This book consists of 3 volumes: Basic Science (Volume 1), Clinical Science (Volume 2) and Technology and Methodology (Volume 3). Volume 2 focuses on the clinical aspects of autophagy research, discussing the role of autophagy in neuropsychiatric disorders, the cardiovascular, immune, digestive and endocrine systems, as well as tumors, infection, the kidney, and the respiratory and hematological systems. It also addresses autophagy-related drug development. Written and edited by a team of 90 experts, and presenting the state of the art in autophagy research, this book is a valuable reference resource for researchers and clinicians alike. It can also be used as supplementary material for graduate students majoring in biology and medicine

Cell adhesion is a fundamental determinant of embryonic development and organogenesis. Cellular Adhesion in Development and Disease, volume 112 in Current Topics in Developmental Biology, comprehensively surveys current developments in understanding how adhesion systems affect organismal development. Topics covered include nectins, nectin-like molecules, and afadin in development; cadherin adhesion, signaling, and morphogenesis; endothelial cell junctions; epidermal development and barrier formation; and more.

Autophagy principally serves an adaptive function to protect organisms against diverse human pathologies, including cancer and neurodegeneration. Recent developments using in vitro, ex vivo and in vivo models show the involvement of the autophagy pathway in immunity and inflammation. Moreover, direct interactions between autophagy proteins and immune signalling molecules have also been demonstrated. Defects in autophagy - similar to cancer, neurodegenerative diseases and aging - through autophagy gene mutation and/or microbial antagonism, may underlie the pathogenesis of many infectious diseases and inflammatory syndromes. In spite of the increasing awareness of the importance of autophagy in these pathophysiological conditions, this process remains underestimated and is often overlooked. As a consequence, its role in the initiation, stability, maintenance, and progression of these diseases are still poorly understood. This book reviews the recent advances regarding the functions of the autophagy pathway and autophagy proteins in immunity and inflammation, focusing on their role in self-nonself distinction, their implications in innate and adaptive immune responses and their dysregulation in the pathology of certain inflammatory and autoimmune diseases.

This expert volume covers an interdisciplinary and rapidly growing area of biomedical research comprising genetic, biochemical, pathological, and clinical studies aimed at the diagnosis and therapy of human diseases which are either caused by or associated with mitochondrial dysfunction. It dedicates itself to showcasing the tremendous efforts and the progress that has been made over the last decades in developing techniques and protocols for probing, imaging, and manipulating mitochondrial functions. Mitochondrial Medicine: Volume II, Manipulating Mitochondrial Function describes techniques developed for manipulating and assessing mitochondrial function under general pathological conditions and specific disease states. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Mitochondrial Medicine provides an essential source of know-how and inspiration to all researchers who are fascinated by this tiny organelle that seems so clearly to control the life and death of a single cell and whole organisms alike.

As the first primer on the effects of exercise on human hypertension, Effects of Exercise on Hypertension: From Cells to Physiological Systems provides the state-of-the-art effects of exercise on the many possible mechanisms underlying essential hypertension in humans. The book contains chapters by distinguished experts on the effects of exercise on physiological systems known to be involved in hypertension development and maintenance as well as less well known aspects of hypertension such as 24-hour ambulatory blood pressure profile and oxidative stress. An emerging area, the effects of resistance exercise training on blood pressure is also covered. A unique aspect of the book is that it covers the effects of exercise mimetics on vascular cell adaptations in order to begin to elucidate some of the cellular mechanisms that may underlie blood pressure reductions with exercise training. Lastly, the book will end with a chapter on the interactive effects of genes and exercise on blood pressure. Chapters are grouped by physiological system or mechanism. The text begins with two overview chapters; one on the general effects of aerobic exercise training and the second on the general effects of resistance exercise training on blood pressure. Each chapter begins with a bulleted list of key points. Effects of Exercise on Hypertension: From Cells to Physiological Systems will be of great value to professional individuals in cardiovascular medicine, the cardiovascular sciences, allied health care professionals, and medical and graduate students in the cardiovascular sciences and medicine.

