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.

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.

This book assembles chapters from experts in the Biophysics of RNA to provide a broadly accessible snapshot of the current status of this rapidly expanding field. The 2006 Nobel Prize in Physiology or Medicine was awarded to the discoverers of RNA interference, highlighting just one example of a large number of non-protein coding RNAs. Because non-protein coding RNAs outnumber protein coding genes in mammals and other higher eukaryotes, it is now thought that the complexity of organisms is correlated with the fraction of their genome that encodes non-protein coding RNAs. Essential biological processes as diverse as cell differentiation, suppression of infecting viruses and parasitic transposons, higher-level organization of eukaryotic chromosomes, and gene expression itself are found to largely be directed by non-protein coding RNAs. The biophysical study of these RNAs employs X-ray crystallography, NMR, ensemble and single molecule fluorescence spectroscopy, optical tweezers, cryo-electron microscopy, and other quantitative tools. This emerging field has begun to unravel the molecular underpinnings of how RNAs fulfill their multitude of roles in sustaining cellular life. The physical and chemical understanding of RNA biology that results from biophysical studies is critical to our ability to harness RNAs for use in biotechnology and human therapy, a prospect that has recently spawned a multi-billion dollar industry.

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.

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.

Neuroimmunology is one of the most rapidly developing branches of Neurobiology, prompted by novel neurochemical, neuroendocrinological and neurophysiological investigations of the central and peripheral nervous system including neuro-endocrine systems. Neuroimmunology can be considered an interdisciplinary science that covers relevant aspects of how the peripheral immune system can influence brain physiology and elicit neuro-endocrine immuno-regulatory responses and also how local interactions between immune and neuronal mediators of the brain influence the occurrence and course of neuropathologic diseases. That explains the reason why we have in this volume chapters that focus on immune-neuro-endocrine interactions underlying the control and regulation of processes involved in both immune and brain physiology and in the pathogenesis of different nervous diseases. Among such diseases are: schizophrenia, HIV, associated dementia, rheumatoid arthritis, several experimental pathologies, multiple sclerosis, autoimmune encephalomyelitis, Theilers virus infection, nervous system demyelination diseases, the primary degenerative disorders such as Alzheimera (TM)s and Parkinsona (TM)s as well as brain injuries resulting from stroke and trauma, the neuroimmunology of gene therapy, amyotrophic lateral sclerosis, prion disease and all theoretical questions covering these pathologies. All of the above mentioned involve autoimmune processes.

It is difficult, indeed, to imagine fundamental neurobiological processes, autoimmune, neuroendocrine and infectious diseases, where immune factors are not of prime importance. The elucidation of the intimate molecular-biological problems ofimmunopathologies requires deep knowledge of the intricate connection between immunomodulators, immune competent cells of blood, brain, and other organs.

This volume contains data on multiple immunomodulators, many of which are also the products of hypothalamic brain cell neurosecretion. Interleukins (IL-1a, IL-1A, IL-2, IL-4, IL-6, TNFa), immunophylin and ubiquitin as well as proline rich peptides, comprised of 10-15 amino acids are being produced in N. Supraopticus and N. Paraventricularis and then secreted into neurohypophysis. Along the neurosecretion of the mentioned cytokines, there are other immunomodulators, the primary structure of which had been completely deciphered such as: Immunophyllins, intracellular receptors of immunosuppressors FK506, cyclosporine A., rapamicin. They are peptidyl-prolyl-cis-trans-isomerases. There are novel immunological hypothalamic factors such as ubiquitin, macrophage migration inhibitory factor (MIF), as well as Thymosin A 4(1-39). This data allowed us to propose the concept of neuroendocrine immune system of the brain.

This book presents a compendium of methodologies for the study of membrane lipids, varying from traditional lab bench experimentation to computer simulation and theoretical models. The volume provides a comprehensive set of techniques for studying membrane lipids with a strong biophysical emphasis. It compares the various available techniques including the pros and cons as seen by the experts.

Apoptosis is the regulated form of cell death. It is a complex process defined by a set of characteristic morphological and biochemical features that involves the active participation of affected cells in a self-destruction cascade. This programmed cell death plays a critical role in physiological functions such as cell deletion during embryonic development, balancing cell number in continuously renewing tissues and immune system development. Additionally, a dysregulation of apoptosis is underlying in numerous pathological situations such as Parkinson, Alzheimer's disease and cancer. A number of studies have pointed out an association between consumption of fruits and vegetables, and certain beverages such as tea and wine, which are rich in polyphenols, with reduced risk of chronic diseases, including cancer. Apoptosis is also the regulatory mechanism involved in the removal of unnecessary cells during development and in tissue homeostasis in a wide range of organisms from insects to mammals. This book presents exciting research in this related field.

Stroke is a global health problem affecting approximately 15 million people annually in the world and about 700,000 in the United States. It is the third leading cause of death and the most common cause of disability in most developed countries.

Acute Ischemic Injury and Repair in the Nervous System is intended to provide the most up-to-date knowledge of the mechanisms of neuronal death and repair after stroke. It is our belief that this volume of the Handbook of Neurochemistry and Molecular Neurobiology provides an excellent review of the tremendous advances of the past decades in the neurochemical and molecular biological aspects of cerebral ischemia. It is hoped that these advances will provide an impetus for basic scientists and clinicians to further their translational research and to promote the insights for development of therapeutic interventions for stroke.

