Planning for pandemics: Lessons from the past decade

It is now 10 years since the disease we now know as SARS-severe acute respiratory syndrome-caused more than 700 deaths around the world and made more than 8,000 people ill. More recently, in 2009 the global community experienced the first influenza pandemic of the 21st century-the 2009 H1N1 influenza pandemic. This paper analyses the major developments in international public health law relating to infectious diseases in the period since SARS and considers their implications for pandemic planning.

Evolutionary relationships between bat coronaviruses and their hosts

Recent studies have suggested that bats are the natural reservoir of a range of coronaviruses (CoVs), and that rhinolophid bats harbor viruses closely related to the severe acute respiratory syndrome (SARS) CoV, which caused an outbreak of respiratory illness in humans during 2002-2003. We examined the evolutionary relationships between bat CoVs and their hosts by using sequence data of the virus RNA-dependent RNA polymerase gene and the bat cytochrome b gene. Phylogenetic analyses showed multiple incongruent associations between the phylogenies of rhinolophid bats and their CoVs, which suggested that host shifts have occurred in the recent evolutionary history of this group. These shifts may be due to either virus biologic traits or host behavioral traits. This finding has implications for the emergence of SARS and for the potential future emergence of SARS-CoVs or related viruses.

Disease Diplomacy

In the age of air travel and globalized trade, pathogens that once took months or even years to spread beyond their regions of origin can now circumnavigate the globe in a matter of hours. Amid growing concerns about such epidemics as Ebola, SARS, MERS, and H1N1, disease diplomacy has emerged as a key foreign and security policy concern as countries work to collectively strengthen the global systems of disease surveillance and control. The revision of the International Health Regulations (IHR), eventually adopted by the World Health Organization’s member states in 2005, was the foremost manifestation of this novel diplomacy. The new regulations heralded a profound shift in international norms surrounding global health security, significantly expanding what is expected of states in the face of public health emergencies and requiring them to improve their capacity to detect and contain outbreaks. Drawing on Martha Finnemore and Kathryn Sikkink’s "norm life cycle" framework and based on extensive documentary analysis and key informant interviews, Disease Diplomacy traces the emergence of these new norms of global health security, the extent to which they have been internalized by states, and the political and technical constraints governments confront in attempting to comply with their new international obligations. The authors also examine in detail the background, drafting, adoption, and implementation of the IHR while arguing that the very existence of these regulations reveals an important new understanding: that infectious disease outbreaks and their management are critical to national and international security. The book will be of great interest to academic researchers, postgraduate students, and advanced undergraduates in the fields of global public health, international relations, and public policy, as well as health professionals, diplomats, and practitioners with a professional interest in global health security.

Coronavirus Infection and Diversity in Bats in the Australasian Region

Following the SARS outbreak, extensive surveillance was undertaken globally to detect and identify coronavirus diversity in bats. This study sought to identify the diversity and prevalence of coronaviruses in bats in the Australasian region. We identified four different genotypes of coronavirus, three of which (an alphacoronavirus and two betacoronaviruses) are potentially new species, having less than 90% nucleotide sequence identity with the most closely related described viruses. We did not detect any SARS-like betacoronaviruses, despite targeting rhinolophid bats, the putative natural host taxa. Our findings support the virus-host co-evolution hypothesis, with the detection of Miniopterus bat coronavirus HKU8 (previously reported in Miniopterus species in China, Hong Kong and Bulgaria) in Australian Miniopterus species. Similarly, we detected a novel betacoronavirus genotype from Pteropus alecto which is most closely related to Bat coronavirus HKU9 identified in other pteropodid bats in China, Kenya and the Philippines. We also detected possible cross-species transmission of bat coronaviruses, and the apparent enteric tropism of these viruses. Thus, our findings are consistent with a scenario wherein the current diversity and host specificity of coronaviruses reflects co-evolution with the occasional host shift.

