick 16S rDNA and rpS4 genes. Normalized Ct-values were compared between groups by one-way ANOVA test with post-hoc Tukey HSD (https://astatsa.com/OneWay_Anova_with_TukeyHSD/; ∗∗p < 0.01; N = 10 biological replicates).(C) Adult female I. scapularis ticks were in vivo capillary fed with blood collected from A. phagocytophilum-infected mice (N = 10) alone or in combination with SpAR92, FrankenSp-MSP4 or FrankenSp-HSP70. For each treatment, 5 ticks were collected and dissected at 72 h post-feeding and individually analyzed in combined internal organs for A. phagocytophilum (msp2 qPCR) and Sphingomonas/Franken Sphingomonas (spt qPCR) as for in vivo fed ticks. DNA levels were normalized against tick 16S rDNA and rpS4 genes.45,46 Normalized Ct-values were compared between groups by one-way ANOVA test with post-hoc Tukey HSD (https://astatsa.com/OneWay_Anova_with_TukeyHSD/; ∗∗p < 0.01, ∗p < 0.05; N = 5 biological replicates). | PMC10165458 | gr6.jpg |
0.399269 | 0d0ad0d5cf3143e38e2500ffa9cf36cc | Results workflow and conclusionsSummary of the results and mechanisms affected by the interactions between A. phagocytophilum and commensal Sphingomonas or Franken Sphingomonas in tick midgut. | PMC10165458 | gr7.jpg |
0.390306 | 3540e25d6b8941d3acfd46b52c46af76 | Trial profile. aPatients could transfer from GP back to the surgeon at any point in time for any reason. No patients were lost to follow-up or withdrew their consent during follow-up. bPatients received usual care after colon cancer treatment, so there were no transfers from the trial arm. cThese patients had already transferred back to the surgeon in the previous year. | PMC10165489 | djad019f1.jpg |
0.392934 | 193c827049ea45f0ba449bc23d93af8f | Cumulative incidence curves (Aalen-Johansen) for recurrences and deaths according to the intention-to-treat principle. 95% confidence intervals are provided at several points in time (t = 1, 1.5, 2, 2.5, and 3 years of follow-up). | PMC10165489 | djad019f2.jpg |
0.437697 | c67115196908440c80e79b2ce32b759d | Restricted mean duration in each health state over a period of 3 years. | PMC10165489 | djad019f3.jpg |
0.424161 | a35c4a617d6a4cddbe26b1293deccf65 | Wnt/β-catenin signaling in chronically HCV-infected Huh7.5 cells and R4-GFP HCV replicon Huh7 cells after HCV clearance by DAA which induced Wnt/β-catenin signaling and chronic HCV infection-induced PKA/GSK-3β/β-catenin signaling in HCV-infected Huh7.5 cells. A Chronic HCV-infected Huh7.5 cells (day 110) were treated with either DAA or interferon-α (IFN). After the treatment, cell lysates were collected for western blotting with indicated antibodies. UT, untreated. B R4-GFP replicon Huh7 cells were treated with DAA. After the treatment, cell lysates were collected for western blotting with indicated antibodies. Parental, Huh7 cells without HCV replicon. UT, untreated. C Uninfected Huh7.5 control cells were treated with DAA. Cell lysates were collected on day 2 and day 9 after treatment for western blotting with indicated antibodies. UT, untreated. D Chronic HCV-infected Huh7.5 cells d135, d140 and d129 were treated with mTOR inhibitor rapamycin, AKT inhibitor triciribine and PKA inhibitor H89, respectively. After 48 h, cell lysates were collected for western blotting with indicated antibodies. E Huh 7.5 cells were infected with GFP-tagged HCV. Cell lysates were taken at the indicated time points after HCV infection for western blotting with indicated antibodies | PMC10165818 | 12964_2023_1081_Fig1_HTML.jpg |
0.40683 | 47a4346edc774f179e98fbad571da2ab | Both repression of HCV replication and reversion of PKA/GSK-3β/β-catenin pathway by PKA inhibition with H89 in chronic HCV-infected Huh7.5 cells. A Cytotoxicity of H89 after 48 h of treatment in Chronic HCV-infected Huh7.5 cells (d129) was performed by MTT assay. B Chronic HCV-infected Huh7.5 cells (d129) were treated with high doses of H89 (20 and 40 μM). After 48 h, cell lysates were collected for western blotting with indicated antibodies. It is noticed that the internal loading control for western blot analysis are in Fig. 1D. C Chronic HCV-infected Huh7.5 cells (d129) were treated with high doses of H89 (20 and 40 μM). After 48 h, fluorescence microscopy was taken. Scale bar = 25 μm. D Chronic HCV-infected Huh7.5 cells (d168) were treated with low doses of H89 (6 and 8 μM). After 12 days, cell lysates were collected for western blotting with indicated antibodies. E Cell counting assay was performed in chronic HCV-infected Huh7.5 cells treated with low doses of H89 for 12 days | PMC10165818 | 12964_2023_1081_Fig2_HTML.jpg |
0.391645 | d53ee7661bce42d0ba592bbaaece2d04 | Both repression of HCV replicon replication and reversion of PKA/GSK-3β/β-catenin pathway by PKA inhibition with H89 in R4-GFP HCV replicon Huh7 cells. A Cytotoxicity of H89 in R4-GFP HCV replicon Huh7 cells in a concentration-dependent manner by MTT assay. B R4-GFP HCV replicon Huh7 cells were treated with low dose of H89 (8 uM). After 14 days and 25 days, cell lysates were collected for western blotting with indicated antibodies. UT, untreated. C R4-GFP HCV replicon Huh7 cells were treated with low dose of H89 (8 μM). After 14 days and 25 days, fluorescence microscopy was taken. Scale bar = 50 μm. UT, untreated | PMC10165818 | 12964_2023_1081_Fig3_HTML.jpg |
0.454241 | 8e2cb27f571149f4b309eef9cdfaf6b7 | ER stress induction and both repression of HCV replication and reversion of ER stress/PKA/GSK-3β/β-catenin pathway by ER stress inhibitor TUDCA in both chronic HCV-infected Huh7.5 cells and R4-GFP HCV replicon Huh7 cells. A Whole cell lysates were taken from chronic HCV-infected Huh7.5 cells (d40 and d72) and uninfected control cells for western blotting with indicated antibodies. B Chronic HCV-infected Huh7 cells (d163) were treated with TUDCA. After 48 h, cell lysates were collected for western blotting with indicated antibodies. C Whole cell lysates were taken from R4-GFP HCV replicon Huh7 cells and parental cells (without HCV replicon) for western blotting with indicated antibodies. D R4-GFP HCV replicon Huh7 cells were treated with TUDCA. After 96 h, cell lysates were collected for western blotting with indicated antibodies | PMC10165818 | 12964_2023_1081_Fig4_HTML.jpg |
0.433839 | be42a0f4e02342cd8f3faef0e0a6a45e | Dose-dependent inhibition of extracellular HCV infection in Huh7.5 cells by targeting ER stress/PKA/GSK-3β/β-catenin pathway by either TUDCA or H89. Huh7.5 cells were infected with contagious extracellular GFP-tagged HCV virions in medium containing different concentration of H89. After 7 days of infection, cell lysates were taken for western blotting with indicated antibodies (A) and cells were prepared for cytospin slides, stained with DAPI and carried out imaging microscopy (Scale bar = 25 μm) (B). Huh7.5 cells were infected with contagious extracellular GFP-tagged HCV virions in medium containing different concentration of TUDCA. After 7 days of infection, cell lysates were taken for western blotting with indicated antibodies (C) and cells were prepared for cytospin slides, stained with DAPI and carried out imaging microscopy (Scale bar = 25 μm.) (D) | PMC10165818 | 12964_2023_1081_Fig5_HTML.jpg |
