H. Wegele, L. M ller, and J. Buchner: Hsp70 and Hsp90 A Relay Team for Protein Folding

R. Sch lein: The Early Stages of the Intracellular Transport of Membrane Proteins: Clinical and Pharmacological Implications

L. Schild: The Epithelial Sodium Channel: From Molecule to Disease

This is the first of three volumes in the "Ion Channels & Transporters in Tumor Biology" collection, which discusses the function of ion transport proteins in cellular and systemic homeostasis. The authors highlight the role of the so-called transportome, which is defined by the entirety of ion transporters and ion channels. Thereby, readers will get a better understanding of the impact dysregulated ion transport has on the whole spectrum of cancer types. Cancers display deficiencies in several, sometimes interdependent members of the transportome. Clinicians will be interested in the fact that controlled expression of ion transport proteins dramatically impacts the life span of cancer patients, as shown in recent studies. These observations offer a promising outlook for biomedical scientists, as members of the transportome could be the tumor markers of tomorrow - both for diagnostic and therapeutic purposes. 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.

TheobservationthatabloodclotspontaneouslydissolveswasfirstdescribedbyDenys in1889. Subsequently,thebloodclottingsystemwasshowntobeinvolvedintumor growth. Forexample,asearlyas1925,Fisherreportedthataviantissueexplantstrans- formedtomalignancybyvirusesgeneratedhighlevelsoffibrinolyticactivityundercon- ditionsinwhichculturesofnormalcellsdidnot. In1958,theconceptthatan equilibriumexistedbetweenthetendencyofbloodtoclotandtoremainfluidwaspro- posedbyAstrup. Atthattime,itwasbelievedthatthishemostaticbalancewasexplained bytheabilityofpolymerizingfibrintoorchestrateitsownclearancebystimulatingfib- rinolyticactivity. Sincethesepioneeringstudies,considerableinformationhasaccumu- latedthathasdefinedthecomponentsofthecoagulationandfibrinolyticsystemsand howtheyareinvolvedinphysiologicalandpathophysiologicalprocesses. Plasminogen: Structure, activation, and regulationfocusesonthebasicprinciplesandrecentdevelop- mentsintheplasminogen/plasminresearchfieldandhowtheseresultsprovideacon- ceptualframeworkforanunderstandingofthephysiologicalroleofplasminogenin healthanddisease. Theenzymaticcascadetriggeredbyactivationofplasminogenhasbeenimplicated inavarietyofnormalandpathologicaleventssuchasfibrinolysis,woundhealing,tis- sueremodeling,embryogenesis,angiogenesis,andtheinvasionandmetastasisoftumor cells. Thisimpressivelistofphysiologicalfunctionsforplasminogenreinforcesthewide diversityofrolesthatplasminogenplaysinvariousphysiologicalprocesses. Productive plasmingenerationrequirestheassemblyofbothplasminogenactivatorsandplasmino- genonasolidsupportsuchasthefibrinpolymerorthecellsurface. Theregulationof plasminproductioninvolvesacomplexinterplaybetweentheseplasminogenactivators, plasminogenactivatorinhibitors,andplasmininhibitors. Clearly,theexplosivegrowth inthisresearchfieldandthemanyexcitingdiscoveriessuggeststhattheresearchefforts inthenextdecadewillrevealthemechanismsbywhichthecomponentsoftheplas- minogensysteminteractandregulatebothplasminactivationandfunctionatacellular level. Plasminogen: Structure, activation, and regulationisdividedintotwosections. Thefirstsectiondealswiththestructureandregulationofplasminogen. Thechapters inthissectionrangefromdiscussionsofthestructureofplasminogenandtheregulation oftheplasminogengenetodiscussionsofthestructureandregulationofplasminogen activatorsandplasminogenactivatorinhibitors. Alsoexaminedistherelativelynewdata concerningthegenerationofanti-angiogenicmoleculesfromplasminogen. Thesecond sectiondealswiththephysiologicalandpathophysiologicalrolesofplasminogenaswell astheconsequencesofplasminogengeneknockout. Discussionsinthissectioninclude examinationoftheroleofplasminogeninhematopoieticmalignancies,tumorcell progression,angiogenesis,mammaryglandinvolution,woundhealing,andbone readsorption. xi xii Preface Inclosing,Iwouldliketothankmyadministrativeassistant,Ms. ViSommerfeld,for herinvaluableassistanceandtimelesseffortswiththeorganizationandeditingofthebook. Lastly,Iwouldliketoacknowledgetheeffortsoftheauthorsoftheindividualchapters, whoareauthorities inthisfield,foragreeingtotaketimefrombusyschedulestoprovide thesechaptersinatimelyfashion. DavidMortonWaisman Contents Part I. Plasminogen: Structure and Regulation 1. Human Plasminogen: Structure, Activation, and Function FrancisJ. Castellino and Victoria A. Ploplis 1. Introduction 3 2. StructureofHumanPlasminogen...3 2. 1. PrimaryProteinStructure...3 2. 2. GeneOrganization 5 3. ActivationofHumanPlasminogen...6 3. 1. ActivationbyPhysiologicalActivators 7 3. 1. 1. Urokinase-typePlasminogenActivator...7 3. 1. 2. Tissue-typePlasminogenActivator...8 3. 2. ActivationbyBacterial-derivedPlasminogenActivators...9 3. 2. 1. Streptokinase 9 3. 2. 2. Staphylokinase...9 4. TargetsforPlasminActivity...9 5. DysplasminogenemiasandPhenotypicManifestations 10 6. Conclusions 11 References...11 2. Plasminogen Activators: Structure and Function Vincent Ellis 1. Introduction ...19 2. SerineProteases...20 3. UrokinasePlasminogenActivator,uPA...21 3. 1. SerineProteaseDomain 22 3. 2. N-terminalDomains...24 3. 2. 1. KRModule 24 3. 2. 2. EGModule 24 4. MechanismsRegulatinguPAFunction...25 4. 1. ZymogenActivation...25 4. 2. ZymogenActivity...26 4. 3. ReciprocalZymogenActivation 27 4. 4. uPARStimulationofPlasminogenActivation...27 4. 4. 1. uPAandtheTemplateMechanism 28 4. 4. 2. PlasminogenandtheTemplateMechanism 29 4. 5. AvianuPA,aSpecialCase? 30 xiii xiv Contents 5. TissuePlasminogenActivator,tPA...30 5. 1. SerineProteaseDomain 31 5. 2. N-terminalDomains ,...33 5. 2. 1. KRModules ,. . ,. . ,...33 5. 2. 2. F1-EGSupermodule 33 6.

