Biology, life sciences Books

Book SynopsisThe book provides a comprehensive detailed summary of current status on skin microbiome research in health and disease as well as key regulatory and legal aspects. In the past decade, interest and technology have greatly advanced to unravel the nature and effect of skin microbiome on our health. Diseases such as atopic dermatitis and acne are at the forefront of this research, but also other conditions such as skin cancer are under investigation. In addition, mapping of the skin microbiome has gone from basic to more detailed with attempts to correlate it to various ages, ethnicities and genders. In parallel to mapping it, a great deal of research is dedicated to understanding its functionality and communication (and hence effect) on human cells. The Skin Microbiome Handbook is a summary of current status of knowledge, research tools and approaches in skin microbiome, in health and disease. It contains the following categories: healthy skin microbiome andTable of ContentsPreface xvii Part 1: Healthy Skin Microbiome and Oral-Skin Interactions 1 1 The Microbiome of Healthy Skin 3Samantha Samaras and Michael Hoptroff 1.1 Introduction 3 1.1.1 Retrospective 3 1.1.2 Next Generation Sequencing 6 1.2 The Skin Microbiome in Health 7 1.2.1 Composition 7 1.2.2 Diversity 10 1.2.3 Uniqueness 13 1.3 Healthy Skin is the Foundation of a Balanced Skin Microbiome 14 1.3.1 Physical Aspects of Skin Impacting the Microbiome 14 1.3.2 Biochemical and Defensive Aspects of Skin Impacting the Microbiome 16 1.3.2.1 The Acid Mantle 16 1.3.2.2 Antimicrobial Lipids (AMLs) 16 1.3.2.3 Antimicrobial Peptides (AMPs) 17 1.3.3 Nutritional and Microenvironmental Aspects of Skin Impacting the Microbiome 18 1.3.3.1 Amino Acids 18 1.3.3.2 Sebaceous Lipids 19 1.3.3.3 Organic Acids and Other Materials 19 1.4 A Balanced Skin Microbiome Supports the Normal Functioning of Healthy Skin 20 1.4.1 Pathogen Exclusion 20 1.4.2 Contribution to Skin pH 20 1.4.3 Microbial Contribution to Skin Barrier Integrity 21 1.5 Conclusion 22 Acknowledgments 23 References 23 2 The Gut Microbiome-Skin Axis: Impact on Skin and Systemic Health 33David Drake 2.1 Introduction 34 2.2 The Gut-Skin Microbiome Axis 35 2.3 The Gut-Skin Microbiome Axis: Principle Pathways 35 2.4 Dysbiosis of the Gut Microbiome and Skin Dyshomeostasis 37 2.4.1 Acne Vulgaris 38 2.4.2 Atopic Dermatitis 39 2.5 Summary and Future Directions 39 References 40 3 The Skin and Oral Microbiome: An Examination of Overlap and Potential Interactions between Microbiome Communities 45Sandra Buerger 3.1 Introduction 45 3.1.1 Focus of the Chapter 45 3.1.2 Definition of Skin Microbiome 47 3.1.3 Definition of Oral Microbiome 48 3.2 Characterization of the Microbiome 48 3.2.1 Variability and Stability of Skin and Oral Microbiome 48 3.2.2 Microbial Community 49 3.2.2.1 Permeant Mutualistic or Commensal Microbes 49 3.2.2.2 Non-Pathogenic Transient Microbes 50 3.2.2.3 Pathogenic Microbes 50 3.3 The Core Skin and Oral Microbiomes 51 3.3.1 Taxonomic Methodology 51 3.3.2 Subgroups of the Microbiome 52 3.3.2.1 Bacteriome 52 3.3.2.2 Mycobiome (and Other Eukaryotic Microbial Members) 52 3.3.2.3 Virome 53 3.4 Interactions Between Skin and Oral Microbiomes 54 3.4.1 Potential for Interactions 54 3.4.2 Quorum Sensing 54 3.4.3 Immune System Development 54 3.4.4 Future Directions 55 3.5 Conclusion 55 Acknowledgments 56 References 56 Part 2: Skin Microbiome Observational Research 59 4 Skin Microbiome Alterations in Skin Diseases 61Travis Whitfill, Gilles R. Dubé and Julia Oh 4.1 Introduction and Background 61 4.2 Interactions Between Microbes and Host 62 4.3 Summary of Known Associations Between Skin Dysbioses and Skin Diseases 64 4.3.1 The Role of S. Aureus in Skin Disease 64 4.3.2 Atopic Dermatitis 64 4.3.3 Acne Vulgaris 66 4.3.4 Psoriasis 67 4.4 Skin Dysbioses in Skin Health 68 4.5 Other Skin Conditions 68 4.6 Therapeutic Approaches to Dysbiosis-Associated Skin Diseases 69 4.6.1 Traditional Methods of Treating Dysbiosis-Associated Skin Diseases 69 4.6.1.1 Atopic Dermatitis 69 4.6.1.2 Acne Vulgaris 69 4.6.2 Emerging Therapeutic Approaches to Treating Dysbiosis-Associated Skin Diseases 70 4.7 Conclusion and Future Directions 71 Acknowledgements 71 References 71 5 The Axillary Microbiome and its Relationship with Underarm Odor 79Alexander Gordon James 5.1 Introduction 80 5.2 Composition of the Axillary Microbiome 86 5.3 16-Androstene Steroids and Axillary Malodour 95 5.4 The Axillary Microbiome, VFAs and Malodour 96 5.5 The Axillary Microbiome, Thioalcohols and Malodour 100 5.6 Perturbation of the Axillary Microbiome 108 5.7 Human Genetics – Influence on Malodour and the Axillary Microbiome 112 5.8 Conclusions and Future Perspectives 115 Acknowledgements 122 References 122 6 Infant Skin Microbiome 131Georgios N. Stamatas 6.1 Introduction 131 6.2 Infant Skin Maturation 132 6.3 Infant Immune System Maturation 133 6.4 Infant Skin Microbiome Dynamics 134 6.5 Mother-Infant Microbial Transmission 137 6.6 Conclusion 138 References 139 Part 3: Skin Microbiome in Disequilibrium and Disease 143 7 Microbiome of Compromised Skin 145Sara Farahmand 7.1 Atopic Dermatitis 146 7.2 Psoriasis 148 7.2.1 Diversity 149 7.2.2 Microbiome Composition 151 