0.42972 | b282263888dc4cbc9f2917e573e10fd1 | Schematic diagram of the ER stress/PKA/GSK-3β-dependent Wnt/β-catenin pathway. A Chronic HCV infection activates ER stress/PKA/GSK-3β-dependent Wnt/β-catenin signaling. B Targeting ER stress/PKA/GSK-3β-dependent Wnt/β-catenin pathway by either PKA or ER stress inhibitor both represses HCV replication and reverses Wnt/β-catenin signaling. C Targeting ER stress/PKA/GSK-3β-dependent Wnt/β-catenin pathway by either PKA or ER stress inhibitor both inhibits extracellular HCV infection, probably through inhibition of viral either entry or replication or both | PMC10165818 | 12964_2023_1081_Fig6_HTML.jpg |
0.477605 | 2ee6fac6d8134350a423660a27704ddf | PcTrim inhibits WSSV replication. A Tissue distribution of PcTrim in crayfish at mRNA level. B–D Expression patterns of PcTrim in hemocytes (B), hepatopancreas (C) and the stomach (D), as detected by qRT‒PCR. 18S rRNA was used as the control. qRT‒PCR and western blotting were used to analyze the amounts of WSSV (vp28 was used as a marker of WSSV copy number). The expression levels of VP28 were analyzed in His-Trim injection crayfish (E, J), anti-Trim antibody injection crayfish (F, K) and dsTrim injection crayfish (H, N), and His-Tag, anti-Actin antibody and dsGFP were used as controls. The expression level of PcTrim was measured by qRT‒PCR (G) and western blotting (M) 48 h after dsTrim injection. I Recombinant expression and purification of PcTrim in E.coli. Lane 1, total proteins from E.coli with PcTrim-pET-32a, without ITPG induction; Lane 2, total proteins from E.coli with PcTrim-pET-32a, with ITPG induction; Lane 3, purified recombinant PcTrim. L
PcTrim was detected using the PcTrim polyclonal antibodies. Crayfish were divided into two groups: the groups were injected with either His-Tag or His-Trim, and then, all the crayfish were injected with WSSV (O); two groups of crayfish were injected with either dsGFP or dsTrim, and then, the crayfish were challenged with WSSV after PcTrim-RNAi treatment (P). The survival rate of crayfish was calculated. The asterisk indicates a significant difference, p < 0.05 | PMC10165819 | 12964_2023_1059_Fig1_HTML.jpg |
0.411246 | 2458b81ada2349faac563a1541bd96f7 | PcTrim interacts with VP26. Far western blot was used to screen the interaction between VPs and Trim. Lysates of gills were incubated with His resin containing His-Trim (A, B, C), and then, three antibodies (anti-VP24, anti-VP26, and anti-VP28) were used to detect the presence of VP24, VP26 and VP28. His-Tag was used as negative control. The β-Actin was used as inner protein control. VP24, VP26 and VP28 were detected in each samples. Only VP26 was detected to interact with His-Trim (B). A pull-down assay was used to analyze the interaction between Trim and VP26. His-Trim was first bound to His-resin, and then, the resin was incubated with GST-VP26. After 3 washes with PBS, protein residues were analyzed via SDS‒PAGE (D). The interaction between GST-VP26 and His-Trim (E) or between GST-VP26 and His-Tag (F) was analyzed using the above methods with GST resin or His resin. The co-IP assay was performed using anti-PcTrim and anti-VP26 antibodies and gill lysates from WSSV-infected crayfish. A tube with antiserum-free protein A resin was used as a control (G) | PMC10165819 | 12964_2023_1059_Fig2_HTML.jpg |
0.422742 | c602d31ca309437e9db0e254b6d70985 | PcTrim inhibits WSSV endocytosis in crayfish. The subcellular localization of PcTrim was detected using an immunocytochemical assay (A) and western blot (B). Dil was used to label the cell membrane, and DAPI was used to label the cell nuclei. The role of PcTrim in phagocytosis was studied by analyzing the phagocytosis rate of FITC-labeled VP28. After RNAi of Trim, FITC-labeled VP28 was injected into crayfish. Hemocytes were collected 30 min after VP28 injection (C), and phagocytosis of VP28 by hemocytes was observed via microscopy. D The phagocytosis rate after Trim-RNAi treatment was calculated using the described formula. dsGFP was used as a control. E After blocking Trim via injection with anti-Trim antibody, the rate of VP28 phagocytosis by hemocytes was analyzed with a fluorescence microscope. F The phagocytosis rate after Trim blocked. Anti-actin was used as a control. G Hemocyte phagocytosis observed under a fluorescence microscope after rTrim injection. H The phagocytosis rate after His-Trim injection. The asterisk indicates a significant difference, p < 0.05 | PMC10165819 | 12964_2023_1059_Fig3_HTML.jpg |
0.362442 | 133f1f7c631542959a5e9b2b11839d26 | PcTrim inhibits AP1 translocation from the cytoplasm into the nucleus. CoIP (A) and pull-down (B, C) assays were used to analyze the interaction between Trim and AP1. D The subcellular localization of AP1 was detected by western blot in intestine after WSSV challenge. GAPDH and H3 were used as controls for the cytoplasmic or nuclear proteins, respectively. AP1 translocation into the nucleus in hemocytes was detected in WSSV-challenged crayfish using an immunocytochemical assay. Normal crayfish were used as a negative control. The amount of AP1 localization in the nucleus was determined (E). The subcellular distribution of AP1 was detected by western blotting after injection of anti-Trim (F) or His-Trim (H) antibody in crayfish. Anti-Actin antibody and His-Tag were used as controls. G, I AP1 translocation into the nucleus in hemocytes was detected with an immunocytochemical assay after anti-Trim antibody (G) or His-Trim (I) injection. Anti-Actin antibody and His-Tag were used as controls. The distribution of AP1 in the nucleus was determined (e, g, i). The asterisk indicates a significant difference, p < 0.05 | PMC10165819 | 12964_2023_1059_Fig4_HTML.jpg |
0.397929 | e385c8f1fdc041778b7da053d45f86b4 | AP1 mediates WSSV endocytosis in crayfish. A The efficiency of AP1-RNAi was detected by western blot. B Hemocyte phagocytosis was observed under a fluorescence microscope after AP1-RNAi. C The phagocytosis rate of VP28 was studied after AP1-RNAi. D The purified antibody against AP1 was analyzed by SDS‒PAGE. E Hemocyte phagocytosis observed under a fluorescence microscope after blocking with anti-AP1 antibody. F The phagocytosis rate of VP28 after AP1 blockade. The asterisk indicates a significant difference, p < 0.05 | PMC10165819 | 12964_2023_1059_Fig5_HTML.jpg |
