Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations

There is emerging evidence that people with successfully treated HIV infection age prematurely, leading to progressive multi-organ disease, but the reasons for this are not known. Here we show that patients treated with commonly used nucleoside analog anti-retroviral drugs progressively accumulate somatic mitochondrial DNA (mtDNA) mutations, mirroring those seen much later in life caused by normal aging. Ultra-deep re-sequencing by synthesis, combined with single-cell analyses, suggests that the increase in somatic mutation is not caused by increased mutagenesis but might instead be caused by accelerated mtDNA turnover. This leads to the clonal expansion of preexisting age-related somatic mtDNA mutations and a biochemical defect that can affect up to 10% of cells. These observations add weight to the role of somatic mtDNA mutations in the aging process and raise the specter of progressive iatrogenic mitochondrial genetic disease emerging over the next decade.     

浅谈高校图书馆服务模式创新和形象塑造

网络化、信息化、数字化时代的到来改变了图书馆的运行环境,使高校图书馆的信息服务出现了危机,因此需要创新服务模式,优化服务流程,即开展个性化服务,设立学科信息服务中心,开展层次化信息服务。     

Exome sequencing identifies GRIN2A as frequently mutated in melanoma

The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (～4%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.     

Chromosome aberrations induced by daunomycin in human leucocyte cultures,with the apparent synergistic effect of arginine

Zusammenfassung Das Antibiotikum und Zytostatikum Daunomycin induziert beträchtliche Chromosomenaberrationen in menschlichen Leukozyten in der Konzentration von 0,02 µg/cm³. Dieser Effekt wird durch Zusatz von Arginin zur Zellkultur wesentlich verstärkt, und die Aberrationen werden auch qualitativ verändert. Es ist nicht bekannt, wie Daunomycin und Arginine aufeinander einwirken.     

iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53

iASPP is one of the most evolutionarily conserved inhibitors of p53, whereas ASPP1 and ASPP2 are activators of p53. We show here that, in addition to the DNA-binding domain, the ASPP family members also bind to the proline-rich region of p53, which contains the most common p53 polymorphism at codon 72. Furthermore, the ASPP family members, particularly iASPP, bind to and regulate the activity of p53Pro72 more efficiently than that of p53Arg72. Hence, escape from negative regulation by iASPP is a newly identified mechanism by which p53Arg72 activates apoptosis more efficiently than p53Pro72.     

Colorectal cancer: mutations in a signalling pathway

Protein kinases are enzymes that are important for controlling cellular growth and invasion, and their malfunction is implicated in the development of some tumours. We analysed human colorectal cancers for genetic mutations in 340 serine/threonine kinases and found mutations in eight genes, including in three members of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway. The discovery of this mutational activation of a key cell-signalling pathway may provide new targets for therapeutic intervention.     

某型航空发动机对插板式进气畸变的响应

为得到较为准确的发动机对进气畸变的稳定性响应模型,首先分析了由实验所得到的某型航空涡扇发动机进口扰流插板产生的稳态总压畸变和紊流分布。相对于压气机转子进口,将周向分布的稳态总压畸变和截面脉动压力处理成为一组不同频率的压力激励波形分布。通过频谱分析得到:在发动机失稳前,稳态畸变形成的波形频率最低,幅值最大,是引起发动机失稳的主要原因。对该组合畸变激励波用一阶响应模型进行动态修正并使用平行压气机分析模型,得到了经修正的压气机喘振边界和得到改善的发动机进气畸变响应模型。最后分别计算了高、低压压气机逐步失稳的工作点移动过程。结果表明:与压气机出口实验失稳波形十分接近,该模型准确可行。     

局部固支功能梯度板的横向弯曲研究

研究了局部固支功能梯度方板在横向均布载荷作用下的静力学问题。假设功能梯度材料由陶瓷和钢组成，材料弹性模量设计为沿着板的厚度方向按照幂指数形式连续变化，功能梯度方板的四个边均为局部固支，应用Kirchhoff薄板理论和虚功原理推导了板的静力学有限元方程。另分别考虑了各边50%固支和25%固支两种情况，在板材料为纯陶瓷和纯钢时，将所得结果与ANSYS软件结果对比，验证了所建模型的准确性。最后，重点分析了梯度指数对板面和边界最大挠度的影响。结果表明梯度指数和固支范围是决定最大挠度的关键参数，其中固支范围对边界上最大挠度的影响更大。