Biology, life sciences Books

Book SynopsisMolecular Neuroendocrinology: From Genome to Physiology, provides researchers and students with a critical examination of the steps being taken to decipher genome complexity in the context of the expression, regulation and physiological functions of genes in neuroendocrine systems. The 19 chapters are divided into four sectors: A) describes and explores the genome, its evolution, expression and the mechanisms that contribute to protein, and hence biological, diversity. B) discusses the mechanisms that enhance peptide and protein diversity beyond what is encoded in the genome through post-translational modification. C) considers the molecular tools that today's neuroendocrinologists can use to study the regulation and function of neuroendocrine genes within the context of the intact organism. D) presents a range of case studies that exemplify the state-of-the-art application of genomic technologies in physiological and behavioural experiments that seek to better understTable of ContentsList of Contributors, vii Series Preface, xi About the Companion Website, xiii Introduction 1 David Murphy and Harold Gainer Part A Genome and Genome Expression 1 Evolutionary Aspects of Physiological Function and Molecular Diversity of the Oxytocin/Vasopressin Signaling System 5 Zita Liutkevicǐūtė and Christian W. Gruber 2 The Neuroendocrine Genome: Neuropeptides and Related Signaling Peptides 25 J. Peter H. Burbach 3 Transcriptome Dynamics 57 David A. Carter, Steven L. Coon, Yoav Gothilf , Charles K. Hwang, Leming Shi, P. Michael Iuvone, Stephen Hartley, James C. Mullikin, Peter Munson, Cong Fu, Samuel J. Clokie, and David C. Klein 4 New Players in the Neuroendocrine System: A Journey Through the Non‐coding RNA World 75 Yongping Wang, Edward A. Mead, Austin P. Thekkumthala, and Andrzej Z. Pietrzykowski 5 Transcription Factors Regulating Neuroendocrine Development, Function, and Oncogenesis 97 Judy M. Coulson and Matthew Concannon 6 Epigenetics 121 Chris Murgatroyd Part B Proteins, Posttranslational Mechanisms, and Receptors 7 Proteome and Peptidome Dynamics 141 Lloyd D. Fricker 8 Neuropeptidomics: The Characterization of Neuropeptides and Hormones in the Nervous and Neuroendocrine Systems 155 Ning Yang, Samuel J. Irving, Elena V. Romanova, Jennifer W. Mitchell, Martha U. Gillette, and Jonathan V. Sweedler 9 Posttranslational Processing of Secretory Proteins 171 Nabil G. Seidah and Johann Guillemot 10 Neuropeptide Receptors 195 Stephen J. Lolait, James A. Roper, Georgina G.J. Hazell, Yunfei Li, Fiona J. Thomson, and Anne‐Marie O’Carroll Part C The Tool Kit 11 Germline Transgenesis 219 Jim Pickel 12 Somatic Transgenesis (Viral Vectors) 243 Valery Grinevich, H. Sophie Knobloch‐Bollmann, Lena C. Roth, Ferdinand Althammer, Andrii Domanskyi, Ilya A. Vinnikov, Marina Eliava, Megan Stanifer, and Steeve Boulant 13 Optogenetics Enables Selective Control of Cellular Electrical Activity 275 Ryuichi Nakajima, Sachiko Tsuda, Jinsook Kim, and George J. Augustine 14 Non‐Mammalian Models for Neurohypophysial Peptides 301 Einav Wircer, Shifra Ben‐Dor, and Gil Levkowitz Part D Case Studies – Integration and Translation 15 Osmoregulation 331 David Murphy, Jose Antunes‐Rodrigues, and Harold Gainer 16 Food Intake, Circuitry, and Energy Metabolism 355 Giles S.H. Yeo 17 Stress Adaptation and the Hypothalamic‐Pituitary‐Adrenal Axis 375 Greti Aguilera 18 Neuroendocrine Control of Female Puberty: Genetic and Epigenetic Regulation 405 Alejandro Lomniczi and Sergio R. Ojeda 19 Oxytocin, Vasopressin, and Diversity in Social Behavior 423 Lanikea B. King and Larry J. Young Glossary 443 Index 459

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Book SynopsisThis book discusses the community of microbial species (the microbiota, microbiome), which inhabits the large bowel of humans. Written from the perspective of an academic who has been familiar with the topic for 40 years, it provides a long-term perspective of knowledge about this high profile and fast-moving topic.Table of ContentsPreface vii Acknowledgements ix 1 Introduction 1 References 4 2 Prime Facts 7 Summary 14 Explanation of Terms 15 References 16 3 A Sense of Community 19 Summary 33 Explanation of Terms 33 References 35 4 Assembling Communities 39 Summary 55 Explanation of Terms 55 References 56 5 Bowel Society 63 References 69 6 Chemostat Bowel 71 Summary 82 Explanation of Terms 82 References 83 7 Revealing Secret Lives 87 Summary 98 Explanation of terms 98 References 101 8 Remembrance of Microbes Past 105 Summary 111 References 112 9 Out of Tune: Dysbiosis 115 Summary 130 Explanation of Terms 130 References 132 10 We may be Lost, but we’re Making Good Time 139 Particularly Important Considerations 143 Running Out of Fuel? 145 The End of the Journey 146 References 146 Addendum: A Brief Summary of Technological Aspects of ]omics 149 General Features of Nucleic Acid-based Technology 149 Older Electrophoretic Methods for Screening Microbiota Compositions 150 Fluorescent Probes (FISH/FC) 151 Measuring the Abundance of Bacterial Groups by qPCR 152 Using DNA Chips to Screen Microbiota Compositions 153 Detailed Phylogenetic Analysis 154 Metagenomics: Determining the Functional Capacity of Microbiotas 155 Metatranscriptomics: Microbiota Biochemical Pathways in Action 156 Metaproteomics 157 Metabolomics 157 Summary 158 References 159 Index 163

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Book SynopsisStem cells, regenerative medicine, and translational medicine, are all areas of burgeoning basic research and clinical application. This dictionary includes the fundamental terminology of each of these areas, the major discoveries and significant scientists that comprise the history and current development of the field, as well as a number of concepts. The vocabulary is presented within the broader lexicon of developmental biology and embryology, which provides context for these three fields. Topics covered range from stem cells (embryonic, adult, and iPSCs) to teratology. The inclusion of extensive cross-referencing of the terms will enable readers to broaden their understanding of them. The Dictionary of Stem Cells, Regenerative Medicine, and Translational Medicine will provide both the basic background terminology needed by pre-health professions/biology major undergraduate students and early-stage graduate students, as well as being a valuable reference for university professoTable of ContentsDedication viiPreface ixA – Z 1References 362

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Book SynopsisOur knowledge of reproductive biology has increased enormously in recent years on cellular, molecular, and genetic levels, leading to significant breakthroughs that have directly benefitted in vitro fertilization (IVF) and other assisted reproductive technologies (ART) in humans and animal systems.Table of ContentsList of Contributors xv 1 Anatomy of the Reproductive System 1Gheorghe M. Constantinescu 1.1 Male Genital Organs in Domestic Mammals 1 1.2 Female Genital Organs in Domestic Mammals 5 1.3 The Genital System in Domestic Mammals Species by Species 9 1.4 Genital Organs in Laboratory Mammals 35 References 56 2 Anatomy of Mammalian (Endocrine) Glands Controlling the Reproduction 59Gheorghe M. Constantinescu 2.1 The Hypothalamus Including the Hypophysis 59 2.2 The Cerebral Epiphysis 61 2.3 The Thyroid Gland 61 2.4 The Adrenal Glands 62 2.5 The Sexual Glands 63 2.6 The Liver 63 References 63 3 Models for Investigating Placental Biology 65Laramie Pence and Bhanu P. Telugu 3.1 Introduction 65 3.2 Classification of Placenta 66 3.3 Development of Human Placenta 69 3.4 Modeling Placental Development and Diseases of Placental Origin 73 3.5 Summary 82 References 82 4 Early Developmental Programming of the Ovarian Reserve, Ovarian Function, and Fertility 91Francesca Mossa, Siobhàn W. Walsh, Alex C.O. Evans, Fermin Jimenez-Krassel, and James J. Ireland 4.1 Introduction 91 4.2 Impact of Prenatal Environmental Challenges on Fetal Oogonia (Germ Cells) 92 4.3 Impact of Prenatal Environmental Challenges on Fetal Follicle/Oocyte Numbers (Healthy versus Atretic) and Oocyte Quality 94 4.4 Impact of Prenatal Environmental Challenges on the Ovarian Reserve (Total Number of Morphologically Healthy Follicles/Oocytes in Ovaries) in Offspring 95 4.5 Impact of Prenatal Environmental Challenges on Ovarian Function (e.g., Pituitary Gonadotropin Secretion, Ovarian Hormone/Growth Factor Production, Response to Gonadotropins, Follicle Development, Irregular Reproductive Cycles, and Ovulation Rate) in Offspring 98 4.6 Impact of Prenatal Environmental Challenges on Fertility (as Measured by Conception Rates, Fecundity, or Age at Puberty or Menopause) in Offspring 100 4.7 Summary and Conclusion 101 References 102 5 Small Non-Coding RNAS in Gametogenesis 109Lukasz Smorag and D. V. Krishna Pantakani 5.1 Small Non-Coding RNAs 109 5.2 Function of sncRNAs in Gametogenesis 109 Acknowledgment 119 References 119 6 The Ovarian Follicle of Cows as a Model for Human 127Marc-André Sirard 6.1 Introduction 127 6.2 A Similar Physiology of Folliculogenesis 128 6.3 Assisted Reproduction 131 6.4 Testing the Competence Hypothesis 136 6.5 Conclusion 136 References 136 7 Production of Energy and Determination of Competence: Past Knowledge, Present Research, and Future Opportunities in Oocyte and Embryo Metabolism 145Jason R. Herrick, Elena Silva, and Rebecca L. Krisher 7.1 Introduction 145 7.2 Measuring Metabolism 145 7.3 The Relationship Between Oocyte Metabolism and Quality 148 7.4 Embryo Metabolism 152 7.5 Metabolic Biomarkers 157 7.6 Toward Personalized Culture Media: Formulating Media for Specific Maternal Conditions 158 7.7 Summary 161 References 162 8 Signal Transduction Pathways in Oocyte Maturation 177François J. Richard, Nicolas Santiquet, Annick Bergeron, and Daulat Raheem Khan 8.1 Introduction 177 8.2 Phosphodiesterase 181 8.3 Gap Junction Communications 192 8.4 Metabolic Switch (AMPK) 193 8.5 Conclusion 198 References 198 9 Pig Models of Reproduction 213B.R. Mordhorst and R.S. Prather 9.1 Introduction 213 9.2 Early Embryonic Development 213 9.3 Oocyte Maturation 215 9.4 Fertilization 216 9.5 Tubouterine Contractility 216 9.6 Development to the Blastocyst Stage 216 9.7 Pregnancy and Developmental Programming 217 9.8 Puberty 222 9.9 Reproductive Disease 223 9.10 Summary 223 Acknowledgments 223 References 223 10 The Mare as an Animal Model for Reproductive Aging in the Woman 235Elaine M. Carnevale 10.1 Introduction 235 10.2 Ovarian Activity and Reproductive Cycles 236 10.3 The Follicle 238 10.4 Fertility 239 10.5 The Oocyte 240 10.6 Conclusions 242 References 242 11 Spotlight on Reproduction in Domestic Dogs as a Model for Human Reproduction 247Shirley J. Wright 11.1 Introduction 247 11.2 Dog Reproduction 255 11.3 Dog-Assisted Reproductive Technology 321 11.4 Dog Contraception 328 11.5 The Dog as a Model for Human Reproduction 328 11.6 Concluding Statements 332 Acknowledgments 333 References 333 12 Animal Models of Inflammation During Pregnancy 359Karen E. Racicot and Keith E. Latham 12.1 Introduction 359 12.2 Local Inflammation of the Pregnant Female Reproductive Tract 360 12.3 Systemic Inflammation During Pregnancy 361 12.4 Genetic Models and Cellular Manipulation to Study Inflammation During Pregnancy 365 12.5 Inflammation During Pregnancy and Offspring Disease 370 12.6 Perspectives and Conclusions 372 Acknowledgments 373 References 373 13 Practical Approaches, Achievements, and Perspectives in the Study on Signal Transduction in Oocyte Maturation and Fertilization: Focusing on the African Clawed Frog Xenopus laevisas an Animal Model 383Ken-ichi Sato 13.1 Introduction to Reproductive Biology of Frog Oocytes and Eggs 383 13.2 Practical Approaches 383 13.3 Achievements and Perspectives 395 Acknowledgments 396 Appendix 396 References 399 14 Prezygotic Chromosomal Examination of Mouse Spermatozoa 401Hiroyuki Watanabe and Hiroyuki Tateno 14.1 Introduction 401 14.2 Procedure of Sperm Chromosome Screening 402 14.3 Practical Use of SCS Before Fertilization 404 14.4 Conclusion 406 Acknowledgments 406 Addendum 406 References 406 15 Molecular and Cellular Aspects of Mammalian Sperm Acrosomal Exocytosis 409Florenza A. La Spina, Cintia Stival, Dario Krapf, and Mariano G. Buffone 15.1 Introduction 409 15.2 Structure of the Acrosome 409 15.3 Intermediate Stages of Exocytosis 412 15.4 Sperm Capacitation Prepare the Sperm to Undergo Acrosomal Exocytosis 412 15.5 Physiological Site for the Occurrence of Acrosomal Exocytosis 414 15.6 SNARES and Other Proteins from the Fusion Machinery 416 15.7 Hyperpolarization 417 15.8 Actin Cytoskeleton 417 15.9 Calcium 418 References 419 16 Sperm Chromatin Dynamics Associated with Male Fertility in Mammals 427Naseer A. Kutchy, Sule Dogan, Abdullah Kaya, Arlindo Moura, and Erdogan Memili 16.1 Introduction 427 16.2 Sperm Chromatin Structure Modulates Sperm Nuclear Shape and Function 429 16.3 The Bull Is a Suitable Model for the Study of Male Fertility in Humans 430 16.4 Conclusions and Prospects 430 Acknowledgments 431 References 431 17 Epigenome Modification and Ubiquitin-Dependent Proteolysis During Pronuclear Development of the Mammalian Zygote: Animal Models to Study Pronuclear Development 435Jan Nevoral and Peter Sutovsky 17.1 Introduction 435 17.2 Milestones of Pronuclear Development 436 17.3 Nuclear Envelope, Nuclear Pore Complexes, and Nuclear Lamina Changes During Pronuclear Development 438 17.4 Molecular Mechanism of Paternal and Maternal Pronucleus Biogenesis 440 17.5 Role of UPS in Pronuclear Biogenesis 442 17.6 Posttranslational Modifications of Pronuclear Histones 443 17.7 Sirtuin Family Histone Deacetylases in Gametogenesis and Development 446 17.8 Clinical and Technological Considerations 447 17.9 Conclusions 450 Acknowledgments 450 References 450 18 Alterations of the Epigenome Induced by the Environment in Reproduction 467Zhao-Jia Ge, Shen Yin, and Heide Schatten 18.1 Introduction 467 18.2 Epigenetic Reprogramming 467 18.3 Environment and Epigenetic Alterations 470 18.4 Animal Models Used in Reproduction to Research Epigenetic Alterations Induced by the Environment 472 18.5 Effects of Environment on Epigenetic Modifications in Humans 475 18.6 Epigenetics and Assisted Reproductive Technology (ART) 475 18.7 Priorities for the Future 476 Acknowledgments 476 References 476 19 Toward Development of Pluripotent Porcine Stem Cells by Road Mapping Early Embryonic Development 485Stoyan Petkov, Kristine Freude, Kaveh Mashayekhi, Poul Hyttel, and Vanessa Hall 19.1 Introduction 485 19.2 Current Status on the Pluripotent State in the Pig Embryo 489 19.3 Current Status of the Establishment of Porcine Embryonic Stem Cells (pESCs) 491 19.4 Current Status in Establishment of Porcine-Induced Pluripotent Stem Cells 494 19.5 Future Perspectives: Use of Global Profiling on Pluripotent Cells from Pig Embryo and Pluripotent Stem Cells 499 19.6 Discussion and Conclusions 501 Acknowledgments 502 References 502 20 Applications of Metabolomics in Reproductive Biology 509Ana Luiza Cazaux Velho, Rodrigo Oliveira, Thu Dinh, Arlindo Moura, Abdullah Kaya, and Erdogan Memili 20.1 Introduction 509 20.2 Metabolomics and Reproductive Biology 510 20.3 Metabolomics Studies in Large Animals as Models for Humans 513 20.4 Conclusions and Future Prospects 513 Acknowledgments 514 Conflict of Interest 514 References 514 21 Cryopreservation of Mammalian Oocytes 519Muhammad Anzar 21.1 Principles of Cryopreservation 519 21.2 Cryopreservation of Mammalian Oocytes 522 Acknowledgments 542 Abbreviations 543 References 543 Index 557

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Book Synopsis4th edition of this classic Ecology text Computational methods have largely been replaced by descriptions of the available software Includes procedure information for R software and other freely available software systems Now includes web references for equipment, software and detailed methodologies Table of ContentsPrefaces xiii About the Companion Website xix 1 Introduction to the Study of Animal Populations 1 1.1 Population estimates 2 1.1.1 Absolute and related estimates 2 1.1.2 Relative estimates 3 1.1.3 Population indices 4 1.2 Errors and confidence 4 References 5 2 The Sampling Programme and the Measurement and Description of Dispersion 7 2.1 Preliminary sampling 7 2.1.1 Planning and fieldwork 7 2.1.2 Statistical aspects 10 2.2 The sampling programme 16 2.2.1 The number of samples per habitat unit (e.g. plant, host or puddle) 16 2.2.2 The sampling unit, its selection, size and shape 20 2.2.3 The number of samples 21 2.2.4 The pattern of sampling 24 2.2.5 The timing of sampling 26 2.3 Dispersion 27 2.3.1 Mathematical distributions that serve as models 28 2.3.2 Biological interpretation of dispersion parameters 40 2.3.3 Nearest-neighbour and related techniques: measures of population size or of the departure from randomness of the distribution 48 2.4 Sequential sampling 51 2.4.1 Sampling numbers 51 2.5 Presence or absence sampling 55 2.6 Sampling a fauna 57 2.7 Biological and other qualitative aspects of sampling 59 2.8 Jack knife and Bootstrap techniques 60 References 62 3 Absolute Population Estimates Using Capture–Recapture Experiments 77 3.1 Capture–recapture methods 78 3.1.1 Assumptions common to most methods 79 3.1.2 Estimating closed populations 86 3.1.3 Estimations for open populations 93 3.2 Methods of marking animals 103 3.2.1 Handling techniques 105 3.2.2 Release 107 3.2.3 Surface marks using paints and solutions of dyes 108 3.2.4 Dyes and fluorescent substances in powder form 112 3.2.5 Pollen 114 3.2.6 Marking formed by feeding on or absorption of dyes 114 3.2.7 Marking by injection, panjet or tattooing 116 3.2.8 External tags 116 3.2.9 Branding 117 3.2.10 Mutilation 118 3.2.11 Natural marks, parasites and genes 118 3.2.12 Rare elements 119 3.2.13 Protein marking 120 3.2.14 Radioactive isotopes 120 3.2.15 Radio and sonic tags 120 References 121 4 Absolute Population Estimates by Sampling a Unit of Habitat – Air, Plants, Plant Products and Vertebrate Hosts 139 4.1 Sampling from the air 139 4.2 Sampling apparatus 140 4.2.1 Exposed cone (Johnson–Taylor) suction trap 140 4.2.2 Enclosed cone types of suction trap including the Rothamsted 12 m trap 141 4.2.3 Rotary and other traps 143 4.3 Comparison and efficiencies of the different types of suction traps 144 4.3.1 Conversion of catch to aerial density 145 4.3.2 Conversion of density to total aerial population 146 4.4 Sampling from plants 146 4.4.1 Assessing the plant 147 4.4.2 Determining the numbers of invertebrates 147 4.4.3 The extraction of animals from herbage and debris 155 4.4.4 Methods for animals in plant tissues 163 4.4.5 Special sampling problems with animals in plant material 165 4.5 Sampling from vertebrate hosts 166 4.5.1 Sampling from living hosts 166 4.5.2 Sampling from dead hosts 169 4.5.3 Sampling from vertebrate ‘homes’ 170 References 171 5 Absolute Population Estimates by Sampling a Unit of Aquatic Habitat 183 5.1 Open water 183 5.1.1 Nets 183 5.1.2 Pumps 187 5.1.3 Water-sampling bottles 187 5.1.4 The Patalas–Schindler volume sampler 187 5.1.5 Particular methods for insects 188 5.2 Vegetation 190 5.2.1 Floating vegetation 191 5.2.2 Emergent vegetation 192 5.2.3 Submerged vegetation 194 5.3 Bottom fauna 195 5.3.1 Hand net sampling of forest litter 196 5.3.2 Sampling from under stones 197 5.3.3 The planting of removable portions of the substrate 199 5.3.4 Cylinders and boxes for delimiting an area 200 5.3.5 Trawls, bottom sledges and dredges 201 5.3.6 Grabs 205 5.3.7 Dendy inverting sampler 208 5.3.8 Box samplers and corers 209 5.3.9 Air-lift and suction devices 211 5.4 Poisons and anaesthetics used for sampling fish in rock pools and small ponds 211 References 213 6 Absolute Population Estimates by Sampling a Unit of Soil or Litter Habitat: Extraction Techniques 221 6.1 Sampling 221 6.2 Bulk staining 224 6.3 Mechanical methods of extraction 224 6.3.1 Dry sieving 224 6.3.2 Wet sieving 225 6.3.3 Soil washing and flotation 226 6.3.4 Flotation separation of plankton, meiofauna and other small animals 229 6.3.5 Separation of plant and insects by differential wetting 231 6.3.6 Centrifugation 233 6.3.7 Sedimentation 233 6.3.8 Elutriation 234 6.3.9 Sectioning 235 6.3.10 Aeration 236 6.4 Behavioural or dynamic methods 236 6.4.1 Dry extractors 237 6.4.2 Wet extractors 243 6.5 Summary of the applicability of the methods 248 References 250 7 Relative Methods of Population Measurement and the Derivation of Absolute Estimates 259 7.1 Factors affecting the size of relative estimates 259 7.1.1 The ‘phase’ of the animal 260 7.1.2 The activity of the animal 261 7.1.3 Differences in the response between species, sexes and individuals 263 7.1.4 The efficiency of the trap or searching method 264 7.2 The uses of relative methods 266 7.2.1 Measures of the availability 266 7.2.2 Indices of absolute population 266 7.2.3 Estimates of absolute population 267 7.2.4 Removal trapping or collecting 268 7.2.5 Collecting 272 7.3 Relative methods: catch per unit effort 272 7.3.1 Observation by radar 272 7.3.2 Hydroacoustic methods 273 7.3.3 Fish counters 274 7.3.4 Electric fishing 274 7.3.5 Aural detection 275 7.3.6 Exposure by plough 276 7.3.7 Collecting with a net or similar device 276 7.3.8 Visual searching and pooting 279 7.4 Relative methods: trapping 280 7.4.1 Interception traps 281 7.4.2 Flight traps combining interception and attraction 290 7.4.3 Light and other visual traps 294 7.5 Traps that attract animals by some natural stimulus or a substitute 304 7.5.1 Shelter traps 304 7.5.2 Trap host plants 305 7.5.3 Baited traps 305 7.5.4 The use of vertebrate hosts or substitutes as bait for insects 308 7.6 Using Sound 314 References 314 8 Estimates of Species Richness and Population Size Based on Signs, Products and Effects 337 8.1 Arthropod products 337 8.1.1 Exuviae 337 8.1.2 Frass 338 8.2 Vertebrate products and effects 341 8.3 Effects due to an individual insect 342 8.4 General effects: plant damage 343 8.4.1 Criteria 344 8.5 Determining the relationship between damage and insect populations 347 References 348 9 Wildlife Population Estimates by Census and Distance Measuring Techniques 355 9.1 Census methods 356 9.2 Point and line survey methods 357 9.2.1 Indices of abundance using transects 357 9.2.2 Methods based on flushing 357 9.2.3 Line transect methods: the Fourier series estimator 360 9.2.4 Point transects 365 9.3 Distance sampling software in R 365 9.4 Spatial distribution and plotless density estimators 367 9.4.1 Closest individual or distance method 367 9.4.2 Nearest-neighbour methods 368 References 369 10 Observational and Experimental Methods for the Estimation of Natality, Mortality and Dispersal 373 10.1 Natality 373 10.1.1 Fertility 373 10.1.2 Numbers entering a stage 375 10.1.3 The birth-rate from mark and recapture data 382 10.2 Mortality 382 10.2.1 Total 382 10.2.2 The death-rate from mark and recapture data 383 10.2.3 Climatic factors 383 10.2.4 Biotic factors 383 10.2.5 Experimental assessment of natural enemies 390 10.3 Dispersal 396 10.3.1 Detecting and quantifying jump dispersal 397 10.3.2 Quantifying neighbourhood dispersal 397 10.4 The measurement and description of home range and territory 410 10.4.1 The minimum convex polygon area method for estimating home range 411 10.4.2 The kernel estimation method for home range 412 10.5 The rate of colonisation of a new habitat and artificial substrates 413 10.6 The direction of migration 413 References 413 11 The Construction, Description and Analysis of Age-specific Life-tables 429 11.1 Types of life-table and the budget 429 11.2 The construction of a budget 430 11.3 Analysis of stage-frequency data 431 11.3.1 Southwood’s graphical method 432 11.3.2 Richards &Waloff’s first method 432 11.3.3 Manly’s method 434 11.3.4 Ruesink’s method 435 11.3.5 Dempster’s method 435 11.3.6 Richards &Waloff’s Second Method 436 11.3.7 Kiritani, Nakasuji & Manly’s method 437 11.3.8 Kempton’s method 438 11.3.9 The Bellows and Birley Method 439 11.4 The description of budgets and life-tables 440 11.4.1 Survivorship curves 440 11.4.2 Stock–recruitment (Moran–Ricker) curves 440 11.4.3 The life-table and life expectancy 443 11.4.4 Life and fertility tables and the net reproductive rate 444 11.4.5 Population growth rates 446 11.4.6 The calculation of r 448 11.5 The analysis of life-table data 449 11.5.1 The comparison of mortality factors within a generation 449 11.5.2 Survival and life budget analysis 451 11.5.3 Sibley’s 𝜆 contribution analysis 458 References 459 12 Age-grouping, Time-specific Life-tables and Predictive Population Models 465 12.1 Age-grouping 465 12.2 Aging young by developmental stage 466 12.3 Aging by using structures 467 12.3.1 Annelids 467 12.3.2 Crustaceans 467 12.3.3 Insects 467 12.3.4 Molluscs 472 12.3.5 Fish 473 12.3.6 Lampreys 474 12.3.7 Reptiles and amphibians 474 12.3.8 Birds 475 12.3.9 Mammals 475 12.4 Time-specific life-tables and survival rates 476 12.4.1 Physiological time 478 12.4.2 Life-table parameters 479 12.4.3 Recruitment in the field 479 12.4.4 Empirical models 479 12.4.5 Intrinsic rate models and variable life-tables 480 12.4.6 Lewis–Leslie matrices and R packages 481 References 484 13 Species Richness, Diversity and Packing 495 13.1 Diversity 496 13.1.1 Description of 𝛼- and 𝛾-diversity 497 13.1.2 Species richness 498 13.1.3 Models for the S:N relationship 505 13.1.4 Non-parametric indices of diversity 509 13.1.5 Which model or index? 512 13.1.6 Comparing communities – diversity ordering 513 13.1.7 Procedure to determine 𝛼-diversity 515 13.1.8 Determining 𝛽-diversity 517 13.2 Similarity and the comparison and classification of samples 520 13.2.1 Measures of complementarity 521 13.2.2 Similarity indices 521 13.2.3 Multivariate analysis 525 13.3 Species packing 530 13.3.1 Measurement of interspecific association 530 13.3.2 Measurement of resource utilisation 534 13.3.3 Niche size and competition coefficients 540 References 542 14 The Estimation of Productivity and the Construction of Energy Budgets 551 14.1 Estimation of standing crop 553 14.1.1 Measurement of biomass 553 14.2 Determination of energy density 554 14.3 Estimation of energy flow 555 14.4 The measurement of production 557 14.5 The measurement of feeding and assimilation 560 14.5.1 The quality of the food eaten 560 14.6 Feeding and assimilation rates 561 14.6.1 Radiotracer techniques 561 14.6.2 Gravimetric techniques 563 14.6.3 Indicator methods 564 14.6.4 Measurement of faecal output 565 14.7 The measurement of the energy loss due to respiration and metabolic process 565 14.7.1 Calorimetric 565 14.7.2 The exchange of respiratory gases 565 14.7.3 The respiratory rate 567 14.8 The energy budget, efficiencies and transfer coefficients 573 14.8.1 The energy budget of a population (or trophic level) 573 14.8.2 Energy transfer across trophic links 574 14.9 Identification of ecological pathways using stable isotopes 576 14.10 Assessment of energy and time costs of strategies 577 References 578 15 Studies at Large Spatial, Temporal and Numerical Scales and the Classification of Habitats 587 15.1 Remote sensing data from satellites 589 15.2 Remote sensing using piloted and unmanned aircraft 591 15.3 Long-term studies 592 15.3.1 Planning spatial and temporal sampling 593 15.3.2 The classification of time series 593 15.3.3 Detecting synchrony 603 15.3.4 Measuring temporal variability 603 15.3.5 Detecting break-points 604 15.4 Geographical information systems 607 15.5 Detection of density dependence in time series 608 15.5.1 Bulmer’s (1975) test 608 15.5.2 Pollard et al.’s (1987) randomisation test 609 15.5.3 Dennis and Taper’s (1994) bootstrap approach 611 15.5.4 Using a battery of approaches to detect density dependence 611 15.6 Citizen science projects 613 15.7 Ecosystem services 613 15.8 Habitat classification 614 15.8.1 Qualitative 614 15.8.2 Quantitative 616 References 617 Index 623 A colour plate section falls between pages 300 and 301

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Book SynopsisInvasion Genetics: the Baker & Stebbins legacy provides a state-of-the-art treatment of the evolutionary biology of invasive species, whilst also revisiting the historical legacy of one of the most important books in evolutionary biology: The Genetics of Colonizing Species, published in 1965 and edited by Herbert Baker and G. Ledyard Stebbins. This volume covers a range of topics concerned with the evolutionary biology of invasion including: phylogeography and the reconstruction of invasion history; demographic genetics; the role of stochastic forces in the invasion process; the contemporary evolution of local adaptation; the significance of epigenetics and transgenerational plasticity for invasive species; the genomic consequences of colonization; the search for invasion genes; and the comparative biology of invasive species. A wide diversity of invasive organisms are discussed including plants, animals, fungi and microbes.Trade Review"The book's format is easy to navigate, with single articles serving as chapters, providing a comfortable route through which one can locate useful references. The three sections are well defined and cohesive, and contain discussions that bring together the thoughts of the contributing authors on the featured articles...This book serves as a great reference source, with clearly defined articles and an easily navigable layout. It would prove similarly useful for those with interests in either evolution, genetics, or both." (Phenotype June 2017)Table of ContentsContributors, x Preface, xiii 1 Foundations of invasion genetics: the Baker and Stebbins legacy, 1SPENCER C. H. BARRETT PART 1 EVOLUTIONARY ECOLOGY, 19 Introduction, 21KATRINA M. DLUGOSCH AND INGRID M. PARKER 2 The influence of numbers on invasion success, 25TIM M. BLACKBURN, JULIE L. LOCKWOOD, AND PHILLIP CASSEY 3 Characteristics of successful alien plants, 40MARK VAN KLEUNEN, WAYNE DAWSON, AND NOËLIE MAUREL 4 Evolution of the mating system in colonizing plants, 57JOHN R. PANNELL 5 The population biology of fungal invasions, 81PIERRE GLADIEUX, ALICE FEURTEY, MICHAEL E. HOOD, ALODIE SNIRC, JOANNE CLAVEL, CYRIL DUTECH, MÉLANIE ROY, AND TATIANA GIRAUD 6 Contemporary evolution during invasion: evidence for differentiation, natural selection, and local adaptation, 101ROBERT I. COLAUTTI AND JENNIFER A. LAU 7 Exotics exhibit more evolutionary history than natives: a comparison of the ecology and evolution of exotic and native anole lizards, 122MATTHEW R. HELMUS, JOCELYN E. BEHM, WENDY A.M. JESSE, JASON J. KOLBE, JACINTHA ELLERS, AND JONATHAN B. LOSOS 8 Causes and consequences of failed adaptation to biological invasions: the role of ecological constraints, 139JENNIFER A. LAU AND CASEY P. terHORST Discussion, 153 PART 2 EVOLUTIONARY GENETICS, 159 Introduction, 161ROBERT I. COLAUTTI AND CAROL EUNMI LEE 9 Evolution of phenotypic plasticity in colonizing species, 165RUSSELL LANDE 10 Chromosome inversions, adaptive cassettes and the evolution of species’ ranges, 175MARK KIRKPATRICK AND BRIAN BARRETT 11 The distribution of genetic variance across phenotypic space and the response to selection, 187MARK W. BLOWS AND KATRINA McGUIGAN 12 Information entropy as a measure of genetic diversity and evolvability in colonization, 206TROY DAY 13 Expansion load: recessive mutations and the role of standing genetic variation, 218STEPHAN PEISCHL AND LAURENT EXCOFFIER 14 The devil is in the details: genetic variation in introduced populations and its contributions to invasion, 232KATRINA M. DLUGOSCH, SAMANTHA R. ANDERSON, JOSEPH BRAASCH, F. ALICE CANG, AND HEATHER D. GILLETTE Discussion, 253 PART 3 INVASION GENOMICS, 261 Introduction, 263LOREN H. RIESEBERG AND KATHRYN A. HODGINS 15 Genetic reconstructions of invasion history, 267MELANIA E. CRISTESCU 16 Comparative genomics in the Asteraceae reveals little evidence for parallel evolutionary change in invasive taxa, 283KATHRYN A. HODGINS, DAN G. BOCK, MIN A. HAHN, SYLVIA M. HEREDIA, KATHRYN G. TURNER, AND LOREN H. RIESEBERG 17 The role of climate adaptation in colonization success in Arabidopsis thaliana, 300JILL A. HAMILTON, MIKI OKADA, TONIA KORVES, AND JOHANNA SCHMITT 18 A genetic perspective on rapid evolution in cane toads (Rhinella marina), 313LEE A. ROLLINS, MARK F. RICHARDSON, AND RICHARD SHINE 19 Epigenetics of colonizing species? A study of Japanese knotweed in Central Europe, 328YUAN]YE ZHANG, MADALIN PAREPA, MARKUS FISCHER, AND OLIVER BOSSDORF Discussion, 341 20 What we still don’t know about invasion genetics, 346DAN G. BOCK, CELINE CASEYS, ROGER D. COUSENS, MIN A. HAHN, SYLVIA M. HEREDIA, SARIEL HÜBNER, KATHRYN G. TURNER, KENNETH D. WHITNEY, AND LOREN H. RIESEBERG Index, 371

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Book SynopsisA scholarly collection of timely essays on the behavioral science of peace With contributions from experts representing a wide variety of scholarly fields (behavioral and social sciences, philosophy, environmental science, anthropology and economics), Peace Ethology offers original essays on the most recent research and findings on the topic of the behavioral science of peace. This much-needed volume includes writings that examine four main areas of study: the proximate causation of peace, the developmental aspects of peace, the function and systems of peace and the evolution of peace. The popular belief persists that, by nature, humans are not pre-disposed to peace. However, archeological and paleontological evidence reveals that the vast majority of our time as a species has been spent in small hunter-gatherer bands that are basically peaceful and egalitarian in nature. The text also reveals that most of the earth's people are living in more peaceful soTable of ContentsList of Contributors ix Foreword xiRobert M.Sapolsky Acknowledgments xv 1 The Nature of Peace 1Peter Verbeek and Benjamin A. Peters Part One Proximate Causation 15 2 A Social‐Psychological Perspective on the Proximate Causation of Peaceful Behavior: The Needs‐Based Model of Reconciliation 17Nurit Shnabel 3 Inclusion as a Pathway to Peace: The Psychological Experiences of Exclusion and Inclusion in Culturally Diverse Social Settings 35Sabine Otten, Juliette Schaafsma, and Wiebren S. Jansen 4 The Peacekeeping and Peacemaking Role of Chimpanzee Bystanders 53Teresa Romero 5 The Experiential Peacebuilding Cycle: Grassroots Diplomacy, Environmental Education, and Environmental Norms 73Saleem H. Ali and Todd Walters Part Two Development 93 6 The Developmental Niche for Peace 95Darcia Narvaez 7 Children’s Peacekeeping and Peacemaking 113Cary J. Roseth 8 The Role of Relationships in the Emergence of Peace 133Ellen Furnari 9 Reintegration of Former Child Soldiers: Communal Approaches to Healing the Wounds and Building Peace in Postconflict Societies 153Michael Wessells and Kathleen Kostelny Part Three Function 171 10 Keeping the Peace or Enforcing Order? Overcoming Social Tension Between Police and Civilians 173Otto Adang, Sara Stronks, Misja van de Klomp, and Gabriel van den Brink 11 Constitutions as Peace Systems and the Function of the Costa Rican and Japanese Peace Constitutions 191Benjamin A. Peters 12 Exploring the Village Republic: Gandhi’s Oceanic Circles as Decentralized Peace Systems 211Joám Evans Pim 13 Building Peace Benefits 231Daniel Hyslop and Thomas Morgan Part Four Evolution 247 14 The Evolutionary Logic of Human Peaceful Behavior 249Douglas P. Fry 15 Trans‐Species Peacemaking: Our Evolutionary Heritage 267Harry Kunneman 16 Natural Peace 287Peter Verbeek Index 321

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Book SynopsisEnvironmental Experience and Plasticity of the Developing Brain goes beyond the genetic basis of neurodevelopment. Chapters illuminate the external factors that can dramatically impact the brain early in life and, consequently, the eventual accomplishment of developmental milestones and the construction of adult behavior and personality.Table of ContentsList of contributors, vii 1 Environmental enrichment and brain development, 1Alessandro Sale, Nicoletta Berardi, and Lamberto Maffei 2 Epigenetic control of visual cortex development and plasticity, 27Paola Tognini, Elena Putignano, and Tommaso Pizzorusso 3 Gene–environment interactions in the etiology of psychiatric and neurodevelopmental disorders, 47Mari A. Kondo and Anthony J. Hannan 4 Critical periods and neurodevelopmental brain disorders, 73Rhiannon M. Meredith 5 Maternal care and DNA methylation, 99Moshe Szyf 6 Neurobiology and programming capacity of attachment learning to nurturing and abusive caregivers, 117Tania L. Roth, Gordon A. Barr, Michael J. Lewis, and Regina M. Sullivan 7 Early environmental manipulations and long-term effects on brain neurotrophin levels, 139Francesca Cirulli and Enrico Alleva 8 Effects of genes and early experience on the development of primate behavior and stress reactivity, 161Sean P. Coyne and Dario Maestripieri 9 Institutional deprivation and neurobehavioral development in infancy, 185Jenalee R. Doom and Megan R. Gunnar 10 Impact of infantile massage on brain development, 215Andrea Guzzetta and Giovanni Cioni Index, 225

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Book SynopsisMoonlighting Proteins: Novel Virulence Factors in Bacterial Infections is a complete examination of the ways in which proteins with more than one unique biological action are able to serve as virulence factors in different bacteria. The book explores the pathogenicity of bacterial moonlighting proteins, demonstrating the plasticity of protein evolution as it relates to protein function and to bacterial communication. Highlighting the latest discoveries in the field, it details the approximately 70 known bacterial proteins with a moonlighting function related to a virulence phenomenon. Chapters describe the ways in which each moonlighting protein can function as such for a variety of bacterial pathogens and how individual bacteria can use more than one moonlighting protein as a virulence factor. The cutting-edge research contained here offers important insights into many topics, from bacterial colonization, virulence, and antibiotic resistance, to protein structure and Table of ContentsList of Contributors xv Preface xix About the Editor xxiii Part I Overview of Protein Moonlighting 1 1 What is Protein Moonlighting and Why is it Important? 3 Constance J. Jeffery 1.1 What is Protein Moonlighting? 3 1.2 Why is Moonlighting Important? 5 1.2.1 Many More Proteins Might Moonlight 5 1.2.2 Protein Structure/Evolution 5 1.2.3 Roles in Health and Disease 8 1.2.3.1 Humans 8 1.2.3.2 Bacteria 10 1.3 Current questions 11 1.3.1 How Many More Proteins Moonlight? 11 1.3.2 How Can We Identify Additional Proteins That Moonlight and all the Moonlighting Functions of Proteins? 11 1.3.3 In Developing Novel Therapeutics, How Can We Target the Appropriate Function of a Moonlighting Protein and Not Affect Other Functions of the Protein? 12 1.3.4 How do Moonlighting Proteins get Targeted to More Than One Location in the Cell? 12 1.3.5 What Changes in Expression Patterns Have Occurred to Enable the Protein to be Available in a New Time and Place to Perform a New Function? 12 1.4 Conclusions 13 References 13 2 Exploring Structure–Function Relationships in Moonlighting Proteins 21 Sayoni Das, Ishita Khan, Daisuke Kihara, and Christine Orengo 2.1 Introduction 21 2.2 Multiple Facets of Protein Function 22 2.3 The Protein Structure–Function Paradigm 23 2.4 Computational Approaches for Identifying Moonlighting Proteins 25 2.5 Classification of Moonlighting Proteins 26 2.5.1 Proteins with Distinct Sites for Different Functions in the Same Domain 27 2.5.1.1 α‐Enolase, Streptococcus pneumonia 27 2.5.1.2 Albaflavenone monooxygenase, Streptomyces coelicolor A3(2) 29 2.5.1.3 MAPK1/ERK2, Homo sapiens 30 2.5.2 Proteins with Distinct Sites for Different Functions in More Than One Domain 30 2.5.2.1 Malate synthase, Mycobacterium tuberculosis 31 2.5.2.2 BirA, Escherichia coli 31 2.5.2.3 MRDI, Homo sapiens 33 2.5.3 Proteins Using the Same Residues for Different Functions 33 2.5.3.1 GAPDH E. coli 33 2.5.3.2 Leukotriene A4 hydrolase, Homo sapiens 33 2.5.4 Proteins Using Different Residues in the Same/Overlapping Site for Different Functions 34 2.5.4.1 Phosphoglucose isomerase, Oryctolagus cuniculus, Mus musculus, Homo sapiens 34 2.5.4.2 Aldolase, Plasmodium falciparum 36 2.5.5 Proteins with Different Structural Conformations for Different Functions 36 2.5.5.1 RfaH, E. coli 36 2.6 Conclusions 37 References 39 Part II Proteins Moonlighting in Prokarya 45 3 Overview of Protein Moonlighting in Bacterial Virulence 47 Brian Henderson 3.1 Introduction 47 3.2 The Meaning of Bacterial Virulence and Virulence Factors 47 3.3 Affinity as a Measure of the Biological Importance of Proteins 49 3.4 Moonlighting Bacterial Virulence Proteins 50 3.4.1 Bacterial Proteins Moonlighting as Adhesins 52 3.4.2 Bacterial Moonlighting Proteins That Act as Invasins 59 3.4.3 Bacterial Moonlighting Proteins Involved in Nutrient Acquisition 59 3.4.4 Bacterial Moonlighting Proteins Functioning as Evasins 60 3.4.5 Bacterial Moonlighting Proteins with Toxin‐like Actions 63 3.5 Bacterial Moonlighting Proteins Conclusively Shown to be Virulence Factors 64 3.6 Eukaryotic Moonlighting Proteins That Aid in Bacterial Virulence 66 3.7 Conclusions 67 References 68 4 Moonlighting Proteins as Cross‐Reactive Auto‐Antigens 81 Willem van Eden 4.1 Autoimmunity and Conservation 81 4.2 Immunogenicity of Conserved Proteins 82 4.3 HSP Co‐induction, Food, Microbiota, and T-cell Regulation 84 4.3.1 HSP as Targets for T‐Cell Regulation 85 4.4 The Contribution of Moonlighting Virulence Factors to Immunological Tolerance 87 References 88 Part III Proteins Moonlighting in Bacterial Virulence 93 Part 3.1 Chaperonins: A Family of Proteins with Widespread Virulence Properties 95 5 Chaperonin 60 Paralogs in Mycobacterium tuberculosis and Tubercle Formation 97 Brian Henderson 5.1 Introduction 97 5.2 Tuberculosis and the Tuberculoid Granuloma 97 5.3 Mycobacterial Factors Responsible for Granuloma Formation 98 5.4 Mycobacterium tuberculosis Chaperonin 60 Proteins, Macrophage Function, and Granuloma Formation 100 5.4.1 Mycobacterium tuberculosis has Two Chaperonin 60 Proteins 100 5.4.2 Moonlighting Actions of Mycobacterial Chaperonin 60 Proteins 101 5.4.3 Actions of Mycobacterial Chaperonin 60 Proteins Compatible with the Pathology of Tuberculosis 102 5.4.4 Identification of the Myeloid‐Cell‐Activating Site in M. tuberculosis Chaperonin 60.1 105 5.5 Conclusions 106 References 106 6 Legionella pneumophila Chaperonin 60, an Extra‐ and Intra‐Cellular Moonlighting Virulence‐Related Factor 111 Karla N. Valenzuela‐Valderas, Angela L. Riveroll, Peter Robertson, Lois E. Murray, and Rafael A. Garduno 6.1 Background 111 6.2 HtpB is an Essential Chaperonin with Protein‐folding Activity 112 6.3 Experimental Approaches to Elucidate the Functional Mechanisms of HtpB 112 6.3.1 The Intracellular Signaling Mechanism of HtpB in Yeast 113 6.3.2 Yeast Two‐Hybrid Screens 118 6.4 Secretion Mechanisms Potentially Responsible for Transporting HtpB to Extracytoplasmic Locations 120 6.4.1 Ability of GroEL and HtpB to Associate with Membranes 121 6.4.2 Ongoing Mechanistic Investigations on Chaperonins Secretion 122 6.5 Identifying Functionally Important Amino Acid Positions in HtpB 124 6.5.1 Site‐Directed Mutagenesis 125 6.6 Functional Evolution of HtpB 126 6.7 Concluding Remarks 127 References 129 Part 3.2 Peptidylprolyl Isomerases, Bacterial Virulence, and Targets for Therapy 135 7 An Overview of Peptidylprolyl Isomerases (PPIs) in Bacterial Virulence 137 Brian Henderson 7.1 Introduction 137 7.2 Proline and PPIs 137 7.3 Host PPIs and Responses to Bacteria and Bacterial Toxins 138 7.4 Bacterial PPIs as Virulence Factors 138 7.4.1 Proposed Mechanism of Virulence of Legionella pneumophila Mip 140 7.5 Other Bacterial PPIs Involved in Virulence 140 7.6 Conclusions 142 References 142 Part 3.3 Glyceraldehyde 3‐Phosphate Dehydrogenase (GAPDH): A Multifunctional Virulence Factor 147 8 GAPDH: A Multifunctional Moonlighting Protein in Eukaryotes and Prokaryotes 149 Michael A. Sirover 8.1 Introduction 149 8.2 GAPDH Membrane Function and Bacterial Virulence 150 8.2.1 Bacterial GAPDH Virulence 151 8.2.2 GAPDH and Iron Metabolism in Bacterial Virulence 153 8.3 Role of Nitric Oxide in GAPDH Bacterial Virulence 153 8.3.1 Nitric Oxide in Bacterial Virulence: Evasion of the Immune Response 154 8.3.2 Formation of GAPDHcys‐NO by Bacterial NO Synthases 155 8.3.3 GAPDHcys‐NO in Bacterial Virulence: Induction of Macrophage Apoptosis 155 8.3.4 GAPDHcys‐NO in Bacterial Virulence: Inhibition of Macrophage iNOS Activity 156 8.3.5 GAPDHcys‐NO in Bacterial Virulence: Transnitrosylation to Acceptor Proteins 157 8.4 GAPDH Control of Gene Expression and Bacterial Virulence 158 8.4.1 Bacterial GAPDH Virulence 159 8.5 Discussion 160 Acknowledgements 162 References 162 9 Streptococcus pyogenes GAPDH: A Cell‐Surface Major Virulence Determinant 169 Vijay Pancholi 9.1 Introduction and Early Discovery 169 9.2 GAS GAPDH: A Major Surface Protein with Multiple Binding Activities 170 9.3 AutoADP‐Ribosylation of SDH and Other Post‐Translational Modifications 172 9.4 Implications of the Binding of SDH to Mammalian Proteins for Cell Signaling and Virulence Mechanisms 173 9.5 Surface Export of SDH/GAPDH: A Cause or Effect? 178 9.6 SDH: The GAS Virulence Factor‐Regulating Virulence Factor 180 9.7 Concluding Remarks and Future Perspectives 183 References 183 10 Group B Streptococcus GAPDH and Immune Evasion 195 Paula Ferreira and Patrick Trieu‐Cuot 10.1 The Bacterium GBS 195 10.2 Neonates are More Susceptible to GBS Infection than Adults 195 10.3 IL‐10 Production Facilitates Bacterial Infection 196 10.4 GBS Glyceraldehyde‐3‐Phosphate Dehydrogenase Induces IL‐10 Production 197 10.5 Summary 199 References 200 11 Mycobacterium tuberculosis Cell‐Surface GAPDH Functions as a Transferrin Receptor 205 Vishant M. Boradia, Manoj Raje, and Chaaya Iyengar Raje 11.1 Introduction 205 11.2 Iron Acquisition by Bacteria 206 11.2.1 Heme Uptake 206 11.2.2 Siderophore‐Mediated Uptake 207 11.2.3 Transferrin Iron Acquisition 207 11.3 Iron Acquisition by Intracellular Pathogens 207 11.4 Iron Acquisition by M. tb 208 11.4.1 Heme Uptake 208 11.4.2 Siderophore‐Mediated Iron Acquisition 209 11.4.3 Transferrin‐Mediated Iron Acquisition 209 11.5 Glyceraldehyde‐3‐Phosphate Dehydrogenase (GAPDH) 210 11.6 Macrophage GAPDH and Iron Uptake 210 11.6.1 Regulation 210 11.6.2 Mechanism of Iron Uptake and Efflux 211 11.6.3 Role of Post‐Translational Modifications 211 11.7 Mycobacterial GAPDH and Iron Uptake 212 11.7.1 Regulation 212 11.7.2 Mechanism of Iron Uptake 215 11.7.3 Uptake by Intraphagosomal M. tb 216 11.8 Conclusions and Future Perspectives 216 Acknowledgements 218 References 219 12 GAPDH and Probiotic Organisms 225 Hideki Kinoshita 12.1 Introduction 225 12.2 Probiotics and Safety 225 12.3 Potential Risk of Probiotics 227 12.4 Plasminogen Binding and Enhancement of its Activation 228 12.5 GAPDH as an Adhesin 229 12.6 Binding Regions 232 12.7 Mechanisms of Secretion and Surface Localization 234 12.8 Other Functions 235 12.9 Conclusion 236 References 237 Part 3.4 Cell‐Surface Enolase: A Complex Virulence Factor 245 13 Impact of Streptococcal Enolase in Virulence 247 Marcus Fulde and Simone Bergmann 13.1 Introduction 247 13.2 General Characteristics 248 13.3 Expression and Surface Exposition of Enolase 249 13.4 Streptococcal Enolase as Adhesion Cofactor 252 13.4.1 Enolase as Plasminogen‐Binding Protein 252 13.4.1.1 Plasminogen‐Binding Sites of Streptococcal Enolases 253 13.4.2 Role of Enolase in Plasminogen‐Mediated Bacterial‐Host Cell Adhesion and Internalization 254 13.4.3 Enolase as Plasminogen‐Binding Protein in Non‐Pathogenic Bacteria 255 13.5 Enolase as Pro‐Fibrinolytic Cofactor 256 13.5.1 Degradation of Fibrin Thrombi and Components of the Extracellular Matrix 257 13.6 Streptococcal Enolase as Cariogenic Factor in Dental Disease 258 13.7 Conclusion 258 Acknowledgement 259 References 259 14 Streptococcal Enolase and Immune Evasion 269 Masaya Yamaguchi and Shigetada Kawabata 14.1 Introduction 269 14.2 Localization and Crystal Structure 271 14.3 Multiple Binding Activities of α‐Enolase 273 14.4 Involvement of α‐Enolase in Gene Expression Regulation 276 14.5 Role of Anti‐α‐Enolase Antibodies in Host Immunity 277 14.6 α‐Enolase as Potential Therapeutic Target 279 14.7 Questions Concerning α‐Enolase 281 References 281 15 Borrelia burgdorferi Enolase and Plasminogen Binding 291 Catherine A. Brissette 15.1 Introduction to Lyme Disease 291 15.2 Life Cycle 292 15.3 Borrelia Virulence Factors 292 15.4 Plasminogen Binding by Bacteria 293 15.5 B. burgdorferi and Plasminogen Binding 294 15.6 Enolase 295 15.7 B. burgdorferi Enolase and Plasminogen Binding 297 15.8 Concluding Thoughts 301 Acknowledgements 301 References 301 Part 3.5 Other Glycolytic Enzymes Acting as Virulence Factors 309 16 Triosephosphate Isomerase from Staphylococcus aureus and Plasminogen Receptors on Microbial Pathogens 311 Reiko Ikeda and Tomoe Ichikawa 16.1 Introduction 311 16.2 Identification of Triosephosphate Isomerase on S. aureus as a Molecule that Binds to the Pathogenic Yeast C. neoformans 312 16.2.1 Co‐Cultivation of S. aureus and C. neoformans 312 16.2.2 Identification of Adhesins on S. aureus and C. neoformans 312 16.2.3 Mechanisms of C. neoformans Cell Death 313 16.3 Binding of Triosephosphate Isomerase with Human Plasminogen 314 16.4 Plasminogen‐Binding Proteins on Trichosporon asahii 314 16.5 Plasminogen Receptors on C. neoformans 316 16.6 Conclusions 316 References 317 17 Moonlighting Functions of Bacterial Fructose 1,6‐Bisphosphate Aldolases 321 Neil J. Oldfield, Fariza Shams, Karl G. Wooldridge, and David P.J. Turner 17.1 Introduction 321 17.2 Fructose 1,6‐bisphosphate Aldolase in Metabolism 321 17.3 Surface Localization of Streptococcal Fructose 1,6‐bisphosphate Aldolases 322 17.4 Pneumococcal FBA Adhesin Binds Flamingo Cadherin Receptor 323 17.5 FBA is Required for Optimal Meningococcal Adhesion to Human Cells 324 17.6 Mycobacterium tuberculosis FBA Binds Human Plasminogen 325 17.7 Other Examples of FBAs with Possible Roles in Pathogenesis 326 17.8 Conclusions 327 References 327 Part 3.6 Other Metabolic Enzymes Functioning in Bacterial Virulence 333 18 Pyruvate Dehydrogenase Subunit B and Plasminogen Binding in Mycoplasma 335 Anne Gründel, Kathleen Friedrich, Melanie Pfeiffer, Enno Jacobs, and Roger Dumke 18.1 Introduction 335 18.2 Binding of Human Plasminogen to M. pneumoniae 337 18.3 Localization of PDHB on the Surface of M. pneumoniae Cells 340 18.4 Conclusions 343 References 344 Part 3.7 Miscellaneous Bacterial Moonlighting Virulence Proteins 349 19 Unexpected Interactions of Leptospiral Ef‐Tu and Enolase 351 Natália Salazar and Angela Barbosa 19.1 Leptospira –Host Interactions 351 19.2 Leptospira Ef‐Tu 352 19.3 Leptospira Enolase 353 19.4 Conclusions 354 References 354 20 Mycobacterium tuberculosis Antigen 85 Family Proteins: Mycolyl Transferases and Matrix‐Binding Adhesins 357 Christopher P. Ptak, Chih‐Jung Kuo, and Yung‐Fu Chang 20.1 Introduction 357 20.2 Identification of Antigen 85 358 20.3 Antigen 85 Family Proteins: Mycolyl Transferases 359 20.3.1 Role of the Mycomembrane 359 20.3.2 Ag85 Family of Homologous Proteins 359 20.3.3 Inhibition and Knockouts of Ag85 360 20.4 Antigen 85 Family Proteins: Matrix‐Binding Adhesins 361 20.4.1 Abundance and Location 361 20.4.2 Ag85 a Fibronectin‐Binding Adhesin 362 20.4.3 Ag85 an Elastin‐Binding Adhesin 363 20.4.4 Implication in Disease 364 20.5 Conclusion 365 Acknowledgement 365 References 365 Part 3.8 Bacterial Moonlighting Proteins that Function as Cytokine Binders/Receptors 371 21 Miscellaneous IL‐1β‐Binding Proteins of Aggregatibacter actinomycetemcomitans 373 Riikka Ihalin 21.1 Introduction 373 21.2 A. actinomycetemcomitans Biofilms Sequester IL‐1β 374 21.3 A. actinomycetemcomitans Cells Take in IL‐1β 375 21.3.1 Novel Outer Membrane Lipoprotein of A. actinomycetemcomitans Binds IL‐1β 375 21.3.2 IL‐1β Localizes to the Cytosolic Face of the Inner Membrane and in the Nucleoids of A. actinomycetemcomitans 377 21.3.3 Inner Membrane Protein ATP Synthase Subunit β Binds IL‐1β 377 21.3.4 DNA‐Binding Histone‐Like Protein HU Interacts with IL‐1β 378 21.4 The Potential Effects of IL‐1β on A. actinomycetemcomitans 379 21.4.1 Biofilm Amount Increases and Metabolic Activity Decreases 379 21.4.2 Potential Changes in Gene Expression 380 21.5 Conclusions 381 References 382 Part 3.9 Moonlighting Outside of the Box 387 22 Bacteriophage Moonlighting Proteins in the Control of Bacterial Pathogenicity 389 Janine Z. Bowring, Alberto Marina, José R. Penadés, and Nuria Quiles‐Puchalt 22.1 Introduction 389 22.2 Bacteriophage T4 I‐TevI Homing Endonuclease Functions as a Transcriptional Autorepressor 391 22.3 Capsid Psu Protein of Bacteriophage P4 Functions as a Rho Transcription Antiterminator 394 22.4 Bacteriophage Lytic Enzymes Moonlight as Structural Proteins 398 22.5 Moonlighting Bacteriophage Proteins De‐Repressing Phage‐Inducible Chromosomal Islands 398 22.6 dUTPase, a Metabolic Enzyme with a Moonlighting Signalling Role 401 22.7 Escherichia coli Thioredoxin Protein Moonlights with T7 DNA Polymerase for Enhanced T7 DNA Replication 404 22.8 Discussion 404 References 406 23 Viral Entry Glycoproteins and Viral Immune Evasion 413 Jonathan D. Cook and Jeffrey E. Lee 23.1 Introduction 413 23.2 Enveloped Viral Entry 414 23.3 Moonlighting Activities of Viral Entry Glycoproteins 415 23.3.1 Viral Entry Glycoproteins Moonlighting as Evasins 416 23.3.2 Evading the Complement System 417 23.3.3 Evading Antibody Surveillance 419 23.3.3.1 The Viral Glycan Shield 419 23.3.3.2 Shed Viral Glycoproteins: An Antibody Decoy 421 23.3.3.3 Antigenic Variations in Viral Glycoproteins 421 23.3.3.4 Shed Viral Glycoproteins and Immune Signal Modulation 423 23.3.4 Evading Host Restriction Factors 423 23.3.5 Modulation of Other Immune Pathways 424 23.4 Viral Entry Proteins Moonlighting as Saboteurs of Cellular Pathways 427 23.4.1 Sabotaging Signal Transduction Cascades 427 23.4.2 Host Surface Protein Sabotage 428 23.5 Conclusions 429 References 429 Index 439

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Book SynopsisThe past 25 years has seen the emergence of a wealth of data suggesting that novel biological functions of known proteins play important roles in biology and medicine. This ability of proteins to exhibit more than one unique biological activity is known as protein moonlighting.Trade Review'The “Protein Moonlighting in Biology and Medicine” book presents a very well-designed, comprehensive account of the basic knowledge and practical aspects of moonlighting proteins that have been culminating over the last two decades. Written by a cell biologist teaming up with two protein evolution and bioinformatics experts, this title provides a very useful digestible read on the structure, function, evolution, and bioinformatics of moonlighting proteins. Readers are oriented to these topics by two relevant introductory chapters. The book also addresses the diverse involvement of moonlighting proteins in cell biology, health maintenance, and idiopathic and infectious diseases. A very useful feature in this book, which is not frequently considered in other multi-authored titles, is the authors’ effort to present a coherent story by bridging chapters together incorporating an ‘introduction’ section at the beginning of each one. It is a very useful, contemporary book for students and researchers in biology, biomedicine and protein science.' Science Progress, 100:4 (2017)Table of ContentsPreface xi 1 An Introduction to the Protein Molecule 1 1.1 Why Study Protein Moonlighting? 1 1.2 A Brief History of Proteins 2 1.3 Protein Biology 4 1.4 Protein Structure and Function 6 1.5 Protein Sequence Determination, Structures, and Bioinformatics 9 1.6 Regulation of Protein Synthesis 11 1.7 Conclusions 12 References 12 2 How Proteins Evolve? 15 2.1 Introduction 15 2.2 A Darwinian View of Molecular Evolution 16 2.3 The Neutral and Nearly Neutral Theories of Molecular Evolution 18 2.4 Mutation, Fitness, and Evolution 20 2.5 Proteins Evolve at Different Rates 24 2.6 Protein Evolution by Gene Duplication 25 2.7 Conclusions 26 References 26 3 A Brief History of Protein Moonlighting 31 3.1 Introduction 31 3.2 Protein Moonlighting: The Early Beginnings 31 3.3 Eye Lens Proteins and Gene Sharing 33 3.4 Multifunctional Metabolic Proteins and Molecular Chaperones 35 3.5 The Return of Moonlighting 37 3.6 A Current View of Protein Moonlighting 39 3.7 The Current Population of Moonlighting Proteins 40 3.8 Conclusions 40 References 40 4 The Structural Basis of Protein Moonlighting 45 4.1 Introduction 45 4.2 The Structural Biology of Protein Moonlighting 48 4.2.1 Exploiting Protein Bulk 49 4.2.2 Catalytic Promiscuity 49 4.2.3 Exploiting Separate Functional Sites 50 4.2.4 Exploiting Alternatively Folded Forms 55 4.2.5 Alternative Oligomerization 56 4.2.6 Posttranslational Modifications 57 4.3 Predicting and Engineering Moonlighting 57 4.4 Conclusions 58 References 60 5 Protein Moonlighting and New Thoughts about Protein Evolution 63 5.1 Introduction 63 5.2 A Darwinian Perspective of Protein Moonlighting 65 5.3 Origin and Evolutionary Stability of Protein Moonlighting 67 5.4 Mutational Robustness and the Persistence of Moonlighting Proteins 68 5.5 Proteins Robust to Mutations Are Highly Evolvable 70 5.6 Moonlighting Proteins and the Rate of Protein Evolution 72 5.7 Molecular Chaperones Buffer the Effects of Mutations on Proteins, Expediting Their Rate of Evolution and Enabling Moonlighting 74 5.8 Protein Moonlighting Can Lead to Functional Specialization 76 5.9 Conclusions 76 References 77 6 Biological Consequences of Protein Moonlighting 81 6.1 Introduction 81 6.2 The Human Genome, Protein]Coding Genes, and Cellular Complexity 81 6.3 How Many Moonlighting Proteins Exist/What Proportion of the Proteome Moonlights? 83 6.4 Secretion of Moonlighting Proteins: A Major Problem Seeking Solution 86 6.5 How Does Protein Moonlighting Influence Systems Biology? 90 6.5.1 Systems Biology and Protein Moonlighting 91 6.5.2 Analysis of the Systems Biology of the Moonlighting Protein Glycerol Kinase 95 6.6 Role of Moonlighting Proteins in the Control of the Biology of the Healthy Cell 97 6.6.1 Do Moonlighting Protein Exhibit Novel Biological Functions? 97 6.6.2 Moonlighting Proteins and Normal Cellular Functions 104 6.6.2.1 Secreted Moonlighting Proteins 105 6.6.2.2 Moonlighting Proteins on the Plasma Membrane 106 6.6.2.3 Moonlighting Proteins in the Nucleus or Interacting with Nucleic Acids 110 6.6.2.4 Moonlighting Proteins in Cellular Vesicular Trafficking 113 6.6.2.5 Moonlighting in the Cell Cytoplasm 113 6.6.2.6 Ribosomal Moonlighting Proteins 115 6.6.2.7 Moonlighting in Cell Division 118 6.6.2.8 Moonlighting Proteins Existing in Multiple Cellular Compartments 118 6.7 Moonlighting Proteins in the Biology of Single]Celled Eukaryotes 119 6.8 Moonlighting Proteins Interacting with Moonlighting Proteins 119 6.9 Moonlighting Proteins and Vision: Are Lens Proteins Moonlighting? 120 6.10 Conclusions 121 References 121 7 Protein Moonlighting and Human Health and Idiopathic Human Disease 143 7.1 Introduction 143 7.2 Mammalian Moonlighting Proteins Involved in the Biology of the Cell 143 7.3 Moonlighting Proteins and Human Physiology (Healthy Interactions of Moonlighting Proteins) 144 7.3.1 Cellular Iron Uptake: GAPDH Binds to Iron]Binding Proteins 144 7.3.2 Moonlighting Proteins Involved with the Vasculature 149 7.3.2.1 Thymidine Phosphorylase 149 7.3.2.2 Protein Disulfide Isomerase (PDI) 150 7.3.2.3 Mitochondrial Coupling Factor (Mcf)6 150 7.3.2.4 Miscellaneous Moonlighting Proteins 151 7.3.3 Secreted and Cell Surface Histones and Human Physiology 152 7.3.4 Moonlighting Proteins in Reproduction 154 7.3.4.1 Chaperonin (Hsp)10 and Pregnancy 154 7.3.4.2 Phosphoglucoisomerase and Implantation in the Ferret 155 7.3.4.3 Miscellaneous Moonlighting Proteins and Pregnancy 155 7.3.4.4 Moonlighting Proteins, Sperm, and Fertilization 156 7.3.5 Moonlighting Proteins Involved in Controlling Inflammation 157 7.3.5.1 Ubiquitin 158 7.3.5.2 Interferon]Stimulated Gene 15 (ISG15) 159 7.3.5.3 Thioredoxin 159 7.3.5.4 TNF]Stimulated Gene 6 (TSG]6) 160 7.3.5.5 Ribosomal Protein L13a 161 7.3.5.6 Ribosomal Protein S19 161 7.3.5.7 Adiponectin and Inflammation 162 7.3.5.8 Miscellaneous Proteins 162 7.3.6 Moonlighting Proteins as Therapeutics 162 7.3.6.1 Hsp10 164 7.3.6.2 BiP 164 7.3.6.3 Ubiquitin 165 7.3.6.4 Moonlighting Proteins Involved in Wound Healing 165 7.4 Moonlighting Proteins in Human Pathology 166 7.4.1 Phosphoglucoisomerase as a Factor in Human Pathology 166 7.4.2 Moonlighting Proteins in Human Cancer 170 7.4.2.1 α]Enolase 170 7.4.2.2 Aldolase 171 7.4.2.3 Phosphofructokinase 171 7.4.2.4 Triosephosphate Isomerase 172 7.4.2.5 GAPDH 172 7.4.2.6 Phosphoglycerate Kinase (PGK) 172 7.4.2.7 Pyruvate Kinase (PK) 173 7.4.2.8 BiP/Grp78 173 7.4.2.9 Hsp90 174 7.4.2.10 Hsp27 175 7.4.2.11 Cyclophilin A (CypA) 176 7.4.2.12 Miscellaneous Proteins 176 7.4.3 Molecular Chaperones and Protein]Folding Catalysts in Human Inflammatory Pathology 177 7.4.3.1 Chaperonin (Heat Shock Protein) 60 in Cardiovascular Disease 177 7.4.3.2 Hsp70 (HSPA1) in Cardiovascular Disease 178 7.4.3.3 Cyclophilin A 179 7.4.3.4 Thioredoxin and Thioredoxin]80 180 7.4.3.5 Peroxiredoxins 181 7.4.4 DAMPs: Moonlighting Proteins in Human Inflammatory Pathology 181 7.4.4.1 S100 Proteins 182 7.4.4.2 High]Mobility Group Box 1 Protein 182 7.4.4.3 Histones 183 7.4.5 Moonlighting Proteins and Vascular Pathology 183 7.4.5.1 Histones 183 7.4.5.2 Mitochondrial Coupling Factor 6 184 7.5 Neomorphic Moonlighting Proteins and Human Diseases 185 7.6 Moonlighting Proteins in Autoimmune Disease 185 7.7 Conclusions 188 References 188 8 Protein Moonlighting and Infectious Disease 223 8.1 Introduction 223 8.2 Microbial Colonization and Infection 224 8.3 Bacterial Virulence Mechanisms 224 8.4 Moonlighting Proteins in Bacterial Virulence 227 8.4.1 Affinities of Binding of Bacterial Moonlighting Proteins 227 8.4.2 Bacteria Utilizing Moonlighting Proteins 229 8.4.3 Identity of the Bacterial Proteins That Moonlight 232 8.5 Biological Activities of Bacterial Moonlighting Proteins as Virulence Factors 237 8.5.1 Bacterial Moonlighting Proteins Acting as Adhesins 237 8.5.2 Bacterial Moonlighting Proteins Acting as Invasins 248 8.5.3 Bacterial Moonlighting Proteins Acting as Evasins 248 8.5.4 Bacterial Moonlighting Proteins with Activity Similar to Bacterial Toxins 252 8.5.5 Bacterial Moonlighting Proteins Acting as Receptors for Nutrients 256 8.5.6 Miscellaneous Actions of Moonlighting Proteins 256 8.5.7 Conclusions 257 8.6 Examples of Bacterial Moonlighting Proteins in Human Infectious Disease 257 8.7 Moonlighting Proteins in Fungi 259 8.8 Moonlighting Proteins in Protozoal Infections 260 8.9 Conclusions 262 References 262 9 Protein Moonlighting: The Future 281 9.1 Introduction 281 9.2 How Prevalent Is Protein Moonlighting? 282 9.3 Evolutionary Biology of Protein Moonlighting 284 9.3.1 Antibodies and Protein Moonlighting 285 9.4 Protein Posttranslational Modification and Protein Moonlighting 286 9.5 Genetics and Protein Moonlighting 287 9.6 Protein Moonlighting and Systems Biology 288 9.7 Moonlighting Proteins and the Response to Drugs 290 9.8 Moonlighting Proteins as Drug Targets 292 9.9 Conclusions 292 References 293 Index 297

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Book SynopsisProvides a tutorial on the computational tools that use mathematical optimization concepts and representations for the curation, analysis and redesign of metabolic networks Organizes, for the first time, the fundamentals of mathematical optimization in the context of metabolic network analysisReviews the fundamentals of different classes of optimization problems including LP, MILP, MLP and MINLPExplains the most efficient ways of formulating a biological problem using mathematical optimizationReviews a variety of relevant problems in metabolic network curation, analysis and redesign with an emphasis on details of optimization formulationsProvides a detailed treatment of bilevel optimization techniques for computational strain design and other relevant problemsTable of ContentsPreface xiii 1 Mathematical Optimization Fundamentals 1 1.1 Mathematical Optimization and Modeling 1 1.2 Basic Concepts and Definitions 7 1.2.1 Neighborhood of a Point 7 1.2.2 Interior of a Set 7 1.2.3 Open Set 8 1.2.4 Closure of a Set 8 1.2.5 Closed Set 8 1.2.6 Bounded Set 8 1.2.7 Compact Set 8 1.2.8 Continuous Functions 9 1.2.9 Global and Local Minima 9 1.2.10 Existence of an Optimal Solution 9 1.3 Convex Analysis 10 1.3.1 Convex Sets and Their Properties 10 1.3.2 Convex Functions and Their Properties 13 1.3.3 Convex Optimization Problems 19 1.3.4 Generalization of Convex Functions 20 Exercises 20 References 22 2 LP and Duality Theory 23 2.1 Canonical and Standard Forms of an LP Problem 23 2.1.1 Canonical Form 24 2.1.2 Standard Form 24 2.2 Geometric Interpretation of an LP Problem 26 2.3 Basic Feasible Solutions 28 2.4 Simplex Method 30 2.5 Duality in Linear Programming 35 2.5.1 Formulation of the Dual Problem 35 2.5.2 Primal‐Dual Relations 38 2.5.3 The Karush‐Kuhn‐Tucker (KKT) Optimality Conditions 39 2.5.4 Economic Interpretation of the Dual Variables 40 2.6 Nonlinear Optimization Problems that can be Transformed into LP Problems 45 2.6.1 Absolute Values in the Objective Function 45 2.6.2 Minmax Optimization Problems with Linear Constraints 46 2.6.3 Linear Fractional Programming 47 Exercises 49 References 50 3 Flux Balance Analysis and LP Problems 53 3.1 Mathematical Modeling of Metabolism 54 3.1.1 Kinetic Modeling of Metabolism 54 3.1.2 Stoichiometric-Based Modeling of Metabolism 54 3.2 Genome‐Scale Stoichiometric Models of Metabolism 55 3.2.1 Gene–Protein–Reaction Associations 55 3.2.2 The Biomass Reaction 56 3.2.3 Metabolite Compartments 57 3.2.4 Scope and Applications 57 3.3 Flux Balance Analysis (FBA) 57 3.3.1 Cellular Inputs, Outputs and Metabolic Sinks 58 3.3.2 Component Balances 59 3.3.3 Thermodynamic and Capacity Constraints 60 3.3.4 Objective Function 61 3.3.5 FBA Optimization Formulation 62 3.4 Simulating Gene Knockouts 67 3.5 Maximum Theoretical Yield 68 3.5.1 Maximum Theoretical Yield of Product Formation 68 3.5.2 Biomass vs. Product Trade‐Off 69 3.6 Flux Variability Analysis (Fva) 71 3.7 Flux Coupling Analysis 73 Exercises 77 References 78 4 Modeling with Binary Variables and MILP Fundamentals 81 4.1 Modeling with Binary Variables 83 4.1.1 Continuous Variable On/Off Switching 83 4.1.2 Condition‐Dependent Variable Switching 83 4.1.3 Condition‐Dependent Constraint Switching 84 4.1.4 Modeling AND Relations 84 4.1.5 Modeling OR Relations 86 4.1.6 Exact Linearization of the Product of a Continuous and a Binary Variable 86 4.1.7 Modeling Piecewise Linear Functions 87 4.2 Solving Milp Problems 89 4.2.1 Branch‐and‐Bound Procedure for Solving MILP Problems 90 4.2.2 Finding Alternative Optimal Integer Solutions 97 4.3 Efficient Formulation Strategies for Milp Problems 97 4.3.1 Using the Fewest Possible Binary Variables 97 4.3.2 Fix All Binary Variables that do not Affect the Optimal Solution 98 4.3.3 Group All Coupled Binary Variables 98 4.3.4 Segregate Binary Variables in Constraints Rather than in the Objective Function 98 4.3.5 Use Tight Bounds for All Continuous Variables 99 4.3.6 Introduce LP Relaxation Tightening Constraints 99 4.4 Identifying Minimal Reaction Sets Supporting Growth 102 Exercises 104 References 106 5 T hermodynamic Analysis of Metabolic Networks 107 5.1 Thermodynamic Assessment of Reaction Directionality 107 5.2 Eliminating Thermodynamically Infeasible Cycles (TICs) 109 5.2.1 Cycles in Cellular Metabolism 109 5.2.2 Thermodynamically Infeasible Cycles 110 5.2.3 Identifying Reactions Participating in TICs 111 5.2.4 Thermodynamics‐Based Metabolic Flux Analysis 111 5.2.5 Elimination of the TICs by Applying the Loop Law 113 5.2.6 Elimination of the TICs by Modifying the Metabolic Model 115 Exercises 116 References 117 6 Resolving Network Gaps and Growth Prediction Inconsistencies in Metabolic Networks 119 6.1 Finding and Filling Network Gaps in Metabolic Models 119 6.1.1 Categorization of Gaps in a Metabolic Model 119 6.1.2 Gap Finding 120 6.1.3 Gap Filling 123 6.2 Resolving Growth Prediction Inconsistencies 126 6.2.1 Quality Metrics for Quantifying the Accuracy of Metabolic Models 127 6.2.2 Automated Reconciliation of Growth Prediction Inconsistencies Using GrowMatch 127 6.2.3 Resolution of Higher‐Order Gene Deletion Inconsistencies 130 6.3 Verification of Model Correction Strategies 132 Exercise 133 References 133 7 Identification of Connected Paths to Target Metabolites 137 7.1 Using Milp to Identify Shortest Paths in Metabolic Graphs 137 7.2 Using Milp to Identify Non‐Native Reactions for the Production of a Target Metabolite 142 7.3 Designing Overall Stoichiometric Conversions 144 7.3.1 Determining the Stoichiometry of Overall Conversion 144 7.3.2 Identifying Reactions Steps Conforming to the Identified Overall Stoichiometry 146 Exercises 151 References 151 8 Computational Strain Design 155 8.1 Early Computational Treatment of Strain Design 156 8.2 Optknock 158 8.2.1 Solution Procedure for OptKnock 159 8.2.2 Improving the Computational Efficiency of OptKnock 164 8.2.3 Connecting Reaction Eliminations with Gene Knockouts 165 8.2.4 Impact of Knockouts on the Biomass vs. Product Trade‐Off 165 8.3 Optknock Modifications 167 8.3.1 RobustKnock 167 8.3.2 Tilting the Objective Function 168 8.4 Other Strain Design Algorithms 168 Exercises 170 References 171 9 N LP Fundamentals 173 9.1 Unconstrained Nonlinear Optimization 173 9.1.1 Optimality Conditions for Unconstrained Optimization Problems 174 9.1.2 An Overview of the Solution Methods for Unconstrained Optimization Problems 176 9.1.3 Steepest Descent (Cauchy or Gradient) Method 176 9.1.4 Newton’s Method 177 9.1.5 Quasi‐Newton Methods 178 9.1.6 Conjugate Gradients (CG) Methods 179 9.2 Constrained Nonlinear Optimization 180 9.2.1 Equality‐Constrained Nonlinear Problems 180 9.2.2 Nonlinear Problems with Equality and Inequality Constraints 186 9.2.3 Karush–Kuhn–Tucker Optimality Conditions 187 9.2.4 Sequential (Successive) Quadratic Programming 189 9.2.5 Generalized Reduced Gradient 192 9.3 Lagrangian Duality Theory 195 9.3.1 Relationships between the Primal and Dual Problems 196 Exercises 196 References 197 10 N LP Applications in Metabolic Networks 199 10.1 Minimization of the Metabolic Adjustment 199 10.2 Incorporation of Kinetic Expressions in Stoichiometric Models 203 10.3 Metabolic Flux Analysis (Mfa) 206 10.3.1 Definition of the Relevant Parameters and Variables 208 10.3.2 Isotopomer Mass Balance 214 10.3.3 Optimization Formulation for MFA 215 Exercises 218 References 220 11 Minlp Fundamentals and Applications 223 11.1 An Overview of the Minlp Solution Procedures 224 11.2 Generalized Benders Decomposition 224 11.2.1 The Primal Problem 225 11.2.2 The Master Problem 226 11.2.3 Steps of the GBD Algorithm 229 11.3 Outer Approximation 230 11.3.1 The Primal Problem 231 11.3.2 The Master Problem 231 11.3.3 Steps of the OA Algorithm 235 11.4 Outer Approximation With Equality Relaxation 236 11.4.1 The Master Problem 237 11.5 Kinetic Optknock 238 11.5.1 k‐OptKnock Formulation 239 11.5.2 Solution Procedure for k‐OptKnock 240 Exercises 242 References 243 Appendix A 245 Index 257

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Book SynopsisRead an interview with the author: Working Toward Gender Parity in the Geosciences The geoscience workforce has a lower proportion of women compared to the general population of the United States and compared to many other STEM fields. This volume explores issues pertaining to gender parity in the geosciences, and sheds light on some of the best practices that increase participation by women and promote parity. Volume highlights include: Lessons learned from NSF-ADVANCE Data on gender composition of faculty at top earth science institutions in the US Implicit bias and gender as a social structure Strategies for institutional change Dual career couples Family friendly policies Role of mentoring Career advancement for women Recruiting diverse faculty Models of institutional transformation Women in the Geosciences iTable of ContentsContributors v Introduction 1 Section I: The Data 1. Who Receives a Geoscience Degree? 13Mary Anne Holmes 2. We are the 20%: Updated Statistics on Female Faculty in Earth Sciences in the U.S 17Jennifer B. Glass Section II: A Framework to Address the Issue 3. A Sociological Framework to Address Gender Parity 25Mary Anne Holmes Section III: Successful Strategies to Address the Issue 4. Best Practices to Achieve Gender Parity: Lessons Learned from NSF’s ADVANCE and Similar Programs 33Mary Anne Holmes Section III. A: Institutional Strategies 5. Strategic Institutional Change to Support Advancement of Women Scientists in the Academy: Initial Lessons from a Study of ADVANCE IT Projects 39Sandra L. Laursen, Ann E. Austin, Melissa Soto and Dalinda Martinez 6. Institutional Transformation: The Lamont]Doherty Earth Observatory Experience 51Kuheli Dutt 7. Dual Career, Flexible Faculty 67Mary Anne Holmes 8. Lactation in the Academy: Accommodating Breastfeeding Scientists 75Suzanne OConnell Section III. B: Interactional and Individual Strategies 9. Implicit Assumption: What It Is, How to Reduce Its Impact 81Mary Anne Holmes 10. Hiring a Diverse Faculty 95Suzanne OConnell and Mary Anne Holmes 11. Multiple and Sequential Mentoring: Building Your Nest 109Suzanne OConnell 12. Mentoring Physical Oceanography Women to Increase Retention 121Susan Lozier and Sarah Clem 13. ASCENT, a Discipline]Specific Model to Support the Retention and Advancement of Women in Science 135A. Gannet Hallar, Linnea Avallone, Heather Thiry and Laura M. Edwards 14. Facilitating Career Advancement for Women in the Geosciences through the Earth Science Women’s Network (ESWN) 149Meredith G. Hastings, Christine Wiedinmyer and Rose Kontak 15. Learning to Develop a Writing Practice 161Suzanne OConnell Index 171 Color plate section located between pages 88 and 89

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Book SynopsisWith the health of the world's oceans threatened as never before, it is becoming increasingly apparent that Marine Protected Areas (MPAs) play a vitally important role in protecting marine and coastal habitats. Management of Marine Protected Areas: A Network Perspectivedraws on the results of a major EU-sponsored research project related to the establishment of networks of MPAs in the Mediterranean and Black Seas that transpired from February 2011 to January 2016. Featuring contributions by leading university- and national research institute-based scientists, chapters utilize the latest research data and developments in marine conservation policy to explore issues related to ways in which networks of MPAs may amplify the effectiveness and conservation benefits of individual areas within them. Topics addressed include the broader socio-economic impacts of MPAs in the Mediterranean and Black Seas; the use of Marine Spatial Planning (MSP) to resolve conflicts between mariTable of ContentsList of Contributors vii Foreword xi Editor’s Preface xv 1 From Marine Protected Areas to MPA Networks 1Ferdinando Boero 2 Ecological Effects and Benefits of Mediterranean Marine Protected Areas: Management Implications 21Antoni Garcia‐Rubies, Emma Cebrian, Patrick J. Schembri, Julian Evans and Enrique Macpherson 3 Typology, Management and Monitoring of Marine Protected Area Networks 49Stephen Beal, Paul D. Goriup and Thomas Haynes 4 Marine Protected Area Governance and Effectiveness Across Networks 69Nigel Dudley and Marc Hockings 5 Marine Protected Areas as Spatial Protection Measures under the Marine Strategy Framework Directive 89Daniel Braun 6 Socioeconomic Impacts of Networks of Marine Protected Areas 103Elena Ojea, Marta Pascual, David March, Isabella Bitetto, Paco Melià, Margaretha Breil, Joachim Claudet and Anil Markandya 7 Multi‐criteria Decision‐Making for Marine Protected Area Design and Management 125Paco Melià 8 Ecosystem‐Based Management for Marine Protected Areas: A Systematic Approach 145Rafael Sardá, Susana Requena, Carlos Dominguez‐Carrió and Josep Maria Gili 9 Developing Collaboration among Marine Protected Area Managers to Strengthen Network Management 163Chloë Webster 10 Eyes Wide Shut: Managing Bio‐Invasions in Mediterranean Marine Protected Areas 18Bella Galil 11 Marine Protected Areas and Marine Spatial Planning, with Special Reference to the Black Sea 207Eva Schachtner 12 Black Sea Network of Marine Protected Areas: European Approaches and Adaptation to Expansion and Monitoring in Ukraine 227Boris Alexandrov, Galina Minicheva and Yuvenaliy Zaitsev 13 Prospects for Marine Protected Areas in the Turkish Black Sea 247Bayram Öztürk, Bettina A. Fach, Çetin Keskin, Sinan Arkin, Bülent Topaloğlu and Ayaka Amaha Öztürk 14 Marine Protected Areas and Offshore Wind Farms 263Natalie Sanders, Thomas Haynes and Paul D. Goriup Index 281

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Book SynopsisInsights on current research and recent developments in understanding global savanna systems Increasingly recognized as synonymous with tropical grassy biomes, savannas are found in tropical and sub-tropical climates as well as warm, temperate regions of North America. Savanna Woody Plants and Large Herbivores examines the interactions between woody plants and browsing mammals in global savannasfocusing primarily on the C4 grassy ecosystems with woody components that constitute the majority of global savannasand discusses contemporary savanna management models and applications. This much-needed addition to current research examines topics including the varying behavior of browsing mammals, the response to browsing by woody species, and the factors that inhibit forage intake. Contributions from an international team of active researchers and experts compare and contrast different savanna ecosystems, offering a global perspective on savanna functioning, the roles of soil and climate in rTable of ContentsList of Contributors xv Preface xix Part I Introduction 1 1 Distribution and Determinants of Savannas 3Sally Archibald, William J. Bond, William Hoffmann, Caroline Lehmann, Carla Staver, and Nicola Stevens 1.1 Introduction 3 1.2 Evolutionary History of Savanna Vegetation and Fauna 4 1.3 Defining Savannas 7 1.3.1 Are Savannas Tropical Systems? 7 1.3.2 Distinguishing Savannas from Grasslands 7 1.3.3 Distinguishing Savannas from Forests 8 1.4 Global Determinants of Savannas 9 1.4.1 Mesic Transition: Points of Contention 10 1.4.1.1 The Role of Nutrients 10 1.4.1.2 Rainfall Seasonality 10 1.4.2 Mesic Transition: Toward Resolution 11 1.4.3 Mesic Transition: Unresolved Ideas 12 1.4.4 Arid Transition 12 1.4.5 Arid Transition: Toward Resolution 13 1.4.6 Determinants of Temperate Savannas 14 1.5 Functional Differences Between Savannas 14 1.5.1 Temperate vs Tropical Savannas 14 1.5.2 Functional Differences Within Tropical Savannas 15 1.6 Conclusions and the Future of Savanna Ecosystems 17 References 17 2 African and Asian Savannas: Comparisons of Vegetation Composition and Drivers of Vegetation Structure and Function 25Jayashree Ratnam, Chintan Sheth, and Mahesh Sankaran 2.1 Introduction 25 2.2 Climate and Vegetation Formations 27 2.3 Fine‐Leaved and Broad‐Leaved Savannas: Vegetation Structure, Composition, and Geographic Distribution 30 2.4 Role of Bottom‐Up Drivers in Regulating Vegetation Structure: Climate and Soil Nutrients 33 2.5 Role of Top‐Down Forces: Fire and Herbivory 36 2.6 African and Asian Savannas in the Anthropocene 40 References 42 3 Savannas of Australia and New Guinea: Vegetation and the Functional Role of Extant and Extinct Fauna 51Garry D. Cook, William J. Bond, Edmund C. February, and Richard J. Williams 3.1 Introduction 51 3.2 The Biota of Australia’s and New Guinea’s Savannas 51 3.3 Climate, Landforms, and Fire 53 3.4 Human History and Impacts 54 3.5 Are Native Mammals Irrelevant? 55 3.6 Was Ecosystem Functioning Different Prior to Human Dispersal to Australia? 57 3.7 Critique of the “Nutrient Poverty/Intense Fire” Theory 58 3.8 Australia’s Lost Megafauna 61 3.9 Habitat Variation and the Pleistocene Megafauna 64 3.10 Impacts of Herbivores in Australian Savannas 64 3.11 Toward a New Hypothesis of Plant–Animal Interactions in Australian Savannas 66 References 67 4 South American Savannas 77Fabian Borghetti, Eduardo Barbosa, Leandro Ribeiro, José Felipe Ribeiro, and Bruno Machado Teles Walter 4.1 Introduction 77 4.2 Origin of South American Savannas 77 4.3 Distribution and Diversity of South American Savannas 78 4.4 Northern Savannas 80 4.4.1 Colombo–Venezuelan Llanos 80 4.4.1.1 Orinoco Llanos 80 4.4.1.2 Llanos Orientales 84 4.4.2 Gran Sabana 85 4.4.3 Rio Branco–Rupununi Savannas 85 4.4.3.1 Rio Branco Savannas 86 4.4.3.2 Rupununi Savannas 86 4.4.4 Savannas of Amapá 87 4.5 Southern Savannas 87 4.5.1 Savannas of Humaitá 87 4.5.2 Savannas of Pará 87 4.5.3 Beni Savannas 88 4.5.4 Cerrado 89 4.5.4.1 Cerrado (Sensu Stricto) 91 4.5.4.2 Cerrado Park 92 4.5.4.3 Palm Groves 92 4.5.4.4 Vereda 92 4.5.4.5 Campo Limpo (“Open Grassland”) 92 4.5.4.6 Campo Sujo (“Dense Grassland”) 92 4.5.4.7 Campo Rupestre (“Rocky Field”) 96 4.5.5 Pantanal 96 4.5.6 Chaco 97 4.6 Effects of Water Deficit, Herbivory, and Fire on Vegetation Dynamics 102 4.6.1 Water Deficit 102 4.6.2 Herbivory 103 4.6.3 Fire 104 4.7 Climate Change, Anthropogenic Pressure, and the Future 106 4.8 Concluding Remarks 109 4.9 Acknowledgments 109 References 110 5 Savannas of North America 123Norma L. Fowler and Brian Beckage 5.1 Introduction 123 5.1.1 Definitions 123 5.1.2 Climatic Patterns 126 5.2 Fire 127 5.3 Grazing 128 5.4 Biodiversity 129 5.5 Conservation 129 5.6 Oak Savannas 130 5.6.1 Central US, South‐Central Canada, Northern Sierra Madre (Mexico) Oak Savannas 130 5.6.2 California Oak Savannas 132 5.6.3 South‐West (Arizona, New Mexico, Northern Mexico) Oak Savannas 132 5.6.4 Pacific Northwest Oak Savannas 132 5.6.5 East‐Central US: Glades, Barrens, and Other Forest Openings 132 5.6.6 Oak‐Dominated Shrub Savannas 133 5.7 Pine Savannas 133 5.7.1 South‐Eastern US Pine Savannas 133 5.7.2 Rocky Mountains Pine Savannas 134 5.8 Juniper Savannas 135 5.8.1 Juniper Savannas in the Western Mountains 135 5.8.2 Eastern Red Cedar Savannas 138 5.8.3 South‐Central US and Northern Sierra Madre Oriental Juniper Savannas 138 5.9 Mesquite Savannas 138 5.10 Northern and High‐Elevation Savannas 140 5.11 Shrub Savannas 140 5.12 Conclusions 141 5.13 Acknowledgments 141 References 141 6 Socioeconomic Value of Savannas 151Wayne Twine 6.1 Introduction 151 6.2 Land Tenure and Land Use 153 6.3 Livestock Farming 155 6.3.1 Overview 155 6.3.2 Commercial Livestock Farming 157 6.3.3 Subsistence Livestock Farming 157 6.4 Wildlife Industry 159 6.4.1 Overview 159 6.4.2 Ecotourism 161 6.4.3 Hunting 162 6.4.4 Animal Products 163 6.4.5 Game Breeding and Live Sales 164 6.5 Commercial Timber 164 6.6 Non‐timber Products 164 6.6.1 Uses 164 6.6.2 Economic Value 166 6.6.2.1 Non‐monetary Income 166 6.6.2.2 Cash Income 167 6.6.2.3 Environmental Income 168 6.7 Conclusion 169 References 170 Part II Herbivores 181 7 Ecology of Smaller Animals Associated with Savanna Woody Plants: The Value of the Finer Details 183Colleen Seymour and Grant Joseph 7.1 Introduction 183 7.2 Woody Plant Seed Herbivory 184 7.2.1 Seed Herbivores 184 7.3 Woody Plant Seed and Fruit Dispersal 187 7.3.1 Diplochory 187 7.3.1.1 Seed Dispersal by Birds 188 7.3.1.2 Invertebrate Seed Dispersal 189 7.3.2 Fruit Dispersal 189 7.4 Woody Plant Seedling Establishment 190 7.5 Leaves and Herbivory 191 7.6 Pollination and Nectarivory 193 7.7 Nutrient Cycling 195 7.8 Conclusions 199 References 201 8 Evolution of Large Mammal Herbivores in Savannas 213Daryl Codron 8.1 Introduction 213 8.2 Herbivore Dietary Niches 215 8.3 Diversification of Browsers and Grazers 220 8.4 Effects of Vegetation Change 223 8.5 Herbivore Body Size 226 8.6 Pleistocene Extinctions and Contemporary Herbivore Diversity 228 8.7 Summary 233 References 234 9 Browser Population–Woody Vegetation Relationships in Savannas: From Bites to Landscapes 245Melissa H. Schmitt and Adrian M. Shrader 9.1 Introduction 245 9.2 Factors Influencing Diet Selection 246 9.2.1 Browser Traits that Influence Foraging 247 9.2.1.1 Body Size 247 9.2.1.2 Gut Morphology 248 9.2.2 Woody Plant Traits that Influence Browsers 248 9.2.2.1 Seasonality 248 9.2.2.2 High Nutrient Levels (Positive) 249 9.2.2.3 Chemical Defenses (Negative) 250 9.2.2.4 Physical Defenses 252 9.2.2.5 Mutualisms 253 9.2.3 Herbivore Coping Mechanisms 253 9.3 Browser Impacts on Vegetation 255 9.3.1 Biomass Removal (Small and Large) 255 9.3.2 Impacts on Seeds 256 9.4 Feedback from Browsed Plants to Browsers 257 9.4.1 Lowered Food Availability 257 9.4.2 Habitat Changes 259 9.4.3 Change in Landscapes of Fear 260 9.4.4 New Growth 261 9.4.5 Nutrient Hot Spots 261 9.4.6 Browsing Lawns 261 9.5 Scaling from Bites to Browser Population Dynamics 262 9.5.1 Population Dynamics 263 9.5.2 Intake and Population Size 263 9.5.3 Food Availability, Food Quality, and Population Dynamics 264 9.5.4 Future Research 265 9.6 Conclusions 265 References 265 10 Predator Effects on Herbivore Dynamics and Behavior: What Mechanisms Lead to Trophic Cascades in Savannas? 279Simon Chamaillé‐Jammes, Marion Valeix, and Joris Cromsigt 10.1 Introduction 279 10.2 Consumptive Effects of Predation 280 10.2.1 Concepts, Theory, and Evidence from Biomes Other than Savanna 280 10.2.1.1 Additive Versus Compensatory Mortality 281 10.2.1.2 Predator Functional Response 282 10.2.1.3 Ecosystem Characteristics 284 10.2.2 Evidence from Savannas 285 10.2.2.1 Additive Versus Compensatory Mortality 286 10.2.2.2 Predator Functional Response 288 10.2.2.3 Ecosystem Characteristics 288 10.3 Non‐consumptive Effects of Predation 290 10.3.1 Concepts, Theory, and Evidence from Biomes Other than Savanna 290 10.3.1.1 Landscape Use 290 10.3.1.2 Vigilance and Grouping Strategies 291 10.3.1.3 The Importance of Food–Safety Trade‐Offs 292 10.3.1.4 Demographic Costs of Behavioral Adjustments 293 10.3.2 Evidence from Savannas 293 10.3.2.1 Landscape Use 293 10.3.2.2 Vigilance and Grouping Strategies 295 10.4 Cascading Effects of Consumptive and Non‐consumptive Effects of Predation on Lower Trophic Levels 296 10.5 The Times they are A‐changin’: Changes in Megaherbivory, Migration Patterns, and Climate 297 References 299 Part III Woody Plants 309 11 Physiological Traits of Savanna Woody Species: Adaptations to Resource Availability 311Edmund C. February, Corli Coetsee, Garry D. Cook, Jayashree Ratnam, and Benjamin Wigley 11.1 Introduction 311 11.2 Soil Nutrients and Root Responses 314 11.3 Leaf Phenology and Available Water 317 11.4 Competition for Resources 321 References 323 12 Patterns and Determinants of Woody Plant Growth in Savannas 331Anthony Swemmer and David Ward 12.1 Introduction: The Relevance of Growth Rates 331 12.2 Determinants of Growth Rates 333 12.2.1 Seedlings 334 12.2.2 Saplings 342 12.2.3 Adults 344 12.2.4 Demographic Significance 344 12.2.4.1 Growth Trajectory 345 12.2.4.2 Size or Age of Individuals 345 12.2.4.3 Above vs Below Ground 345 12.2.4.4 Plant Part 347 12.2.4.5 Interacting Factors 347 12.2.4.6 Experimental Conditions 348 12.2.4.7 Individual vs Population Growth 348 12.2.4.8 Time and Size 348 12.2.4.9 Species 348 12.2.5 The Value of Long‐Term Research 349 12.3 Modeling Growth 350 12.3.1 Insights from Published Data 351 12.3.2 Predicting Rates from Environment or Phylogeny 353 12.3.3 Deficiencies in Growth Rate Data 356 12.4 Conclusions 357 12.A Appendix: Growth Rate Data 358 References 428 13 Fire and Browsers in Savannas: Traits, Interactions, and Continent‐Level Patterns 439Gareth P. Hempson, Sally Archibald, and Carla Staver 13.1 Introduction 439 13.2 Browser and Fire Attributes 440 13.2.1 How do Fire and Browsers Compare as Consumers of Woody Plants? 440 13.2.1.1 Frequency and Seasonality 440 13.2.1.2 Selectivity, Intensity, and Scale 440 13.2.1.3 Elimination Thresholds 442 13.2.2 Plant Responses to Fire and Browsing 442 13.2.2.1 Defense Traits 442 13.2.2.2 Architecture 443 13.2.2.3 Resprouting and Bud Protection 444 13.2.2.4 Fire‐ and Browser‐Traps 445 13.2.2.5 Reproduction and Seedling Recruitment 446 13.3 Fire–Browser Interactions 447 13.3.1 Consequences of Fire for Browsers 447 13.3.1.1 Post‐Fire Environment 448 13.3.1.2 Woody Plant Regeneration 449 13.3.1.3 Decadal Fire Regimes 450 13.3.2 Browser Feedbacks to Fire 451 13.3.2.1 Browser Facilitation of Fire 451 13.3.2.2 Negative Feedbacks of Mixed‐Feeders 451 13.3.3 Fire–Browser Vegetation Impacts 452 13.3.3.1 Sapling Escape 452 13.3.3.2 Elephant Bark Stripping and Canopy Breakage 452 13.4 Biogeography of Fire and Browsing in Africa 453 13.4.1 Continental‐Scale Patterns of Fire and Browsing 455 13.4.2 Fire–Browser Regimes 457 13.4.3 Fine‐ vs Broad‐Leaved Savannas 457 13.5 Synthesis 460 References 460 14 Woody Plant Architecture and Effects on Browsing Herbivores in Savannas 469Tristan Charles‐Dominique, Jean‐Francois Barczi , and Simon Chamaillé‐Jammes 14.1 Introduction 469 14.2 Factors Limiting Bite Size 471 14.3 Factors Limiting Biting Rate 474 14.4 Simulating Plant–Herbivore Interactions at the Individual Plant Scale 476 14.4.1 Plant Growth Model 477 14.4.2 Virtual Browsing and Consequences for Plant Fitness 478 14.4.3 Virtual Experiment Set‐up 478 14.4.4 Simulation Results 480 14.4.4.1 Effect of Leaf Size 481 14.4.4.2 Effect of Short Shoots 481 14.4.4.3 Effect of Spines 482 14.4.4.4 Effect of Cage Architecture 482 14.4.4.5 Effect of Short Shoot Induction 482 14.4.4.6 Effect of Sprouting 482 14.4.5 Significance of Simulation Results 482 14.5 Future Directions for Modeling Plant–Herbivore Interactions 483 Acknowledgments 483 14.A Appendix 484 References 484 15 Browsing Herbivore–Woody Plant Interactions in Savannas 489Peter Frank Scogings and Juan H. Gowda 15.1 Introduction 489 15.1.1 The raison d’être 489 15.1.2 Approach 490 15.2 Feedback Between Woody Individuals and Browsing Herbivores 492 15.2.1 Shoot Growth 492 15.2.2 Spinescence 493 15.2.3 Nutrients and Phenolics 494 15.2.4 Is Positive Feedback Widespread? 495 15.3 Selective Browsing and Shifts in Woody Vegetation Composition and Structure 497 15.3.1 Recruitment and Mortality 497 15.3.2 Community Composition and Structure 500 15.4 Linking Responses of Woody Individuals and Communities to Functional Traits 501 15.5 Future Directions 504 15.5.1 Key Gaps 504 15.5.2 Standardizing Methods 505 References 539 16 Mesobrowser Abundance and Effects on Woody Plants in Savannas 551David J. Augustine, Peter Frank Scogings, and Mahesh Sankaran 16.1 Introduction551 16.2 Mesobrowser Abundance in Savannas 552 16.3 Mesobrowser Diets in Savannas 559 16.4 Mesobrowser Effects on Woody Plant Communities 561 16.4.1 Hluhluwe‐iMfolozi Park, South Africa 564 16.4.2 Central Laikipia, Kenya 565 16.4.3 Chobe National Park, Botswana 567 16.4.4 Kruger National Park, South Africa 568 16.5 Evidence from Long‐Term Perspectives 569 16.6 The Influence of High Densities of Individual Mesobrowser Species 570 16.7 Water, Nutrients, and Mesobrowsers 571 16.8 Synthesis 573 Acknowledgments 576 References 576 17 Megabrowser Impacts on Woody Vegetation in Savannas 585Norman Owen‐Smith, Bruce Page, Gabriella Teren, and Dave J. Druce 17.1 Introduction 585 17.2 Use of Woody Plants Versus Grasses and Other Plant Forms 586 17.3 Selection for Size Classes and Woody Plant Parts 589 17.4 Plant Damage Imposed and Mortality 590 17.5 Plant Species Selected 592 17.6 Landscape Transformations Caused by Elephants, Along with Fire 599 17.7 A Cautionary Note 602 17.8 Overview 602 References 604 18 Indirect Effects of Browsing Herbivores in Savannas 613Corli Coetsee, Dario Fornara, Antoinette Veldtman, and Benjamin Wigley 18.1 Introduction 613 18.2 Indirect Effects of Browsers on Other Fauna 614 18.2.1 Mammals 614 18.2.1.1 Large Herbivore Effects on Rodents 614 18.2.1.2 Mesobrowser Effects on Other Herbivores 615 18.2.1.3 Megaherbivore Effects on Mesoherbivores 616 18.2.1.4 Interactions Among Browsers Where the Type of Browser is Not Apparent 616 18.2.1.5 Interactions Among Megaherbivores 617 18.2.1.6 Summary 617 18.2.2 Birds 617 18.2.2.1 Summary 619 18.2.3 Reptiles and Amphibians 619 18.2.3.1 Summary 619 18.2.4 Invertebrates 619 18.2.4.1 Summary 621 18.3 Effects on Ecosystem Processes 622 18.3.1 Carbon Cycling 622 18.3.1.1 Consumption of Vegetation by Browsers Affects Ecosystem Carbon Pools 622 18.3.1.2 Changes in Litterfall Affect Soil Carbon 625 18.3.1.3 Global Change Can Override the Effects of Herbivory on Soil Carbon 625 18.3.1.4 Summary 626 18.3.2 Soil Nutrient Cycling and Soil Nutrient Pools 626 18.3.2.1 Changes in Litter Quality 626 18.3.2.2 Herbivore Effects on both Litter Quality and Quantity 629 18.3.2.3 Summary 629 18.4 Conclusions 629 References 630 Part IV Synthesis 643 19 Water Limitation, Fire, and Savanna Persistence: A Conceptual Model 645Brian Beckage, Gabriela Bucini, Louis J. Gross, William J. Platt, Steven I. Higgins, Norma L. Fowler, Matthew G. Slocum, and Caroline Farrior 19.1 Introduction 645 19.2 Conceptual Model 646 19.2.1 Water Limitation 648 19.2.2 Fire 650 19.2.3 Fire Feedbacks 651 19.2.4 Other Processes 652 19.3 Summary 653 Acknowledgments 654 References 654 20 Savanna Ecosystem Models: What Should a Clever Modeler Code? 661Gregory Kiker and Peter Frank Scogings 20.1 Introduction 661 20.2 Local‐Scale Aspects of Woody Plant–Browser Interactions 662 20.3 Model Designs for Plant–Herbivore Interactions 663 20.3.1 Plant‐Focused Models 666 20.3.2 Herbivore‐Based Models 668 20.3.3 Integrated Models: Adding Complexity into Plant–Herbivore Models 670 20.4 Discussion 672 References 674 21 Woody Plants and Large Herbivores in Savannas: Ancient Past – Uncertain Future 683Peter Frank Scogings and Mahesh Sankaran 21.1 Introduction 683 21.2 Woody Plants 685 21.3 Large Herbivores 688 21.4 Interactions Between Woody Plants and Browsers 690 21.4.1 Adaptations of Woody Plants to Browsing by Mesobrowsers 690 21.4.2 Woody Community Responses to Mesobrowsers and Megaherbivores 692 21.4.3 Indirect Effects of Browsing 696 21.5 Models 698 21.5.1 General Conceptual (Qualitative) Models 698 21.5.2 Mathematical (Quantitative) Models 700 21.6 The Future 701 References 703 Index 713

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Book SynopsisForest trees and shrubs play vital ecological roles, reducing the carbon load from the atmosphere by using carbon dioxide in photosynthesis and by the storage of carbon in biomass and wood as a source of energy. Autoecology deals with all aspects of woody plants; the dynamism of populations, physiological traits of trees, light requirements, life history patterns, and physiological and morphological characters. Ecophysiology is defined by various plant growth parameters such as leaf traits, xylem water potential, plant height, basal diameter, and crown architecture which are, in turn, influenced by physiological traits and environmental conditions in the forest ecosystem. In short, this book details research advances in various aspects of woody plants to help forest scientists and foresters manage and protect forest trees and plan their future research. Autoecology and Ecophysiology of Woody Shrubs and Trees is intended to be a guide for students of woody plant autoecoTable of ContentsPreface, vii List of contributors, ix 1 Background, 1 Part I: 2 Autoecology, 15 3 Vegetation and biodiversity, 25 4 Case study: A trip to regions of biodiversity and rainforest in Riviera Maya, 31 5 Plant traits, 42 6 Leaf traits, 74 7 Wood characteristics, 83 8 Phenology, 111 9 Phenology, morphology and variability in pollen viability of four woody species (Cordia boissieri, Parkinsonia texana, P. aculeata and Leucophyllum frutescens) exposed to environmental temperature, north-eastern Mexico, 124 10 Pollen biology and plant productivity: A review, 133 11 Seed characteristics, 158 12 Tree mortality, 162 13 Plant traits related to the productivity of trees, 168 Part II: 14 Ecophysiology, 181 15 Research advances in plant ecophysiology, 190 16 Carbon capture, carbon sequestration and carbon fixation, 199 17 Plant nutrients, 220 18 Litterfall and forest productivity, 238 19 Nutrient cycling, 244 20 Plant water relations and forest productivity, 248 21 Cold tolerance of trees, 261 22 Heat stress tolerance of trees, 266 23 Seed characteristics, seed dormancy, germination and plant propagation, 270 24 Root growth, 278 25 Features of boreal forest in Russia: A special study, 285 26 Case study: Autoecology, biodiversity and adaptive characteristics of Prosopis in the Arizona region, 312 Appendix 1: Leaf Morphology, 325 Index, 333

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Book SynopsisFood is an essential means for humans and other animals to acquire the necessary elements needed for survival. However, it is also a transport vehicle for foodborne pathogens, which can pose great threats to human health. Use of antibiotics has been enhanced in the human health system; however, selective pressure among bacteria allows the development for antibiotic resistance. Foodborne Pathogens and Antibiotic Resistance bridges technological gaps, focusing on critical aspects of foodborne pathogen detection and mechanisms regulating antibiotic resistance that are relevant to human health and foodborne illnesses This groundbreaking guide: Introduces the microbial presence on variety of food items for human and animal consumption. Provides the detection strategies to screen and identify the variety of food pathogens in addition to reviews the literature. Provides microbial molecular mechanism of food spoilage along with molecular mechanism of Table of ContentsList of Contributors xiii Preface xix Introduction 1 1 Diversity of Foodborne Bacterial Pathogens and Parasites in Produce and Animal Products and Limitations of Current Detection Practices 5Debabrata Biswas and Shirley A. Micallef 1.1 Introduction 5 1.2 Common Bacterial Pathogens and Parasites Found in Produce and Animal Products 6 1.3 Unusual Bacterial Pathogens and Parasites in Produce and Animal Products 7 1.4 Farming Systems and Mixed (Integrated) Crop‐Livestock Farming 8 1.5 Major Sources of Unusual/Under‐Researched Bacterial Pathogens and Parasites in Food 10 1.6 Diversity of Farming and Processing Practices and Possible Risks 11 1.7 Current Hygienic Practices and Their Effects on These Under‐Researched Pathogens 12 1.8 Current Detection Methods and Their Limitations 13 1.9 Recommendation to Improve the Detection Level 14 1.10 Conclusion 14 References 14 2 Characterization of Foodborne Pathogens and Spoilage Bacteria in Mediterranean Fish Species and Seafood Products 21A. Bolivar, J.C.C.P. Costa, G.D. Posada‐Izquierdo, F. Pérez‐Rodríguez, I. Bascón, G. Zurera, and A. Valero 2.1 Fish Quality Assurance 21 2.2 Microbiological Standards To Be Accomplished 21 2.3 Hazard Analysis and Critical Control Points (HACCP) Implemented in the Fishery Industry 22 2.4 Microbial Ecology of Mediterranean Fishery Products 24 2.5 Fish and Seafood Spoilage: Characterization of Spoilage Microorganisms During Capture, Manufacture, and Distribution of Fishery Products 28 2.6 Foodborne Pathogens in Mediterranean Fishery Products 30 2.7 Molecular Methods for Pathogen Detection in Fishery Products 33 References 34 3 Food Spoilage by Pseudomonas spp.—An Overview 41António Raposo, Esteban Pérez, Catarina Tinoco de Faria, María Antonia Ferrús, and Conrado Carrascosa 3.1 Introduction 41 3.2 Pseudomonas spp. in Milk and Dairy Products 44 3.3 Meat Spoilage by Pseudomonas spp. 47 3.4 Fish Spoilage by Pseudomonas spp. 50 3.5 Water Contamination by Pseudomonas spp. 51 3.6 Pseudomonas spp. in Fruit and Vegetables 55 3.7 Biochemical and Molecular Techniques for Pseudomonas spp. Detection 56 3.8 Conclusions 58 References 58 4 Arcobacter spp. in Food Chain—From Culture to Omics 73Susana Ferreira, Mónica Oleastro, and Fernanda Domingues 4.1 Introduction 73 4.2 Isolation and Detection of Arcobacter 86 References 102 5 Microbial Hazards and Their Implications in the Production of Table Olives 119A. Valero, E. Medina, and F.N. Arroyo‐López 5.1 Table Olives: Origin, Production, and Main Types of Elaborations 119 5.2 Importance of Microorganisms in Table Olives 121 5.3 Molecular Methods for the Study of Microbial Populations in Table Olives 122 5.4 Biological Hazards in Table Olives 124 5.5 Use of Starter Cultures to Reduce Biological Hazards in Table Olives 126 5.6 Hazard Analysis and Critical Control Point (HACCP) System As a Useful Tool to Improve Microbial Safety and Quality of Table Olives 127 5.7 Conclusions 132 References 133 6 The Problem of Spore‐Forming Bacteria in Food Preservation and Tentative Solutions 139Stève Olugu Voundi, Maximilienne Nyegue, Blaise Pascal Bougnom, and François‐Xavier Etoa 6.1 Introduction 139 6.2 Sporulation 139 6.3 Metabolic State of the Spore 140 6.4 Spore Structure and Associated Mechanisms of Resistance 140 6.5 Germination of Spore 142 6.6 Problems of Spore‐Forming Bacteria in Food Preservation 143 6.7 Techniques of Spore Inactivation 146 References 148 7 Insights into Detection and Identification of Foodborne Pathogens 153Jodi Woan‐Fei Law, Vengadesh Letchumanan, Kok‐Gan Chan, Bey‐Hing Goh, and Learn‐Han Lee 7.1 Introduction 153 7.2 Nucleic Acid‐Based Methods 157 7.3 Conclusion 183 References 183 8 Rapid, Alternative Methods for Salmonella Detection in Food 203Anna Zadernowska and Wioleta Chajęcka‐Wierzchowska 8.1 Introduction 203 8.2 Conventional Methods and Their Modifications 203 8.3 Alternative Methods—Definitions, Requirements 205 8.4 Conclusions 208 References 208 9 CRISPR‐Mediated Bacterial Genome Editing in Food Safety and Industry 211Michael Carroll and Xiaohui Zhou 9.1 Introduction 211 9.2 Application of CRISPR for Bacterial Genome Editing 215 9.3 Vaccination of Industrial Microbes 217 9.4 Application of CRISPR in the Development of Antimicrobials 218 9.5 CRISPR Delivery Systems 220 9.6 Concluding Remarks 221 References 222 10 Meat‐borne Pathogens and Use of Natural Antimicrobials for Food Safety 225Ashim Kumar Biswas and Prabhat Kumar Mandal 10.1 Introduction 225 10.2 Incidences of Some Important Foodborne Pathogens 226 10.3 Application of Natural Antimicrobials 230 10.4 Regulatory Aspects of Natural Antimicrobials 238 10.5 Health Benefits of Natural Antimicrobials 239 10.6 Summary 239 References 239 11 Foodborne Pathogens and Their Apparent Linkage with Antibiotic Resistance 247Mariah L. Cole and Om V. Singh 11.1 Introduction 247 11.2 Food Spoilage 248 11.3 Food Processing and Microbial Contamination 254 11.4 Foodborne Pathogens and Antibiotic Resistance 255 11.5 Antibiotics and Alternatives 266 11.6 Genomics and Proteomics of Foodborne Pathogens and Antibiotic Resistance 268 11.7 Conclusion 270 References 270 12 Antimicrobial Food Additives and Disinfectants: Mode of Action and Microbial Resistance Mechanisms 275Meera Surendran Nair, Indu Upadhyaya, Mary Anne Roshni Amalaradjou, and Kumar Venkitanarayanan 12.1 Introduction 275 12.2 Food Additives 275 12.3 Mode of Action and Resistance to Antimicrobial Food Preservatives 277 12.4 Disinfectants 284 12.5 Mode of Action and Resistance to Disinfectants 285 12.6 Plant‐Derived Antimicrobials as Alternatives 289 12.7 Conclusion 291 References 291 13 Molecular Biology of Multidrug Resistance Efflux Pumps of the Major Facilitator Superfamily from Bacterial Food Pathogens 303Ranjana K.C., Ugina Shrestha, Sanath Kumar, Indrika Ranaweera, Prathusha Kakarla, Mun Mun Mukherjee, Sharla R. Barr, Alberto J. Hernandez, T. Mark Willmon, Bailey C. Benham, and Manuel F. Varela 13.1 Foodborne Bacterial Pathogens 303 13.2 Major Classes of Clinically Important Antibacterial Agents 307 13.3 Antimicrobial Agents Used in Food Animals for Treatment of Infections 307 13.4 Antimicrobial Agents Used in Food Animals for Prophylaxis 309 13.5 Antimicrobial Agents Used in Food Animals for Growth Enhancement 309 13.6 Mechanisms of Bacterial Resistance to Antimicrobial Agents 310 13.7 The Major Facilitator Superfamily of Solute Transporters 314 13.8 Key Bacterial Multidrug Efflux Pump Systems of the Major Facilitator Superfamily 314 13.9 Future Directions 318 References 319 14 Prevalence, Evolution, and Dissemination of Antibiotic Resistance in Salmonella 331Brian W. Brunelle, Bradley L. Bearson, and Heather K. Allen 14.1 Introduction 331 14.2 Antibiotic Resistance Prevalence Among Salmonella Serotypes 332 14.3 Antibiotic Treatment of Salmonella 335 14.4 Antibiotics and Resistance Mechanisms 336 14.5 Evolution and Transfer of Antibiotic Resistance 339 14.6 Co‐Localization of Resistance Genes 342 14.7 Conclusions 343 References 343 15 Antibiotic Resistance of Coagulase‐Positive and Coagulase‐Negative Staphylococci Isolated From Food 349Wioleta Chajęcka‐Wierzchowska and Anna Zadernowska 15.1 Characteristics of the Genus Staphylococcus 349 15.2 Coagulase‐Positive Staphylococci 349 15.3 Coagulase‐Negative Staphylococci 350 15.4 Genetic Mechanisms Conditioning Antibiotic Resistance of Staphylococci 350 15.5 Food as a Source of Antibiotic‐Resistant Staphylococci 355 15.6 Summary 359 References 359 16 Antibiotic Resistance in Enterococcus spp. Friend or Foe? 365Vangelis Economou, Hercules Sakkas, Georgios Delis, and Panagiota Gousia 16.1 Introduction 365 16.2 Enterococcus Biology 365 16.3 Enterococcus as a Probiotic 366 16.4 Enterococcus in Food 367 16.5 Antibiotic Resistance 369 16.6 Enterococcus Infection 377 16.7 Enterococcus Epidemiology 380 References 382 17 Antibiotic Resistance in Seafood‐Borne Pathogens 397Sanath Kumar, Manjusha Lekshmi, Ammini Parvathi, Binaya Bhusan Nayak, and Manuel F. Varela 17.1 Human Pathogenic Bacteria in Seafood 397 17.2 An Overview of Bacterial Antimicrobial Resistance Mechanisms 401 17.3 Antibiotic‐Resistant Bacteria in the Aquatic Environment 402 17.4 Antimicrobial Resistance in Seafood‐Borne Pathogens 403 17.5 Antimicrobials in Aquaculture and their Human Health Consequences 407 17.6 Future Directions 410 References 410 18 Antimicrobial Resistance of Campylobacter sp. 417Tareq M. Osaili and Akram R. Alaboudi 18.1 Introduction 417 18.2 Antimicrobial Resistance 418 18.3 Consequences of Foodborne Antimicrobial Resistance on Humans 419 18.4 Antimicrobial Resistance Mechanisms 419 18.5 Antimicrobial Susceptibility Testing of Campylobacter 420 18.6 Campylobacter Antimicrobials Resistance: Global Overview 421 18.7 Antimicrobial Resistance of Campylobacter Isolates From the Middle East Region 423 18.8 Strategies to Prevent Future Emergences of Bacterial Resistance 423 References 425 19 Prevalence and Antibiogram of Pathogenic Foodborne Escherichia coli and Salmonella spp. in Developing African Countries 431Adeyanju Gladys Taiwo (DVM, MVPH) 19.1 Introduction 431 19.2 Factors that Play a Role in the Epidemiology of Foodborne Diseases 432 19.3 Food Poisoning and Food Vending 433 19.4 Foodborne Colibacillosis and Salmonellosis 434 19.5 Antibiotic Resistance 435 19.6 Reasons for Resistance Against Specific Antibiotics 436 19.7 Antibiotic Resistance of Salmonella 436 19.8 Antibiotic Resistance of Escherichia coli 437 19.9 How to Combat Foodborne Diseases And Antibiotic Resistance 437 References 437 20 Evolution and Prevalence of Multidrug Resistance Among Foodborne Pathogens 441Sinosh Skariyachan, Anagha S. Setlur, and Sujay Y. Naik 20.1 Introduction 441 20.2 Major Causes of the Evolution of Bacterial Drug Resistances 441 20.3 Food Poisoning and Foodborne Illness—An Overview 443 20.4 Factors that Influence the Growth of Foodborne Pathogens in Food Products 444 20.5 Food Poisoning and Foodborne Infections 445 20.6 An Illustration of Major Foodborne Gastroenteritis 446 20.7 Major Types of Antibiotics Used to Treat Foodborne Infections 448 20.8 Mechanisms of Evolution of Antibiotic Resistance in Food Products 449 20.9 Evolution of XDR and PDR Bacteria 456 20.10 Need for Caution and WHO/FDA Stands Toward the Development of MDR Pathogens in Foods 457 20.11 Possible Solutions and Recommendations for Prevention 458 20.12 Conclusion 458 References 458 Index 465

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Book Synopsis

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Book SynopsisUltraviolet-B (UV-B) is electromagnetic radiation coming from the sun, with a medium wavelength which is mostly absorbed by the ozone layer. The biological effects of UV-B are greater than simple heating effects, and many practical applications of UV-B radiation derive from its interactions with organic molecules. It is considered particularly harmful to the environment and living things, but what have scientific studies actually shown? UV-B Radiation: From Environmental Stressor to Regulator of Plant Growth presents a comprehensive overview of the origins, current state, and future horizons of scientific research on ultraviolet-B radiation and its perception in plants. Chapters explore all facets of UV-B research, including the basics of how UV-B''s shorter wavelength radiation from the sun reaches the Earth''s surface, along with its impact on the environment''s biotic components and on human biological systems. Chapters also address the dramatic shift in UV-B researTable of ContentsList of Contributors xv Preface xix 1 An Introduction to UV‐B Research in Plant Science 1 Rachana Singh, Parul Parihar, Samiksha Singh, MPVVB Singh, Vijay Pratap Singh and Sheo Mohan Prasad 1.1 The Historical Background 1 1.2 Biologically Effective Irradiance 2 1.3 UV‐B‐induced Effects in Plants 3 1.4 Conclusion and Future Prospects 5 Acknowledgements 6 References 6 2 Stimulation of Various Phenolics in Plants Under Ambient UV‐B Radiation 9 Marija Vidović, Filis Morina and Sonja Veljović Jovanović 2.1 Introduction 9 2.2 UV‐B Radiation 10 2.2 Phenolics 12 2.2.1 Chemistry of Phenolic Compounds 13 2.2.2 Biosynthesis and Subcellular Localization of Phenolics 13 2.2.3 Functions of Phenolic Compounds Depend on Their Localization 15 2.4 UV‐B Radiation Stimulates Phenolic Induction 18 2.4.1 Mechanisms of UV‐B Perception 18 2.4.2 UV‐B‐Induced Accumulation of Phenolic Compounds 20 2.4.1 Interactive Effects of UV‐B with UV‐A Radiation and PAR on Phenolics Accumulation 28 2.4.2 Interactive Effects of UV‐B with other Environmental Factors on Phenolics Accumulation 30 2.5 UV‐B‐Induced Photomorphological Responses 31 2.5.1 Connection Between UV‐B‐Induced Morphological Responses and Phenolics 31 2.5.2 Effect of UV‐B Radiation on Root Morphology in Relation to Phenolics 32 2.6 Photosynthesis Under UV‐B Radiation 33 2.6.1 Interplay of Phenolics and Photosynthesis Under UV‐B Radiation 34 2.7 UV‐B Radiation Induces Phenolics Accumulation in Fruits 37 2.8 Conclusions and Future Perspectives 38 References 39 3 UV‐B Radiation: A Reassessment of its Impact on Plants and Crops 57 Krystyna Żuk‐Gołaszewska 3.1 Introduction 57 3.2 Plant Production 58 3.3 Plant protection Against UVB 60 References 60 4 Interaction of UV‐B with the Terrestrial Ecosystem 65 Rohit Kumar Mishra, Sanjesh Tiwari and Sheo Mohan Prasad 4.1 Introduction 65 4.2 Growth and Development 66 4.3 Secondary Metabolites 67 4.4 Susceptibility to Herbivorous Insects 67 4.5 Plant Sexual Reproduction 67 4.6 Genomic Level 68 4.7 Conclusion 69 References 70 5 A Review of Stress and Responses of Plants to UV‐B Radiation 75 Sonika Sharma, Soumya Chatterjee, Sunita Kataria, Juhie Joshi, Sibnarayan Datta, Mohan G. Vairale and Vijay Veer 5.1 Introduction 75 5.2 Morphological and Yield Response to UV‐B 76 5.3 Targets of UV‐B in the Carbon Fixation Cycle 79 5.4 Photoreceptors and Signalling Pathway in Response to UV‐B Radiation 80 5.5 Acclimatization and Protection in Response to UV‐B 82 5.6 Oxidative Stress and Antioxidant System in Response to UV‐B 82 5.7 DNA Damage and Repair Mechanism 83 5.8 Exclusion of UV Components: Experimental Approach to Study the Effect on Plants 85 5.9 Conclusion and Future Prospective 86 Acknowledgement 87 References 87 6 Oxidative Stress and Antioxidative Defence System in Plants in Response to UV‐B Stress 99 Sunita Kataria 6.1 Introduction 99 6.2 Plant Protection Against UV Radiation 101 6.3 UV‐B and ROS 103 6.4 UV‐B and Antioxidant Enzymes 104 6.5 UV‐B and Antioxidant 107 6.6 UV‐B and Signalling 108 6.7 Conclusions and Perspectives 110 References 111 7 Major influence on phytochrome and photosynthetic machinery under UV‐B exposure 123 Anita Singh, Gausiya Bashri and Sheo Mohan Prasad 7.1 Introduction 123 7.2 Photomorphogenesis in Higher Plants 124 7.2.1 Phytochrome system and its interaction with UV‐B 124 7.2.2 Photomorphogenic responses of UV‐B 125 7.2.3 UV‐B signal transduction (UV‐R8) 127 7.3 Effect of UV‐B Exposure on Photosynthetic Machinery 128 7.3.1 Direct effects of UV‐ B on photosynthetic machinery 128 7.3.1.1 Effects of UV‐B stress on components involved in light reaction 128 7.3.1.2 Effect of UV‐B stress on photosystems and cytochrome b6/f complex 129 7.3.2 Indirect effect of UV‐B stress on components involved in dark reaction 132 7.3.2.1 Impact on regulation of stomata and RuBisCO enzyme 132 7.3.3 UV‐B induced ROS production in plants 133 7.3.4 Protective adaptation 133 7.4 Conclusion and Future Perspectives 135 References 136 8 UV‐B Radiation‐Induced Damage of Photosynthetic Apparatus of Green Leaves: Protective Strategies vis‐a‐vis Visible and/or UV‐A Light 143 Padmanava Joshi 8.1 Introduction 143 8.2 UV‐B Effects on the Photosynthetic Apparatus of Leaves 143 8.3 UV‐A Effects on Photosynthetic Apparatus of Leaves (Damage and Promotion) 145 8.4 UV‐A‐Mediated Modulation of UV‐B‐Induced Damage 145 8.5 PAR‐Mediated Balancing of UV‐B‐Induced Damage 146 8.6 Photosynthetic Adaptation and Acclimation to UV‐B Radiation 146 8.7 Corroboration with Sensible Approach 147 8.8 Conclusion 149 Acknowledgements 149 References 149 9 Ultraviolet Radiation Targets in the Cellular System: Current Status and Future Directions 155 Parul Parihar, Rachana Singh, Samiksha Singh, MPVVB Singh, Vijay Pratap Singh and Sheo Mohan Prasad 9.1 Introduction 155 9.2 Absorption Characteristics of Biomolecules 156 9.3 Action Spectrum 156 9.4 Targets of UV‐B 157 9.4.1 Interaction with Biomolecules 157 9.4.2 Nucleic Acids 158 9.4.3 Ribonucleic Acids 159 9.5 UV‐B Interaction with Proteins 159 9.5.1 Tryptophan 160 9.5.2 Tyrosine 160 9.5.3 Phenylalanine 162 9.5.4 Histidine 162 9.6 The Photosynthetic Machinery 163 9.6.1 Photosystem I and II 164 9.6.2 The Light‐Harvesting Complexes 165 9.7 Cell Division and Expansion 167 9.8 Conclusion and Future Directions 168 Acknowledgements 169 References 169 10 Silicon: A Potential Element to Combat Adverse Impact of UV‐B in plants 175 Durgesh Kumar Tripathi, Shweta, Shweta Singh, Vaishali Yadav, Namira Arif, Swati Singh, Nawal Kishor Dubey and Devendra Kumar Chauhan 10.1 Introduction 175 10.2 The role of Silicon Against UV‐B Exposure on Morphology of Plants 178 10.3 The defensive role of silicon against UV‐B exposure on physiological and biochemical traits of plants 179 10.4 Silicon repairs anatomical structures of plants damaged by UV‐B exposures 180 10.5 UV‐B‐induced oxidative stress and silicon supplementation in plants 181 10.6 Silicon supplementation and the status of antioxidant enzymes in plants exposed to UV‐B 183 10.7 Silicon and level of phenolic compounds under UV‐B stress 184 10.8 Present status and future prospectives 186 References 187 11 Sun‐Screening Biomolecules in Microalgae: Role in UV‐Photoprotection 197 Rajesh P Rastogi, Ravi R Sonani, Aran Incharoensakdi and Datta Madamwar 11.1 Introduction 197 11.2 Global Climate Change and UV Radiation 198 11.3 Effects of UV Radiation on Microalgae 199 11.4 UV‐induced Defence Mechanisms 201 11.5 Sun‐Screening Biomolecules as Key UV Photoprotectants 201 11.5.1 Mycosporine‐Like Amino Acids (MAAs) 202 11.5.2 Scytonemin 204 11.6 UV‐Induced Biosynthesis 206 11.7 Photoprotective Function 207 11.8 Conclusions 208 Acknowledgements 208 References 208 12 Plant Response: UB‐B Avoidance Mechanisms 217 Sunil K Gupta, Marisha Sharma, Farah Deeba and Vivek Pandey 12.1 Introduction 217 12.2 Ultraviolet Radiation: Common Source, Classification and Factors 219 12.2.1 Common Sources of UV‐R 219 12.2.2 Classification 219 12.2.3 Environmental Factors Affecting UV Level 220 12.3 UV‐B and Human Health 220 12.3.1 Effects on the Skin 220 12.3.2 Effects on the Eyes 220 12.4 UV‐B and Plant Responses 220 12.4.1 Morphological Responses 220 12.4.1.1 Visible Symptoms 220 12.4.1.2 Plant Growth and Leaf Phenology 221 12.4.1.3 Reproductive Morphology 222 12.4.1.4 UV‐B‐induced photomorphogenesis 222 12.4.2 Leaf Ultrastructure and Anatomy 222 12.4.3 Crop Yield 223 12.4.4 Photosynthesis 225 12.4.4.1 Pigments 225 12.4.4.2 Photosynthetic Machinery 225 12.4.5 Biochemical Responses 226 12.4.5.1 ROS Production in Plants 226 12.4.5.2 Free Radical Scavenging Mechanism 227 12.4.6 Molecular Responses 227 12.4.6.1 UV‐B and Genes 227 12.4.6.2 UV and Proteins 230 12.5 UV‐B Avoidance and Defence Mechanism 234 12.5.1 Avoidance at Morphological Level 234 12.5.1.1 Epicuticular Waxes 234 12.5.2 Avoidance at Biochemical Level 235 12.5.2.1 Possible Role of Pectin Endocytosis in UV‐B Avoidance 235 12.5.3 Avoidance at the Molecular Level 236 12.5.3.1 DNA Repair 236 12.5.3.2 Genes and Avoidance 237 12.5.3.3 UV‐B perceived by UVR8 Strongly Inhibits Shade Avoidance 237 12.5.4 UV‐B and Secondary Metabolites 238 12.5.4.1 Plant Phenolics 238 12.5.4.2 Anthocyanin 239 12.5.4.3 Alkaloids 240 12.5.4.4 Isoprenoids 240 12.5.4.5 Glucosinolates 240 12.6 UV‐B and its Significance 240 12.6.1 Ecological Significance 240 12.6.2 UV‐B and Plant Competition 241 12.7 Conclusion 242 Acknowledgments 243 References 244 13 Impact of UV‐B Exposure on Phytochrome and Photosynthetic Machinery: From Cyanobacteria to Plants 259 Shivam Yadav, Alok Kumar Shrivastava, Chhavi Agrawal, Sonia Sen, Antra Chatterjee, Shweta Rai and LC Rai 13.1 Introduction 259 13.2 Effect of UV‐B Irradiation on Photosynthetic Machinery of Cyanobacteria 260 13.2.1 Pigments 260 13.2.2 Photosynthetic Electron Transport System 261 13.2.3 Photophosphorylation and CO2 fixation 262 13.3 Effect of UV‐B Irradiation on Photosynthetic Machinery of Algae 262 13.4 Effect of UV‐B Irradiation on Photosynthetic Machinery of Higher Plants 264 13.4.1 Pigments 264 13.4.1.1 Phytochrome 264 13.4.1.2 Chlorophylls, carotenoids and other pigments 265 13.4.2 Photosystem II 265 13.4.2.1 Oxygen‐evolving complex 266 13.4.2.2 Plastoquinones and redox‐active tyrosines 266 13.4.2.3 D1 and D2 proteins 267 13.4.3 Photosystem I 267 13.4.4 Cytochrome B6F complex, ATP synthase and RuBisCO 267 13.4.5 Net photosynthesis 268 13.5 Conclusion and future perspective 268 Acknowledgements 268 References 269 14 Discovery of UVR8: New Insight in UV‐B Research 279 ShivamYadav and Neelam Atri 14.1 Introduction 279 14.2 Photoperception in Plants 280 14.3 Discovery of UVR8: UV‐B Photoreceptor 280 14.4 UVR8 Structure 281 14.4.1 Salt Bridge Interactions Mediate UVR8 Dimerization 281 14.4.2 Chromophore and Key Tryptophan Residues 281 14.5 Physiological Roles of UVR8 283 14.5.1 Photomorphogenic Response Regulation by UVR8 283 14.5.2 Regulation of Flavonoid Biosynthesis 284 14.5.3 Plant‐Pathogen and Plant‐Herbivore Interactions 284 14.6 Conclusion and Future Perspectives 284 References 285 15 UVR8 Signalling, Mechanism and Integration with other Pathways 289 Antra Chatterjee, Alok Kumar Shrivastava, Sonia Sen, Shweta Rai, Shivam Yadav and LC Rai 15.1 Introduction 289 15.2 UVR8‐Arbitrated Signalling 290 15.2.1 Constitutively Photomorphogenic 1 (COP1) 290 15.2.2 Elongated Hypocotyl 5 (HY5) and HYH 291 15.2.3 Repressor of UV‐B Photomorphogenesis 1 (RUP1) and RUP2 292 15.3 Molecular Mechanism of Photoreceptor‐Mediated Signalling 293 15.4 UVR8 Involvements in Different Pathways 296 15.4.1 Protection from Photo‐Inhibition and Photo Oxidative Stress 297 15.4.2 Flavonoid and Alkaloid Pathways 298 15.4.3 DNA Damage Repair 299 15.4.4 Defence Against Pathogens 299 15.4.5 Inhibition of Plant Shade Avoidance 300 15.4.6 Regulation of Leaf Morphogenesis 300 15.4.7 Regulation of Root Growth and Development 300 15.4.8 Circadian Clock 301 15.5 Conclusion and Future Perspectives 301 Acknowledgements 302 References 302 Index 309

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Book SynopsisThere has been a continual expansion in aquaculture, such that total production is fast approaching that of wild-caught fisheries. Yet the expansion is marred by continued problems of disease. New pathogens emerge, and others become associated with new conditions. Some of these pathogens become well established, and develop into major killers of aquatic species. Diagnosis and Control of Diseases of Fish and Shellfish focuses on the diagnosis and control of diseases of fish and shellfish, notably those affecting aquaculture. Divided into 12 chapters, the book discusses the range of bacterial, viral and parasitic pathogens, their trends, emerging problems, and the relative significance to aquaculture. Developments in diagnostics and disease management, including the widespread use of serological and molecular methods, are presented. Application/dose and mode of action of prebiotics, probiotics and medicinal plant products used to control disease are examined, as well as the managementTable of ContentsList of Contributors xiii Preface xv 1 Introduction 1 Brian Austin and Aweeda Newaj-Fyzul Conclusion 3 References 3 2 Bacterial Diagnosis and Control in Fish and Shellfish 5 Mags Crumlish Introduction 5 Bacterial Infections in Aquaculture 5 Bacterial Disease Diagnostics and Control of Infections 6 Modern Approaches in Bacterial Diagnostics 9 Control Strategies Against Bacterial Diseases 10 Emerging Bacterial Diseases 11 Climate Change and Aquatic Bacterial Disease 12 Polymicrobial and Concurrent Infections 13 Public Health and Aquaculture 13 Conclusion 14 References 14 3 Complexities of Diagnostics of Viruses Affecting Farmed Aquatic Species 19 Manfred Weidmann References 29 4 Parasitic Diseases in Aquaculture: Their Biology, Diagnosis and Control 37 Giuseppe Paladini, Matt Longshaw, Andrea Gustinelli, and Andrew P. Shinn Introduction 37 Protista 38 Biology and Taxonomy 38 Life-Cycle 38 Public Health 38 Significant Pathogens within the Group 40 Reviews 40 Identification 41 Diagnostic Methods 41 Myxozoa 42 Biology and Taxonomy 42 Life-Cycle 42 Public Health 43 Significant Pathogens within the Group 43 Reviews 43 Identification 43 Diagnostic Methods 43 Mesomycetozoea, Fungi and Fungal-Like Organisms 44 Biology and Taxonomy 44 Life-Cycle 44 Public Health 45 Significant Pathogens within the Group 45 Reviews 46 Identification 46 Diagnostic Methods 46 Monogenea 46 Biology and Taxonomy 46 Life-Cycle 48 Public Health 48 Significant Pathogens within the Group 49 Reviews 49 Identification 49 Diagnostic Methods 49 Digenea 50 Biology and Taxonomy 50 Life-Cycle 52 Public Health 52 Significant Pathogens within the Group 53 Reviews 54 Identification 54 Diagnostic Methods 54 Cestoda 55 Biology and Taxonomy 55 Life-Cycle 55 Public Health 56 Significant Pathogens within the Group 57 Reviews 57 Identification 57 Diagnostic Methods 57 Nematoda 58 Biology and Taxonomy 58 Life-Cycle 58 Public Health 59 Significant Pathogens within the Group 59 Reviews 60 Identification 60 Diagnostic Methods 60 Acanthocephala 60 Biology and Taxonomy 60 Life-Cycle 61 Public Health 62 Significant Pathogens within the Group 62 Reviews 62 Identification 62 Diagnostic Methods 63 Arthropoda 63 Biology and Taxonomy 63 Life-Cycles 63 Parasitic Copepods 63 Isopods 65 Branchiurans 65 Public Health 65 Significant Pathogens within the Group 66 Reviews 66 Taxonomy and Systematics 66 Identification 67 Diagnostic Methods 68 Treatment, Prophylaxis and Farm Management Practices 69 Chemical Approaches 69 Reviews 70 Parasiticide Mode of Action 71 Non-Chemical Approaches in Parasite Control 72 Biosecurity 72 Farm Infrastructure 72 Husbandry-Based Practices 73 Diet 74 Biological Interventions 74 Genetic Breeding Programmes 74 Physical Measures 75 Mechanical Measures 75 Conclusion 76 References 77 5 Modern Methods of Diagnosis 109 Ahran Kim, Thanh Luan Nguyen, and Do-Hyung Kim Introduction 109 Diagnostic Methods for Aquatic Diseases 110 Conventional Methods 110 Histopathology 110 Parasitology 110 Bacteriology 111 Virology 111 Immunoserological Methods 112 Monoclonal and Polyclonal Antibodies 112 Enzyme-linked Immunosorbent Assay 114 Immunofluorescence Test 114 Immunohistochemistry (IHC) 117 Lateral Flow Immunoassay 119 Molecular Methods 121 Hybridization Methods 121 Nucleic Acid Amplification Methods 123 Molecular Typing Methods 128 Future Diagnostic Methods 129 Nanotechnology-based Strategies for Rapid Detection of Fish Pathogens 129 MALDI-TOF Mass Spectrometry for Microbial Identification 130 High-throughput Sequencing Technologies 132 Whole-genome Sequencing of Bacterial Pathogens 132 Metagenomics Approaches for Pathogen Detection 134 Conclusion 135 References 137 6 Immunostimulant Diets and Oral Vaccination In Fish 147 Eva Vallejos-Vidal, Felipe Reyes-López, and Simon MacKenzie Introduction 147 Commonly Measured Immunological Parameters 148 Plant, Herbal and Algal Extracts 150 Plant and Herb Extracts 151 Andrographis paniculata 151 Aloe barbadensis 151 Chinese Herbs 152 Azadirachta indica 152 Camellia sinensis 152 Cedrus deodara 153 Citrus sinensis 153 Coffea arabica 153 Echinacea 153 Eclipta alba 154 Mentha piperita 154 Ocimum sanctum (Tulsi, Queen of Plants) 154 Psidium guajava l 154 Rehmannia glutinosa 154 Rhizophora apiculata 155 Cotinus coggyria 155 Urtica dioica 155 Viscum album coloratum 155 Zingiber officinale 156 Algae and Fungi Extracts 156 Astaxanthin 156 Navicula 156 Porphyridium cruentum 157 Spirulina platensis 157 Ganoderma lucidum 158 Lentinula edodes 158 Diets Containing Pathogen-Associated Molecular Patterns 158 Beta-Glucan 158 Saccharomyces cerevisiae 161Chitin 162 Receptors Mediating Immunostimulation Via PAMPs 162 Oral Vaccination 164 Gut Immunity 165 Non-encapsulated Vaccines 166 Encapsulated Oral Vaccines 166 Future Perspectives 167 References 168 7 Prebiotics and Synbiotics 185 Seyed Hossein Hoseinifar, Yun-Zhang Sun, and Zhigzhang Zhou The Interactions between Feed Additives and Diseases of Fish and Shellfish 185 Prebiotics and Synbiotics: Definition and History 185 Mode of Actions on Disease Resistance 186 Strengthening the Immune Response 186 Conclusion 187 References 187 8 Probiotics for Disease Control in Aquaculture 189 S.M. Sharifuzzaman and Brian Austin Introduction 189 Definition of Probiotics 190 Source of Probiotics 191 Application Methods and Options 192 Delivery Method 192 Dosage, Frequency and Duration of Administration 193 Use of Single Strain or Combinations 194 Dead, Inactivated or Cell Component 194 Range of Probiotics and their Efficacy 195 Modes of Action 204 Example of Commercial-Scale Application 207 Safety and Regulatory Issues 208 Conclusion 208 References 209 9 Use of Medicinal Plants in Aquaculture 223 Mirian Reverter, Nathalie Tapissier-Bontemps, Pierre Sasal, and Denis Saulnier Introduction 223 Medicinal Plants in Aquaculture 224 Biological Activity of Medicinal Plants in Aquaculture 224 Application of Medicinal Plants in Aquaculture 225 Analysis of Plants Used in Aquaculture 227 Plant Orders Most Frequently Used in Aquaculture 239 Lamiales 239 Fabales 241 Asterales 241 Malpighiales 242 Plant Species Most Widely Used in Aquaculture 242 Analysis of Plant Bioactivity 243 Analysis of Plant Parts Used in Aquaculture 244 Other Plants and Perspectives 244 Conclusion 245 References 246 10 Antibiotics and Disinfectants 263 Brian Austin Introduction 263 Antibiotics 264 Chemotherapy Regimes 264 Bacterial Kidney Disease (BKD) 264 Chryseobacterium scophthalmum 267 Cold-Water Disease/Rainbow Trout Fry Syndrome (RTFS) 267 Cold-Water Vibriosis 267 Columnaris 267 Edwardsiellosis (Edwardsiella ictaluri) 267 Edwardsiellosis (E. tarda) 267 Enteric Redmouth (ERM) 267 Flavobacteriosis 268 Flavobacterium johnsoniae 268 Francisellosis 268 Furunculosis; Carp Erythrodermatitis; Goldfish Ulcer Disease 268 Gaffkemia 268 Lactococcosis and Streptococcosis 268 Motile Aeromonas Septicaemia (Aeromonas hydrophila) 269 Mycobacteriosis 269 Nocardiosis 269 Pasteurellosis 269 Plesiomonas shigelloides 269 Rickettsiosis 269 Sekiten byo; Red Spot 269 Sporocytophaga sp. 269 Staphylococcus aureus 269 Staphylococcus epidermidis 269 Tenacibaculum maritimum 269 Vibriosis (Vibrio anguillarum; V. ordalii) 270 Vibrio alginolyticus 270 Vibrio harveyi 270 Vibrio pelagius 270 Vibrio splendidus 270 Disinfectants 270 Disinfectant Regimes 271 Aeromonas Septicaemia; Fin/Tail Rot 271 Amoebic Gill Disease (AGD) and Sea Lice 271 Bacterial Gill Disease 271 Bacterial Kidney Disease 271 Botulism 271 Citrobacter freundii 271 Cold-Water Disease 271 Columnaris 271 Columnaris and Ichthyobodo necator – Concurrent Infections 272 Crayfish Plague 272 Flavobacterium johnsoniae 272 Gyrodactylus salaris 272 Infectious Haematopoietic Necrosis (IHN) 272 Infectious Pancreatic Necrosis (IPN) 272 Mycobacteriosis 272 Pseudomonas fluorescens 272 Sporocytophaga sp. 273 Conclusion 273 References 273 11 Management Techniques and Disease Control 279 Aweeda Newaj-Fyzul and Brian Austin Introduction 279 Disinfection 279 Hygiene 280 Acquisition of New Stock 280 Stocking Levels 280 Water Flow and Aeration 280 Feed/Feeding Regimes 281 Vermin 281 References 281 12 Conclusions 283 Brian Austin and Aweeda Newaj-Fyzul References 284 Index 289

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Book SynopsisPhytochemicals are naturally occurring bioactive compounds found in edible fruits, plants, vegetables, and herbs. Unlike vitamins and minerals, phytochemicals are not needed for the maintenance of cell viability, but they play a vital role in protecting neural cells from inflammation and oxidative stress associated with normal aging and acute and chronic age-related brain diseases.Neuroprotective Effects of Phytochemicals in Neurological Disordersexplores the advances in our understanding of the potential neuroprotective benefits that these naturally occurring chemicals contain. Neuroprotective Effects of Phytochemicals in Neurological Disordersexplores the role that a number of plant-based chemical compounds play in a wide variety of neurological disorders. Chapters explore the impact of phytochemicals on neurotraumatic disorders, such as stroke and spinal cord injury, alongside neurodegenerative diseases such as Alzheimer's and Parkinson's Disease, as well as neuropsychiatric disoTable of ContentsContributors xi Preface xix Acknowledgments xxiii 1 Use of Phytochemicals against Neuroinflammation 1Wei-Yi Ong, Tahira Farooqui, Christabel Fung-Yih Ho, Yee-Kong Ng, and Akhlaq A. Farooqui 2 Flavonoids in Transgenic Alzheimer’s Disease Mouse Models: Current Insights and Future Perspectives 43Angélica Maria Sabogal-Guáqueta, Edison Osorio, and Gloria Patricia Cardona-Gómez 3 Neuroprotective Effects of Polyphenols in Aging and Age-Related Neurological Disorders 65Giulia Corona and David Vauzour 4 Indian Herbs and their Therapeutic Potential against Alzheimer’s Disease 79Navrattan Kaur, Bibekananda Sarkar, Iqbal Gill, Sukhchain Kaur, Sunil Mittal, Monisha Dhiman, Prasad K. Padala, Regino Perez-Polo, and Anil K. Mantha 5 Garlic and its Effects in Neurological Disorders 113Akhlaq A. Farooqui and Tahira Farooqui 6 Effects of Extra-Virgin Olive Oil in Neurological Disorders 133Akhlaq A. Farooqui and Tahira Farooqui 7 Ginger Components as Anti-Alzheimer Drugs: Focus on Drug Design 149Faizul Azam 8 Phytomedicine: A Possible Tool for Alzheimer’s Disease Therapeutics 167Jai Malik 9 Effects of Phytochemicals on Diabetic Retinoneuropathy 199Mohammad Shamsul Ola, Mohd Imtiaz Nawaz, and Abdullah S. Alhomida 10 Herbal Drugs: A New Hope for Huntington’s Disease 213Jai Malik 11 Neuroprotective Properties of Dietary Polyphenols in Parkinson’s Disease 243Altaf S. Darvesh, McKenna McClure, Prabodh Sadana, Chris Paxos, Werner J. Geldenhuys, Joshua D. Lambert, Tariq M. Haqqi, and Jason R. Richardson 12 Potential of Polyphenols in the Treatment of Major Depression: Focus on Molecular Aspects 265Ashish Dhir 13 Effect of Phytochemicals on Diabetes-Related Neurological Disorders 283Abubakar Mohammed, Kanti Bhooshan Pandey, and Syed Ibrahim Rizvi 14 Neuroprotective Effects of Extra-Virgin Olive Oil and its Components in Alzheimer’s Disease 299Alaa H. Abuznait, Hisham Qosa, Loqman A. Mohamed, Yazan S. Batarseh, and Amal Kaddoumi 15 Protective Role of Black-Tea Extract in a Transgenic Drosophila Model of Parkinson’s Disease 317Yasir Hasan Siddique 16 Apitherapy: Therapeutic Effects of Propolis on Neurological Disorders 335Tahira Farooqui and Akhlaq A. Farooqui 17 Molecular Mechanisms behind the Beneficial Activity of Polyunsaturated Fatty Acids in Alzheimer’s Disease and Related Conditions 359Undurti N. Das 18 Prevention of Neuroinflammation by Resveratrol: Focus on Experimental Models and Molecular Mechanisms 377Justine Renaud and Maria-Grazia Martinoli 19 Modulation of the Estradiol and Neprilysin Pathways by Resveratrol in a Lipopolysaccharide Model of Cognitive Impairment 395Nesrine S. El Sayed 20 Neuroprotective Effect of Resveratrol in Cerebral Ischemia 407Ghosh Nilanjan, Ghosh Rituparna, Mandal C. Subhash, and Mahadeb Pal 21 Effects of Nobiletin in Animal Models of Cognitive Impairment: Current Insights and Future Perspectives 421Akira Nakajima, Yasushi Ohizumi, and Kiyofumi Yamada 22 Potential Neuroprotective Effects of Curcumin against Dementia 435Natascia Brondino, Laura Fusar-Poli, Cristina Panisi, and Pierluigi Politi 23 Neuroprotective Activity of Curcumin and Emblica officinalis Extract against Carbofuran-Induced Neurotoxicity in Wistar Rats 447Ramadasan Kuttan and P.P. Binitha 24 Potential Use of Curcuminoids for the Treatment of Alzheimer’s Disease 463Touqeer Ahmed, Sana Javed, Ameema Tariq, and Anwarul-Hassan Gilani 25 Prevention by Curcumin of Neuroinflammation in Intracerebral Hemorrhage 489Yujie Chen and Hua Feng 26 Effect of Polyphenols on Protein Misfolding 501Rona Banerjee 27 Molecular Mechanisms Involved in the Neuroprotective Action of Phytochemicals 515Aditya Sunkaria, Aarti Yadav, Sunil Kumar Sharma, and Rajat Sandhir 28 Nutraceuticals and Cognitive Dysfunction: Focus on Alzheimer’s Disease 561Virginia Boccardi, Clara Tinarelli, and Patrizia Mecocci 29 Summary and Perspective 581Tahira Farooqui and Akhlaq A. Farooqui Index 595

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Book SynopsisAntimicrobial Resistance in Wastewater Treatment Processes Antimicrobial resistance is arguably the greatest threat to worldwide human health. This book evaluates the roles of human water use, treatment and conservation in the development and spread of antimicrobial resistance.Table of ContentsList of Contributors ix Preface xiii Préface xvii About the Cover Artist xxi List of Abbreviations xxiii 1 Antimicrobial Resistance Genes and Wastewater Treatment 1Mehrnoush Mohammadali and Julian Davies 2 When Pathogens and Environmental Organisms Meet: Consequences for Antibiotic Resistance 15Jose Luis Martinez and Fernando Baquero 3 One Health: The Role Wastewater Treatment Plants Play as Reservoirs, Amplifiers, and Transmitters of Antibiotic Resistance Genes and Antibiotic Resistant Bacteria 35Marilyn C. Roberts 4 Assessing the Impact of Wastewater Treatment Plants on Environmental Levels of Antibiotic Resistance 55Jessica Williams]Nguyen, Irene Bueno, and Randall S. Singer 5 Navigating through the Challenges Associated with the Analysis of Antimicrobials and Their Transformation Products in Wastewater 73Randolph R. Singh, Rachel A Mullen, and Diana S. Aga 6 Metagenomic Approaches for Antibiotic Resistance Gene Detection in Wastewater Treatment Plants 95Ying Yang and Tong Zhang 7 Antimicrobials and Antimicrobial Resistant Bacteria in Australia 109Andrew J. Watkinson and Simon D. Costanzo 8 The Mobile Resistome in Wastewater Treatment Facilities and Downstream Environments 129Roberto B. M. Marano and Eddie Cytryn 9 Bacterial Diversity and Antibiotic Resistance Genes in Wastewater Treatment Plant Influents and Effluents 157Veiko Voolaid, Erica Donner, Sotirios Vasileiadis, and Thomas U. Berendonk 10 The Effect of Advanced Treatment Technologies on the Removal of Antibiotic Resistance 179Popi Karaolia, Stella Michael, and Despo Fatta]Kassinos 11 Antimicrobial Resistance Spread Mediated by Wastewater Irrigation: The Mezquital Valley Case Study 207Melanie Broszat and Elisabeth Grohmann 12 Antimicrobial Resistance Related to Agricultural Wastewater and Biosolids 219Lisa M. Durso and Amy Millmier Schmidt 13 Environmental Antibiotic Resistance Associated with Land Application of Biosolids 241Jean E. McLain, Channah M. Rock, and Charles P. Gerba 14 High Throughput Method for Analyzing Antibiotic Resistance Genes in Wastewater Treatment Plants 253Johanna Muurinen, Antti Karkman, and Marko Virta 15 Antibiotic Resistance and Wastewater Treatment Process 263Thi Thuy Do, Sinéad Murphy, and Fiona Walsh 16 Antibiotic Pollution and Occurrence of Bacterial Antibiotic Resistance Genes in Latin American Developing Countries: Case Study of the Katari Watershed in the Bolivian Highlands 293Denisse Archundia, Celine Duwig, Jean M.F. Martins, Frederic Lehembre, Marie]Christine Morel and Gabriela Flores 17 Antimicrobial Resistance in Hospital Wastewaters 309Judith Isaac]Renton and Patricia L. Keen 18 Curbing the Resistance Movement: Examining Public Perception of the Spread of Antibiotic Resistant Organisms 321Agnes V. MacDonald and Patricia L. Keen 19 Public Health Consequences of Antimicrobial Resistance in the Wastewater Treatment Process 329Patricia L. Keen, Raphaël Fugère, and David M. Patrick Index 339

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Book SynopsisBiofilms are predominant mode of life for microbes under natural conditions. The three-dimensional structure of the biofilm provides enhanced protection from physical, chemical and biological stress conditions to associated microbial communities.Table of ContentsPreface xviii List of Contributors xx 1 Biofilms: An Overview of Their Significance in Plant and Soil Health 1Iqbal Ahmad, Mohammad Shavez Khan, Mohd Musheer Altaf, Faizan Abul Qais, Firoz Ahmad Ansari and Kendra P. Rumbaugh 1.1 Introduction 1 1.2 Biofilm Associated with Plants 3 1.3 Biofilm Formation Mechanisms: Recent Update on Key Factors 4 1.4 Biofilm in Soil and Rhizospheres 7 1.5 Genetic Exchange in Biofilms 7 1.6 Diversity and Function of Soil Biofilms 8 1.7 The Role of Biofilms in Competitive Colonization by PGPR 8 1.8 Biofilm Synergy in Soil and Environmental Microbes 9 1.9 Biofilms in Drought Stress Management 10 1.10 Plant Health and Biofilm 10 1.11 How Microbial Biofilms Influence Plant Health? 10 1.12 Soil Health and Biofilms 12 1.13 How to Assess Soil Health? 13 1.14 Impact of Biofilms on Soil Health 14 1.15 Biofilm EPS in Soil Health 14 1.16 Conclusions and Future Directions 15 References 15 2 Role of PGPR in Biofilm Formations and Its Importance in Plant Health 27Govind Gupta, Sunil Kumar Snehi and Vinod Singh 2.1 Introduction 27 2.2 Rhizosphere: A Unique Source of Microorganisms for Plant Growth Promotion 27 2.3 Plant Growth–Promoting Rhizobacteria 28 2.4 Biofilm Producing Plant Growth–Promoting Rhizobacteria 34 2.5 Role of PGPR in Biofilm Formations 35 2.6 Future Research and Development Strategies for Biofilm Producing Sustainable Technology 35 2.7 Conclusions 36 Acknowledgments 36 References 36 3 Concept of Mono and Mixed Biofilms and Their Role in Soil and in Plant Association 43Janaína J. de V. Cavalcante, Alexander M. Cardoso and Vânia L. Muniz de Pádua 3.1 Introduction 43 3.2 Soil- and Plant-Associated Biofilms 45 3.3 Microbial Signaling, Regulation, and Quorum Sensing 46 3.4 Biotechnology 48 3.5 Outlook 49 Acknowledgments 49 References 49 4 Bacillus Biofilms and Their Role in Plant Health 55 Mohd Musheer Altaf, Iqbal Ahmad, Mohd Sajjad Ahmad Khan and Elisabeth Grohmann 4.1 Introduction 55 4.2 Interaction of Bacillus within Plant Rhizosphere and Biofilm Development 57 4.3 Multispecies Biofilms and Their Significance 59 4.4 Biofilm Detection and Characterization 60 4.5 Bacillus Biofilm and Plant Health Promotion 60 4.6 Conclusion and Future Prospects 62 References 63 5 Biofilm Formation by Pseudomonas spp. and Their Significance as a Biocontrol Agent 69Zaki A. Siddiqui and Masudulla Khan 5.1 Introduction 69 5.2 Biofilms 79 5.3 Mechanisms of Biofilm Formation 81 5.4 Metabolites Affecting Biofilm Formation 84 5.5 Biofilm Formation and Biological Control of Plant Diseases 84 5.6 Conclusion 85 References 86 6 Quorum Sensing Mechanisms in Rhizosphere Biofilms 99Jorge Barriuso 6.1 Background 99 6.2 QS in Biofilms Formation 101 6.3 Conclusions 106 References 107 7 Biofilm Formation and Quorum Sensing in Rhizosphere 111Kusum Harjai and Neha Sabharwal 7.1 Introduction 111 7.2 Importance of Rhizosphere 111 7.3 Constituents of Rhizosphere 112 7.4 Communication in Rhizosphere 113 7.5 Quorum Sensing in Rhizobia 115 7.6 Quorum Sensing in Pseudomonads 118 7.7 Biofilm Formation in Rhizosphere 120 7.8 Conclusions 124 References 124 8 The Significance of Fungal Biofilms in Association with Plants and Soils 131Michael W. Harding, Lyriam L.R. Marques, Bryon Shore and G.C. Daniels 8.1 Introduction 131 8.2 What Is a Biofilm? 132 8.3 Where Do We Find Filamentous Fungal Biofilms? 132 8.4 Fungal Biofilms: What Have We Learned from the Budding Yeasts? 133 8.5 What Does a Filamentous Fungal Biofilm Look Like? 134 8.6 Examples of Filamentous Fungal Biofilms 136 8.7 Examples of Fungal Biofilms in Soils and the Rhizosphere 139 8.8 The Mycorhizosphere 141 8.9 A Biofilm Approach to Plant Disease Management 141 References 143 9 Chemical Nature of Biofilm Matrix and Its Significance 151Mohd Sajjad Ahmad Khan, Mohd Musheer Altaf and Iqbal Ahmad 9.1 Introduction 151 9.2 Structural Composition of EPS 154 9.3 Properties of Matrices 160 9.4 Functions of the Extracellular Polymer Matrix: The Role of Matrix in Biofilm Biology 162 9.5 Conclusion 168 Acknowledgments 168 References 169 10 Root Exudates: Composition and Impact on Plant–Microbe Interaction 179Shamsul Hayat, Ahmad Faraz and Mohammad Faizan 10.1 Introduction 179 10.2 Chemical Composition of Root Exudates and Their Significance 180 10.3 Root Exudates in Mediating Plant–Microbe Interaction in Rhizosphere (Negative and Positive Interactions) 180 10.4 Direct and Indirect Effect of Root Exudates on PGPR, Root Colonization, and in Stress Tolerance 182 10.5 Role of Root Exudates in Biofilm Formation by PGPR 185 10.6 Role of Root Exudates in Protecting Plants Pathogenic Biofilm, Quorum Sensing Inhibition 186 10.7 Isolation of Root Exudates 187 10.8 Conclusion 188 References 189 11 Biochemical and Molecular Mechanisms in Biofilm Formation of PlantAssociated Bacteria 195 Alwar Ramanujam Padmavathi, Dhamodharan Bakkiyaraj and Shunmugiah Karutha Pandian 11.1 Introduction 195 11.2 Plant-Associated Bacteria 196 11.3 Biofilms and Plant Pathogens 196 11.4 Molecular and Biochemical Mechanisms Involved in Biofilm Formation 197 11.5 Conclusion 205 References 205 12 Techniques in Studying Biofilms and Their Characterization: Microscopy to Advanced Imaging System in vitro and in situ 215Elisabeth Grohmann and Ankita Vaishampayan 12.1 Introduction 215 12.2 Classical Techniques to Study Biofilms 216 12.3 The Gold Standard: Flow-Cell Technology and Confocal Laser Scanning Microscopy (CLSM) 218 12.4 The Biofilm Flow Cell 218 12.5 Advanced Digital Analysis of Confocal Microscopy Images 221 12.6 Biofilm Studies at Different Scales 222 12.7 Conclusions and Perspectives 224 Acknowledgments 225 References 225 13 Gene Expression and Enhanced Antimicrobial Resistance in Biofilms 231 Daniel Padilla-Chacón, Israel Castillo-Juárez, Naybi Muñoz-Cazares and Rodolfo García-Contreras 13.1 Introduction 231 13.2 Biofilms in the Plant–Microbe Relationship 232 13.3 Stress Induces Biofilm Formation 236 13.4 Relevance for Bacterial-Associated Plants 237 13.5 Enhanced Antimicrobial Resistance in Biofilms Is Mediated by Biofilm Physicochemical Characteristics and Specific Changes in Gene Expression 237 13.6 Potential for Implementing Antibiofilm Strategies to Protect Crops 239 13.6 Conclusions 244 Acknowledgments 244 References 244 14 In Vitro Assessment of Biofilm Formation by Soil- and Plant-Associated Microorganisms 253Michael W. Harding and G.C. Daniels 14.1 Introduction 253 14.2 How to Make a Biofilm 254 14.3 What Is the Best Way to Make a Biofilm in Vitro? 254 14.4 Flow Systems 255 14.5 Static Reactors 261 14.6 Special Considerations for Filamentous Fungal Biofilms 265 14.7 Biofilm Reactors Used to Characterize Plant-Associated Biofilms 266 14.8 Value-Added Products from Biofilm Reactors 266 References 267 15 Factors Affecting Biofilm Formation in in vitro and in the Rhizosphere 275Firoz Ahmad Ansari, Huma Jafri, Iqbal Ahmad and Hussein H Abulreesh 15.1 Introduction 275 15.2 Process of Biofilm Formation 276 15.3 Factor Influencing Biofilm Formation 278 15.4 Conclusions and Future Direction 285 References 286 16 Ecological Significance of Soil-Associated Plant Growth–Promoting Biofilm Forming Microbes for Stress Management 291Arpita Singh and Puneet Singh Chauhan 16.1 Introduction 291 16.2 Rhizosphere Hub of Plant–Microbe Interactions 292 16.3 Commencement of Rhizosphere Effect and Bacterial Colonization by Root Exudates 293 16.4 Quorum Sensing as a Way of Interaction between Bacteria and Host Plant 295 16.5 Biofilms 296 16.6 Effects of Stress on Plants 302 16.7 Stress Tolerance in Plants 309 16.8 Conclusion 316 16.9 Future Perspectives 317 Acknowledgments 317 List of Abbreviations 317 References 318 17 Developed Biofilm-Based Microbial Ameliorators for Remediating Degraded Agroecosystems and the Environment 327G. Seneviratne, P.C. Wijepala and K.P.N.K. Chandrasiri 17.1 Introduction 327 17.2 Developed Microbial Communities as a Potential Tool to Regenerate Degraded Agroecosystems 328 17.3 Biochemistry of Fungal-Bacterial Biofilms 330 17.4 Endophytic Microbial Colonization with the Application of Fungal Bacterial Biofilms 330 17.5 Biofilm Biofertilizers for Restoration of Conventional Agroecosystems 331 17.6 Developed Microbial Biofilms for Environmental Bioremediation 331 17.7 Conclusion 333 References 333 18 Plant Root–Associated Biofilms in Bioremediation 337Sadaf Kalam, Anirban Basu and Sravani Ankati 18.1 Introduction 337 18.2 Biofilms: Definition and Biochemical Composition 337 18.3 Bioremediation and Its Significance 338 18.4 Root-Associated Biofilms 340 18.5 Bioremediation of Contaminants in Rhizospheric Soils 344 18.6 Implications of Rhizospheric Biofilm Formation on Bioremediation 347 18.7 Conclusion and Future Prospects 348 Acknowledgments 349 References 349 19 Biofilms for Remediation of Xenobiotic Hydrocarbons—A Technical Review 357John Pichtel 19.1 Introduction 357 19.2 Polycyclic Aromatic Hydrocarbons 359 19.3 Chlorinated Ethanes, Ethenes, and Aromatics 364 19.4 Chlorinated Aromatics 369 19.5 Polychlorinated Biphenyls (PCBs) 371 19.6 Polychlorinated Dibenzodioxins 374 19.7 Conclusions 375 References 375 20 Plant Pathogenic Bacteria: Role of Quorum Sensing and Biofilm in Disease Development 387Deepak Dwivedi, Mayuri Khare, Himani Chaturvedi and Vinod Singh 20.1 Introduction 387 20.2 Mechanism of Biofilm Formation 388 20.3 Quorum Sensing Mechanism 391 20.4 Plant Pathogenic Bacteria Diversity and Plant Diseases 395 20.5 Blocking Quorum Sensing and Virulence in Combating Phytopathogen 395 20.6 Conclusion 400 References 400 21 Biofilm Instigation of Plant Pathogenic Bacteria and Its Control Measures 409A. Robert Antony, R. Janani and V. Rajesh Kannan 21.1 Introduction 409 21.2 Plant Pathogens 409 21.3 Plant Physiological Alteration by Plant Pathogens 412 21.4 Virulence Strategies of Plant Pathogenic Bacteria 413 21.5 Biofilm Formations 414 21.6 Biofilm Controlling Strategies in Plant Pathogens 419 21.7 Main Targets and Some Potential Tools to Modify Biofilms 420 21.8 Physical Tools for Modifying Biofilms 421 21.9 Chemical Methods 425 21.10 Biological Methods 426 21.11 Future Prospects of Antibiofilm 429 21.12 Conclusion 430 References 430 22 Applications of Biofilm and Quorum Sensing Inhibitors in Food Protection and Safety 439Ashraf A. Khan, John B. Sutherland, Mohammad Shavez Khan, Abdullah S. Althubiani and Iqbal Ahmad 22.1 Introduction 439 22.2 Biofilm Formation by Foodborne Pathogens 439 22.3 Significance of Biofilms in Food and Food Environments 440 22.4 Biofilm Control Strategies in the Food Industry 441 22.5 Natural Products as Antibiofilm Agents and Their Potential Applications 446 22.6 Role of QS Inhibitors in Biofilm Control 449 22.7 Conclusions 451 Acknowledgments 451 References 451 23 Biofilm Inhibition by Natural Products of Marine Origin and Their Environmental Applications 465Alwar Ramanujam Padmavathi, Dhamodharan Bakkiyaraj and Shunmugiah Karutha Pandian 23.1 Introduction 465 23.2 Unity Is Strength: Benefits of Biofilm Formers 466 23.3 Transition of Slimy Film to Persistent Biofilm 467 23.4 Biofilm-Related Infections in Plants 467 23.5 Need for Antibiofilm Agents 467 23.6 Natural Products of Marine Origin as Antibiofilm Agents 469 23.7 Semi-synthetic Antibiofilm Agents Inspired by Marine Natural Products 469 23.8 Environmental Applications of Antibiofilm Agents 469 23.9 Conclusion 472 References 472 24 Plant-Associated Biofilms Formed by Enteric Bacterial Pathogens and Their Significance 479Meenu Maheshwari, Mohammad Shavez Khan, Iqbal Ahmad, Ashraf A. Khan, John B. Sutherland and Abdullah S. Althubiani 24.1 Introduction 479 24.2 Enteric Pathogens in the Plant Environment 480 24.3 Colonization and Biofilm Formation by Enteric Bacteria on Plant Surfaces 483 24.4 Biofilm Regulation in Enteric Bacteria 484 24.5 Influence of Plant Defense on Survival and Biofilm Formation by Enteropathogens 485 24.6 Plant-Associated Enteric Bacteria in Food Safety and Human Health 486 24.7 Conclusions 487 References 487 25 Anti-QS/Anti-Biofilm Agents in Controlling Bacterial Disease: An in silico Approach 497K. Ahmad, M.H. Baig, Fohad Mabood Husain, Iqbal Ahmad, M.E. Khan, M. Oves, Inho Choi and Nasser Abdulatif Al-Shabib 25.1 Introduction 497 25.2 Biofilm and Its Significance 498 25.3 Bioinformatics Approaches in Drug Target Identification and Drug Discovery 500 25.4 Target Identification Using in silico Technologies 500 25.5 Data Resources for Drug Target Identification 501 25.6 Homology Modeling 501 25.7 Docking 502 25.8 Virtual Screening 503 25.9 Application of Bioinformatics in Development of Anti-QS/anti-biofilm Agents 503 25.10 Virtual Screening for Identification of QS Inhibitors 505 25.11 Conclusion 507 References 507 Index 513

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Book SynopsisA comprehensive resource describing innovative technologies and digital health tools that can revolutionize the delivery of health care in low- to middle-income countries, particularly in remote rural impoverished communities Revolutionizing Tropical Medicine offers an up-to-date guide for healthcare and other professionals working in low-resource countries where access to health care facilities for diagnosis and treatment is challenging. Rather than suggesting the expensive solution of building new bricks and mortar clinics and hospitals and increasing the number of doctors and nurses in these deprived areas, the authors propose a complete change of mindset. They outline a number of ideas for improving healthcare including rapid diagnostic testing for infectious and non-infectious diseases at a point-of-care facility, together with low cost portable imaging devices. In addition, the authors recommend a change in the way in which health care is delivered.Table of ContentsPart I The Health of Low‐ and Middle‐Income Countries Today 1 1 The Burden of Communicable Diseases in Low‐ and Middle‐Income Countries 3Kerry Atkinson and David Mabey 1.1 Introduction 4 1.2 Definition of a Communicable Disease 4 1.3 Definition of Low‐ to Middle‐Income Countries 4 1.4 Definition of Burden of Disease 5 1.5 Definition of Disease Elimination 7 1.6 Definition of Disease Eradication 7 1.7 Definition of the Primary Point‐of‐Care 7 1.8 The 2000 Millennium Development Goals (MDGs) and Their Outcomes 7 1.9 Major Individual Diseases in the LMICs: The Big Three ‐ Malaria, HIV/AIDS and Tuberculosis 9 1.10 Other Important Communicable Diseases in the LMICs 17 1.11 Neglected Tropical Disease (NTDs) Prioritized by the World Health Organisation 29 1.12 A Comparison of Health Metrics in an LMIC (Papua New Guinea) and a Developed Country (Australia) with a 7 km Distance Between them 31 1.13 Conclusions 32 Bibliography 32 Webliography 35 2 The Burden of Non‐communicable Diseases in Low‐ and Middle‐Income Countries 37Heiner Grosskurth 2.1 Introduction 38 2.2 Common Non‐communicable Diseases in Low- and Middle-Income Countries 38 2.3 NCD Epidemiology 38 2.4 Prevention of Non‐communicable Diseases 44 2.5 The Relationship Between Communicable and Non‐communicable Diseases 44 2.6 The Health System Burden of NCDs 46 2.7 The Economic Impact of NCDs 47 2.8 The Response to the NCD Epidemic in LMICs 48 2.9 The Readiness of Primary Healthcare Services in LMICs to Cope with the NCD Burden 50 2.10 Introducing Effective NCD Control at Primary Care Services: A Practical Approach 52 2.11 The Role of Primary Healthcare Services in Cancer Prevention and Care 67 2.12 Evaluating Programmes to Strengthen NCD Services at Primary Care Level 70 2.13 Conclusions 70 Bibliography 70 Webliography 78 Part II How to improve healthcare in low‐ and middle‐income countries by primary point‐of‐care rapid diagnostic testing 81 3 The Optimal Features of a Rapid Point-of-Care Diagnostic Test 83David Mabey and Rosanna Peeling 3.1 Introduction 83 3.2 Accuracy Versus Accessibility 83 3.3 Quality Assurance 84 3.4 The Importance of Connectivity 85 3.5 Environmental Friendliness 86 References 86 Webliography 87 4 Revolutionizing HIV Healthcare Delivery Through Rapid and Point‐of‐Care Testing 88Catherine J. Wedderburn, Debrah I. Boeras, and Rosanna W. Peeling 4.1 Synopsis 88 4.2 Introduction 89 4.3 Diagnostic Tests in Resource‐Limited Settings 89 4.4 Challenges of Using Rapid and Point‐of‐Care Testing Within the Context of the Healthcare System 92 4.5 Recent Advances in HIV Diagnosis and Monitoring and Their Impact 93 4.6 WHO Recommendations: POC Diagnostics for Achieving the 90‐90‐90 Goals 98 4.7 Remaining Challenges – Human Resources, Quality Assurance, and Test Selection and Placement 98 4.8 Moving Forward 99 4.9 Conclusions 100 Bibliography 101 Webliography 103 5 Rapid Point‐of‐Care Diagnostic Tests for Tuberculosis 105Richard Lessells 5.1 Introduction 105 5.2 The Need for Rapid Point‐of‐Care TB Diagnostic Tests 106 5.3 Weaknesses in the TB Diagnostic Cascade 106 5.4 Potential Impact of Rapid Point‐of‐Care Diagnostic Tests 107 5.5 Defining the Diagnostic Needs 107 5.6 Smear Microscopy 107 5.7 Molecular Diagnostic Tests 109 5.8 Loop‐Mediated Isothermal Amplification (LAMP) 112 5.9 Line Probe Assays 113 5.10 Other Molecular Tests 113 5.11 Antigen Tests 114 5.12 Combination Diagnostic Packages 115 5.13 Next Generation Sequencing 117 5.14 Diagnostic Imaging 117 5.15 Other Diagnostics 118 5.16 Conclusions 118 References 119 6 Rapid Diagnostic Tests for Syphilis 126David Mabey, Michael Marks, and Rosanna W. Peeling 6.1 Introduction 126 6.2 The Diagnosis of Syphilis 129 6.3 The Impact of POC Testing for Syphilis 131 6.4 Challenges in the Implementation of POC Testing 133 6.5 The Future 134 References 134 7 Point‐of‐Care and Near‐Point‐of‐Care Diagnostic Tests for Malaria: Light Microscopy, Rapid Antigen‐Detecting Tests and Nucleic Acid Amplification Assays 137Heidi Hopkins, and Jane Cunningham 7.1 Introduction 137 7.2 Diagnosis of Malaria 138 7.3 Light Microscopy of Blood Smears 139 7.4 Rapid Diagnostic Tests for Malaria (mRDTs) 140 7.5 Nucleic Acid Amplification‐Based Tests (NAATs) for Malaria 142 7.6 Impact of Point‐of‐Care Testing for Malaria 143 7.7 Challenges in Implementation of POC Testing for Malaria 144 7.8 The Future 146 Biblography 146 Webliography 156 8 Rapid Diagnostic Tests for Human African Trypanosomiasis 159Veerle Lejon, Epco Hasker, and Philippe Büscher 8.1 Introduction 159 8.2 The Early Introduction of Immunodiagnostic Tests in the Diagnosis of HAT 160 8.3 CATT/T.b. gambiense: A Breakthrough in the Immunodiagnosis of Gambiense‐HAT 161 8.4 The Changing Epidemiology of Gambiense‐HAT: The Need for Improved Rapid Diagnostic Tests 163 8.5 Second Generation RDTs for HAT 165 8.6 Future Perspectives and Challenges 165 References 166 Webliography 169 9 Rapid Diagnostic Tests for Visceral Leishmaniasis 170Marleen Boelaert, Suman Rijal, and François Chappuis 9.1 Introduction 170 9.2 Parasitology, a Reference Standard? 171 9.3 Serological Assays 172 9.4 The First Serological Test for Field Use: The Direct Agglutination Assay 173 9.5 The Early Development an Immunochromatographic Test Using the Recombinant Leishmania Antigen rK39 174 9.6 Impact of the VL RDT 174 9.7 Challenges 175 9.8 Other Tests 175 9.9 Discussion 176 9.10 Conclusions 177 References 177 10 A Rapid Diagnostic Test for Dengue 181Claire Mullender, and James Whitehorn 10.1 Introduction 181 10.2 Clinical Features of Dengue 182 10.3 The Importance of Making a Rapid Diagnosis 183 10.4 The Host Response to Infection 184 10.5 Existing Diagnostic Strategies 184 10.6 Review of Existing Rapid Diagnostic Tests 186 10.7 Future Directions 188 10.8 Conclusions 188 References 188 11 Rapid Diagnostic Tests for Influenza 191A.C. Hurt, and I.G. Barr 11.1 Introduction 191 11.2 Overview of RIDTs 192 11.3 Antigen Detection‐based RIDTs 195 11.4 Nucleic Acid Detection‐based RIDTs 197 11.5 Factors that Alter RIDTs Performance 198 11.6 The Use of RIDTs in LMICs 198 11.7 Conclusions 199 Acknowledgment 199 References 200 12 A Rapid Diagnostic Test for Ebola Virus Disease 202Catherine Houlihan and Colin Brown 12.1 Case Report 202 12.2 Introduction 203 12.3 Diagnostic Methods to Detect Ebola Virus Disease 203 12.4 Rapid Diagnostic Tests for Ebola Virus Disease for Use in a Point‐of‐Care Facility 206 12.5 Conclusions 209 Bibliography 210 Webliography 212 13 Rapid Diagnostic Tests for Yaws 213Michael Marks 13.1 Introduction 213 13.2 Epidemiology 214 13.3 Clinical Features 215 13.4 Diagnostic Quandaries 217 13.5 Diagnostic Tests for Yaws 217 13.6 Rapid Diagnostic Tests for Yaws 218 13.7 Molecular Assays 219 References 221 14 Rapid Diagnostic Tests for the Detection of Sickling Hemoglobin 224Amina Nardo‐Marino and Tom N. Williams 14.1 Sickle Cell Disease 224 14.2 Diagnosing Sickle Cell Disease 225 14.3 Conclusions 229 Bibliography 229 15 Progress Toward the Development of Rapid Diagnostic Tests for Lymphatic Filariasis and Onchocerciasis 231Roger B. Peck, Dunia Faulx, and Tala de los Santos 15.1 Introduction 231 15.2 The Development of Rapid Diagnostic Tests 234 15.3 Rapid Diagnostic Tests for Lymphatic Filariasis 234 15.4 Rapid Diagnostic Tests for Onchocerciasis 236 15.5 Next tests and Steps 240 Bibliography 240 Webliography 242 Part III Other tests that can be performed rapidly at the primary‐point‐of-care 245 16 Point‐of‐Care Testing for Blood Counts, HbA1c, Renal Function, Electrolytes, Acid–Base Balance and Hepatitis 247Mark Shephard, Lara Motta, Brooke Spaeth, Heather Halls, and Lauren Duckworth 16.1 Introduction 248 16.2 Point‐of‐Care Testing for Blood Counts 248 16.3 Point‐of‐Care Testing for HbA1c 252 16.4 Point‐of‐Care Testing for Renal Function 254 16.5 Point‐of‐Care Testing for Electrolytes and Acid–Base Balance 257 16.6 Point‐of‐Care Testing for Hepatitis 261 16.7 Conclusions 265 Bibliography 266 Webliography 268 17 Microscopy Skills: Cell Counts, Gram Stains, Ziehl‐Neelsen Staining (ZN) and Blood Films 270Michael Harrison 17.1 Introduction 270 17.2 Microscopy 271 17.3 Microscopy in a POC Testing Laboratory 273 17.4 Gram Staining 274 17.5 Ziehl‐Neelsen Stain (ZN) for Mycobacterium tuberculosis 275 17.6 Blood Film Preparation, Staining and Reporting 276 17.7 Conclusions 278 Bibliography 280 Webliography 280 18 India Ink Stain and Cryptococcal Antigen Test for Cryptococcal Infection 281Hannah K. Mitchell, Joseph N. Jarvis, and Mark W. Tenforde 18.1 Introduction 281 18.2 Diagnosis of Cryptococcal Meningitis 282 18.3 Cryptococcal Antigen Testing (CrAg) 283 18.4 India Ink Stain 285 18.5 CrAg Testing for the Prevention of Cryptococcal Meningitis 286 18.6 Logistical Challenges of CrAg Screening 288 18.7 Non‐Meningeal Cryptococcal Disease 289 18.8 Conclusions 289 References 290 19 Mid Upper Arm Circumference Tapes for Assessment of Severe Acute Malnutrition 294Jane Crawley, Martha Mwangome, James Berkley, and André Briend 19.1 Introduction 294 19.2 Mid Upper Arm Circumference (MUAC) 296 19.3 Comparison of MUAC with other Anthropometric Indices 296 19.4 MUAC: A Brief Historical Perspective 296 19.5 Technique for Measuring MUAC 297 19.6 MUAC, Mortality Risk, and Definitions of Severe Acute Malnutrition 298 19.7 Conclusions: Use of MUAC in Different Settings 301 References 302 Webliography 304 20 Spirometry for Chronic Obstructive Pulmonary Disease Due to Inhalation of Smoke from Indoor Fires Used for Cooking and Heating 306Janet G. Shaw, Annalicia Vaughan, Emma Smith, Cai Fong, Svetlana Stevanovic, and Ian A. Yang 20.1 Introduction 306 20.2 Indoor Air Pollution from Burning Biomass 307 20.3 Mechanisms of Lung Damage from Exposure to Biomass Smoke 309 20.4 Biomass Smoke‐Related Chronic Obstructive Pulmonary Disease (COPD) 311 20.5 Detecting Airflow Obstruction in Biomass Smoke‐Related COPD 314 20.6 Lessons Learnt from Clinical Guidelines for the Detection of Cigarette Smoking‐Related COPD 317 20.7 Conclusions 319 Acknowledgments 320 Bibliography 320 Webliography 326 21 Point‐of‐Care Pulse Oximetry for Children in Low‐Resource Settings 327Carina King, Hamish Graham, and Eric D. McCollum 21.1 Introduction 327 21.2 Hypoxemia 328 21.3 Pulse Oximetry 330 21.4 Current Situation in Low‐Resource Settings 332 21.5 Current Challenges and Future Opportunities 333 21.6 Conclusions 339 Acknowledgments 339 Bibliography 340 Webliography 343 22 The Use of Near‐Infrared Spectroscopy to Monitor Tissue Oxygenation, Metabolism and Injury in Low Resource Settings 344Gemma Bale, and Ilias Tachtsidis 22.1 Introduction 344 22.2 Near‐Infrared Spectroscopy 346 22.3 Clinical Applications 349 22.4 Research Applications 350 22.5 The Use of NIRS in Low Resource Settings 350 22.6 Conclusions 355 Bibliography 356 Webliography 357 Part IV Cheap imaging technologies 361 23 The Use of Point‐of‐Care Ultrasound in the Resource‐Limited Setting 363Tom Heller, Michaëla A.M. Huson, Sabine Bélard, Dan Kaminstein, and Elizabeth Joekes 23.1 Introduction to Point‐of‐Care Ultrasound (POCUS) 365 23.2 Physics and Technical Aspects of Ultrasound 366 23.3 Most Relevant POCUS Applications in the Resource‐Limited Setting 369 23.4 Considerations for Teaching and Implementation 402 23.5 Conclusions 403 Bibliography 403 Webliography 405 24 The Use of Obstetric Ultrasound in Low Resource Settings 406Helen Allott 24.1 Introduction 406 24.2 Pregnancy‐Related Problems for Which Portable Ultrasound may be Useful 406 24.3 Problems with the Use of Ultrasound Scanning in Limited Resource Settings 407 24.4 Provision of Trained Sonographers 409 24.5 The Perspective of the Pregnant Woman to Antenatal Ultrasound Scanning 410 24.6 Abuse of Ultrasound Scanning in Pregnancy 410 24.7 Advances in Ultrasound Technology (and See Chapter 23) 411 24.8 Targeted Ultrasound Scanning 412 24.9 Conclusions 412 References 413 25 Examining the Optic Fundus and Assessing Visual Acuity and Visual Fields Using Mobile Technology 414Nigel M. Bolster, and Andrew Bastawrous 25.1 Introduction: The Ascent of Mobile Technology 414 25.2 Visual Acuity 418 25.3 Visual Fields 424 25.4 Smartphone Ophthalmoscopy 427 25.5 Discussion 432 25.6 Conclusions 434 Part V Telemedicine 439 26 Telemedicine for Clinical Management of Adults in Remote and Rural Areas 441Farhad Fatehi, Monica Taylor, Liam J. Caffery, and Anthony C. Smith 26.1 Introduction 442 26.2 Definitions 443 26.3 Types of Service 444 26.4 Purposes of Telemedicine 444 26.5 Telemedicine for Improving Access to Care 445 26.6 Establishing a Sustainable Telehealth Network: A Case Study from Brazil 445 26.7 Swinfen Telemedicine: A Case Study of Intercontinental Telemedicine 446 26.8 Telemedicine in Natural Disaster Responses 446 26.9 Telemedicine for Remote Training of Healthcare Professionals 447 26.10 Telemedicine for Mental Health (and see Chapter 29) 449 26.11 The Rise of Mobile Health (mHealth) 451 26.12 Social Networking for Clinical Purposes 452 26.13 The World Health Organization and Telemedicine 456 26.14 Challenges and Barriers to Implementation 457 26.15 Conclusions 459 Bibliography 460 Webliography 461 27 Telemedicine for the Delivery of Specialist Pediatric Services 462Anthony C. Smith, Monica Taylor, Farhad Fatehi, and Liam J. Caffery 27.1 Introduction 463 27.2 Technical Consideration for Telemedicine in LMICs 464 27.3 Models of Care in Telepediatrics 469 27.4 Swinfen Charitable Trust Telemedicine Service 469 27.5 Selected Examples of SCT Referrals 470 27.6 National and International Telemedicine Services 474 27.7 mHealth Applications for LMICs 475 27.8 Telemedicine Screening Services 476 27.9 Telemedicine Support during Disaster Situations 476 27.10 Challenges Associated with Telemedicine Adoption in LMICs 477 27.11 Telepediatric Case Studies in LMICs 478 27.12 Pathology Services 480 27.13 Radiographic (Imaging) Services 480 27.14 Maternal Health Services 481 27.15 Conclusions 481 27.16 Acknowledgements 481 27.17 Useful Websites 481 Bibliography 482 Webliography 486 28 Telemedicine in the Diagnosis and Management of Skin Diseases 488Giselle Prado, Odinaka Anyanwu, and Carrie Kovarik 28.1 Introduction 489 28.2 Methods of Delivering Teledermatology: Store and Forward Versus Live Interactive Methods 490 28.3 The History of Teledermatology 490 28.4 Global Teledermatology Programs 490 28.5 Teledermatology in Africa 491 28.6 BUP: The Botswana – University of Pennsylvania Partnership 493 28.7 Teledermatopathology in Botswana 494 28.8 Diagnostic Concordance 495 28.9 Teledermatology in Asia 497 28.10 Teledermatology in Latin America 497 28.11 Barriers 498 28.12 Costs 499 28.13 Education and Training 499 28.14 Equipment and Internet Access 499 28.15 Privacy Concerns 500 28.16 Cultural Hesitancy 500 28.17 Language Barriers 501 28.18 Availability of Treatments 501 28.19 Legal Issues 501 28.20 Follow‐up 501 28.21 Ensuring Success of a New Teledermatology Initiative 501 28.22 Conclusions 502 Bibliography 502 29 Digital Technology, Including Telemedicine, in the Management of Mental Illness 505John A Naslund, Sophia M. Bartels, and Lisa A. Marsch 29.1 Introduction and Background 505 29.2 Why Mental Disorders? 506 29.3 Growing Access to Digital Technology and New Opportunities 508 29.4 Promising Examples from Low‐ and Middle‐Income Countries 509 29.5 Critical Assessment of the Risks and Limitations 517 29.6 Future Directions and Implications 519 29.7 Conclusions 524 Bibliography 525 Webliography 530 30 The Use of Mobile Chest X‐Rays for Tuberculosis Telemedicine 531Meghan L. Jardon, Kelsey L. Pomykala, Ishita Desai, and Kara‐Lee Pool 30.1 Background 531 30.2 Lack of Access to Radiology 532 30.3 Implementation 532 30.4 Cost 536 30.5 Sustainability 536 30.6 Chest X‐Ray Information Technology (IT) 538 30.7 Mobile Devices 540 30.8 Education to Ensure Sustainability 541 30.9 Conclusions 542 Bibliography 542 Webliography 545 Part VI The future 549 31 An Introduction to Digital Health 551Kerry Atkinson 31.1 Introduction 552 31.2 The Pillars and Components of Digital Health for Use in the LMICs 552 31.3 Smartphones and Internet Access 554 31.4 Wearables 555 31.5 Personal Digital Assistants and Chatbots 558 31.6 Augmented Reality 558 31.7 Big Data 558 31.8 Artificial Intelligence (AI) 558 31.9 The Game Changer – A Smartphone with AI Access 563 31.10 Conclusions 564 Bibliography 564 Webliography 564 32 Digital Health in Low- and Middle-Income Countries 566Martin Seneviratne and David Peiris 32.1 Introduction – The Digital Health Revolution 567 32.2 The Current Landscape 569 32.3 HIV/AIDS 569 32.4 Diabetes Mellitus 570 32.5 Maternal Health 570 32.6 Core Functionalities 571 32.7 Patient‐facing Functions 571 32.8 Clinician‐facing Functions 573 32.9 Electronic Medical Record Management 574 32.10 Point‐of‐Care Diagnostic Tests 575 32.11 Epidemiology 575 32.12 Inventory Management and Supply Chain 575 32.13 Challenges to Scale 575 32.14 Emerging Trends and Future Vision 578 32.15 Conclusions 580 Bibliography 580 Webliography 583 33 Nucleic Acid Detection of Tuberculosis Via Innovative Point‐of‐Care Nanotechnologies Targeted for Low Resource Settings 584Benjamin Y.C. Ng, Eugene J.H. Wee, Nicholas P. West, and Matt Trau 33.1 Introduction 584 33.2 Nucleic Acid Detection of Tuberculosis 585 33.3 The Availability of Rapid Diagnostic Tests at the Peripheral Healthcare Level 585 33.4 Leveraging Innovative Nanotechnologies for Point‐of‐Care TB Diagnosis 587 33.5 Sample Preparation Workflow 589 33.6 Nanotechnologies for TB DNA Sensing and Readouts 590 33.7 Quantitative DNA Detection Methodologies 592 33.8 Drug‐resistant Tuberculosis 594 33.9 Conclusions 595 References 596 34 The Use of Functional Nanoparticles for Water Purification 600Jing Zhang, Chuanping Feng, and Chengzhong Yu 34.1 Introduction 600 34.2 Disinfection 602 34.3 Adsorption 607 34.4 Electrochemistry 609 34.5 Conclusions and Future Perspectives 609 References 610 35 The Use of Drones in the Delivery of Rural Healthcare 615Debrah I. Boeras, Blanche C. Collins, and Rosanna W. Peeling 35.1 Challenges in Healthcare Delivery – Opportunities for Innovation 616 35.2 The Need for Disruptive Solutions for Healthcare Delivery in Rural Areas 616 35.3 The Use of Drones for Healthcare Delivery 617 35.4 Further Focus on Uptake of Drone Technology by Different Countries 621 35.5 Models of Potential Public‐Private Collaboration 622 35.6 Promises and Challenges of the Use of Drones in Healthcare Delivery 623 35.7 Outlook for the Future 624 35.8 Conclusions 626 Bibliography 626 Webliography 630 36 Implementation of Point‐of‐Care Tests: Lessons Learnt 633Rosanna W. Peeling, and Debrah I. Boeras 36.1 Synopsis 633 36.2 Healthcare Needs in Low‐ and Middle‐Income Countries 634 36.3 Rapid Diagnostic Tests for Human Immunodeficiency Virus (HIV) Disease (and See Chapter 4) 636 36.4 Rapid Diagnostic Tests for Syphilis (and See Chapter 6) 637 36.5 Rapid Diagnostic Tests for Tuberculosis (TB) (and See Chapter 5) 638 36.6 Rapid Diagnostic Tests for Malaria (and See Chapter 7) 638 36.7 Lessons Learnt from the Implementation of POC Tests 639 36.8 Lessons Learnt from the Implementation of POC Tests for Three Diseases 640 36.9 The Way Forward 642 36.10 The New Paradigm for Technological Innovation and Implementation 643 36.11 Conclusions 644 Bibliography 644 Webliography 648 37 Useful Electronic Healthcare Resources Available for Those Working in Remote Settings 649Tyler Evans 37.1 Introduction 649 37.2 General Web‐Based Resources 650 37.3 Travel Medicine 651 37.4 The Big Three Communicable Diseases in Low‐ and Middle‐Income Countries (LMICs) 652 37.5 Hepatitis C 656 37.6 Other Infectious Diseases (IDs) 657 37.7 Dermatology 657 37.8 Obstetrics and Gynecology 658 37.9 Pediatrics 658 37.10 Psychiatry 658 37.11 Emergency Medicine (EM) 659 37.12 Preventive Health 659 37.13 Disease Mapping 660 37.14 Pharmaceuticals 660 37.15 Online Courses 661 37.16 Recommended Books 661 37.17 Institutions, Societies and Books 662 Webliography 663 38 The Future – How Do We Get from Here to There? 666Kerry Atkinson and David Mabey 38.1 Progress to Date 667 38.2 Major Factors Adversely Affecting Global Health 670 38.3 Continue Doing What Works 674 38.4 New Measures for Improving Remote Rural Healthcare 674 38.5 The UN 2015 Sustainable Development Goals for 2016–2030 677 38.6 Conclusions 681 Bibliography 682 Webliography 683 Glossary 684 Index 693

