36 research outputs found
Genomes of Helicobacter pylori prophages
Nearly 20% of the Helicobacter pylori genomes carry prophages genes. Recently we were able to clearly differentiate four populations of prophages according to geographical origin of host strain. Interestingly we were able to discriminate between Northern Europe and Southern Europe using a phage sequence typing based on 2 prophage genes of H. pylori (integrase and holin) but present in only a minority of strains.info:eu-repo/semantics/publishedVersio
Reaction forces of laminated glass windows subject to blast loads
Several blast trials on laminated glass windows have been performed in the past, using both full field 3D Digital Image Correlation and strain gauges located on the supporting structure to collect information on the glass pane behaviour. The data obtained during three blast experiments were employed to calculate reaction forces throughout the perimeter supports both before and after the fracture of the glass layers. The pre-crack experimental data were combined with finite element modelling results to achieve this, whilst solely experimental results were employed for post-cracked reactions. The results for the three blast experiments were compared to identify similarities in their behaviour. It is intended that the results can be used to improve the existing spring–mass systems used for the design of blast resistant windows
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Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes
OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis
The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study
Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe
A comparison of cyclosporine A and cyclosporine G in a rabbit heterotopic cardiac transplant model: graft outcome and histological findings
Cervical heterotopic heart transplants
were performed on 20 male New Zealand white
rabbits comprising 4 treatment groups. Animals in each
group were injected daily via the marginal ear vein
and received one of the following regimes: Cyclosporine
A, 10 mglkglday; Cyclosporine G, 15 mglkglday;
cremophor-El, 3mllday; or normal saline. Measurement
of 24 hour trough blood concentrations revealed
no significant differences between the average
concentrations of Cyclosporine A and Cyclosporine
G. Animals were examined daily and the cervical
allografts assessed by palpation for viabilitylrejection.
The duration of the study ended for each animal
when the graft stopped beating at which time the animals
was euthanized and the transplanted heart and
native kidneys harvested and processed for light
microscopy evaluation of rejection and drug toxicity,
respectively.
Graft survival in the Cyclosporine A group
significantly surpassed that seen in the Cyclosporine G
group as well as the control groups, whereas in animals
treated with Cyclosporine G, graft survival was not
different from controls. In the native kidney, there were
no differences in glomerular tuft area or volume density
amongst drug-treated or control animals. In contrast,
tubule atrophy and interstitial fibrosis were markedly
greater in Cyclosporine A-treated vs Cyclosporine Gtreated
animals.
The results of this study indicate that, whereas
Cyclosporine G is less nephrotoxic than Cyclosporine A,
given equivalent blood concentrations Cyclosporine A
delays rejection of a cardiac allograft significantly
longer than Cyclosporine G in this animal species