Functional characterization of kanB by complementing in engineered Streptomycesfradiae ?neo6::tsr

A putative aminotransferase gene, kanB, lies in the biosynthetic gene cluster of Streptomyces kanamyceticus ATCC 12853 and has 66% identity with neo6 in neomycin biosynthesis. Streptomyces fradiae ∆neo6::tsr was generated by disrupting neo6 in the neomycin producer Streptomyces fradiae. Neomycin production was completely abolished in the disruptant mutant but was restored through self-complementation of neo6. S. fradiae HN4 was generated through complementation with kanB in Streptomyces fradiae ∆neo6::tsr. Based on metabolite analysis by ESI/MS and LC/MS, neomycin production was restored in Streptomyces fradiae HN4. Thus, like neo6, kanB also functions as a 2-deoxy-scyllo-inosose aminotransferase that has dual functions in the formation of 2-deoxy-scyllo-inosose (DOS). Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Host–microbe interactions: fungi/viruses/parasites

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Microbiology.     

DREAM/Calsenilin/KChIP3:神经系统的多功能蛋白

新近发现的转录因子DREAM(downstreamregulatoryelementantagonistmodulator)可结合到基因(包括PPD、Hrk、cfos等)的DRE(downstreamregulatoryelement)位点,抑制基因转录。它是第一个已知的可以直接与DNA结合发挥转录抑制作用的Ca2 结合蛋白,为Ca2 调节基因表达除蛋白激酶/磷酸酶这条主要通路外提供了另一条通路。由于DREAM与另两个研究小组发现的蛋白calsenilin和KChIP3实为同一种物质,所以DREAM具有PS(presenilin)作用蛋白、Kv4通道调节蛋白和转录因子的多重功能特性。本文将就DREAM的分布、功能及其调控、DREAM与疼痛的关系作简要综述。     

Large scale isolation of 1,2:3,4-di-O-isopropylidene-α-d-glucoseptanose and 2,3:4,5-di-O-isopropylidene-β-d-glucoseptanose

Isolation of 1,2:3,4-di-O-isopropylidene-α-d-glucoseptanose and 2,3:4,5-di-O-isopropylidene-β-d-glucoseptanose from the mother-liquors from commercial scale preparation of 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose is described.     

HIV/艾滋病疫苗:策略及展望

全球范围内艾滋病的流行使发展安全有效的疫苗势在必行。本文讨论了各种不同类型的艾滋病疫苗的优点和缺点,包括传统疫苗(灭活疫苗、减毒活疫苗)和新型疫苗(病毒颗粒样疫苗、重组亚单位疫苗、重组活载体病毒疫苗),同时也指出了发展艾滋病疫苗所面临的挑战,如病毒的变异、没有充足的动物模型和HIV感染免疫系统本身。概述了正在进行的艾滋病疫苗的临床试验,并对下一步研究进行了展望。     

CRISPR/Cas:新一代基因编辑技术

CRISPR/Cas技术是一项新兴的基因编辑技术,它利用与目标序列互补的向导RNA(sg RNA)引导Cas酶定点切割DNA。由于该技术操作简便、要求低,已成为近几年最受关注的基因编辑技术。而随着该技术的广泛使用和人们对CRISPR/Cas系统了解的不断深入,对该技术优与劣的争论也不断升温。本文就该技术的起源、CRISPR/Cas系统的工作原理,以及目前的主流应用和成果进行了介绍,希望能够帮助人们对CRISPR/Cas技术有一个更全面的了解。     

编者按: 衰老: 老问题，新挑战

衰老是一个古老神秘的科学问题,长生不老是人们从古至今的梦想和追求.在人们为温饱而奋斗的时代,对大多数人来说衰老还算不上他们生活中的重要问题,随着现代社会经济和技术的快速发展,人们在追求和享受着各种优越生活与娱乐的同时,健康也成为当下重要的社会问题和人们追求、关注的生活目标.很多严重威胁人类健康的疾病,如糖尿病、心血管疾病、神经退行性疾病、癌症、代谢性疾病等,均与衰老过程密切相关,衰老是导致这些疾病最重要的危险因素之一.因此,衰老以     

Modification of yttrium alkoxides: β-Ketoesterate-substituted yttrium alkoxo/hydroxo/oxo clusters

Reaction of Y₅O(OiPr)₁₃ (“yttrium iso-propoxide”) with one molar equivalent of isopropyl acetoacetate (iprac) per Y resulted in the formation of Y₉O(OH)₉(OiPr)₈(iprac)₈, a rare example of an yttrium alkoxo/hydroxo/oxo cluster. Reaction in a 1:3 molar ratio gave Y₄(OH)₂(iprac)₁₀ and Y₆(OH)₆(iprac)₁₂ instead. A fourth cluster, Y₉O(OH)₉(iprac)₁₆, structurally closely related to Y₉O(OH)₉(OiPr)₈(iprac)₈, was obtained upon recrystallization of Y₄(OH)₂(iprac)₁₀ from CDCl₃.     

