Protein misfolding and disease: the case of prion disorders

Recent findings strongly support the hypothesis that diverse human disorders, including the most common neurodegenerative diseases, arise from misfolding and aggregation of an underlying protein. Despite the good evidence for the involvement of protein misfolding in disease pathogenesis, the mechanism by which protein conformational changes participate in the disease is still unclear. Among the best-studied diseases of this group are the transmissible spongiform encephalopathies or prion-related disorders, in which misfolding of the normal prion protein plays a key role in the disease. In this article we review recent data on the link between prion protein misfolding and the pathogensis of spongiform encephalopathies. Received 15 July 2002; received after revision 19 August 2002; accepted 23 August 2002 RID="*" ID="*"Corresponding author.     

药物与心理调节治疗胃肠功能紊乱60例疗效观察

目的 观察刺五加、谷维素加心理调节方案对胃肠功能紊乱的疗效。方法 随机分为治疗组和对照组各60例。治疗组除药物治疗,再加心理治疗。结果 治疗组显效51例,有效9例,总有效率100％,对照组总有效率81％,两组有明显的差异(P<0.01)。结论 刺五加具有养血活血、安神定智的功效,提高机体对有害刺激的防御能力;谷维素有中枢性抗功能紊乱作用,解除失眠、焦虑等症状;心理调节排除患者精神障碍。三者并用,疗效显著。     

Developmental genetics

Summary Of particular concern to the human geneticist are the effects of genetic abnormalities on development. To gain an understanding of these effects it is necessary to engage in a reciprocal process of using knowledge of normal developmental events to elucidate the mechanisms operative in abnormal situations and then of using what is learned about these abnormal situations to expand our understanding of the normal. True developmental genes have not been described in man, although it is likely that they exist, but many developmental abnormalities are ascribable to mutations in genes coding for enzymes and structural proteins. Some of these even produce multiple malformation syndromes with dysmorphic features. These situations provide a precedent for asserting that not only monogenic developmental abnormalities, but also abnormalities resulting from chromosome imbalance must ultimately be explicable in molecular terms. However, the major problem confronted by the investigator interested in the pathogenesis of any of the chromosome anomaly syndromes is to understand how the presence of an extra set of normal genes or the loss of one of two sets of genes has an adverse effect on development. Several molecular mechanisms for which limited precedents exist may be considered on theoretical grounds. Because of the difficulties in studying developmental disorders in man, a variety of experimental systems have been employed. Particularly useful has been the mouse, which provides models for both monogenic and aneuploidy produced abnormalities of development. An example of the former is the mutation oligosyndactylism which in the heterozygous state causes oligosyndactyly and in the homozygous state causes early embryonic mitotic arrest. All whole arm trisomies and monosomies of the mouse can be produced experimentally, and of special interest is mouse trisomy 16 which has been developed as an animal model of human trisomy 21 (Down syndrome). In the long run, the most direct approach to elucidating the genetic problems of human development will involve not only the study of man himself but also of the appropriate experimental models in other species.Acknowledgments. This review was written while the author was a Henry J. Kaiser Senior Fellow at the Center for Advanced Study in the Behavioral Sciences, Palo Alto, California. This work was supported by grants from the National Institutes of Health (GM-24309, HD-03132, HD-15583, HD-17001) and the American Cancer Society (CD-119) and by a contract from the National Institute of Child Health and Human Development (NOI-HD-2858).     

能量有效的无线传感器网络数据收集协议

针对无线传感器网络(wireless sensor networks,WSNs)中数据收集易丢失的特点,提出了一种能量有效的数据收集协议?该协议引入链路质量门限来构造骨干投递网,提高链路可靠性?在构造算法中分配的核结点和非核节点分别采用2种不同的时隙调度表来进行数据传输,该调度算法让暂时不参与数据传输的节点进入睡眠模式,降低节点能量消耗?协议采用管道投递(pipeline delivery)模式进行数据传输,避免传输过程中的互干扰?TOSSIM实验仿真表明,与CTP(collection tree protocol)协议相比,该协议在不计算睡眠调度算法获得的能量增益情况下,仍获得较好的传输开销和更高的能量利用率,减小了网络整体能耗?     

一种新的基于增加ONU-BSs间保护时隙的节能算法

文中提出一种同时增加无线网络前端和光网络后端的节能算法.该算法在光网络后端通过增加保护间隙来避免没有或有很少流量要传输的ONU-BSs排队于OLT,使ONU-BSs有更多的时间进行休眠;在无线网络前端,不活跃的SSs或者有很少流量传输的SSs将会从运行状态转换成休眠状态来节省功率消耗.在给定的包延迟状态下,仿真结果表明,文中所提算法能够有效地减少能量消耗.     

