Biology, life sciences Books

Book SynopsisNorth America contains an incredibly diverse array of natural environments, each supporting unique systems of plant and animal life. These systems, the largest of which are biomes, form intricate webs of life that have taken millennia to evolve. This richly illustrated book introduces readers to this extraordinary array of natural communities and their subtle biological and geological interactions. Completely revised and updated throughout, the second edition of this successful text takes a qualitative, intuitive approach to the subject, beginning with an overview of essential ecological terms and concepts, such as competitive exclusion, taxa, niches, and succession. It then goes on to describe the major biomes and communities that characterize the rich biota of the continent, starting with the Tundra and continuing with Boreal Forest, Deciduous Forest, Grasslands, Deserts, Montane Forests, and Temperature Rain Forest, among others. Coastal environments, including the LagunaTrade Review"The disciplines of ecology and biogeography are so closely intertwined that many scholars of theserespective fields are, by necessity and shared interest, well versed in both (Jenkins and Ricklefs2011). This overlap is evident in the layout of Ecology of North America. With a scalable subject suchas ecosystems, the authors could have approached the discussion of their material from various angles. Their decision to employ a biomestructured theme to describe the assemblage of North American ecosystems is both logical and practical. This approach is certain to be appealing to biogeographers who use the textbook. In fact, this book could be used as a supplementary textbookin a biogeography class. Ecology of North America will serve as a good introductory text for students interested in the ecology of the continent. The book begins with an overview chapter of basic ecological principles and terms, including sound explanations of succession, biodiversity, and biogeography. Subsequent chapters are individually devoted to various North American ecosystems/biomes. These chapters define the unique attributes of each biome and fluidly address the important abiotic and biotic components of each, along with representative plant and animal assemblages, interactions, andadaptations, as well as characteristic biome-level disturbances and ecological challenges. Both authorsare wildlife ecology experts, yet their knowledge and understanding of plant ecology and their success in balancing the text between floral and faunal ecological discussions are both refreshing and impressive.....The inclusion of “infoboxes” is a meaningful addition; this type of aside succeeds in adding interest and depth to textbooks. Comprehensive bibliographies are included after each chapter,and the division of each one by chapter subheadings is helpful......The new edition of Ecology of NorthAmerica is a welcome addition to contemporary ecology textbook offerings. The authors have updateda good introductory text that is highly approachable and readable. It offers a worthy additionto textbook options in the discipline, and I recommend it as an essential resource for studentsand teachers of North American ecosystems" (Frontiers of Biogeography- December 2016)Table of ContentsForeword viii Preface ix Acknowledgments xi 1 Introduction 1 A brief overview of ecology 1 The ecosystem 2 Abiotic limits 3 Climate and topography 4 Soils and soil profiles 4 Biotic community 6 Community succession 6 Plant succession: from pioneer to climax 6 Primary and secondary succession 6 Succession and species abundance 7 The biome concept 7 Biodiversity 7 The “species richness gradient” 8 Biodiversity “hotspots” 8 Patterns of distribution 9 Continental patterns 9 Geographical and ecological distribution 10 Some ecological concepts 10 Niches 10 Ecological equivalents 12 Bergmann’s rule 12 Allen’s rule 13 Readings and references 14 2 Tundra 17 Climatic and glacial influences 17 Soils and geological influences 17 Permafrost 18 Patterned ground 18 Eskers and tundra wildlife 20 Glacial refugia 21 Features and adaptations 21 Plant adaptations to harsh conditions 21 Plant growth and reproduction 22 Decomposition and soil nutrients 23 Some animal adaptations 23 Major vegetative communities 24 Shrub tundra 25 Dwarf birch heath 25 Cottongrass heath 25 Fellfields 25 Invertebrates and tundra ecology 25 Selected tundra mammals 26 Lemmings 26 Arctic ground squirrels 27 Arctic foxes 28 Barren]ground caribou 28 Selected tundra birds 29 Gyrfalcons 29 Snowy owl 30 Ross goose 30 Highlights 31 Absentees: amphibians and reptiles 31 Lichens and “reindeer moss” 31 Snow goose “eat outs” 32 Alpine Tundra 33 Fragile Tundra 34 Impacts of human activity 34 Global warming 35 Readings and references 36 3 Boreal Forest 41 Climatic boundaries and soils 41 Features and adaptations 42 Plant adaptations 42 Animal adaptations 42 Frequent fires 42 Niches in the Boreal Forest 43 Selected biotic communities 44 Tree line and forest tundra 44 Muskeg 46 Coniferous swamps 46 Comparative ecology of lakes 46 Appalachian Extension 48 Mountain balds 48 Highlights 49 The 10]year cycle 49 Wolves and moose 50 A wealth of salamanders 52 Red squirrels 53 Ecological challenges 54 Acid rain 54 Spruce budworm and DDT 55 Balsam woolly adelgid 55 The Boreal Forest Agreement 56 Readings and references 57 4 Eastern Deciduous Forest 61 Climatic boundaries and soils 61 Features and adaptations 61 The forest primeval 63 The layered forest 63 Autumn leaves 64 Ground and leaf litter 64 Mast 65 Biotic associations 66 Northern hardwoods conifer forests 66 Beech–Maple–Basswood 67 Mesophytic forest 68 Oak–Hickory 69 Mississippi alluvial plain 70 Southern Mixed Forest 70 Some associated communities 71 Longleaf pine forests 71 New Jersey Pine Barrens 73 Carolina bays 74 Highlights 75 Acorns and blue jays 75 Deer yards 75 Kirtland’s warblers and fire 76 Franklin’s lost tree 77 Cicadas: buzz in the forest 77 Ecological challenges 78 Declines of neotropical migrants 78 Forest destruction by exotic organisms 80 Reintroduction of red wolves 81 Readings and references 82 5 Grasslands: Plains and Prairies 89 Major associations 89 Tallgrass prairie 89 Midgrass prairie 90 Shortgrass prairie 90 Transition zones 93 Aspen parklands 93 Cross Timbers 96 Western transition 96 Features and adaptations 97 Seasonal grasses 97 Soils 99 Role of fire 101 Prairie streams 101 Prairie wetlands and waterfowl 102 Pleistocene extinctions 103 Selected prairie mammals 104 Bison 104 Prairie dogs 104 Pronghorns 106 Selected prairie birds 106 Burrowing owls 106 Prairie chickens 107 Highlights 108 Riparian forests 108 The Platte River 108 Nebraska Sandhills 109 Ants 109 Isolation and contact on the plains 110 Grassland settlement 110 Prairie preservation 111 Readings and references 113 6 Regional Grasslands and Related Areas 120 Regional associations 120 Palouse prairie 120 California Annual Grasslands 122 Southwestern desert grasslands 124 Edwards Plateau 126 Tamaulipan Mezquital 127 Highlights 129 Rodents and vegetation 129 Channeled Scablands 130 Snake River Birds of Prey Conservation Area 130 Mima mounds 131 Desertification 132 Readings and references 132 7 Deserts 136 Physical geography 136 Why deserts are dry 136 Desert mountains and bajadas 138 Ancient lakes 138 Features and adaptations 139 Desert soils and surfaces 139 Plant adaptations 140 Animal adaptations 141 The major deserts 144 Chihuahuan Desert 144 Sonoran Desert 145 Mojave Desert 147 Great Basin Desert 149 Highlights 150 Nurse trees 150 “Trees” for desert woodpeckers 151 Boojums and elephants: unique trees 153 Yucca moths 154 Desert fishes 154 Realm of reptiles 155 Of soils and mice 156 Deserts and predators 157 Pygmies of the sagebrush steppe 158 Desert quail rainfall and vitamin A 159 Sailing stones 159 Wheeled threats to deserts 159 Readings and references 160 8 Chaparral and Pinyon]Juniper Woodlands 167 Features and adaptations of chaparral 168 Coastal (California) chaparral 171 Chamise chaparral 171 Manzanita chaparral 171 Ceanothus chaparral 171 Other chaparral communities 171 Interior (Arizona) chaparral 172 Pinyon]juniper woodlands 172 Distribution and ecology 172 Human uses 173 Chaparral and fire 173 Water]repellant soils 173 Post]fire vegetation 174 Wildlife and chaparral fires 174 Highlights 174 Allelopathy in chaparral 174 Animal associates in coastal chaparral 175 Lizards and burned chaparral 175 Pinyon jays 176 Human influences 176 Readings and references 176 9 Montane Forests 180 Features and adaptations 180 Montane Forest zones 181 Lower montane zone 181 Upper montane zone 181 Subalpine zone 182 Associated habitats 183 Mountain parks and meadows 183 Black Hills 185 Redwoods and sequoias 186 Bristlecone pine forest 188 Fire in montane forests 190 Highlights 192 Western chipmunks and competitive exclusion 192 Squirrels bears and pine cones 194 Sky islands in Arizona 195 Monarchs in winter 196 Bears and moths 196 Readings and references 198 10 Temperate Rain Forest 203 What is old]growth forest? 203 Features and adaptations 204 Valleys of rain forest 204 Epiphytes canopy roots and “scuzz” 206 More about logs 207 Succession on glacial till 208 Highlights 209 Bears salmon and forest enrichment 209 A seabird in the forest 212 Some small mammals and their ecology 213 Banana slugs 213 Pacific yew 214 Giant salamanders and other amphibians 214 Mount St Helens 215 Ecological controversy 217 Readings and references 218 11 Coastal Environments 223 Currents and climates 223 Features and adaptations 224 Rocky seashores and tidal pools 224 Sandy seashores 225 Chesapeake Bay 227 Mother Lagoon 228 Submergent communities 230 Seagrass meadows 230 Forests in the ocean 232 Oyster reefs 233 Emergent communities 235 Atlantic tidal marshes 235 Marshes of the Gulf Coast 236 Mangrove islands and thickets 238 Some associated communities 239 Barrier islands 239 Coral reefs 241 Maritime forests 243 Highlights 243 Synchrony at Delaware Bay 243 Waterbird colonies 245 A whale of a success 247 Ecological challenges 248 Natural disturbances 248 Sea]level rise 250 Readings and references 251 12 A Selection of Special Environments 259 The Grand Canyon 259 Caves 262 Arctic ice cap 265 Niagara Escarpment 267 The “Father of Waters” 268 The Everglades 271 Fossil Lagerstätten: Windows into North America’s ecological past 275 Burgess Shale 275 La Brea tar pits 277 The Florida Keys 278 The Great Lakes 280 Habitat highlights 282 Rivers of ice 282 Hot springs and geysers 283 Forest in the clouds 284 Granite outcrops and inselbergs 285 Palm forest 285 Mineral licks 286 Bogs and their carnivorous plants 287 Readings and references 288 Appendix 296 Glossary 309 Index 321

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Book SynopsisThe comprehensive and authoritative guide to clinical reproductive science The field of clinical reproductive science continues to evolve; this important resource offers the basics of reproductive biology as well as the most recent advance in clinical embryology. The author - a noted expert in the field - focuses on the discipline and covers all aspects of this field. The text explores causes of male and female infertility and includes information on patient consultation and assessment, gamete retrieval and preparation, embryo culture, embryo transfer and cryopreservation. Comprehensive in scope, the text contains an introduction to the field of clinical reproductive science and a review of assisted reproductive technology. The author includes information on a wide range of topics such as gonadal development, the regulation of meiotic cell cycle, the biology of sperm and spermatogenesis, in vitro culture, embryo transfer techniques, fundamentals of fertilisation, oocyte activation aTable of ContentsList of Contributors xi About the Editor xv Preface xvii Acknowledgements xix About the Companion Website xxi Section One Reproductive Science: Fundamentals of Human Reproductive Biology 1 1 Sexual Differentiation, Gonadal Development, and Development of the External Genitalia: A Review of The Regulation of Sexual Differentiation 3Rebecca M. Perrett 2 Male and Female Reproductive Anatomy 35Sara Sulaiman and James Coey 3 Fundamentals of Reproductive Endocrinology 45Derrick Ebot, Haider Hilal, Michael Carroll, and James Coey 4 The Ovaries, Oocytes, and Folliculogenesis 57Jacques Gilloteaux and James Coey 5 The Human Spermatozoa 65Allan Pacey and Katrina Williams 6 The Biology of Fertilization 75Michael Carroll 7 Human Embryo Development: From Zygote Stage to Peri‐Implantation Blastocyst 93Stéphane Berneau and Michael Carroll 8 The Female Reproductive Tract and Early Embryo Development: A Question of Supply and Demand 99Henry J. Leese and Daniel R. Brison Section Two Clinical Reproductive Science: Causes of Male and Female Infertility 109 9 Disorders of Male Reproductive Endocrinology 111Michael Carroll 10 Disorders of Female Reproductive Endocrinology 125Mahshid Nickkho‐Amiry and Cheryl T. Fitzgerald 11 Oocyte Aneuploidy and the Maternal Age Effect 133Mary Herbert 12 Female Reproductive Pathology: Peritoneal, Uterine, and Fallopian Tube Pathologies 147Kenneth Ma Kin Yue, Rosa Trigas, and Edmond Edi‐Osagie 13 Pathologies of the Male Reproductive Tract 159Aarush Sajjad, Muhammad A. Akhtar, and Yasmin Sajjad 14 The Impact of Infections on Reproduction and Fertility 177Val Edwards Jones 15 Nutrition, Fetal Health, and Pregnancy 189Emma Derbyshire 16 The Embryonic Environment and Developmental Origins of Health 195Tom P. Fleming and Congshan Sun 17 Lifestyle and Environmental Impacts on Fertility 205Ana‐Maria Tomova and Michael Carroll Section Three Clinical Reproductive Science In Practice: IVF and Assisted Reproductive Technologies 215 18 Assessing the Infertile Couple 217Narmada Katakam, Ruth Arnesen, Caroline Watkins, Bert Stewart, and Luciano G. Nardo 19 Ovarian Stimulation Protocols 231Nikolaos Tsampras and Cheryl T. Fitzgerald 20 Oocyte Retrieval Techniques and Culture of Oocytes 241Dawn Yell 21 Sperm Preparation: Strategy and Methodology 251Stephen Harbottle 22 Diagnostic Semen Analysis: Uncertainty, Clinical Value, and Recent Advances 265Mathew Tomlinson 23 Surgical Sperm Retrieval 279Muhammad A. Akhtar, Elizabeth Hester, Solmaz Gul Sajjad, and Yasmin Sajjad 24 In Vitro Fertilization and Intracytoplasmic Sperm Injection 291Bryan Woodward 25 Morphological Assessment of Embryos in Culture 303J. Diane Critchlow 26 In Vitro Culture of Gametes and Embryos – The Culture Medium 317Robbie Kerr 27 Incubators in the Assisted Reproductive Technology Laboratory 333Louise Hyslop 28 Embryo Transfer Techniques and Improving Embryo Implantation Rates 341Rachel Cutting 29 Cryopreservation of Gametes and Embryos 351Tope Adeniyi 30 Preimplantation Genetic Diagnosis and Screening 371Colleen Lynch and Brendan Ball 31 Long‐Term Follow‐Up of Children Conceived Through In Vitro Fertilization 385Omar Abdel‐Mannan and Alastair G. Sutcliffe Index 393

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Book SynopsisHarmful Algal Blooms: A Compendium Desk Referenceprovides basic information on harmful algal blooms (HAB) and references for individuals in need of technical information when faced with unexpected or unknown harmful algal events. Chapters in this volume will provide readers with information on causes ofHAB, successful management and monitoring programs, control, prevention, and mitigation strategies, economic consequences of HAB, associated risks to human health, impacts of HAB onfood webs and ecosystems, and detailed information on the most common HAB species. Harmful Algal Blooms: A Compendium Desk Reference will be an invaluable resource to managers, newcomers to the field, those who do not have easy or affordable access to scientific literature, and individuals who simply do not know where to begin searching for the information needed, especially when faced with novel and unexpected HAB events. Edited by three of the world''s leading harmful algal bloTable of ContentsList of Contributors xvii Acknowledgments xxi Introduction xxiii 1 Causes of Harmful Algal Blooms 1Patricia M. Glibert and JoAnn M. Burkholder 1.1 Introduction 1 1.2 “Getting There”: The Classic Perspective on Introduced Species and Links to Cultural Eutrophication 2 1.2.1 Introduced Species 2 1.2.2 Anthropogenically Introduced Nutrients 3 1.3 “Being There”: Blooms and Why They Succeed 5 1.3.1 Nutrient-Related HAB 5 1.3.2 Resource Ratios, Nutrient Stoichiometry, and Optimal Nutrient Ratios 6 1.3.3 Diversity in Use of Forms of Nitrogen 9 1.3.4 Toxicity 10 1.3.5 Mixotrophy: Use of “Packaged” and Dissolved Particulate Nutrients 12 1.3.6 Other Adaptations 13 1.4 “Staying There”: Links to Physical Structure and Climate 14 1.4.1 Physical Structure: Large-Scale and Small-Scale Natural Hydrological Features 14 1.4.2 Physical Dynamics: Anthropogenic Hydrological Changes 15 1.4.3 Reinforcing Feedbacks 16 1.4.3.1 Trophic Disruptions 16 1.4.3.2 Biogeochemical Alterations 17 1.4.4 Climate Change 18 1.5 Conclusions 20 Acknowledgments 21 References 21 2 Detection and Surveillance of Harmful Algal Bloom Species and Toxins 39Gregory J. Doucette, Linda K. Medlin, Pearse McCarron, and Philipp Hess 2.1 Introduction 39 2.2 Organism Detection 41 2.2.1 Visual/Optical 41 2.2.1.1 Light Microscopy (LM)/Utermöhl’s 41 2.2.1.2 Light Microscopy/Flow Cytometry 41 2.2.1.3 In Vivo Fluorometry 42 2.2.1.4 Spectral Absorbance/Spectroradiometry 43 2.2.2 Molecular 43 2.2.2.1 Whole Cell Format 44 2.2.2.2 Cell-Free Format 47 2.3 Toxin Detection 51 2.3.1 In Vivo Assays 53 2.3.1.1 Rat Bioassay 58 2.3.1.2 Mouse Bioassay 58 2.3.2 In Vitro Assays 59 2.3.2.1 Functional Assays 60 2.3.2.2 Structural Assays 66 2.3.2.3 Biosensors 71 2.3.3 Analytical Techniques 72 2.3.3.1 High-Performance Liquid Chromatography with Optical Detection (UV or FLD) 73 2.3.3.2 Liquid Chromatography–Mass Spectrometry (LC-MS) and Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) 75 2.3.3.3 Other Analytical Methods: Capillary Electrophoresis (CE), Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF), and Laser Ablation Electrospray Ionization (LAESI) 78 2.3.3.4 Perspectives 79 2.4 Autonomous, In Situ Technologies 80 2.4.1 Environmental Sample Processor (McLane Research Laboratories) 81 2.4.2 Imaging Flow Cytobot (McLane Research Laboratories) 83 2.4.3 Optical Phytoplankton Discriminator (aka BreveBuster; Mote Marine Laboratory) 84 2.4.4 CytoBuoy (CytoBuoy b.v.) 85 2.4.5 SPATT Passive Samplers 86 2.5 Conclusions and Future Prospects 87 Disclaimer 89 References and Further Reading 89 3 Modeling Marine Harmful Algal Blooms: Current Status and Future Prospects 115Kevin J. Flynn and Dennis J. McGillicuddy, Jr. 3.1 Introduction 115 3.2 Building Models to Describe Ecological Events 117 3.3 Limitations to What Models Can Do, and Why 119 3.3.1 Building Models 119 3.3.2 Model Complexity 119 3.3.3 The Need for Data 120 3.3.4 Validating Models 121 3.4 Modeling T-HAB and ED-HAB Events 121 3.5 How Good Are Current HAB Models? 122 3.6 Future Modeling of T-HAB and ED-HAB: Managing Expectations 128 3.7 Improving Our Capabilities 129 3.7.1 Changes in the Biological–Modeling Interface 129 Acknowledgments 130 References 130 4 Harmful Algal Blooms and Shellfish 135Leila Basti, Hélène Hégaret, and Sandra E. Shumway 4.1 Introduction 135 4.2 Major Shellfish Poisonings 136 4.2.1 Paralytic Shellfish Poisoning (PSP) 136 4.2.2 Diarrheic Shellfish Poisoning (DSP) 137 4.2.3 Neurotoxic Shellfish Poisoning (NSP) 138 4.2.4 Amnesic Shellfish Poisoning (ASP) 139 4.2.5 Azaspiracid Shellfish Poisoning (AZP) 139 4.3 Other Toxins: Pectenotoxins (PTX) and Yessotoxins (YTX) 140 4.4 Emerging Shellfish Poisonings 141 4.5 Toxin Uptake, Accumulation, and Depuration 142 4.6 Shellfish Contamination in North America 143 4.6.1 Bivalves 143 4.6.1.1 Paralytic Shellfish Contamination 143 4.6.1.2 Diarrheic Shellfish Contamination 149 4.6.1.3 Neurotoxic Shellfish Contamination 150 4.6.1.4 Amnesic Shellfish Contamination 151 4.6.2 Gastropods 154 4.6.3 Crustaceans 162 4.7 Impacts on Shellfish 163 4.8 Conclusions and Perspectives 164 References and Further Reading 167 5 Vulnerabilities of Marine Mammals to Harmful Algal Blooms 191Margaret H. Broadwater, Frances M. Van Dolah, and Spencer E. Fire 5.1 Introduction 191 5.2 Overview of Algal Toxins 192 5.2.1 Brevetoxins 193 5.2.2 Ciguatoxins 199 5.2.3 Diarrhetic Shellfish Poisoning Toxins 200 5.2.4 Domoic Acid 201 5.2.5 Paralytic Shellfish Toxins 206 5.2.6 Other Algal and Cyanobacterial Toxins 209 5.3 Impacts of Algal Toxins Specific to Marine Mammals 210 5.3.1 The Effects of Toxin Exposure Depend on Animal Physiology and Behavior 210 5.3.2 Emerging Issues: Non-acute and Multiple Toxin Exposure 211 5.3.3 Prospects for Managing Impacts of HAB 211 5.4 Considerations for the Evaluation of HAB Toxins in Marine Mammals 212 5.4.1 Sampling Marine Mammals for HAB Toxin Analysis 213 5.4.2 Priority Needs for Investigating HAB Toxin Involvement in Marine Mammal Morbidity and Mortality 214 Abbreviations 214 References and Further Reading 215 6 Interactions between Seabirds and Harmful Algal Blooms 223Corinne M. Gibble and Brian A. Hoover 6.1 Introduction 223 6.2 Historical Interactions between HAB and Seabirds 224 6.2.1 Paralytic Shellfish Poisoning (PSP) 224 6.2.2 Neurotoxic Shellfish Poisoning (NSP) 227 6.2.3 Amnesic Shellfish Poisoning 228 6.2.4 Akashiwo sanguinea 228 6.2.5 Diarrheic Shellfish Poisoning (DSP) 229 6.2.6 CyanoHAB 230 6.3 Improved Monitoring and Establishment of Causality 231 6.3.1 Coordinating Monitoring and Pathology to Confirm Relationships between HAB and Seabird Mortality 231 6.3.2 Seabirds as Biological Indicators 233 6.4 Implications for Conservation 234 References 235 7 Food Web and Ecosystem Impacts of Harmful Algae 243JoAnn M. Burkholder, Sandra E. Shumway, and Patricia M. Glibert 7.1 Introduction 243 7.2 Approaches, Pitfalls, Progress, and Goals 277 7.3 High-Biomass Algal Blooms 279 7.4 Emerging Recognition of the Roles of Allelochemicals 282 7.4.1 Microalgae 283 7.4.2 Thalloid Macroalgae 285 7.4.3 Filamentous Mat-Forming Macroalgae 287 7.5 Toxigenic Algae in Aquatic Food Webs 287 7.5.1 Toxic Microcystis aeruginosa Blooms across North America 289 7.5.2 Toxic Prymnesium parvum Blooms and Fish Communities in Two Texas Rivers 290 7.5.3 Toxic Pseudo-nitzschia Blooms in Coastal Upwelling Areas 292 7.5.4 Toxic Alexandrium Blooms in the Northeast 292 7.5.5 Toxic Karenia brevis Blooms along the Florida Coast 293 7.6 Ecosystem-Disruptive Algal Blooms 294 7.7 Future Directions 295 Appendix A: Scientific Names for Organisms Listed by Common Name in This Chapter, Also Indicating Species Affected by Karenia brevis (Kb) 297 References and Further Reading 301 8 Assessing the Economic Consequences of Harmful Algal Blooms: A Summary of Existing Literature, Research Methods, Data, and Information Gaps 337Charles M. Adams, Sherry L. Larkin, Porter Hoagland, and Brian Sancewich 8.1 Introduction 337 8.2 Overview 338 8.3 Research Methodologies 338 8.4 Sources and Types of Data 347 8.5 Spatial and Temporal Scopes 348 8.6 Nature of the Hazard 349 8.7 Current Research Gaps 350 8.8 Conclusion 351 Acknowledgments 351 References and Further Reading 351 9 Public Health and Epidemiology 355Lynn M. Grattan, Joe Schumacker, Andrew Reich, and Sailor Holobaugh 9.1 Introduction 355 9.2 What Is Public Health and Epidemiology? 355 9.3 HAB and Human Illness 356 9.3.1 Paralytic Shellfish Poisoning (PSP) 357 9.3.1.1 Exposure 357 9.3.1.2 Clinical Symptoms 361 9.3.1.3 Treatment 361 9.3.2 Amnesic Shellfish Poisoning (ASP) 361 9.3.2.1 Exposure 361 9.3.2.2 Clinical Syndrome 361 9.3.2.3 Treatment 362 9.3.3 Neurotoxic Shellfish Poisoning (NSP) 362 9.3.3.1 Exposure 362 9.3.3.2 Clinical Illness 363 9.3.3.3 Treatment 363 9.3.4 Brevetoxin Inhalation Syndrome (BIS) 363 9.3.4.1 Exposure 363 9.3.4.2 Clinical Illness 363 9.3.4.3 Treatment 363 9.3.5 Diarrhetic Shellfish Poisoning (DSP) 363 9.3.5.1 Exposure 363 9.3.5.2 Clinical Syndrome 364 9.3.5.3 Treatment 364 9.3.6 Ciguatera Fish Poisoning (CFP) 364 9.3.6.1 Exposure 364 9.3.6.2 Clinical Illness 364 9.3.6.3 Treatment 365 9.3.7 Azaspiracid Shellfish Poisoning (AZP) 365 9.3.7.1 Exposure 365 9.3.7.2 Clinical Syndrome 366 9.3.7.3 Treatment 366 9.3.8 Toxic Cyanobacteria 366 9.3.8.1 Exposure 366 9.3.8.2 Clinical Syndromes 366 9.3.8.3 Treatment 366 9.4 The HAB Manager’s Role in Preventing HAB-Related Illnesses 367 9.4.1 HAB Management Exemplars 367 9.4.2 The Native American Perspective from Washington State, USA: Domoic Acid and Paralytic Shellfish Toxins 367 9.4.2.1 Background 367 9.4.2.2 Tribal Capacity and Inclusion 369 9.4.2.3 Lessons Learned 369 9.4.3 The Florida Department of Health Perspective 369 9.4.3.1 Harmful Algal Blooms 370 9.5 HAB-Related Stressors and Human Resilience 370 9.6 Conclusion 371 References and Further Reading 371 10 Marine Biotoxin and Harmful Algae Monitoring and Management 377Gregg W. Langlois and Steve L. Morton 10.1 Introduction 377 10.2 Identifying Sampling Program Needs 383 10.3 Developing a Sampling Program for Shellfish Monitoring 384 10.3.1 Shellfish Sampling Stations 384 10.3.2 Monitoring Shellfish Toxicity 386 10.4 Developing a Sampling Program for Phytoplankton Monitoring 388 10.4.1 Phytoplankton Sampling Stations 388 10.4.2 Monitoring Phytoplankton 389 10.5 Monitoring Other Fisheries 394 10.6 Novel Approaches and Advanced Tools to Enhance Monitoring Programs 396 10.6.1 Diversifying Program Participation: Volunteer Monitors 396 10.6.2 Field Testing for Toxins: PSP and ASP 399 10.6.3 Screening Tests for Toxins: DSP and PSP 401 10.6.4 SPATT 401 10.6.5 Oceanographic Data 402 10.7 Management Considerations 408 10.7.1 Commercial Shellfish 408 10.7.2 Recreational Shellfishing 411 10.8 Phytoplankton Sampling Protocol Examples 413 10.9 HAB Forecasting Links 413 Acknowledgments 413 References and Further Reading 413 11 Harmful Algal Bloom Education and Outreach 419Mare Timmons, Mary Sweeney-Reeves, and Steve L. Morton 11.1 Introduction 419 11.2 K–12 Education 426 11.3 Web-Based and Distance Learning Education 427 11.4 Citizen Science 428 11.4.1 Contributions of Citizen Science 429 11.4.2 Connecting Citizen Science to Ocean Learning 431 11.4.2.1 Safety 431 11.4.2.2 Training Sessions 431 11.5 Conclusion 432 References and Further Reading 432 12 Prevention, Control, and Mitigation of Harmful Algal Bloom Impacts on Fish, Shellfish, and Human Consumers 435Kevin G. Sellner and J.E. (Jack) Rensel 12.1 Introduction 435 12.2 HAB Prevention 435 12.2.1 Aquaculture Site Selection or Relocation 435 12.2.2 Nutrient Load Reductions 436 12.2.3 Phytoplankton Mixing, Increasing Turbulence, and Decreasing Residence Times (Mostly Freshwater Systems) 440 12.2.4 Reducing HA Introductions 441 12.3 Preventing and Reducing HAB Impacts on Shellfish and Fish 442 12.3.1 Preventing Human and Animal Exposures 442 12.3.1.1 Shellfish and Finfish Monitoring 442 12.3.1.2 Depuration and Detoxification 444 12.3.1.3 Food Processing 444 12.3.1.4 Cooking 445 12.3.1.5 Aerosols 445 12.3.1.6 Medical Treatments 445 12.4 HAB Controls 445 12.4.1 Protections 445 12.4.2 Biomass Removal 446 12.4.3 Capping 446 12.4.4 Nutrient Trapping in Sediments 446 12.4.5 Reductions of Algal Resting Stages (Cysts) 446 12.5 Mitigation of HAB 447 12.5.1 Detection 447 12.5.2 Chemical Additions 448 12.5.3 Flocculation 451 12.5.4 Barely Straw (Hordeum vulgare) 454 12.5.5 Other Treatments 455 12.5.5.1 UV Exposure 455 12.5.5.2 Cavitation 455 12.5.5.3 Ultrasound 455 12.5.5.4 Electrolysis 456 12.5.5.5 Hydraulics and Mixing 456 12.5.5.6 Biological Controls 456 12.6 Shellfish 458 12.7 Fish Mariculture 459 12.7.1 HAB Mitigation for Fish Mariculture 459 12.7.2 Best Management Practices for Fish Mariculture Siting, Including HAB and Eutrophication Issues 460 12.7.2.1 Local Land Use 460 12.7.2.2 Plankton Monitoring and Water Quality Assessments 460 12.7.2.3 Physical Hydrographic Considerations 461 12.7.2.4 Vertical Mixing Considerations 461 12.7.3 Mitigation of HAB at Fish Mariculture Facilities 461 12.7.4 HAB Mitigation Methods for Fish Mariculture 462 12.7.4.1 Feeding and Handling Practices 462 12.8 Conclusions 470 Acknowledgments 474 References 474 Further Reading 492 13 Harmful Algae Introductions: Vectors of Transfer, Mitigation, and Management 493Shauna Murray and Gustaaf Hallegraeff 13.1 Summary 493 13.2 The Biogeographic Ranges of Harmful Algal Bloom Species 493 13.3 Vectors of Transfer 494 13.3.1 Natural Factors 494 13.3.2 Ballast Water 494 13.3.3 Translocation of Aquaculture Products 494 13.4 Molecular Evidence for Introductions of New Species to a Region 494 13.4.1 The Stalk-Forming Freshwater Fouling Diatom Didymosphenia geminata 495 13.4.2 Alexandrium pacificum and A. minutum in European and Japanese Waters 496 13.4.3 Gymnodinium catenatum in Australia and Europe 497 13.5 Prevention and Risk Reduction 498 13.5.1 Code of Practice on Translocation with Aquaculture Products 498 13.5.2 Warning for HAB in Ballast Water-Uptake Zones and When Translocating Aquaculture Products 498 13.5.3 Ballast Water Management 498 13.5.4 Other Precautionary Measures 500 13.6 Emergency Treatment Options 501 References 502 14 Culture and Culture Collections 507Gary H. Wikfors and Steve L. Morton 14.1 Introduction 507 14.2 Step 1: Sampling the Environment 507 14.3 Step 2: Processing a Field Sample in the Laboratory to Confirm Presence of the Target Organism 509 14.4 Step 3: From Spark to Flame 511 14.5 Step 4: Long-Term Perpetuation of HAB Cultures 511 14.6 Epilogue 512 Further Reading 513 15 Harmful Macroalgal Blooms in a Changing World: Causes, Impacts, and Management 515Brian E. Lapointe, JoAnn M. Burkholder, and Kathryn L. Van Alstyne 15.1 Introduction 515 15.2 Freshwater and Other Inland Macroalgae 516 15.3 Estuarine and Coastal Marine Macroalgae 519 15.4 Influences on Bloom Development 525 15.5 Nutrient Pollution 525 15.5.1 Sources 525 15.5.2 Indicators of Nutrient Pollution and Nutrient Sources 526 15.6 Uptake/Adsorption of Other Contaminants 526 15.7 Impacts on Human Health: Macroalgae as Substrata for Pathogens 527 15.8 Non-native Invasions 528 15.9 Ecological and Ecosystem-Level Impacts 529 15.9.1 Regime Shifts 530 15.9.2 Freshwater Macroalgal HAB 532 15.9.2.1 Filamentous Cyanobacteria 532 15.9.2.2 Filamentous Green Algae 533 15.9.3 Estuarine and Coastal Marine HAB 534 15.10 Effects of Blooms on the Chemistry of the Oceans and the Atmosphere 535 15.10.1 Changes to Carbonate Chemistry and pH 535 15.10.2 Release of Materials and Chemicals into Seawater 536 15.10.3 Release of Volatile Compounds 537 15.11 Management Strategies 537 15.12 Economic Impacts 539 15.13 Recycling Macroalgae Biomass 541 15.14 Forecast 542 References and Further Reading 542 16 Harmful Algal Species Fact Sheets 561 Alexandrium 563Allan D. Cembella Amphidomataceae 575Urban Tillmann Aureococcus anophagefferens Hargraves et Sieburth & Aureoumbra lagunensis DeYoe et Stockwell – Brown Tides 583Christopher J. Gobler Ceratium furca (Ehrenberg) Claparede & Lachmann 585Steve L. Morton Chattonella marina 587Carmelo R. Tomas Cochlodinium – Rust Tide 589Christopher J. Gobler Cyanobacteria 591JoAnn M. Burkholder, Christopher J. Gobler, and Judith M. O’Neil Dinophysis 597Steve L. Morton Fibrocapsa japonica 599Carmelo R. Tomas Gambierdiscus 601Michael L. Parsons, Mindy L. Richlen, and Alison Robertson Gymnodinium catenatum 605Allan D. Cembella and Christine J. Band-Schmidt Heterosigma akashiwo 613Carmelo R. Tomas Karenia brevis (Davis) Hansen et Moestrup – Florida Red Tide 615Larry E. Brand Ostreopsis 617Michael L. Parsons, Mindy L. Richlen, and Alison Robertson Pfiesteria piscicida Steidinger & Burkholder and Pfiesteria shumwayae Glasgow & Burkholder 621JoAnn M. Burkholder and Harold G. Marshall Prorocentrum 625Patricia M. Glibert and JoAnn M. Burkholder Prymnesium parvum (Carter) – “Golden Algae” 629Daniel L. Roelke and Schonna R. Manning Pseudo-nitzschia – seriata group; delicatissima group 633Raphael Kudela Takayama 637Larry E. Brand Appendix 1 Websites That Routinely Distribute Bulletins on the Presence of Harmful Algal Blooms (HAB) for Public Health 639 Appendix 2 State Agencies Providing Information and Updates on Toxic and Harmful Algal Blooms and Water Quality 641 Appendix 3 List of General Web Resources 645 Index 647

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Book SynopsisBacteria in various habitats are subject to continuously changing environmental conditions, such as nutrient deprivation, heat and cold stress, UV radiation, oxidative stress, dessication, acid stress, nitrosative stress, cell envelope stress, heavy metal exposure, osmotic stress, and others. In order to survive, they have to respond to these conditions by adapting their physiology through sometimes drastic changes in gene expression. In addition they may adapt by changing their morphology, forming biofilms, fruiting bodies or spores, filaments, Viable But Not Culturable (VBNC) cells or moving away from stress compounds via chemotaxis. Changes in gene expression constitute the main component of the bacterial response to stress and environmental changes, and involve a myriad of different mechanisms, including (alternative) sigma factors, bi- or tri-component regulatory systems, small non-coding RNA's, chaperones, CHRIS-Cas systems, DNA repair, toxin-antitoxin systems, the stringent rTable of ContentsVOLUME 1 Preface, xiii Acknowledgements, xiv List of contributors, xv 1 Introduction, 1Frans J. de Bruijn Section 2: Key overview chapters, 3 2.1 Stress-induced changes in transcript stability, 5Dvora Biran and Eliora Z. Ron 2.2 StressChip for monitoring microbial stress response in the environment, 9Joy D. Van Nostrand, Aifen Zhou and Jizhong Zhou 2.3 A revolutionary paradigm of bacterial genome regulation, 23Akira Ishihama 2.4 Role of changes in σ70-driven transcription in adaptation of E. coli to conditions of stress or starvation, 37Umender K. Sharma 2.5 The distribution and spatial organization of RNA polymerase in Escherichia coli: growth rate regulation and stress responses, 48Ding Jun Jin, Cedric Cagliero, Jerome Izard, Carmen Mata Martin, and Yan Ning Zhou 2.6 The ECF classification: a phylogenetic reflection of the regulatory diversity in the extracytoplasmic function σ factor protein family, 64Daniela Pinto andThorsten Mascher 2.7 Toxin–antitoxin systems in bacteria and archaea, 97Yoshihiro Yamaguchi and Masayori Inouye 2.8 Bacterial sRNAs: regulation in stress, 108Marimuthu Citartan, Carsten A. Raabe, Chee-Hock Hoe, Timofey S. Rozhdestvensky, andThean-Hock Tang 2.9 Bacterial stress responses as determinants of antimicrobial resistance, 115Michael Fruci and Keith Poole 2.10 Transposable elements: a toolkit for stress and environmental adaptation in bacteria, 137Anna Ullastres, Miriam Merenciano, Lain Guio, and Josefa González 2.11 CRISPR–Cas system: a new paradigm for bacterial stress response through genome rearrangement, 146Joseph A. Hakim, Hyunmin Koo, Jan D. van Elsas, Jack T. Trevors, and Asim K. Bej 2.12 The copper metallome in prokaryotic cells, 161Christopher Rensing, Hend A. Alwathnani, and Sylvia F. McDevitt 2.13 Ribonucleases as modulators of bacterial stress response, 174Cátia Bárria, Vánia Pobre, Afonso M. Bravo, and Cecília M. Arraiano 2.14 Double-strand-break repair, mutagenesis, and stress, 185Elizabeth Rogers, Raul Correa, Brittany Barreto, María Angélica Bravo Núñez, P.J. Minnick, Diana Vera Cruz, Jun Xia, P.J. Hastings, and Susan M. Rosenberg 2.15 Sigma factor competition in Escherichia coli: kinetic and thermodynamic perspectives, 196Kuldeepkumar Ramnaresh Gupta and Dipankar Chatterji 2.16 Iron homeostasis and iron–sulfur cluster assembly in Escherichia coli, 203Huangen Ding 2.17 Mechanisms underlying the antimicrobial capacity of metals, 215Joe A. Lemire and Raymond J. Turner 2.18 Acyl-homoserine lactone-based quorum sensing in members of the marine bacterial Roseobacter clade: complex cell-to-cell communication controls multiple physiologies, 225Alison Buchan, April Mitchell,W. Nathan Cude, and Shawn Campagna 2.19 Native and synthetic gene regulation to nitrogen limitation stress, 234J örg Schumacher Section 3: One-, two-, and three-component regulatory systems and stress responses, 247 3.1 Two-component systems that control the expression of aromatic hydrocarbon degradation pathways, 249\Tino Krell 3.2 Cross-talk of global regulators in Streptomyces, 257Juan F. Martín, Fernando Santos-Beneit, Alberto Sola-Landa, and Paloma Liras 3.3 NO–H-NOX-regulated two-component signaling, 268Dhruv P. Arora, Sandhya Muralidharan, and Elizabeth M. Boon 3.4 The two-component CheY system in the chemotaxis of Sinorhizobium meliloti, 277Martin Haslbeck 3.5 Stimulus perception by histidine kinases, 282Hannah Schramke, Yang Wang, Ralf Heermann, and Kirsten Jung Section 4: Sigma factors and stress responses, 301 4.1 The extracytoplasmic function sigma factor EcfO protects Bacteroides fragilis against oxidative stress, 303Ivan C. Ndamukong, Samantha Palethorpe, Michael Betteken, and C. Jeffrey Smith 4.2 Regulation of energy metabolism by the extracytoplasmic function (ECF) σ factors of Arcobacter butzleri, 311Irati Martinez-Malaxetxebarria, Rudy Muts, Linda van Dijk, Craig T. Parker, William G. Miller, Steven Huynh,Wim Gaastra, Jos P.M. van Putten, Aurora Fernandez-Astorga, and Marc M.S.M Wösten 4.3 Extracytoplasmic function sigma factors and stress responses in Corynebacterium pseudotuberculosis, 321Thiago L.P. Castro, Nubia Seyffert, Anne C. Pinto, Artur Silva, Vasco Azevedo, and Luis G.C. Pacheco 4.4 The complex roles and regulation of stress response σ factors in Streptomyces coelicolor, 328Jan Kormanec, Beatrica Sevcikova, Renata Novakova, Dagmar Homerova, Bronislava Rezuchova, and Erik Mingyar 4.5 Proteolytic activation of extra cytoplasmic function (ECF) σ factors, 344JessicaL. Hastie and Craig D. Ellermeier 4.6 The ECF family sigma factor σH in Corynebacterium glutamicum controls the thiol-oxidative stress response, 352Tobias Busche and Jörn Kalinowski 4.7 Posttranslational regulation of antisigma factors of RpoE: a comparison between the Escherichia coli and Pseudomonas aeruginosa systems, 361Sundar Pandey, Kyle L. Martins, and Kalai Mathee Section 5: Small noncoding RNAs and stress responses, 369 5.1 Bacterial small RNAs in mixed regulatory circuits, 371Jonathan Jagodnik, DenisThieffry, and Maude Guillier 5.2 Role of small RNAs in Pseudomonas aeruginosa virulence and adaptation, 383Hansi Kumari, Deepak Balasubramanian, and Kalai Mathee 5.3 Physiological effects of posttranscriptional regulation by the small RNA SgrS during metabolic stress inEscherichia coli, 393Gregory R. Richards 5.4 Three rpoS-activating small RNAs in pathways contributing to acid resistance of Escherichia coli, 402Geunu Bak, Kook Han, Daun Kim, Kwang-sun Kim, and Younghoon Lee 5.5 Thermal stress noncoding RNAs in prokaryotes and eukaryotes: a comparative approach, 412Mercedes de la Fuente and José Luis Martínez-Guitarte Section 6: Toxin-antitoxin systems and stress responses, 423 6.1 Epigenetics mediated by restriction modification systems, 425Iwona Mruk and Ichizo Kobayashi 6.2 Toxin–antitoxin systems as regulators of bacterial fitness and virulence, 437Brittany A. Fleming and Matthew A. Mulvey 6.3 Mechanisms of stress-activated persister formation in Escherichia coli, 446Stephanie M. Amato and Mark P. Brynildsen 6.4 Identification and characterization of type II toxin–antitoxin systems in the opportunistic pathogenAcinetobacter baumannii, 454Edita Sûziedéliené, Milda Jurénaité, and Julija Armalyté 6.5 Transcriptional control of toxin–antitoxin expression: keeping toxins under wraps until the time is right, 463Barbara Kℷedzierska and Finbarr Hayes 6.6 Opposite effects of GraT toxin on stress tolerance of Pseudomonas putida, 473Rita Hõrak and Hedvig Tamman Section 7: Stringent response to stress, 479 7.1 Preferential cellular accumulation of ppGpp or pppGpp in Escherichia coli, 481K. Potrykus and M. Cashel 7.2 Global Rsh-dependent transcription profile of Brucella suis during stringent response unravels adaptation to nutrient starvation and cross-talk with other stress responses, 489Stephan Köhler, Nabil Hanna, Safia Ouahrani-Bettache, Kenneth L. Drake, L. Garry Adams, and Alessandra Occhialini 7.3 The stringent response and antioxidant defences in Pseudomonas aeruginosa, 500Gowthami Sampathkumar, Malika Khakimova, Tevy Chan, and Dao Nguyen 7.4 Molecular basis of the stringent response in Vibrio cholerae, 507Shreya Dasgupta, Bhabatosh Das, Pallabi Basu, and Rupak K. Bhadra Section 8: Responses to UV irradiation, 517 8.1 UV stress-responsive genes associated with ICE SXT/R391 group, 519Patricia Armshaw and J. Tony Pembroke 8.2 Altered outer membrane proteins in response to UVC radiation in Vibrio parahaemolyticus and Vibrio alginolyticus, 528Fethi Ben Abdallah 8.3 Ultraviolet-B radiation effects on the community, physiology, and mineralization of magnetotactic bacteria, 532Yingzhao Wang and Yongxin Pan 8.4 Nucleotide excision repair system and gene expression in Mycobacterium smegmatis, 545Angelina Cordone Section 9: SOS and double stranded repair systems and stress, 551 9.1 The SOS response modulates bacterial pathogenesis, 553Darja ¢§Zgur Bertok 9.2 RNAP secondary-channel interactors in Escherichia coli: makers and breakers of genome stability, 561Priya Sivaramakrishnan and Christophe Herman 9.3 How a large gene network couples mutagenic DNA break repair to stress in Escherichia coli, 570Elizabeth Rogers, P.J. Hastings, María Angélica Bravo Núñez, and Susan M. Rosenberg 9.4 Double-strand DNA break repair in mycobacteria, 577Richa Gupta and Michael S. Glickman Section 10: Adaptation to oxidative stress, 587 10.1 Peroxide-sensing transcriptional regulators in bacteria, 58James M. Dubbs and Skorn Mongkolsuk 10.2 Regulation of oxidative stress–related genes implicated in the establishment of opportunistic infections by Bacteroides fragilis, 603Felipe Lopes Teixeira, Regina Maria Cavalcanti Pilotto Domingues, and Leandro Araujo Lobo 10.3 Investigation into oxidative stress response of Shewanella oneidensis reveals a distinct mechanism, 609Jie Yuan, Fen Wan, and Haichun Gao 10.4 An omics view on the response to singlet oxygen, 619Bork A. Berghoff and Gabriele Klug 10.5 Regulators of oxidative stress response genes in Escherichia coli and their conservation in bacteria, 632Herb E. Schellhorn, Mohammad Mohiuddin, Sarah M. Hammond, and Steven Botts 10.6 Hydrogen peroxide resistance in Bifidobacterium animalis subsp. lactis and Bifidobacterium longum, 638Taylor S. Oberg and Jeff R. Broadbent Section 11: Adaptation to osmotic stress, 647 11.1 Interstrain variation in the physiological and transcriptional responses of Pseudomonas syringae to osmotic stress, 649Gwyn A. Beattie, Chiliang Chen, Lindsey Nielsen, and Brian C. Freeman 11.2 Management of osmotic stress by Bacillus subtilis: genetics and physiology, 657Tamara Hoffmann and Erhard Bremer 11.3 Hyperosmotic response of Streptococcus mutans: from microscopic physiology to transcriptomic profile, 677Lu Wang and Xin Xu 11.4 Defective ribosome maturation or function makes Escherichia coli cells salt-resistant, 687Hyouta Himeno, Takefusa Tarusawa, Shion Ito, and Simon Goto Section 12: Dessication tolerance and drought stress, 693 12.1 Consequences of elevated salt concentrations on expression profiles in the rhizobium S. meliloti 1021 likely involved in heat and desiccation stress, 695Jan A.C. Vriezen, Caroline M. Finn, and Klaus Nüsslein 12.2 Genes involved in the formation of desiccationresistant cysts in Azotobacter vinelandii, 709Guadalupe Espín 12.3 Osmotic and desiccation tolerance in Escherichia coli O157:H7 and Salmonella enterica requires rpoS (σ38), 716Zach Pratt, Megan Shiroda, Andrew J. Stasic, Josh Lensmire, and C.W. Kaspar 12.4 Desiccation of Salmonella enterica induces cross-tolerance to other stresses, 725Shlomo Sela (Saldinger) and Chellaiah Edward Raja Index, i1 VOLUME 2 Preface, xiii Acknowledgements, xiv List of contributors, xv Section 13: Heat shock responses, 737 13.1 Heat shock response in bacteria with large genomes: lessons from rhizobia, 739Ana Alexandre and Solange Oliveira 13.2 Small heat shock proteins in bacteria, 747Martin Haslbeck 13.3 Transcriptome analysis of bacterial response to heat shock using next-generation sequencing, 754Kok-Gan Chan 13.4 Comparative analyses of bacterial transcriptome reorganisation in response to temperature increase, 757Bei-Wen Ying and Tetsuya Yomo 13.5 Participation of Ser–Thr protein kinases in regulation of heat stress responses in Synechocystis, 766Anna A. Zorina, Galina V. Novikova, and Dmitry A. Los Section 14: Chaperonins and stress, 781 14.1 GroEL/ES chaperonin: unfolding and refolding reactions, 783Victor V. Marchenkov, Nataliya A. Ryabova, Olga M. Selivanova, and Gennady V. Semisotnov 14.2 Functional comparison between the DnaK chaperone systems of Streptococcus intermedius and Escherichia coli, 791Toshifumi Tomoyasu and Hideaki Nagamune 14.3 Coevolution analysis illuminates the evolutionary plasticity of the chaperonin system GroES/L, 796Mario A. Fares 14.4 ClpL ATPase: a novel chaperone in bacterial stress responses, 812Pratick Khara and Indranil Biswas 14.5 Duplicated groEL genes inMyxococcus xanthus DK1622, 820Yan Wang, Xiao-jing Chen, and Yue-zhong Li Section 15: Cold shock responses, 827 15.1 Gene regulation by cold shock proteins via transcription antitermination, 829Sangita Phadtare and Konstantin Severinov 15.2 Metagenomic analysis of microbial cold stress proteins in polar lacustrine ecosystems, 837Hyunmin Koo, Joseph A. Hakim, and Asim K. Bej 15.3 Role of two-component systems in cold tolerance of Clostridium botulinum, 845Yâgmur Derman, Elias Dahlsten, and Hannu Korkeala 15.4 Cold shock CspA protein production during periodic temperature cycling in Escherichia coli, 854David Stopar and Tina Ivancic 15.5 Cold shock response in Escherichia coli: a model system to study posttranscriptional regulation, 859Anna Maria Giuliodori 15.6 New insight into cold shock proteins: RNA-binding proteins involved in stress response and virulence, 873Charlotte Michaux and Jean-Christophe Giard 15.7 Light regulation of cold stress responses in Synechocystis, 881Kirill S. Mironov and Dmitry A. Los 15.8 Escherichia coli cold shock gene profiles in response to overexpression or deletion of CsdA, RNase R, andPNPase and relevance to low-temperature RNA metabolism, 890Sangita Phadtare Section 16: Adaptation to acid stress, 897 16.1 Acid-adaptive responses of Streptococcus mutans, and mechanisms of integration with oxidative stress, 899Robert G. Quivey Jr., Roberta C. Faustoferri, Brendaliz Santiago, Jonathon Baker, Benjamin Cross, and Jin Xiao 16.2 Acid survival mechanisms in neutralophilic bacteria, 911Eugenia Pennacchietti, Fabio Giovannercole, and Daniela De Biase 16.3 Two-component systems in sensing and adapting to acid stress in Escherichia coli, 927Yoko Eguchi and Ryutaro Utsumi 16.4 Slr1909, a novel two-component response regulator involved in acid tolerance in Synechocystis sp. PCC 6803, 935Lei Chen, Qiang Ren, Jiangxin Wang, and Weiwen Zhang 16.5 Comparative mass spectrometry–based proteomics to elucidate the acid stress response in Lactobacillusplantarum, 944Tiaan Heunis, Shelly Deane, and Leon M.T. Dicks Section 17: Adaptation to nitrosative stress, 95317.1 Transcriptional regulation by thiol-based sensors of oxidative and nitrosative stress, 955Timothy Tapscott, Matthew A. Crawford, and Andr´es Vázquez-Torres 17.2 Haemoglobins of Mycobacterium tuberculosis and their involvement in management of environmental stress, 967Kanak L. Dikshit 17.3 What is it about NO that you don’t understand? The role of heme and HcpR in Porphyromonas gingivalis’s response to nitrate (NO3), nitrite (NO2), and nitric oxide (NO), 976Janina P. Lewis and Benjamin R. Belvin 17.4 Di-iron RICs: players in nitrosative-oxidative stress defences, 989Lígia S. Nobre and Lí©¥gia M. Saraiva 17.5 The Vibrio cholerae stress response: an elaborate system geared toward overcoming host defenses during infection, 997Karl-Gustav Rueggeberg and Jun Zhu 17.6 Ensemble modeling enables quantitative exploration of bacterial nitric oxide stress networks, 1009Jonathan L. Robinson and Mark P. Brynildsen Section 18: Adaptation to cell envelope stress, 1015 18.1 The Cpx inner membrane stress response, 1017Randi L. Guest and Tracy L. Raivio 18.2 New insights into stimulus detection and signal propagation by the Cpx-envelope stress system, 1025Patrick Hoernschemeyer and Sabine Hunke 18.3 Promiscuous functions of cell envelope stress-sensing systems in Klebsiella pneumoniae and Acinetobacterbaumannii, 1031Vijaya Bharathi Srinivasan and Govindan Rajamohan 18.4 Influence of BrpA and Psr on cell envelope homeostasis and virulence of Streptococcus mutans, 1043Zezhang T.Wen, Jacob P. Bitoun, Sumei Liao, and Jacqueline Abranches 18.5 Modulators of the bacterial two-component systems involved in envelope stress, transport, and virulence, 1055Rajeev Misra Section 19: Iron homeostasis, 1065 19.1 Iron homeostasis and environmental responses in cyanobacteria: regulatory networks involving Fur, 1067María Luisa Peleato, María Teresa Bes, and María F. Fillat 19.2 Interplay between O2 and iron in gene expression: environmental sensing by FNR, ArcA, and Fur in bacteria, 1079Bryan Troxell and Hosni M. Hassan 19.3 The iron–sulfur cluster biosynthesis regulator IscR contributes to iron homeostasis and resistance tooxidants in Pseudomonas aeruginosa, 1090Adisak Romsang, James M. Dubbs, and Skorn Mongkolsuk 19.4 Transcriptional analysis of iron-responsive regulatory networks in Caulobacter crescentus, 1103José F. da Silva Neto 19.5 Protein–protein interactions regulate the release of iron stored in bacterioferritin, 1109Huili Yao, YanWang, and Mario Rivera 19.6 Protein dynamics and ion traffic in bacterioferritin function: a molecular dynamics simulation study onwild-type and mutant Pseudomonas aeruginosa BfrB, 1118Huan Rui, Mario Rivera, and Wonpil Im Section 20: Metal resistance, 1131 20.1 Nickel toxicity, regulation, and resistance in bacteria, 1133Lee Macomber and Robert P. Hausinger 20.2 Metabolic networks to counter Al toxicity in Pseudomonas fluorescens: a holistic view, 1145Christopher Auger, Nishma D. Appanna, and Vasu D. Appanna 20.3 Genomics of the resistance to metal and oxidative stresses in cyanobacteria, 1154Corinne Cassier-Chauvat and Franck Chauvat 20.4 Cross-species transcriptional network analysis reveals conservation and variation in response to metal stress in cyanobacteria, 1165Jiangxin Wang, Gang Wu, Lei Chen, and Weiwen Zhang 20.5 The extracytoplasmic function sigma factor–mediated response to heavy metal stress in Caulobacter crescentus, 1171Rogério F. Lourenco and Suely L. Gomes 20.6 Metal ion toxicity and oxidative stress in Streptococcus pneumoniae, 1184Christopher A. McDevitt, Stephanie L. Begg, and James C. Paton Section 21: Quorum sensing, 1195 21.1 Quorum sensing and bacterial social interactions in biofilms: bacterial cooperation and competition, 1197Yung-Hua Li and Xiao-Lin Tian 21.2 Recent advances in bacterial quorum quenching, 1206Kok-Gan Chan, Wai-Fong Yin, and Kar-Wai Hong 21.3 LuxR-type quorum-sensing regulators that are antagonized by cognate pheromones, 1221Stephen C. Winans, Ching-Sung Tsai, Gina T. Ryan, Ana Lidia Flores-Mireles, Esther Costa, Kevin Y. Shih, Thomas C.Winans, Youngchang Kim, Robert Jedrzejczak, and Gekleng Chhor 21.4 Adaptation to environmental stresses in Streptococcus mutans through the production of its quorum-sensing peptide pheromone, 1232Delphine Dufour, Vincent Leung, and Céline M. Lévesque 21.5 Quorum sensing in Bacillus cereus in relation to cysteine metabolism and the oxidative stress response, 1242Eugénie Huillet and Michel Gohar Section 22: Chemotaxis and biofilm formation, 1253 22.1 The flagellum as a sensor, 1255Rasika M. Harshey 22.2 Flagellar motility and fitness in xanthomonads, 1265Marie-Agnès Jacques, Jean-Françis Guimbaud, Martial Briand, Arnaud Indiana, and Armelle Darrasse 22.3 Understanding Listeriamonocytogenes biofilms: perspectives into mechanisms of adaptation and regulation under stress conditions, 1274Lizziane Kretli Winkelströter, Fernanda Barbosa dos Reis-Teixeira, Gabriela Satti Lameu, and Elaine Cristina Pereira De Martinis 22.4 Biofilm formation and environmental signals in Bordetella, 1279Tomoko Hanawa 22.5 Biofilm formation by rhizobacteria in response to water-limiting conditions, 1287Pablo Bogino, Fiorela Nievas, and Walter Giordano 22.6 Stress conditions triggering mucoid-to-nonmucoid morphotype variation in Burkholderia, and effects onvirulence and biofilm formation, 1295Leonilde M. Moreira, Inês N. Silva, Ana S. Ferreira, and Mário R. Santos 22.7 Effect of environmental conditions present in the fishery industry on the biofilm-forming ability of Staphylococcus aureus, 1304Daniel Vázquez-Sánchez 22.8 Biofilm development and stress response in the cholera bacterium, 1310Anisia J. Silva and Jorge A. Benitez 22.9 Outer membrane vesicle secretion: from envelope stress to biofilm formation, 1322Thomas Baumgarten and Hermann J. Heipieper Section 23: Viable but nonculturable (VBNC) cells, 1329 23.1 Resuscitation of Vibrios fromthe viable but nonculturable state is induced by quorum-sensing molecules, 1331Mesrop Ayrapetyan, Tiffany C. Williams, and James D. Oliver 23.2 Differential resuscitative effects of pyruvate and its analogs on VBNC (viable but nonculturable)Salmonella, 1338Fumio Amano 23.3 Environmental persistence of Shiga toxin–producing E. coli, 1346Philipp Aurass and Antje Flieger 23.4 Of a tenacious and versatile relic: the role of inorganic polyphosphate (poly-P) metabolism in the survival, adaptation, and virulence of Campylobacter jejuni, 1354Issmat I. Kassem and Gireesh Rajashekara Index, i1

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Book SynopsisKnowledge of the evolutionary history of birds has much improved in recent decades. Fossils from critical time periods are being described at unprecedented rates and modern phylogenetic analyses have provided a framework for the interrelationships of the extant groups. This book gives an overview of the avian fossil record and its paleobiological significance, and it is the only up-to-date textbook that covers both Mesozoic and more modern-type Cenozoic birds in some detail. The reader is introduced to key features of basal avians and the morphological transformations that have occurred in the evolution towards modern birds. An account of the Cenozoic fossil record sheds light on the biogeographic history of the extant avian groups and discusses fossils in the context of current phylogenetic hypotheses. This review of the evolutionary history of birds not only addresses students and established researchers, but it may also be a useful source of information for anyone else with an inTrade Review"Of all the works on the evolution of birds, it is the most modern, complete summary, with just enough fossil figures (no reconstructions), including 16 central color pencils, morphological descriptions and of genealogical trees. A mine of reflections that illuminate our current settlements" Ornithos, 24:5 (2017)Table of ContentsForeword ix Preface xi Acknowledgments xiii Chapter 1 An Introduction to Birds, the Geological Settings of Their Evolution, and the Avian Skeleton 1 Birds Are Evolutionarily Nested within Theropod Dinosaurs 2 The Geological Settings of Avian Evolution in a Nutshell 4 Characteristics of the Avian Skeleton 6 Chapter 2 The Origin of Birds 18 Archaeopteryx: The German “Urvogel” and Its Bearing on Avian Evolution 19 The Closest Maniraptoran Relatives of Birds 22 Feather Evolution 32 The Origin of Avian Flight 37 Chapter 3 The Mesozoic Flight Way towards Modern Birds 43 Jeholornithids: Early Cretaceous Long-Tailed Birds 44 Confuciusornis, Sapeornis, and Kin: Basal Birds with a Pygostyle 45 Ornithothoraces and the Origin of Sustained Flapping Flight Capabilities 50 The Ornithuromorpha: Refinement of Modern Characteristics 55 Ornithurae and the Origin of Modern Birds 59 Chapter 4 Mesozoic Birds: Interrelationships and Character Evolution 64 The Interrelationships of Mesozoic Birds: Controversial Phylogenetic Placements and Well-Supported Clades 65 Character Evolution in Mesozoic Birds 68 Ontogenetic Development of Mesozoic Birds 81 Chapter 5 The Interrelationships and Origin of Crown Group Birds (Neornithes) 84 Phylogenetic Interrelationships of Neornithine Birds 85 The Mesozoic Fossil Record of Neornithine-Like and Neornithine Birds 88 Chapter 6 Palaeognathous Birds (Ostriches, Tinamous, and Allies) 94 The Interrelationships of Extant Palaeognathae 95 Early Cenozoic Palaeognathous Birds of the Northern Hemisphere 95 Long-Winged Ostriches, Rheas, and Tinamous 97 Short-Winged Palaeognathous Birds 101 Biogeography: A Textbook Example of Gondwanan Vicariance Has Been Dismantled 105 Chapter 7 Galloanseres: “Fowl” and Kin 107 Galliformes: From Herbivorous Forest Dwellers to Seed Eaters of Open Landscapes 108 The Waterfowl 113 Gastornithids: Giant Herbivorous Birds in the Early Paleogene of the Northern Hemisphere 118 Dromornithids (Mihirungs or Thunderbirds): Gastornis-Like Birds from Australia 120 Pelagornithids: Bony-Toothed Birds 121 Chapter 8 The “Difficult-to-Place Groups”: Biogeographic Surprises and Aerial Specialists 125 The Columbiform Birds: Doves, Sandgrouse, … and Mesites? 126 The Hoatzin: A South American Relict Species 127 Turacos and Cuckoos 129 Bustards 131 The “Wonderful” Mirandornithes, or How Different Can Sister Taxa Be? 132 Strisores: The Early Diversification of Nocturnal Avian Insectivores 136 Chapter 9 Shorebirds, Cranes, and Relatives 147 Charadriiformes: One of the Most Diverse Groups of Extant Birds 148 From Rail to Crane 156 Chapter 10 Aequornithes: Aquatic and Semi-Aquatic Carnivores 161 Loons: Foot-Propelled Divers of the Northern Hemisphere 162 Pelagic Tubenoses and Albatrosses 164 Penguins: More Than 60 Million Years of Flightlessness 168 The Polyphyletic “Pelecaniformes” and “Ciconiiformes” 174 Late Cenozoic Turnovers in Marine Avifaunas 187 Chapter 11 Cariamiforms and Diurnal Birds of Prey 189 Seriemas and Allies: Two Species Now, Many More in the Past 190 Diurnal Birds of Prey: Multiple Cases of Convergence among Raptorial Birds 197 Chapter 12 The Cenozoic Radiation of Small Arboreal Birds 204 The Courol and Mousebirds: Two African Relict Groups 205 The Long Evolutionary History of Owls 210 Parrots and Passerines: An Unexpected Sister Group Relationship and Its Potential Evolutionary Implications 212 Trogons, Rollers, and Woodpeckers: Cavity-Nesters with Diverse Foot Morphologies 223 Chapter 13 Insular Avifaunas Now and Then, on Various Scales 233 Islands and Isolated Continents as Refugia 234 The Evolution of Flightlessness in Predator-Free Environments 235 Insular Gigantism and Islands as Cradles of Unusual Morphologies 241 Glossary 245 References 248 Index 289

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Book SynopsisInfectious diseases constitute a major portion of illnesses worldwide, and microbiology is a main pillar of clinical infectious disease practice. Knowledge of viruses, bacteria, fungi, and parasites is integral to practice in clinical infectious disease.Table of ContentsPreface ix Acknowledgments xi Section I: Laboratory methods in clinical microbiology 1 1 Introduction 3 2 Microbiology laboratory methods 12 Section II: Prions and viruses 47 3 Prions 49 4 General virology 51 5 DNA viruses (excluding hepatitis B virus) 55 6 RNA viruses (excluding hepatitis viruses, arthropod‐borne viruses, and bat and rodent excreta viruses) 74 7 Hepatitis viruses 99 8 Arthropod‐borne viruses (arboviruses), hantaviruses, arenaviruses, and filoviruses 104 Section III: Bacteriology 121 9 Bacteriology 123 10 Gram‐positive cocci 141 11 Gram‐negative cocci 162 12 Gram‐positive rods 168 13 Gram‐negative rods 178 14 Anaerobic bacteria 205 15 Mycoplasmas, Chlamydiae, Rickettsiae, and Ehrlichiae 217 16 Spirochetes 229 17 Mycobacteria 243 Section IV: Mycology 259 18 Fungi 261 19 Yeasts 268 20 Dimorphic endemic fungi 277 21 Molds 289 Section V: Parasitology 303 22 Parasitology 305 23 Intestinal protozoa 312 24 Tissue and blood protozoa 328 25 Helminths 358 26 Ectoparasites 389 Section VI: Clinical cases 397 27 Cases 399 Section VII: Appendices 431 Appendix 1: Taxonomy of infectious agents infecting humans and lists of infectious agents according to their source 433 Appendix 2: Clinical syndromes and their causative organisms 449 Appendix 3: General references and online resources 455 Index 457

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Book SynopsisSeascape Ecology provides a comprehensive look at the state-of-the-science in the application of landscape ecology to the seas and provides guidance for future research priorities.Table of ContentsContributors xiii Foreword xix Preface xxiii Part I Spatial Patterning in the Sea 1 1 Introducing Seascape Ecology 3Simon J. Pittman 1.1 Introduction 3 1.2 Landscape Ecology and the Emergence of Seascape Ecology 4 1.3 What is a Seascape? 6 1.3.1 The Patch-Matrix and Patch-Mosaic Models of Seascape Structure 8 1.3.2 The Spatial Gradient Model of Seascape Structure 11 1.3.3 Combining Spatial Gradients and Patch Mosaics 12 1.3.4 Chemical Seascapes and Ocean Soundscapes 13 1.4 Why Scale Matters in Seascape Ecology 14 1.5 Seascape Ecology can Inform Marine Stewardship 16 1.6 Conclusions and Future Directions 18 References 19 2 Mapping and Quantifying Seascape Patterns 27Bryan Costa, BrianWalker and Jennifer A. Dijkstra 2.1 Introduction 27 2.2 Defining Seascape Applications 30 2.3 Identifying Scales for Seascape Mapping 31 2.4 Sensor Selection for Seascape Mapping 33 2.4.1 Passive and Active Sensors 34 2.4.2 Environmental Conditions Limiting Passive and Active Sensors 36 2.5 Representing Patterns in Seascape Maps 37 2.5.1 The Continuous Gradient Concept 37 2.5.2 The Patch-Mosaic Model 39 2.5.3 Spatial Surrogates (Proxies) 42 2.6 Quantifying Seascape Structure 43 2.6.1 Sensitivity to Scale 45 2.7 Applications of Seascape Maps and Spatial Pattern Metrics 45 2.7.1 Understanding Uncertainty in Seascape Maps 47 2.8 Conclusions and Future Research Priorities 48 References 49 3 Pelagic Seascapes 57Kylie L. Scales, Diego Alvarez-Berastegui, Clare Embling and Simon Ingram 3.1 Introduction 57 3.2 Pattern and Process in the Pelagic Realm 58 3.2.1 Broad-scale Biogeographic Provinces 60 3.2.2 Finer Scale Patchiness and Patch Dynamics 61 3.2.3 Ecoclines and Ecotones in Pelagic Seascapes 62 3.2.4 Beneath the Surface: the Vertical Dimension of Pelagic Seascapes 64 3.3 Spatial Pattern Metrics for Pelagic Seascapes 66 3.3.1 Patch Mosaic Metrics 67 3.3.2 Surface Model Metrics – Identifying Ecoclines and Ecotones 67 3.3.3 Lagrangian Approaches 69 3.4 Spatial Ecoinformatics in the Pelagic Realm: from Physics to Predators 71 3.4.1 Broad-scale Migrations across Pelagic Seascapes 71 3.4.2 Linking AnimalMovements to the Spatial Patterning of Pelagic Seascapes 72 3.4.3 Incorporating the Vertical Dimension in Spatial Ecoinformatics 73 3.5 Conclusions and Future Research Priorities 74 3.6 Glossary 75 References 76 4 Scale and Scaling in Seascape Ecology 89David C. Schneider 4.1 Introduction 89 4.1.1 The Development of the Concept of Scale in the Twentieth Century 90 4.1.2 Prevalence and Usage of ‘Scale‘ in the Scientific Literature 91 4.1.3 Definition of Scale 94 4.2 Expressions of Scale 95 4.2.1 Graphical Expression of Scale 95 4.2.2 Graphical Expression of Scale in Research Planning 98 4.2.3 Formal Expression of Scale: Scope, Similarity and Power Laws 98 4.2.4 Scaling Manoeuvres 101 4.2.5 Ratio of Rates in Research Planning 104 4.3 Spatial and Temporal Scaling in Estimating Uncertainty 107 4.4 Spatial and Temporal Scaling in the Pelagic and Benthic Realms 107 4.5 Looking to the Future: Scaling Concepts and Practice in Seascape Ecology 108 4.5.1 From Useful Fictions to Calculation 108 4.5.2 From Comparative to Confirmatory Modes of Investigation 109 4.5.3 From Hypothesis Testing to Likelihood 110 4.5.4 From Scaling on a Mosaic to Scaling on the Continuum 111 4.6 From Ceteris Paribus to DimensionalThinking 112 4.7 Acknowledgements 112 References 113 Part II Linking Seascape Patterns and Ecological Processes 119 5 Ecological Consequences of Seagrass and Salt-Marsh Seascape Patterning on Marine Fauna 121Christoffer Bostrom, Simon J. Pittman and Charles Simenstad 5.1 Introduction 121 5.1.1 Seagrasses and Salt Marshes: Global Distributions and Ecosystem Functions 122 5.2 Structural Processes and Change in Coastal Seascapes 122 5.2.1 Processes Creating and Maintaining Seagrass Seascapes 125 5.2.2 Processes Creating and Maintaining Salt-Marsh Seascapes 125 5.2.2.1 Tidal Channel Networks in Salt Marshes 128 5.3 Ecological Consequences of Seascape Structure 128 5.3.1 Seagrass Patch-size Effects on Epifauna and Fish 128 5.3.2 Patch Edges: Conceptual Framework and Application 130 5.3.2.1 Seagrass Edge Effects on Faunal Recruitment and Distribution 132 5.3.3 Effects of Salt-Marsh Patch Size, Edges and Connectivity on Faunal Patterns and Processes 133 5.3.4 Faunal Linkages between Salt Marshes and Seagrass Meadows 135 5.4 Challenges and Opportunities in Seascape Ecology 138 References 140 6 Seascape Patch Dynamics 153Emma L. Jackson, Rolando O. Santos-Corujo and Simon J. Pittman 6.1 Introduction 153 6.2 From Patch Dynamics to Seascape Ecology 155 6.3 Scale 158 6.4 Factors Influencing Seascape Patchiness 160 6.5 Mapping and Quantifying Seascape Change 163 6.5.1 Habitat Mapping for Change Analysis 164 6.5.2 Characterization of Spatial Patterns 166 6.5.2.1 Continuous metrics and surface analysis 167 6.5.2.2 Metrics, Scale and Sensitivity Analysis 168 6.5.2.3 Quantifying Seascape Change 168 6.5.3 Seascape Habitat Loss versus Fragmentation 170 6.5.4 Seascape Modelling 173 6.6 The Future of Seascape Dynamics Research 175 References 177 7 AnimalMovements through the Seascape: Integrating Movement Ecology with Seascape Ecology 189Simon J. Pittman, Benjamin Davis and Rolando O. Santos-Corujo 7.1 Introduction 189 7.1.1 Why AnimalMovement is Central to Seascape Ecology 191 7.1.2 Advances in Movement Ecology and its Application in Marine Systems 193 7.1.3 Tracking and Mapping Capabilities 194 7.2 Using Animal Movements to Scale Ecological Studies 196 7.2.1 Building Movement Scales into Conceptual and Operational Frameworks 199 7.2.1.1 Component 1: Build a ConceptualModel 199 7.2.1.2 Component 2: Selecting Scale 199 7.2.1.3 Component 3: Tools Identification 201 7.3 Advances in the Visualization and Quantification of Space-use Patterns 201 7.3.1 Estimating and Mapping Utilization Distributions 201 7.3.2 Analysing Spatiotemporal Utilization Patterns 204 7.3.3 VisualizingMovement Patterns across Three Spatial Dimensions 206 7.4 Linking AnimalMovement Patterns to Seascape Patterns 208 7.4.1 Linking IndividualMovement Trajectories to Seascape Structure 209 7.4.2 IndividualMovement and Seascape Connectivity 211 7.4.3 Linking Species Interactions and Physiology with Movements across Seascapes 212 7.4.4 Experimental Seascapes to Investigate Animal Response to Seascape Patterns 214 7.4.5 Mechanistic Models 215 7.5 Implications of Animal-Seascape Understanding for Marine Stewardship 215 References 217 8 Using Individual-based Models to Explore Seascape Ecology 229Kevin A. Hovel and Helen M. Regan 8.1 Introduction 229 8.1.1 What are IBMs? 229 8.2 Why use IBMs to Study Seascape Ecology? 231 8.2.1 The Effects of Habitat Structure on Populations are Consequences of Organismal Behaviour 231 8.2.2 IBMs Allow for Extensive Manipulation of Seascapes 235 8.2.3 IBMs can be Used to Test for Ecological Effects of Habitat Configuration versus Habitat Amount 239 8.2.4 IBMs Allow Tests of How Seascape Change Influences Ecological Processes 241 8.2.5 IBMs Allow the Coupling of Processes Operating over Different Scales 245 8.3 Data for Parameterizing Seascape Ecology IBMs 246 8.3.1 Parameterization 246 8.3.2 Movement and Habitat Selection 247 8.3.3 Seascape and Habitat Structure 248 8.3.4 Other Factors 249 8.4 Challenges and Future Directions in Using IBMs to Explore Seascapes 249 References 251 Part III Seascape Connectivity 259 9 Connectivity in Coastal Seascapes 261Andrew D. Olds, Ivan Nagelkerken, Chantal M. Huijbers, Ben L. Gilby, Simon J. Pittman and Thomas A. Schlacher 9.1 Introduction 261 9.2 Global Synthesis of Connectivity Research 261 9.2.1 ResearchTheme 263 9.2.2 Geographical Distribution 264 9.2.3 Biological and Functional Consequences 266 9.2.4 Connectivity is Scale Dependent 267 9.3 Quantifying Connectivity: Advances in Key Tools and Techniques 268 9.3.1 Tags and Telemetry 268 9.3.2 Ecogeochemical Markers 269 9.3.3 Genetics 269 9.4 Application of Seascape Connectivity to Coastal Seascapes: Focal Topics 270 9.4.1 Focal Topic 1: Fish Movements Connecting Tropical Coastal Seascapes 270 9.4.2 Focal Topic 2: Connectivity across the Land-Sea Interface 273 9.5 Integrating Connectivity into Marine Spatial Planning 275 9.6 Conclusions and Future Research Priorities 279 References 280 10 Networks for Quantifying and Analysing Seascape Connectivity 293Eric A. Treml and Johnathan Kool 10.1 Introduction 293 10.1.1 Structural Connectivity 295 10.1.2 Functional Connectivity 296 10.1.3 Realized Connectivity 296 10.2 Network Models of Connectivity: Representing Pattern and Process 297 10.2.1 Defining Nodes and Links 297 10.3 Modelling Marine Population Connectivity 300 10.3.1 Empirical Estimates of Marine Population Connectivity 301 10.4 Network Analysis of Marine Population Connectivity 303 10.4.1 Node and Neighbourhood-level Metrics 305 10.4.2 Components, Subgraphs and Clusters 306 10.4.3 Graph-level Metrics 306 10.4.4 Insights from Classic Networks 307 10.4.5 Planar Networks 308 10.4.6 Random Networks 308 10.4.7 Scale-free Networks 308 10.4.8 Small-world Networks 309 10.5 Case Study in Marine Connectivity: Hawaiian Islands 309 10.6 Conclusions and Future Research Priorities 312 10.7 Acknowledgements 313 References 313 11 Linking Landscape and Seascape Conditions: Science, Tools andManagement 319Kirsten L. L. Oleson, Kim A. Falinski, Donna-marie Audas, Samantha Coccia-Schillo,Paul Groves, Lida Teneva and Simon J. Pittman 11.1 Introduction 319 11.2 Landscape Ecology as a Guiding Framework for Integrated Land-sea Management 322 11.3 Modelling and Evaluating the Connections between Land and Sea 324 11.3.1 Measuring Threat Exposure from Land-based Sources 324 11.3.2 SpatialModelling of Land-Sea Processes 325 11.3.2.1 Spatial Proxies 325 11.3.2.2 Hydrological Models 325 11.3.2.3 Nearshore Dynamics 326 11.3.2.4 Ecological Response and Social-ecological Systems Models 327 11.3.3 Decision Analysis and Support 329 11.4 Case Studies 330 11.4.1 Hawai’i 330 11.4.1.1 Estimating Spatial Patterns of Erosion from Land Cover Change and Exposure of Reefs in Maui 331 11.4.2 Caribbean 334 11.4.2.1 Summit to Sea Runoff Modelling for St John, US Virgin Islands 334 11.4.2.2 Land-sea Decision Support Modelling for the Northeast Marine Corridor, Puerto Rico 336 11.4.3 Australia 339 11.4.3.1 Edgecumbe Bay ReceivingWaters (Gregory and Eden Lassie Creek Sub-basins) 342 11.5 Towards Applying Landscape Ecology to Land-Sea Modelling and Management 347 References 350 Part IV People and Seascapes 365 12 Advancing a Holistic Systems Approach in Applied Seascape Ecology 367Simon J. Pittman, Chris A. Lepczyk, Lisa M.Wedding and Camille Parrain 12.1 Introduction 367 12.1.1 What can Landscape Ecology Offer? 369 12.1.2 A Shift towards a more Holistic Systems Approach for Marine Stewardship 370 12.2 People as Part of the Seascape 373 12.3 How Holistic Systems Science can Help Seascape Ecology 375 12.3.1 Properties of an Ecological Systems Approach 376 12.3.2 The Rise ofWhole-of-System Modelling 377 12.4 Connecting Seascape Patterns to Human Health, Livelihoods and Wellbeing 379 12.5 Conclusions and Future Research Priorities 381 References 384 13 Human Ecology at Sea:Modelling andMapping Human-Seascape Interactions 391Steven Saul and Simon J. Pittman 13.1 Introduction 391 13.2 Seascape Ecology, Spatial Patterns and Scale 393 13.2.1 Scale and Scaling 395 13.3 Human Use Data Types and Geographical Information Systems 396 13.3.1 Mapping Human Behaviour across the Seascape 397 13.3.1.1 Remote Sensing 398 13.3.1.2 Participatory Mapping and Spatial Analysis 401 13.3.1.3 Social Sensing 402 13.3.1.4 Mapping Ecosystem Services 402 13.4 Modelling Human-Seascape Interactions with a Systems Approach 403 13.4.1 Custom-built StatisticalModels 405 13.4.2 Predefined Statistical Routines 406 13.4.3 Discrete Choice Models 407 13.4.4 Simulation Modelling 408 13.4.5 Agent-based Models 411 13.4.6 Pattern-orientedModelling 412 13.5 Conclusions and Future Research Priorities 415 References 418 14 Applying Landscape Ecology for the Design and Evaluation of Marine Protected Area Networks 429Mary A. Young, Lisa M.Wedding and Mark H. Carr 14.1 Introduction 429 14.2 Applying Landscape Ecology Principles in the Marine Environment 430 14.3 Case Study: Applying Landscape Ecology to Evaluate a Network of MPAs in California 438 14.3.1 California Seafloor Data Sets 439 14.3.2 MPA Goal: Habitat Replication and Representativeness 441 14.3.3 MPA Goal: Protect Diversity and Abundance of Marine Life 442 14.3.4 MPA Goal: Reduce Movement across Boundaries 444 14.4 Synthesis 448 14.4.1 Mapping Technologies 448 14.4.2 MPA Effects on Biodiversity and Populations 449 14.4.3 Scale of Interaction between Species and Environment 449 14.4.4 Across-system Interactions 450 14.4.5 Population Connectivity 450 14.5 Conclusions and Future Research Priorities 451 References 452 15 Seascape Economics: Valuing EcosystemServices across the Seascape 465Edward B. Barbier 15.1 Introduction 465 15.2 Habitat Connectivity and Seascape Goods and Services 467 15.3 Valuing Seascape Goods and Services 468 15.4 Example of a Mangrove-Coral Reef Seascape 472 15.5 Conclusions and Future Research Priorities 476 References 478 Part V Epilogue 483 16 Landscape Ecologists’ Perspectives on Seascape Ecology 485Simon J. Pittman, JohnA. Wiens, Jianguo Wu and Dean L. Urban 16.1 Introduction 485 16.2 From Landscapes to Seascapes (and Back Again) 485 16.3 Seascape Ecology and Landscape Ecology: Distinct, Related and Synergistic 487 16.3.1 Landscape Ecology 488 16.3.2 Seascape Ecology 488 16.3.3 How can Landscape and Seascape Ecology Interact with Each Other? 489 16.4 Seascape Ecology 491 References 493 Index 495

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Book SynopsisBrings a fresh point of view to the current state of correlative imaging and the future of the field This book provides contributions from international experts on correlative imaging, describing their vision of future developments in the field based on where it is today. Starting with a brief historical overview of how the field evolved, it presents the latest developments in microscopy that facilitate the correlative workflow. It also discusses the need for an ideal correlative probe, applications in proteomic and elemental analysis, interpretation methods, and how correlative imaging can incorporate force microscopy, soft x-ray tomography, and volume electron microscopy techniques. Work on placing individual molecules within cells is also featured. Correlative Imaging: Focusing on the Future offers in-depth chapters on: correlative imaging from an LM perspective; the importance of sample processing for correlative imaging; correlative light and volumeTable of ContentsList of Contributors xi Preface xiii 1 It’s a Small, Small World: A Brief History of Biological Correlative Microscopy 1Christopher J. Guérin, Nalan Liv, and Judith Klumperman 1.1 It All Began with Photons 1 1.2 The Electron Takes Its Place 2 1.3 Putting It Together, 1960s to 1980s 3 1.4 CLEM Matures as a Scientific Tool 1990 to 2017 4 Acknowledgments 13 References 13 2 Challenges for CLEM from a Light Microscopy Perspective 23Kurt Anderson, Tommy Nilsson, and Julia Fernandez‐Rodriguez 2.1 Introduction 23 2.1.1 Electron and Light Microscopy 23 2.1.2 Correlative Microscopy: Two Cultures Collide 25 2.2 Microscopy Multiculturalism 26 2.2.1 When Fluorescence Light Microscopy Resolution is Not Enough 26 2.2.2 The Fluorescence Microscopy (FM), Needle/Haystack Localization 27 2.2.3 Electron Microscopy, Visualizing the Ultrastructure 27 2.2.4 Finding Coordinates 28 2.3 Bridging the Gap between Light and Electron Microscopy 29 2.3.1 Finding the Same Cell Structure in Light and Electron Microscopes 29 2.3.2 Making the Fluorescence Labels Visible in the Electron Microscope 29 2.3.3 Visualizing Membrane Trafficking Using CLEM 30 2.4 Future CLEM Applications and Modifications 31 2.4.1 Correlative Reflection Contrast Microscopy and Electron Microscopy in Tissue Sections 31 2.4.2 Dynamic and Functional Probes for CLEM 32 References 34 3 The Importance of Sample Processing for Correlative Imaging (or, Rubbish In, Rubbish Out) 37Christopher J. Peddie and Nicole L. Schieber 3.1 Introduction 37 3.2 Searching for Correlative Electron Microscopy Utopia 40 3.3 Sample Processing for Correlative Imaging: A Primer for the First Steps 40 3.4 Making It Go Faster (We Want More Speed, More Speed…) 42 3.5 Embedding Resins 44 3.6 Keeping the Region of Interest in Sight 45 3.7 Correlation and Relocation with Dual Modality Probes 48 3.8 Integration of Imaging Modalities, and In‐Resin Fluorescence 49 3.9 Streamlining the Correlative Approaches of the Future: SmartCLEM 51 3.10 How Deep Does the Rabbit Hole Go? 52 3.11 Hold That Thought, Though − Is This All Completely Necessary? 53 3.12 Improving Accessibility to Correlative Workflows 54 3.13 Coming to the End 55 References 55 4 3D CLEM: Correlating Volume Light and Electron Microscopy 67Saskia Lippens and Eija Jokitalo 4.1 Introduction 67 4.2 Imaging in 3D 68 4.3 Comparative and Correlative LM and EM Imaging 69 4.4 CLEM is More than LM + EM 69 4.5 3D CLEM 70 4.6 Two Workflows for 3D CLEM 71 4.7 Where is CLEM Going in the Future? 74 Acknowledgments 76 References 77 5 Can Correlative Microscopy Ever Be Easy? An Array Tomography Viewpoint 81Irina Kolotuev and Kristina D. Micheva 5.1 Introduction 81 5.2 Why Array Tomography? 81 5.3 Array Tomography of Abundant Subcellular Structures: Synapses 82 5.4 Array Tomography of Sparsely Distributed Structures: Cisternal Organelle 84 5.5 Array Tomography of Small Model Organisms: C. elegans 87 5.6 To Summarize: Finding the Right AT Approach 90 5.7 Areas of Improvement 91 5.7.1 Resin 91 5.7.2 Serial Ultrathin Sectioning 91 5.7.3 Antibodies 92 5.7.4 EM Compatible Fluorophores 92 5.7.5 Detectors and EM Resolution 92 5.7.6 Image Registration and Alignment Tools 93 5.7.7 Data Sharing 93 5.7.8 “Dream” Resource 93 5.7.9 Dream Experiments 94 Acknowledgments 95 References 95 6 Correlative Microscopy Using Scanning Probe Microscopes 99Georg Fantner and Frank Lafont 6.1 Introduction 99 6.2 Principles of AFM 100 6.3 AFM and Optical Microscopy Correlative Approaches 103 6.4 Correlation with CLSM 104 6.5 Correlation with Cell Mechanics 104 6.5.1 Correlation with Super‐Resolution Light Microscopy (SRLM) 105 6.5.2 Future Developments 107 6.6 AFM and Correlation with Electron Microscopy 109 6.6.1 Correlation Involving AFM, EM, and Chemical Surface Characterization 110 6.6.2 Future Developments 113 6.7 Future Developments Involving Correlation Microscopy Using HS‐AFM 113 6.8 Concluding Remarks 114 Acknowledgments 114 References 115 7 Integrated Light and Electron Microscopy 119R. I. Koning, A. Srinivasa Raja, R. I. Lane, A. J. Koster, and J. P. Hoogenboom 7.1 Introduction 119 7.2 Large‐Scale and High‐Throughput (Volume) Microscopy 120 7.2.1 Advantages and Challenges for Large‐Scale EM 120 7.2.2 Advantages of CLEM for Large‐Scale EM 121 7.2.3 Prospects for Integrated Microscopy 121 7.3 Super‐Resolution Fluorescence Microscopy 123 7.3.1 Advantages and Challenges for CLEM with Super‐Resolution Fluorescence 123 7.3.2 Implementation of SR‐FM with CLEM 124 7.3.3 Prospects for Integrated SR‐CLEM 124 7.4 Cryo‐Electron Microscopy 125 7.4.1 Advantages of CryoEM 125 7.4.2 Possibilities and Challenges for Correlative Cryo‐Microscopy 126 7.4.2.1 Super‐Resolution Fluorescence Cryo‐Microscopy: Probes and Instruments 126 7.4.2.2 Transfer of Cryo‐Samples between Microscopes 127 7.4.2.3 Sample Thickness 127 7.4.2.4 Data Collection Speed 128 7.4.3 Integrated Systems for CryoCLEM 129 7.4.4 Prospects for Integrated Cryo‐Microscopy 129 7.5 Outlook 130 Acknowledgments 131 References 131 8 Cryo‐Correlative Light and Electron Microscopy: Toward in situ Structural Biology 137Tanmay A.M. Bharat and Wanda Kukulski 8.1 Introduction 137 8.2 Cryo‐CLEM to Support Single Particle Analysis of Purified Macromolecules 138 8.3 Capturing Structural Dynamics of in vitro Reconstituted Systems 141 8.4 Identifying Macromolecules in Plunge‐Frozen Whole Cells 142 8.5 Macromolecular Structures in Thinned Samples from Thick Cell Areas 144 8.6 Enabling Structural Biology in Multicellular Organisms and Tissues by Cryo‐CLEM 145 8.7 Conclusions 147 Acknowledgments 147 References 147 9 Correlative Cryo Soft X‐ray Imaging 155Eva Pereiro, Francisco Javier Chichón, and Jose L. Carrascosa 9.1 Introduction to Cryo Soft X‐ray Microscopy 155 9.2 Cryo‐SXT Correlation with Visible Light Microscopy 159 9.3 Cryo‐SXT Correlation with Cryo X‐ray Fluorescence 160 9.4 Cryo‐SXT Correlation with TEM 163 9.5 Multiple Correlation and Integration of Methods 165 Acknowledgments 165 References 166 10 Correlative Light‐ and Liquid‐Phase Scanning Transmission Electron Microscopy for Studies of Protein Function in Whole Cells 171Niels de Jonge 10.1 Introduction 171 10.2 Limitations of State‐of‐the‐Art Methods 172 10.3 Principle of Liquid STEM 173 10.3.1 Example 1: Determination of ORAI Channel Subunit Stoichiometry by Visualizing Single Molecules Using STEM 175 10.3.1.1 Conclusions 179 10.3.2 Example 2: New Insights into the Role of HER2 179 10.3.2.1 Conclusions 182 10.4 Advantages of Liquid STEM 182 10.5 Future Prospects 184 Acknowledgments 185 References 185 11 Correlating Data from Imaging Modalities 191Perrine Paul‐Gilloteaux and Martin Schorb 11.1 Introduction 191 11.2 Registration during CLEM Stages 194 11.2.1 Registration to Guide Sample Preparation 194 11.2.2 Registration to Guide the Acquisition 195 11.2.2.1 Software Packages 195 11.2.2.2 Typical Features and Fields of View 195 11.2.3 Post‐Acquisition Registration (Accurate Relocation) 196 11.2.3.1 Software and Approaches for Post‐Acquisition Registration 196 11.2.4 Trust in Alignment: Accuracy in Practice 198 11.3 Registration Paradigm 198 11.3.1 Image Features to Guide the Registration 198 11.3.2 Distance Function 199 11.3.3 Transformation Basis 199 11.3.4 Optimization Strategy 200 11.4 Envisioned Future Developments 201 11.4.1 Integrative Microscopy versus Correlative Microscopy 201 11.4.2 Incorporate a Priori Knowledge of the Specimen 202 11.4.3 Toward the Use of Machine Learning 202 11.5 Visualization of Correlation 204 11.6 Conclusion 204 Acknowledgments 205 References 205 12 Big Data in Correlative Imaging 211Ardan Patwardhan and Jason R. Swedlow 12.1 Introduction 211 12.2 The Protein Data Bank 212 12.3 Resources for Cryo‐EM 212 12.4 Light Microscopy Data Resources 214 12.5 EMPIAR 215 12.6 IDR: A Prototype Image Data Resource 216 12.7 Public Resources for Correlative Imaging 217 12.7.1 CLEM Data Formats 217 12.8 Future Directions 218 12.8.1 A BioImage Archive 218 12.8.2 CLEM Data Submission Pipelines 219 12.8.3 Scaling Data Volumes and Usage 219 12.8.4 Community Adoption and International Engagement 220 Acknowledgments 220 References 221 13 The Future of CLEM: Summary 223Lucy Collinson and Paul Verkade Index 227

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Book SynopsisThe book aims to integrate our understanding of mammalian societies into a novel synthesis that is relevant to behavioural ecologists, ecologists, and anthropologists.Trade Review"Mammal Societies is an authoritative and magnificently written synthesis of mammalian social behavior. As Tim Clutton-Brock states in the preface, his goal was to �. . .create an integrated account of mammalian societies. . .,� which he achieves with a seamless elegance honed through decades of long-term research on primates, ungulates, and carnivores. The book explains the fundamental theory underlying sociality, and then applies it to understand the diversity of mammalian behavior. Unlike previous syntheses that separate humans from non-human primates, and primates from non-primates, Clutton-Brock masterfully integrates his knowledge of these disparate literatures, and of behavioral diversity in general, to create a genuinely interesting and stimulating overview and synthesis of what we do and do not know about mammalian social behavioral diversity with implications for understanding ourselves.....Throughout, Clutton-Brock clearly deconstructs hypotheses and critically reviews both the logic and the data supporting them...Mammal Societies is a goldmine for graduate students and those establishing new studies about the adaptive value of sociality in any taxa. It would make an outstanding book to read in a graduate seminar and should be on the desk of any graduate student or academic interested in social behavior in any taxa...In summary, Mammal Societies is an intellectual tour de force that will become a citation classic and will set the stage for the next generation of studies on the adaptive value of sociality. Although not an easy read, it is a must read for anyone interested in the diversity of social behavior and its implications for population demography, and the evolution and maintenance of animal sociality..."(Journal of Wildlife Management-December 2016)Shortlisted for the British Ecological Society�s �Marsh Book of the Year Award 2017', which acknowledges the important role that books have on ecology and its development.Table of ContentsPreface, xi Acknowledgements, xiii 1 Social evolution, 1 1.1 Origins, 1 1.2 Sociality and mating systems, 11 1.3 Reproductive competition, 13 1.4 Mate choice, 17 1.5 Parental care, 20 1.6 Cooperation, 24 1.7 Loaded labels, 34 References, 35 2 Female sociality, 47 2.1 Introduction, 47 2.2 Contrasts in female sociality, 47 2.3 Benefits of grouping, 53 2.4 Costs of grouping, 60 2.5 Sociality and fitness, 63 2.6 Comparative sociality, 65 2.7 The distribution of female sociality, 78 2.8 Group coordination, 79 2.9 Consequences of female sociality, 80 3 Female dispersal and philopatry, 94 3.1 Introduction, 94 3.2 Variation in female philopatry and dispersal, 96 3.3 Benefits of philopatry, 102 3.4 Benefits of dispersing, 104 3.5 Species differences in female philopatry, 111 3.6 Social and ecological consequences of female philopatry, 113 References, 115 4 Female mating decisions, 123 4.1 Introduction, 123 4.2 Direct benefits of mate choice to females, 128 4.3 Genetic benefits of mate choice to females, 128 4.4 Female mating preferences, 130 Maturity, 130 4.5 Mate choice copying, 142 4.6 Partner number and post-copulatory mate choice, 142 4.7 Variation in mate choice and partner number, 145 4.8 Consequences of female mating preferences, 146 References, 147 5 Maternal care, 156 5.1 Introduction, 156 5.2 The evolution of maternal care, 156 5.3 Prenatal investment, 162 5.4 Maternal effects, 166 5.5 Lactation and infant care, 170 5.6 Post-weaning investment, 176 5.7 Investment strategies, 180 5.8 Relationships between siblings, 182 5.9 Parent–offspring conflict, 185 5.10 Consequences of maternal care, 187 References, 188 6 Social development, 196 6.1 Introduction, 196 6.2 Social learning, 197 6.3 Social development, 203 6.4 Play, 204 6.5 Social knowledge, 205 6.6 Individual differences and personality, 210 6.7 Traditions, 212 References, 219 7 Communication, 226 7.1 Introduction, 226 7.2 Types of signal, 230 7.3 Signalling in theory and practice, 250 References, 255 8 Competition between females, 263 8.1 Introduction, 263 8.2 Competitive tactics, 267 8.3 Social structure and competition, 273 8.4 Conflict proliferation and limitation, 282 8.5 Consequences of female competition, 285 9 Cooperation between females, 298 9.1 Introduction, 298 9.2 Cooperation in different contexts, 298 9.3 Cheating in theory and practice, 322 9.4 The evolution of cooperation, 323 9.5 Consequences of cooperation, 324 References, 326 10 Mating systems, 333 10.1 Introduction, 333 10.2 Social monogamy, 335 10.3 Polygynous systems, 339 10.4 Genetic mating systems, 359 10.5 Consequences of polygyny, 360 11 Association between males, 373 11.1 Introduction, 373 11.2 Contrasts in the formation and structure of male groups, 373 11.3 Costs of association to males, 379 11.4 Benefits of association to males, 380 11.5 Kinship, familiarity, cooperation and hostility, 384 11.6 The size of male associations, 386 11.7 Contrasts in reproductive skew, 389 11.8 Consequences of male association, 391 References, 395 12 Male dispersal and its consequences, 401 12.1 Introduction, 401 12.2 Variation in dispersal rates by males, 401 12.3 The costs and benefits of dispersal to males,409 12.4 Secondary dispersal by males, 412 12.5 Sex differences in philopatry, 414 12.6 Dispersal distance, 416 12.7 The social and ecological consequences of male dispersal, 418 References, 421 13 Reproductive competition among males, 427 13.1 Introduction, 427 13.2 The benefits and costs of fighting, 427 13.3 Assessment and the evolution of maledisplays, 434 13.4 Adaptive fighting tactics, 445 13.5 Benefits and costs of mate guarding, 445 13.6 Adaptive guarding tactics, 447 13.7 Alternative tactics, 452 13.8 Sperm competition, 453 13.9 Consequences of reproductive competition between males, 456 References, 458 14 Relationships between males in multi-male groups, 466 14.1 Introduction, 466 14.2 The development of dominance, 467 14.3 Dominance and breeding success, 470 14.4 Reproductive skew in multi-male groups, 474 14.5 Dominance, condition and survival, 476 14.6 Coalitions and alliances, 477 14.7 Market models and the dynamics of supportive relationships, 482 14.8 Punishment, retaliation and reconciliation,482 14.9 The consequences of male hierarchies, 484 References, 486 15 Males and females, 493 15.1 Introduction, 493 15.2 Male mate choice, 494 15.3 Manipulation, 496 15.4 Coercion, 496 15.5 Female counter-strategies to male coercion,507 15.6 Male infanticide, 508 15.7 Female counter-strategies to male infanticide, 516 15.8 Post-copulatory sexual conflict, 521 15.9 Demographic consequences of sexual conflict, 521 References, 524 16 Paternal care, 532 16.1 Introduction, 532 16.2 The distribution of paternal care, 533 16.3 Control mechanisms, 543 16.4 Benefits and costs of paternal care, 545 16.5 Tactical investment, 547 16.6 Conflicts between parents, 548 16.7 Male care and the evolution of mating systems, 548 References, 551 17 Cooperative breeding, 557 17.1 Introduction, 557 17.2 Delayed dispersal, 562 17.3 Reproductive suppression, 564 17.4 Reproductive skew, 570 17.5 Benefits and costs of helping, 574 17.6 Division of labour, 580 17.7 Regulation of workload, 584 17.8 The evolution of cooperative breeding, 586 17.9 Consequences of cooperative breeding, 589 References, 594 18 Sex differences, 605 18.1 Introduction, 605 18.2 Body size, 606 18.3 Weaponry, 608 18.4 Ornaments, 610 18.5 Growth, 610 18.6 Nursing, 615 18.7 Social development, 618 18.8 Feeding ecology, 621 18.9 Mortality, 623 18.10 Sex ratios at birth, 626 18.11 Adult sex ratios, 631 References, 633 19 Hominins and humans, 643 19.1 Introduction, 643 19.2 Human evolution, 644 19.3 Life histories, 649 19.4 Sex differences, 653 19.5 Hominin and human societies, 663 19.6 Why us?, 671 References, 673 20 Human behaviour, 680 20.1 Introduction, 680 20.2 Mate choice, 681 20.3 Parental care, 687 20.4 Allo-parental care, 693 20.5 Cooperation, 698 20.6 The human condition, 713 References, 714 Index, 725

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Book SynopsisThe Behavior of Animals An updated view of animal behavior studies, featuring global experts The Behavior of Animals, Second Edition provides a broad overview of the current state of animal behavior studies with contributions from international experts. This edition includes new chapters on hormones and behavior, individuality, and human evolution. All chapters have been thoroughly revised and updated, and are supported by color illustrations, informative callouts, and accessible presentation of technical information. Provides an introduction to the study of animal behavior Looks at an extensive scope of topics- from perception, motivation and emotion, biological rhythms, and animal learning to animal cognition, communication, mate choice, and individuality. Explores the evolution of animal behavior including a critical evaluation of the assumption that human beings can be studied as if they were any other animal species. Table of Contents List of Contributors vii Foreword xiii Robert A. Hinde Preface xvii 1. The Study of Animal Behavior 1 Johan J. Bolhuis, Luc-Alain Giraldeau, and Jerry A. Hogan 2. Stimulus Perception 12 Harald Burghagen and Jörg-Peter Ewert 3. Motivation and Emotion 48 Jerry A. Hogan 4. Biological Rhythms and Behavior 78 Ralph E. Mistlberger and Benjamin Rusak 5. Brain and Behavior 111 David F. Sherry 6. Hormones and Behavior 136 Jacques Balthazart and Gregory F. Ball 7. Development of Behavior 166 Johan J. Bolhuis 8. Learning and Memory 197 Kimberly Kirkpatrick and Geoffrey Hall 9. Animal Cognition 223 Jerry A. Hogan 10. Applied Animal Behavior and Animal Welfare 251 David Fraser and Daniel M. Weary 11. The Function of Behavior 281 Luc-Alain Giraldeau and Jerry A. Hogan 12. Mate Choice, Mating Systems, and Sexual Selection 315 Anders Pape Møller 13. Animal Personality, the Study of Individual Behavioral Differences 342 Denis Réale and Pierre-Olivier Montiglio 14. Animal Communication 367 William A. Searcy and Stephen Nowicki 15. Evolution of Behavior 397 Michael J. Ryan 16. The Evolution of Hominin Behavior 427 Ian Tattersall 17. Evolutionary Approaches to Human Behavior 456 Gillian R. Brown, Catharine P. Cross, and Kevin N. Laland Name Index 489 Subject Index 500

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Book SynopsisAn inspiring introduction to a vital scientific field. The reader is taken through ten mathematical derivations that lead to important results, explaining in a hands-on manner the key concepts and methods of theoretical population genetics. The derivations are carefully worked out and easy to follow.Table of ContentsIntroduction: On the constancy of allele frequencies 1 Derivation 1 Balance between forward and backward mutation 7 Derivation 2 Heterozygote advantage 23 Derivation 3 Breakdown of linkage disequilibrium 45 Derivation 4 Time to coalescence 63 Derivation 5 The evolution of genetic diversity 85 Derivation 6 Fixation of mutations with and without selection 105 Derivation 7 Nonhomogeneous populations 131 Derivation 8 Cost and benefit of sib-interactions 151 Derivation 9 Selection on a quantitative trait 167 Derivation 10 Evolutionary genetic analysis of the sex ratio 187 What’s next? 205 Epilogue 215 Thanks 217 Glossary 219 Answers 233 References 257 Index 263

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Book SynopsisAwarded Bookauthority''s Best Aquaculture Books of all TimeA comprehensive resource that covers all the aspects of sex control in aquaculture written by internationally-acclaimed scientists Comprehensive in scope, Sex Control in Aquaculture first explains the concepts and rationale for sex control in aquaculture, which serves different purposes. The most important are: to produce monosex stocks to rear only the fastest-growing sex in some species, to prevent precocious or uncontrolled reproduction in other species and to aid in broodstock management. The application of sex ratio manipulation for population control and invasive species management is also included. Next, this book provides detailed and updated information on the underlying genetic, epigenetic, endocrine and environmental mechanisms responsible for the establishment of the sexes, and explains chromosome set manipulation techniques, hybridization and the latest gene knockout approaches.Table of ContentsList of Contributors xv Preface xvii Acknowledgments xix Part I Theoretical and Practical Bases of Sex Control in Aquaculture 1 1 Sex Control in Aquaculture: Concept to Practice 3Han-Ping Wang and Zhi-Gang Shen 2 Sex Determination and Differentiation in Fish: Genetic, Genomic, and Endocrine Aspects 35Yann Guiguen, Alexis Fostier, and Amaury Herpin 3 Epigenetics of Sex Determination and Differentiation in Fish 65Francesc Piferrer 4 Environmental Sex Determination and Sex Differentiation in Teleosts -- How Sex Is Established 85Zhi-Gang Shen and Han-Ping Wang 5 Gene Knockout and Its Principle and Application in Sex Control of Fish Species 117Ze-Xia Gao and Bruce W. Draper 6 Chromosome Manipulation Techniques and Applications to Aquaculture 137Katsutoshi Arai and Takafumi Fujimoto 7 Hybridization and Its Application in Aquaculture 163M. Aminur Rahman, Sang-Go Lee, Fatimah Md. Yusoff, and S.M. Rafiquzzaman 8 Population Consequences of Releasing Sex-Reversed Fish: Applications and Concerns 179Claus Wedekind Part II Sex Determination and Control in Cichlidae 189 9 Sex Control in Tilapias 191Jean-Francois Baroiller and Helena D'Cotta 10 Quantitative Genetics of Sexual Dimorphism in Tilapia and Its Application to Aquaculture 235Nguyen Hong Nguyen Part III Sex Determination and Control in Salmonidae 249 11 Sex Determination and Sex Control in Salmonidae 251Yann Guiguen, Sylvain Bertho, Amaury Herpin, and Alexis Fostier 12 Development and Application of Sex-Linked Markers in Salmonidae 281Cristian Araneda, Natalia Lam, and Patricia Iturra 13 Polyploidy Production in Salmonidae 297James J. Nagler Part IV Sex Determination and Control in Moronidae 305 14 Genetic and Environmental Components of Sex Determination in the European Sea Bass 307Marc Vandeputte and Francesc Piferrer 15 Morphological and Endocrine Aspects of Sex Differentiation in the European Sea Bass and Implications for Sex Control in Aquaculture 327Mercedes Blazquez and Eric Saillant 16 The Induction of Polyploidy, Gynogenesis, and Androgenesis in the European Sea Bass 347Alicia Felip and Francesc Piferrer Part V Sex Determination and Control in Centrarchidae 359 17 Sex Determination, Differentiation, and Control in Bluegill 361Han-Ping Wang, Zhi-Gang Shen, Ze-Xia Gao, Hong Yao, Dean Rapp, and Paul O'Bryant 18 Sex-Determining Mechanisms and Control of Sex Differentiation in Largemouth Bass and Crappies 385Tulin Arslan 19 Hybridization and its Application in Centrarchids 405Zhi-Gang Shen and Han-Ping Wang Part VI Sex Determination and Sex Control in Percidae 429 20 Sex Determination and Monosex Female Production in Yellow Perch 431Han-Ping Wang, Zhi-Gang Shen, Hong Yao, Paul O'Bryant, and Dean Rapp 21 Sex Determination and Control in Eurasian Perch 445Carole Rougeot 22 Sexual Dimorphism in Body Size and Form in Yellow Perch 461Hong-Wei Liang, Han-Ping Wang, Yan Meng, Hong Yao, Zhi-Gang Shen, and Gui-Wei Zou Part VII Sex Determination and Sex Control in Catfish 477 23 Sex Determination, Gonadal Sex Differentiation, and Sex Control in Channel Catfish 479Reynaldo Patino 24 Sexual Size Dimorphism, Sex Determination, and Sex Control in Yellow Catfish 495Jie Mei and Jian-Fang Gui 25 Mechanisms of Feminization and Sex Differentiation in Southern Catfish 509Si-Ping Deng, Zhi-Hao Liu, and De-Shou Wang Part VIII Sex Determination and Sex Control in Flatfishes 525 26 Genomic and Epigenetic Aspects of Sex Determination in Half-Smooth Tongue Sole 527Song-Lin Chen, Qian Zhou, and Chang-Wei Shao 27 Sex Identification and Control in Half-Smooth Tongue Sole 547Song-Lin Chen and Wen-Teng Xu 28 Reproduction and Sex Control in Turbot 565Xoana Taboada, Diego Robledo, Carmen Bouza, Francesc Piferrer, Ana María Vinas, and Paulino Martínez 29 Sex Control in Southern and Summer Flounder 583Xiang-Shan Ji, Song-Lin Chen, Yan Zhao, Jamie Mankiewicz Honeycutt, Russell J. Borski, and J. Adam Luckenbach 30 Gynogenesis and Sex Control in Japanese Flounder 603Ji-Lun Hou and Hai-Jin Liu 31 Sex Determination, Differentiation, and Control in Atlantic Halibut and Pacific Halibut 621Tillmann J. Benfey 32 Sex-Specific Markers, Gynogenesis, and Sex Control in Spotted Halibut 631Hong-Yu Ma, Song-Lin Chen, and Xiang-Shan Ji Part IX Sex Determination and Sex Control in Sturgeons 645 33 Sex Determination in Sturgeon 647Sven Wuertz, Hilal Güralp, Martin Psenicka, and Mikhail Chebanov 34 Hybridization and Polyploidization in Sturgeon 669Milos Havelka and Katsutoshi Arai Part X Sex Determination and Sex Control in Crustaceans 689 35 Sex Control in Cultured Decapod Crustaceans 691Tom Levy, Eliahu D. Aflalo, and Amir Sagi 36 Sex Reversal and Determination and Sex Control in Shrimp and Prawn 705Danitzia A. Guerrero-Tortolero and Rafael Campos-Ramos Part XI Sex Determination and Sex Control in Other Fish Species 723 37 Sex Determination, Differentiation, and Control in Atlantic Cod 725Tillmann J. Benfey 38 Sex Differentiation, Sex Change, and Sex Control in Groupers 735Masaru Nakamura and Yasuhisa Kobayashi 39 Artificial Gynogenesis and Sex Control in Large Yellow Croaker 751Zhi-Yong Wang and Ming-Yi Cai 40 Sex Determination and Control in Eels 775Xian-Cheng Qu 41 Sex Control and Chromosome Manipulation in Cyprinidae: Common Carp and Grass Carp 793Boris Gomelsky and William L. Shelton Index - Species 825 Index - Subjects 832

