A transforming mutation in the pleckstrin homology domain of AKT1 in cancer

Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is a central member of possibly the most frequently activated proliferation and survival pathway in cancer, mutation of AKT1 has not been widely reported. Here we report the identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms new hydrogen bonds with a phosphoinositide ligand. This mutation activates AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia in mice. This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway. Furthermore, the E17K substitution decreases the sensitivity to an allosteric kinase inhibitor, so this mutation may have important clinical utility for AKT drug development.     

Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1

With the emergence of multidrug resistant (MDR) bacteria, it is imperative to develop new intervention strategies. Current antibiotics typically target pathogen rather than host-specific biochemical pathways. Here we have developed kinase inhibitors that prevent intracellular growth of unrelated pathogens such as Salmonella typhimurium and Mycobacterium tuberculosis. An RNA interference screen of the human kinome using automated microscopy revealed several host kinases capable of inhibiting intracellular growth of S. typhimurium. The kinases identified clustered in one network around AKT1 (also known as PKB). Inhibitors of AKT1 prevent intracellular growth of various bacteria including MDR-M. tuberculosis. AKT1 is activated by the S. typhimurium effector SopB, which promotes intracellular survival by controlling actin dynamics through PAK4, and phagosome-lysosome fusion through the AS160 (also known as TBC1D4)-RAB14 pathway. AKT1 inhibitors counteract the bacterial manipulation of host signalling processes, thus controlling intracellular growth of bacteria. By using a reciprocal chemical genetics approach, we identified kinase inhibitors with antibiotic properties and their host targets, and we determined host signalling networks that are activated by intracellular bacteria for survival.     

内蒙古四子王旗带状柠条林根系体积空间分布特征

在内蒙古四子王旗采用挖掘法对不同带间距柠条林地灌草根系体积的空间分布特征进行研究,结果表明:带间灌草根系体积水平分布为全部根系与直径≥0.5 mm根系分布特征相似;直径≤0.2 mm根系对全部根系分布特征的影响在近柠条带1.5 m之内,对16 m带间距林地的影响在2.0 m之后,且呈波状变化;根系体积垂直分布总体上随着土层的加深而减少,随着带间距的加大表土层根系逐渐增加;5 m带间距时遵从y=aebx函数关系,10 m、16 m带间距时遵从y=aLn(x)+b函数关系.16 m带间距林地根系水平分布相对均匀,垂直分布在0～20 cm土层比例较大,是比较适合该地区的灌草复合林地.     

应用激光反射仪研究聚氧乙烯十二烷基醚溶液在硅片表面上的吸附解吸过程(英文)

将激光反射仪应用于溶液吸附上,考察了聚氧乙烯十二烷基醚--一种非离子表面活性剂溶液在硅片表面上的吸附解吸过程,结果表明其吸附过程极快,30s 达到稳定值,且解吸完全.其最大吸附量Г(mg·m-2)是2.45 mg·m-2.在临界表面相关浓度CSAC(0.045 5 mmol·L-1)以下的浓度范围内,吸附模型符合Langmuir模型.     

一种新型的电焊机节能装置

本文根据焊接变压器的基本原理,研究了一种交流弧焊机的节能装置。