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- Coutard, B., et al.
(author)
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The VIZIER project : Preparedness against pathogenic RNA viruses
- 2008
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In: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 78:1, s. 37-46
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Journal article (peer-reviewed)abstract
- Life-threatening RNA viruses emerge regularly, and often in an unpredictable manner. Yet, the very few drugs available against known RNA viruses have sometimes required decades of research for development. Can we generate preparedness for outbreaks of the, as yet, unknown viruses? The VIZIER (VIral enZymes InvolvEd in Replication) (http://www.vizier-europe.org/) project has been set-up to develop the scientific foundations for countering this challenge to society. VIZIER studies the most conserved viral enzymes (that of the replication machinery, or replicases) that constitute attractive targets for drug-design. The aim of VIZIER is to determine as many replicase crystal structures as possible from a carefully selected list of viruses in order to comprehensively cover the diversity of the RNA virus universe, and generate critical knowledge that could be efficiently utilized to jump-start research on any emerging RNA virus. VIZIER is a multidisciplinary project involving (i) bioinformatics to define functional domains, (ii) viral genomics to increase the number of characterized viral genomes and prepare defined targets, (iii) proteomics to express, purify, and characterize targets, (iv) structural biology to solve their crystal structures, and (v) pre-lead discovery to propose active scaffolds of antiviral molecules.
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| 4. |
- Orho-Melander, Marju, et al.
(author)
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Common Missense Variant in the Glucokinase Regulatory Protein Gene Is Associated With Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations
- 2008
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 57:11, s. 3112-3121
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Journal article (peer-reviewed)abstract
- OBJECTIVE-Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCYR locus in samples of non-European ancestry and to fine-map across the associated genomic interval. RESEARCH DESIGN AND METHODS-We performed association studies in 12 independent cohorts comprising >45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the U.S., African Americans from the U.S., Hispanics of Caribbean origin, and Chinese, Malays, and Asian Indians from Singapore). We conducted genetic fine-mapping across the similar to 417-kb region of linkage disequilibrium. spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap single nucleotide polymorphisms (SNPs) and genotyping 104 SNPs across the associated genomic interval. RESULTS-We provide comprehensive evidence that GCYR rs780094 is associated with opposite effects on fasting plasma triglyceride (P-meta = 3 x 10(-56)) and glucose (P-meta = 1 x 10(-13)) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reactive protein (CRP) level (P = 5 x 10(-5)). Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r(2) = 0.93 with rs780094) as the strongest association signal in the region. CONCLUSIONS-These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism. Diabetes 57:3112-3121, 2008
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| 5. |
- Tucker, P, et al.
(author)
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The impact of free-time activities on sleep, recovery and well-being.
- 2008
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In: Appl Ergon. - : Elsevier BV. - 0003-6870 .- 1872-9126. ; 39:5, s. 653-62
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Journal article (other academic/artistic)abstract
- The impact of free-time activities on sleep, recovery and well-being.Tucker P, Dahlgren A, Akerstedt T, Waterhouse J.Department of Psychology, University of Wales Swansea, Swansea SA2 8PP, UK.We compared the effects of different types of free-time activity on subjective and objective indices of sleep, recovery and well-being in an experimental field study. Twelve participants spent four consecutive evenings after work in each of three conditions: pursuing quiet leisure activities at home; undertaking active leisure pursuits; doing additional work. Ratings of rest and recuperation, and of satisfaction, were lowest in the additional work condition. There were few other differences between conditions. However, being satisfied with one's evening activities (regardless of which experimental condition was being undertaken) was associated with improved subsequent sleep (self-reported). Evening activities involving lower mental effort were also associated with better-rated sleep, as well as improved recuperation and fatigue the next day. It is concluded that the nature of activity per se may be less important than (1) whether the activity accords with individual preference and (2) the cumulative demands of daytime and evening activities.
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