Biology, life sciences Books

Book SynopsisIn three volumes, historian Jole Shackelford delineates the history of the study of biological rhythms - now widely known as chronobiology - from antiquity into the twentieth century. Perhaps the most well-known biological rhythm is the circadian rhythm, tied to the cycles of day and night and often referred to as the body clock. But there are many other biological rhythms, and although scientists and the natural philosophers who preceded them have long known about them, only in the past thirty years have a handful of pioneering scientists begun to study such rhythms in plants and animals seriously. Tracing the intellectual and institutional development of biological rhythm studies, Shackelford offers a meaningful, evidence-based account of a field that today holds great promise for applications in agriculture, health care, and public health. Volume 1 follows early biological observations and research, chiefly on plants; volume 2 turns to animal and human rhythms and the disciplinary c

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Book SynopsisA coherent and practical philosophy of interdependence, drawing on vivid examples from the biological sciences.Trade Review"Kriti Sharma has written a remarkable book that moves seamlessly from the empirical world of biology-indeed, the microscales of test tubes and cells and molecules-to the consideration of the broadest philosophical concepts that define how we comprehend existence itself. The writing is lively and the illustrations are drawn from a wide and interdisciplinary range of sources and experiences, yet the development of the ideas is scholarly, careful, and well documented. Interdependence: Biology and Beyond will elevate and churn your thinking. It is Sharma's first book and the reader feels privileged to be present at the start of an exciting intellectual journey." -- -Peter White University of North Carolina at Chapel Hill "In setting forth her vision of contingentism-that objects are really webs of processes contingent on multiple interacting conditions-Sharma moves eloquently back and forth between biology and philosophy. The book is a model of accessible but serious and elegant science writing." -- -Evan Thompson University of British Columbia "It is a rare treat to indulge in reading a work that switches between philosophical reasoning and empirical biology. This is just what Sharma does, illuminating the concept of interdependence from its everyday usage to focus in on the micro-scale network of processes that are contingent on interactions of organisms with one another and their environments." -The Biologist "Interdependence is an exceptionally original work of comprehensive theorizing. Conceptually subtle, empirically rigorous, and compellingly argued, it addresses some of the most fundamental questions in theoretical biology and demonstrates their close relation to central problems in our ideas of knowledge, existence, and reality." -- -Barbara Herrnstein Smith author, Scandalous Knowledge: Science, Truth and the HumanTable of ContentsTable of Contents Introduction - Taking Interdependence Seriously A brief sketch of what's to come Chapter 1 - It Depends: Existence as Contingent Small worlds Introducing key concepts: reality, existence, and contingency Features of contingentism What contingentism is not Signal transduction and the book's organization Encouragement to stick with a challenging topic Chapter 2 - What Do Objects Depend On?: Physical Substance, Matter, and the External World Assumption of the intrinsic boundedness and continuity of objects Assumption of the intrinsic boundedness and continuity of particles Assumption of the intrinsic existence of (emergent) properties Assumption of the intrinsic existence of causal powers Assumption of the unified object of sense perceptions (both within and between observers) Assumption of non-impingement: "Whatever it is, it sure doesn't depend on us" Chapter summary Chapter 3 - What Does Sensing Depend On?: Transduction, Energy, and the Meeting of Worlds An overview of signal transduction Signal transduction and cell sensing Assumption of sameness and difference Assumption of energy as a kind of substance Relating physical and psychological phenomena Re-viewing sensing: new views of transformation and change Chapter summary Chapter 4 - What Do Organisms Depend On?: Bodies, Lives, Selves, and Internal Worlds Assumption of the boundedness and continuity of organisms Assumption of the coordinator and the experiencer Assumption of intrinsically existent "other minds": why do we take one another seriously as subjects? Assumption of a ground: physicalism, idealism, dualism, and contingentism What does your life depend on? Chapter summary Chapter 5 - What Does Order Depend On?: Patterns, Gaps, and the Known World On cognitive patterns and cognitive dissonance: what does order depend on? Assumption of the intrinsic existence of contradictions: what does surprise depend on? Assumption of intrinsic hierarchies of order: what makes a good theory? Assumption of a single origin and a linear history Assumption of knowledge as limited: exactly where are the gaps between organismal experience and reality? Chapter summary Conclusion - Life As We Know It "Nothing but net": thoroughgoing contingency and the absence of inherent existence Why "contingentism"?: genealogies, relations, and intellectual kindred The many forms that wonder takes Coda: Small, vast worlds Acknowledgments: What Does This Book Depend On? References

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Book SynopsisBiodiversity has been identified as a key issue in the general debate about the sustainable use of the world's natural resources. Major international efforts are now underway to assess and maintain biodiversity. However, there is an urgent need to collect, manage and disseminate information related to biodiversity in an efficient and effective way. The purpose of this book is to review the needs and opportunities for information and efficient information flows in support of world priorities in biodiversity. It is based on papers presented at a workshop held in London in July 1996, organized by CAB International with the support of the International Union of Biological Sciences (IUBS), International Union of Forestry Research Organizations (IUFRO), IUCN The World Conservation Union and the United Nations Environment Programme (UNEP). Contributors include leading players from organizations concerned with conserving and managing biodiversity, based in Europe and the USA as well as develoTable of Contents1: Keynote Address 2: The importance of biodiversity information Sir Crispin Tickell, Green College, The Radcliffe Observatory, University of Oxford, Oxford, UK 3: Defining and Meeting Needs for Information 4: Information Needs in Biodiversity Assessments - From Genes to Ecosystems V H Heywood, University of Reading, UK 5: Assessing Information Needs for Sustainable Use and Conservation of Biodiversity Dan H Janzen, University of Pennsylvania, USA and R Gámez, INBio, Santa Domingo de Herdia, Costa Rica 6: Defining and Meeting Needs for Information: Agriculture and Forestry Perspective T J B Boyle, Center for International Forestry Research, Bogor, Indonesia and J M Lenné, International Crops Research Institute for the Semi-Arid Tropics, Patancheru, India 7: Collecting and Managing the Information 8: Information Needs of Inventory Programmes D L Hawksworth and R K Mibey, University of Nairobi, Kenya 9: Wider Use and Application of Indigenous Knowledge, Innovations and Practices: Information Systems and Ethical Concerns D D Posey, The Oxford Centre for the Environment, University of Oxford, Oxford, UK 10: Management of Information to Support Conservation Decision Making J R Busby, World Conservation Monitoring Centre, Cambridge, UK 11: Overview of the UNEP/GEF Biodiversity Data Management Project (BDM) F Duff, United Nations Environment Programme, Nairobi, Kenya 12: Distributing the Information 13: The Role of Information in the Operation of the Convention on Biological Diversity C Juma, UNEP, World Trade Centre, Montreal, Canada 14: Designing Information Systems to Support Biodiversity Conservation B A Stein, The Nature Conservancy, Arlington, USA 15: Networks for Distributing Information V P Canhos, Universidade Estadual de Campinas, Brasil, G P Manfio, Tropical Culture Collection, Fundação de Pesquisas e Tecnologia, Brasil, D A L Canhos, Tropical Database, Fundacao de Pesquisas e Tecnologia, Brasil 16: Biodiversity: The Role of Information Technology in Distributing Information J R Burley, University of Oxford, Oxford, UK, P R Scott, CAB INTERNATIONAL, Wallingford, UK and A W Speedy, University of Oxford, Oxford, UK 17: Overall Conclusions 18: Final Report Recommendations

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Book SynopsisAntioxidants play an important role in the progression of major human degenerative diseases and conditions. This book covers antioxidants and their mechanisms of action; their role in a whole array of conditions including coronary heart disease, malignant disease, diabetes, cataracts, respiratory disease, cystic fibrosis, cognitive functions, and aging; their indicators for oxidative stress; and consumer issues. The majority of chapters have been developed from papers presented at the 6th World Congress in Clinical Nutrition, held in Banff, Canada, July 1997.Table of ContentsSection 1: Antioxidants and Their Mechanisms of Action Section 2: Food Factors as Antioxidants Section 3: Coronary Heart Disease Section 4: Malignant Disease Section 5: Other Diseases Section 6: Indicators of Oxidative Stress Section 7: Consumer Issues

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Book SynopsisGlobal attention to biodiversity has expanded in the past decade. Agricultural biodiversity is the most important part of biodiversity for human survival, yet has been neglected as a topic. This book provides a broad review of current thinking on agrobiodiversity - what it is, how it is conserved, and how it can be better utilized in sustainable farming. It brings together contributions from a wide geographical and disciplinary background. Emphasis is placed on functional interactions between components of agrobiodiversity in a range of farming systems, illustrated by many case studies. The book relates the evolution of agrobiodiversity and its successful management to the broader environment and to the growing need to conserve biodiversity in productive agricultural systems. It is essential reading for ecologists, biologists and agricultural scientists.Table of Contents1: Why agrobiodiversity? 2: The origins of agrobiodiversity in agriculture 3: The nature and role of crop biodiversity 4: Biodiversity in domesticated animals 5: The regulation and functional significance of soil biodiversity in agroecosystems 6: Pathogen biodiversity: its nature, characterization and consequences 7: Insect biodiversity in agroecosystems: function, value and optimization 8: Determinants of agrobiodiversity in the agricultural landscape 9: Traditional management of agrobiodiversity 10: Does plant breeding lead to a loss of genetic diversity? 11: The effects of pest management on biodiversity in agroecosystems 12: The effects of alternative tillage systems on biodiversity in agroecosystems 13: Seed management systems and effects on diversity 14: Conservation of agrobiodiversity 15: A conceptual framework for valuing on-farm genetic resources 16: Regulatory issues 17: Agrobiodiversity and natural biodiversity: some parallels 18: Optimizing biodiversity for productive agriculture

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Book SynopsisOnce a purely technical sub-discipline of hydrology, water quality management is now a social and political discipline, with concerns ranging from ensuring adequate health standards to preserving biological diversity and ecosystem integrity.Table of ContentsPreface vii Acknowledgements xiii 1 Water quality management: an evolving field for changing values 1 2 History of water quality management: the problem and its science 29 3 Attitudes, goals, and management strategies 45 4 Global water resources and how they are used: the expression of goals and objectives 61 5 Developing standards from the traditions of toxicology 79 6 classification and environmental quality assessment: the search for ecologically accurate aquatic metrics 107 7 The role of scale issues in water quality management 127 8 Water and the hydrologic cycle 143 9 rivers and streams: one-way flow systems 159 10 Groundwater and water quality: water to live on 183 11 Coastal zone water quality management 207 12 Lakes and water quality impacts 229 13 Wetlands: productive, vital, cleansing, and threatened 249 14 Structuring water management goals by ecological level 267 15 Responses to stress at the ecosystem, community, population, and individual levels 287 16 Regionalization in natural resource management: Ecoregions 305 17 Effects of land use on water quality 321 18 Management of water quality in a forested landscape 345 19 Management of water quality in an agricultural landscape 371 20 Management of water quality in an urban landscape 397 21 Special issue: cultural eutrophication 425 22 Special issue: acidification of fresh water resources 445 23 Special issue: global change: a proactive management challenge 465 24 Special issue: exotics: a special biological pollutant 487 25 Cultural dimensions of water quality policy 511 26 Paradigms in motion: integrated approaches to water quality policy 535 27 Decision making in practice: case studies 561 Literature Cited and References 589 Index 607

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Book SynopsisAs with all ecosystems, river systems involve a complex interaction of a rich diversity of micro--organisms, plants and animals with their physical and chemical environment.Table of ContentsIntroduction;. Algae;. Macrophytes;. Heterotrophic microbes;. Invertebrates;. Riverine fishes;. Food webs and species interactions;. Detritus processing;. Primary production;. The sampling problem;. Responses of aquatic biota to hydrological change;. Prediction of biological responses.

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Book SynopsisThis text provides an overview of current advances in theoretical ecology and closely related areas in evolution and natural resources management, and aims to familiarize ecologists with the mathematical and statistical approaches used in the different areas.Table of ContentsContributors vii Foreword ix Preface xi Acknowledgements xvii 1 J.M. McGlade: Individual-based models in ecology 1 2 E. Renshaw: Stochastic effects in population models 23 3 M. Keeling: Spatial models of interacting populations 64 4 D.A. Rand: Correlation equations and pair approximations for spatial ecologies 100 5 R. Law: Theoretical aspects of community assembly 143 6 S.L. Pimm: The dynamics of the flows of matter and energy 172 7 W.M. Getz: Population and evolutionary dynamics of consumer resource systems 194 8 P.H. Harvey and A. Purvis: Understanding the ecological and evolutionary reasons for life history variation: mammals as a case study 232 9 M.L. Rosenzweig: Species diversity 249 10 E.J. Milner-Gulland: Ecological economics 282 11 J.M. McGlade: Ecosystem analysis and the governance of natural resources 309 Index 343

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Book SynopsisEcological economics is an exciting interdisciplinary field of study that combines insights from the natural sciences, economics, philosophy and other fields to develop innovative approaches to environmental problems. It draws on a wide range of analytical perspectives, some radical others more conventional, to build a more complete understanding of human-ecosystem interactions. Current research in the field includes work on nature conservation, land use planning, pollution control, natural resource management, and environmental impact assessment/evaluation. Ecological Economics provides a comprehensive introduction to the core themes, presented in a clearly structured style, with chapters tailored specifically to readers without any economic or philosophical training. There is an emphasis throughout on the complementary roles of economics, ethics and ecology in environmental decision-making processes. The book reviews the evolution of important ideas in the field, explTrade Review"The book is very well produced, and each chapter has its own short reading list as well as a longer set of collective references. As an introductory textbook to the field, or as a resource for professionals and scientists to broaden their knowledge of methods and approaches, this book can be strongly recommended." Philip Thornton, Agricultural Systems 72, 2002 Table of ContentsPreface. Part I: Foundations for Ecological Economics:. 1. Introduction. 2. A Brief History of Ecological Economic Thought. 3. Economic Principles for Non-economists. 4. Ethics and Environmental Philosophy. Part II: Value and Valuation Tools:. 5. The Concept of Value. 6. The Economic Approach to Environmental Valuation. 7. The Ecological Approach to Environmental Evaluation. Part III: Frameworks for Decision-Making:. 8. Cost Benefit Analysis. 9. Environmental Impact Assessment. 10. Multicriteria Appraisal. 11. National Income Accounting. Part IV: Applications: Theory and Practice:. 12. Resource Harvesting. 13. Nature Conservation. 14. Pollution and Waste. References. Index

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Book SynopsisThe future is uncertain for the world''s large marine ecosystems. These relatively narrow ocean zones, which produce nearly 95% of useable marine biomass, are becoming increasingly stressed both by natural and anthropogenic changes. The potential for consequent negative effects on global ecologies and economies has aroused major international concern. This new volume is a state-of-the-art update on large marine ecosystems, representing a multidisciplinary effort to develop a more holistic approach to the research, monitoring and mangaement of marine resources.Table of ContentsPart One: Sustainability of Large Marine Ecosystems. - large marine ecosystems as global units for marine resources management. - an ecological perspective;. The large marine ecosystem approach to regional seas action plans and conventions: a geographic perspective;. Scientific and organizational aspects of large marine ecosystems research;. Application of large marine ecosystems management to global marine pollution;. Application of international global change research programs, including GLOBEC, to long-term large marine ecosystems management;. Approaches to forecasting biomass yields in large marine ecosystems;. Part Two: Regional Case Studies - Stress and Mitigation of Large Marine Ecosystems. - long-term viability in the food chains, biomass yields, and oceanography of the Bay of bengal ecosystem;. Effects of physical and biological changes on the biomass yield of the Humboldt Current ecosystem;. Food chains, physical dynamics, perturbations and biomass yields of the Sea of Okhotsk;. Effetcs of long-term physical and biological perturbations on the contemporary biomass yields of the Yellow Sea ecosystem;. Long-term variability in the food chains, biomass yields, and oceanography of the Canary Current ecosystem;. The large marine ecosystem of shelf areas in the Gulf of Guinea: long-term variability induced by climatic changes;. Ecological and fishing features of the Adriatic Sea;. Contrast between recent fishery trends and evidence for nutrient enrichment in two large marine ecosystems: The Mediterranean and The Black Seas;. Startified models of large marine ecosystems: a general approach and an application to the South China Sea;. Marine biogeographic provinces of the Bering, Chukchi and Beaufort Seas;. Effects of climatic changes on the biomass yield of the Barents Sea, Norwegian Sea and West Greenland large marine ecosystems;. The California Current, Benguela Current and Southwestern Atlantic Shelf ecosystems: a comparative approach to identifying factors regulating biomass yields;. Part Three: Sustainability and Management of Large Marine Ecosystems. - regional approach to large marine ecosystems;. Legal regimes for management of large marine ecosystems and their component resources;. Ocean management and the large marine ecosystem concept: taking the next step;. Convention on the conservation of Antarctic marine living resources;. Simulation study of effects of closed areas to all fishing, with particular reference to the North Sea ecosystem;. Research and management in the Northern California Current ecosystem;. Sutainable development of the Great Barrier Reef as a large marine ecosystem;. Role of national political factors in the management of LMEs: evidence from West Africa;. Large marine eocsystems of the Pacific Rim;. Part Four: Technology Applications to the Monitoring Process in Large Marine Ecosystems. - applications of advanced acoustic technology in large marine ecosystem studies;. Application of molecular techniques to large marine ecosystems;. Application of satellite remote sensing and optical buoys/moorings to LME studies

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Book Synopsis

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Book SynopsisThis volume looks at the latest techniques used to perform comparative structure analyses, and predict and evaluate protein-ligand interactions. The chapters in this book cover tools and servers such as LiteMol; Bio3D-Web; DALI; CATH; HoTMuSiC, a contact-base protein structure analysis tool known as CAD-Score; PyDockSaxs and HADDOCK; CombDock and DockStar; the BioMagResBank database; as well as BME and CoNSEnsX+. 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 comprehensive, Structural Bioinformatics: Methods and Protocols is a practical guide for researchers to learn more about the aforementioned tools to further enhance their studies in the growing field of structural bioinformatics. Chapter 13 isavailable open access under a CC-BY 4.0 license via link.springer.Table of ContentsPreface…Table of Contents…Contributing Authors…1. Visualization and Analysis of Protein Structures with LiteMol SuiteDavid Sehnal, Radka Svobodová, Karel Berka, Lukáš Pravda, Adam Midlik, and Jaroslav Koča2 Comparative Protein Structure Analysis with Bio3D-WebBarry J. Grant, Lars Skjærven, and Xin-Qiu Yao3 Using DALI for Protein Structure ComparisonLiisa Holm4. Assessing Protein Function through Structural Similarities with CATHNatalie L. Dawson, Christine Orengo, and Zoltán Gáspári5 Protein Thermal Stability Engineering using HoTMuSiCFabrizio Pucci, Jean Marc Kwasigroch, and Marianne Rooman6 Contact Area-Based Structural Analysis of Proteins and their Complexes using CAD-ScoreKliment Olechnovič, and Česlovas Venclovas7 A Comprehensive Computational Platform to Guide Drug Development using Graph-Based Signature MethodsDouglas E. V. Pires, Stephanie Portelli, Pâmela M. Rezende, Wandré N. P. Veloso, Joicymara S. Xavier, Malancha Karmakar, Yoochan Myung, João P. V. Linhares, Carlos H. M. Rodrigues, Michael Silk, and David B. Ascher8 Systematic Exploration of Binding Modes of Ligands on Drug TargetsCsaba Hetényi and Mónika Bálint9. Using MemBlob to Analyze Transmembrane Regions Based on Cryo-EM MapsGeorgina Csizmadia, Bianka Farkas, Eszter Katona, Gábor E. Tusnády, and Tamás Hegedűs10 Structural Characterization of Protein-Protein Interactions with pyDockSAXSBrian Jiménez-García, Pau Bernadó, and Juan Fernández-Recio11 Protein-Protein Modeling using Cryo-EM RestraintsMikael Trellet, Gydo van Zundert, and Alexandre M.J.J. Bonvin12 Modeling of Multimolecular ComplexesDina Schneidman-Duhovny and Haim J. Wolfson13 Biological Assembly Comparison with VAST+Thomas Madej, Aron Marchler-Bauer, Christopher Lanczycki, Dachuan Zhang, and Stephen H. Bryant14 BioMagResBank (BMRB) as a Resource for Structural BiologyPedro R. Romero, Naohiro Kobayashi, Jonathan Wedell, Kumaran Baskaran, Takeshi Iwata, Masashi Yokochi, Dimitri Maziuk, Hongyang Yao, Toshimichi Fujiwara, Genji Kurisu, Eldon L. Ulrich, Jeffrey C. Hoch, and John L. Markley15 Integrating Molecular Simulation and Experimental Data: A Bayesian/Maximum Entropy Reweighting ApproachSandro Bottaro, Tone Bengtsen, and Kresten Lindorff-Larsen16 Evaluation and Selection of Dynamic Protein Structural Ensembles with CoNSEnsX+Dániel Dudola, Bertalan Kovács, and Zoltán Gáspári

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Book SynopsisThis volume offers a comprehensive collection of experimental approaches to study Solanum tuberosum (potato). Chapters are divided into five sections covering a general overview of potato, the research fields of  molecular biology, omics approaches, and bioinformatics, and finally, the application of the generated knowledge for crop improvement. Written in the format of the highly successful Methods in Molecular Biology series, each wet-lab chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and practical, Solanum tuberosum: Methods and Protocols aims to provide a collection of methods for the potato research community that will enable scientists gain insight into the world of the potato.Chapter 2 is available open access under a Creative ComTable of ContentsImportance of Potato as a Crop and Practical Approaches to Potato Breeding.- Cryopreservation of Potato Shoot Tips for Long Term Storage.- RNA Sequencing Analyses for Deciphering Potato Molecular Response.- Yeast-2-hybrid Screening for Identification of Protein-Protein Interactions in Solanum tuberosum.- Potato as a Model for Field Trials with Modified Gene Functions in Research And Translational Experiments.- DAP-seq Identification of Transcription Factor Binding Sites in Potato.- Mass Spectrometric Monitoring Of Plant Hormone Crosstalk During Biotic Stress Responses In Potato (Solanum tuberosum L.).- A Comprehensive Guide to Potato Transcriptome Assembly.- MapMan visualization of RNA-seq data using Mercator4 functional annotations.- Identification of Resistance Genes Using Diagnostic R-gene Enrichment Sequencing (dRenSeq).- Methodologies for Discovery and Quantitative Profiling of sRNAs in Potato.- Co-expression for Genotype-Phenotype Function Annotation In Potato Research.- Computer Vision and Less Complex Image Analyses to Monitor Potato Traits In Fields.- Quantifying the contribution to virulence of Phytophthora infestans effectors in potato.- Identification of Solanum immune receptors by Bulked Segregant RNA-Seq and high-Throughput Recombinant Screening.- Gene editing in potato using CRISPR-Cas9 technology.- Gene downregulation in potato roots using Agrobacterium rhizogenes-mediated Transformation.- Molecular Detection of Ralstonia solanacearum to Facilitate Breeding for Resistance to Bacterial Wilt in Potato.- Towards the design of potato tolerant to abiotic stress.- Rapid loop-mediated isothermal amplification for detection of the Ralstonia solanacearum species complex bacteria in symptomatic potato tubers and plants.

