The three-dimensional organization of the DNA inside the eukaryotic cell nucleus has emerged a critical regulator of genome integrity and function. Increasing evidence indicates that nuclear pore complexes (NPCs), the large protein channels that connect the nucleus to the cytoplasm, play a critical role in the establishment and maintenance of chromatin organization and in the regulation of gene activity. These findings, which oppose the traditional view of NPCs as channels with only one: the facilitation of nucleocytoplasmic molecule exchange, have completely transformed our understanding of these structures. This book describes our current knowledge of the role of NPCs in genome organization and gene expression regulation. It starts by providing an overview of the different compartments and structures of the nucleus and how they contribute to organizing the genome, then moves to examine the direct roles of NPCs and their components in gene expression regulation in different organisms, and ends by describing the function of nuclear pores in the infection and genome integration of HIV, in DNA repair and telomere maintenance, and in the regulation of chromosome segregation and mitosis. This book provides an intellectual backdrop for anyone interested in understanding how the gatekeepers of the nucleus contribute to safeguarding the integrity and function of the eukaryotic genome.

Since the pioneering discoveries of Hodgkin, Huxley, and Katz, it has been clear that specific ion conductance pathways underlie electrical act- ity. Over the ensuing 50 years, there has been ever increasing, and occasi- ally explosive, changes in the scope of efforts to understand ion channel behavior. The introduction of patch clamp technology by Erwin Neher and Bert Sakmann about 20 years ago led to the realization of the great variety of novel ion channel species, and the subsequent revolution in cl- ing has revealed an even greater diversity of the underlying molecular entities. Today, advances in the study of ion channel structure and function c- tinue at a high pace, from angstrom resolution imaging of crystallized ch- nels to their genetic manipulations in animals. In this regard, the field is a balanced one that inquires not only what ion channel entities are there, or how they operate, but also where are these molecular electronic switches? However, this balance is not particularly well presented to the general sci- tific audience or to specialists in the field. There are plenty of wonderful and useful books and monographs, as well as conferences and meetings on v- tually every aspect of ion channel structure and function. However, we are unaware that the channel localization theme has been considered in a u- fied forum.

Leading experts critically summarize the state of knowledge concerning the molecular, anatomical, physiological, and behavioral aspects of NPY and its congeners. Each article provides a comprehensive and in-depth survey, an overview of the role of NPY in the discipline covered, a discussion of the likely future direction that the field will take, and an up-to-date bibliography.
Chapters include a treatment of the evolution of the PP family of genes, the structure of the NPY gene, and the distribution of NPY on the cardiovascular system, actions of NPY on the electrophysiological properties of nerve cells, and the effects of NPY on feeding and behavior. The chapters are written in an accessible style and serve both as an introduction to the field and as an extensive and detailed treatment of the current state of knowledge.

The Fifth Ir Gene Workshop was held at the Chase-Park Plaza Hotel, St. Louis, MO, August 28-31, 1982; 240 scientists participated in the Workshop. The man uscripts compiled in this book describe the state of the art concerning Ir genes. Although the notion of Ir Genes: Past, Present, and Future has not been ad dressed specifically by each author, the reader is certain to get this flavor from the contributions. In this Preface, we have tried to summarize some of the salient ob servations and discussions from the Workshop. The mUltiple genes of the I region have been defined traditionally by serolog ical analysis of intra-H-2 recombinant mice and the pattern of immune responses to certain antigens developed by these recombinant mice. The application of sev eral new techniques, such as gene cloning and DNA sequencing, production of T and B cell hybridomas, and development of cloned T cell lines has changed this tradition and introduced a new phase into the analysis of the I region, Ia antigens, and Ir genes."

This book surveys the current knowledge concerning the expression and function of small stress proteins (sHsps) in different organisms, ranging from prokaryotes to humans. It provides an overview of the diversity and complex evolutionary history of sHsps and describes their function and expression in different eukaryote models. Additional chapters discuss the involvement of sHsps in pathological conditions and gene therapy approaches towards a control of sHsp expression levels.