7.3 Acne 152 7.4 Rosacea 153 7.5 Seborrheic Dermatitis and Dandruff 155 7.6 Exposome, Skin Barrier, and Skin Microbiome 157 7.6.1 Skin Irritation and Microbiome 157 7.6.2 Diaper Dermatitis 157 7.6.3 Occupational Hand Dermatitis 158 7.6.4 Allergic Contact Dermatitis (ACD) and Skin Microbiome 159 7.7 Conclusion 160 References 163 8 Human Cutaneous Ectoparasites: A Brief Overview and Potential Therapeutic Role for Demodex 171Stephen L. Strobel 8.1 Introduction 171 8.2 Chiggers (Trombiculidae) 172 8.3 Bedbugs (Cimex lectularius and Hemipterus) 173 8.4 Lice 173 8.5 Scabies (Sarcoptes scabiei) 174 8.6 Demodex 175 8.7 The Association Between Demodex, Rosacea and Blepharitis 176 8.8 Hypothesis 177 8.9 Demodex Folliculorum as a Drug Delivery Agent for Early Skin Cancer 177 8.10 Limitations 179 8.11 Conclusion 180 8.12 Future Considerations 181 References 182 9 Dysbiosis of the Skin Microbiome in Atopic Dermatitis 185Joyce Cheng and Tissa Hata 9.1 Introduction 185 9.2 The Healthy Skin Microbiome 186 9.3 The Skin Microbiome in Atopic Dermatitis 187 9.4 Microbiome-Targeted Treatment Strategies 195 9.5 Conclusion 196 References 196 10 The Skin Microbiome of Inverse Psoriasis 203Jennifer Chung, Bruce E. Strober and George M. Weinstock 10.1 Introduction 204 10.2 Methods 205 10.2.1 Subject Population 205 10.2.2 Patient Diagnosis and Characteristics of Populations 206 10.2.3 Specimen Collection 206 10.2.4 Sample DNA Extraction and Sequencing 207 10.2.5 Downstream Sequence Processing and Analysis 207 10.3 Results 208 10.3.1 Cohort Metadata 208 10.3.2 Sequencing Information 208 10.3.3 The Skin Microbiome of Intertriginous Lesion and Non-Lesional Sites on Inverse Psoriasis Subjects 208 10.3.3.1 Psoriasis Lesional Status is Associated with Relative Abundance and Presence of Specific Species 208 10.3.3.2 Psoriatic Lesions Trend to Decrease Taxonomic Diversity 210 10.3.3.3 Psoriatic Lesions are Characterized by Greater Intragroup Variability 212 10.3.4 Inverse Psoriasis vs. Plaque Psoriasis vs. Healthy (All Non-Lesion Sites) 212 10.4 Conclusions & Future Plans 212 Acknowledgements 213 References 214 Part 4: Skin’s Innate Immunity 217 11 Effects of Endogenous Lipids on the Skin Microbiome 219Carol L. Fischer and Philip W. Wertz 11.1 Introduction 219 11.2 Sebaceous Lipids -- Source of Fatty Acids 221 11.3 Stratum Corneum Lipids – Source of Long-Chain Bases 223 11.4 Antimicrobial Activity of Fatty Acids 226 11.5 Antimicrobial Activity of Long-Chain Bases 230 11.6 Conclusion 231 References 231 12 Innate Immunity in Epidermis 237Miroslav Blumenberg 12.1 Introduction 237 12.2 Skin Acts as an Anatomical Physical and Chemical Barrier to Infectious Agents 238 12.3 Epidermal Cells Recognize Conserved Features of Pathogens, as well as the Indicators of Tissue Damage 239 12.4 Defensive Antimicrobial Proteins AMPs 240 12.5 Cytokines, Specific Signals that Activate Inflammation and Further Cellular Protective Mechanisms 242 12.6 Specialized White Blood Cells Identify and Remove Pathogens 243 12.7 Complement System 246 12.8 Innate Immune System Activates the Adaptive Immune System 246 12.9 Antiviral Defenses 247 12.10 Innate Immunity Memory? 247 12.11 Cutaneous Microbiome: A Newly Surfaced Contributor to Innate Immunity 248 12.12 Conclusion 251 12.13 Future Perspectives 252 References 254 Part 5: Testing and Study Design 261 13 Next Generation Sequencing Reveals the Skin Microbiome 263Niamh B O’Hara 13.1 Introduction 263 13.2 Current Approaches to Test the Microbiome 265 13.3 The Genomics Revolution and Metagenomics 266 13.4 Metagenomics and the Skin Microbiome 267 13.5 Our Work at Biotia 268 13.6 Challenges and Solutions in Metagenomics 269 13.7 The Microbial World is our Oyster 272 13.8 The Future of Metagenomics 273 Acknowledgements 273 References 274 14 Three-Dimensional Human Skin Models to Investigate Skin Innate and Immune-Mediated Responses to Microorganisms 277Marisa Meloni and Silvia Balzaretti 14.1 State-of-the-Art and Limits of Skin Microbiota Research 277 14.2 Mechanism-Based Approach to Study Host Response to Associated Microbiome: 3D Skin Models 279 14.3 Understanding S. epidermidis and S. aureus Behavior and Role on Reconstructed Human Epidermis (RHE) 281 14.4 Immuno-Competent Atopic Dermatitis Model 284 14.5 Conclusion and Future Perspectives 286 References 286 15 Cutibacterium acnes (formerly Propionibacterium acnes) In-Vivo Reduction Assay: A Pre-Clinical Pharmacodynamic Assay for Evaluating Antimicrobial/Antibiotic Agents in Development for Acne Treatment 289Stuart R. Lessin and James J. Leyden 15.1 Acne Pathogenesis and the Role of Cutibacterium acnes (formerly Propionibacterium acnes) 290 15.1.1 Introduction 290 15.1.2 Pathogenesis 290 15.1.3 The Role of C. acnes and its Microbiome 290 15.2 Current Therapies and Regulatory Approval 293 15.3 In-Vivo C. acnes Reduction Assay 294 15.4 Correlations of C. acnes Reduction and Clinical Efficacy 297 15.5 Conclusion 300 References 300 Part 6: Regulatory and Legal Aspects for Skin Microbiome Related Products 303 16 Intellectual Property Tools for Protecting, Developing and Growing a Skin Microbiome Brand 305Jeffrey K. Mills 16.1 Introduction 305 16.2 The Tools of Intellectual Property 306 16.2.1 Patents 306 16.2.2 