Structure and function of human perforin

Perforin (P1) is a cytolytic protein with similarity to complement component C9. P1 has been described as a unique component of murine cytolytic T-cell and rat natural killer cell granules Previous studies indicated that human granules and P1 differed from murine granules and P1 in that they appeared to be cytolytically less active and lacked the haemolytic activity characteristic of P1. It has been suggested that P1, like C9, is under the control of the homologous restriction factor. Here we determine the primary structure of human P1, re-examine its functional properties, and address the question of homologous restriction.     

Enterotypes of the human gut microbiome

Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.     

人类微生物组发展态势及建议

近年来,基因组测序与分析技术的进步推动了人类微生物组研究的发展,进一步解析人体微生物组与全生命周期健康、疾病的发生发展、营养/药物功效发挥的关系,并由此带来健康与医疗理念的变革.通过全面分析全球人类微生物组发展趋势,发现当前人类微生物组参考序列解析仍处于起步阶段,由"普查"人类微生物组的构成与分布逐步扩展到解析特定人群...     

2021年人类微生物组研究热点回眸

人类微生物组(human microbiome)指生活在人体上的互生、共生和致病的所有微生物及其遗传物质的总和.近年来,人类微生物组研究加速推进,研究内容愈加广泛和深入,其科学意义愈加凸显,被视作"人体的另一个器官".从人类微生物组的组成和分布特征、在全生命周期中的作用、与疾病发生发展的关系、对营养代谢和药物功能的影响...     

Human nutrition, the gut microbiome and the immune system

Marked changes in socio-economic status, cultural traditions, population growth and agriculture are affecting diets worldwide. Understanding how our diet and nutritional status influence the composition and dynamic operations of our gut microbial communities, and the innate and adaptive arms of our immune system, represents an area of scientific need, opportunity and challenge. The insights gleaned should help to address several pressing global health problems.     

肠道微生物样本库:伦理考量和管理规范

 人体微生物组与健康和疾病的关系是重要的科学问题。而人体微生物样本库的建立是人体微生物组研究的重要基础,这个新兴领域迫切要求对已建立的价值体系和伦理规范进行调整和变革。本文讨论人体微生物样本库建设中的知情同意、样本和数据的所有权、隐私和风险等;并以粪菌库和粪菌移植为典型案例,分析选择"最佳"、"健康"供体所面临的医学和伦理困难;提出了人体微生物样本库监管的政策建议。     

细菌Hfq蛋白的结构、功能及作用机制

非编码小RNA(small RNA, sRNA)是细菌基因转录后调控的一个重要层次,也是近十年来原核生物研究领域的焦点之一。大多数sRNA的作用与Hfq蛋白密切相关,即Hfq可以促进sRNA与其靶标mRNA的互补配对,进而影响翻译的进行或者mRNA的稳定性。笔者对Hfq的结构、Hfq参与sRNA调节作用的机制、Hfq在多种细菌中的功能表型进行了综述。Hfq是一个保守的蛋白质,在很多细菌中广泛存在,并与真核生物中参与mRNA剪切与降解活动的Sm蛋白同源。在结构上,Hfq具有两个非等同的RNA结合面,可以结合并介导多个RNA分子的相互作用,其结构体现了和功能的高度统一性。目前,对Hfq的研究主要集中于革兰氏阴性细菌中,在革兰氏阳性细菌中,Hfq的功能尚不明晰; 此外,在许多重要的细菌中,Hfq影响功能表型的具体机制也不清楚。因此,今后有必要进一步精细研究Hfq的分子结构特征和功能特点,深入分析Hfq对细菌表型多样化的影响机制,探究Hfq影响靶标分子和功能表型的详尽机制。     

Ecology drives a global network of gene exchange connecting the human microbiome

Horizontal gene transfer (HGT), the acquisition of genetic material from non-parental lineages, is known to be important in bacterial evolution. In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence, antibiotic resistance and xenobiotic metabolism to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events. Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human-associated bacteria than among ecologically diverse non-human isolates (P = 3.0 × 10(-270)). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases.     

Structure, expression and function of a schwannoma-derived growth factor

During the development of the nervous system, cells require growth factors that regulate their division and survival. To identify new growth factors, serum-free growth-conditioned media from many clonal cell lines were screened for the presence of mitogens for central nervous system glial cells. A cell line secreting a potent glial mitogen was established from a tumour (or 'schwannoma') derived from the sheath of the sciatic nerve. The cells of the tumour, named JS1 cells, were adapted to clonal culture and identified as Schwann cells. Schwann cells secrete an autocrine mitogen and human schwannoma extracts have mitogenic activity on glial cells. Until now, neither mitogen has been purified. Here we report the purification and characterization of a mitogenic molecule, designated schwannoma-derived growth factor (SDGF), from the growth-conditioned medium of the JS1 Schwann cell line. SDGF belongs to the epidermal growth factor family, and is an autocrine growth factor as well as a mitogen for astrocytes, Schwann cells and fibroblasts.     

