ASSOCIATION OF SERUM VITAMIN D AND KEY CO-NUTRIENTS IN RELATION TO HYPERTENSION: A CROSS-SECTIONAL STUDY BASED ON NHANES DATA

Observational studies demonstrate strong associations between deficient serum vitamin D (25(OH)D) levels and cardiovascular disease. To further examine the association between vitamin D and hypertension (HTN), data from the 2003-2006 National Health and Nutrition Examination Survey were analyzed to assess whether the association between vitamin D and HTN varies by sufficiency of key co-nutrients necessary for metabolic vitamin D reactions to occur. Logistic regression results demonstrate independent effect modification by calcium, magnesium, and vitamin A on the association between vitamin D and HTN. Among non-pregnant adults with adequate renal function, those with low levels of calcium, magnesium, and vitamin D levels had 1.75 times the odds of HTN compared to those with sufficient vitamin D levels (p = <0.0001). Additionally, participants with low levels of calcium, magnesium, vitamin A, and vitamin D had 5.43 times the odds of HTN compared to those with vitamin D sufficiency (p = 0.0103).

STRUCTURE AND FUNCTION OF THE GROUP III CHAPERONINS, A UNIQUE CLADE OF PROTEIN FOLDING NANOMACHINES

The survival and descent of cells is universally dependent on maintaining their proteins in a properly folded condition. It is widely accepted that the information for the folding of the nascent polypeptide chain into a native protein is encrypted in the amino acid sequence, and the Nobel Laureate Christian Anfinsen was the first to demonstrate that a protein could spontaneously refold after complete unfolding. However, it became clear that the observed folding rates for many proteins were much slower than rates estimated in vivo. This led to the recognition of required protein-protein interactions that promote proper folding. A unique group of proteins, the molecular chaperones, are responsible for maintaining protein homeostasis during normal growth as well as stress conditions. Chaperonins (CPNs) are ubiquitous and essential chaperones. They form ATP-dependent, hollow complexes that encapsulate polypeptides in two back-to-back stacked multisubunit rings, facilitating protein folding through highly cooperative allosteric articulation. CPNs are usually classified into Group I and Group II. Here, I report the characterization of a novel CPN belonging to a third Group, recently discovered in bacteria. Group III CPNs have close phylogenetic association to the Group II CPNs found in Archaea and Eukarya, and may be a relic of the Last Common Ancestor of the CPN family. The gene encoding the Group III CPN from Carboxydothermus hydrogenoformans and Candidatus Desulforudis audaxviator was cloned in E. coli and overexpressed in order to both characterize the protein and to demonstrate its ability to function as an ATPase chaperone. The opening and closing cycle of the Chy chaperonin was examined via site-directed mutations affecting the ATP binding site at R155. To relate the mutational analysis to the structure of the CPN, the crystal structure of both the AMP-PNP (an ATP analogue) and ADP bound forms were obtained in collaboration with Sun-Shin Cha in Seoul, South Korea. The ADP and ATP binding site substitutions resulted in frozen forms of the structures in open and closed conformations. From this, mutants were designed to validate hypotheses regarding key ATP interacting sites as well as important stabilizing interactions, and to observe the physical properties of the resulting complexes by calorimetry.