A semiempirical approach to the intra-phycocyanin and inter-phycocyanin fluorescence resonance energy-transfer pathways in phycobilisomes.

A semiempirical methodology to model the intra-phycocyanin and inter-phycocyanin fluorescence resonance energy-transfer (FRET) pathways in the rods of the phycobilisomes (PBSs) from Fremyella diplosiphon is presented. Using the Forster formulation of FRET and combining experimental data and PM3 calculation of the dipole moments of the aromatic portions of the chromophores, transfer constants between pairs of chromophores in the phycocyanin (PC) structure were obtained. Protein docking of two PC hexamers was used to predict the optimal distance and axial rotation angle for the staked PCs in the PBSs' rods. Using the distance obtained by the docking process, transfer constants between pairs of chromophores belonging to different PC hexamers were calculated as a function of the angle of rotation. We show that six preferential FRET pathways within the PC hexameric ring and 15 pathways between hexamers exist, with transfer constants consistent with experimental results. Protein docking predicted the quaternary structure for PCs in rods with inter-phycocyanin distance of 55.6 A and rotation angle of 20.5 degrees . The inter-phycocyanin FRET constant between chromophores at positions beta(155) is maximized at the rotation angle predicted by docking revealing the crucial role of this specific inter-phycocyanin channel in defining the complete set of FRET pathways in the system

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk