科学快讯

《Nature》:重新认识人类基因组科学时报2007年6月15日报道:继"人类基因组计划"后最大的国际合作计划之一——"DNA元件百科全书"计划(Encyclo- pedia of DNA Fiements,简称ENCODE)日前发表了一系列重要文章,挑战了关于人类基因组的传统理论,即人类基因蓝图不是由孤立的基因和大量"垃圾DNA片段"组成的,而是一个复杂的网络系统,单个基因、调控元件以及与编码蛋白无关的其他类型的DNA序列一道,以交叠的方式相互作用,共同控制着人类的生理活动。ENCODE计划产生了许多令人惊讶的发现,为未来进一步认识整个人类基因组的功能蓝图开辟了道路。科学共同体有必要重新考虑长期以来对于基因和基因组功能的认识,这将对与人类疾病相关的基因序列研究产生重大的影响。     

SRSF2基因的生物信息学分析与蛋白质预测

目的:分析富含丝氨酸和精氨酸的剪接因子2(SRSF2)基因序列和表达产物的特征。方法:运用生物信息学相关软件分析和预测人类和小鼠SRSF2基因的同源区段、开放读框、启动子区域、转录因子结合位点、CpG岛分布情况,分析预测小鼠SRSF2基因蛋白产物的功能结构域以及与其他蛋白的相互作用。结果:人类和小鼠SRSF2基因共有3个同源区段、19个开放读框、4个相同的转录因子结合位点,2个基因的CpG岛各项参数基本一致;小鼠SRSF2蛋白会与至少10种其他蛋白因子发生相互作用。结论:SRSF2基因及其蛋白产物的生物信息学分析,为相关研究提供了重要的信息基础。     

灰色系统理论在微生态学中的应用

客观世界是由物质、能量和信息所组成并决定了事物的性质,我们要认识某一客观事物的本质,就必须把握它的整体,这就是系统论的观点。有关系统的概念,一般系统论的创始人路德维格.贝塔朗菲(L.von Bertalanffy)的定义为:系统是处于一定相互联系中的与环境发生关系的各组成成份的总体。灰色系统是指部分信息清楚,部分信息不清楚的系统。自1982年邓聚龙教授提出灰     

低温胁迫下内源脱落酸对马尾松优良种源抗寒性的调节作用

以2个马尾松优良种源苗期的叶片为材料,对系列低温梯度条件下不同种源叶片的内源ABA、内源保护酶系统的动态变化的规律以及相互作用进行研究.结果表明:在降温过程中通过内源ABA的变化来调控内源保护酶的变化趋势,并协调多种酶的相互作用来抵抗低温.内源ABA、SOD对零上低温敏感,属冷害敏感型调节物质,它们在零上低温前达到最高...     

利用条件基因沉默系统研究CHIP对TGF-β信号通路的调控

根据条件基因敲除技术和基因沉默的理论,构建了可被CRE操控的条件基因沉默系统,并应用其研究分子伴侣相互作用蛋白CHIP(C-terminus of Hsc70-interacting protein)对TGF-β信号通路的调控．RT-PCR和免疫印迹结果显示,pLoxP/CHIPi与CRE相互作用后,可以有效地降低内源CHIP的mRNA水平,减少外源和内源CHIP的蛋白质量．荧光素酶报告系统分析表明,条件基因沉默能解除CHIP对TGF-β信号通路的抑制性调控,增强TGF-β信号通路的转录活性．结果表明,CRE依赖的条件基因沉默系统具有高效性、特异性,并通过它反向验证了CHIP对TGF-β信号通路的抑制性调控,为进一步研究与CHIP相关的TGF-β信号通路所致疾病的发生机理提供了有效工具．     

高等植物发育过程中基因表达的调控

一、概述植物的形态建成归根结蒂是由基因控制的,是基因的选择性表达及大分子的修饰和更新的过程。植物特定的基因在环境因素(如光)和体内因子(如内源植物激素、次生代谢物等)相互作用下,依时间和空间顺序表达出特定的 产物。     