0.452757 | 6eb5809a8dcd4ab3b82bf970624fe352 | PcTrim decreases dynamin expression by inhibiting the activity of AP1. A–D The expression of dynamin in crayfish injected with anti-Trim antibody (A), His-Trim (B), anti-AP1 antibody (C) or dsAP1 (D) was analyzed via qRT‒PCR. Anti-Actin antibody, His-Tag and dsGFP were used as controls. E The dynamin RNAi efficiency was analyzed via qRT‒PCR. F Hemocyte phagocytosis was observed under a fluorescence microscope after dynamin RNAi treatment. G The phagocytosis rate of VP28 after dynamin RNAi treatment. (H) The 5’ untranslated region of dynamin was analyzed using the online Promoter Scan tool. Two AP1 binding sites were found in the genomic regulatory region of dynamin. I A ChIP assay was used to detect the AP1 binding sites in the dynamin promoter. J–M The expression level of IE1 in crayfish injected with anti-Trim antibody J, His-Trim K, anti-AP1 antibody L or dsAP1 M was analyzed via qRT‒PCR. The asterisk indicates a significant difference, p < 0.05 | PMC10165819 | 12964_2023_1059_Fig6_HTML.jpg |
0.42647 | e6c335a0987e4156ac998327dfe8dac5 | Model of the PcTrim-mediated antiviral mechanism. In the early stage of WSSV infection in crayfish cells, Trim, which localizes to the membrane, recognizes the WSSV protein VP26 and binds AP1 to inhibit AP1 entry into the nucleus. Activated AP1 enhances the expression of the phagocytosis-related protein dynamin, a host protein on which WSSV invasion depends, thereby promoting the early replication of WSSV | PMC10165819 | 12964_2023_1059_Fig7_HTML.jpg |
0.441007 | 160af992b49c4d75ae7bd408f2219acd | The changes of Galectin‐9 in CLL patients. (A) Serum levels of Galectin‐9 in CLL and HC detected with ELISA. (B) Levels of Galectin‐9 in CLL patients with different Binet stages. (C) The PFS rate of the early and advanced stage in CLL patients (χ
2 = 18.51, p < .01). (D) ROC curve of Galectin‐9 based on the CLL patients of early stages and advanced stages (AUC = 0.81; 95% CI = 0.712–0.933; p < 0.05; sensitivity = 94.44%; specificity = 68.57%). (E) Comparison of PFS for different Galectin‐9 levels (χ
2 = 8.79, p < 0.05). Compared with the HC group: ##
p < .01. *p < .05, **p < .01. AUC, areas under the curve; CI, confidence interval; CLL, chronic lymphocytic leukemia; ELISA, enzyme‐linked immune sorbent assay; HC, healthy control; PFS, progression‐free survival; ROC, receiver operating characteristic. | PMC10165952 | IID3-11-e853-g001.jpg |
0.474889 | f093eea63a73497893627b17205b7eb5 | Changes of MDSCs in CLL patients. (A–C) Cells were first gated from FSC/SSC, then HLA‐DR−Lin‐1‐ cells were detected. (D, F) To analyze MDSC in CD11b and CD33. Frequency of MDSCs in HC and CLL groups. (E, G) Frequency of MDSCs in CLL patients of different Binet stages. The first picture of FSC/SSC flow plots showing the gating strategy used to identified MDSCs (A, B). Compared with the HC group: ##
p < .01. **p < .01. CLL, chronic lymphocytic leukemia; HC, healthy control; MDSC, myeloid‐derived suppressor cell. | PMC10165952 | IID3-11-e853-g002.jpg |
0.438264 | 33d25b95011a430188e3716b263c6016 | ROC cure and correlation analysis. (A) ROC curve of MDSCs based on the CLL patients of early stages and advanced stages (AUC = 0.816; 95% CI = 0.692–0.939; p < .05; sensitivity = 61.11%; specificity = 91.43%). (B) Combination of Galectin‐9 and MDSCs based on the CLL patients of early and advanced stages (AUC = 0.865; 95% CI: 0.716–0.964; p < .05; sensitivity = 94.44%; specificity = 65.71%). (C) Correlation between Galectin‐9 and MDSCs. (D) Levels of Arg‐1 and iNOS in HC and CLL groups. (E) Levels of Arg‐1 and iNOS in CLL patients of different Binet stages. (F) Correlation between Arg‐1 and MDSCs (r = .39, p < .05). (G) Correlation between iNOS and MDSCs (r = .42, p < .05). Compared with the HC group, ##
p < .01. Compared with Binet A group: △
p < .05, △△
p < .01. Compared with Binet B group: *p < .05. Arg‐1, argininase‐1; AUC, areas under the curve; CI, confidence interval; CLL, chronic lymphocytic leukemia; HC, healthy control; iNOS, inducible nitric oxide synthase; MDSC, myeloid‐derived suppressor cell; ROC, receiver operating characteristic. | PMC10165952 | IID3-11-e853-g003.jpg |
0.43584 | 2ae94366b6064f24a562f9cf14f6a0c2 | Tim‐3 expression in CLL patients. (A, B) Tim‐3 protein expression in HC and CLL groups. (C–E) Tim‐3 expression on the surface of T (CD3+, CD4+, and CD8+) cells in HC and CLL groups, as well as different Binet stages of CLL patients. Compared with the HC group: ##
p < .01, *p < .05, **p < .01. HC, healthy control, CLL, chronic lymphocytic leukemia. | PMC10165952 | IID3-11-e853-g004.jpg |
0.388728 | b2c4b76e46a14b3490f03ade7e93ebfb | Colocalization of NEKL-2 and NEKL-3 with endosomal markers in C. elegans.Colocalization assays were carried out in adult worms expressing either NEKL-2::mKate or NEKL-3::mKate with endosomal markers Prab-5::GFP::RAB-5 or Phyp7::GFP::RAB-7. (A–C, A’–C’, G–I, and G’–I’) Representative confocal images of adult worms expressing either NEKL-3::mKate (A–C and A’–C’) or NEKL-2::mKate (G–I and G’–I’), along with the early endosomal marker Prab-5::GFP::RAB-5. (D–F, D’–F’, J–L, and J’–L’) Representative confocal images of adult worms expressing either NEKL-3::mKate (D–F and D’–F’) or NEKL-2::mKate (J–L and J’–L’) and late endosomal marker Phyp7::GFP::RAB-7. Yellow arrowheads indicate overlap. Scale bar in A = 10 μm for A–L. Scale bar in A’ = 1 μm for A’–L’. (M) Manders’ coefficient was calculated for all the worms with the indicated backgrounds and plotted to determine the fraction of overlap between NEKL-2– or NEKL-3–positive pixels and the indicated markers. Error bars represent the 95% confidence intervals. p-Values were obtained by comparing means using an unpaired t-test: ****p < 0.0001, ***p < 0.001, *p < 0.05; ns, not significant (p > 0.05). Raw data are available in S1 File. | PMC10166553 | pgen.1010741.g001.jpg |
0.451005 | be4a7afa9791482da82c2cdac12fea90 | Effects of NEKL-2 or NEKL-3 depletion on endosomal compartments in C. elegans.(A–C, G–I, M–O) Confocal imaging was used to examine the effects of NEKL-2 (B, H, N) and NEKL-3 (C, I, O) loss relative to wild type (WT; A, G, M) in hyp7 of day-2 adult worms after auxin treatment. Representative images are shown. (A–C) Imaged worms expressed Prab-5::GFP::RAB-5 in the indicated backgrounds. (D–F) The mean intensity (D), vesicle area (E), and the roundness of the puncta (F) were plotted for worms expressing Prab-5::GFP::RAB-5. (G–I) Imaged worms expressed Phyp7::GFP::RAB-7 in the indicated backgrounds. (J–L) The mean intensity (J), vesicle area (K), and the number of vesicles (L) were plotted for worms expressing Phyp7::GFP::RAB-7. (M–O) Imaged worms expressed mScarlet::RAB-11, a marker for recycling endosomes, in the indicated backgrounds. (P–R) The mean intensity (P), vesicle area (Q), and perimeter of the vesicles (R) were plotted for individual worms expressing mScarlet::RAB-11. Area is in square pixels; perimeter is the number of pixels in the boundary of the object. Error bars represent the 95% confidence intervals. p-Values were obtained by comparing means using an unpaired t-test: ****p < 0.0001, ***p < 0.001, *p < 0.05; ns, not significant (p > 0.05). Raw data are available in S1 File. | PMC10166553 | pgen.1010741.g002.jpg |