Molecular Mechanisms of Sarcolemar Excitability: Ion Channels and Pumps in Cardiac Function; H.A. Fozzard, G. Lipkind Molecular Mechanisms of K+ Channel Blockade: 4Aminopyridine Interaction with a Cloned Cardiac Transient K+(Kv1.4) Channel; R.L. Rasmusson Integrative Models and Responses in Cardiac Ischemia; S. Horner, M.J. Lab Intracellular Calcium and Muscle Function-SR and Filaments: Sarcomere Function and Crossbridge Cycling; H.E.D.J. ter Keurs Crossbridge Dynamics in Muscle Contraction; A. Landesberg, et al. Mechanisms of the Frank-Starling Phenomena Studies in Intact Hearts; D. Burkhoff, et al. Molecular Manifestations of Cell Adaptation: Metabolic Oscillations in Heart Cells; B. O'Rourke, et al. Regulation of Adenosine Receptors in Cultured Heart Cells; D. ElAni, et al. Ventricular Remodeling in Heart Failure: The Role of Myocardial Collagen; J.S. Janicki, et al. Analysis and Modeling: From Microstructure to Macroperformance: Mechanisms of Endocardial Endothelium Modulation of Myocardial Performance; P. Mohan, et al. Vascular Gene Therapy; M.Y. Flugelman Closure: Toward Modeling the Human Physionome; J.B. Bassingthwaighte 20 additional articles. Index.

