EphA2 Mutation in Lung Squamous Cell Carcinoma Promotes Increased Cell Survival,Cell Invasion,Focal Adhesions,and Mammalian Target of Rapamycin Activation

Non-small cell lung cancer (NSCLC) has a poor prognosis and improved therapies are needed. Expression of EphA2 is increased in NSCLC metastases. In this study, we investigated EphA2 mutations in NSCLC and examined molecular pathways involved in NSCLC. Tumor and cell line DNA was sequenced. One EphA2 mutation was modeled by expression in BEAS2B cells, and functional and biochemical studies were conducted. A G391R mutation was detected in H2170 and 2/28 squamous cell carcinoma patient samples. EphA2 G391R caused constitutive activation of EphA2 with increased phosphorylation of Src, cortactin, and p130^Cas. Wild-type (WT) and G391R cells had 20 and 40% increased invasiveness; this was attenuated with knockdown of Src, cortactin, or p130^Cas. WT and G391R cells demonstrated a 70% increase in focal adhesion area. Mammalian target of rapamycin (mTOR) phosphorylation was increased in G391R cells with increased survival (55%) compared with WT (30%) and had increased sensitivity to rapamycin. A recurrent EphA2 mutation is present in lung squamous cell carcinoma and increases tumor invasion and survival through activation of focal adhesions and actin cytoskeletal regulatory proteins as well as mTOR. Further study of EphA2 as a therapeutic target is warranted.     

The epidemiology of HIV and AIDS in the world

The worldwide epidemic of HIV continues to expand in many regions of the world, particularly in southern Africa, South and Southeast Asia, East Asia and Eastern Europe and Central Asia. Estimates are that at the end of 2005 there were 38.6 million persons living with HIV infection and that 4.1 million new infections and 2.8 million deaths from HIV occurred during the year. Regionally different patterns predominate from generalized heterosexual epidemics in sub-Saharan Africa and parts of the Caribbean to mixes of epidemics in which transmission among injection drug users, their sexual partners, commercial sex workers and their partners intersect. Multilateral and bilateral antiretroviral access campaigns, such as the World Health Organization's 3 x 5 initiative, have resulted in broader access to live-saving therapy for infected persons in low- and middle-income countries, but several million infected people who are clinically eligible for antiretroviral therapy remain untreated. The public health challenge worldwide is to keep the uninfected and to treat and care for those who have already been infected.     

A new class of glycogen phosphorylase inhibitors

A new class of diacid analogues that binds at the AMP site not only are very potent but have approximately 10-fold selectivity in liver versus muscle glycogen phosphorylase (GP) in the in vitro assay. The synthesis, structure, and in vitro and in vivo biological evaluation of these liver selective glycogen phosphorylase inhibitors are discussed.     

甘肃、新疆、内蒙苹果蠹蛾成虫消长规律

苹果蠹蛾Cydia pomonella(L.)是我国重要的果树害虫和检疫对象。2005年至2010年,本研究在甘肃、新疆及内蒙古的不同区县选取了16个果园,使用性信息素诱捕器对其中的苹果蠹蛾成虫发生规律进行长期监测。结果表明,苹果蠹蛾在西北地区每年发生2.5个世代;在正常气候条件下,3个成虫发生高峰分别出现在5月上旬、7月中下旬和8月中下旬,但不同地区及同一地区不同果园之间存在较大差异;化学防治、迷向防治等防治措施对苹果蠹蛾成虫捕获量的影响较大,因此生活史研究为主的监测并不适合在上述果园中开展。综合上述研究结果,未对苹果蠹蛾的季节动态进行准确的预测,需要对苹果蠹蛾除成虫外的其他虫态的季节性变化进行详细研究,并建议选择3个以上的果园进行监测,综合各个果园的监测结果并得出结论。     

Evaluation of physiological importance of metallothionein protein expressed by Tetrahymena cadmium metallothionein 1 (TMCd1) gene in Escherichia coli

TMCd1 is a cadmium inducible metallothionein (MT) gene. In the present study the TMCd1 gene of a ciliate protozoan has been expressed in E. coli and the function of the expressed TMCd1 protein as a metal-binding protein has been evaluated. The growth of E. coli cells expressing the GST fused TMCd1 proteins in the presence of cadmium metal clearly demonstrated the role of TMCd1 as a metal-binding protein. The metal accumulation experiments showed that the bacterial cells expressing the functional TMCd1 protein accumulated 19-fold more cadmium in contrast to control cells that lacked the TMCd1 protein expression. The results clearly demonstrate a physiological role of full length TMCd1 protein of a ciliate, expressed in E. coli, in cadmium metal sequestration and detoxification.     

2′-OH of mRNA are critical for the binding of its codons at the 40S ribosomal P site but not at the mRNA entry site

The roles of 2′-OH groups in the binding of mRNA to human ribosomes were studied using site-directed cross-linking. We found that both mRNA and mDNA analogues bearing a cross-linker can modify ribosomal proteins (rps) S3e and S2e at the mRNA entry site independently on tRNA presence, but only mRNA analogues were capable of a tRNA^Phe-dependent binding to human ribosomes and cross-linking to rpS26e in the mRNA binding centre. Thus, 2′-OH groups of mRNA are unimportant for binding at the entry site but they are crucial for codon-anticodon interactions at the P site, implying the existence of mRNA-ribosome contacts that do not occur in bacteria.     

Race,Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics

We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals.