Publications

COUP-TFII is a central nuclear hormone receptor that tightly regulates the expression of numerous target lipid metabolism genes in vertebrates. However, it remains unclear how COUP-TFII itself is transcriptionally controlled since studies with its promoter and upstream region fail to recapitulate the gene's liver expression. In an attempt to identify liver enhancers in the vicinity of COUP-TFII, we employed a comparative genomic approach. Initial comparisons between humans and mice of the 3470-kb gene-poor region surrounding COUP-TFII revealed 2023 conserved noncoding elements. To prioritize a subset of these elements for functional studies, we performed further genomic comparisons with the orthologous pufferfish (Fugu rubripes) locus and uncovered two anciently conserved noncoding sequences (CNS) upstream of COUP-TFII (CNS-62kb and CNS-66kb). Testing these two elements using reporter constructs in liver cells (HepG2) revealed that CNS-66kb, but not CNS-62kb, yielded robust in vitro enhancer activity. In addition, an in vivo reporter assay using naked DNA transfer with CNS-66kb linked to luciferase displayed strong reproducible liver expression in adult mice, further supporting its role as a liver enhancer. Together, these studies further support the utility of comparative genomics to uncover gene regulatory sequences based on evolutionary conservation and provide the substrates to better understand the regulation and expression of COUP-TFII.

This study examines the relationships that exist between social isolation, support, and capital and nutritional risk in older black and white women and men. The paper reports on 1000 community-dwelling older adults aged 65 and older enrolled in the University of Alabama at Birmingham (UAB) Study of Aging, a longitudinal observational study of mobility among older black and white participants in the USA. Black women were at greatest nutritional risk; and black women and men were the groups most likely to be socially isolated and to possess the least amounts of social support and social capital. For all ethnic-gender groups, greater restriction in independent life-space (an indicator of social isolation) was associated with increased nutritional risk. For black women and white men, not having adequate transportation (also an indicator of social isolation) was associated with increased nutritional risk. Additionally, for black and white women and white men, lower income was associated with increased nutritional risk. For white women only, the perception of a low level of social support was associated with increased nutritional risk. For black men, not being married (an indicator of social support) and not attending religious services regularly, restricting activities for fear of being attacked, and perceived discrimination (indicators of social capital) were associated with increased nutritional risk. Black females had the greatest risk of poor nutritional health, however more indicators of social isolation, support, and capital were associated with nutritional risk for black men. Additionally, the indicators of social support and capital adversely affecting nutritional risk for black men differed from those associated with nutritional risk in other ethnic-gender groups. This research has implications for nutritional policies directed towards older adults.