Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions

Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated PrP27 – 30 detectable by the 3F4 antibody against human PrP109 – 112. We recently identified a new PK-resistant PrP species, designated PrP^*20, in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 – 108 but not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP^*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic mutant PrP accumulate not only PrP^*20 but also a small amount of 3F4-detected PK-resistant PrP27 – 30. Remarkably, during the course of human prion disease, a transition from an increase in 1E4-detected PrP^*20 to the occurrence of the 3F4-detected PrP27 – 30 was observed. Our study suggests that an increase in the level of PrP^*20 characterizes the early stages of prion diseases. Received 17 October 2007; received after revision 5 December 2007; accepted 14 December 2007     

Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer

We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 x 10(-13) and 7.7 x 10(-9), respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease.     

基于LabVIEW软件的虚拟线性拟合仪的设计

虚拟仪器(Virtual Instrument,简称VI)是现代计算机软件技术、通信技术和测量技术相结合的产物.LabVIEW软件是美国M公司推出的一款功能强大的虚拟仪器开发平台.基于LabVIEW的优势,阐述了线性拟合仪原理及设计,实际应用证明它是实验教学的发展方向.     

痕量汞的催化动力学光度法测定

在酸性介质中 ,汞 (Ⅱ )对过氧化氢氧化甲基橙的反应具有强烈的催化作用 .研究了反应的动力学条件 ,建立了测定痕量汞的新方法 ,测定汞的线性范围为 0 .6～ 6 μg/L ,检出限为 4.0× 10 -11g/L .该方法简便、灵敏、选择性好 ,应用于合成水样及污水中痕量汞的测定 ,结果满意 .     

基于有限元模拟的微铜柱互连点热失效分析

采用有限元模拟法,研究了微铜柱互连点在热冲击载荷条件下的应变和应力,并分析了微互连点的裂纹生长情况.结果表明,封装结构最外侧的微互连点为最易失效互连点(关键互连点).累积塑性应变能密度主要集中在芯片侧铜焊盘附近,且由外向内逐渐递减,这表明裂纹形成在芯片侧,并沿着焊盘由外向内扩展,最终贯穿整个互连点.试验结果与模拟分析一...     

基于MultisimV7平台的组合逻辑电路中竞争冒险的分析

MultisimV7应用于分析组合逻辑电路中竞争冒险现象的教学,使教学直观、生动、形象,是对传统教学方法的一种改革,使理论教学与实践更好的紧密结合,实际应用证明MultisimV7是实验教学的发展方向。     

企业领导应有的八种能力

从传统的管理视角看，企业领导需具有组织、领导、协调、沟通和控制等能力。随着经济全球化时代的到来，多元化需求的市场愈发变得硝烟弥漫，在这充满竞争的时代，企业领导究竟具有什么样的能力结构才能在未来竞争中获胜？我认为企业领导，应具备的有别于传统要求的八种能力，才能不断增强自身的领导能力和整体素质。     

Reduced antinociception in mice lacking neuronal nicotinic receptor subunits

Nicotine exerts antinociceptive effects by interacting with one or more of the subtypes of nicotinic acetylcholine receptors (nAChRs) that are present throughout the neuronal pathways that respond to pain. To identify the particular subunits involved in this process, we generated mice lacking the alpha4 subunit of the neuronal nAChR by homologous recombination techniques and studied these together with previously generated mutant mice lacking the beta2 nAChR subunit. Here we show that the homozygous alpha4-/- mice no longer express high-affinity [3H]nicotine and [3H]epibatidine binding sites throughout the brain. In addition, both types of mutant mice display a reduced antinociceptive effect of nicotine on the hot-plate test and diminished sensitivity to nicotine in the tail-flick test. Patch-clamp recordings further reveal that raphe magnus and thalamic neurons no longer respond to nicotine. The alpha4 nAChR subunit, possibly associated with the beta2 nAChR subunit, is therefore crucial for nicotine-elicited antinociception.