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The book dissects the role of oxidative stress in the pathogenesis of the leading causes of global morbidity and mortality, i.e. cardiovascular and metabolic diseases. The chapters discuss topics related to the role reactive oxygen species (ROS) play in hypertension, atherosclerosis, diabetes, obesity and related pathologies. One chapter discusses the clinical efficacy and safety considerations of GLP-1 receptor agonists and SGLT-2 inhibitors in obesity management and the associated cardiovascular complications. Another chapter discusses the context-dependent roles of matrix metalloproteases, and how their activity can be modulated and utilized for the development of improved drugs for cardiometabolic diseases. Moreover, how ROS and aging interplay to precipitate cardiovasculo-metabolic disease is discussed and highlighted. Similarly, how sex and sepsis interplay in the context of cardiorenal disease is teased out in one of the chapters. Preventive measures that can abrogate ROS-induced cardiovasclo-metabolic disease are discussed and clarified in the hope of reducing such a debilitating battery of diseases. Another chapter is fully dedicated to the roles of ROS in atherosclerosis, while another chapter deals with mechanisms and effect of ROS on various phenotypes of adipose tissues in the context of cardiovasculo-metabolic disease. A chapter also discusses the link between traumatic brain injury (TBI) and cardiovascular impairments, and how ROS plays a significant role in TBI-induced cardiovascular disease. A section dedicated to antioxidants as potential therapy is also included. Given the complexity of the mechanisms implicated in ROS-modulated responses, it remains challenging to assert a conclusive argument and pre-determined regimen for incorporating antioxidants into conventional therapies. In all of the chapters, the molecular, cellular, genetic, and pharmacological mechanisms implicated are covered from an applied science perspective. This is an ideal book for basic researchers in the biomedical field, graduate students in biological and biomedical fields, medical students, instructors in medical and graduate schools, and professionals working for pharmaceutical companies.

Mitochondrial Transplantation and Transfer: Biology, Methods, Applications, and Disease, a volume in the Translational and Applied Bioenergetics series, offers a detailed overview of mitochondrial transplantation across fundamental biology, disease and early therapeutics research. Here, more than twenty experts in the field discuss transplantation and transfer of healthy mitochondria and define future steps to improve new therapeutic applications across a variety of diseases. Emphasis is placed on the physiology of mitochondrial transfer, isolation processes and their applications, transfer methods, and diagnostic and treatment use across cardiovascular, metabolic, and neurological diseases, among other disease types. Step-by-step instruction is provided around research protocols and methods discussed, along with careful attention to the ethical implications of mitochondrial transplantation research and application. - Provides an in-depth discussion of mitochondrial transplantation, considering fundamental biology, disease implications, research methods and applications - Discusses recent advances in the field and their meaning for future research and clinical utility - Considers ethical dimensions of mitochondrial transplantation research and use in therapeutics - Examines mitochondrial transplantation across a range of disease types, from neurological to cardiovascular disease and ischemia

Integrins are heterodimeric cell surface receptors which anchor cells to different extracellular matrix proteins or act as cell-cell receptors. They play pivotal roles not only across a wide range of physiological processes including tissue morphogenesis, wound healing, and regulation of cell growth, but also in numerous pathological conditions such as autoimmunity, infectious disease, and carcinogenesis. This book aims to provide readers a summary of the most important integrins and their respective biological functions. Readers will learn about knockout- and animal models to study the functionality of key collagen-, laminin-, and nephronectin-binding integrins. Additionally, the role of integrins in pathological tissue remodeling in joints and in developing and diseased cardiac tissue are discussed. Reviews of the current knowledge of the role of integrins in tissue and tumor fibrosis, angiogenesis and tumor progression are an important part of this work. Finally, the bookdiscusses integrins in the context of the immune system, how to target integrin-ligand interactions with antibodies, and the role of integrins as receptors for bacterial and viral cell invasion. Both experienced researchers and clinicians, as well as PhD students who wish to study the extracellular matrix and cell adhesion molecules will find “Integrins in Health and Disease - Key Effectors of Cell-Matrix and Cell-Cell Interactions” authoritative, easily accessible, and vastly informative.The series Biology of Extracellular Matrix is published in collaboration with the American Society for Matrix Biology and the International Society for Matrix Biology.

Glycolysis: Tissue-Specific Metabolic Regulation in Physio-Pathological Conditions provides an integrated overview of glycolysis, spanning basic biochemistry, patho-physiology and therapeutic applications. The book also instructs in methods available to study the involvement of the glycolytic events in healthy biology and disease pathology. It begins with an overview of fundamental glycobiology followed by chapters dedicated to glycolysis physiology in organs and systems, pathologic conditions related to glycolytic alterations, glycolysis as a therapeutic target and in drug discovery efforts, and methodological approaches to advance new glycolysis research. Disease areas considered range from cancer to heart failure, diabetes, inborn glycolytic pathway defects, hematologic malignancies, osteoporosis, neurodegenerative diseases and viral Infections. Omics and computational modeling, interactive study methods, and glycolysis flux measurement are described in detail, with step-by-step descriptions of experimental protocols, set-up and analysis. - Features chapter contributions from international leaders in the field - Spans fundamental aspects of glycolysis, patho-physiology and drug discovery - Includes step-by-step instruction in a range of research protocols, ranging from Omics to interactive analysis and measuring glycolysis flux

