* Several in vivo assays are currently used in the study of angiogenesis and antiangiogenesis * The chick embryo chorioallantoic membrane is one of the most common and versatile assay to study angiogenesis and antiangiogenesis in vivo * Angiogenesis plays a critical role in tumor progression and metastasis * Antiangiogenesis is one of most promising approach to the treatment of cancer and metastasis The chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane which serves as a gas exchange surface and its function is supported by a dense capillary network. Because of its extensive vascularization and easy accessibility, the CAM has been broadly used to study the morpho-functional aspects of the angiogenesis process in vivo and to investigate the efficacy and mechanisms of action of pro-angiogenic and anti-angiogenic natural and synthetic molecules. The CAM is a suitable site for transplanting tissues, which can survive and develop in the CAM by peripheral anastomoses between graft and original CAM vasculature or by new angiogenic vessels grown from the CAM that invade the graft. While the formation of peripheral anastomoses between host and pre-existing donor vessels is the main, and the most common, mechanism involved in the revascularization of embryonic grafts, the growth of CAM-derived vessels into the graft is only stimulated in tumor grafts. The CAM has long been a favored system for the study of tumor angiogenesis and metastasis, because at this stage the chick immunocompetence system is not fully developed and the conditions for rejection have not been established. Tumors remain avascular for 72 h, after which they are penetrated by new blood vessels and begin a phase of rapid growth. Also, delivery of tumor cells onto the CAM allows the fine study of the effects of tumor derived angiogenic growth factors on blood vessel structure and functionality. The CAM may also used to verify the ability to inhibit th

This volume represents the proceedings of the 9th International Proton Transport Conference, "Mechanisms and Consequences of Proton Transport" held in Leura, Australia, August 19 -21, 200 I. This conference has been held since 1971 every 3 to 4 years with few exceptions in association with the Congress of the International Union of Physiological Sciences. The first meeting was held in Frankfurt, Germany, at the Max-Planck'Institute. Countries hosting the conference have been Germany (twice), Sweden (twice), India, Canada, USA, Great Britain, and now Australia. Over the past 30 years participants at these Proton Transport Conferences have been principal contributors to the major discoveries in the physiology, biochemistry and pharmacology of gastric acid secretion. These include development of the H2-receptor blockers, defining the signaling pathways for the regulation of acid secretion, identifying the gastric proton pump, discovery and development of proton pump inhibitory drugs, and elucidating the physiology and biochemistry of Helicobacter pylori.

Cutting-edge articles review our current understanding of lipid microdomain signaling mechanisms and their physiological and pathological importance. The book describes the role of lipid rafts in learning, memory, and cancer, presents the emerging evidence that lipid rafts play critical roles in signaling pathways and the regulation of synaptic function in the nervous system, and shows how alterations in lipid raft metabolism are implicated in the pathogenesis of neurodegenerative disorders. Techniques are also described for the isolation of lipid rafts, the analysis of the lipid and protein components of lipid rafts, the imaging of lipid rafts in living cells, and the analysis of signal transduction in lipid rafts.

Since the epochal discovery of the radical and highly toxic gas nitric oxide (NO) as a signaling molecule, two other no less toxic gases - carbon monoxide (CO) and hydrogen sulfide (H2S) - have been found to also be involved in a plethora of physiological and pathophysiological functions. The gases termed gasotransmitters play an increasingly important role in understanding how signalling into and between cells is modulated and fine-tuned. The advent of gasotransmitters has profoundly changed our way of thinking about biosynthesis, liberation, storage and action mechanisms in cellular signaling. In recent years an impressive amount of new data, distributed throughout the existing literature, has been generated. For this book the editors have recruited distinguished colleagues in the field to summarize and review important biological, pharmacological and medical functions and their implications, as well as methods for the detection of gasotransmitters.

Death receptors play a central role in directing apoptosis in mammalian cells. This process of active cell death is important for a number of biological processes, e.g. for the regulation of the immune system. Death receptors are cell surface receptors that transmit apoptotic signals initiated by corresponding death ligands. Many complex signaling pathways are activated and apoptosis is the final result of a complex biochemical cascade of events.