0.400078 | 205e12868f494f83af69f533f1cdb82c | Effects of NEKL-2 or NEKL-3 depletion on basolateral cargoes in C. elegans.(A) Cross-sectional view of an adult worm depicting the position of the hyp7 syncytium (blue grey) and seam cell syncytium (red). Specific membrane domains of hyp7 are indicated: apical, facing externally directly underneath the cuticle (brown); basal, facing internally (purple); lateral, facing the sides and bottom of the seam cell (green). Dashed lines indicate the medial imaging plane used to acquire the images. (B) Top-down view of the long axis of the worm’s body indicating the positions of the hyp7 and seam cell syncytium along with indicated membranes as in A. (C–E) Representative confocal images of Phyp-7::SMA-6::GFP expression in auxin-treated wild-type (C), nekl-2::aid (D), and nekl-3::aid (E) day-2 adults. (F, G) Representative confocal images of Phyp-7::DAF-4::GFP expression in auxin-treated wild-type (G), nekl-2::aid (H), and nekl-3::aid (I) day-2 adults. Green and purple arrowheads (D,E,G) indicate seam and basal membranes (where detectable), respectively. Note that it is often not possible to identify the precise lateral/basolateral boundaries of hyp7 in the SMA-6::GFP and DAF-4::GFP lines in wild type because of the curved nature of the lateral membrane and because of low levels of these cargos marking the membrane. Scale bar in C = 10 μm for C–E, F, and G. (F, J) Mean intensity values for Phyp-7::SMA-6::GFP (F) and Phyp-7::DAF-4::GFP (J) expression were plotted for individual adults. The two highest datapoints in nekl-3::aid; DAF-4::GFP (3J; 615 and 1233) were omitted for clarity of presentation. Error bars represent the 95% confidence intervals. Statistical significance was determined using a two-tailed, unpaired t-test: **p < 0.01, ****p < 0.0001. Raw data are available in S1 File. | PMC10166553 | pgen.1010741.g003.jpg |
0.420728 | 904d01bf1383416fb9f758124c464afc | Effects of NEKL-2 or NEKL-3 depletion on cargo sorting in C. elegans.(A–C, E–G, and I–J) Representative confocal images of Phyp-7::MIG-14::GFP (A–C) and Phyp-7::TGN-38::GFP (E–G and I–J) expression within hyp7 in auxin-treated wild-type (A, E), NEKL-2::AID (B, F), NEKL-3::AID (C, G), NEKL-2::AID; cup-5 (I), and NEKL-3::AID; cup-5 (J) day-2 adults. Scale bar in A = 10 μm for A–C, E–G, I, and J. (D, H) Mean pixel intensity values of Phyp-7::MIG-14::GFP and Phyp-7::TGN-38::GFP expression for individual worms. Error bars represent the 95% confidence intervals. Statistical significance was determined using a two-tailed, unpaired t-test: ****p < 0.0001; ns, not significant (p > 0.05). Raw data are available in S1 File. | PMC10166553 | pgen.1010741.g004.jpg |
0.434647 | 1a00b07fe1f644d086bf9c80f834a037 | Effects of NEK6 or NEK7 depletion on mannose 6-phosphate receptor trafficking in human cells.(A) siRNA knockdown of NEK6 and NEK7 was validated by western blotting of HeLa cells that were mock-transfected or transfected with oligonucleotides specific for NEK6 (left panel) or NEK7 (right panel). GAPDH was used as the loading control (lower panels). (B–G) Mock-transfected cells (B and enlarged area in C), NEK6 siRNA–transfected cells (D and enlarged area in E), or NEK7 siRNA–transfected cells (F and enlarged area in G) were plated on coverslips and immunostained with antibodies against mannose 6-phosphate receptor (M6PR). (K, L) The mean intensity of M6PR immunostaining (K) and the mean area of M6PR distribution (L) of individual cells in mock-transfected, NEK6 siRNA–transfected, and NEK7 siRNA–transfected cells. (H–J) Saturated and zoomed micrographs demonstrating the distribution and intensity of mannose 6-phosphate receptor immunostaining in mock-transfected (H), NEK6 siRNA–transfected (I), and NEK7 siRNA–transfected cells (J). The dashed lines indicate individual cells. Scale bar in B = 10 μm for B, D, and F; scale bar in C = 10 μm for C, E, and G; scale bar in J = 10 μm for H–J. Statistical significance was determined using Student’s unpaired t-test. Raw data are available in S1 File. | PMC10166553 | pgen.1010741.g005.jpg |
0.401748 | 1b69b0d274324fb0bf53be40a3b6fced | Effects of NEK6 or NEK7 depletion on EEA1-positive sorting endosomes in human cells.(A) siRNA knockdown of NEK6 (left panel) and NEK7 (right panel) in HeLa cells was confirmed by western blotting (B–G) Mock-transfected cells (B and enlarged area in C), NEK6 siRNA–transfected cells (D and enlarged area in E), or NEK7 siRNA–transfected cells (F and enlarged area in G) were plated on coverslips and immunostained with antibodies against the early/sorting endosome marker protein EEA1. Yellow boxes in B, D, and F indicate the area of higher magnification shown in C, E, and G, respectively. (H) The mean size of EEA1-containing endosomes in mock-transfected, NEK6 siRNA–transfected, and NEK7 siRNA–transfected cells. (I) The number of EEA1-containing endosomes in mock-transfected, NEK6 siRNA–transfected, and NEK7 siRNA–transfected cells. Scale bar in B = 10 μm for B, D, and F; Scale bar in C = 5 μm for C, E, and G. Statistical significance was determined using Student’s unpaired t-test. Raw data are available in S1 File. | PMC10166553 | pgen.1010741.g006.jpg |
0.429883 | b6452cf14bdb4a5c87f2c58bda21a484 | Effects of NEK6 or NEK7 depletion on MICAL-L1–containing tubular recycling endosomes in human cells.(A) siRNA knockdown of NEK6 (left panel) and NEK7 (right panel) was validated by western blotting of HeLa cells. (B–D) Mock-transfected cells (B), NEK6 siRNA–transfected cells (C), or NEK7 siRNA–transfected cells (D) were plated on coverslips and immunostained with antibodies against the tubular recycling endosome marker protein MICAL-L1. (E) The surface area of MICAL-L1–containing endosomes in mock-transfected, NEK6 siRNA–transfected, and NEK7 siRNA–transfected cells. Scale bar in D = 10 μm for B–D. Statistical significance was determined using Student’s unpaired t-test. Raw data are available in S1 File. | PMC10166553 | pgen.1010741.g007.jpg |
0.522918 | f6b0907f72584ea0b6e5bb800e44e409 | Sample of anti-adhesion test. | PMC10166752 | DRJ-20-37-g001.jpg |
0.461309 | fb6ccac672254460927a7711e3a11a9a | PCA plot of association test statistics in the WES-based discovery data | PMC10167099 | 431_2022_4779_Fig1_HTML.jpg |
0.454445 | 1efdfcd4e3e543409083ab9808b49a55 | Manhattan plot of results from exome-wide association analysis of 34 BPD and 32 non-BPD infants | PMC10167099 | 431_2022_4779_Fig2_HTML.jpg |
0.431611 | 959543712e03489dad36f4d6e0bfcfc0 | The mutant genes in our study were overlapped with those in previous studies. The genes with red color are core genes | PMC10167099 | 431_2022_4779_Fig3_HTML.jpg |
0.423197 | e0fa0ecf664d4a919ac5544e4e1b3555 | Predicted 3D structure of DDAH1 wild type and mutant. Close-up of the mutation. Wild-type, and mutant side chain are shown in green and red respectively, the rest of the protein is shown in gray | PMC10167099 | 431_2022_4779_Fig4_HTML.jpg |