In this Edited Volume, a diverse group of exercise metabolism experts, assembled a multi-facetted collection of fascinating contributions. The chapters focus on metabolism during exercise, including anaerobic and aerobic metabolism, carbohydrate metabolism (separate chapters on muscle glycogen and blood glucose), fat metabolism (separate chapters on muscle and adipose tissue) and protein metabolism. Readers will find discussion on various tissues in addition to skeletal muscle, such as liver, heart and brain metabolism during exercise. In addition, the book includes chapters on other perspectives such as thermodynamic and bioenergetic aspects of exercise and a dive into history. Another focal point is on the effects of exercise in relation to training, age, sex, fatigue and the circadian rhythm. This contemporary collection will be an essential resource for Physiologists, Sports Scientists, Coaches, Athletes and students alike.

Clinical Bioenergetics: From Pathophysiology to Clinical Translation provides recent developments surrounding the etiology and pathophysiology of inherited and acquired energy-delated disorders. Across 40 chapters, world leaders in bioenergetics and mitochondrial medicine discuss novel methodologies designed to identify deficiencies in cellular bioenergetics, as well as the safety and efficacy of emerging management strategies to address poor cellular bioenergetics. Topics discussed include the omics landscape of impaired mitochondrial bioenergetics, hormones, tissue bioenergetics and metabolism in humans. Disease-specific case studies, modes of analysis in clinical bioenergetics, and therapeutic opportunities for impaired bioenergetics, addressing both known treatment pathways and future directions for research, are discussed in-depth. Diseases and Disorders examined include brain injury, chronic fatigue syndrome, psychiatric disorders, pulmonary fibrosis, neurodegenerative disorders, heart failure, chronic kidney disease, obesity, and insulin resistance, among others. - Provides a thorough discussion of foundational aspects of bioenergetics and disease, modes of analysis, and treatments for impaired bioenergetics - Discusses the role of bioenergetics and treatment pathways in brain injury, chronic fatigue syndrome, psychiatric disorders, pulmonary fibrosis, neurodegenerative disorders, heart failure, chronic kidney disease, obesity, and insulin resistance, among other diseases and disorders - Features chapter contributions from international leaders in translational bioenergetics research and clinical practice

This book highlights the multifaceted roles of Reactive Oxygen Species (ROS) in modulating normal cellular and molecular mechanisms during the development of different types of heart disease. Each chapter in the book deals with the role that altered redox homeostasis plays in the pathophysiology of heart disease. In addition, the book explains how reactive oxidant species interact with their targets and provides novel strategies for attenuating oxidative stress-induced types of heart disease.The book not only covers ROS-induced response in heart disease at the cellular level, but also demonstrates that an imbalance of redox states has its roots in our genes, and explains the ways gene expression is regulated. In turn, it reviews potential sources of ROS, their pathological effects on the heart, and potential sites for therapeutic interventions.

This book bridges the gap between fundamental and translational research in the area of heart disease. It describes a multidisciplinary approach, and demonstrates biochemical mechanisms associated with dysregulation of redox signaling, which leads heart disease. Presenting recent studies on improved forms of ROS scavenging enzymes; specific inhibitors for different ROS generating enzymes; and oxidant induced signaling pathways and their antagonists that allow subtle modulation of redox signaling, it also discusses the spatial and temporal aspects of oxidative stress in the cardiovascular system, which are of vital importance in developing better strategies for treating heart disease. Each chapter offers researchers valuable insights into identifying targets for drug development for different types of heart disease.

This volume explores the use of mass spectrometry for biomedical applications. Chapters focus on specific therapeutic areas such as oncology, infectious disease, and psychiatry. Additional chapters focus on methodology, technologies and instrumentation, as well as on analysis of protein-protein interactions, protein quantitation, and protein post-translational modifications. Various omics fields such as proteomics, metabolomics, glycomics, lipidomics, and adductomics are also covered. Applications of mass spectrometry in biotechnological and pharmaceutical industry are also discussed. This volume provides readers with a comprehensive and informative manual that will allow them to appreciate mass spectrometry and proteomic research, but also to initiate and improve their own work. This book acts as a technical guide as well as a conceptual guide to the newest information in this exciting field.

This book outlines the interaction of cadmium with the proteome and signalling molecules of mammalian cells. Chapters from expert contributors cover topics such as cadmium chemical biology, membrane receptors and transporters for cadmium and cadmium complexes, and targets of cadmium toxicity. Students and researchers working in bioinorganic chemistry will find this book an important account.

Developed as a one-stop reference source for drug safety and toxicology professionals, this book explains why mitochondrial failure is a crucial step in drug toxicity and how it can be avoided. • Covers both basic science and applied technology / methods• Allows readers to understand the basis of mitochondrial function, the preclinical assessments used, and what they reveal about drug effects• Contains both in vitro and in vivo methods for analysis, including practical screening approaches for drug discovery and development• Adds coverage about mitochondrial toxicity underlying organ injury, clinical reports on drug classes, and discussion of environmental toxicants affecting mitochondria

