Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

A higher dietary ratio of long-chain omega-3 to total omega-6 fatty acids for prevention of COX-2-dependent adenocarcinomas

Compelling evidence that daily low-dose aspirin decreases risk for a number of adenocarcinomas likely reflects the fact that a modest but consistent inhibition of cyclooxygenase-2 (COX-2) activity can have a meaningful protective impact on risk for such cancers. The cancer-promoting effects of COX-2 are thought to be mediated primarily by prostaglandin E2 (PGE2), synthesized from arachidonic acid. The long-chain omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), abundant in many fatty fish, can interfere with the availability of arachidonate to COX-2 by multiple complementary mechanisms; moreover, the PGE3 produced by COX-2 from EPA is a competitive inhibitor of the receptors activated by PGE2. These considerations have given rise to the hypothesis that a high dietary intake of EPA/DHA, relative to omega-6 (from which arachidonate is generated), should lessen risk for a number of adenocarcinomas by impeding PGE2 production and activity - while not posing the risk to vascular health associated with COX-2-specific nonsteroidal antiinflammatory agents. Analyses that focus on studies in which the upper category of fish consumption (not fried or salt-preserved) is 2 or more servings weekly, and on studies that evaluate the association of long-term fish oil supplementation with cancer risk yields a number of findings that are consistent with the hypothesis. Further studies of this nature may help to clarify the impact of adequate regular intakes of long-chain omega-3 on cancer risk, and perhaps provide insight into the dose-dependency of this effect

Effects of dietary chromium polynicotinate supplementation on performance, fat deposition and plasma lipids of broiler chickens

The present study was conducted to determine the effect of chromium polynicotinate supplementation on performance, fat deposition and plasma lipids of broiler chickens. A total of 540 male broiler chicks (Cobb 500) were allotted to 6 dietary treatments. The dietary chromium polynicotinate levels were 0 (Control), 250, 500, 750, 1000 or 1250 &mu;g/kg, respectively. At 10-28 days of age (grower phase), the 500 &mu;g/kg concentration of chromium polynicotinate supplementation had a beneficial effect on feed intake and body weight gain of broilers (P<0.05). At 29-42 days of age (finisher phase), feed conversion ratio was decreased (P<0.05) in broilers fed with chromium polynicotinate supplement at levels of 250, 750, 1000 or 1250 &mu;g/kg. Chromium polynicotinate did not affect the abdominal fat pad deposition. The results indicated that the 500 &mu;g/kg level of chromium polynicotinate supplement decreased the plasma cholesterol concentration in the finisher phases. The chromium concentrations of 1000 and 500 &mu;g/kg were more effective at grower and finisher phases, respectively (P<0.05). Plasma triglyceride was not affected by dietary chromium concentration. The results from this study suggest that supplementation of chromium polynicotinate improved growth performance and influenced blood cholesterol concentrations, but in this respect, there was not dose related effects

Application of zebrafish oculomotor behavior to model human disorders

To ensure high acuity vision, eye movements have to be controlled with astonishing precision by the oculomotor system. Many human diseases can lead to abnormal eye movements, typically of the involuntary oscillatory eye movements type called nystagmus. Such nystagmus can be congenital (infantile) or acquired later in life. Although the resulting eye movements are well characterized, there is only little information about the underlying etiology. This is in part owing to the lack of appropriate animal models. In this review article, we describe how the zebrafish with its quick maturing visual system can be used to model oculomotor pathologies. We compare the characteristics and assessment of human and zebrafish eye movements. We describe the oculomotor properties of the zebrafish mutant belladonna, which has non-crossing optical fibers, and is a particularly informative model for human oculomotor deficits. This mutant displays a reverse optokinetic response, spontaneous oscillations that closely mimic human congenital nystagmus and abnormal motor behavior linked to circular vection