Besides their role in the induction of cell death, evidence now exists that death receptors are able to activate several non-apoptotic signaling pathways which, depending on cellular context, may lead to apoptosis resistance, secretion of pro-inflammatory proteins, proliferation and invasive growth of cancer cells.

This book looks at the molecular basis of death receptor signaling and the role of death receptors in cancer development.

Metastatic dissemination of cancer is a main cause of cancer related deaths, therefore biological mechanisms implicated in metastatic process presents an essential object of cancer research. This research requires creation and utilization of adequate laboratory models. The book describes main approaches to model processes of metastatic cancer dissemination and metastases development. The book is structured in according with various metastatic pathways reflecting molecular specificity of metastatic process as well as anatomical specificity of aria of dissemination. Each chapter is introduced by short discussion of clinical aspects of certain metastatic pathway. Especial attention is paid for methods of visualization, quantification and analysis of the modeled metastases. Additional chapter is devoted to methods of mathematic modeling of tumor spread. The data presented in the book may be helpful for cancer researchers and oncologists.

During the last decade, modern technologies have made a revolutionary change in developmental biology. The molecular and cellular processes in live embryos can now be visualized thanks to technologies using fluorescent proteins. The whole genome information of a wide range of animal species has now become available, confirming the common principles that operate in every species. These and other advances in our understanding of the developmental processes during embryogenesis and tissue regeneration have put forward new principles. Those new principles will also be important in the stem cell biology, branched from developmental biology, in order to generate a particular tissue by manipulating stem cells. This book is planned to introduce these new principles to readers who are working in developmental biology and/or stem cell biology fields, with an emphasis on genetic and cellular processes.

The human body contains many specialized tissues that are capable of fulfilling an incredible variety of functions necessary for our survival. This volume in the Human Cell Culture Series focuses on mesenchymal tissues and cells. The in vitro study of mesenchymal cells is perhaps the oldest form of human cell culture, beginning with the culturing of fibroblasts. Fibroblasts have long been generically described in the literature, arising from many tissue types upon in vitro cell culture. However, recent studies, many enabled by new molecular biology techniques, have shown considerable diversity in fibroblast type and function, as described within this volume. Mesenchymal tissue types that are described within include bone, cartilage, tendons and ligaments, muscle, adipose tissue, and skin (dermis). The proper function of these tissues is predominantly dependent upon the proper proliferation, differentiation, and function of the mesenchymal cells which make up the tissue. Recent advancements in primary human mesenchymal cell culture have led to remarkable progress in the study of these tissues. Landmark experiments have now demonstrated a stem cell basis for many of these tissues, and, furthermore, significant plasticity and inter-conversion of stem cells between these tissues, resulting in a great deal of contemporary excitement and controversy. Newly-developed mesenchymal cell culture techniques have even lead to novel clinical practices for the treatment of disease.

Research over the years has demonstrated that free radicals mediated oxidative stress lies at the helm of almost all patho-physiological phenomena. These findings emphasize on the need to understand the underlying molecular mechanism(s) and their critical role in the pathogenesis. This book aims to focus on these areas to provide readers a comprehensive outlook about the major redox sensitive pathways and networks involved in various disease conditions. In the first chapter of the book, basic information about the oxidative stress, its generation, its biomarkers and its role in body are discussed. In the next three chapters, the role of oxidative stress in various pathologies ranging from neurological disorders, to cardiovascular diseases, cancers, metabolic diseases and ageing have been described. Chapter 5 cumulatively describes the most important molecular signaling pathways that are affected by reactive oxygen species (ROS). These are the mechanisms which are common denominators in various pathological states. In the next part of the book, various antioxidant strategies to target and mitigate ROS have been discussed with details on the mechanisms. Selenium, being the research focus and interest of the authors for years, the role of selenium as an antioxidant as part of selenoproteins has been included in the book. Finally, the book culminates with authors' perspective on the future of the redox biology field. Throughout the book, efforts have been made to use simplified language and suitable figures for ease to understand the contents. Although the authors have tried to touch on all the different aspects of oxidative stress in detail, the fact that it is a continuously growing field with updates coming every day, there might be some areas which might not be described in depth. This book is designed for students, young scientists to get acquainted with the redox biology. Overall, this book is a reference to understand the redox regulation of cellular signaling pathways involved in pathogenesis.

