Amino-terminal cysteine residues of RGS16 are required for palmitoylation and modulation of G(i)- and G(q)-mediated signaling

RGS proteins (Regulators of G protein Signaling) are a recently discovered family of proteins that accelerate the GTPase activity of heterotrimeric G protein α subunits of the i, q, and 12 classes. The proteins share a homologous core domain but have divergent amino-terminal sequences that are the site of palmitoylation for RGS-GAIP and RGS4. We investigated the function of palmitoylation for RGS16, which shares conserved amino-terminal cysteines with RGS4 and RGS5. Mutation of cysteine residues at residues 2 and 12 blocked the incorporation of [3H]palmitate into RGS16 in metabolic labeling studies of transfected cells or into purified RGS proteins in a cell-free palmitoylation assay. The purified RGS16 proteins with the cysteine mutations were still able to act as GTPase-activating protein for Giα. Inhibition or a decrease in palmitoylation did not significantly change the amount of protein that was membrane-associated. However, palmitoylation-defective RGS16 mutants demonstrated impaired ability to inhibit both Gi- and Gq-linked signaling pathways when expressed in HEK293T cells. These findings suggest that the amino-terminal region of RGS16 may affect the affinity of these proteins for Gα subunits in vivo or that palmitoylation localizes the RGS protein in close proximity to Gα subunits on cellular membranes

Strontium isotope stratigraphy and age estimates for the Leisey Shell Pit faunas, Hillsborough County, Florida

The vertebrate fauna of the Leisey Shell Pit near Tampa Bay, Florida, represents one of the more significant lrvingtonian mammalian faunas of North America. The fossil vertebrates occur in thin bone beds bounded above and below by massive shell beds containing a rich invertebrate ( chiefly molluscan) fauna. Debate has arisen concerning the precise age of the faunas at Leisey. Although generally agreed to be Pleistocene, estimates based upon vertebrate biostratigraphy suggest a somewhat older age than do estimates based upon molluscan biostratigraphy. To help resolve this controvefliy, 87Sr/86Sr ratios were determined on molluscan shells throughout the section. These ratios were then correlated to the global sea water 87Sr/86Sr curve for age detennination. The Sr isotopes support an early Pleistocene age for the vertebrate fauna and suggest a complex history for the shell accumulations

The Calan-Hertfordshire Extrasolar Planet Search

The detailed study of the exoplanetary systems HD189733 and HD209458 has given rise to a wealth of exciting information on the physics of exoplanetary atmospheres. To further our understanding of the make-up and processes within these atmospheres we require a larger sample of bright transiting planets. We have began a project to detect more bright transiting planets in the southern hemisphere by utilising precision radial-velocity measurements. We have observed a constrained sample of bright, inactive and metal-rich stars using the HARPS instrument and here we present the current status of this project, along with our first discoveries which include a brown dwarf/extreme-Jovian exoplanet found in the brown dwarf desert region around the star HD191760 and improved orbits for three other exoplanetary systems HD48265, HD143361 and HD154672. Finally, we briefly discuss the future of this project and the current prospects we have for discovering more bright transiting planets.Comment: 4 pages, 2 figures, to appear in the conference proceedings "New Technologies for Probing the Diversity of Brown Dwarfs and Exoplanets" Shanghai 200

The information sources and journals consulted or read by UK paediatricians to inform their clinical practice and those which they consider important: a questionnaire survey

Background: Implementation of health research findings is important for medicine to be evidence-based. Previous studies have found variation in the information sources thought to be of greatest importance to clinicians but publication in peer-reviewed journals is the traditional route for dissemination of research findings. There is debate about whether the impact made on clinicians should be considered as part of the evaluation of research outputs. We aimed to determine first which information sources are generally most consulted by paediatricians to inform their clinical practice, and which sources they considered most important, and second, how many and which peer-reviewed journals they read. Methods: We enquired, by questionnaire survey, about the information sources and academic journals that UK medical paediatric specialists generally consulted, attended or read and considered important to their clinical practice. Results: The same three information sources – professional meetings & conferences, peerreviewed journals and medical colleagues – were, overall, the most consulted or attended and ranked the most important. No one information source was found to be of greatest importance to all groups of paediatricians. Journals were widely read by all groups, but the proportion ranking them first in importance as an information source ranged from 10% to 46%. The number of journals read varied between the groups, but Archives of Disease in Childhood and BMJ were the most read journals in all groups. Six out of the seven journals previously identified as containing best paediatric evidence are the most widely read overall by UK paediatricians, however, only the two most prominent are widely read by those based in the community. Conclusion: No one information source is dominant, therefore a variety of approaches to Continuing Professional Development and the dissemination of research findings to paediatricians should be used. Journals are an important information source. A small number of key ones can be identified and such analysis could provide valuable additional input into the evaluation of clinical research outputs

Effect of cold plasma on polyphenol oxidase inactivation in cloudy apple juice and on the quality parameters of the juice during storage

