This award-winning thesis investigates the mechanisms underlying cardiac arrhythmia development and termination from an entirely new perspective. By viewing the heart as a complex system, the author uses theoretical tools from nonlinear dynamics combined with numerical simulations and experiments to achieve insights into the relationship between its structure and dynamics, thereby paving the way towards innovative low-energy defibrillation strategies. The work tackles, among other things: the effect of substrate heterogeneity on the spatial-temporal dynamics of cardiac arrhythmias and ways in which weak pulsed electric fields can be used to control these dynamics in heterogeneous cardiac tissue. The long-term vision of this research is to replace the current strategy of applying painful and sometimes tissue damaging electric shock - currently the only reliable way to terminate life-threatening fibrillation - by a more subtle but equally effective intervention. The book maps out a number of promising research directions for biophysicists and medical researchers working on the origins and treatment of cardiac arrhythmias.

Since the epochal discovery of the radical and highly toxic gas nitric oxide (NO) as a signaling molecule, two other no less toxic gases - carbon monoxide (CO) and hydrogen sulfide (H2S) - have been found to also be involved in a plethora of physiological and pathophysiological functions. The gases termed gasotransmitters play an increasingly important role in understanding how signalling into and between cells is modulated and fine-tuned. The advent of gasotransmitters has profoundly changed our way of thinking about biosynthesis, liberation, storage and action mechanisms in cellular signaling. In recent years an impressive amount of new data, distributed throughout the existing literature, has been generated. For this book the editors have recruited distinguished colleagues in the field to summarize and review important biological, pharmacological and medical functions and their implications, as well as methods for the detection of gasotransmitters.

Death receptors play a central role in directing apoptosis in mammalian cells. This process of active cell death is important for a number of biological processes, e.g. for the regulation of the immune system. Death receptors are cell surface receptors that transmit apoptotic signals initiated by corresponding death ligands. Many complex signaling pathways are activated and apoptosis is the final result of a complex biochemical cascade of events.

Besides their role in the induction of cell death, evidence now exists that death receptors are able to activate several non-apoptotic signaling pathways which, depending on cellular context, may lead to apoptosis resistance, secretion of pro-inflammatory proteins, proliferation and invasive growth of cancer cells.

This book looks at the molecular basis of death receptor signaling and the role of death receptors in cancer development.

Research over the years has demonstrated that free radicals mediated oxidative stress lies at the helm of almost all patho-physiological phenomena. These findings emphasize on the need to understand the underlying molecular mechanism(s) and their critical role in the pathogenesis. This book aims to focus on these areas to provide readers a comprehensive outlook about the major redox sensitive pathways and networks involved in various disease conditions. In the first chapter of the book, basic information about the oxidative stress, its generation, its biomarkers and its role in body are discussed. In the next three chapters, the role of oxidative stress in various pathologies ranging from neurological disorders, to cardiovascular diseases, cancers, metabolic diseases and ageing have been described. Chapter 5 cumulatively describes the most important molecular signaling pathways that are affected by reactive oxygen species (ROS). These are the mechanisms which are common denominators in various pathological states. In the next part of the book, various antioxidant strategies to target and mitigate ROS have been discussed with details on the mechanisms. Selenium, being the research focus and interest of the authors for years, the role of selenium as an antioxidant as part of selenoproteins has been included in the book. Finally, the book culminates with authors' perspective on the future of the redox biology field. Throughout the book, efforts have been made to use simplified language and suitable figures for ease to understand the contents. Although the authors have tried to touch on all the different aspects of oxidative stress in detail, the fact that it is a continuously growing field with updates coming every day, there might be some areas which might not be described in depth. This book is designed for students, young scientists to get acquainted with the redox biology. Overall, this book is a reference to understand the redox regulation of cellular signaling pathways involved in pathogenesis.

As the current millennium steams towards a close, one cannot help but look with amazement at the incredible amount of progress that has been achieved in medicine in just the last few decades. A key contributing factor to this success has been the importation and blending of ideas and techniques from disciplines outside the traditional borders of medical science. In recent years, the most well-known example is the cross-pollination between molecular biology and medicine. Advances driven by this potent combination have spawned the vision of a future where cures based on gene therapy become commonplace. Yet, as we continue our search for "magic bullets" in the quest to eradicate disease, it important to recognize the value of other less-heralded interdisciplinary efforts that have laid a large part of the foundation of present-day medicine. In pulmonary medicine, the contribution from the bioengineers (a diverse collection of individuals cross-bred to various degrees in mathematical modeling and experimental physiology) has been larger and more sustained than in many other medical specialties. It is easy to point to the vast array of ventilators, blood-gas analyzers, oximeters, pulmonary function devices, and respiration monitors that are present in any modern clinical setting as solid evidence of the successful synergy between engineering science and pulmonary medicine. However, one must not forget the less tangible, but perhaps more important, contributions that have been derived from mathematical modeling and computer simulation, without which many of these modern instruments would not have come into existence.