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Book SynopsisTable of ContentsIntroduction xvii Acknowledgements xxv About the Companion Website xxvii Part I Decay and the Discovery and Recovery of Human Remains 1 1 The Decay of Human Bodies 3 2 The Discovery, Recovery, and Study of Human Bodies 29 Part II DNA Analysis 41 3 Molecular Biology 43 Part III Body Tissues and Fluids and Wound Analysis 81 4 Blood 83 5 Saliva, Semen, Vitreous Humour, Urine, and Faeces 109 6 Human Tissues 123 7 Wounds 157 Part IV Invertebrates 205 8 Invertebrates 1: Biological Aspects 207 9 Invertebrates 2: Practical Aspects 239 Part V Vertebrates and Wildlife Crime 271 10 Vertebrates 273 11 Wildlife Forensics 301 Part VI Plants, Protists, Fungi, and Microbes 327 12 Protists, Fungi, and Plants 329 13 Microbes and Viruses 365 References 397 Index 435

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Book SynopsisMountains, Climate and Biodiversity: A comprehensive and up-to-date synthesis for students and researchers Mountains are topographically complex formations that play a fundamental role in regional and continental-scale climates. They are also cradles to all major river systems and home to unique, and often highly biodiverse and threatened, ecosystems. But how do all these processes tie together to form the patterns of diversity we see today? Written by leading researchers in the fields of geology, biology, climate, and geography, this book explores the relationship between mountain building and climate change, and how these processes shape biodiversity through time and space. In the first two sections, you will learn about the processes, theory, and methods connecting mountain building and biodiversity In the third section, you will read compelling examples from around the world exploring the links between mountains, climate and biodiversity Throughout the 31 peer-reviewed chapters,Table of ContentsList of Contributors xi Acknowledgments xvii Foreword by Peter Raven xix Biography of Editors xxiii Glossary xxv About the Companion Website xxxv 1 Mountains, Climate and Biodiversity: An Introduction 1 Carina Hoorn, Allison Perrigo and Alexandre Antonelli Part I Mountains, Relief and Climate 15 2 Simple Concepts Underlying the Structure, Support and Growth of Mountain Ranges, High Plateaus and Other High Terrain 17 Peter Molnar 3 An Overview of Dynamic Topography: The Influence of Mantle Circulation on Surface Topography and Landscape 37 Caroline M. Eakin and Carolina Lithgow‐Bertelloni 4 Mountain Relief, Climate and Surface Processes 51 Peter van der Beek 5 Dating Mountain Building: Exhumation and Surface Uplift 69 Matthias Bernet, Verónica Torres Acosta and Mauricio A. Bermúdez 6 Stable Isotope Paleoaltimetry: Paleotopography as a Key Element in the Evolution of Landscapes and Life 81 Andreas Mulch and C. Page Chamberlain 7 Phytopaleoaltimetry: Using Plant Fossils to Measure Past Land Surface Elevation 95 Robert A. Spicer 8 Cenozoic Mountain Building and Climate Evolution 111 Phoebe G. Aron and Christopher J. Poulsen 9 Paleoclimate 123 Hemmo A. Abels and Martin Ziegler Part II When Biology Meets Mountain Building 135 10 Mountain Geodiversity: Characteristics, Values and Climate Change 137 John E. Gordon 11 Geodiversity Mapping in Alpine Areas 155 Arie C. Seijmonsbergen, Matheus G.G. De Jong, Babs Hagendoorn, Johannes G.B. Oostermeijer and Kenneth F. Rijsdijk 12 Historical Connectivity and Mountain Biodiversity 171 Suzette G.A. Flantua and Henry Hooghiemstra 13 The Environmental Heterogeneity of Mountains at a Fine Scale in a Changing World 187 Andrés J. Cortés and Julia A. Wheeler 14 Mountains, Climate and Mammals 201 Catherine Badgley, Tara M. Smiley and Rachel Cable 15 Inferring Macroevolutionary Dynamics in Mountain Systems from Fossils 217 Daniele Silvestro and Jan Schnitzler 16 The Interplay between Geological History and Ecology in Mountains 231 Catherine H. Graham, Mauricio Parra, Andrés Mora and Camilo Higuera 17 Mountains and the Diversity of Birds 245 Jon Fjeldså 18 Teasing Apart Mountain Uplift, Climate Change and Biotic Drivers of Species Diversification 257 Fabien L. Condamine, Alexandre Antonelli, Laura P. Lagomarsino, Carina Hoorn and Lee Hsiang Liow 19 Upland and Lowland Fishes: A Test of the River Capture Hypothesis 273 James S. Albert, Jack M. Craig, Victor A. Tagliacollo and Paulo Petry 20 Different Ways of Defining Diversity, and How to Apply Them in Montane Systems 295 Hanna Tuomisto 21 A Modeling Framework to Estimate and Project Species Distributions in Space and Time 309 Niels Raes and Jesús Aguirre‐Gutiérrez Part III Mountains and Biota of the World 321 22 Evolution of the Isthmus of Panama: Biological, Paleoceanographic and Paleoclimatological Implications 323 Carlos Jaramillo 23 The Tepuis of the Guiana Highlands 339 Otto Huber, Ghillean T. Prance, Salomon B. Kroonenberg and Alexandre Antonelli 24 Ice‐Bound Antarctica: Biotic Consequences of the Shift from a Temperate to a Polar Climate 355 Peter Convey, Vanessa C. Bowman, Steven L. Chown, Jane E. Francis, Ceridwen Fraser, John L. Smellie, Bryan Storey and Aleks Terauds 25 The Biogeography, Origin and Characteristics of the Vascular Plant Flora and Vegetation of the New Zealand Mountains 375 Matt S. McGlone, Peter Heenan, Timothy Millar and Ellen Cieraad 26 The East African Rift System: Tectonics, Climate and Biodiversity 391 Uwe Ring, Christian Albrecht and Friedemann Schrenk 27 The Alps: A Geological, Climatic and Human Perspective on Vegetation History and Modern Plant Diversity 413 Séverine Fauquette, Jean‐Pierre Suc, Frédéric Médail, Serge D. Muller, Gonzalo Jiménez‐Moreno, Adele Bertini, Edoardo Martinetto, Speranta‐Maria Popescu, Zhuo Zheng and Jacques‐Louis de Beaulieu 28 Cenozoic Evolution of Geobiodiversity in the Tibeto‐Himalayan Region 429 Volker Mosbrugger, Adrien Favre, Alexandra N. Muellner‐Riehl, Martin Päckert and Andreas Mulch 29 Neogene Paleoenvironmental Changes and their Role in Plant Diversity in Yunnan, South‐Western China 449 Zhe‐Kun Zhou, Tao Su and Yong‐Jiang Huang 30 Influence of Mountain Formation on Floral Diversification in Japan, Based on Macrofossil Evidence 459 Arata Momohara 31 The Complex History of Mountain Building and the Establishment of Mountain Biota in Southeast Asia and Eastern Indonesia 475 Robert J. Morley Index 495

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Book SynopsisThis book addresses the difficulties experienced by wet lab researchers with the statistical analysis of molecular biology related data. The authors explain how to use R and Bioconductor for the analysis of experimental data in the field of molecular biology.Table of ContentsForeword, xiii Preface, xv Acknowledgements, xix About the Companion Website, xxi 1 Introduction to R statistical environment, 1 Why R?, 1 Installing R, 2 Interacting with R, 2 Graphical interfaces and integrated development environment (IDE) integration, 3 Scripting and sourcing, 3 The R history and the R environment file, 4 Packages and package repositories, 4 Comprehensive R Archive Network, 5 Bioconductor, 6 Working with data, 7 Basic operations in R, 8 Some basics of graphics in R, 10 Getting help in R, 12 Files for practicing, 13 Study exercises and questions, 14 References, 14 Webliography, 15 2 Simple sequence analysis, 17 Sequence files, 17 FASTA sequence format, 18 GenBank flat file format, 19 Reading sequence files into R, 20 Obtaining sequences from remote databases, 21 Seqinr package, 21 Ape package, 22 Descriptive statistics of nucleotide sequences, 24 Descriptive statistics of proteins, 28 Aligned sequences, 31 Visualization of genes and transcripts in a professional way, 34 Files for practicing, 37 Study exercises and questions, 38 References, 38 Webliography, 39 Packages, 40 3 Annotating gene groups, 41 Enrichment analysis: an overview, 41 Overview of two different methods, 41 Enrichment analysis results, 42 Common aspects of the two different approaches, 43 Overrepresentation analysis, 46 Hypergeometric test using GOstats, 47 ORA analysis using topGO, 48 Enrichment analysis of microarray sets with topGO, 51 Gene set enrichment analysis, 52 GSEA with R, 56 Files for practicing, 61 Study exercises and questions, 61 References, 62 Webliography, 62 Packages, 63 4 Next-generation sequencing: introduction and genomic applications, 65 High-throughput sequencing background, 65 Experimental background, 66 Single-end and paired-end sequencing reads, 67 Assemble reads, 69 How many reads? Depth of coverage, 71 Storing data in files, 72 FASTQ, 72 SAM and BAM files, 76 Variant call format files, 77 General data analysis workflow, 77 Data processing considerations, 78 Quality checking and screening read sequences, 80 Quality checking for one file, 82 Quality inspection for multiple files in a project, 82 Quality filtering of FASTQ files, 83 Handling alignment files and genomic variants, 84 Alignment and variation visualization, 88 Simple handling of VCF files, 89 Genomic applications: low- and medium-depth sequencing, 91 Aneuploidity sequencing and copy number variation identification, 92 SNP identification and validation, 92 Exome sequencing, 93 Genomic region resequencing, 93 Full genome and metagenome sequencing, 94 Files for practicing, 94 Study exercises and questions, 94 References, 95 Webliography, 97 Packages, 97 5 Quantitative transcriptomics: qRT-PCR, 99 Transcriptome, 99 Polymerase chain reaction, 100 Standards for qPCR, 102 R packages, 104 Understanding delta Ct, 104 Calculation of delta Ct, 105 Requirements for real delta Ct calculations, 107 Absolute quantification, 110 Value prediction, the professional way, 114 Relative quantification using the ddCt method, 115 Comparison of two conditions, 116 Comparison of multiple experimental conditions, 118 Quality control with melting curve, 121 Files for practicing, 123 Study exercises and questions, 123 References, 123 Webliography, 124 Packages, 124 6 Advanced transcriptomics: gene expression microarrays, 125 Microarray analysis: probes and samples, 125 Experimental background, 126 Archiving and publishing microarray data, 128 Minimum information standard, 128 Data preprocessing, 128 Accessing data from CEL files, 129 Quality control, 131 Normalization, 132 Differential gene expression, 133 Annotating results, 136 Creating normalized expression set from Illumina data, 138 Automated data access from GEO, 140 Files for practicing, 142 Study exercises and questions, 142 References, 143 Webliography, 144 Packages, 144 7 Next-generation sequencing in transcriptomics: RNA-seq experiments, 145 High-throughput RNA sequencing background, 145 Experimental background, 145 RNA-seq applications, 146 Differential expression with different resolutions, 147 Preparing count tables, 148 Alignment files to read counts, 148 Differential expression in simple comparison, 151 A naive t-test approach, 151 Single factor analysis with edgeR, 153 Differential expression with DESeq, 156 Complex experimental arrangements, 159 Experimental factors and design matrix, 160 GLM with edgeR, 161 GLMs with DESeq, 162 Heatmap visualization, 163 Files for practicing, 164 Study exercises and questions, 164 References, 165 Webliography, 166 Packages, 166 8 Deciphering the regulome: from ChIP to ChIP-seq, 167 Chromatin immunoprecipitation, 167 Experimental background, 168 Fragment analysis, 168 ChIP data in ENCODE, 169 ChIP with tiling microarrays, 169 High-throughput sequencing of ChIP fragments, 176 Connecting annotation to peaks, 181 Analysis of binding site motifs, 182 Files for practicing, 186 Study exercises and questions, 187 References, 187 Webliography, 188 Packages, 189 9 Inferring regulatory and other networks from gene expression data, 191 Gene regulatory networks, 191 Data for gene network inference, 192 Reconstruction of co-expression networks, 193 Gene regulatory network inference focusing of master regulators, 201 Integrated interpretation of genes with GeneAnswers, 207 Files for practicing, 211 Study exercises and questions, 212 References, 213 Packages, 214 10 Analysis of biological networks, 215 A gentle introduction to networks, 215 Networks and their components and features, 215 Random networks, 220 Biological networks, 221 Files for storing network information, 223 Important network metrics in biology, 227 Distance-based measures, 228 Degree and related measures, 230 Vulnerability, 231 Community structure of a network, 234 Graph visualization, 236 Cytoscape, 240 Files for practicing, 241 Study exercises and questions, 241 References, 242 Webliography, 243 Packages, 243 11 Proteomics: mass spectrometry, 245 Mass spectrometry and proteomics: why and how?, 245 File formats for MS data, 246 Accessing the raw data of published studies, 247 Identification of peptides in the samples, 249 Peptide mass fingerprinting, 249 Peptide identification by using MS/MS spectra, 250 Quantitative proteomics, 254 Getting protein-specific annotation, 258 Files for practicing, 259 Study exercises and questions, 259 References, 259 Webliography, 260 Packages, 260 12 Measuring protein abundance with ELISA, 261 Enzyme-linked immunosorbent assays, 261 Accessing ELISA data, 264 Concentration calculation with a standard curve, 264 Preparing reference data, 267 Fitting linear model, 268 Fitting of a logistic model, 269 Concentration calculations by employing models, 270 Comparative calculations using concentrations, 271 Files for practicing, 277 Study exercises and questions, 277 References, 277 Packages, 278 13 Flow cytometry: counting and sorting stained cells, 279 Theoretical aspects of flow cytometry, 279 Experiment types: diagnosis versus discovery, 280 Measurement arrangements, 281 Fluorescent dyes, 281 Tubes versus plates, 285 Instruments, 285 What about data?, 287 Files, 287 Workflows, 288 Data preprocessing, 289 Handling all samples together, 290 Compensation, 292 Quality assurance, 292 Using workflow objects and transformation, 296 Normalization, 298 Cell population identification, 299 Manual gating, 300 Automatic gating, 304 Relating cell populations to external variables, 305 Reporting results, 307 MIFlowCyt, 307 FlowRepository.org, 308 Files for practicing, 308 Study exercises and questions, 309 References, 309 Webliography, 310 Packages, 310 Glossary, 311 Index, 323

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Book SynopsisRecent technological advances have provided unique opportunities for the exploration of alternatives to the industrial use of chemically produced synthetic colors. The most promising developments in this area have been in bio-pigmentation derived from microorganisms. This groundbreaking book reviews the current state of the science of bio-pigmentation, providing important insights into the molecular mechanisms of microbial biosynthesis of industrial pigments. Featuring contributions by leading researchers from both industry and academe, it explores the latest advances in the use of bio-pigments as safe, sustainable alternatives to chemically synthesized pigments, and provides extensive coverage the most promising sources of bio-pigments within the food, feed, and pharmaceutical industries. Proposes microbial uniqueness of coloration in variety of food, feed and pharmaceuticals Covers the basic science behind bio-pigmentation as well as the latest advances in the fielTable of ContentsList of Contributors xv Introduction xvii 1 Introduction of Natural Pigments From Microorganisms 1Siyuan Wang, Fuchao Xu, and Jixun Zhan 1.1 Introduction 1 1.2 Microbial Pigments from Eukaryotic Sources 2 1.2.1 Pigments from Algae 2 1.2.2 Pigments from Fungi 4 1.2.3 Pigments from Yeasts 7 1.3 Natural Pigments from Prokaryotes 9 1.3.1 Natural Pigments from Cyanobacteria 9 1.3.2 Natural Pigments from Bacteria 10 1.4 Conclusion 16 References 16 2 Establishing Novel Cell Factories Producing Natural Pigments In Europe 23Gerit Tolborg, Thomas Isbrandt, Thomas Ostenfeld Larsen, and Mhairi Workman 2.1 Introduction 23 2.2 Colorants 25 2.2.1 Classification of Colorants 25 2.2.2 Monascus Pigments 26 2.2.3 Biosynthesis of Monascus Pigments 29 2.2.4 Derivatives of Monascus Pigments 31 2.3 Screening for Monascus Pigment-Producing Cell Factories for the European Market 32 2.3.1 Cell Factory Selection and Identification 32 2.3.2 From Single Pigment Producers to High-Performance Cell Factories 33 2.4 Assessment of the Color Yield 34 2.4.1 Pigment Purification and Quantification 34 2.4.2 Detection and Identification 37 2.4.3 Quantification 38 2.4.4 CIELAB 41 2.5 Optimizing Cellular Performance: Growth and Pigment Production 41 2.5.1 Assessment of Classical Physiological Parameters 42 2.5.2 Media Composition 42 2.5.3 Cultivation Parameters 44 2.5.4 Type of Cultivation 46 2.5.5 Metabolic Engineering 48 2.6 Pigment Properties 50 2.7 Conclusion 51 References 51 3 Color-Producing Extremophiles 61Eva García-López, Alberto Alcázar, Ana María Moreno, and Cristina Cid 3.1 Introduction 61 3.2 Color-Producing Extremophiles 62 3.2.1 Thermophiles and Hyperthermophiles 63 3.2.2 Psychrophiles and Psychrotolerants 63 3.2.3 Alkaliphiles 66 3.2.4 Acidophiles 66 3.2.5 Piezophiles and Piezotolerants 66 3.2.6 Halophiles and Halotolerants 67 3.2.7 Radiophiles 67 3.3 Microbial Pigments 68 3.3.1 Chlorophylls and Bacteriochlorophylls 68 3.3.2 Carotenoids and Phycobilins 69 3.3.3 Violacein 70 3.3.4 Prodigiosin 70 3.3.5 Pyocyanin 70 3.3.6 Azaphilones 70 3.3.7 Bacteriorhodopsin 71 3.3.8 Cytochromes 71 3.3.9 Other 72 3.4 Biotechnological Applications of Microbial Pigments from Extremophiles 73 3.4.1 Applications in the Food Industry 74 3.4.2 Applications in the Pharmaceutical Industry 77 3.4.3 Applications in the Textile Industry 78 3.4.4 Applications as Laboratory Tools 78 3.4.5 Applications in Bioremediation 79 3.4.6 Development of Microbial Fuel Cells 79 3.4.7 Biotechnological Production of Natural Pigments 80 3.5 Conclusion 80 Acknowledgments 80 References 80 4 Current Carotenoid Production Using Microorganisms 87Laurent Dufossé 4.1 Introduction 87 4.2 β-carotene 88 4.2.1 B. trispora 88 4.2.2 Phycomyces blakesleeanus 90 4.2.3 Mucor circinelloides 91 4.2.4 Applications 91 4.3 Lycopene 91 4.3.1 B. trispora 92 4.3.2 Fusarium sporotrichioides 93 4.4 Astaxanthin 93 4.4.1 X. dendrorhous, Formerly Phaffia rhodozyma 94 4.4.2 Agrobacterium aurantiacum and Other Bacteria 95 4.4.3 Advantages over Other Carotenoids 95 4.4.4 Astaxanthin for Salmon and Trout Feeds 96 4.4.5 Astaxanthin for Humans 97 4.5 Zeaxanthin 97 4.6 Canthaxanthin 98 4.7 Torulene and Thorularhodin 99 4.8 Prospects for Carotenoid Production by Genetically Modified Microorganisms 99 4.8.1 Escherichia coli and Other Hosts 99 4.8.2 Directed Evolution and Combinatorial Biosynthesis 101 4.9 Conclusion 102 References 104 5 C50 Carotenoids: Occurrence, Biosynthesis, Glycosylation, and Metabolic Engineering For Their Overproduction 107Nadja A. Henke, Petra Peters-Wendisch, Volker F. Wendisch, and Sabine A.E. Heider 5.1 Introduction 107 5.2 Occurrence and Biological Function of C50 Carotenoids 108 5.3 Biosynthesis of C50 Carotenoids 110 5.4 Glycosylation of C50 Carotenoids 114 5.5 Overproduction of C50 Carotenoids by Metabolic Engineering 115 5.6 Conclusion 118 Acknowledgments 119 References 119 6 Biopigments and Microbial Biosynthesis of 𝛃-Carotenoids 127Rosemary C. Nwabuogu, Jennifer Lau, and Om V. Singh 6.1 Introduction 127 6.2 Characterization of Biological Pigments 129 6.2.1 Tetrapyrrole Derivatives 129 6.2.2 N-heterocyclic Derivatives 130 6.2.3 Isoprenoid Derivatives 131 6.2.4 Benzopran Derivatives 132 6.2.5 Quinones 132 6.2.6 Melanins 133 6.3 Biosynthetic Routes of β-carotene 133 6.3.1 Fermentation of β-carotene 138 6.4 Molecular Regulation of β-carotene Biosynthesis 146 6.5 Commercialization of β-carotene 147 6.6 Conclusion 151 References 151 7 Biotechnological Production of Melanins With Microorganisms 161Guillermo Gosset 7.1 Introduction 161 7.2 Microbial Production of Melanins 163 7.3 Production of Melanins with Engineered Microorganisms 165 7.4 Conclusion 169 References 170 8 Biochemistry and Molecular Mechanisms of Monascus Pigments 173Changlu Wang, Di Chen, and Jiancheng Qi 8.1 Introduction 173 8.2 Monascus Pigments 174 8.3 The Properties of Monascus Pigments 176 8.3.1 Solubility 176 8.3.2 Stability 177 8.3.3 Safety 177 8.4 Functional Properties of Monascus Pigments 177 8.4.1 Antimicrobial Activities 178 8.4.2 Anti-inflammatory Activities 178 8.4.3 Anti-obesity Activities 178 8.4.4 Anticancer Activities 178 8.5 Biosynthetic Pathway of Monascus Pigments 179 8.6 Biosynthetic Pathway of Related Genes 181 8.7 Factors Affecting Monascus Pigment Production 184 8.7.1 Solid-State Fermentation 185 8.7.2 Submerged Fermentation 186 8.7.3 Carbon Source 186 8.7.4 Nitrogen Source 187 8.7.5 Temperature 187 8.7.6 Light 187 References 187 9 Diversity and Applications of Versatile Pigments Produced By Monascus Sp 193Sunil H. Koli, Rahul K. Suryawanshi, Chandrashekhar D. Patil, and Satish V. Patil 9.1 Introduction 193 9.2 Pigment-Producing Monascus Strains 195 9.3 Various Types of Monascus Pigments 199 9.4 Extraction and Purification of Monascus Pigments 203 9.5 Detection and Purification 204 9.5.1 UV-Vis Spectrophotometric Methods 204 9.5.2 Column Chromatography 204 9.5.3 Thin-Layer Chromatography 205 9.5.4 High-Performance Liquid Chromatography 205 9.6 Applications 206 9.6.1 Food Colorants 206 9.6.2 Biological Role 206 9.7 Conclusion 209 Acknowledgments 209 References 209 10 Microbial Pigment Production Utilizing Agro-Industrial Waste and Its Applications 215Chidambaram Kulandaisamy Venil, Nur Zulaikha Binti Yusof, Claira Arul Aruldass, and Wan Azlina Ahmad 10.1 Introduction 215 10.2 Agro-industrial Waste Generation: A Scenario 216 10.3 Microbial Pigments 216 10.4 Production of Microbial Pigments Utilizing Agro-industrial Waste from Different Industries 223 10.5 Case Study: Production of Violacein by Chromobacterium violaceum Grown in Agricultural Wastes 225 10.5.1 Introduction 225 10.5.2 Materials and Methods 226 10.5.3 Results and Discussion 229 10.6 Conclusion 235 Acknowledgments 235 References 235 11 Microbial Pigments: Potential Functions and Prospects 241P. Akilandeswari and B.V. Pradeep 11.1 Introduction 241 11.1.1 Pigments 242 11.1.2 Types of Pigments 242 11.1.3 Microbial Pigments 242 11.1.4 Use of Pigments 243 11.1.5 Advantages of Natural Pigments 243 11.1.6 Disadvantages of Synthetic Dyes 243 11.2 Potential Sources of Microbial Pigments 244 11.2.1 Actinomycetes 244 11.2.2 Bacteria 245 11.2.3 Fungi 245 11.3 Physical Factors Influencing Microbial Pigments 246 11.4 Chemical Factors Influencing Microbial Pigments 247 11.5 Fermentation Practices in Pigment Production 248 11.5.1 Solid-State Fermentation 248 11.5.2 Submerged Fermentation 248 11.6 Characterization and Purification Analysis 249 11.7 Biocolors from Microbes and their Potential Functions 250 11.7.1 Pharmaceutical Industry 250 11.7.2 Food Colorants 255 11.7.3 Textile Dyeing 256 References 257 12 The Microbial World of Biocolor Production 263Roshan Gul, Raman Kumar, and Anil K. Sharma 12.1 Introduction 263 12.2 Pigments Produced by Microorganisms 265 12.3 Classification of Pigments 265 12.3.1 Riboflavin 265 12.3.2 β-carotene 265 12.3.3 Canthaxanthin 268 12.3.4 Carotenoids 268 12.3.5 Prodigiosin 268 12.3.6 Phycocyanin 268 12.3.7 Violacein 268 12.3.8 Astaxanthin 268 12.4 Benefits and Applications of Microbial Pigments 269 12.5 Conclusion 272 References 273 Index 279

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Book SynopsisTRANSPORTERS AND DRUG-METABOLIZING ENZYMES IN DRUG TOXICITY Explore up-to-date coverage on the interaction between drug metabolism enzymes, transporters, and drug toxicity with this leading resources Transporters and Drug-Metabolizing Enzymes in Drug Toxicity delivers a comprehensive and updated review of the relationship between drug metabolism, transporters, and toxicity, providing insights into a major challenge in drug development accurate assessment of human drug toxicity. Combining two disciplines frequently considered independently of one another, the book combines drug metabolism and toxicology with a focus on the role of biotransformation on drug toxicity and as a major factor for species and individual differences. Mechanism and species differences in drug metabolizing enzymes and transporters are discussed, as are the methods used to investigate the role of drug metabolizing enzymes and transporters in drug toxicity. Finally, the distinguTable of ContentsPreface xix List of Contributors xxi Part I Overview 1 1 Overview: Drug Metabolism, Transporter-Mediated Uptake and Efflux, and Drug Toxicity 3Albert P. Li 1.1 Drug Toxicity as a Challenge in Drug Development 3 1.2 Fate of an Orally Administered Drug 4 1.3 The Multiple Determinant Hypothesis for Idiosyncratic Drug Toxicity 5 1.4 Concluding Remarks 7 1.4.1 A Comprehensive Approach to Safety Evaluation in Drug Development 7 1.4.2 The Dose Makes the Poison – Paracelsus Updated 8 References 8 2 Transporter, Drug Metabolism, and Drug-Induced Liver Injury in Marketed Drugs 11Minjun Chen, Kristin Ashby, and Yue Wu 2.1 Introduction 11 2.2 Hepatic Metabolism 12 2.2.1 Phase I Metabolism 12 2.2.2 Phase II Metabolism 14 2.3 Reactive Metabolite Formation and Assessment 14 2.3.1 Metabolism and Reactive Metabolites 15 2.3.2 Dose and Reactive Mtabolites 16 2.3.3 Structural Alerts for Avoiding Reactive Metabolites 16 2.3.4 Experimental Approaches for Assessing Reactive Metabolites 18 2.3.4.1 Covalent Binding Assay 18 2.3.4.2 Electrophile Trapping Experiments 18 2.3.4.3 Time Dependent Inactivation of CYP450 Enzymes 19 2.4 Hepatic Transporters 20 2.5 Genetic Variants and Their Impact for Pharmacokinetic Behavior and Safety 24 2.5.1 CYP3A424 2.5.2 CYP3A526 2.5.3 CYP2D626 2.5.4 CYP2C927 2.5.5 CYP2C1927 2.5.6 CYP2B628 2.5.7 UGT1A128 2.5.8 NAT2 28 2.5.9 Hepatic Transporters 29 2.6 Summary 29 Acknowledgment 30 Disclaimer 30 References 30 3 Drug-Metabolism Enzymes and Transporter Activities as Risk Factors of Selected Marketed Drugs Associated with Drug-Induced Fatalities 41Albert P. Li 3.1 Introduction 41 3.2 Acetaminophen 41 3.2.1 Drug Metabolism and Toxicity 42 3.2.2 Transporters and Toxicity 42 3.2.3 Risk Factors 43 3.3 Cerivastatin 43 3.3.1 Drug Metabolism and Toxicity 43 3.3.2 Transporter and Toxicity 44 3.3.3 Risk Factors 44 3.4 Felbamate 45 3.4.1 Drug Metabolism and Toxicity 45 3.4.2 Transporters and Toxicity 46 3.4.3 Risk Factors 46 3.5 Flucloxacillin 46 3.5.1 Drug Metabolism and Toxicity 46 3.5.2 Transporters and Toxicity 47 3.5.3 Risk Factors 47 3.6 Nefazodone 47 3.6.1 Drug Metabolism and Toxicity 48 3.6.2 Transporters and Toxicity 48 3.6.3 Risk Factors 48 3.7 Obeticholic Acid 49 3.7.1 Drug Metabolism and Toxicity 49 3.7.2 Transporters and Toxicity 50 3.7.3 Risk Factors 50 3.8 Sitaxentan 50 3.8.1 Drug Metabolism and Toxicity 51 3.8.2 Transporters and Toxicity 51 3.8.3 Risk Factors 51 3.9 Sorivudine 52 3.9.1 Drug Metabolism and Toxicity 52 3.9.2 Transporters and Toxicity 52 3.9.3 Risk Factors 52 3.10 Tacrine 52 3.10.1 Drug Metabolism and Toxicity 54 3.10.2 Transporters and Toxicity 54 3.10.3 Risk Factors 54 3.11 Terfenadine 55 3.11.1 Drug Metabolism and Toxicity 55 3.11.2 Transporter and Toxicity 56 3.11.3 Risk Factors 56 3.12 Troglitazone (Rezulin®) 56 3.12.1 Drug Metabolism and Toxicity 57 3.12.2 Transporter and Toxicity 57 3.12.3 Risk Factors 58 3.13 Trovafloxacin 58 3.13.1 Metabolism and Toxicity 59 3.13.2 Transporters and Toxicity 59 3.13.3 Risk Factors 59 3.14 Conclusions 60 References 61 Part II Drug Metabolizing Enzymes and Drug Toxicity 79 4 Drug-Metabolizing Enzymes and Drug Toxicity 81Albert P. Li 4.1 Introduction 81 4.2 Drug-Metabolism Enzymes Involved in Metabolic Activation and Detoxification 81 4.3 Cytochrome P450 Monooxygenase (CYP) 82 4.3.1 CYP1A 82 4.3.1.1 Metabolic Activation 82 4.3.1.2 Drug Substrates 83 4.3.1.3 Inducers 83 4.3.1.4 Inhibitors 83 4.3.1.5 Individual Variations 83 4.3.1.6 Involvement in Drug Toxicity 83 4.3.2 CYP2A6 84 4.3.2.1 Substrates 84 4.3.2.2 Inducers 84 4.3.2.3 Inhibitors 84 4.3.2.4 Individual Variations 85 4.3.2.5 Involvement in Drug Toxicity 85 4.3.3 CYP2B6 85 4.3.3.1 Substrates 85 4.3.3.2 Inducers 86 4.3.3.3 Inhibitors 86 4.3.3.4 Individual Variations 86 4.3.3.5 Involvement in Drug Toxicity 86 4.3.4 CYP2C8 87 4.3.4.1 Substrates 87 4.3.4.2 Inducers 87 4.3.4.3 Inhibitors 87 4.3.4.4 Individual Variations 88 4.3.4.5 Involvement in Drug Toxicity 88 4.3.5 CYP2C9 88 4.3.5.1 Substrates 88 4.3.5.2 Inducers 88 4.3.5.3 Inhibitors 88 4.3.5.4 Individual Variations 89 4.3.5.5 Involvement in Drug Toxicity 89 4.3.6 CYP2C19 89 4.3.6.1 Substrates 89 4.3.6.2 Inducers 89 4.3.6.3 Inhibitors 89 4.3.6.4 Individual Variations 90 4.3.6.5 Involvement in Drug Toxicity 90 4.3.7 CYP2D6 90 4.3.7.1 Substrates 90 4.3.7.2 Inducers 90 4.3.7.3 Inhibitors 90 4.3.7.4 Individual Variations 90 4.3.7.5 Involvement in Drug Toxicity 91 4.3.8 CYP2E1 91 4.3.8.1 Substrates 91 4.3.8.2 Inducers 91 4.3.8.3 Inhibitors 91 4.3.8.4 Involvement in Drug Toxicity 91 4.3.9 CYP2J2 92 4.3.9.1 Substrates 92 4.3.9.2 Inhibitors 92 4.3.9.3 Inducers 92 4.3.9.4 Individual Variations 92 4.3.9.5 Involvement in Drug Toxicity 92 4.3.10 CYP3A 93 4.3.10.1 Substrates 93 4.3.10.2 Inducers 93 4.3.10.3 Inhibitors 93 4.3.10.4 Individual Variations 93 4.3.10.5 Involvement in Drug Toxicity 94 4.4 Non-P450 Drug-Metabolizing Enzymes 94 4.4.1 Flavin-Containing Monooxygenases (FMOs) 94 4.4.1.1 Substrates 94 4.4.1.2 Inducers 95 4.4.1.3 Inhibitors 95 4.4.1.4 Individual Variations 95 4.4.1.5 Involvement in Drug Toxicity 95 4.4.2 Monoamine Oxidase (MAO) 95 4.4.2.1 Substrates 96 4.4.2.2 Inducers 96 4.4.2.3 Inhibitors 96 4.4.2.4 Individual Variations 96 4.4.2.5 Involvement in Drug Toxicity 96 4.4.3 Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase (ALDH) 97 4.4.3.1 Substrates 97 4.4.3.2 Inducers 97 4.4.3.3 Inhibitors 97 4.4.3.4 Individual Variations 97 4.4.3.5 Involvement in Drug Toxicity 98 4.4.4 Aldehyde Oxidase (AOX) 98 4.4.4.1 Substrates 98 4.4.4.2 Inducers 98 4.4.4.3 Inhibitors 98 4.4.4.4 Individual Variations 99 4.4.4.5 Involvement in drug toxicity 99 4.4.5 Carboxylesterases (CESs) 99 4.4.5.1 Substrates 99 4.4.5.2 Inducers 99 4.4.5.3 Inhibitors 100 4.4.5.4 Individual Variations 100 4.4.5.5 Involvement in Drug Toxicity 100 4.4.6 N-Acetyltransferase (NAT) 100 4.4.6.1 Substrates 100 4.4.6.2 Inducers 100 4.4.6.3 Inhibitors 101 4.4.6.4 Individual Variations 101 4.4.6.5 Involvement in Drug Toxicity 101 4.4.7 Glutathione Transferase (GST) 101 4.4.7.1 Substrates 101 4.4.7.2 Inducers 102 4.4.7.3 Inhibitors 102 4.4.7.4 Individual Variations 102 4.4.7.5 Involvement in Drug Toxicity 102 4.4.8 Methyltransferase (MT) 103 4.4.8.1 Substrates 103 4.4.8.2 Inhibitors 103 4.4.8.3 Individual Variations 103 4.4.8.4 Involvement in Drug Toxicity 103 4.4.9 Uridine Glucuronosyltransferase (UGT) 103 4.4.9.1 Substrates 104 4.4.9.2 Inducers 104 4.4.9.3 Inhibitors 104 4.4.9.4 Individual Variations 104 4.4.9.5 Involvement in Drug Toxicity 104 4.4.10 Sulfotransferase (SULT) 105 4.4.10.1 Substrates 105 4.4.10.2 Inducers 105 4.4.10.3 Inhibitors 106 4.4.10.4 Individual Variations 106 4.4.10.5 Involvement in Drug Toxicity 106 4.5 Conclusions 106 References 107 5 Genetic Polymorphism of Drug-Metabolizing Enzymes and Drug Transporters in Drug Toxicity 139Ann K. Daly 5.1 Introduction 139 5.2 Drug-Induced Liver Injury 140 5.2.1 Background 140 5.2.2 Polymorphisms Affecting Drug Metabolism and DILI 140 5.2.2.1 Isoniazid 140 5.2.2.2 Diclofenac 146 5.2.2.3 Tolcapone 146 5.2.2.4 Ticlopidine 147 5.2.2.5 Efavirenz 147 5.2.2.6 Troglitazone 147 5.2.3 Polymorphisms Affecting Transporters and DILI 147 5.3 Drug-Induced Skin Injury and Related Hypersensitivity Reactions 149 5.4 Statin-Induced Myopathy 151 5.4.1 Background 151 5.4.2 Cytochromes P450 151 5.4.3 Transporters 152 5.5 Conclusions 154 References 154 6 Acyl Glucuronidation and Acyl-CoA Formation Mechanisms Mediating the Bioactivation and Potential Toxicity of Carboxylic Acid-containing Drugs 167Mark P. Grillo 6.1 Introduction 167 6.2 Phase II Metabolism 171 6.2.1 Glucuronidation 171 6.2.2 Acyl-CoA Thioester Formation 171 6.3 Chemical Stability of Phase II Metabolites 172 6.3.1 Acyl Glucuronide Instability 172 6.3.2 Acyl-CoA Thioester Stability 175 6.4 Phase II Metabolite Chemical Reactivity 176 6.4.1 Acyl Glucuronide Reactivity with Nucleophiles In vitro 176 6.4.2 Acyl-CoA Thioester Reactivity with Nucleophiles In vitro 180 6.5 Phase II Metabolite-Mediated Covalent Binding 183 6.5.1 Acyl Glucuronide-Mediated covalent Binding to protein 183 6.5.2 Acyl-CoA Thioester-Mediated Covalent Binding to Protein 185 6.6 Phase II Metabolite Prediction of Covalent Binding 187 6.6.1 Prediction of Covalent Binding to Protein by Acyl Glucuronides 187 6.6.2 Prediction of Covalent Binding to Protein by Acyl-CoA Thioesters 189 6.7 Studies Directly Comparing Carboxylic Acid Drug Bioactivation by Acyl Glucuronidation and Acyl-CoA Formation 190 6.8 Prediction of Drug-Induced Liver Injury for Carboxylic Acid Drugs 194 6.9 Conclusions 196 References 197 7 Liquid Chromatography-Mass Spectrometry (LC-MS) Quantification of Reactive Metabolites 207Qingping Wang and Chuang Lu 7.1 Introduction 207 7.2 LC-MS Methods Using GSH as a Trapping Reagent 209 7.2.1 LC-MS Approaches at Positive Mode Using Constant Neutral Loss (CNL) Scan or Enhanced Product Ion (EPI) Scan 209 7.2.2 LC-MS Approaches at Negative Mode Using Neutral Loss, Pre-Ion Scan (PIS) and XoPI (Extraction of Product Ion) 212 7.2.3 LC-MS Approaches Using Stable Isotopic-GSH 213 7.2.4 LC-MS Approaches Using Combined XoPI and Stable-Isotopic GSH 214 7.2.5 LC-MS Coupled with Software-Assisted Approach 218 7.2.6 Using GSH Derivatives as Trapping Reagents for Detection and Quantitation 219 7.3 Using Other Trapping Reagents 222 7.4 Identification and Characterization of Rearranged GSH Adducts 222 7.5 Strategies for Optimization and Decision Tree 224 7.6 Summary 226 Acknowledgment 227 Abbreviations 227 References 228 8 Human-Based In Vitro Experimental Approaches for the Evaluation of Metabolism-Dependent Drug Toxicity 235Albert P. Li 8.1 Introduction 235 8.2 Assays for Reactive Metabolites 235 8.2.1 Glutathione Trapping Assay 236 8.2.2 Covalent Binding Assay 236 8.3 Cell-Based Assays for Metabolism-Dependent Toxicity 237 8.4 Primary Human Hepatocyte Assays for Metabolism-Dependent Drug Toxicity 238 8.4.1 In Vitro Screening Assays for Hepatotoxicity 238 8.4.2 Cytotoxic Metabolic Pathway Identification Assay (CMPIA) 238 8.4.3 Metabolic Comparative Cytotoxicity Assay (MCCA) 241 8.4.4 MetMax™ Cryopreserved Human Hepatocytes (MMHH) Metabolic Activation Cytotoxicity Assay (MMACA) 242 8.5 Emerging Hepatocyte Technologies for the Evaluation of Drug Toxicity 242 8.5.1 Human Hepatocytes ROS/ATP Assay for DILI Drugs 242 8.5.2 Long-Term Hepatocyte Cultures 244 8.5.2.1 999Elite™ Long-Term Cultured Human Hepatocytes 244 8.5.2.2 Hepatocyte/Non-Hepatocyte Cocultures 244 8.5.2.3 Human Hepatocyte Spheroids 245 8.5.2.4 Microfluidic 3-Dimensional (3-d) Hepatocyte Cultures 245 8.6 Integrated Discrete Multiple Organ Coculture (IdMOC®) 247 8.7 Conclusion 249 References 251 Part III Drug Transporters and Drug Toxicity 261 9 Mechanism-Based Experimental Models for the Evaluation of BSEP Inhibition and DILI 263William A. Murphy, Chitra Saran, Paavo Honkakoski, and Kim L.R. Brouwer 9.1 Introduction 263 9.1.1 Drug-Induced Liver Injury 263 9.1.2 Bile Acid Homeostasis and Role of Bile Salt Export Pump 264 9.2 Membrane Vesicles to Study BSEP Inhibition 266 9.2.1 Membrane Vesicle Preparations 267 9.2.2 Membrane Vesicle Assays and Data Interpretation 268 9.3 Sandwich-Cultured Hepatocytes to Study BSEP Inhibition 270 9.3.1 B-CLEAR® Assay 270 9.3.2 Uptake and Efflux Studies with Mechanistic Modeling 273 9.4 Other In Vitro Methods to Study BSEP Inhibition 275 9.5 Computational Methods Used to Predict BSEP Inhibition 277 9.6 In Vitro Models as a Predictor of Clinical DILI 278 9.6.1 The C-DILI™ Assay 278 9.7 Preclinical In Vivo Models for the Evaluation of BSEP/Bsep Inhibition and DILI 279 9.8 In Vivo Clinical Biomarkers of BSEP Inhibition and DILI 282 9.8.1 Serum Bile Acids as Clinical Biomarkers 282 9.8.2 Clinical Biomarkers of DILI 283 9.9 Quantitative Systems Toxicology to Predict DILI 284 9.10 Conclusions 287 Funding Information 287 Conflict of Interest 288 Acknowledgments 288 Reference 288 10 Hepatic Bile Acid Transporters in Drug-Induced Cholestasis 307Tao Hu and Hongbing Wang Abbreviations 307 10.1 Introduction 308 10.2 Bile Acid and DIC 308 10.2.1 Bile Acid 309 10.2.1.1 Bile Acid Synthesis 309 10.2.1.2 Bile Acid Transport 310 10.2.2 Cytotoxicity of Bile Acids and DIC 310 10.3 Hepatic Bile Acid Uptake Transporters in DIC 312 10.3.1 Sodium-Taurocholate Cotransporting Polypeptide (NTCP) 312 10.3.1.1 Substrates of NTCP 314 10.3.1.2 Regulation of NTCP 315 10.3.1.3 NTCP and Cholestasis 316 10.3.2 Other Hepatic Bile Acid Uptake Transporters 317 10.4 Hepatic Bile Acid Efflux Transporters in DIC 317 10.4.1 Bile Salt Export Pump (BSEP) 318 10.4.1.1 Substrates of BSEP 318 10.4.1.2 Regulation of BSEP 319 10.4.1.3 Internalization of BSEP 321 10.4.1.4 BSEP and Cholestasis 321 10.4.2 Other Hepatic Bile Acid Efflux Transporters 323 10.4.2.1 MRP2 323 10.4.2.2 MRP3 and MRP4 324 10.5 Bidirectional Bile Acid Transporter OSTα/β 324 10.6 Summary 325 References 326 11 Role of Renal Transporters in Drug–Drug Interactions and Nephrotoxicity 339Yan Zhang and Donald Miller 11.1 Overview of Renal Transporters 339 11.1.1 Basolateral Transporters 340 11.1.2 Apical Transporters 341 11.2 Renal Transporters and Drug–Drug Interactions 343 11.2.1 Impact on the Pharmacokinetics of Drugs 344 11.2.2 Impact on the Drug PD 350 11.3 Renal Transporters and Nephrotoxicity 352 11.3.1 Nephrotoxicity Unrelated to Drug Transporters 353 11.3.2 Nephrotoxicity Related to Drug Transporters 355 11.4 Biomarkers and Nephrotoxicity 359 11.4.1 Biomarkers for Detecting Glomerular Injury 359 11.4.2 Biomarkers for Drug-Induced Injury to Proximal and Distal Tubules 361 11.5 Conclusion 362 References 365 12 Blood–Brain Barrier Transporters and Central Nervous System Drug Response and Toxicity 377Donald W. Miller, Stacey Line, Nur A. Safa, and Yan Zhang 12.1 Over-View of the Brain Barriers 377 12.1.1 Blood–Brain Barrier (BBB) 377 12.1.2 Blood–Cerebrospinal Fluid Barrier (BCSFB) 379 12.1.3 CSF as Predictor of Drug Exposure in the Brain 379 12.1.4 Solute Carriers in the BBB 380 12.1.5 Drug Efflux Transporters in the BBB 380 12.2 General Influence of BBB Transporters on Drug Entry into the Brain 383 12.3 BBB-Transporter Effects on CNS Drug Response 386 12.3.1 Influence of Efflux Transporters on Brain Disposition of Drugs 386 12.3.1.1 Anticancer Agents 386 12.3.1.2 Opioids 388 12.3.2 SLCs and BBB Transport of Drugs 391 12.4 Transporter Considerations Influencing CNS Drug Response 391 12.4.1 Transporter Polymorphisms 391 12.4.1.1 P-gp Polymorphism 391 12.4.1.2 BCRP Polymorphism 393 12.4.1.3 SLC Polymorphism 393 12.4.2 Age-Related Alterations in BBB Transporter Function and Drug Response 394 12.4.3 Disease-Dependent Modulation of BBB Transporters and Drug Response 395 12.4.3.1 Inflammation and Pain 395 12.4.3.2 Epilepsy 396 12.4.4 CNS Toxicity Caused by Drug Interactions at the BBB 398 12.5 Conclusions 400 References 401 13 Ototoxicity and Drug Transport in the Cochlea 413Stefanie Kennon-McGill and Mitchell R. McGill 13.1 Auditory System Anatomy 413 13.1.1 External, Middle, and Inner Ear 413 13.1.1.1 Anatomy of the Inner Ear 414 13.1.1.2 Hair Cell Anatomy 414 13.1.2 Blood–Labyrinth Barrier 415 13.2 Auditory System Physiology 416 13.3 Hearing Loss, Ototoxic Drugs, and Hair Cell Damage 416 13.3.1 Aminoglycosides 417 13.3.2 Platinum Chemotherapeutics 418 13.3.3 Salicylate 419 13.4 Drug Metabolism in the Ear 419 13.4.1 The Importance of Drug Metabolism in the Ear 419 13.4.2 Studies of Drug-Metabolizing Enzymes in Ototoxicity 420 13.4.3 Drug Transporters in the Ear 421 13.5 Conclusion 423 References 423 Part IV Modeling Drug Metabolizing Enzymes-Transporters Interplay for The Prediction of Drug Toxicity 427 14 Application of a PBPK Model Incorporating the Interplay Between Transporters and Drug-Metabolizing Enzymes for the Precise Prediction of Drug Toxicity 429Kazuya Maeda 14.1 Importance of the Consideration of Intracellular Concentration of Drugs in the Tissue for Estimation of Pharmacological/Toxicological Effects of Drugs 429 14.2 Extended Clearance Concept as a Tool to Explain Theoretically Transporter and Drug-Metabolizing Enzyme Interplay 431 14.3 Theoretical Consideration of the Intracellular Concentration of Drugs in the Tissue 433 14.4 The Benefits of Using a PBPK Model for the Accurate Prediction of Pharmacological/Toxicological Effects of Drugs 436 14.5 VCT to Simulate the Distribution of Clinical Outcomes in a Specific Population with Defined Mean and Variability of Parameters in a PBPK Model 440 14.5.1 VCT of Docetaxel to Estimate the Effects on the Risk of Neutropenia of Genetic Polymorphisms in OATP1B3 and MRP2 442 14.5.2 VCT of Oseltamivir and Its Active Metabolite (Ro 64-0802) to Estimate the Effects on Their Brain Exposure of Genetic Polymorphisms in Multiple Uptake/Efflux Transporters 444 14.5.3 VCT of Irinotecan and Its Metabolites to Estimate the Effects of Genetic Polymorphisms in Multiple Uptake/Efflux Transporters on Irinotecan-Induced Side Effects (Neutropenia, Diarrhea) 447 14.6 Conclusions and Future Perspectives 450 References 451 15 The Extended Clearance Model: A Valuable Tool For Drug-Induced Liver Injury Risk Prediction 455Birk Poller, Felix Huth, Vlasia Kastrinou-Lampou, Gerd A. Kullak-Ublick, Michael Arand, and Gian Camenisch 15.1 Introduction 455 15.2 Application of the ECM to Estimate Kpuu Liver 457 15.2.1 Introduction to the ECM: Concepts and Application for the Prediction of Hepatic Clearance and Drug–Drug Interactions 457 15.2.2 Concept of Kpuu Liver 460 15.2.3 Estimation of Kpuu Liver from In Vitro Data Using the ECM 461 15.3 Relevant Concentrations for the DILI Risk Assessment 462 15.3.1 Maximum Plasma Concentrations 464 15.3.2 Maximum Hepatic Inlet Concentrations 464 15.3.3 Maximum Intracellular Hepatocyte Concentrations 465 15.4 Assessing the DIC Risk Using ECM-Based Unbound Intrahepatic Concentrations and Accounting for BSEP Inhibition as a Single Mechanism 465 15.5 Assessing the DILI Risk Using the “1/R-Value Model” to Account for the Inhibition of Multiple Pathways 467 15.5.1 ECM-Based 1/R-Value Model 467 15.5.2 1/R vs Safety Margin Relationship 471 15.6 Discussion and Outlook 473 References 475 Index 481

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Book SynopsisA comprehensive overview of the new business context for biopharma companies, featuring numerous case studies and state-of-the-art marketing models Biotechnology has developed into a key innovation driver especially in the field of human healthcare. But as the biopharma industry continues to grow and expand its reach, development costs are colliding with aging demographics and cost-containment policies of private and public payers. Concurrently, the development and increased affordability of sophisticated digital technologies has fundamentally altered many industries including healthcare. The arrival of new information technology (infotech) companies on the healthcare scene presents both opportunities and challenges for the biopharma business model. To capitalize on new digital technologies from R&D through commercialization requires industry leaders to adopt new business models, develop new digital and data capabilities, and partner with innovators and payers wTable of ContentsForeword By Philip Kotler xi Preface xiii Acknowledgments xvii About The Authors xix Part 1 New Models For Networked Innovation Chapter 1 Digital Evolution of Biotechnology 3 Industry Applications 5 Impact of Megatrends 6 Digital Health Opportunities 6 Infotechnology Initiatives in Healthcare 8 Disruption Risk from Infotech 8 Technology Strategies 11 Big Infotech Strategies 12 Conclusion 21 Summary Points 22 Chapter 2 Biotechnology Financing Strategies 24 The Long Game 24 Financing Strategies for the Long Term at Alnylam 26 Strategic Decisions 30 Geographic Considerations 33 Sources of Financing 33 A Word about Mergers and Acquisitions 43 Summary Points 44 Chapter 3 Success Through Collaboration 46 Alliance Evolution: More Players and New Structures 46 Strategic Alliances: A Stalwart of the Biopharma Industry 50 Janssen and OSE Immunotherapeutics: Deal Strategies in a European Context 52 Alliance versus Acquisition 53 Structure Considerations to Maximize Value 55 Divesting for Focus 55 Doing the Deal 56 Summary Points 65 Part 2 New Business and Marketing Models Chapter 4 Precision Medicine 69 What is Precision Medicine? 69 Targeted Medicines Multiply but Drug-Diagnostic Pairs are Rare 69 Precision Medicine is Happening at Several Levels 71 Multiple Forces, Beyond Science, are Driving Precision Medicine 72 Digital Precision Medicine 74 Precision Medicine in Practice: Lessons from Cancer 75 Challenges: Scientific, Infrastructural, Regulatory, and Commercial 79 Surmounting the Hurdles to Revolutionize Medicine 83 Stakeholder Expansion in Precision Medicine 86 Biopharma Must Drive, not be Driven by, Precision Medicine 87 Precision Medicine’s Future 90 Summary Points 92 Chapter 5 Precision Marketing 94 Introduction 94 Portfolio Shift to Specialty Products 95 Balancing Evidence and Experience 96 R & D and Commercial Coordination 97 Science is the New Marketing 98 Value of Experience: The Consumer Decision Journey 100 Marketing Beyond the Pill 101 Targeting New Consumer Segments 102 New Physician Segments 102 Dual Branding Models 103 New Launch Strategies 105 Companion Diagnostics 105 Global Organization 108 Multichannel Communications 109 Content Marketing 110 Salesforce Strategies 111 Sustainability Strategies: Beyond the Life Cycle 113 Summary Points 118 Chapter 6 Patient Centricity Strategies 120 Introduction 120 Patient Centricity Drivers and Barriers 121 Discovery: Understanding Unmet Needs 123 Designing Patient-Friendly Clinical Trials 125 Connecting the Points of Care 130 Understanding the Patient Journey 135 Organizing for Patient Centricity 138 Who Are You Working For? Bristol-Myers Squibb Employee Engagement Initiative 138 Patient Engagement Metrics 140 Organization Models 142 Summary Points 143 Chapter 7 Drug Pricing In Context 145 Introduction 145 The Economics of Drug Pricing 146 Competing Definitions of Product Value Complicate Drug Pricing 153 Proving Efficacy in the Real World 155 Setting the Pricing Strategy 157 Analyzing New Pricing Models 160 Drug Pricing in the United States: The Pressure Continues to Build 162 Deployment of New Pricing Strategies 163 Experimental Pricing Strategies 165 Financing the Future: Affordability 169 New Tools for Outcomes-Data Capture 170 Conclusion 171 Summary Points 171 Chapter 8 Strategic Payer Engagement 173 Payers Are Not All Alike 173 New Market Forces Increase Payer Power 175 The Increasing Importance of the Consumer in the United States 176 European Payers: High-Level Unity, Low-Level Fragmentation 180 United States Adopts European-Style Cost-Effectiveness Hurdles 181 Payer Engagement Strategies Must be Tailored, Scalable, and Flexible 182 Changing Biopharma-Payer Relationships: From Transactional to Collaborative 185 New Biopharma Organizational Models Needed 187 Biopharma-Payer Engagement Must Move Beyond Experimentation 188 Strategic Payer Engagement Comes in Many Forms 192 Summary Points 193 Part 3 New Models For Digital Health Chapter 9 Digital Health Strategies 197 Introduction 197 Biopharma Digital Strategies 197 Digital Impact on Supply Chain Management 200 Digital Transformation of Commercial Activities 201 Consumer-Centered Trends 206 Provider-Centered Strategies: Telehealth 210 Conclusion 213 Summary Points 213 Chapter 10 Creating Agility Through Data and Analytics 215 Introduction 215 Multiple Forces Converge to Create Data and Analytics Opportunities 216 Healthcare’s Four Data Vectors: Volume, Velocity, Variety, and Veracity 218 Extracting Value from Data Requires New Tools 221 The Analytics Continuum: From Descriptive to Prescriptive 223 Artificial Intelligence: The Potential to Make Drugs Smarter, Faster, and for Less 225 Data Analytics across the Biopharma Value Chain 226 Data and Analytics Challenges 233 Building an Analytics-First Organization: Cultural not Technical Hurdles 238 Conclusion 242 Summary Points 242 Conclusion 243 References 246 Index 273

