This book focusses on the latest results related to the field of bile acids as signaling molecules and describes how these receptors have become a major pharmacological target. It covers all major areas of research in this field, from genetics, chemistry, in silico modeling, molecular biology to clinical applications, offering a cross-country view of the functional role of bile acids as signaling molecules, virtually acting on all major areas of metabolism. While FXR and GPBAR1 are essential bile acid sensors that integrate the de novo bile acid synthesis with intestinal microbiota and liver metabolism, in a broader sense, BARs play a pathogenic role in the development of common human alignments including liver, intestinal and metabolic disorders, such as steatosis (NAFLD) and steato-hepatitis (NASH), diabetes, obesity and atherosclerosis.

Handbook of Opium: History and Basis of Opioids in Therapeutics traces the history of poppy from its prehistory, its use in Greek and Egyptian medicine through the European Renaissance, and the opioid epidemic of the present day. The book explores the discovery of morphine and its alkaloids, reviews its biosynthetic process, and covers the evolution of synthetic opioids. Further, it reviews the biological effects of opium and the molecular basis of its actions, including future perspectives in clinical applications with therapeutic targets. The book is interspersed with numerous notes on the events and great minds in history and medicine who advocated, analyzed and advanced opium through history. The book is a comprehensive review on opium, covering a breadth of topics, including its history, botany, chemistry, trade, physiology, clinical use and molecular biology, with numerous references, tables, vignettes and illustrations included for additional understanding.

The seven papers of this volume present a glimpse into current research on soft tissue mechanics as well as some future directions. The seven papers concern tissues within the cardiovascular system: three focus on arteries, three on the heart, and one on biaxial testing of planar tissues such as heart valves. Given that cardiovascular disease continues to be the leading cause of death in the developed world, the importance of such research is clear.

There are notable common features of the seven papers. First, most of the proposed constitutive relations are motivated directly by data on the underlying microstructure, and especially the orientations of a structurally important protein (collagen) that forms as undulated cross-linked fibers. Another feature of most of the papers is the consideration of the fact that both arteries and the heart contain muscle and that there is a need to quantify the so-called active (contractile) response in addition to the passive (non-contractile) response. Such relations must not only be structurally motivated, they must ultimately include the kinetics of calcium transport in the muscle. Constitutive relations for active behavior are discussed in the majority of the papers. The growth and remodeling of cardiovascular tissues is another common feature of the papers. Over the last twenty years, separate advances in biochemistry, cell biology, genetic engineering, and biomechanics have focused attention on the ubiquitous role of growth and remodeling of tissues. This volume should be of interest to cardiovascular researchers in particular, and to bioengineers and biomechanics soft tissue researchers in general.

The enormous and varied role of calcium in living systems is now widely appreciated by both cell biologists and clinicians. The identification and characterisation of new calcium binding proteins and regulatory pathways is matched by the recognition of the involvement of calcium binding proteins in a growing number of disease states. This book is intended to introduce clinicians to fundamental biological research, whilst at the same time attracting researchers to the clinical world. The publication of the book coincides with the elucidation of the complete Human Genomic Sequence. As a result of this, scientists now have access to an unprecedented array of data, from which new calcium binding proteins and hence new regulatory pathways will undoubtedly be discovered. It is a further aim of this book to provide a key' to open the door to the new postgenomic era. The book is in three parts. The first section introduces the reader to the role of calcium in cell biology, providing an appreciation of how this small, simple, non-metabolisable agent can move rapidly and silently through the different cellular compartments, thereby influencing and controlling the fate of the cell. This section also illustrates and dissects the often-complex interplay between calcium and numerous agents in muscle and endocrine cells, neurons, hepatocytes, and platelets. In the second section the reader will discover the role of calcium and its partners in common diseases such as migraine and drug dependence. New classes of diseases such as annexinopathies, channelopathies, calcium-sensing disorders, and citrullinemia are discussed, and the authors give many new insights into the molecular mechanisms of the diseases, thereby explaining how and why they occur. Such information is clearly of primary importance for the pharmaceutical industry. New ideas and concepts of neurodegenerative diseases are introduced, which should stimulate new approaches. Clinicians will also have access, in a comprehensive and authoritative yet highly readable chapter, to data from recent large-scale clinical studies on the numerous and widely prescribed calcium antagonists. The final section gives information on new methods and devices for calcium imaging, and illustrates how calcium movement and change can be monitored and ingeniously utilised as a fast, cheap, and accurate drug screening instrument.

