Membrane Physiology is a soft-cover book containing portions of Physiology of Membrane Disorders, published in larger, hard-cover form in 1978. The parent volume was divided into five parts, described in detail in the Preface to the hard-cover edition, which is reproduced in this volume. The present version of Membrane Physiology incorporates the first three of these parts, including a section on the Nature of Biological Membranes, a section on Methods for Studying Membranes, and a section on General Problems in Membrane Biology. It is the hope of the Editors that this smaller volume will be of value to individuals interested in general physiology, the methods for studying general physiology, and its potential application to problems of clinical and physiological relevance. The Preface to Physiology of Membrane Disorders indicates our general reasoning for developing such a volume. THOMAS E. ANDREOLI JOSEPH F. HOFFMAN DARRELL D. FANESTIL Vll Preface to Physiology of Membrane Disorders The purpose of this book is to provide the reader with a rational frame of reference for assessing the pathophysiology of those disorders in which derangements of membrane transport processes are a major factor responsible for the clinical manifestations of disease.

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...

Features that characterize the aging process include the gradual accumulation of cell damage after prolonged exposure to oxidative and inflammatory events over a lifetime. In addition to the accretion of lesions, the intrinsic levels of pro-oxidant and aberrant immune responses are elevated with age. These adverse events are often further enhanced by the chronic and slow progressing diseases that characterize the senescent brain and cardiovascular system. The incidence of some disorders such as Alzheimer's disease and vascular diseases are sufficiently prevalent in the extreme elderly that these disorders can arguably be considered "normal". Aging and Aging-Related Disorders examines the interface between normal and pathological aging, and illustrates how this border can sometimes be diffuse. It explores and illustrates the processes underlying the means by which aging becomes increasingly associated with inappropriate levels of free radical activity and how this can serve as a platform for the progression of age-related diseases. The book provides chapters that examine the interactive relationship between systems in the body that can enhance or sometimes even limit cellular longevity. In addition, specific redox mechanisms in cells are discussed. Another important aspect for aging discussed here is the close relationship between the systems of the body and exposure to environmental influences of oxidative stress that can affect both cellular senescence and a cell's nuclear DNA. What may be even more interesting to note is that these external stressors are not simply confined to illnesses usually associated with aging, but can be evident in maturing and young individuals. A broad range of internationally recognized experts have contributed to this book. Their aim is to successfully highlight emerging knowledge and therapy for the understanding of the basis and development of aging-related disorders.

Rapid progress has been made in our understanding of the molecular mechanisms of cell growth and oncogenesis during the past decade. This book comprises recent results on the regulation of cell growth in normal and neoplastic tissues by growth factors including hormones, and by the activation and inactivation of oncogenes and tumor suppressor genes, respectively. Special attention has been given to the presentation of the frequently neglected close correlation between changes in signal transduction and metabolism pathways during oncogenesis.

In 1898, an Austrian microbiologist Heinrich Winterberg made a curious observation: the number of microbial cells in his samples did not match the number of colonies formed on nutrient media (Winterberg 1898). About a decade later, J. Amann qu- tified this mismatch, which turned out to be surprisingly large, with non-growing cells outnumbering the cultivable ones almost 150 times (Amann 1911). These papers signify some of the earliest steps towards the discovery of an important phenomenon known today as the Great Plate Count Anomaly (Staley and Konopka 1985). Note how early in the history of microbiology these steps were taken. Detecting the Anomaly almost certainly required the Plate. If so, then the period from 1881 to 1887, the years when Robert Koch and Petri introduced their key inventions (Koch 1881; Petri 1887), sets the earliest boundary for the discovery, which is remarkably close to the 1898 observations by H. Winterberg. Celebrating its 111th anniversary, the Great Plate Count Anomaly today is arguably the oldest unresolved microbiological phenomenon. In the years to follow, the Anomaly was repeatedly confirmed by all microb- logists who cared to compare the cell count in the inoculum to the colony count in the Petri dish (cf., Cholodny 1929; Butkevich 1932; Butkevich and Butkevich 1936). By mid-century, the remarkable difference between the two counts became a universally recognized phenomenon, acknowledged by several classics of the time (Waksman and Hotchkiss 1937; ZoBell 1946; Jannasch and Jones 1959).