Trademarks 307 16.2.3 Copyrights 308 16.2.4 Trade Secrets/Know-How 309 16.3 Building an Intellectual Property Portfolio for a Skin Microbiome Brand 310 16.3.1 Patents to Define “The Fence” 310 16.3.1.1 Patents “As Sticks” – Enforcement of Infringement 313 16.3.1.2 Patents “As Financial Boosts” – Licensing and Other Agreements 314 16.3.2 Trademarks to Establish Brand Recognition 315 16.3.3 Copyrights to Maintain Information 317 16.3.4 Trade Secrets/Know-How to Keep A Competitive Edge 318 16.4 Conclusion 320 17 Regulatory Aspects of Probiotics and Other Microbial Products Intended for Skin Care: The European Approach 321Atte von Wright 17.1 Introduction 322 17.2 The Governing Bodies and Decision-Making in the EU 322 17.2.1 The Legal Instruments of the EU 323 17.3 Probiotic Foods and the European Regulations 324 17.3.1 The Safety Assessment of Microorganisms by EFSA, The QPS Concept 324 17.3.1.1 The Safety Assessment of Non-QPS Microorganisms 327 17.3.2 The Case of GMMs 328 17.3.3 Microorganisms as Novel Foods 329 17.3.4 Human Probiotics and Functional Claims 329 17.4 Probiotic Skin Care Products as Pharmaceuticals 330 17.4.1 The Authorization Procedure for Medicines 331 17.4.1.1 The Centralized Procedure 332 17.4.1.2 National Authorizations and Authorizations by Mutual Recognition or Decentralized Procedures 333 17.4.2 Bacteria as Medical Devices 334 17.5 Probiotics in Cosmetics 335 17.5.1 Safety Aspects 336 17.5.1.1 Microorganisms on Skin – Problems of Safety Evaluation 337 17.5.2 The Permissible Cosmetic Claims in the EU 338 17.6 Conclusions 338 References 340 Legal Acts and Guidance Documents 340 18 Regulation of Probiotic and Other Live Biologic Products: The United States Approach 343Ronie M. Schmelz 18.1 Introduction 343 18.1.1 U.S. Legislative Landscape 344 18.1.2 Foods 345 18.1.2.1 Permissible Food Claims 350 18.1.2.2 Additional Regulatory Considerations 354 18.1.3 Dietary Supplements 355 18.1.3.1 Permissible Dietary Supplement Claims 357 18.1.3.2 Additional Regulatory Considerations 359 18.1.4 Drugs 360 18.1.4.1 Drug Approval Process 361 18.1.4.2 Additional Regulatory Considerations 364 18.1.5 Cosmetics 364 18.2 Summary of Product Categorization and Regulatory Requirements 365 18.3 Resources 369 18.4 Endnotes 369 19 A Future Research Perspective Is There a Connection Between Sun Exposure, Microbiome and Skin Cancer? 377Nava Dayan 19.1 Introduction 378 19.2 Ultraviolet Light (UV) – The Skin Microbiome and Cancer 378 19.3 Conclusion 386 Acknowledgment 386 References 387 Glossary 389 Index 399

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Book SynopsisMultiblock Data Fusion in Statistics and Machine Learning Explore the advantages and shortcomings of various forms of multiblock analysis, and the relationships between them, with this expert guide Arising out of fusion problems that exist in a variety of fields in the natural and life sciences, the methods available to fuse multiple data sets have expanded dramatically in recent years. Older methods, rooted in psychometrics and chemometrics, also exist. Multiblock Data Fusion in Statistics and Machine Learning: Applications in the Natural and Life Sciences is a detailed overview of all relevant multiblock data analysis methods for fusing multiple data sets. It focuses on methods based on components and latent variables, including both well-known and lesser-known methods with potential applications in different types of problems. Many of the included methods are illustrated by practical examples and are accompanied by a freely available R-package. TTable of ContentsForeword xiii Preface xv List of Figures xvii List of Tables xxxi Part I Introductory Concepts and Theory 1 1 Introduction 3 1.1 Scope of the Book 3 1.2 Potential Audience 4 1.3 Types of Data and Analyses 5 1.3.1 Supervised and Unsupervised Analyses 5 1.3.2 High-, Mid- and Low-level Fusion 5 1.3.3 Dimension Reduction 7 1.3.4 Indirect Versus Direct Data 8 1.3.5 Heterogeneous Fusion 8 1.4 Examples 8 1.4.1 Metabolomics 8 1.4.2 Genomics 11 1.4.3 Systems Biology 13 1.4.4 Chemistry 13 1.4.5 Sensory Science 15 1.5 Goals of Analyses 16 1.6 Some History 17 1.7 Fundamental Choices 17 1.8 Common and Distinct Components 19 1.9 Overview and Links 20 1.10 Notation and Terminology 21 1.11 Abbreviations 22 2 Basic Theory and Concepts 25 2.i General Introduction 25 2.1 Component Models 25 2.1.1 General Idea of Component Models 25 2.1.2 Principal Component Analysis 26 2.1.3 Sparse PCA 30 2.1.4 Principal Component Regression 31 2.1.5 Partial Least Squares 32 2.1.6 Sparse PLS 36 2.1.7 Principal Covariates Regression 37 2.1.8 Redundancy Analysis 38 2.1.9 Comparing PLS, PCovR and RDA 38 2.1.10 Generalised Canonical Correlation Analysis 38 2.1.11 Simultaneous Component Analysis 39 2.2 Properties of Data 39 2.2.1 Data Theory 39 2.2.2 Scale-types 42 2.3 Estimation Methods 44 2.3.1 Least-squares Estimation 44 2.3.2 Maximum-likelihood Estimation 45 2.3.3 Eigenvalue Decomposition-based Methods 47 2.3.4 Covariance or Correlation-based Estimation Methods 47 2.3.5 Sequential Versus Simultaneous Methods 48 2.3.6 Homogeneous Versus Heterogeneous Fusion 50 2.4 Within- and Between-block Variation 52 2.4.1 Definition and Example 52 2.4.2 MAXBET Solution 54 2.4.3 