Jamie A. Goode – författare

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 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.

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.

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.

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.

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.

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.

This book draws together contributions from basic, pharmaceutical and clinical sciences aimed at a better understanding of the structure and function of hERG and the molecular basis for compound binding. 

It features regulatory authority perspectives on preferred preclinical test systems and includes topics on hERG channel gating, regulation of functional expression, pharmacological properties of hERG/IKr channels, drug-induced long QT syndrome and preclinical evaluation and regulatory recommendations for assessing QT prolongation risks. 

Better understanding of the role of the hERG channel in drug-induced cardiac arrhythmias should ultimately lead to the development of important, new and safer medicines.

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.

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.

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.

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.

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.

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.

ATP, the intracellular energy source, is also an extremely important cell–cell signalling molecule for a wide variety of cells across evolutionarily diverse organisms. The extracellular biochemistry of ATP and its derivatives is complex, and the multiple membrane receptors that it activates are linked to many intracellular signalling systems.

Purinergic signalling affects a diverse range of cellular phenomena, including ion channel function, cytoskeletal dynamics, gene expression, secretion, cell proliferation, differentiation and cell death.  Recently, this class of signalling molecules and receptors has been found to mediate communication between neurons and non-neuronal cells (glia) in the central and peripheral nervous systems. Glia are critical for normal brain function, development and response to injury. Neural impulse activity is detected by glia and purinergic signalling is emerging as a major means of integrating functional activity between neurons, glia and vascular cells in the nervous system. These interactions mediate effects of neural activity on the development of the nervous system and in association with injury, neurodegeneration, myelination and cancer.

Bringing together contributions from experts in diverse fields, including glial biologists, neurobiologists and specialists in purinergic receptor structure and pharmacology, this book considers how extracellular ATP acts to integrate communication between different types of glia, and between neurons and glia.  Beginning with an overview of glia and purinergic signalling, it contains detailed coverage of purine release, receptors and reagents, purinergic signalling in the neural control of glial development, glial involvement in information processing, and discussion of the interactions between neurons and microglia.

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.

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.

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 lung Thoroughly examines the major topic of innate immunity in immunology, which is now seen as key to the pathogenesis of and vaccination strategies for infectious diseases Describes 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 damage Covers the roles of cells such as neutrophils, macrophages and dendritic cells and of molecular components such as Toll-like receptors Discusses the clinical applications of the new knowledge regarding innate immunity and how this can be used in both treatment and prevention (vaccination) strategies Includes contributions from an international and interdisciplinary group of experts

Innate 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.

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.

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

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.

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

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 survival The role of bacterial milieu and mucosal bacteria in the IBD and of prebiotic and probiotic therapy The progress towards the identification of susceptibility genes and phenotype-determining genes The pharmacogenetics of IBD Mucosal immunology and therapeutic strategies stemming therefrom

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 ProcessesChair: Denis Noble

252 Generation and effector functions of regulatory lymphocytesChair: Jean-François Bach

The ability at the molecular level to keep track of time is a property shared by organisms ranging from the simplest unicells to humans. The primary feature of these biological clocks is their ability to entrain to environmental stimuli. The dominant stimulus comes from environmental light cues, which requires the existence of photopigments sensitive to light. The exact identity of the molecules involved in circadian photoreception has remained elusive.

The classical view of the circadian system is of diverse physiological rhythms regulated by a centralized clock structure. This book presents evidence that challenges this view. Experiments in both vertebrate and invertebrate systems demonstrate that the circadian timing system is dispersed throughout the animal and suggest that possibly every cell contains an autonomous clock mechanism. A variety of tissues and cells contain have been shown to maintain an oscillation when placed in vitro and removed from any external cues or signals that originate from the classical clock structures and/or the environment.

This book draws together contributions from an international and interdisciplinary group of experts whose work is focused on all aspects of the topic. Coverage includes the mechanisms of light signalling to the vertebrate clock, the connections between central and peripheral clocks, circadian gene expression patterns and output pathways of clock mechanisms.