IgH class switching and translocations use a robust non-classical end-joining pathway

Immunoglobulin variable region exons are assembled in developing B cells by V(D)J recombination. Once mature, these cells undergo class-switch recombination (CSR) when activated by antigen. CSR changes the heavy chain constant region exons (Ch) expressed with a given variable region exon from Cmu to a downstream Ch (for example, Cgamma, Cepsilon or Calpha), thereby switching expression from IgM to IgG, IgE or IgA. Both V(D)J recombination and CSR involve the introduction of DNA double-strand breaks and their repair by means of end joining. For CSR, double-strand breaks are introduced into switch regions that flank Cmu and a downstream Ch, followed by fusion of the broken switch regions. In mammalian cells, the 'classical' non-homologous end joining (C-NHEJ) pathway repairs both general DNA double-strand breaks and programmed double-strand breaks generated by V(D)J recombination. C-NHEJ, as observed during V(D)J recombination, joins ends that lack homology to form 'direct' joins, and also joins ends with several base-pair homologies to form microhomology joins. CSR joins also display direct and microhomology joins, and CSR has been suggested to use C-NHEJ. Xrcc4 and DNA ligase IV (Lig4), which cooperatively catalyse the ligation step of C-NHEJ, are the most specific C-NHEJ factors; they are absolutely required for V(D)J recombination and have no known functions other than C-NHEJ. Here we assess whether C-NHEJ is also critical for CSR by assaying CSR in Xrcc4- or Lig4-deficient mouse B cells. C-NHEJ indeed catalyses CSR joins, because C-NHEJ-deficient B cells had decreased CSR and substantial levels of IgH locus (immunoglobulin heavy chain, encoded by Igh) chromosomal breaks. However, an alternative end-joining pathway, which is markedly biased towards microhomology joins, supports CSR at unexpectedly robust levels in C-NHEJ-deficient B cells. In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations.     

正交试验法优选田七花总黄酮的提取工艺

用正交试验法对田七花中的总黄酮提取工艺进行优化.以田七花中的总黄酮含量为考察指标,采用正交试验L9(34)表进行实验,对提取过程中的乙醇浓度、提取时间、提取次数及料液比四个影响因素进行研究.结果显示影响田七花中的总黄酮提取工艺的显著因素是提取次数,最佳提取工艺是:12倍量的80%的乙醇提取3次,每次1 h.     

马纳斯河流域民主参与式的水资源统一管理

本文针对玛纳斯河流域水资源管理存在逐利、水资源被分割管理,以及缺乏民主参与等问题,提出流域实行水资源统一管理,成立利益相关者参与的民主管理监督机构。     

Rapid disappearance of a warm, dusty circumstellar disk

Stars form with gaseous and dusty circumstellar envelopes, which rapidly settle into disks that eventually give rise to planetary systems. Understanding the process by which these disks evolve is paramount in developing an accurate theory of planet formation that can account for the variety of planetary systems discovered so far. The formation of Earth-like planets through collisional accumulation of rocky objects within a disk has mainly been explored in theoretical and computational work in which post-collision ejecta evolution typically is ignored, although recent work has considered the fate of such material. Here we report observations of a young, Sun-like star (TYC?8241?2652?1) where infrared flux from post-collisional ejecta has decreased drastically, by a factor of about 30, over a period of less than two years. The star seems to have gone from hosting substantial quantities of dusty ejecta, in a region analogous to where the rocky planets orbit in the Solar System, to retaining at most a meagre amount of cooler dust. Such a phase of rapid ejecta evolution has not been previously predicted or observed, and no currently available physical model satisfactorily explains the observations.     

A redox switch in angiotensinogen modulates angiotensin release

Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1?? resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4?? structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.     

LabVIEW和三维虚拟现实技术在物理实验中的应用研究

虚拟仪器技术主要倾向于数据处理的精确性,三维虚拟技术则倾向于形象的仪器展示.利用两者的优势,我们创造性地实现了三维虚拟现实技术与虚拟仪器技术的完美结合,并以"电子示波器的使用"为例,探讨LabVIEW技术和3D技术在物理实验中的应用.     

基于一种扩展分层有限状态机模型的测试生成

为了解决分层有限状态机(HFSM)中数据和约束的问题,对扩展分层有限状态机(E-HFSM)给出了定义对其特征进行了分析,对基于其上的模型所面临的测试问题进行了讨论.考虑了在测试中遇到的控制流和数据流问题,针对其中一种模型(父子EHFSM间不存在数据依赖关系),结合现有的方法工具给出了一种一致性测试生成方法.     

全桥变换器中磁通不平衡的抑制

分析了开关电源在采用全桥变换器的时候磁通不平衡现象的产生原因,并提出了实现抑制磁通不平衡的措施。着重介绍了应用阻隔电容实现磁通平衡的措施,同时进行了相关器件的设计与参数的计算。