SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.     

重油和沥青中芳香碳的定量估计

采用＾１Ｈ－ＮＭＲ和＾Ｓ１３Ｃ－ＮＭＲ谱，结果元素分析等数据，估计了重油和沥青中各种类型芳香碳，建立了较完整的表征方法。在模型混合物核磁共振谱基础上，指定＾１３Ｃ－ＮＭＲ谱中１２９．５～１５０（ｐｐｍ）＋１２３．５～１２６（ＰＰｍ）／３谱带作为非质子芳碳。模型混合物较核表明，用本方法估计的桥头芳碳和环烷并芳碳与实际值吻合良好；估计的四种Ａｌｂｅｒｔａ沥青样品的各种类型芳碳，其结果与Ｓｔｒａｕｓｚ化     

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.     

Rb regulates proliferation and rod photoreceptor development in the mouse retina

The retinoblastoma protein (Rb) regulates proliferation, cell fate specification and differentiation in the developing central nervous system (CNS), but the role of Rb in the developing mouse retina has not been studied, because Rb-deficient embryos die before the retinas are fully formed. We combined several genetic approaches to explore the role of Rb in the mouse retina. During postnatal development, Rb is expressed in proliferating retinal progenitor cells and differentiating rod photoreceptors. In the absence of Rb, progenitor cells continue to divide, and rods do not mature. To determine whether Rb functions in these processes in a cell-autonomous manner, we used a replication-incompetent retrovirus encoding Cre recombinase to inactivate the Rb1(lox) allele in individual retinal progenitor cells in vivo. Combined with data from studies of conditional inactivation of Rb1 using a combination of Cre transgenic mouse lines, these results show that Rb is required in a cell-autonomous manner for appropriate exit from the cell cycle of retinal progenitor cells and for rod development.     

Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland

The NOTCH4 gene was recently reported to be associated with schizophrenia based on TDT analysis of 80 British trios. The strongest evidence for association derived from two microsatellites. We genotyped both loci in a large sample of unrelated Scottish schizophrenics and controls, but failed to replicate the reported association, finding instead that each putative schizophrenia-associated allele had a somewhat lower frequency in schizophrenics than in controls.     

Language-tree divergence times support the Anatolian theory of Indo-European origin

Languages, like genes, provide vital clues about human history. The origin of the Indo-European language family is "the most intensively studied, yet still most recalcitrant, problem of historical linguistics". Numerous genetic studies of Indo-European origins have also produced inconclusive results. Here we analyse linguistic data using computational methods derived from evolutionary biology. We test two theories of Indo-European origin: the 'Kurgan expansion' and the 'Anatolian farming' hypotheses. The Kurgan theory centres on possible archaeological evidence for an expansion into Europe and the Near East by Kurgan horsemen beginning in the sixth millennium BP. In contrast, the Anatolian theory claims that Indo-European languages expanded with the spread of agriculture from Anatolia around 8,000-9,500 years bp. In striking agreement with the Anatolian hypothesis, our analysis of a matrix of 87 languages with 2,449 lexical items produced an estimated age range for the initial Indo-European divergence of between 7,800 and 9,800 years bp. These results were robust to changes in coding procedures, calibration points, rooting of the trees and priors in the bayesian analysis.     

重油组成的分子系综表征法

采用Ｍｏｎｔｅ－Ｃａｒｌｏ模拟方法，建立了表征重组成的等效分子系统法，提出了重油分子构造规则和约束及关计算机算法。Ａｌｂｅｒｔａ重油的模拟结果和实验数据比较表明，其系统计结构基团浓度，密度、沸点、环、桥和侧链分布，饱和烃含量均与实测一致，从而为利用纯化合物物化性质研究复杂的重油建立起桥梁。     

金属固化：从单晶体到微晶体

控制铸件的固化和冷却速度会大大影响合金的宏观结构与微观结构及其最终机械特性。根据期望要得到的结果,金属可以极其缓慢地也可几乎瞬时地予以冷却。要制造单晶体,金属得在模具中以每秒10~(-3)～10~(-1)度的冷却速度予以固化。制造出来的铸件与涡轮叶片的实际形状几乎相同。反之,以每秒10~6度的速度快速固化,则得到粉状或带状物。这些材料晶粒极细,并且合金元素和强化相位分布均匀。单晶体超合金作为航天飞机主发动机高压涡轮泵的涡轮叶片正在鉴定之中。虽然这些叶片将在比飞机涡轮低的稳态温度环境中工作,但是它们经受的疲劳状况势必要严重得多。国家航空航天局的刘易斯研究中心和马歇尔研究中心都在研究如何改善超合金的抗疲劳性以及如何更好地了解氢对超合金的有害影响。     

正癸烷-水二元混合物在5A分子筛上吸附平衡的实用模型

本文提出了一个称为“有效吸附空间充填模型”的实用吸附模型。利用这个模型可以从纯组分平衡吸附容量算得二元吸附时的平衡吸附容量。将这模型与各种纯组分的吸附等温线公式结合,可以推导得出一系列二元吸附等温线公式。经与正癸烷-水二元混合物在5A分子筛上平衡吸附容量实验数据比较,发现下列公式的预测值与实验值的偏差最小,其均方根相对偏差为10%左右,能满足工程计算的需要。