Immunometabolism has emerged as an intersectional crossroad between metabolism and immune response. Over the past decade, it has become clear that most - if not all - immune cell functions are not separated from cellular metabolism. Although seminal works have addressed the metabolic fate of immune cells during differentiation and function, the physiological status of a given tissue is also dependent on the cell metabolism. The dialogue between immune cells and their microenvironment can also modulate cellular metabolism, which can trigger the onset and progression of a multitude of inflammation-mediated diseases. Thus, uncovering the specific characteristics of the metabolism in different immune cells types and in different conditions, can shed light into the molecular mechanisms of disease and help develop new drugs and therapeutic strategies to treat immune diseases. The edited volume Essentials aspects of Immunometabolism will give the readers a broad view on how metabolic pathways can influence many types of immune cells during activation, differentiation and function, in health and disease. Of note, the structure of the book was created thinking not only on the experienced immunologist but also on undergraduate and graduate students, physicians, and all members of the scientific community interested in this exciting field of research.

Nearly everything making up what we call the "environment" of a plant has an infuence on the way it grows. Sunlight, te- perature, moisture contents of soil and atmosphere and vib- tions are all obvious examples of environmental components, and transient variations in their amount or intensity lead the plant to manifest more or less immediate responses. Small changes in carbon dioxide level in the atmosphere can even have effects, but these take a longer time to be registered - at least those that are visible, albeit at the microscopic level. Plants meet the challenges of the environment by means of acclimation. In this respect, plants are notable for the pl- ticity of their development. However, where morphological or physiological plasticity is no longer an option, the responses would be by means of adaptations as a result of genetic - lection or genetic "assimilation" (Waddington 1957). Thus, a feature that was once a facultative transient response to an environmental perturbation becomes a constitutive charac- ristic of plant structure or function. It is in this way that the environment continually molds the way in which plants de- lop, and also defnes the areas upon planet Earth where they will thrive.

The 14th volume in the series will focus on cutting edge research at the interface of hypoxia and exercise. The work will cover the range from molecular mechanisms of muscle fatigue and muscle wasting to whole body exercise on the world 's highest mountains. State of the art papers on training at high altitude for low altitude athletic performance will also be featured.

It is an exciting task to be the editor of the first monograph covering a new area of the biomedical sciences. Since the first report in 1980 by Robert Furchgott and colleagues (see Chapter 1) of the evidence of endothelium-dependent relaxation in isolated arteries, there are ever increasing numbers of vascular physiologists and pharmacologists who are scraping away the endothelium to look into its role in cardiovascular con trol. And the more one looks, the more one discovers. Not only is the list of substances that can induce endothelium-dependent relaxations im pressively long, but these intriguing cells can also secrete vasoconstrictor substances. The ability of the endothelium to modulate the degree of con traction of the underlying smooth muscle is an ancestral property of the blood vessel wall, illustrating the logic of nature, since the endothelial cells are located in the best possible strategic location to continuously monitor the properties (chemical or physical) of the blood. And more and more data emerge suggesting that in several cardiovascular diseases per turbations in endothelium-dependent responses are one of the early signs of the abnormal process. Thus, the importance of endothelium-dependent responses, triggered by the intellectual curiosity of one of the pioneers of vascular physiology and pharmacology, is now recognized not only by basic scientists, but also by all concerned with the cardiovascular diseases. The purpose of this monograph is to provide them with a reference work, so that they know where to start."

