Novartis Foundation Symposia - Böcker

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.

This book features contributions from experts in cell biology, genetics, neurobiology, immunology and structural biology.  The unifying element is that they all study processes of cell shape change and motility.  Several key questions in this field of research are discussed: What are the organising principles behind cell shape change?Are there ‘master switches’ present in every cell type?How are extracellular signals interpreted by the cell in order to activate intracellular mechanisms?What is the influence of the extracellular matrix on cell movement and internal signalling pathways?How do pathogens subvert cellular systems in order to stimulate or block their uptake?The book addresses all of these important questions.  Data are presented on the key proteins that regulate cell shape: the GTP binding proteins of the Rho family. There are also extensive discussions of the potential applications of the data to clinical problems, particularly that of cell motility in cancer.

Seemingly simple behaviours turn out, on reflection, to be discouragingly complex. For many years, cognitive operations such as sensation, perception, comparing percepts to stored models (short-term and long-term memory), decision-making and planning of actions were treated by most neuroscientists as separate areas of research. This was not because the neuroscience community believed these operations to act independently—it is intuitive that any common cognitive process seamlessly interweaves these operations—but because too little was known about the individual processes constituting the full behaviour, and experimental paradigms and data collection methods were not sufficiently well developed to put the processes in sequence in any controlled manner. These limitations are now being overcome in the leading cognitive neuroscience laboratories, and this book is a timely summary of the current state of the art. The theme of the book is how the brain uses sensory information to develop and decide upon the appropriate action, and how the brain determines the appropriate action to optimize the collection of new sensory information. It addresses several key questions. How are percepts built up in the cortex and how are judgments of the percept made? In what way does information flow within and between cortical regions, and what is accomplished by successive (and reverberating) stages of processing? How are decisions made about the percept subsequently acted upon, through their conversion to a response according to the learned criterion for action? How does the predicted or expected sensation interact with the actual incoming flow of sensory signals?  The chapters and discussions in the book reveal how answering these questions requires an understanding of sensory–motor loops: our perception of the world drives new actions, and the actions undertaken at any moment lead to a new ‘view’ of the world.This book is a fascinating read for all clinical and experimental psychologists  and neuroscientists, as well as anyone interested in how we perceive the world and act within it.

The book presents recent advances relating to the factors and mechanisms that regulate the growth, differentiation and function of mast cells and basophils; discussion of new technologies used to study these cells, and integration of the basic scientific findings in the context of therapeutic possibilities for the treatment of diseases such as allergic inflammation and autoimmune disease which are mediated, in part, by these granulocytes.

Oxygen sensing is a key physiological function of many tissues, but the identity of the sensor, the signalling pathways linking the sensor to the effector, and the endpoint effector mechanisms are all subjects of controversy. This book evaluates the various mediators that have been proposed, including the mitochondria, NAD(P)H oxidases, cytochrome p450 enzymes, and direct effects on enzymes and ion channels. There has been a resurgence of interest in the role of mitochondria, based partly on the ability of mitochondrial inhibitors to mimic hypoxia, but there is little consensus concerning mechanisms. Some favour the view that the primary signalling event is a reduction in cell redox state and reactive oxygen species (ROS) due to general inhibition of the electron transport chain (ETC); others support a key role for complex III of the ETC and an increase in ROS generation, while others doubt either of these components is the key intermediary. All these hypotheses are discussed in the book, together with conceptual problems concerning the ability of mitochondria to respond to physiological hypoxia. The other area of controversy covered in the book is the identity of the endpoint effector(s). Some authors favour K+ channel inhibition, followed by depolarization and Ca2+ entry via L-type channels, while others propose that release of Ca2+ from intracellular stores, or capacitative Ca2+ entry and other voltage-independent pathways may be more important. The book also describes evidence for an endothelium-dependent Ca2+-sensitizing pathway involving Rho and possibly other kinases. While some of these differences can be attributed to variation between tissues, many must be related to differences in interpretation or methodology. In this book, experts in the field of acute oxygen sensing working in different tissues address these controversies and their possible origins, and discuss possible approaches whereby these controversies might be resolved. The book will be of great interest to all those working in fields where oxygen sensing is important, particularly cancer and wound healing, as well as researchers in drug discovery and biotechnology.

