The study and modulation of cortical connections is a rapidly growing area in neuroscience. This unique book by prominent researchers in the field covers recent advances in this area. The first section of the book describes studies of cortical connections, modulation of cortical connectivity and changes in cortical connections with activities such as motor learning and grasping in primates. The second section covers the use of non-invasive brain stimulation to study and modulate cortical connectivity in humans. The last section describes changes in brain connectivity in neurological and psychiatric diseases, and potential new treatments that manipulate brain connectivity. This book provides an up-to-date view of the study of cortical connectivity, and covers its role in both fundamental neuroscience and potential clinical applications.

This book provides a concise set of protocols for assessing basic neutrophil functions, investigating specialized areas in neutrophil research, and completing step-by-step diagnostic assays of common neutrophil disorders. Each of the protocols is written by leading researchers in the field and includes hints for success, as well as guidance for troubleshooting. Scientists and clinicians will find this collection an invaluable aid.

This book contains a collection of papers that were presented at the IUTAM Symposium on Mechanics of Biological Tissue, which was held in Graz, A- tria,fromJune27toJuly2,2004.ThesettingofGrazwasveryappropriatefor the symposium since it is the city where such illustriousscientistsasJohannes Kepler, Ernst Mach, Ludwig Boltzmann, Erwin Schr. odinger and Otto Kratky spent parts of their lives, while the cultural life of Graz provided ample - portunity for complementing the scienti?c proceedings. Graz has an historic centre, which is one of the best preserved old town centres in Europe, and which was added to the UNESCO world cultural heritage list in 1999. Thesymposiumbroughttogether96participantsfromuniversities,research centres and clinics in 19 countries. There were 42 oral presentations, incl- ing 7 keynote lectures, and 15 poster presentations. The keynote lectures were given by P.B. Canham (University of Western Ontario, Canada), S.C. Cowin (City University of New York, USA), K. Hayashi (Osaka University, Japan), J.D. Humphrey (Texas A&M University, USA), P.J. Hunter (University of Auckland, New Zealand), R.S. Lakes (University of Wisconsin, USA), and P.D. Richardson (Brown University, USA).

What a journey writing this text has been. The lengthy voyage started well before the idea hatched of authoring a text that contained the word "thermodynamics"! I was informed by my good friend and sometimes colleague Dr. Jose Antonio that by including that word in the title, nutritionists and exercise physiologists might avoid the subject. But almost every step of my expedition was taken on a rather solid foundation of thermodynamics and as such the topic could not possibly be omitted from the title or the text of a book about bioenergetics and energy expenditure. I am not a physicist. In fact I ?rst went to college to become a football coach. That vocational choice began to deteriorate when taking the mandatory anatomy and physiology courses required of all physical education majors. This information was exciting; my interest in physical education began to wane. During sophomore year, I answered an advertisement in the school newspaper requesting research subjects.

The craniofacial musculature, including the extraocular muscles, muscles associated with the

auditory system, the masseter, the tongue, and the laryngeal and pharyngeal muscles, all

participate in functions that are critical to life: vision, intact of nutrition, breathing, and hearing.

Despite their critical importance, the majority of research on skeletal muscle basically has

ignored this collection of muscles. This is most likely due to their complexity in form,

development, fiber types, physiology, and disease profiles. All these make these muscles

extremely difficult to study.

Vision depends on voluntary and reflexive eye movements initiated by the oculomotor system.

The effector arm of this motor system includes the extraocular muscles and their motor neurons.

Mastication, and therefore food intake, depends on the complex movements of the masseter and

tongue musculature. The effector arm of this motor system includes the masseter and tongue

muscles and their motor neurons. Respiration, human phonation, as well as gestation, depend on

the laryngeal and pharyngeal musculature. The effector arm of these motor systems includes the

intrinsic and extrinsic laryngeal muscles and the pharyngeal muscles and their motor neurons.

Recently there has been a renewed interest in understanding the basic cell biology and

pathologies associated with these unusual skeletal muscles. This book will highlight novel

findings on the development of these muscles and their innervation, metabolic design, functional

consequences of their structural organization, and potential reasons for their differential response

to various neuromuscular diseases. In addition, critical areas for future studies will be identified.

Contents

E.I. Christensen and R. Nielsen: Role of Megalin and Cubilin in Renal Physiology and Pathophysiology

G. Zifarelli and M. Pusch: CLC Chloride Channels and Transporters: A Biophysical and Physiological Perspective

S.F.J. van de Graaf, R.J.M. Bindels and J.G.J. Hoenderop: Physiology of Epithelial Ca2 and Mg2+ Transport

This readable and student-friendly guide simplifies and clearly explains the complex concepts and processes of fluids and electrolytes in the human body. It utilizes a step-by-step learning approach and starts with the basics and advances to cover more complex issues. The new edition features revised NCLEX (R) examination-style questions and new case studies. Unique presentation of content allows students to survive and thrive. Material is presented using adult learning principles and various active-learning strategies to engage nursing students of all ages, backgrounds, and learning styles. Consistent chapter format breaks down information into small units and reinforces an effective thinking process. Special icons for Lifespan Considerations, Cultural Implications, Web Links, and Cautions help the student quickly identify special content in the chapter. Memory-reinforcing interactive activities (including fill-in the blank, matching, word jumbles, true/false, and crossword puzzles) promote student learning. Clinical terms and shorthand expressions are highlighted in parentheses to expose students to terminology that they will hear in the hospital setting. Boxed Take Home Points provide the benefit of years of nursing experience that students can use to prepare for their clinical rotation. Original cartoon-character illustrations walk the student through difficult subjects with a lighthearted approach. Cover design and series title better identifies the series as a fun and simple review. What You Will Learn section provides chapter objectives for the reader to aid in their navigation through the chapters. Over 100 NCLEX (R) examination-style review questions have been moved to the ends of chapters to immediately test student knowledge.