Direct cold plasma treatment has been investigated as an alternative non-thermal technology as a means of maintaining and improving quality of fresh cloudy apple juice. Process variables studied included type of plasma discharge, input voltage and treatment time on polyphenol oxidase (PPO) inactivation. Spark discharge plasma at 10.5 kV for 5 min was the best treatment, with near total inactivation of PPO achieved, although good PPO inactivation was also recorded using shorter treatment times. Residual activity (RA) of PPO was 16 and 27.6% after 5 and 4 min of treatment respectively. This PPO inactivation was maintained throughout the storage trials, but decreased with samples treated for a shorter time. Plasma treatment improved key quality parameters of Golden delicious cloudy apple juice, with retention of critical quality parameters during extended storage trials. Color was the most noticeable change, which was enhanced with retention of a greener color. An increase of 69 and 64% was obtained in the total phenolic content after 4 and 5 min of treatment, respectively. Therefore, cold plasma was demonstrated to be a good alternative to traditional heat treatments for enhanced quality retention of fresh cloudy apple juice and over its storage.Spanish Government (MINECO) and the European Regional Development Fund (ERDF) [Project CTQ2015-64396-R] and in part by a research grant from Science Foundation Ireland (SFI) under the Grant Number SFI/16/BBSRC/3391 and the BBSRC under the Grant Reference BB/P008496/

Resting Heart Rate and Metabolic Syndrome in Patients With Diabetes and Coronary Artery Disease in Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

The relation between the metabolic syndrome (MetS) and resting heart rate (rHR) in patients with diabetes and coronary artery disease is unknown. The authors examined the cross-sectional association at baseline between components of the MetS and rHR and between rHR and left ventricular ejection fraction in the population from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized clinical trial. The mean rHR in the MetS group was significantly higher than in those without (68.4±12.3 vs 65.6±11.8 beats per min, P=.0017). The rHR was higher (P<.001 for trend) with increasing number of components for MetS. Linear regression analyses demonstrated that as compared to individuals without MetS, rHR was significantly higher in participants with MetS (regression coefficient, 2.9; P=.0015). In patients with type 2 diabetes and coronary artery disease, the presence of higher rHR is associated with increasing number of criteria of MetS and the presence of ventricular dysfunction.Prev Cardiol. 2010;13:112–116. © 2009 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79383/1/j.1751-7141.2010.00067.x.pd

Conducting retrospective impact analysis to inform a medical research charity’s funding strategies: The case of Asthma UK

© 2013 Hanney et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. METHODS: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. RESULTS: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. CONCLUSIONS: We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.This study was funded by Asthma UK

Associations of cortisol/testosterone and cortisol/sex hormone-binding globulin ratios with atherosclerosis in middle-age women

AbstractBackground and aimsThe cortisol/testosterone (C/T) ratio has been hypothesized to be a better predictor of atherosclerosis than cortisol alone. No study has assessed whether the C/T and C/sex hormone-binding globulin (SHBG) ratios are associated with atherosclerosis in a U.S. population sample.MethodsThis substudy included 367 women who had both cortisol from year 15 and testosterone and SHBG at year 16 of the Coronary Artery Risk Development in Young Adults study, an ongoing observational cohort in the United States. Of these, intima-media thickness (IMT) was available at follow-up year 20 in 339 (n = 332 with measurement at carotid bulb), and 303 were free of prevalent coronary artery calcium (CAC) at year 15. Area under the curve (AUC) of salivary cortisol was available in 302 individuals. Ratios of AUCs of cortisol to total testosterone, free testosterone, and SHBG were categorized into tertiles. Associations with CAC and IMT were assessed by regression models adjusted for age, race, body mass index, systolic blood pressure, menopause, oral contraceptive use, diabetes, alcohol, and smoking.ResultsOnly the highest tertile of the AUC/free testosterone ratio was positively associated with carotid bulb IMT (β = 0.088, P = 0.006). This tertile was also positively associated with new onset CAC between year 15 and 25 (OR 3.45, 95% CI 1.18–10.06). Tertiles of cortisol or testosterone alone were not associated with new onset CAC.ConclusionAUC/Free testosterone ratio may be more associated with atherosclerosis in women than either indicator alone. The ratio may serve as a suitable biomarker of cortisol-linked stress

Early warnings of the potential for malaria transmission in rural Africa using the hydrology, entomology and malaria transmission simulator (HYDREMATS)

<p>Abstract</p> <p>Background</p> <p>Early warnings of malaria transmission allow health officials to better prepare for future epidemics. Monitoring rainfall is recognized as an important part of malaria early warning systems. The Hydrology, Entomology and Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to malaria transmission, and could be used to provide early warnings of malaria epidemics.</p> <p>Methods</p> <p>HYDREMATS is used to make predictions of mosquito populations and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall prediction based on the seasonal mean rainfall for a period two or four weeks into the future.</p> <p>Results</p> <p>Predictions made using this method provided reasonable estimates of mosquito populations and vectorial capacity, two to four weeks in advance. The predictions were significantly improved compared to those made when HYDREMATS was forced with seasonal mean rainfall alone.</p> <p>Conclusions</p> <p>HYDREMATS can be used to make reasonable predictions of mosquito populations and vectorial capacity, and provide early warnings of the potential for malaria epidemics in Africa.</p

Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire: an expert assessment

As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%–85% of permafrost carbon release can still be avoided if human emissions are actively reduced