644 research outputs found

    About the Heads [curators]

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    In the Undercroft to Queen Anne's Court at the Old Royal Naval College lies a collection of stone heads from the turn of the 18th century. The mysterious heads, depicting Neptune and other denizens of the deep, were carved by Robert Jones of Stepney in the early 1700s, and were originally intended for display upon the south elevation of the Painted Hall. A decision to use brick instead of stone meant the heads were abandoned, and for 300 years have languished out of sight. 'About the Heads' is an exhibition at the University of Greenwich Heritage Gallery to rescue them from obscurity, coinciding with the re-opening of the hall after a major restoration. The heads themselves are not on display; instead, three artists from separate disciplines have created responses to their historic and continuing interment

    Perception of carbohydrate availability augments high-intensity intermittent exercise capacity under sleep-low train low conditions

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    The authors tested the hypothesis that perception of carbohydrate (CHO) availability augments exercise capacity in conditions of reduced CHO availability. Nine males completed a sleep-low train model comprising evening glycogen-depleting cycling followed by an exhaustive cycling protocol the next morning in the fasted state (30 min steady state at 95% lactate threshold followed by 1-min intervals at 80% peak power output until exhaustion). After the evening depletion protocol and prior to sleeping, subjects consumed (a) a known CHO intake of 6 g/kg body mass (TRAIN HIGH) or (b) a perceived comparable CHO intake but 0 g/kg body mass (PERCEPTION) or a known train-low condition of 0 g/kg body mass (TRAIN LOW). The TRAIN HIGH and PERCEPTION trials were conducted double blind. During steady state, average blood glucose and CHO oxidation were significantly higher in TRAIN HIGH (4.01 ± 0.56 mmol/L; 2.17 ± 0.70 g/min) versus both PERCEPTION (3.30 ± 0.57 mmol/L; 1.69 ± 0.64 g/min, p < .05) and TRAIN LOW (3.41 ± 0.74 mmol/L; 1.61 ± 0.59 g/min, p < .05). Exercise capacity was significantly different between all pairwise comparisons (p < .05), where TRAIN LOW (8 ± 8 min) < PERCEPTION (12 ± 6 min) < TRAIN HIGH (22 ± 9 min). Data demonstrate that perception of CHO availability augments high-intensity intermittent exercise capacity under sleep-low, train-low conditions, though this perception does not restore exercise capacity to that of CHO consumption. Such data have methodological implications for future research designs and may also have practical applications for athletes who deliberately practice elements of training in CHO-restricted states

    Horizontal gene transfer to a defensive symbiont with a reduced genome in a multipartite beetle microbiome

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    Symbiotic mutualisms of bacteria and animals are ubiquitous in nature, running a continuum from facultative to obligate from the perspectives of both partners. The loss of functions required for living independently but not within a host gives rise to reduced genomes in many symbionts. Although the phenomenon of genome reduction can be explained by existing evolutionary models, the initiation of the process is not well understood. Here, we describe the microbiome associated with the eggs of the beetle Lagria villosa, consisting of multiple bacterial symbionts related to Burkholderia gladioli, including a reduced-genome symbiont thought to be the exclusive producer of the defensive compound lagriamide. We show that the putative lagriamide-producing symbiont is the only member of the microbiome undergoing genome reduction and that it has already lost the majority of its primary metabolism and DNA repair pathways. The key step preceding genome reduction in the symbiont was likely the horizontal acquisition of the putative lagriamide lga biosynthetic gene cluster. Unexpectedly, we uncovered evidence of additional horizontal transfers to the symbiont's genome while genome reduction was occurring and despite a current lack of genes needed for homologous recombination. These gene gains may have given the genome-reduced symbiont a selective advantage in the microbiome, especially given the maintenance of the large lga gene cluster despite ongoing genome reduction. IMPORTANCE Associations between microorganisms and an animal, plant, or fungal host can result in increased dependence over time. This process is due partly to the bacterium not needing to produce nutrients that the host provides, leading to loss of genes that it would need to live independently and to a consequent reduction in genome size. It is often thought that genome reduction is aided by genetic isolation-bacteria that live in monocultures in special host organs, or inside host cells, have less access to other bacterial species from which they can obtain genes. Here, we describe exposure of a genome-reduced beetle symbiont to a community of related bacteria with nonreduced genomes. We show that the symbiont has acquired genes from other bacteria despite going through genome reduction, suggesting that isolation has not yet played a major role in this case of genome reduction, with horizontal gene gains still offering a potential route for adaptation

    Endovascular repair of an inflammatory abdominal aortic aneurysm complicated by aortoduodenal fistulation with an unusual presentation

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    AbstractAortoenteric fistulation (AEF) is a well-documented late complication of open abdominal aortic aneurysm (AAA) repair, occurring in between 0.4% and 4% of cases. In the absence of an anastomosis, AEF is likely to be rare after endovascular aneurysm repair (EVAR) and has only recently been described in the literature as a result of mechanical stent failure or migration. We present the case of a 61-year-old man who underwent EVAR for an AAA with a “nonspecific” periaortic inflammatory mass. Six months postoperatively, an AEF developed, presenting with metastatic sepsis followed by septic infective thromboembolization to his right leg, and amputation was necessary. His stent was well positioned and mechanically intact. We emphasize the need for vigilance about the risk of AEF when adopting an endovascular approach to repair the AAA with a nonspecific periaortic inflammatory mass and highlight the need for awareness about the unusual septic manifestations of AEF. (J Vasc Surg 2001;33:874-9.

    Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking

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    Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=6.9 x 10(-5)). In a third set of European populations (n= approximately 7500) which had been genotyped for approximately 6000 SNPs in approximately 2000 genes, an allele in the same haplotype was associated with CPD (nominal P=2.6 x 10(-6)). These results (in three independent populations of European origin, totaling approximately 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND

    A Systematic Review of Biomarkers and Risk of Incident Type 2 Diabetes: An Overview of Epidemiological, Prediction and Aetiological Research Literature

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    BACKGROUND\textbf{BACKGROUND} Blood-based or urinary biomarkers may play a role in quantifying the future risk of type 2 diabetes (T2D) and in understanding possible aetiological pathways to disease. However, no systematic review has been conducted that has identified and provided an overview of available biomarkers for incident T2D. We aimed to systematically review the associations of biomarkers with risk of developing T2D and to highlight evidence gaps in the existing literature regarding the predictive and aetiological value of these biomarkers and to direct future research in this field. METHODS AND FINDINGS\textbf{METHODS AND FINDINGS} We systematically searched PubMed MEDLINE (January 2000 until March 2015) and Embase (until January 2016) databases for observational studies of biomarkers and incident T2D according to the 2009 PRISMA guidelines. We also searched availability of meta-analyses, Mendelian randomisation and prediction research for the identified biomarkers. We reviewed 3910 titles (705 abstracts) and 164 full papers and included 139 papers from 69 cohort studies that described the prospective relationships between 167 blood-based or urinary biomarkers and incident T2D. Only 35 biomarkers were reported in large scale studies with more than 1000 T2D cases, and thus the evidence for association was inconclusive for the majority of biomarkers. Fourteen biomarkers have been investigated using Mendelian randomisation approaches. Only for one biomarker was there strong observational evidence of association and evidence from genetic association studies that was compatible with an underlying causal association. In additional search for T2D prediction, we found only half of biomarkers were examined with formal evidence of predictive value for a minority of these biomarkers. Most biomarkers did not enhance the strength of prediction, but the strongest evidence for prediction was for biomarkers that quantify measures of glycaemia. CONCLUSIONS\textbf{CONCLUSIONS} This study presents an extensive review of the current state of the literature to inform the strategy for future interrogation of existing and newly described biomarkers for T2D. Many biomarkers have been reported to be associated with the risk of developing T2D. The evidence of their value in adding to understanding of causal pathways to disease is very limited so far. The utility of most biomarkers remains largely unknown in clinical prediction. Future research should focus on providing good genetic instruments across consortia for possible biomarkers in Mendelian randomisation, prioritising biomarkers for measurement in large-scale cohort studies and examining predictive utility of biomarkers for a given context.This study was supported by the Medical Research Council UK (grant reference no. MC_UU_12015/1), http://gtr.rcuk.ac.uk/projects?ref=MC_UU_12015/1; Netherlands Organization for Scientific Research (NWO project number 825.13.004), http://www.nwo.nl/en/research-and-results/research-projects/i/85/10585.html; Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013), http://www.emif.eu/about. GSK provided support in the form of salaries for DW, DJN, AS. Pfizer provided support in the form of salary to JMB

    The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors.

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    ABSTRACT: BACKGROUND: The Psychiatric arm of the population-based CoLaus study (PsyCoLaus) is designed to: 1) establish the prevalence of threshold and subthreshold psychiatric syndromes in the 35 to 66 year-old population of the city of Lausanne (Switzerland); 2) test the validity of postulated definitions for subthreshold mood and anxiety syndromes; 3) determine the associations between psychiatric disorders, personality traits and cardiovascular diseases (CVD), 4) identify genetic variants that can modify the risk for psychiatric disorders and determine whether genetic risk factors are shared between psychiatric disorders and CVD. This paper presents the method as well as somatic and sociodemographic characteristics of the sample. METHODS: All 35 to 66 year-old persons previously selected for the population-based CoLaus survey on risk factors for CVD were asked to participate in a substudy assessing psychiatric conditions. This investigation included the Diagnostic Interview for Genetic Studies to elicit diagnostic criteria for threshold disorders according to DSM-IV and algorithmically defined subthreshold syndromes. Complementary information was gathered on potential risk and protective factors for psychiatric disorders, migraine and on the morbidity of first-degree family members, whereas the collection of DNA and plasma samples was part of the original somatic study (CoLaus). RESULTS: A total of 3,691 individuals completed the psychiatric evaluation (67% participation). The gender distribution of the sample did not differ significantly from that of the general population in the same age range. Although the youngest 5-year band of the cohort was underrepresented and the oldest 5-year band overrepresented, participants of PsyCoLaus and individuals who refused to participate revealed comparable scores on the General Health Questionnaire, a self-rating instrument completed at the somatic exam. CONCLUSIONS: Despite limitations resulting from the relatively low participation in the context of a comprehensive and time-consuming investigation, the PsyCoLaus study should significantly contribute to the current understanding of psychiatric disorders and comorbid somatic conditions by: 1) establishing the clinical relevance of specific psychiatric syndromes below the DSM-IV threshold; 2) determining comorbidity between risk factors for CVD and psychiatric disorders; 3) assessing genetic variants associated with common psychiatric disorders and 4) identifying DNA markers shared between CVD and psychiatric disorders

    Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

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    <p><b>Background:</b> The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.</p> <p><b>Methods:</b> The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.</p> <p><b>Results:</b> Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.</p> <p><b>Conclusion:</b> With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.</p&gt
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