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Book SynopsisA comprehensive introduction to the physiology, biochemistry, and molecular biology of produce growth, paired with cutting-edge technological advances in produce preservation Revised and updated, the second edition of Postharvest Biology and Nanotechnology explores the most recent developments in postharvest biology and nanotechnology. Since the publication of the first edition, there has been an increased understanding of the developmental physiology, biochemistry, and molecular biology during early growth, maturation, ripening, and postharvest conditions. The contributorsnoted experts in the fieldreview the improved technologies that maintain the shelf life and quality of fruits, vegetables, and flowers.This second edition contains new strategies that can be implemented to remedy food security issues, including but not limited to phospholipase D inhibition technology and ethylene inhibition via 1-MCP technology. The text offers an introduction to technologies used in production prTable of ContentsContributors vii Preface xi 1 Enhancing Food Security Through Postharvest Technology: Current and Future Perspectives 1Gopinadhan Paliyath, Autar K. Mattoo, Avtar K. Handa, Kalidas Shetty, and Charles L. Wilson 2 Ripening and Senescence of Fleshy Fruits 15Raheel Anwar, Autar K. Mattoo, and Avtar K. Handa 3 Ethylene Signal Transduction During Fruit Ripening and Senescence 53Priya Padmanabhan and Gopinadhan Paliyath 4 Preharvest and Postharvest Technologies Based on Hexanal: An Overview 89Gopinadhan Paliyath and Priya Padmanabhan 5 Nitric Oxide Signaling in Plants 103Dandan Huang, Xiaokang Zhang, Jie Zhou, and Shuhua Zhu 6 Postharvest Uses of Ozone Application in Fresh Horticultural Produce 129Vijay Yadav Tokala, Zora Singh, and Alan D. Payne 7 Active and Intelligent Packaging for Reducing Postharvest Losses of Fruits and Vegetables 171Ranjeet Shinde, Victor Rodov, Shanthanu Krishnakumar, and Jayasankar Subramanian 8 Application of Hexanal‐containing Compositions and Its Effect on Shelf‐life and Quality of Banana Varieties in Kenya 191Margaret Hutchinson 9 Hexanal Compositions for Enhancing Shelf‐life and Quality in Papaya 199Ilmi Hewajulige, Shanthi Wilson, and Margaret Hutchinson 10 Effect of Hexanal Composition Treatment on Wine Grape Quality 215Moustapha Oke, Priya Padmanabhan, and Gopinadhan Paliyath 11 Benefits of Application of Hexanal Compositions on Apples 225Priya Padmanabhan and Gopinadhan Paliyath 12 Preharvest Spray Application of Blueberry Fruits with Hexanal Formulations Improves Fruit Shelf‐life and Quality 231Priya Padmanabhan, Thilaka Krishnaraj, Alan Sullivan, and Gopinadhan Paliyath 13 Improving Shelf‐life and Quality of Sweet Cherry (Prunus avium L.) by Preharvest Application of Hexanal Compositions 237Priya Padmanabhan and Gopinadhan Paliyath 14 Hexanal Effects on Greenhouse Vegetables 243Priya Padmanabhan and Gopinadhan Paliyath 15 Reduction of Preharvest and Postharvest Losses of Sweet Orange (Citrus sinensis L. Osberck) Using Hexanal in Eastern Tanzania 255Maulid W. Mwatawala, Anna Baltazari, Theodosy J. Msogoya, Hosea D. Mtui, Jaspa Samwel, and Lucy M. Chove 16 Postharvest Technologies in Tender Fruits: Peach, Nectarine, Plum, and Apricot 265Jayasankar Subramanian, Shanthanu Krishnakumar, Ranjeet Shinde, and Walid El Kayal 17 Effect of Hexanal Compositions on Guava Fruits 287Karanbir S. Gill 18 Effect of Hexanal Vapor Treatments on Delay of Flower Senescence 295Priya Padmanabhan and Gopinadhan Paliyath 19 Applications of Nanostructured and Microstructured Materials in Postharvest Packaging of Fresh Fruits and Vegetables 301Loong‐Tak Lim 20 Economic Impact of Hexanal‐based Nanotechnology on Mango Value Chain in Tamil Nadu State, India 327C. Sekar, K.S. Subramanian, G.J. Janavi, and Jayasankar Subramanian 21 Cyclodextrin Inclusion Complex for Smart Delivery of Volatiles in Nano‐Food Systems 365Marimuthu Subramanian, K.S. Subramanian, Vivek Kumar, Jayanthi Rajan, and Viji Nagaraj Glossary 383 Index 389

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Book SynopsisProvides well-organized coverage of statistical analysis and applications in biology, kinesiology, and physical anthropology with comprehensive insights into the techniques and interpretations of R, SPSS, Excel, and Numbers output An Introduction to Statistical Analysis in Research: With Applications in the Biological and Life Sciences develops a conceptual foundation in statistical analysis while providing readers with opportunities to practice these skills via research-based data sets in biology, kinesiology, and physical anthropology. Readers are provided with a detailed introduction and orientation to statistical analysis as well as practical examples to ensure a thorough understanding of the concepts and methodology. In addition, the book addresses not just the statistical concepts researchers should be familiar with, but also demonstrates their relevance to real-world research questions and how to perform them using easily available software packages incluTable of ContentsPreface ix Acknowledgments xi About the Companion Website xiii 1 Experimental Design 1 1.1 Experimental Design Background 1 1.2 Sampling Design 2 1.3 Sample Analysis 7 1.4 Hypotheses 9 1.5 Variables 10 2 Central Tendency and Distribution 13 2.1 Central Tendency and Other Descriptive Statistics 13 2.2 Distribution 18 2.3 Descriptive Statistics in Excel 34 2.4 Descriptive Statistics in SPSS 48 2.5 Descriptive Statistics in Numbers 52 2.6 Descriptive Statistics in R 57 3 Showing Your Data 61 3.1 Background on Tables and Graphs 61 3.2 Tables 62 3.3 Bar Graphs, Histograms, and Box Plots 63 3.4 Line Graphs and Scatter Plots 136 3.5 Pie Charts 165 4 Parametric versus Nonparametric Tests 191 4.1 Overview 192 4.2 Two-Sample and Three-Sample Tests 194 5 t-Test 195 5.1 Student’s t-Test Background 195 5.2 Examples t-Tests 196 5.3 Case Study 201 5.4 Excel Tutorial 205 5.5 Paired t-Test SPSS Tutorial 209 5.6 Independent t-Test SPSS Tutorial 213 5.7 Numbers Tutorial 218 5.8 R Independent/Paired-Samples t-Test Tutorial 223 6 ANOVA 227 6.1 ANOVA Background 227 6.2 Case Study 236 6.3 One-Way ANOVA Excel Tutorial 241 6.4 One-Way ANOVA SPSS Tutorial 247 6.5 One-Way Repeated Measures ANOVA SPSS Tutorial 252 6.6 Two-Way Repeated Measures ANOVA SPSS Tutorial 261 6.7 One-Way ANOVA Numbers Tutorial 272 6.8 One-Way R Tutorial 288 6.9 Two-Way ANOVA R Tutorial 291 7 Mann–Whitney U and Wilcoxon Signed-Rank 297 7.1 Mann–Whitney U and Wilcoxon Signed-Rank Background 297 7.2 Assumptions 298 7.3 Case Study – Mann—Whitney U Test 299 7.4 Case Study –Wilcoxon Signed-Rank 302 7.5 Mann–Whitney U Excel Tutorial 305 7.6 Wilcoxon Signed-Rank Excel Tutorial 313 7.7 Mann–Whitney U SPSS Tutorial 319 7.8 Wilcoxon Signed-Rank SPSS Tutorial 324 7.9 Mann–Whitney U Numbers Tutorial 328 7.10 Wilcoxon Signed-Rank Numbers Tutorial 337 7.11 Mann–Whitney U/Wilcoxon Signed-Rank R Tutorial 350 8 Kruskal–Wallis 353 8.1 Kruskal–Wallis Background 353 8.2 Case Study 1 354 8.3 Case Study 2 358 8.4 Kruskal–Wallis Excel Tutorial 362 8.5 Kruskal–Wallis SPSS Tutorial 368 8.6 Kruskal–Wallis Numbers Tutorial 375 8.7 Kruskal–Wallis R Tutorial 386 9 Chi-Square Test 393 9.1 Chi-Square Background 393 9.2 Case Study 1 394 9.3 Case Study 2 401 9.4 Chi-Square Excel Tutorial 405 9.5 Chi-Square SPSS Tutorial 418 9.6 Chi-Square Numbers Tutorial 426 9.7 Chi-Square R Tutorial 429 10 Pearson’s and Spearman’s Correlation 435 10.1 Correlation Background 435 10.2 Example 435 10.3 Case Study – Pearson’s Correlation 442 10.4 Case Study – Spearman’s Correlation 445 10.5 Pearson’s Correlation Excel and Numbers Tutorial 448 10.6 Spearman’s Correlation Excel Tutorial 455 10.7 Pearson/Spearman’s Correlation SPSS Tutorial 462 10.8 Pearson/Spearman’s Correlation R Tutorial 467 11 Linear Regression 473 11.1 Linear Regression Background 473 11.2 Case Study 480 11.3 Linear Regression Excel Tutorial 484 11.4 Linear Regression SPSS Tutorial 497 11.5 Linear Regression Numbers Tutorial 508 11.6 Linear Regression R Tutorial 517 12 Basics in Excel 523 12.1 Opening Excel 524 12.2 Installing the Data Analysis Tool Pak 525 12.3 Cells and Referencing 529 12.4 Common Commands and Formulas 532 12.5 Applying Commands to Entire Columns 534 12.6 Inserting a Function 536 12.7 Formatting Cells 537 13 Basics in SPSS 539 13.1 Opening SPSS 539 13.2 Labeling Variables 541 13.3 Setting Decimal Placement 543 13.4 Determining the Measure of a Variable 544 13.5 Saving SPSS Data Files 545 13.6 Saving SPSS Output 547 14 Basics in Numbers 551 14.1 Opening Numbers 551 14.2 Common Commands 553 14.3 Applying Commands 555 14.4 Adding Functions 557 15 Basics in R 561 15.1 Opening R 561 15.2 Getting Acquainted with the Console 562 15.3 Loading Data 566 15.4 Installing and Loading Packages 570 15.5 Troubleshooting 576 16 Appendix 579 Flow Chart 579 Literature Cited 581 Glossary 585 Index 591

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Book SynopsisInternational experts present innovative therapeutic strategies to treat cancer patients and prevent disease progression Extracellular Targeting of Cell Signaling in Cancer highlights innovative therapeutic strategies to treat cancer metastasis and prevent tumor progression. Currently, there are no drugs available to treat or prevent metastatic cancer other than non-selective, toxic chemotherapy. With contributions from an international panel of experts in the field, the book integrates diverse aspects of biochemistry, molecular biology, protein engineering, proteomics, cell biology, pharmacology, biophysics, structural biology, medicinal chemistry and drug development. A large class of proteins called kinases are enzymes required by cancer cells to grow, proliferate, and survive apoptosis (death) by the immune system. Two important kinases are MET and RON which are receptor tyrosine kinases (RTKs) that initiate cell signaling pathways outside the cell suTable of ContentsList of Contributors xiii Preface xvii 1 Discovery and Function of the HGF/MET and the MSP/RON Kinase Signaling Pathways in Cancer 1Silvia Benvenuti, Melissa Milan and Paolo M. Comoglio 1.1 Introduction 1 1.2 MET Tyrosine Kinase Receptor and its Ligand HGF: Structure 1 1.2.1 The Invasive growth Program 2 1.2.2 MET Mediated Signaling 4 1.2.2.1 MET Down-regulation 7 1.2.3 Cross-talk between MET and Other Receptors 7 1.2.4 MET Activation in Human Cancers 9 1.2.4.1 MET, Hypoxia and Ionizing Radiations 10 1.2.4.2 MET Expression in Cancer Stem Cells: a Paradigm of Inherence 11 1.2.4.3 Oncogene Addiction and Oncogene Expedience 11 1.2.5 Targeting HGF/MET as a Therapeutic Approach in Human Cancer 12 1.2.5.1 HGF Antagonists 13 1.2.5.2 Tyrosine Kinase Inhibitors 15 1.2.5.3 Anti-MET Monoclonal Antibodies 17 1.2.5.4 Alternative MET Blocking Strategies 18 1.2.6 Primary and Secondary Resistance 18 1.2.6.1 MET Role in Resistance to Anticancer Agents 19 1.2.6.2 Mechanism of Resistance to MET Inhibitors 19 1.2.6.3 Combinatorial Therapeutic Strategies 20 1.3 RON Tyrosine Kinase Receptor and its Ligand MSP 21 1.3.1 Discovery and Structural Biology 21 1.3.2 RON Mediated Signaling 25 1.3.3 Cross-talk between RON and other Receptors 26 1.3.4 RON Activation in Human Cancers 26 1.4 Targeting MSP/RON as a Therapeutic Approach in Human Cancer 27 1.5 Concluding Remarks 28 2 The Role of HGF/MET and MSP/RON Signaling in Tumor Progression and Resistance to Anticancer Therapy 45Lidija Klampfer and Benjamin Yaw Owusu 2.1 Introduction 45 2.2 HGF/MET Signaling in Cancer 47 2.3 MSP/RON Signaling in Cancer 52 2.4 Cross-talk between MET and RON Signaling Pathways 53 2.5 HGF/MET and MSP/RON Signaling Elicit Resistance to Cancer Therapy 55 2.6 Conclusions and Perspectives 58 References 58 3 HGF Activator (HGFA) and its Inhibitors HAI-1 and HAI-2: Key Players in Tissue Repair and Cancer 69Hiroaki Kataoka and Takeshi Shimomura 3.1 Introduction 69 3.2 Discovery of HGFA 70 3.2.1 Tissue Injury-induced Activation of HGF 70 3.2.2 Identification of HGFA as a Serum Activator of pro-HGF 71 3.3 Synthesis of HGFA Zymogen in vivo 71 3.4 Molecular Structure of HGFA 72 3.4.1 The Gene Encoding pro-HGFA: HGFAC 72 3.4.2 ProHGFA Protein and its Activation 72 3.4.3 Structure Biology of HGFA 74 3.5 Substrates of HGFA in vivo 75 3.6 Regulation of HGFA Activity by Endogenous Inhibitors 76 3.6.1 HGF Activator Inhibitor-1 (HAI-1): a Cell Surface Regulator of HGFA Activity 76 3.6.2 HGF Activator Inhibitor-2 (HAI-2) 78 3.6.3 Protein C Inhibitor (PCI; SERPINA5) 78 3.7 Proposed Biological Functions of HGFA in vivo 78 3.8 Roles of HGFA in Cancer 80 3.8.1 Enhanced Activation of pro-HGF and pro-MSP in Cancer Tissues 80 3.8.2 Possible Roles of HGFA in Cancer Progression 80 3.9 Conclusions and Future Perspectives of HGFA Research in Cancer 82 References 83 4 Physiological Functions and Role of Matriptase in Cancer 91Fausto A. Varela, Thomas E. Hyland and Karin List 4.1 Introduction 91 4.2 Discovery of Matriptase 91 4.3 Biochemical and Functional Characteristics of Matriptase – Inhibitors, Substrates and Structure 92 4.3.1 Endogenous Polypeptide Matriptase Inhibitors 92 4.3.2 Matriptase Substrates 94 4.3.3 Matriptase Structure 95 4.4 Physiological and Pathophysiological Functions of Matriptase 96 4.4.1 Matriptase in Epidermal Development and Homeostasis 96 4.4.2 Matriptase in the Gastrointestinal Tract 97 4.4.3 Matriptase in Thymocytes and Salivary Glands 98 4.4.4 Matriptase in Placental/Embryonic Development 98 4.4.5 Matriptase in Neural Tube Closure 99 4.4.6 Pathways requiring Matriptase 99 4.4.7 Matriptase in Viral Infection 101 4.5 Role of Matriptase in Cancer 101 4.5.1 Studying Matriptase in Cultured Cancer Cells and Tumor Grafting Models 108 4.5.2 In vivo Cancer Studies using Genetic Models 111 4.5.2.1 Squamous Cell Carcinoma 111 4.5.2.2 Colitis-associated Colon Carcinogenesis 112 4.5.2.3 Breast Cancer 112 4.6 Conclusions 114 References 114 5 The Cell-Surface, Transmembrane Serine Protease Hepsin: Discovery, Function and Role in Cancer 125Denis Belitškin, Shishir Mani Pant, Topi Tervonen and Juha Klefström 5.1 Biology of Hepsin 125 5.1.1 Discovery of Hepsin 125 5.1.1.1 Cloning of Hepsin, HPN Gene 125 5.1.1.2 Assigning Hepsin to Type II Transmembrane Serine Protease Family 126 5.1.2 Hepsin Gene and Protein 126 5.1.2.1 Expression, Regulation and Structure 126 5.1.2.2 Hepsin Activation and Activity 130 5.1.3 Physiological Functions of Hepsin 131 5.1.3.1 Growth Factor Activation 131 5.1.3.2 Serine Protease Cascades 132 5.1.3.3 Cell Proliferation and Motility 132 5.1.3.4 Epithelial Integrity 133 5.1.3.5 Organ Development 135 5.2 Hepsin in Cancer 137 5.2.1 Gain of Oncogenic Function 137 5.2.1.1 Genetic Alterations 137 5.2.1.2 Altered Subcellular Localization 138 5.2.1.3 Oncogenic Hepsin Function in vivo 140 5.2.1.4 How HPN Promotes Cancer 141 5.2.2 Targeting Hepsin in Cancer 143 5.3 Future Prospects 144 5.3.1 Hepsin’s Role as Guardian of Epithelial Integrity 144 5.3.2 Cancer Disease Progression and Metastasis 145 5.3.2.1 Uncontrolled Proteolysis 145 6 Targeting HGF with Antibodies as an Anti-Cancer Therapeutic Strategy 155Dinuka M. De Silva, Arpita Roy and Donald P. Bottaro 6.1 Introduction 155 6.2 HGF Biology 156 6.2.1 HGF Gene Organization and mRNA Transcripts 156 6.2.2 HGF Protein Isoforms and Proteolytic Processing 156 6.2.2.1 HGF Isoforms 156 6.2.2.2 HGF Activation by Proteolytic Processing 159 6.2.3 Key HGF Interactions: Heparan Sulfate Proteoglycans and Met 160 6.2.3.1 Heparan Sulfate Proteoglycans 160 6.2.3.2 Met and Key Intracellular Effectors 161 6.2.4 Major Sites of HGF Expression: Tissues and Organs 162 6.2.5 HGF Function in Development and Adulthood 162 6.2.5.1 hgf or met altered Mice: Embryogenesis 163 6.2.5.2 hgf or met altered Mice: Late Development and Adulthood 163 6.3 HGF in Cancer 164 6.3.1 Lung Cancer 165 6.3.2 Hepatocellular Carcinoma 165 6.3.3 Genitourinary Malignancies 166 6.3.4 Breast Cancer 167 6.3.5 Colorectal and Gastric Carcinomas 167 6.3.6 Papillary Thyroid Carcinoma 168 6.3.7 Brain Tumors 168 6.3.8 Melanoma 169 6.3.9 Head and Neck Squamous Cell Carcinoma 169 6.3.10 Other Malignancies 169 6.4 Anti-HGF Monoclonal Antibodies as Anti-Cancer Therapeutic Candidates 170 6.4.1 Rilotumumab 170 6.4.2 Ficlatuzumab 174 6.4.3 TAK-701 175 6.5 Conclusions and Future Directions 176 Acknowledgements 177 References 177 7 MET and RON Receptor Tyrosine Kinases as Therapeutic Antibody Targets for Cancer 199Mark Wortinger, Jonathan Tetreault, Nick Loizos, and Ling Liu 7.1 MET as a Therapeutic Antibody Target for Cancer 199 7.2 Challenges in Developing MET Therapeutic Antibodies 200 7.3 Anti-MET Antibody Clinical Diagnostics 203 7.4 Anti-MET Antibodies in the Clinic 204 7.4.1 Onartuzumab – Roche 204 7.4.2 Emibetuzumab – Eli Lilly 206 7.4.3 ABT-700 – AbbVie 208 7.4.4 SAIT301 – Samsung 208 7.4.5 ARGX-111 – Argenx 209 7.4.6 Sym-015 – Symphogen 210 7.5 Additional anti-MET Antibodies 210 7.5.1 DN-30 – University of Turin Medical School 210 7.5.2 Other Preclinical Stage anti-MET Antibodies 210 7.6 Summary– anti-MET Antibodies 211 7.7 RON as a Therapeutic Antibody Target for Cancer 211 7.8 Conclusions and Future Outlook 216 References 216 8 Inhibitory Antibodies of the Proteases HGFA, Matriptase and Hepsin 229Daniel Kirchhofer, Charles Eigenbrot, and Robert A. Lazarus 8.1 Anti-Serine Protease Antibodies for Therapeutic Applications 229 8.2 Antibodies can Inhibit Trypsin-Fold Serine Proteases in Diverse Ways 230 8.2.1 Orthosteric Inhibition (Active Site Binding) 231 8.2.2 Allosteric Inhibition 231 8.2.3 Exosite Inhibition 231 8.2.4 Inhibition of Zymogen Activation 231 8.2.5 Cofactor Inhibition 231 8.2.6 Inactivation of Oligomeric Serine Proteases 232 8.2.7 Comparison of Abs with Natural Occurring Protein Modes of Inhibition 232 8.3 Introduction to Antibodies against HGFA, Matriptase and Hepsin 233 8.4 Inhibitory HGFA Antibodies 234 8.5 Inhibitory Matriptase Antibodies 238 8.6 Inhibitory Hepsin Antibodies 239 8.7 Conclusion 240 References 240 9 Inhibitors of the Growth-Factor Activating Proteases Matriptase, Hepsin and HGFA: Strategies for Rational Drug Design and Optimization 247James W. Janetka and Robert A. Galemmo, Jr 9.1 Introduction 247 9.1.1 Proteolytic Control of HGF/MET Oncogenic Signaling 247 9.1.2 Proteolytic Control of MSP/RON Kinase Signaling 248 9.1.3 The Identification of HGF and MSP Converting Enzyme Activity 249 9.2 Small Molecular Weight Inhibitors of HGFA, Matriptase and Hepsin 251 9.2.1 Mechanism-based Inhibitors derived from Substrate Sequences 251 9.2.2 Approved Drugs as Starting Points for Inhibitor Design 257 9.2.3 Retro-Engineering Inhibitors of Related Proteases 258 9.3 Improving Drug-like Properties of the Current Inhibitors: Lessons from the Oral Anti-Coagulants 264 9.4 Conclusion 269 References 270 10 Cyclic Peptide Serine Protease Inhibitors Based on the Natural Product SFTI-1 277Blake T. Riley, Olga Ilyichova, Jonathan M. Harris, David E. Hoke and Ashley M. Buckle 10.1 Introduction: Naturally Occurring Polypeptide Serine Protease Inhibitors 277 10.1.1 Serpins 277 10.1.2 Standard Mechanism Inhibitors 278 10.1.2.1 Kunitz Type 278 10.1.2.2 Kazal Type 278 10.1.2.3 Bowman–Birk Inhibitor (BBI) Family 278 10.2 Selective Inhibitors of Serine Proteases using the Sunflower Trypsin Inhibitor (SFTI-1) as a Scaffold for Rational Drug Design 279 10.2.1 Trypsin 279 10.2.2 Chymotrypsin, Neutrophil Elastase and Cathepsin G 286 10.2.3 Proteasome 286 10.2.4 Matriptase and other Type II Transmembrane Serine Proteases (TTSPs) 286 10.2.5 MASP-1 and MASP-2 286 10.2.6 Other KLKs (KLK5, 7, 14) 287 10.2.7 KLK4 287 10.3 Normal and Pathophysiological Functions of the Human Tissue Kallikrein (KLK)-related Serine Protease Family 288 10.3.1 Physiological Role for KLKs 288 10.3.2 KLKs and their Role in Prostate Cancer Pathogenesis 289 10.3.3 Kallikrein-related Peptidase 4 as a Point of Therapeutic Intervention 290 10.4 Inhibitors of KLK4 Serine Protease 291 10.4.1 Molecular Basis of KLK4 Inhibition by SFTI-1 291 10.4.2 Use of SFTI-1 as a Scaffold in Ligand Design and Optimization 292 10.4.3 Identification of an Optimal Tetrapeptide Substrate 292 10.4.4 SFTI-1FCQR is a Potent Selective Inhibitor of KLK4 293 10.4.4.1 Structural Basis for Potency and Selectivity of SFTI-1FCQR Derivative 293 10.5 Potential Therapeutic Applications and Challenges 294 10.6 Conclusions/Future Directions 297 References 297 11 Screening Combinatorial Peptide Libraries in Protease Inhibitor Drug Discovery 307Marcin Poreba, Paulina Kasperkiewicz, Wioletta Rut and Marcin Drag 11.1 Introduction 307 11.2 Proteases Involved in Cancer 309 11.2.1 Metalloproteases 309 11.2.2 Serine Proteases 310 11.2.3 Cysteine Proteases 311 11.2.4 Aspartic Proteases 311 11.2.5 Threonine Proteases 312 11.2.6 Target Protease Substrates and Inhibitors 312 11.3 Identification and Optimization of Preferred Substrates 313 11.3.1 Positional Scanning of Substrate Combinatorial Libraries (PS-SCL) 313 11.3.2 Peptide Microarrays 318 11.3.3 Hybrid Combinatorial Substrate Library (HyCoSuL) 318 11.3.4 Counter Selection Substrate Library (CoSeSuL) 320 11.3.5 Combinatorial Substrate Synthesis for Aminopeptidase Screening 320 11.3.6 Internally Quenched Fluorescent (IQF) Substrates 321 11.3.7 Phage Display 322 11.3.8 Protease Substrates – Summary 325 11.4 Design of Covalent Inhibitors Based on Substrates 326 11.4.1 Background and General Characteristics of Inhibitors 326 11.4.2 Substrate-based Inhibitor Design and Discovery 327 11.4.3 PS-SCL Applied to Inhibitors other than Substrates 328 11.4.4 Inhibitors from Phage Display Screening and Directed Evolution of Proteins 331 11.5 Anticancer Drugs – How much Information do We Need? 334 11.6 Conclusions 336 Acknowledgements 337 References 337 12 Chemical Probes Targeting Proteases for Imaging and Diagnostics in Cancer 351Pedro Gonçalves and Steven H. L. Verhelst 12.1 Introduction 351 12.2 Chemical Probes for Proteases 352 12.2.1 Substrate-based Probes 352 12.2.2 Activity-based Probes (ABPs) 356 12.2.3 Photo-crosslinking probes 356 12.2.4 Non-Covalent Probes 358 12.3 Molecular Imaging of Cancer 358 12.3.1 Imaging Tumors with Substrate-based Probes 359 12.3.1.1 Preclinical Model Systems 359 12.3.1.2 Clinical Trials 361 12.3.2 Imaging Tumors with ABPs 362 12.3.2.1 Conventional and multimodal ABPs 362 12.3.2.2 Quenched ABPs 364 12.3.2.3 Towards Clinical Applications 365 12.3.3 Imaging Tumors with Affinity-based Reagents 366 12.3.3.1 Preclinical Models 366 12.3.3.2 Clinical Trials 367 12.4 Conclusions 369 Acknowledgements 370 References 371 13 Cancer Diagnostics of Protease Activity and Metastasis 377Timothy J. O’Brien and John Beard 13.1 Introduction 377 13.2 The Proteins Identified from Patient Tumor Profiling 386 13.2.1 Matriptase 386 13.2.2 Hepsin 387 13.2.3 KLK7 387 13.2.4 KLK6 388 13.2.5 KLK8 388 13.2.6 TMPRSS3 388 13.2.7 MMP-7 389 13.3 ELISA Assay Development 389 13.4 The Role of Markers for Cancer Surveillance and Tumor Monitoring (Early Detection) 390 13.5 Cell Signaling and the Cancer Cascade 399 13.6 Conclusions and Future Prospects 400 References 402 14 Roles of Pericellular Proteases in Tumor Angiogenesis: Therapeutic Implications 411Janice M. Kraniak, Raymond R. Mattingly and Bonnie F. Sloane 14.1 Introduction 411 14.2 Initiation of Angiogenesis 412 14.3 Mechanisms of New Blood Vessel Formation 413 14.3.1 Sprouting Angiogenesis 414 14.3.2 Intussesceptive or Non-sprouting Angiogenesis 415 14.3.3 Neovasculogenesis 415 14.3.4 Vascular Mimicry 416 14.4 Pericellular Proteases and Angiogenesis 417 14.4.1 Metalloproteinases: MMPs, ADAMs and ADAM-TS 418 14.4.1.1 MMPs 418 14.4.1.2 ADAMs and ADAM-TS 422 14.4.2 Serine Proteases 424 14.4.3 Cysteine Cathepsins 425 14.4.3.1 Cysteine Cathepsins in Angiogenesis 426 14.5 Novel Approaches for Targeting Tumor Angiogenesis 428 14.6 Summary 432 Acknowledgements 433 References 433 Index 447

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Book SynopsisTable of Contents1 Organization of the Human Body 1 1.1 Anatomy and Physiology: An Overview 1 1.2 Life Processes 6 1.3 Homeostasis: Maintaining Limits 7 1.4 Aging and Homeostasis 10 1.5 Anatomical Terms 10 1.6 Body Cavities 15 Chapter Review 19 Critical Thinking Applications 20 Answers to Figure Questions 20 2 Introductory Chemistry 21 2.1 Introduction to Chemistry 21 2.2 Chemical Compounds and Life Processes 28 Chapter Review 38 Critical Thinking Applications 39 Answers to Figure Questions 39 3 Cells 40 3.1 A Generalized View of the Cell 40 3.2 The Plasma Membrane 41 3.3 Transport across the Plasma Membrane 43 3.4 Cytoplasm 48 3.5 Nucleus 54 3.6 Gene Action: Protein Synthesis 56 3.7 Somatic Cell Division 59 3.8 Cellular Diversity 61 3.9 Aging and Cells 61 Chapter Review 64 Critical Thinking Applications 66 Answers to Figure Questions 66 4 Tissues 67 4.1 Types of Tissues 67 4.2 Epithelial Tissue 68 4.3 Connective Tissue 78 4.4 Membranes 86 4.5 Muscular Tissue 88 4.6 Nervous Tissue 88 4.7 Tissue Repair: Restoring Homeostasis 88 4.8 Aging and Tissues 89 Chapter Review 90 Critical Thinking Applications 92 Answers to Figure Questions 92 5 The Integumentary System 93 5.1 Skin 93 5.2 Accessory Structures of the Skin 97 5.3 Functions of the Skin 101 5.4 Skin Wound Healing 102 5.5 Aging and the Integumentary System 104 Chapter Review 109 Critical Thinking Applications 110 Answers to Figure Questions 110 6 The Skeletal System 111 6.1 Functions of Bone and the Skeletal System 111 6.2 Types of Bones 112 6.3 Structure of Bone 112 6.4 Bone Formation 116 6.5 Exercise and Bone Tissue 121 6.6 Divisions of the Skeletal System 122 6.7 Skull: An Overview 124 6.8 Unique Features of the Skull 130 6.9 Vertebral Column 132 6.10 Vertebral Regions 134 6.11 Thorax 137 6.12 Pectoral (Shoulder) Girdle 137 6.13 Upper Limb 139 6.14 Pelvic (Hip) Girdle 142 6.15 Lower Limb 144 6.16 Comparison of Female and Male Skeletons 148 6.17 Aging and the Skeletal System 149 Chapter Review 153 Critical Thinking Applications 155 Answers to Figure Questions 155 7 Joints 156 7.1 Classification of Joints 156 7.2 Fibrous Joints 157 7.3 Cartilaginous Joints 159 7.4 Synovial Joints 159 7.5 Types of Movements at Synovial Joints 161 7.6 Types of Synovial Joints 164 7.7 The Knee Joint 166 7.8 Aging and Joints 169 Chapter Review 171 Critical Thinking Applications 172 Answers to Figure Questions 172 8 The Muscular System 173 8.1 Overview of Muscular Tissue 173 8.2 Skeletal Muscle Tissue 174 8.3 Contraction and Relaxation of Skeletal Muscle 178 8.4 Metabolism of Skeletal Muscle Tissue 183 8.5 Control of Muscle Tension 185 8.6 Exercise and Skeletal Muscle Tissue 186 8.7 Cardiac Muscle Tissue 187 8.8 Smooth Muscle Tissue 187 8.9 Aging and Muscular Tissue 189 8.10 How Skeletal Muscles Produce Movement 189 8.11 Principal Skeletal Muscles 190 Chapter Review 218 Critical Thinking Applications 220 Answers to Figure Questions 221 9 Nervous Tissue 222 9.1 Overview of the Nervous System 222 9.2 Histology of Nervous Tissue 224 9.3 Action Potentials 229 9.4 Synaptic Transmission 233 Chapter Review 236 Critical Thinking Applications 237 Answers to Figure Questions 237 10 Central Nervous System, Spinal Nerves, and Cranial Nerves 238 10.1 Spinal Cord Structure 238 10.2 Spinal Nerves 242 10.3 Spinal Cord Functions 243 10.4 Brain 244 10.5 Cranial Nerves 259 10.6 Aging and the Nervous System 261 Chapter Review 263 Critical Thinking Applications 264 Answers to Figure Questions 264 11 Autonomic Nervous System 265 11.1 Comparison of Somatic and Autonomic Nervous Systems 265 11.2 Structure of the Autonomic Nervous System 267 11.3 Functions of the Autonomic Nervous System 271 Chapter Review 275 Critical Thinking Applications 275 Answers to Figure Questions 275 12 Somatic Senses and Special Senses 276 12.1 Overview of Sensations 276 12.2 Somatic Senses 278 12.3 Olfaction: Sense of Smell 281 12.4 Gustation: Sense of Taste 283 12.5 Vision 285 12.6 Hearing and Equilibrium 294 Chapter Review 302 Critical Thinking Applications 303 Answers to Figure Questions 304 13 The Endocrine System 305 13.1 Introduction 305 13.2 Hormone Action 307 13.3 Hypothalamus and Pituitary Gland 309 13.4 Thyroid Gland 314 13.5 Parathyroid Glands 316 13.6 Pancreatic Islets 317 13.7 Adrenal Glands 322 13.8 Ovaries and Testes 325 13.9 Pineal Gland 325 13.10 Other Hormones 325 13.11 The Stress Response 326 13.12 Aging and the Endocrine System 327 Chapter Review 330 Critical Thinking Applications 332 Answers to Figure Questions 332 14 The Cardiovascular System: Blood 333 14.1 Functions of Blood 333 14.2 Components of Whole Blood 334 14.3 Hemostasis 342 14.4 Blood Groups and Blood Types 344 Chapter Review 348 Critical Thinking Applications 349 Answers to Figure Questions 349 15 The Cardiovascular System: Heart 350 15.1 Structure and Organization of the Heart 350 15.2 Blood Flow and Blood Supply of the Heart 357 15.3 Conduction System of the Heart 359 15.4 Electrocardiogram 360 15.5 The Cardiac Cycle 361 15.6 Cardiac Output 362 15.7 Exercise and the Heart 364 Chapter Review 367 Critical Thinking Applications 368 Answers to Figure Questions 368 16 The Cardiovascular System: Blood Vessels and Circulation 369 16.1 Blood Vessel Structure and Function 369 16.2 Blood Flow through Blood Vessels 374 16.3 Circulatory Routes 377 16.4 Hepatic Portal and Fetal Circulations 396 16.5 Checking Circulation 399 16.6 Aging and the Cardiovascular System 400 Chapter Review 402 Critical Thinking Applications 404 Answers to Figure Questions 404 17 The Lymphatic System and Immunity 405 17.1 Lymphatic System 406 17.2 Innate Immunity 410 17.3 Adaptive Immunity 413 17.4 Aging and the Immune System 422 Chapter Review 427 Critical Thinking Applications 428 Answers to Figure Questions 428 18 The Respiratory System 429 18.1 Overview of the Respiratory System 429 18.2 Organs of the Respiratory System 430 18.3 Pulmonary Ventilation 438 18.4 Exchange of Oxygen and Carbon Dioxide 441 18.5 Transport of Respiratory Gases 444 18.6 Control of Breathing 446 18.7 Exercise and the Respiratory System 449 18.8 Aging and the Respiratory System 449 Chapter Review 453 Critical Thinking Applications 454 Answers to Figure Questions 454 19 The Digestive System 455 19.1 Overview of the Digestive System 455 19.2 Layers of the GI Tract and the Omentum 457 19.3 Mouth 459 19.4 Pharynx and Esophagus 462 19.5 Stomach 464 19.6 Pancreas 467 19.7 Liver and Gallbladder 468 19.8 Small Intestine 470 19.9 Large Intestine 476 19.10 Phases of Digestion 479 19.11 Aging and the Digestive System 480 Chapter Review 484 Critical Thinking Applications 485 Answers to Figure Questions 486 20 Metabolism and Nutrition 487 20.1 Metabolism 487 20.2 Metabolism and Body Heat 493 20.3 Nutrients 495 Chapter Review 501 Critical Thinking Applications 502 Answers to Figure Questions 502 21 The Urinary System 503 21.1 Overview of the Urinary System 503 21.2 Structure of the Kidneys 505 21.3 Functions of the Nephron 509 21.4 Transportation, Storage, and Elimination of Urine 516 21.5 Aging and the Urinary System 518 Chapter Review 521 Critical Thinking Applications 522 Answers to Figure Questions 522 22 Fluid, Electrolyte, and Acid–Base Balance 523 22.1 Fluid Compartments and Fluid Balance 523 22.2 Electrolytes in Body Fluids 527 22.3 Acid–Base Balance 530 22.4 Aging and Fluid, Electrolyte, and Acid–Base Balance 532 Chapter Review 533 Critical Thinking Applications 534 Answers to Figure Questions 534 23 The Reproductive Systems 535 23.1 Male Reproductive System 535 23.2 Female Reproductive System 544 23.3 The Female Reproductive Cycle 551 23.4 Birth Control Methods and Abortion 554 23.5 Aging and the Reproductive Systems 557 Chapter Review 562 Critical Thinking Applications 564 Answers to Figure Questions 564 24 Development and Inheritance 565 24.1 Embryonic Period 565 24.2 Fetal Period 574 24.3 Maternal Changes during Pregnancy 575 24.4 Exercise and Pregnancy 577 24.5 Labor and Delivery 577 24.6 Lactation 578 24.7 Inheritance 579 Chapter Review 584 Critical Thinking Applications 585 Answers to Figure Questions 585