This book contains a collection of papers that were presented at the IUTAM Symposium on "Computer Models in Biomechanics: From Nano to Macro" held at Stanford University, California, USA, from August 29 to September 2, 2011. It contains state-of-the-art papers on: - Protein and Cell Mechanics: coarse-grained model for unfolded proteins, collagen-proteoglycan structural interactions in the cornea, simulations of cell behavior on substrates - Muscle Mechanics: modeling approaches for Ca2+-regulated smooth muscle contraction, smooth muscle modeling using continuum thermodynamical frameworks, cross-bridge model describing the mechanoenergetics of actomyosin interaction, multiscale skeletal muscle modeling - Cardiovascular Mechanics: multiscale modeling of arterial adaptations by incorporating molecular mechanisms, cardiovascular tissue damage, dissection properties of aortic aneurysms, intracranial aneurysms, electromechanics of the heart, hemodynamic alterations associated with arterial remodeling following aortic coarctation, patient-specific surgery planning for the Fontan procedure - Multiphasic Models: solutes in hydrated biological tissues, reformulation of mixture theory-based poroelasticity for interstitial tissue growth, tumor therapies of brain tissue, remodeling of microcirculation in liver lobes, reactions, mass transport and mechanics of tumor growth, water transport modeling in the brain, crack modeling of swelling porous media - Morphogenesis, Biological Tissues and Organs: mechanisms of brain morphogenesis, micromechanical modeling of anterior cruciate ligaments, mechanical characterization of the human liver, in vivo validation of predictive models for bone remodeling and mechanobiology, bridging scales in respiratory mechanics

"Research into gastrointestinal motility has received renewed interest in part due to recent advances in the techniques for measuring the structure and function of gastrointestinal cells, tissue and organs. The integration of this wealth of data into biophysically based computation models can aid in interpretation of experimental and clinical measurements and the refinement of measurement techniques."

"The contents of this book span multiple scales - from cell, tissue, organ, to whole body and is divided into four broad sections covering: i) gastrointestinal cellular activity and tissue structure; (ii) techniques for measuring, analyzing and visualizing high-resolution extra-cellular recordings; (iii) methods for sensing gastroelectrical activity using non-invasive bio-electro-magnetic fields and for modulating the underlying gastric electrical activity and finally (iv) methods for assessing manometric and videographic motility patterns and the application of these data for predicting the flow and mixing behavior of luminal contents by using computational fluid dynamic techniques. "

"This book aims to provide both an overview of historical and existing research techniques as well as to highlight future directions and challenges for the community as a whole. It will be suitable for clinicians to understand the cellular and biophysical underpinnings of gastric emptying, gastroenterologists, surgeons, bioengineers and all scientists with interests in gastrointestinal motility research."

In just under three decades, the world has witnessed an enormous rise in obesity with a parallel growth in cardiometabolic disease risk factors characterized by insulin resistance, dyslipidemia, and hypertension, together known as the metabolic syndrome - conditions previously unheard of in children and adolescents. During this time, we have little knowledge of the global and cumulative detrimental health effects of childhood obesity. As obese children age, not only will their health be negatively affected, but infertility and pregnancy complications associated with the metabolic syndrome will affect generations to come. The work force will undoubtedly be affected because of increased sick days and decreased work productivity. Identifying children and adolescents at the earliest stages of chronic disease onset should be the goal of clinical practice, yet there is no clear guidance for defining the risk of metabolic syndrome or appropriate risk-factor thresholds in these groups. If children are identified early in the disease process, lifestyle and clinical interventions can be instituted when they are potentially more effective. Pediatric Metabolic Syndrome: Comprehensive Clinical Review and Related Health Issues approaches the pediatric metabolic syndrome by elucidating its effects on specific organ systems and by considering the problem through understanding the social, psychological and economic consequences of it. The Editors have recruited an invited group of esteemed experts in the field to provide the most timely and informative approaches on how to deal with this health crisis. Through educating our practitioners, our future researchers, our health and community organizations, our legislators and our families and children, we have the best chance at improving the health trajectory of the next generation.

Written for the UK's Access to Higher Education program, yet universally accessible, Access to HE: Anatomy and Physiology provides an easy-to-understand text with diagrams and straightforward notes explaining the human body's structure and systems. The broader issues of progress in disease control and the links between stress and health are also examined in this textbook. This vital introductory source will benefit students entering the health profession.

Covering all aspects of oxygen delivery to tissue, including blood flow and its regulation as well as oxygen metabolism, this book is multidisciplinary and designed to bring together experts and students from a range of research fields including biochemical engineering, physiology, microcirculation, and hematology.

NOTE: Before purchasing, check with your instructor to ensure you select the correct ISBN. This ISBN is for the paperback PhysioEx Lab Manual and does NOT include access to the PhysioEx 10.0 website. The Lab Manual for PhysioEx (TM) 10.0 Laboratory Simulations in Physiology features 12 Exercises that contain 63 easy-to-use laboratory simulation activities to complement or replace wet labs, including those that are expensive or time-consuming to perform in class. PhysioEx allows students to repeat labs as often as they like, perform experiments without harming live animals, and conduct experiments that are difficult to perform in a wet lab environment because of time, cost, or safety concerns. 3 ways students can access the PhysioEx 10.0 website: By purchasing a Mastering A&P title that includes PhysioEx 10.0 -- the most common way students access the PhysioEx 10.0 website. By purchasing instant online access to PhysioEx 10.0 Premium Website (ISBN: 9780136447672 / 0136447678) at www.physioex.com. By purchasing the PhysioEx 10 Lab Manual package (ISBN: 9780136643746 / 0136643744) that includes an access code to the PhysioEx 10.0 website.

This book sheds new light on the molecular mechanisms that generate circadian rhythms. It examines how biological rhythms influence physiological processes such as sleep, hormone synthesis and secretion, immunity, kidney function, the cardiovascular system, blood pressure, and the digestive system. Clinical implications are considered while exploring the impact of rhythms on neuropsychiatric disorders and chronotherapy's potential for reducing cardiovascular risk. Offering a cross-section of expertise in both basic and translational (bench-to-bedside) research, this book serves as a guide for physicians and scientists who wish to learn more about the impact of circadian rhythms on physiological processes in health and disease.

With the explosion of information on autophagy in cancer, this is an opportune time to speed the efforts to translate our current knowledge about autophagy regulation into better understanding of its role in cancer. This book will cover the latest advances in this area from the basics, such as the molecular machinery for autophagy induction and regulation, up to the current areas of interest such as modulation of autophagy and drug discovery for cancer prevention and treatment. The text will include an explanation on how autophagy can function in both oncogenesis and tumor suppression and a description of its function in tumor development and tumor suppression through its roles in cell survival, cell death, cell growth as well as its influences on inflammation, immunity, DNA damage, oxidative stress, tumor microenvironment, etc. The remaining chapters will cover topics on autophagy and cancer therapy. These pages will serve as a description on how the pro-survival function of autophagy may help cancer cells resist chemotherapy and radiation treatment as well as how the pro-death functions of autophagy may enhance cell death in response to cancer therapy, and how to target autophagy for cancer prevention and therapy what to target and how to target it.