Phred/Phrap/Consed/Polyphred:类Unix平台的测序数据管理和SNP识别软件包

尽管二代基因组测序技术日渐流行,Sanger测序依旧是SNP识别和分析的金标准。传统对于Sanger测序结果的分析多依赖Seq Man等软件进行。然而这类软件大多依靠人工操作来识别和记录测序结果中的SNP位点,效率低下且容易发生错误。此外,当对多个个体进行序列测定时,这类软件无法完成对群体数据的管理和输出,给研究人员造成了一定的不便。Phred/Phrap/Consed/Polyphred是华盛顿大学开发的基于类Unix平台的软件包,在大规模测序数据的管理和SNP自动识别、标记与输出方面具有强大的功能。然而,由于其安装和使用较为复杂,在国内较少使用。本研究对该软件包的功能、使用流程、特点等进行了介绍,并将其安装于Ubuntu12.04操作系统并置于VMware虚拟机中,方便遗传学者的下载和使用。     

In memoriam: Gustaf Bolinder 19/12 1888–16/7 1957

Veena Das's work on suffering suggests that the appropriate approach to the subject is one that grounds research in social experience. To honor this pitch of anthropology, I examine the global mediatization of the trauma of political violence and its moral implications. I also describe the professional appropriation of suffering that transforms political economic conditions into medical realities. Because social experience is itself undergoing a profound alteration in the present period of disordered capitalism, the very phenomenological conditions that we have assumed as an ‘existential’ basis for responding to human misery are also being ominously transformed.     

综述: 智力的涌现

星海茫茫,地球因智慧生命的存在而与众不同,我们在追寻生命起源的同时,也追问着智力的源头,什么是智力的本质,智力从何涌现?生命大爆炸不仅带来激增的物种数量,也带来专司信息感知、编码和处理的神经系统.在复杂多变的外部环境中,昆虫已发展演化了近4亿年.在这里,我们借由现代认知神经科学在果蝇中的研究发现,探讨智力的基本层面,提出果蝇的大脑是智力涌现中的一个标杆,是我们揭开智力本质、进入智力王国的第一站.     

编者按: 脂代谢与心血管疾病

心血管病是我国成年人致死的最主要的疾病,而脂代谢异常是心血管疾病的独立危险因素。因此,阐述研究揭示脂代谢异常在心血管疾病发生发展中的作用及其机制,具有重要的理论意义和临床实用价值。本期专题主要一方面综合评述了脂蛋白组分与脂质代谢,以及甘氨酸的心血管疾病保护作用等相关领域的研究新进展,同时并分别展示了国内学者有关于PCSK9/LDLR通路、模拟人apoE结构域的小分子多肽EpK、多不饱和脂肪酸、脂联素、LXRα- ABCA1途径和普罗布考等在脂代谢中的作用及相应分子机制等方面的研究成果,以期让更多的人进一步深入了解脂质代谢以及,了解心血管病发病的复杂机制和及研究现状。     

« Biology/medicine 2.0 »: an overview

In the last decade, the applications known as "web 2.0" (Facebook, Youtube, Twitter…) have changed our daily life and gradually influence the field of research. This article aims at proposing a critical overview of these new services, and emphasizes the changes induced for researchers (practice of scientific publication, sharing and mutualization of research data and discussion between researchers…) especially in the field of biology/medicine. A focus is done on the limitations that prevent most of scientists from using these services in their common practice (lack of knowledge about these tools, time-consuming, fear of sharing data and ideas). Despite these restrictions, some mutations affecting researcher's information uses are unavoidable, and these new tools may rapidly contribute to scientific advances.     

CRISPR/Cas9:基因编辑的新时代

基因编辑技术是通过核酸内切酶对基因组DNA进行定向改造的技术,可以实现对特定DNA碱基的缺失、替换等,常用的四种基因编辑工具分别是:巨型核酸酶、锌指核酸酶、转录激活因子样效应物核酸酶以及CRISPR/Cas9系统。其中CRISPR/Cas9系统作为一种新型的基因组编辑技术具有组成简单、特异性好、切割效率高的优点。该文对CRISPR/Cas9系统的结构组成和功能机制,动植物基因靶向编辑和人类在遗传性疾病、病毒感染性疾病以及肿瘤方面进行综述,旨在对CRISPR/Cas9系统的现状和发展进行总结和展望。     

抗肿瘤药物:PBK/TOPK抑制剂的研究进展

PBK/TOPK是一种丝-苏氨酸蛋白激酶,正常生理情况下,TOPK仅在睾丸和胸腺中表达。近年来研究表明,TOPK在多种恶性肿瘤细胞中呈高表达,调控肿瘤细胞的细胞周期,与肿瘤细胞的增殖、侵袭、转移、抗凋亡过程相关。因此,TOPK成为肿瘤治疗的一个靶标,其特异性抑制剂正在研究当中。目前,使用最多的TOPK抑制剂均能与TOPK分子活性中心结合,直接抑制TOPK的功能,从而达到抑制效果。本文综述了TOPK的结构和功能,以及现用于研究的TOPK抑制剂的抗肿瘤作用。     

Solid-state structure of N-o-, N-m-, and N-p-nitrophenyl-2,3,4-tri-O-acetyl-β-d-xylopyranosylamines

Comprehensive structural analyses were performed for N-o-, N-m-, and N-p-nitrophenyl-2,3,4-tri-O-acetyl-β-d-xylopyranosylamines. Single-crystal X-ray diffraction data were collected and revealed that one compound under investigation undergoes temperature-dependent polymorph transitions (crystal structures of three polymorphs were obtained). The number of molecules in the independent part of the crystal unit cells was in agreement with the number of resonances in solid-state ¹³C NMR spectra. Therefore, the compounds exist as single polymorphs at room temperature, as confirmed by powder X-ray diffraction measurements. Significant differences in ¹³C chemical shifts between solution and solid-state NMR for selected carbon atoms confirmed the existence of intra- and/or intermolecular interactions.