Книги автора: Jamie A. Goode

Retinal dystrophies are the major causes of incurable blindness in the Western world. Our insight into their aetiology has improved remarkably over the past decade and a number of key genes have been identified. Together with a more detailed understanding of disease processes, this knowledge is stimulating new approaches to therapeutic strategies involving gene therapy, growth factors and retinal cell transplantation. Molecular genetic studies have provided detailed information on the pathogenesis of retinal dystrophies. An important proof of principle that gene therapy holds great promise for the treatment of these conditions was demonstrated in the rds mouse: introduction of a functional copy of the peripherin gene subretinally resulted in complete rescue of rod outer segment structure. Novel approaches are being developed based on the manipulation of biochemical pathways that previously were not considered relevant to these diseases. For example, renewed interest in retinal dystrophy pathogenesis led to the successful use of high dose vitamin A treatment in Sorsby fundus dystrophy. This important new book covers all aspects of retinal dystrophies from the molecular and developmental biology of these disorders to possible therapeutic approaches, with special reference to gene therapy. Specific chapters deal with the molecular genetics of gene therapies, clinical genetic studies, molecular and cellular mechanisms of the development of the disease, functional genomics of retinal diseases, animal models of retinal dystrophies, and finally with studies on gene therapeutic approaches to correcting the disorder. With contributions by many of the leading researchers worldwide, this book is likely to be an important milestone in this rapidly developing field.

This book explores the possibility that life exists on Mars. It provides an interdisciplinary overview of the early evolution of life in hydrothermal ecosystems on Earth, focusing on the problem of remote sensing and incorporating geological work relevant to the search for evidence of early life on Earth and Mars. It discusses the belief that studying thermal spring deposits as part of this search may be the best opportunity to test whether life on earth is a «unique experiment,» or whether there is life elsewhere in the solar system.

This book draws together contributions from some of the leading investigators in the field of autism to consider specific problem areas in current research. Each contributor brings expertise from a different field, providing a balanced view of the whole spectrum of study of this disorder. It covers four main areas: Twin and family studies indicate that the heritability of the underlying liability to autism exceeds 90% and point to a multifactorial causation, involving a relatively small number of susceptibility genes. The book discusses this issue in detail, along with the problem of why some additional symptoms are associated with autism while others are not. New techniques are available for examining the neurobiology of autism. The book contains results from imaging studies showing the contributions of different brain regions to autism. It includes neuropathological data and examines the neuropharmacology of autism. There is considerable discussion concerning the fundamental psychological deficit in children with autism. There is good evidence that «Theory of Mind» deficits are associated with autism and this issue is discussed in the book, as are other competing possibilities. The most important practical question facing medical and psychological practitioners is how to help children with autism. The evidence relating to possible psychological or psychiatric interventions for rehabilitation of children with autism is examined in detail. Drug treatments have generally been disappointing in this field and there is one chapter devoted specifically to this problem. The book focusses ultimately on intervention studies and so is of practical relevance to people interested in helping autistic children. In addition, it provides a very convenient summary of the principal controversies which currently exist in research on autism.

Dengue virus is a member of the Flaviviridae family, which includes viruses associated with human diseases such as yellow fever, Japanese encephalitis and hepatitis C. Dengue fever is transmitted by mosquitoes, principally Aedes aegypti. There are four serotypes of dengue virus, of which DENV-2 has been the most prevalent in many recent epidemics. Following primary infection, lifelong immunity develops, preventing repeated assault by the same serotype. However, the non-neutralizing antibodies from a previous infection or maternally acquired antibodies are thought to form complexes with a different serotype during a subsequent infection and cause dengue haemorrhagic fever/dengue shock syndrome, which can be fatal. There is no treatment or vaccine available today that can combat this emerging and uncontrolled disease. This book features contributions from the world’s leading researchers working on dengue and related flaviviruses who examine the current state of the art in the molecular biology of the dengue virus. Particular emphasis is placed on the structure and function of the virus and the targeting of virus proteins by potential antiviral agents. The pathogenesis of dengue and dengue haemorrhagic fever are discussed in detail, especially the target cells and the specific receptors on these cells, thereby developing a clear overview of host and viral factors that contribute to dengue haemorrhagic fever. Finally, the book reviews the therapeutic options, paying particular attention to ways in which vector, host and environment can play a critical role in the spread of this disease. With dengue fever and other emerging viral diseases becoming increasingly prevalent around the world, this book provides valuable insight into the virus that causes this disease and potential ways to manage it. It is essential reading for all those working in tropical diseases, public health and virology. Praise from the reviews: «The book provides an excellent summary of dengue/flavivirus research and is important for individuals and institutions interested in emerging infectious diseases.» MICROBIOLOGY TODAY

