Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma

G protein-coupled receptors (GPCRs), the largest human gene family, are important regulators of signaling pathways. However, knowledge of their genetic alterations is limited. In this study, we used exon capture and massively parallel sequencing methods to analyze the mutational status of 734 GPCRs in melanoma. This investigation revealed that one family member, GRM3, was frequently mutated and that one of its mutations clustered within one position. Biochemical analysis of GRM3 alterations revealed that mutant GRM3 selectively regulated the phosphorylation of MEK, leading to increased anchorage-independent growth and migration. Melanoma cells expressing mutant GRM3 had reduced cell growth and cellular migration after short hairpin RNA-mediated knockdown of GRM3 or treatment with a selective MEK inhibitor, AZD-6244, which is currently being used in phase 2 clinical trials. Our study yields the most comprehensive map of genetic alterations in the GPCR gene family.     

Exome sequencing identifies GRIN2A as frequently mutated in melanoma

The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (～4%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.     

高性能模数转换器ADS8411及其应用

ADS8411是一款2MSPS采样速率的16位逐次逼近(SAR)模数转换器(ADC).该器件再次显著提高了本身已属业界速度最快的16位SAR转换器产品系列的采样率,其主要面向要求高速、高精度的高级应用,例如医学成像、便携式医疗仪器、零等待数据采集系统、数字通信等.文中介绍了ADS8411的性能特点、内部结构及引脚排列,并给出了其和8位通用数据总线微控制器的接口原理图.     

地球在碰撞中运行

对太阳系的探测表明,陨石撞击是行星表面的形成及日后演变的一个重要进程。例如,月亮表面满是陨痕累累的高地及低洼的、布满熔岩的盆地。遍布陨石坑的高地表明,最初的月球外壳及盆地是38亿年以前、月球形成最后阶段中所发生的巨大碰撞的结果。这些盆地是由直径为10～50公里的物体撞击出来的,后来,陨石坑为大熔岩所填充,就成了现在大家所熟知的平坦的玄武岩平原,即月球海。地球表面一定也曾发生过类似的碰撞。这些巨大的碰撞可能是地壳由早先的模样演变成现今海洋和大陆板