转查耳酮合酶基因矮牵牛共抑制的研究

查耳酮合酶是花色素合成途径的一个关键酶. 将查耳酮合酶基因(chalcone synthase A, chsA)导入矮牵牛(Petunia hybrida)后, 转基因植株的外源与内源chsA基因一起发生共抑制, 导致花色改变. 将β-葡糖苷酸酶基因(uidA)连在chsA基因下游形成融合基因, 通过土壤农杆菌介导的途径转化矮牵牛. 利用GUS组织染色检测到共抑制的发生具有发育特异性, 在花组织发育时期开始发生, 发生的起始需要内源基因与外源基因的相互作用. RNA原位杂交实验表明, 共抑制的发生没有组织特异性, 且初步表明共抑制发生后, RNA可能是在细胞质中发生降解的.     

睡眠是如何发生的?

关于睡眠,前文(见《化石》1990—3期:“人类睡眠之谜”)已作过一些介绍。其实,睡眠之谜还远未揭开,而且一直在困扰着人们。人为什么要睡眠?睡眠是怎样发生的?诸如此类的简单大问题,就连学者和科学家们也还没有找到确切的答案。但人类对于睡眠的研究和探索却一刻也没有停止过,坚持不懈的热情与努力业已取得了一些成果,展示给我们的前景是极为可观的。一、从阴阳消长到本能适应受古代哲学和中医阴阳学说的影响,我国古代一些学者曾试图从阴阳平衡的观点来认识和解释睡眠现象,提出过阴阳睡眠学说。认为“天”有昼夜(阴阳),人有阴阳(人体昼夜),人通过觉醒与睡眠之态与日月阴阳相应和协调一致,以达到阴阳消长平衡。如《灵枢·口问篇》中就有“阳气尽,阴气盛则目瞑,阴气尽而阳气盛则寤”之说,并认为如此天人合一,人与天地共阴阳,则有益于健康。否则,若阴阳(昼夜)失调,睡眠异常,“昼不精,夜不瞑”,不利于健康。可见,古人是强调日     

PAX3 基因及其蛋白的生物信息学分析

目的:对PAX3基因和PAX3蛋白进行生物信息学分析,更多的了解该基因的相关信息,为进一步研究PAX3与神经管畸形的相关性研究提供基础。方法:运用生物信息学方法对PAX3基因的基因结构、单核苷酸多态性位点(SNP)、PAX3基因与其他基因的相互作用网络、PAX3蛋白结构域、蛋白二级结构、蛋白间相互作用网络、以及PAX3蛋白所调控和影响的靶基因进行分析。结果:PAX3基因有9中可变剪切形式,编码区存在14个SNP位点,其中错意突变13个,移码突变1个。PAX3蛋白由479个氨基酸组成,分子量52968Da,PAX3蛋白可能调控和影响151个靶基因的转录和表达,与PAX3基因存在相互作用的基因和与PAX3蛋白存在相互作用的蛋白多数与发育相关。结论:通过对PAX3基因和PAX3蛋白的生物信息学分析获得了其相应的分子生物学特征,为进一步研究提供基础。     

利用蛋白质相互作用关系改善基因芯片缺失数据估计的精度

针对基因芯片数据缺失问题,利用蛋白质相互作用关系与基因表达的内在联系,提出了一种利用蛋白质相互作用信息提高基因芯片缺失数据估计精度的方法.将蛋白质间的相互作用关系与基因表达数据间的距离相结合来计算基因间的表达相似度,根据这个新的相似性度量标准为含有缺失数据的基因选择更为合适的用于估计缺失值的基因集合.将新的相似性度量标准与传统的KNNimpute、 LLSimpute方法相结合,描述了对应的改进算法PPI-KNNimpute、 PPI-LLSimpute.对真实的数据集测试表明,蛋白质相互作用信息能有效改善基因缺失数据估计的精度.     

