Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies

Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin. Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to new therapeutic approaches. Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006     

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…     

基于收益-风险模型分析高校学生在线健康咨询服务使用意愿的影响因素

目的:研究高校学生在线健康咨询服务使用意愿的影响因素.方法:采用方便抽样,使用"问卷星"设计和制作调查问卷,并对成都市两所大学的500名大学生进行问卷调查,使用结构方程模型对在线健康咨询服务使用意愿的影响因素进行分析.结果:问卷回收443份,回收率为88.40%,有效442份,有效率为99.77%.感知收益(β=0.368,P<0.001)、网络信任(β=0.147,P<0.05)和医生信任(β=0.129,P<0.05)正向影响使用意愿;感知风险(β=-0.018,P>0.05)、平台信任(β=0.141,P>0.05)对使用意愿的直接影响未得到支持;网络信任和医生信任在感知风险与使用意愿的关系间具有完全中介作用,在感知收益与使用意愿的关系间发挥部分中介作用.结论:增加公众对网络环境和网上医生的信任以及提高患者潜在的利益是提高在线健康咨询服务的使用意愿的关键.     

探讨带参数微分方程边值问题的解法

主要讨论带参数微分方程边值问题的逼近值及渐近值解法,并且利用基础解系、边值函数等概念,解决了带参数的微分方程中参数充分小的范围内解的变化趋势.     

技术转移:企业资助的学术发明对创新的促进

<正>一般认为企业资助的学术研究对其他人来说是不太容易获取且用处不大的,布莱恩D.怀特及其同事提出的数据对这个看法提出了挑战。政府长期以来一直鼓励大学—企业之间的合作,以期对可以带来工作机会、强化投资并生产出改善生活质量产品的创新进行激励。同时,政府在科学上预算的收缩迫使大学通过其他途径寻求经费支持。根据美国国家科学基金会的统计,2012年由企业提供的科研经费只占到美国研究型大学年度科研经费的5%(大约32亿美元)。     

Discovery of 40Mg and 42Al suggests neutron drip-line slant towards heavier isotopes

A fundamental question in nuclear physics is what combinations of neutrons and protons can make up a nucleus. Many hundreds of exotic neutron-rich isotopes have never been observed; the limit of how many neutrons a given number of protons can bind is unknown for all but the lightest elements, owing to the delicate interplay between single particle and collective quantum effects in the nucleus. This limit, known as the neutron drip line, provides a benchmark for models of the atomic nucleus. Here we report a significant advance in the determination of this limit: the discovery of two new neutron-rich isotopes--40Mg and 42Al--that are predicted to be drip-line nuclei. In the past, several attempts to observe 40Mg were unsuccessful; moreover, the observation of 42Al provides an experimental indication that the neutron drip line may be located further towards heavier isotopes in this mass region than is currently believed. In stable nuclei, attractive pairing forces enhance the stability of isotopes with even numbers of protons and neutrons. In contrast, the present work shows that nuclei at the drip line gain stability from an unpaired proton, which narrows the shell gaps and provides the opportunity to bind many more neutrons.