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Book SynopsisThis volume provides protocols for computational, statistical, and machine learning methods that are mainly applied to the study of metabolic engineering, synthetic biology, and disease applications. These techniques support the latest progress in cross-disciplinary research that integrates the different scales of biological complexity. The topics covered in this book are geared toward researchers with a background in engineering, computational analytical, and modeling experience and cover a broad range of topics in computational and machine learning approaches. 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 tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Computational Biology and Machine Learning for Metabolic Engineering and Synthetic Biology is a valuablTable of ContentsPreface…Table of Contents…Contributing Authors…1. Challenges to Ensure a Better Translation of Metabolic Engineering for Industrial ApplicationsFayza Daboussi and Nic D. Lindley2. Synthetic Biology Meets Machine LearningBrendan Fu-Long Sieow, Ryan De Sotto, Zhi Ren Darren Seet, In Young Hwang, and Matthew Wook Chang3. Design and Analysis of Massively Parallel Reporter Assays using FORECASTPierre-Aurelien Gilliot and Thomas E. Gorochowski4. Modelling Protein Complexes and Molecular Assemblies using Computational MethodRomain Launay, Elin Teppa, Jérémy Esque, and Isabelle André5. From Genome Mining to Protein Engineering: A Structural Bioinformatics RouteDerek J. Smith6. Creating De Novo Overlapped GenesDominic Y. Logel and Paul R. Jaschke 7. Design of Gene Boolean Gates and Circuits with Convergent PromotersBiruck Woldai Abraha and Mario Andrea Marchisio8. Computational Methods for the Design of Recombinase Logic Circuits with Adaptable Circuit SpecificationsAna Zúñiga, Jérôme Bonnet, and Sarah Guiziou9. Designing a Model-Driven Approach Towards Rational Experimental Design in Bioprocess OptimizationJing Wui Yeoh and Chueh Loo Poh10. Modeling Subcellular Protein Recruitment Dynamics for Synthetic BiologyKwabena A. Badu-Nkansah, Diana Sernas, Dean E. Natwick, and Sean R. Collins11. Genome-Scale Modeling and Systems Metabolic Engineering of Vibrio Natriegens for the Production of 1,3-PropanediolYe Zhang, Dehua Liu, and Zhen Chen12. Application of GeneCloudOmics: Transcriptomics Data Analytics for Synthetic BiologyMohamed Helmy and Kumar Selvarajoo13. Overview of Bioinformatics Software and Databases for Metabolic EngineeringDeena M.A. Gendoo14. Computational Simulation of Tumor-Induced AngiogenesisMasahiro Sugimoto15. Computational Methods and Deep Learning for Elucidating Protein Interaction NetworksDhvani Sandip Vora, Yogesh Kalakoti, and Durai Sundar16. Machine Learning Methods for Survival Analysis with Clinical and Transcriptomics Data of Breast CancerLe Minh Thao Doan, Claudio Angione, and Annalisa Occhipinti17. Machine Learning Using Neural Networks for Metabolomic Pathway AnalysesRosalin Bonetta Valentino, Jean-Paul Ebejer, and Ingc Gianluca Valentino18. Machine Learning and Hybrid Methods for Metabolic Pathway ModelingMiroslava Cuperlovic-Culf, Thao Nguyen-Tran, and Steffany A.L. Bennett19. A Machine Learning Based Approach Using Multi Omics Data to Predict Metabolic PathwaysVidya Niranjan, Akshay Uttarkar, Aakaanksha Kaul, and Maryanne VargheseSubject Index List…

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Book SynopsisThe volume presents a small selection of state-of-the-art approaches for studying transposable elements(TE). Chapters guide readers through HTS-based approaches, bioinformatic tools, methods to studyTE protein complexes, and the functional impact on the host. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Transposable Elements: Methods and Protocols aims to be a useful practical guide to researches to help further their study in this field. Table of Contents1. An overview of best practices for transposable element identification, classification and annotation in eukaryotic genomes Fernando Rodriguez and Irina R. Arkhipova 2. Assembly-free annotation and quantification of transposable elements with dnaPipeTE Clément Goubert 3. Best practice for the identification of horizontally transferred transposons James D Galbraith, Zhipeng Qu, Atma M Ivancevic, David L Adelson 4. Genotyping of transposable elements insertions segregating in the human populations using short-read re-alignments Xun Chen, Guillaume Bourque, and Clément Goubert 5. A Pangenome approach to detect and genotype TE insertion polymorphisms Cristian Groza, Guillaume Bourque, and Clément Goubert 6. Experimental validation of transposable element insertions using the Polymerase Chain Reaction (PCR) Miriam Merenciano, Marta Coronado-Zamora, and Josefa González 7. Quantification of LINE-1 RNA expression from bulk RNA-seq using L1EM Wilson McKerrow 8. Genome-wide profiling of L1 DNA methylation by bs-ATLAS-seq Claude Philippe and Gael Cristofari 9. Nanopore epigenomic analysis of transposable element DNA modifications Nathan Smits and Geoffrey Faulkner 10. Targeted resequencing and methylation analysis of L1 elements by nanopore sequencing Arpita Sarkar, Sophie Lanciano, and Gael Cristofari 11. Inferring protein-DNA binding profiles at interspersed repeats using HiChIP and PatChER Darren Taylor and Miguel R Branco 12. Affinity-based Interactome Analysis of Endogenous LINE-1 Macromolecules Luciano H. Di Stefano, Leila Saba, Mehrnoosh Oghbaie, Hua Jiang, Wilson McKerrow, Maria Benitez-Guijarro, Martin S. Taylor, and John LaCava 13. LINE-1 retrotransposition assays in embryonic stem cells Marta Garcia-Canadas, Francisco Sanchez-Luque, Laura Sanchez, Johana Rojas, and Jose Garcia Perez 14. Detecting somatic transposable element insertions in Drosophila tissues Katarzyna Siudeja 15. Precise and scarless insertion of transposable elements by Cas9-mediated genome engineering” Vivien M Weber, Aurelien J Doucet, and Gael Cristofari 16. Epigenetic editing of transposable and repetitive elements Joanna M Jachowicz 17. Using CRISPR to investigate the regulatory activity of transposable elements David M Simpson, Conor R Kelly, and Edward B Chuong

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Book SynopsisRecognition Mechanisms of Chiral Selectors: An Overview.- Enantioseparation by Thin Layer Chromatography.- Enantioseparations by Gas Chromatography Using Porous Organic Cages as Stationary Phase.- Chiral Gas Chromatography in Wine Analysis.- Polysaccharide-Based Chiral Stationary Phases for Enantioseparations in Liquid-Phase Techniques: An Overview.- Polysaccharide-Based Chiral Stationary Phases Made with Superficially Porous Silica.- Analysis of Isomers of New Chiral Psychoactive Substances Using Enantioselective High-Performance Liquid Chromatography-Mass Spectrometry.- Preparative Chiral Resolution of Synthetic Cathinones Using Polysaccharide-Based Chiral Stationary Phases.- Enantioselective Analysis of Chiral Agrochemicals with High-Performance Liquid Chromatography.- Application of Chiral HPLC to Medicinal Chemistry-Related Problem Solution.- Chiral High-Performance Liquid Chromatography (HPLC) in Targeted Metabolomics.- Two-Dimensional LC-MS/MS Determination of Chiral Amino Acids in Real-World Samples.- Macrocyclic Glycopeptide-Based Chiral Stationary Phases Applied in Enantioselective Liquid Chromatographic Analyses: An Overview.- Separation and Analysis of Chiral Compounds by Nano-Liquid Chromatography Using Glycopeptide Antibiotics.- Cinchona Alkaloid-Based Zwitterionic Chiral Stationary Phases Applied for Liquid Chromatographic Enantiomer Separations: An Overview.- Fundamental Kinetic Studies for Understanding Chiral Separations in High-Performance Liquid Chromatography.- Molecularly Imprinted Polymer-Based Chiral Stationary Phases for Chromatographic Enantioseparation.- Applications of Chiral Supercritical Fluid Chromatography on Polysaccharide-Based Stationary Phases.- Cyclodextrins as Chiral Selectors in Capillary Electromigration Techniques.- Chiral Separation in Capillary Electrophoresis Using Cyclodextrins in Combination with Hydrophobic Deep Eutectic Solvents.- Application of Amino Acid-Based Chiral Ionic Liquids for Enantioseparation in Capillary Electrophoresis.- Application of Enantioselective Capillary Electrophoresis in Forensic Analysis.- Chiral Separations by Using Capillary Electrochromatography: An Overview.- Molecularly Imprinted Polymer-Based Electrochemical Chiral Sensors.- Nuclear Magnetic Resonance Spectroscopy Experiments to Investigate Separations of Enantiomers by Capillary Electrophoresis.- Application of Molecular Modeling to Capillary Electrophoresis Enantioseparations Promoted by Cyclodextrin-Based Chiral Selectors.

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Book SynopsisLearn how to apply rough-fuzzy computing techniques to solve problems in bioinformatics and medical image processing Emphasizing applications in bioinformatics and medical image processing, this text offers a clear framework that enables readers to take advantage of the latest rough-fuzzy computing techniques to build working pattern recognition models. The authors explain step by step how to integrate rough sets with fuzzy sets in order to best manage the uncertainties in mining large data sets. Chapters are logically organized according to the major phases of pattern recognition systems development, making it easier to master such tasks as classification, clustering, and feature selection. Rough-Fuzzy Pattern Recognition examines the important underlying theory as well as algorithms and applications, helping readers see the connections between theory and practice. The first chapter provides an introduction to pattern recognition and data mining, including the Table of ContentsForeword xiii Preface xv About the Authors xix 1 Introduction to Pattern Recognition and Data Mining 1 1.1 Introduction 1 1.2 Pattern Recognition 3 1.2.1 Data Acquisition 4 1.2.2 Feature Selection 4 1.2.3 Classification and Clustering 5 1.3 Data Mining 6 1.3.1 Tasks, Tools, and Applications 7 1.3.2 Pattern Recognition Perspective 8 1.4 Relevance of Soft Computing 9 1.5 Scope and Organization of the Book 10 References 14 2 Rough-Fuzzy Hybridization and Granular Computing 21 2.1 Introduction 21 2.2 Fuzzy Sets 22 2.3 Rough Sets 23 2.4 Emergence of Rough-Fuzzy Computing 26 2.4.1 Granular Computing 26 2.4.2 Computational Theory of Perception and f -Granulation 26 2.4.3 Rough-Fuzzy Computing 28 2.5 Generalized Rough Sets 29 2.6 Entropy Measures 30 2.7 Conclusion and Discussion 36 References 37 3 Rough-Fuzzy Clustering: Generalized c-Means Algorithm 47 3.1 Introduction 47 3.2 Existing c-Means Algorithms 49 3.2.1 Hard c-Means 49 3.2.2 Fuzzy c-Means 50 3.2.3 Possibilistic c-Means 51 3.2.4 Rough c-Means 52 3.3 Rough-Fuzzy-Possibilistic c-Means 53 3.3.1 Objective Function 54 3.3.2 Cluster Prototypes 55 3.3.3 Fundamental Properties 56 3.3.4 Convergence Condition 57 3.3.5 Details of the Algorithm 59 3.3.6 Selection of Parameters 60 3.4 Generalization of Existing c-Means Algorithms 61 3.4.1 RFCM: Rough-Fuzzy c-Means 61 3.4.2 RPCM: Rough-Possibilistic c-Means 62 3.4.3 RCM: Rough c-Means 63 3.4.4 FPCM: Fuzzy-Possibilistic c-Means 64 3.4.5 FCM: Fuzzy c-Means 64 3.4.6 PCM: Possibilistic c-Means 64 3.4.7 HCM: Hard c-Means 65 3.5 Quantitative Indices for Rough-Fuzzy Clustering 65 3.5.1 Average Accuracy, α Index 65 3.5.2 Average Roughness, ϱ Index 67 3.5.3 Accuracy of Approximation, α⋆ Index 67 3.5.4 Quality of Approximation, γ Index 68 3.6 Performance Analysis 68 3.6.1 Quantitative Indices 68 3.6.2 Synthetic Data Set: X32 69 3.6.3 Benchmark Data Sets 70 3.7 Conclusion and Discussion 80 References 81 4 Rough-Fuzzy Granulation and Pattern Classification 85 4.1 Introduction 85 4.2 Pattern Classification Model 87 4.2.1 Class-Dependent Fuzzy Granulation 88 4.2.2 Rough-Set-Based Feature Selection 90 4.3 Quantitative Measures 95 4.3.1 Dispersion Measure 95 4.3.2 Classification Accuracy, Precision, and Recall 96 4.3.3 κ Coefficient 96 4.3.4 β Index 97 4.4 Description of Data Sets 97 4.4.1 Completely Labeled Data Sets 98 4.4.2 Partially Labeled Data Sets 99 4.5 Experimental Results 100 4.5.1 Statistical Significance Test 102 4.5.2 Class Prediction Methods 103 4.5.3 Performance on Completely Labeled Data 103 4.5.4 Performance on Partially Labeled Data 110 4.6 Conclusion and Discussion 112 References 114 5 Fuzzy-Rough Feature Selection using f -Information Measures 117 5.1 Introduction 117 5.2 Fuzzy-Rough Sets 120 5.3 Information Measure on Fuzzy Approximation Spaces 121 5.3.1 Fuzzy Equivalence Partition Matrix and Entropy 121 5.3.2 Mutual Information 123 5.4 f -Information and Fuzzy Approximation Spaces 125 5.4.1 V -Information 125 5.4.2 Iα-Information 126 5.4.3 Mα-Information 127 5.4.4 χα-Information 127 5.4.5 Hellinger Integral 128 5.4.6 Renyi Distance 128 5.5 f -Information for Feature Selection 129 5.5.1 Feature Selection Using f -Information 129 5.5.2 Computational Complexity 130 5.5.3 Fuzzy Equivalence Classes 131 5.6 Quantitative Measures 133 5.6.1 Fuzzy-Rough-Set-Based Quantitative Indices 133 5.6.2 Existing Feature Evaluation Indices 133 5.7 Experimental Results 135 5.7.1 Description of Data Sets 136 5.7.2 Illustrative Example 137 5.7.3 Effectiveness of the FEPM-Based Method 138 5.7.4 Optimum Value of Weight Parameter β 141 5.7.5 Optimum Value of Multiplicative Parameter η 141 5.7.6 Performance of Different f -Information Measures 145 5.7.7 Comparative Performance of Different Algorithms 152 5.8 Conclusion and Discussion 156 References 156 6 Rough Fuzzy c-Medoids and Amino Acid Sequence Analysis 161 6.1 Introduction 161 6.2 Bio-Basis Function and String Selection Methods 164 6.2.1 Bio-Basis Function 164 6.2.2 Selection of Bio-Basis Strings Using Mutual Information 166 6.2.3 Selection of Bio-Basis Strings Using Fisher Ratio 167 6.3 Fuzzy-Possibilistic c-Medoids Algorithm 168 6.3.1 Hard c-Medoids 168 6.3.2 Fuzzy c-Medoids 169 6.3.3 Possibilistic c-Medoids 170 6.3.4 Fuzzy-Possibilistic c-Medoids 171 6.4 Rough-Fuzzy c-Medoids Algorithm 172 6.4.1 Rough c-Medoids 172 6.4.2 Rough-Fuzzy c-Medoids 174 6.5 Relational Clustering for Bio-Basis String Selection 176 6.6 Quantitative Measures 178 6.6.1 Using Homology Alignment Score 178 6.6.2 Using Mutual Information 179 6.7 Experimental Results 181 6.7.1 Description of Data Sets 181 6.7.2 Illustrative Example 183 6.7.3 Performance Analysis 184 6.8 Conclusion and Discussion 196 References 196 7 Clustering Functionally Similar Genes from Microarray Data 201 7.1 Introduction 201 7.2 Clustering Gene Expression Data 203 7.2.1 k-Means Algorithm 203 7.2.2 Self-Organizing Map 203 7.2.3 Hierarchical Clustering 204 7.2.4 Graph-Theoretical Approach 204 7.2.5 Model-Based Clustering 205 7.2.6 Density-Based Hierarchical Approach 206 7.2.7 Fuzzy Clustering 206 7.2.8 Rough-Fuzzy Clustering 206 7.3 Quantitative and Qualitative Analysis 207 7.3.1 Silhouette Index 207 7.3.2 Eisen and Cluster Profile Plots 207 7.3.3 Z Score 208 7.3.4 Gene-Ontology-Based Analysis 208 7.4 Description of Data Sets 209 7.4.1 Fifteen Yeast Data 209 7.4.2 Yeast Sporulation 211 7.4.3 Auble Data 211 7.4.4 Cho et al. Data 211 7.4.5 Reduced Cell Cycle Data 211 7.5 Experimental Results 212 7.5.1 Performance Analysis of Rough-Fuzzy c-Means 212 7.5.2 Comparative Analysis of Different c-Means 212 7.5.3 Biological Significance Analysis 215 7.5.4 Comparative Analysis of Different Algorithms 215 7.5.5 Performance Analysis of Rough-Fuzzy-Possibilistic c-Means 217 7.6 Conclusion and Discussion 217 References 220 8 Selection of Discriminative Genes from Microarray Data 225 8.1 Introduction 225 8.2 Evaluation Criteria for Gene Selection 227 8.2.1 Statistical Tests 228 8.2.2 Euclidean Distance 228 8.2.3 Pearson’s Correlation 229 8.2.4 Mutual Information 229 8.2.5 f -Information Measures 230 8.3 Approximation of Density Function 230 8.3.1 Discretization 231 8.3.2 Parzen Window Density Estimator 231 8.3.3 Fuzzy Equivalence Partition Matrix 233 8.4 Gene Selection using Information Measures 234 8.5 Experimental Results 235 8.5.1 Support Vector Machine 235 8.5.2 Gene Expression Data Sets 236 8.5.3 Performance Analysis of the FEPM 236 8.5.4 Comparative Performance Analysis 250 8.6 Conclusion and Discussion 250 References 252 9 Segmentation of Brain Magnetic Resonance Images 257 9.1 Introduction 257 9.2 Pixel Classification of Brain MR Images 259 9.2.1 Performance on Real Brain MR Images 260 9.2.2 Performance on Simulated Brain MR Images 263 9.3 Segmentation of Brain MR Images 264 9.3.1 Feature Extraction 265 9.3.2 Selection of Initial Prototypes 274 9.4 Experimental Results 277 9.4.1 Illustrative Example 277 9.4.2 Importance of Homogeneity and Edge Value 278 9.4.3 Importance of Discriminant Analysis-Based Initialization 279 9.4.4 Comparative Performance Analysis 280 9.5 Conclusion and Discussion 283 References 283 Index 287

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Book SynopsisThis book is designed to help researchers achieve success in funding their National Science Foundation (NSF) research proposals. The book discusses aspects of the proposal submission and review process that are not typically communicated to the research community. Written by authors with successful track records in grant writing and years of experience as NSF Program Directors, this book provides an insider's view of successful grantsmanship. Written in a practical approach, this book offers tips that will not be found in official paperwork and provides answers to questions frequently asked of NSF Program Directors. The purpose of the book is to improve your NSF grant-writing skills and improve your chances of funding.Trade Review"[Li and Marrongelle] have done a wonderful job of capturing many of the small details, motivations, and inner workings of the review process that are not obvious to many grant writers." (Amazon review, 2013) "Plan to read this with a highlighter and sticky notes at hand - you'll want to mark things for easy reference later and keep this close by when writing your next NSF proposal." (Amazon review, 2013) "There are bits of information in the book that are impossible to come by any other way." (Amazon review, 2013) have done a wonderful job of capturing many of the small details, motivations, and inner workings of the review process that are not obvious to many grant writers.Table of ContentsPreface viiAbout the Author xi 1 Getting Started 1 2 Preparing Your Proposal 17 3 Submitting Your Proposal 48 4 Reviewing of Your Proposal 58 5 Revising Your Proposal 73 6 Managing Your Grant 87 7 Extending the Horizon 99 Index 108

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Book SynopsisA newly revised edition of the standard reference for the field todayupdated with new terms, major discoveries, significant scientists, and illustrations Developmental biology is the study of the mechanisms of development, differentiation, and growth in animals and plants at the molecular, cellular, and genetic levels. The discipline has gained prominence in part due to new interdisciplinary approaches and advances in technology, which have led to the rapid emergence of new concepts and words. The Dictionary of Developmental Biology and Embryology, Second Edition is the first comprehensive reference focused on the field''s terms, research, history, and people. This authoritative A-to-Z resource covers classical morphological and cytological terms along with those from modern genetics and molecular biology. Extensively cross-referenced, the Dictionary includes definitions of terms, explanations of concepts, and biographies of historical figures. Comparative aspeTrade Review“Dictionary of Developmental Biology and Embryology is a "must-have" reference and resource for students in the field as well as college library collections; professional biologists will also find it convenient and useful to keep handy. Highly recommended.” (Midwest Book Review, 1 March 2013) “It would be best suited for undergraduates taking a developmental biology course or for new graduate students in the field. Summing Up: Recommended. Lower-division undergraduates through graduate students.” (Choice, 1 August 2012) Table of ContentsPreface vii A 1 B 17 C 30 D 51 E 62 F 75 G 82 H 92 I 107 J 114 K 115 L 118 M 123 N 141 O 149 P 155 Q 178 R 179 S 187 T 207 U 216 V 219 W 224 X 227 Y 228 Z 230 Reference 232 Color Plates

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Book SynopsisGENETIC THEORY AND ANALYSIS Understand and apply what drives change of characteristic genetic traits and heredity Genetics is the study of how traits are passed from parents to their offspring and how the variation in those traits affects the development and health of the organism. Investigating how these traits affect the organism involves a diverse set of approaches and tools, including genetic screens, DNA and RNA sequencing, mapping, and methods to understand the structure and function of proteins. Thus, there is a need for a textbook that provides a broad overview of these methods. Genetic Theory and Analysis meets this need by describing key approaches and methods in genetic analysis through a historical lens. Focusing on the five basic principles underlying the fieldmutation, complementation, recombination, segregation, and regulationit identifies the full suite of tests and methodologies available to the geneticist in an age of flourishing geneticTable of ContentsPreface xi Introduction xiii 1 Mutation 1 1.1 Types of Mutations 1 Muller’s Classification of Mutants 2 Nullomorphs 2 Hypomorphs 4 Hypermorphs 5 Antimorphs 6 Neomorphs 8 Modern Mutant Terminology 10 Loss-of-Function Mutants 10 Dominant Mutants 10 Gain-of-Function Mutants 11 Separation-of-Function Mutants 11 DNA-Level Terminology 11 Base-Pair-Substitution Mutants 11 Base-Pair Insertions or Deletions 12 Chromosomal Aberrations 12 1.2 Dominance and Recessivity 13 The Cellular Meaning of Dominance 13 The Cellular Meaning of Recessivity 15 Difficulties in Applying the Terms Dominant and Recessive to Sex-Linked Mutants 16 The Genetic Utility of Dominant and Recessive Mutants 17 1.3 Summary 17 References 17 2 Mutant Hunts 20 2.1 Why Look for New Mutants? 20 Reason 1: To Identify Genes Required for a Specific Biological Process 21 Reason 2: To Isolate more Mutations in a Specific Gene of Interest 31 Reason 3: To Obtain Mutants for a Structure-Function Analysis 32 Reason 4: To Isolate Mutations in a Gene So Far Identified only by Computational Approaches 32 2.2 Mutagenesis and Mutational Mechanisms 32 Method 1: Ionizing Radiation 33 Method 2: Chemical Mutagens 33 Alkylating Agents 34 Crosslinking Agents 35 Method 3: Transposons 35 Identifying Where Your Transposon Landed 37 Why not Always Screen With TEs? 40 Method 4: Targeted Gene Disruption 40 RNA Interference 40 CRISPR/Cas9 41 TALENs 42 So Which Mutagen Should You Use? 43 2.3 What Phenotype Should You Screen (or Select) for? 44 2.4 Actually Getting Started 45 Your Starting Material 45 Pilot Screen 45 What to Keep? 45 How many Mutants is Enough? 46 Estimating the Number of Genes not Represented by Mutants in Your New Collection 46 2.5 Summary 48 References 48 3 Complementation 51 3.1 The Essence of the Complementation Test 51 3.2 Rules for Using the Complementation Test 55 The Complementation Test Can be Done Only When Both Mutants are Fully Recessive 55 The Complementation Test Does Not Require that the Two Mutants Have Exactly the Same Phenotype 56 The Phenotype of a Compound Heterozygote Can be More Extreme than that of Either Homozygote 56 3.3 How the Complementation Test Might Lie to You 57 Two Mutations in the Same Gene Complement Each Other 57 A Mutation in One Gene Silences Expression of a Nearby Gene 57 Mutations in Regulatory Elements 59 3.4 Second-Site Noncomplementation (Nonallelic Noncomplementation) 59 Type 1 SSNC (PoisonousInteractions): The Interaction is Allele Specific at Both Loci 60 An Example of Type 1 SSNC Involving the Alpha- and Beta-Tubulin Genes in Yeast 60 An Example of Type 1 SSNC Involving the Actin Genes in Yeast 62 Type 2 SSNC (Sequestration): The Interaction is Allele Specific at One Locus 66 An Example of Type 2 SSNC Involving the Tubulin Genes in Drosophila 66 An Example of Type 2 SSNC in Drosophila that Does Not Involve the Tubulin Genes 69 An Example of Type 2 SSNC in the Nematode Caenorhabditis elegans 71 Type 3 SSNC (Combined Haploinsufficiency): The Interaction is Allele-Independent at Both Loci 72 An Example of Type 3 SSNC Involving Two Motor Protein Genes in Flies 72 Summary of SSNC in Model Organisms 72 SSNC in Humans (Digenic Inheritance) 73 Pushing the Limits: Third-Site Noncomplementation 74 3.5 An Extension of SSNC: Dominant Enhancers 74 A Successful Screen for Dominant Enhancers 75 3.6 Summary 76 References 77 4 Meiotic Recombination 81 4.1 An Introduction to Meiosis 81 A Cytological Description of Meiosis 88 A More Detailed Description of Meiotic Prophase 89 4.2 Crossing Over and Chiasmata 92 4.3 The Classical Analysis of Recombination 93 4.4 Measuring the Frequency of Recombination 96 The Curious Relationship Between the Frequency of Recombination and Chiasma Frequency 97 Map Lengths and Recombination Frequency 97 The Mapping Function 99 Tetrad Analysis 100 Statistical Estimation of Recombination Frequencies 101 Two-Point Linkage Analysis 101 What Constitutes Statistically Significant Evidence for Linkage? 104 An Example of LOD Score Analysis 105 Multipoint Linkage Analysis 105 Local Mapping via Haplotype Analysis 106 The Endgame 108 The Actual Distribution of Exchange Events 109 The Centromere Effect 110 The Effects of Heterozygosity for Aberration Breakpoints on Recombination 110 Practicalities of Mapping 110 4.5 The Mechanism of Recombination 111 Gene Conversion 111 Early Models of Recombination 112 The Holliday Model 112 The Meselson–Radding Model 114 The Currently Accepted Mechanism of Recombination: The Double-Strand Break Repair Model 114 Class I Versus Class II Recombination Events 116 4.6 Summary 117 References 118 5 Identifying Homologous Genes 126 5.1 Homology 126 Orthologs 127 Paralogs 127 Xenologs 128 5.2 Identifying Sequence Homology 128 Nucleotide–Nucleotide BLAST (blastn) 129 An Example Using blastn 129 Translated Nucleotide–Protein BLAST (blastx) 131 An Example Using blastx 131 Protein–Protein BLAST (blastp) 132 An Example Using blastp 132 Translated BLASTx (tblastx) and Translated BLASTn (tblastn) 133 5.3 How Similar is Similar? 133 5.4 Summary 134 References 134 6 Suppression 136 6.1 Intragenic Suppression 137 Intragenic Suppression of Loss-of-Function Mutations 137 Intragenic Suppression of a Frameshift Mutation by the Addition of a Second, Compensatory Frameshift Mutation 138 Intragenic Suppression of Missense Mutations by the Addition of a Second and Compensatory Missense Mutation 140 Intragenic Suppression of Antimorphic Mutations that Produce a Poisonous Protein 141 6.2 Extragenic Suppression 141 6.3 Transcriptional Suppression 141 Suppression at the Level of Gene Expression 142 A CRISPR Screen for Suppression of Inhibitor Resistance in Melanoma 142 Suppression of Transposon-Insertion Mutants by Altering the Control of mRNA Processing 143 Suppression of Nonsense Mutants by Messenger Stabilization 143 6.4 Translational Suppression 144 tRNA-Mediated Nonsense Suppression 144 The Numerical and Functional Redundancy of tRNA Genes Allows Suppressor Mutations to be Viable 146 tRNA-Mediated Frameshift Suppression 146 6.5 Suppression by Post-Translational Modification 147 6.6 Conformational Suppression: Suppression as a Result of Protein–Protein Interaction 147 Searching for Suppressors that Act by Protein–Protein Interaction in Eukaryotes 148 Actin and Fimbrin in Yeast 148 Mediator Proteins and RNA Polymerase II in Yeast 150 “Lock-and-key” Conformational Suppression 152 Suppression of a Flagellar Motor Mutant in E. coli 152 Suppression of a Mutant Transporter Gene in C. elegans 152 Suppression of a Telomerase Mutant in Humans 153 6.7 Bypass Suppression: Suppression Without Physical Interaction 154 “Push me, Pull You” Bypass Suppression 155 Multicopy Bypass Suppression 156 6.8 Suppression of Dominant Mutations 157 6.9 Designing Your Own Screen for Suppressor Mutations 157 6.10 Summary 158 References 158 7 Epistasis Analysis 163 7.1 Ordering Gene Function in Pathways 163 Biosynthetic Pathways 164 Nonbiosynthetic Pathways 165 7.2 Dissection of Regulatory Hierarchies 167 Epistasis Analysis Using Mutants with Opposite Effects on the Phenotype 167 Hierarchies for Sex Determination in Drosophila 169 Epistasis Analysis Using Mutants with the Same or Similar Effects on the Final Phenotype 170 Using Opposite-Acting Conditional Mutants to Order Gene Function by Reciprocal Shift Experiments 170 Using a Drug or Agent that Stops the Pathway at a Given Point 170 Exploiting Subtle Phenotypic Differences Exhibited by Mutants that Affect the Same Signal State 172 7.3 How Might an Epistasis Experiment Mislead You? 172 7.4 Summary 173 References 173 8 Mosaic Analysis 175 8.1 Tissue Transplantation 176 Early Tissue Transplantation in Drosophila 176 Tissue Transplantation in Zebrafish 177 8.2 Mitotic Chromosome Loss 178 Loss of the Unstable Ring-X Chromosome 179 Other Mechanisms of Mitotic Chromosome Loss 179 Mosaics Derived from Sex Chromosome Loss in Humans and Mice (Turner Syndrome) 180 8.3 Mitotic Recombination 181 Gene Knockout Using the FLP/FRT or Cre-Lox Systems 182 8.4 Tissue-Specific Gene Expression 184 Gene Knockdown Using RNAi 184 Tissue-Specific Gene Editing Using CRISPR/Cas9 185 8.5 Summary 187 References 188 9 Meiotic Chromosome Segregation 191 9.1 Types and Consequences of Failed Segregation 192 9.2 The Origin of Spontaneous Nondisjunction 193 MI Exceptions 194 MII Exceptions 194 9.3 The Centromere 195 The Isolation and Analysis of the Saccharomyces cerevisiae Centromere 195 The Isolation and Analysis of the Drosophila Centromere 198 The Concept of the Epigenetic Centromere in Drosophila and Humans 200 Holocentric Chromosomes 201 9.4 Chromosome Segregation Mechanisms 202 Chiasmate Chromosome Segregation 202 Segregation Without Chiasmata (Achiasmate Chromosome Segregation) 203 Achiasmate Segregation in Drosophila Males 203 Achiasmate Segregation in D. melanogaster Females 204 Achiasmate Segregation in S. cerevisiae 205 Achiasmate Segregation in S. pombe 207 Achiasmate Segregation in Silkworm Females 207 9.5 Meiotic Drive 207 Meiotic Drive Via Spore Killing 207 An Example in Schizosaccharomyces pombe 207 An Example in D. melanogaster 208 Meiotic Drive Via Directed Segregation 208 9.6 Summary 210 References 210 Appendix A: Model Organisms 215 Appendix B: Genetic Fine-Structure Analysis 228 Appendix C: Tetrad Analysis 250 Glossary 262 Index 275