Alzheimer s disease (AD) is a neurodegenerative disease that robs the minds of our elderly population. Approximately one in every eight adults over the age of 65 and nearly half of those over 85 are afflicted with this disease. The aging population in developed societies will impose an ever increasing socioeconomic threat in the future. Current medicines for AD patients are mainly symptomatic treatments and a huge unmet medical need exists to slow the progression of this disease. A great deal of research has been dedicated to understanding the pathogenesis of AD from which comes many ideas for intervening with its progression. Some of these ideas have been fast-tracked to clinical trials due to the availability of medicines with proven clinical efficacies for other diseases (e.g. atorvastatin, simvastatin, rosiglitazone and clioquinol) while others represent novel chemical entities (e.g. glycogen synthase kinase-3 inhibitors).

This volume will first review existing cholinesterase inhibitors prescribed for AD patients followed by some target mechanisms with ongoing clinical trials. It offers a glimpse of what our future medicine cabinets may look like for AD patients. It also provides an interesting read on why and how current medicines for other indications could potentially be used to treat AD."

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.

Medical science and practice have undergone fundamental changes in the last 5 years, as large-scale genome projects have resulted in the sequencing of a number of important microbial, plant and animal genomes. This book aims to combine industry standard software engineering and design principles with genomics, bioinformatics and cancer research. Rather than an exercise in learning a programming platform, the text focuses on useful analytical tools for the scientific community.

With the ever-increasing volume of information in clinical medicine, researchers and health professionals need computer-based storage, processing and dissemination. In this book, leading experts in the field provide a series of articles focusing on software applications used to translate information into outcomes of clinical relevance. This book is the perfect guide for researchers and clinical scientists working in this emerging "omics" era.

Contents include: 'Biochemistry and molecular biology of neural lipids', 'Advances in lipid analysis/lipidomics', 'Metabolism and enzymology of glycerolipids', 'Lipid metabolism in brain development and aging', 'Cellular and subcellular localization of neural lipids', and much more.

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

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

Neural network research often builds on the fiction that neurons are simple linear threshold units, completely neglecting the highly dynamic and complex nature of synapses, dendrites, and voltage-dependent ionic currents. Biophysics of Computation: Information Processing in Single Neurons challenges this notion, using richly detailed experimental and theoretical findings from cellular biophysics to explain the repertoire of computational functions available to single neurons. The author shows how individual nerve cells can multiply, integrate, or delay synaptic inputs and how information can be encoded in the voltage across the membrane, in the intracellular calcium concentration, or in the timing of individual spikes.
Key topics covered include the linear cable equation; cable theory as applied to passive dendritic trees and dendritic spines; chemical and electrical synapses and how to treat them from a computational point of view; nonlinear interactions of synaptic input in passive and active dendritic trees; the Hodgkin-Huxley model of action potential generation and propagation; phase space analysis; linking stochastic ionic channels to membrane-dependent currents; calcium- and potassium-currents and their role in information processing; the role of diffusion, buffering and binding of calcium, and other messenger systems in information processing and storage; short- and long-term models of synaptic plasticity; simplified models of single cells; stochastic aspects of neuronal firing; the nature of the neuronal code; and unconventional models of sub-cellular computation.
Biophysics of Computation: Information Processing in Single Neurons serves as an ideal text for advancedundergraduate and graduate courses in cellular biophysics, computational neuroscience, and neural networks, and will appeal to students and professionals in neuroscience, electrical and computer engineering, and physics.

I am very pleased to present this volume on engineering stem cells in Advances in Biochemical Engineering and Biotechnology. This volume stays abreast of recent developments in stem cell biology and the high expectations concerning the dev- opment of stem cell based regenerative therapies. Regenerative medicine is the focus of current biomedical research, with unique challenges related to scientific, technical and ethical issues of stem cell research, and the potential added value of connecting biomedicine with enabling techno- gies such as materials sciences, mechanical- and nano-engineering. Research activities in regenerative medicine include strategies in endogenous regeneration of injured or degenerated tissues by means of gene therapy or cell transplantation, as well as complex approaches to replace or reconstruct lost or malformed tissue structures, by applying tissue engineering approaches. In most cases, the speci- ized functional cell types of interest cannot be isolated from the diseased organ or expanded to a sufficient degree, and various stem and progenitor cell types rep- sent the only applicable cell source. In almost all cases, stem cells have to be engineered, sometimes for functional improvement, in many cases to produce large numbers of cells, and frequently to achieve efficient and specific differentiation in the cell type(s) of interest.

