Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration

We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations.     

Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes

Double-stranded RNA interference (RNAi) is an effective method for disrupting expression of specific genes in Caenorhabditis elegans and other organisms. Applications of this reverse-genetics tool, however, are somewhat restricted in nematodes because introduced dsRNA is not stably inherited. Another difficulty is that RNAi disruption of late-acting genes has been generally less consistent than that of embryonically expressed genes, perhaps because the concentration of dsRNA becomes lower as cellular division proceeds or as developmental time advances. In particular, some neuronally expressed genes appear refractory to dsRNA-mediated interference. We sought to extend the applicability of RNAi by in vivo expression of heritable inverted-repeat (IR) genes. We assayed the efficacy of in vivo-driven RNAi in three situations for which heritable, inducible RNAi would be advantageous: (i) production of large numbers of animals deficient for gene activities required for viability or reproduction; (ii) generation of large populations of phenocopy mutants for biochemical analysis; and (iii) effective gene inactivation in the nervous system. We report that heritable IR genes confer potent and specific gene inactivation for each of these applications. We suggest that a similar strategy might be used to test for dsRNA interference effects in higher organisms in which it is feasible to construct transgenic animals, but impossible to directly or transiently introduce high concentrations of dsRNA.     

除草剂稀禾定微胶囊的制备

用原位聚合法以脲醛树脂为壁材,制备除草剂稀禾定微胶囊.考察了预聚反应介质pH值、预聚反应温度、缩聚反应催化剂及缩聚反应终点pH值对微胶囊的结构、包覆效果和包埋率等的影响.结果表明:预聚反应pH值为8.0,预聚反应温度为70℃,反应时间60 min,可得到以二羟甲脲为主的水溶性透明黏稠预聚物,用此预聚物进行缩聚反应,以NH4Cl做缩聚催化剂,芯皮比为1∶1.5(质量比),控制缩聚反应终点pH值为3.0,可制得结构紧密、包埋率为30.6%的流动性球形缓释性固体微胶囊.     

Purification and cloning of amyloid precursor protein beta-secretase from human brain

Proteolytic processing of the amyloid precursor protein (APP) generates amyloid beta (Abeta) peptide, which is thought to be causal for the pathology and subsequent cognitive decline in Alzheimer's disease. Cleavage by beta-secretase at the amino terminus of the Abeta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated carboxy-terminal fragment. Cleavage of the C-terminal fragment by gamma-secretase(s) leads to the formation of Abeta. The pathogenic mutation K670M671-->N670L671 at the beta-secretase cleavage site in APP, which was discovered in a Swedish family with familial Alzheimer's disease, leads to increased beta-secretase cleavage of the mutant substrate. Here we describe a membrane-bound enzyme activity that cleaves full-length APP at the beta-secretase cleavage site, and find it to be the predominant beta-cleavage activity in human brain. We have purified this enzyme activity to homogeneity from human brain using a new substrate analogue inhibitor of the enzyme activity, and show that the purified enzyme has all the properties predicted for beta-secretase. Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase.     

非负张量谱半径上下界的估计不等式

通过张量分析,给出一个具有一般形式的非负张量谱半径的上下界估计不等式,在特别情况下改进了相关非负张量谱半径的估计不等式.     

Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.

Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.     

水合锰(Ⅱ)结构的量子化学和ABEEM/MM研究

应用新一代可极化分子力场——原子-键电负性均衡浮动电荷分子力场ABEEM/MM,结合精密量子化学方法, 构建了精确的Mn²⁺-H₂O 相互作用的势能函数, 确定了相关参数.将该势能函数用于计算[Mn(H₂O)_n]²⁺(n=1~12)的结构和结合能, 得到了与量子化学一致的结果. 进一步对Mn²⁺水溶液进行ABEEM/MM 动力学模拟, 得到的Mn²⁺–O 径向分布函数的第一和第二最高峰分别处于0.218 和0.435 nm 处, 积分得到第一和第二水合层的配位水分子数分别为7.03 和17.74; 对于O–Mn²⁺–O 角度分布函数, 其第一和第二最高峰分别位于80°和140°附近, 这些结果与实验和其他理论方法的结果有很好的一致性. Mn²⁺的极化作用使得第一水合层中水分子的键长明显增长, 键角明显减小; 而Mn²⁺对第二水合层及外层水分子的结构影响较小. 分析体系的电荷分布表明, 与ABEEM-7P 纯水相比, Mn²⁺水溶液中参与形成氢键的氢原子和孤对电子的电荷变化较大, 且Mn²⁺和其邻近的水分子间存在明显的电荷转移.     

A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas.

A gene has been identified that is expressed specifically in stromal cells surrounding invasive breast carcinomas. On the basis of its sequence, the product of this gene, named stromelysin-3, is a new member of the family of metalloproteinase enzymes which degrade the extracellular matrix. The suggestion is that stromelysin-3 is one of the stroma-derived factors that have long been postulated to play an important part in progression of epithelial malignancies.     

基于可持续发展的区域主导产业的选择

针对传统主导产业的选择较多地侧重于经济标准和指标,对社会因素和环境因素重视程度不够等问题,在可持续发展要求下,以传统经济标准和指标为基础,构建反映区域可持续发展贡献的可持续发展标准及废物利用率、水资源消耗量、煤炭资源消耗量等指标,以及反映促进社会进步情况的社会进步标准和吸纳就业人数比、人均收入占区域所有产业人均收入比等指标,体现了经济发展、环境保护与社会进步三方面的要求,并利用AHP方法建立了区域可持续发展主导产业选择模型,对陕西省工业主导产业的发展具有指导作用.     

进水碳磷比对连续流反硝化除磷工艺脱氮除磷效果的影响

针对连续流双污泥反硝化除磷工艺,考察进水碳磷质量比(m(C)/m(P))对化学需氧量(COD)、氨氮和总磷(TP)去除效果的影响.系统进水COD和氨氮分别保持在250和45 mg/L左右,通过改变进水TP浓度来调整m(C)/m(P).实验结果表明:在m(C)/m(P)比分别为64.1,42.0,33.0和17.8的情况下,TP去除率分别为93.2％,92.0％,78.3％和65.8％,除磷效率明显降低.在m(C)/m(P)＞42.0的情况下,出水TP低于0.5 mg/L.随着m(C)/m(P)的降低,反硝化聚磷污泥释磷量和净聚磷量增加,净聚磷量分别为3.63,5.33,6.26和10.3mg/L.m(C)/m(P)减小有利于提高生物除磷系统的稳定性,但出水磷浓度会有所增加,可通过适当延长后置曝气池停留时间来降低出水磷浓度.m(C)/m(P)对COD的去除和脱氮的效果影响不大,COD去除率保持在85.6％～93.1％,氨氮的去除率大于93％.