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Book SynopsisExplores the utility and potential of extremophiles in sustainability and biotechnology Many extremophilic bio-products are already used as life-saving drugs. Until recently, however, the difficulty of working with these microbes has discouraged efforts to develop extremophilic microbes as potential drug reservoirs of the future. Recent technological advances have opened the door to exploring these organisms anew as sources of products that might prove useful in clinical and environmental biotechnology and drug development. Extremophiles features outstanding articles by expert scientists who shed light on broad-ranging areas of progress in the development of smart therapeutics for multiple disease types and products for industrial use. It bridges technological gaps, focusing on critical aspects of extremolytes and the mechanisms regulating their biosynthesis that are relevant to human health and bioenergy, including value-added products of commercial signTable of ContentsContributors xv Introduction xix 1 MOLECULAR EVOLUTION OF EXTREMOPHILES 1 Debamitra Chakravorty, Ashwinee Kumar Shreshtha, V. R. Sarath Babu, and Sanjukta Patra 1.1 Introduction 1 1.2 Molecular Evolution of Thermophiles 2 1.3 Molecular Evolution of Psychrophiles 4 1.4 Molecular Evolution of Halophiles 6 1.5 Molecular Evolution of Alkaliphiles 7 1.6 Molecular Evolution of Acidophiles 8 1.7 Molecular Evolution of Barophiles 10 1.8 Engineering Extremophiles 12 1.9 Case Studies 17 1.10 Implications of Engineered Extremophiles on Ecology, Environment, and Health 20 1.11 Conclusions and Recommendations 20 2 ATTAINING EXTREMOPHILES AND EXTREMOLYTES: METHODOLOGIES AND LIMITATIONS 29 Debamitra Chakravorty and Sanjukta Patra 2.1 Introduction 29 2.2 Extremophiles: Types and Diversity 30 2.3 Extremolytes 54 2.4 Conclusions 64 3 STRATEGIES FOR THE ISOLATION AND CULTIVATION OF HALOPHILIC MICROORGANISMS 75 Aharon Oren 3.1 Introduction 75 3.2 Thalassohaline and Athalassohaline Hypersaline Environments 76 3.3 Case Studies 79 3.4 The Upper Salinity Limits of Different Types of Energy Generation 85 3.5 Final Comments 88 4 HALOPHILIC PROPERTIES AND THEIR MANIPULATION AND APPLICATION 95 Tsutomu Arakawa, Hiroko Tokunaga, Matsujiro Ishibashi, and Masao Tokunaga 4.1 Introduction 95 4.2 Industrial Applications of Halophilic Organisms and Their Proteins 96 4.3 Extreme and Moderate Halophiles and Their Proteins 98 4.4 Generation of Low-Salt Stable Extreme-Halophilic Proteins 99 4.5 Interconversion of Halophilic and Nonhalophilic Proteins 105 4.6 Soluble Expression of Recombinant Proteins 110 4.7 Natively Unfolded Proteins 113 4.8 Organic Solvent Tolerance 113 5 FEATURES AND APPLICATIONS OF HALOPHILIC ARCHAEA 123 Ximena C. Abrevaya 5.1 Introduction 123 5.2 General Features 124 5.3 Applications of Halophilic Archaea 130 5.4 Concluding Remarks 143 6 BIOTECHNOLOGICAL APPLICATIONS OF COLD-ADAPTED BACTERIA 159 Laura Garcia-Descalzo, Alberto Alcazar, Fernando Baquero, and Cristina Cid 6.1 Introduction 159 6.2 Molecular Mechanisms of Adaptation to Cold Environments 162 6.3 Exopolysaccharides 163 6.4 Lipids 164 6.5 Proteins 164 6.6 Biotechnological Applications of Cold-Adapted Enzymes 168 6.7 Biodegradation and Bioremediation in Cold Environments 169 6.8 Conclusions 172 7 ECOLOGY AND BIOTECHNOLOGY OF EXTREMOPHILIC MICROORGANISMS, PARTICULARLY ANAEROBIC HERMOPHILES 175 Francesco Canganella 7.1 Introduction 175 7.2 Thermophiles 176 7.3 Acidophiles 187 7.4 Alkaliphiles 191 7.5 Halophiles 193 7.6 Piezophiles 194 8 THE ROLE OF EXTREMOPHILIC MICROORGANISMS AND THEIR BIOPRODUCTS IN FOOD PROCESSING AND PRODUCTION 205 Jane A. Irwin 8.1 Introduction 205 8.2 Enzymes from Extremophiles in Food Processing 206 8.3 Alkaliphiles, Acidophiles, and Piezophiles 217 8.4 Extremophiles in Food Spoilage and Contamination 218 8.5 Extremophiles as Pathogens of Food Species 221 8.6 Conclusions 222 9 EXTREMOPHILES AND THEIR APPLICATION TO BIOFUEL RESEARCH 233 M.P. Taylor, R. Bauer, S. Mackay, M. Tuffin, and D.A. Cowan 9.1 Introduction 233 9.2 Extremophiles and Fuels 235 9.3 Exploiting Extremophilic Enzymes in Biomass Conversion to Biofuel 241 9.4 Conclusions and Future Prospects 249 10 SUSTAINABLE ROLE OF THERMOPHILES IN THE SECOND GENERATION OF ETHANOL PRODUCTION 267 Anuj K. Chandel, Ellen C. Giese, Om V. Singh, and Silvio Silverio da Silva 10.1 Introduction 267 10.2 Thermophilic Cellulases for Deconstruction of the Plant Cell Wall 269 10.3 Ethanol Production at Elevated Temperatures 274 10.4 Future Perspectives and Challenges 281 10.5 Conclusions 283 11 ECOFRIENDLY ASPECTS OF THE USE OF EXTREMOPHILIC ENZYMES IN TEXTILE SUBSTRATES 291 Bipin J. Agrawal and Sandhya Mishra 11.1 Introduction 291 11.2 Biopolymeric Fibers 292 11.3 Extremophilic Enzymes and Their Use in the Textile Industry 293 11.4 Utilization of Extremophilic Enzymes in Textile Wet Processing 297 11.5 Finishing with Extremophilic Enzymes 306 11.6 Role of Enzymes in Textile After-Care 311 11.7 Role of Enzymes in Effluent Treatment of Textiles 314 11.8 Conclusions 315 12 THE USE OF EXTREMOPHILIC MICROORGANISMS IN THE INDUSTRIAL RECOVERY OF METALS 319 Carlos A. Jerez 12.1 Introduction 319 12.2 Biomining Extremophiles and Their Industrial Applications 320 12.3 Molecular Studies in Acidophilic Biomining Microorganisms 322 12.4 Microbial Resistance to Acid and Metals 324 13 BACTERIAL POLYMERS PRODUCED BY EXTREMOPHILES: BIOSYNTHESIS, CHARACTERIZATION, AND APPLICATIONS OF EXOPOLYSACCHARIDES 335 Nicolaus Barbara, Anzelmo Gianluca, and Poli Annarita 13.1 Introduction 335 13.2 EPS Produced by Extremophilic Bacteria 336 13.3 Examples of Proposed EPS Biosynthesis from Extremophiles 345 13.4 Physicochemical Investigations for Potential Applications 349 14 BIOMEDICAL APPLICATIONS OF EXOPOLYSACCHARIDES PRODUCED BY MICROORGANISMS ISOLATED FROM EXTREME ENVIRONMENTS 357 Ignacio J. Molina, Carmen Ruiz-Ruiz, Emilia Quesada, and Victoria B´ejar 14.1 Introduction 357 14.2 Chemical Composition and Structure of EPSs 358 14.3 Physical Properties of EPSs 358 14.4 Biological Functions of EPSs 359 14.5 Exopolysaccharides Deriving from Extremophilic Organisms 359 14.6 Clinical Applications of EPSs 359 14.7 Exopolysaccharides of Halophilic Microorganisms 361 14.8 Concluding Remarks 362 15 BIOSYNTHESIS OF EXTREMOLYTES: RADIATION RESISTANCE AND BIOTECHNOLOGICAL IMPLICATIONS 367 Erin Copeland, Nicholas Choy, Prashant Gabani, and Om V. Singh 15.1 Introduction 367 15.2 Biotechnological Implications of Extremolytes 369 15.3 Fermentative Production of Extremolytes 371 15.4 Commercialization of Extremolytes and Extremozymes 380 15.5 Product Recovery 382 15.6 Conclusions 383 16 SMART THERAPEUTICS FROM EXTREMOPHILES: UNEXPLORED APPLICATIONS AND TECHNOLOGICAL CHALLENGES 389 Raj Kumar and Ajeet Singh 16.1 Introduction 389 16.2 Extremolytes as Protein Protectants 391 16.3 Extremolytes as Cell Protectants 391 16.4 Novel Therapeutics in the Developmental Stage 393 16.5 Homeland Security and Military Medicine 394 16.6 Technological Gaps in Therapeutic Product Development Using Extremophiles 396 16.7 Conclusions 397 Acknowledgment 398 References 398 Index 403

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Book SynopsisThis volume offers readers an opportunity to learn about how genomes are sequenced, what discoveries have so far come out of this scientific revolution, and about the ethical dimensions of this advancing technology.Table of ContentsForeward: Still, The Genomic Revolution ix Acknowledgments xi Introduction: Welcome Back to the Genome xiii 1 From Mendel to Molecules 1 2 The Building Blocks of Gene Sequencing 31 3 Sequencing the Genome 47 4 The Next Generation 65 5 Making the Genome Safe 81 6 The Meanings of Genetic Diversity: Part I 121 7 The Meanings of Genetic Diversity: Part II 143 8 The Tree of Life: 4 Billion Years of Divergence 161 9 Sequencing the Small and Infamous: A Look at Metagenomics and Microbiomes 195 10 The World to Come: Agriculture 213 Conclusion: Don’t Believe the Hype (Including Ours) 245 Index 249

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Book SynopsisGenetic Analysis of Complex Diseases An up-to-date and complete treatment of the strategies, designs and analysis methods for studying complex genetic disease in human beings In the newly revised Third Edition of Genetic Analysis of Complex Diseases, a team of distinguished geneticists delivers a comprehensive introduction to the most relevant strategies, designs and methods of analysis for the study of complex genetic disease in humans. The book focuses on concepts and designs, thereby offering readers a broad understanding of common problems and solutions in the field based on successful applications in the design and execution of genetic studies. This edited volume contains contributions from some of the leading voices in the area and presents new chapters on high-throughput genomic sequencing, copy-number variant analysis and epigenetic studies. Providing clear and easily referenced overviews of the considerations involved in genetic analysis of compTable of ContentsList of Contributors xv Foreword xvii 1 Designing a Study for Identifying Genes in Complex Traits 1 William K. Scott, Marylyn D. Ritchie, Jonathan L. Haines,and Margaret A. Pericak-Vance Introduction 1 Components of a Disease Gene Discovery Study 3 Define Disease Phenotype 4 Clinical Definition 4 Determining that a Trait Has a Genetic Component 5 Identification of Datasets 5 Develop Study Design 5 Family-Based Studies 6 Population-Based Studies 6 Approaches for Gene Discovery 7 Analysis 7 Genomic Analysis 7 Statistical Analysis 8 Bioinformatics 8 Follow-up 8 Variant Detection 8 Replication 9 Functional Studies 9 Keys to a Successful Study 10 Foster Interaction of Necessary Expertise 10 Develop Careful Study Design 11 References 11 2 Basic Concepts in Genetics 13 Kayla Fourzali, Abigail Deppen, and Elizabeth Heise Introduction 13 Historical Contributions 13 Segregation and Linkage Analysis 13 Hardy–Weinberg Equilibrium 14 DNA, Genes, and Chromosomes 17 Structure of DNA 17 Genes and Alleles 19 Genes and Chromosomes 20 Genes, Mitosis, and Meiosis 22 When Genes and Chromosomes Segregate Abnormally 25 Inheritance Patterns in Mendelian Disease 25 Autosomal Recessive 25 Autosomal Dominant 25 X-linked Inheritance 28 Mitochondrial Inheritance 29 Y-linked 29 Genetic Changes Associated with Disease/ Trait Phenotypes 29 Mutations Versus Polymorphisms 29 Point Mutations 30 Sickle Cell Anemia 30 Achondroplasia 30 Deletion/Insertion Mutations 31 Duchenne and Becker Muscular Dystrophy 31 Cystic Fibrosis 31 Charcot-Marie- Tooth Disease 31 Nucleotide Repeat Disorders 32 Susceptibility Versus Causative Genes 32 Summary 34 References 34 3 Determining the Genetic Component of a Disease 36 Allison Ashley Koch and Evadnie Rampersaud Introduction 36 Study Design 37 Selecting a Study Population 37 Population-Based 38 Clinic-Based 38 Ascertainment 38 Single Affected Individual 39 Relative Pairs 40 Extended Families 40 Healthy or Unaffected Controls 41 Ascertainment Bias 42 Approaches to Determining the Genetic Component of a Disease 44 Co-segregation with Chromosomal Abnormalities and Other Genetic Disorders 44 Familial Aggregation 44 Family History Approach 44 Example of Calculating Attributable Fraction 46 Correlation Coefficients 46 Twin and Adoption Studies 47 Recurrence Risk in Relatives of Affected Individuals 48 Heritability 49 Example Using Correlation Coefficients to Calculate Heritability 50 Segregation Analysis 51 Summary 52 References 53 4 Study Design for Genetic Studies 58 Dana C. Crawford and Logan Dumitrescu Introduction 58 Selecting a Study Population 58 Family- Based Studies (Linkage) 59 Family- Based Studies (Association) 60 Studies of Unrelated Individuals (Association) 61 Cohort Studies 61 Cross- Sectional Studies 66 Case– Control Studies 66 Other Study Designs 68 Biobanks 69 Other Biobanks 71 Biospecimens for Biobanks 72 Summary 73 References 74 5 Responsible Conduct of Research in Genetic Studies 79 Susan Estabrooks Hahn, Adam Buchanan, Chantelle Wolpert,and Susan H. Blanton Introduction 79 Research Regulations and Genetics Research 80 Addressing Pertinent ELSI in Genetic Research 83 Genetic Discrimination 83 Privacy and Confidentiality 84 Certificate of Confidentiality 85 Coding Data and Samples 85 Secondary Subjects 86 Future Use of Samples/Data Sharing 87 Handling of Research Results 88 CLIA Regulations: Separation of Research and Clinical Laboratories 89 Releasing Children’s Genetic Research Results 90 DNA Ownership 90 DNA Banking 90 Family Coercion 91 Practical Methods for Efficient High-Quality Genetic Research Services 91 The Investigator as the Genetic Study Coordinator 92 Time Spent 92 Recruitment 93 Support Groups and Organizations 93 Referrals from Health Care Providers 93 Research Databases and the Internet 94 Institution Databases 94 Medical Clinics 94 Recruitment by Family Members 95 Informed Consent 95 Vulnerable Populations 96 Minors 97 Persons with Cognitive Impairment 97 Data and Sample Collection 97 Sample Collection 97 Confirmation of Diagnosis 98 The Art of Field Studies 99 Referring for Additional Medical Services 99 Maintaining Contact with Participants 100 Future Considerations 100 References 100 6 Linkage Analysis 105 Susan H. Blanton Disease Gene Discovery 107 Ability to Detect Linkage 116 Real World Example of LOD Score Calculation and Interpretation 117 Disease Gene Localization 120 Multipoint Analysis 121 Effects of Misspecified Model Parameters in LOD Score Analysis 124 Impact of Incorrect Disease Allele Frequency 124 Impact of Incorrect Mode of Inheritance 125 Impact of Incorrect Disease Penetrance 125 Impact of Incorrect Marker Allele Frequency 126 Control of Scoring Errors 127 Genetic Heterogeneity 128 Practical Approach for Model-Based Linkage Analysis of Complex Traits 131 Nonparametric Linkage Analysis 133 Identity by State and Identity by Descent 134 Methods for Nonparametric Linkage Analysis 136 Tests for Linkage Using Affected Sibling Pairs (ASP) 137 Test Based on Identity by State 137 Tests Based on Identity by Descent in ASPs 138 Simple Tests 138 Tests Applicable When IBD Status Cannot Be Determined 139 Multipoint Affected Sib-Pair Methods 141 Handling Sibships with More Than 2 Affected Siblings 142 Methods Incorporating Affected Relative Pairs 142 NPL Analysis 143 Fitting Population Parameters 145 Power Analysis and Experimental Design Considerations for Qualitative Traits 147 Factors Influencing Power of Sib-pair Methods 147 The Example of Testicular Cancer 148 Examples of Sib-Pair Methods for Mapping Complex Traits 150 Mapping Quantitative Traits 151 Measuring Genetic Effects in Quantitative Traits 152 Study Design for Quantitative Trait Linkage Analysis 154 Haseman–Elston Regression 155 Variance Components Linkage Analysis 156 Nonparametric Methods 158 The Future 159 Software Available 160 References 160 7 Data Management 169 Stephen D. Turner and William S. Bush Developing a Data Organization Strategy 170 A Brief Overview of Data Normalization 170 Database Management System (DBMS) and Structured Query Language (SQL) 172 Partitioning Data by Type 173 Sequence-Level Data 174 Sample-Level Data 174 Database Implementation 175 Hardware and Software Requirements 175 Implementation and Performance Tuning 175 Interacting with the Database Directly 176 Security 177 Other Tools for Data Management and Manipulation 177 R 177 PLINK 178 SAMtools 178 Workflow Management and Cloud Computing 178 Conclusion 179 References 179 8 Linkage Disequilibrium and Association Analysis 182 Eden R. Martin and Ren-HuaChung Introduction 182 Linkage Disequilibrium 182 Measures of Allelic Association 183 Causes of Allelic Association 184 Mapping Genes Using Linkage Disequilibrium 186 Tests of Association 187 Case–Control Tests 188 Test Statistics 188 Measures of Disease Association and Impact 189 Assessing Confounding Bias 191 Family-Based Tests of Association 192 The Transmission/Disequilibrium Test 192 Tests Using Unaffected Sibling Controls 194 Tests Using Extended Pedigrees 195 Regression and Likelihood-Based Methods 196 Association Tests with Quantitative Traits 197 Analysis of Haplotype Data 197 Genome-Wide Association Studies (GWAS) 198 Special Populations 199 HapMap 200 1000 Genomes Project 200 Summary 201 References 201 9 Genome-Wide Association Studies 205 Jacob L. McCauley, Yogasudha Veturi, Shefali Setia Verma, and Marylyn D. Ritchie Introduction 205 Definition of GWAS 206 Purpose of GWAS 206 Design 206 Technologies for High-Density Genotyping 206 Discrete and Quantitative Trait Analysis 208 Case–Control, Family-Based, and Cohort Study Designs 209 Statistical Power for Association and Correction for Testing Multiple Hypotheses 211 Data Analysis 212 Quality Control on Genotyping Call Data 212 Initial Genotyping Quality Control 213 Sample-Level Quality Control 214 SNP-Level Quality Control 215 Software Programs for Quality Control 215 Population Structure 216 Imputation 219 Genetic Association Testing 220 Meta-Analysis and “Mega-Analysis” 221 Whole-Genome Regression-Based GWAS 222 Conclusion 222 References 222 10 Bioinformatics of Human Genetic Disease Studies 228 Dale J. Hedges Introduction 228 Common Threads Genome Analysis 229 A Brief Note on Study Design 229 Data Format Manipulation 229 Planning for Adequate Computational Resources 230 Storage 231 Processing and Memory 232 Networking 232 Genomics in the Cloud 232 Processing and Analysis of Genomic Data 233 Array-Based Data 233 DNA Arrays and High-Throughput Genotyping 233 Preprocessing and Initial Quality Control 234 Genotype Calling 234 Call Efficiency 235 Data Cleaning and Additional Quality Control 236 Inferring Structural Variation From SNP-based Array Data 236 A Note on Statistical Analysis and Interpretation of Results 236 Array-Based Analysis of Gene Expression 237 Batch Effects and Data Normalization 237 Differential Expression 238 Classification and Clustering Methods 239 Visualization of Expression Data 240 Pathway and Network Analyses 240 Direct Counting and Other Expression Assay Procedures 241 Additional Uses for Oligonucleotide Arrays 242 High-Throughput Sequencing Methods for Genomics 243 Introduction 243 High-Throughput Sequencing for Genotype Inference 244 Expression Analysis from High-Throughput Sequencing Data – RNA-Seq 252 ChIP-Seq and Methylation-based Sequences 255 Bioinformatics Resources 256 Annotation of Genomic Data 257 Genome Browsers as Versatile Tools 258 Bioinformatics Frameworks and Workflows 259 Crowdsourcing and Troubleshooting 260 Data Sharing 260 References 261 11 Complex Genetic Interactions/Data Mining/Dimensionality Reduction 265 William S. Bush and Stephen D. Turner Human Diseases Are Complex 265 Complexity of Biological Systems 266 Genetic Heterogeneity 267 Statistical and Mathematical Concepts of Complex Genetic Models 268 Analytic Approaches to the Detection of Complex Interactions 270 Linkage Analysis/Genomic Sharing 270 Association Analysis 270 Genome‐Wide Association Analysis 272 Conclusion 273 References 273 12 Sample Size, Power, and Data Simulation 278 Sarah A. Pendergrass and Marylyn D. Ritchie Introduction 278 Sample Size and Power 279 Power Calculations and Simulation 282 Power Studies for Association Analysis 282 Software for Calculating Power for Association Studies, Family- or Population-Based 283 PGA: Power for Genetic Association Analyses 283 Fine-Mapping Power Calculator 284 Quanto 284 PAWE: Power for Association with Errors 284 PAWE-3D 284 GPC: Genetic Power Calculator 284 CaTS 284 INPower 284 Software for Calculating Power for Transmission Disequilibrium Testing (TDT) and Affected Sib-Pair Testing (ASP) 284 GPC: Genetic Power Calculator 284 TDT-PC: Transmission Disequilibrium Test Power Calculator 284 TDTASP 285 TDTPOWER 285 ASP/ASPSHARE 285 Simulation Software for Association Study Power Assessment 285 Backward and Forward Model Simulations 285 Coalescent Model Simulation – Short Genetic Sequences 286 Larger Coalescent Simulated Models 286 Forward Model Simulations – Short Genetic Sequences 286 Forward Model Simulations – Large Genetic Sequences 286 Resampling Simulation Tools 287 Software for Simulation of Phenotypic Data 287 Power Simulations for Linkage Analysis 288 Definitions for Power Assessments for Linkage Analysis 288 Computer Simulation Methods for Linkage Analysis of Mendelian Disease 289 SIMLINK 289 SLINK: Simulation Program for Linkage Analysis 289 SUP: Slink Utility Program 290 ALLEGRO 290 MERLIN: Multipoint Engine for Rapid Likelihood Inference 290 SimPED 290 Power Studies for Linkage Analysis – Complex Disease 290 Inclusion of Unaffected Siblings 291 Affected Relative Pairs of Other Types 291 Other Considerations 291 Genomic Screening Strategies: One-Stage versus Two-Stage Designs 291 Software for Designing Linkage Analysis Studies of Complex Disease 292 SIMLA 292 Quantitative Traits 292 Extreme Discordant Pairs 292 Sampling Consideration for the Variance Component Method 293 Software for Designing Linkage Analysis Studies for Quantitative Traits 294 SOLAR: Sequential Oligogenic Linkage Analysis Routines 294 MERLIN: Multipoint Engine for Rapid Likelihood Inference 294 SimuPOP 294 Summary 294 References 294 Index 298

