摘要：Fungi are nature’s recyclers,allowing for ecological nutrient cycling and,in turn,the continuation of life on *** fungi inhabit the human microbiome where they can provide health benefits,while others are opportunistic pathogens that can cause ***,members of the fungal kingdom,have been domesticated by humans for the production of beer,bread,and,recently,medicine and ***,the great untapped potential exists within the diverse fungal ***,many yeasts are intractable,preventing their use in biotechnology or in the development of novel treatments for pathogenic ***,as a first step for the domestication of new fungi,an efficient DNA delivery method needs to be ***,we report the creation of superior conjugative plasmids and demonstrate their transfer via conjugation from bacteria to 7 diverse yeast species including the emerging pathogen Candida *** create our superior plasmids,derivatives of the 57 kb conjugative plasmid pTA-Mob 2.0 were built using designed gene deletions and insertions,as well as some unintentional ***,a cluster mutation in the promoter of the conjugative gene traJ had the most significant effect on improving conjugation to *** addition,we created Golden Gate assembly-compatible plasmid derivatives that allow for the generation of custom plasmids to enable the rapid insertion of designer genetic ***,we demonstrated that designer conjugative plasmids harboring engineered restriction endonucleases can be used as a novel antifungal agent,with important applications for the development of next-generation antifungal therapeutics.

摘要：热休克蛋白90(Hsp90)通过对几百种蛋白质底物(客户蛋白质)进行合理的折叠、成熟其构象并且激活,在肿瘤细胞的生长和繁殖中发挥重要作用.因此,Hsp90成为非常有吸引力、有前途的抗肿瘤药物靶点,并且超过20种抑制剂已经进入临床实验阶段.我们在这里设计并合成了一个小分子抑制剂:FS36.收集了Hsp90~N-FS36复合物晶体结构的X射线衍射实验数据.高分辨率X射线晶体结构表明,FS36在ATP结合位点上与Hsp90~N相互作用,并且FS36可能替代核苷酸与Hsp90~N结合.FS36和Hsp90~N的复合物晶体结构和相互作用为后期设计和优化新型抗肿瘤药物奠定基础.

摘要：背景:儿童如果发生结核病,通常会假设其传染源是生活在同一家庭的成年传染性病例。本研究应用限定性片断长度多态性分析技术(RFLP)来确定从传染源到儿童的传播。设计:收集1993年到1998年诊断的成人及儿童结核病例和他们的结核分枝杆菌培养物。通过访视和结核分枝杆菌菌株的RFLP分析来确定流行病学联系及证实家庭内传播。结果:1291名成人中有1139名(91％)和417名儿童中有65名(16％)籍培养结果证实为结核病。由于要重新收集痰标本和提取DNA的问题,仅对其中的832名成人和35名儿童进行了RFLP分析:19名(54％)儿童有家庭成员确诊为结核病,12名儿童 有与其家庭成员相同的菌株。分离自儿童的29株(83％)菌株构成了社区簇的一部分,但与传染源有明确接触史者只有15株。结论:在具有传染性成人肺结核病例的家庭中,儿童患有结核病并不意味着必然是成人对儿童的传播。儿童可能是在社区也可能是在家庭中受到感染。此结果对在高发病率地区的接触者追踪及治疗策略有意义。