Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons

Using a novel single-molecule PCR approach to quantify the total burden of mitochondrial DNA (mtDNA) molecules with deletions, we show that a high proportion of individual pigmented neurons in the aged human substantia nigra contain very high levels of mtDNA deletions. Molecules with deletions are largely clonal within each neuron; that is, they originate from a single deleted mtDNA molecule that has expanded clonally. The fraction of mtDNA deletions is significantly higher in cytochrome c oxidase (COX)-deficient neurons than in COX-positive neurons, suggesting that mtDNA deletions may be directly responsible for impaired cellular respiration.     

Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon

Kras is commonly mutated in colon cancers, but mutations in Nras are rare. We have used genetically engineered mice to determine whether and how these related oncogenes regulate homeostasis and tumorigenesis in the colon. Expression of K-Ras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek-dependent manner. N-Ras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc-mutant colonic tumor, activation of K-Ras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This K-Ras tumor phenotype was associated with attenuated signaling through the MAPK pathway, and human colon cancer cells expressing mutant K-Ras were hypersensitive to inhibition of Raf, but not Mek. These studies demonstrate clear phenotypic differences between mutant Kras and Nras, and suggest that the oncogenic phenotype of mutant K-Ras might be mediated by noncanonical signaling through Ras effector pathways.     

小凉山的俘虏、亲属和奴隶

20世纪50年代集体化改革之前小凉山奴隶制度特有的社会经济进程表明,诺苏社会曾是一个拥有奴隶的社会,但它并不是奴隶社会。该结论基于其他关于奴隶制研究中的传统观念即在奴隶社会中奴隶制是体系得以维持的关键所在。1956年之前,小凉山的生产目的是生计而不是市场。此外,小凉山的精英阶层更依赖于系谱或继嗣,而不是财富;另一个相关论点是,在诺苏身份和认同的决定中,亲属比等级发挥了更为基础的作用。     

Melatonin antagonizes colchicine-induced mitotic arrest

Summary Melatonin, in concentrations up to 10^–3 M, showed no effect on mitosis in cultures of HeLa or KB cells. However, when melatonin at 10^–4 M was preincubated with HeLa cells prior to addition of 10^–7 M colchicine, a reduction in the mitotic index, in comparison to colchicine alone, was observed.This work was supported by PHS Grant No. CA 16425.     

Characterization of the domestic horse (Equus caballus) karyotype using G-and C-banding techniques

Summary Giemsa banding techniques have been used to identify the chromosomes of the domestic horse.     

Dystrophic mutation (dy2J) affecting regulation of lactate dehydrogenase (LDH) and pyruvate kinase (PK) in C57BL/6J mice

Summary The genotype difference (dystrophic vs nondystrophic) in the LDH isozymes is observed in kidney. These differences are evident only at birth and at early developmental stages (before the expression of dystrophic symptoms). The tissue specific genotype differences for PK are limited to the thigh muscle (M form) and heart (L form), after the onset of the condition. These differences may reflect the pleiotropic effect of the dy^2J locus during the temporal regulation of these and other enzymes implicated in muscular dystrophy (MD).This research was financed by a Natural Sciences and Engineering Research Council Canada grant to S.M.S.     

A heuristic model of creativity

Zusammenfassung Im Rahmen eines heuristischen Modells und unter dem Einfluss der psychoanaleptischen Drogc Psilocybin wird die regulierend-complementierende geistige Tätigkeit untersucht. Gesunde, junge Volontäre vermögen nach oraler Verabreichung von 10–12 mg Psilocybin gedruckte Texte zu lesen, obgleich der obere Teil jeder Zeile bis zu 74% unsichtbar ist.     

声学多孔材料的孔结构优化

介绍了一种基于微结构的声学模型,可用来对多孔材料的微组织结构进行优化,从而使多孔材料具备最佳的声学性能.该模型是一种适用于低雷诺数的非稳态线性声学模型,主要微结构考虑平行排列的柱形杆件或圆球列阵,包括3个子模型:①声波传播方向平行于圆柱形杆件的子模型;②声波传播方向垂直于圆柱形杆件的子模型;③声波在圆球列阵中传播和吸收的子模型.前2个子模型通过考虑多边形周期边界条件的影响,计及了相邻圆柱形杆件间的交互作用.由于模型是线性的,因此可以结合起来描述任意角度入射声波的传播特性.第3个子模型可用于描述胞状多孔材料中节点处的情形.文中利用这3个子模型来扩大吸声材料的设计空间,根据不同用途所要求的声学特性计算最优的胞元结构,并对这种模型的应用领域进行了分析讨论.