Homeostasis. The health of an organism is influenced by external and internal changes that may lead to the loss of homeostasis. Under healthy conditions organisms compensate these changes. If compensation fails disease ensues. Attention will be paid to lifestyle, environmental changes, genetic makeup and health system. It willbe answered how lifestyle, environment, genetic makeup and social conditions help to maintain or upset the biological balance and lead to cancer.
Tumor formation. To understand this process the transfer of intracellular and the pathways of extracellular information (signal transduction) will be reviewed briefly. Loss of cellular balance may lead to cell death (.e.g. apoptosis) or to rapid cell growth of cells leading to tumor formation.
Metastasis. Animal tumor models serve to understand the spread of the primary tumor cells to distant locations of the organism. Different types of tumors and metastases will be reviewed. "

The book contains chapters written by leaders in the research on the structure and function of respiratory complex I. It will provide a concise and authoritative summary of the current knowledge on complex I of respiratory chains. This enzyme is central to energy metabolism and is implicated in many human neurodegenerative diseases, as well as in aging. Until recently it was poorly understood on a structural level, and this book will provide a timely reference resource. Such a book was not published previously. The last time a minireview series on complex I were published was in 2001, and since then complex I field changed quite dramatically.

Membrane proteins play a key role in numerous pathologies such as cancer, cystic fibrosis, epilepsy, hyperinsulinism, and Alzheimer s disease, yet studies on these and other disorders are hampered by a lack of information about the proteins involved. In Heterologous Expression of Membrane Proteins: Methods and Protocols, expert researchers provide an overview of the different heterologous expression systems available to produce these proteins for structural analysis, helping us to understand how these proteins function, and additionally, how their functions can be modified through drug treatment. Chapters examine membrane protein solubilization, purification, and instability in solution, and investigate the strategies that helped to determine the structure of the first heterologously expressed mammalian membrane proteins. Composed in the highly successful Methods in Molecular Biology series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls.

Far-reaching and innovative, Heterologous Expression of Membrane Proteins: Methods and Protocols, is an essential guide for novice and experienced researchers alike, providing detailed methods for existing expression systems alongside cutting-edge strategies for future use in the field."

This volume provides a state-of-art-report on the new methodologies in tissue engineering and developments in the biomaterials field based on the extracellular matrix-relevant discovery. Extracellular Matrix for Tissue Engineering and Biomaterials opens with an overview of the latest extracellular matrix research and in Part I, focuses on its biology and its role on cell behavior and cell fate relevant for the design of biomimetic surfaces. Part II details issues regarding the strategies currently applied in the research of biologically inspired materials and material systems for the replacement, repair and regeneration of tissues and organs. Part III presents the latest development methods applying knowledge from biology towards nanotechnology, to promote the restoration of the functionality of a living tissue. The book ranges from fundamental biology associated with tissue regeneration for the development of biomimetic approaches to controlling tissue formation, cell function, differentiation and angiogenesis using factors involved in normal tissue development and function. With the breadth and depth of the coverage of this topic, this book will serve as a valuable reference for anyone working in tissue engineering or biomaterials - from scientists, chemists and biologists through physicists, bioengineers and clinicians.

This volume focuses on the use of system genetic methods and the use of murine models to study the role of gene variants and environmental factors on human health and disease-what is now often called personalized or precision health care. The protocols in this book will help readers analyze genetic causes of heritable variation across a wide range of systems and traits using rodent models. The chapters in this book are separated into three sections that cover: 1) resources for systems genetics; 2) tools for analysis and integration in systems genetics; and 3) systems genetics use cases. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and tools, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and thorough, Systems Genetics: Methods and Protocols is a valuable resource for anyone who is interested in this diverse field.

