Induced pluripotent stem cells in cardiovascular research.- TRPs in the brain.-The channel physiology of the skin."

The Stressed Heart is truly unique in concept and will provide an eXCItmg adventure to the reader no matter what his or her field of expertise and interest. The title, although quite appropriate, does not adequately indicate the range of topics considered or the rational interrelationships among them. Indeed, perhaps the most important point to be learned from the book is that a serious consideration of the response of the heart to mechanical overload, ischemia, or excessive humoral stimuli must include evaluation of each of the topics in the table of contents. The heart responds to stress through alterations in both structure and function. How these changes are brought about is the subject of the initial chapters. These consider first the normal regulation of gene expression in the heart, the rapid response to mechanical overload that leads to both quantitative and qualitative changes in the contractile proteins, and our current understand ing of the signals that might be elicited by stress and alter gene expression. One chapter emphasizes the fact that, regardless of the nature of the stress, the common denominator is a discrepancy between energy requirements and expenditure. The central role of cellular acidosis in initiating the sequence of responses to stress and the possible roles of peptide regulators of transcription and protein regulators of translation are considered in detail."

This volume describes the current state of our knowledge on the neurobiology of muscle fatigue, with consideration also given to selected integrative cardiorespiratory mechanisms. Our charge to the authors of the various chapters was twofold: to provide a systematic review of the topic that could serve as a balanced reference text for practicing health-care professionals, teaching faculty, and pre-and postdoctoral trainees in the biomedi cal sciences; and to stimulate further experimental and theoretical work on neurobiology. Key issues are addressed in nine interrelated areas: fatigue of single muscle fibers, fatigue at the neuromuscular junction, fatigue of single motor units, metabolic fatigue studied with nuclear magnetic resonance, fatigue of the segmental motor system, fatigue involving suprasegmental mechanisms, the task dependency of fatigue mechanisms, integrative (largely cardiorespiratory) systems issues, and fatigue of adapted systems (due to aging, under-and overuse, and pathophysiology). The product is a volume that provides compre of processes that operate from the forebrain to the contractile proteins."

Being the crucial components of living cells, ion channels are important targets of therapeutic agents. Historically, it has been challenging to develop drugs on this target class. A major issue with targets based on ion channel drug development is the identification of effective small chemical leads for medicinal chemistry optimization to the clinical candidate status. Thus enough attention has been paid to the study of structure and functions of ion channels and their potential inhibitors. The present book compiles important chapters authored by eminent workers in the field to cover important recent advances in the studies of the structure and functions of ion channels and their inhibitors, such as sodium Ion, potassium Ion, chloride Ion, calcium Ion channel inhibitors. The book may be of great use to the students and scientists working in the area of molecular biology, biochemistry, physiology, and neurobiology, and medicinal chemistry.

Bilateral Communication Between the Endocrine and Immune Systems, "Volume 7" in the Springer-Verlag "Endocrinology and " "Metabolism" Series, offers the most current information and recent advances in the area of communication and regulation between the Immune and Endocrine Systems. Immune-Endocrine Interactions are reported to play pivotal roles in both activation and down-regulation of immune responses and this volume provides the most up-to-date research and findings on the immune-endocrine relationship. The contributing authors are internationally recognized experts in this area and have written chapters on such diverse topics as Interactions between the Pituitary and Immune Systems, Effects of Estrogens and Androgens on Immune Response, The Role of Sex Steroids in Immune System Regulation, and Neuroendocrine and Thymus Interactions During Development and Aging. This volume is a must for all endocrinologists and endocrinology residents.

Cancerremainstobeoneofthemostdevastatingdiseasesworldwidesincelong ago. Thepoorprognosisofcancerislargelyduetometastasis. Metastasisisoften depictedasamultistageprocessinwhichmalignantcellsspreadfromtheprimary locustodistantorgansviacirculation. Whereasgeneticalterationsweresuggested tobeessentialfortransformationofprimarytumorcellsintometastaticphenotype, epigeneticeventsareequallyimportant,whichmaybetriggeredbymetastaticf- torswhereverintheprimarytumorlocus,bloodcirculationandthesecondaryloci. Signaltransductionsinitiatedbythemetastaticfactorsareresponsibleformediating themolecularandcellularprocessesleadingtometastasis. Blockadeoftherelevant molecularpathwaysisoneofthemosteffectivestrategiesforpreventionoftumor metastasis. Clinicaltrialsareunderwaywithpromisingoutcome. Inthisbook, wetakecomprehensive review inregard withthisexciting eld ofcancerresearch. Chapter1takesabriefoverviewofrecentlyidenti edsignal mechanismsforeachstepoftumormetastasisincludingtheinitiationstage,intra- sation,anti-anoikisinbloodcirculation,homing,extravasationand nalsurvivalin themetastaticsite. Chapter2makesacompletedreviewforthemolecularandcel- lareventsinvolvedininitiationofmetastasis. Especially,thesignalingmechanisms formediatingtumorprogressioninducedbysomeimportantmetastaticfactorsare described. InChapters3and4,thecentralrolesofMAPKanditsdownstreameff- torsMAPKAPKplayineachstepoftumormetastasisarewelldelineated. Chapter5 furtherdescribesdetailedlyabouthowGrb2andotheradaptorproteins,upstreamof MAPK cascade, contribute tometastasis. InChapter 6, therole ofreactive o- genspecies(ROS)intumorprogressionarehighlighted. Moreover,thepotential contribution of ROS to cross talk between major signaling cascades that lead to sustainedMAPKactivationareproposedinChapter7. Chapter8takesaninsight intothesignalingmechanismsfordynamictraf ckingandturnoveroffocalad- sionproteinsinregulationoftractionandretractionforces,whichareneededfor celllocomotionandinvasion. Chapter9describestheinvolvementofNotchsign- ingpathwaywhichisnotonlyessentialforembryonicdevelopmentbutalsoplays importantroleintumorprogression. Chapter10reviewedtherecentlyidenti ed cancer- and metastasis-initiating cells involved in tumor progression. Especially, signal pathways that are frequently deregulated in cancer stem/progenitor cells v vi Preface duringcancerprogressionarehighlighted. Chapter11describestheroleoflipid rafts, a special component within membrane lipid domain, in signal transd- tion triggered by growth factor receptors leading to tumor metastasis. Finally, Chapters12,Chapters13,andChapters14presentthesignalingpathwaysresp- sibleformetastaticprogressionofspeci ctumorsincludingovariancancer,uveal melanomaandhepatoma,respectively. WethankallthecontributorsofeveryChapterinthebookincludingJia-RuWu, Chi-TanHu,LaureVoisin,StephanieDuhamel,SylvainMeloche,AlexeyShiryaev, MarijkeVanGhelue,UgoMoens,AlessioGiubellino,PraveenR. Arany,Moulay A. Alaoui-Jamali, Krikor Bijian, Panagiota Toliopoulos, Pingyu Zhang, Patrick A. Zweidler-McKay,MurielleMimeault,SurinderK. Batra,SamirKumarPatra, LydiaW. T. Cheung,CarmanK. M. Ip,AliceS. T. Wong,CecileLaurent,Jerome Couturier,XavierSastre-Garau,LaurenceDesjardins,EmmanuelBarillot,Sophie Piperno-Neumann,SimonSauleandRajagopalN. Aravalli. Wehopethisbookmightstimulatemorecancerbiologiststoemphasizethis eld whichbene tsdevisingmoreeffectivemoleculartargetingstrategiesforprevention ofcancermetastasis. Hualien,Taiwan Wen-ShengWu Chi-TanHu Contents 1 Overview of Signal Transduction in Tumor Metastasis...1 Wen-ShengWuandJia-RuWu 2 Microenvironment Triggers EMT, Migration and Invasion of Primary Tumor via Multiple Signal Pathways ...9 Wen-ShengWuandChi-TanHu 3 The ERK1/2 MAP Kinase Signaling Pathway in Tumor Progression and Metastasis ...25 LaureVoisin,StephanieDuhamel,andSylvainMeloche 4 Mitogen-Activated Protein Kinase-Activated Protein Kinases and Metastasis...41 AlexeyShiryaev,MarijkeVanGhelue,andUgoMoens 5 Grb2 and Other Adaptor Proteins in Tumor Metastasis ...77 AlessioGiubellinoandPraveenR. Arany 6 The Role of ROS Signaling in Tumor Progression...103 Wen-ShengWuandJia-RuWu 7 Signal Cross Talks for Sustained MAPK Activation and Cell Migration Mediated by Reactive Oxygen Species: The Involvement in Tumor Progression...

Essentials of Medical Biochemistry, Third Edition offers a condensed, yet detailed overview of clinical biochemistry, spanning fundamentals and relevant physiologic and pathophysiologic concepts. Pivotal clinical case studies aid in understanding basic science in the context of diagnosis and treatment of human diseases, and the text illuminates key topics in molecular immunology and hemostasis. Users will find fundamental concepts aiding students and professionals in biochemistry, medicine, and other healthcare disciplines. The text is a useful refresher that will help users meet USMLE and other professional licensing examination requirements, providing thorough introductions, key points, multicolored illustrations of chemical structures and figures, fact-filled tables, and recommended reading lists. This Third Edition has been fully updated to address evolving techniques in the biological sciences, including genomics, metabolomics, transcriptomics, epigenomics, proteomics, and gene therapy, among other methods. In addition, each chapter has been fully revised for current science and now features learning objectives and chapter summaries, supplemental reading, and 5 clinical case based multiple choice questions. New clinical cases have been added throughout.

The mammalian central nervous system depends almost - clusively on glucose as its major energy source. In addition, g- cose participates in other cerebral metabolic functions including the biosynthesis of neurotransmitters, such as acetylcholine and the amino acids. This volume of Neuromethods assembles currently available methods for the study of cerebral glucose and energy metabolism in vitro and in mm. In the first chapter, Lust et al. describe the various methods available for the appropriate fixation of brain tissue necessary for the study of cerebral energy metabolism. Different fixation methods are compared, and some concerns raised by the USDHHS in their guidelines for the care and use of laboratory animals are addressed. Specific fixation methods pertinent to the various measurements are also covered in other chapters. In vitro p- parations have, despite certain limitations, been found to be useful in the study of brain metabolism, since the biochemical envir- ment is amenable to rapid, controlled manipulation. The chapter by Lai and Clark describes methods for the isolation and characterization of metabolically active preparations of synaptic and non-synaptic mitochondria from brain, and studies of - zymes involved in glucose metabolism and glucose-derived neurotransmitter synthesis in these preparations are summarized. The chapter by Whittingham discusses methods of preparations of hippocampal slices for use in the study of energy metabolism. Measurement of glucose and of glycolytic and dicarboxylic acid cycle intermediates in neural tissues are described in the chapter by Bachelard.

In addition to its metabolic and endocrinologic effects, obesity and adipose tissue have now been shown to be associated with low grade inflammation resulting in cellular and humoral inflammatory factors of which the latter may act by endocrine, paracrine and autocrine mechanisms. These inflammatory mediators have increasingly been suggested as contributing to the obesity link to carcinogenesis and cancer promotion.

This volume of Energy Balance and Cancer will focus on recent developments and cutting edge research pointing to inflammation and inflammatory factors as key mediators of this linkage. The volume first provides information on inflammation as an important link between obesity and insulin resistance, which is in itself linked to promotion of cancer through hyperinsulinemia. The volume then covers some of the most important mechanisms by which obesity leads to inflammation, including the novel inflammasome concept, alterations in chromatin structure, circulating inflammatory factors, unique cellular interactions between adipocytes and macrophages and the direct link of dietary fat to inflammation and cancer.

Overall, this volume will provide important insight to help understand how inflammation may help modulate the linkage between obesity and cancer and serve as a platform for developing future research in this area.

Advances in methodologies and experimental models are pivotal to furthering our understanding of central nervous system (CNS) functions in mammals. "Isolated Central Nervous System Circuits" examines the application a variety of technologies to mostly active "in vitro" preparations from basically different CNS regions with a diversity of functions. From patch-clamp, multiphoton imaging, live fluorescent protein expression, or immunohistochemistry techniques to acute or 'organotypic' slices and "en bloc" preparations, this detailed volume features key protocols and examples for exciting results from the labs of renowned experts. Written for the popular "Neuromethods" series, chapters include the kind of thorough implementation advice that is vital for achieving successful results.

Comprehensive and cutting-edge, "Isolated Central Nervous System Circuits" will greatly aid scientists to further improve models and to develop corresponding models of not yet intensively studied structures such as "nucleus ruber," "superior colliculus," or basal ganglia."

Following many years when a great deal of attention was directed towards the intracellular roles of purines, there is expanding interest in the field of extracellular purinergic signalling. In this book we focus on the actions of purines in cardiovascular biology, where it is clear that they play major roles in both normal and pathophysiological conditions. Activation of different purinoceptor subtypes by purines can regulate cardiac contractility and electrical activity, modulate catecholamine-mediated responses both pre- and post-junctionally, trigger and mediate ischaemic preconditioning, cause vasodilation and vasoconstriction and enhance endothelial proliferation and apoptosis as well as inhibit platelet and neutrophil function. This book covers the cardiovascular actions mediated by the major P1 and P2 subclasses of purinoceptors and emphasizes the interactions between these two signalling systems. Cardiovascular Biology of Purines covers topics ranging from molecular and cellular to systemic and clinical. It also aims to highlight how basic advances have led to the identification of novel targets for cardiovascular therapeutic developments. We hope that our book will prove to be timely and helpful.

Authoritative researchers and clinicians review our latest understanding of andrology in both basic science and clinical medicine. Topics range from explaining the biology of androgens-from several different perspectives-to illuminating their role in the development and modulation of physiologic systems. Authors demonstrate in a number of cases that testosterone can be a useful adjunct to the treatment of a variety of disease states. Other chapters consider important topics such as androgens use in athletes, the potential of androgens to improve physical function and quality of life in older men, and androgens as potential male contraceptives.

After yet another decade of leaming, experimenting, and inves tigating since my first book, Arterial System Dynamics, the many new medical breakthroughs and technological advances have inspired me to write this book to bridge the gap between basic research and clinical applications. The application of physical principles and quantitative approaches to the understanding of the arterial circulation and its interactions with the heart in normal and diseased conditions form the basis of The Arterial Circulation. Knowledge of the physiology and rheology of arteries, as well as all of their structural-functional corre lates, is a necessary prerequisite to the proper hemodynamic interpretatiqn of pressure-flow relations and the pulsatile transmis sion characteristics in different arteries. The natural coupling and interactions of the heart, the coronary circulation, and the arterial system necessitate analysis of alterations to global functioning. Modeling provides a tool for isolating and predicting parameter changes and is employed throughout the book. Experimental data are provided for model validations, and also for more realistic interpretations. Techniques and new methods for clinical hemo dynamic measurement and diagnosis are included to help the reader un derstand the physical principles underlying such abnormal cardiovascular functions as hypertension, stenosis, and myocardial ischemia. The progressive changes in vascular properties during aging are also discussed. Modem approaches utilizing computer mode ling and allomery are presented with selected examples, such as combined hypertension and aortic valve stenosis, and ventricular hypertrophy."

The leading text on human physiology for more than four decades-enhanced by all new video tutorials For more than four decades, Ganong's Review of Medical Physiology has been helping those in the medical field understand human and mammalian physiology. Applauded for its interesting and engagingly written style, Ganong's concisely covers every important topic without sacrificing depth or readability, and delivers more detailed, high-yield information per page than any other similar text or review. Thoroughly updated to reflect the latest research and developments in important areas such as chronic pain, reproductive physiology, and acid-base homeostasis, Ganong's Review of Medical Physiology, Twenty-Sixth Edition incorporates examples from clinical medicine to illustrate important physiologic concepts. Ganong's will prove valuable to students who need a concise review for the USMLE, or physicians who want to keep pace with the ever-changing world of medical physiology. *More than 600 full-color illustrations*Two types of review questions: end-of-chapter and board-style*NEW! Increased number of clinical cases and flow charts*NEW! Video tutorials from the author; high-yield Frequently Asked Question feature with detailed explanations; improved legends that eliminate the need to refer back to the text

