SPLUNC1 Regulates Cell Progression and Apoptosis through the miR-141-PTEN/p27 Pathway,but Is Hindered by LMP1

Little is known about the role of the host defensive protein short palate, lung and nasal epithelium clone 1 (SPLUNC1) in the carcinogenesis of nasopharyngeal carcinoma (NPC). Here we report that SPLUNC1 plays a role at a very early stage of NPC carcinogenesis. SPLUNC1 regulates NPC cell proliferation, differentiation and apoptosis through miR-141, which in turn regulates PTEN and p27 expression. This signaling axis is negatively regulated by the EBV-coded gene LMP1. Therefore we propose that SPLUNC1 suppresses NPC tumor formation and its inhibition by LMP1 provides a route for NPC tumorigenesis.     

Yeast-based automated high-throughput screens to identify anti-parasitic lead compounds

We have developed a robust, fully automated anti-parasitic drug-screening method that selects compounds specifically targeting parasite enzymes and not their host counterparts, thus allowing the early elimination of compounds with potential side effects. Our yeast system permits multiple parasite targets to be assayed in parallel owing to the strains’ expression of different fluorescent proteins. A strain expressing the human target is included in the multiplexed screen to exclude compounds that do not discriminate between host and parasite enzymes. This form of assay has the advantages of using known targets and not requiring the in vitro culture of parasites. We performed automated screens for inhibitors of parasite dihydrofolate reductases, N-myristoyltransferases and phosphoglycerate kinases, finding specific inhibitors of parasite targets. We found that our ‘hits’ have significant structural similarities to compounds with in vitro anti-parasitic activity, validating our screens and suggesting targets for hits identified in parasite-based assays. Finally, we demonstrate a 60 per cent success rate for our hit compounds in killing or severely inhibiting the growth of Trypanosoma brucei, the causative agent of African sleeping sickness.     

基于MaxEnt模型预测气候变化下杉木在中国的潜在地理分布

为研究杉木在中国的分布特征及其对气候变化的响应模式,本研究基于现有分布记录,应用最大熵(MaxEnt)模型和地理信息系统方法,结合气候、地形等环境要素,预测杉木在当前和未来气候变化下的潜在适生区。结果表明: 影响杉木分布的最主要因素是年平均降水量,在当前气候下,杉木适生区合计面积328万km²,占全国陆地总面积的34.5%,低、中和高适生区分别占18.3%、29.7%与52.0%。在未来气候情景下,杉木生长的适宜性在我国总体上呈上升趋势,适生区面积随气候变化增大,且明显向北扩张,南方湿润亚热带地区形成集中连片高适生区。模型经受试者工作特征曲线检验,训练集平均受试者工作特征曲线下面积为0.91,可信度高。     

在实验动物水平通过恢复和改善胰岛β细胞功能的糖尿病治疗新进展

糖尿病是一个世界性问题,在中国就有超过1.3亿人患有糖尿病.糖尿病主要分为1型糖尿病和2型糖尿病.遗憾的是,糖尿病至今尚未达成有效的预防和治愈手段.但是,近年来的一系列突破性的研究成果,让我们看到了治愈糖尿病的希望.在这里我们回顾了目前关于1型糖尿病和2型糖尿病可能的治愈途径的研究进展.这些途径包括胰岛移植和1型糖尿病...     

Chemical modification of tyrosine residues in glyoxalase I from yeast and human erythrocytes

1. Yeast glyoxalase I was inactivated by N-acetylimidazole and tetranitromethane, the latter process following pK app 7.31 and irreversibly producing a protein with a spectrum typical of 3-nitrotyrosine. 2. For yeast glyoxalase I, amino-acid analysis and protection studies with S-(p-bromobenzyl)glutathione, a competitive inhibitor, indicated two classes of tetranitromethane-reactive tyrosine residues, fast- and slow-reacting, with the latter class containing the crucial tyrosine(s). 3. Human erythrocyte glyoxalase I was inactivated by tetranitromethane in fast and slow processes, protection studies in this case indicating the important tyrosine(s) as fast-reacting.