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Book SynopsisThe first comprehensive overview of preprocessing, mining, and postprocessing of biological data Molecular biology is undergoing exponential growth in both the volume and complexity of biological data?and knowledge discovery offers the capacity to automate complex search and data analysis tasks. This book presents a vast overview of the most recent developments on techniques and approaches in the field of biological knowledge discovery and data mining (KDD)?providing in-depth fundamental and technical field information on the most important topics encountered. Written by top experts, Biological Knowledge Discovery Handbook: Preprocessing, Mining, and Postprocessing of Biological Data covers the three main phases of knowledge discovery (data preprocessing, data processing?also known as data mining?and data postprocessing) and analyzes both verification systems and discovery systems. BIOLOGICAL DATA PREPROCESSING Part A: Biological Data Trade Review“This book is a unique resource for practitioners and researchers in computer science, life science, and mathematics.” (Zentralblatt MATH, 1 June 2015) Table of ContentsPREFACE xiii CONTRIBUTORS xv SECTION I BIOLOGICAL DATA PREPROCESSING PART A: BIOLOGICAL DATA MANAGEMENT 1 GENOME AND TRANSCRIPTOME SEQUENCE DATABASES FOR DISCOVERY, STORAGE, AND REPRESENTATION OF ALTERNATIVE SPLICING EVENTS 5 Bahar Taneri and Terry Gaasterland 2 CLEANING, INTEGRATING, AND WAREHOUSING GENOMIC DATA FROM BIOMEDICAL RESOURCES 35 Fouzia Moussouni and Laure Berti-Equille 3 CLEANSING OF MASS SPECTROMETRY DATA FOR PROTEIN IDENTIFICATION AND QUANTIFICATION 59 Penghao Wang and Albert Y. Zomaya 4 FILTERING PROTEIN–PROTEIN INTERACTIONS BY INTEGRATION OF ONTOLOGY DATA 77 Young-Rae Cho PART B: BIOLOGICAL DATA MODELING 5 COMPLEXITY AND SYMMETRIES IN DNA SEQUENCES 95 Carlo Cattani 6 ONTOLOGY-DRIVEN FORMAL CONCEPTUAL DATA MODELING FOR BIOLOGICAL DATA ANALYSIS 129 Catharina Maria Keet 7 BIOLOGICAL DATA INTEGRATION USING NETWORK MODELS 155 Gaurav Kumar and Shoba Ranganathan 8 NETWORK MODELING OF STATISTICAL EPISTASIS 175 Ting Hu and Jason H. Moore 9 GRAPHICAL MODELS FOR PROTEIN FUNCTION AND STRUCTURE PREDICTION 191 Mingjie Tang, Kean Ming Tan, Xin Lu Tan, Lee Sael, Meghana Chitale, Juan Esquivel-Rodrýguez, and Daisuke Kihara PART C: BIOLOGICAL FEATURE EXTRACTION 10 ALGORITHMS AND DATA STRUCTURES FOR NEXT-GENERATION SEQUENCES 225 Francesco Vezzi, Giuseppe Lancia, and Alberto Policriti 11 ALGORITHMS FOR NEXT-GENERATION SEQUENCING DATA 251 Costas S. Iliopoulos and Solon P. Pissis 12 GENE REGULATORY NETWORK IDENTIFICATION WITH QUALITATIVE PROBABILISTIC NETWORKS 281 Zina M. Ibrahim, Alioune Ngom, and Ahmed Y. Tawfik PART D: BIOLOGICAL FEATURE SELECTION 13 COMPARING, RANKING, AND FILTERING MOTIFS WITH CHARACTER CLASSES: APPLICATION TO BIOLOGICAL SEQUENCES ANALYSIS 309 Matteo Comin and Davide Verzotto 14 STABILITY OF FEATURE SELECTION ALGORITHMS AND ENSEMBLE FEATURE SELECTION METHODS IN BIOINFORMATICS 333 Pengyi Yang, Bing B. Zhou, Jean Yee-Hwa Yang, and Albert Y. Zomaya 15 STATISTICAL SIGNIFICANCE ASSESSMENT FOR BIOLOGICAL FEATURE SELECTION: METHODS AND ISSUES 353 Juntao Li, Kwok Pui Choi, Yudi Pawitan, and Radha Krishna Murthy Karuturi 16 SURVEY OF NOVEL FEATURE SELECTION METHODS FOR CANCER CLASSIFICATION 379 Oleg Okun 17 INFORMATION-THEORETIC GENE SELECTION IN EXPRESSION DATA 399 Patrick E. Meyer and Gianluca Bontempi 18 FEATURE SELECTION AND CLASSIFICATION FOR GENE EXPRESSION DATA USING EVOLUTIONARY COMPUTATION 421 Haider Banka, Suresh Dara, and Mourad Elloumi SECTION II BIOLOGICAL DATA MINING PART E: REGRESSION ANALYSIS OF BIOLOGICAL DATA 19 BUILDING VALID REGRESSION MODELS FOR BIOLOGICAL DATA USING STATA AND R 445 Charles Lindsey and Simon J. Sheather 20 LOGISTIC REGRESSION IN GENOMEWIDE ASSOCIATION ANALYSIS 477 Wentian Li and Yaning Yang 21 SEMIPARAMETRIC REGRESSION METHODS IN LONGITUDINAL DATA: APPLICATIONS TO AIDS CLINICAL TRIAL DATA 501 Yehua Li PART F: BIOLOGICAL DATA CLUSTERING 22 THE THREE STEPS OF CLUSTERING IN THE POST-GENOMIC ERA 521 Raffaele Giancarlo, Giosu´e Lo Bosco, Luca Pinello, and Filippo Utro 23 CLUSTERING ALGORITHMS OF MICROARRAY DATA 557 Haifa Ben Saber, Mourad Elloumi, and Mohamed Nadif 24 SPREAD OF EVALUATION MEASURES FOR MICROARRAY CLUSTERING 569 Giulia Bruno and Alessandro Fiori 25 SURVEY ON BICLUSTERING OF GENE EXPRESSION DATA 591 Adelaide Valente Freitas, Wassim Ayadi, Mourad Elloumi, Jose Luis Oliveira, and Jin-Kao Hao 26 MULTIOBJECTIVE BICLUSTERING OF GENE EXPRESSION DATA WITH BIOINSPIRED ALGORITHMS 609 Khedidja Seridi, Laetitia Jourdan, and El-Ghazali Talbi 27 COCLUSTERING UNDER GENE ONTOLOGY DERIVED CONSTRAINTS FOR PATHWAY IDENTIFICATION 625 Alessia Visconti, Francesca Cordero, Dino Ienco, and Ruggero G. Pensa PART G: BIOLOGICAL DATA CLASSIFICATION 28 SURVEY ON FINGERPRINT CLASSIFICATION METHODS FOR BIOLOGICAL SEQUENCES 645 Bhaskar DasGupta and Lakshmi Kaligounder 29 MICROARRAY DATA ANALYSIS: FROM PREPARATION TO CLASSIFICATION 657 Luciano Cascione, Alfredo Ferro, Rosalba Giugno, Giuseppe Pigola, and Alfredo Pulvirenti 30 DIVERSIFIED CLASSIFIER FUSION TECHNIQUE FOR GENE EXPRESSION DATA 675 Sashikala Mishra, Kailash Shaw, and Debahuti Mishra 31 RNA CLASSIFICATION AND STRUCTURE PREDICTION: ALGORITHMS AND CASE STUDIES 685 Ling Zhong, Junilda Spirollari, Jason T. L. Wang, and Dongrong Wen 32 AB INITIO PROTEIN STRUCTURE PREDICTION: METHODS AND CHALLENGES 703 Jad Abbass, Jean-Christophe Nebel, and Nashat Mansour 33 OVERVIEW OF CLASSIFICATION METHODS TO SUPPORT HIV/AIDS CLINICAL DECISION MAKING 725 Khairul A. Kasmiran, Ali Al Mazari, Albert Y. Zomaya, and Roger J. Garsia PART H: ASSOCIATION RULES LEARNING FROM BIOLOGICAL DATA 34 MINING FREQUENT PATTERNS AND ASSOCIATION RULES FROM BIOLOGICAL DATA 737 Ioannis Kavakiotis, George Tzanis, and Ioannis Vlahavas 35 GALOIS CLOSURE BASED ASSOCIATION RULE MINING FROM BIOLOGICAL DATA 761 Kartick Chandra Mondal and Nicolas Pasquier 36 INFERENCE OF GENE REGULATORY NETWORKS BASED ON ASSOCIATION RULES 803 Cristian Andres Gallo, Jessica Andrea Carballido, and Ignacio Ponzoni PART I: TEXT MINING AND APPLICATION TO BIOLOGICAL DATA 37 CURRENT METHODOLOGIES FOR BIOMEDICAL NAMED ENTITY RECOGNITION 841 David Campos, Sergio Matos, and José Luýs Oliveira 38 AUTOMATED ANNOTATION OF SCIENTIFIC DOCUMENTS: INCREASING ACCESS TO BIOLOGICAL KNOWLEDGE 869 Evangelos Pafilis, Heiko Horn, and Nigel P. Brown 39 AUGMENTING BIOLOGICAL TEXT MINING WITH SYMBOLIC INFERENCE 901 Jong C. Park and Hee-Jin Lee 40 WEB CONTENT MINING FOR LEARNING GENERIC RELATIONS AND THEIR ASSOCIATIONS FROM TEXTUAL BIOLOGICAL DATA 919 Muhammad Abulaish and Jahiruddin 41 PROTEIN–PROTEIN RELATION EXTRACTION FROM BIOMEDICAL ABSTRACTS 943 Syed Toufeeq Ahmed, Hasan Davulcu, Sukru Tikves, Radhika Nair, and Chintan Patel PART J: HIGH-PERFORMANCE COMPUTING FOR BIOLOGICAL DATA MINING 42 ACCELERATING PAIRWISE ALIGNMENT ALGORITHMS BY USING GRAPHICS PROCESSOR UNITS 971 Mourad Elloumi, Mohamed Al Sayed Issa, and Ahmed Mokaddem 43 HIGH-PERFORMANCE COMPUTING IN HIGH-THROUGHPUT SEQUENCING 981 Kamer Kaya, Ayat Hatem, Hatice Gulcin Ozer, Kun Huang, and Umit V. Catalyurek 44 LARGE-SCALE CLUSTERING OF SHORT READS FOR METAGENOMICS ON GPUs 1003 Thuy Diem Nguyen, Bertil Schmidt, Zejun Zheng, and Chee Keong Kwoh SECTION III BIOLOGICAL DATA POSTPROCESSING PART K: BIOLOGICAL KNOWLEDGE INTEGRATION AND VISUALIZATION 45 INTEGRATION OF METABOLIC KNOWLEDGE FOR GENOME-SCALE METABOLIC RECONSTRUCTION 1027 Ali Masoudi-Nejad, Ali Salehzadeh-Yazdi, Shiva Akbari-Birgani, and Yazdan Asgari 46 INFERRING AND POSTPROCESSING HUGE PHYLOGENIES 1049 Stephen A. Smith and Alexandros Stamatakis 47 BIOLOGICAL KNOWLEDGE VISUALIZATION 1073 Rodrigo Santamarýa 48 VISUALIZATION OF BIOLOGICAL KNOWLEDGE BASED ON MULTIMODAL BIOLOGICAL DATA 1109 Hendrik Rohn and Falk Schreiber INDEX 1127

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Book SynopsisPerinatal Stem Cells, 2nd Edition builds on the first edition to provide an updated tutorial on perinatal stem cells, including stem cells harvested from the amniotic fluid, placenta, maternal blood supply, umbilical cord and Wharton''s Jelly. As in the first edition, coverage includes the underlying biology of each of the sources of pregnancy related stem cells, cell culture, and potential therapeutic uses, as well as insights on the impact of these stem cells from obstetricians and gynecologists, cardiologists, hematologists, tissue engineers, and cord blood bankers. Normally discarded as medical waste, perinatal stem cells offer a powerful therapeutic tool box alternative to the controversial embryonic stem cells. Since publication of the first edition, a burgeoning commerical industry has developed around various sources of perinatal cells, and the second edition now includes an overview of this growing industry. With contributions from some ofthe top academic steTrade Review“A classic text, focuses on recent research and advances in the clinical use of mesenchyme stem cells from pregnancy sources.” (Pediatric Endocrinology Reviews, 1 June 2014)Table of ContentsContributors xi Introduction xv 1 AMNIOTIC FLUID STEM CELLS 1 Sean Vincent Murphy and Anthony Atala Introduction 1 Development of Gestational Stem Cells 2 Isolation and Characterization of Amniotic Fluid Stem Cells 2 Multipotency of Amniotic Fluid Stem Cells 3 Clinical Application of Amniotic Fluid Stem Cells 8 Conclusion 13 References 13 2 CORD BLOOD TRANSPLANTS: PERINATAL STEM CELLS IN CLINICAL PRACTICE 17 Richard L. Haspel and Karen K. Ballen Introduction 17 Hematopoietic Stem Cell Transplants: Adult Donor Collection 17 Hematopoietic Stem Cell Transplants: HLA Matching 18 Collection and Processing of Cord Blood Units 19 Hematopoietic Stem Cell Transplants: Recipient Issues 20 Bone Marrow versus Single Cord Blood: Pediatric 21 Bone Marrow versus Cord Blood: Adults 23 Cord Blood Transplant: Advantages and Disadvantages 23 Double Cord Blood Transplants: Ablative Regimens 24 Double Cord Blood Transplant: Non-Myeloablative Regimens 26 Are Two Cords Better Than One? 27 Chimerism 28 Predicting the Winner 28 Other Experimental Strategies 30 Summary 31 References 31 3 HEMATOPOIETIC STEM CELL DEVELOPMENT IN THE PLACENTA 37 Katrin E.R. Ericson, Akanksha Chhabra, and Hanna K.A. Mikkola Introduction 37 The Hematopoietic System 37 Historical Perspective on Placental Hematopoiesis 38 The Development and Structure of the Mouse Placenta 39 Hematopoietic Activity in the Mouse Placenta 40 Identification of Placental HSCs 42 The Origin and Localization of Placental HSCs 43 Hematopoietic Activity in the Human Placenta 45 Hematopoietic Microenvironment in the Placenta 46 Conclusions and Perspectives 47 References 49 4 PERINATAL MESENCHYMAL STEM CELL BANKING FOR UMBILICAL CORD BLOOD TRANSPLANTATION AND REGENERATIVE MEDICINE 53 Rouzbeh R. Taghizadeh Introduction 53 Hematopoiesis 54 Hematopoietic Transplantations 54 Umbilical Cord: Source of Perinatal HSCs and MSCs 56 Hematopoietic Transplantations of Umbilical Cord Blood 57 Strategies to Overcome the Transplant-Related Limitations of Umbilical Cord Blood 58 Umbilical Cord Tissue MSC Banking 61 References 63 5 MAKING ORGAN AND STEM CELL TRANSPLANTATION SAFER: THE ROLE OF MESENCHYMAL STEM CELLS 71 Hans Klingemann Introduction 71 MSC to Prevent Rejection After Solid Organ Transplantation 72 MSC in the Treatment of Graft-versus-Host Disease 73 MSC to Support Hematopoietic Recovery of Stem Cells After Stem Cell Transplantation 74 References 75 6 WHARTON’S JELLY MESENCHYMAL STEM CELLS AND IMMUNE MODULATION: REGENERATIVE MEDICINE MEETS TISSUE REPAIR 77 Rita Anzalone, Felicia Farina, Melania Lo Iacono, Simona Corrao, Tiziana Corsello, Giovanni Zummo, and Giampiero La Rocca Introduction 77 Expression of Relevant Immunomodulatory Molecules in Vitro by MSCs 79 Tolerance Induction by MSCs: Rediscovering the Embryo Immune Evasion Mechanisms 79 Immune Modulation in Vivo: Contrasting Data on the Immune Privilege of MSCs 80 WJ-MSC in in Vivo Models: Enhancing the Immunomodulatory Features of Adult MSC Populations 82 Conclusions and Future Perspectives 83 References 84 7 IMMUNOGENICITY VERSUS IMMUNOMODULATION OF PERINATAL STEM CELLS 89 Bram Lutton and Raimon Duran-Struuck Introduction 89 Mechanisms of Immunomodulation by Umbilical Cord- and Bone Marrow-Derived MSCs 90 Innate Immune System 90 Adaptive Immune System 92 Natural Tolerance and Umbilical Cord Tissues 94 Tolerance versus Immunogenicity: The Yin and Yang of Host Responses to Umbilical Cord-Derived Cells 95 Conclusions 97 References 98 8 THE TRANSLATIONAL POTENTIAL OF PERINATAL STEM CELLS IN CLINICAL MEDICINE: MESENCHYMAL STEM CELLS 105 Radbeh Torabi, Vincenzo Villani, Christopher A. Mallard, and Curtis L. Cetrulo, Jr. Introduction 105 Graft-versus-Host Disease 106 Acute GVHD 107 Chronic GVHD 108 GVHD Prevention 109 Hematopoetic Recovery and HCT Engraftment 109 Hematopoietic Recovery 110 HCT Engraftment 111 MSC Potential Uses 111 References 113 9 NEWBORN STEM CELLS: IDENTITY, FUNCTION, AND CLINICAL POTENTIAL 119 Anthony Park, Louis Chan, Mayur Danny I. Gohel, Sean Murphy, Ursula Manuelpillai, Ann Chidgey, and Richard Boyd Introduction 120 The Newborn Offers an Enormous Opportunity for Stem Cells 120 Amnion 120 Isolation and Phenotypic Characterization of Amnion Cells 121 Therapeutic Potential of Amnion Membrane 123 Mechanisms of AEC-Enhanced Wound Repair 125 Therapeutic Potential of Amnion as Single Cells 127 Amnion Immunogenicity and Immunosuppressive Properties 127 Amnion-Derived Mesenchymal Stromal Cells 128 Umbilical Cord Mesenchymal Stromal Cells 130 Chorion MSCs 131 References 133 10 BIOMEDICAL POTENTIAL OF HUMAN PERINATAL STEM CELLS 139 Oleg V. Semenov and Christian Breymann Role of Stem Cells in Regenerative Medicine 139 Perinatal Stem Cell Sources 140 Properties of Perinatal Mesenchymal Stem Cells 143 Properties of Perinatal Hematopoietic Stem Cells 144 Biomedical Applications of Human Perinatal Stem Cells 145 Perspectives and Obstacles 147 References 148 11 PROGENITOR CELL THERAPY FOR THE TREATMENT OF TRAUMATIC BRAIN INJURY 155 Alex Bryan Olsen, Robert A. Hetz, Supinder S. Bedi, and Charles S. Cox, Jr. Introduction 155 Cellular Therapy for the Treatment of TBI 159 Neural Stem Progenitor Cells 159 Human Multipotent Adult Progenitor Cells 160 Mesenchymal Stem Cells 163 Umbilical Cord Blood 165 Wharton’s Jelly 166 Amniotic Fluid-Derived Stem Cells 167 The Inflammatory Reflex 168 Conclusion 170 References 171 12 THE HUMAN AMNIOTIC MEMBRANE: A TISSUE WITH MULTIFACETED PROPERTIES AND DIFFERENT POTENTIAL CLINICAL APPLICATIONS 177 Maddalena Caruso, Antonietta Silini, and Ornella Parolini Introduction 177 Structure and Histology of the Human Amniotic Membrane 178 Preparation, Preservation, and Sterilization of the Human Amniotic Membrane 179 Biological and Structural Properties of the Human Amniotic Membrane Generally Invoked to Explain Its Effects in Vivo 180 Established Clinical Applications of the Human Amniotic Membrane 183 Prospective Applications of the Human Amniotic Membrane: Lessons from Preclinical Studies 187 Conclusions and Perspectives 190 References 190 13 ADVANCES AND POSSIBLE APPLICATIONS OF HUMAN AMNION FOR THE MANAGEMENT OF LIVER DISEASE 197 Fabio Marongiu, Maria Paola Serra, Marcella Sini, Ezio Laconi, Marc C. Hansel, Kristen J. Skvorak, Roberto Gramignoli, and Stephen C. Strom Introduction 197 Human Amnion for the Management of Liver Fibrosis 198 Amnion-Derived Hepatocytes and Their Possible Applications 199 Conclusions 204 References 205 14 AMNION-DERIVED CELLS FOR STROKE RESTORATIVE THERAPY 209 Naoki Tajiri, Loren E. Glover, and Cesar V. Borlongan Introduction 209 Stem Cell Therapy: Beyond Stroke Neuroprotection 210 Therapeutic Potential of Adult Stem Cells 210 The Biology of Amnion-Derived Cells 211 Amnion-Derived Cells for Cell Therapy 212 Conclusion 215 References 216 15 PREGNANCY-ACQUIRED FETAL PROGENITORS AS NATURAL CELL THERAPY 221 Elke Seppanen, Nicholas M. Fisk,and Kiarash Khosrotehrani Introduction 221 Fetal Cell Microchimerism, a Widespread Phenomenon 222 The Kinetics of Fetal Cell Detection 222 Factors Modifying the Level of Microchimerism 222 Detecting FMC 223 Homing and Plasticity of FMC 224 Hematopoietic Capacity of FMC 224 Epithelial, Neuronal and Hepatic Capacity of FMC 228 Mesenchymal Capacity of FMC 228 FMC Includes Functional Endothelial Progenitor Cells that Contribute to Tissue Repair 229 FMC Likely Includes Cells of Placental Origin 230 Conclusions 230 References 231 INDUSTRY REVIEW 235 16 PERINATAL STEM CELLS: AN INDUSTRY PERSPECTIVE 237 Kyle J. Cetrulo Introduction 237 The Public Cord Blood Banking Industry 238 The Private Banking Industry 239 Research and Cord Blood Clinical Trials 240 The Mesenchymal Stem Cell Regenerative Medicine Industry 241 Wharton’s Jelly/Cord Tissue 242 Placental Stem Cells and Placental Tissue 243 Amniotic Fluid 244 Conclusion 245 References 245 17 PATENT PROTECTION OF STEM CELL INNOVATIONS 249 John R. Wetherell The Role of Patents in Commercialization 249 Background of the Patent System 250 Patentable Subject Matter 251 Statutory Requirements for a Patent 252 Written Description/Enablement/Best Mode 254 Important Future Changes 256 18 INTERVIEW WITH FRANCES VERTER, FOUNDER OF PARENT’S GUIDE TO CORD BLOOD FOUNDATION 259 Frances Verter and Kyle J. Cetrulo References 269 19 UMBILICAL CORD BLOOD BANKING: AN OBSTETRICIAN’S PERSPECTIVE 271 Jordan H. Perlow References 277 Index 279

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Book SynopsisThe newfound stability of carbenes has led to their development as catalysts and ligands for metal complexes of vast potential, including biomolecule labeling and surface modification of materials.Trade Review“Overall I think that this book is generally well presented and free of obvious mistakes. I very much like the fact that there is consistency in structure throughout each chapter, indicating that the editorial process has been thorough. In particular, the conclusion and outlook sections provide a valuable summary of the state-of-the-art in each area, and how the future is foreseen.” (Applied Organometallic Chemistry, 10 October 2014) Table of ContentsPreface PART 1: PROPERTIES AND REACTIONS OF CARBENES 1 Carbene Stability S. Gronert and R. M. O’Ferrall 2 Stable Carbenes J. P. Moerdyk and C. W. Bielawski 3 Acid-Base Chemistry of Carbenes A. M. O’Donoghue and R. S. Massey 4 Computational Methods for the Study of Carbenes and their Excited States H. L. Luk, S. Vyas, and C. M. Hadad 5 Dynamics in Carbene Reactions D. Merrer, K. Houk, and L. Xu 6 Ultrafast Kinetics of Carbene Reactions G. Burdzinski and M. S. Platz 7 Tunneling in the Reactions of Carbenes and Oxacarbenes D. Gerbig and P. R. Schreiner 8 Carbodicarbenes G. Frenking and R. Tonner 9 Catalytic Reactions with N-Mesityl Substituted N-Heterocyclic Carbenes J. Mahatthananchai and J. W. Bode 10 Supramolecular Carbene Chemistry U. Brinker, J.-L. Mieusset, and M. G. Rosenberg PART 2: METAL CARBENES 11 Modern Lithium Carbenoid Chemistry V. Capriati 12 Rhodium Carbenes H. Davies and B. Parr 13 Ruthenium Carbenes S. T. Diver and J. M. French 14 Nucleophilic Carbenes of the Chromium Triad Z. J. Tonzetich 15 Cobalt-Mediated Carbene Transfer Reactions X. Cui and X. P. Zhang 16 Gold Carbenes L. Zhang

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Book SynopsisAn update to the popular guide to proteomics technology applications in biomedical research Building on the strength of the original edition, this book presents the state of the art in the field of proteomics and offers students and scientists new tools and techniques to advance their own research. Written by leading experts in the field, it provides readers with an understanding of new and emerging directions for proteomics research and applications. Proteomics for Biological Discovery begins by discussing the emergence of proteomics technologies and summarizing the potential insights to be gained from proteome-level research. The tools of proteomics, from conventional to novel techniques, are thoroughly covered, from underlying concepts to limitations and future directions. Later chapters provide an overview of the current developments in post-translational modification studies, structural proteomics, biochemical proteomics, applied proteomics, and bioiTable of ContentsForeword vii List of Contributors ix 1. Quantitative Proteomics for Differential Protein Expression Profiling 1Christian K. Frese, Henk van den Toorn, Albert J.R. Heck, and Shabaz Mohammed 2. Protein Microarrays 29Fernanda Festa and Joshua LaBaer 3. Protein Biomarker Discovery: An Integrated Concept 63Andrei P. Drabovich, Eduardo Martinez‐Morillo, and Eleftherios P. Diamandis 4. Biomarker Discovery with Mass Spectrometry Imaging and Profiling 89Sage J.B. Dunham, Elizabeth K. Neumann, Eric J. Lanni, Ta-Hsuan Ong, and Jonathan V. Sweedler 5. Protein–Protein Interactions 125Claire M. Delahunty and John R. Yates III 6. Mass Spectrometry of Intact Protein Complexes 145Jonathan T.S. Hopper and Carol V. Robinson 7. Cross‐linking Applications in Structural Proteomics 175Evgeniy V. Petrotchenko, Jason J. Serpa, and Christoph H. Borchers 8. Functional Proteomics: Systematic Characterization of the Physical and Functional Organization of Cell Systems 197Pierre C. Havugimana, Pingzhao Hu, and Andrew Emili 9. High‐Resolution Interrogation of Biological Systems via Mass Cytometry 215Heather M. Grundhofer, Michelle M. Kuhns, and Edgar A. Arriaga 10. Characterization of Drug–Protein Interactions by Chemoproteomics 247Markus Schirle, Marcus Bantscheff, and Bernhard Kuster 11. Phosphorylation 265Timothy D. Veenstra 12. Large‐Scale Phosphoproteomics 291John R. Yates III 13. Probing Glycoforms of Individual Proteins Using Antibody‐Lectin Sandwich Arrays: Methods and Findings from Studies of Pancreatic Cancer 311Brian B. Haab Index 329