This book presents a timely collection of reviews by experts in periconception and fertilization. The book provides a good introduction for those new to the field as well as those who have worked in this field for some time, but not have been able to keep up-to-date with recent advances on the topic. The book reviews the current knowledge in this field, then focuses its attention on short-term and long-term effects of the periconception period, both from a physiological and medical perspective. Finally the volume covers the examination of the potential mechanisms involved in controlling periconception period. From the early days of discovery about the basics of the fertilization process, scientists have known that early events happening during conception play a major part in the creation of new offspring. However, until nearly a decade ago we thought these events were just concerned with the conception and nothing to do with lifelong health and welfare, or wellbeing of the offspring. Early indications from IVF in sheep and cattle suggested that the embryo culture conditions employed in the laboratory could result in unusually large and unhealthy offspring. These observations sounded alarm bells and stimulated research into the impacts of in vivo and in vitro conditions on the health of embryos and offspring. This book provides a summary of the state-of-the-art research being done to more fully understand the importance of the periconception environment.

Nervous System Actions and Interactions: Concepts in Neurophysiology approaches the nervous system from a functional, rather than structural, point of view.

While all of the central topics of functional neuroscience are covered, these topics are organized from a neurophysiological perspective yielding chapters on subjects such as information storage and effector actions. Each chapter is organized around general concepts that then are further developed in the text. The authors attempt to establish a dialogue with the reader by means of proposed experiments and open ended questions that are designed to both reinforce and question the text. This volume is intended to be a book of ideas for the novice or seasoned researcher in neuroscience.

Leading researchers are specially invited to provide a complete understanding of a key topic within the multidisciplinary fields of physiology, biochemistry and pharmacology. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.

The great variety in structure and function of arthropod sensory organs is due to the huge number of species living in spatially and temporally different environments and to great variation in behavioral patterns. This atlas compiles the electron microscopic anatomy of arthropod sensory organophotoreceptors, chemoreceptors, and others in relation to function, behavior, and environment. The authors show how each sensory receptor is finely tuned to detect the necessary information in the arthropods surroundings and how the sensory receptors dynamically change their fine structures according to their functional and adaptational states. In each two-page spread of the book, electron or light micrographs are shown on the right, with diagrammatic illustrations and accompanying text on the left, in a format that is attractive and easy to understand. The atlas thus provides an important bridge between the physiology and morphology of arthropod sensory receptors.

Volume 39, devoted solely to the vital research area on molybdenum and tungsten and their role in biology, offers a comprehensive and timely account of this fascinating topic by 40 distinguished international authorities. With more than 2200 references to assist further research, Molybdenum and Tungsten: Their Roles in Biological Processes is an essential resource for scientists and students in many disciplines, including bioinorganic, inorganic, and coordination chemistry; biochemistry; biophysics; molecular biology; enzymology; pharmacology; physiology; clinical chemistry; nutrition; toxicology; and environmental sciences.

The most recent research findings on the important genes, key molecules, and mechanisms in neural development and regeneration are presented in this volume. The papers collected here were delivered at the second of the Keio University International Symposia for Life Sciences and Medicine, held in Mita (Tokyo), Japan, and are in eight main sections: Early Neurogenesis and Pattern Formation, Regional and Cellular Specification, Trophic Factors, Adhesion Molecules, Glial Cell Lineage and Myelination, Circuit Formation, Synaptic Refinement and Neurotransmitter Release, and Neural Regeneration. Together, they present the concept of neural development and regeneration and its vital importance at the frontiers of medical science today.
Neural Development is an invaluable resource and reference for researchers, clinicians, and students in physiology and the medical sciences.

