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| 每日一文(0305) |
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| May 31,2003 | Novel Therapies Based on Mechanisms of HIV-1 Cell Entry | ||||||||
| Infection with human immunodeficiency virus type 1 (hiv-1), the retrovirus that causes the acquired immunodeficiency syndrome (AIDS), is one of the leading causes of death worldwide. All currently available antiretroviral agents inhibit essential HIV-1 enzymes — either the reverse transcriptase or the protease(Fig. 1). Recent advances have markedly improved the outcome for many patients who receive these classes of antiretroviral drugs. However, the success of current therapy is limited by the emergence of drug-resistant viruses, the necessity of sustained adherence to complex regimens, and the potential for toxic effects. Novel classes of safe and effective agents with a low risk of cross-resistance with other antiretroviral drugs are needed. | |||||||||
| May 30,2003 | The SARS Coronavirus:A Postgenomic Era | ||||||||
| The complete
sequences of the ~30,000- nucleotide RNA genomes of two isolates of the
SARS coronavirus (SARS-CoV) are reported on pages 1399 and 1394 of this
issue , a remarkable achievement since the virus was identified less than 2 months ago. Additional sequences in GenBank, and complete genome sequences of nine virus isolates from five patients allow comparison between different SARS-CoV isolates. Sequence analysis reveals the genome organization and phylogeny of SARS-CoV . The genome has all the features characteristic of a coronavirus, but is sufficiently different from all previously known coronaviruses to represent a new coronavirus group. |
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| May 29,2003 | Identification and containment of an outbreak of SARS in a community hospital | ||||||||
| Background: It is important
to understand the transmission of SARS in hospitals and to
evaluate methods for its containment in health care institutions. We
describe how we cared for the first 2 patients with SARS admitted to our
419-bed community hospital in Richmond Hill, Ont., and the response to a
SARS outbreak within our institution. Methods: We collected clinical and epidemiological data about patients and health care workers at our institution who during a 13-day period had a potential unprotected exposure to 2 patients whose signs and symptoms were subsequently identified as meeting the case definition for probable SARS. The index case at our hospital was a patient who was transferred to our intensive care unit (ICU) from a referral hospital on Mar. 16, 2003, where he had been in close proximity to the son of the individual with the first reported case of SARS in Toronto. After 13 days in the ICU, a diagnosis of probable SARS was reached for our index case. Immediately upon diagnosis of our index case, respiratory isolation and barrier precautions were instituted throughout our hospital and maintained for a period of 10 days, which is the estimated maximum incubation period reported for this disease. Aggressive surveillance measures among hospital staff, patients and visitors were also maintained during this time. Results: During the surveillance period, 15 individuals (10 hospital staff, 3 patients and 2 visitors) were identified as meeting the case definition for probable or suspected SARS, in addition to our index case. All but 1 individual had had direct contact with a symptomatic patient with SARS during the period of unprotected exposure. No additional cases were identified after infection control precautions had been implemented for 8 days. No cases of secondary transmission were identified in the 21 days following the implementation of these precautions at our institution. Interpretation: SARS can easily be spread by direct personal contact in the hospital setting. We found that the implementation of aggressive infection control measures is effective in preventing further transmission of this disease. |
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| May 28,2003 | INTEGRATING BIOLOGICAL DATABASES | ||||||||
