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.

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.

Pathological heart rhythms are a major health issue. In this book experts from various fields provide an important context for understanding the complicated molecular and cellular mechanisms that underlie normal and pathophysiological cardiac rhythms.

Individual chapters cover a full range of topics, including the ionic basis of pacemaking, the role of specific channels and transporters in sinoatrial node pacemaking, altered intracellular Ca2+ handling in response to disease, computer modeling of the action potentials of pacemaker and working cardiomyocytes, genetic and molecular basis of inherited arrhythmias and a review of established and novel antiarrhythmic agents. Due to the key importance of the specialized pacemaker cells and tissue (sinoatrial and atrioventricular nodes) in maintaining heart rate and rhythm, special emphasis is placed on the peculiar electrophysiology of these cells.

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).

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.

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

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).

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.

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.

"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."

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.

"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.

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.

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.

Awarded with the 2018 Prose Award in Clinical Medicine, the third edition of Principles of Gender-Specific Medicine explored and described exciting new areas in biomedicine that integrated technology into the treatment of disease and the augmentation of human function. Novel topics such as the sex-specific aspects of space medicine, the development and the use of genderized robots and a discussion of cyborgs were included in the third edition, providing a preview of the expanding world of sex-specific physiology and therapeutics. This Fourth Edition is a continuation of the mission to trace the relevance of biological sex to normal function and to the experience of disease in humans. We are now twenty years into the postgenomic era. The investigation of how the genome produces the phenome has led to fascinating insights as well as yet unanswered questions. Principles of Gender-Specific Medicine, Fourth Edition, has a central theme: discuss advances in understanding the role of epigenetics in regulating gene expression in a dynamic, sex-specific way during human life. It explores the protean role of epigenetics in human physiology, the relevance of environmental experience to human function, the therapeutic promise of cutting-edge methodologies like gene manipulation, the preparation of humans for space travel, the use of artificial intelligence in detection and therapeutic decisions concerning disease states, the possibilities for technological support of not only compromised individuals but of the augmentation of human function, and an analysis of the benefits, limitations and issues that surround our current expectations of personalized medicine.

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.

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.

This volume entitled 'The Role of Chemistry in the Evolution of Molecular Medicine' contains a collection of papers that form the proceedings of the Symposium held at the University of Szeged (27-29 June 2003).
As well as covering developments in the field over the last 60 years, the proceedings of this Symposium has laid the foundations for the future of the field of molecular medicine. Contributors span a wide range of molecular science disciplines including mathematics, physics, computer science, chemistry, biochemistry, biology and medicine, and cover the whole territory in agreement with the legacy of Professor Albert Szent-Gyorgyi.
This volume was particularly inspired by the booklet published in 1960 by Albert Szent-Gyorgyi under the title 'Introduction to submolecular biology', and the contents of this booklet have been included here in its entirety as an Appendix.
General topics include:
- Advanced computations
- Molecular computations
- Drug discovery"

Topics covered in this volume include pheromone reception in mammals, elucidation of mammalian bitter taste, synaptic modulation in pain pathways, the vertebrate phototransduction cascade, and amplification and termination mechanisms.

In today's world, three great classes of non-infectious diseases - the metabolic syndromes (such as type 2 diabetes and atherosclerosis), the cancers, and the neurodegenerative disorders - have risen to the fore. These diseases, all associated with increasing age of an individual, have proven to be remarkably complex and difficult to treat. This is because, in large measure, when the cellular signaling pathways responsible for maintaining homeostasis and health of the body become dysregulated, they generate equally stable disease states. As a result the body may respond positively to a drug, but only for a while and then revert back to the disease state. Cellular Signaling in Health and Disease summarizes our current understanding of these regulatory networks in the healthy and diseased states, showing which molecular components might be prime targets for drug interventions. This is accomplished by presenting models that explain in mechanistic, molecular detail how a particular part of the cellular signaling web operates properly in health and improperly in disease.

The stability of the health- and disease-associated states is dynamic and supported by multiple feedback loops acting positively and negatively along with linkages between pathways. During the past few years an ongoing series of important discoveries have been made that advance our understanding of how the body works and may guide us on how to better deal with these diseases. These include the discovery of chronic inflammation as a causal factor in all of these disease classes, the appearance of reactive oxygen species as a messenger molecule that can act both positively and negatively, the propensity of proteins to misfold into aggregation- and disease-prone forms, and the rise of epigenetics including the emergence of small non-coding RNA with important regulatory functions out of the so-called junk RNA. Chapters are devoted to each of these classes of findings with additional details integrated into the chapters dealing directly with the diseases. The connections responsible for maintaining stability are explored in depth.

Although 20 million Americans are affected by thyroid disease (85 per cent of them women), misinformation about the disease continues to spread. An up-to-date comprehensive resource, this book helps readers understand just what is, and is not, thyroid disease. Including recent medical developments, patient profiles, photos and illustrations, and a section on 'Thyroid Newsmakers' -- from Muhammed Ali to Joe Piscopo -- the book contains answers to all the questions you think of after you leave the doctor's office.

Detection of Change: Event-Related Potential and fMRI Findings presents the first systematic overview of how event-related brain potential (ERP), cognitive electroencephalography (EEG), and functional magnetic imaging (fMRI) measures reflect the mental events arising from changes in sensory stimulation. Reviews by leading experts provide clarifying introductory background material that is well integrated with the cogently collated findings. Topics include the empirical and theoretical analysis of mismatch negativity, P300, human lesion studies, and stimulus binding. These areas provide the backdrop for summaries of auditory/visual ERP interactions, the conjoint use of fMRI methods, and neuroelectric processing models of attention and memory. The contents are fresh, the literature distillations highly informative, and the range of topics extremely useful. This book fills a major need by making contemporary results highly assessable to cognitive neuroscientists, psychologists, and researchers interested in the neural underpinnings of how the brain responds to stimulus change.

Over the past decades, the pathogenesis, diagnosis, treatment and prevention of cardiovascular diseases have been benefited significantly from intensive research activities. In order to provide a comprehensive "manual" in a field that has become as broad and deep as cardiovascular medicine, this volume of "Methods in Molecular Medicine" covers a wide spectrum of in vivo and in vitro techniques encompassing biochemical, pharmacological and molecular biology disciplines which are currently used to assess vascular disease progression. Each chapter included in this volume focuses on a specific vascular biology technique and describes various applications as well as caveats of these techniques. The protocols included here are described in detail, allowing beginners with little experience in the field of vascular biology to embark on new research projects.