Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.     

How do Shp2 mutations that oppositely influence its biochemical activity result in syndromes with overlapping symptoms?

Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes. Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1, Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the possibility that LS mutations may not simply exhibit dominant negative activity. Received 30 November 2006; received after revision 8 February 2007; accepted 13 March 2007     

Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia

Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia.     

GSM中归属位置寄存器数据库的设计与实现

基于某种移动通信系统（ＧＳＭ）数字程控交换机归属位置寄存器（ＨＬＲ）数据库系统的工作原理,对ＨＬＲ数据库内容特别是用户数据进行详细分析,针对用户数据容量大的特点,设计出模块数据存储方案;并且通过定义数据特征描述表给出了独立于存储结构的用户访问模型和一组高效的ＡＰＩ函数。整个数据库设计方案数据冗余度小,操作简单快速,在应用层较好地屏蔽了数据的存储结构,数据调整灵活。     

Seed germination in response to diurnal fluctuations of temperature

Diurnal fluctuations in temperature may initiate or accelerate germination in certain flowering plants, and the effectiveness of the stimulus varies according to the amplitude of fluctuation and the presence or absence of light. Attempts to assess the adaptive significance of the phenomenon, however, have been limited by the scarcity of data for species of contrasted ecology. We report here an investigation of germination responses to fluctuating temperatures, conducted on seeds of herbaceous species collected from native populations near Sheffield. The results suggest that requirements for diurnal fluctuations in temperature are characteristic of the germination of species from particular types of habitat and provide mechanisms which cause seeds to germinate at times and in places favourable for seedling establishment.     

拨打越洋长途省钱三大绝招

“表达思念,怎么也不如一次见面。”不记得是什么品牌的补品广告了,但弄得很感人的样子。确实如此,见面是最亲近的表达思念的方式,不过世界太大了,常见面的只能是邻居。     

浅谈过冷度产生原因及消除方法

1．过冷度对机组运行经济性和安全性的影响 凝结水过冷度表征了凝汽器热井中凝结水的过冷却程度，凝汽器热井出口凝结水温度与凝汽器在排汽压力下对应的饱合温度之差即称为过冷度。