This second book of the three-volume collection "Ion Transport in Tumor Biology" helps readers gain comprehensive knowledge of the pathophysiology of cancer. The authors highlight that ion transport proteins, channels and transporters - collectively referred to as the transportome - are significantly involved in the development and progression of cancer. Nearly 90% of malignant tumor diseases originate from epithelial cells, the function of which, for the most part, is based on the transportome. This volume focuses on molecular principles by showing that dysregulated expression and/or function of ion transporters have been correlated with malignancy in the vast majority of tumor diseases. Within the story of the various chapters, the authors line out various malfunctions of the transportome and where they can be found at different stages of the metastatic cascade. The authors describe how the interactions between the tumor cells' transportome and the environment reinforce mesenchymal behaviour of cancer cells and contribute to their uncontrolled proliferation, migration, invasion, intra- and extravasation up to the formation of metastases. As part of a three-volume collection, this book will fascinate members of the active research community, as well as clinicians from the cancer field.

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.

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.

The structures of living tissues are continually changing due to growth and response to the tissue environment, including the mechanical environment. Tissue Mechanics is an in-depth look at the mechanics of tissues. Tissue Mechanics describes the nature of the composite components of a tissue, the cellular processes that produce these constituents, the assembly of the constituents into a hierarchical structure, and the behavior of the tissue's composite structure in the adaptation to its mechanical environment. Organized as a textbook for the student needing to acquire the core competencies, Tissue Mechanics will meet the demands of advanced undergraduate or graduate coursework in Biomedical Engineering, as well as, Chemical, Civil, and Mechanical Engineering. Key features: Detailed Illustrations Example problems, including problems at the end of sections A separate solutions manual available for course instructors A website (http://tissue-mechanics.com/) that has been established to provide supplemental material for the book, including downloadable additional chapters on specific tissues, downloadable PowerPoint presentations of all the book's chapters, and additional exercises and examples for the existing chapters. About the Authors: Stephen C. Cowin is a City University of New York Distinguished Professor, Departments of Biomedical and Mechanical Engineering, City College of the City University of New York and also an Adjunct Professor of Orthopaedics, at the Mt. Sinai School of Medicine in New York, New York. In 1985 he received the Society of Tulane Engineers and Lee H. Johnson Award for Teaching Excellence and a recipient of the European Society of Biomechanics Research Award in 1994. In 1999 he received the H. R. Lissner medal of the ASME for contributions to biomedical engineering. In 2004 he was elected to the National Academy of Engineering (NAE) and he also received the Maurice A. Biot medal of the American Society of Civil Engineers (ASCE). Stephen B. Doty is a Senior Scientist at Hospital for Special Surgery, New York, New York and Adjunct Professor, School of Dental and Oral Surgery, Columbia University, New York, NY. He has over 100 publications in the field of anatomy, developmental biology, and the physiology of skeletal and connective tissues. His honors include several commendations for participation in the Russian/NASA spaceflights, the Spacelab Life Science NASA spaceflights, and numerous Shuttle missions that studied the influence of spaceflight on skeletal physiology. He presently is on the scientific advisory board of the National Space Biomedical Research Institute, Houston, Texas.

Current Presentation of his Work; De Marneffe. Anatomy and Physiology: Morphology and Distribution of Blood Vessels and Blood Flow in Bone; M. Brookes. Methods of Investigation: Measurement of Bone Blood Flow in Animals; P. Tothill. Fracture Healing and Bone Grafts: The Role of Vasculature in Fracture Healing; S.P.F. Hughes, et al. Circulatory Aspects of Bone Disorders: Bone Turnovers in Osteoporosis; A.M. Peters. Osteonecrosis: General Aspects of Osteonecrosis: Pathophysiology of Osteonecrosis; J.P. Jones. Methods of Diagnosis: Diagnosis of Osteonecrosis of the Femoral Head; D.S. Hungerford, L.C. Jones. Treatment: Long Term Results in Electromagnetic Fields Treatment of Osteonecrosis; M. Hinsenkamp, et al. ARCO Perspective for Staging: Methodologic Problems in Staging and Evaluating Osteonecrosis; B.N. Stulberg, J.W.M. Gardeniers. 34 additional articles. Index.

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.

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.

