The fermentation of sugar by cell-free yeast extracts was demonstrated more than a century ago by E. Buchner (Nobel Prize 1907). Buchner's observations put an end to previous animistic theories regarding cellular life. It became clear that metabolism and all cellular functions should be accessible to explication in chemical terms. Equally important for an understanding of living systems was the concept, explained in physical terms, that all living things could be cons- ered as energy converters [E. Schroedinger (Nobel Prize 1933)] which generate complexity at the expense of an increase in entropy in their environment. Bioenergetics was established as an essential branch of the biochemical sciences by the investigations into the chemistry of photosynthesis in i- lated plant organelles [O. Warburg (Nobel Prize 1931)] and by the discovery that mitochondria were the morphological equivalent that catalyzed cellular respiration. The ?eld of bioenergetics also encompasses a large variety of ad- tional processes such as the molecular mechanisms of muscle contraction, the structure and driving mechanisms of microbial ?agellar motors, the energetics of solute transport, the extrusion of macromolecules across membranes, the transformation of quanta of light into visual information and the maintenance of complex synaptic communications. There are many other examples which, in most cases, may perform secondary energy transformations, utilizing - ergy stored either in the cellular ATP pool or in electrochemical membrane potentials.

This book covers the tremendous progress in the current understanding of the molecular physiology of voltage-gated calcium channels. This book includes unparalleled insights into structural features of calcium channels due to X-ray crystallography and cryo-EM, which in turn yielded critical information into how these channels function under normal and pathophysiological conditions, and how they interact with calcium channel therapeutics. The chapters investigate how, with the advent of high throughput genome sequencing, numerous mutations in various calcium channel genes have been identified in patients with neurological, cardiovascular, neuropsychiatric and other disorders. This is further complemented through a much larger in vivo toolkit such as knock-out and knock-in mice. The chapters further discuss the increased complexity of calcium channel physiology that arises from mRNA editing and splicing. Finally, the book also provides an overview of the updated research on calcium channel inhibitors that can be used both in vivo and in vitro, and which may serve as a spring board for new calcium channel therapeutics for human disease. Voltage-Gated Calcium Channels is useful for academic researchers at all levels in neuroscience, biophysics, cell biology and drug discovery.

The fluid-mosaic model of membrane structure formulated by Singer and Nicolson in the early 1970s has proven to be a durable concept in terms of the principles governing the organization of the constituent lipids and proteins. During the past 30 or so years a great deal of information has accumulated on the composition of various cell membranes and how this is related to the dif ferent functions that membranes perform. Nevertheless, the task of explaining particular functions at the molecular level has been hampered by lack of struc tural detail at the atomic level. The reason for this is primarily the difficulty of crystallizing membrane proteins which require strategies that differ from those used to crystallize soluble proteins. The unique exception is bacteriorhodopsin of the purple membrane of Halobacterium halobium which is interpolated into a membrane that is neither fluid nor in a mosaic configuration. To date only 50 or so membrane proteins have been characterised to atomic resolution by diffraction methods, in contrast to the vast data accumulated on soluble proteins. Another factor that has been difficult to explain is the reason why the lipid compliment of membranes is often extremely complex. Many hundreds of different molecular species of lipid can be identified in some membranes. Remarkably, the particular composition of each membrane appears to be main tained within relatively narrow limits and its identity distinguished from other morphologically-distinct membranes.

This volume explores pericytes' roles under distinct pathological conditions, ranging from tumors, ALS, Alzheimer's disease, Multiple Sclerosis, stroke, diabetes, atherosclerosis, muscular dystrophies and more. Together with its companion volumes Pericyte Biology in Different Organs and Pericyte Biology - Novel Concepts, Pericyte Biology in Disease presents a comprehensive update on the latest information and most novel functions attributed to pericytes. To those researchers newer to this area, it will be useful to have the background information on these cells' unique history. It will be invaluable for both advanced cell biology students as well as researchers in cell biology, stem cell biology and clinicians involved with these specific diseases.

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

Mesenchymal stem cells (MSCs), a type of adult stem cells, have attracted the attention of scientists and physicians alike due to their unique biological properties and potential for disease treatment. As stem cell research is complex and progressing rapidly, it is important that the experts in this field share their views and perspectives. This book, co-edited by leading global researchers, is divided into three major sections and covers a broad range of topics concerning MSCs during their transition from benchside to bedside. The book is intended for researchers and clinicians in the field of stem cells. Dr. Robert Chunhua Zhao, MD. Ph.D is Cheung Kong Professor of Stem Cell Biology, Professor of Cell Biology at the Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, China Director of Center for Tissue Engineering, PUMC Chief scientist of 973 program Regional Editor of Stem Cells and Development.

This book describes the three gasotransmitters nitric oxide (NO), hydrogen sulphide (H2S) and carbon monoxide (CO) and their function as intracellular signalling molecules in plants. Common properties are shared by NO, H2S and CO: they are beneficial at low concentrations but hazardous in higher amounts; they are small molecules of gas; they can freely cross cell membranes; their effects do not rely on receptors; they are generated enzymatically and their production is regulated; their functions can be mimicked by exogenous application; and their cellular effects may or may not be mediated by second messengers, but have specific cellular and molecular targets. In plants, many aspects of the biology of gasotransmitters remain completely unknown and generate intriguing questions, which will be discussed in this book.

The potato (Solanum tuberosum L. ) tuber is a major food source in many countries of the world, and subsequently potato has been the target of a good deal of effort directed at engineering disease and herbicide tolerance, and improvements in various crop characteristics. Consequently investigations into the regulation of gene expression in tubers is relevant to these endeavours, as tubers are the main target organ for modification of gene expression. We have been interested in the regulation of genes in tubers for these reasons. Morphologically tubers are modified stems, which have enlarged radially by limited cell division and substantial expansion. At the molecular level, tuber development is characterised by a massive increase in starch deposition and the synthesis of a limited number of abundant proteins. These include proteinase inhibitors and a 40kd group of proteins called patatin, which are acyl hydrolases. Together these proteins account for over 50% of tuber proteins (reviewed by Bevan, 1991). The synthesis of these proteins has parallels to the synthesis of other somatic storage proteins, especially the VSP proteins of soybean. In both potato and soybean, removal of the sink for these proteins (tubers and pods, respectively) causes deposition in other tissues (Staswick, 1990). It is hypothesised that transcriptional control of the genes encoding these proteins is regulated in part by source-sink relationships of metabolites or other factors. In the case of VSPs, both amino acid levels and jasmonic acid play a major regulatory role (Staswick et aI.

In the recent years, a significant amount of research has emerged connecting the link between alcohol and cancer. The field has rapidly advanced, especially since the complex connection between alcohol and cancer has several unique sub areas that are being investigated. This proceedings volume will contain chapters based upon the presentation of the 2nd International Conference on Alcohol and Cancer in Colorado, 2013. The various topics explore the affects of alcohol on: liver and breast cancer; cell signaling and cancer; stem cells; biomarkers and metabolomics; aerodigestive cancers; cancer and the immune system and more.

All the information necessary to set up and run a tissue culture facility is provided in this introductory book.; ; Includes an overview of all the basic tissue culture techniques and describes in detail both the theoretical background and the practical a

In recent years, a new understanding of cell-penetrating peptides has emerged, helping researchers to expand beyond a number of long-held dogmas. In Cell-Penetrating Peptides: Methods and Protocols, expert researchers explore the latest information on cell-penetrating peptides (CPPs), providing insight into the most important and contemporary areas of CPP research. Chapters address the historical background of CPP studies, provide an overview of the growing field of research, investigate methods for testing CPP mechanisms, present a summary of methods that attempt to use properties of CPPs to study biochemical intracellular mechanisms of interaction and signal transduction, and include new ideas for turning CPP-based strategies into drugs. Composed in the highly successful Methods in Molecular Biology(TM) 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. Innovative and current, Cell-Penetrating Peptides: Methods and Protocols is an essential guide that allows researchers to study intracellular mechanisms in new ways, and to promote the future development of novel drugs.

This book describes these exciting new developments, and presents experimental and computational findings that altogether describe the frontier of knowledge in cellular and biomolecular mechanics, and the biological implications, in health and disease. The book is written for bioengineers with interest in cellular mechanics, for biophysicists, biochemists, medical researchers and all other professionals with interest in how cells produce and respond to mechanical loads.

Encyclopedia of Cancer, Third Edition, Three Volume Set provides a comprehensive, up-to-date overview of the multiple facets of the disease, including research, treatment and societal impact. This new edition comprises 180 contributions from renown experts who present the latest in Mechanisms, Hallmarks of Cancer, Causes of Cancer, Prevention and Control, Diagnosis and Therapy, Pathology and the Genetics of specific Cancers. Readers will find a comprehensive overview of the main areas of oncology, including etiology, mechanisms, prevention, and treatments, from basic science to clinical applications and public health, all set alongside the latest advances and hot topics that have emerged since the previous edition. Topics of interest in the field, including genomics and epigenomics, our understanding of the causes of cancer and the approaches to preventing it (e.g., HPV vaccination, role of obesity and nutrition, molecular markers of environmental exposures), new screening techniques (e.g., low-dose CT for lung cancer) and improvements in the treatment of many cancers (e.g., breast cancer, lung adenocarcinoma) are comprehensively and authoritatively presented.