Structure and function of the AAA+ protein CbbX, a red-type Rubisco activase

Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyses the fixation of atmospheric CO(2) in photosynthesis, but tends to form inactive complexes with its substrate ribulose 1,5-bisphosphate (RuBP). In plants, Rubisco is reactivated by the AAA(+) (ATPases associated with various cellular activities) protein Rubisco activase (Rca), but no such protein is known for the Rubisco of red algae. Here we identify the protein CbbX as an activase of red-type Rubisco. The 3.0-? crystal structure of unassembled CbbX from Rhodobacter sphaeroides revealed an AAA(+) protein architecture. Electron microscopy and biochemical analysis showed that ATP and RuBP must bind to convert CbbX into functionally active, hexameric rings. The CbbX ATPase is strongly stimulated by RuBP and Rubisco. Mutational analysis suggests that CbbX functions by transiently pulling the carboxy-terminal peptide of the Rubisco large subunit into the hexamer pore, resulting in the release of the inhibitory RuBP. Understanding Rubisco activation may facilitate efforts to improve CO(2) uptake and biomass production by photosynthetic organisms.     

当代建筑多元文化现象背后的技术操纵力

文章针对20世纪50年代后现代建筑从单一意象走向多元文化的现象,分别从多元文化的深层基础——社会文化心理变迁、多元文化的主体之一——地域建筑文化的表现和多元文化的表层现象——建筑多样表现形式3个方面入手,分析了技术在其中所起的作用,指出技术帮助了这一过程的完成。     

Ⅱ型胶原蛋白的结构、功能及其最新研究进展

Ⅱ型胶原蛋白是动物体内透明软骨的主要成分,具有良好的生物相容性、可降解性、可促进细胞生长和再分化等生物学特性,可作为人体组织工程材料,也可应用于食品、日化、包装等领域。利用基因工程技术生产重组Ⅱ型胶原蛋白是该领域的研究热点。综述了Ⅱ型胶原蛋白的结构、功能及应用,阐述了基因工程技术生产重组Ⅱ型胶原蛋白的最新研究进展,对未来羟化胶原蛋白在大肠杆菌中的大规模生产进行了展望,以期为Ⅱ型胶原蛋白的进一步开发和同行研究提供指导和帮助。     

Structure of the human class I histocompatibility antigen, HLA-A2

The class I histocompatibility antigen from human cell membranes has two structural motifs: the membrane-proximal end of the glycoprotein contains two domains with immunoglobulin-folds that are paired in a novel manner, and the region distal from the membrane is a platform of eight antiparallel beta-strands topped by alpha-helices. A large groove between the alpha-helices provides a binding site for processed foreign antigens. An unknown 'antigen' is found in this site in crystals of purified HLA-A2.     

Structure and function of PBS model complex

A complex of phycobiliproteins, containing phycoerythrocyanin (PEC), C-phycovyanin (C-PC) and allo-phycocyanin (APC) as well as some linker polypeptides, was reconstructed. The absorption and fluoreacence spectra of the complex were compared with those of native phycobilisomes (PBS) and the phycobiliproteins. Based on the measured data, it can be concluded that the complex can be taken as a model of PBS and is an entirely functional group for excitation energy transfer step by step from peripheral PEC to APC. The single terminal emitter feature of the complex makes it favorable for clarifying energy transfer pathways and the kinetics in comparison with native PBS. Further research is carried on in the lab.     

肝内胆管结石和胆汁中细菌多样性分析

运用培养法和聚合酶链式反应-变性梯度凝胶电泳(PCR-DGGE)技术对6个病人肝内胆管结石和胆汁中的细菌群落进行了分析.胰蛋白胨大豆肉汤(TSB)培养法结果显示,从6个胆石和5个胆汁样品中分别分离到15株和12株细菌,均属于Escherichia和Enterococcus两个属,而同一病人胆石及胆汁中细菌种类并不完全相同,其中一份胆汁样在两种方法检测中皆为阴性;PCR-DGGE结果表明,胆石及胆汁样品中除培养法中发现的两个属外,还包含Pseudomonas、Morganella、Citrobacter、Baterioides、Serratia、Clostridiales和Aeromonas共7个属的细菌.在5组PCR阳性的胆石和胆汁的DGGE指纹图谱相似性分析中,每组内胆石和胆汁间细菌群落结构的最高相似性仅为32.3%.两种检测方法的结果表明,Escherichia coli在胆石和胆汁中的检出率最高,胆石和胆汁中细菌多样性存在差异,PCRDGGE技术比培养法能更好检测到胆石和胆汁中的细菌多样性.     

风沙区农田防护林营建多样性及景观效益

在各树种不同配置方式试验研究基础上,提出了风沙区构建多样性、稳定性农防林的框架,结果表明,营建针叶常绿林带或针阔混交林带在防护效果和观赏价值上皆优于纯阔叶林带.针对风沙区农防林单纯林带比重大、空间分布欠合理等问题,提出景观补救方法引入新"斑块"扩大混交比例,增加观赏价值高的树种种类,采取人工抚育、修枝等措施创造适宜的观赏环境.