Protein Kinase C and Anaplastic Lymphoma Kinase Targeted Compounds

The protein kinases (PKs) belong to the largest single family of enzymes, phosphotransferases, which catalyze the phosphorylation of other enzymes and proteins and function primarily in signal transduction. Consequently, PKs regulate cell mechanisms such as growth, differentiation, and proliferation. Dysfunction of these cellular mechanisms may lead to cancer, a major predicament in health care. Even though there is a range of clinically available cancer-fighting drugs, increasing number of cancer cases and setbacks such as drug resistance, constantly keep cancer research active. At the commencement of this study an isophthalic acid derivative had been suggested to bind to the regulatory domain of protein kinase C (PKC). In order to investigate the biological effects and structure-activity relationships (SARs) of this new chemical entity, a library of compounds was synthesized. The best compounds induced apoptosis in human leukemia HL-60 cells and were not cytotoxic in Swiss 3T3 fibroblasts. In addition, the best apoptosis inducers were neither cytotoxic nor mutagenic. Furthermore, results from binding affinity assays of PKC isoforms revealed the pharmacophores of these isophthalic acid derivatives. The best inhibition constants of the tested compounds were measured to 210 nM for PKCα and to 530 nM for PKCδ. Among natural compounds targeting the regulatory domain of PKC, the target of bistramide A has been a matter of debate. It was initially found to activate PKCδ; however, actin was recently reported as the main target. In order to clarify and to further study the biological effects of bistramide A, the total syntheses of the natural compound and two isomers were performed. Biological assays of the compounds revealed accumulation of 4n polyploid cells as the primary mode of action and the compounds showed similar overall antiproliferative activities. However, each compound showed a distinct distribution of antimitotic effect presumably via actin binding, proapoptotic effect presumably via PKCδ, and pro-differentiation effect as evidenced by CD11b expression. Furthermore, it was shown that the antimitotic and proapoptotic effects of bistramide A were not secondary effects of actin binding but independent effects. The third aim in this study was to synthesize a library of a new class of urea-based type II inhibitors targeted at the kinase domain of anaplastic lymphoma kinase (ALK). The best compounds in this library showed IC50 values as low as 390 nM for ALK while the initial low cellular activities were successfully increased even by more than 70 times for NPM-ALK- positive BaF3 cells. More importantly, selective antiproliferative activity on ALK-positive cell lines was achieved; while the best compound affected the BaF3 and SU-DHL-1 cells with IC50 values of 0.5 and 0.8 μM, respectively, they were less toxic to the NPM-ALK-negative human leukemic cells U937 (IC50 = 3.2 μM) and BaF3 parental cells (IC50 = 5.4 μM). Furthermore, SAR studies of the synthesized compounds revealed functional groups and positions of the scaffold, which enhanced the enzymatic and cellular activities.

Control dynamics of severe acute respiratory syndrome transmission

Severe acute respiratory syndrome (SARS) is a serious disease with many puzzling features. We present a simple, dynamic model to assess the epidemic potential of SARS and the effectiveness of control measures. With this model, we analysed the SARS epidemic data in Beijing. The data fitting gives the basic case reproduction number of 2.16 leading to the outbreak, and the variation of the effective reproduction number reflecting the control effect. Noticeably, our study shows that the response time and the strength of control measures have significant effects on the scale of the outbreak and the lasting time of the epidemic.

Phage M13Ko7 Detection With Biosensor Based On Imaging Ellipsometry And Afm Microscopic Confirmation

A rapid detection and identification of pathogens is important for minimizing transfer and spread of disease. A label-free and multiplex biosensor based on imaging ellipsometry (BIE) had been developed for the detection of phage M13KO7. The surface of silicon wafer is modified with aldehyde, and proteins can be patterned homogeneously and simultaneously on the surface of silicon wafer in an array format by a microfluidic system. Avidin is immobilized on the surface for biotin-anti-M13 immobilization by means of interaction between avidin and biotin, which will serve as ligand against phage M13KO7. Phages M13KO7 are specifically captured by the ligand when phage M13KO7 solution passes over the surface, resulting in a significant increase of mass surface concentration of the anti-M13 binding phage M13KO7 layer, which could be detected by imaging ellipsometry with a sensitivity of 10(9) pfu/ml. Moreover, atomic force microscopy is also used to confirm the fact that phage M13KO7 has been directly captured by ligands on the surface. It indicates that BIE is competent for direct detection of phage M13KO7 and has potential in the field of virus detection. (C) 2008 Elsevier B.V. All rights reserved.

Methods of feeding of some macrothricids (Cladocera, Macrothricidae). [Translation from: Informatsionnyi Byulleten Biologiya Vnutrennikh Vod 16, 29-34, 1973.]

The feeding methods of macrothricids was investigated in three species — Ophryoxus gracilis G.O. Sars, Ilyocryptus sordidus (Lievin) and Lathonura rectirostris O.F.Muller. The procuring of food in those species follows two methods: filtration of dispersed particles or scraping off and collecting food from the surface of the substrate. When collecting food by scraping off is the sole method of feeding (as in Lathonura rectirostris), movement along the substrate and feeding are combined so intimately that they appear as parts of one and the same mechanism.