New Frontiers in Angiogenesis starts with a comprehensive overview of the field and continues with topics that have been minimally explored. The topics deal with dynamics of vasculogenesis using imaging techniques, bone marrow-derived endothelial cell precursors as potential therapeutic tools, regulation of post-angiogenic vessel regression, vascular mimicry, design and construction of artificial vessels, bioengineering of angiogenesis, and lymphangiogenesis recapitulating angiogenesis in health and disease states. Each chapter is written by leading experts of the subjects. It is hoped that this volume will challenge all of us interested in the field of angiogenesis and cardiovascular biology, in particular those in academia and industries, to think "outside the box" and explore angiogenesis from a fresh angle. It is hoped that New Frontiers in Angiogenesis is thought provoking and serve as a road map for discovering new findings to help betterments of human health.

Protein transport events occurring at the endoplasmic reticulum (ER) of eukaryotic cells and the cytoplasmic membrane of prokaryotic organisms share many similarities. Resident proteins of both membranes span the lipid bilayer once or several times by a-helical stretches and their integration is usually mediated by uncleaved signal-anchor sequences. Proteins that are translocated across either membrane, collectively also termed secretory proteins, harbour cleavable N-terminal signal sequences. Prokaryotic and eukaryotic signal sequences have the same modular structure and are functionally exchangeable. Integration of membrane proteins and translocation of secretory proteins basically occur at the same sites (pores) within each membrane. In both types of membranes, these pores are c- posed of homologous components forming the Sec translocons. Parts of the Sec trans- cons are found populated by ribosomes, the membrane-bound ribosomes. Bacterial m- brane and eukaryotic secretory proteins are targeted to the Sec translocons by the same molecular mechanism involving signal recognition particle (SRP) and its receptor (SRP - ceptor, SR). Structure and assembly of the SRP The functional core of SRP The functional core of this ribonucleoprotein complex consists of the signal sequence binding subunit (SRP54 in eukaryotes and Ffh in prokaryotes) and the SRP RNA molecule (see Fig. 1). This core is conserved in all organisms, with the intriguing exception of chloroplasts, where the SRP lacks the RNA subunit.

Interest in angiogenesis research remains strong in recent years and exciting new discoveries, about modulators of angiogenesis, their receptors, the transduction mechanisms and the angiogenic genes involved, have contributed to our present day understanding of this complex process. This knowledge has provided the basis and broadened the scope of angiogenesis - based therapy in oncology and many other clinical conditions. This monograph contains the contributions to the NATO Advanced Study Institute on "Angiogenesis: Models, Modulators and Clinical Applications," which was held in Rhodes, Greece, from June 20-30, 1997. This was the fourth of a series of NATO supported international meetings on Angiogenesis aiming to bring together basic scientists with clinicians to exchange ideas, disseminate new knowledge and discuss the present status and potential new directions in this fast moving area of biomedical research. The International Organising Committee that included Drs. E. Dejana, C Haudenschild, M. Hackel, H. Kleinman, P. Lelkes, M. Presta, P. Polverini, D. Thompson, has provided invaluable help with their insightful suggestions in the formulation of the scientific program for which I am grateful. I wish to thank all the participants for their enthusiastic participation and their complimentary comments on the success of the conference.

Because of developments in powerful computer technology, computational techniques, advances in a wide spectrum of diverse technologies, and other advances coupled with cross disciplinary pursuits between technology and its greatly significant applied implications in human body processes, the field of biomechanics is evolving as a broadly significant area. The four volumes of Biomechanical Systems: Techniques and Applications presents the advances in widely diverse areas with significant implications for human betterment that occur continuously at a high rate. These include dynamics of musculo-skeletal systems; mechanics of hard and soft tissues; mechanics of muscle; mechanics of bone remodeling; mechanics of implant-tissue interfaces; cardiovascular and respiratory biomechanics; mechanics of blood flow, air flow, flow-prosthesis interfaces; mechanics of impact; dynamics of man machine interaction; and numerous other areas. The great breadth and depth of the field of biomechanics on the international scene requires at least four volumes for adequate treatment. These four volumes constitute a well integrated set that can be utilized as individual volumes. They provide a substantively significant and rather comprehensive, in-depth treatment of biomechanic systems and techniques that is most surely unique on the international scene.