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Book SynopsisA comprehensive and timely review of developments in the field, Cell and Molecular Biology of Stem Cell Imaging features original and review articles written by experts in their fields.Table of ContentsContributors vii Preface xi 1 Cell and Molecular Biology and Imaging of Stem Cells: Stem Cells from the Amniotic Fluid and Placenta 1Amritha Kidiyoor, Sean V. Murphy, and Anthony Atala 2 Biomaterials as Artificial Niches for Pluripotent Stem Cell Engineering 21Kyung Min Park and Sharon Gerecht 3 Low-Intensity Ultrasound in Stem Cells and Tissue Engineering 45Byung Hyune Choi, Kil Hwan Kim, Mrigendra Bir Karmacharya, Byoung-Hyun Min and So Ra Park 4 Mammalian Neo-Oogenesis from Ovarian Stem Cells In Vivo and In Vitro 67Antonin Bukovsky and Michael R. Caudle 5 Oct4-EGFP Transgenic Pigs as a New Tool for Visualization of Pluripotent and Reprogrammed Cells 137Monika Nowak-Imialek and Heiner Niemann 6 Regulation of Adult Intestinal Stem Cells through Thyroid Hormone-Induced Tissue Interactions during Amphibian Metamorphosis 153Atsuko Ishizuya-Oka 7 Stem Cell Therapy for Veterinary Orthopedic Lesions 173Anna Paula Balesdent Barreira and Ana Liz Garcia Alves 8 Sex Steroid Combinations in Regenerative Medicine for Brain and Heart Diseases: The Vascular Stem Cell Niche and a Clinical Proposal 193Antonin Bukovsky and Michael R. Caudle 9 Hair Follicle Stem Cells 211Hilda Amalia Pasolli 10 The Potential of Using Induced Pluripotent Stem Cells in Skin Diseases 223Shigeki Ohta, Ophelia Veraitch, Hideyuki Okano, Manabu Ohyama, and Yutaka Kawakami 11 Mitochondrial Differentiation in Early Embryo Cells and Pluripotent Stem Cells 247Heide Schatten, Qing-Yuan Sun, and Randall S. Prather 12 The Role of Centrosomes in Cancer Stem Cell Functions 259Heide Schatten Index 281

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Book SynopsisPresents a variety of scanning and transmission electron microscope images of the major systems of the human body. This book looks at the structure and function of tissues at the subcellular and molecular level, an important perspective in understanding and combating diseases.Table of ContentsPreface xi Acknowledgments xiii Note to readers xiv I. Cellular organelles and surface specializations 1 A. Nuclei and nucleoli 1 B. Mitochondria 6 C. Golgi complex 8 D. Rough endoplasmic reticulum and smooth Endoplasmic reticulum 10 E. Lysosomes 12 F. Cytoplasmic inclusions 13 G. Plasma membrane junctions 16 H. Microvilli 18 I. Cilia and centrioles 21 J. Plasma membrane infoldings 25 II. Blood cells 27 A. Blood composition 27 B. Red blood cells 39 C. Sickle cell anemia 39 D. Granular leukocytes—Neutrophils, Eosinophils, and Basophils 44 E. Nongranular leukocytes—Lymphocytes and Monocytes 55 F. Blood platelets—Blood clots 70 III. Connective tissues 77 A. Composition 77 B. Resident cells—Fibroblasts, Adipocytes, Mast cells 90 C. Blood cell derivatives—Neutrophils, Eosinophils, Lymphocytes, Macrophages, and Plasma cells 125 D. Loose connective tissue example: Lamina propria 132 E. Dense irregular connective tissue examples: Dermis and Capsules of organs 132 F. Dense regular connective tissue 132 G. Cartilage—Hyaline cartilage and Fibrocartilage 144 H. Bone—Compact bone and Cancellous bone 161 IV. Muscle tissues 179 A. Overview 179 B. Smooth muscle—Wall of colon, Branched fibers in wall of ureter, Walls of blood vessels 179 C. Skeletal muscle 201 D. Cardiac muscle—Atrium 227 V. Nerve tissues 253 A. Overview 253 B. Peripheral nerves—Optic nerve, Sciatic nerve, Nerve in wall of colon, Myelinated and Unmyelinated nerves 253 C. Central nervous system—Cerebrum 287 VI. Cardiovascular system 303 A. Overview 303 B. Arteries 303 C. Veins 328 D. Capillaries 336 E. Heart-atrium 354 VII. Lymphatic tissues 359 A. Overview 359 B. Spleen 361 C. Thymus 365 D. Lymph nodes, lymph nodules/diffuse lymphatic tissue 365 E. Tonsils 374 VIII. Gastrointestinal tract 385 A. Oral cavity 385 B. Overview of the alimentary canal 405 C. Esophagus 405 D. Stomach 408 E. Small intestines—Duodenum, Jejunum, and Ileum 441 F. Large intestine (colon) and appendix 474 IX. Liver and gall bladder 507 A. Liver 507 B. Gall bladder 520 X. Pancreas 543 XI. Respiratory tract 561 A. Overview 561 B. Trachea, bronchi, and bronchioles 562 C. Lungs 579 XII. Urinary tract 609 A. Overview 609 B. Kidney 609 C. Ureters, bladder, and urethra 656 XIII. Skin 671 A. Overview 671 B. Epidermis 671 C. Dermis and hypodermis 725 D. Skin parasites 743 XIV. Eye 749 XV. Ear 797 A. Overview 797 B. Middle ear 797 C. Inner ear 802 XVI. Male reproductive system 819 A. Testis and epididymis 819 B. Vas deferens 841 C. Seminal vesicle 844 D. Prostate gland 849 E. Bulbourethral glands, Glands of littre, and The penis 856 XVII. Female reproductive system 857 A. Overview and ovary 857 B. Oviduct 860 C. Uterus and cervix 873 D. Vagina 888 E. Placenta 896 F. Mammary gland (inactive) 903 XVIII. Thyroid, parathyroid, and adrenal Glands—examples of endocrine organs 911 A. Thyroid gland 911 B. Parathyroid glands 924 C. Adrenal glands 930 References 941 Index 943

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Book SynopsisMicroRNAs in Medicine provides an access point into the current literature on microRNA for both scientists and clinicians, with an up-to-date look at what is happening in the emerging field of microRNAs and their relevance to medicine.Table of ContentsForeword ix Sir David Baulcombe Preface xi Contributors xiii 1 MICRORNAS: A BRIEF INTRODUCTION 1 Charles H. Lawrie PART I: MICRORNAS AS PHYSIOLOGICAL REGULATORS 25 2 MICRORNA REGULATION OF STEM CELL FATE AND REPROGRAMMING 27 Erika Lorenzo Vivas, Gustavo Tiscornia, and Juan Carlos Izpisua Belmonte 3 MICRORNAS AS REGULATORS OF IMMUNITY 41 Donald T. Gracias and Peter D. Katsikis 4 REGULATION OF SENESCENCE BY MICRORNAS 59 Ioannis Grammatikakis and Myriam Gorospe 5 THE EMERGENCE OF GEROMIRS: A GROUP OF MICRORNAS IMPLICATED IN AGING 77 Alejandro P. Ugalde, Agnieszka Kwarciak, Xurde M. Caravia, Carlos López-Otín, and Andrew J. Ramsay 6 MICRORNAS AND HEMATOPOIESIS 91 Sukhinder K. Sandhu and Ramiro Garzon 7 MICRORNAS IN PLATELET PRODUCTION AND ACTIVATION 101 Leonard C. Edelstein, Srikanth Nagalla, and Paul F. Bray PART II: MICRORNAS IN INFECTIOUS DISEASE: HOST–PATHOGEN INTERACTIONS 117 8 MICRORNAS AS KEY PLAYERS IN HOST-VIRUS INTERACTIONS 119 Aurélie Fender and Sébastien Pfeffer 9 MICRORNA EXPRESSION IN AVIAN HERPESVIRUSES 137 Yongxiu Yao and Venugopal Nair 10 FUNCTION OF HUMAN CYTOMEGALOVIRUS MICRORNAS AND POTENTIAL ROLES IN LATENCY 153 Natalie L. Reynolds, Jon A. Pavelin, and Finn E. Grey 11 INVOLVEMENT OF SMALL NON-CODING RNA IN HIV-1 INFECTION 165 Guihua Sun, John J. Rossi, and Daniela Castanotto 12 MICRORNA IN MALARIA 183 Panote Prapansilp and Gareth D.H. Turner PART III: CANCER 199 13 THE MICRORNA DECALOGUE OF CANCER INVOLVEMENT 201 Tanja Kunej, Irena Godnic, Minja Zorc, Simon Horvat, and George A. Calin 14 MICRORNAS AS ONCOGENES AND TUMOR SUPPRESSORS 223 Eva E. Rufi no-Palomares, Fernando J. Reyes-Zurita, Jose Antonio Lupiáñez, and Pedro P. Medina 15 LONG NON-CODING RNAS AND THEIR ROLES IN CANCER 245 Yolanda Sánchez and Maite Huarte 16 REGULATION OF HYPOXIA RESPONSES BY MICRORNA EXPRESSION 267 Carme Camps, Adrian L. Harris, and Jiannis Ragoussis 17 CONTROL OF RECEPTOR FUNCTION BY MICRORNAS IN BREAST CANCER 287 Claudia Piovan and Marilena V. Iorio 18 MICRORNAS IN HUMAN PROSTATE CANCER: FROM PATHOGENESIS TO THERAPEUTIC IMPLICATIONS 311 Mustafa Ozen and Omer Faruk Karatas 19 MICRORNA SIGNATURES AS BIOMARKERS OF COLORECTAL CANCER 329 Katrin Pfütze, Xiaoya Luo, and Barbara Burwinkel 20 GENETIC VARIATIONS IN MICRORNA-ENCODING SEQUENCES AND MICRORNA TARGET SITES ALTER LUNG CANCER SUSCEPTIBILITY AND SURVIVAL 343 Ming Yang and Dongxin Lin 21 MICRORNA IN MYELOPOIESIS AND MYELOID DISORDERS 353 Sara E. Meyer and H. Leighton Grimes 22 MICRORNA DEREGULATION BY ABERRANT DNA METHYLATION IN ACUTE LYMPHOBLASTIC LEUKEMIA 371 Xabier Agirre and Felipe Prósper 23 ROLE OF MIRNAS IN THE PATHOGENESIS OF CHRONIC LYMPHOCYTIC LEUKEMIA 383 Veronica Balatti, Yuri Pekarsky, Lara Rizzotto, and Carlo M. Croce 24 MICRORNA IN B-CELL NON-HODGKIN’S LYMPHOMA: DIAGNOSTIC MARKERS AND THERAPEUTIC TARGETS 403 Nerea Martínez, Lorena Di Lisio, and Miguel Angel Piris 25 MICRORNAS IN DIFFUSE LARGE B-CELL LYMPHOMA 419 Izidore S. Lossos and Alvaro J. Alencar 26 THE ROLE OF MICRORNAS IN HODGKIN’S LYMPHOMA 435 Wouter Plattel, Joost Kluiver, Arjan Diepstra, Lydia Visser, and Anke van den Berg 27 MICRORNA EXPRESSION IN CUTANEOUS T-CELL LYMPHOMAS 449 Cornelis P. Tensen PART IV: HEREDITARY AND OTHER NON-INFECTIOUS DISEASES 463 28 MICRORNAS AND HEREDITARY DISORDERS 465 Matías Morín and Miguel A. Moreno-Pelayo 29 MICRORNAS AND CARDIOVASCULAR DISEASES 477 Koh Ono 30 MICRORNAS AND DIABETES 495 Romano Regazzi 31 MICRORNAS IN LIVER DISEASES 509 Patricia Munoz-Garrido, Marco Marzioni, Elizabeth Hijona, Luis Bujanda, and Jesus M. Banales 32 MICRORNA REGULATION IN MULTIPLE SCLEROSIS 523 Andreas Junker 33 THE ROLE OF MICRORNAS IN ALZHEIMER’S DISEASE 539 Shahar Barbash and Hermona Soreq 34 CURRENT VIEWS ON THE ROLE OF MICRORNAS IN PSYCHOSIS 553 Aoife Kearney, Javier A. Bravo, and Timothy G. Dinan PART V: CIRCULATING MICRORNAS AS CELLULAR MESSENGERS AND NOVEL BIOMARKERS 567 35 CIRCULATING MICRORNAS AS NON-INVASIVE BIOMARKERS 569 Heidi Schwarzenbach and Klaus Pantel 36 CIRCULATING MICRORNAS AS CELLULAR MESSENGERS 589 Kasey C. Vickers 37 RELEASE OF MICRORNA-CONTAINING VESICLES CAN STIMULATE ANGIOGENESIS AND METASTASIS IN RENAL CARCINOMA 607 Federica Collino, Cristina Grange, and Giovanni Camussi PART VI: THERAPEUTIC USES OF MICRORNAS: CURRENT PERSPECTIVES AND FUTURE DIRECTIONS 623 38 MICRORNA REGULATION OF CANCER STEM CELLS AND MICRORNAS AS POTENTIAL CANCER STEM CELL THERAPEUTICS 625 Can Liu and Dean G. Tang 39 THERAPEUTIC MODULATION OF MICRORNAS 639 Achim Aigner and Hannelore Dassow 40 LOCKED NUCLEIC ACIDS AS MICRORNA THERAPEUTICS 663 Henrik Ørum Index 673

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Book SynopsisA quick, concise reference to pathogenic microorganisms and the diseases they cause, this book is divided into specific groups of pathogenic microorganisms including bacteria, protozoa, fungi, viruses, and prions.Table of ContentsPreface xi About the Authors xiii 1 Introduction 1 Koch’s Postulate 2 Terminology 3 Major Categories of Pathogenic Microorganisms 4 Transmission of Infectious Disease (Mode of Dissemination) 5 Universal Precautions 6 2 Host-Microbe Interactions 9 Resident Microbiota 9 Host Defenses 11 3 Antibiotics and Other Chemotherapeutic Agents 17 Classification of Antibiotics 17 Summary of the Mechanisms of Action 24 4 Antiseptics and Disinfectants 25 Physical Control of Microorganisms 25 Chemical Control of Microorganisms 27 5 Gram-Positive Cocci 31 Bacterial Taxonomy (An Overview) 31 Clinically Important Gram-Positive Cocci 32 Gram-Positive Cocci Related to Streptococcus Species 38 6 Gram-Positive Bacilli 41 Clostridium Species 41 Lactobacillus Species 46 Bacillus Species 46 Listeria Species 49 7 Gram-Positive Bacteria with Rudimentary Filaments 53 Corynebacterium diphtheriae 53 Mycobacterium Species 54 8 Gram-Negative Cocci 61 Neisseria Species 61 Moraxella catarrhalis 64 Haemophilus influenzae 65 An Overview of Gram-Negative Bacteria 67 9 Gram-Negative Bacilli 69 Specimen Collection 69 Media and Laboratory Diagnosis 69 Enterobacteriaceae 71 Glucose Nonfermenters 78 Uncommon Nonfermentative Taxa 81 10 Miscellaneous Gram-Negative Bacteria 83 Brucella melitensis 83 Bordetella pertussis 85 Francisella tularensis 86 Pasteurella Species 87 Vibrio cholerae 88 Aeromonas Species 90 Campylobacter Species 90 Legionella Species 92 Gardnerella vaginalis 93 Chlamydia Species 94 Rickettsia rickettsii 95 Bacteroides Species 96 Calymmatobacterium granulomatis 96 Cardiobacterium hominis 96 Streptobacillus moniliformis 96 Spirillum minus 97 11 Spirochetes and Bacteria without a Cell Wall 99 Spirochetes 99 Bacteria without a Cell Wall 103 12 Actinomycetes 107 Anaerobic Actinomycetes 108 Aerobic Actinomycetes 108 Thermophilic Actinomycetes 112 13 Introduction to Pathogenic Fungi and Superficial Mycoses 113 Yeast-Like Fungi 113 Molds or Filamentous Fungi 114 Dimorphic Fungi 114 Superficial Mycoses 115 Mucocutaneous Mycoses 121 14 Subcutaneous and Systemic Mycoses 125 Subcutaneous Mycoses 125 Systemic Mycoses 127 Diseases Caused by Dimorphic Fungi 127 Diseases Caused by Yeast-Like Fungi 135 Diseases Caused by Filamentous Fungi 138 Diseases Caused by Miscellaneous Filamentous Fungi 143 15 Unicellular Parasites 145 Laboratory Methods in Parasitology 145 Diseases Caused by Lumen-Dwelling Protozoa 146 Blood- and Tissue-Dwelling Protozoa 149 16 Multicellular Parasites 155 Lumen-Dwelling Helminths 155 Blood- and Tissue-Dwelling Helminths 161 17 Viruses and Prions 165 Laboratory Diagnosis 166 Double-Stranded DNA Viruses 166 Single-Stranded DNA Viruses 171 Double-Stranded RNA Viruses 171 Single-Stranded RNA Viruses 171 Prions 179 Bibliography and Suggested Reading 181 Index 185

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Book Synopsis* Integrated textbook combining three subjects, haematology, clinical biochemistry and immunology to provide a one-stop text on blood science, in line with the new IBMS and NHS training structure * Suitable for blood science courses opening in many universities at senior Undergraduate level (units) and Masters level.Table of ContentsPreface, xiii Acknowledgements, xv List of Abbreviations, xvii About the Companion Website, xxi 1 Introduction to Blood Science, 1 1.1 What is blood science?, 1 1.2 Biochemistry, 6 1.3 Blood transfusion, 8 1.4 Genetics, 10 1.5 Haematology, 14 1.6 Immunology, 17 1.7 The role of blood science in modern healthcare, 19 1.8 What this book will achieve, 22 Summary, 23 References, 23 Further reading, 23 Web sites, 23 2 Analytical Techniques in Blood Science, 25 2.1 Venepuncture, 25 2.2 Anticoagulants, 26 2.3 Sample identification and tracking, 27 2.4 Technical and analytical confidence, 27 2.5 Major techniques, 32 2.6 Molecular genetics, 43 2.7 Point of care testing, 47 2.8 Health and safety in the laboratory, 48 Summary, 49 Further reading, 50 Web sites, 50 3 The Physiology of the Red Blood Cell, 51 3.1 Introduction, 51 3.2 The development of blood cells, 52 3.3 Erythropoiesis, 56 3.4 The red cell membrane, 58 3.5 The cytoplasm of the red cell, 60 3.6 Oxygen transport, 66 3.7 Recycling the red cell, 68 3.8 Red cell indices in the full blood count, 69 3.9 Morphology of the red cell, 72 Summary, 74 Further reading, 74 4 The Pathology of the Red Blood Cell, 75 4.1 Introduction: diseases of red cells, 75 4.2 Anaemia resulting from attack on, or stress to, the bone marrow, 78 4.3 Anaemia due to deficiency, 80 4.4 Intrinsic defects in the red cell, 85 4.5 External factors acting on healthy cells, 100 4.6 Erythrocytosis and polycythaemia, 103 4.7 Molecular genetics and red cell disease, 105 4.8 Inclusion bodies, 105 4.9 Case studies, 105 Summary, 107 References, 107 Further reading, 107 5 White Blood Cells in Health and Disease, 109 5.1 Introduction, 109 5.2 Leukopoiesis, 111 5.3 Neutrophils, 115 5.4 Lymphocytes, 116 5.5 Monocytes, 117 5.6 Eosinophils, 118 5.7 Basophils, 119 5.8 Leukocytes in action, 120 5.9 White cells in clinical medicine, 127 5.10 Case studies, 132 Summary, 132 Further reading, 133 6 White Blood Cell Malignancy 135 6.1 The genetic basis of leukocyte malignancy, 135 6.2 Tissue techniques in haemato-oncology, 139 6.3 Leukaemia, 141 6.4 Lymphoma, 149 6.5 Myeloma and related conditions, 152 6.6 Myelofibrosis and myelodysplasia, 157 6.7 Case studies, 157 Summary, 158 Further reading, 159 Guidelines, 159 7 The Physiology and Pathology of Haemostasis, 161 7.1 The blood vessel wall, 162 7.2 Platelets, 163 7.3 The coagulation pathway, 165 7.4 Haemostasis as the balance between thrombus formation and removal, 168 7.5 The haemostasis laboratory, 171 7.6 The pathology of thrombosis, 173 Summary, 175 Further reading, 175 8 The Diagnosis and Management of Disorders of Haemostasis, 177 8.1 Thrombosis 1: overactive platelets and thrombocytosis, 177 8.2 Thrombosis 2: overactive coagulation, 181 8.3 Haemorrhage 1: platelet underactivity and thrombocytopenia, 193 8.4 Haemorrhage 2: coagulation underactivity, 199 8.5 Disseminated intravascular coagulation, 203 8.6 Molecular genetics in haemostasis, 204 8.7 Case studies, 205 Summary, 206 References, 206 Further reading, 207 Guidelines, 207 Web sites, 207 9 Immunopathology, 209 9.1 Introduction, 209 9.2 Basics of the immune system, 210 9.3 Humoral immunity, 212 9.4 Immunopathology 1: immunodeficiency, 215 9.5 Immunopathology 2: hypersensitivity, 221 9.6 Immunopathology 3: autoimmune disease, 226 9.7 Immunotherapy, 232 9.8 The immunology laboratory, 234 9.9 Case studies, 238 Summary, 239 References, 240 Further reading, 240 Guidelines, 240 Web sites, 240 10 Immunogenetics and Histocompatibility, 241 10.1 The genetics of antigen recognition, 241 10.2 Human leukocyte antigens, 245 10.3 Transplantation, 251 10.4 Autoimmunity and human leukocyte antigens, 257 Summary, 260 Further reading, 260 Guidelines, 260 Web sites, 260 11 Blood Transfusion, 261 11.1 Blood collection and processing, 262 11.2 Blood groups, 265 11.3 Laboratory practice of blood transfusion, 273 11.4 Clinical practice of blood transfusion, 279 11.5 Hazards of blood transfusion, 281 Summary, 284 References, 284 Further reading, 284 Guidelines, 284 Web sites, 285 12 Waste Products, Electrolytes and Renal Disease, 287 12.1 Renal anatomy and physiology, 287 12.2 Homeostasis, 288 12.3 Excretion, 295 12.4 Renal endocrinology, 297 12.5 Renal disease, 298 12.6 Case studies, 301 Summary, 303 Further reading, 303 Guidelines, 303 Web sites, 303 13 Hydrogen Ions, pH, and Acid–Base Disorders, 305 13.1 Ions and molecules, 305 13.2 Blood gases, 308 13.3 Acidosis (pH <7.3), 312 13.4 Alkalosis (pH >7.5), 313 13.5 Mixed acid–base conditions, 314 13.6 Clinical interpretation, 314 13.7 Case studies, 315 Summary, 316 Further reading, 317 Web site, 317 14 Glucose, Lipids and Atherosclerosis, 319 14.1 Glucose, 319 14.2 Dyslipidaemia, 333 14.3 Atherosclerosis, 343 14.4 Case studies, 347 Summary, 348 Further reading, 348 Guidelines, 349 Web sites, 349 15 Calcium, Phosphate, Magnesium and Bone Disease, 351 15.1 Calcium, 352 15.2 Phosphates, 355 15.3 Magnesium, 355 15.4 The laboratory, 355 15.5 Disorders of calcium homeostasis, 357 15.6 Disorders of phosphate homeostasis, 360 15.7 Disorders of magnesium homeostasis, 362 15.8 Bone physiology, 363 15.9 Bone disease, 364 15.10 Case studies, 368 Summary, 369 Further reading, 370 Guidelines, 370 Web sites, 370 16 Nutrients and Gastrointestinal Disorders, 371 16.1 Nutrients, 371 16.2 The intestines, 375 16.3 Case studies, 381 Summary, 382 Further reading, 382 Guidelines, 382 17 Liver Function Tests and Plasma Proteins, 383 17.1 Anatomy and physiology of the liver, 384 17.2 Liver function tests, 389 17.3 Diseases of the liver, 390 17.4 Plasma proteins, 396 17.5 Case studies, 405 Summary, 406 Further reading, 406 Web sites, 406 18 Hormones and Endocrine Disorders, 407 18.1 Endocrine physiology, 407 18.2 The pathology of the endocrine system, 417 18.3 Case studies, 434 Summary, 435 Further reading, 435 Web sites, 436 19 Cancer and Tumour Markers, 437 19.1 General concepts in cancer biology, 437 19.2 Blood science and cancer, 440 19.3 Molecular genetics, 444 19.4 Case studies, 445 Summary, 446 Further reading, 446 Guidelines, 447 Web sites, 447 20 Inherited Metabolic Disorders, 449 20.1 The genetics of inheritance, 449 20.2 Molecular inherited metabolic disorders, 451 20.3 Organelle inherited metabolic disorders, 455 20.4 Antenatal diagnosis and neonatal screening, 455 20.5 Case studies, 456 Summary, 457 Further reading, 457 21 Drugs and Poisons, 459 21.1 Toxicology, 459 21.2 Toxicology of specific compounds, 461 21.3 Therapeutic drug monitoring, 465 21.4 Case studies, 468 Summary, 469 References, 469 Further reading, 469 22 Case Reports in Blood Science, 471 Abbreviations, 471 Case report 1, 472 Anaemia, hypercalcaemia, proteinuria, myeloma Case report 2, 473 Diabetes, glycated haemoglobin, chronic renal failure Case report 3, 474 Acute kidney injury, leucocytosis, neutrophilia, viruses Case report 4, 475 Part 1: Obesity, colorectal cancer, CEA, hypothyroidism. Part 2: Alcoholism, raised GGT and triacylglycerols Case report 5, 477 Part 1: No abnormalities. Part 2: Asthma, raised IgE. Part 3: Falling haemoglobin, rising ESR, lung cancer Case report 6, 479 Hypothyroidism, marginally reduced haemoglobin Case report 7, 480 Raised CRP, ESR, rheumatoid factor and anti-nuclear antibodies; borderline anti-dsDNA antibodies, low C3, low eGFR and so mild renal failure, systemic lupus erythematosus Case report 8, 481 Normal blood results in renal transplantation Case report 9, 482 Falling albumin, eGFR, haemoglobin, red cell count and platelets, rising ESR, white cell count and neutrophila, CRP, urea and creatinine, septicaemia Case report 10, 484 Microcytic anaemia, thrombocytopenia, lymphocytosis, abnormal LFTs, falling albumin, raised CRP, myositis with raised CK, viruses Case report 11, 486 Acidosis, hyperglycaemia, diabetic ketoacidosis, acute renal injury, raised urea and creatinine Case report 12, 487 Low haemoglobin, thrombocytopenia, raised CRP and d-dimers, abnormal LFTs, malaria, pregnancy Case report 13, 488 Raised aldosterone, hypernatraemia, hypokalaemia, Conn’s syndrome Case report 14, 489 Paediatric diabetic ketoacidosis, hyperglycaemia, low bicarbonate, raised phosphates, ALP and proteins References, 490 Appendix: Reference Ranges, 491 Further Reading, 493 Glossary, 495 Index, 519