MAXNEAR Solution 54 2.4.4 PLS2 Solution 55 2.4.5 CCA Solution 55 2.4.6 Comparing the Solutions 56 2.4.7 PLS, RDA and CCA Revisited 56 2.5 Framework for Common and Distinct Components 60 2.6 Preprocessing 63 2.7 Validation 64 2.7.1 Outliers 64 2.7.1.1 Residuals 64 2.7.1.2 Leverage 66 2.7.2 Model Fit 67 2.7.3 Bias-variance Trade-off 69 2.7.4 Test Set Validation 70 2.7.5 Cross-validation 72 2.7.6 Permutation Testing 75 2.7.7 Jackknife and Bootstrap 76 2.7.8 Hyper-parameters and Penalties 77 2.8 Appendix 78 3 Structure of Multiblock Data 87 3.i General Introduction 87 3.1 Taxonomy 87 3.2 Skeleton of a Multiblock Data Set 87 3.2.1 Shared Sample Mode 88 3.2.2 Shared Variable Mode 88 3.2.3 Shared Variable or Sample Mode 88 3.2.4 Shared Variable and Sample Mode 89 3.3 Topology of a Multiblock Data Set 90 3.3.1 Unsupervised Analysis 90 3.3.2 Supervised Analysis 93 3.4 Linking Structures 95 3.4.1 Linking Structure for Unsupervised Analysis 95 3.4.2 Linking Structures for Supervised Analysis 96 3.5 Summary 98 4 Matrix Correlations 99 4.i General Introduction 99 4.1 Definition 99 4.2 Most Used Matrix Correlations 101 4.2.1 Inner Product Correlation 101 4.2.2 GCD coefficient 101 4.2.3 RV-coefficient 102 4.2.4 SMI-coefficient 102 4.3 Generic Framework of Matrix Correlations 104 4.4 Generalised Matrix Correlations 105 4.4.1 Generalised RV-coefficient 105 4.4.2 Generalised Association Coefficient 106 4.5 Partial Matrix Correlations 108 4.6 Conclusions and Recommendations 110 4.7 Open Issues 111 Part II Selected Methods for Unsupervised and Supervised Topologies 113 5 Unsupervised Methods 115 5.i General Introduction 115 5.ii Relations to the General Framework 115 5.1 Shared Variable Mode 117 5.1.1 Only Common Variation 117 5.1.1.1 Simultaneous Component Analysis 117 5.1.1.2 Clustering and SCA 123 5.1.1.3 Multigroup Data Analysis 125 5.1.2 Common, Local, and Distinct Variation 126 5.1.2.1 Distinct and Common Components 127 5.1.2.2 Multivariate Curve Resolution 130 5.2 Shared Sample Mode 133 5.2.1 Only Common Variation 133 5.2.1.1 SUM-PCA 133 5.2.1.2 Multiple Factor Analysis and STATIS 135 5.2.1.3 Generalised Canonical Analysis 136 5.2.1.4 Regularised Generalised Canonical Correlation Analysis 139 5.2.1.5 Exponential Family SCA 140 5.2.1.6 Optimal-scaling 143 5.2.2 Common, Local, and Distinct Variation 146 5.2.2.1 Joint and Individual Variation Explained 146 5.2.2.2 Distinct and Common Components 147 5.2.2.3 PCA-GCA 148 5.2.2.4 Advanced Coupled Matrix and Tensor Factorisation 153 5.2.2.5 Penalised-ESCA 156 5.2.2.6 Multivariate Curve Resolution 158 5.3 Generic Framework 159 5.3.1 Framework for Simultaneous Unsupervised Methods 159 5.3.1.1 Description of the Framework 159 5.3.1.2 Framework Applied to Simultaneous Unsupervised Data Analysis Methods 161 5.3.1.3 Framework of Common/Distinct Applied to Simultaneous Unsupervised Multiblock Data Analysis Methods 161 5.4 Conclusions and Recommendations 162 5.5 Open Issues 164 6 ASCA and Extensions 167 6.i General Introduction 167 6.ii Relations to the General Framework 167 6.1 ANOVA-Simultaneous Component Analysis 168 6.1.1 The ASCA Method 168 6.1.2 Validation of ASCA 176 6.1.2.1 Permutation Testing 176 6.1.2.2 Back-projection 178 6.1.2.3 Confidence Ellipsoids 178 6.1.3 The ASCA+ and LiMM-PCA Methods 181 6.2 Multilevel-SCA 182 6.3 Penalised-ASCA 183 6.4 Conclusions and Recommendations 185 6.5 Open Issues 186 7 Supervised Methods 187 7.i General Introduction 187 7.ii Relations to the General Framework 187 7.1 Multiblock Regression: General Perspectives 188 7.1.1 Model and Assumptions 188 7.1.2 Different Challenges and Aims 188 7.2 Multiblock PLS Regression 190 7.2.1 Standard Multiblock PLS Regression 190 7.2.2 MB-PLS Used for Classification 194 7.2.3 Sparse Multiblock PLS Regression (sMB-PLS) 196 7.3 The Family of SO-PLS Regression Methods (Sequential and Orthogonalised PLS Regression) 199 7.3.1 The SO-PLS Method 199 7.3.2 Order of Blocks 202 7.3.3 Interpretation Tools 202 7.3.4 Restricted PLS Components and their Application in SO-PLS 203 7.3.5 Validation and Component Selection 204 7.3.6 Relations to ANOVA 205 7.3.7 Extensions of SO-PLS to Handle Interactions Between Blocks 212 7.3.8 Further Applications of SO-PLS 215 7.3.9 Relations Between SO-PLS and ASCA 215 7.4 Parallel and Orthogonalised PLS (PO-PLS) Regression 217 7.5 Response Oriented Sequential Alternation 222 7.5.1 The ROSA Method 222 7.5.2 Validation 225 7.5.3 Interpretation 225 7.6 Conclusions and Recommendations 228 7.7 Open Issues 229 Part III Methods for Complex Multiblock Structures 231 8 Complex Block Structures; with Focus on L-Shape Relations 233 8.i General Introduction 233 8.ii Relations to the General Framework 234 8.1 Analysis of L-shape Data: General Perspectives 235 8.2 Sequential Procedures for L-shape Data Based on PLS/PCR and ANOVA 236 8.2.1 Interpretation of X1, Quantitative X2-data, Horizontal Axis First 236 8.2.2 Interpretation of X1, Categorical X2-data, Horizontal Axis First 238 8.2.3 Analysis of Segments/Clusters of X1 Data 240 8.3 The L-PLS Method for Joint Estimation of Blocks in L-shape Data 246 8.3.1 The Original L-PLS Method, Endo-L-PLS 247 8.3.2 Exo- Versus Endo-L-PLS 250 8.4 Modifications of the Original L-PLS Idea 252 8.4.1 