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.

Cl- absorption and HCO3- secretion are intimately associated processes vital to epithelial function, itself a key physiological activity. Until recently the transporters responsible remained obscure, but a breakthrough occurred with the discovery of the SLC26 transporters family. It is now clear that the SLC26 transporters have broad physiological functions since mutations in several members are linked to a variety of diseases. This book describes the properties of this family in detail, with contributions from the leading global researchers in the field. Complementary views from experts on other ion channels are offered in the discussions, which make fascinating reading. This family consists of at least 10 genes, each of which has several splice variants. Most members of the family are expressed in the luminal membrane of epithelial cells. Characterization of anion transport by three members has revealed that all function as Cl-/HCO3- exchangers, suggesting that SLC26 transporters are responsible for the luminal Cl-/HCO3- exchange activity. The SLC26 transporters are activated by the CF transmembrane conductance regulator and activate it in turn, leading to a model in which these molecules act together to mediate epithelial Cl- absorption and HCO3- secretion. The book includes chapters on the transport of other molecules by the SLC26 family, including oxalate in the kidney and sugars in cochlear hair cells amongst others. It also describes recent discoveries that most SLC26 transporters bind to scaffold proteins and that they all contain a conserved domain predicted to participate in protein-protein interactions. These suggest the SLC26 transporters exist in complexes with other Cl- and HCO3- transporters, and possibly other regulatory proteins. This book explores the functional role of these interactions, leading to better understanding of transepithelial fluid and electrolyte secretion and the diseases associated with it.

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

Cigarette smoking is estimated to lead to 4.9 million premature deaths per year worldwide. This is predicted to rise to 10 million by 2020. In western countries it kills half of all smokers who fail to stop. The prevailing model for tobacco addiction is that nicotine from cigarettes rewards smoking and punishes abstinence, tapping into a motivational system of operant conditioning that requires no conscious awareness. However, there are also accounts which involve cognitive biases and the effect of nicotine on impulse control. The brain pathways involved have been studied extensively, but the role of different nicotine receptor subtypes and other neurotransmitter systems is still subject to debate. In western countries, cigarette smoking as an adult has a heritability of 30-50% and candidate genes have been identified that may contribute in part to addiction susceptibility. Many socio-cultural correlates of cigarette smoking have been established, but a comprehensive model that accounts for these and links them with the psychobiological aspects of nicotine addiction has not been forthcoming. Structured behavioural support programmes aid cessation attempts, as do a number of pharmacotherapies, most notably nicotine replacement treatments and bupropion, but the underlying mechanisms are unclear. This book deals with the problems involved in understanding and treating nicotine and tobacco addiction. Topics covered include the nature of the worldwide health problem posed by cigarette smoking, the psychodynamics of cigarette addiction, and the basic pharmacology and biochemistry of nicotine and its effect on the brain. Further chapters analyse the genetic basis of susceptibility to nicotine addiction. Finally, the contributors address approaches to therapy. A continuing theme in the discussions throughout the book is how best to treat nicotine addiction, given that many smokers would like to stop smoking but are unable to do so because of their addiction. This book will be of great value to all psychologists and psychiatrists working on addiction, specifically to nicotine but also to other compounds and behaviours. It will also be of interest to neuroscientists and pharmacologists working on nicotine receptors and the brain pathways involved in dependence, as well as to biochemists, molecular biologist and to public health officials.

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 specificdiscusses the importance of developing criteria for establishing the significance of these different categories of disease-associated loci.