The discovery and genetic engineering of fluorescent proteins has revolutionized cell biology. What was previously invisible in the cell often can be made visible with the use of fluorescent proteins. In Vivo Cellular Imaging Using Fluorescent Proteins: Methods and Protocols presents state-of-the-art research that has contributed to the fluorescent protein revolution to visualize biological processes in the live animal. This volume covers an array of topics from the employment of the chick CAM model using fluorescent proteins and other fluorescent probes, to intravital fluorescent imaging, as well as 3-dimensional imaging, and design instructions on how to create new and improved far-red and infrared fluorescent proteins, to name a few. Written in the successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, In Vivo Cellular Imaging Using Fluorescent Proteins: Methods and Protocols is the first volume in the new field of in vivo cell biology and it serves both professionals and novices with its well-honed methodologies.

This book sheds new light on the physiology, molecular biology and pathophysiology of epithelial ion channels and transporters. It combines the basic cellular models and functions by means of a compelling clinical perspective, addressing aspects from the laboratory bench to the bedside. The individual chapters, written by leading scientists and clinicians, explore specific ion channels and transporters located in the epithelial tissues of the kidney, intestine, pancreas and respiratory tract, all of which play a crucial part in maintaining homeostasis. Further topics include the fundamentals of epithelial transport; mathematical modeling of ion transport; cell volume regulation; membrane protein folding and trafficking; transepithelial transport functions; and lastly, a discussion of transport proteins as potential pharmacological targets with a focus on the pharmacology of potassium channels.

This book covers topics on mechanosensing, mechanotransduction, and actin cytoskeletal dynamics in cell motility. It will contribute to a better understanding of how cells functionally adapt to their mechanical environment as well as highlighting fundamental concepts for designing material niches for cell manipulation. With topics from multidisciplinary fields of the life sciences, medicine and engineering, the book is the first of its kind, providing comprehensive, integrated coverage of innovative approaches to cell biomechanics. It provides a valuable resource for seniors and graduate students studying cell biomechanics and is also suitable for researchers interested in the application of methods and strategies in connection with the innovative approaches discussed. Each section of the book has been supplemented with concrete examples and illustrations to facilitate understanding even for readers unfamiliar with cell biomechanics.

This book deals with many recent advances made in uncovering the molecular and cellular basis of phagocytosis of apoptotic and necrotic dying cells as well as with the methods used for studying their clearance. There are important practical and clinical reasons for attempting to understand the molecular mechanisms of phagocytosis of dying cells, because inadequate clearance of dying cells may contribute to the development of autoimmune diseases (e.g. systemic lupus erythematosus), as well as atherosclerosis and chronic lung diseases (e.g. chronic obstructive pulmonary disease, asthma and cystic fibrosis). Furthermore, in this book we examine the possibility of using apoptotic cells in the prevention and treatment of graft rejection and in the rational design of immunotherapy and vaccines for cancer treatment. The role of environmental factors in phagocytosis of dying cells is also addressed.

This comprehensive volume integrates the most innovative and current findings from several related disciplines of scientific research, including pathology, immunology, genetics, and cellular and molecular biology. It is divided into two sections: "Molecular mechanisms of phagocytosis of dying cells" and "Impairment of phagocytosis of dying cells and its role in the development of diseases." No other recent books devoted to this subject are available.

All of the contributors are experts working at the forefront of scientific discovery, and the reviews they present systematically examine the most exciting and innovative aspects of their particular areas of expertise. Both researchers and physicians will find this volume of major benefit because it covers the immunological and molecular biological aspects of phagocytosis of dying cells as well as its clinical relevance.

