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SourceAvailable from: Claire Waterton[Show abstract] [Hide abstract]
ABSTRACT: Conventional modes of environmental governance, which typically exclude those stakeholders that are most directly linked to the specific place, frequently fail to have the desired impact. Using the example of lake water management in Loweswater, a small hamlet within the English Lake District, we consider the ways in which new "collectives" for local, bottom-up governance of water bodies can reframe problems in ways which both bind lay and professional people to place, and also recast the meaning of "solutions" in thought-provoking ways.PLoS Biology 03/2015; 13(3):e1002081. DOI:10.1371/journal.pbio.1002081
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ABSTRACT: Author Summary The H-1 protoparvovirus (H-1PV) is the first replication-competent member of the Parvoviridae family to undergo a phase I/IIa clinical trial in patients suffering from glioblastoma multiforme. Although the intrinsic oncotropism and oncolytic activity of protoparvoviruses are well known, the underlying molecular mechanisms remain elusive. Here we identify a PV-induced intracellular loop-back mechanism that promotes PV replication and cytotoxicity through PI3-kinase-independent stimulation of PDK1 and of the PKC and PKB/Akt1 downstream kinases. This mechanism involves PKCη/Rdx-mediated phosphorylation of PDK1 (at S138 in mouse or S135 in human). Interestingly, this phosphorylation appears as a hallmark of highly aggressive brain tumors. Although H-1PV does not promote it in normal human cells, experimentally administered activated PDK1 variants were able to sensitize these cells to virus infection. These data lead us to propose PDK1phosphoS135 as a new candidate marker for monitoring tumor progression and responsiveness to oncolytic parvovirotherapy, particularly in the case of highly aggressive brain tumors. Furthermore, the sensitivity of PDK1phosphoS135-positive cell lines to inhibitors of PKCη/Rdx argues for considering this complex as a potential target for anticancer drug development.PLoS Pathogens 02/2015; 11(3):e1004703. DOI:10.1371/journal.ppat.1004703
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ABSTRACT: This study aimed to use primary care electronic health records to evaluate the prevalence of overweight and obesity in 2-15-year-old children in England and compare trends over the last two decades. Cohort study of primary care electronic health records. 375 general practices in England that contribute to the UK Clinical Practice Research Datalink. Individual participants were sampled if they were aged between 2 and 15 years during the period 1994-2013 and had one or more records of body mass index (BMI). Prevalence of overweight (including obesity) was defined as a BMI equal to or greater than the 85th centile of the 1990 UK reference population. Data were analysed for 370 544 children with 507 483 BMI records. From 1994 to 2003, the odds of overweight and obesity increased by 8.1% per year (95% CI 7.2% to 8.9%) compared with 0.4% (-0.2% to 1.1%) from 2004 to 2013. Trends were similar for boys and girls, but differed by age groups, with prevalence stabilising in 2004 to 2013 in the younger (2-10 year) but not older (11-15 year) age group, where rates continued to increase. Primary care electronic health records in England may provide a valuable resource for monitoring obesity trends. More than a third of UK children are overweight or obese, but the prevalence of overweight and obesity may have stabilised between 2004 and 2013. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.Archives of Disease in Childhood 01/2015; 100(3). DOI:10.1136/archdischild-2014-307151
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