Weighting Information from X3 and X1 in L-PLS Using a Parameter α252 8.4.2 Three-blocks Bifocal PLS 253 8.5 Alternative L-shape Data Analysis Methods 254 8.5.1 Principal Component Analysis with External Information 254 8.5.2 A Simple PCA Based Procedure for Using Unlabelled Data in Calibration 255 8.5.3 Multivariate Curve Resolution for Incomplete Data 256 8.5.4 An Alternative Approach in Consumer Science Based on Correlations Between X3 and X1 257 8.6 Domino PLS and More Complex Data Structures 258 8.7 Conclusions and Recommendations 258 8.8 Open Issues 260 Part IV Alternative Methods for Unsupervised and Supervised Topologies 261 9 Alternative Unsupervised Methods 263 9.i General Introduction 263 9.ii Relationship to the General Framework 263 9.1 Shared Variable Mode 263 9.2 Shared Sample Mode 265 9.2.1 Only Common Variation 265 9.2.1.1 DIABLO 265 9.2.1.2 Generalised Coupled Tensor Factorisation 266 9.2.1.3 Representation Matrices 267 9.2.1.4 Extended PCA 272 9.2.2 Common, Local, and Distinct Variation 273 9.2.2.1 Generalised SVD 273 9.2.2.2 Structural Learning and Integrative Decomposition 273 9.2.2.3 Bayesian Inter-battery Factor Analysis 275 9.2.2.4 Group Factor Analysis 276 9.2.2.5 OnPLS 277 9.2.2.6 Generalised Association Study 278 9.2.2.7 Multi-Omics Factor Analysis 278 9.3 Two Shared Modes and Only Common Variation 281 9.3.1 Generalised Procrustes Analysis 282 9.3.2 Three-way Methods 282 9.4 Conclusions and Recommendations 283 9.4.1 Open Issues 284 10 Alternative Supervised Methods 287 10.i General Introduction 287 10.ii Relations to the General Framework 287 10.1 Model and Focus 288 10.2 Extension of PCovR 288 10.2.1 Sparse Multiblock Principal Covariates Regression, Sparse PCovR 288 10.2.2 Multiway Multiblock Covariates Regression 289 10.3 Multiblock Redundancy Analysis 292 10.3.1 Standard Multiblock Redundancy Analysis 292 10.3.2 Sparse Multiblock Redundancy Analysis 294 10.4 Miscellaneous Multiblock Regression Methods 295 10.4.1 Multiblock Variance Partitioning 296 10.4.2 Network Induced Supervised Learning 296 10.4.3 Common Dimensions for Multiblock Regression 298 10.5 Modifications and Extensions of the SO-PLS Method 298 10.5.1 Extensions of SO-PLS to Three-Way Data 298 10.5.2 Variable Selection for SO-PLS 299 10.5.3 More Complicated Error Structure for SO-PLS 299 10.5.4 SO-PLS Used for Path Modelling 300 10.6 Methods for Data Sets Split Along the Sample Mode, Multigroup Methods 304 10.6.1 Multigroup PLS Regression 304 10.6.2 Clustering of Observations in Multiblock Regression 306 10.6.3 Domain-Invariant PLS, DI-PLS 307 10.7 Conclusions and Recommendations 308 10.8 Open Issues 309 Part V Software 311 11 Algorithms and Software 313 11.1 Multiblock Software 313 11.2 R package multiblock 313 11.3 Installing and Starting the Package 314 11.4 Data Handling 314 11.4.1 Read From File 314 11.4.2 Data Pre-processing 315 11.4.3 Re-coding Categorical Data 316 11.4.4 Data Structures for Multiblock Analysis 317 11.4.4.1 Create List of Blocks 317 11.4.4.2 Create data.frame of Blocks 317 11.5 Basic Methods 318 11.5.1 Prepare Data 319 11.5.2 Modelling 319 11.5.3 Common Output Elements Across Methods 319 11.5.4 Scores and Loadings 320 11.6 Unsupervised Methods 321 11.6.1 Formatting Data for Unsupervised Data Analysis 321 11.6.2 Method Interfaces 322 11.6.3 Shared Sample Mode Analyses 322 11.6.4 Shared Variable Mode 322 11.6.5 Common Output Elements Across Methods 323 11.6.6 Scores and Loadings 324 11.6.7 Plot From Imported Package 325 11.7 ANOVA Simultaneous Component Analysis 325 11.7.1 Formula Interface 325 11.7.2 Simulated Data 325 11.7.3 ASCA Modelling 325 11.7.4 ASCA Scores 326 11.7.5 ASCA Loadings 326 11.8 Supervised Methods 327 11.8.1 Formatting Data for Supervised Analyses 327 11.8.2 Multiblock Partial Least Squares 328 11.8.2.1 MB-PLS Modelling 328 11.8.2.2 MB-PLS Summaries and Plotting 328 11.8.3 Sparse Multiblock Partial Least Squares 328 11.8.3.1 Sparse MB-PLS Modelling 328 11.8.3.2 Sparse MB-PLS Plotting 329 11.8.4 Sequential and Orthogonalised Partial Least Squares 330 11.8.4.1 SO-PLS Modelling 330 11.8.4.2 Måge Plot 331 11.8.4.3 SO-PLS Loadings 332 11.8.4.4 SO-PLS Scores 333 11.8.4.5 SO-PLS Prediction 334 11.8.4.6 SO-PLS Validation 334 11.8.4.7 Principal Components of Predictions 336 11.8.4.8 CVANOVA 336 11.8.5 Parallel and Orthogonalised Partial Least Squares 337 11.8.5.1 PO-PLS Modelling 337 11.8.5.2 PO-PLS Scores and Loadings 338 11.8.6 Response Optimal Sequential Alternation 339 11.8.6.1 ROSA Modelling 339 11.8.6.2 ROSA Loadings 340 11.8.6.3 ROSA Scores 340 11.8.6.4 ROSA Prediction 340 11.8.6.5 ROSA Validation 341 11.8.6.6 ROSA Image Plots 342 11.8.7 Multiblock Redundancy Analysis 343 11.8.7.1 MB-RDA Modelling 343 11.8.7.2 MB-RDA Loadings and Scores 343 11.9 Complex Data Structures 344 11.9.1 L-PLS 344 11.9.1.1 Simulated L-shaped Data 344 11.9.1.2 Exo-L-PLS 344 11.9.1.3 Endo-L-PLS 344 11.9.1.4 L-PLS Cross-validation 345 11.9.2 SO-PLS-PM 345 11.9.2.1 Single SO-PLS-PM Model 346 11.9.2.2 Multiple Paths in an SO-PLS-PM Model 346 11.10 Software Packages 347 11.10.1 R Packages 347 11.10.2 MATLAB Toolboxes 348 11.10.3 Python 349 11.10.4 Commercial Software 349 References 351 Index 373