Foremost neurophysiologists and psychophysicists provide pertinent information on the nature of representation at the earliest stages as this will constrain the disposition of all subsequent processing. This processing is discussed in several different types of visual perception.

Tissue engineering takes advantages of the combined use of cultured living cells and three-dimensional scaffolds to reconstruct adult tissues that are absent or malfunctioning. This book brings together scientists and clinicians working on a variety of approaches for regenerating of damaged or lost cartilage and bone to assess the progress of this dynamic field. In its early days, tissue engineering was driven by material scientists who designed novel bio-resorbable scaffolds on which to seed cells and grow tissues. This ground-breaking work generated high expectations, but there have been significant stumbling blocks holding back the widespread use of these techniques in the clinic. These challenges, and potential ways of overcoming them, are given thorough coverage in the discussions that follow each chapter. The key questions addressed in this book include the following. How good must cartilage repair be for it to be worthwhile? What is the best source of cells for tissue engineering of both bone and cartilage? Which are the most effective cell scaffolds? What are the best preclinical models for these technologies? And when it comes to clinical trials, what sort of outcome measures should be used? With contributions from some of the leading experts in this field, this timely publication will prove essential reading for anyone with an interest in the field of tissue engineering.

This title provides an extremely helpful analysis of genes that may be associated with autoimmunity, and answers questions such as how these genes can be identified, and how the functions of the gene products can be elucidated. Incorporating data on disease-associated chromosomal loci that has been accumulated from inbred mice, the title: descibes how some susceptibility loci may be common to many diseases, whereas others are relatively disease specific discusses the importance of developing criteria for establishing the significance of these different categories of disease-associated loci.

Over recent decades vast amounts of biological data have been accumulated. However, it is becoming increasingly difficult to apply traditional theoretical methods to the formulation of coherent pictures of cell and organ function because it is no longer possible for a human theorist to integrate all of the available information. Instead, computer technologies must now be used to perform this integration. This book brings together contributions from many different fields to summarize the current status of computer-assisted modelling of biological processes. The initial chapters deal with fundamental developments in hardware, software and mathematics that underlie current approaches to biological modelling. Next, different approaches to collating data on gene structure and function are presented. These databases form a vital resource for any investigator trying to construct an integrated picture of particular biological systems. Cell signalling systems form a particularly complicated aspect of all cellular function and are important both in the understanding of basic cellular processes and in selecting targets for drugs. Recent approaches to integrating data on cell signalling into computer models are covered. Further chapters build on these approaches to show how computerized models of intact cells can be developed. Finally, approaches to the computer modelling of whole organs such as the heart are presented. The role of computer modelling in drug design is the subject of the final chapter and is also touched on throughout the discussions.

This book features scientists from a broad spectrum of disciplines discussing recent data on aggression in laboratory animals with particular reference to possible implications for understanding human aggression. Chapters focus on the major current experimental issues in the study of aggression in humans and animals. The extensive discussions deal with specific problems of interpretation at the molecular level, as well as general issues relating to our understanding of human and animal aggression.