0.47525 | 945e9a2bdd9b44a983e01d33347459f8 | Venn diagram of risk genes for BPD development reported in four previous studies [16–19] and ours | PMC10167099 | 431_2022_4779_Fig5_HTML.jpg |
0.400817 | 433d9709b7ef4c1f9df9c7f47c034526 | Linkage disequilibrium analysis among the top 10 SNPs associated with BPD | PMC10167099 | 431_2022_4779_Fig6_HTML.jpg |
0.386823 | db612d34eb32431a899f5f124f9dfd89 | GO and KEGG enrichment analysis of differential genes associated with BPD. a GO enrichment analysis biological process, b GO enrichment analysis, cellular component, c GO enrichment analysis molecular function, d KEGG enrichment analysis | PMC10167099 | 431_2022_4779_Fig7_HTML.jpg |
0.426153 | 2528502ece564f4eac1dc2e282c9d417 | Situated of Warsaw and Powsin Culture Park—a research area, b mobile weather station | PMC10167111 | 484_2023_2455_Fig1_HTML.jpg |
0.410603 | 2bb11c4a3c2e4025b1799cc92f52b997 | The frequency of thermal sensation (%) in relation to PET ranges. The latter were determined for Central Europe by Matzarakis and Mayer (1996) | PMC10167111 | 484_2023_2455_Fig2_HTML.jpg |
0.43181 | e79d0b6df83e4ecaaff727f55224d719 | Recreationists’ in the sun and in the shade mean thermal sensation votes (MTSV) in reference to PET categories (a) and on the box plot with statistic characteristics (b) | PMC10167111 | 484_2023_2455_Fig3_HTML.jpg |
0.430305 | 1b5886aa87414ca896bf261248cd271c | Percentage (%) of respondent’s votes for a thermal sensation votes (TSV) and b thermal preferences votes (TPV) during summer 2019 (N = 776) | PMC10167111 | 484_2023_2455_Fig4_HTML.jpg |
0.453833 | baf0e8370d784e379ac8882d1bfb69fd | Mean thermal sensation votes (MTSV) compared PET variables (a). The range of PET variables for neutral sensations (TSV = 0) in summer versus PET variables (b) | PMC10167111 | 484_2023_2455_Fig5_HTML.jpg |
0.473362 | 1be21cb61a9a4acc95b99d6e0ea79daa | Mean preference votes (MPV) for meteorological parameters: a air temperature, b relative humidity, c wind speed, d global solar radiation | PMC10167111 | 484_2023_2455_Fig6_HTML.jpg |
0.508011 | 6e0931a5d0874fc8ac94e8c2e4b4bdfc | Mean thermal preferences votes (MTPV) in relation to PET variables at 1 °C in summer | PMC10167111 | 484_2023_2455_Fig7_HTML.jpg |
0.40974 | 801b5b588c1142538614324999247fa6 | Respondents’ mean thermal preference votes in relation to mean thermal sensations votes in 1 °C PET ranges | PMC10167111 | 484_2023_2455_Fig8_HTML.jpg |
0.413901 | 50688910995642319997e544f3ef6e89 | Percentage (%) votes on thermal sensation (TSV) and thermal preference votes (TPV) in relation to individual respondents’ characteristics: a gender, b age, c type of diseases. TSV: − 3—“cold,” − 2—“cool,” − 1—“slightly cool,” 0—“neutral,” + 1—“slightly warm,” + 2—“warm,” + 3—“hot” | PMC10167111 | 484_2023_2455_Fig9_HTML.jpg |
0.430349 | 7ce7438e2c9a4f80b5e9162dd55c50e5 | Study flow chart. This figure presents the inclusion and exclusion criteria; the patients included in the study were stratified by patients that develop Major Adverse Cardiac Events (MACE). | PMC10167415 | gr1_lrg.jpg |
0.441666 | 6db0933ac3d743678a9069b3000ce487 | Clinical diagnosis of Major Adverse Cardiovascular Events (MACE) and its prevalence by sex and age group. In panel A, we present a Venn diagram with the number of patients suffering from each clinical diagnosis included in MACE. The percentages are calculated based on the number of patients that developed MACE. In panel B, we present the number of patients broken down by age and sex. The bar is filled with the number of patients that developed each clinical diagnosis included in MACE per age group. | PMC10167415 | gr2_lrg.jpg |
0.407562 | 8480198acb5e46ce89a0d42672966947 | An Alluvial plot of the relation between comorbidities and Major Adverse Cardiovascular Events (MACE). This figure illustrates the frequency of comorbid conditions stratified by each clinical diagnosis included in MACE. | PMC10167415 | gr3_lrg.jpg |
0.441653 | b1dc5d21b62e4461992dd3863e45ab5d | Relations among comorbid conditions, systemic complications, and treatments utilised during the hospitalisation due to severe COVID-19. These heat maps with dendrograms illustrate the correlation between comorbid conditions, complications, and treatments. In panel A the colour scale of each cell shows the concordance between each of the evaluated comorbid conditions and the complications developed by the patients. In panels B and C, the colour scale of each cell, respectively, shows the concordance between the previous comorbid conditions or complications reported at hospital admission with the treatments received. Dendrograms show the hierarchical clustering of the nine treatments (y-axis) and the complications or comorbidities. | PMC10167415 | gr4_lrg.jpg |
0.451777 | fed09ddb79764692a4d29e3990099a0f | Multivariate model to identify the risk factors associated with the development of Major Adverse Cardiovascular Events (MACE). Panel A shows the forest plot of the Odds Ratios (OR) obtained in the logistic regression of the different risk factors included in the model. Mean closed circles present ORs, and whiskers represent the 95% confidence interval (95% CI). Panel B shows the cross-validation ROC curves and area under the curve (AUC) of the model developed. | PMC10167415 | gr5_lrg.jpg |
0.467359 | 42451560c0534c02a357f71f3b3e1aac | Relation among the Odd Ratios (OR) obtained in the models to predict Major Adverse Cardiovascular Events (MACE) and 28-day or 90-day mortality. The circles represent the mean of each OR obtained in the model to identify the risk factors for MACE (y-axis) and the model to identify risk factors for 28-day mortality (x-axis, panel A) or 90-day mortality (x-axis, panel B). All error bars represent the 95% confidence interval (95% CI). Horizontal and vertical dotted lines separate the variables as protective or risky, and the diagonal dotted line is a visual reference to assess the association between the ORs. | PMC10167415 | gr6_lrg.jpg |
0.461955 | 07ff9fb1100247568ccb6024dd65bef4 | Oral Fentanyl Self-Administration. |A) Timeline of oral fentanyl self-administration (SA), extinction, and cued-reinstatement testing. Self-administration behavior in male (n=10) and female (n=12) rats including B) active lever presses, C) inactive lever presses, D) total rewards earned, E) total fentanyl consumed, F) total head entries, G) and head entry latency. A separate cohort of male (n=8) and female (n=8) rats underwent between-sessions behavioral economics and hot-plate procedures. H) Total responses at varying fentanyl concentrations. I) Demand curves highlighting intake at zero cost (Q0) and demand elasticity (α). J) Paw lick latency before and after one hour of oral SA at 70 μg/mL fentanyl demonstrates a decreased sensitivity to pain after fentanyl taking in both sexes. In all panels, orange data reflects females and purple data reflects males. *p<0.05, **p<0.01. | PMC10168304 | nihpp-2023.04.27.538613v2-f0001.jpg |
