Summary statistics for Single SNP GWAS

Summary statistics for Single SNP GWAS for for blood lipid traits (high-density lipoprotein (HDL), low-density lipoprotein (LDL), plasma concentrations of total cholesterol (TC) and triglycerides (TG) in R Data file

Additional file 1 of Implementing personalised care planning for older people with frailty: a process evaluation of the PROSPER feasibility trial

Additional file 1: Observation Template. Process Evaluation of Personalised Care Planning (PCP) for Older Adults (OA) with Frailty

Summary statistics for Regional Heritability Mapping

Summary statistics for Regional Heritability Mapping method for blood lipid traits (high-density lipoprotein (HDL), low-density lipoprotein (LDL), plasma concentrations of total cholesterol (TC) and triglycerides (TG) in R Data file

<i>In vivo</i> effects of cabozantinib treatment in E98 xenografts.

<p>Panels A and B show representative examples of IHC for the hypoxia marker MCT4 in control and cabozantinib-treated tumor bearing animals. Hypoxia in compact tumor regions is significantly increased after treatment (Students <i>t</i>-test, p = 0.003, panel C). D and E show examples of Ki67 stainings in compact tumor areas. Proliferation indices were significantly different in these regions (Students <i>t-</i>test p = 0.04), but no difference was detected in diffuse tumor areas (panel F). Panels G and H show representative examples of GLUT-1 vessel staining. Automated quantification revealed no differences between vessel densities of diffuse tumor areas in control vs treated mice (I). Numbers of CD34-positive vessels were lower in cabozantinib treated mice (see panels J and K, arrows point at blood vessels), but these data were not quantified because vessels without CD34 expression were also observed in these mice. L: Western blot analysis of protein extracts (50 µg protein/lane), derived from cabozantinib-treated xenografts reveals a substantial, though not complete, reduction of c-MET phosphorylation. As a loading control, γ-tubulin was included. Immunohistochemistry for phospho-c-MET (Y1234/1235) also shows the presence of phosphorylated c-MET in treated animals, as visualized in panel K. Size bars: A–B 2 mm, D–E 100 µm, G, H, J, K 200 µm,</p

Cabozantinib prolongs survival of mice bearing orthotopic E98- xenografts.

<p>Mice were treated with 100 mg/kg cabozantinib from day 12 post tumor inoculation, when tumor was detected via abnormalities in T2 images (see panel A for a representative example). B) Survival curves for placebo (n = 10) and cabozantinib (n = 10) treated animals. Note that, for ethical reasons, mice were sacrificed when excessive weight loss and signs of neurological dysfunction occurred. Median survival was significantly different between the groups (20 and 32 days respectively, log rank test, <i>p</i><0.0001). C) Representative examples of T1-weighted MRI of control (upper row) and treated (lower row) E98 bearing animals before (pre) and 2–3 minutes after (post) Gd-DTPA injection. [Post-pre]/pre represents subtracted images. Note the complete loss of contrast enhancement in treated animals. Panel D shows H&E staining of sections, corresponding to the slices shown in the MR images. Bars: overviews 2 mm, zoom 200 µm.</p

<i>In vitro</i> effects of Cabozantinib on c-MET and VEGFR2 signaling.

<p>Panel A shows a Western blot of E98NT cell extracts (20 µg per lane) treated for 30 minutes with different concentrations of cabozantinib as indicated. Protein extracts were analyzed for c-MET, phospho-c-MET, AKT, and ERK1/2, using α-tubulin as a loading control. B) MTT assays were done to determine the IC₅₀ concentration of cabozantinib on E98NT cells. Experiments were performed at least in triplicate. C) Effects of cabozantinib on cell migration. Shown are representative examples of DAPI-stained spheroids after 24 hr incubation with indicated concentrations. Number of outgrowing and migrating cells per spheroid are shown in panel D (***: p<0.001). Number of migrating cells were significantly different between groups (one-way ANOVA, p<0.0001). Post-hoc Tukey's Multiple Comparison Test revealed significant differences groups as indicated (***: p<0.001). E) Western blot of cell lysates of E98NT and HUVEC extracts, treated with 10 ng/ml VEGF with or without cabozantinib, and stained for VEGFR2, phospho-VEGFR2 and α-tubulin as an internal control. Note the absence of VEGFR2 in E98NT cells. F) Western blot of treated E98NT cell extracts with the anti-apoptotic antibody U1-70. Control sample consists of Jurkat cells treated with anisomycin.</p

c-MET is activated in E98 xenografts.

<p>Panel A shows a Western blot containing protein extracts of different xenografts as indicated (40 µg/lane) and stained with a pan and an Y1234/1235 phosphorylated (P-) c-MET specific antibody. As a loading control, γ-tubulin was included. Immunohistochemical analysis reveals prominent c-MET expression and activation in orthotopic E98 xenografts (C–F). Gross appearances of an E98 tumor are shown in C and E, while D and F show magnifications of the boxed areas in C and E. The H&E section in B illustrates the diffuse nature of these tumors, arrows pointing at white matter tracts and comparison with D shows homogeneous expression of c-MET by tumor cells. Arrow in E points at diffuse infiltrative tumor cells in white matter with activated c-MET, while the arrowhead points at a more compact paraventricular tumor area. The inset in E represents an area with compact leptomeningeal growth partly positive for activated c-MET. The pictures shown are representative for this xenograft model. Size bars: B, D, F 200 µm; C 1 mm and E 500 µm.</p

Additional file 13: of Exploration of haplotype research consortium imputation for genome-wide association studies in 20,032 Generation Scotland participants

GS_HRC_imputed_Waist_Hip_Ratio_significant_SNPS. (XLSX 8 kb

Manželské mýty

Phenotype heritabilities. Figure S2. Miami plot for height. Figure S3. Miami plot for BMI. Figure S4. Miami plot for waist circumference. Figure S5. Miami plot for waist-to-hip ratio. Figure S6. Miami plot for body fat percentage. Figure S7. Miami plot for diastolic blood pressure. Figure S8. Miami plot for creatinine. Figure S9. Miami plot for urea. Figure S10. Miami plot for fasting glucose (all individuals included). Figure S11. Miami plot for fasting glucose (excluding diabetics and measurements of >7 mmol/L). Figure S12. Miami plot for HDL cholesterol. Figure S13. Miami plot for total cholesterol. Figure S14. Miami plot for total cholesterol adjusted for statin use. Figure S15. QQ plots for all traits analysed. Figure S16. Comparison of effect sizes for GUGC top hits in the GS:SFHS EHR analysis. (PDF 2160 kb

Functional consequences of variants in the <i>SERPINA6/A1</i> locus significantly associated with morning plasma cortisol in GWAMA, and of the Leuven variant, in CROATIA-Korcula.

a<p>Data for total cortisol is from the whole Croatia-Korcula sample, n = 898.</p>b<p>Samples selected for measured free cortisol assay were age and sex matched homozygotes at rs12589136.</p>c<p>adjusted for age, sex, and first three principal components, using kinship matrix derived from GWAS data.</p><p>Data are geometric mean (95% CI)[n]. Cortisol values are nmol/L, CBG µmol/L, cortisol binding activity nmol/L, and α1-antitrypsin g/L. RCL = reactive centre loop.</p