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Book SynopsisThe fourth medical atlas in this new series on the human body and filled with detailed pictures, this atlas details the topographical and pathotopographical anatomy of the pelvis, spine, and limbs, a useful reference for medical professionals and students alike. Written by an experienced and well-respected physician and professor, this new volume, building on the previous volume, Ultrasonic Topographical and Pathotopographical Anatomy, and its sequels, also available from Wiley-Scrivener, presents the ultrasonic topographical and pathotopographical anatomy of the pelvis, spine, and limbs, offering further detail into these important areas for use by medical professionals. This series of atlases of topographic and pathotopographic human anatomy is a fundamental and practically important series designed for doctors of all specializations and students of medical schools. Here you can find almost everything that is connected with the topographic and pathotopoTable of ContentsIntroduction vii Part 1: The Pelvis 1 Part 2: The Spine 69 Part 3: The Limbs 91 Conclusion 185 About the Author 199

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Book SynopsisPresents the latest knowledge of improving the stress tolerance, yield, and quality of rice crops One of the most important cereal crops, rice provides food to more than half of the world population. Various abiotic stressescurrently impacting an estimated 60% of crop yieldsare projected to increase in severity and frequency due to climate change. In light of the threat of global food grain insecurity, interest in molecular rice breeding has intensified in recent years. Progress has been made, but there remains an urgent need to develop stress-tolerant, bio-fortified rice varieties that provide consistent and high-quality yields under both stress and non-stress conditions. Molecular Breeding for Rice Abiotic Stress Tolerance and Nutritional Quality is the first book to provide comprehensive and up-to-date coverage of this critical topic, containing the physiological, biochemical, and molecular information required to develop effective engineering strategies for enhancing rice yield.Table of ContentsPreface xix List of Contributors xxi 1 Rice Adaptation to Climate Change: Opportunities and Priorities in Molecular Breeding 1Vikram Jeet Singh, Kunnummal Kurungara Vinod, Subbaiyan Gopala Krishnan and Ashok K. Singh 2 Molecular Breeding for Improving Salinity Tolerance in Rice: Recent Progress and Future Prospects 26Sandeep Chapagain, Lovepreet Singh, Richard Garcia, Rajat Pruthi, Jonathan Concepcion, Sapphire Coronejo and Prasanta K. Subudhi 3 Molecular Breeding for Improving Drought Tolerance in Rice: Recent Progress and Future Perspectives 53Ratna R. Majumder, Sandeep Sakhale, Shailesh Yadav, Nitika Sandhu, Lutful Hassan, Md. Amir Hossain and Arvind Kumar 4 Molecular Breeding for Improving Flooding Tolerance in Rice: Recent Progress and Future Perspectives 75Ramani K. Sarkar, Jangi N. Reddy and Satya R. Das 5 Molecular Breeding for Improving Heat Stress Tolerance in Rice: Recent Progress and Future Perspectives 92Bui Chi Buu, Cho Young Chan and Nguyen Thi Lang 6 Molecular Breeding for Improving Cold Tolerance in Rice: Recent Progress and Future Perspectives 120Ning Xiao and Jian-Min Chen 7 Molecular Breeding for Lower Cadmium Accumulation in Rice Grain: Progress and Perspectives 131Dongping Li, Xiaohua Hao and Liangbi Chen 8 Molecular Breeding for Improving Arsenic Stress Tolerance in Rice: Recent Progress and Future Perspectives 163Nourollah Ahmadi and Julien Frouin 9 Molecular Breeding for Improving Ozone Tolerance in Rice: Recent Progress and Future Perspectives 180Md. Ashrafuzzaman, Robert Henry and Michael Frei 10 Molecular Breeding Strategies for Enhancing Rice Yields Under Low Light Intensity 201Mayank Rai, Suvendhu S. Dutta and Wricha Tyagi 11 Harnessing Tolerance to Low Phosphorus in Rice: Recent Progress and Future Perspectives 215Wricha Tyagi, Erneica N. Nongbri and Mayank Rai 12 Molecular Breeding for Improving Nitrogen Use Efficiency in Rice: Progress and Perspectives 234Chirravuri N. Neeraja, Sitapati R. Voleti, Subrahmanyam Desiraju, Surekha Kuchi, Sonali Bej, Krishnakanth Talapanti and Raghuveer R. Puskur 13 Dissecting the Molecular Basis of Drought-Induced Oxidative Stress Tolerance in Rice 249Amit K. Pradhan, Sabnoor Y. Jyoti, Zina M. Shandilya, Mehzabin Rehman, Debanjali Saikia, Junu Poudel, Jyotirmay Kalita, Kongkona Borborah, Uma K. Chowra, Jnandabhiram Chutia, Lakshminarayana R. Vemireddy and Bhaben Tanti 14 Manipulation of Photosynthesis to Increase Rice Yield Potential 274Prabuddha Dehigaspitiya and Saman Seneweera 15 Molecular Breeding for Improved β-carotene Synthesis in Golden Rice: Recent Progress and Future Perspectives 287Swapan K. Datta, Shuvobrata Majumder and Karabi Datta 16 Increasing Grain Zinc Concentration in Rice 304Naoya Miyazaki, Miki Ogasawara and Ryo Ishikawa 17 Molecular Breeding for Iron Bio-Fortification in Rice Grain: Recent Progress and Future Perspectives 315Elssa Pandit, Swapnil Pawar, Priyadarshini Sanghamitra and Sharat K. Pradhan 18 Aromatic Rices: Evolution, Genetics and Improvement through Conventional Breeding and Biotechnological Methods 341Lakshminarayana R. Vemireddy, Bhaben Tanti, Lipika Lahkar and Zina M. Shandilya 19 Genetic Engineering for Increasing Antioxidant Content in Rice: Recent Progress and Future Perspectives 358Qinlong Zhu, Jiantao Tan, Bin Wang and Yao-Guang Liu 20 Molecular Breeding Approaches for Improvement and Development of Water Saving Aerobic Rice 382Rahul K. Meena, Kuldeep Kumar, Saurabh K. Dubey, Ashish K. Singh, Adarsh Kumar, Deepanshu Jayaswal, Badal Singh, Rajinder Jain and Sunita Jain 21 Targeting the Ascorbate-Glutathione Pathway and the Glyoxalase Pathway for Genetic Engineering of Abiotic Stress-Tolerance in Rice 398Mohammad A. Hossain, Tahsina S. Hoque, Abbu Zaid, Shabir H. Wani, Mohammad G. Mostofa and Robert Henry Index 428