0.503131 | 4bd3c69e13f54b229a98d38d0c0c892b | Individual differences In Self-Administration Behavior and Fentanyl Use Severity |Behavioral distributions for different componenets of fentanyl use severity, including A) fentanyl intake, B) fentanyl seeking (defined as total head entries), C) cue-association (defined as head entry latency), D) escalation (defined as slope of total intake), E) persistence in extinction (defined as total presses during extinction), and F) relapse (defined as total pressed during cued reinstatement). G) Cross-correlation of individual risk severity measures. H) Calculation of individual fentanyl use severity scores. I) Principal component “Bi-Plot” analysis showing high-risk male and female rats in separate quadrants associated with different components of fentanyl use severity. In all panels, orange data reflects females and purple data reflects males. *p<0.05. | PMC10168304 | nihpp-2023.04.27.538613v2-f0002.jpg |
0.372154 | 1d9feb2eee434ba3906191707f6e2741 | USV Evidence for an Affective Opponent Process during Fentanyl SA |A) Automatic classification of 12 USV categories based on variational autoencoder embeddings and contour parameterization. B) Projection of USV categories in 2D space using UMAP to reduce latent feature space. All categories of USVs are used across each phase of fentanyl self-administration, including C) training, D) extinction, and E) reinstatement testing. However, the time course of long 22 kHz USVs differs from all other USV categories during F) training, G) extinction, and H) reinstatement. I) Simplified categorization of USVs into positive and negative affective calls based on well-established frequency criteria. J) Positive affective USVs are used early in each session during drug loading, while negative affective calls are produced later, during maintenance. In panels I and J, red data reflects ~22 kHz and blue data reflects ~50 kHz calls. **p<0.01 | PMC10168304 | nihpp-2023.04.27.538613v2-f0003.jpg |
0.464419 | 1e8829e9aa2b4d0f995d15c9a72f5c4e | Oral Fentanyl SA Has Distinct Positive-Affective Loading and Negative-Affective Maintenance Phases |A) Individual example of estimated brain-fentanyl concentration and B) corresponding cumulative response pattern, together showing distinct loading and maintenance phases. C) Average estimated brain-fentanyl concentration for all males and females on days 5, 10, and 15. D) Corresponding cumulative response pattern for all animals on days 5, 10, and 15. E) Average estimated brain-fentanyl concentration for all animals on all training days and corresponding cumulative response pattern. Loading and maintenance are defined by the elbow of the cumulative response curve, where the rate of responding clearly shifts. F) USV probability density function showing all USVs from all animals. 50 kHz USVs occur during loading, then rapidly shift to 22 kHz USVs which peak concurrent with max drug level. Orange data reflects females and purple data reflects males, while blue data reflects ~50 kHz calls (loading) and red data reflects ~22 kHz calls (maintenance). Green data reflects fentanyl reward deliveries, and pink data reflects estimated brain fentanyl concentration. | PMC10168304 | nihpp-2023.04.27.538613v2-f0004.jpg |
0.494178 | 9a45ba9531784997853333b5a3b6f4e3 | LHb Differentially Processes Fentanyl Cues and Consumption Dependent on Self-Administration Phase |A) For fiber photometry, rats received pGP-AAV1-syn-jGCaMP7f-WPRE into the right LHb, followed by a borosilicate optical fiber. B) Histological verification of injection targeting and fiber placement. C) Example raw trace from the isosbestic control 405 nm LED and calcium signal generating 465 nm LED. D) Processed fluorescence signal (%ΔFF) was used to compare across animals and conditions. E) LHb activity increased to the cued lever press early in training, but this signal diminishes over training, and is only present during maintenance during F) week 2 and G) week 3 and is completely absent during H) reinstatement testing. I) LHb activity decreases during fentanyl consumption (rewarded head entry) early in training, but this signal diminishes over training, and is only present during maintenance during J) week 2 and is completely absent during K) week 3. Blue data reflects LHb activity from loading and red data reflects LHb activity from maintenance. Bootstrap CIα for ERTs = 0.05. | PMC10168304 | nihpp-2023.04.27.538613v2-f0005.jpg |
0.453219 | 223640c891c5451faefe83b74fbf564e | Chest X-ray obtained at admission showing an enlarged cardiac silhouette with a cardiothoracic ratio of 0.60. | PMC10169241 | CRIPE2023-4374552.001.jpg |
0.42212 | 2ac0eb350d5045439ec68a247310d828 | Parasternal short-axis view of transthoracic echocardiograms during the acute illness revealing 8.6-mm pericardial effusion thickness. | PMC10169241 | CRIPE2023-4374552.002.jpg |
0.385756 | 1f6d0a6750234796b2eba5f84ec99aae | Electrocardiography findings on admission indicating sinus tachycardia, PR depression, and concave ST elevation in leads II, III, aVF, and V2–V6 as well as PR elevation and ST depression in aVR and V1. | PMC10169241 | CRIPE2023-4374552.003.jpg |
0.449095 | e5ec2cdba04541b6a791a96e83add0a7 | Contrast-enhanced computed tomography scan of the chest showing a pericardial effusion and left partial atelectasis. | PMC10169241 | CRIPE2023-4374552.004.jpg |
0.482195 | 8f7b4c0265704232b63bf5f2cea124c1 | STROBE flow chart of the study protocol. ICI, immune checkpoint inhibitor; irAE, immune-related adverse event; STROBE, strengthening the reporting of observational studies in epidemiology. | PMC10169823 | fimmu-14-1140677-g001.jpg |
0.414385 | ee9a7e00cf0944eaa7304a16183fc8c8 | Chiauranib exhibits potent antitumor activity against NKTL in vitro and in vivo.NKYS and SNK6 cell lines were treated with DMSO or various concentrations of Chiauranib for 0, 12 h, 24 h, and 48 h, respectively. CCK8 assay was performed in both A, B NKYS and C, D SNK6 cell lines. NKYS and SNK6 cell lines were treated with various concentrations of Chiauranib for 48 h. E, F The cells were further incorporated with EdU and detected with flow cytometry. G, H Cell cycle analysis through PI staining was followed by flow cytometry for NKYS and SNK6 cell lines after treatment. I, J Female 4-week-old NOD/SCID mice was intraperitoneally implanted with SNK6 cells. Three weeks after the inoculation of NKTL, cell tumors were excised and processed for immunostaining using a rat anti-mouse CD31 endothelial marker (shown in red arrow). The MVD of the tumors was determined by counting CD31-positive areas in 10 fields/serial tumor sections from five animals per group (shown in red arrow). | PMC10169864 | 41419_2023_5833_Fig1_HTML.jpg |