Sirtuins in Health and Disease, Volume 154 presents the reactions catalyzed by sirtuins in terms of their unique coenzyme NAD+-dependent catalytic mechanisms, the ways to elucidate these mechanisms, and the design of the inhibitory compounds against the sirtuin-catalyzed reactions as potential therapeutic agents for human diseases. Sections cover the concepts and chemical tools in sirtuin research, SIRT4 and SIRT7, the regulatory effects of NAD metabolic pathways on sirtuin activity, sirtuins as modifiers of Huntington's Disease (HD) pathology, parasite sirtuins as targets for novel chemotherapeutic agents, targeting sirtuins – substrate specificity and inhibitor design, and chemical probes in sirtuin research. This book focuses on the outstanding issues in the sirtuin field and implications for future sirtuin research. - Presents an excellent subject, excellent structural organization, and authoritative contributions from world-renowned scholars in the sirtuin field - Provides the latest updates on sirtuins in health and disease

Taurine 10 contains original articles and critical reviews based on the oral and poster presentations of XX International Taurine Meeting held in Seoul, Korea in May 2016. The purpose of the book is to present current ideas, new avenues and research regarding biological functions and clinical applications of taurine and taurine derivatives. It focuses on all aspects of taurine research including the cardiovascular system, the immune system, diabetes, the central nervous system, endocrine system and the role of taurine supplements in nutrition. It also includes presentations of novel animal experimental models using Cdo1 and CSAD knock-out mice.

The Scientists Guide to Cardiac Metabolism combines the basic concepts of substrate metabolism, regulation, and interaction within the cell and the organism to provide a comprehensive introduction into the basics of cardiac metabolism. This important reference is the perfect tool for newcomers in cardiac metabolism, providing a basic understanding of the metabolic processes and enabling the newcomer to immediately communicate with the expert as substrate/energy metabolism becomes part of projects. The book is written by established experts in the field, bringing together all the concepts of cardiac metabolism, its regulation, and the impact of disease. - Provides a quick and comprehensive introduction into cardiac metabolism - Contains an integrated view on cardiac metabolism and its interrelation in metabolism with other organs - Presents insights into substrate metabolism in relation to intracellular organization and structure as well as whole organ function - Includes historical perspectives that reference important investigators that have contributed to the development of the field

This essential volume comprehensively discusses redox-active therapeutics, focusing particularly on their molecular design, mechanistic, pharmacological and medicinal aspects. The first section of the book describes the basic aspects of the chemistry and biology of redox-active drugs and includes a brief overview of the redox-based pathways involved in cancer and the medical aspects of redox-active drugs, assuming little in the way of prior knowledge. Subsequent sections and chapters describe more specialized aspects of central nervous system injuries, neurodegenerative diseases, pain, radiation injury and radioprotection (such as of brain, lungs, head and neck and erectile function) and neglected diseases (e.g., leishmaniasis). It encompasses several major classes of redox-active experimental therapeutics, which include porphyrins, salens, nitrones, and most notably metal-containing (e.g., Mn, Fe, Cu, Zn, Sb) drugs as either single compounds or formulations with nanomaterials and quantum dots. Numerous illustrations, tables and figures enhance and complement the text; extensive references to relevant literature are also included. Redox-Active Therapeutics is an invaluable addition to Springer's Oxidative Stress in Applied Basic Research and Clinical Practice series. It is essential reading for researchers, clinicians and graduate students interested in understanding and exploring the Redoxome—the organism redox network—as an emerging frontier in drug design, redox biology and medicine.

Systems Biology represents a new paradigm aiming at a whole-organism-level understanding of biological phenomena, emphasizing interconnections and functional interrelationships rather than component parts. The study of network properties, and how they control and regulate behavior from the cellular to organism level, constitutes a main focus of Systems Biology. This book addresses from a novel perspective a major unsolved biological problem: understanding how a cell works and what goes wrong in pathology. The task undertaken by the authors is in equal parts conceptual and methodological, integrative and analytical, experimental and theoretical, qualitative and quantitative, didactic and comprehensive. Essentially, they unravel the spatio-temporal unfolding of interacting mass-energy and information networks at the cellular and organ levels, as well as its modulation through activation or repression by signaling networks to produce a certain phenotype or (patho)physiological response. Starting with the historical roots, in thirteen chapters this work explores the Systems Biology of signaling networks, cellular structures and fluxes, organ and microorganism functions. In doing so, it establishes the basis of a 21st century approach to biological complexity.

The heart has a very high energy demand but very little energy reserves. In order to sustain contractile function, the heart has to continually produce a large amount of ATP. The heart utilizes free fatty acids mainly and carbohydrates to some extent as substrates for making energy and any change in this energy supply can seriously compromise cardiac function. It has emerged that alterations in cardiac energy metabolism are a major contributor to the development of a number of different forms of heart disease. It is also now known that optimizing energy metabolism in the heart is a viable and important approach to treating various forms of heart disease.Cardiac Energy Metabolism in Health and Disease describes the research advances that have been made in understanding what controls cardiac energy metabolism at molecular, transcriptional and physiological levels. It also describes how alterations in energy metabolism contribute to the development of heart dysfunction and how optimization of energy metabolism can be used to treat heart disease. The topics covered include a discussion of the effects of myocardial ischemia, diabetes, obesity, hypertrophy, heart failure, and genetic disorders of mitochondrial oxidative metabolism on cardiac energetics. The treatment of heart disease by optimizing energy metabolism is also discussed, which includes increasing overall energy production as well as increasing the efficiency of energy production and switching energy substrate preference of the heart. This book will be a valuable source of information to graduate students, postdoctoral fellows, and investigators in the field of experimental cardiology as well as biochemists, physiologists, pharmacologists, cardiologists, cardiovascular surgeons and other health professionals.