Cancerremainstobeoneofthemostdevastatingdiseasesworldwidesincelong ago. Thepoorprognosisofcancerislargelyduetometastasis. Metastasisisoften depictedasamultistageprocessinwhichmalignantcellsspreadfromtheprimary locustodistantorgansviacirculation. Whereasgeneticalterationsweresuggested tobeessentialfortransformationofprimarytumorcellsintometastaticphenotype, epigeneticeventsareequallyimportant,whichmaybetriggeredbymetastaticf- torswhereverintheprimarytumorlocus,bloodcirculationandthesecondaryloci. Signaltransductionsinitiatedbythemetastaticfactorsareresponsibleformediating themolecularandcellularprocessesleadingtometastasis. Blockadeoftherelevant molecularpathwaysisoneofthemosteffectivestrategiesforpreventionoftumor metastasis. Clinicaltrialsareunderwaywithpromisingoutcome. Inthisbook, wetakecomprehensive review inregard withthisexciting eld ofcancerresearch. Chapter1takesabriefoverviewofrecentlyidenti edsignal mechanismsforeachstepoftumormetastasisincludingtheinitiationstage,intra- sation,anti-anoikisinbloodcirculation,homing,extravasationand nalsurvivalin themetastaticsite. Chapter2makesacompletedreviewforthemolecularandcel- lareventsinvolvedininitiationofmetastasis. Especially,thesignalingmechanisms formediatingtumorprogressioninducedbysomeimportantmetastaticfactorsare described. InChapters3and4,thecentralrolesofMAPKanditsdownstreameff- torsMAPKAPKplayineachstepoftumormetastasisarewelldelineated. Chapter5 furtherdescribesdetailedlyabouthowGrb2andotheradaptorproteins,upstreamof MAPK cascade, contribute tometastasis. InChapter 6, therole ofreactive o- genspecies(ROS)intumorprogressionarehighlighted. Moreover,thepotential contribution of ROS to cross talk between major signaling cascades that lead to sustainedMAPKactivationareproposedinChapter7. Chapter8takesaninsight intothesignalingmechanismsfordynamictraf ckingandturnoveroffocalad- sionproteinsinregulationoftractionandretractionforces,whichareneededfor celllocomotionandinvasion. Chapter9describestheinvolvementofNotchsign- ingpathwaywhichisnotonlyessentialforembryonicdevelopmentbutalsoplays importantroleintumorprogression. Chapter10reviewedtherecentlyidenti ed cancer- and metastasis-initiating cells involved in tumor progression. Especially, signal pathways that are frequently deregulated in cancer stem/progenitor cells v vi Preface duringcancerprogressionarehighlighted. Chapter11describestheroleoflipid rafts, a special component within membrane lipid domain, in signal transd- tion triggered by growth factor receptors leading to tumor metastasis. Finally, Chapters12,Chapters13,andChapters14presentthesignalingpathwaysresp- sibleformetastaticprogressionofspeci ctumorsincludingovariancancer,uveal melanomaandhepatoma,respectively. WethankallthecontributorsofeveryChapterinthebookincludingJia-RuWu, Chi-TanHu,LaureVoisin,StephanieDuhamel,SylvainMeloche,AlexeyShiryaev, MarijkeVanGhelue,UgoMoens,AlessioGiubellino,PraveenR. Arany,Moulay A. Alaoui-Jamali, Krikor Bijian, Panagiota Toliopoulos, Pingyu Zhang, Patrick A. Zweidler-McKay,MurielleMimeault,SurinderK. Batra,SamirKumarPatra, LydiaW. T. Cheung,CarmanK. M. Ip,AliceS. T. Wong,CecileLaurent,Jerome Couturier,XavierSastre-Garau,LaurenceDesjardins,EmmanuelBarillot,Sophie Piperno-Neumann,SimonSauleandRajagopalN. Aravalli. Wehopethisbookmightstimulatemorecancerbiologiststoemphasizethis eld whichbene tsdevisingmoreeffectivemoleculartargetingstrategiesforprevention ofcancermetastasis. Hualien,Taiwan Wen-ShengWu Chi-TanHu Contents 1 Overview of Signal Transduction in Tumor Metastasis...1 Wen-ShengWuandJia-RuWu 2 Microenvironment Triggers EMT, Migration and Invasion of Primary Tumor via Multiple Signal Pathways ...9 Wen-ShengWuandChi-TanHu 3 The ERK1/2 MAP Kinase Signaling Pathway in Tumor Progression and Metastasis ...25 LaureVoisin,StephanieDuhamel,andSylvainMeloche 4 Mitogen-Activated Protein Kinase-Activated Protein Kinases and Metastasis...41 AlexeyShiryaev,MarijkeVanGhelue,andUgoMoens 5 Grb2 and Other Adaptor Proteins in Tumor Metastasis ...77 AlessioGiubellinoandPraveenR. Arany 6 The Role of ROS Signaling in Tumor Progression...103 Wen-ShengWuandJia-RuWu 7 Signal Cross Talks for Sustained MAPK Activation and Cell Migration Mediated by Reactive Oxygen Species: The Involvement in Tumor Progression...

This book deals with the role of water in cell function. Though long recognized to be central to cell function, water's role has not received the attention lately that it deserves. This book brings the role of water front and central. It presents the most recent work of the leading authorities on the subject, culminating in a series of sometimes astonishing observations. Water is a subject of interest to virtually everyone. It is becoming increasingly important in health therapy, in the environment, in chemistry and physics, and certainly in cells. Thus, this groundbreaking volume will be of great interest to a broad audience, well beyond those in biology alone. The reader will be richly awarded with insights difficult or impossible to obtain in current textbooks, which generally treat water merely as a background carrier with limited significance.

This book presents the latest findings in mechanosensitive ion channel research compiled by a number of internationally recognized experts in the field of mechanosensitivity, specializing in mechanosensitive or mechanically gated ion channels and the underlying mechanosensitive signaling cascades. The book provides a comprehensive description of mechanotransduction, which is defined as the biochemical response of cells to mechanical stimulation, and provides the reader with the latest vision of signaling cascades. Descriptions of the most widely used experimental models, the methods of choice and references to experimental protocols, the latest experimental findings and current vision, and potential problems in data interpretation, will be of considerable use to all those interested in this field of research.