Phagocytosis is the engulfment of particulate matter by cells. It is a fundamental (and probably "primitive") cell biological process which is important in single celled organisms such as amoeba; multicellular animals including coelenterates; and in higher animals. In humans and other mammals, specialised immune cells (phagocytes) utilise phagocytosis in their crucial role of engulfing and destroying infecting microbes. Yet, surprisingly, the biophysics and biochemistry underlying the process has only become clear recently with the advent of genetic manipulation and advances in single cell imaging. In this volume, the aim is to bring together recent fundamental advances that give a clear picture of the underlying mechanism involved in phagocytosis. Not only is this an important topic in its own right, but a full understanding of the process will have a potential impact on human medicine, since as antibiotics become less effective in fight infection, researchers are looking at alternative approaches, including enhancing the "natural" immunity brought about by immune phagocytes. The aim is to provide a comprehensive volume on the topic, with separate chapters on identified recent advances, each written by the major contributors in each area. In addition, the volume will attempt to give a wider overview than is often the case in single author reviews, with an emphasis here on the cell biological understanding of phagocytosis using biophysical approaches alongside the biochemical and imaging approaches.

This edited volume focuses on the interplay between sleep and circadian rhythms with health, aging and longevity. Sleep is absolutely important for human health and survival, as insufficient sleep is associated with a plethora of conditions, including the poor quality of life, onset of several diseases, and premature death. The sleep-wake cycle is an evolutionary conserved neurobiological phenomenon, and is a prominent manifestation of the biological clocks localised in the suprachiasmatic nucleus (SCN). Understanding bidirectional relationship between sleep and circadian rhythms is of utmost importance and urgency, especially in the context of modern lifestyle where sleep is often out of phase with the internal body clocks, social jetlag, artificial lights and so on. The 25 chapters by leading researchers and experts from 11 countries are arranged into seven sections: understanding sleep and clock interlink in health and longevity; sleep, aging and longevity; clock, aging and longevity; melatonin, sleep and clock; genetic regulation of sleep and clock; therapeutic interventions in sleep disorders and clock misalignment; and experimental models to study sleep and clocks in aging and longevity. This book is useful for advanced undergraduate and graduate students, and researchers, educators, and other biomedical professionals.

Abiotic stresses such as high temperature, low-temperature, drought, and salinity limit crop productivity worldwide. Understanding plant responses to these stresses is essential for rational engineering of crop plants. In Arabidopsis, the signal transduction pathways for abiotic stresses, light, several phytohormones and pathogenesis have been elucidated. A significant portion of plant genomes (most studies are Arabidopsis and rice genome) encodes for proteins involves in signaling such as receptor, sensors, kinases, phosphatases, transcription factors and transporters/channels. Despite decades of physiological and molecular effort, knowledge pertaining to how plants sense and transduce low and high temperature, low-water availability (drought), water-submergence and salinity signals is still a major question before plant biologists. One major constraint hampering our understanding of these signal transduction processes in plants has been the lack or slow pace of application of molecular genomic and genetics knowledge in the form of gene function. In the post-genomic era, one of the major challenges is investigation and understanding of multiple genes and gene families regulating a particular physiological and developmental aspect of plant life cycle. One of the important physiological processes is regulation of stress response, which leads to adaptation or adjustment in response to adverse stimuli. With the holistic understanding of the signaling pathways involving not only one gene family but multiple genes or gene families, plant biologists can lay a foundation for designing and generating future crops that can withstand the higher degree of environmental stresses (especially abiotic stresses, which are the major cause of crop loss throughout the world) without losing crop yield and productivity.

Polymer and cell dynamics play an important role in processes like tumor growth, metastasis, embryogenesis, immune reactions and regeneration. This volume based on an international workshop on numerical simulations of polymer and cell dynamics in Bad Honnef (Germany) in 2000 provides an overview of the relevant mathematical and numerical methods, their applications and limits. The contributions are from the fields of applied and numerical mathematics, scientific computing, theoretical physics, molecular biophysics, cell and molecular biology as well as chemical and biomedical engineering. The volume will be of interest to scientists and advanced undergraduates in the fields of biotechnology, biomedicine, applied mathematics, biomathematics, biophysics and bioinformatics."