Empathy is the process that allows us to share the feelings and emotions of others, in the absence of any direct emotional stimulation to the self. Humans can feel empathy for other people in a wide array of contexts: for basic emotions and sensation such as anger, fear, sadness, joy, pain and lust as well as for more complex emotions such as guilt, embarrassment and love. It has been proposed that, for most people, empathy is the process that prevents us doing harm to others. Although empathy seems to be an automatic response of the brain to others’ emotional reactions, there are circumstances under which we do not share the same feeling as others.  Imagine, for example, that someone who does the same job as you is paid twice as much. In this case, that person might be very satisfied with their extra salary, but you would not share this satisfaction. This case illustrates the ubiquitous feeling of fairness and justice.Our sense of fairness has also become the focus of modern economic theories. In contrast to the prominent self-interest hypothesis of classic economy assuming that all people are exclusively motivated by their self-interest, humans are also strongly motivated by other-regarding preferences such as the concern for fairness and reciprocity. The notion of fairness is not only crucial in personal interaction with others in the context of families, workplace or interactions with strangers, but also guides people’s behaviour in impersonal economic and political domains.This book brings together work from a wide range of disciplines to explain processes underlying empathy and fairness. The expert contributors approach the topic of empathy and fairness from different viewpoints, namely those of social cognitive neuroscience, developmental psychology, evolutionary anthropology, economics and neuropathology. The result is an interdisciplinary and unitary framework focused on the neuronal, developmental, evolutionary and psychological basis of empathy and fairness. With its extensive discussions and the high calibre of the participants, this important new book is essential reading for anyone with an interest in this topic.

Part of the prestigious Novartis Foundation series, this volume uniquely addresses the use of innate immunity to treat or prevent infectious diseases of the lung. Innate Immunity to Pulmonary Infection: Provides a comprehensive overview of pulmonary infectious diseases, including basic pathology, current and potential therapies, and detailed consideration of the innate biological resistance mechanisms in the lungThoroughly examines the major topic of innate immunity in immunology, which is now seen as key to the pathogenesis of and vaccination strategies for infectious diseasesDescribes the genetic and environmental factors which determine the outcome of infection, such as latency of Tuberculosis, blood stream invasion from local infection, and local target tissue damageCovers the roles of cells such as neutrophils, macrophages and dendritic cells and of molecular components such as Toll-like receptorsDiscusses the clinical applications of the new knowledge regarding innate immunity and how this can be used in both treatment and prevention (vaccination) strategiesIncludes contributions from an international and interdisciplinary group of expertsInnate Immunity to Pulmonary Infection is an essential resource for researchers in both industry and academia. It is of interest for all those interested in the disciplines of immunology, virology, biology, biotechnology and 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.

Sepsis: New Insights, New Therapies brings together contributions from an international group of experts in diverse fields to consider how the various pathways implicated in early and late sepsis interact, with a particular emphasis on novel concepts and potential new therapeutic approaches. Topics covered include adaptive immunity, inflammation, neuroendocrinology, bioenergetics and metabolism. Several chapters in the latter half of the book are particularly concerned with treatment strategies involving modulation of the neuroendocrine response. Addresses the frequent, but under-recognised condition of sepsis and discusses new ways to prevent and treat itDescribes numerous pharmacological approaches to therapy for early and late sepsisIncludes detailed discussion of the various physiological systems implicated in sepsisPresents an international perspective, featuring contributions from experts from laboratories worldwide involved in the study of sepsisSepsis: New Insights, New Therapies is an invaluable resource for all critical care physicians and researchers. It is also informative reading for immunologists, endocrinologists, neuroendocrinologists, physiologists, and pharmacologists.