| Over the past two decades, databases of biological knowledge have grown from a cottage industry that was only of interest to a few specialized disciplines, to become essential resources that are used daily by biologists around the world. Examples abound, and include such diverse databases as: PubMed, the searchable compendium of biological literature that is maintained by the National Center for Biotechnology Information (NCBI); Ensembl, the database of human gene predictions that is maintained by the European Bioinformatics Institute (EBI) and the Wellcome Trust; the UCSC Genome Browser a human, mouse and rat genome browser that is maintained by David Haussler's group at the University of California at Santa Cruz; FlyBase, the Drosophila research community database that is maintained by the FlyBase Consortium; WormBase, the Caenorhabditis elegans model-organism database; and the Gene Ontology (GO) database of gene function, process and location terms.Many readers of this article will find it difficult to imagine conducting their work without access to one or more of these databases. | |||||||||
| May 27,2003 | Stem Cell Programs | ||||||||
| the U.S. National Institutes of Health place a high priority on support for research using human embryonic stem cells, as well as other types of stem cells, that will also be useful for basic, translational, and clinical studies. Research using human embryonic stem cells offers the potential to inform us about the earliest molecular and cellular processes that regulate normal development and provides a tool to discover how a cell is able to be both pluripotent and indefinitely self-renewing. In addition, researchusing human embryonic stem cells will help the scientific community to understand the molecular signals that specify differentiation into specific cell types, some of which may ultimately be useful for cellbased treatment of disorders that involve loss of a specific cell type (such as type 1 diabetes or Parkinson's disease, to cite two of many examples). | |||||||||
| May 26,2003 | Transmission Dynamics and Control of Severe Acute Respiratory Syndrome | ||||||||
| Severe acute respiratory syndrome (SARS) is a recently described illness of humans that has spread widely over the past 6 months. Using detailed epidemiologic data from Singapore and the epidemic curves from other settings,we estimated the reproductive number for SARS both in the absence of interventions and in the presence of control efforts. We estimate that a single infectious case of SARS will infect about 3 secondary cases in a population that has not yet instituted control measures. Public health efforts to reduce transmission are expected to have a significant impact on reducing the size of the epidemic. | |||||||||
| May 25,2003 | Transmission Dynamics of the Etiological Agent of SARS in Hong Kong: Impact of Public Health Interventions | ||||||||
| We present an analysis of the first 10 weeks of the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. The epidemic to date has been characterized by two large clusters, initiated by two separate “super-spread”events (SSEs), and ongoing community transmission. By fitting a stochastic model to data on 1512 cases, including these clusters, we show that the etiological agent of SARS is moderately transmissible. Excluding SSEs, we estimate 2.7 secondary infections were generated per case on average at the start of the epidemic, with a substantial contribution from hospital transmission. Transmission rates fell during the epidemic, primarily due to reductions in population contact rates and improved hospital infection control, but also as a result of more rapid hospital attendance by symptomatic individuals. As a result, the epidemic is now in decline, though continued vigilance is necessary for this to be maintained. Restrictions on longer-range population movement are shown to be a potentially useful additional control measure in some contexts. We estimate that most currently infected persons are now hospitalized, emphasizing the importance of control of nosocomial transmission. | |||||||||
| May 24,2003 | Molecular Biology of Coronaviruses | ||||||||
| 这篇文章是Paul Masters（美国著名分子遗传学家）在国际SARS急性传染病讨论会上的开篇稿，主要讲述了冠状病毒的分子生物学基础，简单的描述了冠状病毒的Spike (S) Protein、Membrane (M) Protein、Envelope (E) Protein、Nucleocapsid (N) Protein、RNA Genome Characteristics、Gene 1 Polyprotein和Nonstructural Proteins等，让大家对冠状病毒有一个总体的把握，现把这篇文章作为这期的每日一文奉献给大家。更多的有关会议的文章请参阅Cmbi的Report－国际SARS专题讨论会。 | |||||||||
| May 23,2003 | SARS:Status of the outbreak and lessons for the immediate future | ||||||||