TCM Database@Taiwan: the world's largest traditional Chinese medicine database for drug screening in silico

Rapid advancing computational technologies have greatly speeded up the development of computer-aided drug design (CADD). Recently, pharmaceutical companies have increasingly shifted their attentions toward traditional Chinese medicine (TCM) for novel lead compounds. Despite the growing number of studies on TCM, there is no free 3D small molecular structure database of TCM available for virtual screening or molecular simulation. To address this shortcoming, we have constructed TCM Database@Taiwan (http://tcm.cmu.edu.tw/) based on information collected from Chinese medical texts and scientific publications. TCM Database@Taiwan is currently the world's largest non-commercial TCM database. This web-based database contains more than 20,000 pure compounds isolated from 453 TCM ingredients. Both cdx (2D) and Tripos mol2 (3D) formats of each pure compound in the database are available for download and virtual screening. The TCM database includes both simple and advanced web-based query options that can specify search clauses, such as molecular properties, substructures, TCM ingredients, and TCM classification, based on intended drug actions. The TCM database can be easily accessed by all researchers conducting CADD. Over the last eight years, numerous volunteers have devoted their time to analyze TCM ingredients from Chinese medical texts as well as to construct structure files for each isolated compound. We believe that TCM Database@Taiwan will be a milestone on the path towards modernizing traditional Chinese medicine.     

Synthetic lethality theory approaches to effective substance discovery and functional mechanisms elucidation of anti-cancer phytomedicine

BackgroundLongstanding, successful use of combinations of phytopharmaceuticals in traditional Chinese medicine (TCM) has caught the attention of several pharmacologists to natural medicines. However, the development and popularisation of TCM is mainly limited because of the unavailability of reports clarifying the mechanisms of action and pharmacologically active ingredients in such formulations. Previous studies on natural medicines have mostly focused on their dominant components using forward pharmacology which often neglects trace components. It is necessary to assess the pharmacological and therapeutic superiority of many such trace components in comparison with single constituents.PurposeIn this study, we aimed to propose a new pharmacological research strategy for TCM. In particular, we presented the possibility that the effective mechanism of action of trace components of TCM is based on synthetic lethality. We sincerely hope to explore this theory further.MethodWe obtained retrieve published research information related to synthetic lethality, phytochemicals and Chinese medicine from PubMed and Google scholar. Based on the inclusion criteria, 71 studies were selected and discussed in this review.ResultsAs an interaction among genes, synthetic lethality can amplify co-regulatory biological effects exponentially. Synthetic strategies have been successfully applied for research and development of anti-tumour agents, including poly ADP-ribose polymerase inhibitors and clinical combination of chemotherapeutic agents for efficacy enhancement and toxicity reduction. TCM drugs contain several secondary metabolites to combat environmental stresses, providing a multi-component basis for corresponding synergistic targets. Therefore, we aimed to study whether this method could be used to identify active components present in trace amounts in TCM drugs. Based on a reverse concept of target–component–effect and identified synergistic targets, we explored the mechanisms of action of weakly active components present in trace amounts in TCM drugs to assess combinations of potential synergistic components.ConclusionThis pattern of synthetic lethality not only elucidated the mechanisms of action of TCM drugs from a new perspective but also inspired future studies on discovering naturally occurring active components.     

The chronic fatigue syndrome: a comparative pathway analysis.

In this paper, we introduce a method to detect pathological pathways of a disease. We aim to identify biological processes rather than single genes affected by the chronic fatigue syndrome (CFS). So far, CFS has neither diagnostic clinical signals nor abnormalities that could be diagnosed by laboratory examinations. It is also unclear if the CFS represents one disease or can be subdivided in different categories. We use information from clinical trials, the gene ontology (GO) database as well as gene expression data to identify undirected dependency graphs (UDGs) representing biological processes according to the GO database. The structural comparison of UDGs of sick versus non-sick patients allows us to make predictions about the modification of pathways due to pathogenesis.     

中医心理疗法辅助中药治疗斑秃的研究

斑秃患者由于沉重的心理压力和负担,对于本病的恢复具有重要负面影响,与躯体症状形成交互的恶性循环,因此,加强患者的心理调适对于本病的治疗具有重要意义。中医在心理治疗方面有着丰富的经验,中医临床采用的心理治疗方法可概括为：转移注意、劝说开导、暗示开疑、顺情从欲等方法。笔者几年来采用中医心理疗法辅助中药治疗斑秃取得了较好的疗效,在这里与各位同仁共同探讨。     

肾阴虚证的现代研究进展

肾阴虚证是中医学的基本证型之一.对中医证的研究,基本方法是运用现代科技手段,通过动物实验与临床研究,探讨疾病发生后"证"与人体生理变化、病理、生化等客观指标的关系,尝试揭示证的实质.几十年来,不少学者从细胞、分子等水平上对肾阴虚证本质做了深入地研究,并已取得了一定的成果,某些方面已形成了共识.这不仅丰富和发展了传统的中医肾阴虚理论,而且为肾阴虚证的临床诊断、治疗、预后判断提供了更客观的、更全面的指导作用.本文从神经内分泌、免疫、微量元素、脂代谢、自由基、细胞因子与介质、基因等方面对肾阴虚证病理生理的客观化研究进展进行了详细地阐述.     