"Metallomics and the Cell" provides in an authoritative and timely manner in 16 stimulating chapters, written by 37 internationally recognized experts from 9 nations, and supported by more than 3000 references, several tables, and 110 illustrations, mostly in color, a most up-to-date view of the "metallomes" which, as defined in the "omics" world, describe the entire set of biomolecules that interact with or are affected by each metal ion. The most relevant tools for visualizing metal ions in the cell and the most suitable bioinformatic tools for browsing genomes to identify metal-binding proteins are also presented. Thus, MILS-12 is of relevance for structural and systems biology, inorganic biological chemistry, genetics, medicine, diagnostics, as well as teaching, etc.

This fifth edition of "Engineering Physiology" has the same purpose as the earlier prints: to provide physiological information which engineers, designers, supervisors, managers and other planners need to make work and equipment "fit the human." Chapters have been revised, figures and tables updated. New material discusses, among other topics, models of the human body that provide practical and design-oriented information, biomechanics describing the body's capabilities and limitations, effects of shift work / sleep loss on attitude and performance, and new techniques to measure body sizes and the resultant changes in applications of that information. The book does not replace standard (biological-medical-chemical) textbooks on human physiology; instead, it provides information on human features and functions which are basic to ergonomics or human (factors) engineering, terms often used interchangeably. It helps lay the foundations for teamwork among engineers and physiologists, biologists and physicians. Bioengineering topics concern bones and tissues, neural networks, biochemical processes, bio- and anthromechanics, biosensors, perception of information and related actions, to mention just a few areas of common interest. Such understanding provides the underpinnings for devising work tasks, tools, workplaces, vehicles, work-rest schedules, human-machine systems, homes and designed environments so that we humans can work and live safely, efficiently and comfortably.

Spanning biological, mathematical, computational, and engineering sciences, computational biofluiddynamics addresses a diverse family of problems involving fluid flow inside and around living organisms, organs, tissue, biological cells, and other biological materials. Computational Hydrodynamics of Capsules and Biological Cells provides a comprehensive, rigorous, and current introduction to the fundamental concepts, mathematical formulation, alternative approaches, and predictions of this evolving field. In the first several chapters on boundary-element, boundary-integral, and immersed-boundary methods, the book covers the flow-induced deformation of idealized two-dimensional red blood cells in Stokes flow, capsules with spherical unstressed shapes based on direct and variational formulations, and cellular flow in domains with complex geometry. It also presents simulations of microscopic hemodynamics and hemorheology as well as results on the deformation of capsules and cells in dilute and dense suspensions. The book then describes a discrete membrane model where a surface network of viscoelastic links emulates the spectrin network of the cytoskeleton, before presenting a novel two-dimensional model of red and white blood cell motion. The final chapter discusses the numerical simulation of platelet motion near a wall representing injured tissue. This volume provides a roadmap to the current state of the art in computational cellular mechanics and biofluiddynamics. It also indicates areas for further work on mathematical formulation and numerical implementation and identifies physiological problems that need to be addressed in future research. MATLAB (R) code and other data are available at http://dehesa.freeshell.org/CC2

3D Printing in Podiatric Medicine compiles an interdisciplinary range of scientific literature, laboratory developments, industrial implications and futuristic avenues in this field. The book provides recent developments and research breakthroughs in 3D printing in podiatric medicine, such as functionalized feedstock systems, smart products, process characteristics, modeling and optimization of printed systems and products, and industrial applications. It covers best practices for 3D printing methods to capture, document and validate challenges at the early stage of the design process. The book's content then goes into mitigating design strategies to address these challenges without compromising the cost, safety and quality of the device. This book supports new and emerging specializations and provides a comprehensive collection of technical notes, research designs, design methods and processes and case studies.

New experimental observations often require fresh concepts for their interpretation, and at times even changes of paradigms. This is the situation with the recent realization that circulating endothelial progenitor cells may have an important contribution to the maintenance and formation of new endothelium in adult organisms, in a surprisingly wide variety of situations. The classical paradigm of angiogenesis, centered on the notion of "sprouting" can hardly accommodate them. It was previously realized that it needs to be "stretched out" to include alternative mechanisms of microvascular development, such as intussusception and capillary fusion. However, a major debate where to reconsider the sprouting mechanism, and to promote alternative views, did not take place yet. The number of publications in this field increased exponentially in the last years. Nevertheless, the concepts and notions so much needed to describe and to explain the new observations are still scarce, and heterogeneous. Within the larger community dedicated to the study of angiogenesis, the researchers involved in investigation of circulating precursor endothelial cells biology represent a subgroup with specific preoccupations and opinions. Many of them did not meet each other so far, and no major scientific events have been dedicated before exclusively to their interests. For the above reasons, the idea to organize a symposium addressing the new developments in angiogenesis research was received with enthusiasm by all those involved in its preparation.