This book offers physiology teachers a new approach to teaching their subject that will lead to increased student understanding and retention of the most important ideas. By integrating the core concepts of physiology into individual courses and across the entire curriculum, it provides students with tools that will help them learn more easily and fully understand the physiology content they are asked to learn. The authors present examples of how the core concepts can be used to teach individual topics, design learning resources, assess student understanding, and structure a physiology curriculum.

Diagnosis and Treatment of Spinal Cord Injury will enhance readers' understanding of the complexities of the diagnosis and management of spinal cord injuries. Featuring chapters on drug delivery, exercise, and rehabilitation, this volume discusses in detail the impact of the clinical features, diagnosis, management, and long-term prognosis of spinal cord injuries on the lives of those affected. The book has applicability for neuroscientists, neurologists, clinicians, and anyone working to better understand spinal cord injuries. Spinal injury affects about 10 million people annually worldwide, impacting on the family unit and causing lifelong disabilities, with varied symptoms including paresthesia, spasticity, loss of motor control, and often severe pain. Cellular, Molecular, Physiological, and Behavioral Aspects of Spinal Cord Injury will enhance readers' understanding of the biological and psychological effects of spinal cord injury. Featuring chapters on gene expression, metabolic effects, and behavior, this volume discusses in detail the impact of spinal cord injury to better understand the underlying pathways and processes. The book has applicability for neuroscientists, neurologists, clinicians, and anyone working to better understand these injuries.

This book is concernced with the process of cell death in human cells by programmed cell death or apoptosis, and the modulation of this process by drugs. This is a new field of study and this volume represents the first comprehensive treatment of this subject matter. Its focus is on human biology and medicine. Apoptosis is a very prevalent type of cell death with importance in human diseases such as cancer, Alzheimer's disease and autoimmune disorders. The book combines the expertise of leading scientists and writers from fields as diverse as neurosciences, immunology, pathology and cancer research. There is detailed analysis of the molecular and cellular aspects of apoptosis including the specific genes and molecules involved in the regulation of this special form of programmed cell death. Scientists, clinicians and researchers involved in studies of human biology and medicine will find this book an excellent resource.

Fetal & Neonatal Physiology provides neonatologist fellows and physicians with the essential information they need to effectively diagnose, treat, and manage sick and premature infants. Fully comprehensive, this 2-volume resource continues to serve as an excellent reference tool, focusing on the basic science needed for exam preparation and the key information required for full-time practice. The 5th edition is the most substantially updated and revised edition ever. In the 5 years since the last edition published, there have been thousands of publications on various aspects of development of health and disease; Fetal and Neonatal Physiology synthesizes this knowledge into definitive guidance for today's busy practitioner. Offers definitive guidance on how to effectively manage the many health problems seen in newborn and premature infants. Chapters devoted to clinical correlation help explain the implications of fetal and neonatal physiology. Allows you to apply the latest insights on genetic therapy, intrauterine infections, brain protection and neuroimaging, and much more. Expert Consult eBook version included with purchase. This enhanced eBook experience allows you to search all of the text, figures, images, and references from the book on a variety of devices. Features a fantastic new 4-color design with 1,000 illustrations, 170+ chapters, and over 350 contributors. 16 new chapters cover such hot topics as Epigenetics; Placental Function in Intrauterine Growth Restriction; Regulation of Pulmonary Circulation; The Developing Microbiome of the Fetus and Newborn; Hereditary Contribution to Neonatal Hyperbilirubinemia; Mechanistic Aspects of Phototherapy for Neonatal Hyperbilirubinemia; Cerebellar Development; Pathophysiology of Neonatal Sepsis; Pathophysiology of Persistent Pulmonary Hypertension of the Newborn; Pathophysiology of Meconium Aspiration Syndrome; Pathophysiology of Ventilator Dependent Infants; Pathophysiology of Hypoxic-Ischemic Brain Injury; Pathophysiology of Neonatal White Matter Injury; Pathophysiology of Meningitis; Pathophysiology of Preeclampsia; and Pathophysiology of Chorioamnionitis. New Pathophysiology of Neonatal Diseases section highlights every process associated with a disease or injury, all in one place. In-depth information, combined with end-of-chapter summaries, enables deep or quick use of the text.