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Book SynopsisNeuropsychopharmacology is a relatively new subject area in the neurosciences.Table of ContentsPreface xiii About the Companion Website xv 1 Introduction to Neuropsychopharmacology 1 1.1 Overview 1 1.2 A Brief Overview of the Anatomy and Function of the Brain 2 1.2.1 The Brainstem 2 1.2.2 The Metencephalon 3 1.2.3 Diencephalon 4 1.2.4 The Telencephalon 5 1.2.5 The Cerebral Ventricles and Cerebrospinal Fluid 7 1.3 Important Neurotransmitters 7 1.3.1 GABA and GABA Receptors 7 1.3.2 Glutamate and Glutamate Receptors 10 1.4 Central Nervous System Stimulant and Depressant Drugs 11 1.5 Central Nervous System (CNS) Stimulant Drugs 13 1.5.1 Psychomotor Stimulants 13 1.5.2 Analeptic Drugs 19 1.6 Depressant Drugs 21 1.6.1 Benzodiazepines 21 1.6.2 Other Depressant Drugs 23 1.7 Genetics 23 1.8 Electroencephalography and Imaging Techniques 24 1.8.1 Electroencephalography 24 1.8.2 X-Rays 24 1.8.3 Computed Tomography 24 1.8.4 Positron Emission Tomography 25 1.8.5 Magnetic Resonance Imaging 25 1.8.6 Functional MRI 25 1.9 Diagnostic Criteria for Mental Disorders 25 1.10 Animals Models for CNS Disorders 26 1.11 Summary 27 2 Parkinson’s Disease 28 2.1 Overview 28 2.2 Historical Background 28 2.3 Epidemiology 29 2.4 Primary Clinical Features 29 2.5 Secondary Clinical Features 30 2.6 Parkinson’s Disease and the Extrapyramidal System 31 2.7 Neurotransmission in the Extrapyramidal System and Parkinson’s Disease 33 2.7.1 Modulation of the Direct and Indirect Pathways 35 2.8 Causes of Parkinson’s Disease 36 2.8.1 Genes and Parkinson’s Disease 37 2.8.2 Environmental Neurotoxins 39 2.8.3 Oxidative Stress 41 2.9 Summary 42 2.10 Pharmacotherapy for Parkinson’s Disease 42 2.10.1 L-DOPA (L-Dihydroxyphenylalanine) 43 2.10.2 L-DOPA Treatment 44 2.10.3 Adverse Effects of L-DOPA 44 2.10.4 Adverse Effects after Long-Term Treatment 46 2.10.5 Alternative Formulations of L-DOPA and Other Pharmacological Agents 48 2.11 Nonmotor Symptoms of Parkinson’ Disease and the Development of a New Hypothesis 53 2.12 Pharmacological and Nonpharmacological Strategies for Treatment of Other Motor and Nonmotor Symptoms of Parkinson’s Disease 55 2.13 Other Nonpharmacological Methods of Treating Parkinson’s Disease 56 2.13.1 Lesions of the Globus Pallidus or Subthalamic Nucleus 56 2.13.2 Neurostimulation 57 2.13.3 Brain Grafts 57 2.14 Possible Future Strategies to Treat Parkinson’s Disease 58 2.14.1 Stem Cell Therapy 58 2.14.2 Gene Therapy 58 2.15 Early Diagnosis for Treatment of Parkinson’s Disease 59 2.16 Summary and Conclusions 59 3 Memory, Dementia and Alzheimer’s Disease 61 3.1 Overview 61 3.2 Learning and Memory 61 3.2.1 Temporal Stages of Learning, Memory and Recall 62 3.2.2 Where are STM and LTM Stored in the Brain? 67 3.3 Overview of Dementia 69 3.4 Alzheimer’s Disease (AD) 71 3.4.1 Clinical Symptoms of Alzheimer’s Disease 72 3.4.2 Neuropathological Changes 74 3.4.3 Molecular Pathology 74 3.4.4 Staging of Alzheimer’s Disease 80 3.4.5 Onset of Alzheimer’s Disease 80 3.4.6 Neurochemical Changes in Alzheimer’s Disease 82 3.4.7 Pharmacotherapy of Alzheimer’s Disease 85 3.4.8 Future Pharmacological Strategies in the Treatment of Alzheimer’s Disease 88 3.4.9 Cardiovascular Disease 91 3.4.10 Conclusions 91 3.5 Summary 92 4 Epilepsy 93 4.1 Overview 93 4.2 Background 94 4.3 Classification and Types of Epilepsy 94 4.3.1 Focal Seizures 94 4.3.2 Generalized Seizures 95 4.3.3 Epilepsy Syndromes 97 4.3.4 Epidemiology 98 4.4 Underlying Causes of Epilepsy 98 4.5 Epileptic Mechanisms 99 4.5.1 Electrophysiological Mechanisms 99 4.5.2 Mechanisms Underpinning Drug Treatment of Epilepsy 100 4.6 Pharmacotherapy 101 4.6.1 Valproate (Valproic Acid and Sodium Valproate) 101 4.6.2 Phenytoin 105 4.6.3 Carbamazepine 106 4.6.4 Ethosuximide 107 4.6.5 Gabapentin 107 4.6.6 Pregabalin 108 4.6.7 Lamotrigine 109 4.6.8 Tiagabine 109 4.6.9 Topiramate 110 4.6.10 Levetiracetam 110 4.6.11 Retigabine 111 4.6.12 Zonisamide 111 4.6.13 Benzodiazepines 112 4.6.14 Barbiturates 112 4.7 Vagal Nerve Stimulation 113 4.8 Summary 113 5 Attention Deficit Hyperactivity Disorder 115 5.1 Overview 115 5.2 Background to ADHD 116 5.3 Diagnostic Criteria for ADHD 118 5.4 ADHD and Comorbidity 119 5.5 Epidemiology 120 5.6 Aetiology of ADHD 120 5.6.1 Genetic Factors 120 5.6.2 Environmental Factors 121 5.7 The Pathophysiology of ADHD 122 5.7.1 The Prefrontal Cortex, Executive Function and ADHD 122 5.7.2 Frontocortical-Striatal Networks and ADHD 126 5.8 The Biochemical Hypothesis of ADHD 130 5.9 Executive Functional Skills, Neurodevelopment and ADHD 132 5.10 Summary of the Pathophysiology of ADHD 135 5.11 Management of ADHD 135 5.11.1 Pharmacotherapy 136 5.11.2 Nonpharmacological Management of ADHD 142 5.12 Summary and Conclusions 144 6 Affective Disorders 1: Depression 147 6.1 Outline 147 6.2 Emotion, Mood and Affective Disorders 148 6.3 Background to Depression 149 6.4 Clinical Features of Major Depressive Disorder 150 6.4.1 Subtypes of Depressive Disorders 150 6.5 Epidemiology 152 6.6 Causes of Depression 153 6.6.1 Genetic Influences 153 6.6.2 Biochemical Hypotheses of Depression 154 6.7 Stress, Learned Helplessness and Depression 163 6.7.1 Stress and MDD 164 6.7.2 What is Stress? 164 6.7.3 Stress and Depression 166 6.7.4 Brain Derived Neurotropic Factor, Neurotropic Effects and Depression 167 6.7.5 Genetics, Stress and Depression 168 6.7.6 Early-Life Stress, Depression and Epigenetics 169 6.7.7 Depression and Inflammation 171 6.7.8 Depression and Glutamate 171 6.7.9 Depression and Physical Diseases 171 6.8 Drug Treatment of Depression 172 6.8.1 Overview 172 6.8.2 Types of Antidepressant Drug 174 6.8.3 Possible Future Drugs for MDD 186 6.9 Nonpharmacological Treatments for Depression 187 6.9.1 Electroconvulsive Therapy 187 6.9.2 Transcranial Magnetic Stimulation 188 6.9.3 Vagus Nerve Stimulation 189 6.9.4 Phototherapy (Light Therapy) 189 6.9.5 Deep Brain Stimulation 190 6.9.6 Cognitive Behavioural Therapy 190 6.9.7 Interpersonal Therapy 191 6.9.8 Behavioural Therapy 192 6.9.9 Mindfulness-Based Cognitive Therapy 192 6.10 Summary 192 7 Affective Disorders 2: Bipolar Disorder 194 7.1 Outline 195 7.2 Background to Bipolar Disorder 195 7.3 Clinical Features of Bipolar Disorder and Diagnostic Criteria 196 7.3.1 Symptoms of Mania 196 7.3.2 Symptoms of Hypomania 197 7.3.3 Symptoms of Depression 197 7.3.4 Categories of Bipolar Disorder 197 7.3.5 Rapid Cycling 197 7.3.6 Mixed Features 197 7.3.7 Cyclothymia 198 7.3.8 Suicide 198 7.3.9 Course of Illness 198 7.4 Epidemiology 198 7.5 Cause of Bipolar Disorder 199 7.5.1 Genetic Factors 199 7.5.2 Environmental Factors 199 7.5.3 Neurobiology of Bipolar Disorder 199 7.6 Management of Bipolar Disorder 201 7.6.1 Pharmacotherapy 201 7.6.2 Drugs Used in the Treatment of Bipolar Disorder 204 7.7 Pregnancy and Bipolar Disorder 208 7.8 Psychological Treatments 208 7.8.1 Psychoeducation 208 7.8.2 Family-Focused Treatment 209 7.8.3 Cognitive Behavioural Therapy 209 7.8.4 Interpersonal and Social Rhythm Therapy 209 7.8.5 Lifestyle Changes 210 7.9 Summary and Conclusions 210 8 Anxiety Disorders 211 8.1 Overview 211 8.2 Background 212 8.3 Anxiety Disorders and Diagnostic Criteria 212 8.3.1 Generalized Anxiety Disorder 212 8.3.2 Social Anxiety Disorder 213 8.3.3 Panic Attack and Panic Disorder 214 8.3.4 Agoraphobia 215 8.3.5 Others Types of Anxiety Disorders 216 8.4 Neurobiology of Anxiety Disorders 216 8.4.1 Fear and the Amygdala 216 8.4.2 Anatomy and Circuitry of the Amygdala 217 8.4.3 Physiological Responses to Fear-Eliciting Stimuli 217 8.4.4 Conditioned Fear Response 220 8.4.5 Conditioned Fear Extinction 223 8.5 Worry 224 8.6 Are there Other Anxiety Circuits? 225 8.7 Neurotransmitters and Anxiety Disorders 225 8.8 Management of Anxiety Disorders 226 8.8.1 Pharmacotherapy 226 8.8.2 Psychosocial Therapies 232 8.9 Summary and Outcomes 234 9 Sleep and Sleep Disorders 236 9.1 Overview 236 9.2 Introduction 237 9.3 Physiology of Sleep 238 9.3.1 Stages of Sleep 238 9.3.2 The Ascending Reticular Activating System 240 9.3.3 Slow Wave Sleep Mechanisms 242 9.3.4 Rapid Eye Movement Sleep Mechanisms 245 9.4 Sleep Disorders 246 9.4.1 Insomnia 246 9.4.2 Hypersomnia or Hypersomnolence 254 9.5 Summary and Conclusions 257 10 Schizophrenia 259 10.1 Overview 259 10.2 Background 260 10.3 Clinical Features of Schizophrenia 264 10.3.1 Phases of Schizophrenia 264 10.3.2 Diagnostic Criteria for Schizophrenia 265 10.3.3 Violence, Self-Harm and Suicide 265 10.3.4 General Physical Health and Mortality 266 10.4 Epidemiology 266 10.5 Pathology 266 10.6 Aetiology 267 10.6.1 Genetics of Schizophrenia 267 10.6.2 Environmental Risk Factors 268 10.7 Developmental Hypothesis of Schizophrenia 270 10.8 Biochemical Hypotheses 270 10.8.1 Dopamine and the Dopamine Hypothesis of Schizophrenia 270 10.8.2 The Mesolimbic System and Schizophrenia 273 10.8.3 The Mesocortical System and Schizophrenia 273 10.8.4 Glutamate, GABA and Dopamine: A Revised Hypothesis of Schizophrenia 274 10.9 Management of Schizophrenia 277 10.9.1 Pharmacotherapy 277 10.9.2 Nonpharmacological Management of Schizophrenia 288 10.10 Summary and Conclusions 288 11 Drug Abuse and Addiction 290 11.1 Outline 290 11.2 Background 291 11.3 Neurobiology of Substance Abuse and Addiction 293 11.3.1 The Mesolimbic Reward Systems and Addictive Drugs 293 11.3.2 Extensions of the Hypothesis 298 11.3.3 Transition from Hedonic Actions to Habits to Compulsions 300 11.3.4 Summary 301 11.4 Risk Factors 301 11.4.1 Environmental Factors 301 11.4.2 Genetic Factors 302 11.5 Management of Addiction 302 11.5.1 Alcohol 306 11.5.2 Heroin 307 11.6 Summary 308 References 310 Index 327

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Book SynopsisA global perspective on the management and prevention of emerging and re-emerging diseases Emerging infectious diseases are newly identified or otherwise previously unknown infections that cause public health challenges. Re-emerging infectious diseases are due to both the reappearance of and an increase in the number of infections from a disease that is known, but which had formerly caused so few infections that it was no longer considered a public health problem. The factors that cause the emergence or re-emergence of a disease are diverse. This book takes a look at the world''s emerging and re-emerging diseases. It covers the diagnosis, therapy, prevention, and control of a variety of individual diseases, and examines the social and behavioral issues that could contribute to epidemics. Each chapter focuses on an individual disease and provides scientific background and social history as well as the current basics of infection, epidemiology, and control. Table of ContentsPreface xv Acknowledgments xvii Chapter 1 Prologue 3 Introduction 3 Causative Factors 7 Salient Features 11 Emerging Epidemics 11 Re-Emerging Epidemics 17 Antimicrobial Resistance 18 Public Health Implications 20 References 22 Chapter 2 Epidemics Fundamentals 24 Introduction 24 Definitions 24 Types of Epidemics 26 Epidemiological Triad 29 Forecasting an Epidemic 31 Contingency Plan 33 Investigation of Epidemics 35 Management of Epidemics 38 Control of Epidemics 39 Principles of Planning Emergency Services 41 References 44 Chapter 3 Disasters and Epidemics 46 Fundamentals 46 Contributory Factors 51 Investigation of Rumors 52 References 54 Chapter 4 Biosafety 56 Introduction 56 Components 57 Hand Washing 61 Preventing Needlestick Injuries 62 Safe Transport of Biological Material 64 Safe Decontamination of Spills 65 Safe Handling of Dead Bodies 67 Personal Protective Equipment 69 Management of Biomedical Waste 69 Infection Control Check List 71 Biosafety Levels 71 Accreditation of Hospitals and Laboratories 74 References 75 Chapter 5 Tuberculosis 76 History 76 Magnitude 78 Agent Factors 81 Host Factors and High-Risk Groups 88 Environmental Factors 89 Modes of Transmission 90 Pathology and Immunology 91 Clinical Manifestations 96 Diagnosis of Tuberculosis 101 Directly Observed Treatment, Short Course (DOTS) 119 Tuberculosis and HIV 135 Drug-Resistant Tuberculosis 140 Prevention and Control 142 Social and Cultural Factors 145 References 148 Chapter 6 Plague 154 History of Plague 154 Magnitude 155 Agent Factors 157 Host Factors 158 Environmental Factors 159 Reservoir 159 Mode of Transmission 160 Clinical Manifestations 161 Laboratory Diagnosis 164 Differential Diagnosis 170 Clinical Management 170 Prevention and Control 172 References 174 Chapter 7 Leptospirosis 176 Introduction 176 Magnitude 176 Agent Factors 177 Host Factors 179 Environmental Factors 182 Mode of Transmission 183 Pathology and Immunology 183 Clinical Manifestations 185 Laboratory Diagnosis 189 Clinical Management 206 Surveillance 210 Investigation of an Outbreak 211 Prevention and Control 213 References 217 Chapter 8 Dengue 220 Introduction 220 Magnitude 221 Agent Factors 222 Host Factors 228 Environmental Factors 230 Vector Biology 231 Clinical Features 235 Laboratory Diagnosis 244 Immune Response to Dengue Virus 245 Clinical Management 248 Investigation of Outbreaks 253 Prevention and Control 257 References 259 Chapter 9 Japanese Encephalitis 263 History 263 Magnitude of the Problem 264 Epidemiology 266 Vector Biology 270 Clinical Features 270 Differential Diagnosis 271 Laboratory Diagnosis 272 Case Management 275 Prevention and Control 278 References 280 Chapter 10 Chikungunya Fever 283 Introduction 283 Epidemiology 284 The Chikungunya Virus 284 Clinical Features 291 Laboratory Diagnosis 298 Differential Diagnosis 300 Clinical Management 301 Investigation of Outbreaks 306 Treatment 307 Prevention and Control 308 References 311 Chapter 11 West Nile Fever 316 Epidemiology 316 Global Scenario 317 The Etiological Agent 318 Clinical Features 322 Laboratory Diagnosis 324 Clinical Management 326 Investigation of Outbreaks 327 Prevention and Control 330 References 336 Chapter 12 Chandipura Virus Encephalitis 340 Epidemiology 340 The Chandipura Virus 341 Clinical Features 350 Laboratory Diagnosis 351 Differential Diagnosis 353 Clinical Management 354 Investigation of Outbreaks 356 Prevention and Control 358 References 359 Chapter 13 Kyasanur Forest Disease 361 Introduction 361 Epidemiology 362 Vector Biology 363 Clinical Features 366 Differential Diagnosis 366 Laboratory Diagnosis 368 Case Management 369 Prevention and Control 371 References 374 Chapter 14 Hantavirus Disease 375 Introduction 375 Epidemiology and Global Scenario 376 The Etiological Agent 381 Clinical Features 387 Differential Diagnosis 390 Laboratory Diagnosis 390 Case Management 393 Prevention and Control 394 References 396 Chapter 15 Influenza 400 Historical Aspects 400 Global Scenario 402 Agent Factors 405 Host Factors 418 Environmental Factors 419 Mode of Transmission 421 Clinical Manifestations 422 Immune Response to Influenza 424 Laboratory Diagnosis 427 Clinical Management 431 Surveillance 434 Investigation of an Outbreak 437 Prevention and Control 441 Avian Influenza 445 Swine Influenza 447 References 450 Chapter 16 Severe Acute Respiratory Syndrome 455 Introduction 455 Epidemiology 455 Causative Agent 456 Transmission of Severe Acute Respiratory Syndrome Virus 456 Clinical Features 457 Laboratory Diagnosis 457 Treatment 458 Prevention and Control 461 References 461 Chapter 17 Nipah Virus 462 Introduction 462 Epidemiology 463 Etiological Agent 463 Transmission 463 Clinical Features 466 Laboratory Diagnosis 467 Prevention and Control 468 References 469 Chapter 18 Paragonimiasis 470 Magnitude of the Problem 470 The Parasite: Paragonimus 471 Epidemiology 475 Clinical Manifestations 478 Radiological Features of Paragonimiasis 481 Laboratory Diagnosis 484 Differential Diagnosis 487 Clinical Management 487 Public Health Importance 488 References 489 Chapter 19 Melioidosis 492 Introduction 492 Epidemiology 493 The Etiological Agent: Burkholderia pseudomallei 495 Clinical Manifestations 498 Laboratory Diagnosis 501 Clinical Management 503 Investigation of an Outbreak 504 Prevention and Control of Melioidosis 506 Public Health Importance 508 References 508 Chapter 20 Biowarfare and Bioterrorism 513 Introduction 513 Historical Aspects 514 Potential Agents 519 Epidemiological Clues 545 Laboratory Diagnosis 548 Clinical Management 566 Biosurveillance 568 Investigation of an Outbreak 573 Preparedness and Containment 576 References 578 Chapter 21 Antimicrobial Resistance 585 Introduction 585 Global Scenario 586 Drug-Resistant Organisms 588 Causes of Drug Resistance 593 Mechanisms of Drug Resistance 595 Host Factors 598 Health-Related and Economic Hazards 599 Laboratory Diagnosis 601 Managing Antimicrobial Resistance 607 Prevention and Control 610 References 612 Chapter 22 Conventional Methods for Mosquito Control 615 Mosquito: Habits and Attractants 615 Environmental Management 618 Antilarval Measures 623 Chemical Adulticides 627 Repellents 630 Insecticide-Impregnated Bed Nets and Screens 632 References 633 Chapter 23 New and Potential Techniques: Mosquito Control 635 Myco-Insecticides 635 Entomopathogenic Bacteria and Viruses 637 Hormonomimetic and Plant-Derived Substances 639 Larvivorous Fish and Crustaceans 640 Dragonfly Nymphs 643 Protozoa 643 Mermithid Nematodes 644 Predator Larvae 645 Genetic Engineering 646 References 648 Chapter 24 Other Disease Vectors and Their Control 651 Housefly 651 Sand Fly 653 Deer Fly 653 Black Fly 655 Tsetse Fly 655 Water Flea (Cyclops) 656 Sand Flea (Jigger or Chigoe Flea) 657 Rat Flea 658 Reduviid Bug 658 Ticks (Hard and Soft) 659 Lice 662 Cockroach 663 Mites (Chiggers) 664 General Principles of Vector Control 666 Integrated Vector Management 667 Rodents 670 Methods for Rodent Control 671 References 672 Glossary 674 Index 683

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Book SynopsisMetabolic Syndrome and Neurological Disorders compiles data and analyses of the cluster of common pathologies to generate a complete, updated guide to the link between metabolic syndrome and neurological disorders.Table of ContentsForeword Mark P. Mattson xi Preface Tahira Farooqui and Akhlaq A. Farooqui xiii Acknowledgments Tahira Farooqui and Akhlaq A. Farooqui xv Contributors xvii 1 Insulin Resistance and Metabolic Failure Underlie Alzheimer Disease 1 Suzanne M. de la Monte and Ming Tong 2 Insulin Receptor and the Pathophysiology of Alzheimer Disease 31 Johanna Zemva and Markus Schubert 3 Contribution of Insulin Resistance in Pathogenesis of Alzheimer Disease 51 Adnan Erol 4 Insulin–Leptin Signaling in the Brain 75 Vicente Barrios, Emma Burgos-Ramos, and Jes´us Argente 5 The Janus Face of Insulin in Brain 85 Ana Duarte, Emanuel Candeias, S´onia C. Correia, Renato X. Santos, Cristina Carvalho, Susana Cardoso, Ana I. Pl´acido, Maria S. Santos, Catarina R. Oliveira, and Paula I. Moreira 6 Modulation of Cognition by Insulin and Aging: Implications for Alzheimer Disease 115 Maite Solas and Maria J. Ram´ýrez 7 Contribution of Phospholipid, Sphingolipids, and Cholesterol-Derived Lipid Mediators in the Pathogenesis of Metabolic Syndrome and Neurological Disorders 137 Akhlaq A. Farooqui and Tahira Farooqui 8 Lipids, Cholesterol, and Oxidized Cholesterol in Alzheimer Amyloid Beta-Mediated Neurotoxicity 163 Mun’delanji C. Vestergaard, Masamune Morita, Tsutomu Hamada, and Masahiro Takagi 9 Of Sound Mind and Body: Dietary Lifestyles, Promotion of Healthy Brain Aging, and Prevention of Dementia in Healthy Individuals 179 Giulio Maria Pasinetti, Amanda Bilski, Lap Ho, Jun Wang, Mario Ferruzzi, Masahito Yamada, Kenjiro Ono, and Salvatore Mannino 10 Metabolic Syndrome as an Independent Risk Factor of Silent Brain Infarction 191 Jae-Sung Lim and Hyung-Min Kwon 11 Neurochemical Linkage Among Metabolic Syndrome, Alzheimer Disease, and Depression 197 Undurti N. Das 12 Alterations in the Endocannabinoid System as a Link Between Unbalanced Energy Homeostasis, Neuroinflammation, and Neurological and Neuropsychiatric Disorders 219 Tiziana Bisogno and Vincenzo Di Marzo 13 Metabolic Syndrome, Alzheimer Disease, Schizophrenia, and Depression: Role for Leptin, Melatonin, Kynurenine Pathways, and Neuropeptides 235 George Anderson and Michael Maes 14 Binge Eating and Metabolic Syndrome 249 Ignacio J´auregui-Lobera 15 Phytochemical Principles in the Traditional Indian System of Medicine Used for the Management of Metabolic Syndrome 261 Syed Ibrahim Rizvi and Neetu Mishra 16 Oxidative Stress and Obesity: Their Impact on Metabolic Syndrome 275 Morihiro Matsuda and Iichiro Shimomura 17 The Relationship Among Obesity, Inflammation, and Insulin Resistance 283 Jean-Philippe Bastard and Bruno F`eve 18 Involvement of Adipocytokines in Pathogenesis of Insulin Resistance, Obesity, and Metabolic Syndrome 297 Hardik Gandhi and Ramachandran Balaraman 19 Obesity, Inflammation, and Vascular Disease: Novel Insight in the Role of Adipose Tissue 311 Paolo Calabro, Enrica Golia, Valeria Maddaloni, Giuseppe Limongelli, Brunella Ziello, Fabio Fimiani, Ilaria Jane Romano, Mario Crisci, Maria Giovanna Russo, Edward T.H. Yeh, and Raffaele Calabro 20 Is Diabetes a Risk Factor for Parkinson Disease? 327 Akhlaq A. Farooqui and Tahira Farooqui 21 Role of Iron in the Pathogenesis of Diabetes and Metabolic Syndrome 335 Lu Cai 22 Contributions of AMP Kinase to the Pathogenesis of Type 2 Diabetes and Neurodegenerative Diseases 363 Mohamed Kodiha, Hicham Mahboubi, and Ursula Stochaj 23 A_ Deposition, Insulin Signaling, and Tau Phosphorylation in Animal Models of Alzheimer Disease and Diabetes 383 Naoyuki Sato and Ryuichi Morishita 24 In Vivo Evidence of the Convergence of Type 2 Diabetes and Alzheimer Disease 395 Sun Ah Park 25 Metabolic Syndrome and its Impact on Cardiovascular Disease 409 John A. Larry 26 Contribution of Inflammation, Adiponectin, and Obesity in Cardiovascular Diseases 423 Harald Mangge and Gunter Almer 27 Brain and Cardiovascular Diseases: Molecular Aspects 439 Ewa Szczepanska-Sadowska 28 Molecular Aspects of Dietary–Exercise Regimen for the Prevention of Metabolic Syndrome 461 Wataru Aoi 29 Ghrelin, Lipid Metabolism, and Metabolic Syndrome 475 Pablo B. Mart´ýnez de Morentin, Sulay Tovar, Rub´en Nogueiras, Miguel L´opez, and Carlos Di´eguez 30 Leptin and Cognitive Function 485 Jenni Harvey 31 Fructose, Sugar Consumption, and Metabolic Diseases 501 Virgile Lecoultre and Luc Tappy 32 Inflammation-Mediated Cognitive and Emotional Alterations in Experimental Models of Metabolic Syndrome 515 Nathalie Castanon and Sophie Lay´e 33 Summary and Perspective 529 Tahira Farooqui and Akhlaq A. Farooqui Index 539 Color plate section is located between pages 196 and 197.

