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.

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.

Nuclear Receptors focuses on the structural analysis of nuclear receptors from the initial work using isolated protein domains to the more recent exciting developments investigating the conformational shape of full-length receptor complexes. The book also reviews the structure of key nuclear receptor co-regulatory proteins. It brings together, for the first time, a comprehensive review of nuclear receptor structure and the importance of receptor conformation underpinning allosteric regulation by different ligands (hormone, drugs, DNA response elements, protein-protein interactions) and receptor activity. The nuclear receptor superfamily, including receptors for steroid hormones and non-steroid ligands, are pivotal to normal physiology, regulating processes as diverse as reproduction, metabolism, the immune system and brain development. The first members of the family were cloned over 25 years ago, which heralded in the idea of a superfamily of intracellular receptor proteins that bound small molecule ligands: classical steroid hormones, vitamins, fatty acids and other products of metabolism. These signals are then transmitted through multiprotein receptor-DNA complexes, leading to the regulation of target genes, often in a cell-selective manner. The cloning of the receptor cDNAs also ushered in an era of unparalleled analysis of the mechanisms of action of these ligand-activated transcription factors.

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.

This volume of the Handbook of Neurochemistry and Molecular Biology focuses on molecular events involved in synapse formation, synaptic plasticity and ongoing neural activity. The volume explores axonal growth cones, synapse development, and mechanisms of LTP and LTD, and calcium dynamics. Particular attention is given to function and trafficking of membrane proteins including various ion channels, aquaporines, gap junctions.

Modern cell biology has brought improvements in therapy for advanced malignant diseases through immunomodulation, hematopoietic stem cell transplantation, and other advanced techniques. Collected here are selected papers from the Fifth International Symposium of Keio University for Life Sciences and Medicine on Cell Therapy.
All chapters include innovative basic research for clinical application: immunotherapy, cancer vaccination, molecular biology of hematopoietic stem cells, stem cell processing, and gene therapy.
The book is divided into three parts: Immunotherapy for malignant diseases; Hematopoietic stem cell biology and clinical application; and International collaboration in hematopoietic stem cell transplantation. Included in the third part is information on bone marrow registries from around the world.
The book thus presents up-to-date information on biological and clinical aspects of treatment, with insight into the future of cell therapy.

Initially believed to be inactive molecules, glycans are now considered essential for life, both under normal and pathological conditions.

This volume of the series "Biology of Extracellular Matrix " reviews the most recent findings on the role of glycans in the development of diseases and the possible therapeutic use of this class of molecules. It shows how the interaction of glycans with growth factors, growth factor binding proteins, extracellular proteases, protease inhibitors, chemokines, morphogens, and adhesive proteins regulates inflammation, infection, cancer, atherosclerosis, thrombosis and embryonic stem cell biology. Furthermore, an extensive survey about the structure and pharmacological effects of unique marine glycosaminoglycans is discussed as well as the possibility of using these glycans as therapeutic agents.

Human Protein Metabolism is a succinct review of hundreds of studies on the regulation of protein mass and protein turnover in the human body. The biochemistry of protein synthesis and breakdown is summarized, and the methods that are used to examine protein metabolism in humans are explained, and their limitations discussed. The book includes chapters that review the effects of nutrition, hormones, metabolic substrates, and physical activity. Various topics of clinical interest are covered, including cancer, diabetes, tissue injury, pregnancy, renal disease, muscular dystrophies, and other conditions. Normal values are presented for turnover of proteins in the whole body and individual organs, and for turnover of many individual proteins. This book will be a valuable resource for physiologists, nutritionists, and clinicians interested in the regulation of body protein stores in health and disease. For scientists primarily interested in the basic aspects of protein metabolism, it shows how the basic knowledge is being applied to the study of humans.

This volume will cover a series of reviews on stem cells including adult and embryonic stem cells. Speakers were invited to present these talks during the Stem Cell Symposia in fall of 2010, in Samsun, Turkey. Unique aspect of this volume is that it brings a multidisciplinary aspect of stem cells extracted from a symposium.

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.

Being the crucial components of living cells, ion channels are important targets of therapeutic agents. Historically, it has been challenging to develop drugs on this target class. A major issue with targets based on ion channel drug development is the identification of effective small chemical leads for medicinal chemistry optimization to the clinical candidate status. Thus enough attention has been paid to the study of structure and functions of ion channels and their potential inhibitors. The present book compiles important chapters authored by eminent workers in the field to cover important recent advances in the studies of the structure and functions of ion channels and their inhibitors, such as sodium Ion, potassium Ion, chloride Ion, calcium Ion channel inhibitors. The book may be of great use to the students and scientists working in the area of molecular biology, biochemistry, physiology, and neurobiology, and medicinal chemistry.

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 volume focuses on apoptotic and non-apoptotic programmed cell death, including necroptosis, pyroptosis, and ferroptosis, and presents recent findings in the field. It discusses the crucial role that apoptotic and non-apoptotic cell death play in various pathological conditions, such as skin diseases, inflammatory bowel diseases, and virus infections. Further, it highlights the mechanisms underlying the recognition and clearance of dead cells, and the subsequent biological responses triggered by phagocytosed macrophages and factors released from dying cells. Offering insights into cell death, it is a valuable resource for researchers and clinicians developing novel strategies to treat various diseases that are closely associated with cell death.

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.