This detailed volume provides a comprehensive overview of state-of-the-art metabolomics methods based on mass spectrometry (MS), and their application in food, nutrition, and biomedical research. The chapters assembled herein cover hot topics related to sample preparation, chromatographic and electrophoretic separation, MS-based analysis, as well as data processing and analysis. 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 cutting-edge, Mass Spectrometry for Metabolomics serves as a timely guide for chemists, biochemists, biologists, nutritionists, clinicians, and other experts working in the growing and exciting field of metabolomics.

This volume introduces different concepts and methods of detecting RNA in biological material in a variety of model systems. The chapters in this book discuss methods that will answer numerous biological questions that arise in the study of RNAs. Some of the topics covered in this book are single mRNA molecule detection in embryos and neurons; detection of mRNA and associated molecules by ISH-IEM on frozen sections; optimizing molecular beacons for intracellular analysis of RNA; imaging translation dynamics of single mRNA molecules in live cells; preparation of high-throughput sequencing libraries; and capturing RNA binding proteins in embryos and in cell-culture. 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. Cutting-edge and comprehensive, RNA Detection: Methods and Protocols is a valuable resource for novel and experiences scientist in the expanding field of RNAs.

Many organisms have evolved the ability to enter into and revive from a dormant state. They can survive for long periods in this state (often even months to years), yet can become responsive again within minutes or hours. This is often, but not necessarily, associated with desiccation. Preserving onea (TM)s body and reviving it in future generations is a dream of mankind. To date, however, we have failed to learn how cells, tissues or entire organisms can be made dormant or be effectively revived at ambient temperatures. In this book studies on organisms, ranging from aquatic cyanobacteria that produce akinetes to hibernating mammals, are presented, and reveal common but also divergent physiological and molecular pathways for surviving in a dormant form or for tolerating harsh environments. Attempting to learn the functions associated with dormancy and how they are regulated is one of the great future challenges. Its relevance to the preservation of cells and tissues is one of the key concerns of this book.

Living beings require constant information processing for survival. In cells, information is being processed and propagated at various levels, from the gene regulatory network to chemical pathways, to the interaction with the environment. How this is achieved and how information is coded is still poorly understood. For example, what a cell interprets as information in the temporal level of an mRNA and what is interpreted as noise remains an open question. Recently, information theoretical methods and other tools, developed in the context of engineering and natural sciences, have been applied to study diverse biological processes. This book covers the latest findings on how information is processed in various biological processes, ranging from information processing and propagation in gene regulatory networks to information processing in natural language. An overview is presented of the state-of-the-art in information processing in biological systems and the opinion of current leaders in this research field on future research directions.

The past decade has witnessed an explosion of our knowledge on the structure, coding capacity and evolution of the genomes of the two DNA-containing cell organelles in plants: chloroplasts (plastids) and mitochondria. Comparative genomics analyses have provided new insights into the origin of organelles by endosymbioses and uncovered an enormous evolutionary dynamics of organellar genomes. In addition, they have greatly helped to clarify phylogenetic relationships, especially in algae and early land plants with limited morphological and anatomical diversity. This book, written by leading experts, summarizes our current knowledge about plastid and mitochondrial genomes in all major groups of algae and land plants. It also includes chapters on endosymbioses, plastid and mitochondrial mutants, gene expression profiling and methods for organelle transformation. The book is designed for students and researchers in plant molecular biology, taxonomy, biotechnology and evolutionary biology.

This book discusses advancements in the applications of nanoparticles in tissue engineering. It examines the applications of nanobiomaterials in hard tissue regeneration, fabrication, and characterization. The book also analyzes the implication of three-dimensional and four-dimensional fabrication techniques for the production of the scaffold in tissue engineering and their advantages over conventional scaffold production techniques. Further, it presents smart materials used in making 4-D scaffolds that imitate the dynamic response of tissue against natural stimuli and adapt to the microenvironment by changing their conformation or other properties. It also summarizes the growing field of biomolecular detection and biosensors in tissue engineering and the increasing prominence of nanoparticles in the biosensors. Further, it provides the future outlook and associated challenges of the application of nanomaterials in tissue engineering.