0.465902 | d6c57ea7d96d4e4f96c7a61895eb5e62 | Chiauranib induces apoptosis in NKTL cell lines and NKTL xenograft mice.Annexin V-PI staining of A NKYS and B SNK6 cells exposed to Chiauranib. Cells were treated with Chiauranib, Colchicine (5 μM), and DMSO for 24 h and 48 h, respectively, before staining. C Hoechst staining of NKYS and SNK6 cells treated by DMSO or Chiauranib for 48 h, nucleus fragmentations were as shown. Bar = 50 µm. D, E Representative pictures of tumor tissues and tumor weight of NKTL xenograft mice were measured 3 weeks after inoculation (n = 5 per group). F, G Tunnel assay of mice tumor tissue was performed. Bar = 50 µm. | PMC10169864 | 41419_2023_5833_Fig2_HTML.jpg |
0.460587 | 781c210de1e54f8db4627d796e5f385a | Apoptosis induced by Chiauranib in NKTL cell lines was not promoted by the classical mitochondrial apoptosis pathway.A Protein extracts from SNK6 cells were analyzed by immunoblotting for cleaved caspase 8, 9, 3, and β-actin. SNK6 cells were treated with DMSO or Chiauranib for 24 h. B Immunoblotting analysis of mitochondria and cytosol enriched fractions of SNK6 cells treated with Chiauranib or DMSO for 24 h. C, D Annexin V-PI staining of SNK6 cells treated by DMSO or Chiauranib with or without Z-VAD-FMK (50 μM). | PMC10169864 | 41419_2023_5833_Fig3_HTML.jpg |
0.401723 | 22f549f2734d46df817eb621c34940fc | Chiauranib induces apoptosis by regulating the Apoptosis-inducing factor (AIF) in NKTL cell lines.A, B Immunofluorescence staining for AIF (green) and DAPI (blue) of SNK6 cells treated with Chiauranib or DMSO 24 h. Bar = 50 µm. C Immunoblotting analysis of mitochondria and nucleus enriched fractions of SNK6 cells treated with Chiauranib or DMSO for 24 h. COX-IV and Histone serve as loading controls for mitochondrial and cytosolic fractions, respectively. D, E Annexin V-PI staining of SNK6 cells transduced with control shRNA or shRNA targeting AIF. Cells were exposed to Chiauranib or DMSO for 24 h before staining. Efficacy of shRNA is shown in Supplementary Fig. 1A. F Immunoblotting of SNK6 cells treated with Chiauranib or DMSO for detecting the total amount of m-calpain in SNK6 cells. G Activity of m-calpain was detected by Fluorescence calpain activity assay after treatment of Chiauranib or DMSO. The positive control group is labeled as “+”. H, I Flow cytometry detection of Fluo-3 was used to observe the calcium activity after Chiauranib or DMSO treatment in SNK6 cells. | PMC10169864 | 41419_2023_5833_Fig4_HTML.jpg |
0.432125 | cbc5221d4f5143af879a8371ead7d155 | Chiauranib promotes AIF release into the nucleus via the AKT-GSK3B-VDAC pathway, thereby inducing apoptosis.A–D SNK6 cells were treated with Chiauranib or DMSO for 24 h. SNK6 were pretreated with 5 µM SC-79 or 5 mM LiCl for 30 min before Chiauranib treatment. Immunoblotting analysis of the AKT-GSK3B-VDAC pathway was performed. C, D Immunoblotting analysis of mitochondria and nucleus enriched fractions of SNK6 cells. siNC (control) and siVDAC-3 was transfected into SNK6 before experiment. The efficacy of siRNA is shown in Supplementary Fig. 1B. E, F Annexin V-PI staining of SNK6 cells treated with Chiauranib or DMSO for 24 h with or without SC-79, LiCl. | PMC10169864 | 41419_2023_5833_Fig5_HTML.jpg |
0.440445 | ce78d806a83d4b659f7d796828017403 | NKTL lacks BAX expression, which leads to the inability to induce mitochondrial cyt-C released apoptosis.A Immunoblotting analysis of Bax expression in different types of lymphoma cell lines. B, C Immunohistochemistry assay of Bax expression in human NKTL, DLBCL, and PTCL tissue (shown in red arrow). n for independent patient number. D Immunoblotting analysis of caspase pathway in Bax overexpressed SNK6 cells treated with Chiauranib or DMSO. Bax overexpression is shown in Supplementary Fig. 1C. E Immunoblotting analysis of mitochondria and cytosol enriched fractions of SNK6 cells after Bax overexpression. | PMC10169864 | 41419_2023_5833_Fig6_HTML.jpg |
0.445694 | 9bac33dc8080438789732019b16cc5a2 | Chiauranib induces AIF-dependent apoptosis and eliminates tumor growth of NKT lymphoma in vivo.Female 4-week-old NOD/SCID mice were randomly divided into four groups, five mice per group. Each group was intraperitoneally implanted with SNK6 cells transduced with control shRNA or shAIF. Human recombinant IL-2 (42 U/g) was intraperitoneal injected every other day. Mice received Chiauranib or DMSO treatment (0.18 μmol/g, intraperitoneal injection, every other day) for 1 week after inoculation with NKTL cells. A Representative pictures of tumor tissues from four groups of mice. B Tumor weight (g) was measured 3 weeks after the inoculation of NKTL cells after implantation; n = 5 per group. C Protein extracts from mice tumor tissue were analyzed by immunoblotting for the AKT-GSK3B-VDAC pathway. D, E Tunnel assay of mice tumor tissue. Bar = 50 µm. | PMC10169864 | 41419_2023_5833_Fig7_HTML.jpg |
0.417306 | 2b6ade62c96d4ce7aa56245438fc4174 | Chiauranib and L-asparaginase exhibited a synergistic effect of apoptosis in NKTL.A Immunoblotting analysis of SNK6 cells treated with L-asparaginase (0.5 UI/ml). B, C Annexin V-PI staining of SNK6 cells treated with Chiauranib and L-asparaginase, respectively, and combinate. D, E Male 4-week-old NOD/SCID mice injected with SNK6 cells were randomized and divided into four groups respectively (n = 4 in each group). Two weeks later, mice received DMSO, 330 IU/kg of L-asparaginase, 0.18 μmol/g Chiauranib, or a combination of both every other day. Representative pictures and the weight of the tumor were shown. F Chiauranib can eliminate NKTL growth by triggering AIF-dependent apoptosis. The release of AIF from mitochondria is due to (1) mitochondrial m-calpain activation truncates VDAC in a Ca2+-dependent manner, and cleavage of VDAC promotes the release of AIF from mitochondria. (2) The AKT-GSK3β signaling pathway was triggered to potentiate VDAC1 phosphorylation, which contributes to the stability of VDAC1, therefore, allowing AIF to enter the nucleus and induce DNA fragmentation and chromatin condensation. Meanwhile, lack of BAX expression in NKTL leads to the inability to induce mitochondrial cyt-C released apoptosis. L-asparaginase triggered CD95(Fas/Apo-1)-caspase 8-caspase 3 apoptotic pathway in NKTL cells, and the combination of Chiauranib and L-asparaginase exhibited a synergistic effect, suggesting the feasibility of combining these two drugs for effective treatment of NKTL. | PMC10169864 | 41419_2023_5833_Fig8_HTML.jpg |
0.461808 | 03af7d16345e4b55817eefd51f20afce | SPRE device based on BiFeO3-graphene layers. | PMC10170057 | 11468_2023_1867_Fig1_HTML.jpg |
0.475144 | cbe783d0d56f4667b999997111485822 | Reflectance profile of the proposed SPRE sensor. a without BiFeO3 and b with a BiFeO3 layer | PMC10170057 | 11468_2023_1867_Fig2_HTML.jpg |