| This document describes the evolution of severe acute respiratory syndrome, or SARS, and explains some of the features that make this new disease an especially challenging threat to international public health. Brief examples of economic, social, and political repercussions illustrate the wide-ranging impact a new disease can have in a closely interconnected and highly mobile world. Lessons learned from efforts to contain SARS, particularly concerning the strengths and weaknesses of systems for surveillance and response, are then used to assess global capacity to respond to other infectious disease threats, most notably the next influenza pandemic and the possible deliberate use of a biological agent to cause harm. Priority areas for urgent improvement are identified and discussed. | |||||||||
| May 22,2003 | Approaches to Vaccines and Drug Development | ||||||||
| 继上次每日一文刊出国际SARS急性传染病讨论会的video后，反映很好，现将上期所缺的会议的另一部分video（关于SARS疫苗和药物研究的进展）也一起奉献给大家。请先下载并使用Realplayer观看录像。 | |||||||||
| May 21,2003 | 国际SARS专题讨论会 | ||||||||
| 5月17日由美国纽约科学院主持召开了一次国际SARS急性传染病讨论会，此次会议反应了当前国际学术界对SARS和冠装病毒引起的传染病的研究的最新成果 ，并讨论了未来研究的方向和前景。现将会议报告和录像全部上载，以供大家参考。请先下载并使用Realplayer观看录像。 | |||||||||
| May 20,2003 | SARS冠状病毒基因组、蛋白质与侵入宿主细胞过程研究近况 | ||||||||
| 自SARS爆发以来，cmbi就一直对该疾病从发病状况、生物信息资源、研究文献、防治动态等各方面，予以密切关注与跟踪，并及时在cmbi上给予发布和更新。在4月12日SARS冠状病毒基因组测序完成之后，我工作人员应用生物信息学的分析方法对SARS的基因组、蛋白质和病毒进入细胞的机理也进行了分析和研究，总结了目前国际上所有有关SARS所发表的全部论文和研究成果，并在几个层面上加以总结综述。现将cmbi的两篇综述作为今天的每日一文发表于上，希望能让大家对SARS有一个更清晰、快捷的了解，也为更准确有效地找到自己工作的切入点提供参考。 | |||||||||
| May 19,2003 | 非典型肺炎的临床和治疗进展 | ||||||||
| 自2002年11月中国广东省报道首例SARS病例以来，截至到2003年5月14日SARS已经波及到32个国家和地区，其中疫情以中国大陆、中国香港尤为严重。其传染性强，死亡率高，影响了世界各国经济的发展。但在全球各界人士的合作努力下，目前多处疫情已经得到了控制。笔者收集整理分析了目前全球对SARS防治研究的成果，对其从流行病学、临床特点、诊断、治疗、预防和转归等六个方面进行阐述，力图为有关人士提供一幅比较全面、清晰和前沿的草图，为战斗在抗击SARS前线的工作者提供一些帮助。 | |||||||||
| May 18,2003 | Hypertension Treatment Guidelines | ||||||||
| The WHO has estimated that high blood pressure causes 1 in every 8 deaths worldwide,making hypertension the third leading killer in the worls.The JNC 7 report,published in this issue of THE JOURNAL,summarizes how the burden of hypertension can be decreased. Among the messages emphasized is that systolic blood pressure control should be the focus of treatment. Cardiovascular risk from systolic hypertension begins at 115mmHg and risk from diastolic hypertension begins at 75mmHg.Individuals who are normotensive at 55 years have a 90% likelihood of developing high blood pressure during the 25 years, and lowering blood pressure toward the new goal level of 120/80mmHg will decrease heart attacks,heart failure,stroke.kidney disease,and will save lives. | |||||||||
| May 17,2003 | Five postulates for resolving outbreaks of infectious disease | ||||||||
| Outbreaks of infection challenge the surveillance of infectious disease, but they also offer opportunities to improve and refine it. An outbreak may be the first sign of an emerging pathogen or it may draw attention to a new risk group or route of infection. Postulates analogous to those used a century ago by Robert Koch to prove the microbial aetiology of infectious diseases can be employed to verify the existence of an outbreak, demonstrate its cause and pinpoint its origins. In doing this, high-resolution molecular finger printing of micro-organisms has now assumed a crucial role. Without formal analysis based on postulates, the existence, extent and source of outbreaks may be overlooked and public health interventions misapplied or lost. | |||||||||
| May 16,2003 | Lung pathology of fatal severe acute respiratory syndrome | ||||||||
| Severe acute respiratory syndrome (SARS) is a novel infectious disease with global impact. A virus from the family Coronaviridae has been identified as the cause, but the pathogenesis is still unclear.Post-mortem tissue samples from six patients who died from SARS in February and March, 2003, and an open lung biopsy from one of these patients were studied by histology and virology. Only one full autopsy was done. Evidence of infection with the SARS-associated coronavirus (SARS-CoV) and human metapneumovirus was sought by reverse-transcriptase PCR and serology. Pathological samples were examined by light and electron microscopy and immunohistochemistry. | |||||||||
| May 15,2003 | SARS-Associated Coronavirus | ||||||||
| The discovery that a novel coronavirus is the probable cause of the newly recognized severe acute respiratory syndrome (SARS), reported by Ksiazek et al., Drosten et al., and Peiris et al.1 provides a dramatic example of an emerging coronavirus disease in humans, described by Poutanen et al., Tsang et al., and Lee et al.. Although human coronaviruses cause up to 30 percent of colds, they rarely cause lower respiratory tract disease. In contrast, coronaviruses cause devastating epizootics of respiratory or enteric disease in livestock and poultry... | |||||||||