Diabetes has long been recognized as a disease of high blood sugar, and there has been a continuous search of the exact reason for its development and effective treatment. In 2005, the World Health Organization had estimated that more than 180 million people worldwide suffer from diabetes mellitus and indicated that this figure is likely to double within the next 20 years. Among the 3.8 million deaths each year associated with diabetes, about two thirds are attributable to cardiovascular complications, and diabetes is now considered to be a major metabolic risk factor for the occurrence of heart disease.Diabetic Cardiomyopathy: Biochemical and Molecular Mechanisms is a compilation of review articles devoted to the study on the topic with respect to biochemical and molecular mechanisms of hyperglycaemia. The wide range of areas covered here is of interest to basic research scientists, clinicians and graduate students, who are devoted to study the pathogenesis of diabetes-induced cardiovascular dysfunction. Furthermore, some chapters are directed towards increasing our understanding of novel ways for the prevention/treatment of cardiomyopathy.Twenty five articles in this book are organized in three sections. The first section discusses general aspects of the metabolic derangements in diabetic cardiomyopathy including metabolic alterations and substrate utilization as well as cardiac remodelling in the heart; role of diet in the development of metabolic syndrome in the heart; effect of hyperglycaemia in terms of biochemical and structural alterations in heart. In the second section, several cellular and molecular mechanisms are discussed indicating that diabetic cardiomyopathy is a multifactorial and complex problem. The third section discusses the prevention and treatment of diabetes using appropriate diet, proper supplements including antioxidants, angiotensin inhibitors and some other drugs. All in all, this book discusses the diverse mechanisms of diabetic cardiomyopathy with some information on new therapeutic approaches for finding solutions to prevent or reverse the development of cardiac dysfunction.

Advanced Exercise Endocrinology presents a comprehensive examination of the relationship between physical activity and hormone function. As the newest addition to Human Kinetics'Advanced Exercise Physiology Series, this resource offers the most up-to-date information on the quickly advancing field of exercise endocrinology. Written by leading exercise endocrinologist Katarina Borer, Advanced Exercise Endocrinology is an essential reference for exercise physiologists, physiotherapists, and other health professionals researching the connections between exercise, hormone function, and health. Advanced Exercise Endocrinology explains how the human body responds to exercise in order to support the increased energy demand. Readers will explore topics including body fluid balance during exercise and at rest, endocrine and autonomic control of cardiorespiratory function, hormonal control of energy expenditure, and the role of reproductive hormones in exercise. The text offers an integrative perspective and includes the following unique features: • An emphasis on the effects of hormones during exercise in the context of biological functions or physiological events to help readers appreciate the complexity of hormonal response from a functional, whole-body perspective • A discussion of hormone actions in exercise with an emphasis on the mechanisms of action, which is key to developing an advanced understanding of metabolism and somatic and physiological adaptations to training • A chapter that brings together research on nonhormonal signaling in exercise, a topic not often presented in a comprehensive manner • An introduction to the principles of hormone measurements, which will be especially helpful to students considering a future in research Combining foundational concepts and research, this text offers engaging and accessible coverage of this advanced field of study. Chapter summaries help readers focus on the most significant issues presented for each topic, and extensive illustrations, figures, and graphs provide visual reinforcement of key concepts and important research findings. Special sidebars highlight analyses of interesting research findings and practical applications. In examining current research, readers will be able to identify emerging topics and possible directions for future exploration. While the connection between exercise, hormones, and health is well acknowledged, the field had yet to be fully explored. Advanced Exercise Endocrinology will help students and professionals from many health fields better understand how interactions between physical activity and hormone action work to maintain health, improve exercise performance, and prevent metabolic disabilities. Human Kinetics'Advanced Exercise Physiology Series offers books for advanced undergraduate and graduate students as well as professionals in exercise science and kinesiology. These books highlight the complex interaction of various systems both at rest and during exercise. Each text in this series offers a clear and concise explanation of the system and details how each is affected by acute exercise and chronic exercise training. Advanced Exercise Endocrinology is the fourth volume in the series.

Hypertension is recognized to be one of the major risk factors for the development of peripheral vascular disease. The last decade has witnessed several major advances in therapy for hypertension, including the development of angiotensin-converting enzyme inhibitors and calcium channel blockers. These compounds have greatly improved the ability to control blood pressure and to reduce the impact of this risk factor on morbidity and mortality. In spite of these advances, cardiovascular disease remains a major health problem in most modern industrialized countries with related deaths exceeding those from all other causes combined. In contrast to these advances in therapy, our understanding of the basic mechanisms responsible for the pathogenesis of hypertension remains incomplete. Recent studies have produced new insights into the nature of the regulation of muscle contraction in both heart and blood vessels as well as the changes in muscle function that occur in hypertension. However, the effects of antihypertensive therapy, both in terms of restoring normal function and in producing reversal of hypertension-associated changes, has not been as thoroughly studied, especially in the vasculature. Studies in the heart suggest that the efficacy of different therapeutic agents in restoring normal function and reversing hypertensive changes vary substantially with the mechanism of action of the therapeutic agent. It has also been recently determined that some therapeutic agents produce adverse effects on plasma lipid profiles, which could lead to the secondary acceleration of the atherosclerotic process, while at the same time normalizing blood pressure.