This textbook presents for the first time a comprehensive body of the latest knowledge in the field of neuropeptides and their action on energy balance. It contains a detailed and comprehensive account of the specific hypothalamic peptides in regards to their roles in energy balance, food intake control and co-morbidities, to better understand the patho-physiology of obesity. The textbook includes an examination the history of the evolution of human society from a thin to the obese phenotype and, within that context, how modern society habits and industrial food production did not respect the evolutionary trait resulting in changes in the energy balance set point. It provides a novel conceptualization of the problem of obesity when considering the biochemistry of peptide hormones and entertaining novel ideas on multiple approaches to the problems of energy balance, as well as demonstrates and explains why alterations in pro-hormone processing are paramount to understand metabolic disease. This text is excellent material for teaching graduate and medical school courses, as well as a valuable resource for researchers in biochemistry, cell, and molecular biology, neuroscientists, physician endocrinologists, and nutritionists.

Biology of Cardiovascular and Metabolic Diseases combines physiology and pathophysiology of selected metabolic and cardiovascular diseases with health relevance. Written in a concise and easy to read manner, the book allows readers to gain an understanding on a number of topics, including cardiovascular physiology and pathophysiology and how it relates to the development of insulin resistance, diabetes and other metabolic diseases. The book also highlights the relevance of obesity in the development of cardiovascular and metabolic diseases and emphasizes the benefits of exercise as a preventative measure and way to treat underlying conditions.

Mesenchymal Stromal Cell (MSC) biology has been studied for more than 4 decades and the cells have been investigated for potential clinical applications for more than 15 years. Progress has become exponential over the past decade due mainly to the broad therapeutic potential of these cells. However, MSC studies have also been subject to controversy and increasing scrutiny as new mechanisms of action are reported and ever-expanding therapeutic applications pursued. In this book, leading authorities from all over the world, who are actively involved in this field, provide state-of-the-art knowledge of the basic biology, translational requirements and latest clinical experience with MSCs. This cutting edge book is the ideal resource for scientists and clinicians interested in pursuing an important and rapidly developing field of research that will eventually help patients and address urgent unmet medical needs. Features include: coverage of the biology of MSCs, latest understanding of mechanisms of action, and role in tissue homeostasis and regeneration; identifying the potential of MSCs in proceeding from bench to bedside from regulatory, GMP production, ethical and safety aspects; and critical analysis of clinical studies and the potential of MSCs to treat a wide variety of human diseases and tissues.

Upon completion of the human genome project over 800 G protein-coupled receptor 1 (GPCR) genes, subdivided into five categories, were identified. These receptors sense a diverse array of stimuli, including peptides, ions, lipid analogues, light and odour, in a discriminating fashion. Subsequently, they transduce a signal from the ligand-receptor complex into numerous cellular responses. The importance of GPCRs is further reflected in the fact that they constitute the most common target for therapeutic drugs across a 2 wide range of human disorders. Phylogenetic analysis of GPCRs produced the GRAFS classification system, which subdivides GPCRs into five discrete families: glutamate, rhodopsin, adhesion, frizzled/taste2 and secretin receptors. The adhesion-GPCR family 2 can be further subdivided into eight groups. The field of adhesion-GPCR biology has indeed become large enough to require a volume dedicated solely to this field. The contributors to this book have made a courageous effort to address the key concepts of adhesion-GPCR biology, including the evolution and biochemistry of adhesion-GPCRs; there are extensive discussions on the functional nature of these receptors during development, the immune response and tumourgenesis. Finally, there are chapters dedicated to adhesion-GPCR signalling, an area of intense investigation.

This book is an edited collection of the literature on leptin beginning with the discovery of leptin and a study of its affect on animals and in humans. Chapters will focus on the discovery, history, roles and regulation of leptin in all the major areas of physiology, as well as on assay methods, phylogeny and genetics. The timing of this volume is long overdue and is the first comprehensive coverage of leptin physiology in the field.