The number of mouse models that are available for the study of human genetic neurological disorders is large and growing rapidly. Therefore, it was difficult to select the models that were reviewed in this volume. Clearly, there are important models that are not discussed, and perhaps a volume twice this size would have been more appropriate. Moreover, the pace at which new models are being developed and analyzed is rapid. As this volume goes to press, I am sure that additional mouse genes responsible for naturally occurring neurological disorders are being discovered and that many new transgenic and mutant mouse strains are being developed. Therefore, this volume should not be viewed as a comprehensive compendium, but rather as an update of work in progress. It is exhilarating to witness the fast pace at which these models are being established as important tools in the study of basic neuroscience and neurological disorders. It will be even more exciting to see their utilization in the development and testing of therapeutic interventions for these diseases. I would like to thank each of the authors who have contributed to this volume for their time and their expertise. I would also like to thank Drs. Timothy Coetzee and Joshua Corbin for their advice in the selection of the topics covered. I am deeply indebted to Dr. Kunihiko Suzuki, who first approached me with the idea for this volume, for his guidance throughout its preparation.

Experienced physicians concisely explain the pathophysiology and clinical manifestations of endocrine disorders and survey all the latest laboratory diagnostics. Topics range widely from an overview of the diagnosis of diabetes and the long-term monitoring of its complications to the evaluation of menstrual dysfunction. Coverage is also given to the diagnosis of pituitary tumors, Cushing's syndrome, thyroid disease, and hypoglycemia; the evaluation of endocrine-induced hypertension; the assessment of dyslipidemia and obesity; and approaches to diagnosing hyper- and hypocalcemia. There are also discussions of osteoporosis, hypogonadism and erectile dysfunction, and hyperandrogenism in women. The authors each review the complex physiological basis of the relevant endocrine processes and provide richly instructive recommendations for followup and long-term management of patients.

Research of 5-HT2c receptors stretches back twenty-five years, and while much of it has been productive, the past decade of research has been extraordinary in terms of both amount produced and insights gained. It is hardly surprising that 5-HT2c receptor research has grown so fruitful, given that it is a prominent central serotonin receptor subtype widely expressed within the central and the peripheral nervous system and is thought to play a major role in the regulation of numerous behaviors. It has further been shown by experimental and clinical observation that it may represent a possible therapeutic target for the development of drugs for a range of central nervous system disorders. The time, therefore, is more than appropriate to offer the first ever overview of the research of 5-HT2c receptors. Part of the popular and important series, "The Receptors," The 5-HT2c Receptor provides a thorough update of the functional status of the 5-HT2c receptor. It covers the molecular, cellular, anatomical, biochemical and behavioral aspects of this receptor so as to highlight its distinctive regulatory properties and the emerging functional significance of constitutive activity and RNA-editing in vivo. In addition, the book investigates the receptors' therapeutic potential in a range of different diseases, treated individually in separate chapters, including depression, drug abuse, schizophrenia, eating disorders, Parkinson's disease, Prader-Willi Syndrome, Alzheimer's disease and epilepsy. While not exhaustive, this text is a vital tool in understanding the past and inspiring the future of interdisciplinary research on the 5-HT2c receptor.

An attempt to create a framework for understanding the complexities of human performance by specifying the capacities that man brings to the performance of intellectual and physical skills.

Nuclear Receptors focuses on the structural analysis of nuclear receptors from the initial work using isolated protein domains to the more recent exciting developments investigating the conformational shape of full-length receptor complexes. The book also reviews the structure of key nuclear receptor co-regulatory proteins. It brings together, for the first time, a comprehensive review of nuclear receptor structure and the importance of receptor conformation underpinning allosteric regulation by different ligands (hormone, drugs, DNA response elements, protein-protein interactions) and receptor activity. The nuclear receptor superfamily, including receptors for steroid hormones and non-steroid ligands, are pivotal to normal physiology, regulating processes as diverse as reproduction, metabolism, the immune system and brain development. The first members of the family were cloned over 25 years ago, which heralded in the idea of a superfamily of intracellular receptor proteins that bound small molecule ligands: classical steroid hormones, vitamins, fatty acids and other products of metabolism. These signals are then transmitted through multiprotein receptor-DNA complexes, leading to the regulation of target genes, often in a cell-selective manner. The cloning of the receptor cDNAs also ushered in an era of unparalleled analysis of the mechanisms of action of these ligand-activated transcription factors.

