Bioinformatics as a discipline has come of age, and there are now numerous databases and tools that are widely used by researchers in the biomedical field. However, successful development of future bioinformatics applications will depend on an appropriately formalised representation of domain knowledge.

This book provides a timely and first-of-its-kind collection of contributed chapters on anatomy ontologies. It is interdisciplinary in its approach, bringing together relevant expertise from computing and biomedical studies, and covering both theoretical and applied aspects, with an emphasis on newer work relevant to the emerging Semantic Web.

Topics and Features:

a [ Provides a comprehensive discussion of the foundations of anatomical ontologies and the state of the art in existing computational tools and applications

a [ Considers a number of fundamental modelling principles

a [ Includes chapters about research on algorithms to systematically align anatomy ontologies and to mine data in the literature, using anatomy terms

a [ Explains recent efforts to develop a common anatomy reference ontology

a [ Discusses anatomy in the context of spatio-temporal biomedical atlases

a [ Describes systems and tools for linking anatomy ontologies with each other and with other on-line resources, such as the biomedical literature

a [ Highlights the challenges of dealing with anatomy-based information on the Semantic Web

Although primarily written for readers who will be involved in developing the next generation of IT applications in the areas of life sciences, biomedical sciences and health care, this unique volume will be of interest to anyone who will furtherdevelop anatomy ontologies, who will use them, and who will be involved in the actual development of relevant (semantic) web applications.

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.

This timely volume explores the use of CRISPR-Cas9 for genome editing, presenting cutting-edge techniques and their applications in treatment of disease. The chapters describe latest methods such as use of targetable nucleases, investigation of the non-coding genome, mouse genome editing, increasing of knock-in efficiency in mouse zygotes, and generation of reporter stem cells; the text contextualizes these methods in treatment of cardiovascular disease, diabetes mellitus, retinitis pigmentosa, and others. The final chapters round out the book with a discussion of controversies and future directions. Genome Editing is an essential, of-the-moment contribution to this rapidly growing field. Drawing from a wealth of international perspectives, it presents novel techniques and applications for the engineering of the human genome. This book is essential reading for all clinicians and researchers in stem cells, regenerative medicine, genomics, biochemical and biomedical engineering- especially those interested in learning more about genome editing and applying it in a targeted, specific way.

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 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

This volume will explore the latest findings in research into the genetics of breast and reproductive cancers, covering the epidemiological aspects of these cancers, their etiology, the effect of environment on genes and cancer etiology, and how research in this area can lead to development of preventative measures and treatments.

Epigenetics is a rapidly expanding field in medical and biological research which concerns heritable traits that are not attributable to changes in the DNA sequence. Epigenetic mechanisms play key roles in many biological processes, and it has become clear that their disruption can gives rise to diverse pathologies in humans. Edited by preeminent experts, Sophie Rousseaux and Saadi Khochbin, this volume in the Epigenetics and Human Health' series discusses the role of epigenetics in human reproduction. The book presents epigenetic transitions that are important at defined stages of gametogenesis and during meiosis. Several of the sixteen chapters written by experts in the field cover fundamental concepts discovered through cellular and biochemical work and from research on animal models. In other chapters, key examples are provided of how disruption of these mechanisms affects germ cell development and fertility, and contributes to the germinal cancers. Finally, the book discusses how in vitro manipulation and culture in assisted reproduction can epigenetically perturb germ cells, and how this can trigger disease phenotypes in the next generation. Conceived towards advanced students, medical professionals and research scientists, this is the first comprehensive textbook on this topic that will serve as a valuable reference during the years to come.

"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."

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 volume presents a valuable and readily reproducible collection of established and emerging techniques on modern genetic analyses. Chapters focus on statistical or data mining analyses, genetic architecture, the burden of multiple testing, genetic variance, measuring epistasis, multifactor dimensionality reduction, and ReliefF. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Epistasis: Methods and Protocols aids scientists in continuing to study elucidate epistasis in the context of modern data availability.

Ever wondered why your life and health can sometimes be so hard to control? Or why it seems so easy for other people? Mark Hanson and Lucy Green draw on their years of experience as scientists and educators to cut through the usual information on genetics and lifestyle to reveal the secrets of early development which start to make each of us unique, during our first 1,000 days from the moment of conception. Some surprising discoveries, based on little-known new research, show how events during our first 1,000 days make each of us who we are and explain how we control our bodies, processes that go way beyond just the genes which we inherited. Provoking new ways of thinking about being parents, this book empowers individuals and society to give the next generation the gift of a good start to life and future health.

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.

This unique book explores the role of retrotransposons in human health and disease. The ability of retrotransposons to affect the structure of human genes is recognized since the late 80's. However, the advances of deep-sequencing technologies have shed new light on the extent of retrotransposon-mediated genome variations. These progresses have also led to the discovery that retrotransposon activity is not restricted to the germline - resulting in inheritable genetic variations - but can also mobilize in somatic tissues, such as embryonic stem cells, neuronal progenitor cells, or in many cancers. This book covers topics related to the effects of retrotransposon insertions, and their consequences on germline and somatic genome dynamics, but also discuss the role and impact of retrotransposons sequences in a broader context, including a number of novel topics that emerged recently (long non-coding RNA, neuronal disorders, exaptation) with unexpected connections between retrotransposons, stem cell maintenance, placentation, circadian cycles or aging.

The first book to provide a detailed analysis of the body-trafficking networks of the dead poor that underpinned the expansion of medical education from Victorian times. With an even-handed approach to the business of anatomy, Hurren uses remarkable case histories which still echo a vibrant body-business on the internet today in a biomedical age.

