Digenic inheritance of severe insulin resistance in a human pedigree

Impaired insulin action is a key feature of type 2 diabetes and is also found, to a more extreme degree, in familial syndromes of insulin resistance. Although inherited susceptibility to insulin resistance may involve the interplay of several genetic loci, no clear examples of interactions among genes have yet been reported. Here we describe a family in which five individuals with severe insulin resistance, but no unaffected family members, were doubly [corrected] heterozygous with respect to frameshift/premature stop mutations in two unlinked genes, PPARG and PPP1R3A these encode peroxisome proliferator activated receptor gamma, which is highly expressed in adipocytes, and protein phosphatase 1, regulatory subunit 3, the muscle-specific regulatory subunit of protein phosphatase 1, which are centrally involved in the regulation of carbohydrate and lipid metabolism, respectively. That mutant molecules primarily involved in either carbohydrate or lipid metabolism can combine to produce a phenotype of extreme insulin resistance provides a model of interactions among genes that may underlie common human metabolic disorders such as type 2 diabetes.     

Origin and fate of Lake Vostok water frozen to the base of the East Antarctic ice sheet

The subglacial Lake Vostok may be a unique reservoir of genetic material and it may contain organisms with distinct adaptations, but it has yet to be explored directly. The lake and the overlying ice sheet are closely linked, as the ice-sheet thickness drives the lake circulation, while melting and freezing at the ice-sheet base will control the flux of water, biota and sediment through the lake. Here we present a reconstruction of the ice flow trajectories for the Vostok core site, using ice-penetrating radar data and Global Positioning System (GPS) measurements of surface ice velocity. We find that the ice sheet has a significant along-lake flow component, persistent since the Last Glacial Maximum. The rates at which ice is frozen (accreted) to the base of the ice sheet are greatest at the shorelines, and the accreted ice layer is subsequently transported out of the lake. Using these new flow field and velocity measurements, we estimate the time for ice to traverse Lake Vostok to be 16,000-20,000 years. We infer that most Vostok ice analysed to date was accreted to the ice sheet close to the western shoreline, and is therefore not representative of open lake conditions. From the amount of accreted lake water we estimate to be exported along the southern shoreline, the lake water residence time is about 13,300 years.     

Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines

During Drosophila development and mammalian embryogenesis, exit from the cell cycle is contingent on tightly controlled downregulation of the activity of Cyclin E-Cdk2 complexes that normally promote the transition from G1 to S phase. Although protein degradation has a crucial role in downregulating levels of Cyclin E, many of the proteins that function in degradation of Cyclin E have not been identified. In a screen for Drosophila mutants that display increased cell proliferation, we identified archipelago, a gene encoding a protein with an F-box and seven tandem WD (tryptophan-aspartic acid) repeats. Here we show that archipelago mutant cells have persistently elevated levels of Cyclin E protein without increased levels of cyclin E RNA. They are under-represented in G1 fractions and continue to proliferate when their wild-type neighbours become quiescent. The Archipelago protein binds directly to Cyclin E and probably targets it for ubiquitin-mediated degradation. A highly conserved human homologue is present and is mutated in four cancer cell lines including three of ten derived from ovarian carcinomas. These findings implicate archipelago in developmentally regulated degradation of Cyclin E and potentially in the pathogenesis of human cancers.     

圆管结构螺栓法兰接头强度分析

本文对各种圆管结构与压力容器的螺栓法兰接头的计算方法进行了分析,指出了这些方法中所存在的问题。文中推导出一般情况下圆形螺栓法兰接头的弹性解,这一解可被应用于不同类型的接头上。利用这一解可以求出管与法兰之间的相互作用力以及管与法兰中的最大应力。文中以一个圆管结构中的螺栓法兰接头作为实例进行了分析,并与有限单元法计算結果进行了比较。     

Stereochemical course of pheromone biosynthesis in the arctiid moth,Creatonotos transiens

Summary The biosynthetic conversion of a pyrrolizidine alkaloid (heliotrine,IV) to a male moth pheromone (hydroxydanaidal,III) is found to proceed with inversion of configuration at the remaining asymmetric center (C-7).Acknowledgments. The partial support of this research by a grant from the N.I.H. (AI-12020) and by the Deutsche Forschungsgemeinschaft (SFB4-B6) is acknowleded with pleasure.Please address correspondence regarding the chemical aspects of this communication to either T.W. Bell (Stony Brook) or J. Meinwald (Ithaca); inquiries regarding biological aspects should be sent to M. Boppré (Regensburg) or D. Schneider (Seewiesen).     

Effects of acid deposition on crops and forests

Summary Acid deposition includes the gases, sulphur dioxide and nitrogen oxides, and their derivative acids which are dissolved in various forms of precipitation. The effects of both dry and wet deposition on crops and forests are reviewed, including interactions between these two categories of pollutant. Particular emphasis is given to the current forest decline in central Europe, including the possible role of ozone.     

Applying Systemic Project Management Approaches for the UK National Health Service

This paper sets out some observations arising from on-going research into the use of systemic methods in the planning of complex projects within the National Health Service (NHS) in Staffordshire and Shropshire in the UK. This brief paper sets out the main reasons for the application of systemic approaches, the nature of the methodologies put in place and some of the outcomes and reflections of those involved in the various workshops. Whilst not attempting to be definitive in our conclusions, the authors believe that the results of the application of systemic methods by Health and Care professionals show a range of strengths going forward.Published with the kind permission of Staffordshire and Shropshire Workforce Development Directorate.