Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum

Throughout the latter half of this century, the development and spread of resistance to most front-line antimalarial compounds used in the prevention and treatment of the most severe form of human malaria has given cause for grave clinical concern. Polymorphisms in pfmdr1, the gene encoding the P-glycoprotein homologue 1 (Pgh1) protein of Plasmodium falciparum, have been linked to chloroquine resistance; Pgh1 has also been implicated in resistance to mefloquine and halofantrine. However, conclusive evidence of a direct causal association between pfmdr1 and resistance to these antimalarials has remained elusive, and a single genetic cross has suggested that Pgh1 is not involved in resistance to chloroquine and mefloquine. Here we provide direct proof that mutations in Pgh1 can confer resistance to mefloquine, quinine and halofantrine. The same mutations influence parasite resistance towards chloroquine in a strain-specific manner and the level of sensitivity to the structurally unrelated compound, artemisinin. This has important implications for the development and efficacy of future antimalarial agents.     

Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14

The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome.     

The pathogenic basis of malaria

Malaria is today a disease of poverty and underdeveloped countries. In Africa, mortality remains high because there is limited access to treatment in the villages. We should follow in Pasteur's footsteps by using basic research to develop better tools for the control and cure of malaria. Insight into the complexity of malaria pathogenesis is vital for understanding the disease and will provide a major step towards controlling it. Those of us who work on pathogenesis must widen our approach and think in terms of new tools such as vaccines to reduce disease. The inability of many countries to fund expensive campaigns and antimalarial treatment requires these tools to be highly effective and affordable.     

The structure of malaria pigment beta-haematin

Despite the worldwide public health impact of malaria, neither the mechanism by which the Plasmodium parasite detoxifies and sequesters haem, nor the action of current antimalarial drugs is well understood. The haem groups released from the digestion of the haemoglobin of infected red blood cells are aggregated into an insoluble material called haemozoin or malaria pigment. Synthetic beta-haematin (FeIII-protoporphyrin-IX)2 is chemically, spectroscopically and crystallographically identical to haemozoin and is believed to consist of strands of FeIII-porphyrin units, linked into a polymer by propionate oxygen-iron bonds. Here we report the crystal structure of beta-haematin determined using simulated annealing techniques to analyse powder diffraction data obtained with synchrotron radiation. The molecules are linked into dimers through reciprocal iron-carboxylate bonds to one of the propionic side chains of each porphyrin, and the dimers form chains linked by hydrogen bonds in the crystal. This result has implications for understanding the action of current antimalarial drugs and possibly for the design of new therapeutic agents.     

Identification of an antimalarial synthetic trioxolane drug development candidate

The discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. Available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive activation by haem, released as a result of haemoglobin digestion by the malaria-causing parasite. This irreversible redox reaction produces carbon-centred free radicals, leading to alkylation of haem and proteins (enzymes), one of which--the sarcoplasmic-endoplasmic reticulum ATPase PfATP6 (ref. 7)--may be critical to parasite survival. Notably, there is no evidence of drug resistance to any member of the artemisinin family of drugs. The chemotherapy of malaria has benefited greatly from the semi-synthetic artemisinins artemether and artesunate as they rapidly reduce parasite burden, have good therapeutic indices and provide for successful treatment outcomes. However, as a drug class, the artemisinins suffer from chemical (semi-synthetic availability, purity and cost), biopharmaceutical (poor bioavailability and limiting pharmacokinetics) and treatment (non-compliance with long treatment regimens and recrudescence) issues that limit their therapeutic potential. Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project.     

开发海洋能源，建设海洋强国

 海洋能源开发是海洋强国建设的重要支撑。论述了近年来科技创新为海洋能源勘探开发做出的巨大贡献，提出了中国海洋能源开发未来的主攻方向及建议：加大近海非常规油气开发技术攻关，为中国油气工业提供更多现实的贡献；加大深海油气勘探开发力度，打造中国油气产业未来的重要接替区；突破天然气水合物规模化开发关键技术，早日实现商业化开采；打造深海能源开发装备舰队，支撑海洋强国建设；抢占先机，布局并推进大洋矿产的勘探开发；进一步加强极地科研攻关，深度参与极地开发。     

野棉花研究综述

野棉花主要含有皂苷、有机酸类、甾类和挥发性成分等化学成分,主治泄泻、痢疾、黄疸、疟疾、蛔虫病、清湿热和解毒杀虫等.本文从名称考证、化学成分及药理活性等方面进行综述,旨在为进一步开发利用野棉花提供科学依据.     

乘科技创新东风，创广西科学院新辉煌——广西科学院建院40周年回顾和展望

总结和分析过去，才能更好地谋划未来。广西科学院发展的40年，是不平凡的40年。本文对广西科学院40年的发展进行总结和回顾，并在此基础上分析其面临的挑战和机遇，提出广西科学院未来发展新思路：必须建立高质量发展和高水平开放的发展定位，对全院学科进行合理布局，做优特色学科和优势新兴学科，形成清晰的学科发展思路；通过建立新型研发机构等多种方式扩增科技人员的体量，壮大全院科技人员队伍；建立科技成果倒推机制，引导广西科学院相关科技资源服务产业和经济社会，把论文写在祖国大地上；实行人才强院政策，通过引进和培养相结合，将广西科学院打造成高层次人才集聚地和高端科技智库；进行科技体制机制改革，不断完善广西科学院的治理体系，使之成为面向东盟，国内一流的综合性地方科学院。     

青蒿素类药物专利技术分布研究

青蒿素是中国科学家自主创新的倍半萜内酯类抗疟化合物。经几十年的发展，该类药物已经成为
治疗疟疾的首选药物。然而，在巨大的国际市场中，中国企业却基本处于产业链的底端。该文力图从专利保
护的角度分析中国青蒿素产业缺乏市场竞争力的原因，并提出解决问题的建议。     

2008年山西省独立科研机构统计调查报告

通过时2008年山西省独立科研机构调查数据与过去几年的比较,从科技活动人员情况、科技经费情况、课题投入强度、R&D投入情况、科技论文、科技著作及专利情况等方面分析说明了山西省独立科研机构的动态以及未来走向.     