The formation of blood vessels is an essential aspect of embryogenesis in vertebrates. It is a central feature of numerous post-embryonic processes, including tissue and organ growth and regeneration. It is also part of the pathology of tumour formation and certain inflammatory conditions. In recent years, comprehension of the molecular genetics of blood vessel formation has progressed enormously and studies in vertebrate model systems, especially the mouse and the zebrafish, have identified a common set of molecules and processes that are conserved throughout vertebrate embryogenesis while, in addition, highlighting aspects that may differ between different animal groups.The discovery in the past decade of the crucial role of new blood vessel formation for the development of cancers has generated great interest in angiogenesis (the formation of new blood vessels from pre-existing ones), with its major implications for potential cancer-control strategies. In addition, there are numerous situations where therapeutic treatments either require or would be assisted by vasculogenesis (the de novo formation of blood vessels). In particular, post-stroke therapies could include treatments that stimulate neovascularization of the affected tissues.The development of such treatments, however, requires thoroughly understanding the developmental properties of endothelial cells and the basic biology of blood vessel formation.While there are many books on angiogenesis, this unique book focuses on exactly this basic biology and explores blood vessel formation in connection with tissue development in a range of animal models. It includes detailed discussions of relevant cell biology, genetics and embryogenesis of blood vessel formation and presents insights into the cross-talk between developing blood vessels and other tissues.With contributions from vascular biologists, cell biologists and developmental biologists, a comprehensive and highly interdisciplinary volume is the outcome.

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.

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.

Part of the prestigious Novartis Foundation, this is the first book to review the pathology associated with acetaldehyde, a known toxic agent found in cigarette smoke and other pollutants and derived from ingested alcohol, amongst other sources. In the body, acetaldehyde affects several tissues, particularly the brain and liver, causing various diseases, including cancer, alcoholic liver disease and Alzheimer’s. Acetaldehyde-Related Pathology describes the toxic effects of acetaldehyde at the tissue and cellular levels, reviewing enzyme biochemistry, transgenic mouse models of alcohol dehydrogenase mutants, and the cell-signalling pathways implicated in alcohol-related pathology. It explores the mechanisms of acetaldehyde-induced damage to tissues, often a first step in carcinogenesis, including the oral cavity, the human airway, and the GI tract. The book considers pharmacological strategies and treatments for reducing oral and intestinal acetaldehyde. Acetaldehyde-Related Pathology features in-depth, round-table discussions by an international array of scientists from major laboratories worldwide involved in studies of acetaldehyde-related pathology.This book is essential reading for anyone interested in the effects of this compound - pathologists, biochemists, toxicologists, cell and molecular biologists.

To understand the brain and its devastating diseases, we need to reveal the mechanisms that produce it and the ways in which it can constantly change throughout a lifetime.  This book features a timely and insightful discussion between developmental neurobiologists and clinicians who deal with disorders of the nervous system. Chapters in this book deal specifically with cell fate determination, cell migration and disorders of cell migration; current concepts and new ideas about cortical arealisation, and disorders which can arise from incorrect arealisation; genes implicated in the development of cortical connectivity and related pathologies such as schizophrenia and synaesthesia; and susceptibility genes for cognitive disorders such as schizophrenia, autism, dyslexia, and attention deficit disorder.

The past decade has seen mounting global concern regarding viral outbreaks such as SARS, avian influenza and West Nile virus. In 2004 and 2005, reports of bird-to-human, and possible human-to-human, transmissions of the H5N1 influenza viruses raised fears that these viruses could cause a pandemic on the scale of the Spanish flu pandemic of 1918.   Previous to this, a novel coronavirus had been identified as the aetiological agent of the severe acute respiratory syndrome (SARS), a new respiratory viral disease that emerged at the end of 2002 and caused profound disturbances in over 30 countries worldwide in 2003. It is not known whether the SARS coronavirus will re-emerge, especially since its origins and potential reservoir(s) are unresolved. However, these outbreaks have shown that these viruses can emerge in any part of the world at any time. This book critically evaluates the latest scientific evidence on novel or re-emerging viral diseases and brings together contributions from world experts on this topic, explaining best practice in their area, and discussing lessons learned and how best to collaborate to prevent and control future outbreaks. Topics covered include: the latest advances in virology, particularly in the area of epidemiologydiagnosticsanimal models for viral infectionantiviral and vaccine developmentNovel and Re-emerging Respiratory Viral Diseases offers a comprehensive and interdisciplinary account of all aspects of the topic, from basic molecular biology to public health issues, and is therefore essential reading for virologists, infectious disease specialists, public health managers, researchers and epidemiologists, as well as those working in vaccine development, pharmaceutical medicine and drug discovery

