Carboxy terminus of vasopressin required for activity but not binding

Vasopressin antagonists are valuable pharmacological tools for investigating physiological and behavioural functions of the nonapeptide arginine-vasopressin (AVP). The removal of glycinamide from the carboxy terminus of AVP drastically reduces its characteristic vasopressor and antidiuretic activities. In contrast to this we show here that removal of the carboxy-terminal glycinamide or the glycine at position 9 from several vasopressin antagonists makes little difference to their ability to block vasopressor and antidiuretic responses to AVP. These data demonstrate the critical structural requirements of the carboxy-terminal position for receptor activation, in contrast to the lack of such requirements for receptor binding. They also provide an avenue to a wide variety of antagonists substituted at the carboxy terminus (for example radiolabelled derivatives and affinity ligands) and suggest clues for the development of more potent and/or selective antagonists.     

Catalytic C-H functionalization by metal carbenoid and nitrenoid insertion

Novel reactions that can selectively functionalize carbon-hydrogen bonds are of intense interest to the chemical community because they offer new strategic approaches for synthesis. A very promising 'carbon-hydrogen functionalization' method involves the insertion of metal carbenes and nitrenes into C-H bonds. This area has experienced considerable growth in the past decade, particularly in the area of enantioselective intermolecular reactions. Here we discuss several facets of these kinds of C-H functionalization reactions and provide a perspective on how this methodology has affected the synthesis of complex natural products and potential pharmaceutical agents.     

基于模因论的英语听说教学实验研究

以模因论为指导，将模因生命周期的同化、记忆、表达、传输4个阶段结合运用于为期1年的英语听说教学实验，证实了该实验能促进学生英语听说能力的提高，对中等程度的学生比低等程度的学生更有效，实验中学生的模因识别与输出受到不同的听力题材和听说练习要求的影响。     

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.     

一种新型纤维增强复合材料加筋透水沥青路面

透水沥青路面因其能够快速排水等优点常用于多雨地区城市道路和高速公路的建设。为提升道路结构耐久性,多雨地区通常选择水泥混凝土或无机结合料稳定基层,因而反射裂缝问题普遍存在,路表水沿裂缝持续下渗会造成路基沉降从而破坏整体道路结构。水损害防治是道路质量控制的关键问题,为此本文提出一种新型纤维增强复合材料（fiber reinforced plastic,FRP）加筋透水沥青路面结构,可在不提高配筋率的条件下,极大减小降雨对基层的影响,同时不增加沥青路面车辙等病害风险。为了验证新型路面结构效果,开展了相关的室内实验并修筑了实验路段。在实验路段中,使用了部分FRP智能筋,同时还布设了土壤湿度传感器,以对路面结构长期性能进行监测。结果证明了新型FRP加筋透水沥青路面结构的可行性和效果。     

Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness

Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.