This book summarizes present knowledge of different mechanisms involved in the development of positive and negative consequences of cardiac adaptation. Particular attention is paid to the still underestimated adaptive cardiac responses during development, to adaptation to the frequently occurring pressure and volume overload as well as to cardiac changes, induced by enduring exercise and chronic hypoxia. Cardiac Adaptations will be of great value to cardiovascular investigators, who will find this book highly useful in their cardiovascular studies for finding solutions in diverse pathological conditions; it will also appeal to students, fellows, scientists, and clinicians interested in cardiovascular abnormalities.

This volume contains the proceedings of an International Symposium on `Second Messenger Systems - Molecular, Cellular and Behavioural Aspects', which was held at Tobago on June 16-17, 1994. The interaction of an extracellular agonist (First Messenger) with its plasma membrane receptor leads to the transmission of a signal across the cell membrane and results in the production and/or activation of other signalling molecules (Second Messengers). These Second Messengers control the action of many protein kinases and protein phosphatases and so lead to cellular responses. Although the biochemical basis of the transduction of signals in the main signalling systems in eukaryotic cells is probably largely known, intensified research is ongoing in the following areas: the discovery of specific substrates for many protein kinases, elucidation of the biological significance of the differential tissue expression and heterogeneity of many signalling proteins, and the unravelling of diverse interactions (such as signal potentiation, synergism, antagonism and neuronal co-transmission) between signalling systems. As knowledge from such studies accumulates, it is becoming clear that the `cross talk'interactions between signalling systems are important features of dynamic cell regulation. This volume is designed to summarize some aspects of the current work on various Second Messenger Systems and the integration of signals with respect to plasma membrane receptors. Second Messenger generation and degradation, protein kinase and phosphatase, cell cycle control, and cellular learning and memory.

The main objective of Cardiac Remodeling: Molecular Mechanisms is to summarize the major research advances in molecular, biochemical and translational aspects of cardiac remodeling over the last 2 to 3 decades under one cover and touch on future directions. It provides a high profile and valuable publication resource on molecular mechanisms of cardiac remodeling for both the present and future generations of researchers, teachers, students and trainees. This book should stimulate future translational research targeted towards discovery and development for preventing, limiting and reversing bad remodeling over the next few decades, with the ultimate goal of preventing progression to systolic and/or diastolic heart failure. The chapters suggest potential novel strategies that should receive attention for translating basic research knowledge to application in patients at the bedside.

Diabetes mellitus is a disease with tremendous health and economic burden. A better understanding of how normal glucose homeostasis is maintained and the pathogenesis is important to identify new ways for diabetes treatment. This book addresses multiple aspects of this area of research. - Written by experts in the field - Informs on important topics related to the regulation of glucose homeostasis and the pathogenesis of diabetes mellitus, a field of intense research interest

The International Hypoxia Symposium convenes biannually to bring together international experts from many fields to explore the state of the art in normal and pathophysiological responses to hypoxia. Representatives from five continents and 32 countries joined together in February 2003 for four days in the dramatic mountains of Banff, Alberta. As editors of the Proceedings of the International Hypoxia Symposia, we strive to maintain a 26 six year tradition of presenting a stimulating blend of clinical and basic science papers focused on hypoxia. Topics covered in 2003 include hibernation and hypoxia, hypoxia and fetal development and new advances in high altitude pathophysiology, oxidative stress and membrane damage, hypoxic regulation of blood flow, heat shock proteins in hypoxia, and future directions in hypoxia research. In 2003 we also had the privilege ofhonoring John W. Severinghaus as a friend, colleague, mentor and inspiration to many in the field. Tom Hornbein's personal tribute to John Severinghaus is the first chapter in this volume, followed by an entertaining update of the history of the discovery of oxygen written by John Severinghaus.

This special issue of Molecular and Cellular Biochemistry good source of information in this regard. contains original research papers as well as invited reviews We wish to thank all of the contributors for their help and dedicated, on the occasion of the 40th anniversary of the in­ cooperation. We also wish to thank Mrs. Verona Kuhle for auguration of the Heart Research Group in Beriin-Buch that her secretarial help. We are grateful to Dr. Naranjan S. Dhalla, today forms a part there ofthe Max Delbriick Center for Mo­ Editor-in-Chief of Molecular and Cellular Biochemistry for his lecular Medicine, to Professor Albert Wollenberger, founder interest and encouragement, and for agreeing to publish this of the Heart Research Group and for 21 years its head. issue in honor of Albert Wollenberger. The papers in this issue are written by researchers work­ ing in the field of cardiovascular research who together with ERNST-GEORG KRAUSE and ROLAND VETTER Albert Wollenberger share the belief that an integrative ap­ Max Delbriick Center for Molecular Medicine plication of advances in molecular and cellular biology will Robert-Rossle-StraBe 10 lead to new concepts for treatment and prevention of cardio­ 13122 Beriin-Buch vascular diseases. We hope that this special will serve as a Gennany ALBERT WOLLENBERGER, Professor, Ph. D. (Harvard), Dr. Sc. Med. (Berlin) The dedication is accorded to Prof.