Prospective Isolation and Characterization of Human Bone Marrow-Derived MSCs, by A. Harichandan, K. Sivasubramaniyan, H.-J. Buhring Urine as a Source of Stem Cells, by Christina Benda, Ting Zhou, Xianming Wang, Weihua Tian, Johannes Grillari, Hung-Fat Tse, Regina Grillari-Voglauer, Duanqing Pei, Miguel A. Esteban Expansion of Mesenchymal Stem/Stromal Cells under Xenogenic-Free Culture Conditions, by Sven Kinzebach, Karen Bieback Adipose-Derived Mesenchymal Stem Cells: Biology and Potential Applications, by Danielle Minteer, Kacey G Marra, J Peter Rubin Potential for Osteogenic and Chondrogenic Differentiation of MSC, by Antonina Lavrentieva, Tim Hatlapatka, Anne Neumann, Birgit Weyand, Cornelia Kasper Potential for Neural Differentiation of Mesenchymal Stem Cells, by Letizia Ferroni, Chiara Gardin, Ilaria Tocco, Roberta Epis, Alessandro Casadei, Vincenzo Vindigni, Giuseppe Mucci, Barbara Zavan Migratory Properties of Mesenchymal Stem Cells, by Thomas Dittmar, Frank Entschladen Dissecting Paracrine Effectors for Mesenchymal Stem Cells, by Stefania Bruno, Federica Collino, Ciro Tetta, Giovanni Camussi Proteomics Approaches in the Identification of Molecular Signatures of Mesenchymal Stem Cells, by Yin Xiao, Jiezhong Chen Does the Adult Stroma Contain Stem Cells?, by Richard Schafer

This volume looks at the state-of-the-science in stem cells, discusses the current challenges, and examines the new directions the field is taking. Dr. Turksen, editor-in-chief of the journal "Stem Cell Reviews and Reports," has assembled a volume of internationally-known scientists who cover topics that are both clinically and research-oriented. The contents range from sources of stem cells through their physiological role in health and disease, therapeutic applications in regenerative medicine, and ethics and society. An initial overview and a final summary bookend the contents into a cohesive and invaluable volume.

A panel of leading investigators summarizes and synthesizes the new discoveries in the rapidly evolving field of histone acetylation as a key regulatory mechanism for gene expression. The authors describe what has been learned about these proteins, including the identification of the enzymes, the elucidation of the enzymatic mechanisms of action, and the identification of their substrates and their partners. They also review the structures that have been solved for a number of enzymes-both alone and in complex with small molecule inhibitors-and the biological roles of the several histone deacetylases (HDAC) genes that have been knocked out in mice.

The aquaporin field has matured at an exceptionally fast pace and we are at the verge to develop serious strategies to therapeutically modulate aquaporin function directly or via regulatory networks. Key prerequisites are available today: i. a considerable (and growing) number of aquaporin crystal structures for the rational design of inhibitory molecules, ii. elaborate molecular dynamics simulation techniques for theoretical analyses of selectivity mechanisms and docking experiments, iii. comprehensive data on aquaporin immunohistochemistry, iv. aquaporin knockout animals for physiological studies, and v. assay systems for compound library screenings. The structure of this volume on aquaporins follows the points laid out above and thus covers the developments from basic research to potential pharmacological use. Situated between pharmacology textbooks and recent scientific papers this book provides a timely overview for readers from the fundamental as well as the applied disciplines.

Covering all aspects of oxygen delivery to tissue, including blood flow and its regulation as well as oxygen metabolism, this book is multidisciplinary and designed to bring together experts and students from a range of research fields including biochemical engineering, physiology, microcirculation, and hematology.

Nanotechnology is a collective term describing a broad range of relatively novel topics. Scale is the main unifying theme, with nanotechnology being concerned with matter on the nanometer scale. A quintessential tenet of nanotechnology is the precise self-assembly of nanometer-sized components into ordered devices. Nanotechnology seeks to mimic what nature has achieved, with precision at the nanometer level down to the atomic level. Nanobiotechnology, a division of nanotechnology, involves the exploitation of biomaterials, devices or methodologies in the nanoscale. In recent years a set of b- molecules has been studied and utilized. Virus particles are natural nanomaterials and have recently received attention for their tremendous potential in this field. The extensive study of viruses as pathogens has yielded detailed knowledge about their biological, genetic, and physical properties. Bacterial viruses (bacte- ophages), plant and animal eukaryotic viruses, and viruses of archaea have all been characterized in this manner. The knowledge of their replicative cycles allows manipulation and tailoring of particles, relying on the principles of self-assembly in infected hosts to build the base materials. The atomic resolution of the virion structure reveals ways in which to tailor particles for higher-order functions and assemblies.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases. The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.

