Automated DNA sequencing and the analysis of the human genome

The Human Genome Initiative is a complex, multifaceted, international effort to establish a massive data base of map and sequence information for humans and other organisms. The success of this initiative is dependent upon the development of new technologies for the analysis of genomes. In this paper, an overview of the Human Genome Initiative is presented, and the current status of efforts to automate large-scale DNA sequence analysis is reviewed.     

Out of the woods: forest biotechnology enters the genomic era

Trees represent a unique life form of upmost importance for mankind, as these organisms have developed a perennial lifestyle that produces the majority of terrestrial biomass. The difference between trees and annual plants is one of the main arguments behind the effort to sequence the entire genome of the poplar tree. This initiative is being backed up with a full-scale functional genomics effort on trees that will set a completely new agenda for forest research.     

Keep all the pieces: Systematics 2000 and world conservation

Conserving biological diversity requires a major effort in conducting survey and inventories, establishing priorities, selecting protected areas, managing resources and monitoring the effects of management. Systematics has an important contribution to make to each of these five major activities. Further, the new Convention on Biological Diversity requires systematics information to support action under virtually all of its substantive conservation and sustainable use articles. It seems apparent that large reference collections contribute directly to development, and development assistance agencies should recognize that investing in maintaining these collections is a legitimate form of development assistance.     

An Introduction to a Special Issue on Large‐Scale Submerged Aquatic Vegetation Restoration Research in the Chesapeake Bay: 2003–2008

The Chesapeake Bay is one of the world's largest estuaries. Dramatic declines in the abundance and distribution of submerged aquatic vegetation (SAV) in the Chesapeake Bay over the last few decades led to a series of management decisions aimed at protecting and restoring SAV populations throughout the bay. In 2003, the Chesapeake Bay Program established a goal of planting 405 ha of SAV by 2008. Realizing that such an ambitious goal would require the development of large‐scale approaches to SAV restoration, a comprehensive research effort was organized, involving federal and state agencies, academia, and the private sector. This effort differs from most other SAV restoration programs due to a strong emphasis on the use of seeds rather than plants as planting stock, a decision based on the relatively low labor requirements of seeding. Much of the research has focused on the development of tools and techniques for using seeds in large‐scale SAV restoration. Since this research initiative began, an average of 13.4 ha/year of SAV has been planted in the Chesapeake Bay, compared to an average rate of 3.6 ha/year during the previous 21 years (1983–2003). The costs of conducting these plantings are on a downward trend as the understanding of the limiting factors increases and as new advances are made in applied research and technology development. Although this effort was focused in the Chesapeake Bay region, the tools and techniques developed as part of this research should be widely applicable to SAV restoration efforts in other areas.     

Building integrated approaches for the proteomics of complex, dynamic systems: NIH programs in technology and infrastructure development

Proteomics technology and methods remain inadequate. Technological constraints contribute to an artificially static view of complex biological systems and a barrier between quantitative and interaction studies. Several NIH programs combine proteomics technology development with research on challenging biological problems to drive progress. A new initiative of the NIH Roadmap focuses on characterization of dynamic systems. The success of these programs will be judged by their impact on relevant biological problems.     

Medical Product Development, Innovation, and Life-Cycle Regulation: The Challenges for Biostatistics

The article provides a perspective on the challenges for biostatistics as well as on contributions that biostatisticians are making and can make to medical product development and regulation and what the future might be in these areas. The current environment in the United States for pharmaceutical development and regulation is discussed along with the expectations that the public has for how medical products should contribute to public heath. The globalization of research and the use of study designs that incorporate multi-regional populations present new challenges for design and inference. The emerging interest in and development of the science of safety assessment and quantitative approaches to risk evaluation is considered. Guidance development, especially in the area of clinical trials design, continues to be one of the needs that FDA is asked to meet. Guidance development is proceeding for non-inferiority study designs, adaptive designs, multiple endpoints in clinical trials, and missing outcome data in clinical trials. Biostatisticians will be asked and challenged to take on leadership roles in new areas such as personalized medicine, biomarker and genomics, development of new tools for visual display of clinical data, quality assurance and monitoring in clinical trials.     

Genomics, public health and developing countries: the case of the Mexican National Institute of Genomic Medicine (INMEGEN)

In 2004, the government of Mexico established the National Institute of Genomic Medicine (INMEGEN), to carry out disease-related genomic studies that will address national health problems and stimulate scientific and technological development by generating new commercial products and services in genomic medicine. Towards this end, INMEGEN is carrying out a large-scale genotyping project to map genomic variation within its own population. The initiative is expected to generate a key resource for local researchers to understand disease susceptibility and variation in drug responses, which will contribute to Mexico's goal of developing public health genomics - a field in which Mexico is proving to be a leader amongst emerging economies.     