The chapters in this volume are the Proceedings of the Satellite Symposium of the XVIth World Congress of the International Society for Heart Research on `Signal Transduction in Normal and Diseased Myocardium'which was held in Rotterdam at the Faculty of Medicine & Health Sciences of the Erasmus University, June 30 and July 1, 1995. Diverse and distinct auto-, para-, and endocrine stimuli arriving at the surface of endothelium, smooth muscle cells, cardiomyocytes and fibroblasts within the myocardium, engage cell type-specific receptors, which lead to transmission of signals across the cell plasma membrane and result in the production and activation of second messengers. The most common mechanism by which these second messengers function is via direct or indirect activation of specific protein kinases. The current challenge for scientists is to identify the specific substrates (e.g. metabolic enzymes, Ca2+-regulating proteins, transcription and mitotic factors) for the many protein kinases, to elucidate the biological significance of the cell type-specific expression heterogeneity of signalling proteins (e.g. membrane receptors, isoenzymes of protein kinase C, G-proteins) and to unravel the cross-talk interaction between the signalling systems (e.g. phospholipase C with adenylate cyclase and phospholipase C with phospholipase D). The multiplicity of receptor types, G-proteins, effector proteins, second messengers and protein kinases, their substrate proteins and the `cross-talk'interactions in the myocardium raises fundamental questions about the mechanisms that ensure the precision and timing of the myocardial responses to hormonal and pharmacological stimuli. This book provides an up-to-date source of information for all scientists and clinicians interested in the mechanisms by which external signals are transmitted to the interior and regulation of a variety of physiological, pathological and pharmacological responses.

This special issue of Molecular and Cellular Biochemistry contains original research papers as well as invited reviews dedi­ cated, on the occasion of the 40th anniversary of the inauguration of the Heart Research Group in Berlin-Buch that today forms a part there of the Max Delbriick Center for Molecular Medicine, to Professor Albert Wollenberger, founder of the Heart Research Group and for 21 years its head. The papers in this issue are written by researchers working in the field of cardiovascular research who together with Albert Wollenberger share the belief that an integrative application of advances in molecular and cellular biology will lead to new concepts for treatment and prevention of cardiovascular diseases. We hope that this special will serve as a good source of information in this regard. We wish to thank all of the contributors for their help and cooperation. We also wish to thank Mrs. Verona Kuhle for her secretarial help. We are grateful to Dr. Naranjan S. Dhalla, Editor-in-Chief of Molecular and Cellular Biochemistry for his interest and encouragement, and for agreeing to publish this issue in honor of Albert Wollenberger. ROLAND VETTER and ERNST -GEORG KRAUSE Max Delbriick Center for Molecular Medicine, Robert-Rossle-StraBe 10, 13122 Berlin-Buch, Germany PART I CARDIAC DEVELOPMENT AND REGULATION Molecular and Cellular Biochemistry 163/164: 5-11, 1996. © 1996 Kluwer Academic Publishers.

This volume continues the discussion of the problems of in vivo and in vitro. The recently solved X-ray structure of the mitochondrial creatine kinase and its molecular biology cellular bioenergetics - the tradition we started in 1994 by publication of the focused issue of Molecular and Cellular are analyzed with respect to its molecular physiology and Biochemistry, volume 133/134 and a book'Cellular Bio­ functional coupling to the adenine nucleotide translocase, as energetics: role of coupled creatine kinases'edited by V. Saks well as its participation, together with the adenylate kinase and R. Ventura-Clapier and published by Kluwer Publishers, system, in intracellular energy transfer. The results of the Dordrecht -Boston. In the present volume, use of quantitative studies of creatine kinase deficient transgenic mice are methods of studies of organized metabolic systems, such as summarized and analyzed by using mathematical models of mathematical modeling and Metabolic Control Analysis, for the compartmentalized energy transfer, thus combining two investigation of the problems of bioenergetics of the cell is powerful new methods of the research. All these results, described together with presentation of new experimental together with the physiological and NMR data on the cardiac results. The following central problems of the cellular bio­ metabolic and mitochondrial responses to work-load changes energetics are the focus of the discussions: the mechanisms concord to the concept of metabolic networks of energy of regulation of oxidative phosphorylation in the cells in vivo transfer and feedback regulation.

Most of the information on the functional role, structure and molecular biology of creatine kinase is scattered in several hundreds of publications. The editors of this volume invited all authors who are most active at present in experimental research on creatine kinases to summarize their work and make the information easily available to a wider scientific audience, especially to young investigators who are entering this field. Since the functional role of coupled creatine kinases is directly related to the phenomenon of compartmentation and structural organization of metabolic networks, we also invited experts in the related areas to contribute to the volume. Almost all invited authors responded enthusiastically and the results of this collective work are presented here. For biochemists, biophysicists, physiologists, and medical research workers.

In October 1995, the 1st Colloquium on Mitochondria and Myopathies in Halle/Saale was organized in Halle/Saale by the editors of this focused issue. The meeting took up what might be called an East German tradition: from 1976 to 1990 Andreas Schmidt organized seven clinically orientated Colloquia on Myology in Jena, and from 1974 to 1990 a series of twelve Colloquia on Mitochondria focused on basic research aspects was arranged by Wolfgang Kunz in Magdeburg. At those meetings, East Germany was a mediator between East European, West European and American scientists. In continuation of this tradition, scientists from more than 17 countries working on mitochondria as neurologists, biochemists, geneticists, or as physiologists came to Halle. The title of the colloquium indicated the combination of both basic and clinical mitochondrial research. The most important contributions of this meeting are now published in this focused issue. We thank all authors for their patience and cooperation that have made it possible to produce this unique collection of papers representing current knowledge on detection of mitochondrial causes of diseases. We especially thank Prof. N.S. Dhalla for making it possible to publish these contributions together in this focused issue and also as a hard-cover book.