The multiple actions of estrogens on different cell types have not only intrigued endocrinology researchers but also inspired the development of selective estrogen receptor modulators, or SERMs, that modulate estrogen signaling in a cell type-specific manner. Current molecular understanding of estrogen action has greatly profited from advances in molecular cell biology to dissect the mechanisms of estrogen-regulated gene expression in target cells, from in vivo analyses using genetic models deficient in estrogen signaling and from synthetic estrogen receptor ligands with isoform- or pathway-selective activity. These advances, and their implications for clinical use, were discussed by leading researchers from industry and academia during an international symposium held in Berlin, 1-3 March 2006.

Atherosclerosis leading to coronary heart disease and to cerebrovascular disorders is the number one cause of death in industrialized societies. For the last two decades, great ad vances have been made in understanding the pathogenesis of those disorders. Recent studies have revealed that the earliest event in atherogenesis is the adhesion of circulating leukocytes to the vascular endothelial cells and their migration into the subendothelial space. These cells are known to playa central role in the formation of a fatty streak consist ing of lipid-laden foam cells. As pathological events continue, the lesion is converted to a more fibrous lesion associated with vascular smooth muscle cells. To solve the enigma of this complicated process, intensive studies in molecular biology have disclosed the genes involved in those events. Some of the genes have been verified by creation of novel animal models, which have led to novel therapeutic strategies for subjects with atherosclerosis. This volume contains papers presented at the International Symposium on Lipoprotein Metabolism and Atherogenesis held in Kyoto December 5-8, 1998, supported in part by the Japan Intractable Diseases Research Foundation. The following three topics were the focus of the three-day program: I) The molecular approach to studying risk factors and prevention 2) The creation of novel animal models 3) Lipoprotein disorder as a cause of activation of vascular endothelial cells Thirty distinguished researchers from the United States, the United Kingdom, Austria, Finland, Australia, and Japan were invited.

This authoritative work presents the basic knowledge and state-of-the-art techniques necessary to carry out investigations of the cardiovascular system using modeling and simulation. The book provides a survey of relevant cell components and processes, with detailed coverage of the electrical and mechanical behaviors of vascular cells, tissues, and organs. Biological and mechanical glossaries are provided.

Lipobiology is an interdisciplinary field which incorporates critical aspects of lipid and lipoprotein chemistry into the disciplines of cell biology and physiology. During the last decade, advances in our understanding of the structure and function of lipids, biological membranes and lipid-derived second messengers have underscored the importance of lipids in the regulation of cellular function. This series focuses on salient aspects of the role of lipids in metabolic regulation and cellular activation, with emphasis on emerging concepts and technologies. One goal of this series is to formulate cohesive criteria upon which a foundation for the evaluation of recent work can be based and future directions of research identified.

This book discusses the relationship between cellular immunity and tryptophan metabolism, as well as its products, serotonin and melatonin, in the development of several diseases and reappraises the common signal transduction pathways of the neurodegenerative diseases, carcinogenesis, immune tolerance, inflammation, hypersensitivity reactions, neuropsychiatric disorders, in addition to bacterial tryptophan biosynthesis and novel antimicrobials. Tryptophan Metabolism: Implications for Biological Processes, Health and Disease presents fundamental information on tryptophan related metabolic pathways and metabolites, implications of these products for specific biological processes, diseases and conditions. This book focuses on effects of tryptophan metabolites on human health and will appeal to researchers, clinicians and students within this field.

Our purpose in writing this book was to produce a clinically-oriented, non-multi-au- thored textbook ofcardiac electrophysiology that would be useful to practicing electro- physiologists, cardiologists, fellows in training as well as associated electrophysiology professionals, including nurses and technologists. While all clinical textbooks risk be- coming outdated even before they're published, and few textbooks ofa manageable size can claim to be completely comprehensive, our goal was to produce a book that system- atically presents a thorough discussion ofthe fundamental principles and concepts im- portant to the practice of clinical electrophysiology. We do not discuss basic cellular electrophysiology for its sake alone, but instead include basic science material only when itis helpful in explaining the overlying clinical principles. Cardiac electrophysiology, as with any subspecialty, behaves as a living organism with continuous evolution of its standards and practices. However, even though the details and tools of management (catheters, drugs, devices, etc. ) may change with dazzling speed, the fundamental princi- ples ofdiagnosis and management generally change very little and they remain the criti- cal underpinning ofthe day-to-day management ofpatients with cardiac arrhythmias. In the first third ofthe book we present the principles ofclinical cardiac electrophysiolo- gy as it is currently practiced.