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Book SynopsisProvides a broad snapshot of recent findings showing how the environment and genes influence behavior The great debate of nature versus nurture rages on but our understanding of the genetic basis of many behaviors has expanded over the last decade, and there is now very good evidence showing that seemingly complex behaviours can have relatively simple genetic underpinnings, but also that most behaviours have very complicated genetic and environmental architecture. Studies have also clearly shown that behaviors, and other traits, are influenced not just by genes and the environment, but also by the statistical interaction between the two. This book aims to end the nature versus nurture argument by showing that behaviors are nature and nurture and the interaction between the two, and by illustrating how single genes can explain some of the variation in behaviors even when they are seemingly complex. Genes and Behaviour: Beyond Nature-Nurture puts to rest tTable of ContentsList of Contributors xiii Preface xv 1 Nature, Nurture, and Nature-by-Nurture – Killing the Dichotomy 1David J. Hosken, John Hunt and Nina Wedell Acknowledgements 7 References 7 2 Ultimate (Re)Thinking for Behavioural Biology 11Sasha R. X. Dall, John M. McNamara and Alastair J. Wilson 2.1 Evolutionary Reasoning in Modern Behavioural Biology 13 2.2 A Quantitative Genetic View of Behavioural Evolution 15 2.3 Short-Term Ultimate Reasoning: Behavioural Genetics in a Functional Context 20 2.4 Concluding Remarks 21 References 22 3 How the Dual Inheritance of Genes and Culture Shapes Behaviour: A Critical Review with a Focus on Human Culture and Behavioural Diversity 27Thomas E. Currie 3.1 Culture and Behaviour 27 3.2 Cultural Evolution 30 3.2.1 Processes of Cultural Evolution 31 3.2.1.1 Variation 31 3.2.1.2 Inheritance 32 3.2.1.3 Selection and Fitness 34 3.3 Insights from Cultural Evolutionary Approaches 37 3.3.1 Adaptive and Maladaptive Behaviour 37 3.4 Cultural History 39 3.5 Culture and the Evolution of Co-operation 42 3.6 Gene–Culture Coevolution 45 3.7 Conclusion 48 Acknowledgements 50 References 50 4 Beyond Genes and Environments: Indirect Genetic Effects and the Evolution of Behaviour 61John Hunt, James Rapkin, Clarissa M. House and Alastair J. Wilson 4.1 A Quantitative Genetic View of Behavioural Evolution without IGEs 63 4.2 Adding IGEs to the Traditional Theory 66 4.2.1 'Trait-Based' and 'Variance Partitioning' Models of IGEs 67 4.3 From Theory Towards Empiricism 68 4.3.1 Using Trait-Based Models 69 4.3.2 Using Variance Partitioning Models 71 4.3.3 Is Knowledge of the Interactor Trait Critical to Your Study? 72 4.4 Empirical Evidence for IGEs on Behavioural Traits 73 4.4.1 Social Plasticity of Behaviour is Widespread 73 4.4.2 Does Social Plasticity Generate IGEs on Focal Behaviour? 78 4.5 What are the Evolutionary Consequences of IGEs? 81 4.5.1 What about the Role of Social Selection? 82 4.5.2 What Happens When Ψ is Also Able to Evolve? 83 4.5.3 Can IGEs Influence Other Important Evolutionary Processes? 83 4.5.4 What are the Longer Term Consequences of IGEs? 85 4.6 Conclusions and Future Directions 85 References 87 5 Genes and Behaviour 93Chelsea A. Weitekamp and Laurent Keller 5.1 Genetic Architecture of Phenotypic Traits 94 5.2 Effects of Single Genes on Behaviour 95 5.2.1 The Foraging Gene and Food-Search Behaviour 97 5.2.2 Arginine Vasopressin Receptor and Pair-Bonding Behaviour 98 5.2.3 Neuropeptide Y Homolog, Sensory Neurons, and Social Feeding Behaviour 98 5.3 Effects of Supergenes on Behaviour 99 5.3.1 Social Organization in Ants 100 5.3.2 Alternative Mating Tactics in Birds 100 5.4 Evolvability of Behaviour-Associated Genes 101 5.5 Are Behavioural Traits Unique? 101 5.6 Conclusion 103 Acknowledgements 103 References 103 6 Genes and Environments in Drosophila Sex 111David J. Hosken, Amanda Bretman, Stephen F. Goodwin and C. Ruth Archer 6.1 Some Challenges 111 6.2 Introducing Drosophila 112 6.3 The Behaviours 112 6.4 The Genes 113 6.4.1 Single Genes 113 6.4.2 Many Additive Genes 115 6.5 The Environments and the Interactions 116 6.5.1 Social Environments 116 6.5.2 Abiotic Environments 119 6.6 Conclusions 120 Acknowledgements 120 References 120 7 Nature and Nurture in Parental Care 131Nick J. Royle and Allen J. Moore 7.1 Genetics Underlying Parental Care 133 7.1.1 Quantitative Genetic Studies 134 7.1.2 Molecular Genetic Studies 135 7.2 Parental Care is Environmentally Sensitive 137 7.2.1 Hormonal Mediation of Parental Care 138 7.3 Gene by Family Environment Interactions 141 7.3.1 GxFE Studies 141 7.3.2 Heritability of the Social Environment and IGEs 143 7.3.3 Coadaptation and Correlational Selection (Social Epistasis as a Special Case of GxFE) 145 7.4 Summary and Conclusion 147 References 148 8 The Effect of Non-Self Genes on the Behaviour of Hosts 157Nina Wedell 8.1 What are Non-Self Genes (NSGs)? 158 8.2 Indirect Effects of NSGs 158 8.3 Direct Effects of NSGs 159 8.4 Host Responses 160 8.5 Odour is a Key Signal 161 8.6 Kin Recognition 162 8.7 Mate Choice and Reproductive Behaviour 163 8.8 Aggressiveness 166 8.9 Activity, Aggregation, and Dispersal 167 8.10 Feeding 168 8.11 Learning and Memory 170 8.12 Summary and Conclusion 171 References 172 9 The Nature and Nurturing of Animal Minds 181Alex Thornton and Neeltje J. Boogert 9.1 Cognition Evolves 183 9.1.1 Adaptive Cognitive Specializations 183 9.1.2 Heritability of Cognitive Traits 185 9.2 Cognition Develops 187 9.2.1 Cognitive Consequences of a Poor Start in Life 187 9.2.2 Cognitive Silver Spoons 188 9.2.3 Adaptive Developmental Plasticity in Cognition 189 9.3 Cognitive Reaction Norms: Mind-Moulding Gene-by-Environment Interactions 191 9.3.1 The Mystery of (the Lack of) Cognitive Resilience 192 9.3.2 Practice Makes Perfect: Genetic Quality and Cognitive Silver Spoons 193 9.3.3 Cultural and Epigenetic Inheritance of Cognitive Traits 194 9.3.4 Gene by Environment and Methodological Issues in Comparative Cognition 194 9.4 Conclusion 195 References 196 10 Evolution and Human Behaviour: Helping to Make Sense of Modern Life 203Louise Barrett and Gert Stulp 10.1 Understanding Interaction 204 10.2 Understanding the Scope and Limits of an Evolutionary Approach 205 10.3 Evolutionary Thinking as Puzzle Solving 206 10.4 Recognizing the Consequences of Our Actions 208 10.5 Thinking Differently about Fertility Control 210 10.6 Modern Contraception and Mate Choice 212 10.7 Evolution and Assisted Reproductive Technologies 214 10.8 No Free Lunch 216 10.9 Conclusion 217 References 218 11 Next-Gen and the Study of Behaviour 223Simone Immler 11.1 Current Sequencing Technologies 223 11.1.1 Genome-Wide Association Study (GWAS) and Linkage Mapping 224 11.1.1.1 Microarrays 226 11.1.1.2 RAD Sequencing 227 11.1.1.3 Exome Sequencing 227 11.1.1.4 Whole-Genome Sequencing 227 11.1.2 Gene Expression Analyses 228 11.1.2.1 RNA Sequencing (RNAseq) 228 11.1.3 Epigenetic Analyses 228 11.1.3.1 CHiP Sequencing (CHiPseq) 228 11.1.3.2 Bisulfite Sequencing 229 11.2 Caveats and Challenges and Some Solutions 229 11.2.1 Solid Phenotype 229 11.2.2 Sample Quality 230 11.2.3 Sampling 230 11.2.4 Libraries and Sample Pools 230 11.2.5 Reference Genome 231 11.2.6 Sample Size 232 11.2.7 Replication 232 11.2.8 Coverage 232 11.2.9 Pilot Studies 233 11.2.10 Time and Planning 233 11.2.11 Bioinformatics 233 11.2.12 Collaboration 234 11.3 Linking Behavioural Phenotypes to Genotypes using NGS 234 11.4 What’s Next 237 11.4.1 Understanding the Non-Coding Regions of the Genome 238 11.4.2 Gene Knock-down and Knock-out in Non-Model Organisms 238 11.5 Concluding Remarks 240 References 240 12 Nature-Nurture in the Twenty-First Century 245Nina Wedell, John Hunt and David J. Hosken Acknowledgements 249 References 249 Index 253

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Book SynopsisComprehensively explores sexually transmitted diseases, from epidemiology, causative pathogens, clinical impact, and immunology, to management strategies utilizing new strategies of genomics and next-generation diagnostic tools Sexually transmitted infections (STI) are very common worldwide. More than 20 different STIs have been identified, and about 19 million men and women are infected each year in the United States alone. This book looks at the complete picture of common STIs how they form, evolve, and transmit, as well as how they can be treated and managed with modern techniques, medicines, and tools. Diagnostics to Pathogenomics of Sexually Transmitted Infections runs the spectrum of discussion ranging from introduction of causative pathogen, their pathogenesis to epidemiology, immunology, to anatomy and physiology of human genitalia and management strategies. The book offers in-depth chapter coverage on effect of probiotics on reproductive health; mucosal immunity in sexuallyTable of ContentsAbout the Editor xv Contributors xvii Preface xxi 1 Mucosal Immunity in Sexually Transmitted Infections 1Jiri Mestecky and Michael W. Russell 1.1 Introduction 1 1.2 Innate Immunity in the Genital Tract 2 1.2.1 Humoral Defense Factors in Female Secretions 2 1.2.2 Innate Defense Factors in the Male Tract 4 1.3 Immunoglobulins in Secretions of the Genital Tract 4 1.3.1 Female Genital Tract Secretions 4 1.3.2 Origin of Igs in Human Genital Tract Secretions 7 1.3.3 Functions of Genital Tract Antibodies 8 1.4 Cells of the Mucosal Immune System of the Genital Tract 10 1.4.1 Epithelial Cells 10 1.4.2 Immunoglobulin‐Producing Cells 10 1.4.3 T Cells and Other Cell Types 11 1.5 Induction of Immune Responses in the Genital Tract 12 1.5.1 Induction of Humoral Immune Responses in Human Male Genital Tract Secretions 14 1.5.2 Immune Responses in the Genital Tract after Infections 15 1.5.2.1 Gonorrhea 15 1.5.2.2 Chlamydia 15 1.5.2.3 Human Immunodeficiency Virus (HIV) 16 1.5.2.4 Human Papilloma Virus 16 1.6 Concluding Remarks 17 References 17 2 The Role of Circumcision in Preventing Sexually Transmitted Infections 27Kourosh Afshar, Behnam Kazemi, and Andrew E. MacNeily 2.1 Introduction 27 2.2 Biological Mechanisms 27 2.3 Methods of Circumcision 28 2.4 Complications 28 2.5 Role of MC in Transmission of HIV 29 2.5.1 Male‐to‐Female Transmission 29 2.5.2 Female‐to‐Male Transmission 29 2.5.3 Male‐to‐Male Transmission 30 2.6 Human Papilloma Virus (HPV) 30 2.7 Nonulcerative STIs 31 2.7.1 Gonorrhea 31 2.7.2 Trichomonas Vaginalis (Tv) 32 2.7.3 Chlamydia Trachomatis (Ct) 32 2.8 Ulcerative STIs/Genital Ulcer Disease (GUD) 32 2.8.1 Syphilis 33 2.8.2 Chancroid 34 2.9 Use of Male Circumcision as a Public Health Measure 34 2.10 Female Genital Mutilation (FGM) 35 References 36 3 Effect of Probiotics on Reproductive Health 41Piotr Kochan, Magdalena Strus, and Piotr B. Heczko 3.1 Introduction 41 3.2 Definition of Probiotics 43 3.3 Vaginal Microflora (Microbiota) 46 3.4 Applications of Probiotics in Vaginal and Reproductive Health 49 3.4.1 Vaginitis (Aerobic Vaginitis (AV), Bacterial Vaginosis (BV), and Vulvovaginal Candidiasis (VVC)) 50 3.4.2 UTI 52 3.4.3 Pregnancy 52 3.4.4 Other Obstetrics and Gynecology (OB/GYN) Uses of Probiotics 53 3.5 Conclusions 53 References 54 4 Human Immunodeficiency Virus (HIV) Infection 61Santosh Kumar Singh and Sunit K. Singh 4.1 Introduction 61 4.2 HIV Structure/Genome 62 4.3 Routes of Transmission 64 4.3.1 Sexual Transmission 64 4.3.1.1 STDs and Sexual Transmission of HIV 64 4.3.1.2 Vulnerability of Female Genital Tract for HIV Transmission 66 4.3.2 Transmission by Contaminated Blood/Blood Product Transfusion 68 4.3.3 Transmission by Sharing Syringe and Needles 68 4.3.4 Transmission from Mother to Fetus or Newborn Babies 68 4.3.5 Occupational Risk in Healthcare Workers 68 4.4 Host Factors Influencing HIV Infectivity in Sexual Transmission 69 4.4.1 Systemic Host Factors 69 4.4.2 Local Host Factors 69 4.5 Viral Factors Influencing HIV Infectivity in Sexual Transmission 70 4.6 Mechanism of Pathogenesis 71 4.7 Diagnosis of HIV Infections 72 4.8 Therapeutics 73 4.8.1 Antiretroviral Therapies (ARTs) 73 4.8.2 Combinational ARTs 74 4.9 Conclusion 74 References 75 5 Genital Herpes 83Andreas Sauerbrei 5.1 Introduction 83 5.2 Pathogen 83 5.3 Epidemiology 84 5.4 Pathogenesis and Immunity 84 5.5 Clinical Features 86 5.6 Diagnosis 87 5.7 Treatment 90 5.8 Prevention and Control 93 5.9 Conclusion 94 References 95 6 Molluscum Contagiosum 101Tugba Kevser Uzuncakmak and Ayse Serap Karadag 6.1 Introduction 101 6.2 Epidemiology 101 6.3 Molecular Pathogenesis 102 6.4 Diagnosis 103 6.5 Clinical Features 106 6.6 Mode of Spread of Infections 107 6.7 Treatment 107 6.7.1 Treatment Options 108 6.7.1.1 Watchful Waiting 108 6.7.1.2 Procedure‐Based Treatments 109 6.7.1.3 Chemical Agents 110 6.7.1.4 Immune Modulators 111 6.7.1.5 Antiviral Agents 112 6.7.1.6 Immunocompromised Patients 112 6.8 Conclusion 113 References 113 7 Genital Warts 119Filip Rob 7.1 Introduction 119 7.2 Human Papillomavirus 119 7.2.1 Taxonomy 119 7.2.2 Life Cycle 120 7.2.3 Interaction with Immune System 120 7.2.4 Transmission 120 7.2.5 Clearance 120 7.3 Epidemiology 121 7.4 Risk and Protective Factors 121 7.4.1 Risk Factors 121 7.4.2 Protective Factors 122 7.5 Clinical Features 122 7.5.1 Physical Signs 122 7.5.2 Symptoms 123 7.6 Diagnostics 124 7.6.1 Clinical Investigation 124 7.6.2 3–5% Acetic Acid 124 7.6.3 Histopathology 124 7.6.4 HPV DNA Detection 125 7.6.5 HPV Antibodies 125 7.7 Differential Diagnosis 125 7.8 Treatment 126 7.8.1 Cryotherapy 126 7.8.2 Laser Therapy (CO2 laser, Er:YAG laser) 127 7.8.3 Electrocautery 127 7.8.4 Surgical Excision 127 7.8.5 Trichloracetic Acid (80–90% solution) 127 7.8.6 Podophyllotoxin (0.05% solution or 0.15% gel) 127 7.8.7 Imiquimod (3.75% or 5% cream) 127 7.8.8 Sinecatechins (10% or 15% ointment) 129 7.9 Specific Groups 129 7.9.1 Immunocompromised Patients 129 7.9.2 Pregnant Women 129 7.9.3 Children 129 7.10 HPV Vaccination 130 References 131 8 Chlamydia Trachomatis Urogenital Infections: Epidemiology, Clinical Presentations, and Pathogenesis 135Charles W. Armitage, Alison J. Carey, Danica K. Hickey, and Kenneth W. Beagley 8.1 Introduction 135 8.2 Epidemiology 135 8.3 Chlamydial Biology 136 8.3.1 The Attachment and Entry of Chlamydial EBs 136 8.3.2 The Chlamydial Inclusion 137 8.3.3 Chlamydial Replication and Persistence 137 8.4 Clinical Features 138 8.4.1 Urogenital Tract Infections 139 8.4.2 Female Urogenital Tract 139 8.4.3 Infection and Pregnancy 141 8.4.4 Male Urogenital Tract 142 8.4.5 Anorectal Tract Infections 143 8.4.6 Gastrointestinal Chlamydial Infections and Persistence 144 8.4.7 Lymphogranuloma Venereum 144 8.5 Pathogenesis of Chlamydial Infections 145 8.5.1 Pathogenesis of Female Genital Tract Chlamydial Infections 145 8.5.2 Lower FRT Pathogenesis 146 8.5.3 Upper FRT Pathogenesis 146 8.5.4 Pathogenesis of Male Urogenital Tract 148 8.5.5 Chlamydial Urethritis and Prostatitis 148 8.5.6 Chlamydial Infections of the Upper MRT 148 8.5.7 Chlamydial Epididymitis 149 8.5.8 Chlamydial Orchitis 149 8.6 Diagnosis and Treatment 150 8.7 Prevention and Control 151 8.8 Conclusion 152 References 153 9 Donovanosis 167Sarita Martins De Carvalho Bezerra, Marcio Martins Lobo Jardim, and Juliana Uchiyama 9.1 Introduction 167 9.2 Epidemiology 168 9.3 Pathology 168 9.4 Incubation Period 169 9.5 Clinical Pictures 170 9.6 Sites of Involvement 174 9.7 Complications and Sequelae 175 9.8 Diagnosis 175 9.9 Differential Diagnosis 176 9.10 Treatment 176 9.11 Prevention and Control 177 9.12 Disease Control and Prevention 178 References 178 10 Gonorrhea 181 María Teresa Pérez‐Gracia and Beatriz Suay‐García 10.1 Introduction 181 10.2 Pathogen 182 10.2.1 Morphology 182 10.2.2 Virulence Factors 183 10.2.2.1 Type IV Pili (Tfp) 183 10.2.2.2 Por Proteins 183 10.2.2.3 Opacity Proteins (Opa) 184 10.2.2.4 Rmp Proteins 184 10.2.2.5 Lipooligosaccharide (LOS) 184 10.2.2.6 IgA Protease 185 10.2.3 Physiology 185 10.2.4 Genome 185 10.3 Pathogenesis and Immunity 185 10.4 Epidemiology 186 10.5 Clinical Features 188 10.5.1 Gonococcal Infection in Men 188 10.5.2 Gonococcal Infection in Women 188 10.5.3 Extragenital Locations 188 10.6 Diagnosis 189 10.6.1 Samples 189 10.6.2 Staining 191 10.6.3 Culture 191 10.6.4 Identification 193 10.6.5 Neisseria gonorrhoeae Genotyping 193 10.6.6 Nucleic Acid Amplification Tests (NAATs) 197 10.7 Treatment 198 10.8 Prevention and Control 200 10.9 Conclusion 202 References 202 11 Sexually Transmitted Treponematoses 211Lenka Mikalová and David Šmajs 11.1 Introduction 211 11.2 Genetics of TPA and TEN Strains 212 11.3 Virulence Factors of Syphilis and Bejel 214 11.4 Diagnostics of Syphilis and Bejel 215 11.5 Treatment of Syphilis and Bejel 217 11.6 Molecular Typing of Syphilis and Bejel Treponemes 220 11.7 Vaccine Development for Syphilis and Bejel 222 References 223 12 Genital Mycoplasmas 233Suncanica Ljubin‐Sternak 12.1 Introduction 233 12.2 Biology 234 12.3 Pathogenesis 235 12.3.1 Adhesion Proteins 236 12.3.2 Antigenic Variation 236 12.3.3 Production of Enzymes 236 12.3.4 Facultative Intracellular Localization 237 12.3.5 Capacity to Induce Host Immune Response 237 12.4 Epidemiology 237 12.5 Clinical Presentation 238 12.5.1 Urogenital Infections in Women 238 12.5.1.1 Bacterial Vaginosis 238 12.5.1.2 Cervicitis 239 12.5.1.3 Pelvic Inflammatory Disease (PID) and Its Sequalae 239 12.5.1.4 Infections in Pregnancy 240 12.5.2 Urogenital Infections in Men 241 12.5.2.1 Nongonococcal Urethritis (NGU) 241 12.5.2.2 Epididymitis and Prostatitis 241 12.5.2.3 Infertility 241 12.5.3 Rare Manifestations and Clinical Features in Immunocompromised Persons 242 12.5.3.1 Urinary Calculi 242 12.5.3.2 Systemic Infection and Arthritis 242 12.5.3.3 Infection in Immunocompromised Patients 242 12.6 Laboratory Diagnosis 243 12.6.1 Specimen Collection 243 12.6.2 Culture Methods 243 12.6.3 Molecular Methods 245 12.6.4 Serology 246 12.7 Treatment 247 12.8 Prevention and Control 248 References 249 13 Bacterial Vaginosis 257Aliona Rosca and Nuno Cerca 13.1 Introduction 257 13.2 Implication of G. vaginalis in Bacterial Vaginosis 258 13.3 Epidemiology and Risk Factors 260 13.4 Pathogenesis and Immunity 261 13.5 Clinical Features 263 13.6 Diagnosis 263 13.7 Treatment 266 13.8 Conclusions 268 References 268 14 Chancroid 277Margaret E. Bauer and Diane M. Janowicz 14.1 Introduction 277 14.2 Epidemiology of Chancroid and H. ducreyi 277 14.3 Clinical Features 278 14.4 The Pathogen 279 14.5 Pathogenesis and Immunity 280 14.5.1 Overview of Pathogenesis 280 14.5.2 Virulence Mechanisms 280 14.5.3 Regulation of Virulence 282 14.5.4 Immune Response 283 14.6 Diagnosis, Treatment, and Prevention 284 14.7 Chronic Limb Ulcers Caused by H. ducreyi 285 14.8 Conclusions 286 References 287 15 Vulvovaginal Candidosis 293Gilbert G.G. Donders, Katerina S. Ruban, Gert Bellen, and Sivtrigaile Grinceviciene 15.1 Introduction 293 15.2 Etiology 293 15.2.1 Pathogens 293 15.2.2 Morphology 294 15.3 Epidemiology 294 15.3.1 Prevalence 294 15.3.1.1 Asymptomatic Colonization 294 15.3.1.2 Symptomatic Infection 295 15.3.2 Risk Factors 298 15.3.3 Sexual Transmission 298 15.3.4 Young and Elderly Women 298 15.4 Pathogenesis and Immunity 300 15.4.1 Hormones 300 15.4.2 Pregnancy 300 15.4.3 Impaired Glucose Tolerance 301 15.4.4 Genetic Predisposition 301 15.4.4.1 STAT1 Gain of Function Mutations 302 15.4.4.2 CARD9 302 15.4.4.3 AIRE Mutation 302 15.4.4.4 NALP3/CIAS1 304 15.4.4.5 Interleukin-4 304 15.4.4.6 Dectin-1 304 15.4.4.7 Mannose‐Binding Lectin (MBL) 304 15.4.5 Other Factors Affecting Pathogenesis 305 15.5 Symptoms and Signs 305 15.5.1 Acute/Episodic Infection 305 15.5.2 Recurrent Vulvovaginal Candidosis 306 15.6 Diagnosis and Differential Diagnosis 306 15.6.1 Clinical Signs 306 15.6.2 Clinical Examination 306 15.6.3 Wet Mount Microscopy 307 15.6.4 Vaginal pH 309 15.6.5 Vaginal Mycological Culture 310 15.6.6 Molecular Biology 310 15.6.7 Histology 310 15.6.8 Differential Diagnosis 310 15.7 Treatment 311 15.7.1 General Principles of Treatment 311 15.7.2 Treatment of Uncomplicated Acute Infection 311 15.7.3 Treatment of Complicated Acute Infection 312 15.7.3.1 Severe Symptoms, C. albicans Vulvovaginitis 314 15.7.3.2 Non‐Albicans Candida Infection 314 15.7.3.3 Poorly Controlled Diabetes, Immune Suppression 315 15.7.3.4 Pregnancy and Breastfeeding 315 15.7.4 Recurrent Vulvovaginal Candidiasis (RVVC) 316 15.7.4.1 Azole‐Resistant C. albicans 317 15.7.4.2 Elimination of Risk Factors of Recurrence in RVVC Patients 317 15.7.4.3 Underlying Reasons for Failing Maintenance Therapy 318 References 319 16 Tinea Cruris 329Anuradha Bishnoi and Rahul Mahajan 16.1 Introduction 329 16.2 Etiology and Epidemiology 330 16.3 Tinea Cruris as a Sexually Transmitted Infection (STI) 331 16.4 Transmission 331 16.5 Pathogenesis 332 16.5.1 Environmental Factors 332 16.5.2 Agent Factors 332 16.5.3 Host Factors 332 16.5.4 Host Immune Response 333 16.5.5 Clinical Features 333 16.5.6 Variants 335 16.5.6.1 Tinea incognito 335 16.5.6.2 Vesico‐Bullous Tinea Cruris 335 16.5.6.3 White Paint Dots and Pseudomembranous Tinea 335 16.6 Differential Diagnoses 336 16.6.1 Candidiasis 336 16.6.2 Erythrasma 336 16.6.3 Hyperpigmented Pityriasis Versicolor 336 16.7 Laboratory Diagnosis 336 16.7.1 Direct Examination 336 16.7.2 Culture 337 16.7.3 Nucleic Acid Amplification Tests 337 16.8 Treatment of Tinea Cruris and Genitalis 337 16.8.1 Topicals 337 16.8.2 Systemic 337 16.8.3 Recalcitrant/Resistant Tinea: Pathomechanisms and Treatment 338 16.8.4 General Measures to Prevent Tinea Cruris 338 16.9 Conclusion 338 Acknowledgments 339 References 339 17 Trichomonas Vaginalis 341Barbara Van Der Pol 17.1 Introduction 341 17.2 Epidemiology of T. vaginalis 342 17.3 HIV and Trichomonas 344 17.4 Biology and Pathogenesis of T. vaginalis 345 17.5 Clinical Features of T. vaginalis Infection 346 17.6 Diagnosis of T. vaginalis 348 17.6.1 Laboratory Diagnosis 349 17.7 Treatment of T. vaginalis 350 17.8 Conclusion 351 References 351 18 Scabies 357Giuseppe Micali, Giorgia Giuffrida, and Francesco Lacarrubba 18.1 Introduction 357 18.2 Epidemiology 357 18.3 Etiopathogenesis 358 18.4 Clinical Features 359 18.5 Diagnosis 363 18.5.1 Microscopy 363 18.5.2 Dermatoscopy/Videodermatoscopy 363 18.5.3 Histopathology 365 18.5.4 Other Diagnostic Procedures 366 18.6 Treatment 366 18.6.1 Topical Agents 366 18.6.2 Oral Agents 367 18.6.3 Treatment for Crusted Scabies 367 18.7 Prevention and Control 368 18.8 Conclusion 368 References 368 Index 373

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Book SynopsisModel Animals in Neuroendocrinology: From Worm to Mouse to Man offers a masterclass on the opportunities that different model animals offer to the basic understanding of neuroendocrine functions and mechanisms of action and the implications of this understanding. The authors review recent advances in the field emanating from studies involving a variety of animal models, molecular genetics, imaging technologies, and behavior assays. These studies helped unravel mechanisms underlying the development and function of neuroendocrine systems. The book highlights how studies in a variety of model animals, including, invertebrates, fish, birds, rodents and mammals has contributed to our understanding of neuroendocrinology. Model Animals in Neuroendocrinology provides students, scientists and practitioners with a contemporary account of what can be learnt about the functions of neuroendocrine systems from studies across animal taxonomy. This is the seventh volume in the Table of ContentsList of Contributors, vii Series Preface, xiii Preface, xv Acknowledgments, xix About the Companion Website, xxi 1 Neuroendocrine Regulation in the Genetic Model C. elegans, 1Charline Borghgraef, Pieter Van de Walle, Sven Van Bael, Liliane Schoofs,Wouter De Haes, and Isabel Beets 2 Neuroendocrine Control of Reproduction in Aplysia by the Bag Cell Neurons, 29Raymond M. Sturgeon, Alamjeet K. Chauhan, and Neil S. Magoski 3 Neurohormonal Regulation of Metamorphosis in Decapod Crustaceans, 59Scott F. Cummins and Tomer Ventura 4 Drosophila as a Model for Neuroendocrine Control of Renal Homeostasis, 81Julian A.T. Dow, Kenneth A. Halberg, Selim Terhzaz, and Shireen A. Davies 5 Development and Function of the Zebrafish Neuroendocrine System, 101Jakob Biran, Janna Blechman, Einav Wircer, and Gil Levkowitz 6 The Organization and Activation of Sexual Behavior in Quail, 133Charlotte A. Cornil 7 Hamsters as Model Species for Neuroendocrine Studies, 161Jo E. Lewis and Francis J. P. Ebling 8 The Socially Monogamous Prairie Vole: a Rodent Model for Behavioral Neuroendocrine Research, 181Meghan Donovan, Yan Liu, and Zuoxin Wang 9 Brain Dead: The Dynamic Neuroendocrinological Adaptations during Hypometabolism in Mammalian Hibernators, 207Samantha M. Logan, Alex J. Watts, and Kenneth B. Storey 10 Genetically Altered Mice as an Approach for the Investigation of Obesity and Metabolic Disease, 233Rebecca Dumbell and Roger D. Cox 11 HAB/LAB Mice and Rats: Approaching the Genetics and Epigenetics of Trait Anxiety, 257Ludwig Czibere, Rebekka P. Diepold, Alexey E. Umriukhin, Rainer Landgraf, and Sergey V. Sotnikov 12 The Brattleboro Rat: The First and Still Up-to-Date Mutant Rodent Model for Neuroendocrine Research, 279Dora Zelena and Mario Engelmann 13 The Marmoset as a Model for Primate Parental Behavior, 297Atsuko Saito 14 Domestication: Neuroendocrine Mechanisms of Canidae-human Bonds, 313Yury E. Herbeck, Rimma G. Gulevich, Marina Eliava, Darya V. Shepeleva,Lyudmila N. Trut, and Valery Grinevich 15 Sheep as a Model for Control of Appetite and Energy Expenditure, 335Belinda A. Henry and Iain J. Clarke 16 The Horse: An Unexpected Animal Model for (Unexpected) Neuroendocrinology, 361Anne Duittoz, Juliette Cognié, Caroline Decourt, Flavie Derouin, Auréline Forestier, François Lecompte, Abderrahim Bouakkaz, and Fabrice Reigner 17 Humans – The Ultimate Model for the Study of Neuroendocrine Systems, 383Lisa Yang, Chioma Izzi-Engbeaya, and Waljit S. Dhillo Glossary, 407 Index, 421

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Book SynopsisTable of Contents1 What is Life? 1 1.1 Living Organisms Display Nine Specific Characteristics 2 1.2 Human Biology is Structured and Logical 4 1.3 Scientists Approach Questions Using the Scientific Method 9 1.4 Scientific Findings Often Lead to Ethical Dilemmas 13 2 Where Do We Come from and Where Do We Fit? 16 2.1 What are the Origins of Modern Humans? 17 2.2 What Does the Human Body Have in Common with the World Around It? 23 2.3 We Reflect Our Environment: We Have a Habitat and a Niche 29 3 Everyday Chemistry of Life 33 3.1 Life Has a Unique Chemistry 34 3.2 Water is Life’s Essential Chemical 41 3.3 Carbohydrates, Lipids, and Proteins Provide Form and Function 43 3.4 Nucleic Acids Carry Information and Direct Protein Formation 50 4 Cells: Organization and Communication 57 4.1 The Cell is Highly Organized and Dynamic 58 4.2 The Cell Membrane Delineates the Cell 60 4.3 The Components of a Cell are Called Organelles 65 4.4 Cell Communication is Important to Cellular Success 73 5 Tissues 77 5.1 Some Tissues Provide Covering, Protection, and Support 78 5.2 Other Tissues Provide Movement, Heat, and Integration 84 5.3 Organization Increases with Organs, Organ Systems, and the Organism 88 5.4 Scientists Use a Road Map to the Human Body 92 6 The Skeletomuscular System 97 6.1 The Skeletomuscular System is Multifunctional and Dynamic 98 6.2 Bone is Strong and Light Tissue 100 6.3 The Skeleton Holds It All Together 105 6.4 Skeletal Muscles Exercise Power 114 6.5 Whole-Muscle Contractions Require Energy 120 7 The Nervous System 127 7.1 The Nervous System is Categorized by Structure and Function 128 7.2 Neurons Work Through Action Potentials 132 7.3 The Meninges Protect the Brain’s Delicate Structures 139 7.4 The Functions of the Brain and Spinal Cord are Related 145 7.5 The Peripheral Nervous System Extends the Central Nervous System 150 8 The Special Senses 156 8.1 The Special Senses Tell Us about Our Environment 157 8.2 Vision is Our Most Acute Sense 163 8.3 The Special Senses are Our Connection to the Outside World 169 9 Immunity and the Lymphatic System 173 9.1 How Do We Adapt to Stress? 174 9.2 Skin and Mucous Membranes are the First Line of Defense 177 9.3 We Have a Second Line of Innate Defense 182 9.4 The Lymphatic System Comprises Our Third Line of Defense 184 9.5 Specific Immunity Targets Pathogens 189 9.6 Immunity Can Be Acquired Actively or Passively 195 10 Infectious Disease and Epidemiology 200 10.1 The Study of Epidemics is Global in Scope 201 10.2 Bacteria are Single-Celled Wonders That Can Cause Disease 205 10.3 Viruses Can Reproduce and Kill, but They are Not Alive 211 10.4 AIDS and HIV Attack the Immune System 217 10.5 Other Pathogens Carry Other Dangers 222 11 The Human Microbiome 226 11.1 What is the Human Microbiome? 227 11.2 Our Microbiome Helps Maintain Homeostasis 233 11.3 The Microbiome in Diagnoses and Treatments 238 12 Cancer 245 12.1 Cancer Cells Develop in Distinct Ways 246 12.2 Cancer Has Many Causes 251 12.3 Cancer Can Strike Almost Any Part of the Body 256 12.4 Cancer Can Be Diagnosed and Treated Effectively 261 13 The Cardiovascular System 268 13.1 The Heart Ensures Continual, 24/7 Nutrient Delivery 269 13.2 Blood Transport Involves Miles of Sophisticated Plumbing 278 13.3 Cardiovascular Disorders Have Life-Threatening Consequences 281 13.4 Blood Consists of Plasma and Formed Elements 285 13.5 Red Blood Cells and Platelets Help Maintain Homeostasis 290 14 The Respiratory System: Movement of Air 297 14.1 The Respiratory System Has an Upper and Lower Tract 298 14.2 The Lower Respiratory Tract Exchanges Gases 302 14.3 Air is Moved Into and Out of the Respiratory System 308 14.4 Respiration Relies on the Cardiovascular System 311 14.5 Respiratory Health is Critical to Survival 315 15 Nutrition: You are What You Eat 322 15.1 Nutrients are Life Sustaining 323 15.2 Nutrients are Metabolized 332 15.3 Health Can Be Hurt by Nutritional Disorders 336 16 The Digestive System 343 16.1 Digestion Begins in the Oral Cavity 344 16.2 The Stomach Puts Food to the Acid Test 349 16.3 The Intestines and Accessory Organs Finish the Job 352 16.4 Digestion is Both Mechanical and Chemical 360 17 The Urinary System 365 17.1 The Kidneys are the Core of the Urinary System 366 17.2 Urine is Made, Transported, and Stored 369 17.3 The Urinary System Maintains the Body’s Fluid and Solute Balance 375 17.4 Life-Threatening Diseases Affect the Urinary System 378 18 The Endocrine System and Development 383 18.1 Hormones are Chemical Messengers 384 18.2 The Endocrine Glands Secrete Directly into the Bloodstream 388 18.3 Maintaining Homeostasis Requires Glands, Hormones, and Feedback 393 18.4 Development Takes Us from Infancy to Adulthood 401 19 The Reproductive Systems: Maintaining the Species 407 19.1 Survival of the Species Depends on Gamete Formation 408 19.2 The Male Reproductive System Produces, Stores, and Delivers Sperm 410 19.3 The Female Reproductive System Produces and Nourishes Eggs 417 19.4 Human Reproductive Cycles are Controlled by Hormones 422 19.5 There are Many Birth Control Choices 428 19.6 Sexual Contact Carries a Danger: Sexually Transmitted Diseases 435 20 Pregnancy: Development from Conception to Newborn 439 20.1 Days 1 Through 14 Include Fertilization and Implantation 440 20.2 The Embryonic Stage is Marked by Differentiation and Morphogenesis 446 20.3 Fetal Development is a Stage of Rapid Organ Growth 452 20.4 Labor Initiates the End of Pregnancy 457 21 Inheritance, Genetics, and Molecular Biology 464 21.1 Traits are Inherited in Specific Patterns 465 21.2 Modern Genetics Uncovers a Molecular Picture 471 21.3 Genetic Theory is Put to Practical Use 474 21.4 Biotechnology Has Far-Reaching Effects 479 21.5 Biotechnology Assists in Medical and Societal Issues 484 Appendix A Periodic Table A-1 Appendix B Measurements B-1 Glossary GL-1 Index I-1

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Book SynopsisThis new approach to insect modeling discusses population dynamics' regularities, control theory, theory of transitions, and describes methods of population dynamics and outbreaks modeling for forest phyllophagous insects and their effects on global climate change. Research in insect population dynamics is important for more reasons than just protecting forest communities. Insect populations are among the main ecological units included in the analysis of stability of ecological systems. Moreover, it is convenient to test new methods of analyzing population and community stability on the insect-related data, as by now ecologists and entomologists have accumulated large amounts of such data. In this book, the authors analyze population dynamics of quite a narrow group of insects forest defoliators. It is hoped that the methods proposed herein for the analysis of population dynamics of these species may be useful and effective for analyzing population dynamics of other animal species Table of ContentsAuthors ix Introduction xi 1 Population Dynamics of Forest Insects: Outbreaks in Forest Ecosystems 1 1.1 Approaches to modeling population dynamics of forest insects 1 1.2 The role of insects in the forest ecosystem 4 1.3 The phenomenological theory of forest insect population dynamics: the principle of stability of flexible ecologicalsystems 10 1.4 Classification of the factors of forest insect population dynamics 12 1.5 Delayed and direct regulation mechanisms 14 2 Ways of Presenting Data on Forest Insect Population Dynamics 17 2.1 Representation of population dynamics data 17 2.2 Presenting the data on forest insect population dynamics through changes in density over time 18 2.3 Presenting the data on populatiozn dynamics as a phase portrait 24 2.4 The probability of the population leaving the stability zone and reaching an outbreak density: a model of a one-dimensional potential well 40 2.5 Presenting the data on forest insect population dynamics as a potential function 47 3 The Effects of Weather Factors on Population Dynamics of Forest Defoliating Insects 53 3.1 The necessary and sufficient weather conditions for the development of outbreaks of defoliating insects in Siberia 53 3.2 Weather influence on the development of the pine looper Bupalus piniarius L. outbreaks 55 3.3 Siberian silk moth Dendrolimus sibiricus Tschetv. population dynamics as related to weather conditions 61 3.4 Synchronization of weather conditions on vast areas as a factor of the occurrence of pan-regional outbreaks 64 4 Spatial and Temporal Coherence of Forest Insect Population Dynamics 79 4.1 Coherence and synchronicity of population dynamics 79 4.2 Spatiotemporal coherence of the population dynamics of defoliating insects in pine forests of Middle Siberia 83 4.3 Spatiotemporal coherence of population dynamics of defoliating insects in the Alps 90 4.4 Global coherence of pine looper population dynamics in Eurasia 94 4.5 Synchronization of the time series of gypsy moth population dynamics in the South Urals 96 5 Interactions Between Phytophagous Insects and Their Natural Enemies and Population Dynamics of Phytophagous Insects During Outbreaks 101 5.1 Entomophagous organisms as a regulating factor in forest insect population dynamics 101 5.2 A “phytophagous – entomophagous insect” model 106 6 Food Consumption by Forest Insects 113 6.1 Energy balance of food consumption by insects: an optimization model 113 6.2 A population-energy model of insect outbreaks 127 7 AR- and ADL-Models of Forest Insect Population Dynamics 139 7.1 An ADL-model (autoregressive distributed lag) of insect population dynamics 139 7.2 A model of population dynamics of the gypsy moth in the South Urals 145 7.3 Modeling population dynamics of the larch bud moth in the Alps 155 7.4 Simulation models of population dynamics of defoliating insects in the Krasnoturansk pine forest 165 7.5 Modeling and predicting population dynamics of the European oak leaf-roller 172 7.6 Gain margin of the AR-models of forest insect population dynamics 176 8 Modeling of Population Dynamics and Outbreaks of Forest Insects as Phase Transitions 183 8.1 Models of phase transitions for describing critical events in complex systems 183 8.2 Population buildup and development of an outbreak of forest insects as a first-order phase transition 185 8.3 Possible mechanisms of the development of forest insect outbreaks 192 8.4 Colonization of the tree stands by forest insects as a second-order phase transition 194 8.5 Risks of elimination of the population from the community 201 9 Forecasting Population Dynamics and Assessing the Risk of Damage to Tree Stands Caused by Outbreaks of Forest Defoliating Insects 207 9.1 Methods of forecasting forest insect population dynamics 207 9.2 Long-term forecast of population dynamics of defoliating insects 217 9.3 Assessment of the maximum risk of damage to tree stands caused by insects 223 9.4 Modeling and forecasting of eastern spruce budworm population dynamics 225 10 Global Warming and Risks of Forest Insect Outbreaks 233 10.1 Climate change and forest insect outbreaks in the Siberian taiga 233 10.2 Stress testing of insect impact on forest ecosystems under different scenarios of climate changes in the Siberian taiga 236 10.3 Risks of outbreaks of forest insect species with the stable type of population dynamics 244 Conclusion 251 References 255 Index 285

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Book SynopsisTHE UPDATED NEW EDITION OF THE POPULAR COLLECTION OF HIGH-RESOLUTION CHROMOSOME PHOTOGRAPHS?FOR GENETICISTS, MAMMOLOGISTS, AND BIOLOGISTS INTERESTED IN COMPARATIVE GENOMICS, SYSTEMATICS, AND CHROMOSOME STRUCTURE Filled with a visually exquisite collection of the banded metaphase chromosome karyotypes from some 1,000 species of mammals, the Atlas of Mammalian Chromosomes offers an unabridged compendium of the state of this genomic art form. The Atlas??contains the best karyotype produced, the common and Latin name of the species, the published citation, and identifies the contributing authors. Nearly all karyotypes are G-banded, revealing the chromosomal bar codes of homologous segments among related species. The Atlas brings together information from a range of cytogenetic literature and features high-quality karyotype images for nearly every mammal studied to date. When the Atlas was first published, only three mammals were sequenced. Today, that nTable of ContentsAcknowledgments l Contributors li Foreword 1 by Malcolm A. Ferguson‐Smith lviii Foreword 2 by Denis M. Larkin lxiii Introduction lxviii MAMMALIA Time Tree 1 MONOTREMATA Time Tree 2 Order Monotremata 3 MARSUPIALIA Time Tree 6 Order Didelphimorphia 7 Order Paucituberculata 14 Order Microbiotheria 14 Order Dasyuromorphia 15 Order Peramelemorphia 21 Order Notoryctemorphia 22 Order Diprotodontia 22 AFROTHERIA Time Tree 38 Order Afrosoricida Order Sirenia 53 Order Proboscidea 55 XENARTHRA Time Tree 64 Superorder Xenarthra 65 Order Pilosa Order Cingulata EUARCHONTOGLIRES Time Tree 79 Order Scandentia Time Tree 80 Order Dermoptera 84 Order Primates Time Tree 87 Order Rodentia Time Tree 186 LAURASIATHERIA Time Tree 465 Order Eulipotyphla (Insectivora) Time Tree 466 Order Chiroptera Time Tree 502 Order Pholidota Time Tree 703 Order Cetartiodactyla Time Tree 706 Order Perissodactyla Time Tree 858 References 881 Afterword Chromosomes: Much More Than DNA by Jennifer A. Marshall Graves 902 Index 904 Index of Painting Probes 930