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 focuses on a development for assessing mental changes using eye pupil reactions, namely extracting emotional change from the response to evaluate the viewer's interest in visual information. The pupil of the eye reacts to both brightness and emotional state, including interest, enjoyment, and mental workload. Because pupillary change is a biological signal, various artifacts influence measurements of eye images. Technical procedures are required to extract mental activities from pupillary changes, and they are summarized here step by step, although some procedures contain earlier techniques such as analog video processing. This study examines the possibility of estimating the viewer's interest and enjoyment of viewing movies by measuring the dynamic pupillary changes, blinking, and subjective interest responses. In evaluation of pupil size, there was a significant difference in pupil size between the higher and the lower shot for the degree of subject interest response in each kind of movies. The first part of the book shows a pupil reaction model for brightness changes to extract mental activities. Pupil reactions were observed for various visual stimuli in brightness changes. With regard to the characteristics of pupillary changes, a model with a three-layer neural network was developed and the performance was evaluated. Characteristics of pupil reactions during model development are summarized here. The second part examines the possibility of estimating the viewer's interest and enjoyment of television programs by measuring dynamic pupillary changes, blinking, and subjective interest responses. The final part describes a development of estimation model of pupil size for blink artifact. The model development was able to estimate pupillary changes and pupil size while the viewer was blinking and was applied to pupillary changes in viewing television programs.

This book is the proceedings of the Falk Symposium No. 138 on "State of the Art of Hepatology: Molecular and Cell Biology" (part of the XII International Falk Liver Week 2003 in honour of Hans Poppera (TM)s 100th birthday, held on October 20--11, 2003), and reflects the tremendous advances in the science of hepatology both at the molecular as well as the cellular level.

The book comprises four major sections. In Section I, the basic aspects of liver cell biology are covered, including RNA metabolism, regeneration, transport and metabolic functions, as well as fibrogenesis and malignant transformation. In Section II, the novel field of stem cell plasticity and cell therapy for liver diseases is discussed in detail, including stem cell biology, hepatocyte transdifferentiation from extrahepatic stem cells and their therapeutic use for liver cell repopulation, as well as hepatocyte transplantation. In Section III, novel therapeutic strategies for liver cirrhosis and hepatocellular carcinoma are presented, including the reversal of liver fibrosis, oncolytic biotherapy and different concepts of gene therapy for hepatocellular carcinoma. In Section IV, novel aspects of gene therapy and prevention of liver diseases are addressed, including small interfering RNAs, ribozymes, antisense oligonucleotides, as well as DNA vaccination.

An international faculty of outstanding scientists from different research areas presents the state of the art on these most important aspects of hepatology and their perspectives for future developments. Molecular and cell biology are at the very centre of research developments in modern hepatology and are of interest and importance to both basic scientists aswell as clinicians involved in patient care.

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.

As cells mature they naturally stop dividing and enter a period called senescence. But cellular senescence can also be induced prematurely by certain oncogenes involved in cancer development. Cellular senescence, a growth-arrest program that limits the lifespan of mammalian cells and prevents unlimited cell proliferation, is attracting considerable interest because of its links to tumor suppression.

This volume explores databases containing genome-based data and genome-wide analyses. This book covers databases from all eukaryotic taxa, except plants. The chapters describe database contents and classic use-cases, which assist in accessing eukaryotic genomic data and encouraging comparative genomic research. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, step-by-step, readily reproducible computational protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and authoritative, Eukaryotic Genomic Databases: Methods and Protocols is a valuable resource for geneticists and molecular biologists who are interested in the latest eukaryotic genomics data. The chapters 'PomBase: The Scientific Resource for Fission Yeast' and 'The Ensembl Genome Browser: Strategies for Accessing Eukaryotic Genome Data' are available open access under a CC BY 4.0 license via link.springer.com.

This detailed volume explores the latest methods that can be used to probe mRNA decay pathways and identify mRNA-binding protein targets as well as miRNA targets. Subjects include metabolic labelling and RNAseq methods for determining RNA decay rates, approaches for discovering RNA-binding protein targets, bioinformatics, miRNA targets and novel components of the miRNA-directed decay pathway, and recently developed approaches for studying nonsense-mediated mRNA decay, among other areas. Written for the highly popular Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, mRNA Decay: Methods and Protocols serves as an ideal guide for molecular biologists, geneticists, and developmental biologists with an interest in understanding how normal development and tissue homeostasis is regulated and how these processes are perturbed in inherited and acquired diseases.

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.

Human cell culture is not a new topic, but the development of new molecular techniques and reagents which can be used to investigate cell function and the responsible intracellular mechanisms make it a continuing requirement. This third edition of Human Cell Culture Protocols expands upon the previous editions with current, detailed protocols for the isolation and culture of a range of primary cells from human tissues. With new chapters on pancreatic cells needed for basic studies on the pathogenesis of diabetes and for their application for islet transplantation, the book also delves into protocols for hepatocytes, skin cells, lung cells, parathyroid cells, gastric cells, renal cells, adipocytes, ovarian cells, bone cells, vascular smooth muscle cells, vascular endothelial cells, regulatory T cells, blood mononuclear cells, as well as new techniques being applied to human cell culture, particularly the use of biocompatible scaffolds to grow cells, the in vitro use of laser microdissection to isolate cells from culture, and automated cell culture. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Human Cell Culture Protocols, Third Edition makes it possible for a worker with basic cell culture training, whether in the fields of cell biology, gene therapy, and cell transplantation, to prepare cell cultures of the specific cell type necessary to forward their vital research.