Investigations involving incisive mechanistic dissection of various types of synaptic plasticity have revealed that it plays key roles in neural development, sensory information processing, cortical remapping following brain injury, perception, and behavioral learning and memory. Disruptions of synaptic plasticity may underlie neurological and behavioral disorders such as Alzheimer disease, Fragile-X syndrome, autism, and drug addiction. Multidisciplinary Tools for Investigating Synaptic Plasticity, therefore, assembles expert contributions that highlight techniques and strategies used in probing the cellular and molecular mechanisms of synaptic plasticity in the nervous systems of vertebrate and invertebrate species. Divided into three sections, this meticulous volume describes biochemical and genetic strategies for studying synaptic plasticity, behavior, neural development, and synaptogenesis, and also includes cellular electrophysiological and optical methods for interrogating a diverse array of mechanistic issues. As part of the Neuromethods series, this book contains the kind of detail and key implementation advice that maximizes successful results. Authoritative and invaluable, Multidisciplinary Tools for Investigating Synaptic Plasticity serves as an ideal primer for introducing researchers to specific techniques that will enhance their success at addressing novel questions in synaptic plasticity at the lab bench.

This third and final volume in the "Ion Transport in Tumor Biology" collection presents novel diagnostic and therapeutic approaches in cancer based on the exploitation of ion transport proteins. The authors critically examine several transportome members, particularly Na+, K+, Ca2+, and Cl- channels, as well as organic solute carriers regarding their suitability as therapeutic targets. Synergistic effects resulting from the combined use of classical cytostatics with ion transport-inhibiting drugs are pointed out, and the capability of bispecific antibodies to function as anticancer drugs is discussed. As readers will also learn, the use of ion channel inhibitors could improve the outcome of radiotherapy because the development of radio-resistance during radiotherapeutic treatment often correlates with increases in the expression levels and conductance of ion channels. The translational topics of this volume form a bridge between biochemical research and therapeutic application. As part of a three-volume collection, this book will fascinate members of the active research community, as well as clinicians in the cancer field.

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.

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.

Novel Approaches into the Origins of Neurodevelopmental Disorders: The Fetal Physiology Foundation Over the past two decades, autism, a neurodevelopmental disorder that is defined by behavior and was once believed to be rare, became recognized in increasing numbers of children and recently received distinction as an "epidemic" [1]. While numbers of affected children have steadily increased, our knowledge is still ins- ficient to explain autism's diverse causes and broad range of presentations. Despite remarkable progress in research, available medical diagnostic testing applies only to a small minority of affected children. Thus, scientifically based explanations with which physicians can diagnose and treat the majority of children with autism and advise their parents are quite limited. Our society and scientific community were unprepared for the rise in autism, which explains our present inability to understand most of its causes. Researchers in neurodevelopmental disorders have long been aware of other disorders that, despite extensive efforts, have not yielded clear genetic or environmental origins, and autism has become symbolic of the need for new approaches to research into these complex conditions. Although autism has captured our attention in recent years, the prevalence of other neurodevelopmental disorders such as attention de- cit hyperactivity disorder (ADHD) and bipolar disorder, among others, also has been increasing [2-4].

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.

Information is central to the evolution of biological complexity, a physical system relying on a continuous supply of energy. Biology provides superb examples of the consequent Darwinian selection of mechanisms for efficient energy utilisation. Genetic information, underpinned by the Watson-Crick base-pairing rules is largely encoded by DNA, a molecule uniquely adapted to its roles in information storage and utilisation.This volume addresses two fundamental questions. Firstly, what properties of the molecule have enabled it to become the predominant genetic material in the biological world today and secondly, to what extent have the informational properties of the molecule contributed to the expansion of biological diversity and the stability of ecosystems. The author argues that bringing these two seemingly unrelated topics together enables Schroedinger's What is Life?, published before the structure of DNA was known, to be revisited and his ideas examined in the context of our current biological understanding.

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.

This edition of the companion volumes Muscle Pain: Understanding the Mech- isms and Muscle Pain: Diagnosis and Treatment is essential reading for those interested in clinical approaches to acute and chronic pain conditions involving muscle tissues and in the mechanisms underlying these conditions. The volumes cover a very important topic in pain medicine, since muscle pain is very common and can often be dif?cult to diagnose and treat effectively. Furthermore, chronic pain involving muscle and other components of the musculoskeletal system increases with age, such that it is a common complaint of those of us who are middle-aged or older. Indeed, as changing population demographics in "west- nized" countries result in higher proportions of the population living longer and being middle-aged and elderly, chronic muscle pain will likely become even more of a health problem. In the case of acute muscle pain, this can often be very intense, and in the short term can limit or modify the use of components of the musculoskeletal system associated with the sensitive muscle. Chronic muscle pain can also be intense, as well as unpleasant and disabling, and it is in many cases the over-riding symptom of most musculoskeletal disorders that are associated with long-term deleterious changes in musculoskeletal function.