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Book SynopsisA guide to environmental fluctuations that examines photosynthesis under both controlled and stressed conditions Photosynthesis, Productivity and Environmental Stress is a much-needed guide that explores the topics related to photosynthesis (both terrestrial and aquatic) and puts the focus on the basic effect of environmental fluctuations. The authorsnoted experts on the topicdiscuss photosynthesisunder both controlled and stressed conditions and review new techniques for mitigating stressors including methods such as transgeneics, proteomics, genomics, ionomics, metabolomics, micromics, and more. In order to feed our burgeoning world population, it is vital that we must increase food production. Photosynthesis is directly related to plant growth and crop production and any fluctuation in the photosynthetic activity imposes great threat to crop productivity. Due to the environmental fluctuations plants are often exposed to the different environmental stresses that cause decreased photTable of ContentsList of Contributors xiii Preface xvii About the Editors xxi 1 Effects of Organic Pollutants on Photosynthesis 1 Rupal Singh Tomar, Bhupendra Singh, and Anjana Jajoo 1.1 Introduction to Organic Pollutants 1 1.2 Characteristics of the Organic Pollutants 3 1.3 Sources of Organic Pollutants 3 1.4 Uptake and Accumulation of Organic Pollutants in Plants 4 1.5 Effects of Organic Pollutants on Plant Growth 5 1.6 Effects of Organic Pollutants on Photosynthesis 7 1.6.1 Effects of Pesticides on the Light Reactions 7 1.6.2 Effects of Pesticides on the Dark Reactions 9 1.6.3 Effects of Antibiotics on the Light Reactions 11 1.6.4 Effects of Antibiotics on the Dark Reactions 13 1.6.5 Effects of Bisphenol A on the Light Reactions 13 1.6.6 Effects of Bisphenol A on the Dark Reactions 14 1.6.7 Effects of Polycyclic Aromatic Hydrocarbons on the Light Reactions 14 1.6.8 Effects of Polycyclic Aromatic Hydrocarbons on the Dark Reactions 16 1.7 Conclusion and Future Prospects 17 References 18 2 Cold Stress and Photosynthesis 27 Aditya Banerjee and Aryadeep Roychoudhury 2.1 Introduction 27 2.2 Primary Targets of Cold Stress in Plants 27 2.3 Cold Stress Distorts the Chloroplast Membrane Integrity 28 2.4 Cold Stress Damages the Photosynthetic Apparatus 28 2.5 Cold Stress Affects Carbon Dioxide (CO2) Fixation 31 2.6 Strategies to Ameliorate Cold Stress and Improve Photosynthesis 32 2.7 Conclusion and Future Perspectives 33 Acknowledgements 33 References 33 3 High‐Temperature Stress and Photosynthesis Under Pathological Impact 39 Murat Dikilitas, Eray Simsek, Sema Karakas, and Parvaiz Ahmad 3.1 Introduction 39 3.2 High‐Temperature Stress on Crop Plants 41 3.3 High‐Temperature Stress on Photosynthesis Mechanisms 43 3.4 Impact of Pathogens on Photosynthesis Mechanisms Under Temperature Stress 45 3.5 Genomic, Biochemical, and Physiological Approaches for Crop Plants Under Temperature and Pathogenic Stresses 51 3.6 Conclusions and Future Prospects 55 References 55 4 Effect of Light Intensity on Photosynthesis 65 Rinukshi Wimalasekera 4.1 Introduction 65 4.2 Characteristics of Light 66 4.2.1 Photosynthetically Active Radiation (PAR) 66 4.3 Light Absorption and Pigments 67 4.3.1 Dissipation of Excess Light Energy 67 4.3.2 Photoinhibition 68 4.4 Light Absorption by Leaves 68 4.4.1 Light Absorption and the Anatomy, Morphology, and Biochemical Characteristics of Leaves 68 4.4.2 Light‐Mediated Leaf Movement 69 4.4.3 Light Absorption by Sun and Shade Adapted Leaves 69 4.5 Light and Photosynthetic Responses 70 4.6 Conclusion and Future Prospects 70 References 71 5 Regulation of Water Status, Chlorophyll Content, Sugar, and Photosynthesis in Maize Under Salinity by Mineral Mobilizing Bacteria 75 Yachana Jha 5.1 Introduction 75 5.2 Mineral Mobilizing Bacteria 76 5.3 Isolation and Identification of Mineral Mobilizing Bacteria 77 5.4 Mineral Mobilizing Bacteria Maintain the Photosynthetic Efficiency of Maize Under Salinity 78 5.5 Mineral Mobilizing Bacteria Maintain the Photosynthetic Efficiency of Plants by Regulating Chlorophyll Content 79 5.6 Mineral Mobilizing Bacteria Maintain the Photosynthetic Efficiency of Plants by Regulating Relative Water Content 80 5.7 Mineral Mobilizing Bacteria Maintain the Photosynthetic Efficiency of Plants by Regulating Stomatal Behavior 82 5.8 Mineral Mobilizing Bacteria Maintain Photosynthesis to Regulate Soluble Sugar by Altering Vascular Tissue 83 5.9 Mineral Mobilizing Bacteria Maintain the Photosynthetic Efficiency of Plants by Accumulating Various Osmoprotectants 84 5.10 Mineral Mobilizing Bacteria Maintain the Photosynthetic Efficiency of Plants by Regulating Sugar Biosynthesis 87 5.11 Mineral Mobilizing Bacteria Maintain the Photosynthetic Efficiency of Plants by Reducing Ethylene Biosynthesis 88 5.12 Mineral Mobilizing Bacteria Maintain the Photosynthetic Efficiency of Plants by Inducing Various Signaling Molecule 89 5.13 Conclusion 90 References 90 6 Regulation of Photosynthesis Under Metal Stress 95 Mumtaz Khan, Neeha Nawaz, Ifthekhar Ali, Muhammad Azam, Muhammad Rizwan, Parvaiz Ahmad, and Shafaqat Ali 6.1 Introduction 95 6.2 Effects of Metals on Photosynthesis 96 6.2.1 Reduction in CO2 Stomatal Conductance and Mesophyll Transport 96 6.2.2 Inhibition of Biosynthesis of Photosynthetic Pigments 97 6.2.3 Changes in Leaf Morphology and Chloroplast Ultrastructure 97 6.2.4 Induction of Reactive Oxygen Species 98 6.2.5 Metal‐Induced Hormonal Changes 98 6.2.6 Alterations in Photosynthetic Enzymes 99 6.3 Mechanisms of Photosynthesis Regulation under Metal Stress 99 6.3.1 Cell Signaling and Growth Hormones 99 6.3.2 Avoiding and Scavenging Reactive Oxygen Species 100 6.3.3 Interconversion of Chlorophylls 101 6.3.4 Role of Alleviatory Agents in Photosynthesis Regulation 101 6.3.5 Photosynthesis Regulation Through Overexpression of Genes 102 6.4 Conclusions 102 References 102 7 Heavy Metals and Photosynthesis: Recent Developments 107 Zahra Souri, Amanda A. Cardoso, Cristiane J. da‐Silva, Letuzia M. de Oliveira, Biswanath Dari, Debjani Sihi, and Naser Karimi 7.1 Introduction 107 7.2 Heavy Metals and Hyperaccumulation 109 7.2.1 Characteristics of Hyperaccumulator Plants 110 7.2.2 Hyperaccumulation and Photosynthesis 112 7.3 Heavy Metals and Chloroplast Structure 113 7.4 Heavy Metals and Gas‐Exchange 115 7.5 Heavy Metals and Photosynthetic Pigments 115 7.6 Heavy Metals and Photosystems (PSI and PSII) 117 7.7 Heavy Metals and Key Photosynthetic Enzymes 120 7.8 Heavy Metals and Antioxidant Defense Mechanism of the Photosynthetic System 121 7.9 Conclusion and Further Prospects 123 References 125 8 Toward Understanding the Regulation of Photosynthesis under Abiotic Stresses: Recent Developments 135 Syed Sarfraz Hussain 8.1 Introduction: Abiotic Stresses, Photosynthesis and Plant Productivity 135 8.1.1 Impact of Abiotic Stress on the Photosynthetic System of Plants 137 8.1.2 Drought Stress 137 8.1.3 Salinity Stress 139 8.1.4 Cold Stress 142 8.1.5 Heat Stress 144 8.2 Overexpression of Photosynthesis Related Genes and Transcription Factors 145 8.3 Conclusions and Future Perspectives 146 References 147 9 Current Understanding of the Regulatory Roles of miRNAs for Enhancing Photosynthesis in Plants Under Environmental Stresses 163 Syed Sarfraz Hussain, Meeshaw Hussain, Muhammad Irfan, and Bujun Shi 9.1 Introduction: Interaction Between miRNAs and Plant Growth/Functional Diversity of miRNAs and Their Impact in Plant Growth 163 9.2 miRNAs Involved in Photosynthesis and Other Downstream Biological Processes 165 9.3 Abiotic Stresses Drastically Affect Photosynthesis and Plant Productivity 166 9.4 Genome Wide miRNA Profiling Under Abiotic Stresses 168 9.5 Functional Characterization of miRNAs Associated with Photosynthesis 170 9.6 miRNAs and Shoot/Tiller Development 172 9.7 miRNAs in Root Development 173 9.8 miRNAs in Controlling Stomatal Density 175 9.9 miRNAs in Hormone Signaling 175 9.10 miRNAs in Controlling Nodule Development in Leguminous Crops 176 9.11 Conclusion and Future Perspective 177 References 178 10 Mineral Mobilizing Bacteria Mediated Regulation of Secondary Metabolites for Proper Photosynthesis in Maize Under Stress 197 Yachana Jha 10.1 Introduction 197 10.2 Isolation and Inoculation of Mineral Mobilizing Bacteria 198 10.2.1 Mineral Mobilizing Bacteria Mediated Regulation of Nutrients for Secondary Metabolites Production and Photosynthesis 200 10.2.2 Mineral Mobilizing Bacteria Mediated Regulation of Chlorophyll Content for Secondary Metabolites Production and Photosynthesis 201 10.2.3 Mineral Mobilizing Bacteria Mediated Regulation of Carbon/Sugar Metabolites for Secondary Metabolites Production and Photosynthesis 203 10.2.4 Mineral Mobilizing Bacteria Mediated Regulation of Nitrogen Metabolites for Secondary Metabolites Production and Photosynthesis 206 10.2.5 Mineral Mobilizing Bacteria Mediated Regulation of Secondary Metabolites Production and Photosynthesis Under Biotic Stress 207 10.2.6 Mineral Mobilizing Bacteria Mediated Regulation of Secondary Metabolites Production and Photosynthesis Under Abiotic Stress 207 10.2.7 Mineral Mobilizing Bacteria Mediated Regulation of Gene Expression for Secondary Metabolites Production and Photosynthesis 208 10.3 Conclusion 210 References 210 11 Role of Plant Hormones in Improving Photosynthesis 215 Belur Satyan Kumudini and Savita Veeranagouda Patil 11.1 Introduction 215 11.2 Phytohormones: Watchdogs of Plant Growth and Development 216 11.2.1 Auxins 216 11.2.2 Gibberellins or Gibberellic Acids 217 11.2.3 Cytokinins 217 11.2.4 Ethylene 218 11.2.5 Abscisic Acid 218 11.2.6 Jasmonic Acid 220 11.2.7 Salicylic Acid 220 11.2.8 Brassinosteroids 220 11.2.9 Strigolactones 221 11.3 Photosynthesis 221 11.3.1 Role of Plant Hormones in Photosynthesis 222 11.4 Phytohormones and Abiotic Stress Tolerance vis‐a‐vis Photosynthesis 223 11.4.1 Heavy Metals 223 11.4.2 Salinity 224 11.4.3 Drought 225 11.5 Deciphering the Role of Phytohormones in Perceiving Photosynthesis During Biotic Stress 225 11.6 Interplay Between the Phytohormones to Facilitate Photosynthesis Under Stress 227 11.7 Conclusion and Future Prospects 228 Acknowledgments 228 References 228 12 Promising Monitoring Techniques for Plant Science: Thermal and Chlorophyll Fluorescence Imaging 241 Aykut Saglam, Laury Chaerle, Dominique Van Der Straeten, and Roland Valcke Abbreviations 241 12.1 Introduction 241 12.2 Thermal Imaging 242 12.2.1 Plant Water Status and Drought Stress 243 12.2.2 Salt Stress 245 12.2.3 Herbicide Stress 245 12.2.4 Air Humidity and Air Pollutants 245 12.2.5 Ice Nucleation and Freezing 246 12.2.6 Plant–Pathogen Interactions 247 12.2.7 Herbivory Effects 249 12.3 Chlorophyll Fluorescence Imaging 249 12.3.1 Drought Stress 251 12.3.2 Light Stress 252 12.3.3 Herbicide Stress 252 12.3.4 Air Pollutants 254 12.3.5 Mineral Deficiency and Toxicity 255 12.3.6 Pathogen Effects 256 12.3.7 Herbivory Effects 258 12.4 Conclusions and Future Perspectives 259 References 260 13 Introgression of C4 Pathway Gene(s) in C3 Plants to Improve Photosynthetic Carbon Assimilation for Crop Improvement: A Biotechnological Approach 267 Sonam Yadav and Avinash Mishra 13.1 Introduction 267 13.2 Carbon Assimilation 268 13.2.1 CO2 Assimilation in C3 Plants: Photorespiration a Major Constraint 268 13.2.2 CO2 Assimilation in C4 Plants: Efficient Photosynthesis 269 13.2.3 C3 vs. C4 Plants 271 13.3 Evolution of C4 Metabolism in Higher Plants 271 13.3.1 Environmental Imperatives/Obligations 272 13.3.2 Evolution of C4 Photosynthesis Gene(s) 272 13.4 Effect of Elevated CO2 on C3 and C4 Plants 273 13.5 Ectopic Expression of C4 Photosynthesis Genes in C3 Plants 274 13.5.1 Single Gene Introgression 274 13.5.2 Double Gene Introgression 275 13.6 Conclusion 275 Acknowledgment 276 References 276 14 Interaction of Photosynthesis, Productivity, and Environment 283 Ulduza Ahmad Gurbanova, Tofig Idris Allahverdiyev, Hasan Garib Babayev, Shahnigar Mikayil Bayramov, and Irada Mammad Huseynova 14.1 Introduction 283 14.2 Plant Materials 286 14.3 Effect of Drought Stress on Some Physiological Traits, Yield, and Yield Components of Durum (Triticum durum Desf.) and Bread (Triticum aestivum L.) Wheat Genotypes 286 14.4 Subcellular Localization of the NADP‐Malic Enzyme and NAD‐Malic Enzyme Activity in the Leaves of the Wheat Genotypes Under Soil Drought Conditions 299 14.5 Physico‐Chemical Parameters of NADP‐Malic Enzyme and NAD‐Malic Enzyme in the Leaves of the Barakatli 95 and Garagylchyg 2 Genotypes Under Soil Drought Conditions 302 14.6 Conclusion 310 Acknowledgement 311 References 311 Index 315

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Book SynopsisTable of ContentsPart I The Microbes 1 The Microbial World 1 1.1 The Microbes 3 Mini-Paper: A Focus on the Research the Three Domains of Life 9 Toolbox 1.1 Polymerase Chain Reaction Amplification of rRNA Genes 11 1.2 Microbial Physiology, Genetics, and Cultivation 14 Perspective 1.1 Creating Life in the Laboratory: The Miller–Urey Experiment 17 1.3 Microbial Ecology and Biotechnology 23 1.4 Microbes and Disease 25 2 Bacteria 35 2.1 Morphology of Bacterial Cells 36 Perspective 2.1 Making the Microbiology Laboratory Accessible 39 2.2 The Cytoplasm 40 2.3 The Bacterial Cytoskeleton 43 Mini-Paper: A Focus on the Research Magnetosomes: Uncovering the Structure of Bacterial Organelles 44 2.4 The Cell Envelope 46 Toolbox 2.1 The Gram Stain 55 Perspective 2.2 The Protective Shells of Endospores 56 2.5 The Bacterial Cell Surface 60 2.6 Diversity of Bacteria 67 3 Eukaryal Microorganisms 75 3.1 Morphology of Eukaryal Cells 76 Mini-Paper: A Focus on the Research Lipid Rafts: Organized Clustering of Lipids within a Membrane 82 Toolbox 3.1 Using Microscopy to Examine Cell Structure 85 Perspective 3.1 Hijacking the Cytoskeleton 88 3.2 Diversity of Eukaryal Microorganisms 89 3.3 Replication of Eukaryal Microorganisms 94 3.4 The Origin of Eukaryal Cells 97 Perspective 3.2 Secondary endosymbiosis: The origins of an organelle with four membranes 101 3.5 Interactions Between Eukaryal Microorganisms and Animals, Plants, and the Environment 102 4 Archaea 109 4.1 Evolution of Archaea 111 4.2 Archaeal Cell Structure 113 Toolbox 4.1 Vaccine Delivery Strategies 117 4.3 Diversity of Archaea 121 Mini-Paper: A Focus on the Research The Role of Archaea in Our Digestive System 124 Perspective 4.1 Extremophiles and Biotechnology 129 5 Viruses 136 5.1 A Basic Overview of Viruses 137 Mini-Paper: A Focus on the Research New Findings in the Packaging of DNA by the Model Bacteriophage T4 146 5.2 Origins of Viruses 148 Perspective 5.1 Ribozymes: Evidence for an RNA-Based World 149 5.3 Cultivation, Purification, and Quantification of Viruses 150 Toolbox 5.1 Cell Culture Techniques 151 Perspective 5.2 Measurement of HIV Viral Load 155 5.4 Diversity of Viruses 158 Toolbox 5.2 Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) 162 5.5 Virus-Like Particles 163 5.6 Virology Today 166 6 Metabolism 172 6.1 Acquisition of Carbon, Energy, and Electrons 174 6.2 Energy, Enzymes, and ATP 176 Perspective 6.1 Who Needs Vitamins? 179 6.3 Central Processes in ATP Synthesis 180 6.4 Carbon Utilization in Microorganisms 185 6.5 Respiration and the Electron Transport System 195 Perspective 6.2 Electricigenic Bacteria and Microbial Fuel Cells 198 6.6 Metabolism of Non-glucose Carbon Sources 202 Toolbox 6.1 Metabolism and Rapid Bacterial Identification Systems 204 6.7 Phototrophy and Photosynthesis 206 Mini-Paper: A Focus on the Research Genome Sequence of a Deep Sea Symbiont 216 6.8 Nitrogen and Sulfur Metabolism 217 6.9 Biosynthesis of Cellular Components 222 Part II Microbial Genetics 7 Cultivating Microorganisms 231 7.1 Factors Affecting Microbial Growth 233 Toolbox 7.1 Phenotype Microarrays for Examining Microbial Growth 234 7.2 Growing Microorganisms in the Laboratory 238 Perspective 7.1 The Discovery of Helicobacter pylori 243 Toolbox 7.2 FISHING for Uncultivated Microorganisms 246 Mini-Paper: A Focus on the Research Bringing to Life the Previously Unculturable Using the Soil Substrate Membrane System (SSMS) 247 7.3 Measuring Microbial Population Growth 249 Perspective 7.2 Mycobacterium leprae, An Extraordinarily Slow-growing Pathogen 255 Perspective 7.3 The Human Intestine: A Continuous Culture 257 7.4 Eliminating Microbes and Preventing their Growth 257 8 DNA Replication and Gene Expression 267 8.1 The Role of DNA 269 8.2 DNA Replication 276 Mini-Paper: A Focus on the Research Telomeres with Promoter Activity 283 8.3 Transcription 284 Toolbox 8.1 Using a Gel Shift Assay to Identify DNA-binding Proteins 287 8.4 Translation 291 8.5 The Effects of Mutations 297 Perspective 8.1 Using Mutations to Control Viral Infections 301 9 Viral Replication Strategies 306 9.1 Recognition of Host Cells 308 Perspective 9.1 Identifying Emerging Viral Pathogens 310 Toolbox 9.1 The Western Blot 312 9.2 Viral Entry and Uncoating 315 9.3 Viral Replication 319 Mini-Paper: A Focus on the Research The Discovery of Reverse Transcriptase 326 Perspective 9.2 Phage Therapy: Biocontrol for Infections 328 9.4 Viral Assembly and Egress 330 10 Bacterial Genetic Analysis and Manipulation 335 10.1 Bacteria as Subjects of Genetic Research 336 10.2 Mutations, Mutants, and Strains 340 Toolbox 10.1 Isolating Nutritional Mutants 342 10.3 Restriction Enzymes, Vectors, and Cloning 347 10.4 Recombination and DNA Transfer 354 Perspective 10.1 Plasmids That Produce Pathogens 359 Mini-Paper: A Focus on the Research The Discovery of Transduction 367 11 Microbial Genomics 372 11.1 Genome Sequencing 373 Perspective 11.1 Rate of DNA Sequencing 377 Toolbox 11.1 Genome databases 383 11.2 Genomic Analysis of Gene Expression 385 11.3 Comparative Genomics 391 Mini-Paper: A Focus on the Research Genome Sequence of a Killer Bug 391 Perspective 11.2 The Minimal Genome 393 11.4 Metagenomics and Related Analyses 396 12 Regulation of Gene Expression 402 12.1 Differential Gene Expression 404 12.2 The Operon 405 Mini-Paper: A Focus on the Research Tuning Promoters for Use in Synthetic Biology 412 12.3 Global Gene Regulation 413 Perspective 12.1 The Use of Lactose Analogs in Gene Expression Studies 415 12.4 Post-Initiation Control of Gene Expression 419 Toolbox 12.1 Using RNA molecules to decrease gene expression 421 12.5 Quorum Sensing 423 12.6 Two-Component Regulatory Systems 425 12.7 Chemotaxis 428 13 Biogeochemical Cycles 435 13.1 Nutrient Cycling 437 Toolbox 13.1 Using Microarrays to Examine Microbial Communities: The GeoChip 439 13.2 Cycling Driven by Carbon Metabolism 440 Perspective 13.1 CO2 as a Greenhouse Gas and Its Influence on Climate Change 440 13.3 Cycling Driven by Nitrogen Metabolism 451 Mini-Paper: A Focus on the Research The First Isolation and Cultivation of a Marine Archaeon 454 13.4 Other Cycles and their Connections 456 Perspective 13.2 Life in a World without Microbes 457 Perspective 13.3 The Microbiology of Environmentally Toxic Acid Mine Drainage 458 Toolbox 13.2 Biogeochemistry in a Bottle: The Winogradsky Column 461 Part III Microbial Physiology and Ecology 14 Microbial Ecosystems 465 14.1 Microbes in the Environment 467 14.2 Microbial Community Analysis 472 Toolbox 14.1 Flow Cytometry 477 Perspective 14.1 Naming the Uncultured and Uncharacterized 479 Mini-Paper: A Focus on the Research Insights into the Phylogeny and Coding Potential of Microbial Dark Matter 479 14.3 Aquatic Ecosystems 481 Perspective 14.2 Dead Zones 482 14.4 Terrestrial Ecosystems 489 14.5 Deep Subsurface and Geothermal Ecosystems 495 15 Microbial Symbionts 504 15.1 Types of Microbe-Host Interactions 506 15.2 Symbionts of Plants 508 Perspective 15.1 The Possible Impossible Vegan Patty 510 15.3 Symbionts of Humans 513 Toolbox 15.1 Germ-free and Gnotobiotic Animals 518 Perspective 15.2 Food Probiotics—Do They Work? 519 Mini-Paper: A Focus on the Research Fecal Bacteriotherapy: “Repoopulation” of the Gut 522 15.4 Symbionts of Herbivores 525 Perspective 15.3 Cows Contribute to Climate Change 531 15.5 Symbionts of Invertebrates 531 Perspective 15.4 Midichlorians—Not Just for Jedi 536 Perspective 15.5 Death of Coral Reefs 539 16 Microbial Biotechnology 544 16.1 Microbes for Biotechnology 546 Perspective 16.1 Bioprospecting: Who Owns the Microbes? 548 16.2 Molecular Genetic Modification 550 Toolbox 16.1 Site-Directed Mutagenesis 552 Toolbox 16.2 Fusion Protein Purification 559 Mini-Paper: A Focus on the Research Making a Synthetic Genome 561 Perspective 16.2 The International Genetically Engineered Machine (iGEM) Competition, Standard Biological Parts, and Synthetic Biology 564 16.3 Red Biotechnology 565 16.4 White Biotechnology 566 Perspective 16.3 Biofuels: Biodiesel and Algae 570 16.5 Green Biotechnology 576 Toolbox 16.3 Plant Transformation Using Bacteria 578 17 The Microbiology of Food and Water 586 17.1 Food Spoilage 588 17.2 Food Preservation 591 17.3 Food Fermentation 598 17.4 Foodborne and Waterborne Illness 605 17.5 Microbiological Aspects of Water Quality 607 Perspective 17.1 Implications of Sludge Bulking 613 Toolbox 17.1 Measuring Biochemical Oxygen Demand (BOD) 614 Mini-Paper: A Focus on the Research Enhanced Biological Removal of Phosphorus 616 Toolbox 17.2 Most Probable Number (MPN) Method 619 Part IV Microbes and Disease 18 Introduction to Infectious Diseases 624 18.1 Pathogenic Microbes 627 Toolbox 18.1 Measuring the Virulence of Pathogens 629 18.2 Microbial Virulence Strategies 631 Perspective 18.1 Genome Editing: A powerful and Controversial New Technique 637 18.3 The Transmission of Infectious Diseases 638 Mini-Paper: A Focus on the Research Epidemiology of an Infectious Disease 645 18.4 Proving Cause and Effect in Microbial Infections 648 Perspective 18.2 The Armadillo—An Ideal Animal Model? 651 18.5 The Evolution of Pathogens 652 19 Innate Host Defenses Against Microbial Invasion 661 19.1 Immunity 682 19.2 Barriers to Infection 664 Perspective 19.1 Messy Mucus 666 Perspective 19.2 Alzheimer’s Disease: Aluminium, B-amyloid, Gum Disease: Which Is It? 666 19.3 The Inflammatory Response 669 19.4 The Molecules of the Innate System 671 Mini-Paper: A Focus on the Research Mammalian Cells Can Recognize Bacterial DNA 673 Toolbox 19.1 The Complement Fixation Test 677 19.5 The Cells of Innate Immunity 682 19.6 Invertebrate Defenses 690 Toolbox 19.2 The Limulus Amoebocyte Assay for LPS 692 20 Adaptive Immunity 696 20.1 Features of Adaptive Immunity 698 20.2 T Cells 701 20.3 Antigen Processing 705 20.4 Antigen-Presenting Cells 708 20.5 Humoral and Cell-Mediated Immune Responses 712 Perspective 20.1 Too Much of a Good Thing? 714 Mini-Paper: A Focus on the Research Attempting to Engineer a Virus to Improve Immunocontraception 715 20.6 B Cells and the Production of Antibody 716 Perspective 20.2 Vaccines Against T-independent Antigens 720 Toolbox 20.1 Monoclonal Antibody (mAb) Production 721 Toolbox 20.2 Enzyme-linked Immunosorbent Assay (ELISA) 727 Perspective 20.3 Turning Antibody Upside Down 729 21 Bacterial Pathogenesis 735 21.1 Bacterial Virulence Factors 737 Mini-Paper: A Focus on the Research Escherichia Coli Injects Its Own Receptor 742 Perspective 21.1 Iron, Vampires, Fashion, and the White Plague 747 21.2 Bacterial Virulence Factors—Toxins 748 Toolbox 21.1 Serotyping 749 Perspective 21.2 The Good, The Bad, and The Ugly Side of Botulinum Toxin 756 Perspective 21.3 Superabsorbent Tampons and Superantigens 762 21.3 Survival in the Host: Strategies and Consequences 764 Toolbox 21.2 The Tuberculin Test for Tuberculosis 772 21.4 Evolution of Bacterial Pathogens 772 Perspective 21.4 Antibiotics Trigger Toxins? 776 22 Viral Pathogenesis 782 22.1 Recurring Themes in Viral Pathogenesis 784 Perspective 22.1 Vertical Transmission of HIV 789 22.2 Interactions with the Host: Strategies and Consequences 791 Perspective 22.2 Viral Induction of Apoptosis 793 22.3 Viral Infections and Cancer 796 Toolbox 22.1 Immunoprecipitation 799 Mini-Paper: A Focus on the Research Viruses that Cause Cancer by Affecting Cellular Proliferation 800 Perspective 22.3 SV40 and Human Cancers 802 22.4 Evolution of Viral Pathogens 806 Perspective 22.4 What is it about Bats? 809 Perspective 22.5 Ethical Concerns about Avian Flu Research 812 23 Eukaryal Pathogenesis 816 23.1 Mechanisms of Eukaryal Pathogenesis 818 Mini-Paper: A Focus on the Research An Experimental System for the Genomic Study of Dutch Elm Disease 821 Perspective 23.1 Pneumocystis Jirovecii or Carinii : The Evolving Field of Taxonomy 824 Perspective 23.2 Magic Mushrooms 830 23.2 Pathogen Study: Plasmodium Falciparum 831 Toolbox 23.1 Testing for Malaria 835 23.3 Macroscopic Eukaryal Pathogens 837 23.4 Evolution of Eukaryal Pathogens 839 Perspective 23.3 Chytrid Fungus: An Emerging Fungal Pathogen 840 Perspective 23.4 What if the Parasites Disappeared? 842 24 Control of Infectious Diseases 846 24.1 Historical Aspects of Infectious Disease Treatment and Control 848 24.2 Antimicrobial Drugs 849 24.3 Antimicrobial Drug Resistance 863 Mini-Paper: A Focus on the Research Tracking Acquisition of Antibiotic Resistance In Real Time 865 Toolbox 24.1 Drug Susceptibility Testing and MIC 869 Perspective 24.1 The Pursuit of New Antibiotics: Why Bother? 874 Perspective 24.2 Health Care-Associated Infections: A Recipe for Resistance 875 24.4 Predicting and Controlling Epidemics 876 24.5 Immunization and Vaccines 879 Perspective 24.3 Variolation: Deliberate Infection with Smallpox Virus 880 Perspective 24.4 The War Against Vaccines 885 Appendix A Scientific Articles A-1 Appendix B Microscopy A-10 Appendix C Taxonomy and Nomenclature of Microbes A-14 Appendix D Origin of Blood Cells A-16 Glossary / Index

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Book SynopsisTable of Contents1 The Microbial World 1 1.1 The Microbes 2 A Brief Survey of the Microbial World 3 The Dominant Form of Life on Earth 4 1.2 The Conflicts 6 Growth and Control of Microbes 6 The Role of the Immune System 8 What a Microbiologist Sees: Wrestling and the Spread of Skin Pathogens 8 Pathogenesis 9 Antimicrobial Drugs 10 1.3 Infectious Disease 11 Epidemiology and Healthy Practices 11 Host Defenses and Microbial Pathogenesis Strategies 12 Infectious Disease Statistics 12 The Microbiologist’s Toolbox: MALDI-TOF Mass Spectrometry 13 Case Study: Vaccination: A Casualty of War 15 1.4 Microbial Ecology and Commercial Applications 16 The Importance of Environmental Microbes 16 The Industrial Use of Microorganisms 17 Clinical Application: Pasteurization 18 2 An Introduction to the Chemical Basis of Life 24 2.1 Atoms, Elements, and Molecules 25 Elements and the Periodic Table 25 Basic Atomic Structure 27 Electron Configuration and Bonding 28 Chemical Interactions 30 What a Microbiologist Sees: Microbe Diagnosis Using Colorimetric Chemical Reactions 31 2.2 Water: Life’s Most Essential Molecule 31 Water’s Unique Properties 31 Aqueous Solutions 33 Acids and Bases 34 The Microbiologist’s Toolbox: Diagnosis Using pH-Sensitive Chemical Reactions 36 Case Study: Trading One Infection for Another 37 2.3 Carbon’s Key Role in Biochemistry 38 The Diversity of Carbon Chemistry 38 Isomers 39 Clinical Application: Isomers as a New Antibacterial Mechanism of Action 39 Building Complex Organic Molecules 40 3 The Biochemistry of Macromolecules 45 3.1 Proteins 46 The Four Levels of Protein Structure 46 Protein Diversity and Function 49 What a Microbiologist Sees: The Effect of Modified Tertiary Binding on Protein Structure 52 3.2 Enzymes 53 Enzyme Action 53 Factors Influencing the Rate of Enzyme Activity 55 3.3 Carbohydrates 57 Simple and Complex Carbohydrates 57 The Functional Diversity of Carbohydrates 59 Clinical Application: Rapid Glycogen Breakdown in a Diabetic Patient in Shock 60 3.4 Lipids 60 The Structural Classes of Lipids 61 Case Study: Acne—A Bacterial Interaction with Skin Oils 62 Lipid Functions 65 The Microbiologist’s Toolbox: Ziehl–Neelsen Acid-Fast Staining of Mycolic Acid Cell Walls 66 3.5 Nucleic Acids 67 The Structures of DNA and RNA 67 Nucleic Acid Functions 68 4 Microscopy 75 4.1 Principles of Microscopy 76 Magnification 77 Resolution 78 4.2 Microscopy Used for Clinical Diagnosis 79 Bright-field Microscopy 79 Dark-field Microscopy 80 Fluorescence Microscopy 81 The Microbiologist’s Toolbox: The Direct Fluorescent Antibody Assay 81 4.3 Microscopy Used for Research Investigations 82 Light Microscopy 82 What a Microbiologist Sees: Differential Interference Contrast Microscopy 83 Electron Microscopy 84 Nanoprobe-based Microscopy 84 4.4 Specimen Preparation and Staining 86 Basic Staining Procedures 86 Case Study: Diagnosing Gonorrhea Using the Gram Stain 88 Special Staining Procedures 88 Clinical Application: Diagnosing Tuberculosis Using Acid-fast Staining 89 5 Prokaryotic Organisms 95 5.1 The Prokaryote’s Place in the Living World 96 Sustaining Life 96 What a Microbiologist Sees: Prokaryotes—The Dominant Form of Life on Earth 97 Symbiotic Relationships 98 5.2 Bacterial Cell Shapes and Arrangements 99 Bacterial Shapes 99 Bacterial Arrangements 99 5.3 The Bacterial Cell Wall 101 Cell Wall Structure 102 Gram-positive and Gram-negative Cell Walls 103 Atypical Cell Walls 104 Case Study: A Walking Pneumonia Outbreak at a University 105 5.4 External Structures of Bacterial Cells 106 The Glycocalyx 106 Fimbriae and Pili 106 Flagella 107 The Microbiologist’s Toolbox: The Flagella Stain 108 5.5 Internal Structures of Bacterial Cells 109 The Plasma Membrane 109 The Nucleoid 110 Ribosomes 111 Plasmids, Inclusion Bodies, and Membranous Structures 112 Endospores 113 Clinical Application: Endospore-forming Bacteria 113 5.6 Prokaryotic Evolution and Classification 115 The Tree of Life 115 The Clinical Classification of Prokaryotes 117 6 The Eukaryotic Cell 122 6.1 An Introduction to Eukaryotic Cells 123 Cell Size 123 Multicellular Organisms 123 6.2 The Plasma Membrane and Cell Wall 124 The Plasma Membrane 124 The Microbiologist’s Toolbox: Fluorescence-Activated Cell Sorting (FACS) 125 The Cell Wall 125 Clinical Application: Agar—The Ideal Solid Medium for Bacterial Culture 126 6.3 Internal Structures 127 The Nucleus and Genetic Material 128 Ribosomes 130 The Endomembrane System 130 Mitochondria and Chloroplasts 131 The Cytoskeleton 132 6.4 External Structures and Other Cellular Forms 134 Cellular Junctions 134 Flagella, Cilia, and Pseudopodia 134 Spores 134 Cysts and Sporocysts 136 Case Study: Valley Fever 136 What a Microbiologist Sees: O&P Examination of Stool 137 6.5 Eukaryotic Evolution and Classification 138 The Autogenous and Endosymbiotic Hypotheses 138 The Evolution of Multicellular Organisms 140 Eukarya: A Classification Overview 140 7 Eukaryotic Organisms 145 7.1 The Algae 146 General Characteristics and Unique Features 146 A Survey of Algae 146 Pathogenic Algae 146 The Microbiologist’s Toolbox: Sabouraud Dextrose Agar 148 7.2 The Protozoans 149 General Characteristics and Unique Features 149 A Survey of Protozoans 149 Pathogenic Protozoans 151 7.3 The Fungi 152 General Characteristics and Unique Features 153 What a Microbiologist Sees: The Morphological Plasticity of Candida 154 A Survey of Fungi 155 Pathogenic Fungi 157 Clinical Application: Candida auris: An Emerging Fungal Pathogen 157 7.4 The Helminths 159 General Characteristics and Unique Features 159 A Survey of the Helminths 159 Pathogenic Helminths 161 Case Study: Cravings 162 7.5 The Arthropods 163 A Survey of the Arthropods 163 Pathogenic Arthropods and Arthropod Vectors 163 8 Viruses and Infectious Particles 169 8.1 Viral Structure and Classification 170 The Structure of Viruses 170 The Classification of Viruses 172 8.2 Viral Replication Cycles 175 Viruses Replicating in Animal Cells 175 The Microbiologist’s Toolbox: Presumptive Diagnosis of a Viral Infection Using CPE Analysis 179 Viruses Replicating in Bacterial Cells 179 8.3 Viruses and Human Health 181 The Clinical Cultivation of Viruses 181 The Impact of Viral Infections 181 Case Study: A Bad Case of the Flu 182 Viruses, Recurrent Infections, and Cancer 183 What a Microbiologist Sees: Connecting Symptoms with the Progression of HIV 183 8.4 Prevention and Treatment of Viral Infections 184 The Prevention of Viral Infections 185 Antiviral Therapies 185 Clinical Application: Protecting the Most Vulnerable Patients 185 Viral Influences on Bacterial Infections 187 8.5 Viruslike Infectious Agents 190 Viroids 190 Satellites 191 Prions 191 9 Metabolism 197 9.1 The Role of Energy in Life 198 Basic Energy Principles 198 Energy and Chemical Reactions 198 The Microbiologist’s Toolbox: Identifying Bacteria by Metabolic Differences 200 9.2 Energy Production Principles 200 Oxidation-Reduction Reactions 200 ATP 201 9.3 Glycolysis and Fermentation 203 Glycolysis 204 Fermentation 204 Clinical Application: The Clinical Importance of Alcohol Throughout History 207 9.4 Aerobic Cellular Respiration 208 Pyruvate Oxidation and the Citric Acid Cycle 208 The Electron Transport System 210 Lipid and Protein Catabolism 211 Integrated Metabolic Pathways 213 What a Microbiologist Sees: Microbial Bioremediation of an Oil Spill 213 9.5 Photosynthesis 214 Reactions of Photosynthesis 214 Chemosynthesis in Bacteria 219 Case Study: A Metabolic Imbalance in Grand Lake St. Mary’s 220 10 Microbial Genetics and Genetic Engineering 226 10.1 DNA as the Genetic Material 227 DNA Structure and Functions 227 DNA Replication in Bacteria 228 10.2 From DNA to Protein 230 Transcription 230 Translation 232 10.3 Sources of Genetic Variation 234 Mutation 234 Recombination 237 Transposition 237 Case Study: The Spread of a Drug-Resistant Gene 239 10.4 Regulation of Gene Expression 240 Transcriptional Control 240 Pre-and Posttranscriptional Control 240 10.5 Recombinant DNA Technology 242 Recombinant DNA Tools and Gene Cloning 242 The Microbiologist’s Toolbox: Gel Electrophoresis 243 Applications of Recombinant DNA Technology 244 What a Microbiologist Sees: Manipulating the Bacterial Genome for Agricultural Benefits 246 Ethical and Safety Concerns 247 10.6 Genomics 248 DNA Sequencing 248 Genomic Analysis 248 Applications of Genomics 250 Clinical Application: Screening for Genetic Diseases—BRCA1 Mutation 251 11 Microbial Growth and Control 257 11.1 Requirements for Microbial Growth 258 Energy Sources 258 Physical Requirements 258 Case Study: Foodborne Illness from Home-Prepared Fermented Tofu 259 Chemical Requirements 261 11.2 Bacterial Reproduction and Growth 262 Cell Division 263 Growth Rate of Bacteria 263 Phases of Growth 264 Methods of Quantifying Bacterial Growth 265 The Microbiologist’s Toolbox: Dilution Plating 267 11.3 Laboratory Growth of Microorganisms 268 Obtaining a Pure Culture 268 Growth Media 269 Bacteria That Cannot Be Cultured 272 What a Microbiologist Sees: Biofilm Formation on Teeth 272 11.4 Microbial Cultures in Clinical Practice 273 Specimen Collection 273 Specimen Analysis 275 11.5 Controlling Microbial Growth 277 Physical Methods 277 Radiation 278 Chemical Methods 279 Clinical Application: Alcohol-Based Hand Sanitizers in Health Care Settings 281 12 Antimicrobial Agents 287 12.1 Principles of Antimicrobial Chemotherapy 288 The Discovery and Development of Antimicrobial Agents 288 Choosing the Best Antimicrobial Agent 289 The Microbiologist’s Toolbox: The Broth Dilution Test 292 12.2 Antibacterial Agents 293 Inhibitors of Cell Wall Synthesis 293 Inhibitors of Protein Synthesis 296 Inhibitors of Nucleic Acid Synthesis 299 Agents That Target the Bacterial Plasma Membrane 300 Clinical Application: The Fight Against Drug-Resistant Tuberculosis 300 Antimycobacterial Agents 301 12.3 Antiviral Agents 303 Inhibitors of HIV 304 Inhibitors of Hepatitis B and C Viruses 306 Inhibitors of Influenza A and B Viruses 307 Inhibitors of Herpes Viruses 307 12.4 Antifungal and Antiparasitic Agents 308 Antifungal Agents 308 Antiparasitic Agents 310 Case Study: Problems with Malaria Medication in Mozambique 312 12.5 Antimicrobial Drug Resistance 313 Principles of Drug Resistance 314 Mechanisms of Drug Resistance 314 Human Factors Contributing to Antimicrobial Resistance 316 What a Microbiologist Sees: Livestock-Associated Drug-Resistant S. aureus 316 13 Innate Immunity 323 13.1 An Introduction to Immunity 324 The Benefits and Consequences of the Immune Response 324 Innate Versus Adaptive Immunity 324 The Basic Anatomy of the Immune System 326 13.2 First-Line Defense Mechanisms 330 Physical Defenses 330 Chemical Defenses 331 What a Microbiologist Sees: The Benefits of Fever 331 Case Study: No Spicy Food for Me! 332 13.3 Innate Cellular Defense Mechanisms 334 Hematopoiesis 334 Leukocytes 335 The Microbiologist’s Toolbox: The Differential Count 337 Phagocytosis 338 Inflammation 338 13.4 Protein-Mediated Defense Mechanisms 341 The Complement Pathways 341 Interferons 343 Other Protein-Mediated Defense Mechanisms 343 14 Adaptive Immunity 351 14.1 Introduction to Adaptive Immunity 352 Hallmarks of Adaptive Immunity 352 Antigens and Immunogenicity 352 Lymphocyte Maturation and Clonal Selection 354 Clinical Application: Conjugate Vaccines 354 The Major Histocompatibility Complex 357 What a Microbiologist Sees: Transplant Rejection 357 14.2 Cell-Mediated Responses 358 T-Cell Categories 358 Antigen Processing and Presentation 359 The T-Cell Receptor Complex and Associative Recognition 362 14.3 T-Cell Activation 363 Early Stages of T-Cell Activation 363 Completion of T-Cell Activation 363 Case Study: The Mantoux Test 364 14.4 Antibody-Mediated Responses 365 Basic Antibody Structure 365 The Microbiologist’s Toolbox: The Coagulase Agglutination Assay 366 Immunoglobulin Classes and Their Specific Functions 367 14.5 B-Cell Activation 368 B-Cell Receptors and Pathogen Binding 368 Antibody Production and Clonal Expansion 368 B-Cell Effector Mechanisms 372 15 Vaccination, Immunoassays, and Immune Disorders 378 15.1 Vaccines and Vaccination 379 A Brief History of Vaccination 379 Modern Vaccines 379 Case Study: Prioritizing Immunizations 381 Vaccines and Public Health 383 Vaccine Safety and Misconceptions 386 15.2 Immunoassays 388 Monoclonal Antibodies 388 Types of Immunoassays 390 The Microbiologist’s Toolbox: Human Monoclonal Antibody Therapy for Non-Hodgkin’s Lymphoma 390 153 Hypersensitivities 394 Type I Hypersensitivity 395 Type II Hypersensitivity 396 Type III Hypersensitivity 397 What a Microbiologist Sees: Fetal Rh Incompatibility 397 Type IV Hypersensitivity 398 15.4 Autoimmune Diseases and Immunodeficiencies 399 Autoimmune Diseases 399 Immunodeficiencies 400 Clinical Application: Bone Marrow Transplants for Immunodeficient Patients 402 16 Microbial Pathogenesis 408 16.1 Transmission of Microbes 409 Microbial Reservoirs 409 Modes of Transmission 410 Case Study: The Cholera Epidemic in Goma, Zaire 411 Horizontal and Vertical Transmission 412 16.2 Entering and Adhering to the Host 413 Portals of Entry and Exit 413 Adhering to Host Cells 413 16.3 Overcoming Host Defenses 415 Evading Immune Attack 416 Altering Pathogen Antigens 417 Damaging the Host Immune System 418 16.4 Damaging Host Tissues 420 Direct Damage 420 Enzymes 421 Endotoxins 421 Exotoxins 423 Clinical Application: Toxoid-Based Vaccines 424 Immunopathy 426 The Microbiologist’s Toolbox: Analysis of Hemolysis on Blood Agar 426 16.5 Factors Influencing Disease Outcomes 427 Host Factors 428 What a Microbiologist Sees: Stress and Infection 428 Microbial Factors 429 17 Epidemiology and Infection Control 434 17.1 Epidemiology and Public Health 435 Early Epidemiological Successes 435 Significant Accomplishments of Epidemiology 435 17.2 Epidemiological Surveillance 437 What a Microbiologist Sees: Antibiotic-Impregnated Bone Cement 438 Prevalence, Incidence Rates, and Mortality Rates 438 Epidemic Curves 439 Disease Surveillance 439 17.3 Epidemiological Studies and Clinical Trials 441 Case-Control and Cohort Studies 442 Clinical Trials 442 Case Study: A Foodborne Outbreak among Inmates at a County Jail 443 17.4 Health Care–Associated Infections 445 Common Health Care–Associated Infections 445 Surgical Site Infections 445 Clinical Application: Reducing the Risk of Bloodstream Infections 446 CAUTIs 446 PICC Line Infections 447 CLABSIs 450 17.5 Preventing Pathogen Spread in Health Care Settings 450 Hand Hygiene 450 Universal and Standard Precautions and PPE 450 Screening 452 Isolation Procedures 453 The Microbiologist’s Toolbox: MRSA Screening Procedures in the Clinical Laboratory 454 18 Diseases of the Respiratory System 460 18.1 The Conflicts 461 Host Defenses 461 Microbial Pathogenic Strategies 461 Normal Microbiota 462 18.2 Bacterial Diseases of the Respiratory System 463 Diphtheria 463 Pertussis 464 Case Study: Whooping Cough Outbreak 465 Tuberculosis 466 18.3 Viral Diseases of the Respiratory System 468 The Common Cold 468 Influenza 470 What a Microbiologist Sees: Unpredictable Behavior 473 18.4 Diseases of the Respiratory System Caused by Multiple Pathogens 474 Sinusitis and Otitis Media 474 Pharyngitis 475 The Microbiologist’s Toolbox: Diagnosis of Strep Throat 478 Laryngitis, Croup, Tracheitis, and Epiglottitis 479 Bronchitis and Bronchiolitis 479 18.5 Pneumonia 480 General Characteristics of Pneumonia 480 Clinical Application: Sputum Samples 481 Epidemiology of Pneumonia 481 Causes of Pneumonia 482 Emerging Pathogens 484 19 Diseases of the Skin and Eyes 491 19.1 The Conflicts 492 Host Defenses 492 Microbial Pathogenic Strategies 492 Normal Microbiota 493 19.2 Bacterial Diseases of the Skin 495 Staphylococcal and Streptococcal Skin Diseases 495 The Microbiologist’s Toolbox: Mannitol Salt Agar—A Versatile Selective/Differential Medium 498 Pseudomonal Skin Diseases 499 Miscellaneous Bacterial Skin Diseases 499 19.3 Viral Diseases of the Skin 501 Pediatric Viral Rashes 501 Clinical Application: An App to Improve Hand Hygiene 502 Shingles 504 Warts 506 Smallpox 506 19.4 Skin Diseases Caused by Eukaryotic Pathogens 508 Fungal Skin Diseases 508 What a Microbiologist Sees: Oral Thrush and Immune System Status 509 Protozoan Skin Diseases 509 Helminthic Skin Diseases 510 Arthropod Skin Diseases 510 Case Study: Kindergarten Contact 512 19.5 Diseases of the Eye 513 Host Defenses and Microbial Pathogenic Strategies 514 Conjunctivitis 514 Other Eye Diseases 516 20 Diseases of the Gastrointestinal System 524 20.1 The Conflicts 525 Host Defenses 525 Microbial Pathogenic Strategies 525 Normal Microbiota 525 20.2 Bacterial Diseases of the Mouth and Upper GI Tract 527 Dental Caries 527 Gingivitis and Periodontal Disease 528 What a Microbiologist Sees: Oral Hygiene for Patients with Ventilators 529 Clinical Application: Periodontitis and Alzheimer’s Disease 529 Peptic Ulcer Disease 530 Staphylococcus aureus Food Intoxication 530 20.3 Bacterial Diseases of the Lower GI Tract 531 Diseases Caused by Salmonella 532 Diarrheagenic E. coli Infections 532 Campylobacteriosis 532 The Microbiologist’s Toolbox: Preparing and Analyzing a Fecal Culture 533 Shigellosis 534 Cholera 535 Opportunistic Infections 535 20.4 Viral Diseases of the GI System 538 Cold Sores 538 Mumps 538 Viral Gastroenteritis 539 Hepatitis A 539 Case Study: A Norovirus Outbreak Among Nurses 540 20.5 Protozoan Diseases of the GI System 541 Giardiasis 541 Amoebic Dysentery 542 Cryptosporidiosis 542 20.6 Helminthic Diseases of the GI System 543 Trematode Infections 543 Cestode Infections 544 Nematode Infections 545 21 Diseases of the Urogenital System 554 21.1 The Conflicts 555 Host Defenses 555 Microbial Pathogenic Strategies 555 Normal Microbiota 555 21.2 Bacterial Diseases of the Urinary System 558 Cystitis 558 Pyelonephritis 559 What a Microbiologist Sees: Cranberry Juice for UTI Prevention 560 Leptospirosis 561 Case Study: Pyelonephritis in a Toddler 561 21.3 Bacterial Diseases of the Reproductive Systems 563 Prostatitis 563 Chlamydia 563 Gonorrhea 565 The Microbiologist’s Toolbox: The Challenge of Culturing Neisseria gonorrhoeae 566 Pelvic Inflammatory Disease 566 Syphilis 568 21.4 Viral Diseases of the Reproductive Systems 570 Genital Warts 570 Clinical Application: Winning the War on Cervical Cancer 571 Genital Herpes 572 Molluscum Contagiosum 573 21.5 HIV Infection and AIDS 574 HIV Origins and Characteristics 574 HIV Replication and Pathogenicity 576 HIV Testing, Treatment, and Outcomes 577 21.6 Fungal and Protozoan Diseases of the Reproductive Systems 579 Vaginal Yeast Infections 579 Trichomoniasis 581 22 Diseases of the Nervous System 587 22.1 The Conflicts 588 Host Defenses 588 Microbial Pathogenic Strategies 588 22.2 Bacterial Diseases of the Nervous System 590 Bacterial Meningitis 590 Tetanus 593 Botulism 593 Case Study: The High Cost of Forgoing Tetanus Vaccination 594 Clinical Application: Clinical Use of Botulism Toxin 595 Hansen’s Disease (Leprosy) 597 22.3 Viral Diseases of the Nervous System 597 Viral Meningitis 597 Encephalitis 598 Polio 599 What a Microbiologist Sees: Polio Eradication 600 Rabies 601 Other Viral Diseases of the Nervous System 603 22.4 Fungal and Protozoan Diseases of the Nervous System 604 Fungal Meningitis 604 The Microbiologist’s Toolbox: India Ink Staining of CSF for Cryptococcus 604 Toxoplasmosis 605 22.5 Prion Diseases of the Nervous System 606 Animal Spongiform Encephalopathies 606 Human Prion Diseases 606 23 Diseases of the Cardiovascular and Lymphatic Systems 613 23.1 The Conflicts 614 Host Defenses 614 Microbial Pathogenic Strategies 614 23.2 Sepsis and Cardiac Diseases 616 Sepsis 616 Cardiac Diseases 619 The Microbiologist’s Toolbox: The Blood Culture 620 23.3 Bacterial Diseases of the Cardiovascular and Lymphatic Systems 621 Brucellosis 622 Anthrax 623 Lyme Disease 625 Plague 627 Other Bacterial Diseases 628 23.4 Viral Diseases of the Cardiovascular and Lymphatic Systems 630 Leukocyte-Associated Cardiovascular and Lymphatic Diseases 630 What a Microbiologist Sees: The Diagnosis of Mononucleosis 631 Viral Hemorrhagic Diseases 631 Hepatitis 633 Clinical Application: HIV Status and the Spread of Hepatitis 634 23.5 Fungal, Protozoan, and Helminthic Diseases of the Cardiovascular and Lymphatic Systems 635 Systemic Candida auris Infection 635 Systemic Protozoan Diseases 636 Case Study: The Kissing Bug 637 Systemic Helminthic Diseases 639 24 Environmental and Industrial Microbiology 646 24.1 Microbial Ecology 647 The Ecological Hierarchy 647 Microbes in Earth’s Ecosystems 647 Biofilms 651 Clinical Application: A Potential New Therapy for Medical Biofilm Elimination 652 24.2 Biogeochemical Cycles 653 The Nitrogen Cycle 653 The Carbon Cycle 654 The Phosphorus Cycle 656 The Sulfur Cycle 657 What a Microbiologist Sees: Habitat for Acidophiles 658 24.3 Bioremediation 659 Principles of Bioremediation 659 Sewage Treatment 660 Water Treatment 661 24.4 Microorganisms Used in Manufacturing 662 Products of Biotechnology 662 Food Production 662 Case Study: Bacon Beer 665 24.5 Safe Product Processing and Packaging 666 Food Safety Regulation 666 Chemical and Physical Controls in Food Production 667 Canning 668 Microbial Control in Health Care Settings 669 The Microbiologist’s Toolbox: The Autoclave 669 Appendix A Answers to Self-Tests A-1 Appendix B Physiological Reference Ranges B-5 Glossary G-1 Index I-1

