Continuous multiparametric monitoring of cell metabolism in response to transient overexpression of the sirtuin deacetylase SIRT3

The analysis and visualisation of research data in an environment which is most similar to living conditions belong to the most challenging claims of present scientific research endeavours. To date, the effect of protein function on cell metabolism is most commonly assessed from a series of end point analyses, which finally allows an approximate estimation on how a specific effect takes its course. In the study presented herein, we demonstrate how the combination of transient transfection and a biosensor chip system gives the opportunity to analyse the effect of a specific protein on cell metabolism in living cells through real-time monitoring of metabolically relevant parameters, such as oxygen consumption, acidification rate and cell adhesion. In addition, this method allows online monitoring of the time course of metabolic changes due to changes in expression levels of metabolic regulative proteins from the time of transfection to maximum overexpression. The methodology presented herein was assessed for the transient overexpression of the sirtuin deacetylase SIRT3, a mitochondrial key element in the regulation of energy metabolism, metabolic disease, cancer and ageing

Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis

Background. We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. Methods. Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination. Results. Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. Conclusion. Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. © 2010 Christiansen et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

Propagation of the Madden–Julian Oscillation and scale interaction with the diurnal cycle in a high-resolution GCM

The Madden–Julian Oscillation (MJO) is the chief source of tropical intra-seasonal variability, but is simulated poorly by most state-of-the-art GCMs. Common errors include a lack of eastward propagation at the correct frequency and zonal extent, and too small a ratio of eastward- to westward-propagating variability. Here it is shown that HiGEM, a high-resolution GCM, simulates a very realistic MJO with approximately the correct spatial and temporal scale. Many MJO studies in GCMs are limited to diagnostics which average over a latitude band around the equator, allowing an analysis of the MJO’s structure in time and longitude only. In this study a wider range of diagnostics is applied. It is argued that such an approach is necessary for a comprehensive analysis of a model’s MJO. The standard analysis of Wheeler and Hendon (Mon Wea Rev 132(8):1917–1932, 2004; WH04) is applied to produce composites, which show a realistic spatial structure in the MJO envelopes but for the timing of the peak precipitation in the inter-tropical convergence zone, which bifurcates the MJO signal. Further diagnostics are developed to analyse the MJO’s episodic nature and the “MJO inertia” (the tendency to remain in the same WH04 phase from one day to the next). HiGEM favours phases 2, 3, 6 and 7; has too much MJO inertia; and dies out too frequently in phase 3. Recent research has shown that a key feature of the MJO is its interaction with the diurnal cycle over the Maritime Continent. This interaction is present in HiGEM but is unrealistically weak

Socio-economic drivers of specialist anglers targeting the non-native European catfish (Silurus glanis) in the UK.

Information about the socioeconomic drivers of Silurus glanis anglers in the UK were collected using questionnaires from a cross section of mixed cyprinid fisheries to elucidate human dimensions in angling and non-native fisheries management. Respondents were predominantly male (95%), 30-40 years of age with £500 per annum. The proportion of time spent angling for S. glanis was significantly related to angler motivations; fish size, challenge in catch, tranquil natural surroundings, escape from daily stress and to be alone were considered important drivers of increased time spent angling. Overall, poor awareness of: the risks and adverse ecological impacts associated with introduced S. glanis, non-native fisheries legislation, problems in use of unlimited ground bait and high fish stocking rates in angling lakes were evident, possibly related to inadequate training and information provided by angling organisations to anglers, as many stated that they were insufficiently informed

Neighborhood fast food restaurants and fast food consumption: A national study

<p>Abstract</p> <p>Background</p> <p>Recent studies suggest that neighborhood fast food restaurant availability is related to greater obesity, yet few studies have investigated whether neighborhood fast food restaurant availability promotes fast food consumption. Our aim was to estimate the effect of neighborhood fast food availability on frequency of fast food consumption in a national sample of young adults, a population at high risk for obesity.</p> <p>Methods</p> <p>We used national data from U.S. young adults enrolled in wave III (2001-02; ages 18-28) of the National Longitudinal Study of Adolescent Health (n = 13,150). Urbanicity-stratified multivariate negative binomial regression models were used to examine cross-sectional associations between neighborhood fast food availability and individual-level self-reported fast food consumption frequency, controlling for individual and neighborhood characteristics.</p> <p>Results</p> <p>In adjusted analysis, fast food availability was not associated with weekly frequency of fast food consumption in non-urban or low- or high-density urban areas.</p> <p>Conclusions</p> <p>Policies aiming to reduce neighborhood availability as a means to reduce fast food consumption among young adults may be unsuccessful. Consideration of fast food outlets near school or workplace locations, factors specific to more or less urban settings, and the role of individual lifestyle attitudes and preferences are needed in future research.</p

Genome-Wide Detection of Allele Specific Copy Number Variation Associated with Insulin Resistance in African Americans from the HyperGEN Study

African Americans have been understudied in genome wide association studies of diabetes and related traits. In the current study, we examined the joint association of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the HyperGEN study, a family based study with proband ascertainment for hypertension. This analysis is restricted to 1,040 African Americans without diabetes. We generated allele specific CNV genotypes at 872,243 autosomal loci using Birdsuite, a freely available multi-stage program. Joint tests of association for SNPs and CNVs were performed using linear mixed models adjusting for covariates and familial relationships. Our results highlight SNPs associated with fasting insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10−7≤P≤1.1*10−5) near ATPase, class V, type 10A (ATP10A), and the L Type voltage dependent calcium channel (CACNA1D, rs1401492, P≤5.2*10−6). ATP10A belongs to a family of aminophospholipid-transporting ATPases and has been associated with type 2 diabetes in mice. CACNA1D has been linked to pancreatic beta cell generation in mice. The two most significant copy variable markers (rs10277702 and rs361367; P<2.0*10−4) were in the beta variable region of the T-cell receptor gene (TCRVB). Human and mouse TCR has been shown to mimic insulin and its receptor and could contribute to insulin resistance. Our findings differ from genome wide association studies of fasting insulin and other diabetes related traits in European populations, highlighting the continued need to investigate unique genetic influences for understudied populations such as African Americans