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Book SynopsisI thoroughly enjoyed reading this book as it has taken me on a journey through time, across the globe and through multiple disciplines. Indeed, we need to be thinking about these concepts and applying them every day to do our jobs better. Farah Magrabi, Macquarie University, Australia The reader will find intriguing not only the title but also the content of the book. I'm also pleased that public health, and even more specifically epidemiology has an important place in this ambitious discussion. Elena Andresen, Oregon Health & Science University, USA This book is very well written and addresses an important topic. It presents many reasons why basic scientists/researchers should establish collaborations and access information outside traditional means and not limit thinking but rather expand such and perhaps develop more innovative and translational research ventures that will advance science and not move it laterally. Gerald Pepe, Eastern VirginiaTable of ContentsPreface vii Part One Outcomes of Research 1 1 Pathways of the Research Innovator 3 2 First Dimension: Scientific Impact 21 3 Second Dimension: Public Health Value 37 4 Third Dimension: Economic Development 53 Part Two Headwinds of Research Innovation 69 5 Slowdown and Erosion 71 6 Non‐reproducible Research 89 7 Red Tape and Litigation 109 Part Three Boosters of Research Productivity 131 8 Humanism for Innovation 133 9 Desire to Understand First 151 10 Learning from the Best 169 11 Cracking Public Health Needs 183 12 Engaged Research 197 13 Cross‐cultural Convergence 215 14 Targeting and Repurposing 229 15 Trailblazing Technologies 243 16 Emulating Nature 259 17 Scientific Modeling 273 18 Mastering Bioentrepreneurship 291 19 Art of Scientific Communication 309 Part Four Atmosphere of Excellence 329 20 Quality and Performance Improvement 331 21 Institutional and National Strategies 345 22 International Collaboration and Competition 365 List of of award-winning scientists and serial innovators 381 Subject Index 387

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Book SynopsisAn essential guide to healthcare data problems, sources, and solutions Strategies in Biomedical Data Science provides medical professionals with much-needed guidance toward managing the increasing deluge of healthcare data.Table of ContentsForeword xi Acknowledgments xv Introduction 1 Who Should Read This Book? 3 What’s in This Book? 4 How to Contact Us 6 Chapter 1 Healthcare, History, and Heartbreak 7 Top Issues in Healthcare 9 Data Management 16 Biosimilars, Drug Pricing, and Pharmaceutical Compounding 18 Promising Areas of Innovation 19 Conclusion 25 Notes 25 Chapter 2 Genome Sequencing: Know Thyself, One Base Pair at a Time 27 Content contributed by Sheetal Shetty and Jacob Brill Challenges of Genomic Analysis 29 The Language of Life 30 A Brief History of DNA Sequencing 31 DNA Sequencing and the Human Genome Project 35 Select Tools for Genomic Analysis 38 Conclusion 47 Notes 48 Chapter 3 Data Management 53 Content contributed by Joe Arnold Bits about Data 54 Data Types 56 Data Security and Compliance 59 Data Storage 66 SwiftStack 70 OpenStack Swift Architecture 78 Conclusion 94 Notes 94 Chapter 4 Designing a Data-Ready Network Infrastructure 105 Research Networks: A Primer 108 ESnet at 30: Evolving toward Exascale and Raising Expectations 109 Internet2 Innovation Platform 111 Advances in Networking 113 InfiniBand and Microsecond Latency 114 The Future of High-Performance Fabrics 117 Network Function Virtualization 119 Software-Defined Networking 121 OpenDaylight 122 Conclusion 157 Notes 157 Chapter 5 Data-Intensive Compute Infrastructures 163 Content contributed by Dijiang Huang, Yuli Deng, Jay Etchings, Zhiyuan Ma, and Guangchun Luo Big Data Applications in Health Informatics 166 Sources of Big Data in Health Informatics 168 Infrastructure for Big Data Analytics 171 Fundamental System Properties 186 GPU-Accelerated Computing and Biomedical Informatics 187 Conclusion 190 Notes 191 Chapter 6 Cloud Computing and Emerging Architectures 211 Cloud Basics 213 Challenges Facing Cloud Computing Applications in Biomedicine 215 Hybrid Campus Clouds 216 Research as a Service 217 Federated Access Web Portals 219 Cluster Homogeneity 220 Emerging Architectures (Zeta Architecture) 221 Conclusion 229 Notes 229 Chapter 7 Data Science 235 NoSQL Approaches to Biomedical Data Science 237 Using Splunk for Data Analytics 244 Statistical Analysis of Genomic Data with Hadoop 250 Extracting and Transforming Genomic Data 253 Processing eQTL Data 256 Generating Master SNP Files for Cases and Controls 259 Generating Gene Expression Files for Cases and Controls 260 Cleaning Raw Data Using MapReduce 261 Transpose Data Using Python 263 Statistical Analysis Using Spark 264 Hive Tables with Partitions 268 Conclusion 270 Notes 270 Appendix: A Brief Statistics Primer 290 Content Contributed by Daniel Peñaherrera Chapter 8 Next-Generation Cyberinfrastructures 307 Next-Generation Cyber Capability 308 NGCC Design and Infrastructure 310 Conclusion 327 Note 330 Conclusion 335 Appendix A The Research Data Management Survey: From Concepts to Practice 337 Brandon Mikkelsen and Jay Etchings Appendix B Central IT and Research Support 353 Gregory D. Palmer Appendix C HPC Working Example: Using Parallelization Programs Such as GNU Parallel and OpenMP with Serial Tools 377 Appendix D HPC and Hadoop: Bridging HPC to Hadoop 385 Appendix E Bioinformatics + Docker: Simplifying Bioinformatics Tools Delivery with Docker Containers 391 Glossary 399 About the Author 419 About the Contributors 421 Index 427

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Book SynopsisThe GnRH Neuron and its Control examines the developmental biology of GnRH neurons including their birth in the nasal placode of the early embryo, perinatal programming, and sexual differentiation, in addition to the hypothalamic mechanisms that control GnRH neurons in adulthood to generate pulsatile and surge modes of GnRH secretion throughout the major life stages including aging. The morphology, electrophysiology, signal transduction pathways, transcriptional regulators, and genomics underlying function of the adult GnRH neuron is discussed in detail, as is the neuroendocrinology and cell biology governing the generation of both modes of GnRH release. The book also reviews the neurobiological mechanisms and circuitry responsible for the modulation of the activity of GnRH neurons by season, stress, nutrition, and metabolism, and covers the current and potential therapeutic approaches to regulating GnRH secretion and action. Filled with newly identified research and classical fundaTable of ContentsList of Contributors, vii Series Preface, xi Preface, xiii About the Companion Website, xv PART I Historical Introduction to the GnRH Neuron 1 The Framework Upon Which Current Research on the GnRH Neuron and its Control is Built, 3Tony M. Plant and Allan E. Herbison PART II GnRH Neuron Development 2 Prenatal Development of GnRH Neurons, 15Yufei Shan and Susan Wray 3 Fetal/perinatal Programming Causing Sexual Dimorphism of the Kisspeptin–GnRH Neuronal Network, 43Hiroko Tsukamura, Kei]ichiro Maeda and Yoshihisa Uenoyama 4 Postnatal Development of GnRH Neuronal Function, 61Ei Terasawa PART III GnRH Neuron Biology 5 Regulation of GnRH Gene Expression, 95Hanne M. Hoffmann and Pamela L. Mellon 6 Morphology of the Adult GnRH Neuron, 121Rebecca E. Campbell 7 The Anatomy of the GnRH Neuron Network in the Human, 149Katalin Skrapits and Erik Hrabovszky 8 Electrophysiology of Rodent GnRH Neurons, 177Richard Piet and Allan E. Herbison 9 Anatomy and Physiology of GnRH Neurons and Their Control of Pituitary Function in Fish, 203Yoshitaka Oka PART IV Regulation of GnRH Neuron Function 10 Unveiling the Importance of Glia and Vascular Endothelial Cells in the Control of GnRH Neuronal Function, 227Vincent Prevot and Ariane Sharif 11 Genetic Strategies Examining Kisspeptin Regulation of GnRH Neurons, 259Michael Candlish, Philipp Wartenberg and Ulrich Boehm 12 KNDy Hypothesis for Generation of GnRH Pulses: Evidence from Sheep and Goats, 289Robert L. Goodman, Satoshi Okhura, Hiroaki Okamura, Lique M. Coolen, and Michael N. Lehman 13 Generation of the GnRH Surge and LH Surge by the Positive Feedback Effect of Estrogen, 325Iain Clarke 14 Influence of Stress on the GnRH Neuronal Network, 357Pasha Grachev and Kevin T. O’Byrne 15 Metabolic Regulation of GnRH Neurons, 383Maggie C. Evans and Greg M. Anderson 16 Seasonal Control of the GnRH Neuronal Network as a Means of Uncovering Novel Central Mechanisms Governing Mammalian Reproduction, 411Sébastien Milesi, Paul Klosen and Valerie Simonneaux PART V GnRH in the Clinic 17 Human Genetics of GnRH Neuron Function, 445A. Kemal Topaloglu and L. Damla Kotan 18 Modulators of GnRH Secretion and Therapeutic Applications, 469Claire L. Newton, Ross C. Anderson and Robert P. Millar Index, 499

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Book SynopsisExtensively revised and updated, this fourth edition of Physiology at a Glance continues to provide a thorough introduction to human physiology, covering a wealth of topics in a comprehensive yet succinct manner.Table of ContentsPreface vii Acknowledgements viii Abbreviations ix About the companion website xi Part 1 Introduction 1 1 Homeostasis and the physiology of proteins 2 2 Body water compartments and physiological fluids 4 3 Cells, membranes and organelles 6 4 Membrane transport and ion channels 8 5 Biological electricity 10 6 Conduction of action potentials 12 7 Cell signalling 14 8 The autonomic nervous system 16 9 Blood 18 10 Platelets and haemostasis 20 11 Defence: inflammation and immunity 22 12 Principles of diffusion and flow 24 13 Thermoregulation 26 14 Altitude and aerospace physiology 28 Part 2 Muscles 31 15 Skeletal muscle and its contraction 32 16 Neuromuscular junction and whole muscle contraction 34 17 Motor units, recruitment and summation 36 18 Cardiac and smooth muscle 38 Part 3 The cardiovascular system 41 19 Introduction to the cardiovascular system 42 20 The heart 44 21 The cardiac cycle 46 22 Initiation of the heart beat and excitation–contraction coupling 48 23 Control of cardiac output and Starling’s law of the heart 50 24 Blood vessels 52 25 Control of blood pressure and blood volume 54 26 The microcirculation, filtration and lymphatics 56 27 Local control of blood flow and specific circulations 58 Part 4 The respiratory system 61 28 Introduction to the respiratory system 62 29 Lung mechanics 64 30 Transport of gases and the gas laws 66 31 Carriage of oxygen and carbon dioxide by the blood 68 32 Control of breathing 70 33 Ventilation–perfusion matching and right to left shunts 72 Part 5 The renal system 75 34 Introduction to the renal system 76 35 Renal filtration 78 36 Reabsorption, secretion and the proximal tubule 80 37 The loop of Henle and distal nephron 82 38 Regulation of plasma osmolality and fluid volume 84 39 Control of acid–base status 86 Part 6 The gut and metabolism 89 40 Gastrointestinal tract: overview and the mouth 90 41 Oesophagus and stomach 92 42 Small intestine 94 43 The exocrine pancreas, liver and gallbladder 96 44 Large intestine 98 Part 7 Endocrinology and reproduction 101 45 Endocrine control 102 46 Control of metabolic fuels 104 47 The hypothalamus and pituitary gland 106 48 Thyroid hormones and metabolic rate 108 49 Growth factors 110 50 Somatic and skeletal growth 112 51 Control of plasma calcium 114 52 The adrenal glands and stress 116 53 Endocrine control of reproduction 118 54 Sexual differentiation and function 120 55 Fertilization, pregnancy and parturition 122 56 Lactation 124 Part 8 The sensory and motor systems 127 57 Introduction to sensory systems 128 58 Sensory receptors 130 59 Special senses: taste and smell 132 60 Special senses: vision 134 61 Special senses: hearing and balance 136 62 Motor control and the cerebellum 138 63 Proprioception and reflexes 140 Glossary 142 Appendix I Comparison of the properties of skeletal, cardiac and smooth muscle 144 Appendix II Normal physiological values 145 Index 148

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Book SynopsisA comprehensive review of the fundamental molecular mechanisms in fermentation and explores the microbiology of fermentation technology and industrial applications Microbial Sensing in Fermentation presents the fundamental molecular mechanisms involved in the process of fermentation and explores the applied art of microbiology and fermentation technology. The text contains descriptions regarding the extraordinary sensing ability of microorganisms towards small physicochemical changes in their surroundings. The contributors noted experts in the field cover a wide range of topics such as microbial metabolism and production (fungi, bacteria, yeast etc); refined and non-refined carbon sources; bioprocessing; microbial synthesis, responses and performance; and biochemical, molecular and extra/intracellular controlling. This resource contains a compilation of literature on biochemical and cellular level mechanisms for microbial controlled production and includes the most significant recTable of ContentsList of Contributors xi 1 Biochemical Aspects of Microbial Product Synthesis: a Relook 1G. Gallastegui, A. Larrañaga, Antonio Avalos Ramirez, and Thi Than Ha Pham 1.1 Introduction 1 1.2 History of Industrial Production of Microbial Products 2 1.2.1 Advances of Biochemical Engineering and Their Effects on Global Market of Microbial Products 3 1.2.2 Importance of Microbial Sensing in Product Formation 6 1.3 Conclusion 7 Acknowledgments 8 References 8 2 Cellular Events of Microbial Production: Important Findings So Far 11Devangana Bhuyan and Ratul Kumar Das 2.1 Introduction 11 2.2 Microbial Metabolism and Evolution of Metabolic Pathways 12 2.3 Microbial Fermentation 12 2.4 The Microbial Cellular Events 15 2.5 Cell Signalling in Microorganisms 19 2.6 Microbial Performance Under Stress Conditions 21 Acknowledgment 24 References 24 3 Microbial Metabolism in a Refined Carbon Source: Generalities 27Vinayak Laxman Pachapur, Preetika Rajeev Kuknur, Satinder Kaur Brar, and Rosa Galvez-Cloutier 3.1 Introduction 27 3.2 Microbial Metabolism in Presence of Pure and Crude Substrate 29 3.3 Microbial Metabolism in Presence of Pure and Mixed Cultures 31 3.4 Microbial Metabolism in the Presence of Co‐Substrate 33 3.5 Microbial Metabolism in the Presence of Input Parameters 35 3.6 Microbial Metabolism in the Presence of Varying Fermentation Conditions 37 3.7 Pros and Cons of Refined Substrate for Metabolic Metabolisms 38 3.8 Conclusions 39 Acknowledgment 40 References 40 4 Non‐refined Carbon Sources and Microbial Performance 43Guneet Kaur 4.1 Introduction 43 4.2 Non‐refined Carbon Sources: a Brief Account 43 4.3 Microbial Assimilation of Non‐Refined Carbon Sources 45 4.4 Microbial Sensing to Non‐Refined Carbon Sources 48 4.4.1 Microbial Metabolism and Regulatory Circuits 48 4.4.2 CCR Regulation of Carbon Uptake and Metabolism 51 4.5 Guiding Product Outcomes via Rewiring of Cellular Regulatory Circuit 53 4.5.1 Cellular Engineering in E. Coli for Bioprocessing of Non‐Refined Carbon Sources 54 4.5.2 Rewiring S. cerevisiae for Accumulation and Conversion of Non‐refined Carbon Sources 55 4.6 Conclusions 56 References 57 5 Cellular versus Biochemical Control over Microbial Products 61Carlos S. Osorio-González, Krishnamoorthy Hegde, and Satinder Kaur Brar 5.1 Introduction 61 5.2 3 Hydroxy‐propionic Acid 62 5.3 Fumaric Acid 64 5.4 Itaconic Acid 65 5.5 Glucaric Acid 67 5.6 Butanol 68 5.7 Malic Acid 69 5.8 Gluconic Acid 71 5.9 Aminovalaric Acid 71 5.10 Glutamic Acid 73 5.11 Cadaverine (1,5‐diaminopentane) 74 5.12 Conclusion 76 Acknowledgment 76 References 76 6 Pre‐Treatment of Alternative Carbon Source: How Does it Make Sense to Microorganism at Cellular Level? 89Joseph Sebastian, Pratik Kumar, Krishnamoorthy Hegde, Satinder Kaur Brar, Mausam Verma, and Ratul Kumar Das 6.1 Introduction 89 6.2 Pre‐ Treated Carbon Source and Microbial Assimilation: Cellular and Biochemical Aspects 91 6.2.1 Alcohols 94 6.2.1.1 Bioethanol 94 6.2.1.2 Butanol and Acetone 96 6.2.2 Hydrogen 98 6.2.3 Methane/biogas 101 6.2.4 Organic Acids 103 6.3 Challenges of Inhibitory Hydrolysis Products and Strategic Solution 106 6.3.1 Inhibitory Products: Pretreatment Metabolites or By‐products 106 6.3.1.1 Aliphatic Compounds 106 6.3.1.2 Aromatic Compounds 107 6.3.1.3 Furan Aldehydes 108 6.3.2 Strategies to Control Inhibitory Effects 109 6.3.2.1 Biological Detoxification Strategy for the Inhibitors 110 6.3.2.2 Understanding the Mechanism of Microorganism Adaptation for The Detoxification of Inhibitory Compounds 110 6.3.2.2.1 Homeostasis 110 6.3.2.2.2 Enzymatic Detoxification 111 6.3.2.3 Physical and Chemical Detoxification Strategy for Inhibitors 112 6.3.3 Correlation (Synergistic Effects) of Inhibitory Compounds and their Detoxification 118 6.4 Conclusion 126 Acknowledgments 127 References 127 7 Microbial Metabolic Pathways in the Production of Valued‐added Products 137Gilberto V. de Melo Pereira, Ana M. Finco, Luiz A. J. Letti, Susan Grace Karp, Maria G. B. Pagnoncelli, Juliana de Oliveira, Vanete Thomaz Soccol, Satinder Kaur Brar, and Carlos Ricardo Soccol 7.1 Introduction 137 7.2 Microbial Molecular Structure 138 7.3 Biomass Production 140 7.3.1 Single Cell Oil 140 7.3.2 Single Cell Protein 142 7.4 Enzymes 148 7.5 Biofuels 150 7.6 Alkaloids, Terpenoids, Polyketides and Flavonoids 153 7.7 Organic Acids 155 7.8 Rare Sugars 156 7.9 Conclusions 157 References 158 8 Communication for a Collective Response to Environmental Stress: Bacterial and Fungal Perspectives 169Azadeh Kermanshahi Pour 8.1 Introduction 169 8.2 Quorum Sensing in Bacteria and the Related Phenotypes 172 8.3 Fermentation and Quorum Sensing in Bacteria 177 8.4 Quorum Sensing in Fungi and the Related Phenotypes 183 8.5 Fermentation and Quorum Sensing in Fungi 186 8.6 Quorum Sensing in Bacteria and Fungi: Similarities and Differences 188 Acknowledgment 189 References 189 9 Biochemical and Cellular Events in Controlling Microbial Performance: A Comparative Account 201Shadab Ahmed, Shreyas Niphadkar, Somnath Nandi, Satya Eswari, Vishal Pandey, Aishwarya Shankapal, and Aishvarya Agrawal 9.1 Biochemical vs. Molecular Cues for Microbial Performances 201 9.1.1 Nutritional Parameters Optimization 201 9.1.2 Process Condition Optimization 202 9.1.3 Process Improvement by Using Batch and Fed‐Batch via Process and Modeling 203 9.1.4 Metabolic Engineering for Improving Microbial Performance 203 9.1.4.1 Metabolic Flux Balance Analysis 203 9.1.4.1.1 Constraint Based Flux Balance Analysis 203 9.1.4.1.2 Defining Biological Objective to Optimize a Phenotype 204 9.1.4.1.3 Applications of Flux Analysis 204 9.1.5 Strain Improvement for Microbial Performance 205 9.1.5.1 Mutagenesis for Strain Improvement 205 9.1.5.1.1 Physical Mutagenesis 205 9.1.5.1.2 Chemical Mutagenesis 206 9.1.5.1.3 Biological Mutagenesis 206 9.2 Sequential Evidences of Biochemical and Molecular Controlling Over Microbial Performances 206 9.3 Biochemically Influenced Molecular Events and Vice Versa 208 9.4 Facts at the Interface of Biochemical and Molecular Controlling: Products vs Applied Parameters 208 9.4.1 Sulfur‐Delivery into Biosynthetic Pathway 208 9.4.2 Synthetic Biochemistry Platform for Production of Glucose 212 9.4.3 Biochemical and Molecular Aspects of Metabolic Engineering Approaches 212 9.4.3.1 Engineering Regulatory Network 212 9.4.3.2 Heterologous Expression of Entire Gene Cluster 213 9.4.3.3 Rerouting Metabolic Pathway 213 9.4.3.4 Integration of Metabolic Engineering and Process Engineering 213 9.5 Conclusions 214 References 214 10 Qualitative vs. Quantitative Control Over Microbial Products 223Rachna Goswami, Vijay Kumar Mishra, and Radhika Pilli 10.1 Introduction 223 10.2 Qualitative vs. Quantitative Control Over Microbial Products/Fungal Products 224 10.2.1 Qualitative Control and Fungal Product 225 10.2.1.1 Diffusion Techniques 226 10.2.1.2 Thin Layer Chromatography (TLC) 229 10.2.1.3 Chromatography‐bioautography for Screening of Antimicrobial Activity 231 10.2.1.4 High‐performance Liquid Chromatography (HPLC) 232 10.2.2 Quantitative Control of Fungal Products 232 10.2.3 Speeding Up Fungal Product 234 10.3 Fungal Morphology and Product Spectrum: a Representative Theme 237 10.4 Effectiveness of Qualitative Domain for Different Microorganisms 241 10.5 Emphasizing the Need: Qualitative and Quantitative Importance 245 10.6 Conclusions 246 References 247 11 Microbes and Their Products as Sensors in Industrially Important Fermentations 253Ritu Raval and Keyur Raval 11.1 Introduction 253 11.2 Sensors 254 11.3 Transducers in Conjunction With Microbe Sensors 254 11.3.1 Dissolved Oxygen (DO) Electrode 254 11.3.2 Electron Transfer Measuring Systems 255 11.4 Metabolite Measuring Systems 256 11.5 Other Measuring Systems 257 11.5.1 Bioluminescence Biosensor 257 11.6 Applications of Microbe Sensors in Some Commercially Important Products 258 11.6.1 Red Wine 260 11.6.2 Fermentation of Cereal Products 260 11.6.3 Mevalonate Production 261 11.6.4 Bioaerosols 261 11.6.5 Aptamers 262 11.7 Conclusions 263 References 263 12 Practical Aspects and Case Studies of Industrial Scale Fermentation 267Sara Magdouli, Thana Saffar, Tayssir Guedri, Rouissi Tarek, Satinder Kaur Brar, and Jean François Blais 12.1 Introduction 267 12.2 Scale Up Challenges 269 12.2.1 Agitation 269 12.2.2 Mass Transfer of Oxygen (Mass Transfer, Morphology, and Rheology) 270 12.2.3 “Shear Damage” 271 12.2.4 Measurements for Control 273 12.2.5 Other Aspects 273 12.3 Microbial Tolerance 274 12.4 Phage Invasion 274 12.5 Process Failures 277 12.6 Potent Inhibitors (e.g. Substrate Inhibition) 278 12.7 Case Studies: Biofuels (Biodiesel, Ethanol) Enzymes (Novozymes), Antibiotics, Platform Chemicals 281 12.7.1 Biofuels (Biodiesel, Ethanol) 281 12.7.2 Enzymes (Novozymes) 283 12.7.3 Antibiotics 286 12.7.4 Platform Chemicals 288 12.8 Conclusions 289 Acknowledgments 290 References 290 13 Future Market and Policy Initiatives of New High Value Products 299Ha Thi Thanh Pham, Maria Puig‐Gamero, Luz Sanchez‐Silva, Paula Sánchez, José Luis Valverde, Michele Heitz, and Antonio Avalos Ramirez 13.1 Introduction 299 13.2 Market Analysis, Market Trends and Statistics 299 13.2.1 Biofuels 299 13.2.2 Bio‐surfactants 302 13.2.3 Enzymes 305 13.3 Public Mobilization Initiatives and Government Policies 306 13.3.1 Public Mobilization Initiatives 306 13.3.2 Government Policies 307 13.3.3 Regional Policy Development for Growing Bio‐based Production 307 13.4 Regulations and Conformity – Case of Biofuels 307 13.5 Global Marketing and Competitiveness in Biofuel Sector 309 References 309 Index 311

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Book SynopsisThis book provides a comprehensive review of the chemistry and research illustrating the benefits of polyurethane for immobilizing cells, with dozens of case studies in medical devices and environmental engineering. Offers an essential resource for medical and environmental scientists Provides a multidisciplinary and lucid writing style that uses little or no jargon Extrapolates current technology into advanced areas, especially environmental remediation and medical devices Fills the gap between immobilization research and practical applicationsTable of ContentsPreface ix 1 Polyurethane Chemistry 1 Introduction 1 The Chemistry 2 The Isocyanates 3 The Polyol 5 Cross-Linking 5 The Water Reaction 6 Process 8 The One-Shot Process 8 The Prepolymer Process 10 Post Processing 12 Architecture of Polyurethane Foam 14 Grafting to the Polyurethane Foam 16 Biodegradable PUR 19 Mechanism of Biodegradation 23 More Examples 24 Conclusion 25 References 26 2 Laboratory Practice 29 Introduction 29 Prepolymers 30 Preparation of an Elastomer 30 Preparation of Foam 32 Hydrophobic Foams 32 Hydrophilic Foams 34 Custom Prepolymers, Foams, and Scaffolds 40 Examples 43 Structure–Property Relationships 48 The Special Case of Hydrophilic Polyurethane Foams 50 Physical and Chemical Testing 50 Physical Testing 52 Biocompatibility Testing 54 Process Equipment 54 Metering Pump 55 Mixing Head 55 Tank/Material Retaining Container 55 Machine Manufacturers 56 References 56 3 Scaffolds 59 Introduction 59 Bioscaffolds 61 Examples of Biofilter 65 Elimination of Tobacco Odor from a Cigarette-Manufacturing Plant 67 Treatment of VOCs from an Industrial Plant 68 The Liver as Biofilter 68 Scaffolds for Medical Applications (In Vivo and Extracorporeal) 70 The Liver Model 71 The Extracellular Matrix as Scaffold 72 The Physical Scaffold 73 Design of an Ideal Scaffold 74 Drug Discovery 75 Materials of Construction 77 Ceramics 77 Metals 80 Polymer Scaffolds 82 Poly(lactic Acid) 82 Poly(glycolic Acid) 82 Polycaprolactone 83 Polyurethanes 83 The “Ideal” Scaffold 87 Pore Size and Distribution 89 Void Volume 91 Interconnectedness 96 Surface Area 98 Mechanical Properties 100 Surface Chemistry 100 Specifications of the Ideal Scaffold 101 References 105 4 Immobilization 109 Introduction 109 Methods of Immobilization 111 Immobilization by Adsorption 113 Biofiltration 113 Biotrickling Filter Setup and Operating Conditions 115 The Toluene Reactor 116 The H2S Reactor 120 Biological Treatment of Aquarium Tanks 123 Protein Adsorption 125 The Avidin–Biotin System 126 Application of the Avidin–Biotin System to Cell Adhesion to a Scaffold 128 Adsorption to a Tricalcium Phosphate (TCP) Scaffold Using the Avidin–Biotin System 128 Hepatic Cells on a Fabricated Polycaprolactone Scaffold 131 Summary of Immobilization by Adsorption 132 Immobilization by Extraction 133 Extraction of Pesticides 138 Summary 144 Immobilization by Entrapment 145 Alginate Encapsulation 146 Encapsulation of Pancreatic Islet Cells 148 Encapsulation of Osteoblasts 148 Introduction to the Pancreas Model 149 The Pancreas Model 150 Summary of Encapsulation 154 Immobilization by Covalent Bonding 154 Overview of Covalent Immobilization 156 Substrates Used for Immobilization 157 Alginates 158 Albumin 159 Collagen 159 Synthetic Polymers as Supports 159 Polyethylene 159 Poly l-Lactic Acid 160 Immobilization to Polyvinyl Chloride 161 Ceramics 163 Summary 163 Polyurethane Immobilization 164 Fundamental Principles 164 Prepolymer Chemistry 168 The Immobilization Chemistry 169 Structure and Chemistry of Biomolecules 170 Preparation of Immobilized Biomolecules 171 Notable Uses of Polyurethane for Immobilization 174 Organophosphates 174 Lipases 177 Fibroblasts 178 Collagen 180 Amyloglucosidase 182 Novel Reactor System 184 Endothelialization 185 Creatinine 186 Conclusion to Immobilization 187 References 189 5 Controlled Release from a Hydrogel Scaffold 195 Introduction 195 Release Rates 198 Examples of Hydrogels Used for Controlled Release 198 Polysaccharides 199 Pectin 199 Alginates 200 Carrageenan 200 Agar 200 Starch 200 Proteins 200 Gelatin 200 Casein 201 Other Proteins 201 Controlled Release by Diffusion 201 Reservoir Layer 202 Diffusion Experiments 206 Islet Encapsulation 208 Other Controlled Release Examples 211 Targeted Delivery 211 Stomach 212 Small Intestines 212 Colon 212 Summary and Conclusions 213 References 213 Index 215

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Book SynopsisA comprehensive, edited volume pulling together research on manipulation of the crop microbiome for climate resilient agriculture Microbes for Climate Resilient Agriculture provides a unique collection of data and a holistic view of the subject with quantitative assessment of how agricultural systems will be transformed in coming decades using hidden treasure of microbes. Authored by leaders in the field and edited to ensure conciseness and clarity, it covers a broad range of agriculturally important crops, discusses the impact of climate change on crops, and examines biotechnologically and environmentally relevant microbes. The book encapsulates the understanding of microbial mediated stress management at field level, and will serve as a springboard for novel research findings and new applications in the field. Chapter coverage includes: the role of the phytomicrobiome in maintaining biofuel crop production in a changing climate; the impact of agriculture on soil microbial communitTable of ContentsABOUT THE EDITORS xv LIST OF CONTRIBUTORS xix PREFACE xxiii 1 THE ROLE OF THE PHYTOMICROBIOME IN MAINTAINING BIOFUEL CROP PRODUCTION IN A CHANGING CLIMATE 1Gayathri Ilangumaran, John R. Lamont and Donald L. Smith 1.1 General Background on Climate Change 1 1.2 More Extreme Weather More Often – More Crop Stress 2 1.3 Biofuel Crops – Alternative to Fossil Fuels 3 1.4 Avoiding Competition with Food Production 4 1.5 Fuel Crops Grown on Marginal Lands – Constraints 4 1.6 Plant Response to Stresses Related to Climate Change and Marginal Lands 6 1.7 Sustaining Biofuel Crops Under Stressful Environments 7 1.8 The Phytomicrobiome and Climate Change Conditions 8 1.9 The Phytomicrobiome and Abiotic Plant Stress 8 1.10 Mechanisms of Stress Tolerance in the Phytomicrobiome 9 1.11 Phytomicrobiome Engineering 11 1.12 The Phytomicrobiome in Biofuel Plants 12 1.13 Role of the Phytomicrobiome in Phytoremediation by Biofuel Plants 13 References 14 2 THE IMPACT OF AGRICULTURE ON SOIL MICROBIAL COMMUNITY COMPOSITION AND DIVERSITY IN SOUTHEAST ASIA 25Binu M. Tripathi, Itumeleng Moroenyane and Jonathan M. Adams 2.1 Introduction 25 2.2 The Extent of Soil Microbial Diversity and their Status in Tropical Soils 27 2.3 The Composition and Function of Microbial Communities in Tropical Soils of Southeast Asia 29 2.3.1 Unique Soil Microbial Communities of Southeast Asia and their Potential Drivers 29 2.4 The Impact of Land use Change on Soil Microbial Community Structure and Diversity 31 2.5 The Impact of Land use Change on Soil Functional Gene Diversity 34 2.6 Conclusions 35 References 35 3 CLIMATE CHANGE IMPACT ON PLANT DISEASES: OPINION, TRENDS AND MITIGATION STRATEGIES 41Sachin Gupta, Deepika Sharma and Moni Gupta 3.1 Introduction 41 3.2 Climate Change and Agriculture 42 3.3 Interactions among Global Change Factors 43 3.4 Pathogen–Host Plant Relationship under Changed Scenario 44 3.5 Effect of Climate Change on Plant Diseases 44 3.5.1 Temperature 46 3.5.2 Drought 48 3.5.3 Rainfall 48 3.5.4 CO2 Concentration 48 3.6 Adaptation and Mitigation Strategies for Climate Change 49 3.6.1 Adaptation Strategies 49 3.6.2 Mitigation Strategies 50 3.7 Conclusion and Future Directions 51 References 51 4 MICROALGAE: POTENTIAL AGENTS FOR CARBON DIOXIDE MITIGATION 57Preeti Singh, Rahul Kunwar Singh and Dhananjay Kumar 4.1 Introduction 57 4.2 Carbon Capture and Storage 60 4.3 Carbon Capture by Photosynthesis 60 4.4 CO2 Mitigation by Microalgal Culture 60 4.4.1 The Open Pond System 61 4.4.2 The Closed Photobioreactor System 62 4.4.3 The Environmentally Controlled System 62 4.5 Advantages 62 4.5.1 Integration of Microalgal Culture in Waste Water Treatment 62 4.5.2 Ability of Microalgae to Tolerate the Greenhouse Gases 62 4.6 Carbon Concentrating Mechanism of Microalgae 65 4.7 CO2 Sequestration by Microalgae 65 4.8 Cost Effectiveness 66 4.8.1 Biofertilizer 66 4.8.2 Biofuel 67 4.8.3 Other Products 67 4.9 Conclusion 68 References 68 5 PHOTOSYNTHETIC MICROORGANISMS AND BIOENERGY PROSPECTS: CHALLENGES AND POTENTIAL 75Balkrishna Tiwari, Sindhunath Chakraborty, Ekta Verma and Arun Kumar Mishra 5.1 Introduction 75 5.2 Photosynthetic Microbes 78 5.3 Anoxigenic Photosynthetic Microbes 79 5.3.1 Green Photosynthetic Bacteria 79 5.3.2 Purple Bacteria 82 5.3.3 Heliobacteria 84 5.3.4 Prospects of Anoxigenic Photosynthetic Microbes in Bioenergy Production 86 5.4 Oxygenic Photosynthetic Microbes 87 5.4.1 Cyanobacteria 89 5.4.2 Microalgae 93 5.5 Biomass Production and Challenges 95 5.6 Some Important Issues Associated with Biofuel Production 96 5.6.1 Use of Water 96 5.6.2 Nutrients and Competition with Crops 96 5.6.3 Minimizing Algae Death from Biotic and Abiotic Factors 96 5.6.4 Competition with Petroleum in Terms of Price 97 5.7 Conclusions 97 Acknowledgements 98 References 98 6 AMELIORATION OF ABIOTIC STRESSES IN PLANTS THROUGH MULTI‐FACETED BENEFICIAL MICROORGANISMS 105Usha Chakraborty, Bishwanath Chakraborty and Jayanwita Sarkar 6.1 Introduction 105 6.2 Temperature Stress Alleviation 107 6.2.1 Alleviation by Bacteria 107 6.2.2 Alleviation by Fungi 110 6.3 Water and Salinity Stress Alleviation 112 6.3.1 Alleviation by Bacteria 112 6.3.2 Alleviation by Fungi 118 6.4 Alleviation of Heavy Metal Toxicity 124 6.5 Conclusions 131 References 132 7 ROLE OF METHYLOTROPHIC BACTERIA IN CLIMATE CHANGE MITIGATION 149Manish Kumar, Raghvendra Saxena, Rajesh Singh Tomar, Pankaj K. Rai and Diby Paul 7.1 Introduction 149 7.2 Methylotrophic Bacteria and their Role in Agriculture 151 7.3 Volatile Organic Carbon Mitigation and Methylotrophs 152 7.4 Carbon Cycling and Climate Change 152 7.5 Methylotrophs Mitigating Methane 154 7.6 Methylotrophs Mitigating Methane in Paddy Fields 158 7.7 Conclusions 160 Acknowledgements 160 References 160 8 CONSERVATION AGRICULTURE FOR CLIMATE CHANGE RESILIENCE: A MICROBIOLOGICAL PERSPECTIVE 165Raj Pal Meena and Ankita Jha 8.1 Introduction 165 8.2 The Effect of Climate Change on Agricultural Production 169 8.3 Concepts and Principles of Conservation Agriculture 173 8.4 The Ecological Role of Microbial Biodiversity in Agro‐Ecosystems 177 8.5 Role of Microbial Population in C‐Sequestration, N, P Cycle 179 8.6 Restoring Diversity in Large‐Scale Monocultures 180 8.7 Enhancing Crops vis‐a‐vis Microbial Biodiversity to Reduce Vulnerability 181 8.8 Conclusions 183 References 183 9 ARCHAEAL COMMUNITY STRUCTURE: RESILIENCE TO CLIMATE CHANGE 191M. Thomas, K.K. Pal and R. Dey 9.1 Introduction 191 9.2 Possible Role of Archaea in Agricultural Sustainability 192 9.3 Ecology and Phylogeny of Domain Archaea 193 9.4 Archaeal Contribution to Global Climate Change 194 9.4.1 Archaeal Response to Increased Temperatures 195 9.4.2 Archaeal Response to Biogeochemical Cycles 196 9.5 Archaeal Mechanisms of Adaptation with Respect to Abiotic Changes 200 9.6 Conclusions 200 References 201 10 MYCORRHIZA – HELPING PLANTS TO NAVIGATE ENVIRONMENTAL STRESSES 205Raghvendra Pratap Singh, Geetanjali Manchanda, Mian Nabeel Anwar, Jun Jie Zhang and Yue Zhang Li 10.1 Introduction 205 10.2 Arbuscular Mycorrhizae 207 10.3 Elevated CO2 Levels 209 10.4 High Temperature 211 10.5 Salinity 214 10.6 Conclusions 219 References 220 11 ENDOPHYTIC MICROORGANISMS: FUTURE TOOLS FOR CLIMATE RESILIENT AGRICULTURE 235R. Dey, K.K. Pal, M. Thomas, D.N. Sherathia, V.B. Mandaliya, R.A. Bhadania, M.B. Patel, P. Maida, D.H. Mehta, B.D. Nawade and S.V. Patel 11.1 Introduction 235 11.1.1 Climate Change – Impact and Need for Adaptation 236 11.2 Endophytes and Climate Resilience 239 11.2.1 High Temperature Stress 239 11.2.2 Low Temperature Stress 240 11.2.3 Moisture‐Deficit Stress 240 11.2.4 Salinity Stress 242 11.2.5 Waterlogging Stress 244 11.3 Endophytes and Biotic Stress 245 11.3.1 Plant Diseases 245 11.3.2 Nematode Infestation 247 11.3.3 Insect Pests 247 11.4 Conclusions 247 References 248 12 BACILLUS THURINGIENSIS: GENETIC ENGINEERING FOR INSECT PEST MANAGEMENT 255Gothandapani Sellamuthu, Prabhakaran Narayanasamy and Jasdeep Chatrath Padaria 12.1 Introduction 255 12.2 Biology of Bacillus Thuringiensis 257 12.2.1 Natural Occurrence of Bacillus thuringiensis 257 12.2.2 Classification of Bt Toxins 258 12.2.3 Mode of Action 260 12.3 Biotechnological Approaches of Microbial Genes for Insect Pest Management 261 12.3.1 Microbial Genes and Gene Pyramiding 261 12.3.2 Alternative Insecticidal Genes 262 12.3.3 Gene Pyramiding 262 12.4 Methods for Development of Transgenic Crops 263 12.4.1 Direct Gene Transfer 264 12.4.2 Indirect Gene Transfer 266 12.5 Field Evaluation and Commercially Available Insecticidal Crops 267 12.5.1 Environmental Safety 269 12.5.2 Ecological Balance and Food Safety 270 12.6 Insecticide Resistance 270 12.7 Conclusions 271 References 271 13 MICROBIAL NANOTECHNOLOGY FOR CLIMATE RESILIENT AGRICULTURE 279Prem Lal Kashyap, Pallavi Rai, Raj Kumar, Shikha Sharma, Poonam Jasrotia, Alok Kumar Srivastava and Sudheer Kumar 13.1 Introduction 279 13.2 Microbe Mediated Fabrication of Nanoparticles 281 13.2.1 Bacteria 281 13.2.2 Fungi 286 13.2.3 Algae 287 13.2.4 Viruses 292 13.2.5 Actinomycetes 293 13.3 Nanomaterials for Biotic and Abiotic Stress Management 295 13.3.1 Biotic Stress Management 295 13.3.2 Abiotic Stress Management 306 13.4 Nano‐Fertilizers for Balanced Crop Nutrition 314 13.5 Conclusion and Future Directions 315 References 316 INDEX 345

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Book SynopsisA comprehensive resource on the recent developments of stem cell use in wound healing With contributions from experts in the field, Wound Healing offers a thorough review of the most recent findings on the use of stem cells to heal wounds. This important resource covers both the basic and translational aspects of the field. The contributors reveal the great progress that has been made in recent years and explore a wide range of topics from an overview of the stem cell process in wound repair to inflammation and cancer. They offer a better understanding of the identities of skin stem cells as well as the signals that govern their behavior that contributes to the development of improved therapies for scarring and poorly healing wounds. Comprehensive in scope, this authoritative resource covers a wealth of topics such as: an overview of stem cell regeneration and repair, wound healing and cutaneous wound healing, the role of bone marrow derived stems cells,Table of ContentsList of Contributorsvii 1 Stem Cell Regeneration and Repair – Overview 1Clement D. Marshall, Alessandra A. Moore, Michael T. Longaker, and H. Peter Lorenz 2 Cadherins as Central Modulators of Wound Repair 15Melissa Crawford and Lina Dagnino 3 Tight Junctions and Cutaneous Wound Healing 31Thomas Volksdorf and Johanna M. Brandner 4 The Role of Microvesicles in Cutaneous Wound Healing 43Alexandra Laberge and Véronique J. Moulin 5 Wound Healing and Microenvironment 67Elgin Türköz Uluer, Hafize Seda Vatansever, and Feyzan Őzdal Kurt 6 Wound Healing and the Non-cellular Microenvironment 79Hayley S. Ramshaw, Jasreen Kular, and Michael S. Samuel 7 Contribution of Adipose-Derived Cells to Skin Wound Healing 89Barbara Gawronska-Kozak, Joanna Bukowska, Xiying Wu, Amy Lin Strong, Trivia Frazier, Bruce A. Bunnell, and Jeffrey M. Gimble 8 Role of Bone Marrow-Derived Stem Cells in Wound Healing 103Feyzan Özdal Kurt, Hafize Seda Vatansever, and Elgin Türköz Uluer 9 Role of Vitamin D and Calcium in Epidermal Wound Repair 113Daniel D. Bikle, Chia-ling Tu, and Yuko Oda 10 Oral Mucosal Healing 125Luisa A. DiPietro and Megan Schrementi 11 Role of Adipose-Derived Stem Cells in Wound Healing: An Update from Isolation to Transplantation 133Selami Demirci, Ayşegül Doğan, and Fikrettin Şahin 12 The Hair Follicle as a Wound Healing Promoter and Its Application in Clinical Practice 149Francisco Jimenez, María Luisa Martínez, Eduardo Escario, and Ander Izeta 13 Impaired Wound Healing in Diabetic Ulcers: Accelerated Healing Through Depletion of Ganglioside 167Duncan Hieu M. Dam, Sophia A. Jelsma, and Amy S. Paller 14 Inflammation in Wound Repair: Role and Function of Inflammation in Wound Repair 177Amanda S. MacLeod and Jeffery T. Kwock 15 Inflammation, Wound Healing, and Fibrosis 195Shibnath Ghatak, Vincent C. Hascall, Ricardo Moreno Rodriguez, Roger R. Markwald, and Suniti Misra 16 The Potential Role of Photobiomodulation and Polysaccharide-Based Biomaterials in Wound Healing Applications 211Heidi Abrahamse, Sathish Sundar Dhilip Kumar, and Nicolette Nadene Houreld 17 Is Understanding Fetal Wound Repair the Holy Grail to Preventing Scarring? 225Olivier A. Branford and Kerstin J. Rolfe 18 Inflammation and Cancer 239Suniti Misra, Vincent C. Hascall, Roger R. Markwald, Paul E. O’Brien, and Shibnath Ghatak Index 275

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Book SynopsisCloses the gap between bioscience and mathematics-based process engineering This book presents the most commonly employed approaches in the control of bioprocesses. It discusses the role that control theory plays in understanding the mechanisms of cellular and metabolic processes, and presents key results in various fields such as dynamic modeling, dynamic properties of bioprocess models, software sensors designed for the online estimation of parameters and state variables, and control and supervision of bioprocesses Control in Bioengineering and Bioprocessing: Modeling, Estimation and the Use of Sensors is divided into three sections. Part I, Mathematical preliminaries and overview of the control and monitoring of bioprocess, provides a general overview of the control and monitoring of bioprocesses, and introduces the mathematical framework necessary for the analysis and characterization of bioprocess dynamics. Part II, Observability and control conceptsTable of ContentsPreface xi Part I Overview of the Control and Monitoring of Bioprocesses and Mathematical Preliminaries 1 1 Introduction 3 1.1 Overview of the Control and Monitoring of Bioprocesses 3 1.1.1 Why Nonlinear Control in Bioprocesses? 3 1.2 Improvements to Bioprocesses Productivity 13 1.2.1 Cell Lines 16 1.2.1.1 Cell Culture Process General 18 1.2.2 Microorganism Growth Under Controlled Conditions 18 1.2.3 On the Environment for the Microorganism’s Growth 19 1.2.4 Improving the Productivity for Specific Metabolic Products 21 1.3 Bioprocess Control 22 1.3.1 What is a Bioprocess? 22 1.3.2 Bioprocess Monitoring and Control 23 1.3.3 Stability of Bioprocess 25 1.3.4 Basic Concepts and Controllers 27 1.3.5 Advanced Control Schemes: Multivariable Control, Robust, Fuzzy Logic, Model Predictive Control, or Others 30 1.4 Process Measurements 32 1.4.1 The Drawback for Monitoring Bioprocess 32 1.4.2 Primary on-Line Sensor (e.g. Dissolved Oxygen, Temperature, Culture pH, Pressure, Agitation Rate, Flow Rates, Redox, CO2, and Others) 33 1.4.3 Primary in-Line Sensor 33 1.4.4 Process Analytical Technologies (Gas Analysis, Spectrometers, Infrared, HPLC, PCR, and Others) 34 1.4.5 Software Sensor (e.g. Cell Mass Estimation Via Complex Medium, Primary Carbon Substrate, Concentration Product of Line, Metabolites, Sensor to Computer Via Wireless) 36 1.5 Dynamic Bioprocess Models 40 1.5.1 Bioprocess Modeling for Control Purposes 40 1.5.2 Mass and Energy Balance of the Bioprocess 41 1.5.2.1 Dynamical Mass Balance 41 1.5.2.2 Batch Process 42 1.5.2.3 Fed-Batch 42 1.5.2.4 Continuous 43 1.5.2.5 Energy Balance 43 1.5.3 Black Box, White Box, and Gray Box Models 45 1.5.3.1 Black Box 45 1.5.3.2 White Box 45 1.5.3.3 Gray Box 45 1.5.4 Linear and Nonlinear Models 45 1.5.5 Segregated and Non-segregated Models 46 1.5.6 Structured and Unstructured Models 46 1.5.7 Structured Models 47 1.6 Process Optimization 51 1.6.1 Off-Line and On-Line Optimization of Bioprocesses 51 References 53 2 Mathematical Preliminaries 63 2.1 Systems of Ordinary Differential Equations 63 2.1.1 Differential Equations, Vector Fields, and State-Space Description 64 2.2 Linear Systems 70 2.2.1 The Fundamental Theorem for Linear Systems 70 2.2.2 Linear Systems in R2 71 2.2.3 Complex Eigenvalues 71 2.2.4 Multiple Eigenvalues 72 2.3 Nonlinear Dynamical Systems and its Analysis 72 2.3.1 Preliminary Concepts and Definitions 72 2.3.1.1 Continuous Dynamical Systems 73 2.3.1.2 Phase Space and Phase Portrait 73 2.3.1.3 Trajectories of Autonomous and Non-Autonomous Systems 73 2.3.1.4 The Vector Field 74 2.3.1.5 Lipschitz Condition 74 2.3.2 Existence-Uniqueness Theorem 75 2.3.2.1 Algebraic Properties of Lipschitz Continuous Functions 76 2.3.3 Dependence on Initial Conditions and Parameters 77 2.3.4 The Flow Defined by a Differential Equation 78 2.3.4.1 Differential Flow 78 2.3.5 Equilibrium Points 79 2.3.5.1 Equilibrium 79 2.3.6 The Hartman–Grobman Theorem 80 2.3.7 The Stable Manifold Theorem 81 2.3.8 Saddles, Nodes, Foci, and Centers 82 2.3.9 Center Manifold Theory 84 2.4 Stability Theory via Lyapunov Approach 84 2.4.1 Stability Notions 84 2.4.1.1 Stability 84 2.4.1.2 Asymptotic Stability 85 2.4.1.3 Exponential Stability 86 2.4.2 The Direct Method of Lyapunov (Second Method) 86 2.4.2.1 Positive Function 86 2.4.2.2 Theorem of Lyapunov 87 2.4.2.3 Globally Uniformly Asymptotically Stable of Lyapunov 88 2.4.2.4 Definition Matrices and Functions 88 2.4.3 The Indirect Method of Lyapunov (First Method) 90 2.4.3.1 Linearization 90 2.4.3.2 Stability by Linearization 90 2.4.4 Lasalles Invariance Principle 91 2.4.5 Invariant Set 91 2.4.6 Input/Output Stability 92 2.4.7 General Properties of Linear and Nonlinear Systems 93 2.4.8 Advanced Stability Theory 93 2.4.8.1 Concepts of Stability for Non-Autonomous Systems 93 2.4.8.2 Lyapunov-like Analysis Using Barbalat’s Lemma 94 2.5 Bifurcation Theory 94 2.5.1 Periodic Orbit 95 2.5.2 Limit Cycle 95 2.5.3 Bifurcation of Maps 95 2.5.4 Hyperbolic and Non-Hyperbolic Equilibrium Points 96 2.5.5 Bifurcation Point 96 2.5.6 Lyapunov Exponent 96 2.5.7 Chaos 97 2.5.8 Topological Equivalence 97 2.5.9 Example Bifurcations and Structural Stability of Dynamical Systems 98 2.6 Overview of Non-Smooth Dynamical Systems 99 References 101 Part II Observability and Control Concepts 107 3 State Estimation and Observers 109 3.1 Observability 109 3.1.1 Context and Motivations 109 3.1.2 Linear Observability 112 3.1.3 Nonlinear Observability 113 3.1.4 Geometric Conditions of Observability 114 3.1.4.1 Differential-Algebraic Observability Approach 115 3.1.5 Analytic Conditions for Observability 116 3.1.6 Detectability 116 3.1.7 Unobservable Subspaces 116 3.1.7.1 A Geometric Characterization 117 3.1.8 Unconstructive Subspaces 117 3.2 Observer Designs for Linear Structures 117 3.2.1 Luenberger Observer 118 3.2.2 Kalman Filter 119 3.2.3 Wiener Filter 120 3.3 Observer Designs for Nonlinear Structures 121 3.3.1 Extended Luenberger Observer 121 3.3.2 Extended Kalman Filter 122 3.3.2.1 First-Order Extended Kalman Filter 122 3.3.3 Asymptotic Observers 124 3.3.3.1 High-Gain Observer 124 3.3.4 Adaptive-Gain Observers 126 3.3.4.1 Adaptive High-Gain Observer 126 3.3.5 Sliding-Mode Observers 127 3.3.5.1 Sliding Mode Observers for Linear Uncertain Systems 127 3.3.5.2 Nonlinear Approaches to Sliding Mode Observer Design 130 References 131 4 Control of Bioprocess 135 4.1 The Control Idea 135 4.1.1 General Definitions 136 4.1.2 Controllability of Input/State/Output Systems 138 4.1.3 Steady-Output Controllability 139 4.1.4 Linear Controllability Analysis LTI Test 140 4.1.4.1 Controllable and Reachable Subspaces 140 4.1.4.2 Controllable Matrix Test 140 4.1.4.3 Eigenvector Test for Controllability 140 4.1.4.4 Popov–Belevitch–Hautus 141 4.1.4.5 Lyapunov Test for Controllability 141 4.1.5 Stabilizability 141 4.2 Controllers for Linear Systems 141 4.2.1 Linear Feedback 141 4.2.2 Proportional, Proportional-Integral, Proportional-Integral-Derivative 143 4.2.3 Optimal Control 143 4.2.4 Observer Based Controllers 144 4.3 Nonlinear Controllers 145 4.3.1 Nonlinear Controllability 145 4.3.2 Exact Feedback Linearization 147 4.3.3 Input-Output Linearization 147 4.3.3.1 Lyapunov-Based Control Design Methods 148 4.3.3.2 Back-Stepping Control 148 4.3.4 Nonlinear Sliding Mode 149 4.3.4.1 Sliding Surface Design 149 4.3.4.2 Control Law First-Order Sliding Mode Control 150 4.3.4.3 Control Law Second-Order Sliding Mode Control 151 4.3.4.4 Twisting Algorithm 152 4.3.4.5 Super Twisting Algorithm 152 4.3.4.6 Variable Structure Systems 152 4.3.5 Model Predictive Control 154 4.3.6 Control Using Neural Network 155 4.3.7 Nonlinear Design of Adaptive Controllers 156 4.3.7.1 Identification of Unknown Parameters 156 4.3.7.2 Observer-Based Identification 157 4.3.7.3 Adaptive Control Under Matching Conditions 157 4.3.7.4 Indirect Adaptive Control 158 4.3.7.5 Model Reference Adaptive Control 158 References 161 Part III Software Sensors and Observer-Based Control Schemes for Bioprocess 169 5 Dynamical Behavior of a 3-Dimensional Continuous Bioreactor 171 5.1 Introduction 171 5.2 Bioreactor Modeling 173 5.2.1 Estimation of the Kinetic Parameters 173 5.3 Main Results 175 5.4 Concluding Remarks 181 References 182 6 Observability Analysis Applied to 2D and 3D Bioreactors with Inhibitory and Non-inhibitory Kinetics Models 185 6.1 Introduction 185 6.2 Materials and Methods 186 6.2.1 Kinetic Models of Inhibition 186 6.2.1.1 Dynamics Models 187 6.2.2 Observability Criterion 188 6.3 Results and Discussion 188 6.4 Implementation of a Linear Observer to Check the Results of the Observability Analysis 200 6.5 Conclusion 201 References 202 7 Production System Myco-Diesel for Implementation of “Quality” of the Observability 205 7.1 Introduction 205 7.2 Methodology 206 7.2.1 Local Observability Quality 206 7.2.2 Bioreactor Model 207 7.3 Main Results 208 7.4 Conclusions 213 References 214 8 Regulation of a Continuously Stirred Bioreactor via Modeling Error Compensation 217 8.1 Introduction 217 8.2 Materials and Methods 219 8.2.1 Bioreactor Modeling 219 8.2.2 Mathematical Model 219 8.2.3 Mass Balance Modeling 219 8.3 Input–Output Identified Model 221 8.4 Control Design 221 8.5 Main Results 225 8.6 Concluding Remarks 228 References 229 9 Development of Virtual Sensor Based on the Just-In-Time Model for Monitoring of Biological Control Systems 233 9.1 Introduction 233 9.2 Materials and Methods 235 9.2.1 Kinetic and Simulated Mycoparasitism T. harzianum – C. cladosporioides 235 9.2.2 Mathematical Model 236 9.3 On-line Monitoring (Proposed Nonlinear Observer) 239 9.3.1 Sketch of Proof of Proposition 9.1 240 9.4 Such Approaches, Known as Proposed Just-in-Time Modeling “Hybrid Systems” 242 9.5 Results 243 9.6 Conclusions 249 References 250 10 Virtual Sensor Design for State Estimation in a Photocatalytic Bioreactor for Hydrogen Production 255 10.1 Introduction 255 10.2 Material and Methods 257 10.2.1 Methods 257 10.2.2 Desulfovibrio Alaskensis 6SR 258 10.3 Mathematical Model Development 258 10.3.1 Basic Concepts 258 10.3.2 Proposed Model 258 10.3.3 Determination of Kinetic Parameters 261 10.4 Virtual Sensor Design 262 10.5 Results and Discussion 265 10.6 Conclusions 272 References 273 Index 277

