SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus

Diet restriction retards aging and extends life span by triggering adaptive mechanisms that alter behavioral, physiological, and biochemical responses in mammals. Little is known about the molecular pathways evoking the corresponding central response. One factor that mediates the effects of diet restriction is the mammalian nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1. Here we demonstrate that diet restriction significantly increases SIRT1 protein levels and induces neural activation in the dorsomedial and lateral hypothalamic nuclei. Increasing SIRT1 in the brain of transgenic (BRASTO) mice enhances neural activity specifically in these hypothalamic nuclei, maintains a higher range of body temperature, and promotes physical activity in response to different diet-restricting paradigms. These responses are all abrogated in Sirt1-deficient mice. SIRT1 up-regulates expression of the orexin type 2 receptor specifically in these hypothalamic nuclei in response to diet-restricting conditions, augmenting response to ghrelin, a gut hormone whose levels increase in these conditions. Our results suggest that in the hypothalamus, SIRT1 functions as a key mediator of the central response to low nutritional availability, providing insight into the role of the hypothalamus in the regulation of metabolism and aging in mammals

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients with Coronary Artery Disease and Diabetic Nephropathy: A Single Center Experience

Background Patients with diabetic nephropathy (DN) and coronary artery disease (CAD) represent a subset of patients with high cardiovascular morbidity and mortality. The optimal revascularization strategy using either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. The purpose of this study was to compare the clinical outcomes of PCI to CABG in DN patients with CAD. Methods The clinical and angiographic records of DN patients with CAD who underwent either CABG (n=52) or PCI (n=48) were retrospectively analyzed. Results The baseline characteristics were similar in the two groups except for the severity of the CAD. At 30 days, the death rate (PCI: 2.1% vs. CABG: 9.6%, p=0.21) and major adverse cardiac events (MACE) rate (PCI: 2.1% vs. CABG: 9.6%, p=0.21) were similar in comparisons between the PCI and CABG groups. At three years, the death rate (PCI: 18.8% vs. CABG: 19.2%, p=0.94) was similar between the PCI and CABG groups but the MACE rate (PCI: 47.9% vs. CABG: 21.2%, p=0.006) was higher in the PCI group compared to the CABG group. In addition, the repeat revascularization rate was higher in the PCI group compared to the CABG group (PCI: 12.5% vs. CABG: 1.9%, p=0.046). Conclusions The CABG procedure was associated with a lower incidence of MACE and repeat revascularization for up to three years of follow-up in DN patients with CAD. However, the overall survival rate was similar in the CABG and PCI groups. Therefore, CABG may be superior to PCI with regard to MACE and repeat revascularization.ope

Plant responses to elevated CO2 levels in soils: distinct CO2 and O2-depletion effects

To investigate potential environmental effects in the context of carbon dioxide (CO2) leakage from Carbon Capture and Storage (CCS) schemes, the University of Nottingham ASGARD (Artificial Soil Gassing And Response Detection) facility, was used to inject CO2 into the soil in replicated open-air field plots over several seasons to measure the effects on UK crop species. However, this system lacked a way of distinguishing the concomitant effects of oxygen (O2)-depletion (occurring as a consequence of high CO2 levels in the soil). As plants are aerobic, they require O2 for functional integrity of root processes. Here a complementary laboratory system was used to specifically identify distinct CO2 and O2-depletion effects on two crop species, beetroot and wheat. Parameters measured (photosynthetic rate, transpiration rate, stomatal conductance and biomass) between CO2-gassed, nitrogen (N2)-gassed (O2-depletion control) and non-gassed control plants showed distinct differences in response to CO2 gassing and O2-depletion. Differences between field and laboratory studies illustrate effects of variable meteorological conditions in the field, whilst more stable laboratory conditions show differences between crop species. Results show that the interactions of these two stresses (very high soil CO2 and O2 depletion) on crop physiology are discrete and complex

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Data from: Computational and experimental characterization of dVHL establish a Drosophila model of VHL syndrome

The von Hippel-Lindau (VHL) cancer syndrome is associated with mutations in the VHL gene. The pVHL protein is involved in response to changes in oxygen availability as part of an E3-ligase that targets the Hypoxia-Inducible Factor for degradation. pVHL has a molten globule configuration with marginal thermodynamic stability. The cancer-associated mutations further destabilize it. The Drosophila homolog, dVHL, has relatively low sequence similarity to pVHL, and is also involved in regulating HIF1-α. Using in silico, in vitro and in vivo approaches we demonstrate high similarity between the structure and function of dVHL and pVHL. These proteins have a similar fold, secondary and tertiary structures, as well as thermodynamic stability. Key functional residues in dVHL are evolutionary conserved. This structural homology underlies functional similarity of both proteins, evident by their ability to bind their reciprocal partner proteins, and by the observation that transgenic pVHL can fully maintain normal dVHL-HIF1-α downstream pathways in flies. This novel transgenic Drosophila model is thus useful for studying the VHL syndrome, and for testing drug candidates to treat it