The overall scope of this new series will be to evolve an understanding of the genetic basis of (1) how early mesoderm commits to cells of a heart lineage that progressively and irreversibly assemble into a segmented, primary heart tube that can be remodeled into a four-chambered organ, and (2) how blood vessels are derived and assembled both in the heart and in the body. Our central aim is to establish a four-dimensional, spatiotemporal foundation for the heart and blood vessels that can be genetically dissected for function and mechanism. Since Robert DeHaan's seminal chapter "Morphogenesis of the Vertebrate Heart" pub lished in Organogenesis (Holt Reinhart & Winston, NY) in 1965, there have been surprisingly few books devoted to the subject of cardiovascular morphogenesis, despite the enormous growth of interest that occurred nationally and internationally. Most writings on the subject have been schol arly compilations of the proceedings of major national or international symposia or multiauthored volumes, often without a specific theme. What is missing are the unifying concepts that can make sense out of a burgeoning database of facts. The Editorial Board of this new series believes the time has come for a book series dedicated to cardiovascular morphogenesis that will serve not only as an important archival and didactic reference source for those who have recently come into the field but also as a guide to the evolution of a field that is clearly coming of age."

Human-Like Biomechanics is a comprehensive introduction into modern geometrical methods to be used as a unified research approach in two apparently separate and rapidly growing fields: mathematical biomechanics and humanoid robotics. The term human-like biomechanics is used to denote this unified modelling and control approach to humanoid robotics and mathematical biomechanics, based on theoretical mechanics, differential geometry and topology, nonlinear dynamics and control, and path-integral methods. From this geometry-mechanics-control modelling perspective, "human" and "humanoid" means the same. This unified approach enables both design of humanoid systems of immense complexity and prediction/prevention of subtle neuro-musculo-skeletal injuries. This approach has been realized in the form of the world-leading human-motion simulator with 264 powered degrees of freedom, called Human Biodynamics Engine (developed in Defence Science & Technology Organisation, Australia).

The book contains six Chapters and an Appendix. The first Chapter is an Introduction, giving a brief review of mathematical techniques to be used in the text. The second Chapter develops geometrical basis of human-like biomechanics, while the third Chapter develops its mechanical basis, mainly from generalized Lagrangian and Hamiltonian perspective. The fourth Chapter develops topology of human-like biomechanics, while the fifth Chapter reviews related nonlinear control techniques. The sixth Chapter develops covariant biophysics of electro-muscular stimulation. The Appendix consists of two parts: classical muscular mechanics and modern path integral methods, which are both used frequently in the main text. Thewhole book is based on the authorsa (TM) own research papers in human-like biomechanics.

Gain a foundational understanding of how endocrine and metabolic physiology affects other body systems in health and disease, including the clinical dimensions of reproductive endocrinology. Endocrine and Reproductive Physiology, a volume in the Mosby Physiology Series, explains the fundamentals of this complex subject in a clear and concise manner, while helping you bridge the gap between normal function and disease with pathophysiology content throughout the book. Helps you easily master the material in a systems-based curriculum with learning objectives, Clinical Concept boxes, highlighted key words and concepts, chapter summaries, self-study questions, and a comprehensive exam. Includes nearly 200 clear, 2-color diagrams that simplify complex concepts. Features clinical commentaries that show you how to apply what you've learned to real-life clinical situations. Keeps you current with recent advances in endocrine physiology with expanded material on reproductive endocrinology and metabolism, and many updates at the molecular and cellular level. Covers the latest developments in fertilization, pregnancy, and lactation, as well as fetal development, puberty, and the decline of reproductive function with age. Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices. Complete the Mosby Physiology Series! Systems-based and portable, these titles are ideal for integrated programs. Blaustein, Kao, & Matteson: Cellular Physiology and Neurophysiology Johnson: Gastrointestinal Physiology Koeppen & Stanton: Renal Physiology Cloutier: Respiratory Physiology Pappano & Weir: Cardiovascular Physiology Hudnall: Hematology: A Pathophysiologic Approach

