c case-control, cross-sectional, and longitudinal analyses the investigators will determine if these putative diabetes alleles are associated with incident and prevalent diabetes, with obesity and weight gain, with hyperinsulinemia in non-diabetic individuals with the presence of an adverse cardiovascular risk factor profile, and with atherosclerosis progression and cardiovascular disease incidence over 12 years of follow up. The investigators will assess how behavioral and environmental factors such as obesity, diet, and physical activity, influence the expression of genetically conferred risk. Strength of this proposal include the close collaboration between clinical, epidemiologic, and laboratory researchers, a wealth of prospectively collected data from an NIH sponsored study, and a sample size large enough to detect modest gene effects and to investigate gene-gene and gene-environmental interactions. Most important, this study will provide unique information on the expression of diabetes susceptibility genes in the general population and possibly suggest genetic explanations for the excess prevalence of type 2 diabetes and obesity in African Americans.

The Tat gene of human immunodeficiency virus (HIV) plays a central role in the activation and life cycle of HIV. Tat exerts its effects at the level of transcriptional initiation and elongation. We have previously reported the direct physical interaction between the HIV-1 Tat protein and the basal transcription factor, TBP/TFIID. Affinity chromatography demonstrated that wild type Tat, but not a transactivation mutant of Tat, was capable of depleting TBP/TFIID from cell extracts. These experiments represented the first demonstration of a basal transcription factor that binds, in an activation-dependent manner, to Tat. We now report that the Tat-TBP interaction can be detected in HIV-1-infected cells. The domain of TBP interacting with Tat has been mapped from amino acids 163 to 196 using deletion and site-specific mutants of TBP. This domain of TBP, which inc