Heart failure is the main cause of death and disability in the industrialized world. There is a major need for novel therapeutics for prevention and reversal of cardiac pathology associated with heart failure and cardiac enlargement. Over recent years, dramatic progress has been made in unravelling the cellular circuitry involved in cardiac failure, as well as in normal cardiac growth, development and apoptosis. This work has revealed new and unexpected therapeutic targets in the heart. In addition, advances in understanding the role of stem cells in cardiac physiology have suggested strategies for cardiac repair and regeneration once thought impossible. This book describes the work of leading investigators studying the basic mechanisms of cardiac growth, function and dysfunction. There are also exciting contributions from researchers developing novel therapeutic strategies for cardiac disease. The unique feature is the discussions amongst the contributors, which always return to the same basic problem: how can new data from biological studies be used to design novel therapies for the treatment of cardiac dysfunction following myocardial infarction, hypertension and other disorders? With its strong emphasis on translational research, this book will appeal to both scientists and clinicians interested in diminishing the impact of the current epidemic of cardiac diseases.

Dengue virus is a member of the Flaviviridae family, which includes viruses associated with human diseases such as yellow fever, Japanese encephalitis and hepatitis C. Dengue fever is transmitted by mosquitoes, principally Aedes aegypti. There are four serotypes of dengue virus, of which DENV-2 has been the most prevalent in many recent epidemics. Following primary infection, lifelong immunity develops, preventing repeated assault by the same serotype. However, the non-neutralizing antibodies from a previous infection or maternally acquired antibodies are thought to form complexes with a different serotype during a subsequent infection and cause dengue haemorrhagic fever/dengue shock syndrome, which can be fatal. There is no treatment or vaccine available today that can combat this emerging and uncontrolled disease. This book features contributions from the world’s leading researchers working on dengue and related flaviviruses who examine the current state of the art in the molecular biology of the dengue virus. Particular emphasis is placed on the structure and function of the virus and the targeting of virus proteins by potential antiviral agents. The pathogenesis of dengue and dengue haemorrhagic fever are discussed in detail, especially the target cells and the specific receptors on these cells, thereby developing a clear overview of host and viral factors that contribute to dengue haemorrhagic fever. Finally, the book reviews the therapeutic options, paying particular attention to ways in which vector, host and environment can play a critical role in the spread of this disease. With dengue fever and other emerging viral diseases becoming increasingly prevalent around the world, this book provides valuable insight into the virus that causes this disease and potential ways to manage it. It is essential reading for all those working in tropical diseases, public health and virology. Praise from the reviews: «The book provides an excellent summary of dengue/flavivirus research and is important for individuals and institutions interested in emerging infectious diseases.» MICROBIOLOGY TODAY

Prominent clinicians and researchers from diverse disciplines discuss the basic cell and molecular biology of steroid action and sex steroids' effects on the nervous and immune systems. Provides an integrated evaluation of the advantages and disadvantages of hormone replacement therapy.

Environmental statistics is a rapidly growing discipline that is important not only as a division of professional and academic statistics, but also in the accumulation of data on environmental effects and in the formulation of environmental policy by government agencies. This book features contributions from policy makers, scientists actively involved in collection of data, and professional, academic and government statisticians. These explore the interfaces between the different areas of application of environmental statistics and consider the future applications of methods arising from this discipline. Some of the chapters deal specifically with environmental models and methods. Here, the contributors explain specialized statistical techniques that have been developed for analysing environmental data and mathematical models that have been applied to the problem of integrating large amounts of environmental data into a coherent picture of particular environmental systems. Several of the contributions deal specifically with the problems involved in co-ordinating data collection over large geographical areas and over many dimensions of measurement. Finally, the book discusses the problems of formulating specific environmental policies given the nature of the information that has been made available using environmental statistical methods.

This book is a comprehensive and up-to-date account of where we stand in immunological strategies for preventing or treating type 1 diabetes (T1D). Brings together contributions from the leaders in the arena of clinical immunotherapy, not limited to the diabetes field exclusively, in order to delineate a road-map that would lead to future clinical trials. The book integrates information from human and animal studies. The book considers T1D within the broader context of autoimmune disease. The format contains several discussions, which address specific questions and provides guidelines for future strategies and solutions for discovering a cure.