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Book SynopsisPresents an integrated view of the expression of bacterial genetic information, genome architecture and function, and bacterial physiology and pathogenesis This book blends information from the very latest research on bacterial chromosome and nucleoid architecture, whole-genome analysis, cell signaling, and gene expression control with well-known gene regulation paradigms from model organisms (including pathogens) to give readers a picture of how information flows from the environment to the gene, modulating its expression and influencing the competitive fitness of the microbe. Structure and Function of the Bacterial Genome explores the governance of the expression of the genes that make a bacterium what it is, and updates the basics of gene expression control with information about transcription promoter structure and function, the role of DNA as a regulatory factor (in addition to its role as a carrier of genetic information), small RNAs, RNAs that sense chemical signals, ribosomeTable of ContentsPreface xiii 1 The Bacterial Genome – Where the Genes are 1 1.1 Genome Philosophy 1 1.2 The Bacterial Chromosome 4 1.3 Chromosome Replication: Initiation 6 1.4 Chromosome Replication: Elongation 11 1.5 Chromosome Replication: Termination 12 1.6 Replication Produces Physically Connected Products 13 1.7 Decatenating the Sister Chromosomes 13 1.8 Resolving Chromosome Dimers 14 1.9 Segregating the Products of Chromosome Replication 15 1.10 Polar Tethering of Chromosome Origins 20 1.11 Some Bacterial Chromosomes are Linear 20 1.12 Some Bacteria Have More than One Chromosome 21 1.13 Plasmids 22 1.14 Plasmid Replication 22 1.15 Plasmid Segregation 26 1.16 The Nucleoid 28 1.17 The Chromosome Has Looped Domains 29 1.18 The Macrodomain Structure of the Chromosome 29 1.19 The Chromosome Displays Spatial Arrangement Within the Cell 30 1.20 SeqA and Nucleoid Organisation 31 1.21 MukB, a Condensin-Like Protein 32 1.22 MatP, the matS Site and Ter Organisation 33 1.23 MaoP and the maoS Site 34 1.24 SlmA and Nucleoid Occlusion 34 1.25 The Min System and Z Ring Localisation 34 1.26 DNA in the Bacterial Nucleoid 36 1.27 DNA Topology 36 1.28 DNA Topoisomerases: DNA Gyrase 38 1.29 DNA Topoisomerases: DNA Topoisomerase IV 40 1.30 DNA Topoisomerases: DNA Topoisomerase I 40 1.31 DNA Topoisomerases: DNA Topoisomerase III 41 1.32 DNA Replication and Transcription Alter Local DNA Topology 41 1.33 Transcription and Nucleoid Structure 41 1.34 Nucleoid-associated Proteins (NAPs) and Nucleoid Structure 43 1.35 DNA Bending Protein Integration Host Factor (IHF) 44 1.36 HU, a NAP with General DNA-binding Activity 46 1.37 The Very Versatile FIS Protein 47 1.38 FIS and the Early Exponential Phase of Growth 48 1.39 FIS and the Stringent Response 49 1.40 FIS and DNA Topology 49 1.41 Ferritin-Like Dps and the Curved-DNA-binding Protein CbpA 51 1.42 The H-NS Protein: A Silencer of Transcription 53 1.43 StpA: A Paralogue of H-NS 57 1.44 H-NS Orthologues Encoded by Plasmids and Phage 58 1.45 H-NSB/Hfp and H-NS2: H-NS Homologues of HGT Origin 58 1.46 A Truncated H-NS-Like Protein 59 1.47 Hha-like Proteins 59 1.48 Other H-NS Homologues: The Ler Protein from EPEC 60 1.49 H-NS Functional Homologues 62 1.50 H-NS Functional Homologues: Rok from Bacillus spp. 63 1.51 H-NS Functional Homologues: Lsr2 from Actinomycetes 63 1.52 H-NS Functional Homologues: MvaT from Pseudomonas spp. 63 1.53 The Leucine-responsive Regulatory Protein, LRP 64 1.54 Small, Acid-soluble Spore Proteins, SASPs 65 2 Conservation and Evolution of the Dynamic Genome 67 2.1 Disruptive Influences: Mutations 67 2.2 Repetitive Sequences in the Chromosome and Their Influence on Genetic Stability 69 2.3 Contingency Loci and the Generation of Microbial Variety 70 2.4 Rhs: Rearrangement Hotspots 71 2.5 REP Sequences 72 2.6 RIB/RIP, BIME-1, and BIME-2 Elements 73 2.7 ERIC Sequences 73 2.8 Repeat-Mediated Rearrangements: Mechanisms and Frequency 74 2.9 Site-specific Recombination and Phenotypic Variety 74 2.10 Site-Specific Recombination: Bacteriophage Lambda 75 2.11 The Lambda Lysis/Lysogeny Decision 76 2.12 Tyrosine Integrases 77 2.13 Serine Invertases 78 2.14 Large Serine Recombinases 79 2.15 Transposition and Transposable Elements 80 2.16 Pathways of Transposition 82 2.17 Peel-and-paste Transposition 85 2.18 Control of Transposition 88 2.19 Host Factors and Transposition 91 2.20 Integrative and Conjugative Elements (ICE) 91 2.21 Integrons 93 2.22 Introns 96 2.23 Horizontal Gene Transfer 96 2.24 Distinguishing Self from Non-self 99 2.25 Distinguishing Self and Non-self: CRISPR-Cas Systems 99 2.26 Distinguishing Self and Non-self: Argonaute Proteins 102 2.27 Distinguishing Self and Non-self: Restriction Enzymes/Methylases 103 2.28 Distinguishing Self and Non-self: BREX 103 2.29 Self-sacrifice and Other Behaviours Involving Toxin—antitoxin Systems 104 2.30 Conservative Forces: DNA Repair and Homologous Recombination 104 2.31 The RecA Protein 105 2.32 RecA, LexA, and the SOS Response 106 2.33 Holliday Junction Resolution 108 2.34 Mismatch Repair 109 2.35 Non-homologous End Joining 110 3 Gene Control: Transcription and Its Regulation 113 3.1 Transcription: More Than Just Transcribing Genetic Information 113 3.2 RNA Polymerase 113 3.3 The Core Enzyme 114 3.4 The Sigma Factors (and Anti-Sigma Factors) 116 3.5 Promoter Architecture 120 3.6 Stringently Regulated Promoters 120 3.7 Transcription Factors and RNA Polymerase 121 3.8 Transcription Initiation 124 3.9 Transcription Elongation 125 3.10 Transcription Termination: Intrinsic and Rho-Dependent Terminators 127 3.11 Rho and Imported Genes 128 3.12 Rho, R-Loops, and DNA Supercoiling 128 3.13 Rho and Antisense Transcripts 128 3.14 Anti-Termination: Insights from Phage Studies 129 3.15 Transcription Occurs in Bursts 129 4 Gene Control: Regulation at the RNA Level 133 4.1 Antisense Transcripts and Gene Regulation in cis 134 4.2 RNA that Regulates in trans 134 4.3 DsrA and the RpoS/H-NS Link 138 4.4 sRNA Turnover 140 4.5 DEAD-box Proteins 140 4.6 RNA Chaperone Proteins 141 4.7 StpA, H-NS, and RNA Binding 142 4.8 Degradation of mRNA 143 4.9 RNA Folding and Gene Regulation 144 4.10 Transcription Attenuation 145 4.11 Riboswitches 145 4.12 RNA as a Structural Component in the Nucleoid 146 5 Gene Control: Regulation at the Protein Level 149 5.1 Control Beyond DNA and RNA 149 5.2 Translation Machinery and Control: tRNA and rRNA 149 5.3 Translation Machinery and Control: The Ribosome 150 5.4 Translation Initiation 152 5.5 Translation Elongation 154 5.6 Elongation Factor P (EF-P) 155 5.7 Translation Termination 156 5.8 Protein Secretion 157 5.9 Protein Secretion: The Sec Pathway 157 5.10 The Twin Arginine Translocation (Tat) Pathway of Protein Secretion 159 5.11 Type 1 Secretion Systems (T1SS) 160 5.12 Type 2 Secretion Systems (T2SS) 161 5.13 Type 3 Secretion Systems (T3SS) 162 5.14 Type 4 Secretion Systems (T4SS) 164 5.15 Type 5 Secretion Systems (T5SS): The Autotransporters 165 5.16 Type 6 Secretion Systems (T6SS) 166 5.17 Protein Secretion in Gram-Positive Bacteria: SecA1, SecA2, and SrtA 167 5.18 Type 7 Secretion Systems (T7SS) 168 5.19 Protein Modification: Acetylation 168 5.20 Protein Modification: Glycosylation 169 5.21 Protein Modification: Phosphorylation 169 5.22 Protein Splicing 171 5.23 Small Proteins 172 5.24 Selenocysteine and Pyrrolysine: The 21st and 22nd Amino Acids 173 6 Gene Control and Bacterial Physiology 175 6.1 The Bacterial Growth Cycle 175 6.2 Physiology Changes Throughout the Growth Cycle 176 6.3 Generating Physiological Variety from Genetic Homogeneity 178 6.4 Bacterial Economics – Some Basic Principles 179 6.5 Carbon Sources and Metabolism 180 6.6 Gene Control and Carbon Source Utilisation 183 6.7 Anaerobic Respiration 183 6.8 ArcA, Mobile Genetic Elements, and HGT 184 6.9 Stress and Stress Survival in Bacterial Life 185 6.10 Oxygen Stress 185 6.11 Iron Starvation 186 6.12 Siderophores and Iron Capture 188 6.13 TonB-Dependent Transporters 188 6.14 Gene Regulation and Iron Transport 190 6.15 Iron Storage and Homeostasis 191 6.16 Osmotic Stress andWater Relations in Bacteria 191 6.17 Signal Molecules and Stress 193 6.18 The Stringent Response 194 6.19 Regulation of the Acid Stress Response 196 6.20 Alkaline pH Stress Response 200 6.21 Motility and Chemotaxis 201 6.22 Quorum Sensing 203 6.23 Biofilms 205 6.24 ‘Cheating’ as a Lifestyle Strategy 206 6.25 Thermal Regulation 207 6.26 Epigenomics and Phasevarions 209 6.27 Some Unifying Themes 210 7 Gene Control: Global Regulation by H-NS 211 7.1 H-NS is a Global Regulator 211 7.2 H-NS and Foreign DNA 211 7.3 H-NS and Xenogenic Silencing: Three Case Studies 212 7.4 The H-NS Virulence Regulon in Vibrio cholerae 212 7.5 HGT in V. cholerae: The CTXϕ Phage and the VPI1 Island 213 7.6 The ToxRS, ToxT, TcpPH Regulatory Network 215 7.7 Control by VpsR, VpsT, and HapR 215 7.8 Quorum Sensing and Cholera 217 7.9 Chitin and HGT 217 7.10 The H-NS Virulence Regulon in Shigella flexneri 219 7.11 Shigella Infection 221 7.12 The VirF AraC-Like Transcription Factor 222 7.13 VirB: A Recruit from a Plasmid-Partitioning System 222 7.14 The Shigella Virulence Plasmid 223 7.15 The Salmonella H-NS Virulence Gene Regulon 223 7.16 Salmonella’s Pathogenicity Islands (SPI) 224 7.17 SlyA, PhoP/Q, and SPI Gene Expression 227 7.18 Gene Control in SPI1 and SPI2 227 8 An Integrated View of Genome Structure and Function 231 8.1 Networks versus Hierarchies 231 8.2 Regulons, Stimulons, and Heterarchies/Netarchies 232 8.3 Transcription Burstiness and Regulatory Noise 233 8.4 The Significance of Gene Position 234 8.5 Messenger RNA May Not Be Free to Diffuse Far in Bacteria 236 8.6 RNA Polymerase Activity and Genome Organisation 237 8.7 Gene–Gene Interactions in the Folded Chromosome 239 8.8 DNA Supercoiling as a Global Regulator 240 8.9 Modelling the Nucleoid 243 8.10 Synthetic Biology 243 References 247 Index 379

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Book SynopsisTable of ContentsPreface xxi Acknowledgements xxvii Part I Virology and Viral Disease 1 Chapter 1 Introduction – The Impact of Viruses on Our View of Life 3 Chapter 2 An Outline of Virus Replication and Viral Pathogenesis 15 Chapter 3 Virus Disease in Populations and Individual Animals 27 Chapter 4 Patterns of Some Viral Diseases of Humans 43 Part II Basic Properties of Viruses and Virus–cell Interaction 65 Chapter 5 Virus Structure and Classification 67 Chapter 6 The Beginning and End of the Virus Replication Cycle 85 Chapter 7 The Innate Immune Response: Early Defense Against Pathogens 105 Chapter 8 Strategies to Protect Against and Combat Viral Infection 131 Part III Working with Virus 153 Chapter 9 Visualization and Enumeration of Virus Particles 155 Chapter 10 Replicating and Measuring Biological Activity of Viruses 163 Chapter 11 Physical and Chemical Manipulation of the Structural Components of Viruses 181 Chapter 12 Characterization of Viral Products Expressed in the Infected Cell 197 Chapter 13 Viruses Use Cellular Processes to Express their Genetic Information 217 Part IV Replication Patterns of Specific Viruses 245 Chapter 14 Replication of Positive‐Sense RNA Viruses 247 Chapter 15 Replication Strategies of RNA Viruses Requiring RNA‐directed mRNA Transcription as the First Step in Viral Gene Expression 277 Chapter 16 Replication Strategies of Small and Medium‐sized DNA Viruses 307 Chapter 17 Replication of Some Nuclear‐replicating Eukaryotic DNA Viruses with Large Genomes 335 Chapter 18 Replication of Cytoplasmic DNA Viruses and “Large” Bacteriophages 363 Chapter 19 Retroviruses: Converting RNA to DNA 385 Chapter 20 Human Immunodeficiency Virus Type 1 (HIV‐1) and Related Lentiviruses 403 Chapter 21 Hepadnaviruses: Variations on the Retrovirus Theme 415 Part V Molecular Genetics of Viruses 437 Chapter 22 The Molecular Genetics of Viruses 439 Chapter 23 Molecular Pathogenesis 467 Chapter 24 Viral Bioinformatics 477 Chapter 25 Viruses and the Future – Problems and Promises 489 Appendix – Resource Center 503 Technical Glossary 509 Index 533

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Book SynopsisIntegrates the various disciplines of the science of health disparities in one comprehensive volume The Science of Health Disparities Research is an indispensable source of up-to-date information on clinical and translational health disparities science. Building upon the advances in health disparities research over the past decade, this authoritative volume informs policies and practices addressing the diseases, disorders, and gaps in health outcomes that are more prevalent in minority populations and socially disadvantaged communities. Contributions by recognized scholars and leaders in the fieldfeaturing contemporary research, conceptual models, and a broad range of scientific perspectivesprovide an interdisciplinary approach to reducing inequalities in population health, encouraging community engagement in the research process, and promoting social justice. In-depth chapters help readers better understand the specifics of minority health and health disparities while demonstrating the importance of advancing theory, refining measurement, improving investigative methods, and diversifying scientific research. In 26 chapters, the book examines topics including the etiology of health disparities research, the determinants of population health, research ethics, and research in African American, Asians, Latino, American Indian, and other vulnerable populations. Providing a unified framework on the principles and applications of the science of health disparities research, this important volume: Defines the field of health disparities science and suggests new directions in scholarship and researchExplains basic definitions, principles, and concepts for identifying, understanding and addressing health disparitiesProvides guidance on both conducting health disparities research and translating the resultsExamines how social, historical and contemporary injustices may influence the health of racial and ethnic minoritiesIllustrates the increasing national and global importance of addressing health disparitiesDiscusses population health training, capacity-building, and the transdisciplinary tools needed to advance health equity A significant contribution to the field, The Science of Health Disparities Research is an essential resource for students and basic and clinical researchers in genetics, population genetics, and public health, health care policymakers, and epidemiologists, medical students, and clinicians, particularly those working with minority, vulnerable, or underserved populations.Table of ContentsList of Contributors ix Foreword xxi Acknowledgements xxiii 1 Definitions, Principles, and Concepts for Minority Health and Health Disparities Research 1Eliseo J. Pérez-Stable, Jennifer Alvidrez, and Carl V. Hill 2 Getting Under the Skin: Pathways and Processes that Link Social and Biological Determinants of Disease 13Chandra L. Jackson, Rada K. Dagher, Jung S. Byun, Tilda Farhat, and Kevin L. Gardner 3 Racial/Ethnic, Socioeconomic, and Other Social Determinants 39Tiffany L. Gary-Webb, Sara E. Baumann, Erik J. Rodriquez, Lydia A. Isaac, and Thomas A. LaVeist 4 Behavioral Determinants in Population Health and Health Disparities Research 59Amelie G. Ramirez, Patricia Chalela, Melanie D. Sabado-Liwag, and Kelvin Choi 5 Sociocultural Environments and Health Disparities Research: Frameworks, Methods, and Promising Directions 77Hortensia Amaro, Samantha Garcia, Inna Arnaudova, and Monica P. Jolles 6 Physical Environment, and Minority Health and Health Disparities Research 95Tracy Bastain, Carrie Breton, Shohreh Farzan, Rima Habre, Jill Johnston, Derrick C. Tabor, Claudia Toledo-Corral, and Elizabeth Vang 7 Genome-wide Genetic Approaches to Metabolic and Inflammatory Health Disparities 109Cheryl A. Winkler 8 Biologic Factors and Molecular Determinants in Inflammatory and Metabolic Diseases 125Marquitta White, Esteban Burchard, Page Goddard, Anup K. Nair, Leslie J. Baier, Federico Fuentes, and Jeffrey B. Kopp 9 Insights into the Genomic Landscape of African Ancestry Populations: Implications for Health and Disease Disparities 139Charles N. Rotimi, Amy R. Bentley, Ayo P. Doumatey, Guanjie Chen, Daniel Shriner, and Adebowale Adeyemo 10 Applying Self‐report Measures in Minority Health and Health Disparities Research 153Mariana Sanchez, Bertha Hidalgo, Adelaida Rosario, Ligia Artiles, Anita L. Stewart, and Anna M. Nápoles 11 Conducting Community-based Participatory Research with Minority Communities to Reduce Health Disparities 171Tung T. Nguyen, Nina Wallerstein, Rina Das, Melanie D. Sabado-Liwag, Valarie Blue Bird Jernigan, Tvli Jacob, Tamela Cannady, Linda Sprague Martinez, Uchenna J. Ndulue, Abigail Ortiz, Andrea Williams Stubbs, Latrice C. Pichon, Sora Park Tanjasiri, Jane Pang, and Kent Woo 12 Racial/Ethnic Health and Healthcare Disparities Measurement: The Application of the Principles and Methods of Causal Inference 187Benjamin Cook, Sarah Forrester, Timothy Creedon, Joan Wasserman, Meryl Sufian, and Jeroan Allison 13 Small Area Estimation and Bayesian Disease Mapping for Minority Health and Health Disparities 203Xingyou Zhang, Benmei Liu, Shumei Yun, and Robert L. Phillips 14 Applications of Big Data Science and Analytic Techniques for Health Disparities Research 221Irene Dankwa-Mullan, Xinzhi Zhang, Phuong-Tu Le, and William T. Riley 15 Complex Systems Science 243Matt Kasman, Nancy Breen, and Ross A. Hammond 16 Improving Equity in Healthcare through Multilevel Interventions 257Margarita Alegria, Jacqueline J. Lloyd, Naomi Ali, and Karissa DiMarzio 17 Using Implementation Science to Move from Knowledge of Disparities to Achievement of Equity 289Lisa A. Cooper, Tanjala S. Purnell, Michael Engelgau, Kristina Weeks, and Jill A. Marsteller 18 Healthcare and Public Policy: Challenges and Opportunities for Research 309Olveen Carrasquillo, Sonjia Kenya, Stuti Dang, Cynthia Lebron, and Tilda Farhat 19 Addressing Disparities in Access to High-quality Care 321Milda Saunders, Regina James, Kesi Williams, and Marshall Chin 20 Health Communication as a Mediator of Health and Healthcare Disparities 339Neda Ratanawongsa, Benyam Hailu, and Dean Schillinger 21 Comparative Effectiveness Research in Health Disparity Populations 359William V. Padula, Rick A. Berzon, Priscah Mujuru, and David O. Meltzer 22 The Role of Electronic Health Records and Health Information Technology in Addressing Health Disparities 375Irene Dankwa-Mullan, Sherine El-Toukhy, Jessamine Winer-Jones, Nora Haney, Morgan Foreman, Kesi Williams, and Anil Jain 23 Precision Medicine and Health Disparities 391Consuelo H. Wilkins, Nancy J. Cox, Sarah C. Stallings, Maria F. Lima, Roy E. Weiss, and Nishadi Rajapakse 24 Recruitment, Inclusion, and Diversity in Clinical Trials 413Bernadette Boden-Albala, Salina P. Waddy, Noa Appleton, Heather Kuczynski, Emily Nangle, and Nina S. Parikh 25 Sexual and Gender Minority Health Disparities: Concepts, Methods, and Future Directions 429Mark L. Hatzenbuehler and John E. Pachankis 26 Workforce Diversity and Capacity Building to Address Health Disparities 445Hannah A. Valantine and Alison F. Davis Index 455

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Book SynopsisProvides a comprehensive description of mass spectrometry basics, applications, and perspectives Mass spectrometry is a modern analytical technique, allowing for fast and ultrasensitive detection and identification of chemical species. It can serve for analysis of narcotics, counterfeit medicines, components of explosives, but also in clinical chemistry, forensic research and anti-doping analysis, for identification of clinically relevant molecules as biomarkers of various diseases. This book describes everything readers need to know about mass spectrometryfrom the instrumentation to the theory and applications. It looks at all aspects of mass spectrometry, including inorganic, organic, forensic, and biological MS (paying special attention to various methodologies and data interpretation). It also contains a list of key terms for easier and faster understanding of the material by newcomers to the subject and test questions to assist lecturers. Knowing how cruciaTable of ContentsList of Contributors xvii Preface xxi 1 Introduction 1Jerzy Silberring and Marek Smoluch 2 A Brief History of Mass Spectrometry 5Marek Smoluch and Jerzy Silberring 3 Basic Definitions 9Marek Smoluch and Kinga Piechura 4 Instrumentation 13 4.1 Ionization Methods 13 4.1.1 Electron Ionization (EI) 13Claudio Iacobucci 4.1.2 Chemical Ionization (CI) 15Claudio Iacobucci 4.1.2.1 Principle of Operation: Positive and Negative Ion Modes 15 4.1.3 Atmospheric Pressure Ionization (API) 21 4.1.3.1 Atmospheric Pressure Chemical Ionization (APCI) 21Claudio Iacobucci 4.1.3.2 Electrospray Ionization (ESI) 22Piotr Suder 4.1.3.3 Nanoelectrospray 38Piotr Suder 4.1.3.4 Desorption Electrospray Ionization (DESI) 42Anna Bodzon‐Kulakowska and Anna Antolak 4.1.3.5 Laser Ablation Electrospray Ionization (LAESI) 49Anna Bodzon‐Kulakowska and Anna Antolak 4.1.3.6 Photoionization 51Jerzy Silberring 4.1.4 Ambient Plasma‐Based Ionization Techniques 54Marek Smoluch 4.1.4.1 Introduction 54 4.1.4.2 Direct Analysis in Real Time (DART) 54 4.1.4.3 Flowing Atmospheric Pressure Afterglow (FAPA) 59 4.1.4.4 Dielectric Barrier Discharge Ionization (DBDI) 61 4.1.5 Matrix‐Assisted Laser Desorption/Ionization (MALDI) 64 4.1.5.1 Introduction 64Przemyslaw Mielczarek and Jerzy Silberring 4.1.5.2 The Role of Matrix 66Przemyslaw Mielczarek and Jerzy Silberring 4.1.5.3 Atmospheric Pressure MALDI 67Giuseppe Grasso 4.1.5.4 MALDI Mass Spectra Interpretation 71Przemyslaw Mielczarek and Jerzy Silberring 4.1.5.5 Desorption/Ionization on Porous Silicon (DIOS) 72Przemyslaw Mielczarek and Jerzy Silberring 4.1.5.6 Surface‐Enhanced Laser Desorption/Ionization (SELDI) 73Przemyslaw Mielczarek and Jerzy Silberring 4.1.5.7 Nanostructure‐Enhanced Laser Desorption/Ionization (NALDI) 74Przemyslaw Mielczarek and Jerzy Silberring 4.1.5.8 Summary 75Przemyslaw Mielczarek and Jerzy Silberring 4.1.6 Inductively Coupled Plasma Ionization (ICP) 78Aleksandra Pawlaczyk and Małgorzata Iwona Szynkowska 4.1.6.1 Introduction 78 4.1.6.2 ICP as a Technique of Elemental Analysis and ICP Principle 78 4.1.6.3 Ionization of Elements and Ionization Efficiency 81 4.1.6.4 Mechanism of ICP Formation 82 4.1.6.5 Ways of Plasma View and Plasma Generation 84 4.1.6.6 Sample Introduction 84 4.1.6.7 Measurement in the ICP‐MS Technique 87 4.1.6.8 Analyzers in ICP‐MS Spectrometers 87 4.1.7 Secondary Ion Mass Spectrometry with Time‐of‐Flight Analyzer (TOF‐SIMS) 93Nunzio Tuccitto 4.1.7.1 Introduction 93 4.1.7.2 TOF‐SIMS Principle of Operation 93 4.1.7.3 The Sputtering of the Sample Surface 94 4.1.7.4 Ionization (Generating Secondary Ions) 95 4.1.7.5 Construction of TOF‐SIMS 96 4.1.7.6 Analytical Capabilities of TOF‐SIMS 98 4.1.7.7 Examples and Spectra Interpretation 102 4.2 Analyzers 107 4.2.1 Time of Flight (TOF) 107Anna Bodzon-Kulakowska and Anna Antolak 4.2.1.1 Introduction 107 4.2.1.2 The Working Rule of TOF Analyzer 108 4.2.1.3 Linear Mode of Operation of TOF 109 4.2.1.4 The Spread of the Kinetic Energy Regarding the Ions of the Same Mass 110 4.2.1.5 Delayed Ion Extraction 111 4.2.1.6 The Reflection Mode 113 4.2.1.7 Orthogonal Acceleration TOF Analyzer 114 4.2.1.8 Summary 116 4.2.2 Ion Mobility Analyzer (IM) 118Anna Antolak and Anna Bodzon-Kulakowska 4.2.2.1 Principle of IM Operation 118 4.2.2.2 Drift Time IMS 118 4.2.2.3 High Field Asymmetric Waveform Ion Mobility Spectrometer (FAIMS) 119 4.2.2.4 Traveling Wave Ion Guides (TWIG) 121 4.2.2.5 IM Spectrum 122 4.2.2.6 Applications 122 4.2.3 Quadrupole Mass Analyzer 124Anna Antolak and Anna Bodzon-Kulakowska 124 4.2.3.1 Construction and Principles of Operation of a Quadrupole 124 4.2.3.2 Behavior of an Ion Inside the Quadrupole 126 4.2.3.3 How Mass Spectrum Is Generated? Changes of U and V 128 4.2.3.4 Spectrum Quality 128 4.2.3.5 Applications of the Quadrupole Analyzer 129 4.2.3.6 Quadrupoles, Hexapoles, and Octapoles as Focusing Elements: Ion Guides 129 4.2.4 Ion Trap (IT) 131Anna Bodzon-Kulakowska and Anna Antolak 4.2.4.1 Introduction 131 4.2.4.2 Behavior of an Ion Inside the Ion Trap 132 4.2.4.3 Analysis of the Ions 133 4.2.4.4 Mass Selective Instability Mode 134 4.2.4.5 Resonant Ejection Mode 135 4.2.4.6 Axial Modulation 137 4.2.4.7 Nonlinear Resonance 137 4.2.4.8 Linear Ion Trap (LIT) 137 4.2.4.9 Applications 139 4.2.5 High‐Resolution Mass Spectrometry 141Piotr Stefanowicz and Zbigniew Szewczuk 4.2.5.1 Introduction 141 4.2.6 Ion Cyclotron Resonance (ICR) 142Piotr Stefanowicz and Zbigniew Szewczuk 4.2.6.1 Introduction 142 4.2.6.2 Cyclotron Frequency 142 4.2.6.3 ICR: Principles of Operation 143 4.2.6.4 Injection of Ions into the ICR Cell 144 4.2.6.5 Trapping Electrodes 145 4.2.6.6 Excitation Electrodes 145 4.2.6.7 Detection Electrodes and Fourier Transform 145 4.2.6.8 FT‐ICR Properties as m/z Analyzer 147 4.2.7 Orbitrap 150Piotr Stefanowicz and Zbigniew Szewczuk 4.2.7.1 History of Development and Principles of Operation 150 4.2.7.2 Analyzing Ions in the Orbitrap 151 4.2.7.3 Orbitrap Properties as m/z Analyzer 152 4.2.7.4 Analytical and Proteomic Applications of Orbitrap 153 4.2.8 Hybrid Mass Spectrometers 158Giuseppe Di Natale 4.2.8.1 A Brief Comparison of Mass Analyzers 158 4.2.8.2 Triple Quadrupoles 159 4.2.8.3 Q‐IT 162 4.2.8.4 Q‐Orbitrap 162 4.2.8.5 Q‐TOF 163 4.2.8.6 IT‐TOF 165 4.2.8.7 IT‐Orbitrap 165 4.2.9 Sector Instruments 169Anna Antolak and Anna Bodzon-Kulakowska 4.2.9.1 Introduction 169 4.2.9.2 Rule of Operation of Magnetic Analyzer (B) 169 4.2.9.3 Electrostatic Sector (E) 172 4.2.9.4 Mass Spectrometers with Magnetic and Electrostatic Sector 174 4.3 Ion Detectors 176 4.3.1 Introduction 176 4.3.2 Electron Multiplier 176 4.3.3 Microchannel Detector 177 4.3.4 Medipix/Timepix Detector 178 4.3.5 Ion Detection in ICR and Orbitrap‐Based Mass Spectrometers 179 5 Hyphenated Techniques 181 5.1 Gas Chromatography Combined with Mass Spectrometry (GC‐MS) 181Anna Drabik 5.1.1 Introduction 181 5.1.2 Detectors 183 5.1.3 Chemical Modifications: Derivatization 186 5.1.4 GC‐MS Analysis 186 5.1.5 Two‐Dimensional Gas Chromatography Linked to Mass Spectrometry 2D GC‐MS 187 5.2 Liquid Chromatography Linked to Mass Spectrometry (LC‐MS) 193 5.2.1 Introduction 193Francesco Bellia 5.2.2 Introduction to Liquid Chromatography 193Anna Drabik 5.2.3 Types of Detectors 195Anna Drabik 5.2.4 Chromatographic Columns 197Anna Drabik 5.2.5 Chromatographic Separation and Quantitation Using MS as a Detector 200Anna Drabik 5.2.6 Construction of an Interface Linking Liquid Chromatograph to the Mass Spectrometer 202Anna Drabik 202 5.2.6.1 Introduction 202 5.2.6.2 ESI Interface 203 5.2.6.3 APCI Connection to MS 204 5.2.6.4 APPI Interface 205 5.2.6.5 LC Connection to MALDI‐MS 205 5.2.6.6 Multidimensional Separations 206 5.3 Capillary Electrophoresis Linked to Mass Spectrometry 209Przemysław Mielczarek and Jerzy Silberring 5.3.1 Introduction 209 5.3.2 Types of Electrophoretic Techniques 210 5.3.3 Capillary Electrophoresis Linked to ESI 211 5.3.3.1 Introduction 211 5.3.3.2 Liquid Sheath Connection 212 5.3.3.3 Sheath‐Free Connection 212 5.3.3.4 Liquid Junction 213 5.3.4 Capillary Electrophoresis Linked to Matrix‐Assisted Laser Desorption/Ionization 214 5.3.4.1 Offline CE‐MALDI‐TOF 214 5.3.4.2 Direct CE‐MALDI‐TOF 214 5.3.4.3 Online CE‐MALDI‐TOF 215 5.3.5 Summary 215 6 Mass Spectrometry Imaging 217Anna Bodzon‐Kulakowska and Anna Antolak 6.1 Introduction 217 6.2 SIMS 218 6.3 MALDI‐IMS 220 6.4 DESI 221 6.5 Analysis of Tissue Sections Using MSI Techniques 221 6.6 Analysis of Individual Cells and Cell Cultures Using MSI Techniques 223 6.7 Analysis with MSI Techniques: Examples 224 6.8 Combinations of Different Imaging Techniques 225 6.9 Summary 227 7 Tandem Mass Spectrometry 231Piotr Suder 7.1 Introduction 231 7.2 Principles 231 7.3 Strategies for MS/MS Experiments 233 7.3.1 Tandem in Space 233 7.3.2 Tandem in Time 234 7.3.3 Multiple Fragmentation 236 7.4 Fragmentation Techniques 236 7.4.1 Introduction 236 7.4.2 (Low‐Energy) Collision‐Induced Dissociation (CID) 237 7.4.3 High‐Energy Collisional Dissociation (HCD) 237 7.4.4 Pulsed Q Collision‐Induced Dissociation (PQD) 238 7.4.5 Electron Capture Dissociation (ECD) 239 7.4.6 Electron Transfer Dissociation (ETD) 239 7.4.7 Electron Detachment Dissociation (EDD) 241 7.4.8 Negative Electron Transfer Dissociation (NETD) 241 7.4.9 Infrared Multiphoton Dissociation (IRMPD) 241 7.4.10 Blackbody Infrared Radiative Dissociation (BIRD) 242 7.4.11 Post‐source Decay (PSD): Metastable Ion Dissociation 242 7.4.12 Surface‐Induced Dissociation (SID) 243 7.4.13 Charge Remote Fragmentation 243 7.4.14 Chemically Activated Fragmentation (CAF) 243 7.4.15 Proton Transfer Reaction (PTR) 244 7.5 Practical Aspects of Fragmentation in Mass Spectrometers 245 7.5.1 In‐Source Fragmentation 245 7.5.2 Triple Quadrupole Fragmentation 246 7.5.3 Ion Traps 249 7.5.4 Time‐of‐Flight Analyzers 250 7.5.5 Combined Time‐of‐Flight Analyzers (TOF/TOF) 251 7.5.6 Hybrid Instruments 252 7.5.7 Mass Spectrometers Equipped with Orbitrap Analyzer 253 7.6 Applications of Tandem Mass Spectrometry in Life Sciences 254 7.7 SWATH Fragmentation 256 8 Mass Spectrometry Applications 261 8.1 Mass Spectrometry in Proteomics 261 8.1.1 Introduction 261Vincenzo Cunsolo and Salvatore Foti 8.1.2 Bottom‐Up Versus Top‐Down Proteomics 262Vincenzo Cunsolo and Salvatore Foti 8.1.2.1 Bottom‐Up Proteomics 262 8.1.2.2 Top‐Down Proteomics 265 8.1.3 Database Search and Protein Identification 267 8.1.4 In‐Depth Structural Characterization of a Single Protein: An Example 269 8.1.5 Quantitative Analysis in Proteomics 273Joanna Ner‐Kluza, Anna Drabik, and Jerzy Silberring 8.1.5.1 Introduction 273 8.1.5.2 Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) 274 8.1.5.3 Isotope‐Coded Affinity Tagging (ICAT) 276 8.1.5.4 Stable Isotope Labeling in Culture (SILAC) 279 8.1.5.5 Stable Isotope Labeling of Mammals (SILAM) 280 8.1.5.6 Mass‐Coded Abundance Tagging (MCAT) 281 8.1.5.7 Label‐Free Techniques 281 8.2 Food Proteomics 285Vera Muccilli and Rosaria Saletti 8.3 Challenges in Analysis of Omics Data Generated by Mass Spectrometry 293Katarzyna Pawlak, Emma Harwood, Fang Yu, and Pawel Ciborowski 8.3.1 Introduction 293 8.3.1.1 How Big Must Big Data Be? 294 8.3.1.2 Do Omics Experiments Generate Unstructured Data? 294 8.3.2 Targeted and Full Unbiased Omics Analysis Based on MS Technology 295 8.3.2.1 Factors Affecting Data Quality 296 8.3.2.2 Speed of MS Data Acquisition: Why Does It Matter? 297 8.3.2.3 Analytical Strategies in Omics Studies 298 8.3.3 Data Analysis and Visualization of Mass Spectrometry Omics Data 300 8.3.3.1 A Brief Introduction to Data Visualization 301 8.3.3.2 Exploration and Preparation of Data for Downstream Statistics and Visualization 304 8.3.3.3 Differential Expression Analysis 305 8.3.3.4 Strategies for Visualization Beyond Three Dimensions 310 8.3.3.5 Bioinformatics Tools 312 8.3.4 Databases and Search Algorithms 315 8.3.4.1 Databases for Proteomics 315 8.3.5 Validation of High‐Throughput Data: Current Challenges 318 8.3.5.1 Analytical Validation 319 8.3.5.2 Statistical Validation 320 8.3.5.3 Bioinformatics Validation 321 8.3.6 Summary and Conclusions 322 8.4 Application of the Mass Spectrometric Techniques in the Earth Sciences 326Robert Anczkiewicz 8.4.1 Introduction 326 8.4.2 Conventional Geochronology 326 8.4.3 In Situ Geochronology 327 8.4.4 Geochemical and Isotopic Tracing 331 8.5 Mass Spectrometry in Space 335Kathrin Altweg 8.5.1 Solar Wind and Plasma 339 8.5.2 Atmospheres of Planets and Moons 339 8.5.3 Comets 340 8.5.4 Interstellar and Cometary Dust 341 8.6 Mass Spectrometry in the Study of Art and Archaeological Objects 345Giuseppe Spoto 8.6.1 Introduction 345 8.6.2 MS Methods for the Study of Inorganic Components of Art and Archaeological Objects 345 8.6.3 MS Methods for the Study of Organic Components of Art and Archaeological Objects 346 8.7 Application of ICP‐MS for Trace Elemental and Speciation Analysis 351Aleksandra Pawlaczyk and Małgorzata Iwona Szynkowska 8.7.1 Introduction 351 8.7.2 Speciation Analysis by ICP‐MS: Examples of Applications 352 8.7.3 Single‐Particle and Single‐Cell Analysis by ICP‐MS: Examples of Applications 353 8.7.4 Imaging by LA‐ICP‐MS Technique 355 8.7.5 Improvements of LA‐ICP‐MS Technique 358 8.7.6 LA‐ICP Mass Spectrometer with LIBS 359 8.8 Mass Spectrometry in Forensic Research 362Marek Smoluch and Jerzy Silberring 8.8.1 Introduction 362 8.8.2 Forgery in Art 362 8.8.3 Psychoactive Substances and Narcotics 363 8.8.4 Counterfeit Drugs and Generation of Metabolites 366 8.8.5 Terrorism/Explosives/Chemical Warfare 367 8.8.6 Future Prospects 368 8.9 Doping in Sport 372Dorota Kwiatkowska 8.10 Miniaturization in Mass Spectrometry 384Marek Smoluch and Jerzy Silberring 9 Appendix 389Kinga Piechura and Marek Smoluch 389 9.1 Pressure Units 389 9.2 Most Commonly Detected Fragments Generated by Electron Impact (EI) Ionization 389 9.3 Trypsin Autolysis Products 393 9.4 Proteolytic Enzymes for Protein Identification 394 9.5 Molecular Masses of Amino Acid Residues 395 9.6 Molecular Masses of Less Common Amino Acid Residues 397 9.7 Internet Databases 400 9.7.1 Literature Databases 400 9.7.2 Scientific Journals 401 9.7.2.1 Journals Related to Mass Spectrometry 402 9.7.3 Bioinformatics Databases 402 9.7.3.1 Protein Databases 402 9.7.3.2 Database of Structures and Functions of Protein 403 9.7.3.3 Other Databases 404 9.7.4 Bioinformatics Tools 404 9.7.5 Useful Websites 405 10 Abbreviations 407Kinga Piechura and Marek Smoluch Index 413

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Book SynopsisPresents basic concepts, experimental methodology and data acquisition, and processing standards of in vivo NMR spectroscopy This book covers, in detail, the technical and biophysical aspects of in vivo NMR techniques and includes novel developments in the field such as hyperpolarized NMR, dynamic 13C NMR, automated shimming, and parallel acquisitions. Most of the techniques are described from an educational point of view, yet it still retains the practical aspects appreciated by experimental NMR spectroscopists. In addition, each chapter concludes with a number of exercises designed to review, and often extend, the presented NMR principles and techniques. The third edition of In Vivo NMR Spectroscopy: Principles and Techniques has been updated to include experimental detail on the developing area of hyperpolarization; a description of the semi-LASER sequence, which is now a method of choice; updated chemical shift data, includingTable of ContentsPreface xv Abbreviations xvii Supplementary Material xxiv 1 Basic Principles 1 1.1 Introduction 1 1.2 Classical Magnetic Moments 3 1.3 Nuclear Magnetization 5 1.4 Nuclear Induction 9 1.5 Rotating Frame of Reference 11 1.6 Transverse T2 and T2 * Relaxation 12 1.7 Bloch Equations 16 1.8 Fourier Transform NMR 17 1.9 Chemical Shift 20 1.10 Digital NMR 23 1.10.1 Analog‐to‐digital Conversion 23 1.10.2 Signal Averaging 25 1.10.3 Digital Fourier Transformation 25 1.10.4 Zero Filling 25 1.10.5 Apodization 26 1.11 Quantum Description of NMR 28 1.12 Scalar Coupling 30 1.13 Chemical and Magnetic Equivalence 33 Exercises 37 References 40 2 In Vivo NMR Spectroscopy – Static Aspects 43 2.1 Introduction 43 2.2 Proton NMR Spectroscopy 43 2.2.1 Acetate (Ace) 51 2.2.2 N‐Acetyl Aspartate (NAA) 52 2.2.3 N‐Acetyl Aspartyl Glutamate (NAAG) 53 2.2.4 Adenosine Triphosphate (ATP) 54 2.2.5 Alanine (Ala) 55 2.2.6 γ‐Aminobutyric Acid (GABA) 56 2.2.7 Ascorbic Acid (Asc) 57 2.2.8 Aspartic Acid (Asp) 58 2.2.9 Branched‐chain Amino Acids (Isoleucine, Leucine, and Valine) 58 2.2.10 Choline‐containing Compounds (tCho) 59 2.2.11 Creatine (Cr) and Phosphocreatine (PCr) 61 2.2.12 Ethanol 62 2.2.13 Ethanolamine (EA) and Phosphorylethanolamine (PE) 63 2.2.14 Glucose (Glc) 63 2.2.15 Glutamate (Glu) 64 2.2.16 Glutamine (Gln) 65 2.2.17 Glutathione (GSH) 66 2.2.18 Glycerol 67 2.2.19 Glycine 68 2.2.20 Glycogen 68 2.2.21 Histidine 69 2.2.22 Homocarnosine 70 2.2.23 β‐Hydoxybutyrate (BHB) 70 2.2.24 2‐Hydroxyglutarate (2HG) 71 2.2.25 myo‐Inositol (mI) and scyllo‐Inositol (sI) 72 2.2.26 Lactate (Lac) 73 2.2.27 Macromolecules 74 2.2.28 Nicotinamide Adenine Dinucleotide (NAD+) 76 2.2.29 Phenylalanine 76 2.2.30 Pyruvate 77 2.2.31 Serine 78 2.2.32 Succinate 79 2.2.33 Taurine (Tau) 79 2.2.34 Threonine (Thr) 80 2.2.35 Tryptophan (Trp) 80 2.2.36 Tyrosine (Tyr) 80 2.2.37 Water 81 2.2.38 Non‐cerebral Metabolites 82 2.2.39 Carnitine and Acetyl‐carnitine 82 2.2.40 Carnosine 84 2.2.41 Citric Acid 86 2.2.42 Deoxymyoglobin (DMb) 87 2.2.43 Lipids 87 2.2.44 Spermine and Polyamines 89 2.3 Phosphorus‐31 NMR Spectroscopy 90 2.3.1 Chemical Shifts 90 2.3.2 Intracellular pH 92 2.4 Carbon‐13 NMR Spectroscopy 93 2.4.1 Chemical Shifts 93 2.5 Sodium‐23 NMR Spectroscopy 96 2.6 Fluorine‐19 NMR Spectroscopy 102 2.7 In vivo NMR on Other Non‐proton Nuclei 104 Exercises 106 References 108 3 In Vivo NMR Spectroscopy – Dynamic Aspects 129 3.1 Introduction 129 3.2 Relaxation 129 3.2.1 General Principles of Dipolar Relaxation 129 3.2.2 Nuclear Overhauser Effect 133 3.2.3 Alternative Relaxation Mechanisms 134 3.2.4 Effects of T1 Relaxation 137 3.2.5 Effects of T2 Relaxation 138 3.2.6 Measurement of T1 and T2 Relaxation 141 3.2.6.1 T1 Relaxation 141 3.2.6.2 Inversion Recovery 141 3.2.6.3 Saturation Recovery 142 3.2.6.4 Variable Nutation Angle 142 3.2.6.5 MR Fingerprinting 143 3.2.6.6 T2 Relaxation 143 3.2.7 In Vivo Relaxation 144 3.3 Magnetization Transfer 147 3.3.1 Principles of MT 149 3.3.2 MT Methods 150 3.3.3 Multiple Exchange Reactions 152 3.3.4 MT Contrast 152 3.3.5 Chemical Exchange Saturation Transfer (CEST) 156 3.4 Diffusion 160 3.4.1 Principles of Diffusion 160 3.4.2 Diffusion and NMR 160 3.4.3 Anisotropic Diffusion 169 3.4.4 Restricted Diffusion 173 3.5 Dynamic NMR of Isotopically‐Enriched Substrates 175 3.5.1 General Principles and Setup 177 3.5.2 Metabolic Modeling 177 3.5.3 Thermally Polarized Dynamic 13C NMR Spectroscopy 184 3.5.3.1 [1‐13C]‐Glucose and [1,6‐13C2]‐Glucose 184 3.5.3.2 [2‐13C]‐Glucose 185 3.5.3.3 [U‐13C6]‐Glucose 187 3.5.3.4 [2‐13C]‐Acetate 187 3.5.4 Hyperpolarized Dynamic 13C NMR Spectroscopy 189 3.5.4.1 Brute Force Hyperpolarization 189 3.5.4.2 Optical Pumping of Noble Gases 190 3.5.4.3 Parahydrogen‐induced Polarization (PHIP) 191 3.5.4.4 Signal Amplification by Reversible Exchange (SABRE) 193 3.5.4.5 Dynamic Nuclear Polarization (DNP) 193 3.5.5 Deuterium Metabolic Imaging (DMI) 196 Exercises 197 References199 4 Magnetic Resonance Imaging 211 4.1 Introduction 211 4.2 Magnetic Field Gradients 211 4.3 Slice Selection 212 4.4 Frequency Encoding 215 4.4.1 Principle 215 4.4.2 Echo Formation 216 4.5 Phase Encoding 219 4.6 Spatial Frequency Space 221 4.7 Fast MRI Sequences 225 4.7.1 Reduced TR Methods 225 4.7.2 Rapid k‐Space Traversal 226 4.7.3 Parallel MRI 229 4.7.3.1 SENSE 230 4.7.3.2 GRAPPA 233 4.8 Contrast in MRI 234 4.8.1 T1 and T2 Relaxation Mapping 236 4.8.2 Magnetic Field B0 Mapping 239 4.8.3 Magnetic Field B1 Mapping 241 4.8.4 Alternative Image Contrast Mechanisms 242 4.8.5 Functional MRI 243 Exercises 245 References 249 5 Radiofrequency Pulses 253 5.1 Introduction 253 5.2 Square RF Pulses 253 5.3 Selective RF Pulses 259 5.3.1 Fourier‐transform‐based RF Pulses 260 5.3.2 RF Pulse Characteristics 262 5.3.3 Optimized RF Pulses 266 5.3.4 Multifrequency RF Pulses 269 5.4 Composite RF Pulses 271 5.5 Adiabatic RF Pulses 273 5.5.1 Rotating Frame of Reference 275 5.5.2 Adiabatic Condition 276 5.5.3 Modulation Functions 278 5.5.4 AFP Refocusing 280 5.5.5 Adiabatic Plane Rotation of Arbitrary Nutation Angle 282 5.6 Multidimensional RF Pulses 284 5.7 Spectral–Spatial RF Pulses 284 Exercises 286 References 288 6 Single Volume Localization and Water Suppression 293 6.1 Introduction 293 6.2 Single‐volume Localization 294 6.2.1 Image Selected In Vivo Spectroscopy (ISIS) 295 6.2.2 Chemical Shift Displacement 297 6.2.3 Coherence Selection 301 6.2.3.1 Phase Cycling 302 6.2.3.2 Magnetic Field Gradients 302 6.2.4 STimulated Echo Acquisition Mode (STEAM) 304 6.2.5 Point Resolved Spectroscopy (PRESS) 307 6.2.6 Signal Dephasing with Magnetic Field Gradients 309 6.2.7 Localization by Adiabatic Selective Refocusing (LASER) 314 6.3 Water Suppression 317 6.3.1 Binomial and Related Pulse Sequences 318 6.3.2 Frequency‐Selective Excitation 321 6.3.3 Frequency‐Selective Refocusing 323 6.3.4 Relaxation‐Based Methods 323 6.3.5 Non‐water‐suppressed NMR Spectroscopy 326 Exercises 327 References 330 7 Spectroscopic Imaging and Multivolume Localization 335 7.1 Introduction 335 7.2 Principles of MRSI 335 7.3 k‐Space Description of MRSI 338 7.4 Spatial Resolution in MRSI 339 7.5 Temporal Resolution in MRSI 341 7.5.1 Conventional Methods 343 7.5.1.1 Circular and Spherical k‐Space Sampling 343 7.5.1.2 k‐Space Apodization During Acquisition 343 7.5.1.3 Zoom MRSI 345 7.5.2 Methods Based on Fast MRI 346 7.5.2.1 Echo‐planar Spectroscopic Imaging (EPSI) 346 7.5.2.2 Spiral MRSI 349 7.5.2.3 Parallel MRSI 350 7.5.3 Methods Based on Prior Knowledge 351 7.6 Lipid Suppression 353 7.6.1 Relaxation‐based Methods 353 7.6.2 Inner Volume Selection and Volume Prelocalization 355 7.6.3 Outer Volume Suppression (OVS) 357 7.7 MR Spectroscopic Image Processing and Display 360 7.8 Multivolume Localization 364 7.8.1 Hadamard Localization 365 7.8.2 Sequential Multivolume Localization 366 Exercises 368 References370 8 Spectral Editing and 2D NMR 375 8.1 Introduction 375 8.2 Quantitative Descriptions of NMR 375 8.2.1 Density Matrix Formalism 376 8.2.2 Classical Vector Model 377 8.2.3 Correlated Vector Model 378 8.2.4 Product Operator Formalism 379 8.3 Scalar Evolution 380 8.4 J‐Difference Editing 384 8.4.1 Principle 384 8.4.2 Practical Considerations 385 8.4.3 GABA, 2HG, and Lactate 389 8.5 Multiple Quantum Coherence Editing 395 8.6 Spectral Editing Alternatives 400 8.7 Heteronuclear Spectral Editing 402 8.7.1 Proton‐observed, Carbon‐edited (POCE) MRS 402 8.7.2 Polarization Transfer – INEPT and DEPT 407 8.8 Broadband Decoupling 410 8.9 Sensitivity 414 8.10 Two‐dimensional NMR Spectroscopy 415 8.10.1 Correlation Spectroscopy (COSY) 416 8.10.2 J‐resolved Spectroscopy (JRES) 422 8.10.3 In vivo 2D NMR Methods 424 Exercises 429 References 432 9 Spectral Quantification 439 9.1 Introduction 439 9.2 Data Acquisition 440 9.2.1 Magnetic Field Homogeneity 440 9.2.2 Spatial Localization 442 9.2.3 Water Suppression 442 9.2.4 Sensitivity 442 9.3 Data Preprocessing 443 9.3.1 Phased‐array Coil Combination 443 9.3.2 Phasing and Frequency Alignment 444 9.3.3 Line‐shape Correction 444 9.3.4 Removal of Residual Water 444 9.3.5 Baseline Correction 446 9.4 Data Quantification 447 9.4.1 Time‐ and Frequency‐domain Parameters 447 9.4.2 Prior Knowledge 450 9.4.3 Spectral Fitting Algorithms 453 9.4.4 Error Estimation 457 9.5 Data Calibration 460 9.5.1 Partial Saturation 461 9.5.2 Nuclear Overhauser Effects 462 9.5.3 Transverse Relaxation 462 9.5.4 Diffusion 462 9.5.5 Scalar Coupling 462 9.5.6 Localization 463 9.5.7 Frequency‐dependent Amplitude‐ and Phase Distortions 463 9.5.8 NMR Visibility 463 9.5.9 Internal Concentration Reference 464 9.5.10 External Concentration Reference 466 9.5.11 Phantom Replacement Concentration Reference 466 Exercises 467 References 469 10 Hardware 473 10.1 Introduction 473 10.2 Magnets 473 10.3 Magnetic Field Homogeneity 478 10.3.1 Origins of Magnetic Field Inhomogeneity 478 10.3.2 Effects of Magnetic Field Inhomogeneity 482 10.3.3 Principles of Spherical Harmonic Shimming 485 10.3.4 Practical Spherical Harmonic Shimming 489 10.3.5 Alternative Shimming Strategies 491 10.4 Magnetic Field Gradients 493 10.4.1 Eddy Currents 498 10.4.2 Preemphasis 499 10.4.3 Active Shielding 503 10.5 Radiofrequency (RF) Coils 503 10.5.1 Electrical Circuit Analysis 503 10.5.2 RF Coil Performance 509 10.5.3 Spatial Field Properties 510 10.5.3.1 Longitudinal Magnetic Fields 512 10.5.3.2 Transverse Magnetic Fields 513 10.5.4 Principle of Reciprocity 514 10.5.4.1 Electromagnetic Wave Propagation 515 10.5.5 Parallel Transmission 517 10.5.6 RF Power and Specific Absorption Rate (SAR) 519 10.5.7 Specialized RF Coils 520 10.5.7.1 Combined Transmit and Receive RF Coils 521 10.5.7.2 Phased‐Array Coils 522 10.5.7.3 1H‐[13C] and 13C‐[1H] RF Coils 522 10.5.7.4 Cooled and Superconducting RF Coils 525 10.6 Complete MR System 526 10.6.1 RF Transmission 526 10.6.2 Signal Reception 527 10.6.3 Quadrature Detection 528 10.6.4 Dynamic Range 529 10.6.5 Gradient and Shim Systems 530 Exercises 531 References 534 Appendix A 541 A.1 Matrix Calculations 541 A.2 Trigonometric Equations 543 A.3 Fourier Transformation 543 A.3.1 Introduction 543 A.3.2 Properties 544 A.3.2.1 Linearity 544 A.3.2.2 Time and Frequency Shifting 544 A.3.2.3 Scaling 545 A.3.2.4 Convolution 545 A.3.3 Discrete Fourier Transformation 545 A.4 Product Operator Formalism 546 A.4.1 Cartesian Product Operators 546 A.4.2 Shift (Lowering and Raising) Operators 548 References 550 Further Reading 551 Index 553