Natural Killer (NK) cells are large granular lymphocytes of the innate immune system. They are widespread throughout the body, being present in both lymphoid organs and non-lymphoid peripheral tissues. NK cells are involved in direct innate immune reactions against viruses, bacteria, parasites and other triggers of pathology, such as malignant transformation, all of which cause stress in affected cells. Importantly, NK cells also link the innate and adaptive immune responses, contributing to the initiation of adaptive immune responses and executing adaptive responses using the CD16 FcgRIIIA immunoglobulin Fc receptor. Such responses are mediated through two major effector functions, the direct cytolysis of target cells and the production of cytokines and chemokines. The authors focus here on the nature of recognition events by NK cells and address how these events are integrated to trigger these distinct and graded effector functions.

Dendritic cells are vital to induce potent anti-viral immune responses. It will become clear to the reader that dendritic cells often play a dual role during viral infections. On the one hand they are able to mount potent antiviral immune responses, and on the other hand several viruses, including HIV-1, use DC as a vector to be transferred from the periphery to the lymph nodes where they infect their prime target.

Cell-cell and cell-matrix interactions are of fundamental importance for the development and the maintenance of tissues and organs in multicellular organisms. Adhesive processes are mediated and controlled by an increasingly large and complex number of cell adhesion molecules that are anchored to the cell surface membrane by transmembrane domains. According to their structural and functional features, cell adhesion molecules have been classified into at least four major families: the integrins, selectins, cadherins and members of the immunoglobulin superfamily. Apart from linking cells to each other or to components of the extracellular matrix, cell adhesion molecules function also as receptors that interact via their cytoplasmic domain with numerous signalling molecules including protein kinases and phosphatases, G-proteins, or proteins of the beta-catenin/armadillo family. Cell adhesion molecules can activate various signalling pathways and as a consequence play a crucial role in the regulation of cell differentiation, proliferation, migration and apoptosis. During the last decade it has been recognized that acquired as well as inherited defects of cell adhesion molecules and adhesion-linked signalling molecules are the molecular basis of various types of disease including cancer, infectious and inflammatory disease, connective tissue disorders or blistering disease.
This book is the proceedings of a Falk Workshop held in Berlin, Germany, on January 23-24, 2003, which brought together experts in different fields of research to stimulate the transfer of findings from basic research to clinical application. Section I focuses on cell adhesion molecules of the liver and their role inhepatocarcinogenesis and inflammatory liver disease. Section II deals with infection and fibrosis and with transforming growth factor beta (TGF-beta). Morphogenesis, cell migration and inflammation are the subject of Section III with a focus on the role of integrins in blood cell-endothelial interactions. In Section IV the importance of cell adhesion molecules for cancer and their role as potential target for cancer therapy will be discussed.

In 1898, an Austrian microbiologist Heinrich Winterberg made a curious observation: the number of microbial cells in his samples did not match the number of colonies formed on nutrient media (Winterberg 1898). About a decade later, J. Amann qu- tified this mismatch, which turned out to be surprisingly large, with non-growing cells outnumbering the cultivable ones almost 150 times (Amann 1911). These papers signify some of the earliest steps towards the discovery of an important phenomenon known today as the Great Plate Count Anomaly (Staley and Konopka 1985). Note how early in the history of microbiology these steps were taken. Detecting the Anomaly almost certainly required the Plate. If so, then the period from 1881 to 1887, the years when Robert Koch and Petri introduced their key inventions (Koch 1881; Petri 1887), sets the earliest boundary for the discovery, which is remarkably close to the 1898 observations by H. Winterberg. Celebrating its 111th anniversary, the Great Plate Count Anomaly today is arguably the oldest unresolved microbiological phenomenon. In the years to follow, the Anomaly was repeatedly confirmed by all microb- logists who cared to compare the cell count in the inoculum to the colony count in the Petri dish (cf., Cholodny 1929; Butkevich 1932; Butkevich and Butkevich 1936). By mid-century, the remarkable difference between the two counts became a universally recognized phenomenon, acknowledged by several classics of the time (Waksman and Hotchkiss 1937; ZoBell 1946; Jannasch and Jones 1959).