Animal cell technology is a growing discipline of cell biology which aims not only to understand structures, functions and behaviors of differentiated animal cells but also to uncover their abilities for industrial and medical purposes. The goal of animal cell technology includes clonal expansion of differentiated cells with useful abilities, optimization of their culture conditions on the industrial scale, modulation of their ability in order efficiently to produce medically and pharmaceutically important proteins, and application of animal cells to gene therapy and formation of artificial organs. This Volume gives the readers a complete review of the present state of the art in Japan, a country where this field is well advanced, as well as in Asia, Europe and the United States. The Proceedings will be useful for cell biologists, biochemists, molecular biologists, biochemical engineers and those in other disciplines related to animal cell culture, working in academic environments as well as in the biotechnology and pharmaceutical industries.

Applications of EPR in Radiation Research is a multi-author contributed volume presented in eight themes: I. Elementary radiation processes (in situ and low temperature radiolysis, quantum solids); II: Solid state radiation chemistry (crystalline, amorphous and heterogeneous systems); III: Biochemistry, biophysics and biology applications (radicals in biomaterials, spin trapping, free-radical-induced DNA damage); IV: Materials science (polymeric and electronic materials, materials for treatment of nuclear waste, irradiated food); V: Radiation metrology (EPR-dosimetry, retrospective and medical applications); VI: Geological dating; VII: Advanced techniques (PELDOR, ESE and ENDOR spectroscopy, matrix isolation); VIII: Theoretical tools (density-functional calculations, spectrum simulations).

This book sheds light on how dysregulated organelle functions contribute to the pathology and progression of human diseases. To offer a broad perspective, they discuss basic, translational, and clinical aspects across scales, from molecules to cells, tissues and organisms. Rather than providing a comprehensive introduction to the field, the authors focus on recent advances in organelle research, with each chapter inviting readers to consider today's key questions in the respective field. This book reviews the endoplasmic reticulum, Golgi Appartus, Lysosomes and other membrane-enclosed organelles, demonstrating how their dysregulated function contributes to various pathologies. The chapters not only offer a platform for new perspectives but also stimulate further investigations. Given the translational nature of this subject, this book is a valuable resource for physiologists and clinicians alike. Chapter "Lipid Droplets in Cancer" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Knowledge of cholesterol and its interaction with protein molecules is of fundamental importance in both animal and human biology. This book contains 22 chapters, dealing in depth with structural and functional aspects of the currently known and extremely diverse unrelated families of cholesterol-binding and cholesterol transport proteins. By drawing together this range of topics the Editor has attempted to correlate this broad field of study for the first time. Technical aspects are given considerable emphasis, particularly in relation cholesterol reporter molecules and to the isolation and study of membrane cholesterol- and sphingomyelin-rich "raft" domains. Cell biological, biochemical and clinical topics are included in this book, which serve to emphasize the acknowledged and important benefits to be gained from the study of cholesterol and cholesterol-binding proteins within the biomedical sciences and the involvement of cholesterol in several clinical disorders. It is hoped that by presenting this topic in this integrated manner that an appreciation of the fact that there is much more that needs to be taken into account, studied and understood than the widely discussed "bad and good cholesterol" associated, respectively, with the low- and high-density lipoproteins, LDL and HDL. Content Level Professional/practitioner

This book demonstrates the applications of synchrotron radiation in certain aspects of cell microbiology, specifically non-destructive elemental analyses, chemical-state analyses and imaging (distribution) of the elements within a cell. The basics for understanding and applications of synchrotron radiation are also described to make the contents more easily understood for a wide group of researchers in medical and biological sciences who might not be familiar with the physics of synchrotron radiation.