A systematic approach to dynamic programming in bioinformatics

MOTIVATION: Dynamic programming is probably the most popular programming method in bioinformatics. Sequence comparison, gene recognition, RNA structure prediction and hundreds of other problems are solved by ever new variants of dynamic programming. Currently, the development of a successful dynamic programming algorithm is a matter of experience, talent and luck. The typical matrix recurrence relations that make up a dynamic programming algorithm are intricate to construct, and difficult to implement reliably. No general problem independent guidance is available. RESULTS: This article introduces a systematic method for constructing dynamic programming solutions to problems in biosequence analysis. By a conceptual splitting of the algorithm into a recognition and an evaluation phase, algorithm development is simplified considerably, and correct recurrences can be derived systematically. Without additional effort, the method produces an early, executable prototype expressed in a functional programming language. The method is quite generally applicable, and, while programming effort decreases, no overhead in terms of ultimate program efficiency is incurred.     

Advances in the Diagnosis of Endemic Treponematoses: Yaws,Bejel, and Pinta

Improved understanding of the differential diagnosis of endemic treponematoses is needed to inform clinical practice and to ensure the best outcome for a new global initiative for the eradication of yaws, bejel, and pinta. Traditionally, the human treponematoses have been differentiated based upon their clinical manifestations and epidemiologic characteristics because the etiologic agents are indistinguishable in the laboratory. Serological tests are still considered standard laboratory methods for the diagnosis of endemic treponematoses and new rapid point-of-care treponemal tests have become available which are extremely useful in low-resource settings. In the past ten years, there has been an increasing effort to apply polymerase chain reaction to treponematoses and whole genome fingerprinting techniques have identified genetic signatures that can differentiate the existing treponemal strains; however, definitive diagnosis is also hampered by widespread unavailability of molecular diagnostics. We review the dilemmas in the diagnosis of endemic treponematoses, and advances in the discovery of new diagnostic tools.     

Early aspects of gonadal sex differentiation in Xenopus tropicalis with reference to an antero-posterior gradient

In an effort to contribute to the development of Xenopus tropicalis as an amphibian model system, we carried out a detailed histological analysis of the process of gonadal sex differentiation and were able to find evidence that gonadal differentiation in X. tropicalis follows an antero-posterior gradient. Although the main reason for the presence of a gradient of sex differentiation is still unknown, this gradient enabled us to define the early events that signal ovarian and testicular differentiation and to identify the undifferentiated gonad structure. Given the various advantages of this emerging model, our work paves the way for experiments that should contribute to our understanding of the dynamics and mechanisms of gonadal sex differentiation in amphibians.     

《生物资源学》教材与课程建设初探

生物资源与水资源、土地资源、矿产资源、能源资源和气候资源等都是人类赖以生存与发展的最为重要的物质基础,其中生物资源主要包括生物遗传资源、生物质资源和生物信息资源三大类型。生物资源学是现代生命科学、资源科学和工程科学等相关领域交叉和衍生出的新兴学科,已在国内外部分高校作为新专业进行开设。《生物资源学导论》是在高等教育出版社和中国生物工程学会生物资源专委会的倡议与指导下完成的国内首部生物资源系列教材,在出版后的两年多时间内,已在国内部分高等院校的课程建设中得到使用。本文简要地综述了《生物资源学导论》教材的二次开发与利用和新形态教材的建设与应用,以及《生物资源学》课程建设的基本情况,以期为我国生物资源学学科教育事业的发展尽绵薄之力。     

Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures

The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.     

Areas of endemism: an improved optimality criterion

The grid-based method to identify areas of endemism proposed by Szumik et al. is extended. The improvements include the ability to assign scores of endemicity to sets of disjoint areas, and to have each species contribute more to the score of endemicity of an area, or less, according to how well its distribution matches the area. The modified method also allows for partially overlapping areas; an area partially overlapping with another one of higher score is retained when the set of lower score has a minimum proportion of species endemic to it. Algorithms to evaluate areas of endemism under this criterion are discussed, and implemented in a computer program (NDM). The new algorithms allow evaluation of much larger data sets.     