Despite the many milestones in cystic fibrosis (CF) research, progress towards curing the disease has been slow, and it is increasingly difficult to grasp and use the already wide and still growing range of diverse methods currently employed to study CF so as to understand it in its multidisciplinary nature. Cystic Fibrosis: Diagnosis and Protocols aims to provide the CF research community and related researchers with a very wide range of high-quality experimental tools, as an easy way to grasp and use classical and novel methods applied to cystic fibrosis. Volume I: Approaches to Study and Correct CFTR Defects focuses on the cystic fibrosis transmembrane conductance regulator (CFTR) and its expression, biogenesis, structure, and function in terms of the defects causing CF. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Cystic Fibrosis: Diagnosis and Protocols will provide readers with optimal working tools to address pressing questions in the best technical way, while helping all of us, as a research and clinical community, to move faster hand-in-hand toward unravelling the secrets of this challenging disorder and cure it.

This book is concernced with the process of cell death in human cells by programmed cell death or apoptosis, and the modulation of this process by drugs. This is a new field of study and this volume represents the first comprehensive treatment of this subject matter. Its focus is on human biology and medicine. Apoptosis is a very prevalent type of cell death with importance in human diseases such as cancer, Alzheimer's disease and autoimmune disorders. The book combines the expertise of leading scientists and writers from fields as diverse as neurosciences, immunology, pathology and cancer research. There is detailed analysis of the molecular and cellular aspects of apoptosis including the specific genes and molecules involved in the regulation of this special form of programmed cell death. Scientists, clinicians and researchers involved in studies of human biology and medicine will find this book an excellent resource.

Mesenchymal Stromal Cell (MSC) biology has been studied for more than 4 decades and the cells have been investigated for potential clinical applications for more than 15 years. Progress has become exponential over the past decade due mainly to the broad therapeutic potential of these cells. However, MSC studies have also been subject to controversy and increasing scrutiny as new mechanisms of action are reported and ever-expanding therapeutic applications pursued. In this book, leading authorities from all over the world, who are actively involved in this field, provide state-of-the-art knowledge of the basic biology, translational requirements and latest clinical experience with MSCs. This cutting edge book is the ideal resource for scientists and clinicians interested in pursuing an important and rapidly developing field of research that will eventually help patients and address urgent unmet medical needs. Features include: coverage of the biology of MSCs, latest understanding of mechanisms of action, and role in tissue homeostasis and regeneration; identifying the potential of MSCs in proceeding from bench to bedside from regulatory, GMP production, ethical and safety aspects; and critical analysis of clinical studies and the potential of MSCs to treat a wide variety of human diseases and tissues.

Upon completion of the human genome project over 800 G protein-coupled receptor 1 (GPCR) genes, subdivided into five categories, were identified. These receptors sense a diverse array of stimuli, including peptides, ions, lipid analogues, light and odour, in a discriminating fashion. Subsequently, they transduce a signal from the ligand-receptor complex into numerous cellular responses. The importance of GPCRs is further reflected in the fact that they constitute the most common target for therapeutic drugs across a 2 wide range of human disorders. Phylogenetic analysis of GPCRs produced the GRAFS classification system, which subdivides GPCRs into five discrete families: glutamate, rhodopsin, adhesion, frizzled/taste2 and secretin receptors. The adhesion-GPCR family 2 can be further subdivided into eight groups. The field of adhesion-GPCR biology has indeed become large enough to require a volume dedicated solely to this field. The contributors to this book have made a courageous effort to address the key concepts of adhesion-GPCR biology, including the evolution and biochemistry of adhesion-GPCRs; there are extensive discussions on the functional nature of these receptors during development, the immune response and tumourgenesis. Finally, there are chapters dedicated to adhesion-GPCR signalling, an area of intense investigation.

The Encyclopedia of Cell Biology, Four Volume Set offers a broad overview of cell biology, offering reputable, foundational content for researchers and students across the biological and medical sciences. This important work includes 285 articles from domain experts covering every aspect of cell biology, with fully annotated figures, abundant illustrations, videos, and references for further reading. Each entry is built with a layered approach to the content, providing basic information for those new to the area and more detailed material for the more experienced researcher. With authored contributions by experts in the field, the Encyclopedia of Cell Biology provides a fully cross-referenced, one-stop resource for students, researchers, and teaching faculty across the biological and medical sciences.

The problem of the long-term proliferation of cells is a seminal one. It has always been a hot subject in biology, a source of far-reaching hypotheses, even more so now when explanations for the mechanisms of cell prolifera tive mortality or immortality seem within our reach. A question which is still debated is whether an infinite division potential can be a normal trait or is always the result of modifications leading to abnormal cell growth and escape from homeostasis. In general, investigators have been advocates of one of the two extremes, universal limited or unlim ited normal proliferative potential. Since the long-term proliferative potential of cells concerns regulation of development, regeneration of tissues, and homeostatic control of cell growth, in brief survival of living organisms, and since the regulation of these processes is so different along the evolutionary scale, it is not surpris ing that there does not seem to be any universal trait. The question of whether cells are endowed with finite or infinite prolifera tive phenotypes has to be seen using the perspective of comparative biology."

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.

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.

This monograph, written by experts in the field, is devoted to the molecular analysis of addiction pathways in the brain. It provides an intensive overview of the fundamentals, state?of?the?art advances, and major gaps in the cell and molecular biology of drug addiction within the broader context of neuroscience. Addiction research is a branch of neuroscience and psychology. The emphasis in this book is on hard science and the market for it will be found among research investigators and grad students within the field of neuroscience. The research presented is not only applicable to the study of drug abuse and addiction, but has clear implications for clarifying mechanisms of learning and memory, neuroadaptation, perception, volitional behavior, motivation, reward, and other disciplines of neuroscience.