Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer

Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer.     

Massive dissociation of gas hydrate during a Jurassic oceanic anoxic event

In the Jurassic period, the Early Toarcian oceanic anoxic event (about 183 million years ago) is associated with exceptionally high rates of organic-carbon burial, high palaeotemperatures and significant mass extinction. Heavy carbon-isotope compositions in rocks and fossils of this age have been linked to the global burial of organic carbon, which is isotopically light. In contrast, examples of light carbon-isotope values from marine organic matter of Early Toarcian age have been explained principally in terms of localized upwelling of bottom water enriched in 12C versus 13C (refs 1,2,5,6). Here, however, we report carbon-isotope analyses of fossil wood which demonstrate that isotopically light carbon dominated all the upper oceanic, biospheric and atmospheric carbon reservoirs, and that this occurred despite the enhanced burial of organic carbon. We propose that--as has been suggested for the Late Palaeocene thermal maximum, some 55 million years ago--the observed patterns were produced by voluminous and extremely rapid release of methane from gas hydrate contained in marine continental-margin sediments.     

Genome-wide functional analysis of pathogenicity genes in the rice blast fungus

Rapid translation of genome sequences into meaningful biological information hinges on the integration of multiple experimental and informatics methods into a cohesive platform. Despite the explosion in the number of genome sequences available, such a platform does not exist for filamentous fungi. Here we present the development and application of a functional genomics and informatics platform for a model plant pathogenic fungus, Magnaporthe oryzae. In total, we produced 21,070 mutants through large-scale insertional mutagenesis using Agrobacterium tumefaciens-mediated transformation. We used a high-throughput phenotype screening pipeline to detect disruption of seven phenotypes encompassing the fungal life cycle and identified the mutated gene and the nature of mutation for each mutant. Comparative analysis of phenotypes and genotypes of the mutants uncovered 202 new pathogenicity loci. Our findings demonstrate the effectiveness of our platform and provide new insights on the molecular basis of fungal pathogenesis. Our approach promises comprehensive functional genomics in filamentous fungi and beyond.     

血糖指数在耐力运动中应用的研究进展

综述长时间、大强度运动前、中、以及运动后恢复期间不同血糖指数的含碳水化合物(CHO)食物的补充对耐力运动能力及代谢的影响,目的在于为教练员、运动员及体育科研人员提供更为有益的运动营养补充方式,使营养补充与提高运动能力之间的关系达到更加优化的程度。     

甲烷预混气螺旋爆轰的定量不稳定性研究

针对CH4这种特别气体,对其实验结果运用数字化处理方法研究CH4稳定性.在内径50.8 mm圆形管道内获得CH4+2O2预混气在不同初始压力条件下的胞格爆轰结果并使用烟膜记录,且测得的平均爆轰速度数据与CJ爆轰速度接近,在初始压力高于5 kPa时爆轰可稳定传播.烟膜上形成的三波点轨迹十分不规则.为减少人为误差,使用改进后的数字化处理烟膜图像的技术方法,从烟膜轨迹中得出柱状图及自相关函数结果,发现CH4+2O2是一种爆轰十分不稳定的气体,并给出CH4+2O2预混气的爆轰胞格尺寸及差距,结果显示人为测量结果偏大而数字化处理方法更为准确.这种方法能计算CH4+2O2预混气胞格尺寸及不稳定度,完善了定量化预混气不稳定程度的方法.