Biologically active peptides: prospects for drug development

Biologically active peptides aree typified by their unbiquity of distribution, their high receptor affinity and an almost infinite diversity of structure. For these reasons, considerable effort is now being expended to elucidate the possible role of peptides in brain function. This effort has been stimulated by the discovery of a number of new endogenous peptides, such as the enkephalins, endorphins, vasoactive intestinal peptide and neurotensin. At present, there is no clearly defined role for these peptides, although they may form an important basis for the chemical coding of various brain functions, including pain, mood and memory. At present, the potential for drug development of peptide agonists remains in fairly circumscribed areas such as analgesia, pituitary hormone control, and gastrointestinal motor and secretory control. Peptide antagonists may provide a vast field for future development, although only one area, that of antifertility drugs based on LHRH antagonists, shows any promise of immediate success. Industrial research approaches to new peptide agonists and antagonists mainly rely at present on rational drug design through structural analogies. Other fruitful approaches to be considered are the screening of natural microbial and plant products and the possible application of genetic engineering techniques.     

Storage metabolism in the Pacific oyster (Crassostrea gigas) in relation to summer mortalities and reproductive cycle (west coast of France)

We describe seasonal changes in the biochemical composition of digestive gland, adductor muscle and gonad and surrounding mantle area in Crassostrea gigas from the Western Atlantic coast of France. Seasonality in histology of storage tissues and glycogen storage capacity in isolated vesicular cells were also studied. Proteins, the main muscle components did not contribute to the gametogenetic effort. Glycogen and lipids were stored in the digestive gland, gonad and surrounding mantle area during the wintering period and the gonad and surrounding mantle area represented the main storage compartment supplying the reproductive effort. Gametogenesis in spring and summer was associated with an increase in lipid and protein contents and took place at the expense of glycogen reserves. Histological study of storage tissue in the gonad led us to define four seasonal stages of storage tissue development. In vitro, glycogen storage capacity in isolated vesicular cells was high from November to March and markedly reduced during gametogenesis, decreasing below detectable levels after spawning. This physiological state should be taken into account with relation to summer mortalities occurring in commercial growing areas.     

基于建构主义学习理论的微生物学实验课程教学新模式

建构主义学习理论在高等院校人才培养模式改革中日益受到关注.运用建构主义学习理论观点,在微生物实验课程教学中构建基础实验和自主实验专题相结合的实验教学内容新体系,运用多媒体和网络技术创造良好的学习情境和高效的师生沟通平台,建立更为全面、客观和合理的多重实验考核体系.这有利于激发学生对微生物学实验的兴趣,调动学生的主观能动性,提高微生物学实验教学的实际效率和教学质量.     

The Okinawa Infectious Diseases Initiative

At the Kyushu-Okinawa Group of Eight summit in 2000, Japan announced the Okinawa Infectious Diseases Initiative (IDI) and pledged to spend US$3 billion over a five year period to combat infectious and parasitic diseases in developing countries. The IDI has exceeded expectations, spending more than US$4 billion over four years. The IDI is a unique initiative with its own philosophical basis and specifically tailored interventions and measures that helped to initiate worldwide political and financial commitments in the fight against infectious diseases. Notably, it promoted partnerships among stakeholders and emphasized comprehensive and inter-sectoral approaches (i.e. coordination and collaboration between health and other sectors). It helped to create a new vision of what is possible in the global effort against communicable diseases and has been instrumental in shaping the changing environments of development assistance, poverty reduction and other trends to reduce the impact of infectious and parasitic diseases.     

Measles immunisation: results of a local programme to increase vaccine uptake.

Investigations showed that the measles immunisation programme in our health board was a failure. Surveys of health care staff and parents to determine the cause of the problem identified several aspects of concern: the immunisation of children was often left to parental initiative, with only 29% of general practitioners playing an active part in recalling children by the 15th month of age; general practitioners, clinical medical officers, paediatricians, and health visitors all required education on several aspects of measles immunisation; parents also required more information about the importance of preventing this disease. A coordinated effort to remedy these problems was introduced which achieved an increase of 13% in vaccine uptake during 1984. These findings may have implications beyond our own area.     

Evaluation of clinical practice guidelines.

Compared with the current focus on the development of clinical practice guidelines the effort devoted to their evaluation is meagre. Yet the ultimate success of guidelines depends on routine evaluation. Three types of evaluation are identified: evaluation of guidelines under development and before dissemination and implementation, evaluation of health care programs in which guidelines play a central role, and scientific evaluation, through studies that provide the scientific knowledge base for further evolution of guidelines. Identification of evaluation and program goals, evaluation design and a framework for evaluation planning are discussed.