Endosomes are a heterogeneous population of endocytic vesicles and tubules that have captivated the interest of biologists for many years, partly due to their important cellular functions and partly due to their intriguing nature and dynamics. Endosomes represent a fascinating interconnected network of thousands of vesicles that transport various cargoes, mainly proteins and lipids, to distant cellular destinations. How endosomes function, what co-ordinates the molecular determinants at each step of their dynamic life cycle and what their biological and medical relevance is, are among the questions addressed in this book.

Harnessing the sun s energy via photosynthesis is at the core of sustainable production of food, fuel, and materials by plants, algae, and cyanobacteria. Photosynthesis depends on photoprotection against intense sunlight, starting with the safe removal of excess excitation energy from the light-harvesting system, which can be quickly and non-destructively assessed via non-photochemical quenching of chlorophyll fluorescence (NPQ). By placing NPQ into the context of whole-organism function, this book aims to contribute towards identification of plant and algal lines with superior stress resistance and productivity. By addressing agreements and open questions concerning photoprotection s molecular mechanisms, this book contributes towards development of artificial photosynthetic systems. A comprehensive picture from single molecules to organisms in ecosystems, and from leading expert s views to practical information for non-specialists on NPQ measurement and terminology is presented."

This book on cardiac extracellular matrix (ECM) features three sections, Fundamental Science, Pre-Clinical and Translational Science, and Clinical Applications. In the Fundamental Science section, we will cover the spectrum of basic ECM science from ECM's role in development, biomechanical properties, cardiac ECM influence of cardiomyocyte biology, pathophysiology of ECM in heart disease, and ECM in tissue engineering. Section two, Preclinical and Translational Science, will discuss cardiac ECM technologies in the clinical pipeline including approaches to ECM as a therapeutic, animal models of cardiac research, tracking and imaging methods of cardiac ECM, and cGMP manufacturing and regulatory considerations for ECM based therapeutics. Finally, the third section, Clinical Applications, will highlight the clinical experience around cardiac ECM including therapeutic strategies targeting scar tissue in the heart, Clinical trial design and regulatory considerations, current human clinical trials in cardiovascular medicine and the role of pharmaceutical and biotech companies in the commercialization of ECM technologies for cardiovascular indications. This book provides a comprehensive review for basic and translational researchers as well as clinical practitioners and those involved in commercialization, regulatory and entrepreneurial activities.

This book highlights recent advances in and diverse techniques for exploring the plasma membrane's structure and function. It starts with two chapters reviewing the history of membrane research and listing recent advances regarding membrane structure, such as the semi-mosaic model for red blood cell membranes and the protein layer-lipid-protein island model for nucleated tissue cell membranes. It subsequently focuses on the localization and interactions of membrane components, dynamic processes of membrane transport and transmembrane signal transduction. Classic and cutting-edge techniques (e.g. high-resolution atomic force microscopy and super-resolution fluorescence microscopy) used in biophysics and chemistry are presented in a very comprehensive manner, making them useful and accessible to both researchers in the field and novices studying cell membranes. This book provides readers a deeper understanding of the plasma membrane's organization at the single molecule level and opens a new way to reveal the relationship between the membrane's structure and functions, making it essential reading for researchers in various fields.

Lipobiology is an interdisciplinary field which incorporates critical aspects of lipid and lipoprotein chemistry into the disciplines of cell biology and physiology. During the last decade, advances in our understanding of the structure and function of lipids, biological membranes and lipid-derived second messengers have underscored the importance of lipids in the regulation of cellular function. This series focuses on salient aspects of the role of lipids in metabolic regulation and cellular activation, with emphasis on emerging concepts and technologies. One goal of this series is to formulate cohesive criteria upon which a foundation for the evaluation of recent work can be based and future directions of research identified.

Cells in the developing embryo depend on signals from the extracellular environment to help guide their differentiation. An important mediator in this process is the extracellular matrix -- secreted macromolecules that interact to form large protein networks outside the cell. During development, the extracellular matrix serves to separate adjacent cell groups, participates in establishing morphogenic gradients, and, through its ability to interact directly will cell-surface receptors, provides developmental clocks and positional information. This volume discusses how the extracellular matrix influences fundamental developmental processes and how model systems can be used to elucidate ECM function. The topics addressed range from how ECM influences early development as well as repair processes in the adult that recapitulate developmental pathways. The series Biology of Extracellular Matrix is published in collaboration with the American Society for Matrix Biology.