This book is a volume in the Penn Press Anniversary Collection. To mark its 125th anniversary in 2015, the University of Pennsylvania Press rereleased more than 1,100 titles from Penn Press's distinguished backlist from 1899-1999 that had fallen out of print. Spanning an entire century, the Anniversary Collection offers peer-reviewed scholarship in a wide range of subject areas.

Cajal's Neuronal Forest: Science and Art continues the tradition set forth by its sister volume Cajal's Butterflies of the Soul (OUP, 2009). This new collection contains hundreds of beautiful rarely-seen-before figures produced throughout the nineteenth century and the beginning of the twentieth century by famed father-of-modern-neuroscience Santiago Ramon y Cajal (1852-1934) and his contemporaries. Cajal was captivated by the beautiful shapes of the cells of the nervous system. He and his fellow scientists saw neurons as trees and glial cells as bushes. Given their high density and arrangement, neurons and glial resembled a thick forest, a seemingly impenetrable terrain of interacting cells mediating cognition and behavior. In unraveling the mysteries of the brain, these researchers encountered an almost infinite number of cellular forms with an extraordinary beauty, which they could not help but put pen to paper, allowing them to discover a new artistic world- the neuronal forest- that gave free rein not only to their imagination, but to a new way of viewing the brain as well. This book has been divided into two parts. The first focuses on the scientific atmosphere in Cajal's times, on the history of the neuron, and the anatomical challenge posed in studying neuronal connections. It also delves into the artistic skills of Cajal and other important pioneers in neuroscience and how the neuronal forests have served as an unlimited source of artistic inspiration. The second consists of 275 original drawings by Cajal. All were published over the course of his scientific career and cover virtually all of his research fields of interest, including the spinal cord, the optic lobe and retina, cerebral cortex, and many other regions of the brain. Cajal's Neuronal Forest: Science and Art is a testament to the natural beauty found in science. Despite the common misconception that the drawings of Cajal and other scientists of the time are pieces of art, these drawings are in fact copies of histological preparations and contributed greatly to the discoveries made in the field of neuroscience. This book is a gem in any library, whether serving as a medical history or a gallery of stunning sketches.

The manipulation and control of cells and sub-cellular structures through magnetic nanoparticle-based actuation is a relatively new technique that has led to novel and exciting biomedical applications. Nanomagnetic actuation is being used in laboratory studies of stem cells to determine how these mechanical cues can be used to control stem cell differentiation for regenerative medicine applications. This book explores this rapidly expanding field. It will interest industry bioscientists and biomedical engineers as well as academics in cellular biomechanics, cell and tissue engineering, and regenerative medicine. Key Features Focuses on the fundamentals and applications of magnetic actuation Includes contributions by world-class researchers from several countries and is edited by a well-known researcher in this field Offers multidisciplinary coverage and applications Supplies extensive references at the end of each chapter

The Biology and Therapeutic Application of Mesenchymal Cells comprehensively describes the cellular and molecular biology of mesenchymal stem cells and mesenchymal stromal cells, describing their therapeutic potential in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models. Chapters also discuss the current status of the use of mesenchymal stem and stromal cells in clinical trials in a wide range of human diseases and disorders, for many of which there are limited, or no other, therapeutic avenues. Provides coverage on both the biology of mesenchymal stem cells and stromal cells, and their therapeutic applications Describes the therapeutic potential of mesenchymal stem and stromal cells in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models Discusses the current status of mesenchymal stem and stromal cells in clinical trials in a wide range of human diseases and disorders, for many of which there are limited, or no other, therapeutic avenues Written and edited by leaders in the field The Biology and Therapeutic Application of Mesenchymal Cells is an invaluable resource for those studying stem cells, cell biology, genetics, gene or cell therapy, or regenerative medicine. About the Author Kerry Atkinson, MBBS MD DTM&H FRCP FRACP, is an Adjunct Professor at the University of Queensland Centre for Clinical Research in Brisbane, Australia, an Adjunct Professor in the Stem Cell Laboratories, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia and a Specialist in Internal Medicine at the Salisbury Medical Centre, Brisbane, Queensland, Australia.

Cysts are pathological cavities that may or may not be lined by the epithelium and are filled with either gas, fluid or semi-solid materials. Once formed, a cyst could go away on its own or may have to be removed through surgery. In this book, the authors present current research in the study of the causes, diagnosis and treatment options of cysts. Topics discussed include recent advances in the diagnostic imaging of cysts and pseudocysts in the oral and maxillofacial region; inflammatory odontogenic cysts; cystic renal pathology; non-parasitic benign liver cysts; and the malignant potential of epidermal and verrucous cutaneous cysts.