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Book SynopsisWritten by a team of leading international specialists, this book comprehensively covers current knowledge of the chemical ecology of insect parasitoids. Chapters are organized in order to present the most significant discoveries of the last few decades, and on their potential application in pest control strategies.Trade Review“This volume will contribute to future syntheses and help integrate insect parasitoids within chemical and community ecology and, hopefully, eventual strategic applications in pest management programs. Summing Up: Recommended. Graduate students, researchers/faculty, and professionals.” (Choice, 1 January 2014) Table of ContentsContributors xi 1 Chemical ecology of insect parasitoids: towards a new era 1 Stefano Colazza and Eric Wajnberg Abstract 1 1.1 Introduction 1 1.2 Integrating behavioural ecology and chemical ecology in insect parasitoids 3 1.3 The use of chemical ecology to improve the efficacy of insect parasitoids in biological control programmes 4 1.4 Overview 5 1.5 Conclusions 6 Acknowledgements 6 References 7 Part 1 Basic concepts 9 2 Plant defences and parasitoid chemical ecology 11 Paul J. Ode Abstract 11 2.1 Introduction 12 2.2 Plant defences against a diversity of attackers 13 2.2.1 Plant defence signalling pathways 13 2.2.2 Plant volatiles and parasitoids 16 2.2.3 Plant toxins and parasitoids 18 2.2.4 Cross-talk between plant defence pathways 21 2.3 Above-ground–below-ground interactions and parasitoids 24 2.4 Climate change and parasitoid chemical ecology 25 2.5 Conclusions 28 Acknowledgements 28 References 28 3 Foraging strategies of parasitoids in complex chemical environments 37 Nicole Wäschke, Torsten Meiners and Michael Rostás Abstract 37 3.1 Introduction 37 3.2 Chemical complexity 40 3.2.1 Plant species diversity and habitat location 40 3.2.2 Variability in host plant traits and their effects on parasitoid host location 42 3.3 Foraging strategies of parasitoids in chemically complex environments 48 3.3.1 Behavioural responses to chemical complexity 48 3.3.2 Learning, sensory fi lters and neural constraints affecting strategies for dealing with complexity 50 3.3.3 Infl uences of life history traits on foraging strategy 51 3.4 Conclusions 53 References 54 4 Chemical ecology of insect parasitoids in a multitrophic above- and below-ground context 64 Roxina Soler, T. Martijn Bezemer and Jeffrey A. Harvey Abstract 64 4.1 Introduction 65 4.2 Influence of root feeders on above-ground insect herbivores 67 4.3 Influence of soil-borne symbionts on above-ground insect herbivores 69 4.4 Plant-mediated effects of root feeders and soil-borne symbionts on growth and development of parasitoids 70 4.5 Effects of root-feeding insects on HIPVs and host location of parasitoids 74 4.6 Expanding an above–below-ground bitrophic reductionist perspective 76 Acknowledgement 79 References 79 5 A hitch-hiker’s guide to parasitism: the chemical ecology of phoretic insect parasitoids 86 Martinus E. Huigens and Nina E. Fatouros Abstract 86 5.1 Phoresy 87 5.2 Prevalence of phoretic parasitoids 87 5.3 Important parasitoid and host traits 90 5.3.1 Parasitoid traits 90 5.3.2 Host traits 92 5.4 Chemical espionage on host pheromones 93 5.4.1 Espionage on male aggregation pheromone 93 5.4.2 Espionage on sex pheromones 98 5.4.3 Espionage on anti-sex pheromones 99 5.5 Coevolution between phoretic spies and hosts 100 5.6 Biological control 103 5.7 Future perspectives 103 Acknowledgements 104 References 105 6 Novel insights into pheromone-mediated communication in parasitic hymenopterans 112 Joachim Ruther Abstract 112 6.1 Introduction 113 6.2 Pheromones and sexual behaviour 119 6.2.1 Volatile sex attractants 119 6.2.2 Female-derived courtship pheromones 124 6.2.3 Male-derived courtship pheromones 127 6.3 Other pheromones 128 6.3.1 Marking pheromones 128 6.3.2 Putative alarm and appeasement pheromones 129 6.3.3 Aggregation pheromones 130 6.3.4 Anti-aggregation pheromones 130 6.4 Variability in pheromone-mediated sexual behaviour 131 6.4.1 Innate plasticity of pheromone behaviour 131 6.4.2 Learnt plasticity of pheromone behaviour 131 6.4.3 Plasticity of pheromone behaviour caused by abiotic factors 132 6.5 Pheromone biosynthesis 132 6.6 Evolution of parasitoid sex pheromones 133 6.7 Conclusions and outlook 135 References 136 7 Chemical ecology of tachinid parasitoids 145 Satoshi Nakamura, Ryoko T. Ichiki and Yooichi Kainoh Abstract 145 7.1 Introduction 146 7.2 Long-range orientation 155 7.2.1 Long-range orientation by direct type parasitoids 155 7.2.2 Long-range orientation by indirect type parasitoids 157 7.2.3 Host pheromones used by direct type parasitoids 158 7.3 Short-range orientation 159 7.3.1 Short-range orientation by direct type parasitoids 159 7.3.2 Short-range orientation by indirect type parasitoids 161 7.4 Conclusions 163 Acknowledgements 163 References 164 8 Climate change and its effects on the chemical ecology of insect parasitoids 168 Jarmo K. Holopainen, Sari J. Himanen and Guy M. Poppy Abstract 168 8.1 On climate change and chemical ecology 169 8.2 Direct climate change impacts on parasitoids 171 8.3 Climate change and bottom-up impacts on parasitoids: herbivore host and plant host quality 172 8.4 Impacts of climate change-related abiotic stresses on parasitoid ecology and behaviour 175 8.4.1 Impacts of elevated temperature 175 8.4.2 Precipitation and drought 176 8.4.3 Gaseous reactive air pollutants 177 8.4.4 Atmospheric CO2 concentration 179 8.4.5 Parasitoid response to combined abiotic stresses 180 8.5 Climate change impacts on biological control 181 8.6 Ecosystem services provided by parasitoids: impact of changing climate 182 8.7 Future research directions and conclusions 184 References 185 Part 2 Applied concepts 191 9 Chemical ecology of insect parasitoids: essential elements for developing effective biological control programmes 193 Torsten Meiners and Ezio Peri Abstract 193 9.1 Introduction 194 9.2 Essential elements in parasitoid chemical ecology 196 9.3 Manipulation of the population levels of natural enemies by semiochemicals 201 9.4 Limits and perspectives of behavioural manipulation of parasitoids by applying semiochemicals 204 9.5 Cautionary example: interspecifi c competitive interactions in parasitoids 210 9.6 Conclusions 212 References 213 10 The application of chemical cues in arthropod pest management for arable crops 225 Maria Carolina Blassioli-Moraes, Miguel Borges and Raul Alberto Laumann Abstract 225 10.1 Arable crops: characteristics of the systems and trophic interactions mediated by chemical cues 226 10.2 Methodologies for using chemical cues to attract and retain parasitoids in arable crops 227 10.2.1 Direct application of semiochemicals 228 10.2.2 Environmental manipulation 236 10.3 Final considerations 237 Acknowledgements 239 References 239 11 Application of chemical cues in arthropod pest management for orchards and vineyards 245 Stefano Colazza, Ezio Peri and Antonino Cusumano Abstract 245 11.1 Introduction 246 11.2 Pheromone-based tactics in orchards and vineyards 247 11.2.1 Host sex pheromones 247 11.2.2 Parasitoid pheromones 248 11.3 Allelochemical-based manipulation in orchards and vineyards 249 11.3.1 Herbivore-induced plant volatiles (HIPVs) 249 11.3.2 Host-associated volatiles (HAVs) 257 11.4 Conclusions 260 Acknowledgement 261 References 261 12 Application of chemical cues in arthropod pest management for organic crops 266 Marja Simpson, Donna M.Y. Read and Geoff M. Gurr Abstract 266 12.1 Introduction: organic farming and compatibility of chemical cues 267 12.2 Overview of plant defences involving plant volatiles 268 12.3 The use of synthetic HIPVs in pest management 269 12.4 Arthropod pest management strategies used in organic farming 273 12.5 Potential for extending chemical cue use in organic systems 275 12.6 Conclusions 277 References 277 13 Application of chemical cues in arthropod pest management for forest trees 282 Timothy D. Paine Abstract 282 13.1 Forest insect herbivores and natural enemy host/prey finding 283 13.2 Introduction to forest systems 285 13.3 Examples from North America 287 13.3.1 Native bark beetles in plantation and unmanaged forests 287 13.3.2 Introduced defoliator in urban and unmanaged forests 288 13.3.3 Introduced wood borer in plantation and urban environments 289 13.4 Conclusions 290 References 291 Index 296

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Book SynopsisStem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem cells in drug discovery and therapeutic applications in spinal cord injury, brain damage, neurological and autoimmune disorders, among others. Written by a leader in the field, Stem Cells: A Short Course appeals to both students and instructors alike, appealing to academic enthusiasm for stem cell research and applications.Table of ContentsPreface to the Professor xvii Preface to the Student xxi Acknowledgments xxiii List of Figures xxv List of Tables xxxvii List of Case Studies xxxix List of Focus Boxes xli 1 A HISTORY OF STEM CELL RESEARCH 1 Early Studies 1 Hematopoietic Stem Cell Discovery 4 Mouse Embryonic Stem Cell Discovery 6 Successful Neural Stem Cell Culture 7 The Discovery of Cancer Stem Cells 8 Human Embryonic Stem Cell Discovery 9 Stem Cells And Cloning 11 Cord Blood Embryonic]Like Stem Cells—An Alternative to Es and Adult Stem Cells 14 Breakthrough In Spinal Cord Injury Repair 15 The Generation of ips Cells 16 iPS Cells Derived from Keratinocytes 20 iPS Induction Without the Use of Viruses 20 Transposon]Mediated iPS 21 Protein]Based iPS 22 The Discovery of Human Amniotic Stem Cells 24 Human Embryonic Stem Cells Generated Without Embryo Destruction 25 Human Cloning 25 Mesenchymal Stem Cell]Derived Human Knee Cartilage 27 The First Clinical Trial Using Human Embryonic Stem Cells 28 Mitochondrial DNA: A Barrier To Autologous Cell Therapeutics 29 Induced Pluripotency And The Potential To Save Endangered Species 30 Chapter Summary 33 Key Terms 37 Review Questions 39 Thought Question 40 Suggested Readings 40 2 FUNDAMENTALS OF STEM CELLS 43 Basic in Vitro Cell Culture—A Historical Perspective 43 Stem Cell Culture—Optimal Conditions and Techniques 48 Embryonic Stem Cell Culture 49 Hematopoietic Stem Cell Culture 52 Notch Regulation of HSC Proliferation 52 Other Drivers of HSC Proliferation 53 Adipose]Derived Stem Cell Culture 54 The Study of Embryonic Development 56 Embryonic Development and the Origin of Stem Cells 56 Early Events in Embryogenesis 56 Germ Cell Development 61 Basic Properties of Stem Cells 63 Long]Term Self]Renewal 63 Different Potency Capabilities 63 Totipotency 64 Pluripotency 65 Multipotency 68 Oligopotency 68 Unipotency 69 Types of Stem Cells 70 Embryonic Stem Cells 70 Fetal Stem Cells 70 Amniotic Stem Cells 71 Adult Stem Cells 71 Induced Pluripotency (iPS) Cells 71 Cancer Stem Cells 71 The Potential of Stem Cells in Medicine and Medical Research 71 Therapeutics 71 Tissue Engineering 71 Cell Therapy 73 Cell]Based Drug Screening 75 Chapter Summary 77 Key Terms 80 Review Questions 83 Thought Question 84 Suggested Readings 85 3 EMBRYONIC STEM, FETAL, AND AMNIOTIC STEM CELLS 87 ES Cells 87 Basic Properties 87 Pluripotency 87 Indefinite Replicative Capacity 89 Signaling and Transcriptional Control of ES Cell Replication 90 Examples of ES Cells 92 Mouse ES Cells 92 Rat ES Cells 95 Nonhuman Primate ES Cells 97 Human ES Cells 100 EC Cells 103 Embryonal Germ Cells 105 EG Cell Growth Factor Signaling 105 Comparing Embryonically Derived Cells 106 Fetal Stem Cells 108 Basic Properties 108 Amniotic Fluid Stem Cells 108 Wharton’s Jelly Stem Cells 109 Amniotic Membrane Stem Cells 110 Placental Stem Cells 110 Chapter Summary 112 Key Terms 114 Review Questions 115 Thought Question 116 Suggested Reading 116 4 ADULT STEM CELLS 118 Discovery and Origin of ASCs 118 Basic Properties of ASCs 118 Self]Renewal 119 Multipotency 119 Examples of ASCs 120 Hematopoietic Stem Cells 122 Morphology and Marker Expression 123 Sources 123 Signaling and Multipotency 123 Muscle]Derived Stem Cells 127 Myosatellite Cell Morphology and Marker Expression 129 Sources 129 Signaling, Transcriptional Control, and Multipotency 129 Adipose]Derived Stem Cells 130 Morphology and Marker Expression 130 Sources 131 Signaling and Multipotency 132 Mesenchymal Stem Cells 134 Morphology and Marker Expression 134 Sources 136 Signaling and Multipotency 136 Neural Stem Cells 140 Morphology and Marker Expression 141 Sources and Origins 143 Signaling and Multipotency 146 Endothelial Stem Cells 150 Morphology and Marker Expression 150 Sources and Origins 152 Signaling and Multipotency 153 Chapter Summary 156 Key Terms 158 Review Questions 161 Thought Question 162 Suggested Readings 162 5 NUCLEAR REPROGRAMMING 164 Examples of Nuclear Reprogramming in Nature 166 Cell Fusion 166 Cell Fusion for the Generation of Hybridomas 169 Mechanisms of Cell Fusion 172 Comparison of Cell Fusion Techniques 173 Electrofusion 173 Pegylation 173 Viral Induction 173 Mechanism of Nuclear Reprogramming in Cell Fusion 175 Somatic Cell Nuclear Transfer 176 Method for the Production of SCNT]Derived Cells 177 Somatic Cell Nuclear Transfer for the Creation of Stem Cells 178 Basic Properties of SCNT]Derived Stem Cells 180 Examples of SCNT]Derived Stem Cells 181 A Note Regarding Genomic Abnormalities in SCNT]Derived Clones 182 Telomeric Length 182 DNA Methylation and Epigenetics 183 X]Chromosome Inactivation 185 Induced Pluripotency 185 Breakthrough in the Production of iPS Cells 187 Methods for the Production of iPS Cells 191 Retroviral and Lentiviral Gene Delivery 192 Adenoviral Gene Delivery 195 Sendai Viral Gene Delivery 196 Plasmid]Based Gene Delivery 196 mRNA Delivery 198 MicroRNA Induction 199 Transposon Delivery 200 Direct Protein Delivery 200 Basic Properties of iPS Cells 201 A General Comparison of iPS Cells and Embryonic Stem Cells 203 Examples of Derived iPS Cells 205 Mouse Embryonic Fibroblast]Derived iPS Cells 206 Human Adult Skin]Derived iPS Cells 209 Advantages of ips Cells Over Other Cell Types 210 Origin and Bioethics 211 Patient Specificity 211 Broad Lineage Differentiation Potential 211 “Unlimited” Supply 211 Ease of Generation 212 Chapter Summary 212 Key Terms 214 Review Questions 217 Thought Question 218 Suggested Readings 218 6 CANCER STEM CELLS 220 Background on The Origins of Cancer 220 Discovery and Origin of Cancer Stem Cells 221 Basic Properties of Cancer Stem Cells 225 A Comparison of Cancer Stem Cells and Normal Stem Cells 226 Signaling Pathways Involved in Cancer Stem Cell Transformation 228 Examples of Cancer Stem Cells 229 Breast 229 Central Nervous System 229 Colon 231 Ovary 233 Pancreas 233 Prostate 234 Melanoma 235 Multiple Myeloma 237 Strategies for Treatment Targeting Cancer Stem Cells 238 Melanoma Treatment Targeting Chimeric Antigen Receptor 238 Multiple Myeloma Treatment Targeting CD20 239 Chapter Summary 240 Key Terms 241 Review Questions 243 Thought Question 244 Suggested Readings 244 7 STEM CELLS AS DRUG DISCOVERY PLATFORMS 245 Embryonic Stem Cells and Mouse Models of Gene Function 245 Stem Cell]Based Screening Assays 250 Stem Cells as Lineage Resources for HTS 250 Embryonic Stem Cells as a Resource 251 Adult Stem Cells as a Resource 253 iPS Cells as a Resource 254 Cancer Stem Cell Screens 256 Reprogramming Screens 258 Analysis of Disease Pathways 261 Stem Cells As A Toxicity]Testing Platform 267 Stem Cells as a Resource for Developmental Toxicity Testing 267 Stem Cells as a Source for Post]Natal Environmental Toxicity Testing 268 Cardiotoxicity 269 Hepatotoxicity 272 Chapter Summary 273 Key Terms 274 Review Questions 276 Thought Question 277 Suggested Readings 277 8 THERAPEUTIC APPLICATIONS OF STEM CELLS 279 History of Stem Cells as Therapeutics 279 History of Tissue Engineering 279 Disease]Specific Treatment and Patient Trials 282 Stem Cell]Based Patient Trials: An Overview 282 Cardiomyopathy and Cardiovascular Disease (CV) 284 Neuropathies and Neurodegenerative Diseases 286 Spinal Cord Injury 286 Brain Damage 288 Parkinson’s Disease 292 Autoimmune Disorders 292 Corneal Defects 296 Hematopoietic Disorders 297 Sickle Cell Disease 297 Wiskott–Aldrich Syndrome 299 Cancer 300 Muscular Dystrophy 301 Liver Disorders 303 Veterinary Applications 306 Equine 307 Canine 309 Osteoarthritis (OA) 309 Myocardial Infarction 311 Spinal Cord Injury 313 Stem Cells as an Emerging Industry 314 Seminal Discoveries Driving the Growth of a New Industry 317 Regulation and Reimbursement of Stem Cell Commercialization 320 A Word about Induced Pluripotency and Commercialization 320 Chapter Summary 321 Key Terms 324 Review Questions 326 Thought Question 327 Suggested Readings 328 About the Author 330 Index 331

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Book SynopsisWnt signaling in Development and Disease: Molecular Mechanisms and Biological Functions reviews the core topics in Wnt signaling, from molecular pathway mechanisms to its role in embryogenesis, adult tissue homeostasis, and chronic disease. Written by a team of expert reviewers, the book provides clear and concise coverage of the core foundations of Wnt signaling before advancing to discussion of cutting-edge scientific research. Focused on the biological insights and current scientific questions of Wnt signaling, this book will be a comprehensive and definitive resource for a wide range of researchers and students in cell signaling, cell physiology, developmental biology, and biomedical engineering, as well as anyone interested in learning more about this important and complex protein network. A definitive source of information on Wnt signaling and its role in development and disease, written by leaders in the field. Explores the role of Wnt signalingTable of ContentsContributors vii Preface xi Part 1 Molecular Signaling Mechanisms: From Pathways to Networks 1 1 Wnt Signal Production, Secretion, and Diffusion 3 Madelon M. Maurice and Hendrik C. Korswagen 2 Wnt Signaling at the Membrane 15 Gary Davidson and Christof Niehrs 3 Wnt Signal Transduction in the Cytoplasm: an Introduction to the Destruction Complex 33 Tony W. Chen, Heather A. Wallace, Yashi Ahmed, and Ethan Lee 4 An Overview of Gene Regulation by Wnt/β-Catenin Signaling 51 Chen U. Zhang and Ken M. Cadigan 5 Finding a Needle in a Genomic Haystack: Genome-Wide Approaches to Identify Wnt/TCF Transcriptional Targets 73 Chandan Bhambhani and Ken M. Cadigan 6 Introduction to β-Catenin-Independent Wnt Signaling Pathways 89 Susanne Kühl and Michael Kühl 7 Molecular Mechanisms of Wnt Pathway Specificity 101 Alexandra Schambony, Guido J.R. Zaman, and Folkert Verkaar 8 Modulation of Wnt Signaling by Endocytosis of Receptor Complexes 113 Akira Kikuchi, Shinji Matsumoto, Katsumi Fumoto, and Akira Sato 9 New Insights from Proteomic Analysis of Wnt Signaling 125 Matthew P. Walker, Dennis Goldfarb, and Michael B. Major 10 New Insights about Wnt/β-Catenin Pathway Mechanisms from Global siRNA Screens 137 Tenzin Gocha and Ramanuj DasGupta 11 Mathematical Models of Wnt Signaling Pathways 153 Michael Kühl, Barbara Kracher, Alexander Groß, and Hans A. Kestler 12 The Wnt’s Tale: On the Evolution of a Signaling Pathway 161 Jenifer C. Croce and Thomas W. Holstein Part 2 Selected Key Molecules in Wnt Signaling 177 13 Secreted Wnt Inhibitors or Modulators 179 Paola Bovolenta, Anne-Kathrin Gorny, Pilar Esteve, and Herbert Steinbeisser 14 Frizzleds as G Protein-Coupled Receptors 195 Gunnar Schulte 15 Dishevelled at the Crossroads of Pathways 207 Vítìzslav Bryja and Ondøej Bernatík 16 β-Catenin: a Key Player in Both Cell Adhesion and Wnt Signaling 217 Jonathan Pettitt 17 Evolutionary Diversification of Vertebrate TCF/LEF Structure, Function, and Regulation 225 Stefan Hoppler and Marian L. Waterman 18 Insights from Structural Analysis of Protein–Protein Interactions by Wnt Pathway Components and Functional Multiprotein Complex Formation 239 Zhihong Cheng and Wenqing Xu Part 3 Wnt Signaling in Embryonic Development and Adult Tissue Homeostasis 251 19 Wnt Signaling in Early Vertebrate Development: From Fertilization to Gastrulation 253 Eliza Zylkiewicz, Sergei Y. Sokol, and Stefan Hoppler 20 Wnt/β-Catenin Signaling in Embryonic Stem Cells: Insights into Early Mammalian Development 267 Kathryn C. Davidson 21 Wnt Signaling in Neural Development 279 Richard I. Dorsky 22 Wnt Signaling in Heart Organogenesis 293 Stefan Hoppler, Silvia Mazzotta, and Michael Kühl 23 Wnt Signaling in Kidney Organogenesis 303 Kimmo Halt and Seppo Vainio 24 Wnt Signaling Regulation of Tissue Architecture (EMT and MET) and Morphogenesis: Consequences for Colorectal and Liver Cancer 315 Theodora Fifis, Bang M. Tran, Renate H.M. Schwab, Timothy M. Johanson, Nadia Warner, Nick Barker, and Elizabeth Vincan 25 Wnt Signaling in Adult Stem Cells: Tissue Homeostasis and Regeneration 329 Frank J.T. Staal and Riccardo Fodde 26 Restoring Tissue Homeostasis: Wnt Signaling in Tissue Regeneration After Acute Injury 339 Günes Özhan and Gilbert Weidinger Part 4 Wnt Signaling in Chronic Disease 357 27 Wnt Signaling and Colorectal Cancer 359 Kevin Myant and Owen J. Sansom 28 Wnt Signaling in Melanoma 369 Jamie N. Anastas and Andy J. Chien 29 Wnt Signaling in Mood and Psychotic Disorders 379 Stephen J. Haggarty, Karun Singh, Roy H. Perlis, and Rakesh Karmacharya 30 Neuropsychiatric Disease-Associated Genetic Variation in the Wnt Pathway 393 Stephen J. Haggarty, Karun Singh, Roy H. Perlis, and Rakesh Karmacharya 31 Wnt Signaling in Dementia 411 Stephen J. Haggarty 32 Therapeutic Targeting of the Wnt Signaling Network 421 Felicity Rudge and Trevor Dale Index 445

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Book SynopsisDNA technology is evolving rapidly, with new methods and a fast-growing vocabulary. This unique dictionary offers current, detailed and accessible information on DNA technology to lecturers, researchers and students throughout the biomedical and related sciences. The third edition is a major update, with over 3000 references from mainstream journals and data from the very latest research going well beyond the remit of most science dictionaries. It provides clear explanations of terms, techniques, and tests, including commercial systems, with detailed coverage of many important procedures and methods, and includes essay-style entries on many major topics to assist newcomers to the field. It covers topics relevant to medicine (diagnosis, genetic disorders, gene therapy); veterinary science; biotechnology; biochemistry; pharmaceutical science/drug development; molecular biology; microbiology; epidemiology; genomics; environmental science; plant science/agriculture; taxonomy; anTrade Review“It might be worth keeping this excellent reference book in mind though.” (Reference Reviews, 1 November 2013) “Summing Up: Recommended. Upper-level undergraduates and above.” (Choice, 1 August 2013) Table of ContentsPreface vii Notes for the user ix Ready reference xiii Dictionary 1 Appendix: Alphabetical list of genera 505

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Book SynopsisIntroduction to Pain and its relation to Nervous System Disorders provides an accessible overview of the latest developments in the science underpinning pain research, including, but not limited to, the physiological, pathological and psychological aspects.Table of ContentsList of contributors ix Foreword xiii Acknowledgements xv Notes on authors xvii Introduction 1Anna A. Battaglia Section I: Neurobiology of pain: Recent advances 11 1 Anatomy of pain pathways 13Andrew J. Todd 2 Spinal plasticity of the nociceptive system: The role of central sensitisation in chronic pain states 35Alban Latrémolière 3 Symptoms and pathology in neuropathic pain 89Matthew Thakur and Stephen B. McMahon 4 Recent advances in neuroimmune interactions in neuropathic pain: The role of microglia 123Elizabeth A. Old, Louise S. C. Nicol and Marzia Malcangio 5 Genetics and epigenetics of pain 149Franziska Denk and Stephen B. McMahon 6 The cannabinoid system and its role in nociception 169Massimiliano Beltramo 7 EphB receptors and persistent pain 201Isabella Gavazzi Section II: Pain in the brain 225 8 Brain imaging in experimental pain 227Massieh Moayedi and Tim V. Salomons 9 Placebo effects in pain 249Luana Colloca, Adam P. Horin and Damien Finniss 10 Psychology and pain 267Lance M. McCracken Section III: Pain in the lifecycle and in nervous system disorders 281 11 Pain in neonates and infants 283Fiona Moultrie, Segzi Goksan, Ravi Poorun and Rebeccah Slater 12 How do people with autism spectrum disorders (ASD) experience pain? 295Cecile Rattaz, Amandine Dubois and Amaria Baghdadli 13 Pain and depression: The janus factor of human suffering 317Angela Iannitelli and Paola Tirassa 14 Pain in multiple sclerosis: From classification to treatment 345Claudio Solaro and Michele Messmer Uccelli 15 Pain perception in dementia 361Miriam Kunz and Stefan Lautenbacher 16 The role of cognitive impairment in the placebo and nocebo effects 373Martina Amanzio 17 An overview of pain in Parkinson’s disease 387Panagiotis Zis, Elisaveta Sokolov and Kallol Ray Chaudhuri Appendix: Interviews with chronic pain patients 409 Index 413