This book provides a comprehensive, up-to-date review of the distribution, pharmacology and physiology of central 5-hydroxytryptamine (5-HT)4 receptors. The 5-HT receptor subtypes exhibit a unique pharmacology, distribution and function, of which the 5-HT4 receptor has been one of the most intensively studied in recent years, both from a basic research standpoint and as a target for novel therapeutics.

Proteases form one of the largest and most diverse families of enzymes known. Once considered primarily as "enzymes of digestion," it is now clear that proteases are involved in every aspect of cellular function. Members of the diverse families of proteases act to promote cellular proteolysis found in nature, and their deregulation may result in different pathophysiological conditions, such as tumor progression, vascular remodeling, atherosclerotic plaque progression, ulcer, rheumatoid arthritis, and Alzheimer's disease. Many micro-organisms require proteases for replication or use proteases as virulence factors, which have facilitated the development of protease-targeted therapies for a variety of parasitic diseases. Proteases in Health and Disease represents a comprehensive overview of the fascinating field of proteases by various renowned experts, and focuses on the recently elucidated functions of complex proteolytic systems in physiology and pathophysiology. Part A, Molecular and Biochemical Aspects of Proteases, illustrates some of the major proteases, such as calpains, matrix metalloproteases, fibrinolytic serine proteases, and aspartic proteases, which play a significant role in a variety of pathologies and may be a target for therapy either by their up regulation or down regulation. Part B, Involvement of Proteases in Diseases Processes, deals with the functional roles of the individual proteases in the progression of diseases such as cardiovascular and inflammatory lung disease, malaria, cholera, autism spectrum disorder, hepatitis, and ischemia-reperfusion injury induced cardiac diseases. With this multi-disciplinary scope, the book bridges the gap between fundamental research and biomedical and pharmaceutical applications, making this a thought-provoking reading for basic and applied scientists engaged in biomedical research.

Tissue Repair, Contraction and the Myofibroblast summarizes the latest findings concerning the biology of the myofibroblast, a cell involved in the evolution and contraction of granulation tissue and of fibrotic changes. Coverage shows that the myofibroblast is responsible for the development of hypertrophic scars, pulmonary and renal fibrosis and bronchial asthma. Reviews the cell biology and pathology of the myofibroblast as well as mechanisms of fibrosis evolution in many organs and tissues.

Transcriptome Profiling: Progress and Prospects assists readers in assessing and interpreting a large number of genes, up to and including an entire genome. It provides key insights into the latest tools and techniques used in transcriptomics and its relevant topics which can reveal a global snapshot of the complete RNA component of a cell at a given time. This snapshot, in turn, enables the distinction between different cell types, different disease states, and different time points during development. Transcriptome analysis has been a key area of biological inquiry for decades. The next-generation sequencing technologies have revolutionized transcriptomics by providing opportunities for multidimensional examinations of cellular transcriptomes in which high-throughput expression data are obtained at a single-base resolution. Transcriptome analysis has evolved from the detection of single RNA molecules to large-scale gene expression profiling and genome annotation initiatives. Written by a team of global experts, key topics in Transcriptome Profiling include transcriptome characterization, expression analysis of transcripts, transcriptome and gene regulation, transcriptome profiling and human health, medicinal plants transcriptomics, transcriptomics and genetic engineering, transcriptomics in agriculture, and phylotranscriptomics.

"Biomimetics and Stem Cells: Methods and Protocols" collects a series of approaches to demonstrate the role and value of biomimetics for the better understanding of stem cell behavior and the acceleration of their application in regenerative medicine. Recent advances in tissue engineering are enabling scientists to instruct stem cells toward differentiating into the right phenotypes, in the right place and at the right time. Given these advances, biomimetic environments are being designed to recapitulate, in vitro, the combinations of factors known to guide tissue development and regeneration in vivo and thereby help unlock the full potential of the stem cells. 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.Practical and essential, "Biomimetics and Stem Cells: Methods and Protocols" focuses on the use of biomimetic systems for stem cells in order to aid in moving this vital field of study forward."