GM070785 final report

Issued as final reportUnited States. Dept. of Health and Human Service

Molecular Dynamics on a Model for Nascent High-Density Lipoprotein: Role of Salt Bridges

AbstractThe results of an all-atom molecular dynamics simulation on a discoidal complex made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and a synthetic α-helical 18-mer peptide with an apolipoprotein-like charge distribution are presented. The system consists of 12 acetyl-18A-amide (Ac-18A-NH2) (Anantharamaiah et al., 1985. J. Biol. Chem. 260:10248–10255) molecules and 20 molecules of POPC in a bilayer, 10 in each leaflet, solvated in a sphere of water for a total of 28,522 atoms. The peptide molecules are oriented with their long axes normal to the bilayer (the “picket fence” orientation). This system is analogous to complexes formed in nascent high-density lipoprotein and to Ac-18A-NH2/phospholipid complexes observed experimentally. The simulation extended over 700ps, with the last 493ps used for analysis. The symmetry of this system allows for averaging over different helices to improve sampling, while maintaining explicit all-atom representation of all peptides. The complex is stable on the simulated time scale. Several possible salt bridges between and within helices were studied. A few salt bridge formations and disruptions were observed. Salt bridges provide specificity in interhelical interactions

Ketogenic Diets and Exercise Performance

The ketogenic diet (KD) has gained a resurgence in popularity due to its purported reputation for fighting obesity. The KD has also acquired attention as an alternative and/or supplemental method for producing energy in the form of ketone bodies. Recent scientific evidence highlights the KD as a promising strategy to treat obesity, diabetes, and cardiac dysfunction. In addition, studies support ketone body supplements as a potential method to induce ketosis and supply sustainable fuel sources to promote exercise performance. Despite the acceptance in the mainstream media, the KD remains controversial in the medical and scientific communities. Research suggests that the KD or ketone body supplementation may result in unexpected side effects, including altered blood lipid profiles, abnormal glucose homeostasis, increased adiposity, fatigue, and gastrointestinal distress. The purpose of this review article is to provide an overview of ketone body metabolism and a background on the KD and ketone body supplements in the context of obesity and exercise performance. The effectiveness of these dietary or supplementation strategies as a therapy for weight loss or as an ergogenic aid will be discussed. In addition, the recent evidence that indicates ketone body metabolism is a potential target for cardiac dysfunction will be reviewed

Local Axion Cosmic Strings from Superstrings

Axionic cosmic string solutions are investigated in a superstring motivated model with a pseudo-anomalous U(1) gauge symmetry. The inclusion of a gauge field and spatially varying dilaton allow local defect solutions with finite energy per unit length to be found. Fermion zero modes (whose presence is implied by supersymmetry) are also analysed. The corresponding fermion currents suggest strong cosmological bounds on the model. It is shown that the unusual form of the axion strings weakens these bounds. Other cosmological constraints on the underlying theory are also discussed.Comment: 17 page

Structural and Electrostatic Characterization of Pariacoto Virus: Implications for Viral Asembly

This is the peer reviewed version of the following article:Devkota, B., Petrov, A., Lemieux, S., Boz, M. B., Tang, L., Schneemann, A., … Harvey, S. C. (2009). Structural and Electrostatic Characterization of Pariacoto Virus: Implications for Viral Asembly. Biopolymers, 91(7), 530–538. http://doi.org/10.1002/bip.21168, which has been published in final form at doi.org/10.1002/bip.21168. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingWe present the first all-atom model for the structure of a T=3 virus, pariacoto virus (PaV), which is a non-enveloped, icosahedral RNA virus and a member of the Nodaviridae family. The model is an extension of the crystal structure, which reveals about 88% of the protein structure but only about 35% of the RNA structure. Evaluation of alternative models confirms our earlier observation that the polycationic protein tails must penetrate deeply into the core of the virus, where they stabilize the structure by neutralizing a substantial fraction of the RNA charge. This leads us to propose a model for the assembly of small icosahedral RNA viruses: nonspecific binding of the protein tails to the RNA leads to a collapse of the complex, in a fashion reminiscent of DNA condensation. The globular protein domains are excluded from the condensed phase but are tethered to it, so they accumulate in a shell around the condensed phase, where their concentration is high enough to trigger oligomerization and formation of the mature virus

Testing for Co-explosive Behaviour in Financial Time Series

This article proposes a test to determine if two price series that each contain an explosive autoregressive regime consistent with the presence of a bubble are related in the sense that a linear combination of them is integrated of order zero. We refer to such a phenomenon as ‘co-explosive behaviour’, and propose a test based on a stationarity testing framework. The test allows the explosive episode in one series to lead (or lag) that in the other by a number of time periods. We establish the asymptotic properties of the test statistic and propose a wild bootstrap procedure for obtaining critical values that are robust to heteroskedasticity. Simulations show that the proposed test has good finite sample size and power performance. An empirical application to detect whether co-explosive behaviour exists among a set of precious and non-ferrous metals is presented

MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. The MAVIDOS Study Group.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.UNLABELLED: MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR. BACKGROUND: Osteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented. METHODS/DESIGN: Women have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years. DISCUSSION: As far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology.Published versio

Physical activity levels and motivational responses of boys and girls: A comparison of direct instruction and Tactical Games Models of games teaching in physical education

The purpose of this study was to independently determine the levels of moderate-to-vigorous physical activity (MVPA) and self-determined motivation of both boys and girls as they participated in prolonged units of invasion games (i.e. 6-12 lessons) through two pedagogical models; direct instruction and the Tactical Games Model (TGM). It was hypothesized that given the differences in domain interaction and lesson structure, both boys and girls would gain higher levels of physical activity (PA) and possess higher quality motivation during TGM-based lessons when compared to direct instruction lessons. Seventy-two children aged 11-12 years; (42 boys, 30 girls) were randomly assigned to either a control or intervention group (TGM). Children wore RT3® triaxial accelerometers over a 12 week period to objectively measure time spent in MVPA. The System for observing Fitness Instruction Time (SOFIT) tool was completed during each lesson to additionally assess lesson context information and teacher behavior. SDT questionnaires were also completed, pre and post-intervention. Boys in the TGM condition displayed significantly higher levels of MVPA in both rugby and football activities in comparison to the control group although no significant differences in motivation were noted post-intervention. While girls in the TGM condition recorded comparable PA levels in the football sessions, they recorded significantly lower PA activity levels in the netball lessons. There were no significant differences in girls’ motivation post-intervention. It is recommended that future studies build on this research by continuing to examine PA and the quality of student motivation while using GCAs over prolonged unit lengths (i.e. greater than 12 lessons) using structural equation modeling techniques to assess the relationships between, and mediating influences of, SDT constructs on PA levels

Some Simple Criteria for Gauged R-parity

We catalog some simple conditions which are sufficient to guarantee that R-parity survives as an unbroken gauged discrete subgroup of the continuous gauge symmetry in certain supersymmetric extensions of the standard model.Comment: 11 pages, UFIFT-HEP-92-22. v2: TeX formatting fixed, no other change