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Book SynopsisEEG Signal Processing and Machine Learning Explore cutting edge techniques at the forefront of electroencephalogram research and artificial intelligence from leading voices in the field The newly revised Second Edition of EEG Signal Processing and Machine Learning delivers an inclusive and thorough exploration of new techniques and outcomes in electroencephalogram (EEG) research in the areas of analysis, processing, and decision making about a variety of brain states, abnormalities, and disorders using advanced signal processing and machine learning techniques. The book content is substantially increased upon that of the first edition and, while it retains what made the first edition so popular, is composed of more than 50% new material. The distinguished authors have included new material on tensors for EEG analysis and sensor fusion, as well as new chapters on mental fatigue, sleep, seizure, neurodevelopmental diseases, BCI, and psychiatric abnormalities. In addition to including aTable of ContentsPreface to the Second Edition xvii Preface to the First Edition xxi List of Abbreviations xxiii 1 Introduction to Electroencephalography 1 1.1 Introduction 1 1.2 History 2 1.3 Neural Activities 5 1.4 Action Potentials 6 1.5 EEG Generation 8 1.6 The Brain as a Network 12 1.7 Summary 12 References 13 2 EEG Waveforms 15 2.1 Brain Rhythms 15 2.2 EEG Recording and Measurement 18 2.2.1 Conventional Electrode Positioning 21 2.2.2 Unconventional and Special Purpose EEG Recording Systems 24 2.2.3 Invasive Recording of Brain Potentials 26 2.2.4 Conditioning the Signals 27 2.3 Sleep 28 2.4 Mental Fatigue 30 2.5 Emotions 30 2.6 Neurodevelopmental Disorders 31 2.7 Abnormal EEG Patterns 32 2.8 Ageing 33 2.9 Mental Disorders 34 2.9.1 Dementia 34 2.9.2 Epileptic Seizure and Nonepileptic Attacks 35 2.9.3 Psychiatric Disorders 39 2.9.4 External Effects 40 2.10 Summary 41 References 42 3 EEG Signal Modelling 47 3.1 Introduction 47 3.2 Physiological Modelling of EEG Generation 47 3.2.1 Integrate-and-Fire Models 49 3.2.2 Phase-Coupled Models 49 3.2.3 Hodgkin–Huxley Model 51 3.2.4 Morris–Lecar Model 54 3.3 Generating EEG Signals Based on Modelling the Neuronal Activities 57 3.4 Mathematical Models Derived Directly from the EEG Signals 61 3.4.1 Linear Models 61 3.4.1.1 Prediction Method 61 3.4.1.2 Prony’s Method 62 3.4.2 Nonlinear Modelling 64 3.4.3 Gaussian Mixture Model 66 3.5 Electronic Models 67 3.5.1 Models Describing the Function of the Membrane 67 3.5.1.1 Lewis Membrane Model 68 3.5.1.2 Roy Membrane Model 68 3.5.2 Models Describing the Function of a Neuron 68 3.5.2.1 Lewis Neuron Model 68 3.5.2.2 The Harmon Neuron Model 71 3.5.3 A Model Describing the Propagation of the Action Pulse in an Axon 72 3.5.4 Integrated Circuit Realizations 72 3.6 Dynamic Modelling of Neuron Action Potential Threshold 72 3.7 Summary 73 References 73 4 Fundamentals of EEG Signal Processing 77 4.1 Introduction 77 4.2 Nonlinearity of the Medium 78 4.3 Nonstationarity 79 4.4 Signal Segmentation 80 4.5 Signal Transforms and Joint Time–Frequency Analysis 83 4.5.1 Wavelet Transform 87 4.5.1.1 Continuous Wavelet Transform 87 4.5.1.2 Examples of Continuous Wavelets 89 4.5.1.3 Discrete-Time Wavelet Transform 89 4.5.1.4 Multiresolution Analysis 90 4.5.1.5 Wavelet Transform Using Fourier Transform 93 4.5.1.6 Reconstruction 94 4.5.2 Synchro-Squeezed Wavelet Transform 95 4.5.3 Ambiguity Function and the Wigner–Ville Distribution 96 4.6 Empirical Mode Decomposition 100 4.7 Coherency, Multivariate Autoregressive Modelling, and Directed Transfer Function 101 4.8 Filtering and Denoising 104 4.9 Principal Component Analysis 107 4.9.1 Singular Value Decomposition 108 4.10 Summary 110 References 110 5 EEG Signal Decomposition 115 5.1 Introduction 115 5.2 Singular Spectrum Analysis 115 5.2.1 Decomposition 116 5.2.2 Reconstruction 117 5.3 Multichannel EEG Decomposition 118 5.3.1 Independent Component Analysis 118 5.3.2 Instantaneous BSS 122 5.3.3 Convolutive BSS 126 5.3.3.1 General Applications 127 5.3.3.2 Application of Convolutive BSS to EEG 128 5.4 Sparse Component Analysis 129 5.4.1 Standard Algorithms for Sparse Source Recovery 130 5.4.1.1 Greedy-Based Solution 130 5.4.1.2 Relaxation-Based Solution 131 5.4.2 k-Sparse Mixtures 131 5.5 Nonlinear BSS 133 5.6 Constrained BSS 134 5.7 Application of Constrained BSS; Example 135 5.8 Multiway EEG Decompositions 136 5.8.1 Tensor Factorization for BSS 139 5.8.2 Solving BSS of Nonstationary Sources Using Tensor Factorization 143 5.9 Tensor Factorization for Underdetermined Source Separation 149 5.10 Tensor Factorization for Separation of Convolutive Mixtures in the Time Domain 153 5.11 Separation of Correlated Sources via Tensor Factorization 153 5.12 Common Component Analysis 154 5.13 Canonical Correlation Analysis 154 5.14 Summary 155 References 155 6 Chaos and Dynamical Analysis 165 6.1 Introduction to Chaos and Dynamical Systems 165 6.2 Entropy 166 6.3 Kolmogorov Entropy 166 6.4 Multiscale Fluctuation-Based Dispersion Entropy 167 6.5 Lyapunov Exponents 167 6.6 Plotting the Attractor Dimensions from Time Series 169 6.7 Estimation of Lyapunov Exponents from Time Series 169 6.7.1 Optimum Time Delay 172 6.7.2 Optimum Embedding Dimension 172 6.8 Approximate Entropy 173 6.9 Using Prediction Order 174 6.10 Summary 175 References 175 7 Machine Learning for EEG Analysis 177 7.1 Introduction 177 7.2 Clustering Approaches 181 7.2.1 k-Means Clustering Algorithm 181 7.2.2 Iterative Self-Organizing Data Analysis Technique 183 7.2.3 Gap Statistics 183 7.2.4 Density-Based Clustering 184 7.2.5 Affinity-Based Clustering 184 7.2.6 Deep Clustering 184 7.2.7 Semi-Supervised Clustering 185 7.2.7.1 Basic Semi-Supervised Techniques 185 7.2.7.2 Deep Semi-Supervised Techniques 186 7.2.8 Fuzzy Clustering 186 7.3 Classification Algorithms 187 7.3.1 Decision Trees 188 7.3.2 Random Forest 189 7.3.3 Linear Discriminant Analysis 190 7.3.4 Support Vector Machines 191 7.3.5 k-Nearest Neighbour 199 7.3.6 Gaussian Mixture Model 200 7.3.7 Logistic Regression 200 7.3.8 Reinforcement Learning 201 7.3.9 Artificial Neural Networks 201 7.3.9.1 Deep Neural Networks 203 7.3.9.2 Convolutional Neural Networks 205 7.3.9.3 Autoencoders 207 7.3.9.4 Variational Autoencoder 208 7.3.9.5 Recent DNN Approaches 209 7.3.9.6 Spike Neural Networks 210 7.3.9.7 Applications of DNNs to EEG 212 7.3.10 Gaussian Processes 212 7.3.11 Neural Processes 213 7.3.12 Graph Convolutional Networks 213 7.3.13 Naïve Bayes Classifier 213 7.3.14 Hidden Markov Model 214 7.3.14.1 Forward Algorithm 216 7.3.14.2 Backward Algorithm 216 7.3.14.3 HMM Design 216 7.4 Common Spatial Patterns 218 7.5 Summary 222 References 223 8 Brain Connectivity and Its Applications 235 8.1 Introduction 235 8.2 Connectivity through Coherency 238 8.3 Phase-Slope Index 240 8.4 Multivariate Directionality Estimation 240 8.4.1 Directed Transfer Function 241 8.4.2 Direct DTF 242 8.4.3 Partial Directed Coherence 243 8.5 Modelling the Connectivity by Structural Equation Modelling 243 8.6 Stockwell Time–Frequency Transform for Connectivity Estimation 246 8.7 Inter-Subject EEG Connectivity 247 8.7.1 Objectives 247 8.7.2 Technological Relevance 247 8.8 State-Space Model for Estimation of Cortical Interactions 249 8.9 Application of Cooperative Adaptive Filters 251 8.9.1 Use of Cooperative Kalman Filter 253 8.9.2 Task-Related Adaptive Connectivity 254 8.9.3 Diffusion Adaptation 255 8.9.4 Brain Connectivity for Cooperative Adaptation 256 8.9.5 Other Applications of Cooperative Learning and Brain Connectivity Estimation 257 8.10 Graph Representation of Brain Connectivity 258 8.11 Tensor Factorization Approach 259 8.12 Summary 262 References 263 9 Event-Related Brain Responses 269 9.1 Introduction 269 9.2 ERP Generation and Types 269 9.2.1 P300 and its Subcomponents 273 9.3 Detection, Separation, and Classification of P300 Signals 274 9.3.1 Using ICA 275 9.3.2 Estimation of Single-Trial Brain Responses by Modelling the ERP Waveforms 277 9.3.3 ERP Source Tracking in Time 278 9.3.4 Time–Frequency Domain Analysis 280 9.3.5 Application of Kalman Filter 284 9.3.6 Particle Filtering and its Application to ERP Tracking 286 9.3.7 Variational Bayes Method 291 9.3.8 Prony’s Approach for Detection of P300 Signals 293 9.3.9 Adaptive Time–Frequency Methods 297 9.4 Brain Activity Assessment Using ERP 298 9.5 Application of P300 to BCI 299 9.6 Summary 300 References 301 10 Localization of Brain Sources 307 10.1 Introduction 307 10.2 General Approaches to Source Localization 308 10.2.1 Dipole Assumption 309 10.3 Head Model 311 10.4 Most Popular Brain Source Localization Approaches 313 10.4.1 EEG Source Localization Using Independent Component Analysis 313 10.4.2 MUSIC Algorithm 313 10.4.3 LORETA Algorithm 317 10.4.4 FOCUSS Algorithm 318 10.4.5 Standardized LORETA 319 10.4.6 Other Weighted Minimum Norm Solutions 320 10.4.7 Evaluation Indices 323 10.4.8 Joint ICA–LORETA Approach 323 10.5 Forward Solutions to the Localization Problem 325 10.5.1 Partially Constrained BSS Method 325 10.5.2 Constrained Least-Squares Method for Localization of P3a and P3b 326 10.5.3 Spatial Notch Filtering Approach 328 10.6 The Methods Based on Source Tracking 333 10.6.1 Deflation Beamforming Approach for EEG/MEG Multiple Source Localization 333 10.6.2 Hybrid Beamforming – Particle Filtering 336 10.7 Determination of the Number of Sources from the EEG/MEG Signals 337 10.8 Other Hybrid Methods 340 10.9 Application of Machine Learning for EEG/MEG Source Localization 340 10.10 Summary 342 References 343 11 Epileptic Seizure Prediction, Detection, and Localization 351 11.1 Introduction 351 11.2 Seizure Detection 357 11.2.1 Adult Seizure Detection from EEGs 357 11.2.2 Detection of Neonatal Seizure 363 11.3 Chaotic Behaviour of Seizure EEG 366 11.4 Seizure Detection from Brain Connectivity 369 11.5 Prediction of Seizure Onset from EEG 369 11.6 Intracranial and Joint Scalp–Intracranial Recordings for IED Detection 384 11.6.1 Introduction to IED 384 11.6.2 iEED-Times IED Detection from Scalp EEG 386 11.6.3 A Multiview Approach to IED Detection 391 11.6.4 Coupled Dictionary Learning for IED Detection 391 11.6.5 A Deep Learning Approach to IED Detection 392 11.7 Fusion of EEG–fMRI Data for Seizure Prediction 396 11.8 Summary 398 References 399 12 Sleep Recognition, Scoring, and Abnormalities 407 12.1 Introduction 407 12.1.1 Definition of Sleep 407 12.1.2 Sleep Disorder 408 12.2 Stages of Sleep 409 12.2.1 NREM Sleep 409 12.2.2 REM Sleep 411 12.3 The Influence of Circadian Rhythms 414 12.4 Sleep Deprivation 415 12.5 Psychological Effects 416 12.6 EEG Sleep Analysis and Scoring 416 12.6.1 Detection of the Rhythmic Waveforms and Spindles Employing Blind Source Separation 416 12.6.2 Time–Frequency Analysis of Sleep EEG Using Matching Pursuit 417 12.6.3 Detection of Normal Rhythms and Spindles Using Higher-Order Statistics 421 12.6.4 Sleep Scoring Using Tensor Factorization 423 12.6.5 Application of Neural Networks 425 12.6.6 Model-Based Analysis 426 12.7 Detection and Monitoring of Brain Abnormalities during Sleep by EEG and Multimodal PSG Analysis 428 12.7.1 Analysis of Sleep Apnoea 428 12.7.2 EEG and Fibromyalgia Syndrome 431 12.7.3 Sleep Disorders of Neonates 431 12.8 Dreams and Nightmares 432 12.9 EEG and Consciousness 433 12.10 Functional Brain Connectivity for Sleep Analysis 433 12.11 Summary 434 References 435 13 EEG-Based Mental Fatigue Monitoring 441 13.1 Introduction 441 13.2 Feature-Based Machine Learning Approaches 443 13.2.1 Hidden Markov Model Application 443 13.2.2 Kernel Principal Component Analysis and Hidden Markov Model 444 13.2.3 Regression-Based Fatigue Estimation 444 13.2.4 Regularized Regression 445 13.2.5 Other Feature-Based Approaches 445 13.3 Measurement of Brain Synchronization and Coherency 446 13.3.1 Linear Measure of Synchronization 446 13.3.2 Nonlinear Measure of Synchronization 448 13.4 Evaluation of ERP for Mental Fatigue 451 13.5 Separation of P3a and P3b 457 13.6 A Hybrid EEG–ERP-Based Method for Fatigue Analysis Using an Auditory Paradigm 463 13.7 Assessing Mental Fatigue by Measuring Functional Connectivity 465 13.8 Deep Learning Approaches for Fatigue Evaluation 472 13.9 Summary 474 References 474 14 EEG-Based Emotion Recognition and Classification 479 14.1 Introduction 479 14.1.1 Theories and Emotion Classification 480 14.1.2 The Physiological Effects of Emotions 482 14.1.3 Psychology and Psychophysiology of Emotion 485 14.1.4 Emotion Regulation 487 14.1.4.1 Agency and Intentionality 490 14.1.4.2 Norm Violation 490 14.1.4.3 Guilt 491 14.1.4.4 Shame 491 14.1.4.5 Embarrassment 491 14.1.4.6 Pride 491 14.1.4.7 Indignation and Anger 491 14.1.4.8 Contempt 491 14.1.4.9 Pity and Compassion 492 14.1.4.10 Awe and Elevation 492 14.1.4.11 Gratitude 492 14.1.5 Emotion-Provoking Stimuli 492 14.2 Effect of Emotion on the Brain 494 14.2.1 ERP Change Due to Emotion 494 14.2.2 Changes of Normal Brain Rhythms with Emotion 497 14.2.3 Emotion and Lateral Brain Engagement 498 14.2.4 Perception of Odours and Emotion: Why Are They Related? 498 14.3 Emotion-Related Brain Signal Processing and Machine Learning 499 14.3.1 Evaluation of Emotion Based on the Changes in Brain Rhythms 500 14.3.2 Brain Asymmetricity and Connectivity for Emotion Evaluation 501 14.3.3 Changes in ERPs for Emotion Recognition 504 14.3.4 Combined Features for Emotion Analysis 504 14.4 Other Physiological Measurement Modalities Used for Emotion Study 507 14.5 Applications 510 14.6 Pain Assessment Using EEG 510 14.7 Emotion Elicitation and Induction through Virtual Reality 512 14.8 Summary 513 References 514 15 EEG Analysis of Neurodegenerative Diseases 525 15.1 Introduction 525 15.2 Alzheimer’s Disease 527 15.2.1 Application of Brain Connectivity Estimation to AD and MCI 528 15.2.2 ERP-Based AD Monitoring 532 15.2.3 Other Approaches to EEG-Based AD Monitoring 532 15.3 Motor Neuron Disease 537 15.4 Parkinson’s Disease 537 15.5 Huntington’s Disease 541 15.6 Prion Disease 542 15.7 Behaviour Variant Frontotemporal Dementia 544 15.8 Lewy Body Dementia 545 15.9 Summary 545 References 546 16 EEG As A Biomarker for Psychiatric and Neurodevelopmental Disorders 551 16.1 Introduction 551 16.1.1 History 551 16.1.1.1 Different Psychiatric and Neurodevelopmental Disorders 553 16.1.1.2 NDD Diagnosis 554 16.2 EEG Analysis for Different NDDs 554 16.2.1 ADHD 554 16.2.1.1 ADHD Symptoms and Possible Treatment 554 16.2.1.2 EEG-Based Diagnosis of ADHD 555 16.2.2 ASD 559 16.2.2.1 ASD Symptoms and Possible Treatment 559 16.2.2.2 EEG-Based Diagnosis of ASD 560 16.2.3 Mood Disorder 561 16.2.3.1 EEG for Monitoring Depression 562 16.2.3.2 EEG for Monitoring Bipolar Disorder 564 16.2.4 Schizophrenia 565 16.2.4.1 Schizophrenia Symptoms and Management 565 16.2.4.2 EEG as the Biomarker for Schizophrenia 566 16.2.5 Anxiety (and Panic) Disorder 568 16.2.5.1 Definition and Symptoms 568 16.2.5.2 EEG for Assessing Anxiety 569 16.2.6 Insomnia 571 16.2.6.1 Symptoms of Insomnia 571 16.2.6.2 EEG for Insomnia Analysis 572 16.2.7 Schizotypal Personality Disorder 572 16.2.7.1 What Is Schizotypal Disorder? 572 16.2.7.2 EEG Manifestation of Schizotypal 573 16.3 Summary 573 References 574 17 Brain–Computer Interfacing Using EEG 581 17.1 Introduction 581 17.1.1 State of the Art in BCI 584 17.1.2 BCI Terms and Definitions 585 17.1.3 Popular BCI Directions 585 17.1.4 Virtual Environment for BCI 586 17.1.5 Evolution of BCI Design 587 17.2 BCI-Related EEG Components 588 17.2.1 Readiness Potential and Its Detection 588 17.2.2 ERD and ERS 588 17.2.3 Transient Beta Activity after the Movement 593 17.2.4 Gamma Band Oscillations 593 17.2.5 Long Delta Activity 593 17.2.6 ERPs 594 17.3 Major Problems in BCI 594 17.3.1 Preprocessing of the EEGs 595 17.4 Multidimensional EEG Decomposition 597 17.4.1 Space–Time–Frequency Method 599 17.4.2 Parallel Factor Analysis 599 17.5 Detection and Separation of ERP Signals 601 17.6 Estimation of Cortical Connectivity 603 17.7 Application of Common Spatial Patterns 606 17.8 Multiclass Brain–Computer Interfacing 609 17.9 Cell-Cultured BCI 610 17.10 Recent BCI Applications 610 17.11 Neurotechnology for BCI 614 17.12 Joint EEG and Other Brain-Scanning Modalities for BCI 617 17.12.1 Joint EEG–fNIRS for BCI 617 17.12.2 Joint EEG–MEG for BCI 618 17.13 Performance Measures for BCI Systems 618 17.14 Summary 619 References 620 18 Joint Analysis of EEG and Other Simultaneously Recorded Brain Functional Neuroimaging Modalities 631 18.1 Introduction 631 18.2 Fundamental Concepts 631 18.2.1 Functional Magnetic Resonance Imaging 631 18.2.1.1 Blood Oxygenation Level Dependence 633 18.2.1.2 Popular fMRI Data Formats 635 18.2.1.3 Preprocessing of fMRI Data 635 18.2.2 Functional Near-Infrared Spectroscopy 636 18.2.3 Magnetoencephalography 640 18.3 Joint EEG–fMRI 640 18.3.1 Relation Between EEG and fMRI 640 18.3.2 Model-Based Method for BOLD Detection 642 18.3.3 Simultaneous EEG–fMRI Recording: Artefact Removal from EEG 644 18.3.3.1 Gradient Artefact Removal from EEG 644 18.3.3.2 Ballistocardiogram Artefact Removal from EEG 645 18.3.4 BOLD Detection in fMRI 652 18.3.4.1 Implementation of Different NMF Algorithms for BOLD Detection 653 18.3.4.2 BOLD Detection Experiments 654 18.3.5 Fusion of EEG and fMRI 659 18.3.5.1 Extraction of fMRI Time Course from EEG 659 18.3.5.2 Fusion of EEG and fMRI; Blind Approach 659 18.3.5.3 Fusion of EEG and fMRI; Model-Based Approach 664 18.3.6 Application to Seizure Detection 664 18.3.7 Investigation of Decision Making in the Brain 666 18.3.8 Application to Schizophrenia 666 18.3.9 Other Applications 667 18.4 EEG–NIRS Joint Recording and Fusion 668 18.5 MEG–EEG Fusion 672 18.6 Summary 672 References 673 Index 681

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Book SynopsisThese volumes teach readers to think beyond apoptosis and describes all of the known processes that cells can undergo which result in cell death This two-volume source on how cells dies is the first, comprehensive collection to cover all of the known processes that cells undergo when they die. It is also the only one of its kind to compare these processes. It seeks to enlighten those in the field about these many processes and to stimulate their thinking at looking at these pathways when their research system does not show signs of activation of the classic apoptotic pathway. In addition, it links activities like the molecular biology of one process (eg. Necrosis) to another process (eg. apoptosis) and contrasts those that are close to each. Volume 1 of Apoptosis and Beyond: The Many Ways Cells Die begins with a general view of the cytoplasmic and nuclear features of apoptosis. It then goes on to offer chapters on targeting the cell death mechanism; microTable of ContentsList of Contributors ix Volume 1 1 General View of the Cytoplasmic and Nuclear Features of Apoptosis 1Humberto De Vitto, Juan P. Valencia, and James A. Radosevich 2 Mitochondria in Focus: Targeting the Cell-Death Mechanism 13Humberto De Vitto, Roberta Palorini, Giuseppina Votta, and Ferdinando Chiaradonna 3 Microbial Programmed Cell Death 49Neal D. Hammer 4 Autophagy 71Mollie K. Rojas, Juel Chowdhury, Khatja Batool, Zane Deliu, and Abdallah Oweidi 5 Cell Injury, Adaptation, and Necrosis 83Sarah G. Fitzpatrick and Sara C. Gordon 6 Necroptosis 99Ben A. Croker, James A. Rickard, Inbar Shlomovitz, Arshed Al-Obeidi, Akshay A. D’Cruz, and Motti Gerlic 7 Ferroptosis 127Ebru Esin Yoruker and Ugur Gezer 8 Anoikis Regulation: Complexities, Distinctions, and Cell Differentiation 145Marco Beauséjour, Ariane Boutin, and Pierre H. Vachon 9 Cornification 183Leopold Eckhart 10 Excitotoxicity 197Julie Alagha, Sulaiman Alshaar, and Zane Deliu 11 Molecular Mechanisms Regulating Wallerian Degeneration 205Mohammad Tauseef and Madeeha Aqil 12 Pyronecrosis 225Maryam Khalili and James A. Radosevich 13 Phenoptosis: Programmed Death of an Organism 237M.V. Skulachev and V.P. Skulachev 14 Molecular Mechanisms Underlying Oxytosis 289Amalia M. Dolga, Sina Oppermann, Maren Richter, Birgit Honrath, Sandra Neitemeier, Anja Jelinek, Goutham Ganjam, and Carsten Culmsee 15 Pyroptosis 317Kate E. Lawlor, Stephanie Conos, and James E. Vince 16 Paraptosis 343Maryam Khalili and James A. Radosevich 17 Hematopoiesis and Eryptosis 367Mollie K. Rojas, Chintan C. Gandhi, and Lawrence E. Feldman Volume 2 18 Cyclophilin D-Dependent Necrosis 375Jatin Mehta and Chandi Charan Mandal 19 Role of Phospholipases in Cell Death 395Manikanda Raja, Juel Chowdhury, and James A. Radosevich 20 TRIAD (Transcriptional Repression-Induced Atypical Death) 411Takuya Tamura and Hitoshi Okazawa 21 Alkylating-Agent Cytotoxicity Associated with O6-Methylguanine 427Latha M. Malaiyandi, Lawrence A. Potempa, Nicholas Marschalk, Paiboon Jungsuwadee, and Kirk E. Dineley 22 Entosis 463Jamuna A. Bai and Ravishankar Rai V. 23 Mitotic Catastrophe 475Raquel De Souza, Lais Costa Ayub, and Kenneth Yip 24 NETosis and ETosis: Incompletely Understood Types of Granulocyte Death and their Proposed Adaptive Benefits and Costs 511Marko Radic 25 Parthanatos: Poly ADP Ribose Polymerase (PARP)-Mediated Cell Death 535Amos Fatokun 26 Methuosis: Drinking to Death 559Madeeha Aqil 27 Oncosis 567Priya Weerasinghe, Sarathi Hallock, Robert Brown, and L. Maximilian Buja 28 Autoschizis: A Mode of Cell Death of Cancer Cells Induced by a Prooxidant Treatment In Vitro and In Vivo 583J. Gilloteaux, J.M. Jamison, D. Arnold, and J.L. Summers 29 Programmed Death 1 (PD1)-Mediated T-Cell Apoptosis and Cancer Immunotherapy 695Chandi Charan Mandal, Jatin Mehta, and Vijay K. Prajapati

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Book SynopsisA comprehensive resource to sustainability and its application to the environmental, industrial, agricultural and food security sectors Sustainability fills a gap in the literature in order to provide an important guide to the fundamental knowledge and practical applications of sustainability in a wide variety of areas. The authors noted experts who represent a number of sustainability fields bring together in one comprehensive volume the broad range of topics including basic concepts, impact assessment, environmental and the socio-economic aspects of sustainability. In addition, the book covers applications of sustainability in environmental, industrial, agricultural and food security, as well as carbon cycle and infrastructural aspects. Sustainability addresses the challenges the global community is facing due to population growth, depletion of non-renewable resources of energy, environmental degradation, poverty, excessive generation of wastesTable of ContentsEditor Biographies xxiii List of Contributors xxvii Preface xxxiii Part I Fundamentals and Framework 1 1 Introduction to Sustainability and Sustainable Development 3 Prangya R. Rout, Akshaya K. Verma, Puspendu Bhunia, Rao Y. Surampalli, Tian C. Zhang, R.D. Tyagi, S.K. Brar, and M.K. Goyal 1.1 Background and Definition 3 1.2 Basic Concepts and Issues 4 1.3 Evolution of Sustainability and Sustainable Development 7 1.4 Challenges and Solutions 8 1.5 Adaptation and Resilience 8 1.6 Economic, Ecological, Social, Technological and Systems Perspectives 13 1.7 Conclusions 16 References 17 2 The Need, Role and Significance of Sustainability 21 Anita Talan, A.N. Pathak, and R.D. Tyagi 2.1 Introduction 21 2.2 Three Pillars of Sustainability 21 2.3 Primary Goals of Sustainability 27 2.4 Significance of Sustainability 34 2.5 Challenges Toward Sustainability 35 2.6 Sustainable Future 39 2.7 Conclusions 39 References 40 3 Sustainable Development: Dimensions, Intersections and Knowledge Platform 43 Pritee Sharma and Kanak Singh 3.1 Introduction 43 3.2 Understanding Complex Systems 44 3.3 Dimensions of Sustainable Development: Economic Dimension 47 3.4 Dimensions of Sustainable Development: Environmental Dimension 53 3.5 Dimensions of Sustainable Development: Social Dimension 56 3.6 Mapping Social Development Through Sustainable Development Goals (SDGs) 58 3.7 Sustainable Development Indicators 60 3.8 Exploring Knowledge Systems for Sustainability 61 3.9 Conclusion 65 References 65 4 Measurement of Sustainability 69 Rajneesh Singh, Akash Kumar Gupta, Puspendu Bhunia, Rao Y. Surampalli, Tian C. Zhang, Pengzhi Lin, and Yu Chen 4.1 Introduction 69 4.2 Types and Choice of Indicators 70 4.3 Framework of Lifecycle-Based Sustainability Metrics 72 4.4 Technological Aspects of Supply Chain and Process Sustainability 73 4.5 Sustainable Economy Indices 74 4.6 Environmental Indicator for Manufacturing Competitiveness 75 4.7 Monitoring and Evaluation Processes 77 4.8 Conclusion 79 References 79 5 Sustainable Impact Assessment 83 L.R. Kumar, Anita Talan and R.D. Tyagi 5.1 Introduction 83 5.2 Types of Impact Assessment (IA) 83 5.3 Sustainable Impact Assessment (SIA) 86 5.4 Advantages of Conducting Sustainable Impact Assessment 89 5.5 Recent Evolution of Impact Assessment 90 5.6 Different Approaches of SIA 91 5.7 Determining Criteria for Sustainability 93 5.8 Procedure to Follow Impact Assessment 94 5.9 ToSIA – Software Tool for Sustainable Impact Assessment 99 5.10 Case Studies for Use of Sustainable Impact Assessment 103 5.11 Conclusions 106 References 107 6 Analytical Tools and Methodologies to Evaluate Sustainable Development Goals of the United Nations with Special Reference to Asia 111 Gamini Herath 6.1 Introduction 111 6.2 Sustainable Development Goals of the United Nations 112 6.3 Planning and Decision Making Methodologies for the Sustainable Development Goals 112 6.4 Tools to Tackle Interlinked Goals and Policy Incoherence 113 6.5 Carrying Capacity (CC) 116 6.6 Evalution Models Under Uncertainty 117 6.7 Adaptive Management 119 6.8 Multicriteria Decision Analysis (MCDA) 119 6.9 Multiattribute Utility Theory 121 6.10 Conclusions 124 References 124 7 Resilience Engineering and Quantification for Sustainable Systems 129 Anita Talan, Bhoomika Yadav, L.R. Kumar, and R.D. Tyagi 129 7.1 Introduction 129 7.2 Resilience and Sustainability: Definitions, Differences and Similarities 130 7.3 Technical Purposes of Resilience Engineering 132 7.4 Resilience Assessment Approaches 133 7.5 Indicators for Quantifying Successful Resilience and Sustainability 138 7.6 Some Resilient Systems and Associated Codes/Standards 140 7.7 Communal Resilience and Built Environment Sustainability 144 7.8 Risk Analysis and Resilience 149 7.9 Integration of Sustainability and Resilience 151 7.10 Conclusions 152 References 154 Part II Dimensions and Different Aspects 157 8 Economic Development and Sustainability 159 L.R. Kumar, Anita Talan, and R.D. Tyagi 8.1 Introduction 159 8.2 Different Perspectives of Economic Development 159 8.3 Indicators for Economic Development 160 8.4 Economic Development for Sustainability 162 8.5 Economic Policies for Sustainable Development 167 8.6 Economic Development and Environment 170 8.7 Economic Analysis of Sustainable Development 174 8.8 Future Directions for Achieving Economic Sustainable Development 177 8.9 Conclusions 178 References 179 9 Social Dimensions of Sustainability 183 Anita Talan, R.D. Tyagi, and Rao Y. Surampalli 9.1 Introduction 183 9.2 Concepts and Definitions of Social Sustainability 184 9.3 Social Sustainability 185 9.4 Dimensions of Social Sustainability 188 9.5 Gaps in Dimensions of Social Sustainability 193 9.6 Research-based Policies and Federal Perspective Toward Social Sustainability 195 9.7 Social Sustainability – an Integrated Approach 200 9.8 Safety and Security 202 9.9 Future Perspective and Conclusions 203 References 204 10 Social Engineering and Sustainability: Revisiting Popper’s “Piecemeal Approach” 207 Neeraj Mishra 10.1 Introduction 207 10.2 Emergence of Sustainability on the Global Agenda 208 10.3 Concept of Social Engineering 209 10.4 Karl Popper’s Description of Social Engineering 211 10.5 Social Engineering as a Tool for Sustainable Development 214 10.6 Promoting Sustainable Consumption and Bio‐Politics of Sustainability 217 10.7 Social Engineering, Sustainability and Industrial Production 221 10.8 Conclusions 224 References 225 11 Environment Modeling for Sustainable Development 229 Lalit Borana, Bhaskar Jyoti Deka, Jiaxin Guo, and Alicia Kyoungjin An 11.1 Introduction 229 11.2 Environmental Indicators in the Context of Sustainable Development 231 11.3 Overview of Sustainable Development 235 11.4 Role of Sustainability in Environmental Development 237 11.5 Case Studies: Sustainability Management 241 11.6 Modeling of Sustainability 246 11.7 Modeling Tools for Sustainable Development Policies: Vision 2030 – United Nations Department of Economic and Social Affairs 249 11.8 Summary 251 References 251 12 Biodiversity and Sustainability 255 Akshaya K. Verma, Prangya R. Rout, Eunseok Lee, Puspendu Bhunia, Jaeho Bae, Rao Y. Surampalli, Tian C. Zhang, Rajeshwar D. Tyagi, Pengzhi Lin, and Yu Chen 12.1 Introduction 255 12.2 Threats to Biodiversity 257 12.3 Role of Biodiversity in Sustainable Development 268 12.4 Trends of Biodiversity 269 12.5 Conclusions 270 References 271 13 Sustainability of Ecosystem Services (ESs) 277 Carlos S. Osorio‐González, Niranjan Suralikerimath, Krishnamoorthy Hegde, and Satinder K. Brar 13.1 Introduction 277 13.2 Historical Evolution of Ecosystem Services Definition 278 13.3 Framework for Assessing Ecosystem Services 280 13.4 Utilization of Ecosystem Services for Sustainable Development 281 13.5 Recent Advances in Mapping and Measuring Multiple Services 283 13.6 Possible Approaches for Sustainable Use of Ecosystem Services 284 13.7 Challenge and Interlinkage Themes for Researchers 287 13.8 Future Directions and Conclusions 288 References 289 14 Sustainable Infrastructure 295 Gilbert Hinge, Rao Y. Surampalli, and Manish Kumar Goyal 14.1 Infrastructure − An Introduction 295 14.2 Mitigation Policies 299 14.3 Strategic Environmental Assessment 301 14.4 Recycling Reuse and Reclamation 304 14.5 Reverse Logistics 305 14.6 Deconstruction 307 14.7 Summary 308 References 309 15 Industrial Practices in Sustainability 313 K.K. Brar, Dalila Larios Martinez, Mitra Naghdi, Satinder K. Brar, Bhupinder Singh Chadha, Preetinder Singh, and Rao Y. Surampalli 15.1 Introduction 313 15.2 Causes of Environmental Deterioration 314 15.3 Effects of Environmental Degradation 315 15.4 Human-Induced Eye-Opening Environmental Incidents 318 15.5 Sustainable Development 319 15.6 Benefits of Being a Sustainable Business 320 15.7 How to Achieve Sustainable Development 321 15.8 Commitment Toward the Environment 322 15.9 Future Action Needed 335 References 336 16 Challenges of Sustainability in Agricultural Management 339 Jew Das, Srinidhi Jha, Manish Kumar Goyal, and Rao Y. Surampalli 16.1 Introduction 339 16.2 An Overview of Indian Agriculture 341 16.3 Agricultural Sustainability: Environmental, Economic and Social Perspectives 347 16.4 Challenges to Agricultural Sustainability 348 16.5 Road to Sustainable Agriculture: Possible Solutions 352 16.6 Conclusions 354 References 355 17 Food Security and Sustainability 357 Preetika Kuknur Pachapur, Vinayak Laxman Pachapur, Satinder K. Brar, Rosa Galvez, Yann Le Bihan, and Rao Y. Surampalli 17.1 Introduction 357 17.2 Food Needs 358 17.3 Population Growth 359 17.4 Impact of Climate Change on Food Security 360 17.5 International Case Studies 361 17.6 Biofuels and Food Security 364 17.7 Water–Energy–Food Security Nexus 367 17.8 Genetically Modified Foods for Food Security 368 17.9 Horizontal Gene Transfer for Food Security 369 17.10 Future Plans for Food Security 369 References 371 18 Sustainable Healthcare Systems 375 Carlos S. Osorio‐González, Krishnamoorthy Hegde, Satinder K. Brar, Antonio Avalos‐ Ramírez, and Rao Y. Surampalli 18.1 Introduction 375 18.2 Classification of Healthcare Systems 376 18.3 Sustainability and Healthcare Systems 377 18.4 Sustainability Challenges in Healthcare Systems 379 18.5 Categories of Sustainability in Healthcare Systems 381 18.6 Overview of Sustainable Healthcare Systems 384 18.7 Conclusion 390 References 391 19 Ethical Aspects of Sustainability 397 Anita Talan, Rajwinder Kaur, R.D. Tyagi, and Tian C. Zhang 19.1 Introduction 397 19.2 Juxtaposing Ethics, Morality and Sustainable Development 398 19.3 Approaches to Ethics 400 19.4 The Neoliberal Era and Adaptation into the Sustainability Framework 402 19.5 Global Flora and Sustainability 405 19.6 Adaptation and Mitigation of Climate Change: Ethical Perspective 405 19.7 Conclusions 409 References 410 20 Education and Human Resource Development for Sustainability 413 Anita Talan, and R. D Tyagi 20.1 Introduction 413 20.2 Education for Sustainability 413 20.3 Objectives of Education for Sustainable Development 416 20.4 Potential Improvements via Education for Sustainable Development 421 20.5 Global Education and Global Actions of ESD 424 20.6 Sustainability as Human Resource Development 429 20.7 HRD Indicators 432 20.8 Change in HRD for Sustainability 433 20.9 HRD Resources for Sustainable Development 434 20.10 Conclusion 435 References 436 Part III Applications 439 21 Climate Change Adaptation for Sustainable Management of Water in India: Issues and Challenges 441 Adani Azhoni 21.1 Introduction 441 21.2 Climate Change Challenges to India’s Water Management 443 21.3 Adaptation Approaches 444 21.4 Water Management Institutions and Their Role in Adaptation 449 21.5 Indian Water Institutions 450 21.6 Recent Initiatives to Address Climate Change in India 452 21.7 Adaptation for Sustainability: Two Examples 452 21.8 Discussion and Conclusion 454 References 455 22 Sustainability of Carbon Storage and Sequestration 465 Gilbert Hinge, Rao Y. Surampalli, and Manish Kumar Goyal 22.1 Introduction 465 22.2 Carbon Sources and Sinks 466 22.3 Types of Carbon Sequestration 466 22.4 Methods for Quantification of Soil Organic Carbon Stocks 468 22.5 Adaptation and Mitigation Policy for Carbon Management 475 22.6 Conclusions 479 References 479 23 Environmental Degradation and Sustainability 483 Yong Qi, Puspendu Bhunia, Tian C. Zhang, F. Luo, Pengzhi Lin, and Yu Chen 23.1 Introduction 483 23.2 Desertification and Associated Sustainable Strategies 484 23.3 Environmental Pollution and Associated Impacts 486 23.4 Snow Ablation and Glacier Retreat 491 23.5 Dams and Resettlement 492 23.6 Strategies for Sustainable Development While Addressing Environmental Pollution and Degradation 494 23.7 Future Trends 501 23.8 Conclusions 502 References 502 24 Sustainability of River Water Resources Under the Influence of Climate Change 507 Shivam Gupta and Manish Kumar Goyal 24.1 Introduction 507 24.2 Effects of Global Warming on Observed Changes 508 24.3 Water Stress – the Supply Demand Balance 510 24.4 Impacts of Climate Change on Glaciers and Mountainous Water Resources 511 24.5 Sustainable Management of River Water Resources 512 24.6 Case Studies 513 24.7 Conclusions 523 References 523 25 Sustainable Systems for Groundwater Resource Management 527 Manish Kumar Goyal, Srinidhi Jha, and Rao Y. Surampalli 25.1 Introduction 527 25.2 Occurrence and Distribution 530 25.3 Groundwater Usage in the World 533 25.4 Two Main Challenges 536 25.5 Toward Groundwater Sustainability 539 25.6 Looking for Possible Solutions: Primary Solutions 542 25.7 Intuitional and Organizational Reforms: Secondary Solutions 546 25.8 Conclusions 548 References 549 26 Sustainability and Energy Management in Facilities for Wastewater Treatment and Reuse 553 Joseph Sebastian, Pratik Kumar, Krishnamoorthy Hegde, Satinder K. Brar, Mausam Verma, and Rao Y. Surampalli 26.1 Introduction 553 26.2 Sustainable Wastewater Treatment and Reuse 554 26.3 Approaches for Sustainable Wastewater Treatment and Reuse 557 26.4 Sustainable Energy Derived from Wastewater 564 26.5 Conclusions 575 References 576 27 Energy Needs for Sustainable Buildings and Transportation 583 Rehan Khan, Suchit Deshmukh, and Ritunesh Kumar 27.1 Introduction 583 27.2 Building and Energy 584 27.3 Energy for Transportation 594 27.4 Conclusions 602 References 602 28 Remote Sensing and GIS Applications in Sustainability 605 Manish Kumar Goyal, Ashutosh Sharma, and Rao Y. Surampalli 28.1 Introduction 605 28.2 Remote Sensing for Earth Observation (EO) and Data Acquisition 609 28.3 Sustainable Resource Management Using Remote Sensing and GIS 612 28.4 Case Study 613 28.5 Future Perspectives 619 28.6 Conclusions 620 References 620 29 Artificial Intelligence and Computational Sustainability 627 S.K. Ram and R.D. Tyagi 29.1 Introduction 627 29.2 Basic Elements of AI Implementation 628 29.3 Concept of Computational Sustainability 629 29.4 Computational Sustainability and Ecological Preservation 631 29.5 Potential Applications of AI in Various Sectors 632 29.6 AI for UN Sustainable Development Goals 638 29.7 Challenges Associated with AI 638 29.8 AI and Its Socio‐Economic Impact 641 29.9 AI for Developing Countries: A Case Study of Zimbabwe 643 29.10 Conclusions and Future Prospects 645 References 645 Index 651

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Book SynopsisEssentials of Chemical Biology Discover a detailed knowledge of concepts and techniques that shape this unique multi-discipline Chemical Biology is devoted to understanding the way that Biology works at the molecular level. This is a problem-driven multi-discipline, incorporating as it does Organic, Physical, Inorganic, and Analytical Chemistry alongside newer emerging molecular disciplines. In recent years, Chemical Biology has emerged as a vibrant and growing multi-discipline distinct from Biochemistry that is focused on the quantitative analyses of the structures and functions of biological macromolecules and macromolecular lipid assemblies, at first in isolation, then in vitro and in vivo. The second edition of the Essentials of Chemical Biology begins with a thorough introduction to the structure of biological macromolecules and macromolecular lipid assemblies, before moving on to the principles of chemical and biological synthesis, foTable of ContentsPreface x Glossary of Physical and Chemical Terms xii About the Companion Website xviii 1 The Structures of Biological Macromolecules and Lipid Assemblies 1 1.1 General introduction 1 1.2 Protein structures 3 1.3 Carbohydrate structures 20 1.4 Nucleic acid structures 31 1.5 Macromolecular lipid assemblies 53 1.6 Structural forces in biological macromolecules 60 2 Chemical and Biological Synthesis 68 2.1 Introduction to synthesis in chemical biology 68 2.2 Chemical synthesis of peptides and proteins 68 2.3 Chemical synthesis of nucleic acids 75 2.4 Chemical synthesis of oligosaccharides 84 2.5 Chemical synthesis of lipids 87 2.6 Biological synthesis of biological macromolecules 89 2.7 Directed biological synthesis of proteins 97 2.8 Biological syntheses of nucleic acids, oligosaccharides and lipids 102 3 Molecular Biology as a Toolset for Chemical Biology 104 3.1 Key concepts in molecular biology 104 3.2 Tools and techniques in molecular biology 108 3.3 Cloning and identification of genes in DNA 117 3.4 Integrating cloning and expression 123 3.5 Site-directed mutagenesis 125 4 Electronic and Vibrational Spectroscopy 128 4.1 Electronic and vibrational spectroscopy in chemical biology 128 4.2 Ultraviolet-visible spectroscopy 128 4.3 Circular dichroism spectroscopy 134 4.4 Vibrational spectroscopy 138 4.5 Fluorescence spectroscopy 141 4.6 Probing metal centres by absorption spectroscopy 163 5 Magnetic Resonance 164 5.1 Magnetic resonance in chemical biology 164 5.2 Key principles of NMR 164 5.3 Two-dimensional NMR 176 5.4 Multidimensional NMR 180 5.5 Biological macromolecule structural information 183 5.6 Electron paramagnetic resonance spectroscopy: key principles 193 6 Diffraction and Microscopy 199 6.1 Diffraction and microscopy in chemical biology 199 6.2 Key principles of X-ray diffraction 199 6.3 Structural information from X-ray diffraction 206 6.4 Neutron diffraction 216 6.5 Key principles of electron microscopy 217 6.6 Key principles of scanning probe microscopy 224 7 Molecular Recognition and Binding 232 7.1 Molecular recognition and binding in chemical biology 232 7.2 Theoretical models of binding 245 7.3 Analysing molecular recognition and binding 251 7.4 Biological molecular recognition studies 263 8 Kinetics and Catalysis 278 8.1 Catalysis in chemical biology 278 8.2 Steady state kinetic schemes 300 8.3 Pre-steady-state kinetics 323 8.4 Theories of biocatalysis 328 8.5 Electron transfer 346 9 Mass Spectrometry and Proteomics 348 9.1 Mass spectrometry in chemical biology 348 9.2 Key principles in mass spectrometry 349 9.3 Structural analysis of biological macromolecules and lipids by mass spectrometry 359 9.4 The challenge of proteomics 368 9.5 Genomics: assigning function to genes and proteins 375 10 Molecular Selection and Evolution 378 10.1 Chemical biology and the origins of life 378 10.2 Molecular breeding: natural selection acting on self-organisation 383 10.3 Directed evolution of protein function 385 10.4 Directed evolution of nucleic acids 390 10.5 Catalytic antibodies 398 11 Chemical Biology of Cells 401 11.1 General introduction 401 11.2 Array technologies, microfluidics and miniaturisation 401 11.3 Chemical genetics and potential new therapeutics 403 11.4 Chemical cellular dynamics 412 11.5 Chemical biology and in vivo cell connectomics 415 12 Chemical Biology of Stem Cells to Tissue Engineering 421 12.1 General introduction 421 12.2 Chemical stem cell biology 421 12.3 The road to cell therapies 437 12.4 Tissue engineering 439 13 Chemical Biology, Nanomedicine and Advanced Therapeutics 441 13.1 General introduction 441 13.2 The chemical biology approach to gene therapy 441 13.3 Biophysical characterisation of LNPs 467 13.4 Applications of LNPs with small molecule drugs 471 14 Chemical Biology and Advanced Diagnostics Leading to Precision Therapeutic Approaches 472 14.1 General introduction 472 14.2 MRI basic principles leading to diagnostic applications 472 14.3 PET/CT and SPECT fundamentals 477 14.4 Understanding how to control nanoparticle biodistribution behaviour in vivo 478 14.5 Theranostics 479 15 DNA Nanotechnology 489 15.1 Background 489 15.2 Three-dimensional DNA nanostructures 491 15.3 Dynamic DNA nanostructures 496 15.4 Biomedical applications of DNA nanostructures 500 Bibliography 502 Index 519