This detailed volume collects updates on the technical advances in hematopoietic stem cell research and incorporates new techniques focused on the molecular/genetic, cellular, and whole organism levels. Exploring methods that apply stress to hematopoiesis, the book also contains chapters focused on better understanding the role of hematopoietic niches and their cellular components, as well as in vivo models that test and quantitate stem cell function and are key to further development of therapeutic applications. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Hematopoietic Stem Cells: Methods and Protocols serves as a valued addition to laboratories focused on understanding hematopoietic stem cell biology and the therapeutic advances that can be derived from it.

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

Concentrating on proven data and adopting a structure-function approach, this text provides grounding for an intricate understanding of the molecular biology, physiological mechanisms, and routine clinical use in disease settings of colony-stimulating factors (CSFs). This edition includes eight additional chapters, with updates of recently-discovered and established CSFs, each indexed individually.

Several years ago, when the discovery of catalytic RNA was recognized in a public manner,many people asked if new ?elds of therapy would soon be available. Although some tentative positive answers were given,nobody would say with certainty that RNA of various kinds was a truly promising means of altering gene expression. In fact,over the past decade,both our knowledge of RNAs with different functions and the utility of RNA in the inhibition or enhancement of gene expression have occurred with great drama. We proceeded in terms of possible therapeutic tools from RNase P and group I introns through "hammerhead" RNA enzymes, antisense technology, and more recently, to RNAi and its derivatives. A useful practical method of RNA delivery in animals will complete the picture. The diversity of RNA and the varied role of it inside cells and in therapy should be a tremendous challenge for young molecular biologists. This volume will make their task easier. Sidney Altman Sterling Professor of Molecular,Cellular & Devel- mental Biology,Nobel Laureate Department of Molecular,Cellular and Developm- tal Biology Yale University V NGTPR 4/23/05 1:00 PM Page VI VI Foreword Delivery of nucleic acids to cells in an animal remains a challenging problem. It is the major obstacle to success of therapeutic approaches using genes and oli- nucleotides,including siRNAs. Solutions found so far by chemists are satisfactory only for transfection of cells in culture.

T-type calcium channels are prevalent in every organ of the body, and are believed to play a part in a variety of physiological processes, including contraction, shape change, secretion, endo- and exocytosis, cell proliferation and differentiation, modulation of enzyme function, and cell cycle progression. As such, research on the roles of these channels in a wide range of diseases has attracted increasing attention in recent years. The purpose of this book is to present a series of unique and comprehensive reviews of our current understanding of T-type calcium channels at the level of the basic sciences as well as the clinical sciences. For key organ systems, information is provided on the correlation between the molecular, biophysical and pharmacological properties of the channels, their cellular mechanisms, and their potential roles in the pathogenesis of various diseases. The compilation presents both commonplace and less well-known findings on these channels in a format designed to appeal to both casual readers and specialists in basic and clinical research on these transporters.

This volume provides the most widely used protocols and techniques employed in lipopolysaccharide( LPS) transport studies. Chapters detail identification and analysis of essential genes and crucial mutations in LPS transport-related genes, LPS profile determination, LPS chemical analysis, protein-LPS interaction, and LPS visualization. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Lipopolysaccharide Transport: Methods and Protocols aims to deliver an overview on the multidisciplinary study of LPS transport and to identify new and innovative antibacterial strategies.

This volume examines the role of mitochondria in different types of cell death, including apoptotic and necrotic cell deaths. Topics discussed include mitochondrial outer membrane permeabilization (MOMP) and the permeability transition pore; core processes such as calcium handling, fission and fusion, reactive oxygen species generation, and maintenance of mitochondrial DNA fidelity and protein folding homeostasis; and retrograde signaling between mitochondria and other cellular components, including the important role of mitochondria in antiviral immunity. The expertly authored chapters are drawn from multidisciplinary international perspectives, lending a nuanced and comprehensive approach to the material. Mitochondria and Cell Death, part of the Cell Death in Biology and Diseases series, is invaluable reading for graduate students, researchers, and clinicians in the fields of neuroscience, oncology, gastroenterology, and hepatology, as well as those interested in the study of mitochondria and cell biology.

A comprehensive collection of optimized methods for dissecting the mechanisms that control epidermal growth factors (EGF) and their regulators in both normal and pathological states. These readily reproducible techniques range from the study of purified EGF receptor to complex signaling and processing networks in intact cells, including a chapter on the clinical and pharmacological considerations of their use in cancer therapy. The protocols follow the successful Methods in Molecular Biology (TM) series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.