Changes in the organism of females of some Cladocera in transition to gamogenesis. [Translation from: Zoologicheskie Zhurnal 49 1573-1575, 1970. ]

In species of Cladocera not forming ephippia, the latent eggs have a sheath formed by glands of the reproductive canals. Representatives of the families Daphniidae and Moinidae Goulden, 1968, in connection with the formation of their complex-structured ephippia, lost these glands. It was investigated whether there are such glands in species the latent eggs of which are enclosed in primitive ephippia. For this, with the help of histological methods, 55 females of Acroperus elongatus (Sars) (Chydoridea) and 88 females of Lathonura rectirostris (O. F. Muller), (Macrothricidae) were collected near Leningrad, were studied.

A Century of Copepods: The U.S. Fisheries Steamer Albatross

The marine invertebrates of North America received little attention before the arrival of Louis Agassiz in 1846. Agassiz and his students, particularly Addison E. Verrill and Richard Rathbun, and Agassiz's colleague Spencer F. Baird, provided the concept and stimulus for expanded investigations. Baird's U.S. Commission of Fish and Fisheries (1871) provided a principal means, especially through the U.S. Fisheries Steamer Albatross (1882). Rathbun participated in the first and third Albatrossscientific cruises in 1883-84 and published the fist accounts of Albatross parasitic copepods. The first report of Albatross planktonic copepods was published in 1895 by Wilhelm Giesbrecht of the Naples Zoological Station. Other collections were sent to the Norwegian Georg Ossian Sars. The American Charles Branch Wilson eventually added planktonic copepods to his extensive published works on the parasitic copepods from the Albatross. The Albatross copepods from San Francisco Bay were reported upon by Calvin Olin Esterly in 1924. Henry Bryant Bigelow accompanied the last scientific cruise of the Albatross in 1920. Bigelow incorporated the 1920 copepods into his definitive study of the plankton of the Gulf of Maine. The late Otohiko Tanaka, in 1969, published two reviews of Albatross copepods. Albatross copepods will long be worked and reworked. This great ship and her shipmates were mutually inspiring, and they inspire us still.

分子系统学分析平台的建立和应用

分子系统学建立在实验和计算的基础之上。DNA快速测序技术的普及为分子系统学家提供了大量数据，而序列分析技术则是探索数据发现知识的重要工具。在基因组时代，随着大量模式生物完整基因组序列的获得，分子系统学正面临着前所未有的机遇和挑战。一方面，生命之树计划有助于确定新的模式生物和开展相应的基因组计划;另一方面，模式生物的基因组计划有助于阐明它们之间的进化关系和基因组的进化模式。更为重要的是，分子系统学序列分析技术已经发展成为探索与整合基因组数据的强有力工具，从而在生命科学中发挥重要作用。事实上，分子系统学和基因组学的相互渗透正在形成一门崭新的交叉学科——系统发育基因组学。 为了奠定分子系统学研究中信息管理和数据分析工作的坚实基础，我们建立了分子系统发育分析平台。该平台为研究人员提供专业数据库服务和数据分析技术支持，以及相关的网络资源。 分子系统发育分析平台包括了3个专业数据库。第一个是DNA凭证标本数据库。该数据库中的记录包括了7项字段：英文科名、中文科名、物种拉丁名、采集人、采集号、采集地和采集时间。用户可以通过设定单个或多个字段的取值进行检索。截止2004年6月1日，该数据库共包括3491条标本记录。第二个是引物数据库。PCR引物是分子系统学实验的重要条件之一。该数据库中的记录包括3项字段：引物名称、序列内容和退火温度。用户可以通过设定单个或多个字段的取值进行检索。截止2004年6月1日，该数据库共包括170条用于扩增植物细胞核、叶绿体和线粒体基因组DNA序列的引物记录。第三个是生物计算数据库。该数据库为研究人员提供传输和保存序列分析数据和结果文件的服务。 为了确保数据库的安全性和使用性，我们开发了数据库的接口和检索工具，以及系统管理员和用户资格认证程序。通过前者，使用者可以进行数据的上传、下载、管理和检索等操作。而后者则是对不同使用者身份和权限进行设定。管理员的权限高于用户，主要负责本系统的日常维护和管理工作，以及对新增管理员和用户进行资格认证。 分析技术支持旨在帮助用户快速掌握常用的系统发育分析方法，进行有效的数据分析，从复杂的统计学算法和计算机程序中解放出来，将精力集中于计算结果的生物学解释。在该部分中，我们首先简要介绍了常用的分析方法，并且针对分子系统学中的不同问题提供了相应的解决方案。这些问题包括：系统发育重建、替代速率和分歧时间的估计、祖先分布区的重建、性状进化假说的检验、以及密码子水平适应性进化的检测。我们特别强调了似然比检验和贝叶斯推测作为方法论上的重要进展在分子系统学中所发挥的关键作用。本部分还包括大量常用的分子系统学程序或软件包及其快速使用说明和命令模块。下载安装之后，用户即可按照说明使用命令模块进行数据分析。 此外，该平台还提供了一些常用的网络资源地址，如生物信息中心、分子进化和系统发育实验室、专业期刊和相关数据库等。 最后还给出了4个应用实例，即针对特定分子系统学问题的解决方案和初步的分析结果。 第一个例子说明系统发育重建方法的应用。为了确定杨梅科的系统学位置，对6种DNA序列和叶绿体trnL-F区内的间隔性状进行了分析。单个分析表明这6种序列之间在系统学信息上存在显著差异。叶绿体基因组序列的合并分析强烈支持杨梅科和（木麻黄科，（桦木科，核果桦科））的姐妹群关系，而间隔性状的存在能够充分提高其分辨率和支持率。 第二个例子说明如何推测历史生物地理学过程。我们对壳斗目8科25属植物叶绿体基因组的trnL-F、matK、rbcL和atpB的合并序列进行了最大简约分析，得到唯一的最大简约树。基于该系统树和25属植物的地理分布数据，采用扩散－替代分析方法重建了系统树每个节点上的祖先分布区，推测了壳斗目的分布历史。结果表明，壳斗目的历史生物地理学过程由3次替代事件和20次扩散事件组成。其中最重要的替代事件是由于冈瓦纳大陆和劳亚大陆分离所导致的南青冈科及其姐妹群之间的分化。另外，在壳斗科和核心高等金缕梅类中多次发生从欧亚大陆到北美洲、甚至南美洲的平行扩散事件。 第三个例子说明如何估计分歧时间。我们仍然使用扩散－替代分析中所用的最大简约树作为分析的依据，并根据等级制似然比检验确定的最优替代模型对该系统树的支长进行了最大似然优化。似然比检验表明，该系统树不服从分子钟假说。我们以冈瓦纳大陆和劳亚大陆分离的地质事件和5个属的最早化石记录作为标定点，采用罚分似然法在没有分子钟的条件下估计了壳斗目的科间分歧时间。结果表明，绝大多数科间分歧事件都发生在白垩纪。 第四个例子说明如何检测密码子水平的适应性进化。分支间可变选择压力模型的似然比检验表明SARS冠状病毒的S基因在跨种传播过程中发生了正选择。