Much recent research in evolutionary developmental biology has focused on the origin of new body plans. However, most evolutionary change at the population and species level consists of tinkering: small-scale alterations in developmental pathways within a single body plan. Such microevolutionary events have been well studied on a population genetic level and from the perspective of adaptive phenotypic evolution, but their developmental mechanisms remain poorly studied. This book explores both theoretical and practical issues of tinkering. It features a wide range of perspectives to address several fundamental questions. How does tinkering occur developmentally, and how is it manifested phenotypically? Are the developmental mechanisms by which tinkering occur different from those that underlie larger evolutionary changes? What are the developmental constraints on tinkering? And how do we test hypotheses about microevolutionary shifts in development from the fossil record? With contributions from experts in a range of fields, this fascinating book makes exciting reading for anyone studying evolution, developmental biology or genetics.

This book explores existing and potential strategies for using the genome sequences of human, mouse, other vertebrates and human pathogens to solve key problems in the treatment of immunological diseases and chronic infections. The assembled genome sequences now provide important opportunities for solving these problems, but a major bottleneck is the identification of key sequences and circuits controlling the relevant immune reactions. This will require innovative, interdisciplinary and collaborative strategies of a scale and complexity we are only now beginning to comprehend. Specific problems addressed include the following: What kinds of information are we lacking to understand how the genome sequence specifies the differentiation and response of immune system cells, and system behaviour such as immunological memory and tolerance? Which genome sequences and cellular circuits cause or prevent pathological immune responses to foreign pathogens, allergens or self-tissues? Which host and pathogen genome sequences and cellular circuits explain the failure of sterilizing immune responses to sophisticated human pathogens such as the agents of tuberculosis, malaria, metazoan parasites and chronic viruses? Containing contributions from a range of leading experts in the field, this book provides an important new perspective for clinical immunologists and basic researchers alike.

Degeneration of sensory receptors or of the nerves innervating them leads to a sensory deficit. Various strategies have been tried for promoting regrowth of sensory receptors, particularly in the eye and ear. The latest data from experimental studies in animals are presented in the book including applications of BDNF and CNTF in the eye and epidermal growth factor in the ear.

The potential lipotoxic effect of accumulation of fatty acids in non-adipose tissues is thought to be a major component in the development of insulin resistance. Chronic exposure to high concentrations of free fatty acids in the blood affects pancreatic β cell function, insulin secretion and lipid synthesis in the liver, and storage in adipose tissue. Maintaining the normal levels of fatty acids requires coordinated regulation between the liver, adipose tissue and skeletal muscle. This book deals with the molecular aspects of fatty acid action in obesity and insulin resistance. The topics include lipid metabolism and adipose tissue biology, and β cell function and insulin resistance. Chapters deal with the molecular genetics and molecular physiology of energy homeostasis.

The astounding diversity of the immune system and the complexity of its regulatory pathways makes immunology a combinatorial science. Computational analysis has therefore become an essential element of immunology research and this has led to the creation of the emerging field of immunoinformatics. This book is the first to feature thorough coverage of this new field. Immunoinformatics facilitates the understanding of immune function by modelling the interactions among immunological components. Biological research provides ever deeper insights into the complexity of living organisms while computer science provides an effective means to store and analyse large volumes of complex data. Combining the two fields increases the efficiency of biological research and offers the potential for major advances in the study of biological systems. This book encompasses key developments in immunoinformatics, including immunological databases, sequence analysis, structure modelling, mathematical modelling of the immune system, simulation of laboratory experiments, statistical support for immunological experimentation and immunogenomics. The difficulties in effective application of bioinformatic tools in immunology arise at both ends of the spectrum: most immunologists have only a limited comprehension of sophisticated data analysis and applicability and limitations, while the average computer scientist lacks knowledge of the depth and complexity of biological data. The purpose of this book, therefore, is to present contributions from a multidisciplinary team of biologists and computer scientists to explore the issues related to better understanding of immune function and, in particular, to help apply new computer science methods to immunological research. Related Novartis Foundation symposia: 247 In Silico Simulation of Biological Processes Chair: Denis Noble 252 Generation and effector functions of regulatory lymphocytes Chair: Jean-François Bach