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Book SynopsisProvides a timely update to a key textbook on human drug metabolism The third edition of this comprehensive book covers basic concepts of teaching drug metabolism, starting from extreme clinical consequences to systems and mechanisms and toxicity. It provides an invaluable introduction to the core areas of pharmacology and examines recent progress and advances in this fast moving field and its clinical impact. Human Drug Metabolism, 3rd Edition begins by covering basic concepts such as clearance and bioavailability, and looks at the evolution of biotransformation, and how drugs fit into this carefully managed biological environment. More information on how cytochrome P450s function and how they are modulated at the sub-cellular level is offered in this new edition. The book also introduces helpful concepts for those struggling with the relationship of pharmacology to physiology, as well as the inhibition of biotransformational activity. Recent advances inTable of ContentsPreface xv 1 Introduction 1 1.1 Therapeutic window 1 1.1.1 Introduction 1 1.1.2 Therapeutic index 3 1.1.3 Changes in dosage 3 1.1.4 Changes in rate of removal 4 1.2 Consequences of drug concentration changes 4 1.2.1 Drug failure 4 1.2.2 Drug toxicity 5 1.3 Clearance 6 1.3.1 Definitions 6 1.3.2 Clearance and elimination 7 1.3.3 Biotransformation prior to elimination 7 1.3.4 Intrinsic clearance 8 1.3.5 Clearance: influencing factors 8 1.4 First pass and drug extraction 9 1.4.1 First pass: gut contribution 9 1.4.2 First pass: hepatic contribution 10 1.4.3 First pass: low‐extraction drugs 12 1.5 First pass and plasma drug levels 13 1.5.1 Introduction 13 1.5.2 Changes in clearance and plasma levels 14 1.6 Drug and xenobiotic metabolism 14 References 15 2 Drug Biotransformational Systems – Origins and Aims 17 2.1 Biotransforming enzymes 17 2.2 Threat of lipophilic hydrocarbons 18 2.3 Cell communication 19 2.3.1 Signal molecule evolution 19 2.3.2 Lipophilic hydrocarbons as signal molecules 20 2.4 False signal molecules: bioprotection 22 2.4.1 Endocrine disruption 22 2.4.2 Endocrine disruption: problems and solutions 23 2.4.3 Endocrine disruption: cosmetic and nutraceutical aspects 24 2.4.4 Endocrine disruption: microRNAs 25 2.5 Sites of biotransforming enzymes 26 2.6 Biotransformation and xenobiotic cell entry 27 2.6.1 Role of the liver 27 2.6.2 Drug and xenobiotic uptake: transporter systems 29 2.6.3 Hepatic and gut uptake (influx) transporter systems 30 2.6.4 Aims of biotransformation 31 2.6.5 Task of biotransformation 32 2.6.6 Phase’s I–III of biotransformation: descriptions and classifications 33 2.6.7 Biotransformation and drug action 34 References 34 3 How Oxidative Systems Metabolise Substrates 37 3.1 Introduction 37 3.2 Capture of lipophilic molecules 37 3.3 Cytochrome P450s: nomenclature and methods of study 38 3.3.1 Classification 38 3.3.2 Methods of analysis 40 3.3.3 CYP key features and capabilities 42 3.4 CYPs: main and associated structures 44 3.4.1 General structure 44 3.4.2 Haem moiety 44 3.4.3 CYP flexible regions 45 3.4.4 Substrate binding in CYPs 46 3.4.5 Homotropic binding in CYPs 47 3.4.6 Heterotropic binding in CYPs 49 3.4.7 CYP complex formation 50 3.4.8 CYP REDOX partners (i): P450 oxidoreductase (POR) 50 3.4.9 CYP REDOX partners (ii): Cytochrome b5 52 3.5 Human CYP families and their regulation 54 3.5.1 CYP regulation: lifespan 55 3.5.2 CYP regulation: transcriptional 56 3.5.3 CYP regulation: post‐translational 58 3.6 Main human CYP families 59 3.6.1 CYP1A series 59 3.6.2 CYP2 series 61 3.6.3 CYP3A series 69 3.7 Cytochrome P450 catalytic cycle 71 3.7.1 Substrate binding 72 3.7.2 Oxygen binding 72 3.7.3 Oxygen scission (splitting) 74 3.7.4 Insertion of oxygen into substrate 75 3.7.5 Release of product 75 3.7.6 Reductions 76 3.8 Flavin monooxygenases (FMOs) 76 3.8.1 Introduction 76 3.8.2 Structure 77 3.8.3 Mechanism of catalysis 78 3.8.4 Variation and expression 80 3.8.5 FMOs in drug development 80 3.9 How CYP isoforms operate in vivo 81 3.9.1 Illustrative use of structures 82 3.9.2 Primary purposes of CYPs 82 3.9.3 Role of oxidation 83 3.9.4 Summary of CYP operations 84 3.10 Aromatic ring hydroxylation 84 3.10.1 Nature of aromatics 84 3.10.2 Oxidation of benzene 85 3.11 Alkyl oxidations 86 3.11.1 Saturated alkyl groups 86 3.11.2 Unsaturated alkyl groups 87 3.11.3 Pathways of alkyl metabolism 89 3.12 Rearrangement reactions 90 3.12.1 Dealkylations 90 3.12.2 Deaminations 93 3.12.3 Dehalogenations 94 3.13 Other oxidation processes 94 3.13.1 Primary amine oxidations 94 3.13.2 Oxidation of alcohol and aldehydes 96 3.13.3 Monoamine oxidase (MAO) 96 3.14 Control of CYP metabolic function 97 References 97 4 Induction of Cytochrome P450 Systems 109 4.1 Introduction 109 4.1.1 How living systems self‐regulate: overview 109 4.1.2 Self‐regulation in drug metabolism 112 4.1.3 Self‐regulatory responses to drugs: summary 117 4.2 Causes of accelerated clearance 117 4.3 Enzyme induction 118 4.3.1 Types of inducers 118 4.3.2 Common features of inducers and clinical significance 120 4.4 Mechanisms of enzyme induction 121 4.4.1 Introduction 121 4.4.2 CYPs 1A1/1A2 and 1B1 induction 122 4.4.3 CYP 2B6 2C8/2C9/C19 and 3A4 induction 126 4.4.4 CYP 2E1 induction 138 4.4.5 CYP2D6 140 4.4.6 Reversal of induction 141 4.4.7 Cell transport systems and induction: P‐glycoprotein 143 4.4.8 Induction processes: summary 148 4.5 Induction: general clinical aspects 149 4.5.1 Introduction 149 4.5.2 Anti‐epileptic agents 150 4.5.3 OTC (over the counter) and online herbal preparations 155 4.5.4 Anticoagulant drugs 158 4.5.5 Oral contraceptives/steroids 160 4.5.6 Antiviral/antibiotic drugs 161 4.5.7 Anticancer drugs 163 4.6 Induction: practical considerations 165 4.7 Induction vs. inhibition: which ‘wins’? 165 4.8 Induction: long‐term impact 166 References 167 5 Cytochrome P450 Inhibition 183 5.1 Introduction 183 5.2 Inhibition of metabolism: general aspects 186 5.3 Mechanisms of reversible inhibition 187 5.3.1 Introduction 187 5.3.2 Competitive inhibition 188 5.3.3 Noncompetitive inhibition 195 5.3.4 Uncompetitive inhibition 196 5.4 Mechanisms of irreversible inhibition 196 5.4.1 Introduction 196 5.4.2 Mechanism‐based quasi‐irreversible inhibitors 198 5.4.3 Mechanism‐based irreversible inhibitors 198 5.5 Clinical consequences of irreversible inhibition 200 5.5.1 Introduction 200 5.5.2 Quasi‐irreversible inhibitors: the SSRIs 201 5.5.3 Mechanism‐based inhibitors: grapefruit juice 213 5.5.4 Mechanism‐based inhibitors: other juice products 216 5.5.5 OTC herbal remedy inhibitors 218 5.6 Cell transport systems and inhibition 220 5.6.1 Uptake (Influx) transporters: OATPs 220 5.6.2 Efflux transporters: P‐glycoprotein (P‐gp) 222 5.7 Major clinical consequences of inhibition of drug clearance 226 5.7.1 Introduction 226 5.7.2 Torsades de pointes (TdP) 227 5.7.3 Sedative effects 232 5.7.4 Muscle damage (rhabdomyolysis) 233 5.7.5 Excessive hypotension 234 5.7.6 Ergotism 235 5.7.7 Excessive anticoagulation 235 5.8 Use of inhibitors for positive clinical intervention 236 5.8.1 Introduction 236 5.8.2 CYP inhibitors and female hormone‐dependent tumours 237 5.8.3 CYP inhibitors and male hormone‐dependent tumours 238 5.8.4 CYP inhibitors and manipulation of prescription drug disposition 239 5.8.5 Use of inhibitors to increase drug efficacy 241 5.8.6 Use of inhibitors to reduce toxic metabolite formation 242 5.8.7 Use of inhibitors to reduce drug costs 245 5.8.8 Use of inhibition in alcoholism 246 5.9 Summary 246 References 246 6 Conjugation and Transport Processes 263 6.1 Introduction 263 6.2 Glucuronidation 265 6.2.1 UGTs 265 6.2.2 UGT mode of operation 266 6.2.3 UGT isoforms 268 6.2.4 UGTs and bilirubin 271 6.2.5 UGTs and bile acids 272 6.2.6 Role of glucuronidation in drug clearance 273 6.2.7 Types of glucuronides formed 274 6.2.8 Control of UGTs 276 6.2.9 Induction of UGTs: clinical consequences 278 6.2.10 UGT inhibition: bilirubin metabolism 280 6.2.11 UGT inhibition: drug clearance 281 6.2.12 Microbiome and drug metabolism: passengers or crew? 282 6.3 Sulphonation 285 6.3.1 Introduction 285 6.3.2 SULT structure related to catalytic operation 287 6.3.3 Control of SULT enzymes 289 6.3.4 SULTs and cancer 289 6.4 The GSH system 290 6.4.1 Introduction 290 6.4.2 GSH system maintenance 292 6.5 Glutathione S‐transferases 293 6.5.1 Structure and location 293 6.5.2 Mode of operation 295 6.5.3 GST classes 296 6.5.4 Control of GSTs: overview 300 6.5.5 Control of GSTs and reactive species 301 6.5.6 Control of GSTs: the nrf2 system 302 6.6 Epoxide hydrolases 304 6.6.1 Nature of epoxides 304 6.6.2 Epoxide hydrolases 304 6.6.3 Epoxide hydrolases: structure, mechanisms of action, and regulation 306 6.7 Acetylation 307 6.8 Methylation 309 6.9 Esterases/amidases 311 6.10 Amino acid conjugation (mainly glycine) 314 6.11 Phase III transport processes 315 6.11.1 Introduction 315 6.11.2 ABC Efflux transporters 315 6.11.3 RLIP76 320 6.12 Biotransformation: integration of processes 320 References 322 7 Factors Affecting Drug Metabolism 331 7.1 Introduction 331 7.2 Genetic polymorphisms 332 7.2.1 Introduction 332 7.2.2 Clinical implications 336 7.2.3 Genetic polymorphisms in CYP systems 341 7.2.4 Genetic polymorphisms in nonconjugative systems 369 7.2.5 Conjugative polymorphisms: acetylation 374 7.2.6 Conjugative polymorphisms: methylation 381 7.2.7 Conjugative polymorphisms: UGT 1A1 385 7.2.8 Conjugative polymorphisms: sulphonation 388 7.2.9 Other conjugative polymorphisms: Glutathione S‐transferases 389 7.2.10 Transporter polymorphisms 390 7.2.11 Polymorphism detection: clinical and practical issues 392 7.3 Effects of age on drug metabolism 395 7.3.1 The elderly 395 7.3.2 Drug clearance in neonates and children 398 7.4 Effects of diet on drug metabolism 401 7.4.1 Polyphenols 401 7.4.2 Barbecued meat 402 7.4.3 Cruciferous vegetables 403 7.4.4 Other vegetable effects on metabolism 404 7.4.5 Caffeine 404 7.4.6 Diet: general effects 405 7.5 Gender effects 406 7.6 Smoking 409 7.7 Effects of ethanol on drug metabolism 412 7.7.1 Context of ethanol usage 412 7.7.2 Ethanol metabolism 413 7.7.3 Ethanol and inhibitors of ALDH 414 7.7.4 Mild ethanol usage and drug clearance 414 7.7.5 Heavy ethanol usage and paracetamol 415 7.7.6 Alcoholic liver disease 416 7.7.7 Effects of cirrhosis on drug clearance 420 7.8 Artificial livers 422 7.9 Effects of disease on drug metabolism 424 7.10 Summary 425 References 426 8 Role of Metabolism in Drug Toxicity 447 8.1 Adverse drug reactions: definitions 447 8.2 Predictable drug adverse effects: type A 448 8.2.1 Intensification of pharmacologic effect: type A1 448 8.2.2 Off‐target reversible effects and methaemoglobin formation: type A2 449 8.2.3 Predictable overdose toxicity: type A3 455 8.3 Unpredictable drug adverse effects: type B 470 8.3.1 Idiosyncratic and overdose toxicity: similarities and differences 470 8.3.2 Type B1 necrosis: troglitazone 471 8.3.3 Type B1 necrosis: trovafloxacin 473 8.3.4 Type B2 reactions: immunotoxicity 476 8.4 Nature of drug‐mediated immune responses 489 8.4.1 Anaphylaxis 489 8.4.2 DRESS/Anticonvulsant hypersensitivity syndrome (AHS) 491 8.4.3 Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) 492 8.4.4 Blood dyscrasias 494 8.4.5 Prediction of idiosyncratic reactions 499 8.5 Type B3 reactions: role of metabolism in cancer 500 8.5.1 Sources of risks of malignancy 500 8.5.2 Risks of malignancy and drug development 501 8.5.3 Environmental carcinogenicity risks 502 8.5.4 Occupational carcinogens 503 8.5.5 Dietary carcinogens: acrylamide 513 8.5.6 Dietary carcinogens: aflatoxins 516 8.6 Summary of biotransformational toxicity 520 References 521 Appendix A Drug Metabolism in Drug Discovery 531 A.1 The pharmaceutical industry 531 A.2 Drug design and biotransformation: strategies 533 A.3 Animal and human experimental models: strategies 537 A.4 In vitro metabolism platforms and methods 539 A.4.1 Analytical techniques 539 A.4.2 Human liver microsomes 541 A.4.3 Heterologous recombinant systems 542 A.4.4 Liver slices 543 A.4.5 Human hepatocytes 543 A.5 Animal model developments in drug metabolism 550 A.5.1 Introduction 550 A.5.2 Genetic modification of animal models 551 A.5.3 ‘Humanized’ mice 552 A.6 Toxicological assays 553 A.6.1 Aims 553 A.6.2 Cell viability assays 554 A.6.3 ‘One compartment’ cell models 555 A.6.4 ‘Two compartment’ models 555 A.6.5 DNA and chromosomal toxicity assays 556 A.6.6 The Ames test 556 A.6.7 Comet assay 557 A.6.8 Micronucleus test 557 A.6.9 Toxicology in drug discovery 558 A.7 In silico approaches 561 A.8 Summary 564 References 565 Appendix B Metabolism of Major Illicit Drugs 571 B.1 Introduction 571 B.2 Opiates 572 B.3 Cocaine 582 B.4 Hallucinogens 585 B.5 Amphetamine derivatives 591 B.6 Cannabis 603 B.7 Dissociative anaesthetics 609 B.8 Charlie Don’t Surf! 616 References 617 Appendix C Examination Techniques 627 C.1 Introduction 627 C.2 A first‐class answer 627 C.3 Preparation 629 C.4 The day of reckoning 632 C.5 Foreign students 633 Appendix D Summary of Major CYP Isoforms and Their Substrates, Inhibitors, and Inducers 635 Index 639

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Book SynopsisWritten by an experienced and well-respected physician and professor, this new volume, building on the previous volume, Ultrasonic Topographical and Pathotopographical Anatomy, also available from Wiley-Scrivener, presents the ultrasonic topographical and pathotopographical anatomy of the head and neck, offering further detail into these important areas for use by medical professionals. This atlas of topographic and pathotopographic human anatomy is a fundamental and practically important book designed for doctors of all specializations and students of medical schools. Here you can find almost everything that is connected with the topographic and pathotopographic human anatomy, including original graphs of logical structures of topographic anatomy and development of congenital abnormalities, topography of different areas in layers, pathotopography, computer and magnetic resonance imaging (MRI) of topographic and pathotopographic anatomy. Also you can find here new theoTable of ContentsAbout the Author vii Introduction ix Part 1 The Head 1 Topographic Anatomy of the Head 1 Cerebral Cranium 1 Basis Cranii Interna 15 The Brain 18 Surgical Anatomy of Congenital Disorders 41 Pathotypography of the Cerebral Part of the Head 42 Facial Head Region 47 The Lymphatic System of the Head 89 Congenital Face Disorders 92 Pathotypography of the Facial Part of the Head 94 Attachment 1: Neurocranial Part Topography 102 Attachment 2: Facial Part Topography 103 Part 2 The Neck 105 Topographic Anatomy of the Neck 105 Fasciae, Superficial and Deep Cellular Spaces and their Relationship with Spaces Adjacent Regions 107 Triangles of the Neck 113 Organs of the Neck 135 Pathography of the Neck 144 Attachment 3: Topography of the Neck 155 Appendix A: Adult 157 Appendix B: Child 165

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Book SynopsisAll organisms produce nucleobases, nucleosides, and nucleotides of purines and pyrimidines. However, while there have been a number of texts on nucleotide metabolism in microorganisms and humans, the presence of these phenomena in plant life has gone comparatively unexplored. This ground-breaking new book is the first to focus exclusively on the aspects of purine nucleotide metabolism and function that are particular to plants, making it a unique and essential resource. The authors provide a comprehensive break down of purine nucleotide structures and metabolic pathways, covering all facets of the topic. Furthermore, they explain the role that purine nucleotides can play in plant development, as well as the effects they may have on human health when ingested. Plant Nucleotide Metabolism offers a unique and important resource to all students, researchers, and lecturers working in plant biochemistry, physiology, chemistry, agricultural sciences, nutrition, and asTable of ContentsPreface xv Part I General Aspects of Nucleotide Metabolism 1 1 Structures of Nucleotide-Related Compounds 3 1.1 Introduction 3 1.2 Nomenclature and Abbreviations of Nucleotide-Related Compounds 3 1.3 Chemical Structures of Nucleotide-Related Compounds 5 1.3.1 Purines 5 1.3.1.1 Purine Bases 5 1.3.1.2 Purine Nucleosides 6 1.3.1.3 Purine Nucleotides 7 1.3.2 Pyrimidines 8 1.3.2.1 Pyrimidine Bases 9 1.3.2.2 Pyrimidine Nucleosides 9 1.3.2.3 Pyrimidine Nucleotides 10 1.3.3 Pyridines 11 1.4 Summary 11 References 11 2 Occurrence of Nucleotides and Related Metabolites in Plants 13 2.1 Purines and Pyrimidines 13 2.1.1 Concentration of Purine and Pyrimidine Nucleotides 14 2.1.2 Concentration of Purine and Pyrimidine Bases and Nucleosides 16 2.2 Pyridine Nucleotides 17 2.2.1 Concentration of Pyridine Nucleotides 17 2.2.2 Concentration of Nicotinate and Nicotinamide 18 2.3 Concentration of Cytokinins 18 2.4 Alkaloids Derived from Nucleotides 18 2.5 Summary 19 References 19 3 General Aspects of Nucleotide Biosynthesis and Interconversions 21 3.1 Introduction 21 3.2 De Novo Biosynthesis of Ribonucleoside Monophosphates 21 3.3 Interconversion of Nucleoside Monophosphates, Nucleoside Diphosphates, and Triphosphates 23 3.3.1 Nucleoside-Monophosphate Kinase 23 3.3.2 Specific Nucleoside-Monophosphate Kinases 24 3.4 Conversion of Nucleoside Diphosphates to Nucleoside Triphosphates 24 3.4.1 ATP Synthesis by Electron Transfer Systems 25 3.4.2 Substrate-Level ATP Synthesis 26 3.4.3 Nucleoside-Diphosphate Kinase 26 3.5 Biosynthesis of Deoxyribonucleotides 29 3.6 Nucleic Acid Biosynthesis 29 3.7 Supply of 5-Phosphoribosyl-1-Pyrophosphate 30 3.8 Supply of Amino Acids for Nucleotide Biosynthesis 33 3.9 Nitrogen Metabolism and Amino Acid Biosynthesis in Plants 33 3.10 Summary 34 References 35 Part II Purine Nucleotide Metabolism 39 4 Purine Nucleotide Biosynthesis De Novo 41 4.1 Introduction 41 4.2 Reactions and Enzymes 43 4.2.1 Synthesis of Phosphoribosylamine 44 4.2.2 Synthesis of Glycineamide Ribonucleotide 46 4.2.3 Synthesis of Formylglycineamide Ribonucleotide 46 4.2.4 Synthesis of Formylglycinamidine Ribonucleotide 47 4.2.5 Synthesis of Aminoimidazole Ribonucleotide 47 4.2.6 Synthesis of Aminoimidazole Carboxylate Ribonucleotide 48 4.2.7 Synthesis of Aminoimidazole Succinocarboxamide Ribonucleotide 48 4.2.8 Synthesis of Aminoimidazole Carboxamide Ribonucleotide 49 4.2.9 Synthesis of IMP via Formamidoimidazole Carboxamide Ribonucleotide 49 4.2.10 Synthesis of AMP 50 4.2.11 Synthesis of GMP 51 4.3 Summary 52 References 52 5 Salvage Pathways of Purine Nucleotide Biosynthesis 55 5.1 Introduction 55 5.2 Characteristics of Purine Salvage in Plants 56 5.3 Properties of Purine Phosphoribosyltransferases 59 5.3.1 Adenine Phosphoribosyltransferase 59 5.3.2 Hypoxanthine/Guanine Phosphoribosyltransferase 59 5.3.3 Xanthine Phosphoribosyltransferase 62 5.4 Properties of Nucleoside Kinases 62 5.4.1 Adenosine Kinase 62 5.4.2 Inosine/Guanosine Kinase 64 5.4.3 Deoxyribonucleoside Kinases 64 5.5 Properties of Nucleoside Phosphotransferase 65 5.6 Role of Purine Salvage in Plants 66 5.7 Summary 66 References 66 6 Interconversion of Purine Nucleotides 71 6.1 Introduction 71 6.2 Deamination Reactions 71 6.2.1 Routes of Deamination of Adenine Ring 73 6.2.2 AMP Deaminase 73 6.2.3 Routes of Deamination of Guanine Ring 74 6.2.4 Guanosine Deaminase 75 6.3 Dephosphorylation Reactions 75 6.4 Glycosidic Bond Cleavage Reactions 76 6.4.1 Adenosine Nucleosidase 76 6.4.2 Inosine/Guanosine Nucleosidase 78 6.4.3 Non-specific Purine Nucleosidases 78 6.4.4 Recombinant Non-Specific Nucleosidases 78 6.5 In Situ Metabolism of 14C-Labelled Purine Nucleotides 79 6.5.1 Metabolism of Adenine Nucleotides 79 6.5.2 Metabolism of Guanine Nucleotides 80 6.6 In Situ Metabolism of Purine Nucleosides and Bases 80 6.6.1 Metabolism of Adenine and Adenosine 82 6.6.2 Metabolism of Guanine and Guanosine 83 6.6.3 Metabolism of Hypoxanthine and Inosine 84 6.6.4 Metabolism of Xanthine and Xanthosine 84 6.6.5 Metabolism of Deoxyadenosine and Deoxyguanosine 85 6.7 Summary 88 References 89 7 Degradation of Purine Nucleotides 95 7.1 Introduction 95 7.2 (S)-Allantoin Biosynthesis from Xanthine 97 7.2.1 Xanthine Dehydrogenase 99 7.2.2 Urate Oxidase 100 7.2.3 Allantoin Synthase 101 7.3 Catabolism of (S)-Allantoin 101 7.3.1 Allantoinase 103 7.3.2 Allantoate Amidohydrolase 104 7.3.3 (S)-Ureidoglycine Aminohydrolase 104 7.3.4 Allantoate Amidinohydrolase 105 7.3.5 Ureidoglycolate Amidohydrolase 105 7.3.6 (S)-Ureidoglycolate-urea Lyase 105 7.3.7 Urease 105 7.4 Purine Nucleotide Catabolism in Plants 106 7.5 Accumulation and Utilization of Ureides in Plants 107 7.5.1 Ureides in Plant Tissues and Xylem Sap 107 7.5.2 Role of Ureides in Nitrogen Storage and Transport 109 7.5.3 Role of Ureides in Germination and Development of Seeds 109 7.5.4 Ureide Formation in Nodules of Tropical Legumes 110 7.5.5 Other Role of Ureides in Plants 110 7.6 Summary 111 References 111 Part III Pyrimidine Nucleotide Metabolism 117 8 Pyrimidine Nucleotide Biosynthesis De Novo 119 8.1 Introduction 119 8.2 Reactions and Enzymes of the De Novo Biosynthesis 121 8.2.1 Synthesis of Carbamoyl-phosphate 121 8.2.2 Formation of Carbamoyl-aspartate 123 8.2.3 Formation of Dihydroorotase from Carbamoyl-aspartate 123 8.2.4 Formation of Orotate from Dihydroorotate 124 8.2.5 Synthesis of UMP from Orotate 125 8.2.6 Synthesis of CTP from UTP 126 8.3 Control Mechanism of De Novo Pyrimidine Ribonucleotide Biosynthesis 127 8.3.1 Fine Control of the De Novo Pathway 127 8.3.2 Coarse Control of the De Novo Pathway 129 8.4 Biosynthesis of Thymidine Nucleotide 129 8.4.1 Formation of dUMP 129 8.4.2 Conversion of UMP to dUMP via dUTP 130 8.4.3 Conversion of dUMP to dTMP 130 8.4.4 Thymidine Monophosphate Kinase 131 8.5 Summary 131 References 131 9 Salvage Pathways of Pyrimidine Nucleotide Biosynthesis 137 9.1 Introduction 137 9.2 Characteristics of Pyrimidine Salvage in Plants 137 9.3 Enzymes of Pyrimidine Salvage 139 9.3.1 Uracil Phosphoribosyl Transferase 140 9.3.2 Uridine/Cytidine Kinase 142 9.3.3 Thymidine Kinase 143 9.3.4 Deoxyribonucleoside Kinase 144 9.3.5 Nucleoside Phosphotransferase 144 9.4 Role of Pyrimidine Salvage in Plants 145 9.5 Summary 146 References 146 10 Interconversion of Pyrimidine Nucleotides 149 10.1 Introduction 149 10.2 Deaminase Reactions 149 10.2.1 Cytidine Deaminase 149 10.2.2 Cytosine Deaminase 152 10.2.3 Deoxycytidylate Deaminase 152 10.3 Nucleosidase and Phosphorylase Reactions 152 10.3.1 Uridine Nucleosidase 152 10.3.2 Thymidine Phosphorylase 153 10.4 In Situ Metabolism of 14C-Labelled Pyrimidines 153 10.4.1 Metabolic Fate of Orotate 154 10.4.2 Metabolic Fate of Uridine and Uracil 154 10.4.3 Metabolic Fate of Cytidine and Cytosine 156 10.4.4 Metabolic Fate of Deoxycytidine 157 10.4.5 Metabolic Fate of Thymidine 158 10.5 Summary 159 References 160 11 Degradation of Pyrimidine Nucleotides 165 11.1 Introduction 165 11.2 Enzymes Involved in the Degradation Routes of Pyrimidines 166 11.2.1 Dihydropyrimidine Dehydrogenase 167 11.2.2 Dihydropyrimidinase 167 11.2.3 𝛽-Ureidopropionase 168 11.3 The Metabolic Fate of Uracil and Thymine 168 11.4 Summary 169 References 170 Part IV Physiological Aspects of Nucleotide Metabolism 173 12 Growth and Development 175 12.1 Introduction 175 12.2 Embryo Maturation 175 12.3 Germination 180 12.3.1 Purine Metabolism in Germination 180 12.3.2 Pyrimidine Metabolism in Germination 183 12.4 Organogenesis 185 12.5 Breaking Bud Dormancy 186 12.6 Fruit Ripening 186 12.7 Storage Organ Development and Sprouting 186 12.8 Suspension-Cultured Cells 187 12.8.1 Nucleotide Pools 187 12.8.2 Nucleotide Biosynthesis 188 12.8.3 Nucleotide Availability 188 12.9 Molecular Studies 189 12.10 Summary 189 References 189 13 Environmental Factors and Nucleotide Metabolism 195 13.1 Introduction 195 13.2 Effect of Phosphate on Nucleotide Metabolism 195 13.3 Effect of Salts on Nucleotide Metabolism 199 13.4 Effect of Water Stress 202 13.5 Effect of Wound Stress 202 13.6 Effect of Iron Deficiency 205 13.7 Effect of Light 206 13.8 Summary 206 References 206 Part V Purine Alkaloids 211 14 Occurrence of Purine Alkaloids 213 14.1 Introduction 213 14.2 Chemical Structure of Purine Alkaloids 213 14.3 Occurrence of Purine Alkaloids in Plants 215 14.3.1 Purine Alkaloids in Tea and Related Species 215 14.3.2 Purine Alkaloids in Coffee and Related Species 218 14.3.3 Purine Alkaloids in Maté 220 14.3.4 Purine Alkaloids in Cacao and Related Species 221 14.3.5 Purine Alkaloids in Cola Species 223 14.3.6 Purine Alkaloids in Guaraná and Related Species 223 14.3.7 Purine Alkaloids in Citrus Species 224 14.3.8 Purine Alkaloids in Other Plants 225 14.4 Summary 226 References 226 15 Biosynthesis of Purine Alkaloids 231 15.1 Introduction 231 15.2 A Brief History of Caffeine Biosynthesis Research 231 15.3 Caffeine Biosynthesis Pathway 234 15.3.1 N-Methyltransferase Nomenclature 236 15.3.2 Formation of 7-Methylxanthine from Xanthosine 236 15.3.3 7-Methylxanthosine Synthase 237 15.3.4 N-Methylnucleosidase 240 15.3.5 Formation of Caffeine from 7-Methylxanthine 241 15.3.6 Caffeine Synthase 241 15.3.7 Theobromine Synthase 244 15.4 Genes and Proteins of Caffeine Synthase Family 245 15.5 Xanthosine Biosynthesis from Purine Nucleotides 249 15.5.1 De Novo Purine Route 249 15.5.2 Adenosine Monophosphate Route 251 15.5.3 S-Adenosyl-L-methionine Cycle Route 251 15.5.4 Nicotinamide Adenine Diphosphate Catabolism Route 252 15.5.5 Guanosine Monophosphate Route 253 15.6 Summary 253 References 253 16 Physiological and Ecological Aspects of Purine Alkaloid Biosynthesis 259 16.1 Introduction 259 16.2 Physiology of Caffeine Biosynthesis 259 16.2.1 Purine Alkaloid Biosynthesis in Different Species 261 16.2.2 Camellia 261 16.2.3 Coffea 264 16.2.4 Theobroma 264 16.2.5 Maté 266 16.2.6 Guaraná 267 16.2.7 Citrus 268 16.3 Subcellular Localization of Caffeine Biosynthesis 268 16.3.1 Caffeine Synthase 268 16.3.2 The De Novo Route Enzymes 269 16.3.3 The AMP Route Enzymes 270 16.3.4 The SAM Route Enzymes 270 16.3.5 Subcellular Localization and Transport of Intermediates 270 16.4 Regulation of Caffeine Biosynthesis 270 16.5 Ecological Roles of Caffeine 271 16.5.1 Allelopathic Function Theory 271 16.5.2 Effect of Caffeine on Plant Growth 272 16.5.3 Allelopathy in Natural Ecosystems 273 16.5.4 Chemical DefenceTheory 274 16.6 Summary 274 References 275 17 Metabolism of Purine Alkaloids and Biotechnology 281 17.1 Introduction 281 17.2 Metabolism of Purine Alkaloids 281 17.2.1 Methylurate Biosynthesis 281 17.2.2 The Major Pathway of Caffeine Degradation 282 17.2.3 Purine Catabolic Pathways in Alkaloid Plants 284 17.3 Diversity of Purine Alkaloid Metabolism in Plants 285 17.3.1 Coffea Species 285 17.3.2 Camellia Species 286 17.3.3 Maté Species 290 17.3.4 Cacao Species 290 17.3.5 Other Plant Species 290 17.3.6 Bacteria 291 17.4 Biotechnology of Purine Alkaloids 293 17.4.1 Decaffeinated Coffee Plants 293 17.4.2 Decaffeinated Tea Plants 294 17.5 Caffeine-Producing Transgenic Plants 295 17.5.1 Antiherbivore Activity 295 17.5.2 Antipathogen Activity 296 17.6 Summary 298 References 298 Part VI Pyridine Nucleotide Metabolism 301 18 Pyridine (Nicotinamide Adenine) Nucleotide Biosynthesis De Novo 303 18.1 Introduction 303 18.2 Two Distinct Pathways of De Novo Nicotinate Mononucleotide Biosynthesis 303 18.3 The Outline of the De Novo Pathway of NAD Biosynthesis in Plants 304 18.4 Enzymes Involved in De Novo NAD Synthesis in Plants 307 18.4.1 l-Aspartate Oxidase and Quinolinate Synthase 308 18.4.2 Quinolinate Phosphoribosyltransferase 309 18.4.3 Nicotinate Mononucleotide Adenylyltransferase 309 18.4.4 NAD Synthetase 310 18.4.5 NAD Kinase 310 18.5 Summary 310 References 310 19 Pyridine Nucleotide Cycle 315 19.1 Introduction 315 19.2 Pyridine Nucleotide Cycle 315 19.2.1 Major Pyridine Nucleotide Cycles in Plants 317 19.2.2 Alternative Pyridine Nucleotide Cycles in Plants 318 19.2.3 Rate-Limiting Step of the Pyridine Cycle 319 19.3 Catabolism of NAD 320 19.3.1 Reactions from NAD to Nicotinate 320 19.3.2 Degradation of Pyrimidine Ring 320 19.3.3 Nicotinate Conversion to Nicotinate-N-Glucoside and N-Methylnicotinate 321 19.4 Enzymes Involved in NAD Catabolism 321 19.4.1 Direct NAD Cleavage Enzymes 321 19.4.2 NAD Pyrophosphatase 321 19.4.3 5′-Nucleotidase and Nicotinamide Riboside Nucleosidase 322 19.4.4 Nicotinamidase and Nicotinamide Riboside Deaminase 322 19.5 Salvage of Nicotinamide and Nicotinate 323 19.5.1 Nicotinate Phosphoribosyltransferase 323 19.5.2 Nicotinate Riboside Kinase 324 19.6 Summary 325 References 325 Part VII Pyridine Alkaloids 329 20 Occurrence and Biosynthesis of Pyridine Alkaloids 331 20.1 Introduction 331 20.2 Occurrence of Pyridine Alkaloids 333 20.2.1 Trigonelline in Plants 333 20.2.2 Other Pyridine Alkaloids in Plants 334 20.3 Biosynthesis of Pyridine Alkaloids 335 20.3.1 Trigonelline Biosynthesis 335 20.3.2 Nicotinate N-Glucoside Biosynthesis 336 20.3.3 The Diversity of Biosynthetic Reactions 337 20.3.3.1 Ferns 338 20.3.3.2 Gymnosperms 338 20.3.3.3 Angiosperms 339 20.3.3.4 Nicotinate Conjugate Formation 340 20.3.4 Biosynthesis of Ricinine 341 20.3.5 Biosynthesis of Nicotine (Pyridine Ring) 343 20.4 Summary 345 References 345 21 Physiological Aspect and Biotechnology of Trigonelline 351 21.1 Introduction 351 21.2 Physiological Aspect of Trigonelline Biosynthesis 351 21.2.1 Coffee 351 21.2.2 Leguminous Plants 354 21.3 Physiological Aspect of Nicotinate N-Glucoside Biosynthesis 356 21.4 The Role of Trigonelline in Plants 356 21.4.1 Role of Trigonelline as a Nutrient Source 357 21.4.2 Role of Trigonelline as a Compatible Solute 357 21.4.3 Trigonelline and Nyctinasty 358 21.4.4 Cell Cycle Regulation 358 21.4.5 Detoxification of Nicotinate 359 21.4.6 Signal Transduction 360 21.4.7 Role of Host Selection by Herbivores 360 21.5 Biotechnology of Trigonelline 360 21.6 Summary 362 References 363 Part VIII Other Nucleotide-Related Metabolites 367 22 Sugar Nucleotides 369 22.1 Introduction 369 22.2 The Sugar Nucleotide Moiety 370 22.3 Enzymes of Sugar Nucleotide Biosynthesis 371 22.3.1 UDP-Glucose Pyrophosphorylase 371 22.3.2 UDP-Sugar Pyrophosphorylase 374 22.3.3 Sucrose Synthase 376 22.4 Localization of UDP-Glucose-Producing Enzymes 377 22.5 UDP-Glucose-Interconversion 377 22.6 Other Metabolites 379 22.6.1 Cyclic Nucleotides 379 22.6.2 Diadenosine Tetraphosphate 381 22.6.3 Purine Alkaloid Glucosides 382 22.7 Summary 382 References 382 23 Cytokinins 387 23.1 Introduction 387 23.2 Adenosine Phosphate-Isopentenyl Formation 388 23.3 trans-Zeatin Phosphate Synthesis 389 23.4 Formation of Cytokinin Bases 389 23.5 Effect of Nucleotide Enzymes in Cytokinins 390 23.5.1 Cytokinin Inactivation by Adenine Phosphoribosyltransferase 390 23.5.2 Homeostasis of Cytokinin by Adenosine Kinase 392 23.5.3 Endodormancy of Potato and Purine Nucleoside Phosphorylase 392 23.6 New Purine-Related Plant Growth Regulators 392 23.7 Summary 393 References 394 Part IX Dietary Plant Alkaloids, Their Bioavailability, and Potential Impact on Human Health 397 24 Bioavailability and Potential Impact on Human Health of Caffeine, Theobromine, and Trigonelline 399 24.1 Caffeine 399 24.1.1 Dietary Caffeine 399 24.1.2 Bioavailability and Bioactivity of Caffeine 400 24.2 Theobromine 404 24.2.1 Interactions with Flavan-3-ols 404 24.2.2 Toxicity ofTheobromine 406 24.3 Trigonelline 406 24.3.1 Dietary Trigonelline 406 24.3.2 Bioavailability and Bioactivity of Trigonelline 407 24.4 Summary 409 References 409 Index 415

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Book SynopsisFOREST ECOLOGY Authoritative resource covering traditional plant ecology topics and contemporary components such as climate change, invasive species, ecosystem services, and more Forest Ecology provides comprehensive coverage of the field, focusing on traditional plant ecology topics of tree structure and growth, regeneration, effects of light and temperature on tree physiology, forest communities, succession, and diversity. The work also reviews abiotic factors of light, temperature, physiography (landforms and topography), soil, and disturbance (especially fire), and provides coverage of ecosystem-level topics including carbon storage and balance, nutrient cycling, and forest ecosystem productivity. The 5th edition of Forest Ecology retains the readability and accessibility of the previous editions and includes important additional topical material that has surfaced in the field. All topics are approached with a landscape ecosystemTable of ContentsPreface xxiii PART 1 Forest Ecology and Landscape Ecosystems 1 Concepts of Forest Ecology 3 2 Landscape Ecosystems at Multiple Scales 15 PART 2 The Forest Tree 3 Forest Tree Variation 35 4 Regeneration Ecology 69 5 Tree Structure and Growth 95 PART 3 The Physical Environment 6 Light 123 7 Temperature 143 8 Physiography 167 9 Soil 195 10 Fire 219 11 Site Quality and Ecosystem Evaluation and Classification 237 PART 4 Forest Communities 12 Animals in Forest Ecosystems 269 13 Forest Communities 291 14 Diversity in Forests 327 PART 5 Forest Ecosystem Dynamics 15 Long-Term Forest Ecosystem and Vegetation Change 367 16 Disturbance 381 17 Forest Succession 413 18 Carbon Balance of Trees and Ecosystems 449 19 Nutrient Cycling 487 PART 6 Forests of the Future 20 Climate Change and Forest Ecosystems 537 21 Invasive Species in Forest Ecosystems 587 22 Forest Landscape Ecology 611 23 Sustainability of Forest Ecosystems 639 References 651 Scientific Names of Trees and Shrubs 731 Index 739

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Book SynopsisTable of ContentsPreface xiii Acknowledgements xv 1 Introduction 1 Lessons from the Past 1 Ecological versus Historical Biogeography, and Plants versus Animals 4 Biogeography and Creation 5 The Distribution of Life Today 7 Evolution – a Flawed and Dangerous Idea! 8 Enter Darwin – and Wallace 10 World Maps – the Biogeographical Regions of Plants and Animals 13 Getting Around the World 15 The Origins of Modern Historical Biogeography 20 The Development of Ecological Biogeography 23 Living Together 24 Marine Biogeography 27 Island Biogeography 28 Biogeography Today 30 Section I: The Challenge of Existing 37 2 Patterns of Distribution: Finding a Home 39 Limits of Distribution 42 The Niche 44 Overcoming the Barriers 45 Climatic Limits: The Palms 46 A Successful Family: The Daisies (Asteraceae) 48 Patterns Among Plovers 51 Magnolias: Evolutionary Relicts 55 The Strange Case of the Testate Amoeba 57 Climatic Relicts 58 Topographical Limits and Endemism 65 Physical Limits 67 Species Interactions: A Case of the Blues 73 Competition 75 Reducing Competition 76 Predators and Prey, Parasites and Hosts 79 Migration 83 Invasion 85 3 Communities and Ecosystems: Living Together 97 The Community 97 The Ecosystem 100 Ecosystems and Species Diversity 103 Biotic Assemblages on a Global Scale 108 Mountain Biomes 112 Global Patterns of Climate 116 Climate Diagrams 119 Modelling Biomes and Climate 122 4 Patterns of Biodiversity 127 Measuring Biodiversity: How Many Species are There? 128 Latitudinal Gradients of Diversity 132 Is Evolution Faster in the Tropics? 139 The Legacy of Glaciation 141 Latitude and Species Ranges 142 Diversity and Altitude 143 Biodiversity Hotspots 146 Diversity in Space and Time 148 The Intermediate Disturbance Hypothesis 151 Dynamic Biodiversity and Neutral Theory 151 Section II: The Engines of The Planet 157 5 Plate Tectonics 159 The Evidence for Plate Tectonics 159 Changing Patterns of Continents 164 How Plate Tectonics Changes the World 164 Islands and Plate Tectonics 172 Terranes 174 6 Evolution, the Source of Novelty 179 The Origin of Novelty 179 From Populations to Species 180 Sympatry versus Allopatry 183 Defining the Species 188 Microevolution versus Macroevolution 189 Adaptive Radiations 189 Naming and Cataloguing the Living World 189 Charting the Course of Evolution 190 Morphology Gives Way to Molecules 193 Darwin’s Finches Updated 194 Section III: Islands and Oceans 197 7 Life, Death and Evolution on Islands 199 Types of Island 200 Getting There: The Challenges of Arriving 200 Dying There: The Problems of Survival 202 Adapting and Evolving 203 The Hawaiian Islands 206 Integrating the Data: The Theory of Island Biogeography 214 Modifying the Theory 216 The General Dynamic Model for Oceanic Island Biogeography 219 Nestedness 221 Living Together: Incidence and Assembly Rules 221 Building an Ecosystem: The History of Rakata 223 8 Patterns in the Oceans 235 Zones in the Ocean and on the Sea Floor 237 Basic Biogeography of the Seas 240 The Open‐Sea Environment 240 The Ocean Floor 246 The Shallow‐Sea Environment 250 And Finally … Marine Biogeographical Realms of the World 263 Section IV: Historical Biogeography 269 9 From Evolution to Patterns of Life 271 Studying the Patterns 272 Methods of Analyzing the Patterns 273 Studying Organisms and their Molecules 287 An Integrative Approach to Historical Biogeography 290 Investigating the More Distant Past 292 10 Geography, Life and Climates Through Time 299 Introduction 299 Early Land Life on the Moving Continents 300 Animal Life Through the Mesozoic 304 The End of the Mesozoic World 308 Climates and Plants Through Time 309 Reconstructing Plant Life and Biomes 310 Evolution of the Mammals 318 The Mesozoic Roots of the Radiation of Modern Mammals 320 11 Patterns of Life Today 327 The Biogeographical Regions Today 327 The History of Today’s Biogeographical Regions 334 The Old World Tropics: Africa, India and Southeast Asia 334 Australia 342 New Caledonia 345 New Zealand 346 The West Indies 348 South America 351 The Northern Hemisphere: Holarctic Mammals and Boreal Plants 359 12 The Arrival of the Ice Ages 367 Climatic Wiggles 368 Interglacials and Interstadials 369 Biological Changes in the Pleistocene 371 The Last Glacial 375 Causes of Glaciation 382 The Current Interglacial: A False Start 388 Forests on the Move 390 The Dry Lands 393 Changing Sea Levels 396 A Time of Warmth 398 Climatic Cooling 399 Recorded History 400 Atmosphere and Oceans: Short‐Term Climate Change 402 The Future 403 Section V: People and Problems 409 13 The Human Intrusion 411 The Emergence of Humans 411 Modern Humans and the Megafaunal Extinctions 420 Plant Domestication and Agriculture 423 Animal Domestication 428 The Diversification of Homo sapiens 430 The Biogeography of Human Parasitic Diseases 431 The Environmental Impact of Early Human Cultures 434 14 Conservation Biogeography 439 Welcome to the Anthropocene 439 The Sixth Mass Extinction? 440 Less, and Less Interesting 444 What’s Behind the Biodiversity Crisis? 445 Crisis Management: Responding to Biodiversity Loss 451 The Birth of Conservation Biogeography 452 The Scope of Conservation Biogeography 453 Conservation Biogeography in Action 459 The Future is Digital 462 Conclusions 463 Glossary 471 Index 481 Colour plates between pages 240 and 241

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Book SynopsisThe most up-to-date reference on phytomicrobiomes available today The Plant Microbiome in Sustainable Agriculture combines the most relevant and timely information available today in the fields of nutrient and food security. With a particular emphasis on current research progress and perspectives of future development in the area, The Plant Microbiome in Sustainable Agriculture is an invaluable reference for students and researchers in the field, as well as those with an interest in microbiome research and development. The book covers both terrestrial and crop associated microbiomes, unveiling the biological, biotechnological and technical aspects of research. Topics discussed include: Developing model plant microbiome systems for various agriculturally important cropsDefining core microbiomes and metagenomes in these model systemsDefining synthetic microbiomes for a sustainable increase in food production and quality The Plant Microbiome in Sustainable Agriculture is written to allTable of ContentsPreface vii List of Contributors ix About the Editors xiii 1 Plant Microbiome: Past, Present and Future 1Akhilendra Pratap Bharati, Ashutosh Kumar, Sunita Kumari, Anjney Sharma, Prem Lal Kashyap, Sudheer Kumar, Madhumita Srivastava, and Alok Kumar Srivastava 2 The Plant Microbiome in Agricultural Sustainability: From Microbe to Microbiome 31Jose Pedro Fonseca, Yuan Wang, and Kirankumar S. Mysore 3 Seed Microbiome and Its Implication in Plant Growth Promotion and Health 47Padmavathi Tallapragada and Usha Seshachla 4 Microbiome: The Holobiont, Its Application and Effect on the Plant System 65Pragati Sahai and Vimlendu Bhushan Sinha 5 Ecology of the Diazotrophic Microbiome 81Preeti Singh, Rahul Kunwar Singh, Dhananjay Kumar, and Shree Prakash Tiwari 6 Functional Microbiome for Crop Improvement Under a Changing Environment 101Abbaci Hocine, Bensidhoum Leila, Houali Karim, and Nabti Elhafid 7 Functional Importance of the Phyllosphere Microbiome and Its Implications in Agriculture 119Parasuraman Paramanantham, Subhaswaraj Pattnaik, and Siddhardha Busi 8 Microbial Consortia: Emerging Conglomerate for Better and Superior Sustainable Agricultural Practices 141Rishi Kumar Verma, Manisha Sachan, and Shivesh Sharma 9 Rhizomicrobiome for Sustainable Crop Growth and Health Management 157Tualar Simarmata, Mieke R. Setiawati, Betty N. Fitriatin, and Diyan Herdiyantoro 10 Mycorrhizal Microbiome: An Ideal Association in Sustainable Agriculture 195Baby Summuna, Sachin Gupta, and Moni Gupta 11 Microbiome-Driven Nutrient Fortification in Plants: The Role of Microbiota in Chemical Transformation and Nutrient Mobilization 211Irina Sidorova and Elena Voronina 12 Engineering Microbes to Improve Crop Health: A New Dimension for Sustainable Agricultural Productivity 231P. Veera Bramhachari, A.M.V.N. Prathyusha, and Ganugula Mohana Sheela 13 Biotechnology of Plant-Associated Microbiomes 243Son Truong Dinh, Van T. Luu, Long Hoa Hoang, Xuan Canh Nguyen, and Cuong Tu Ho 14 Microbiome Genomics and Functional Traits for Agricultural Sustainability 279Amy Novinscak, Antoine Zboralski, Roxane Roquigny, and Martin Filion Index 299

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Book SynopsisExplores the use of conventional and novel technologies to enhance fermentation processes Fermentation Processes reviews the application of both conventional and emerging technologies for enhancing fermentation conditions, examining the principles and mechanisms of fermentation processes, the microorganisms used in bioprocesses, their implementation in industrial fermentation, and more. Designed for scientists and industry professionals alike, this authoritative and up-to-date volume describes how non-conventional technologies can be used to increase accessibly and bioavailability of substrates by microorganisms during fermentation, which in turn promotes microbial?growth and?can improve processes and?productivity across the agri-food, nutraceutical, pharmaceutical, and beverage industries. The text begins by covering the conventional fermentation process, discussing cell division and growth kinetics, current technologies and developments in industrial fermentatTable of ContentsChapter 1. Introduction to conventional fermentation processes 1. 1. Bioprocesses 1.1.1. Production of microbial biomass 1.1.2. Production of microbial metabolites 1.1.3. Production of microbial enzymes 1.1.4. Production of recombinant proteins 1.1.5. Production of microbial plasmids 1.1.6. Bioconversion 1.2. Energetic metabolism 1.2.1. Energy transfer and redox reactions 1.2.2. Aerobic respiration 1.2.3. Anaerobic respiration 1.2.4. Fermentation 1.3. Microorganisms used in fermentation processes 1.3.1. Bacteria 1.3.2. Fungi 1.4. Fermentation technology 1.5. Conclusions 1.6. References Chapter 2. Current developments in industrial fermentation processes 2.1. Introduction 2.2. Main achievements in industrial fermentation 2.2.1. Fermentation processes in food industry 2.2.1.1. Alcoholic beverages 2.2.1.2. Enzymes 2.2.2. Fermentation processes in chemical industry 2.2.2.1. Biofuels 2.2.2.2. Organic acids 2.2.2.3. Triacylglycerols and Polyhydroxyalkanoates 2.2.2.4. Syngas fermentation 2.2.3. Fermentation processes in the pharmaceutical industry 2.2.3.1. Drugs 2.2.3.2. Recombinant proteins 2.3. Current developments in industrial fermentation 2.3.1. Microorganisms 2.3.2. Fermentation Media 2.3.2.1. Types of media sources 2.3.3. Fermentation systems 2.3.3.1. Solid-state fermentation bioreactors 2.3.3.2. Ultrasonic fermentation process 2.3.3.3. Electro fermentation 2.3.4. Fermentation optimization 2.3.5. Fermentation process modeling 2.3.5.1. Mechanistic models 2.3.5.2. Computational fluid dynamics (CFD) 2.3.6. Inhibition of fermentation processes 2.3.6.1. Substrate inhibition 2.3.6.2. pH inhibition 2.3.6.3. Inhibition by un-dissociated acids 2.3.6.4. Temperature inhibition 2.3.6.5. Nitrogen inhibition 2.3.6.6. Inhibition by phosphate 2.3.6.7. Inhibition by sulfide 2.3.6.8. Inhibition by lactic acid bacteria 2.3.6.9. Inhibition by metals 2.3.6.10. Inhibition by phenolic and furanic mixtures 2.4. Conclusions 2.5. References Chapter 3. Culture condition changes for enhancing fermentation processes 3.1. Introduction 3.1.1. Fermentation 3.2. Culture media used for fermentation 3.2.1. The culture media purpose 3.2.2. Media types 3.2.3. Culture media: a quantitative approach 3.2.4. Culture media: a compositional approach 3.2.4.1. Water 3.2.4.2. Energy sources 3.2.4.3. Carbon sources 3.2.4.4. Examples of commonly used carbon sources 3.2.4.5. Nitrogen sources 3.2.4.6. Minerals 3.2.4.7. Chelators 3.2.4.8. Growth factors 3.2.4.9. Buffers 3.2.4.10. Precursors and metabolic regulators to media 3.2.4.11. Precursors and inhibitors 3.2.5. Impact of culture conditions on fermentation processes 3.2.5.1. The temperature 3.2.5.2. The pH 3.2.5.3. The cell concentration 3.2.5.4. The carbon dioxide 3.2.5.5. The ethanol 3.3.1. Pasteur effect 3.3.2. Crabtree effect 3.3.3. Custer effect 3.3.4 Oxygen requirements 3.4. Conclusions 3.5. References Chapter 4. Emerging technologies and their mechanism of action on fermentation 4.1. Introduction 4.2. High hydrostatic pressure (HHP) processing 4.3. Ultrasound (US) 4.4. Pulsed Electric Fields 4.5. Microwaves (MV) 4.6. Conclusions 4.7. References Chapter 5. Biomass fractionation using emerging technologies 5.1. Introduction 5.2. Ultrasound application for biomass fractionation 5.3. Microwave application for biomass fractionation 5.4. Pulsed-electric fields application for biomass fractionation 5.5. Enzyme-assisted fractionation of biomass 5.6. Supercritical fluid fractionation of biomass 5.7. Conclusions 5.8. References Chapter 6. Enhancing microbial growth using emerging technologies 6.1. Introduction 6.2. Microbial stimulation using electric fields 6.3. Microbial stimulation using ultrasounds 6.4. Microbial stimulation using high pressure 6.5. Conclusions 6.6. References