基于脑-肠-微生物轴的肠易激综合征机制与治疗研究进展

肠易激综合征(irritablebowelsyndrome,IBS)是常见的功能性肠病之一,目前尚缺乏可用器质性疾病解释的临床特征,最新研究将其机制描述为脑-肠-微生物轴紊乱,强调了肠道微生物群在调节脑肠互动中的中介作用,而中医药对于脑肠稳态调节有着悠久广泛的治疗经验并取得了良好疗效,但两者关联性缺乏论述。因此,本文以脑肠轴为切入点,以肠道微生物作为介质,基于脑肠轴-中医药的良性互动,结合我们相关工作,综述了目前与脑-肠-微生物轴相关的IBS的中西医研究,为同行提供参考。     

CardioGenBase: A Literature Based Multi-Omics Database for Major Cardiovascular Diseases

Cardiovascular diseases (CVDs) account for high morbidity and mortality worldwide. Both, genetic and epigenetic factors are involved in the enumeration of various cardiovascular diseases. In recent years, a vast amount of multi-omics data are accumulated in the field of cardiovascular research, yet the understanding of key mechanistic aspects of CVDs remain uncovered. Hence, a comprehensive online resource tool is required to comprehend previous research findings and to draw novel methodology for understanding disease pathophysiology. Here, we have developed a literature-based database, CardioGenBase, collecting gene-disease association from Pubmed and MEDLINE. The database covers major cardiovascular diseases such as cerebrovascular disease, coronary artery disease (CAD), hypertensive heart disease, inflammatory heart disease, ischemic heart disease and rheumatic heart disease. It contains ~1,500 cardiovascular disease genes from ~2,4000 research articles. For each gene, literature evidence, ontology, pathways, single nucleotide polymorphism, protein-protein interaction network, normal gene expression, protein expressions in various body fluids and tissues are provided. In addition, tools like gene-disease association finder and gene expression finder are made available for the users with figures, tables, maps and venn diagram to fit their needs. To our knowledge, CardioGenBase is the only database to provide gene-disease association for above mentioned major cardiovascular diseases in a single portal. CardioGenBase is a vital online resource to support genome-wide analysis, genetic, epigenetic and pharmacological studies.     

Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease

Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for rare genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients’ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation(s) underlying disease. In this review, we discuss the application of Next Generation Sequencing (NGS) to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases: Leber’s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt’s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinformatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine.     

Treat Alzheimer's disease by traditional Chinese medicine?

Upregulated phosphodiesterase 4D (PDE4D) disrupts the regulation of calcium ion channel in the central nerve system, and hence it is considered as one of the causes of Alzheimer's disease. We employed structure-based drug design techniques and the world's largest traditional Chinese medicine (TCM) database for identifying potential TCM-based PDE4D inhibitors. We then applied multiple linear regression (MLR) and support vector machine (SVM) for quantitative structure–activity relationship model, as well as for molecular dynamics simulation analysis. Screening results suggested that metal cations, Zn²⁺ and Mg²⁺, played key roles in mediating stable protein–ligand interactions with the ligand-binding residues, Asp367 and Asp484. In addition, each ligand was shown to interfere with the active residue His326 that suggested inhibitory effects. The MLR and SVM prediction models further implied the PDE4D inhibitory effect of each TCM compound. The molecular simulation further suggested the binding stability of each compound in the PDE4D binding site. We identified three TCM compounds, such as mumefural, 2-O-feruloyl tartaric acid and kainic acid, as potential PDE4D inhibitors. In addition, we further identified the key interaction features associated with the protein–ligand-binding stabilities.