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.

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.

Since the first gap junction protein (connexin) was cloned over a decade ago, more than a dozen connexin genes have been cloned. Consequently, a wealth of information on the molecular basis of gap junctional communication has been accumulated. This book pays tribute to this exciting era in the history of cell communication research by documenting the great strides made in this field as a result of the merging of biophysics and molecular biology, two of the most powerful approaches to studying the molecular basis of membrane channel behavior. Twenty-eight comprehensive chapters, authored by internationally recognized leaders in the field, discuss the biophysical, physiological, and molecular characteristics of cell-to-cell communication via gap junctions. Key aspects of molecular structure, formation, gating, conductance, and permeability of vertebrate and invertebrate gap junction channels are highlighted. In addition, a number of chapters focus on recent discoveries that implicate connexin mutations and alterations of gap junctional communication in the pathogenesis of several diseases, including the X-linked Charcot-Marie-Tooth demyelinating disease, some forms of inherited sensorineural deafness, malignant transformation, cardiac malformations and arrhythmia, eye lens cataract, and Chagas disease.

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.

A study of mast cells and basophils, designed for the use of immunologists, biochemists and medical researchers. Detailed chapters cover all aspects of mast cell and basophil research, from cell development, proteases, histamine, cysteinyl leukotrienes, physiology and pathology to the role of these cells in health and disease. Chapters also discuss the clinical implications of histamine receptor antagonists.

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).

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.

Alternative Sources of Adult Stem Cells: Human Amniotic Membrane, by S. Wolbank, M. van Griensven, R. Grillari-Voglauer, and A. Peterbauer-Scherb;
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Mesenchymal Stromal Cells Derived from Human Umbilical Cord Tissues: Primitive Cells with Potential for Clinical and Tissue Engineering Applications, by P. Moretti, T. Hatlapatka, D. Marten, A. Lavrentieva, I. Majore, R. Hass and C. Kasper;
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Isolation, Characterization, Differentiation, and Application of Adipose-Derived Stem Cells, by J. W. Kuhbier, B. Weyand, C. Radtke, P. M. Vogt, C. Kasper and K. Reimers;
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Induced Pluripotent Stem Cells: Characteristics and Perspectives, by T. Cantz and U. Martin;
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Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology, by D. Pei, J. Xu, Q. Zhuang, H.-F. Tse and M. A. Esteban;
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Production Process for Stem Cell Based Therapeutic Implants: Expansion of the Production Cell Line and Cultivation of Encapsulated Cells, by C. Weber, S. Pohl, R. Poertner, P. Pino-Grace, D. Freimark, C. Wallrapp, P. Geigle and P. Czermak;
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Cartilage Engineering from Mesenchymal Stem Cells, by C. Goepfert, A. Slobodianski, A.F. Schilling, P. Adamietz and R. Poertner;
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Outgrowth Endothelial Cells: Sources, Characteristics and Potential Applications in Tissue Engineering and Regenerative Medicine, by S. Fuchs, E. Dohle, M. Kolbe, C. J. Kirkpatrick;
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Basic Science and Clinical Application of Stem Cells in Veterinary Medicine, by I. Ribitsch, J. Burk, U. Delling, C. Geissler, C. Gittel, H. Julke, W. Brehm;
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Bone Marrow Stem Cells in ClinicalApplication: Harnessing Paracrine Roles and Niche Mechanisms, by R. M. El Backly, R. Cancedda;
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Clinical Application of Stem Cellsin the Cardiovascular System, C. Stamm, K. Klose, Y.-H. Choi"

The Handbook is intended to be a service to the neuroscience community, to help in finding available and useful information, to point out gaps in our knowledge, and to encourage continued studies. It represents the valuable contributions of the many authors of the chapters and the guidance of the editors and most important, it represents support for research in this discipline. Based on the rapid advances in the years since the second edition

Medical image technologies play a significant role in visualization and interpretation methods in medical diagnosis and practice using decision making, pattern classification, diagnosis, and learning. Progressions in the field of medical imaging lead to interdisciplinary discovery in microscopic image processing and computer-assisted diagnosis systems, and aids physicians in the diagnosis and early detection of diseases. Histopathological Image Analysis in Medical Decision Making provides emerging research exploring the theoretical and practical applications of image technologies and feature extraction procedures within the medical field. Featuring coverage on a broad range of topics such as image classification, digital image analysis, and prediction methods, this book is ideally designed for medical professionals, system engineers, medical students, researchers, and medical practitioners seeking current research on problem-oriented processing techniques in imaging technologies.

Understanding the biology of brain function is a great challenge and a major goal of modern science. The brain is one of the last great frontiers in science, and the unraveling of its mysteries is comparable in complexity to efforts in space exploration. A fundamental goal of neuroscience is to understand how neurons generate behavior and the pathophysiology of different mental and neurological diseases. The aim of this book is to describe recent discoveries about the basic operations of the brain and to provide an introduction to the adaptations for specific types of information processing.

Androgens play a critical role in the development and maintenance of the male reproductive system and affect important physiological processes and pathological conditions, including the homeostasis of the normal prostate and prostate cancer. Androgen Action: Methods and Protocols is designed to provide a tool box to study various phases of androgen action, from its entry to the cell to the phenotypic response that the cell mounts, with up-to-date techniques for biochemists, molecular biologists, cell biologists, geneticists, and pathologists. The volume opens with a brief review of the research history on androgen action and prostate carcinogenesis, followed by chapters that cover state-of-the-art methods to determine androgen levels in biological tissues and fluids, experimental procedures to study the various aspects of androgen receptor activity, and methodology to study salient examples of interactions between androgen signalling and other major signalling pathways in cells. 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, Androgen Action: Methods and Protocols provides a comprehensive overview of, and practical guidance on, the diverse methodologies that are propelling androgen action research forward, both for normal physiology as well as in disease states.

Aging of somatic stem cells reduces cell function and results in dysfunctional organs and tissues, making it an underlying cause of diseases associated with aging. It might even be the primary cause for age-associated attrition of tissue function in organs that heavily rely on stem cells for maintaining homeostasis, like the skin, blood and intestines. Understanding the molecular and cellular mechanisms involved is critical for developing approaches to attenuate stem cell aging and could pave the way for improved quality of life among the elderly. Written by highly prominent experts in the field, this book presents the current state of knowledge on these mechanisms. It offers insights into stem cell function, explains in detail the mechanisms of stem cell aging in model organisms as well as mammalian systems and describes related diseases and approaches to attenuating stem cell aging or achieving rejuvenation. The book is intended for all scientists and clinicians working with stem cells, aging mechanisms or age-related diseases.