Serotonin (5-HT) was isolated and chemically characterized nearly four decades ago, and is now generally accepted to function as a neurotransmitter and neuromodulatory agent. Early research focused on the measurement of concentrations, synthesis, and metabolism of 5-HT, and only recently has the focus shifted to characterization of 5-HT receptors. Gaddum and Picarelli first sug gested in 1957 that the effect of 5-HT in the guinea pig ileum is mediated by two pharmacologically distinguishable receptors; however, the possibility of dual5-HT receptors was not explored systematically or successfully until the past decade. It is now clear that more, perhaps many more, subclasses of 5-HT receptors exist. The purpose of this book is to provide an up-to-date report on 5-HT receptors. This is a difficult task considering the astonishing speed at which research in this field is expanding. As the first of what we can expect to be a steady stream of monographs focusing on 5-HT receptors, the book confirms that we are in an exciting time in the history of 5-HT. For those of us who have been work ing on 5-HT for many years, our dream of equal progress and recognition with the more extensively studied catecholamines is finally being realized. We now have a Serotonin Club that held its first international scientific meeting in 1987, and several more international meetings are in the planning stages."

This monograph is dedicated to the lives and scientific achievements of the physiology pioneers Warren and Margaret Lewis. Their story spans the first half of the 20th century, from their respective educations through early, independent research to joint research from 1910 to 1955. Among the numerous developments they initiated, were the discovery of pinocytosis, the beginnings of video microscopy and the development of the first mammalian tissue cultures. Their research expanded the theoretical knowledge of cell structure and function. On a more practical level, they advanced many laboratory methods, like the first recipes for culture media. The text is beautifully enriched with personal anecdotes about their lives. This is the story of two scientific pioneers in the context of early 20th century biology and physiology. It is an inspiration for senior and aspiring researchers.

'This book is a 'must have' for any biologists interested in the formation of wood, who might think of buying two copies - one for lab, where it will most definitely see heavy use, and one for the office as an excellent reference book.' - Malcolm M. Campbell, University of Oxford - New Phytologist

'...this book is highly recommended and should become a standard not only for libraries, but also as a personal copy for scientists working with woody tissues. It also serves as a rich source of scientific information regarding both structural and biochemical aspects of wood formation.' - Annals of Botany

Platelet-Rich Plasma (PRP) has gained tremendous popularity in recent years as a treatment option for specialties including Orthopedics, Dentistry, Sports Medicine, Otorhinolaryngology, Neurosurgery, Ophthalmology, Urology, Vascular, Cardiothoracic and Maxillofacial Surgery, and Veterinarian Medicine. Nowadays, PRP and Stem Cell Science have added an exciting dimension to tissue repair.

This book begins by giving the reader a broad overview of current progress as well as a discussion of the technical aspects of preparation and therapeutic use of autologous PRP. It is followed by a review of platelet structure, function and major growth factors in PRP (PDGF and TGF ).The third chapter outlines the basic principles of biochemical cellular metabolism that increases the efficacy of PRP. Analogous to the preparation of soil for a garden, restoring cellular health should be the first consideration in Regenerative Medicine. Standardization of PRP preparation to clinical use still remains a challenging prospect. In this sense, a feasible strategy for studying PRP preparation is illustrated, which also allows to modulate and tailor the quality of PRP for further clinical applications.

The science behind PRP and stem cells, on tissue regeneration, cell proliferation and mesenchyme stem-cells are emphasized and reviewed. Various specific uses of PRP are described with detailed illustrations of various personal experiences mainly in orthopedic injuries, ligament and tendon repair, degenerative diseases, sports medicine, chronic wound healing as well as rehabilitation aspects in tendinopathy.

Expertly written by leading scientists in the field, this book provides for beginners and experienced readers scientific fundamentals, the state of art of PRP, specific uses and personal experiences with a practical approach and reference for current trends in use. Finally, this book paves the way for future developments."