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Book SynopsisWritten and edited by some of the most well-respected authors in the area of the adaptation of plants and animals to climate change, this groundbreaking new work is an extremely important scientific contribution to the study of global warming. Global climate change is one of the most serious and pressing issues facing our planet. Rather than a silver bullet or a single study that solves it, the study of global climate change is like a beach, with each contribution a grain of sand, gathered together as a whole to create a big picture, moving the science forward. This new groundbreaking study focuses on the adaptation and tolerance of plants and animal life to the harsh conditions brought on by climate change or global warming. Using the papers collected here, scientists can better understand global climate change, its causes, results, and, ultimately, the future of life on our planet. The first section lays out a methodology and conceptual direction of the work aTable of ContentsPreface xvii Abstract xix Contributing Authors xxi Modeling and Approaches 1 1 Critical Impacts on Complex Biological and Ecological Systems: Basic Principles of Modeling 3Rem G. Khlebopros, Vladislav G. Soukhovolsky 1.1 Complex Ecological Systems: The Principle of Decomposition, Taking into Account the Characteristic Times of Components 5 1.2 Analysis of Critical Impacts on Complex Systems and Extreme Principles of Modeling 12 1.2.1 Meta-Models of Phase Transitions for Describing Critical Events in Complex Systems 13 1.2.2 A Model of Outbreak as Second-Order Phase Transition 14 1.2.3 The Effect of Modifying Factors on the Development of an Outbreak 21 1.2.4 The Impact of Chemical Compounds on Biological Objects 23 References 26 2 Criticality Concept and Some Principles for Sustainability in Closed Biological Systems and Biospheres 29Nicholas P. Yensen, Karl Y. Biel 2.1 Introduction 31 2.2 History of Manmade Closed Ecosystems 32 2.3 Classification of Closed Biological Systems 33 2.3.1 Terminology 33 2.3.2 Micro Systems 35 2.3.3 Macro Systems 37 2.3.4 The Term Biosphere 39 2.3.5 Noosphere 40 2.4 The Concept of Criticality 40 2.4.1 The Volume-Criticality Principle 42 2.5 Microbiospheres: Descriptions and Discussion 44 2.5.1 The Ecosphere, a Synthetic Microbiosphere 44 2.6 Bioboxes 45 2.7 Experimental vs. Mathematical Models 45 2.7.1 Retrograde Phylogenetic Extinction 46 2.8 Humanospheres: Examples and Discussion 46 2.8.1 Biotubes 47 2.8.2 Shepelev, BIOS 1, 2, and 3 49 2.8.3 Biosphere 2 Laboratory 51 2.8.4 Closed System Missions 52 2.8.5 Open System Missions 53 2.8.6 The End of Biosphere 2 Laboratory or a New Era for Biosphere 2 Laboratory? 54 2.9 The Earth (Biosphere 1) Description and Discussion 55 2.9.1 Earth, a Sample Size of One 55 2.9.2 Biosphere 1 Properties 55 2.10 Oxygen Flux in Closed Systems 59 2.11 The Future of Closed System Work: Concepts and Strategies 61 2.11.1 Education, Research and Consortium Concepts 61 2.11.2 Ecosystems for Space 62 2.11.3 Closed System Challenges 63 2.12 General Conclusions 63 Abbreviations 64 Literature Cited and Used 64 Appendix I. A Description of Biosphere 2 Laboratory 70 3 Accelerated Method for Measuring and Predicting Plants’ Stress Tolerance 73Karl Y. Biel, John N. Nishio 3.1 Introduction 75 3.2 Background 75 3.2.1 Interaction between Anabolism and Catabolism 76 3.2.2 Cooperation between Photosynthesis and Respiration under Stress 78 3.3 How is Stress Tolerance Measured? 79 3.3.1 Testing Possible Artifacts of the Stress Test 81 3.3.2 Effect of Temperature and Chemical Additions on the Oxygen Evolution Stress Assay 84 3.4 Practical Applications 88 3.4.1 Whole Leaf Physiological Responses 90 3.4.2 Effect of Dark and Sodium Nitrate on the Photosynthetic Stress Resistance Index and Photosynthesis in Leaf Slices under Anoxic Conditions 97 3.4.3 Post-Illumination Respiration 98 3.5 Discussion 98 3.6 Perspectives for Application of Method 107 Acknowledgments 109 Abbreviations 110 References 110 Appendix I. Additional Materials and Methods 117 Appendix II. Preliminary Analysis of the Utility of a Novel Stress Resistance Assay on Three Garst Lines of Zea mays, a C4 Plant 118 Results 119 General Conclusion 122 Suggestions 122 Hypotheses 123 4 The Hypotheses of Halosynthesis, Photoprotection, Soil Remediation via Salt-Conduction, and Potential Medical Benefits 125Karl Y. Biel, Nicholas P. Yensen 4.1 Introduction 127 4.2 The Haloconductor Theory 128 4.2.1 The Remediation of Saline Soils 128 4.2.2 New Approach for Soil Remediation via Salt Conducting Plants 130 4.2.3 Advantages of Conductor Plants for Soil Remediation 133 4.2.4 Productivity Considerations 134 4.2.5 Intriguing Productivity Curves in a Clonal Conductor Plant 136 4.3 The Halosynthesis Hypothesis 138 4.3.1 Concept Description and Terminology 139 4.3.2 Hydraulic Considerations and Salt Gradient from Soil to Shoot Surface 140 4.3.3 Salt Glands and Evapotranspirational Halosynthesis 143 4.3.4 The Photoelectric Effect 144 4.3.5 Epidermal Electro-Halosynthesis 144 4.3.6 Salt-Gland Electro-Halosynthesis 144 4.4 Physico- and Bio-Chemical Protection Synergisms 148 4.4.1 Biochemical Protection against Oxygen Radicals 151 4.5 A Case Study, Distichlis 153 4.5.1 Ecophysiology 153 4.5.2 Taxonomy and Geographic Distribution 153 4.5.3 Root-Soil Restructuring Capacity 154 4.5.4 Salt Tolerance 155 4.5.5 Photosynthesis 155 4.5.6 Ammonia Nutrition as a Protector against Salinity 157 4.5.7 Soil Salt Removal and Benefits to Changes in Soil Properties 158 4.6 Potential Medical Benefit of Photo-Halosynthesis 159 4.7 Predictions and Potential Tests of Hypotheses 163 4.7.1 Salt Conduction 163 4.7.2 Halodispersion 165 4.7.3 Metabolism 166 4.7.4 Protection 166 4.7.5 Halosynthesis 166 4.8 General Conclusions 167 Acknowledgments 167 References 167 5 Protective Role of Silicon in Living Organisms 175Vladimir V. Matichenkov, Irina R. Fomina, Karl Y. Biel 5.1 Introduction 176 5.1.1 Agriculture 176 5.1.2 Medicine 177 5.1.3 Microorganisms and Plants 177 5.2 Forms of Silicon 179 5.3 Silicon Cycle in Soil–Plant System 182 5.4 Silicon and Flora 183 5.4.1 Localization of Silicon in Plants 184 5.4.2 Forms of Silicon in Plants 187 5.4.3 Silicon and Water Storage in Plants 188 5.5 Silicon and Plants’ Resistance to Extreme Environments 189 5.6 Silicon as Matrix for Organic Compounds Synthesis 191 5.6.1 Hypothesis on Silicon Participation in Protection of Living Organisms under Stress Conditions 192 5.6.1.1 Premises of Hypothesis 192 5.6.1.2 Hypothesis 195 5.7 New Technologies 197 5.8 General Conclusion 198 Acknowledgments 199 References 199 6 Methanol as Example of Volatile Mediators Providing Plants’ Stress Tolerance 209Karl Y. Biel, Irina R. Fomina 6.1 Introduction 211 6.2 Methanol Application for the Regulation of Productivity 212 6.3 Emission of Methanol from Plants 213 6.3.1 Factors Affecting the Methanol Emission 214 6.3.2 Methanol Sources in Plants 216 6.3.3 Pectin Methylesterases 216 6.3.4 Utilization of Methanol by Plants 218 6.3.5 Ethanol-Water-Soluble Fraction in Different Parts of Plants 219 6.3.6 Ethanol-Water-Insoluble Fractions in Plants 222 6.3.7 DNA Methylation in Plants 223 6.4 Hypothesis of Methanol Influence on Different Levels of Cell Metabolism in C3 Plants 226 6.5 Conclusion 231 Acknowledgments 231 Abbreviations 232 References 232 Experiments 249 7 Patterns of Carbon Metabolism within Leaves 251Karl Y. Biel, Irina R. Fomina, Galina N. Nazarova, Vladislav G. Soukhovolsky, Rem G. Khlebopros, John N. Nishio 7.1 Introduction 253 7.2 Interactions among Light, Leaf Anatomy, the Metabolic Activity, and Environmental Stress Tolerance across Leaves 253 7.2.1 Anatomy and Pattern of Enzymes within the Leaf of Spinacia oleracea 255 7.2.1.1 Leaf Anatomy 255 7.2.1.2 What are the Roles of the Different Cells? 259 7.2.2 Enzyme Activity 263 7.2.2.1 How Does Inverting the Leaves Alter the Distribution of Enzyme Activity within Spinacia oleracea Leaf? 263 7.2.2.2 Summary of Enzyme Activity across Leaves 267 7.2.2.3 Functional Significance to Profiles of Enzyme Activity across Spinacia oleracea Leaves 268 7.2.3 CO2/O2 Gas Exchange 271 7.2.3.1 CO2 Gas Exchange 271 7.2.3.2 HCO3 –-Dependent Oxygen Evolution 274 7.2.4 Enzyme Activity, Carbon Metabolism, and Stress Tolerance across Spinacia oleracea Leaves 276 7.2.5 Light Regulation of Photosynthetic Enzyme Activity across Leaves 281 7.3 Model of Optimal Photosynthesis within a Mesophytic Leaf 282 7.4 General Conclusion 287 Acknowledgments 288 References 288 8 4-Hydroxyphenethyl Alcohol and Dihydroquercetin Increase Adaptive Potential of Barley Plants under Soil Flooding Conditions 301Tamara I. Balakhnina 8.1 Introduction 302 8.1.1 Effect of Soil Flooding on Plants 302 8.2 Effect of 4-Hydroxyphenethyl Alcohol on Growth and Adaptive Potential of Barley Plants at Optimal Soil Watering and Flooding 304 8.2.1 Plant Reactions 304 8.2.1.1 Seed Germination 304 8.2.1.2 Plant Growth 305 8.2.1.3 Lipid Peroxidation Intensity 308 8.2.1.4 Guaiacol Peroxidase Activity 309 8.2.1.5 Discussion 311 8.3 Dihydroquercetin Protects Barley Seeds against Mold and Increases Seedling Adaptive Potential Under Soil Flooding 313 8.3.1 Plant Reactions 313 8.3.1.1 Seed Germination 313 8.3.1.2 Growth Parameters 313 8.3.1.3 Intensity of Lipid Peroxidation 316 8.3.1.4 Activity of Ascorbate Peroxidase 318 8.3.1.5 Discussion 320 Acknowledgments 322 Abbreviations 322 References 323 9 Cooperation of Photosynthetic and Nitrogen Metabolisms 329Anatoly A. Ivanov, Anatoly A. Kosobryukhov 9.1 Introduction 331 9.2 Carbon Uptake and Rubisco 332 9.2.1 Dependence of Carbon Assimilation on Nitrogen Supply 334 9.3 Alternative Electron Acceptors in Photosynthesis 336 9.4 Nitrogen Metabolism 337 9.4.1 Primary Assimilation of Inorganic Nitrogen 337 9.4.1.1 Nitrate Reductase 339 9.4.1.2 Ferredoxin-Dependent Nitrite Reductase 342 9.4.1.3 Glutamine Synthetase/Glutamate Synthase (GS/GOGAT) Cycle 343 9.4.1.4 Glutamate Dehydrogenase 346 9.4.2 Relationship of Photorespiration and Nitrogen Metabolism 346 9.5 Relationship of Carbon and Nitrogen Metabolism in Stress Conditions 349 9.5.1 High CO2 Concentration in the Atmosphere 349 9.5.1.1 Plants’ Growth 349 9.5.1.2 Rubisco Content 350 9.5.1.3 Photosynthetic Acclimation 351 9.5.1.4 Photosynthesis and Nitrogen Content 353 9.5.1.5 Metabolic Changes 355 9.5.2 Low CO2 Concentration in the Atmosphere 360 9.5.3 Water Stress 368 9.5.3.1 Osmotic Homeostasis 368 9.5.3.2 Variability of Plant Response to Drought 369 9.5.3.3 Reactive Oxygen Species 370 9.5.3.4 Metabolic Changes 371 9.5.3.5 Stomata Conductivity and Rubisco Activity 371 9.5.3.6 Enzymes of Nitrogen Metabolism 373 9.5.3.7 Sucrose-Phosphate Synthase 375 9.5.3.8 Increased Plant Resistance to Drought by Nitrogen Supply 376 9.5.4 Salt Stress 377 9.5.4.1 Assimilation of Nitrogen in Salinity Conditions 378 9.5.4.2 Isocitrate Dehydrogenase and Fd-GOGAT 379 9.5.4.3 Proline Accumulation 380 9.5.4.4 Photosynthesis, Photorespiration and Reactive Oxygen Species 380 9.6 Conclusion 381 Abbreviations 382 References 382 10 Physiological Parameters of Fucus vesiculosus and Fucus serratus in the Barents Sea during a Tidal Cycle 439Inna V. Ryzhik, Anatoly A. Kosobryukhov, Evgeniya F. Markovskaya, Mikhail V. Makarov 10.1 Introduction 441 10.2 Materials and Methods 442 10.3 Results 444 10.3.1 Water Content in Algal Thalli 444 10.3.2 The Rate of Photosynthesis 445 10.3.3 Photosynthetic Pigments: Content and Proportion 445 10.3.4 Dependence of the Photosynthetic Rate on the Water Content in the Thallus 446 10.3.5 Potential Rate of Photosynthesis of Fucus vesiculosus 446 10.3.6 Lipid Peroxidation and Catalase Activities in Fucus vesiculosus 448 10.4 Discussion 449 Abbreviations 455 References 455 History and Biography – Tribute 461 11 Benson’s Protocol 463Arthur M. Nonomura, Karl Y. Biel, Irina R. Fomina, Wai-Ki “Frankie” Lam, Daniel P. Brummel, Allison Lauria, Michael S. McBride 11.1 Introduction 465 11.2 Benson–Bassham–Calvin and Lectin Cycles 468 11.3 Types of Photosynthetic Carbon Metabolism in Prokaryotes and Eukaryotes 471 11.4 Regulation of Photosynthates 471 11.5 The Origin and Development of the Carbon Reactions of Photosynthesis 472 11.6 The Next Steps 473 11.6.1 Materials and Methods 474 11.6.2 Results 480 11.6.3 Conclusion 498 11.7 Felicitation 499 References 502 12 Recollection of Yuri S. Karpilov’s Scientific and Social Life 509Karl Y. Biel, Irina R. Fomina 12.1 Introduction 510 12.2 Some Contradictory Discoveries 510 12.3 Official Statement of a Young Scientist in the USSR and His Deed 511 12.4 From the Memories, by Karl Biel 515 12.5 Australian Scientist Professor Barry Osmond Visited Karpilov’s Laboratory in 1971 525 12.6 Moving from Tiraspol to Pushchino, Moscow Region, to the Institute of Photosynthesis of the USSR Academy of Sciences 527 12.7 International Botanical Congress… 530 12.8 And after That, Soon… Unexpected Tragedy 530 12.9 Short Biography of Yuri S. Karpilov 533 Acknowledgments 534 Abbreviations 534 References 534 13 Dr. Nicholas Yensen’s Curriculum Vitae 543Karl Y. Biel, Irina R. Fomina 13.1 Introduction 544 13.2 Biographical Note about Dr. Nicholas Patrick Yensen 545 13.2.1 Education 545 13.2.2 Teaching Experience 545 13.2.3 Founder and Leader of Scientific Organizations 546 13.2.4 Member of Board of Directors, Consultant, and Chairman 546 13.2.5 Languages 547 13.2.6 Oratorical Talent 547 13.2.7 Dr. Yensen’s International Teamwork, Expeditions and Visitations 547 13.2.8 Distinctions 549 13.2.9 Articles, Videos and Documentaries about Dr. Yensen’s Work 549 13.2.10 Skill and Avocation 550 13.3 Conclusion 550 13.4 Addendum 552 Acknowledgements 552 Publications (selected) 553 14 Rem Khlebopros: Life in Science 557Vladislav G. Soukhovolsky, Irina R. Fomina 14.1 Introduction 558 14.2 Life in Science 559 14.3 Selected Scientific Publications and Speeches by Rem G. Khlebopros 566 14.3.1 Video-Interviews about Ecology in Krasnoyarsk 566 14.3.2 Books 566 14.3.3 Articles 567 Acknowledgments 571 Index 573

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Book SynopsisA comprehensive review of stress signaling in plants using genomics and functional genomic approaches Improving agricultural production and meeting the needs of a rapidly growing global population requires crop systems capable of overcoming environmental stresses. Understanding the role of different signaling components in plant stress regulation is vital to developing crops which can withstand abiotic and biotic stresses without loss of crop yield and productivity. Emphasizing genomics and functional genomic approaches, Protein Kinases and Stress Signaling in Plants is a comprehensive review of cutting-edge research on stress perception, signal transduction, and stress response generation. Detailed chapters cover a broad range of topics central to improving agricultural production developing crop systems capable of overcoming environmental stresses to meet the needs of a rapidly growing global population. This book describes the field of protein kinasesTable of ContentsList of Contributors xv Editor Biography xx Preface xxii 1 Two Component Mediated Stress Signaling in Plants: A Comparative Profiling in Monocots and Dicots 1Priyanka Gupta, Chhaya Yadav, Deepti Singh, Ramsong Chantre Nongpiur, Sneh Lata Singla-Pareek, and Ashwani Pareek 2 Lectin Receptor like Kinase: Spy Eye on Environmental Factors 20Nishat Passricha, Shabnam K. Saifi, Himani Negi, and Narendra Tuteja 3 Photoactivated Protein Kinases in Green Algae and Their Functional Role in Abiotic Stress 37Kumari Sushmita, Manish Singh Kaushik, Irina Sizova, and Suneel Kateriya 4 Emerging Role of Plant GSK3/SHAGGY-like Protein Kinases in Stress Signaling Pathways: A Phylogenetic and Functional Genomic Perspective 86Barkha Ravi, Pooja Verma, and Girdhar K. Pandey 5 Balancing Growth and Defense: Role of Target of Rapamycin and SNF1-Related Protein Kinase 1 in Stress Signaling in Plants 105Mohan Sharma, Muhammed Jamsheer K., Harshita B. Saksena, Sunita Jindal, Manvi Sharma, Dhriti Singh, Archna Tiwari, Prakhar Awasthi, and Ashverya Laxmi 6 SnRK2s: Part and Parcel of ABA Signaling in Plants 133Suhas Balasaheb Karle, Bhavya Nair, and Kundan Kumar 7 Lipid Mediated Regulation of Protein Kinases 147Shatakshi Pandit and Girish Mishra 8 Calcium Dependent Protein Kinases in Plants 192Jamshaid Hussain, Gulnaz Bibi, and Sarfraz Shafiq 9 Regulation of Stress Responses in Plants by Calcium Dependent Protein Kinases 226Deepika, Komal Vitthalrao Mali, Amit Kumar, and Amarjeet Singh 10 Calmodulin-Binding Kinases: Transducers of Abiotic Stress Response in Plants 248Supreet Singh, Amardeep Singh Virdi, and Prabhjeet Singh 11 Calcium/Calmodulin Activated Protein Kinases in Stress Signaling in Plants 266Tushar Khare, Amrita Srivastav, and Vinay Kumar 12 Role of CBL-Interacting Protein Kinases in Regulating Plant Stress Responses 281Pavithran Narayanan, Sibaji K. Sanyal, and Girdhar K. Pandey 13 Casein Kinase2 and Its Dynamism in Abiotic Stress Management 310Tanushree Agarwal and Sudipta Ray 14 Cyclin-Dependent Protein Kinases in the Control of Cell Cycle in Plants 347Hirofumi Harashima and Masami Sekine 15 MAP Kinase as Regulators for Stress Responses in Plants: An Overview 369Deepika Sharma, Neetu Verma, Chandana Pandey, Deepanjali Verma, Prakash Kumar Bhagat, Stanzin Noryang, Kirti Singh, Sumaira Tayyeba, Gopal Banerjee, and Alok Krishna Sinha 16 A Network View of MAP Kinase Pathways in Plant Defense Regulation: What We Have Learned from Genetic Modification Studies? 393Tim Xing and Nora A. Foroud 17 Role of MAP Kinase Signaling in Xanthomonas Pathogen-Rice Interaction 408Durga Bhavani and Subhadeep Chatterjee 18 Role of MAPK Cascade in Local and Systemic Immunity of Plants 422Vishal Patil and Ashis Kumar Nandi 19 Role of Plant Kinases in Combined Stress 445Mahesh Patil and Muthappa Senthil-Kumar 20 Protein Tyrosine Phosphorylation in Plants: Role Under Stress Responses 459Swati Mahiwal, Sibaji K. Sanyal, and Girdhar K. Pandey 21 Role of Kinases for Regulating K+ Homeostasis Under Salt and Drought Stress Conditions 479Jayant Kulkarni, Ashish K. Srivastava, and Suprasanna Penna 22 Plant Peroxisomal Protein Kinases Implicated in Stress-Related Responses 501Amr R.A. Kataya, Jianping Hu, Douglas G. Muench, and Greg B. Moorhead Index 518

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Book SynopsisA comprehensive primer and reference, this book provides pharmacists and health practitioners the relevant science and policy concepts behind biologics, biosimilars, and biobetters from a practical and clinical perspective. Explains what pharmacists need to discuss the equivalence, efficacy, safety, and risks of biosimilars with physicians, health practitioners, and patients about Guides regulators on pragmatic approaches to dealing with these drugs in the context of rapidly evolving scientific and clinical evidence Balances scientific information on complex drugs with practical information, such as a checklist for pharmacists Table of ContentsList of Contributors vii Foreword ix Preface xi 1 Innovator Biologics, Biosimilars, and Biobetters: Terminology, Nomenclature, and Definitions 1 2 Approved Biologic Medicines and Biosimilars in Major Regulatory Jurisdictions 17 3 Status of Biologic Drugs in Modern Therapeutics-Targeted Therapies vs. Small Molecule Drugs 31 4 Major Classes of Biotherapeutics 47 5 Drug Targets for Biologics 71 6 Pivotal Biology, Chemistry, Biochemistry, and Biophysical Concepts of Biologics and Biosimilars 89 7 Biosimilarity and Interchangeability of Biologic Drugs-General Principles, Biophysical Tests, and Clinical Requirements to Demonstrate Biosimilarity 109 8 Pharmacokinetics of Biologics 125 9 Pharmacogenomics of Biologics 147 10 International Regulatory Processes and Policies for Innovator Biologics, Biosimilars, and Biobetters 159 11 Pharmacovigilance of Innovator Biologics and Biosimilars 177 12 Pharmacoeconomics of Biologic Medicines and Biosimilars 195 13 New Emerging Biotherapies: Cutting-Edge Research to Experimental Therapies 213 14 Optimizing Use of Biologic Medicines Using a Quality Use of Medicines Approach 237 15 Knowledge Areas and Competency Standards on Biologic Medicines for Pharmacists and Pharmacy Students 253 16 A Checklist for Pharmacists on Biologics and Biosimilars: Tips to Enhance Patient-Centered Discussions 267 Index 295

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Book SynopsisImmerse yourself in the spectacular visuals and dynamic content of Principles of Human Anatomy, 14th Edition. Designed for the 1-term Human Anatomy course, this 14th edition raises the standard for excellence in this discipline with its enhanced illustration program, refined narrative, and dynamic resources. Principles of Human Anatomy offers a rich experience, giving students the ability to learn and explore human anatomy both inside and outside of the classroom.Table of Contents1 AN INTRODUCTION TO THE HUMAN BODY 1 1.1 Anatomy Defined 2 1.2 Levels of Body Organization and Body Systems 3 1.3 Life Processes 9 1.4 Basic Anatomical Terminology 9 Anatomical Position 9 Regional Names 9 Planes and Sections 10 1.5 Body Cavities 14 Thoracic and Abdominal Cavity Membranes 15 1.6 Abdominopelvic Regions and Quadrants 18 1.7 The Human Body and Disease 19 1.8 Aging 20 1.9 Medical Imaging 20 1.10 Measuring the Human Body 23 Chapter Review and Resource Summary 23 / Critical Thinking Questions 25 / Answers to Figure Questions 25 2 CELLS 26 2.1 A Generalized Cell 27 2.2 The Plasma Membrane 28 Structure of the Membrane 28 Functions of Membrane Proteins 29 Membrane Permeability 29 Transport Across the Plasma Membrane 29 Kinetic Energy Transport 30 / Transport by Transporter Proteins 30 / Transport in Vesicles 30 2.3 Cytoplasm 33 Cytosol 33 Organelles 34 Centrosome 35 / Cilia and Flagella 35 / Ribosomes 35 / Endoplasmic Reticulum (ER) 37 / Golgi Complex 37 / Lysosomes 39 / Peroxisomes 40 / Proteasomes 40 / Mitochondria 40 2.4 Nucleus 42 2.5 Cell Division 43 Somatic Cell Division 45 Interphase 45 Mitotic Phase 45 Control of Cell Destiny 47 Reproductive Cell Division 48 Meiosis 48 2.6 Cellular Diversity 51 2.7 Aging and Cells 52 Key Medical Terms Associated with Cells 54 / Chapter Review and Resource Summary 54 / Critical Thinking Questions 56 / Answers to Figure Questions 57 3 TISSUES 58 3.1 Types of Tissues 59 3.2 Cell Junctions 60 Tight Junctions 61 Adherens Junctions 61 Desmosomes 61 Hemidesmosomes 61 Gap Junctions 61 3.3 Comparison Between Epithelial and Connective Tissues 61 3.4 Epithelial Tissue 62 Classification of Surface Epithelium 63 Surface Epithelium 64 Glandular Epithelium 71 Structural Classification of Exocrine Glands 72 / Functional Classification of Exocrine Glands 72 3.5 Connective Tissue 73 General Features of Connective Tissue 73 Connective Tissue Cells 73 Connective Tissue Extracellular Matrix 75 Ground Substance 75 / Fibers 75 Classification of Connective Tissue 76 Embryonic Connective Tissue 76 Mature Connective Tissue 77 Connective Tissue Proper 77 Supporting Connective Tissue 81 Liquid Connective Tissue 84 3.6 Membranes 85 Epithelial Membranes 85 Mucous Membranes 85 / Serous Membranes 85 / Cutaneous Membrane 87 Synovial Membranes 87 3.7 Muscular Tissue 87 3.8 Nervous Tissue 89 3.9 Aging and Tissues 89 Key Medical Terms Associated with Tissues 90 / Chapter Review and Resource Summary 90 / Critical Thinking Questions 92 / Answers to Figure Questions 93 4 DEVELOPMENT 94 4.1 Principles of Development 95 4.2 Embryonic Period 96 First Week of Development 96 Fertilization 96 / Cleavage of the Zygote 97 / Blastocyst Formation 97 / Implantation 98 Second Week of Development 100 Development of the Trophoblast 100 / Development of the Bilaminar Embryonic Disc 100 / Development of the Amnion 100 / Development of the Yolk Sac 100 Development of Sinusoids 102 / Development of the Extraembryonic Coelom 102 / Development of the Chorion 102 Third Week of Development 102 Gastrulation 102 / Neurulation 104 / Development of Somites 106 / Development of the Intraembryonic Coelom 106 / Development of the Cardiovascular System 106 / Development of the Chorionic Villi and Placenta 106 Fourth Week of Development 108 Fifth Through Eighth Weeks of Development 110 4.3 Fetal Period 111 4.4 Maternal Changes During Pregnancy 113 4.5 Labor 114 Key Medical Terms Associated with Development 115 /Chapter Review and Resource Summary 116 / CriticalThinkingQuestions 117 / Answers to Figure Questions 117 5 THE INTEGUMENTARY SYSTEM 118 5.1 Structure of the Skin 119 Epidermis 119 Stratum Basale 120 / Stratum Spinosum 122 / Stratum Granulosum 122 / Stratum Lucidum 123 / Stratum Corneum 123 / Keratinization and Growth of the Epidermis 123 Dermis 123 Blood Supply of the Integumentary System 125 The Structural Basis of Skin Color 125 / Tattooing and Body Piercing 126 Subcutaneous Layer or Hypodermis 126 5.2 Accessory Structures of the Skin 127 Hair 127 Anatomy of a Hair 128 / Hair Growth 129 / Types of Hairs 130 / Hair Color 130 Skin Glands 130 Sebaceous Glands 130 / Sudoriferous Glands 131 / Ceruminous Glands 132 Nails 132 5.3 Types of Skin 134 5.4 Functions of the Skin 135 5.5 Development of the Integumentary System 136 5.6 Aging and the Integumentary System 138 Key Medical Terms Associated with the Integumentary System 139 / Chapter Review and Resource Summary 140 / Critical Thinking Questions 141 / Answers to Figure Questions 141 6 BONE TISSUE 142 6.1 Functions of Bone and the Skeletal System 143 6.2 Types of Bones 143 6.3 Anatomy of a Bone 144 6.4 Bone Surface Markings 145 6.5 Histology of Bone Tissue 146 Compact Bone Tissue 148 Spongy Bone Tissue 149 6.6 Blood and Nerve Supply of Bone 150 6.7 Bone Formation 151 Initial Bone Formation in an Embryo and Fetus 151 Intramembranous Ossification 151 Endochondral Ossification 153 Bone Growth During Infancy, Childhood, and Adolescence 154 Growth in Length 154 / Growth in Thickness 155 Remodeling of Bone 155 6.8 Fractures 158 6.9 Exercise and Bone Tissue 161 6.10 Aging and Bone Tissue 161 6.11 Factors Affecting Bone Growth 161 Key Medical Terms Associated with Bone Tissue 163 / Chapter Review and Resource Summary 163 / Critical Thinking Questions 165 / Answers to Figure Questions 165 7 THE SKELETAL SYSTEM: THE AXIAL SKELETON 166 7.1 Divisions of the Skeletal System 167 7.2 Skull 169 General Features and Functions 169 Nasal Septum 188 Orbits 188 Foramina 190 Unique Features of the Skull 190 Sutures 190 / Paranasal Sinuses 191 / Fontanels 191 Cranial Fossae 192 Age-related Changes in the Skull 194 Sexual Differences in the Skull 195 7.3 Hyoid Bone 196 7.4 Vertebral Column 197 Normal Curves of the Vertebral Column 197 Intervertebral Discs 197 Parts of a Typical Vertebra 199 Vertebral Body 199 / Vertebral Arch 199 / Processes 200 Regions of the Vertebral Column 201 Age-related Changes in the Vertebral Column 201 7.5 Thorax 210 Key Medical Terms Associated with the Axial Skeleton 214 / Chapter Review and Resource Summary 214 / Critical Thinking Questions 215 / Answers to Figure Questions 215 8 THE SKELETAL SYSTEM: THE APPENDICULAR SKELETON 216 8.1 Skeleton of the Upper Limb 217 8.2 Skeleton of the Lower Limb 230 8.3 False and True Pelves 235 8.4 Comparison of Female and Male Pelves 236 8.5 Comparison of Pectoral and Pelvic Girdles 236 8.6 Development of the Skeletal System 246 Key Medical Terms Associated with Appendicular Skeleton 248 / Chapter Review and Resource Summary 248 / Critical Thinking Questions 249 / Answers to Figure Questions 249 9 JOINTS 250 9.1 Joint Classifications 251 Ligaments 251 9.2 Fibrous Joints 252 Sutures 252 Syndesmoses 253 Interosseous Membranes 253 9.3 Cartilaginous Joints 253 Synchondroses 253 Symphyses 253 Epiphyseal Cartilages 253 9.4 Synovial Joints 254 Structure of Synovial Joints 254 Articular Capsule 254 / Synovial Fluid 255 / Accessory Ligaments, Articular Discs, and Labra 255 / Nerve and Blood Supply 256 Bursae and Tendon Sheaths 256 9.5 Types of Movements at Synovial Joints 256 Gliding 256 Angular Movements 257 Flexion, Extension, Lateral Flexion, and Hyperextension 257 / Abduction, Adduction, and Circumduction 258 Rotation 258 Special Movements 259 9.6 Types of Synovial Joints 261 Plane Joints 261 Hinge Joints 261 Pivot Joints 261 Condyloid Joints 261 Saddle Joints 263 Ball-and-Socket Joints 263 9.7 Factors Affecting Contact and Range of Motion at Synovial Joints 264 9.8 Selected Joints of the Body 265 9.9 Aging and Joints 281 Key Medical Terms Associated with Joints 283 / Chapter Review and Resource Summary 283 / Critical Thinking Questions 284 / Answers to Figure Questions 285 10 MUSCULAR TISSUE 286 10.1 Overview of Muscular Tissue 287 Types of Muscular Tissue 287 Functions of Muscular Tissue 287 Properties of Muscular Tissue 287 10.2 Skeletal Muscle Tissue Structure 288 Gross Anatomy of a Skeletal Muscle 288 Connective Tissue Coverings 288 Nerve and Blood Supply 290 Microscopic Anatomy of a Skeletal Muscle Fiber (Cell) 290 Sarcolemma, T Tubules, and Sarcoplasm 290 / Myofibrils and Sarcoplasmic Reticulum 291 / Filaments and the Sarcomere 292 Muscle Proteins 293 10.3 Skeletal Muscle Tissue Function 296 Contraction and Relaxation of Skeletal Muscle Fibers 296 Sliding Filament Mechanism 296 / The Neuromuscular Junction 296 / The Contraction Cycle 299 / Excitation–Contraction Coupling 300 Muscle Tone 301 Isotonic and Isometric Contractions 302 10.4 Types of Skeletal Muscle Fibers 303 Slow Oxidative Fibers 303 Fast Oxidative-Glycolytic Fibers 303 Fast Glycolytic Fibers 303 10.5 Exercise and Skeletal Muscle Tissue 305 Effective Stretching 305 Strength Training 305 10.6 Cardiac Muscle Tissue 305 10.7 Smooth Muscle Tissue 307 10.8 Development of Muscles 309 10.9 Aging and Muscular Tissue 310 Key Medical Terms Associated with Muscular Tissue 310 / Chapter Review and Resource Summary 310 / Critical Thinking Questions 312 / Answers to Figure Questions 313 11 THE MUSCULAR SYSTEM 314 11.1 How Skeletal Muscles Produce Movements 315 Muscle Attachment Sites: Origin and Insertion 315 Lever Systems 316 Effects of Fascicle Arrangement 318 Muscle Actions 319 Coordination Among Muscles 319 Structure and Function of Muscle Groups 319 11.2 How Skeletal Muscles Are Named 320 11.3 Principal Skeletal Muscles 320 Key Medical Terms Associated with the Muscular System 415 / Chapter Review and Resource Summary 416 / Critical Thinking Questions 417 / Answers to Figure Questions 417 12 THE CARDIOVASCULAR SYSTEM: BLOOD 418 12.1 Functions of Blood 419 12.2 Physical Characteristics of Blood 419 12.3 Components of Blood 419 Blood Plasma 421 Formed Elements 421 12.4 Formation of Blood Cells 422 12.5 Red Blood Cells 425 RBC Anatomy 425 RBC Functions 425 RBC Life Cycle 426 Erythropoiesis: Production of RBCs 426 Blood Group Systems 427 12.6 White Blood Cells 428 WBC Anatomy and Types 428 Granular Leukocytes 428 / Agranular Leukocytes 428 / WBC Functions 428 12.7 Platelets 430 12.8 Stem Cell Transplants from Bone Marrow and Cord-Blood 431 Key Medical Terms Associated with Blood 432 / Chapter Review and Resource Summary 433 / Critical Thinking Questions 434 / Answers to Figure Questions 434 13 THE CARDIOVASCULAR SYSTEM: THE HEART 435 13.1 Location and Surface Projection of the Heart 436 13.2 Structure and Function of the Heart 438 Pericardium 438 Layers of the Heart Wall 440 Chambers of the Heart 440 Right Atrium 442 / Right Ventricle 444 / Left Atrium 444 / Left Ventricle 444 Myocardial Thickness and Function 444 Fibrous Skeleton of the Heart 445 Heart Valves 445 Atrioventricular Valves 445 / Semilunar Valves 447 13.3 Circulation of Blood 447 Systemic and Pulmonary Circulations 447 Coronary Circulation 448 Coronary Arteries 448 / Coronary Veins 450 13.4 Cardiac Conduction System and Innervation 451 Cardiac Conduction System 451 Cardiac Nerves 453 13.5 Cardiac Cycle (Heartbeat) 453 13.6 Heart Sounds 453 13.7 Exercise and the Heart 454 13.8 Development of the Heart 458 Key Medical Terms Associated with the Heart 460 Chapter Review and Resource Summary 460 Critical Thinking Questions 462 Answers to Figure Questions 462 14 THE CARDIOVASCULAR SYSTEM: BLOOD VESSELS 463 14.1 Anatomy of Blood Vessels 464 Basic Structure of a Blood Vessel 464 Tunica Interna (Intima) 464 / Tunica Media 466 / Tunica Externa 466 Arteries 466 Elastic Arteries 466 / Muscular Arteries 466 Anastomoses 467 Arterioles 467 Capillaries 468 Venules 469 Veins 469 Blood Distribution 471 14.2 Circulatory Routes—Systemic Circulation 472 14.3 Circulatory Routes—Hepatic Portal Circulation 511 14.4 Circulatory Routes—Pulmonary Circulation 512 14.5 Circulatory Routes—Fetal Circulation 513 14.6 Development of Blood Vessels and Blood 515 14.7 Aging and the Cardiovascular System 516 Key Medical Terms Associated with Blood Vessels 517 / Chapter Review and Resource Summary 518 / Critical Thinking Questions 519 / Answers to Figure Questions 519 15 THE LYMPHATIC (LYMPHOID) SYSTEM AND IMMUNITY 520 15.1 The Concept of Immunity 521 15.2 Lymphatic System Structure and Functions 521 Structure 521 Functions 521 15.3 Lymphatic Vessels and Lymph Circulation 523 Lymphatic Capillaries 523 Lymph Trunks and Ducts 524 Formation and Flow of Lymph 524 15.4 Lymphatic Organs and Tissues 526 Thymus 526 Lymph Nodes 527 Spleen 529 Lymphatic Nodules 531 15.5 Principal Groups of Lymph Nodes 531 15.6 Development of Lymphatic Tissues 542 15.7 Aging and the Lymphatic System 542 Key Medical Terms Associated with the Lymphatic System and Immunity 544 / Chapter Review and Resource Summary 544 / Critical Thinking Questions 545 / Answers to Figure Questions 545 16 NERVOUS TISSUE 546 16.1 Overview of the Nervous System 547 Structures of the Nervous System 547 Organization of the Nervous System 547 Anatomical Organization 547 / Functional Organization 548 16.2 Histology and Functions of Neurons 548 Neurons 549 Parts of a Neuron 549 / Cell Body 549 / Nerve Fibers 550 Synapses 552 Neuromuscular Junction 552 / Synapses Between Neurons 552 / Neurotransmitters 553 / Structural Diversity in Neurons 553 16.3 Histology and Function of Neuroglia 555 Neuroglia of the CNS 555 Neuroglia of the PNS 556 Myelination 556 Gray and White Matter 558 16.4 Neural Circuits 558 16.5 Regeneration and Neurogenesis 560 Key Medical Terms Associated with Nervous Tissue 560 / Chapter Review and Resource Summary 561 / Critical Thinking Questions 562 / Answers to Figure Questions 562 17 THE SPINAL CORD AND THE SPINAL NERVES 563 17.1 Spinal Cord Anatomy 564 Protective Structures 564 Vertebral Column 564 / Meninges 564 External Anatomy of the Spinal Cord 565 Internal Anatomy of the Spinal Cord 568 17.2 Spinal Nerves 569 Structure of a Single Nerve 569 Organization of Spinal Nerves 571 Branches of Spinal Nerves 572 Intercostal Nerves 572 / Plexuses 572 Dermatomes Versus Cutaneous Fields 573 17.3 Spinal Cord Functions 584 Sensory and Motor Tracts 584 Reflexes and Reflex Arcs 585 Key Medical Terms Associated with the Spinal Cord and the Spinal Nerves 586 / Chapter Review and Resource Summary 587 / Critical Thinking Questions 588 / Answers to Figure Questions 588 18 THE BRAIN AND THE CRANIAL NERVES 589 18.1 Development and General Structure of the Brain 590 Brain Development 590 Major Parts of the Brain 592 18.2 Protection and Blood Supply 593 Protective Coverings of the Brain 593 Cerebrospinal Fluid 594 Formation of CSF in the Ventricles 594 / Functions of CSF 595 / Circulation of CSF 595 Brain Blood Flow and the Blood–Brain Barrier 598 18.3 The Brainstem and Reticular Formation 599 Medulla Oblongata 599 Pons 601 Midbrain 601 Reticular Formation 603 18.4 The Cerebellum 604 18.5 The Diencephalon 604 Thalamus 606 Hypothalamus 607 Epithalamus 608 Circumventricular Organs 608 18.6 The Cerebrum 608 Structure of the Cerebrum 609 Cerebral White Matter 610 Basal Nuclei 611 The Limbic System 612 18.7 Functional Organization of the Cerebral Cortex 614 Sensory Areas 614 Motor Areas 615 Association Areas 615 Hemispheric Lateralization 617 Memory 617 Brain Waves 617 18.8 Aging and the Nervous System 618 18.9 Cranial Nerves 618 Key Medical Terms Associated with the Brain and the Cranial Nerves 633 / Chapter Review and Resource Summary 633 / Critical Thinking Questions 635 / Answers to Figure Questions 635 19 THE AUTONOMIC NERVOUS SYSTEM 636 19.1 Comparison of Somatic and Autonomic Nervous Systems 637 Somatic Nervous System 637 Autonomic Nervous System 637 Comparison of Somatic and Autonomic Motor Neurons 638 19.2 Anatomy of Autonomic Motor Pathways 639 Understanding Autonomic Motor Pathways 639 Migration of the Neural Crest Tissue 641 Shared Anatomical Components of an Autonomic Motor Pathway 641 Motor Neurons and Autonomic Ganglia 641 / Autonomic Plexuses 641 19.3 Structure of the Sympathetic Division 643 Sympathetic Preganglionic Neurons 643 Sympathetic Ganglia and Postganglionic Neurons 645 Sympathetic Trunk Ganglia 645 / Prevertebral Ganglia 646 19.4 Structure of the Parasympathetic Division 646 Parasympathetic Preganglionic Neurons 646 Parasympathetic Ganglia and Postganglionic Neurons 648 19.5 ANS Neurotransmitters and Receptors 650 Cholinergic Neurons and Receptors 650 Adrenergic Neurons and Receptors 651 19.6 Functions of the ANS 651 Sympathetic Responses 651 Parasympathetic Responses 652 19.7 Integration and Control of Autonomic Functions 655 Autonomic Reflexes 655 Autonomic Control by Higher Centers 655 Key Medical Terms Associated with the Autonomic Nervous System 655 / Chapter Review and Resource Summary 656 / Critical Thinking Questions 657 / Answers to Figure Questions 657 20 SOMATIC SENSES AND MOTOR CONTROL 658 20.1 Overview of Sensations 659 Definition of Sensations 659 Characteristics of Sensations 659 Classification of Sensations 659 Types of Sensory Receptors 659 20.2 Somatic Sensations 660 Tactile Sensations 661 Touch 661 / Pressure 661 /Vibration 662 / Itch and Tickle 662 Thermal Sensations 662 Pain Sensations 662 Types of Pain 662 / Localization of Pain 662 Proprioceptive Sensations 663 Muscle Spindles 663 / Tendon Organs 665 / Joint Kinesthetic Receptors 665 20.3 Somatic Sensory Pathways 666 Posterior Column–Medial Lemniscus Pathway to the Cerebral Cortex 666 Anterolateral (Spinothalamic) Pathways to the Cerebral Cortex 667 Mapping the Primary Somatosensory Area 667 Somatic Sensory Pathways to the Cerebellum 668 20.4 Somatic Motor Pathways 669 Origin of Motor Pathways 670 Direct Motor Pathways 670 Indirect Motor Pathways 673 Roles of the Basal Nuclei in Movement 673 Roles of the Cerebellum in Movement 673 Role of the Brainstem in Movement 673 Vestibular Nuclei in the Medulla and Pons 673 / Reticular Formation in the Medulla, Pons, and Midbrain 673 / Superior Colliculus in the Midbrain 674 20.5 Integration of Sensory Input and Motor Output 675 Key Medical Terms Associated with Somatic Senses and Motor Control 675 / Chapter Review and Resource Summary 675 / Critical Thinking Questions 677 / Answers to Figure Questions 677 21 SPECIAL SENSES 678 21.1 Olfaction: Sense of Smell 679 Anatomy of Olfactory Receptors 679 The Olfactory Pathway 681 21.2 Gustation: Sense of Taste 681 Anatomy of Gustatory Receptors 681 The Gustatory Pathway 683 21.3 Vision 683 Accessory Structures of the Eye 683 Eyelids 683 / Eyelashes and Eyebrows 685 / The Lacrimal Apparatus 685 / Extrinsic Eye Muscles 685 Anatomy of the Eyeball 685 Fibrous Tunic 685 / Vascular Tunic 685 / Retina 687 / Lens 690 / Interior of the Eyeball 690 The Visual Pathway 691 Processing of Visual Input in the Retina 692 / Pathway in the Brain 692 21.4 Hearing and Equilibrium 693 Anatomy of the Ear 693 External (Outer) Ear 693 / Middle Ear 694 / Internal (Inner) Ear 695 Mechanism of Hearing 699 The Auditory Pathway 701 Mechanism of Equilibrium 702 Otolithic Organs: Saccule and Utricle and Static Equilibrium 702 / Semicircular Ducts and Dynamic Equilibrium 702 Equilibrium Pathways 705 21.5 Development of the Eyes and Ears 707 Development of the Eyes 707 Development of the Ears 708 21.6 Aging and the Special Senses 709 Key Medical Terms Associated with Special Senses 709 / Chapter Review and Resource Summary 710 / Critical Thinking Questions 711 / Answers to Figure Questions 711 22 THE ENDOCRINE SYSTEM 712 22.1 Endocrine Glands Defined 713 22.2 Hormones 713 22.3 Hypothalamus and Pituitary Gland 715 Anterior Pituitary 716 Posterior Pituitary 718 22.4 Pineal Gland and Thymus 719 22.5 Thyroid Gland and Parathyroid Glands 720 22.6 Adrenal Glands 723 Adrenal Cortex 723 Adrenal Medulla 725 22.7 Pancreas 726 22.8 Ovaries and Testes 728 22.9 Other Endocrine Tissues 729 22.10 Development of the Endocrine System 730 22.11 Aging and the Endocrine System 731 Key Medical Terms Associated with the Endocrine System 732 / Chapter Review and Resource Summary 732 / Critical Thinking Questions 734 / Answers to Figure Questions 734 23 THE RESPIRATORY SYSTEM 735 23.1 Respiratory System Anatomy 736 23.2 Upper Respiratory System Anatomy 736 Nose 736 Pharynx 740 23.3 Lower Respiratory System Anatomy 741 Larynx 741 The Structures of Voice Production 743 Trachea 744 Bronchi 745 Lungs 749 Lobes, Fissures, and Lobules 751 / Alveolar Sacs and Alveoli 753 / Blood Supply to the Lungs 755 Patency of the Respiratory System 755 23.4 Mechanics of Pulmonary Ventilation (Breathing) 757 Inhalation 757 Exhalation 757 23.5 Regulation of Breathing 758 Role of the Respiratory Center 758 Medullary Respiratory Center 759 / Pontine Respiratory Group 760 Regulation of the Respiratory Center 760 Cortical Influences on Breathing 760 Chemoreceptor Regulation of Breathing 761 / Role of Lung Inflation in Stimulation of Breathing 761 23.6 Exercise and the Respiratory System 761 23.7 Development of the Respiratory System 762 23.8 Aging and the Respiratory System 763 Key Medical Terms Associated with the Respiratory System 763 / Chapter Review and Resource Summary 764 / Critical Thinking Questions 765 / Answers to Figure Questions 765 24 THE DIGESTIVE SYSTEM 766 24.1 Overview of the Digestive System 767 24.2 Layers of the GI Tract 768 Mucosa 768 Submucosa 769 Muscularis 769 Serosa 770 24.3 Peritoneum 770 24.4 Mouth 772 Salivary Glands 773 Tongue 775 Teeth 775 24.5 Pharynx 779 24.6 Esophagus 779 Histology of the Esophagus 779 Functions of the Esophagus 780 24.7 Stomach 781 Anatomy of the Stomach 781 Histology of the Stomach 783 Functions of the Stomach 784 24.8 Pancreas 786 Anatomy of the Pancreas 786 Histology of the Pancreas 787 Functions of the Pancreas 787 24.9 Liver and Gallbladder 788 Anatomy of the Liver and Gallbladder 788 Histology of the Liver and Gallbladder 789 Blood and Nerve Supply of the Liver and Gallbladder 792 Functions of the Liver and Gallbladder 793 24.10 Small Intestine 793 Anatomy of the Small Intestine 793 Histology of the Small Intestine 794 Functions of the Small Intestine 797 24.11 Large Intestine 800 Anatomy of the Large Intestine 800 Histology of the Large Intestine 802 Functions of the Large Intestine 803 24.12 Development of the Digestive System 805 24.13 Aging and the Digestive System 806 Key Medical Terms Associated with the Digestive System 806 / Chapter Review and Resource Summary 807 / Critical Thinking Questions 809 / Answers to Figure Questions 809 25 THE URINARY SYSTEM 810 25.1 Overview of the Urinary System 811 25.2 Anatomy of the Kidneys 813 External Anatomy of the Kidneys 813 Internal Anatomy of the Kidneys 813 Blood and Nerve Supply of the Kidneys 816 25.3 The Nephron 817 Parts of a Nephron 817 Histology of the Nephron and Collecting Duct 819 Glomerular Capsule 821 / Renal Tubule and Collecting Duct 821 25.4 Functions of Nephrons 822 Glomerular Filtration 823 Tubular Reabsorption 824 Tubular Secretion 824 25.5 Urine Transportation, Storage, and Elimination 825 Ureters 825 Urinary Bladder 828 Urethra 829 25.6 Development of the Urinary System 831 25.7 Aging and the Urinary System 832 Key Medical Terms Associated with the Urinary System 832 / Chapter Review and Resource Summary 833 / Critical Thinking Questions 834 / Answers to Figure Questions 834 26 THE REPRODUCTIVE SYSTEMS 835 26.1 Male Reproductive System 836 Scrotum 836 Testes 838 Sperm 842 Reproductive System Ducts in Males 843 Ducts of the Testis 843 / Epididymis 843 / Ductus Deferens 844 / Ejaculatory Ducts 845 / Urethra 845 Spermatic Cord 845 Accessory Sex Glands in Males 845 Seminal Vesicles 845 / Prostate 845 / Bulbourethral Glands 845 Semen 847 Penis 847 26.2 Female Reproductive System 849 Ovaries 849 Histology of the Ovaries 851 / Oogenesis and Follicular Development 853 Uterine Tubes 856 Uterus 859 Vagina 861 Vulva 862 Perineum 863 Mammary Glands 866 26.3 Female Reproductive Cycle 866 Menstrual Phase 867 Events in the Ovaries 867 / Events in the Uterus 867 Preovulatory Phase 868 Events in the Ovaries 868 / Events in the Uterus 868 Ovulation 868 Postovulatory Phase 868 Events in the Ovaries 868 / Events in the Uterus 870 26.4 Birth Control Methods and Abortion 870 Birth Control Methods 870 Surgical Sterilization 870 / Non-incisional Sterilization 870 / Hormonal Methods 871 / Intrauterine Devices 871/Spermicides 871 / Barrier Methods 871 / Periodic Abstinence 872 Abortion 872 26.5 Development of the Reproductive Systems 872 26.6 Aging and the Reproductive Systems 874 Key Medical Terms Associated with the Reproductive Systems 875 / Chapter Review and Resource Summary 876 / Critical Thinking Questions 878 / Answers to Figure Questions 878 27 SURFACE ANATOMY 880 27.1 Overview of Surface Anatomy 881 Chapter Review and Resource Summary 903 / Critical Thinking Questions 904 / Answers to Figure Questions 904 APPENDIX A Measurements A-1 APPENDIX B Answers A-2 Glossary G-1 Index I-1

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Book SynopsisAs an applied science, Enology is a collection of knowledge from the fundamental sciences including chemistry, biochemistry, microbiology, bioengineering, psychophysics, cognitive psychology, etc., and nourished by empirical observations. The approach used in the Handbook of Enology is thus the same. It aims to provide practitioners, winemakers, technicians and enology students with foundational knowledge and the most recent research results. This knowledge can be used to contribute to a better definition of the quality of grapes and wine, a greater understanding of chemical and microbiological parameters, with the aim of ensuring satisfactory fermentations and predicting the evolution of wines, and better mastery of wine stabilization processes. As a result, the purpose of this publication is to guide readers in their thought processes with a view to preserving and optimizing the identity and taste of wine and its aging potential. This third English edition of TheTable of ContentsForeword xi Preface to the Second Edition xiii Preface to the First Edition xv Remarks Concerning the Expression of Certain Parameters of Must and Wine Composition xix Part I – Chemistry of Wine 1 1 Organic Acids in Wine 3 1.1Introduction 3 1.2The Main Organic Acids 3 1.3Different Types of Acidity 8 1.4The Concept of pH and Its Applications 10 1.5Tartrate Precipitation Mechanism and Predicting Its Effects 24 1.6Tests for Predicting Wine Stability 32 1.7Preventing Tartrate Precipitation 41 References 55 2 Alcohols and Other Volatile Compounds 57 2.1Ethanol 57 2.2Other Simple Alcohols 59 2.3Polyols 62 2.4Aliphatic Fatty Acids 65 2.5Esters 66 2.6Miscellaneous Compounds 71 References 74 3 Carbohydrates 75 3.1Introduction 75 3.2Glucose and Fructose 76 3.3Other Sugars 79 3.4Chemical Properties of Sugars 82 3.5Sugar Derivatives 85 3.6Pectic Substances in Grapes 87 3.7Exocellular Polysaccharides from Microorganisms 95 References 101 4 Dry Extract and Minerals 105 4.1Introduction 105 4.2Dry Extract 106 4.3Ash 108 4.4Inorganic Anions 109 4.5Inorganic Cations 109 4.6Iron and the Iron Casse Mechanism 111 4.7Copper and Copper Casse 117 4.8Heavy Metals 121 References 125 5 Nitrogen Compounds 127 5.1Introduction 127 5.2The Various Forms of Nitrogen 127 5.3Amino Acids 130 5.4Other Forms of Nitrogen 136 5.5Proteins and Protein Haze 142 5.6Preventing Protein Haze 151 References 159 6 Phenolic Compounds 161 6.1Introduction 161 6.2Types of Substances 162 6.3Chemical Properties of Anthocyanins and Tannins 173 6.4Anthocyanin and Tannin Assays: Sensory Properties 196 6.5Evolution of Anthocyanins and Tannins as Grapes Ripen 212 6.6Extracting Tannins and Anthocyanins During Winemaking 225 6.7Chemical Reactions Occurring During Bulk and Bottle Aging 228 6.8Precipitation of Coloring Matter (Color Stability) 233 6.9Origin of the Color of White Wines 235 References 238 7 Varietal Aroma 243 7.1The General Concept of Varietal Aroma 243 7.2Terpene Compounds 245 7.3C13-Norisoprenoid Derivatives 253 7.4Methoxypyrazines 257 7.5Sulfur Compounds with a Thiol Function 260 7.6Furanones 270 7.7Lactones 271 7.8Aromas of American Species 274 References 274 Part II – Wine Stabilization and Treatments 281 8 Main Sensory Defects: Chemical Nature, Origins and Consequences 283 8.1Introduction 283 8.2Oxidative Defects 285 8.3Effect of Various Forms of Bacterial Spoilage 289 8.4Microbiological Origin and Properties of Volatile Phenols 294 8.5Cork Taint 310 8.6Sulfur Derivatives and Reduction Odors 316 8.7Premature Aging of Wine Aroma 331 8.8Sensory Defects Associated with Grapes Affected by Various Types of Rot 336 8.9Miscellaneous Defects 343 References 346 9 The Concept of Clarity and Colloidal Phenomena 351 9.1Clarity and Stability 351 9.2The Colloidal State 354 9.3Colloid Reactivity 357 9.4Protective Colloids and Gum Arabic Treatment 363 References 368 10 Clarification and Stabilization Treatments: Fining Wine 369 10.1 Treating Wine 369 10.2 Sedimentation of Particles in Suspension 372 10.3 Racking: Role and Techniques 374 10.4 Theory of Protein Fining 377 10.5 Tannin-Protein Interactions 385 10.6 Effect of Fining on the Organoleptic Quality of Wine: Concept of Overfining 387 10.7 Products Used in Fining 389 10.8 Fining Techniques 396 10.9 Bentonite Treatment 398 10.10 Miscellaneous Clarification Treatments 403 References 406 11 Clarifying Wine by Filtration and Centrifugation 409 11.1 Principles of Filtration 410 11.2 Laws of Filtration 411 11.3 Methods for Assessing Clarification Quality 414 11.4 Filtration Equipment and Filter Aids 416 11.5 How Filter Layers Function 421 11.6 Filtration through Diatomaceous Earth (or Kieselguhr) Precoats 424 11.7 Filtration Through Cellulose-Based Filter Pads 431 11.8 Membrane Filtration 436 11.9 Crossflow Filtration 439 11.10 Effect of Filtration on the Composition and Organoleptic Character of Wine 443 11.11 Centrifugation 447 References 450 12 Stabilizing Wine by Physical and Physicochemical Processes 451 12.1 Introduction 451 12.2 Heat Stabilization 452 12.3 Wine Stabilization Through Physical Processes Under Development 455 12.4 Cold Stabilization 456 12.5 Ion Exchangers 459 12.6 Electrodialysis Applications in Winemaking 466 References 470 13 Aging Red Wines in Tanks and Barrels: Phenomena Occurring During Aging 471 13.1 Oxidation–Reduction Phenomena 471 13.2 Oxidation–Reduction Potential 473 13.3 Influence of Various Factors on Oxidation–Reduction Potential 478 13.4 Development of the Phenolic Characteristics of Red Wines (Color and Flavor) During Aging 484 13.5 Evolution of Aromatic Thiol Composition in Red Wines During Aging 492 13.6 Bottle Aging of Red Wines 498 13.7 Cellar Practices 505 13.8 Barrel Aging of Red Wines 508 13.9 Effect of Barrel Type on the Development of Red Wine 514 13.10 Constraints and Risks of Barrel Aging 525 References 527 Index 531

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