Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations

Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer, but account for only a small fraction of breast cancer susceptibility. To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (refs 3,4,5). We show that CHEK2(*)1100delC, a truncating variant that abrogates the kinase activity, has a frequency of 1.1% in healthy individuals. However, this variant is present in 5.1% of individuals with breast cancer from 718 families that do not carry mutations in BRCA1 or BRCA2 (P = 0.00000003), including 13.5% of individuals from families with male breast cancer (P = 0.00015). We estimate that the CHEK2(*)1100delC variant results in an approximately twofold increase of breast cancer risk in women and a tenfold increase of risk in men. By contrast, the variant confers no increased cancer risk in carriers of BRCA1 or BRCA2 mutations. This suggests that the biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCA2 mutations, which is consistent with participation of the encoded proteins in the same pathway.     

TLR4 mutations are associated with endotoxin hyporesponsiveness in humans

There is much variability between individuals in the response to inhaled toxins, but it is not known why certain people develop disease when challenged with environmental agents and others remain healthy. To address this, we investigated whether TLR4 (encoding the toll-like receptor-4), which has been shown to affect lipopolysaccharide (LPS) responsiveness in mice, underlies the variability in airway responsiveness to inhaled LPS in humans. Here we show that common, co-segregating missense mutations (Asp299Gly and Thr399Ile) affecting the extracellular domain of the TLR4 receptor are associated with a blunted response to inhaled LPS in humans. Transfection of THP-1 cells demonstrates that the Asp299Gly mutation (but not the Thr399Ile mutation) interrupts TLR4-mediated LPS signalling. Moreover, the wild-type allele of TLR4 rescues the LPS hyporesponsive phenotype in either primary airway epithelial cells or alveolar macrophages obtained from individuals with the TLR4 mutations. Our findings provide the first genetic evidence that common mutations in TLR4 are associated with differences in LPS responsiveness in humans, and demonstrate that gene-sequence changes can alter the ability of the host to respond to environmental stress.     

国学的术语规范问题

国学的术语规范指的是国学所属各学科的术语规范。国学术语的规范既是术语学和国学的研究对象,也是语言规划的重要内容,同时它还是建设有中国特色术语学的重要组成部分。文章从国学术语的概念划分、科学定义、术语定名和译介等方面对国学的术语规范问题作了系统阐述。     

人工关节材料及其表面改性研究进展

人工关节是替代病变或损伤关节的植入性假体,除了应满足生物相容性要求外,必须具备足够的抗磨损能力。本文综述了目前使用的不同人工关节材料的性能,以及为提高抗磨损能力而对各种材料进行改性处理的新方法,提出在人工关节表面加工微纳结构来提高其抗磨损性能和生物相容性的新思路。     

基于小波与BP神经网络的太阳黑子时间序列分析预测

太阳黑子年平均数序列是典型的非线性、复杂时间序列.本文利用小波变换,将太阳黑子年平均数序列进行分解重构,对信号的周期特性进行分析,然后采用BP神经网络对重构信号进行预测,建立太阳黑子年平均数的预测序列.结果表明,该模型具有较高的预测精度.     

山西省R＆D经费投入状况分析

通过对山西省R&D经费投入状况的分析,指出了其不足与存在的问题,并进一步提出应加大山西省R&D经费投入力度,使R&D活动真正成为促进山西省经济发展的主要动力。     

西安市住宅价格波动状况及政策建议

研究西安市住宅价格的波动特性及其产生原因,建立系统动力学中的因果回路图模型,分析住宅价格的因果反馈环.得出西安市住宅价格近年来处于上涨态势,但与一线城市和其它部分二线城市住宅价格波动幅度相比,波动幅度小并趋于稳定上升状态.为此提出,政府应坚持房地产调控不动摇,根据不同的需求层次合理地开发住宅产业,引导住宅需求的梯度消费,同时加强保障性安居工程建设.     

浅谈居住小区规划技术标准的修改

针对当前《城市居住区规划设计规划》中部分指标老化给居住小区规划带来的负面影响,分别分析了城市居住小区户均人口下降、人均居住用地指标增大、机动车交通迅速增长、城市社会人口年龄结构变化以及人们日常生活需求的变化对小区规划产生的影响,指出应相应调整《规范》中关于小区规模、道路与停车设施、配套公共设施及小区绿地的规划设计指标,并应进一步完善指标体系,从而使小区规划更科学合理。     

几种可用于化学课堂观察的量化研究工具简析

本文主要站在化学课堂观察的角度,按照时间轴简单介绍了目前较为活跃的可以应用于化学课堂观察的量化取向的课堂观察量表、模型和范式,以及应用在化学课堂观察中可能出现的情况,并简单地分享化学课堂观察的量化研究发展历程给笔者的一些启示.