| May 14,2003 | Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of anti-SARS Drugs | ||||||||
| A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (Mpro, also called 3CLpro), controlling the activities of the coronavirus replication complex, represents an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) Mpro and for an inhibitor complex of porcine coronavirus (transmissible gastroenteritis virus, TGEV) Mpro, and constructed a homology model for SARS coronavirus (SARS-CoV) Mpro. The structures reveal a remarkable degree of conservation of the substratebinding sites, which is further supported by recombinant SARS-CoV Mpro-mediated cleavage of a TGEV Mpro substrate. Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for SARS therapy. | |||||||||
| May 13,2003 | Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs | ||||||||
| RNA interference is a cellular process of gene silencing in which small duplexes of RNA specifically target a homologous sequence for cleavage by cellular ribonucleases. The introduction of≈22-nt small interfering RNAs (siRNAs) into mammalian cells can specifi- cally silence cellular mRNAs without induction of the nonspecific IFN responses that are activated by longer RNA duplexes. We investigate in this article whether siRNAs can also silence the expression of the cytoplasmically replicating hepatitis C virus (HCV) RNAs by using a replicon system that supports robust HCV replication, but not the production of infectious virions. | |||||||||
| May 12,2003 | Short constrained peptides that inhibit HIV-1 entry | ||||||||
| 最近，香港大学医学院微生物学系冠状病毒研究小组和艾滋病研究专家何大一对导致"非典"的冠状病毒进行了蛋白序列研究，发现病毒侵入人体细胞的方式与艾滋病毒类似，其空间结构也与之相似，因此，想尝试将合成多肽阻止艾滋病毒的原理运用在治疗"非典"上。为此我们选择了这篇2002年在美国PNAS上发表的有关抗HIV的文章作为今天的每日一文，这篇文章主要讲述了科学家们通过结构分析发现Short C-peptides可以和HIV-1 gp41螺旋状疏水区域结合进而抑制HIV-1病毒进入靶细胞，但这种短c肽的缺点是结合力差、抑制作用小，为了提高它的抑制作用，科学家们运用化学方法合成非天然的短肽使其稳定，这项结果表明是经过修饰后的限制性短肽在起作用。同时，热力学研究也惊奇的发现这种对HIV-1起抑制作用的是一种能够对热量改变起良好平衡作用的限制性短肽而不是人们平时认为的有着高螺旋倾向的短肽。这篇文章不仅解释了限制性短肽抑制作用的热力学基础，并对将来限制性多肽的设计埋下了伏笔。 | |||||||||
| May 11,2003 | SARS
Co-V & Host Cell Interaction |
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| SARS－CoV感染宿主细胞是病毒致病的关键所在，PUCHG通过分子生物学研究发现SARS－CoV可能是通过细胞内吞作用进入宿主细胞的。而Caveolin（凹陷蛋白）在这个过程中起重要作用，因此我们推测说冠状病毒在感染、复制的多个阶段涉及脂膜融合，很可能宿主细胞的Caveolae
和Caveolin参与这些过程，特别是Caveolin-1 在呼吸道上皮细胞高表达。 我们知道SARS virus是冠状病毒的一种新的变种，其基因组与蛋白的结构与已知的冠状病毒有所不同，但也有区域是相对保守(如Spike protein－即S蛋白)。Cmbi运用生物学方法对SARS virus的Spike protein进行了初步分析发现SARS virus的Spike protein与鼠肝炎病毒的S蛋白具有一定的同源性，因此我们估计SARS virus感染宿主细胞的分子机制应该与CEACAMs家族有关。CEACAMs（carcinoembryonic antigen-related cell adhesion molecule）――也被称之为鼠肝炎病毒受体（MHVR）可能是冠状病毒进入宿主细胞后与病毒Spike Proein结合，介导病毒感染宿主细胞的关键分子。 Nucleocapsid protein (N蛋白)是冠状病毒(Coronavirus)一种重要的结构蛋白。它在病毒RNA的复制以及翻译中都有着比较重要的作用。Cmbi通过分子生物学方法发现N蛋白含有核转移信号序列，而这个核转移信号序列在其它冠状病毒N蛋白中不存在，因此我们推测可能SARS病毒在侵入宿主细胞以后是通过这个核转移信号序列进入到细胞核中，并整合到宿主DNA中，进而发挥生物学作用的。 |
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| May 10,2003 | The First Book on SARS | ||||||||
| It starts with a history of the epidemic, and has chapters on the virology, transmission, epidemiology, diagnosis and treatment of SARS. It is well footnoted with hyperlinks to medical journals and relevant parts of the CDC and WHO's websites, and the chapter on virology is written by WHO medical experts.It will be updated every month. | |||||||||
| May 9,2003 | Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia - a prospective study | ||||||||
| The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage. | |||||||||
| May 8,2003 | Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong | ||||||||
| After the initial phase of exponential growth, the rate of confirmed cases fell to less than 20 per day by April 28. Public-health interventions included encouragement to report to hospital rapidly after the onset of clinical symptoms, contact tracing for confirmed and suspected cases, and quarantining, monitoring, and restricting the travel of contacts. The mean incubation period of the disease is estimated to be 6·4 days (95% CI 5·2–7·7). The mean time from onset of clinical symptoms to admission to hospital varied between 3 and 5 days, with longer times earlier in the epidemic. The estimated case fatality rate was 13·2% (9·8–16·8) for patients younger than 60 years and 43·3% (35·2–52·4) for patients aged 60 years or older assuming a parametric distribution. A non-parametric method yielded estimates of 6·8% (4·0–9·6) and 55·0% (45·3–64·7), respectively. Case clusters have played an important part in the course of the epidemic. | |||||||||