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Book SynopsisUnderstand new modes of analysing metabolomic data Metabolomics is the study of metabolites, small molecules and chemical substrates within cells or larger structures which collectively make up the metabolome. The field of metabolomics stands to benefit enormously from chemometrics, an approach which brings advanced statistical techniques to bear on data of this kind. Data Analysis and Chemometrics for Metabolomics constitutes an accessible introduction to chemometric techniques and their applications in the field of metabolomics. Thoroughly and accessibly written by a leading expert in chemometrics, and printed in full-colour, it brings robust data analysis into conversation with the metabolomic field to the immense benefit of practitioners. Data Analysis and Chemometrics for Metabolomics readers will also find: Statistical insights into the nature of metabolomic hypothesis testing, validation, and more All metabolomics data sets from the book on a companion website Case studies from

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Book SynopsisDemystifies the academic career path with practical advice With the number of people being awarded PhDs growing far more rapidly than the supply of academic jobs, those at an early-career stage must think strategically in order to be competitive and successful. Navigating an Academic Career: A Brief Guide for PhD students, Post docs, and New Faculty is a concise and conversational manual that guides readers through starting their academic journey, surviving the demands of their first academic position, and thriving in academia and beyond. Volume highlights include: Firsthand perspective on the characteristics of a successful academic Guidance on interviewing, negotiating, branding, and other essential soft skills Tips for effective time management and writing high-impact research papers Insights into developing leadership skills and mentoring others The American Geophysical Union promotes discovTable of ContentsPreface vii About the Author ix Part I: The PhD Student and Postdoc Years 1 1 An Academic Career 3 2 Traits of Successful Scientists 7 3 Avoiding a PhD in Anxiety 11 4 Getting Your First Academic Job 15 5 The Academic Matthew Effect 19 Part II: Surviving and Thriving in the First Few Years 23 6 Paper Writing Gone Hollywood 25 7 The Perfect Department 27 8 Ethics in the Real World 31 9 Research Brand Identity 35 10 The 1‐Hour Workday 39 11 Orchestrating a Powerful Research Group 41 12 Proposal Writing Hacks 43 Part III: Tenure and Beyond 47 13 Mentoring the Middle 49 14 Research Visits and Academic Growth Spurts 53 15 On Leadership 57 16 The Sustainable Professor 61 17 A Scientist Looks at 60 63 Postface 67 Acknowledgments 69 Notes 73 Further Reading 77 Index 81

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Book SynopsisAn insightful and illuminating discussion of the impact humans have had on Earth In A Primer on Human Impacts on the Environment: The Conceptual Approach, distinguished environmental scientist Liam Heneghan explores the intricate relationships between humanity and Earth in an accessible and engaging style. Replete with real-world examples and drawing from classic and contemporary scholarship, the author adapts the fundamental conceptual models of the environmental disciplines to assess the risks human beings are taking with their home planet. The conceptual approach of this primer challenges readers to think across multiple disciplines to reveal the ?big picture? that is all too often lost in the details of contemporary environmental studies. Readers will also find: A thorough introduction to conceptual modeling, showing how systems models can be adapted and applied in a rapidly changing world Comprehensive explorations of the human impact on thTable of ContentsPreface Chapter 1 A Manifesto for Conceptual Thinking in Environmental Disciplines Chapter 2 A Conceptual Approach to Environmental Science Chapter 3 A Short Chapter on the Definition of Definitions Chapter 4 Everything is connected (but some things are more connected than are others) Chapter 5 Complex Environmental Systems Chapter 6 All or nothing? Or, what, exactly, is an environment? Chapter 7 Life and environment: the indissoluble link Chapter 8 Gaia, the Noösphere, and the Anthropocene Chapter 9 The Anthropocene and the Concept of Limits Chapter 10 Limited and limiting models Chapter 11 Collapse and the Anthropocene Chapter 12 How to conceive a (climate) crisis Chapter 13 Risking Life: Basics of Biological Diversity Chapter 14 Risking life: Is the Sixth Extinction Catastrophic? Chapter 15 Conceiving a Future: the need for interdisciplinarity Chapter 16 The Three Futures Index