Apoptosis is the regulated form of cell death. It is a complex process defined by a set of characteristic morphological and biochemical features that involves the active participation of affected cells in a self-destruction cascade. This programmed cell death plays a critical role in physiological functions such as cell deletion during embryonic development, balancing cell number in continuously renewing tissues and immune system development. Additionally, a dysregulation of apoptosis is underlying in numerous pathological situations such as Parkinson, Alzheimer s disease and cancer. A number of studies have pointed out an association between consumption of fruits and vegetables, and certain beverages such as tea and wine, which are rich in polyphenols, with reduced risk of chronic diseases, including cancer. Apoptosis is also the regulatory mechanism involved in the removal of unnecessary cells during development and in tissue homeostasis in a wide range of organisms from insects to mammals. This book focuses on cell apoptotic signalling.

This volume is a collection of a variety of brain proteins and peptides whose structures and functions are relatively well known. Each chapter provides a succinct and up-to-date summary of a protein or peptide as well as a review of the individual's contributions to the field. The volume explores the progress that has been made in the field over the past few years and provides insight into the field today.

Cancer Morbidity and mortality result from invasive and metastatic spread. Currently, no therapies are aimed at the underlying mechanisms that enable this progression due to only nascent recognition of the distinct biology which occurs only during tumor dissemination. Recent advances have highlighted the central role of cell motility during the dynamic and transient process of tumor invasion and metastasis. This book includes state-of-the-art updates by international leaders in these studies. Chapters first present the novel model systems that enable new investigations and insights. Chapters then describe in depth the key processes and molecules that may be therapeutically targeted. Finally, the role of cell motility and its signals is explored in a number of key tumor types. This compilation should be useful to researchers in basic and translational oncology as well as those developing novel agents to prevent tumor invasion and metastasis.

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.

A comprehensive one-source guide to the most current information on red blood cell formation and the action of recombinant human erythropoietins. Topics covered include: erythropoiesis, recombinant protein discovery and production, and treatment of patients with anemia. The newest theories in erythropoiesis (receptors, signaling), manufacturing, new formulations, and clinical research are discussed. The text is ideal for researchers and clinical investigators in academia, biotechnology, and pharmaceutical companies, as well as clinical research associates, clinical monitors, and physician investigators. This softcover volume is an unchanged second printing of the hardcover edition published in 2003.

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.

Brain Control of Wakefulness and Sleeping explores the history of efforts to understand the nature of waking and sleeping states from a biological point of view. This research represents the synthesis of the work of two individuals who have devoted their careers to investigating the mysterious states of the mind. This landmark book will interest the beginner scientist/researcher as well as the sleep clinician, with chapters on subjects including Neuronal Control of REM Sleep, Motor Systems and the Role of Active Forebrain, and Humoral Systems in Sleep Control. The authors explore the behavioral and physiological events of waking and sleep, analyzing the current realities and the future possibilities of unifying basic studies on anatomy and cellular psychology.

The brain is an enormously dynamic organ. Even when we sleep connections are made, signals sent and messages delivered. One of the key ways that the brain operates is via chemical stimuli which permits different parts of the brain to communicate between themselves and with the rest of the body. Determining what these chemicals, proteins and molecules are is an important way to not only discover how the brain works, but provide novel targets that may be useful in the treatment of disease, for instance in dealing with memory loss in dementia. This new book brings together international research in a broad range of topics, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism, as well as the neurochemistry of neurological and psychiatric disorders of the CNS.

The brain is an enormously dynamic organ. Even when we sleep connections are made, signals sent and messages delivered. One of the key ways that the brain operates is via chemical stimuli which permits different parts of the brain to communicate between themselves and with the rest of the body. Determining what these chemicals, proteins and molecules are is an important way to not only discover how the brain works, but provide novel targets that may be useful in the treatment of disease, for instance in dealing with memory loss in dementia.. This new book brings together international research in a broad range of topics including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.

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.

Welcome to the City of Groningen, the center of the North of the Netherlands. Groningen is proud of the long lasting tradition of scientific symposia organised by the Sanquin Blood Bank. These Sanquin International Symposia on Blood Transfusion have become a true traditional event in Groningen, marking the early academic year and have contributed to the specific reputation of Groningen and its University in the scientific field of Transfusion Medicine. The growing tradition has also contributed to initiatives of both University, Province and the City of Groningen to bring science and industry together - BioMedCity Groningen. Such repu- tion does not just happen, but is the result of creative and scientific leadership, of vision and an open mind, to explore in a team spirit horizons. Groningen is particularly proud of this reputation thanks to its leadership, the Sanquin Blood Bank North-East. This year in particular the theme chosen some two years ago is extremely timely as it illustrates the activities and scientific interest of an integrated team which includes our regional Sanquin Blood Bank North-East and fits in the City initiatives within the concept of BioMedCity, Groningen.

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.

Ion channels are a diverse class of transmembrane proteins responsible for rapid passive movement of selected ions across cell membranes. They play a crucial role in regulating diverse cell functions in both electrically excitable and non-excitable cells, and have been found in organisms ranging from viruses and bacteria to plants and mammals. An increasing number of diseases are associated with dysfunction of ion channels. In particular, many human neurological and muscular disorders have been traced to defects in voltage-gated and ligand-gated ion channels. Furthermore, ion channels provide paradigms for other, possibly more complex, membrane transport proteins. In this respect, they present an almost unique opportunity to use computational approaches to attempt to understand the function of membrane proteins, starting with an atomic resolution structure and progressing through a hierarchy of theoretical descriptions until one can account quantitatively for their physiological function. This important book results from a meeting of physiologists, structural biologists and theorists who came together to discuss their work and help define future directions. Topics covered include the X-ray structure of channels and pores, computer simulation of channel function, and detailed data on individual ion channels.