冠状病毒

冠状病毒(coronavirus)是一种常见的单链、非片段化、线性、正链RNA包膜病毒，能感染脊椎动物而引起，特别 是呼吸系统疾病。此病毒可分三大类，感染不同动物，其遗传物质RNA表现出一种特殊的、有趣的、目前并不为人们 完全所知的策略完成其自身繁殖。最近，科学家发现“非典型肺炎”的病原体为一种新型的冠状病毒，表现出其特别 的基因组结构，有别于已知的典型冠状病毒，相关研究正在进行中。

中国枝角类四新记录亚种(鳃足纲:双甲目)

本文描述了采自四川等省的、我国首次发现的4个枝角类亚种,即美弧网纹溞Ceriodaphnia pulchella pseudohamata Bowkiewcz,1925,西方笔纹溞Graptoleberis testudinaria occidentalis Sars,1901,无常平直溞Pleuroxus laevis incertus Brehm,1934以及宽尾平直潘P.aduncus latic-audatus Brehm,1933。解剖观察描述了盘肠溞科枝角类的头孔,并首次将我国淡水枝角类的分类

武昌东湖的数种介形类甲壳动物

<正> 介形类是底栖的切甲类甲壳动物,部分种类的触角上具有发达的游泳刚毛,所以在通常采到的浮游生物标本中亦很常见。早在1903年,G.O.Sars 氏曾经报导过采自我国的介形类共三属五新种。1923年,V.Brehm 也报导过采自我国广州、北京、四川等地的数种介形类,其中还有一新属,三新种及一新变种。

武昌的秀体溞

<正> 秀体溞(Diaphanosoma)是枝角类栉足族仙达溞科(Sididae)中包括种类最多的一个属,根据已往的记录,共计约有20种。关于我国秀体溞的计载,总共只有7种。最早是由 Spandl 在广东记述了镰角秀体溞(D.excisum Sars)一种。上野益三曾发表过有关我国枝角类的文章多篇,他报告了浙江、四川、台湾、黑龙江、吉林以及内蒙古等地的秀体溞共有6种,即:短尾秀体溞[D.brachyurum(Liévin)],长肢秀体溞