This comprehensive volume completes Frederic Holmes's notable and detailed biography of Hans Krebs, from the investigator's early development through the major phase of his groundbreaking investigation, which lay the foundations upon which the modern structure of intermediary metabolism is built. With access to Krebs's research notebooks as well as to Krebs himself through more than five years of personal interviews, the author provides an insightful analysis of Hans Krebs and of the scientific process as a whole. The first volume, published in 1991, covered Krebs's formative years in Germany, his work with Otto Warburg, and his discovery of the urea cycle in 1932. This second volume reconstructs the investigative pathway and the professional and personal life of Hans Krebs, from the time of his arrival in England in 1933 until 1937, when he made the discovery for which he is best known-the formulation of the citric acid cycle. Holmes portrays Krebs's activity at the intimate level of daily interactions of thought and action, from which the characteristic patterns of scientific creativity can best be seen. Holmes's fascinating portrait of Krebs integrates the great scientist's investigative pathways with his personal life. The result is an illuminating analysis of both man and scientist that will be of interest to biochemists and historians of science.

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

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

The eukaryotic translation machinery must recognize the site on a messenger RNA (mRNA) where decoding should begin and where it should end. The selection of the translation start site is generally given by the ?rst AUG codon encoding the amino acid methionine. D- ing initiation soluble translation initiation factors (eukaryotic translation initiation factors [eIFs] in eukaryotes and prokaryotic translation initiation factors [IFs] in prokaryotes) bind the mRNA, deliver the initiator Met-tRNA, and assemble to form a complete 80S ribosome from the 40S and 60S subunits. By progressing along the mRNA in the 5 -to-3 direction the ribosome decodes the information and translates it into the polypeptide chain. During this process, repeated delivery of amino-acyl tRNA (aa-tRNA) to the ribosome, peptide bond formation, movement of the mRNA, and the growing peptidyl-tRNA is mediated by both soluble elongation factors (eukaryotic translation elongation factors [eEFs] in euka- otes and prokaryotic translation elongation factors [EFs] in prokaryotes) and the activity of the ribosome. The ?nal step in the translation process occurs when one of the three t- mination codons occupies the ribosomal A-site. Translation comes to an end and soluble release factors (eukaryotic translation termination factors [eRFs] in eukaryotes and proka- otic translation termination factors [RFs] in prokaryotes) facilitate hydrolytical release of the polypeptide chain (for recent reviews, see Inge-Vechtomov et al. 2003; Kisselev et al. 2003; Wilson and Nierhaus 2003; Kapp and Lorsch 2004).

"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."

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.

Biological rhythms time the ebb and flow of virtually every physiological process, and their mutual coordination guarantees the integrity of the organism over space and time. Aging leads to the disintegration of this coordination, as well as to changes in the amplitude and/or frequency of the underlying rhythms. The results of this are accelerated loss of health during aging, and in experimental model systems curtailed lifespan occurs. This book will examine the machinery that constitutes circadian systems and how they impact physiologic processes. It will also discuss how disturbances of circadian rhythms can lead to complex diseases associated with aging. Much of this treatment will focus on metabolism and genome stability. Importantly, the chapters in this book will encompass work in several different models, in addition to human. The book will conclude with a discussion of modeling approaches to biologic cycles and chronotherapy, for future research and translation.

Immediate access to expert advice ... Every so often a physician will be confronted with a patient who has an inborn error of metabolism. This can be a challenging situation, particularly in an emergency when rapid, specific investigations and effective treatment are essential for a good outcome. It is exactly then that it is good to have the Vademecum Metabolicum at hand. This concise book ... explains the typical presentation patterns of the various metabolic disease groups; describes essential differential diagnostic procedures; summarises the main features of all metabolic diseases from the clinician's point of view. With its unique approach, easy accessibility, and availability in 10 different Languages, Vademecum Metabolicum is the most successful book on inborn errors of metabolism worldwide! Highly valued by practitioners in all specialities (particularly paediatricians, geneticists, general physicians, neurologists, laboratory physicians) as well as midwives, nurses and medical students.

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.

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.

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.

The Multiple Inert Gas Elimination Technique (MIGET) is a complex methodology involving specialized gas chromatography and sophisticated mathematics developed in the early 1970's. Essentially, nobody possesses knowledge of all its elements except for its original developers, and while some practical and theoretical aspects have been published over the years, none have included the level of detail that would be necessary for a potential user to adopt and understand the technique easily. This book is unique in providing a highly detailed, comprehensive technical description of the theory and practice underlying the MIGET to help potential users set up the method and solve problems they may encounter. But it is much more than a reference manual - it is a substantial physiological and mathematical treatise in its own right. It also has a wide applicability - there is extensive discussion of the common biological problem of quantitative inference. The authors took measured whole-lung gas exchange variables, and used mathematical procedures to infer the distribution of ventilation and blood flow from this data. In so doing, they developed novel approaches to answer the question: What are the limits to what can be concluded when inferring the inner workings from the "black box" behavior of a system? The book details the approaches developed, which can be generalized to other similar distributed functions within tissues and organs. They involve engineering approaches such as linear and quadratic programming, and uniquely use mathematical tools with biological constraints to obtain as much information as possible about a "black box" system. Lastly, the book summarizes the hundreds of research papers published by a number of groups over the decades in a way never before attempted in order to marshal the world's literature on the topic and to provide in one place the wealth of important discoveries, both physiological a nd clinical, enabled by the technique.

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.

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.

"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.