The prefrontal cortex is known to play important roles for performing a variety of higher cognitive functions. Among regions of the prefrontal cortex, the dorsolateral prefrontal cortex plays the most important roles for these functions. This book focuses on functions of the dorsolateral prefrontal cortex, summarizes research results obtained mainly by non-human primate studies, and describes neural mechanisms of executive functions that the dorsolateral prefrontal cortex participates. First, to understand the feature of the dorsolateral prefrontal cortex and how its function has been understood, anatomical and functional features of the dorsolateral prefrontal cortex and historical overview of prefrontal functions are described. To understand functions of the prefrontal cortex and neural mechanisms of executive functions, working memory is an important concept and sustained activation during the memory period of working memory tasks is known as a neural mechanism of working memory. Therefore, this book describes features of sustained memory-related activity based on neurophysiological results obtained in the prefrontal cortex and how memory-related activity contributes to executive functions including control of attention, inhibitory control, task management, and planning. And further, this book describes how the dorsolateral prefrontal cortex contributes to neural mechanisms for sensory and motor processing, memory control in multi-task performance, decision-making, metacognition, and top-down control. Thus, this book provides important information regarding neural mechanisms of dorsolateral prefrontal functions to neuroscientists and helps to plan further investigation to understand prefrontal functions in primates and human subjects.

Essentials of Anatomy & Physiology blends up-to-date science, stimulating writing, high-quality art, and cutting-edge educational technology to provide the most effective teaching and learning program available in the one-semester anatomy and physiology course. The distinctive pedagogy of the text revolves around the theme of "Elevate Learning". From "Base Camp" to "Assess Your Learning Outcomes", the student experiences a clear sense of the path ahead, a convenient means of charting progress, and a satisfying sense of accomplishment at the end.

This book presents cutting edge methods that provide insights into the pathways by which salt and water traverse cell membranes and flow in an orchestrated fashion amongst the many compartments of the body. It focuses on a number of molecular, cellular and whole animal studies that involve multiple physiological systems and shows how the internal milieu is regulated by multifactorial gene regulation, molecular signaling, and cell and organ architecture. Topics covered include: water channels, the urinary concentrating mechanism, angiotensin, the endothelin system, miRNAs and MicroRNA in osmoregulation, desert-adapted mammals, the giraffe kidney, mosquito Malpighian tubules, and circadian rhythms. The book highlights how different approaches to explaining the same physiological processes greatly increase our understanding of these fundamental processes. Greater integration of comparative, evolutionary and genetic animal models in basic science and medical science will improve our overall grasp of the mechanisms of sodium and water balance.

Transmissible spongiform encephalopathies (TSE), known as prion diseases, have been recognized for nearly 300 years in animals and almost 100 years in humans. Modern studies, including the protein-misfolding cyclic amplification (PMCA), have greatly advanced our understanding of the pathogenesis of prion diseases and facilitated the identification of new prion diseases in animals and humans. In the second edition of Prions and Diseases, more than 60 leading researchers and clinicians worldwide provide an up-to-date discussion of these unique infectious pathogens and their associated diseases. The book provides up-to-date knowledge about the etiology, pathogenesis, classification, histopathological, and clinical aspects of the full range of animal and human prion diseases. As a result, the book contains by far the most authoritative views about the past, present, and future of prions and prion diseases. The new second edition covers such important emerging topics such as inherited human prion disease, stem-cell models in prion research, human prion disease surveillance, and gene therapy strategies.

A successful Wall Street trader turned neuroscientist reveals how risk taking and stress transform our body chemistry
Before he became a world-class scientist, John Coates ran a derivatives trading desk in New York City. He used the expression "the hour between dog and wolf" to refer to the moment of Jekyll-and-Hyde transformation traders passed through when under pressure. They became cocky and irrationally risk-seeking when on a winning streak, tentative and risk-averse when cowering from losses. In a series of groundbreaking experiments, Coates identified a feedback loop between testosterone and success--one that can cloud men's judgment in high-pressure decision-making. Coates demonstrates how our bodies produce the fabled gut feelings we so often rely on, how stress in the workplace can impair our judgment and even damage our health, and how sports science can help us toughen our bodies against the ravages of stress. Revealing the biology behind bubbles and crashes, "The Hour Between Dog and Wolf "sheds new and surprising light on issues that affect us all.