Traumatic brain injury has complex etiology and may arise as a consequence of physical abuse, violence, war, vehicle collisions, working in the construction industry, and sports. Cellular, Molecular, Physiological, and Behavioral Aspects of Traumatic Brain Injury will improve readers' understanding of the detailed processes arising from traumatic brain injury. Featuring chapters on neuroinflammation, metabolism, and psychology, this volume discusses the impact of these injuries on neurological and body systems to better understand underlying pathways. This book will be relevant for neuroscientists, neurologists, clinicians, and anyone working to better understand traumatic brain injury.

The importance of polyamines for all living cells has been recognized since spermine was discovered in human semen more than 300 years ago. Polyamine research intensified when analytical methods were developed for their determination, particularly in tissues and biological fluids. Discovering their close correlation with cancer, and that polyamine concentrations change during the cell cycle, gave reason for further research in this topic. Polyamines in Health and Nutrition concentrates on the direction of polyamine research which has the capacity to influence and benefit our health and which can explain some of the discrepancies and failures of earlier research. It is important to recognize the dietary contribution to the polyamine body pool and to investigate how the polyamine content of the diet can be changed, with the ultimate aim of using this information to improve our health.

This book highlights the advancements in different fields of clinical electrophysiology and gives the reader a good background of the established practices. To tackle such a wide topic, the book focuses on two main aspects: ablation and pacing, discussing the novel energy sources and approaches to rhythm restoration and control; devices and signal processing, highlighting the new available technologies and numerical approaches aiding practice and home medicine. It also presents the reader with selected strategies that could be a paradigm shifts for the field: in situ cell reprogramming, exploiting the newly founded achievements in epigenetic modification of somatic cells; artificial intelligence; cardiac digital twinning, which aims to collect the information from imaging, mechanics and electrophysiology and condense it into a patient-specific model for personalized treatment.

The Copenhagen Muscle Research Centre was founded in 1994 with the support of a grant from the Danish National Research Foundation. Among the goals for the Centre is the organization of research symposia, with the aim of bringing a limited number ofintemation ally renowned scientists together to discuss the latest developments and perspectives in their field. The first Copenhagen Muscle Research Centre Conference was held in 1995 and dealt with cardiovascular regulation. The Second Copenhagen Muscle Research Centre Confer ence was held from October 23-26, 1997. The topic of the Symposium was Muscle Metabo lism: Regulation, Exercise, and Diabetes. Seventy invited scientists from all over the world discussed their latest research related to skeletal muscle metabolism. The speakers were asked to expand on their presentations and to write short, but comprehensive, chapters about their given topics. The result is 28 peer-reviewed and edited chapters covering many if not all aspects of muscle energy metabolism related to exercise and diabetes. Emphasis is on regulation of glucose and fatty acid metabolism and the mechanisms regulating their use as fuels for the muscle during exercise. In addition, abnormalities in the regulation of glucose metabolism in the diabetic state are described. However, amino acid and protein metabolism are also thoroughly discussed. We believe that this volume brings an unparralleled, up to date, and comprehensive review of the frontiers in muscle metabolism. Erik A."

Excess of homocysteine, a product of the metabolism of the essential amino acid methionine, is associated with poor health, is linked to heart and brain diseases in general human populations, and accelerates mortality in heart disease patients. Neurological and cardiovascular abnormalities occur in patients with severe genetic hyperhomocysteinemia and lead to premature death due to vascular complications. Although it is considered a non-protein amino acid, studies over the past dozen years have discovered mechanisms by which homocysteine becomes a component of proteins. Homocysteine-containing proteins lose their normal biological function and become auto-immunogenic and pro-thrombotic. In this book, the author, a pioneer and a leading contributor to the field, describes up-to date studies of the biological chemistry of homocysteine-containing proteins, as well as pathological consequences and clinical implications of their formation. This is a comprehensive account of the broad range of basic science and medical implications of homocysteine-containing proteins for health and disease.