University of Utah

About: University of Utah is a education organization based out in Salt Lake City, Utah, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 52894 authors who have published 124076 publications receiving 5265834 citations. The organization is also known as: The U & The University of Utah.

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.

Family Acceptance in Adolescence and the Health of LGBT Young Adults

Abstract: ISSUE: The role of family acceptance as a protective factor for lesbian, gay, bisexual, and transgender (LGBT) adolescents and young adults has not been established. METHODS: A quantitative measure with items derived from prior qualitative work retrospectively assessed family accepting behaviors in response to LGBT adolescents' sexual orientation and gender expression and their relationship to mental health, substance abuse, and sexual risk in young adults (N= 245). FINDINGS: Family acceptance predicts greater self-esteem, social support, and general health status; it also protects against depression, substance abuse, and suicidal ideation and behaviors. CONCLUSIONS: Family acceptance of LGBT adolescents is associated with positive young adult mental and physical health. Interventions that promote parental and caregiver acceptance of LGBT adolescents are needed to reduce health disparities.

Asset Growth and the Cross-Section of Stock Returns

Abstract: We test for firm-level asset investment effects in returns by examining the cross-sectional relation between firm asset growth and subsequent stock returns. As a test variable, we use the year-on-year percentage change in total assets. Asset growth rates are strong predictors of future abnormal returns. Asset growth retains its forecasting ability even on large capitalization stocks, a subgroup of firms for which other documented predictors of the cross-section lose much of their predictive ability. When we compare asset growth rates with the previously documented determinants of the cross-section of returns (i.e., book-to-market ratios, firm capitalization, lagged returns, accruals, and other growth measures), we find that a firm's annual asset growth rate emerges as an economically and statistically significant predictor of the cross-section of U.S. stock returns.

The prevalence of pituitary adenomas: a systematic review.

Abstract: BACKGROUND Pituitary adenomas display an array of hormonal and proliferative activity. Once primarily classified according to size (microadenomas, < 1 cm; macroadenomas, ≥ 1 cm), these tumors are now further classified according to immunohistochemistry and functional status. With these additional classifications in mind, the goals of the current study were to determine the prevalence of pituitary adenomas and to explore the clinical relevance of the findings. METHODS The authors conducted a metaanalysis of all existing English-language articles in MEDLINE. They used the search string (pituitary adenoma or pituitary tumor) and prevalence and selected relevant autopsy and imaging evaluation studies for inclusion. RESULTS The authors found an overall estimated prevalence of pituitary adenomas of 16.7% (14.4% in autopsy studies and 22.5% in radiologic studies). CONCLUSIONS Given the high frequency of pituitary adenomas and their potential for causing clinical pathologies, the findings of the current study suggest that early diagnosis and treatment of pituitary adenomas should have far-reaching benefits. Cancer 2004. © 2004 American Cancer Society.

Intrinsic dynamics of an enzyme underlies catalysis

Abstract: A unique feature of chemical catalysis mediated by enzymes is that the catalytically reactive atoms are embedded within a folded protein. Although current understanding of enzyme function has been focused on the chemical reactions and static three-dimensional structures, the dynamic nature of proteins has been proposed to have a function in catalysis. The concept of conformational substates has been described; however, the challenge is to unravel the intimate linkage between protein flexibility and enzymatic function. Here we show that the intrinsic plasticity of the protein is a key characteristic of catalysis. The dynamics of the prolyl cis-trans isomerase cyclophilin A (CypA) in its substrate-free state and during catalysis were characterized with NMR relaxation experiments. The characteristic enzyme motions detected during catalysis are already present in the free enzyme with frequencies corresponding to the catalytic turnover rates. This correlation suggests that the protein motions necessary for catalysis are an intrinsic property of the enzyme and may even limit the overall turnover rate. Motion is localized not only to the active site but also to a wider dynamic network. Whereas coupled networks in proteins have been proposed previously, we experimentally measured the collective nature of motions with the use of mutant forms of CypA. We propose that the pre-existence of collective dynamics in enzymes before catalysis is a common feature of biocatalysts and that proteins have evolved under synergistic pressure between structure and dynamics.