家族性和三阴性乳腺癌血清中miR-21的表达

目的:检测血清miR-21在乳腺癌中的表达差异,为进一步阐明miR-21在家族性和三阴性乳腺癌发病机制中的作用.方法:收集健康女性体检者、具有患乳腺癌高风险者、不同种类乳腺癌患者的血清.以线虫miR-39为外参,通过实时荧光定量PCR检测77份血清中miR-21的表达水平.结果:家族性乳腺癌组、三阴性乳腺癌组和乳腺癌高风险组血清miR-21水平显著高于正常对照组、其他乳腺癌组(P0.01).血清miR-21的表达水平与淋巴结转移、Ki67高表达有关(P0.01).结果显示血清miR-21表达量在家族性和三阴性乳腺癌中升高,且与淋巴结转移和Ki67表达有关.结论:血清miR-21与三阴性、家族性乳腺癌的发生有紧密联系,其表达增高与乳腺癌的遗传性、恶性程度及预后判断有关.     

基于WIMAX网络的IEEE802.16e PSC TypeⅡ休眠机制

针对宽带移动通信中移动站短时间休眠带来的能量效率下降问题,研究IEEE 802.16e休眠模式的节能机制.为了保证实时性的同时降低能量消耗,提出一种动态调整时间门限的方案,通过设立动态检测时间并启发式调整休眠时间建立的休眠模式的马尔可夫链分析模型,分析该方案对能量效率和数据包延时的影响.通过NS2仿真验证所提动态算法比标准中的能量效率获得明显提高.     

Neuroanatomy and neurochemistry of sleep

Sleep is regulated by homeostatic and circadian factors, and the regulation of sleep of mammals shares many molecular properties with the rest state of submammalian species. Several brain structures take part in waking: the basal forebrain, posterior and lateral hypothalamus, and nuclei in the tegmentum and pons. Active sleep mechanisms are located to the preoptic/anterior hypothalamic area. In addition to acetylcholine and monoamines, glutamate and hypocretin/orexin are important waking factors. Gamma-aminobutyric acid and several peptide factors, including cytokines, growth hormone-releasing hormone and prolactin, are related to sleep promotion. Adenosine is an important homeostatic sleep factor acting in basal forebrain and preoptic areas through A1 and A2A receptors. Prolonged waking activates inducible nitric oxide synthase in the basal forebrain, which through energy depletion causes adenosine release and recovery sleep. Numerous genes have been found differentially displayed in waking compared with sleep, and they relate to neural transmission, synaptic plasticity, energy metabolism and stress protection. The genetic background of a few sleep disorders has been solved.     

两种新生大鼠皮质发育障碍模型的差异基因表达谱研究

目的研究两种不同的方法构建皮质发育障碍(DCDs)动物模型中的共同差异表达基因,为进一步研究DCDs形成机制提供基因水平筛选的研究平台。方法用两种方法制备DCDs模型:①射线损伤模型(射线组):采用剂量为1.45 Gy的γ射线照射妊娠15 d的SD大鼠制作子代大鼠DCDs模型;②卡莫司汀(BCNU)药物损伤模型(药物组):妊娠15 d的SD大鼠,腹腔注射BCNU制作子代大鼠DCDs模型。同时设正常对照组。对两种DCDs模型的子代新生鼠(P0)全脑做基因芯片扫描,结果与正常对照组比较,获得两种模型共有的差异基因。结果射线组大鼠与正常比较得到170个差异基因,其中25个上调,145个下调;药物组大鼠与正常比较得到259个差异基因,其中67个上调,192个下调。两组重合的基因共54个,其中3个上调,51个下调。结论皮质发育障碍是一个复杂的病理过程,本实验运用基因芯片技术,对两种不同方法构建的DCDs模型进行了研究,获得两种DCDs模型共有的基因差异表达谱,为进一步研究DCDs形成机制提供了分子生物学平台。     

睡眠脑电的非线性动力学方法

在8例健康成年人的睡眠脑电监测实验基础上,利用已有的专家人工分期结果,提取睡眠各阶段特征数据,应用近似熵、复杂度和功率谱熵三种方法进行分析,从客观量化的复杂性度量来刻划睡眠深度的变化情况,对每个睡眠分期选取5000点数据,数据窗取1000点,逐次延时一个采样间隔得到几个时间序列,分别求复杂度,最后取均值即得此分期复杂性测度值,结果表明三种方法均与专家人工分期结果相吻合,近似熵算法复杂不适合在线分析;复杂度算法较简单,但数据粗粒化处理容易丢失信息;功率谱熵算法简单、快速及有效,因而用统计分析方法分析,表明功率谱熵能较好地反映睡眠深度的变化情况。