Recent Advances in Prolactin Research summarizes the current knowledge of prolactin (PRL), PRL receptor, PRL-dependent signaling pathways, the role of PRL in oncogenesis and PRL crosstalk with other oncogenic factors. The chapters are written by experts in these fields and focus on identifying and reviewing timely experimental findings that provide new insights into the expanding role of PRL in the pathophysiology associated with a variety of human conditions. Prolactin is a peptide hormone that is best known for its role in lactation. Prolactin also has an influence on hematopoiesis and angiogenesis, and is involved in the regulation of blood clotting through several pathways. Although PRL was discovered more than 80 years ago, the understanding of PRL signaling and its relationship to various pathologies is still very incomplete. PRL is not only a pituitary hormone with an important role in reproduction, but PRL also acts as a cytokine, modulating a wide variety of physiological processes. For example, data gathered during the last decade have demonstrated that locally produced PRL acts as the autocrine/paracrine factor and plays a contributory role during breast oncogenesis. In fact, the scientific and clinical communities have suggested that the manipulation of the PRL axis may lead to the successful treatment of breast cancer. However, recent work has demonstrated that the role of the PRL axis is much more complex than first envisaged.

The bright colour of haemoglobin has, from the very beginning, played a significant role in both the investigation of this compound as well as in the study of blood oxygen transport. Numerous optical methods have been developed for measuring haemoglobin concentration, oxygen saturation, and the principal dyshaemoglobins in vitro as well as in vivo. Modern applications include pulse oximeters, fibre optic oximeters, multiwavelength haemoglobin photometers ('co-oximeters') and instruments for near infrared spectroscopy in vivo. Knowledge of the light absorption spectra of the common haemoglobin derivatives is a prerequisite for the development and understanding of these techniques.
In the 1960s a reference method based on the absorptivity of a single derivative (haemiglobincyanide; HiCN) at a single wavelength (540 nm) was established for measuring the total haemoglobin concentration. Thus an anchor value was provided on which the absorptivity spectra of all other haemoglobin derivatives could be based.
This monograph presents absorption spectra and absorptivity data in the wavelength range of 480 to 1000 nm of the major haemoglobin derivatives for human adult and foetal haemoglobin and for haemoglobin of several animals (cow, dog, horse, pig, rat, and adult and foetal sheep). A detailed description of the methods used to acquire these data has been included to allow future investigators to reproduce and expand on the data.
The second part of the monograph includes chapters on the principles and development, in historical perspective, of the principal methods for measuring total haemoglobin concentration for two, three, and multi-component analysis of haemoglobin derivatives, and for blood oxygen saturation measurement. Accurate quantitative data pertaining to haemoglobin in human blood are presented, together with a description of methods for measuring haemoglobin oxygen capacity and oxygen affinity. These chapters have been written with a view to foster knowledge and insight concerning the principles, purposes, and limitations of the various methods of all who use these methods in research and patient care.

Gastric acid plays a primary role in digestion as well as in the sterilization of food and water. Gastric juice contains the most concentrated physiological acid solution (pH~1) as a result + - of H and Cl ion secretion [hydrochloric acid (HCl) production] by parietal cells in the oxyntic mucosa of the stomach. The combined output of the parietal cells leads to the sec- tion of 1-2 l of HCl at a concentration of 150-160 mmol/l into the interior of the stomach. In order to facilitate the production of acid, the parietal cell relies on the generation of a high + concentration of H ions that are transported into the lumen of the gland. This process is fa- + + cilitated by activation of the gastric H ,K -ATPase, which translocates to the apical pole of + - the parietal cell. K as well as ATP hydrolysis and Cl all play critical roles in the activation + + of gastric H ,K -ATPase and are essential for the functioning of the enzyme (Reenstra and Forte 1990). This review will examine the classical proteins that have been linked to acid secretion as well as some recently identi?ed proteins that may modulate gastric acid secretion, in - dition we discuss the known secretagogues, and their receptors including a new receptor, which upon stimulation can lead to acid secretion.