With the recent renaissance in mitochondrial biology and increasing recognition of their role in many diseases, this book provides a timely summary of the current state-of-the-art in mitochondrial research. The book opens with the regulation of mitochondrial replication and biogenesis and reviews the mechanisms and functional consequences of mitochondrial fission and fusion. Further chapters address mitochondria and oxidative stress and their roles in cell signalling and cell death. The book includes extensive, fascinating discussion of the biochemistry of mitochondrial cell signalling (especially involving calcium) and of oxidative stress. The nature of the proteins engaged in these processes, many only recently discovered, is covered in detail. Mitochondria have been strongly implicated in neurodegenerative diseases such as Parkinson’s, Huntington’s and amyotrophic lateral sclerosis. They are also affected in cancer, ageing and cardiovascular disease. The final section of the book reviews mitochondrial mutations and their consequences in ageing and other phenotypic manifestations. The authors discuss how mitochondrial proteins might constitute important therapeutic targets and describe initial attempts to develop compounds that can regulate their function.

Inflammatory bowel disease (IBD) comprises a group of idiopathic diseases of the intestine characterized by chronic inflammation of the bowel with periods of exacerbation and remission. Although the exact cause of IBD remains undetermined, the condition appears to be related to a combination of genetic and environmental factors resulting in an aberrant activation of the mucosal immune system. This book contains a series of interdisciplinary discussions between clinical and basic scientists focusing on key issues such as: Epithelial cell and molecular biology, including apoptosis, necrosis and cell survivalThe role of bacterial milieu and mucosal bacteria in the IBD and of prebiotic and probiotic therapyThe progress towards the identification of susceptibility genes and phenotype-determining genesThe pharmacogenetics of IBDMucosal immunology and therapeutic strategies stemming therefrom

Understanding stem cells at the molecular level is essential to understanding their behaviour in a physiological context. This volume in our acclaimed Novartis Foundation series features animated discussion from the world’s experts in this topic on the important ethical issues that are raised by research on stem cells. They review the various regulatory regimes, which apply in different countries – a key factor in determining where future stem cell research is carried out. Potential clinical applications covered in the book include the production of cardiomyocytes to replace damaged heart tissue, the production of insulin-producing cells for patients with diabetes, and the generation of neurons for the treatment of patients with Parkinson’s disease or spinal cord injury. Particular attention is paid to the factors that maintain stem cells in a pluripotent state or which drive them to create differentiated and lineage-committed cells in vitro and in vivo.  Nuclear reprogramming, the process by which a nucleus acquires developmental potential, is covered here as well. It is relevant to stem cell research generally, and also to research on the cloning of animals by nuclear transfer. This book is an essential purchase for all those engaged in stem cell research, whether in the laboratory, the clinic or the regulatory authorities.From the reviews:"...this book provides: a comprehensive overview of current issues in stem cell research, with contributions from leading figures..."—BRITISH SOCIETY OF CELL BIOLOGY

This book draws together contributions from cell and developmental biologists, structural biologists, geneticists and clinical scientists aimed at a better understanding of the cellular and molecular basis of these diseases. Topics include: How nuclear structure and location within a nucleus affect gene expressionChromatin organization and cell differentiationThe nature of the interactions between the nuclear envelope and the cytoskeletonThe extent to which the cytoskeleton mediates communication between the cell membrane and nucleus in regulating gene expression and whether disruption of such communication might underlie the disease processesIt is hoped that a better understanding of the mechanisms leading to disease pathogenesis may ultimately lead to more rational and appropriate treatments.