广西雅长保护区兰科植物保育研究进展

为了解广西雅长兰科植物国家级自然保护区(以下简称雅长保护区)兰科植物保育研究概况,通过文献检索统计分析并结合实际,对雅长保护区在兰科植物资源特征、兰科植物繁育、传粉生物学等研究进行梳理总结,提出兰科植物研究科学发展建议,为今后保护区兰科植物保育研究提供参考方向及借鉴资料。     

关于建立高校科研管理创新体系的几点思考

从高校科研管理创新体系入手,分析了科研管理创新的构架、创新的内容、创新原则以及当前应强化的几种创新意识。全面论述了创新体系的思想基础,形成过程以及发展趋势,是今后高校科研管理创新的重要途径。对于建立国家创新体系,实施科教兴国战略有着重要现实意义。     

治疗输入性疟疾30例临床特征分析

目的了解输入性疟疾的临床特点、抗疟药治疗效果,为临床诊治提供参考依据.方法对收治的30例非洲务工疟疾患者的临床表现、实验室检查、治疗方案进行回顾性分析.结果血检疟原虫阳性19例,其中,恶性疟原虫6例,间日疟原虫5例,分型不详8例;30例中单用蒿甲醚治疗10例,青蒿琥酯治疗8例,双氢青蒿素哌喹片治疗5例,氯喹治疗1例,蒿甲醚联合双氢青蒿素哌喹片治疗6例;疗程最短2 d,最长15 d,所有病例最终均有效控制症状.结论输入性疟疾临床症状典型,有急性肝损害、急性血管内溶血、急性肾衰竭、脑型疟疾及肺病变等常见并发症,血检疟原虫阳性率较高,常用抗疟药物能有效控制症状.     

国家重点实验室体系建设发展现状及战略思考

概述了国家重点实验室36年的建设发展历程,介绍了国家重点实验室在国家科技创新和经济社会发展方面发挥的重要作用,分析了国家重点实验室"新形势、新使命、新要求"的时代背景特征,从贯彻新发展理念、开创新发展格局等战略层面提出发展建议.     

基于代谢组学研究的新策略在体育科学中的应用展望

体育科学的发展离不开生物医学的发展,随着后基因组时代的到来,代谢组学研究的策略在体育科学中有了长足的应用。对代谢组学的含义、产生的背景、研究领域以及代谢组学在体育科学中的应用等方面内容进行了介绍,并对当前代谢组学在体育科学研究中存在的问题以及今后的发展趋势试作了探讨,提出了我国体育科学工作者利用代谢组学研究技术进行功能基因组学研究的必要性和可能性。     

国防生物科技技术预见应用研究

国防生物科技是关系未来国防和军队建设的战略性科技领域,开展国防生物科技技术预见是科学制定国防生物科技发展战略的重要前提和基础。本研究采用技术预见研究方法,首次通过情报监测和专家咨询遴选候选技术领域及相关关键技术,并运用层次分析法构建国防生物科技技术预见指标体系,对国内军事专家、战略专家、勤务专家以及各个领域的生物科技专家进行问卷调查,对我国国防生物科技未来发展的技术领域和关键技术进行综合评价。     

实物期权理论在研发项目投资决策中的应用

提出了一种基于实物期权理论的研发项目投资决策方法.研发项目投资具有未来收益不确定性、投资成本不可逆性、投资管理的灵活性等特征,由于研发项目投资的经济价值包括获得市场高收益、期权价值等,利用实物期权理论对研发项目进行评价不仅能克服贴现现金流法的不足,而且能使研发投资决策更加科学合理.在阐述研发项目投资特征的基础上,构建了适合研发项目的期权定价模型,案例分析证明了该方法的有效性,最后对模型参数进行了敏感性分析.     

冷冻电镜技术的应用与发展

近年来,冷冻电镜技术获得了突飞猛进的发展,取得了许多具有开创性意义的成果,为科学研究起到了积极的推进作用。系统地综述了冷冻电镜技术与方法在科学研究中的应用,简要介绍了冷冻电镜技术的流程、发展、原理及解析方法,列举实例说明了冷冻电镜在结构生物学、生物医学、药物筛选方面的研究进展,分析了冷冻电镜技术与其他技术比较所具备的优越性以及存在的问题,并展望未来的发展。     

Comparative genomics of the neglected human malaria parasite Plasmodium vivax

The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.     

应用型科研院所项目开发观念及方法的转变

科研项目的开发是科研院所工作的核心所在,改变科研项目开发的观念及方法,是科研院所适应市场的切入点。同时,必须对项目开发的全过程有深入的了解,进行科学的组织管理,并不断强化知识管理。