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Book SynopsisCircadian rhythms, the biological oscillations based around our 24-hour clock, have a profound effect on human physiology and healthy cellular function.Table of ContentsList of Contributors xiii Preface xvii Part I Fundamental Concepts 1 1 Cytosolic and Transcriptional Cycles Underlying Circadian Oscillations 3Michael H. Hastings and John S. O’Neill 1.1 Introduction 3 1.2 Assembling the transcriptional feedback loop 5 1.3 Keeping the transcriptional clockworks in tune 9 1.4 Building posttranslational mechanisms into the circadian pacemaker 13 1.5 Is the transcriptional clock paramount? 15 1.6 Conclusion: cytoscillators, clocks and therapies 18 References 18 2 Molecular Determinants of Human Circadian Clocks 25Steven A. Brown 2.1 Molecular elements of human clocks: a brief review 25 2.2 Peripheral and central clocks 26 2.3 Signaling to peripheral circadian clocks 28 2.4 Human peripheral and central clocks 29 2.5 Human genetics 29 2.6 Technologies for measurement of human circadian clocks 30 2.7 Cellular methods 30 2.8 Omics]based methods to analyze human clocks 32 2.9 Summary and outlook 33 References 33 3 The Suprachiasmatic Nucleus (SCN): Critical Points 37Christopher S. Colwell, Paul Witkovsky, and Rae Silver 3.1 SCN is site of master circadian pacemaker in mammals 37 3.2 SCN receives photic information through a specialized light detection pathway 39 3.3 SCN neurons are endogenous single cell oscillators that generate rhythms in neural activity 40 3.4 The SCN has circuit level organization that is just beginning to be unraveled 42 3.5 Coupling with the SCN circuit is mediated by a set of peptides with VIP on top of the hierarchy 44 3.6 SCN outputs 44 3.7 SCN in aging and disease 50 References 51 4 Sleep and Circadian Rhythms: Reciprocal Partners in the Regulation of Physiology and Behavior 57Ralph Mistlberger 4.1 Introduction 57 4.2 What is sleep 59 4.3 Circadian regulation of sleep 60 4.4 Reciprocity: sleep–wake feedback to the circadian clock 69 4.5 Conclusions: Circadian clocks and sleep are intertwined processes 73 References 73 5 Circadian Regulation of Arousal and its Role in Fatigue 81David R. Bonsall and Mary E. Harrington 5.1 Defining arousal 81 5.2 Brain structures important for arousal 83 5.3 Neurochemicals signaling the states of arousal 84 5.4 Circadian regulation of the arousal system 86 5.5 Influence of input pathways on circadian regulation of arousal 88 5.6 Sustained states of fatigue: a disorder of the arousal network? 88 5.7 Conclusions 90 References 91 Part II Circadian Regulation of Major Physiological Systems 95 6 Physiology of the Adrenal and Liver Circadian Clocks 97Alexei Leliavski and Henrik Oster 6.1 Introduction 97 6.2 Circadian control of adrenal function 98 6.3 Circadian control of liver function 101 6.4 Conclusion 105 References 105 7 Nutrition and Diet as Potent Regulators of the Liver Clock 107Yu Tahara and Shigenobu Shibata 7.1 Introduction 107 7.2 Food is a “zeitgeber”: The FEO in the brain 107 7.3 The FEO in peripheral tissues 109 7.4 What should we eat? What types of food can stimulate the peripheral clock? 110 7.5 When should we eat? Application to human life science 112 7.6 Circadian rhythm and obesity and diabetes 113 References 116 8 The Cardiovascular Clock 119R. Daniel Rudic 8.1 Introduction 119 8.2 The vascular clock 119 8.3 Circadian clock regulation of the endothelial cell layer of blood vessels 120 8.4 The circadian clock in vascular disease 121 8.5 The circadian clock and vascular cell signaling 122 8.6 The circadian rhythm in blood pressure, nighttime hypertension, and cardiovascular disease in humans 123 8.7 Diabetes, obesity, and blood pressure 125 8.8 AT influences the circadian rhythm in experimental hypertension 126 8.9 The circadian clock and fluid balance 127 8.10 The circadian clock and peripheral vascular resistance 127 8.11 Conclusion 130 References 130 9 Hypertension Caused by Disruption of the Circadian System: Blood Pressure Regulation at Multiple Levels 135Hitoshi Okamura, Miho Yasuda, Jean]Michel Fustin, and Masao Doi 9.1 Introduction 135 9.2 Effects of deleting Cry genes 135 9.3 Reduced a-adrenoceptor responsiveness in peripheral vessels and primary aldosteronism of Cry-null mice 138 9.4 Rapid blood pressure control system: enhanced baroreflex in Cry-null mice 139 9.5 Conclusion 141 References 141 10 Chronobiology of Micturition 143Akihiro Kanematsu and Hiromitsu Negoro 10.1 Introduction 143 10.2 Human studies 144 10.3 Animal models 146 10.4 The circadian clock and micturition 147 10.5 The clock in the bladder 148 10.6 Future directions 150 References 151 11 Disruption of Circadian Rhythms and Development of Type 2 Diabetes Mellitus: Contributions to Insulin Resistance and Beta]cell Failure 155Aleksey V. Matveyenko 11.1 Introduction 155 11.2 Mechanisms underlying pathophysiology of Type 2 diabetes mellitus: interaction between insulin resistance and beta-cell failure 156 11.3 Mechanisms underlying the association between circadian disruption and T2DM; potential role of obesity and insulin resistance 160 11.4 Mechanisms underlying the association between circadian disruption and T2DM; potential role of impaired beta-cell secretory function and mass 162 11.5 Conclusion 165 References 166 12 Circadian Clock Control of the Cell Cycle and Links to Cancer 169T. Katherine Tamai and David Whitmore 12.1 Introduction 169 12.2 Epidemiology 169 12.3 Does circadian clock disruption have any relevance in a clinical setting? 170 12.4 Circadian clock control of the cell cycle in healthy tissues 171 12.5 How might the cellular circadian clock regulate cell cycle timing? 173 12.6 Clock disruption and cancer 177 12.7 Does alteration in clock gene expression in human tumors correlate with the survival of patients? 178 12.8 Circadian]based chemotherapy (Chronotherapy): timing cancer treatment to improve survival 178 12.9 Conclusion 180 References 180 13 How Shift Work and a Destabilized Circadian System may Increase Risk for Development of Cancer and Type 2 Diabetes 183An Pan, Elizabeth Devore, and Eva S. Schernhammer 13.1 Introduction 183 13.2 Shift work and cancer 184 13.3 Shift work and obesity, metabolic syndrome, and type 2 diabetes 194 13.4 Conclusions and perspective of future studies 205 References 205 14 Circadian Rhythms in Immune Function 211Kandis Adams, Oscar Castanon-Cervantes, and Alec J. Davidson 14.1 Introduction 211 14.2 Daily variations in health and disease 212 14.3 Early evidence of circadian regulation on immunity 212 14.4 Clinical relevance of circadian regulation of the immune system 213 14.5 The circadian system communicates time of day information to immune cells and tissues 214 14.6 Immune effector cells under circadian regulation 214 14.7 Circadian disruption role in immune pathology and disease 216 14.8 The effects of clock gene alterations on immune functions 217 14.9 Conclusions 217 References 218 Part III Clocks in the Central Nervous System 221 15 Circadian Clock, Reward and Addictive Behavior 223Urs Albrecht 15.1 Introduction 223 15.2 Evidence for a time of day basis of addictive behavior 223 15.3 Drugs, circadian clock genes and addictive behavior 224 15.4 Links between feeding, addictive behavior and the clock 228 15.5 Treatment of addiction changing the circadian clock 229 References 231 16 How a Disrupted Clock may Cause a Decline in Learning and Memory 235Christopher S. Colwell 16.1 Introduction 235 16.2 Molecular clockwork expressed in brain regions central to learning and memory including the hippocampus, amygdala, and cortex 236 16.3 The circadian clockwork regulates intracellular signaling pathways known to be important to learning and memory 237 16.4 The circadian system impacts electrical activity and synaptic plasticity 238 16.5 The circadian system regulates neuroendocrine secretions that are well known to alter learning and memory processes 240 16.6 Disruptions of the circadian timing system alter learned behavior 241 16.7 Conclusions 245 References 245 17 Circadian Rhythms in Mood Disorders 249Colleen A. McClung 17.1 Introduction 249 17.2 Categories of rhythm disruptions 251 17.3 Seasonal affective disorder 252 17.4 Treatments for mood disorders alter rhythms 253 17.5 Human genetic studies 257 17.6 Animal studies 257 17.7 SCN output]rhythmic hormones and peptides 260 17.8 Regulation of mood]related brain circuits by the SCN and circadian genes 262 17.9 Neuroinflammation 263 17.10 Cell cycle regulation/neurogenesis 264 17.11 Conclusions 265 References 265 18 Sleep and Circadian Rhythm Disruption in Psychosis 271Stuart N. Peirson and Russell G. Foster 18.1 Introduction 271 18.2 Psychosis 273 18.3 Sleep and circadian rhythm disruption in psychosis 275 18.4 Possible mechanisms underlying SCRD in psychosis 277 18.5 Conclusions 280 References 281 19 Alzheimer’s Disease and the Mistiming of Behavior 283Roxanne Sterniczuk and Michael Antle 19.1 Introduction 283 19.2 Behavioral changes 283 19.3 Physiological changes 285 19.4 Neurological changes 286 19.5 Modeling AD 289 19.6 Chronobiological treatment of AD symptomology 290 19.7 Conclusion 292 References 293 20 Circadian Dysfunction in Parkinson’s Disease 295Christopher S. Colwell 20.1 Introduction 295 20.2 Dysfunction in the circadian system may contribute to the nonmotor symptoms of PD 296 20.3 Dopaminergic treatments for the motor symptoms of PD may contribute to circadian disruption 297 20.4 PD models show sleep and possible circadian disruption 298 20.5 Possible underlying mechanisms 300 20.6 Conclusion 301 References 302 21 Circadian Dysfunction in Huntington’s Disease 305A. Jennifer Morton 21.1 Introduction 305 21.2 Mechanisms underlying sleep and circadian rhythm generation 305 21.3 Circadian disruption in HD 306 21.4 Circadian disruption in animal models of HD 306 21.5 Circadian disruption of peripheral clocks and metabolism in HD 311 21.6 Pharmacological manipulation of circadian disruption in HD mice 311 21.7 Environmental modulation of circadian disruption in HD mice 311 21.8 Clinical changes in sleep in HD 312 21.9 Disturbance in sleep architecture in HD 312 21.10 Pathology underlying changes in sleep and circadian activity in HD 313 21.11 The orexin system in HD 313 21.12 The role of non]SCN oscillators in HD 314 21.13 Consequences of sleep–wake disturbance in HD 314 21.14 Cognitive dysfunction and mood disturbance in HD 315 21.15 Management of circadian disturbance in HD 315 21.16 Conclusions 317 References 318 22 The Aging Clock 321Stephan Michel, Gene D. Block, and Johanna H. Meijer 22.1 Introduction 321 22.2 The effects of aging on rhythmic behaviors 321 22.3 The effects of aging on components of the circadian system 323 22.4 Molecular rhythms in steady state 328 22.5 The effects of aging on the resetting behavior of central and peripheral oscillators 329 22.6 The effects of the circadian system on aging and age]related disease: Circadian misalignment andlongevity 330 22.7 Therapeutic possibilities for agerelated circadian disorders 331 22.8 Conclusions 332 References 332 23 Can we Fix a Broken Clock? 337Analyne M. Schroeder and Christopher S. Colwell 23.1 Introduction 337 23.2 Light therapy 339 23.3 Scheduled meals 340 23.4 Scheduled exercise 341 23.5 Scheduled sleep 343 23.6 Pharmacological targeting of the circadian system 343 23.7 Conclusions 345 References 346 Index 351

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Book Synopsis* Provides broad overview of the developmental biology of both Xenopus laevis and Xenopus tropicalis * Cellular to systems development in key biomedical model organisms * Timely synthesis of the field of Xenopus biology * Highlights key biomedical and basic biological findings unlocked by Xenopus .Table of ContentsContributors vii Preface ix Section I Oocyte and Early Embryo 1 1 Transcription in the Xenopus Oocyte Nucleus 3 Joseph G. Gall 2 RNA Localization during Oogenesis in Xenopus laevis 16 James O. Deshler 3 From Oocyte to Fertilizable Egg: Regulated mRNA Translation and the Control of Maternal Gene Expression 38 Chad E. Cragle & Angus M. MacNicol 4 Polarity of Xenopus Oocytes and Early Embryos 60 Malgorzata Kloc 5 Germ-Cell Specification in Xenopus 75 Mary Lou King Section II Midblastula Transition, Gastrulation, and Neurulation 101 6 The Xenopus Embryo as a Model System to Study Asymmetric Furrowing in Vertebrate Epithelial Cells 103 Jacek Z. Kubiak, Isabelle Chartrain, & Jean-Pierre Tassan 7 Induction and Differentiation of the Xenopus Ciliated Embryonic Epidermis 112 Marie Cibois, Pierluigi Scerbo, Virginie Thomé, Andrea Pasini, & Laurent Kodjabachian 8 Wnt Signaling during Early Xenopus Development 130 François Fagotto 9 Neural Tube Closure in Xenopus 163 Hitoshi Morita, Makoto Suzuki, & Naoto Ueno Section III Metamorphosis and Organogenesis 187 10 Primordial Germ Cell Migration 189 Aliaksandr Dzementsei & Tomas Pieler 11 Development of Gonads, Sex Determination, and Sex Reversal in Xenopus 199 Rafa³ P. Piprek & Jacek Z. Kubiak 12 The Xenopus Pronephros: A Kidney Model Making Leaps toward Understanding Tubule Development 215 Rachel K. Miller, Moonsup Lee, & Pierre D. McCrea 13 Development of Neural Tissues in Xenopus laevis 239 William A. Muñoz, Amy K. Sater, & Pierre D. McCrea 14 The Development of the Immune System in Xenopus 264 Louis Du Pasquier 15 Neural Regeneration in Xenopus Tadpoles during Metamorphosis 293 Mauricio Moreno, Karina Tapia, & Juan Larrain Section IV Novel Techniques and Approaches 309 16 Atomic Force Microscopy Imaging of Xenopus laevis Oocyte Plasma Membrane 311 Francesco Orsini 17 Size Scaling of Subcellular Organelles and Structures in Xenopus laevis and Xenopus tropicalis 325 Lisa J. Edens & Daniel L. Levy 18 A Model for Retinal Regeneration in Xenopus 346 Masasuke Araki 19 The Xenopus Model for Regeneration Research 368 Ying Chen & Gufa Lin 20 Genomics and Genome Engineering in Xenopus 383 Léna Vouillot, Aurore Thélie, Thibault Scalvenzi, & Nicolas Pollet Index 403

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Book SynopsisTranslational Gastroenterology: Organogenesis to Disease bridges the gap between basic and clinical research by providing information on GI (gastrointestinal) organ development discovered through scientific inquiry, alongside clinical observations of acquired and congenital abnormalities. Paired chapters, written from basic science and clinical viewpoints, review the major biological pathways and molecules at work in organ ontogeny and disease. In addition to a comprehensive survey of GI organ development and pathologies, the book also highlights model organisms and new areas of research, with chapters devoted to recent advances in the field of GI stem cell biology, and the potential for tissue engineering of GI organs. The topics covered provide a unique window onto current activity in the field of gastroenterology, fostering enhanced knowledge for developmental biologists as well as for clinical practitioners. Notable features include the following: BaTable of ContentsList of Contributors ix Foreword xiii Preface xv 1 Endoderm Development: From Progenitors to Organ Buds 1David A.F. Loebel, Keren Kaufman-Francis, Yoji Kojima, Henry C.Y. Chung, and Patrick P.L. Tam 2 Genetic and Cellular Mechanisms Regulating Esophageal Development 15Wei-Yao Ku and Jianwen Que 3 Congenital and Acquired Diseases of the Esophagus 27Iljana Gaffar, Yousef El-Gohary, and George Gittes 4 Basic Science of Stomach Development 43Tae-Hee Kim and Ramesh A. Shivdasani 5 Congenital and Acquired Diseases of the Stomach 57Ramon U. Jin and Jason C. Mills 6 The Pylorus: Development and Disease 73Ajay Prakash, Aaron M. Udager, and Deborah L. Gumucio 7 Basic Science of Small Intestinal Development 85Cayla A. Thompson and Michele A. Battle 8 Clinical Small Intestine 99Michael A. Helmrath and Kavita Deonarine 9 Basic Science of Colon Development 113Mattheus C.B. Wielenga and Gijs R. van den Brink 10 Congenital and Acquired Diseases of the Colon 125Jennifer J. Freeman and Daniel H. Teitelbaum 11 Intestinal Serosa 139Nichelle I. Winters and David M. Bader 12 Basic Science of Liver Development 151Ann DeLaForest and Stephen A. Duncan 13 Congenital and Acquired Diseases of the Liver 165Zahida Khan, Edgar N. Tafaleng, Kyle A. Soltys, and Ira J. Fox 14 Developmental Biology of the Pancreas 179L. Charles Murtaugh 15 Congenital Disorders of the Pancreas 193Mark Lowe 16 Enteric Nervous System Development 209E. Michelle Southard-Smith and Melissa A. Musser 17 Congenital and Acquired Disorders of the Enteric Nervous System 225Robert O. Heuckeroth 18 Gut Development in the Sea Urchin 241Megan L. Martik and David R. McClay 19 Intestinal Stem Cell Specification in the Drosophila Midgut 253Neus Rafel and Benjamin Ohlstein 20 The Caenorhabditis elegans Intestine 263James D. McGhee, Tobias Wiesenfahrt, and Aidan E. Dineen 21 Xenopus as a Model for GI Development 275Zheng Zhang and Aaron M. Zorn 22 Zebrafish Models of GI Development and Disease 289Ashley Alvers and Michel Bagnat 23 Gastrointestinal Stem Cells 303Elise S. Demitrack and Linda C. Samuelson 24 Translating Embryonic Development into Models of Human Gastrointestinal Development and Disease 317Stacy R. Finkbeiner and Jason R. Spence Index 327

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Book Synopsis* Thoroughly reviews our current understanding of malarialbiology * Explores the subject with insights from post-genomictechnologies * Looks broadly at the disease, vectors of infection, andtreatment and prevention strategies * A timely publication with chapters written by globalresearchers leaders .Table of ContentsList of contributors xiii Foreword xvii Preface xix 1 Introduction: An overview of malaria and Plasmodium 1 Virander S. Chauhan, Chetan E. Chitnis, and Deepak Gaur History 1 The life cycle of Plasmodium 3 A significant milestone in malaria research: Adaptation of Plasmodium to laboratory culture 4 The advent of present‐day technologies and their applications in malaria research 5 Bibliography 6 2 Exoerythrocytic development of Plasmodium parasites 9 Volker T. Heussler, Annika Rennenberg, and Rebecca R. Stanway The sporozoite’s journey from the skin to the liver 10 Sporozoite invasion 14 Parasite development 15 Protein export from the parasite into the host cell 20 Parasite egress 23 The role of innate immune responses during merosome formation 26 Acknowledgments 27 Bibliography 27 3 Molecular basis of erythrocyte invasion by Plasmodium merozoites 33 Deepak Gaur, Chetan E. Chitnis, and Virander S. Chauhan The structure of the merozoite 39 The steps of erythrocyte invasion 41 Redundancy and ligand–receptor interactions that mediate parasite adhesion during erythrocyte invasion 57 Signaling events during erythrocyte invasion by malaria parasites 74 Summary and conclusions 75 Bibliography 75 4 The biology of malaria transmission 87 Robert E. Sinden Purpose 87 History 87 The current research agenda 88 Biology 88 Population dynamics 106 Transmission‐blocking interventions 110 Bibliography 114 5 Comparative and functional genomics of malaria parasites 125 Martine M. Zilversmit, Sittiporn Pattaradilokrat, and Xin‐zhuan Su An Introduction to Plasmodium genomes 125 Genome structure of malaria parasites 127 From genome sequences to gene function 133 Summary 139 Acknowledgments 139 Bibliography 139 6 Gene regulation: New insights and possible intervention strategies 149 Artur Scherf, Nicholas A. Malmquist, Rafael M. Martins, Shruthi S. Vembar, and Jose‐Juan Lopez‐Rubio Introduction 149 Modes of gene regulation 150 Drug targeting 164 Perspectives 169 Bibliography 171 7 Molecular genetic approaches to malaria research 179 Brendan Elsworth, Mauro F. Azevedo, Brendan S. Crabb, and Paul R. Gilson Transfection methods 179 Genetic approaches for deriving gene function 184 Conditional knockdown of protein function 187 Protein reporters 190 Conclusions 192 Bibliography 192 8 Transcriptomics and proteomics 197 Archana P. Gupta, Zbynek Bozdech, and Peter R. Preiser Transcriptional profiling throughout the parasite life cycle 198 Transcriptional regulation 201 Transcriptional variation 205 Biological insights 208 Proteomics 208 Translational regulation 209 Conclusion 212 Bibliography 212 9 The biochemistry of Plasmodium falciparum: An updated overview 219 Hagai Ginsburg MPMP 219 Carbohydrates 219 Lipid metabolism 227 Amino acids 240 Nucleotide metabolism 252 Cofactors 256 Redox metabolism 265 Mitochondrial functions 268 Hemoglobin digestion and hemozoin production 273 Some reflections for the future 276 Bibliography 277 10 Signaling in malaria parasites 291 Pushkar Sharma and Sudhir Kumar Protein phosphorylation in Plasmodium 291 Calcium‐mediated signaling in Plasmodium 292 Phosphoinositide signaling and trafficking in malaria parasites 295 Cyclic nucleotide signaling in the malaria parasite 296 Future challenges 300 Bibliography 300 11 Membrane transport proteins as therapeutic targets in malaria 307 Sanjay A. Desai, Kempaiah Rayavara, Paresh Sharma, Sayeed K. Syed, Wang Nguitragool, and Praveen Balabaskaran Nina Host erythrocyte membrane: A shared ion and nutrient channel 308 Parasitophorous vacuolar membrane: Protein export and solute uptake 311 Parasite plasma membrane: Similar to other eukaryotic cells, but different 314 Digestive vacuole: A specialized lysosome‐equivalent in the parasite 316 Mitochondrial inner membrane: An unusual ATP synthase with uncertain function 318 Conclusions 319 Acknowledgments 319 Bibliography 319 12 The proteolytic repertoire of malaria parasites 325 Puran Singh Sijwali and Philip J. Rosenthal Aspartic proteases 325 Cysteine proteases 330 Metalloproteases 333 Serine proteases 335 Threonine proteases 338 Roles of proteases in parasite development 340 Summary and conclusions 343 Acknowledgments 343 Bibliography 343 13 Development of medicines for the control and elimination of malaria 353 Jeremy N. Burrows and Timothy N. C. Wells Targets for the development of future medicines for malaria 356 The process of drug development 359 Advances in drug development made in the 21st century 365 The global pipeline of new medicines for treating malaria 368 Medicines in the broader context of malaria eradication 370 Conclusion 377 Acknowledgments 377 Bibliography 377 14 Antimalarial drug resistance 383 Naman K. Shah and Neena Valecha Background 383 Causes of drug resistance 386 Detection of drug resistance 390 Managing drug resistance 397 Conclusion 401 Disclosures 401 Bibliography 401 Further reading 407 15 Epidemiology of Plasmodium falciparum malaria 409 Alberto L. García‐Basteiro, Quique Bassat, and Pedro L. Alonso Burden of disease 409 Geographical distribution of the disease 411 Chain of transmission and infection cycle 413 Malaria endemicity and malaria transmission 415 Malaria elimination and eradication 423 Bibliography 424 16 Malaria pathogenesis 427 Bronner P. Gonçalves, Michal Fried, and Patrick E. Duffy Malaria illness 427 Host susceptibility 439 Parasite virulence 444 Conclusions 450 Bibliography 451 17 Host genetics 465 Thomas N. Williams What evidence is there that the risk of malaria is genetically determined? 465 Identifying the genes involved 466 Why is genetic resistance important? 467 Genetic polymorphisms of the red blood cell 468 Hemoglobinopathies 474 G6PD deficiency 478 Non–red blood cell polymorphisms 479 Concluding remarks 481 Bibliography 481 18 The immune response in mild and severe malaria: Two sides of the same coin 495 Michael Waisberg, Peter D. Crompton, Louis H. Miller, and Susan K. Pierce The picture of the acquisition of resistance to uncomplicated and severe malaria: Framing the questions 495 Searching for host genes that confer immune resistance to severe malaria 506 SLE susceptibility and resistance to severe malaria 507 The relationship between the pathogen environment and susceptibility to severe malaria 510 Summary 511 Acknowledgments 511 Bibliography 512 19 Progress in development of malaria vaccines 521 Chetan E. Chitnis, Deepak Gaur, and Virander S. Chauhan Immunity to malaria 521 Life cycle of malaria parasites and points of intervention with vaccines 522 Pre‐erythrocytic stage vaccines 524 Blood‐stage vaccines 526 Transmission‐blocking vaccines 533 Live attenuated vaccines for malaria 534 Conclusion 535 Bibliography 535 20 Plasmodium vivax: Insights on burden and pathobiology 547 Ivo Mueller, Quique Bassat, Marcus V. G. Lacerda, and Hernando A. del Portillo Burden of Plasmodium vivax infection and disease 547 Severe Plasmodium vivax malaria 550 Molecular basis of severe disease 552 Concluding remarks and outstanding research questions 558 Bibliography 558 Index 565

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