Diabetes is an autoimmune, inflammatory disease affecting many different organ systems and exhibiting both primary and secondary defects. Because diabetes affects a wide range of cellular systems, a multidisciplinary effort has been mounted over the past several decades using a wide range of investigative techniques and methodologies in order to identify molecular mechanisms responsible for cellular dysfunction. Because primary defects at various levels of sub-cellular signaling, intracellular calcium handling, protein expression and energy regulation are often a primary consequence of diabetes. This volume is a compilation of new multidisciplinary research that will broaden our current understanding of diabetes and cardiovascular disease as well as provide the basis for the development of novel therapeutic interventions.

Pathophysiology of Cardiovascular Disease has been divided into four sections that focus on heart dysfunction and its associated characteristics (hypertrophy, cardiomyopathy and failure); vascular dysfunction and disease; ischemic heart disease; and novel therapeutic interventions. This volume is a compendium of different approaches to understanding cardiovascular disease and identifying the proteins, pathways and processes that impact it.

For those like me who witnessed the beginning of the adventure of human mitochon­ drial pathology, one can only be astounded by the extent and unexpectedness of what the field has come to offer. Extent because nobody could have imagined the sheer size of the domain. Unexpectedness because hitherto it was impossible to imagine the clinical polymorphism that this pathology would represent. The starting point was clear. Initially, there was the exceptional, and for a long time unique, observation of euthyroidian hypermetabolism that Luft and colleagues analyzed remarkably in biochemical and clinical terms. Thereafter, there was the support provided by the electron microscopy studies of Afzelius, and the very first visualization of mitochondrial abnormalities. That was way back in 1958. A few years later, progress in the cytology and cytochemistry of skeletal muscle tissue was to provide the means of detecting such abnormalities by examining sections with light microscopy. The colorful term'ragged red fibers', coined by W. K. Engel, became uni­ versally accepted, and this typical aspect with Gomori trichrome stain was to throw light on the frequency with which these mitochondrial abnormalities could occur under pathological conditions which, until then, had remained a total mystery regard­ ing their mechanism: syndromes such as the ocular myopathies with their descending evolution and the oculocraniosomatic syndromes. We were at the beginning of the 1970s.

The development of vertebrate muscle has long been a major area of research in developmental biology. During the last decade, novel technical approaches have allowed us to unravel to a large extent the mechanisms underlying muscle formation, and myogenesis has become one of the best-understood paradigms for cellular differentiation. This book concisely summarizes our current knowledge about muscle development in vertebrates, from the determination of muscle precursors to terminal differentiation. Each chapter has been written by an expert in the field, and particular emphasis has been placed on the different developmental and molecular pathways followed by the three types of vertebrate musculature - skeletal, heart and smooth muscle.

The renin angiotensin system (RAS) maintains the cardiovascular homeostasis and is involved in the pathogenesis of several disorders related to heart and kidney. There are several peptides under RAS in which angiotensin (Ang) II is the major contributor. In this book, the authors present topical research on angiotensin. Some of the topics discussed include the influence of renin-angiotensin-aldosteron system genes on hypertrophy development in hypertrophic caradiomyopathy; cardiac renin angiotensin system and exercise training; the role of the counter-regulatory renin angiotensin system in the heart and new roles for the neuropeptide angiotensin II.

In high-performance sport an optimal diet and nutritional interventions can make the difference between victory and defeat. In recent years, sport nutrition research has increased. This publication provides scientifically-based information with regard to the bioefficacy of trendy sport supplements and dietary approaches off the mainstream. International experts in the specific fields inform and clarify under which circumstances the application of certain supplements and nutritional interventions would be beneficial, either for the performance or health of the athletes. A broad spectrum of recent topics in sport nutrition is provided: selected sport supplements aside of mainstream, nutritional interventions and athlete‘s health, hydration and fluid balance and current aspects in exercise and exercise recovery. Finally, the publication concludes with recent information about the risk of supplementation and inadvertent doping. The book will be of benefit to sport physicians and scientists, nutritionists, coaches and athletes, as well as to the sport nutrition trade and related industries.

This must-have cell signaling title will appeal to researchers across molecular biology, biochemistry, cell biology and genetics. The articles are written and edited by experts in the field and emphasize signaling to and from intracellular compartments including transcriptional responses to cytoplasmic and nuclear signaling events, chromatin remodeling and stress responses, the regulation of endoplasmic reticulum function, control of cell cycle progression and apoptosis and the modulation of the activities of mitochondria and other organelles. - Articles written and edited by experts in the field - Thematic volume covering regulation of endoplasmic reticulum function, regulation of cell cycle progression, and quality control and assurance in mitochondrion events - Up-to-date research on events in membrane proteins and proteins of intracellular matrix

Membrane proteins continue to be prime drug targets because they perform essential processes in the cell including controlling the flow of information and materials between cells and mediating activities like hormone action and nerve impulses. The study of membrane proteins could lead to new and improved pharmaceutical treatments for a wide range of illnesses such as heart disease, cystic fibrosis and depression. Membrane Proteins as Drug Targets reviews the latest developments in the field. - Discusses new discoveries, approaches, and ideas in the field of membrane proteins and reviews how they are being used to develop new drugs - Contributions from leading scholars and industry experts - Reference guide for researchers involved in molecular biology and related fields

Signal Transduction in Cardiovascular System Health and Disease highlights the major contributions of different signaling systems in modulating normal cardiovascular functions and how a perturbation in these signaling events leads to abnormal cell functions and cardiovascular disorders. This title is volume 3 in the new Springer series, Advances in Biochemistry in Health and Disease.