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Book SynopsisTable of Contents1 Nutrition: Everyday Choices 1 1.1 Food Choices and Nutrient Intake 2 1.2 Nutrients and Their Functions 6 1.3 Nutrition in Health and Disease 9 1.4 Choosing a Healthy Diet 13 1.5 Evaluating Nutrition Information 15 2 Guidelines for a Healthy Diet 24 2.1 Nutrition Recommendations 25 2.2 Dietary Reference Intakes (DRIs) 31 2.3 The Dietary Guidelines for Americans 33 2.4 MyPlate: Putting the Guidelines into Practice 38 2.5 Food and Supplement Labels 42 3 Digestion: From Meals to Molecules 51 3.1 The Organization of Life 52 3.2 The Digestive System 55 3.3 Digestion and Absorption of Nutrients 57 3.4 The Digestive System in Health and Disease 65 3.5 Delivering Nutrients and Eliminating Wastes 74 3.6 An Overview of Metabolism 78 4 Carbohydrates: Sugars, Starches, and Fibers 83 4.1 Carbohydrates in Our Food 84 4.2 Types of Carbohydrates 87 4.3 Carbohydrate Digestion and Absorption 90 4.4 Carbohydrate Functions 95 4.5 Carbohydrates in Health and Disease 99 4.6 Meeting Carbohydrate Needs 106 5 Lipids: Fats, Phospholipids, and Sterols 116 5.1 Fats in Our Food 117 5.2 Types of Lipids 118 5.3 Absorbing and Transporting Lipids 123 5.4 Lipid Functions 128 5.5 Lipids in Health and Disease 132 5.6 Meeting Lipid Needs 137 6 Proteins and Amino Acids 147 6.1 Proteins in Our Food 148 6.2 The Structure of Amino Acids and Proteins 150 6.3 Protein Digestion and Absorption 153 6.4 Protein Synthesis and Functions 154 6.5 Protein in Health and Disease 159 6.6 Meeting Protein Needs 162 6.7 Vegetarian Diets 168 7 Vitamins 175 7.1 A Vitamin Primer 176 7.2 Vitamins and Energy Metabolism 185 7.3 Vitamins and Healthy Blood 193 7.4 Antioxidant Vitamins 203 7.5 Vitamins in Gene Expression 207 7.6 Meeting Needs with Dietary Supplements 218 8 Water and Minerals 226 8.1 Water 227 8.2 An Overview of Minerals 234 8.3 Electrolytes: Sodium, Potassium, and Chloride 241 8.4 Minerals and Bone Health 249 8.5 Minerals and Healthy Blood 258 8.6 Antioxidant Minerals 262 8.7 Minerals and Energy Metabolism 266 9 Energy Balance and Weight Management 273 9.1 The Obesity Epidemic 274 9.2 Body Weight and Health 278 9.3 Energy Balance 283 9.4 What Determines Body Size and Shape? 288 9.5 Managing Body Weight 293 9.6 Medications and Surgery for Weight Loss 300 9.7 Eating Disorders 303 10 Nutrition, Fitness, and Physical Activity 314 10.1 Food, Physical Activity, and Health 315 10.2 The Components of Fitness 317 10.3 Recommendations for Physical Activity 320 10.4 Fueling Activity 325 10.5 Energy and Nutrient Needs for Physical Activity 331 10.6 Food and Drink to Optimize Performance 337 10.7 Ergogenic Aids 341 11 Nutrition During Pregnancy and Infancy 352 11.1 Changes in the Body During Pregnancy 353 11.2 Nutritional Needs During Pregnancy 358 11.3 Factors That Increase Pregnancy Risks 365 11.4 Lactation 370 11.5 Nutrition for Infants 373 12 Nutrition from 1 to 100 384 12.1 The Nutritional Health of America’s Youth 385 12.2 Nutrition for Children 390 12.3 Nutrition for Adolescents 397 12.4 Nutrition for the Adult Years 402 12.5 The Impact of Alcohol Throughout Life 412 13 How Safe Is Our Food Supply? 420 13.1 Keeping Food Safe 421 13.2 Pathogens in Food 424 13.3 Preventing and Controlling Microbial Food-Borne Illness 432 13.4 Agricultural and Industrial Chemicals in Food 436 13.5 Technology for Keeping Food Safe 442 13.6 Biotechnology 448 14 Feeding the World 456 14.1 The Two Faces of Malnutrition 457 14.2 Causes of Hunger Around the World 459 14.3 Causes of Hunger in the United States 464 14.4 Eliminating World Hunger 466 14.5 Eliminating Food Insecurity in the United States 473 Appendix A Dietary Reference Intakes A-1 Online Appendices Appendix A Dietary Reference Intakes Appendix B Healthy Dietary Patterns Appendix C U.S. Nutrition Guidelines and Recommendations Appendix D Energy Expenditure for Various Activities Appendix E Standards for Body Size Appendix F Normal Physiological Standards of Nutritional Relevance Appendix G Choice (Exchange) Lists Appendix H Food and Supplement Labels Appendix I World Health Organization Nutrition Recommendations Appendix J Calculations and Conversions Appendix K Popular Dietary Supplements Appendix L Answers to Thinking It Through Glossary GL-1 References R-1 Index I-1

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Book SynopsisTable of Contents1 Introduction to the Study of Cell and Molecular Biology 1 1.1 The Discovery of Cells 2 1.2 Basic Properties of Cells 3 1.3 Two Fundamentally Different Classes of Cells 8 1.4 Viruses and Viroids 26 1.5 Green Cells: Volvox, an Experiment in Multicellularity 35 1.6 Engineering Linkage: Tissue Engineering 36 2 The Chemical Basis of Life 39 2.1 Covalent Bonds 40 2.2 Engineering Linkage: Radionuclides for Imaging and Treatment 43 2.3 Noncovalent Bonds 44 2.4 Acids, Bases, and Buffers 48 2.5 The Nature of Biological Molecules 49 2.6 Green Cells: Chemical Fertilizers 52 2.7 Four Types of Biological Molecules 53 2.8 The Formation of Complex Macromolecular Structures 95 3 Bioenergetics, Enzymes, and Metabolism 99 3.1 Bioenergetics 100 3.2 Enzymes as Biological Catalysts 108 3.3 Metabolism 123 3.4 Green Cells: Regulation of Metabolism by the Light/Dark Cycle 134 3.5 Engineering Linkage: Using Metabolism to Image Tumors 135 4 The Structure and Function of the Plasma Membrane 137 4.1 Introduction to the Plasma Membrane 138 4.2 The Chemical Composition of Membranes 142 4.3 Membrane Proteins 148 4.4 Membrane Lipids and Membrane Fluidity 156 4.5 The Dynamic Nature of the Plasma Membrane 159 4.6 The Movement of Substances across Cell Membranes 166 4.7 Membrane Potentials and Nerve Impulses 189 4.8 Green Cells: Electrical Signaling in Plants 198 4.9 Engineering Linkage: Neurotechnology 199 5 Aerobic Respiration and the Mitochondrion 203 5.1 Mitochondrial Structure and Function 204 5.2 Aerobic Metabolism in the Mitochondrion 209 5.3 The Role of Mitochondria in the Formation of ATP 215 5.4 Engineering Linkage: Measuring Blood Oxygen 224 5.5 Establishment of a Proton-Motive Force 225 5.6 The Machinery for ATP Formation 226 5.7 Peroxisomes 233 5.8 Green Cells: Glyoxysomes 237 6 Photosynthesis and the Chloroplast 239 6.1 The Origin of Photosynthesis 240 6.2 Chloroplast Structure 241 6.3 An Overview of Photosynthetic Metabolism 243 6.4 The Absorption of Light 244 6.5 Green Cells: Chromoplasts 246 6.6 Photosynthetic Units and Reaction Centers 247 6.7 Photophosphorylation 255 6.8 Carbon Dioxide Fixation and the Synthesis of Carbohydrate 256 6.9 Engineering Linkage: Photodynamic Therapy 264 7 Interactions Between Cells and Their Environment 267 7.1 Extracellular Interactions 268 7.2 Engineering Linkage: Organoids 277 7.3 Interactions of Cells with Extracellular Materials 278 7.4 Interactions of Cells with Other Cells 284 7.5 Tight Junctions: Sealing the Extracellular Space 294 7.6 Intercellular Communication 296 7.7 Cell Walls 303 7.8 Green Cells: Cell Walls and Plant Terrestrialization 306 8 Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking 307 8.1 An Overview of the Endomembrane System 308 8.2 A Few Approaches to the Study of Endomembranes 311 8.3 The Endoplasmic Reticulum 317 8.4 The Golgi Complex 330 8.5 Types of Vesicle Transport 335 8.6 Engineering Linkage: Extracellular Vesicles for Drug Delivery 347 8.7 Lysosomes 348 8.8 Green Cells: Plant Cell Vacuoles 350 8.9 The Endocytic Pathway: Moving Membrane and Materials into the Cell Interior 351 8.10 Posttranslational Uptake of Proteins by Peroxisomes, Mitochondria, and Chloroplasts 363 9 The Cytoskeleton and Cell Motility 369 9.1 Overview of the Major Functions of the Cytoskeleton 370 9.2 Structure and Function of Microtubules 372 9.3 Green Cells: Why the Woodbine Twineth 376 9.4 Motor Proteins: Kinesins and Dyneins 377 9.5 Microtubule-Organizing Centers (MTOCs) 383 9.6 Structure and Function of Cilia and Flagella 390 9.7 Intermediate Filaments 398 9.8 Actin and Myosin 402 9.9 Muscle Organization and Contraction 410 9.10 Engineering Linkage: Muscle Biomechanics 416 9.11 Actin-Binding Proteins 417 9.12 Cellular Motility 420 9.13 The Bacterial Cytoskeleton 430 10 The Nature of the Gene and the Genome 433 10.1 The Concept of a Gene as a Unit of Inheritance 434 10.2 The Discovery of Chromosomes 435 10.3 Chromosomes as the Carriers of Genetic Information 436 10.4 The Chemical Nature of the Gene 441 10.5 The Complexity of the Genome 452 10.6 The Stability of the Genome 458 10.7 Sequencing Genomes: The Footprints of Biological Evolution 464 10.8 Engineering Linkage: Engineering Genomes 467 10.9 The Genetic Basis of “Being Human” 468 10.10 Green Cells: Gene Transfer by Agrobacterium tumefaciens 475 11 The Central Dogma: DNA to RNA to Protein 477 11.1 The Relationships among Genes, Proteins, and RNAs 478 11.2 An Overview of Transcription in Both Prokaryotic and Eukaryotic Cells 483 11.3 Synthesis and Processing of Eukaryotic Ribosomal and Transfer RNAs 487 11.4 Synthesis and Structure of Eukaryotic Messenger RNAs 491 11.5 Small Regulatory RNAs and RNA Silencing Pathways 507 11.6 Green Cells: Long-Range siRNA Movement 512 11.7 CRISPR and Other Noncoding RNAs 513 11.8 Encoding Genetic Information 514 11.9 Decoding the Codons: The Role of Transfer RNAs 517 11.10 Translating Genetic Information 520 11.11 Engineering Linkage: DNA Origami 534 12 Control of Gene Expression 537 12.1 Control of Gene Expression in Bacteria 538 12.2 Engineering Linkage: Building Digital Logic with Genes 542 12.3 Structure of the Nuclear Envelope 543 12.4 Chromosomes and Chromatin 550 12.5 The Nucleus as an Organized Organelle 567 12.6 An Overview of Gene Regulation in Eukaryotes 570 12.7 Transcriptional Control 571 12.8 Green Cells: The ABC Model and MADS Domain Transcription Factors 592 12.9 RNA Processing Control 593 12.10 Translational Control 594 12.11 Posttranslational Control: Determining Protein Stability 601 13 DNA Replication and Repair 605 13.1 DNA Replication 606 13.2 DNA Replication in Bacterial Cells 610 13.3 The Structure and Functions of DNA Polymerases 617 13.4 Replication in Viruses 621 13.5 Engineering Linkage: Storing Data in DNA 621 13.6 DNA Replication in Eukaryotic Cells 622 13.7 DNA Repair 628 13.8 Green Cells: Gamma Gardens 632 13.9 Between Replication and Repair 633 14 Cell Division 637 14.1 The Cell Cycle 638 14.2 M Phase: Mitosis and Cytokinesis 651 14.3 Engineering Linkage: The Role of Membrane Tension in Cell Division 672 14.4 Green Cells: Unique Aspects of Plant Cell Division 673 14.5 Meiosis 673 15 Cell Signaling and Signal Transduction: Communication between Cells 685 15.1 The Basic Elements of Cell Signaling Systems 686 15.2 A Survey of Extracellular Messengers and Their Receptors 689 15.3 G Protein-Coupled Receptors and Their Second Messengers 690 15.4 Engineering Linkage: Biosensors in Medicine and Biology 709 15.5 Protein-Tyrosine Phosphorylation as a Mechanism for Signal Transduction 710 15.6 Green Cells: Auxin Signaling 721 15.7 The Role of Calcium as an Intracellular Messenger 721 15.8 Convergence, Divergence, and Cross-Talk among Different Signaling Pathways 726 15.9 The Role of NO as an Intracellular Messenger 729 15.10 Apoptosis (Programmed Cell Death) 731 16 Cancer 737 16.1 Basic Properties of a Cancer Cell 738 16.2 The Causes of Cancer 741 16.3 Cancer: A Genetic Disorder 747 16.4 Engineering Linkage: Therapeutic Radiation 767 16.5 Green Cells: Plant-Based Chemotherapies 767 16.6 Strategies for Combating Cancer 768 17 The Immune Response 775 17.1 An Overview of the Immune Response 776 17.2 Green Cells: The Plant Immune System 780 17.3 The Clonal Selection Theory as It Applies to B Cells 781 17.4 T Lymphocytes: Activation and Mechanism of Action 787 17.5 Selected Topics on the Cellular and Molecular Basis of Immunity 790 17.6 Engineering Linkage: Adoptive T-cell Therapy 808 17.7 Signal Transduction Pathways in Lymphocyte Activation 809 18 Techniques in Cell and Molecular Biology 811 18.1 The Light Microscope 812 18.2 Transmission Electron Microscopy 822 18.3 Scanning Electron and Atomic Force Microscopy 828 18.4 The Use of Radioisotopes 830 18.5 Cell Culture 831 18.6 The Fractionation of a Cell’s Contents by Differential Centrifugation 833 18.7 Isolation, Purification, and Fractionation of Proteins 834 18.8 Determining the Structure of Proteins and Multisubunit Complexes 840 18.9 Fractionation of Nucleic Acids 842 18.10 Nucleic Acid Hybridization 845 18.11 Chemical Synthesis of DNA 846 18.12 Recombinant DNA Technology 847 18.13 Enzymatic Amplification of DNA by PCR 851 18.14 DNA Sequencing 853 18.15 DNA Libraries 855 18.16 DNA Transfer into Eukaryotic Cells and Mammalian Embryos 857 18.17 Gene Editing and Silencing 860 18.18 The Use of Antibodies 864 Additional Readings A-1 Glossary G-1 Index I-1

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Book SynopsisThis second edition of Studies in Viral Ecology is designed to serve as a means of updating the knowledge of virologists regarding the broader aspects of viral ecology. As with the first edition, this book explains the ecology of viruses by examining their interactive dynamics with their hosting species (covering both animals and plants), including the types of transmission cycles that viruses have evolved encompassing principal and alternate hosts, vehicles and vectoring species. Examining virology from an organismal biology approach and focusing on the concept that viral infections represent areas of overlap in the ecologies of the involved species, Viral Ecology is essential for students and professionals who either may be non-virologists or virologists whose previous familiarity has been very specialized.This second edition of Studies in Viral Ecology is designed to serve as a means of updating the knowledge of virologists regarding the broader aspects of viral ecology. ATable of ContentsSection I: An Introduction to the Ecology of Viruses Chapter 1. Defining the Ecology of VirusesChriston J. Hurst Section II: Viruses Of Other Microorganisms Chapter 2. Bacteriophage and Viral Ecology in the ‘Omics AgeJessica Chopyk, Daniel J. Nasko, and Eric G. Sakowski Chapter 3. Viruses of Eukaryotic MicroalgaeVictoria L. N. Jackson, Michael J. Allen and Adam Monier Chapter 4. Viruses of SeaweedsDeclan C. Schroeder and Dean A. McKeown Chapter 5. The Ecology and Evolution of Fungal VirusesBradley I. Hillman and Michael G. Milgroom Section III: Viruses of Vascular Plants Chapter 6. Ecology of Plant Infecting Viruses, with Special Reference to GeminivirusesBasavaprabhu L. Patil and Claude M. Fauquet Chapter 7. Viroids and Viroid Diseases of PlantsRicardo Flores, Francesco Di Serio, Beatriz Navarro, Nuria Duran-Vila and Robert A. Owens Section IV: Viruses of Invertebrate Animals Chapter 8. Viruses Infecting Marine MolluscsTristan Renault Chapter 9. Viruses Affecting CrustaceansKelly S. Bateman Chapter 10. Viruses of InsectsDeclan C. Schroeder and Jessica L. Kevill Section V: Viruses of Vertebrate Animals Chapter 11. Viruses of FishAudun Helge Nerland, Aina-Cathrine Øvergård and Sonal Patel Chapter 12. Ecology of Viruses Infecting Ectothermic Vertebrates—The Impact of Ranavirus Infections on AmphibiansV. Gregory Chinchar, Amanda L.J. Duffus, Jesse L. Brunner Chapter 13. Viruses of ReptilesRachel E. Marschang, Jonathan I. Meddings, and Ellen Ariel Chapter 14. Ecology of Avian VirusesJosanne H. Verhagen Chapter 15. Viruses of Terrestrial MammalsLaura D. Kramer and Norma P. Tavakoli Chapter 16. Viruses of Marine MammalsSasan Fereidouni Chapter 17. The Relationship Between Humans, Their Viruses, and PrionsChriston J. Hurst

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Book SynopsisContents 1. Maria Isabel Andrade: Sweetpotato Breeder, Technology Transfer Specialist, and Advocate 1 2. Development of Cold Climate Grapes in the Upper Midwestern U.S.: The Pioneering Work of Elmer Swenson 31 3. Candidate Genes to Extend Fleshy Fruit Shelf Life 61 4. Breeding Naked Barley for Food, Feed, and Malt 95 5. The Foundations, Continuing Evolution, and Outcomes from the Application of Intellectual Property Protection in Plant Breeding and Agriculture 121 6. The Use of Endosperm Genes for Sweet Corn Improvement: A review of developments in endosperm genes in sweet corn since the seminal publication in Plant Breeding Reviews, Volume 1, by Charles Boyer and Jack Shannon (1984) 215 7. Gender and Farmer Preferences for Varietal Traits: Evidence and Issues for Crop Improvement 243 8. Domestication, Genetics, and Genomics of the American Cranberry 279 9. Images and Descriptions of Cucurbita maxima in Western Europe in the Sixteenth and Seventeenth Centuries 317Table of ContentsContributors ix 1. Maria Isabel Andrade: Sweetpotato Breeder, Technology Transfer Specialist, and Advocate 1Jan W. Low and Edward Carey I. Early Years 3 II. Research for Devlopment in Southern Africa 7 III. The Advocate and Team Player 18 IV. The Mentor at Work and in her Community 21 V. Awards and Service 24 Literature Cited 25 Publications 26 2 Development of Cold Climate Grapes in the Upper Midwestern U.S.: The Pioneering Work of Elmer Swenson 31Matthew D. Clark I. A Cold Climate Grape Industry 32 II. Elmer Swenson 37 III. Grape Improvement in the Midwest 53 IV. Summary and Future Prospects 57 Acknowledgments 57 Literature Cited 58 3 Candidate Genes to Extend Fleshy Fruit Shelf Life 61Haya Friedman I. Introduction 62 II. Available Methods for Breeding and Genetic Manipulations 66 III. Cuticle Structure and Effect on Fruit Shelf Life 68 IV. Candidate Genes for Cell‐Wall Modification and Fruit Softening 69 V. Ethylene‐Biosynthesis Pathway and Effect on Fruit Ripening 77 VI. Usefulness of Components of the Ethylene‐Response Pathway for Delay of Fruit Ripening 79 VII. Fruit‐Ripening Delay Based on Manipulation of Upstream Transcription Factors 81 VIII. Concluding Remarks and Future Prospects 84 Acknowledgments 85 Literature Cited 86 4 Breeding Naked Barley for Food, Feed, and Malt 95Brigid Meints and Patrick M. Hayes I. Introduction 96 II. The Nud Gene 97 III. Traits of Interest Related to Nud 98 IV. Selecting for β‐Glucan and Starch Type 102 V. Feed Barley Breeding and Quality 104 VI. Food Barley Breeding and Quality 106 VII. Malting Barley Breeding and Quality 108 VIII. Brewing 111 IX. Distilling 112 X. Conclusions and Future Directions 113 Acknowledgments 114 Literature Cited 114 5 The Foundations, Continuing Evolution, and Outcomes from the Application of Intellectual Property Protection in Plant Breeding and Agriculture 121Stephen Smith I. Intellectual Property, Intellectual Property Rights, and the Thesis Underlying this Review 125 II. The Philosophical Basis of IP and IPR and the Need to Establish Appropriate Balances 128 III. Intellectual Property, Intellectual Property Rights, and their Associations with Plant Breeding and Agriculture 133 IV. The Global Framework within which IPR Applicable to Plant Breeding Resides 143 V. The Development of Formal Mechanisms of Intellectual Property Rights for Plant Varieties and Plant‐Related Subject Matter 148 VI. Forms of Intellectual Property Protection Available to Plant Breeders and Trait Developers 156 VII. Associations Between IP Systems and the Generation of Benefits 176 VIII. Concluding Comments: Looking to the Future 188 Literature Cited 192 6 The Use of Endosperm Genes for Sweet Corn Improvement: A review of developments in endosperm genes in sweet corn since the seminal publication in Plant Breeding Reviews, Volume 1, by Charles Boyer and Jack Shannon (1984) 215William F. Tracy, Stacie L. Shuler, and Hallie Dodson‐Swenson I. Introduction 217 II. Economics 218 III. Endosperm Development 219 IV. Endosperm Mutants, Germination, and Seedling Vigor in Sweet Corn 233 V. Future Prospects 234 Literature Cited 235 7 Gender and Farmer Preferences for Varietal Traits: Evidence and Issues for Crop Improvement 243Eva Weltzien, Fred Rattunde, Anja Christinck, Krista Isaacs, and Jacqueline Ashby I. Introduction 245 II. Methods 247 III. Cases Documenting Gender Differentiation for Trait Preferences 250 IV. Findings on Gender‐Specific Trait Preferences 256 V. Issues for Gender‐Responsive Crop Improvement 264 Acknowledgments 273 Literature Cited 273 8 Domestication, Genetics, and Genomics of the American Cranberry 279Nicholi Vorsa and Juan Zalapa I. Domestication and Breeding 281 II. Life History Parameters 285 III. Taxonomy 287 IV. Cytology 288 V. Traits of Interest 289 VI. Heritability of Traits 297 VII. Molecular Markers 297 VIII. Nuclear and Organellar Genome Assembly 302 IX. Linkage Mapping and SNP Markers 303 X. Marker‐Trait Association Studies 305 XI. Future Prospects 308 Acknowledgments 310 Literature Cited 310 9 Images and Descriptions of Cucurbita maxima in Western Europe in the Sixteenth and Seventeenth Centuries 317Alice K. Formiga and James R. Myers I. Introduction 318 II. Challenges of Identifying Cucurbits in Historical Sources 319 III. Distinguishing Cucurbita maxima 321 IV. Where was Cucurbita maxima Present in South America Before the Arrival of Europeans and how Early Could it have Arrived in Europe? 327 V. Cucurbita maxima in Herbals and Botanical and Agricultural Books 329 VI. Cucurbita maxima in Art 335 VII. Cucurbita maxima in Botanical Paintings 344 VIII. Cucurbita maxima in Genre Paintings and Still Lifes 346 IX. Conclusion and Future Prospects 349 Acknowledgments 350 Literature Cited 351 Author Index 357 Subject Index 365

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Book SynopsisTable of ContentsPreface v Introduction EXERCISE 1 Anatomical Language 1 EXERCISE 2 Organ Systems and Body Cavities 13 Cell and Tissues EXERCISE 3 Compound Light Microscope 25 EXERCISE 4 Cell Structure and Cell Cycle 33 EXERCISE 5 Transport Across the Plasma Membrane 43 EXERCISE 6 Tissues 53 Integumentary System EXERCISE 7 The Integumentary System Structure and Function 85 Skeletal System and Joints EXERCISE 8 Bone Structure and Function 97 EXERCISE 9 Axial Skeleton 107 EXERCISE 10 Appendicular Skeleton 139 EXERCISE 11 Joints and Synovial Joint Movements 161 Muscular System: Skeletal Muscles EXERCISE 12 Skeletal Muscle Structure 175 EXERCISE 13 Contraction of Skeletal Muscle 187 EXERCISE 14 Skeletal Muscles and Their Actions 199 Surface Anatomy EXERCISE 15 Surface Anatomy 241 Nervous System EXERCISE 16 Nervous Tissue 263 EXERCISE 17 Spinal Cord Structure and Function 277 EXERCISE 18 Spinal Nerves 287 EXERCISE 19 Somatic Reflexes 299 EXERCISE 20 Brain Structure and Function 309 EXERCISE 21 Cranial Nerves 333 EXERCISE 22 Autonomic Nervous System Structure and Function 343 EXERCISE 23 General Senses 355 EXERCISE 24 Special Senses 369 Endocrine System EXERCISE 25 Endocrine Structure and Function 401 Cardiovascular System EXERCISE 26 Blood Components and Blood Tests 421 EXERCISE 27 Heart Structure and Function 441 EXERCISE 28 Cardiac Cycle 461 EXERCISE 29 Blood Vessel Structure and Function 473 EXERCISE 30 Blood Vessel Identification 489 Lymphatic and Immune Systems EXERCISE 31 Lymphoid System and Immunity 517 Respiratory System EXERCISE 32 Respiratory System Structure and Function 537 EXERCISE 33 Pulmonary Ventilation 555 Digestive System EXERCISE 34 Digestive System Structure and Function 571 EXERCISE 35 Mechanical and Chemical Digestion 599 Urinary System EXERCISE 36 Urinary System Structure and Function 607 EXERCISE 37 Urine Formation and Urinalysis 625 Reproductive Systems EXERCISE 38 Male Reproductive System Structure and Function 637 EXERCISE 39 Female Reproductive System Structure and Function 653 Human Development and Heredity EXERCISE 40 Human Development 671 EXERCISE 41 Heredity 685 Answer Key to Activities 699 Appendix A: Word Roots 719 Appendix B: Skeletal Muscle Origins and Insertions 721 Appendix C: Measurements 727 Index 729

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Book SynopsisTable of ContentsPreface iv 1 An Introduction to the Human Body 1 2 The Chemical Level of Organization 29 3 The Cellular Level of Organization 63 4 The Tissue Level of Organization 111 5 The Integumentary System 149 6 The Skeletal System: Bone Tissue 177 7 The Skeletal System: The Axial Skeleton 202 8 The Skeletal System: The Appendicular Skeleton 242 9 Joints 269 10 Muscular Tissue 305 11 The Muscular System 344 12 Nervous Tissue 419 13 The Spinal Cord and Spinal Nerves 461 14 The Brain and Cranial Nerves 493 15 The Autonomic Nervous System 546 16 Sensory, Motor, and Integrative Systems 569 17 The Special Senses 600 18 The Endocrine System 647 19 The Cardiovascular System: The Blood 696 20 The Cardiovascular System: The Heart 727 21 The Cardiovascular System: Blood Vessels and Hemodynamics 771 22 The Lymphoid (Lymphatic) System and Immunity 846 23 The Respiratory System 891 24 The Digestive System 941 25 Metabolism and Nutrition 1000 26 The Urinary System 1042 27 Fluid, Electrolyte, and Acid– Base Homeostasis 1087 28 The Genital (Reproductive) Systems 1106 29 Development and Inheritance 1160 Appendix A Measurements A- 1 Appendix B Periodic Table B- 3 Appendix C Normal Values for Selected Blood Tests C- 4 Appendix D Normal Values for Selected Urine Tests D- 6 Appendix E Answers to Critical Thinking Questions E- 8 Appendix F Medical Eponyms F- 14 Glossary G- 1 Index I- 1

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Book SynopsisPlant Breeding Reviewspresents state-of-the-art reviews on plant genetics and the breeding of all types of crops by both traditional means and molecular methods. Many of the crops widely grown today stem from a very narrow genetic base; understanding and preserving crop genetic resources is vital to the security of food systems worldwide. The emphasis of the series is on methodology, a fundamental understanding of crop genetics, and applications to major crops.Table of ContentsContributors ix 1 Salvatore Ceccarelli: Plant Breeder, Mentor, and Farmers’ Friend 1Stefania Grando I. Biographical Sketch and Background 2 II. Research 6 III. The Man 17 IV. The Mentor and Inspirer 19 V. The Innovator 20 VI. The Supporter of National Programs 21 VII. The Advocate of Farmers 21 Acknowledgments 22 Literature Cited 22 Selected Publications of Salvatore Ceccarelli 25 2 Maize Cross Incompatibility and the Promiscuous Ga1‐m Allele 31Major M. Goodman, Zachary G. Jones, G. Jesus Sanchez, and Jerry L. Kermicle I. Historical Background 33 II. Ga1 (Gametophyte‐Factor 1), Ga2 (Gametophyte‐Factor 2), and Tcb1 (Teosinte‐Crossing‐Barrier 1) 34 III. Ga1‐m (Gametophyte‐Factor 1‐Male) 35 IV. Locus Composition 35 V. Gametophytic Selective Advantage 36 VI. Silk Reactions 36 VII. Mapping Gametophytic Loci 38 VIII. Geographical Distribution of Ga1 Alleles 38 IX. Distribution of Ga1 Alleles in Commercial Materials 41 X. Teosinte and Maize 41 XI. Popcorn and Organic Isolations 43 XII. Exceptionally Strong Cross‐Incompatible Sources Within Maize 44 XIII. Caution Concerning Use of Ga1‐m 45 XIV. Genetic Modifiers 46 XV. Molecular Characterizations 47 XVI. Recent Conclusions 47 XVII. Practical Use of Pollen‐Blockers 47 XVIII. Future Prospects 50 Acknowledgments 54 Literature Cited 54 3 Development of the Genetically Modified Innate® Potato 57Craig M. Richael I. Introduction 58 II. Innate® Generation 1 Potato Varieties 65 III. Innate® Generation 2 Potato Varieties 71 IV. Future Innate® Potato Varieties 74 V. Conclusions 75 Literature Cited 76 4 Cucumis sativus Chromosome Evolution, Domestication, and Genetic Diversity: Implications for Cucumber Breeding 79Yiqun Weng I. Introduction 81 II. Chromosome Evolution in the Making of Cucumber 83 III. Chromosome Evolution During Cucumber Domestication 86 IV. Diffusion of Cucumber to the World From its Center of Diversity and the Formation of Market Groups 90 V. Types of Cucumbers: Fresh Market vs Processing 92 VI. Genetic Diversity and Population Structure of Cucumber Collection 94 VII. Genetic Basis of Domestication‐Related Traits in Cucumbers 96 VIII. Chromosome Evolution, Domestication, and Genetic Diversity: Implications for Cucumber Breeding 101 Acknowledgments 104 Literature Cited 104 5 Freelance Plant Breeding 113Carol S. Deppe I. Introduction 115 II. Evolution of a Freelance Plant Breeder 116 III. Who and Where 119 IV. How Freelancers Learn the Plant Breeding Trade 130 V. Why—Motivations and Values 136 VI. Crops 139 VII. Goals 146 VIII. Methods 151 IX. Sources of Germplasm 161 X. Economics of Freelance Plant Breeding 164 XI. Freelance Plant Breeding That Doesn’t Fit Commercial Models 174 XII. Open Source Seed Initiative and Freelance Plant Breeding 176 XIII. Future Prospects 180 Acknowledgments 183 Literature Cited 183 6 Meadowfoam Breeding 187Jennifer G. Kling I. Introduction 189 II. Botany and Taxonomy of Limnanthes 190 III. Meadowfoam Breeding Organizations 195 IV. Seed Production Requirements 197 V. Greenhouse and Field Plot Techniques 201 VI. Selection Methods 206 VII. Breeding Populations and Molecular Resources 216 VIII. Meadowfoam Seed Oil 222 IX. Biotic Constraints 225 X. Glucosinolates and Other Seed Meal Components 230 XI. Meadowfoam in Cropping Systems 234 XII. Conclusions and Future Directions 235 Acknowledgments 237 Literature Cited 237 7 Reconsidering Approaches to Selection in Winter Squash Improvement: Improved Quality and Breeding Efficiency 247Michael Mazourek, Christopher Hernandez, and Jack Fabrizio I. Introduction 249 II. Genomic Resources for Winter Squash Improvement 251 III. Insight into Winter Squash Metabolism Related to Fruit Quality 253 IV. Winter Squash Quality Phenotyping 258 V. Squash Breeding Schemes 260 VI. Applying Genomic Selection in Cucurbita 264 VII. Conclusion 268 Acknowledgments 268 Literature Cited 269 8 Development of the Arctic® Apple 273Evan Stowe and Amit Dhingra I. Introduction 274 II. Genetic Engineering of Apple 275 III. Development and Evaluation of the Arctic® Apple 280 Literature Cited 292 Author Index 297 Subject Index 305

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Book SynopsisHorticultural Reviews presents state-of-the-art reviews on topics in horticultural science and technology covering both basic and applied research. Topics covered include the horticulture of fruits, vegetables, nut crops, and ornamentals. These review articles, written by world authorities, bridge the gap between the specialized researcher and the broader community of horticultural scientists and teachers.Table of ContentsContributors ix Dedication: Gregory L. Reighard xiiiJuan Carlos Melgar, Ksenija Gasic and Ian Warrington 1. Pollination-Induced Changes in the Morphology and Physiology of Dendrobium Orchid Flowers Prior toFertilization: The Roles of Ethylene and Auxin 1 Wouter G. van Doorn and Saichol Ketsa I. Introduction 2 II. Orchid Flower Structure 3 III. Post-Pollination Effects in Orchids other than Dendrobium 5 IV. Role of Hormones in Orchids other than Dendrobium 6 V. Pollination in Dendrobium 8 VI. Visible Post-Pollination Effects in Dendrobium 13 VII. Role of Hormones in the Visible Post-Pollination Phenomena in Dendrobium 21 VIII. Conclusions 31 Acknowledgment 31 Literature Cited 32 2. Actinidia arguta (Kiwiberry): Botany, Production, Genetics, Nutritional Value, and Postharvest Handling 37Piotr Latocha, Filip Debersaques and Iago Hale I. Introduction 39 II. Botany 41 III. Cultivation and Management 54 IV Genetics and Breeding 84 V. Chemical Composition, Nutritional Value, and Health Benefits 105 VI. Harvesting and Postharvest Handling 119 VII. Utilization 128 VIII. Conclusions 131 Literature Cited 133 3. Advances in Cassava-Based Multiple-Cropping Systems 153V. Ravi, G. Suja, R. Saravanan and Sanket J. More I. Introduction 156 II. Intercropping Cassava 170 III. Crop Rotation Involving Cassava 206 IV. Cassava-Based Sequential/Intercropping Systems Involving Pulses and/or Rice 208 V. Cassava + Plantation Crops 209 VI. Pests and Diseases in Cassava-Based Intercropping 212 VII. Conclusions and Future Prospects 214 Literature Cited 219 4. Arrowroot (Maranta arundinacea L.): Botany, Horticulture, and Uses 233Vitor Brito, Renata Nascimento, Jeniffer Narcisa-Oliveira, Nathalia Joffer, André Fattori, Marney Cereda, Carina Oliveira, Reginaldo Costa, Lorene Tiburtino-Silva and Josemar Maciel I. Introduction 234 II. Occurrence and Distribution 236 III. Botany: Taxonomy, Morphology, and Genetics 238 IV. Horticultural Aspects 248 V. Processing 252 VI. Uses and Applications 253 VII. Conclusions 264 Acknowledgment 264 Literature Cited 265 5. Jamun (Syzygium cumini L. Skeels): A Promising Fruit for the Future 275Babak Madani, Amin Mirshekari, Elhadi M. Yahia, John B. Golding, Shokrollah Hajivand and Abdolmajid Mirzaalian Dastjerdy I. Introduction 276 II. Economic Significance 277 III. Botany, Taxonomy, and Genetics 278 IV. Cultivation Practices 281 V. Nutritional Value 286 VI. Health-Promoting Effects 289 VII. Postharvest Practices 290 VIII. Processing 297 IX. Conclusions 299 Literature Cited 300 6. Coconut Micropropagation and Cryopreservation 307Ana S. Lédo and Wagner A. Vendrame I. Introduction 309 II. In Vitro Propagation Technology 311 III. Bioreactor Technology 320 IV. Cryopreservation 322 V. Summary and Conclusions 330 Literature Cited 33 7. The Puzzling Phenomenon of Seedling Yellows Recovery and Natural Spread of Asymptomatic Infections of Citrus Tristeza Virus: Two Sides of the Same Coin 339Moshe Bar-Joseph, Antonino F. Catara and Grazia Licciardello I. Introduction 341 II. The CTV Genome and Biology 341 III. A Short Account of the Israeli CTV Suppression Program (1970–1986) 343 IV. Comparisons of Severe and Mild CTV-VT Isolates From Sicily 347 V. Discussion 352 Acknowledgments 356 Literature Cited 357 8. Yield Alternation: Horticulture, Physiology, Molecular Biology, and Evolution 363Eliezer E. Goldschmidt and Avi Sadka I. Introduction 365 II. Molecular Mechanisms of Flowering Control in Model Plants and Fruit Trees 366 III. Effect of Fruit Load on Changes in Gene Expression, Protein, and Metabolite Levels in Leaves and Buds 377 IV. The Effect of Fruit Load on Hormone Homeostasis 381 V. Mitigation of Alternate Bearing 385 VI. Discussion 393 Acknowledgment 402 Literature Cited 402 Subject Index 419 Cumulative Subject Index 421 Cumulative Contributor Index 455

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