Apoptosis is a form of cell death that occurs in a controlled manner and is generally noninflammatory in nature. Apoptosis, or programmed cell death, implies a cell death that is part of a normal physiological process of pruning of unneeded cells. However, many disease conditions utilize apoptosis for pathological ends, resulting in inappropriate cell death and tissue destruction. This book starts with an introduction that reviews the general characteristics of apoptosis, its regulation and its role in physiology and disease. Next, the book focuses on three areas as they relate to inflammatory cells and diseases. The first area consists of chapters on signals for apoptosis important to inflammatory cells, namely growth factors and arachidonic acid metabolism. The next area that the book focuses on are effects at the cellular level, on cell survival versus cell death and signals critical for cell function in both normal and disease states. These topics are covered in chapters on lymphocytes, granulocytes, chondrocytes and keratinocytes. The last area that the book focuses on are events at the level of tissue and disease, looking at the evidence for altered apoptosis and/or apoptotic processes in immune and inflammatory diseases. These topics are covered in chapters on rheumatoid arthritis, osteoarthritis, lupus, psoriasis and renal disease. Together, these chapters will provide the reader with the latest insight in the role of apoptosis in inflammatory cells and diseases. This book starts with an introduction that reviews the general characteristics of apoptosis, its regulation and its role in physiology and disease. Next, the book focuses on three areas as they relate to inflammatory cells and diseases. The first area consists of chapters on signals for apoptosis important to inflammatory cells, namely growth factors and arachidonic acid metabolism. The next area that the book focuses on are effects at the cellular level, on cell survival versus cell death and signals critical for cell function in both normal and disease states. These topics are covered in chapters on lymphocytes, granulocytes, chondrocytes and keratinocytes. The last area that the book focuses on are events at the level of tissue and disease, looking at the evidence for altered apoptosis and/or apoptotic processes in immune and inflammatory diseases. These topics are covered in chapters on rheumatoid arthritis, osteoarthritis, lupus, psoriasis and renal disease. Together, these chapters will provide the reader with the latest insight in the role of apoptosis in inflammatory cells and diseases.

In this volume of Reviews of Physiology, Biochemistry and Pharmacology there a contributions by M.D. Swope, E. Lolis, F.Hofmann, L. Lacinova, N. Klugbauer, M. Hermann, P. Berger, S.S. Shen, J.S. Kim, M.E. Weksler, M. Hirsch-Kauffmann and M.Schweiger.

The immune system is not bound by a single tissue but is instead bestowed with the challenge of warding off invading pathogens throughout the body. Constant surveillance of the body requires that the immune system be highly mobile and able to purge pathogens from all tissues. Because each tissue presents its own unique architecture and milieu, it is necessary for the immune system to be as malleable as it is dynamic. For example, how the immune system handles a pathogen in the lung can differ significantly from a pathogen encountered in the gut.

Understanding immune complexity in diverse tissue environments is a challenge for researchers. However, advances in imaging have greatly improved our ability to probe the immune system. From snap-shots in time to 4D movies, imaging systems have been used to generate stunning visualizations of immune cells in action throughout the body. These visualizations are not only aesthetically pleasing but they have yielded great advances in our understanding of immune function. This volume provides a synopsis of major insights in immunology revealed using imaging approaches. "Seeing is truly believing," and this volume was assembled to recognize past accomplishments and to provide visions of what the future holds in store in this exciting field.

Food or calorie restriction has been shown in many short-lived animals and the rhesus monkey to prolong life-span. Life-long nutrition studies are not possible in humans because of their long survival. Studies over two to six years in healthy adult humans have, however, shown that a 20% reduction in food or calorie intake slows many indices of normal and disease-related aging. Thus, it is widely believed that long-term reduction in calorie or food intake will delay the onset of age-related diseases such as heart disease, diabetes and cancer, and so prolong life.

Over the last 20 or more years there has been a progressive rise in food intake in many countries of the world, accompanied by a rising incidence of obesity. Thus our increasing food and calorie intake has been linked to the rising incidence of cardiovascular disease and diabetes in early adult life. It is accepted that overeating, accompanied by reduced physical exercise, will lead to more age-related diseases and shortening of life-span. The answer is to reduce our calorie intake, improve our diet, and exercise more. But calorie restriction is extremely difficult to maintain for long periods. How then can we solve this problem?

Edited by a team of highly distinguished academics, this book provides the latest information on the beneficial effects of calorie restriction on health and life-span. This book brings us closer to an understanding at the molecular, cellular and whole organism level of the way forward.