Springer Handbook of Enzymes provides data on enzymes sufficiently well characterized. It offers concise and complete descriptions of some 5,000 enzymes and their application areas. Data sheets are arranged in their EC-Number sequence and the volumes themselves are arranged according to enzyme classes. This new, second edition reflects considerable progress in enzymology: many enzymes are newly classified or reclassified. Each entry is correlated with references and one or more source organisms. New datafields are created: application and engineering (for the properties of enzymes where the sequence has been changed). The total amount of material contained in the Handbook has more than doubled so that the complete second edition consists of 39 volumes as well as a Synonym Index. In addition, starting in 2009, all newly classified enzymes are treated in Supplement Volumes. Springer Handbook of Enzymes is an ideal source of information for researchers in biochemistry, biotechnology, organic and analytical chemistry, and food sciences, as well as for medicinal applications.

In this first integrated view, practically each of the world's leading experts has contributed to this one and only authoritative resource on the topic. Bringing systems biology to cellular energetics, they address in detail such novel concepts as metabolite channeling and medical aspects of metabolic syndrome and cancer.

Methods for Obtaining X-Ray Diffraction Patterns from Drosophila 198 Diffraction Patterns from Drosophila IFM 203 Concluding Remarks 211 Note Added in Proof 211 17. Functional and Ecological Effects of Isoform Variation in Insect Flight Muscle 214 James H. Marden Abstract 214 Introduction 215 Nature's Versatile Engine 215 The Underlying Genetics: An Underinflated Genome and a Hyperinflated Transcriptome and Proteome 216 Functional Effects of Isoform Variation 219 Alternative Splicing and the Generation of Combinatorial Complexity 220 Functional Consequences of Naturally Occurring Isoform Variation 220 18. Muscle Systems Design and Integration 230 Fritz- OlafLehmann Abstract 230 Power Requirements for Flight 230 Power Reduction 233 Power Constraints on Steering Capacity 234 Balancing Power and Control 236 Changes in Muscle Efficiency in Vivo 238 Concluding Remarks 239 From the Inside Out 19. Molecular Assays for Acto-Myosin Interactions 242 John C. Sparrow and Michael A. Geeves Abstract 242 Introduction 242 Myosin Purification and Preparation of the SI Fragment 243 Purification of Flight Muscle Actin 244 Assays of Myosin and Acto-Myosin 244 Major Conclusions Relating to the Enzymatic Properties of Insect Flight Muscle Acto-Myosin 247 Major Questions about Insect Flight Muscle Acto-Myosin Kinetics That Remain 249 20.

This unique volume provides a comprehensive review of the biochemistry of exercise. Written by internationally renowned experts, the publication has been completely revised and updated. The present edition follows the new concepts of applied biochemistry which have emerged recently in the scientific literature. Genomics, proteomics, and metabolomics are nowadays common terms used to the elucidation of gene function, expression of proteins and comprehensive analysis of all the metabolites in a tissue. The major steps of biochemistry are considered in active survey in this new 3rd edition of an already acclaimed publication. The book is a valuable source for all exercise biochemists and physiologists, sports physicians, graduate students in physical education and physical therapy, and postgraduate research fellows.

This first book dedicated to the topic relates the known physiological functions of porins to their molecular structure and mechanism, as documented by various in vitro and in vivo methods, including the generation of null mutants in mice. For the first time, it brings together biophysical evidence with studies performed in a cellular context, presenting a unified picture of the fundamental importance of porins for cellular function. With 16 contributions by an interdisciplinary team of leading porin researchers, this reference is essential reading for every molecular or structural biologist with an interest in this essential protein family.

The Proceedings of the 12th International Symposium on Bioluminescence (BL) and Chemiluminescence (CL) contains up-to-date information on the latest developments in BL and CL presented by scientists from around the world.Light-emitting reactions are now a vital component of many key technologies in research and in routine analytical laboratories — replacing radionuclides in many situations. This volume presents a compilation of the latest developments from key experts and leading-edge researchers in this area.

Skeletal muscle development is perhaps one of the best understood processes at the molecular, cellular and organismal level due in large part to the fact that primary myogenic cells (myoblasts) will grow and subsequently differentiate into myotubes in culture. With the advent of reverse mouse genetics, many of the observations gained through the study of myogenic cells in vitro have been directly tested in vivo. What has emerged is a complex but cohesive story of how myogenic cells are initially specified in the vertebrate embryo and how muscle fibers ultimately achieve their respective identities (i.e. fast versus slow) to perform their function. This collection of chapters is focused on these developments. The book discusses old and new directions for the skeletal muscle field and points out directions where the field may eventually progress.