How is the heartbeat generated? What controls the strength of contraction of heart muscle? What are the links between cardiac structure and function? How does our understanding of skeletal and smooth muscle and non-muscle cells influence our thinking about force development in the heart? Are there important species differences in how contraction is regulated in the heart? How do the new molecular data fit together in understanding the heart beat? What goes wrong in ischemia, hypertrophy, and heart failure? This book paints a modern portrait' of how the heart works and in this picture the author shows a close-up of the structural, biochemical, and physiological links between excitation and contraction. The author takes the reader through a series of important, interrelated topics with great clarity and continuity and also includes many useful illustrations and tables. The book starts by considering the cellular structures involved in excitation-contraction coupling and then described the characteristics of the myofilaments as the end effector of excitation-contraction coupling. A general scheme of calcium regulation is described and the possible sources and sinks of calcium are discussed in simple, but quantitative terms. The cardiac action potential and its many underlying currents are reviewed. Then the characteristics of some key calcium transport systems (calcium channels, sodium/calcium exchange and SR calcium uptake and release) are discussed in detail. This is then built into a more integrated picture of calcium regulation in succeeding chapters by detailed discussions of excitation-calcium coupling mechanisms (in skeletal, cardiac, and smooth muscle), the interplay betweencalcium regulatory processes, and finally mechanisms of cardiac inotropy, calcium overload, and dysfunction (e.g., ischemia, hypertrophy, and heart failure). Excitation-Contraction Coupling and Cardiac Contractile Force &endash; Second Edition is an invaluable source of information for anyone who is interested in how the heart beat is controlled and especially suited for students of the cardiovascular system at all levels from medical/graduate students through senior investigators in related fields.

Thebook comprises the contribution of several authors who are among the mostrenowned scientists working in the field of mathematical modeling and numerical simulation of the human cardiocirculatory system. The contributions cover a wide range of topics, from the pre processing of clinical data, to the set up of mathematical equations, their numerical solution, both in-vivo and in-vitro validation. They address the flow in the systemic arterial tree and the complex electro-fluid-mechanical coupling in the human heart. Many examples of patient-specific simulations are addressed. This book is addressed to all scientists (from PhD level up to professional scientists) interested in the mathematical modeling and numerical simulation of the human cardiocirculatory system."

This volume is a collection of a variety of brain proteins and peptides whose structures and functions are relatively well known. Each chapter provides a succinct and up-to-date summary of a protein or peptide as well as a review of the individual's contributions to the field. The volume explores the progress that has been made in the field over the past few years and provides insight into the field today.

Now in a fully revised and updated fourth edition, Science and Soccer is still the most comprehensive and accessible introduction to the physiology, biomechanics and psychology behind the world's most popular sport. Offering important guidance on how science translates into practice, the book examines every key facet of the sport, with a particular focus on the development of expert performers. The topics covered include: • anatomy, physiology, psychology; sociology and biomechanics; • principles of training; • nutrition; • physical and mental preparation; • playing surfaces and equipment; injury • decision-making and skill acquisition; • coaching and coach education; • performance analysis; • talent identification and youth development. Science and Soccer: Developing Elite Performers is a unique resource for students and academics working in sports science. It is essential reading for all professional support staff working in the game, including coaches at all levels, physiotherapists, conditioning specialists, performance analysts, club doctors and sport psychologists.

Internationally eminent scientists illuminate the most important scientific aspects of essential fatty acids (EFAs)-from their biochemistry to their physiological consequences in both health and illness. The distinguished contributors integrate a wide range of topics, including the basic biochemistry of EFAs and lipid metabolism, the role of EFAs in the neuronal membrane, the effects of EFAs and lipids in various diseases, and the effects of normal levels and EFA deficiencies on cognition and behavior. The book's consolidation of our knowledge of the biology and metabolism of the EFAs lays the groundwork for dramatic advances in our understanding of these ubiquitous biochemicals and their role in health and illness.

This third edition provides 2900 multiple choice questions on human anatomy and physiology, and some biophysical science, separated into 20 chapters and 68 categories. In addition, there are 64 essay topics. The answer to each question is accompanied by an explanation. Each chapter has an introduction to set the scene for the questions to come. However, not all possible information is provided within these Introductions, so an Anatomy and Physiology textbook is an indispensable aid to understanding the answers. The textbook offers a more holistic approach to the subjects of anatomy and physiology by also including biomechanics, biophysics and biochemistry. The questions have been used in end-of-semester examinations for undergraduate anatomy and physiology courses, and as such, reflect the focus of these particular courses and are pitched at this level to challenge students that are beginning their training in anatomy and physiology. The question and answer combinations are intended for use by teachers, to select questions for their next examinations, and by students, when studying for an upcoming test. Students enrolled in the courses for which these questions were written include nursing, midwifery, paramedic, physiotherapy, occupational therapy, nutrition and dietetics, health sciences, exercise science, and students taking an anatomy and physiology course as an elective.