Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons

Many have hypothesized that cell death in Parkinsons disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP⁺ (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP⁺ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, –8, –6 and –7. A time-course study indicated that activation of caspase-2 and –8 occurred upstream of caspase-6 and caspase-7. Upon MPP⁺ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.Received 20 September 2004; received after revision 5 November 2004; accepted 22 November 2004     

Statistical tests on two characteristics of the shapes of cluster diagrams

A cluster diagram is a rooted planar tree that depicts the hierarchical agglomeration of objects into groups of increasing size. On the null hypothesis that at each stage of the clustering procedure all possible joins are equally probable, we derive the probability distributions for two properties of these diagrams: (1)S, the number of single objects previously ungrouped that are joined in the final stages of clustering, and (2)m _k, the number of groups ofk+1 objects that are formed during the process. Ecological applications of statistical tests for these properties are described and illustrated with data from weed communities of Saskatchewan fields.This work was supported by the Natural Sciences and Engineering Research Council of Canada.     

动态链接库实现程序跨平台技术

讨论了 Win32下用 C语言创建动态库的原则 ;阐述了 CB4、VC6编译系统形成自定义动态库的方法 ;提出了如何在 Authorware4、CB4、VB6使用自定义动态库的思路。     

“五环四步”教学模式建构与实践

\"五环四步\"教学模式是以能力本位职业教育思想为指导建构的中职课堂教学的循序性框架结构.教学运行按照\"能力发展动员、基础能力诊断、能力发展训练、能力发展鉴定和能力教学反思\"五个环节进行,其中,能力发展训练环节按照\"明确任务、协作行动、展示成果、同学互评\"四个步骤展开.与其他教学模式比较,具有需求导向的动机引导、前诊断后鉴定的目标控制、教少学多的时间分配和集中与分组结合的教学形式等创新点.     

地球内核的地震波速各向异性与其自转有关

地球内核相对于外部地球存在差异的转动,固体内核表面相对于液态外核运动的线速度在赤道上最大,在两极为零,因此内核生长速度在赤道附近比两极处快,引力作用将驱动某内部的物质内赤道向两极流动使其保持近似球形,与这一流动相应的轴对称应力场使得六方紧密堆积（ｈｃＰ）铁晶体的ｃ轴沿内核自转轴方向排列,导致地震波速度各向异性。     

植物标签技术

传统的正向遗传学主要用于克隆表型或功能已确定的基因。转座子标签突变体可用随机标签法从带有活性转座子的自交后代中筛选得到,或用定向标签法从杂交一代中筛选得到,即用目的基因的隐性突变统合体与具高度活性转座号的统合体杂交,极大多数的FI个体为正常表型,但其中会有极少量的表现隐性性状的转庄子插入突变体。正向基因标签和克隆法在利用异源和低拷贝数品系时尤其有用。采用反向fCR或热不对称交替PCR（TAIL－PCR）且很容易从单拷贝或低拷贝数品系中获得插入于两侧的基因组序列。TAIL－PCR由三轮连续的半巢式PCR组成,所…     

Crystal structure of the β2 adrenergic receptor-Gs protein complex

G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β(2) adrenergic receptor (β(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the β(2)AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β(2)AR include a 14 ? outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.     

Taming theory with thought experiments: Understanding and scientific progress

I claim that one way thought experiments contribute to scientific progress is by increasing scientific understanding. Understanding does not have a currently accepted characterization in the philosophical literature, but I argue that we already have ways to test for it. For instance, current pedagogical practice often requires that students demonstrate being in either or both of the following two states: 1) Having grasped the meaning of some relevant theory, concept, law or model, 2) Being able to apply that theory, concept, law or model fruitfully to new instances. Three thought experiments are presented which have been important historically in helping us pass these tests, and two others that cause us to fail. Then I use this operationalization of understanding to clarify the relationships between scientific thought experiments, the understanding they produce, and the progress they enable. I conclude that while no specific instance of understanding (thus conceived) is necessary for scientific progress, understanding in general is.