| May 7,2003 | Clinical Features and Short-term Outcomes of 144 Patients With SARS in the Greater Toronto Area | ||||||||
| The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure. In the event that contact history becomes unreliable, several features of the clinical presentation will be useful in raising the suspicion of SARS. Although SARS is associated with significant morbidity and mortality, especially in patients with diabetes or other comorbid conditions, the vast majority (93.5%) of patients in our cohort survived. | |||||||||
| May 6,2003 | Immunological hurdles to lung gene therapy | ||||||||
| Gene delivery has the potential to offer effective treatment to patients with life-threatening lung diseases such as cystic fibrosis,a1-antitrypsin deficiency and lung cancer. Phase I/II clinical trials have shown that, in principle, gene transfer to the lung is feasible and safe. However, gene expression from both viral and non-viral gene delivery systems has been inefficient. In addition to extra- and intracellular barriers, the host innate and acquired immune system represents a major barrier to successful gene transfer to the lung. Results from studies in experimental animals and clinical trials have shown that inflammatory, antibody and T cell responses can limit transgene expression duration and readministration of the gene transfer vector.…… | |||||||||
| May 5,2003 | Virus-encoded proteinases and proteolytic processing in the Nidovirales | ||||||||
| On the basis of similarities in their genome
organization and replication strategy, RNA viruses can now be classified
into ` supergroups ' that often include both animal and plant viruses
(Goldbach & Wellink, 1988; Strauss & Strauss, 1988).This concept is
also increasingly reflected in the taxonomy of viruses ; in particular
by the introduction of the taxon ` order ', which combines virus families
for which a common ancestry seems highly probable (Mayo & Pringle, 1998).………… ------- 这是在英国Journal of General Virology杂志（2000年）上发表的一篇有关冠状病毒的综述，之所以选择这个时候刊出，是因为这篇文章非常有代表意义，它详细地介绍了冠状病毒的特点及其转录、翻译及其蛋白水解过程，了解了它，对于我们继续探讨和研究SARS-CoV的来源、变异、发病机理及治疗有着重要的意义。 |
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| May 4,2003 | A complete sequence and comparative analysis of strain (BJ01) of the SARS-associated virus | ||||||||
| We report the complete genome sequence and comparative analysis of a strain, (BJ01) of the coronavirus, which has been recognized as a pathogen for SARS. The genome size is 29.725 kb with 6 putative protein coding sequences and 5 uncharacterized ORFs (Open Reading Frames). Its gene order is identical to that of other known coronaviruses. The whole genome is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 2 ORFs overlapped by a single nucleotide) and a variable region representing 4 viral structural genes (the S, E, M, N proteins). | |||||||||
| May 3,2003 | Characterization
of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome The Genome Sequence of the SARS-Associated Coronavirus |
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| 2003年三月，科学家们发现了导致SARS的元凶SARS-CoV，并且成功的完成了SARS-CoV基因组的完整测序。SARS-CoV基因组有29727个核苷酸、11个开放阅读框（Opening Reading Frames）组成。它的基因组结构和其他的冠状病毒非常相似,但通过比较遗传史和序列比对也发现了一些显著的差异。基因组序列将有助于人类SARS病毒感染、潜在动物宿主的诊断检测（使用PCR和免疫测试法），有助于发展抗病毒制剂(包括中和抗体)和找出公认的疫苗抗原决定簇。 |
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| May 2,2003 | Preliminary Analyze the structure and function of the putative spike protein of SARS virus The Preliminary Analysis of the Mutation of SARS Coronaviruses Genes' Sequences |
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| 应用已经得到的SARS病毒全基因组序列,通过序列比对发现一个和鼠肝炎病毒mouse
hepatitis viruses (MHVs)的surface projection glycoprotein高度同源的CDS,很有可能就是SARS病毒的Spike
protein. |
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| May 1,2003 | The Preliminary Analysis of SARS Proteins' Sequences － (I)、(II)、(III) | ||||||||
| 背景：根据前文，我们分析SARS冠状病毒基因组可以编码25个蛋白质（11个cds,其中一个cds:putative
orf1ab polyprotein, 编码了一个多聚蛋白质，这个蛋白由14个蛋白组成，见图）。 目的：通过运用生物信息学的工具，对这25个蛋白进行序列上的分析，试图根据分析结果推测蛋白质的功能和在SARS发病过程中的作用。 |
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