Male-pattern baldness susceptibility locus at 20p11

We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 x 10(-14) for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 x 10(-15)).     

Evidence for the intracellular accumulation of anandamide in adiposomes

Anandamide is a lipid messenger that carries out a wide variety of biological functions. It has been suggested that anandamide accumulation involves binding to a saturable cellular component. To identify the structure(s) involved in this process, we analyzed the intracellular distribution of both biotinylated and radiolabeled anandamide, providing direct evidence that lipid droplets, also known as adiposomes, constitute a dynamic reservoir for the sequestration of anandamide. In addition, confocal microscopy and biochemical studies revealed that the anandamide-hydrolase is also spatially associated with lipid droplets, and that cells with a larger adiposome compartment have an enhanced catabolism of anandamide. Overall, these findings suggest that adiposomes may have a critical role in accumulating anandamide, possibly by connecting plasma membrane to internal organelles along the metabolic route of this endocannabinoid. S. Oddi, F. Fezza: These authors contributed equally to the study.     

Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor

Constitutional abnormalities at the imprinted 11p15 growth regulatory region cause syndromes characterized by disordered growth, some of which include a risk of Wilms tumor. We explored their possible contribution to nonsyndromic Wilms tumor and identified constitutional 11p15 abnormalities in genomic lymphocyte DNA from 13 of 437 individuals (3%) with sporadic Wilms tumor without features of growth disorders, including 12% of bilateral cases (P = 0.001) and in one familial Wilms tumor pedigree. No abnormality was detected in 220 controls (P = 0.006). Abnormalities identified included H19 DMR epimutations, uniparental disomy 11p15 and H19 DMR imprinting center mutations (one microinsertion and one microdeletion), thus identifying microinsertion as a new class of imprinting center mutation. Our data identify constitutional 11p15 defects as one of the most common known causes of Wilms tumor, provide mechanistic insights into imprinting disruption and reveal clinically important epigenotype-phenotype associations. The impact on clinical management dictates that constitutional 11p15 analysis should be considered in all individuals with Wilms tumor.     

De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy

Early infantile epileptic encephalopathy with suppression-burst (EIEE), also known as Ohtahara syndrome, is one of the most severe and earliest forms of epilepsy. Using array-based comparative genomic hybridization, we found a de novo 2.0-Mb microdeletion at 9q33.3-q34.11 in a girl with EIEE. Mutation analysis of candidate genes mapped to the deletion revealed that four unrelated individuals with EIEE had heterozygous missense mutations in the gene encoding syntaxin binding protein 1 (STXBP1). STXBP1 (also known as MUNC18-1) is an evolutionally conserved neuronal Sec1/Munc-18 (SM) protein that is essential in synaptic vesicle release in several species. Circular dichroism melting experiments revealed that a mutant form of the protein was significantly thermolabile compared to wild type. Furthermore, binding of the mutant protein to syntaxin was impaired. These findings suggest that haploinsufficiency of STXBP1 causes EIEE.     

星际传输的审判

"博士,我不知道自己是谁." "你是安德拉-波隆斯基律师." "我还是不明白." "你是怎么了,律师先生?" "我不知道从何说起." "你不会是得健忘症了吧?"     

Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon

Kras is commonly mutated in colon cancers, but mutations in Nras are rare. We have used genetically engineered mice to determine whether and how these related oncogenes regulate homeostasis and tumorigenesis in the colon. Expression of K-Ras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek-dependent manner. N-Ras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc-mutant colonic tumor, activation of K-Ras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This K-Ras tumor phenotype was associated with attenuated signaling through the MAPK pathway, and human colon cancer cells expressing mutant K-Ras were hypersensitive to inhibition of Raf, but not Mek. These studies demonstrate clear phenotypic differences between mutant Kras and Nras, and suggest that the oncogenic phenotype of mutant K-Ras might be mediated by noncanonical signaling through Ras effector pathways.     

利用14N(d，p)15N核反应对各品系小麦种子中蛋白质含量分析初探

粮食作物提供的植物蛋白是人体所需要的蛋白质中最基本、最重要的来源 ,提高粮食作物中的蛋白质含量 ,对改善食品质量、提高营养水平有着重要意义 ,国际上一直把改善谷物蛋白质含量作为重要研究课题 .测定植物样品中蛋白质含量的传统方法是Ｋ氏 (Ｋｊｅｌｄａｈｌ)化学分析法 ,但Ｋ氏法是破坏性的 ,同时又很费时 ,难以满足在选种培育计划中对大批量样品进行快速分析的需要 .因此由基于对氮元素成分的分析出发 ,从而促进了确定蛋白质含量的核技术在这一需求下得到迅速的发展[1] ,如快中子活化法、热中子活化法、光子活化分析法和由质子、α粒…     

乌利雅诺天的母亲——百岁诞辰(三月六日)纪念

玛丽亚·亚历亚山大罗夫娜·乌利雅诺夫瓦,单因为她是乌拉狄米尔·伊里奇·乌利雅诺夫(即列宁)的母亲这一点,谁都不能忘记她的,即使他不大知道她的话.事实上,人人的心中都透明的记念着她这不仅因为她的伟大的儿子的光荣反射在她身上,而且因为她本人也值得社会的注意,她的美丽和温雅是世所罕有的.我毫不怀疑的说,她儿子们所稟有的精神上的财富,其中不少的部分是得自母亲或由母亲而获得的.她把家庭弄得非常的亲睦,从来没有吵嘴,或不     

感知和认识的控制论

感知和认识问题与哲学的历史一样古老；它是认识论的首要问题。古往今来的哲学家都议论过这样一个事实：虽然到达我们眼睛、耳朵和其他感觉器官的感觉信息在不停变换，但我们却能感知到稳固的物体、人物和经常发生的可辨认的事件。古希腊人谈沦感觉世界的     

大维广义Beta矩阵极限谱分布函数

在Beta矩阵定义的基础上,针对运用大维Beta矩阵的极限谱分布函数的形式及其线形谱统计量的中心极限定理,可以得到检验函数的置信水平,却无法得到准确的势函数问题,进行了拓展,给出了广义大维Beta矩阵极限谱分布函数,由此不仅可以得到检验函数的置信水平,还可得到准确的势函数.