Carry the same authoritative, useful knowledge that readers of Guyton and Hall have come to trust - in an easily accessible, pocket format. Pocket Companion to Guyton and Hall Textbook of Medical Physiology, 14th Edition, echoes the structure and content of the world's foremost physiology textbook, making it ideal for a quick, portable review or entry point into complex topics. Grasp key information quickly thanks to concise, readable text. Benefit from updated content of the 14th edition of the bestselling text in a condensed synopsis format. Quickly locate more in-depth discussions inside the parent text with abundant cross-references and a parallel chapter organization. Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices.

This book is the proceedings of the Falk Symposium No. 135 held in Prague, Czech Republic, on September 12-13, 2003, and is dedicated to the important issue of immunological aspects of diseases of the liver and gut. Without any doubt, immunological pathways are among the most important and universal factors in the pathogenesis of all diseases. Their importance is also constantly increasing, because these principles have been adopted in clinical practice for both diagnostic and therapeutic procedures. Chapters by prominent experts will stimulate new ideas and set the scene for productive discussion on this topic.

Systems and Signal Processing of Capnography as a Diagnostic Tool for Asthma Assessment provides a comprehensive overview of groundbreaking tools and techniques for the diagnosis and monitoring of asthma. Sections cover an introduction to the human respiratory system and the pathophysiology of asthma before analyzing current assessment concepts, tools and techniques. The book describes spirometry and the peak flow meter as existing tools in assessing asthma along with their limitations. In addition, a detailed description of capnography as a new approach is included with various studies conducted on its analysis. Academicians and researchers in biomedical engineering, particularly in the course of biomedical signal processing and biomedical instrumentation will find the book useful.

Nanotechnology is a collective term describing a broad range of relatively novel topics. Scale is the main unifying theme, with nanotechnology being concerned with matter on the nanometer scale. A quintessential tenet of nanotechnology is the precise self-assembly of nanometer-sized components into ordered devices. Nanotechnology seeks to mimic what nature has achieved, with precision at the nanometer level down to the atomic level. Nanobiotechnology, a division of nanotechnology, involves the exploitation of biomaterials, devices or methodologies in the nanoscale. In recent years a set of b- molecules has been studied and utilized. Virus particles are natural nanomaterials and have recently received attention for their tremendous potential in this field. The extensive study of viruses as pathogens has yielded detailed knowledge about their biological, genetic, and physical properties. Bacterial viruses (bacte- ophages), plant and animal eukaryotic viruses, and viruses of archaea have all been characterized in this manner. The knowledge of their replicative cycles allows manipulation and tailoring of particles, relying on the principles of self-assembly in infected hosts to build the base materials. The atomic resolution of the virion structure reveals ways in which to tailor particles for higher-order functions and assemblies.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases. The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.

The role of vitamin A in living organisms has been known throughout human history. In the last 100 years, the biochemical nature of vitamin A and its active derivative, retinoic acid, its physiological impact on growth processes, and the essential details of its mechanism of action have been revealed by investigations carried out by researchers using vertebrate and more recently invertebrate models to study a multiplicity of processes and conditions, encompassing embryogenesis, postnatal development to old age. A wealth of intercellular interactions, intracellular signaling systems, and molecular mechanisms have been described and the overall conclusion is that retinoic acid is essential for life. This book series, with chapters authored by experts in every aspect of this complex field, unifies the knowledge base and mechanisms currently known in detailed, engaging, well-illustrated, focused chapters that synthesize information for each specific area. In view of the recent information explosion in this field, it is timely to publish a contemporary, comprehensive, book series recapitulating the most exciting developments in the field and covering fundamental research in molecular mechanisms of vitamin A action, its role in physiology, development, and continued well-being, and the potential of vitamin A derivatives and synthetic mimetics to serve as therapeutic treatments for cancers and other debilitating human diseases. Volume II is divided into nine chapters contributed by prominent experts in their respective fields. Each chapter starts with the history of the area of research. Then, the key findings that contributed to development of the field are described, followed by a detailed look at key findings and progress that are being made in current, ongoing research. Each chapter is concluded with a discussion of the relevance of the research and a perspective on missing pieces and lingering gaps that the author recommends will be important in defining future directions in vitamin A research.