0.519692 | 008c5f5bf7c04dc88c71e8b89e693856 | Sensitivity optimization. a Sensitivity versus the thickness of silver at dBT = 1 nm and M = 1. b Sensitivity versus the thickness of BiFeO3 at dAg = 60 nm and M = 1. c Sensitivity versus the number of graphene sheets at dAg = 60 nm and dBF = 7 nm. d Sensitivity versus the chemical potential of graphene at dAg = 60 nm, dBF = 7 nm and M = 2 | PMC10170057 | 11468_2023_1867_Fig3_HTML.jpg |
0.482046 | e0365658c1d340c2b123344cbe2b600e | a Reflectance curve of the proposed SPRE sensors for different concentrations. b Sensitivity versus the analyte RIX for the proposed SPRE structure | PMC10170057 | 11468_2023_1867_Fig4_HTML.jpg |
0.487808 | 3c9d889e65ba4bbfb2c00ddc46436555 | Flow chart of the vaccine model with variables and parameters shown in table 1. | PMC10170348 | rsos221277f01.jpg |
0.476175 | a1fdac6c729c416fa51dadbac0ba320a | The proportion of people in each stage over time. | PMC10170348 | rsos221277f02.jpg |
0.50328 | c466d618bb454b3e961000e1437dcddc | The proportion of people in each category of compartment over time. | PMC10170348 | rsos221277f03.jpg |
0.453043 | 2fecca78b5224bffbb0f8e136e2a59d4 | The change of infected fraction over time. (a) For all four stages. (b) For I2 and I3 only. | PMC10170348 | rsos221277f04.jpg |
0.413061 | 8f6824c92e144655a61421be8abca482 | The change of Re(t). | PMC10170348 | rsos221277f05.jpg |
0.448613 | 1691dc20695443c1ac4f6cb7fa4261ce | Changes in infected fraction I(t)/N for different σ−1, and values used for other parameters are shown in table 1. | PMC10170348 | rsos221277f06.jpg |
0.483657 | 7abb3993b7a442ea88529e0d3341ae16 | Changes in infected fraction I(t)/N for different ω−1 and ω′−1, and values used for other parameters are shown in table 1. | PMC10170348 | rsos221277f07.jpg |
0.417906 | decf5c8b13334fccab3149b34ce6aed9 | Changes in infected fraction I(t)/N for different ϵ, and values used for other parameters are shown in table 1. | PMC10170348 | rsos221277f08.jpg |
0.461468 | 922699fc63984db283405c6154e43963 | Changes in infected fraction I(t)/N for different ϵ′, and values used for other parameters are shown in table 1. | PMC10170348 | rsos221277f09.jpg |
0.426406 | bc40af5e724f41599a7457b30e082122 | Changes in infected fraction I(t)/N for different γ−1, and values used for other parameters are shown in table 1. | PMC10170348 | rsos221277f10.jpg |
0.449521 | b1e03a4d6c0c457181ade4ceca793f7c | Changes in infected fraction I(t)/N for different Rc, and values used for other parameters are shown in table 1. | PMC10170348 | rsos221277f11.jpg |
0.474003 | 1e328596b5e04c668b49df10933d0452 | Arthroscopic-assisted latissimus dorsi tendon transfer was performed in the lateral decubitus position. A 5-cm incision was made along the anterior (axillary) border of the scapula. | PMC10170606 | 10.1177_23259671231160248-fig1.jpg |
0.404541 | 10e0302ab00041e797c7492636240f26 | Deletion of Wls in Col1a1-expressing cells protects BM HSCs from TBI-mediated oxidative stress and senescence. Four-week-old Wlsfl/fl and Col-Cre;Wlsfl/fl mice were exposed to sub-lethal TBI (5 Gy), and (A) the BM frequency of HSCs and their numbers positive for (B) MitoSox, (C) C12FDG, or (D) p16INK4a were evaluated by flow cytometry 4 weeks post-TBI (n = 11). The p values were determined by unpaired Student’s t-test. | PMC10187694 | AD-14-3-919-g1.jpg |
0.406279 | e2cc9bec8e50482ab72a98801684b876 | Ablation of Wls in Col1a1-expressing cells inhibits TBI-mediated skewing of BM HSCs toward myeloid progenitor and lineage and protects the colony forming potential of HPCs. Four-week-old Wlsfl/fl and Col-Cre;Wlsfl/fl mice were exposed to sub-lethal TBI, and at 4 weeks after TBI, the BM numbers of (A) GMP, (B) CMP, (C) MEP, and (D) CLP cells were determined by flow cytometry (n = 7). At the same time post-TBI, the proportions of (E) circulating granulocytes (positive to Gr-1), (F) monocytes (to CD11b), (G) T cells (to CD3), and (H) B cells (to B220) were flow cytometrically determined in PB (n = 7). BM HPCs were isolated from Wlsfl/fl and Col-Cre;Wlsfl/fl mice 4 weeks post-TBI and cultured in methylcellulose-based medium. After 12 days of incubation, the numbers of (I,J) CFU-GM, (K) BFU-E, and (L) CFU-GEMM were counted (n = 6). Photograph in panel I show a representative result from six different samples. The p values were determined by unpaired Student’s t-test. | PMC10187694 | AD-14-3-919-g2.jpg |
0.417487 | 54e42260000d42a19234d04b3c669c8c | Ablation of Wls in Col1a1-expressing cells improves donor cell repopulation, BM engraftment, and lineage distribution of HSCs in lethally irradiated transplant recipients and protects recipient survival. (A) Scheme illustrating competitive and serial transplantation of BM HSCs or BM cells into recipients exposed to lethal TBI (10 Gy). (B) Long-term competitive repopulating activity of donor cells in the recipients of serial transplantation was determined by flow cytometry (n = 7). (C) Donor cell engraftment was assessed by measuring the number of BM HSCs in the 1° TP recipients 5 months post-transplantation using a flow cytometric analysis (n = 7). (D) Levels of C12FDG activity and p16INK4a expression in donor-derived HSCs in the 1° TP recipients were measured after the removal of lineage cells by magnetic cell sorting (n = 9). (E and F) The proportions of circulating, donor cell-derived cells of the myeloid and lymphoid lineages were evaluated in PB from the 1° TP recipients 3 months post-transplantation (n = 9). (G) Mice exposed to lethal TBI received HSC transplants isolated from the BM of the 1° TP recipients, and the survival rate was monitored for up to 12 months post-transplantation (n = 10). The p values were determined by unpaired Student’s t-test. | PMC10187694 | AD-14-3-919-g3.jpg |
0.438215 | cd5b0a919b2b46cca28c08fe22c33ec2 | Deletion of Wls from Col1a1-expressing cells does not affect Wls expression or the secretion and senescence of HSCs in the spleens of TBI-exposed mice. Four-week-old Wlsfl/fl and Col-Cre;Wlsfl/fl mice were exposed to sub-lethal TBI, and (A) splenic Wls mRNA and (B) Wnt3a and Wnt5a protein levels in spleen supernatants were determined 4 weeks post-TBI by qRT-PCR and ELISA, respectively (n = 6). At the same time post-TBI, (C) the number of HSCs and (D) MitoSox- or (E) C12FDG-positive HSCs in the spleens of those mice were determined by flow cytometry (n = 5). Col1a1-Cre activity was determined in (F) the trabecular and cortical zones of the femur and (G) the spleens of mutant and control mice 4 weeks post-TBI. The representative images in panel (F) show regions stained with X-gal (blue), which indicate the active Cre recombinase sites in the sections. Here, the images exhibiting the X-gal-specific intensity at average level among five different samples were represented. The p values in panels A and B were determined by unpaired Student’s t-test. The p values in panels C-E were calculated using unpaired non-parametric Wilcoxon t-test. ns, not significant. | PMC10187694 | AD-14-3-919-g4.jpg |
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