The recent identification of susceptibility genes for schizophrenia, depression and learning and memory dysfunction suggest that psychiatric disorders may be influenced by a small number of genes with multiple actions. This is the first book to investigate the role of growth factors in these disorders, which should provide clues to the underlying biochemical mechanisms. For example, recent studies have substantiated the provocative finding that neuregulin 1 (NRG1)is a candidate gene for schizophrenia. Neuregulin and its receptors, the ErbB tyrosine kinases, are essential for development of the cardiovascular and nervous systems. Lack of NRG1 function may be involved in dysregulation of synaptogenesis and synaptic plasticity in the adult mediated through glutamate receptor function. Polymorphisms for BDNF (brain-derived neurotrophic factor) have also been implicated in the pathogenesis of schizophrenia. BDNF is a prevalent neurotrophic factor that plays an important role in the pathophysiology of depression, bipolar disease and other psychiatric disorders. Other topics addressed in this book include neuroplasticity and neurotrophic factors, signal transduction by neurotrophins, intracellular trafficking of growth factors, trophic factors and cognitive functions, neurotrophins and depression, and pharmacological treatments of schizophrenia.

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.

The heat shock, or cell stress, response was first identified in the polytene chromosomes of Drosophila. This was later related to the appearance of novel proteins within stressed cells, and the key signal stimulating this appearance was identified as the presence of unfolded proteins within the cell. It is now known that this is a key mechanism enabling cells to survive a multitude of physical, chemical and biological stresses. Since the promulgation of the ‘molecular chaperone’ concept as a general cellular function to control the process of correct protein folding, a large number of molecular chaperones and protein folding catalysts have been identified, and it has been recognized that not all molecular chaperones are stress proteins and vice versa. The discovery of molecular chaperones as folding proteins went hand-in-hand with their recognition as potent immunogens in microbial infection. It was subsequently shown that administration of molecular chaperones such as Hsp60, Hsp70 or Hsp90 could inhibit experimental autoimmune diseases and cancer.More recently evidence has accumulated to show that certain molecular chaperones are also present on the surface of cells or in extracellular fluids. A new paradigm is emerging: at least some molecular chaperones are secreted proteins with pro- or anti-inflammatory actions, regulating the immune response in human diseases such as coronary heart disease, diabetes and rheumatoid arthritis. In addition to having direct effects on cells, molecular chaperones can bind peptides and present them to T cells to modulate immune responses. This may be significant in the treatment of cancer.This is the first book bringing leading researchers in this field together to review and discuss: our current knowledge of cell stress response and molecular chaperonesthe changing paradigms of protein trafficking and functioncell stress proteins as immunomodulators and pro- and anti-inflammatory signalling moleculesthe role of these proteins in various chronic diseases and their potential as preventative or therapeutic agents.The Biology of Extracellular Molecular Chaperones is of particular interest to immunologists, cell and molecular biologists, microbiologists and virologists, as well as clinical researchers working in cardiology, diabetes, rheumatoid arthritis and other inflammatory diseases.

The object of this book is to gather together workers in the fields of epilepsy, those concerned with the basic science of resistance and the blood-brain barrier, and those with clinical experience of drug resistance in cancer, with a view to stimulating further work on drug resistance in epilepsy. Whilst resistance in cancer has been extensively studied, and trials of reversal of resistance have been undertaken, with some success, resistance in epilepsy has only just begun to be addressed.

Nature employs a wide variety of sex determining mechanisms and it is only comparatively recently that the tools have become available for these to be explored at the cellular and molecular levels.  A major landmark was the discovery in 1990 of the SRY gene and the subsequent demonstration of its key role in triggering male sex determination in transgenic mice.  This book reviews and discusses our current understanding of the molecular genetic pathways of sex determination, with special emphasis on vertebrates. It features comparisons with other modes of sex determination, consideration of the biology of sexual development and discussion of the evolution of sex-determining mechanisms.By bringing together an international and interdisciplinary group of experts who study many different aspects of the problem, the book highlights much new and exciting work in this area and serves to identify and stimulate promising new research directions.