The Handbook is intended to be a service to the neuroscience community, to help in finding available and useful information, to point out gaps in our knowledge, and to encourage continued studies. It represents the valuable contributions of the many authors of the chapters and the guidance of the editors and most important, it represents support for research in this discipline. Based on the rapid advances in the years since the second edition.

This book series consists of 3 volumes covering the basic science (Volume 1), clinical science (Volume 2) and the technology and methodology (Volume 3) of autophagy. Volume 3 focuses on the technical aspects of autophagy research. It is comprised of two parts. The first part discusses the basic process of autophagy, including its overall classification and individual stages in the life cycle of autophagosomes. The second part discusses the tools, strategies, and model systems in current autophagy research, including cell and animal models, detection and manipulation methods, as well as screening, genomic, proteomic and bioinformatic approaches. The book is written and edited by a team of active scientists. It is intended as a practical reference resource for interested researchers to get started on autophagy studies.

With the recent renaissance in mitochondrial biology and increasing recognition of their role in many diseases, this book provides a timely summary of the current state-of-the-art in mitochondrial research. The book opens with the regulation of mitochondrial replication and biogenesis and reviews the mechanisms and functional consequences of mitochondrial fission and fusion. Further chapters address mitochondria and oxidative stress and their roles in cell signalling and cell death. The book includes extensive, fascinating discussion of the biochemistry of mitochondrial cell signalling (especially involving calcium) and of oxidative stress. The nature of the proteins engaged in these processes, many only recently discovered, is covered in detail.

Mitochondria have been strongly implicated in neurodegenerative diseases such as Parkinson's, Huntington's and amyotrophic lateral sclerosis. They are also affected in cancer, ageing and cardiovascular disease. The final section of the book reviews mitochondrial mutations and their consequences in ageing and other phenotypic manifestations. The authors discuss how mitochondrial proteins might constitute important therapeutic targets and describe initial attempts to develop compounds that can regulate their function.

This book consists of 3 volumes: Basic Science (Volume 1), Clinical Science (Volume 2) and Technology and Methodology (Volume 3). Volume 2 focuses on the clinical aspects of autophagy research, discussing the role of autophagy in neuropsychiatric disorders, the cardiovascular, immune, digestive and endocrine systems, as well as tumors, infection, the kidney, and the respiratory and hematological systems. It also addresses autophagy-related drug development. Written and edited by a team of 90 experts, and presenting the state of the art in autophagy research, this book is a valuable reference resource for researchers and clinicians alike. It can also be used as supplementary material for graduate students majoring in biology and medicine

This book series consists of 3 volumes covering the basic science (Volume 1), clinical science (Volume 2) and the technology and methodology (Volume 3) of autophagy. Volume 1 focuses on the biology of autophagy, including the signaling pathways, regulating processes and biological functions. Autophagy is a fundamental physiological process in eukaryotic cells. It not only regulates normal cellular homeostasis, and organ development and function, but also plays an important role in the pathogenesis of a wide range of human diseases. Thanks to the rapid development of molecular biology and omic technologies, research on autophagy has boomed in recent decades, and more and more cellular and animal models and state-of the-art technologies are being used to shed light on the complexity of signaling networks involved in the autophagic process. Further, its involvement in biological functions and the pathogenesis of various diseases has attracted increased attention around the globe. Presenting cutting-edge knowledge, this book series is a useful reference resource for researchers and clinicians who are working on or interested in autophagy.

Vast numbers of different prokaryotic microorganisms shape the biosphere, with diverse metabolic capabilities. Determination of genome sequences for a wide range of bacteria and archaea now requires an in-depth knowledge of prokaryotic metabolic function to give biochemical, physiological and ecological meaning to the genomic information. This new edition describes up-to-date knowledge of the key metabolic processes that occur under different conditions, and the cellular processes that determine prokaryotic roles in the environment, biotechnology and human health. Essential for students of microbiology, applied microbiology, biotechnology, genomics and systems biology, this advanced textbook covers prokaryotic structure, composition, nutrient transport, biosynthesis and growth. Newly characterised metabolic pathways are included, as well as the latest understanding of metabolic regulation and stress responses. Additionally, the link between energetics, growth and survival is discussed as well as the maintenance of genetic integrity by the bacterial immune system.