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Book SynopsisA guide to the role microbes play in the enhanced production and productivity of agriculture to feed our growing population Phytomicrobiome Interactions and Sustainable Agricultureoffers an essential guide to the importance of Phytomicrobiome' and explores its various components. The authors noted experts on the topic explore the key benefits of plant development such as nutrient availability, amelioration of stress and defense to plant disease. Throughout the book, the authors introduce and classify the corresponding Phytomicrobiome components and then present a detailed discussion related to its effect on plant development: controlling factors of this biome, its behaviour under the prevailing climate change condition and beneficial effects. The book covers the newly emerging technical concept of Phytomicrobiome engineering, which is an advanced concept to sustain agricultural productivity in recent climatic scenario. The text is filled with comprehensive, cutting edge data, makiTable of ContentsList of Contributors xii Preface xvi About the Editors xviii 1 Plant Root Exudate Analysis: Recent Advances and Applications 1Shulbhi Verma and Amit Verma 1.1 Introduction 1 1.2 Root Exudates Composition: Collection and Analysis 3 1.3 Role of Root Exudates in Shaping Rhizospheric Microbiomes 5 1.4 Applications of Root Exudation 6 1.5 Conclusion and Future Prospects 7 References 10 2 Phytoproteomics: A New Approach to Decipher Phytomicrobiome Relationships 15Prachie Sharma and Kapila Kumar 2.1 Introduction 15 2.2 Phytomicrobiome 16 2.3 Phytomicrobiome: The Communication via Signaling 18 2.4 Proteomics 19 2.4.1 Gel-Based Protein Separation Techniques 21 2.4.2 Non-Gel Protein Separation Techniques 21 2.5 Analysis of Phytomicrobial Interactions Using Proteomics Approaches 22 2.6 Conclusion and Future Prospects 26 References 28 3 Metagenomics: An Approach to Unravel the Plant Microbiome and Its Function 32Ravindra Soni, Deep Chandra Suyal, Balram Sahu, and Suresh Chandra Phulara 3.1 Introduction 32 3.2 Metagenomics 33 3.3 Metagenomics of Plant Rhizosphere 33 3.4 Metagenomics of Plant Phyllosphere 35 3.5 Metagenomics of Plant Endosphere 36 3.6 In-silico Tools for Metagenome Analysis 37 3.6.1 Mothur 37 3.6.2 Quantitative Insights into Microbial Ecology (QIIME) 37 3.6.3 MEta Genome Analyzer (MEGAN) 38 3.7 Recent Progress in Metagenomic Studies of Plant Microbiome 38 3.8 Conclusion and Future Prospects 38 References 38 4 Combating the Abiotic Stress Through Phytomicrobiome Studies 45Hemant S. Maheshwari, Abhishek Bharti, Richa Agnihotri, Ajinath Dukare, B. Jeberlin Prabina, Saurabh Gangola, and Mahaveer P. Sharma 4.1 Introduction 45 4.1.1 Abiotic Stress and Phytomicrobiome 45 4.1.2 Role of Signaling in Phytomicrobiome Interactions 46 4.2 Phytomicrobiome Signaling Compounds 47 4.2.1 Root Exudates and Plant Volatiles Compounds 47 4.2.2 Microbial Volatile Organic Compounds 47 4.2.3 Quorum Sensing 48 4.2.4 Underground Phytomicrobiome Signaling 48 4.3 Mechanisms of Phytomicrobiome Associated with Abiotic Stress Tolerance 49 4.3.1 Drought Stress Alleviation 50 4.3.2 Salinity Stress Mitigation 53 4.3.3 Heavy Metal Toxicity 55 4.3.4 Low-Temperature Stress 56 4.3.5 Nutrient Deficiency 56 4.3.6 Flooding or Water Submergence 56 4.4 Importance of Phytomicrobiome Engineering for Crop Stress Alleviation 57 4.5 Omics Strategies in Phytomicrobiome Studies 58 4.6 Conclusion and Future Prospects 59 Acknowledgments 59 References 60 5 Microbial Diversity of Phyllosphere: Exploring the Unexplored 66Rakhi Dhankhar, Aparajita Mohanty, and Pooja Gulati 5.1 Introduction 66 5.2 Origin of Phyllosphere Microflora 67 5.3 Tools to Study Phyllomicrobiome 68 5.3.1 Conventional Methods 69 5.3.2 Microscopic Techniques 69 5.3.3 First-Generation Molecular Techniques 70 5.3.4 Next-Generation Sequencing Methods 70 5.3.5 Omics and Bioinformatics Approaches 76 5.3.6 Other Molecular Methods 77 5.4 Biodiversity of Phyllosphere 77 5.5 Microbial Adaptation to Phyllosphere 78 5.5.1 Adaptation to Abiotic Stresses 79 5.5.2 Adaptation to Biotic Stresses 80 5.5.3 Adaptation to Nutrient Scarcity 81 5.6 Interaction of Phyllomicrobiota with Plants 81 5.6.1 Positive Interactions 82 5.6.2 Negative Interactions 83 5.7 Significance of Phyllomicrobiome Studies 83 5.8 Conclusion and Future Prospects 84 References 85 6 Rhizosphere Engineering: An Effective Approach for Sustainable Modern Agriculture 91Reema Mishra, Tripti Grover, Pooja Gulati, and Aparajita Mohanty 6.1 Introduction 91 6.2 Natural Plant–Microbe Interactions in Rhizosphere 92 6.3 Molecular Mechanisms in Plant–Microbe Interactions in Rhizosphere 93 6.4 Biochemical Components in Rhizosphere Signaling 94 6.5 Tools and Techniques in Rhizosphere Engineering 96 6.5.1 Stable Isotope Probing (SIP) 96 6.5.2 DNA Arrays 97 6.5.3 Fluorescence In Situ Hybridization (FISH) 97 6.5.4 Bioreporters 97 6.5.5 Genomics 98 6.5.6 Transcriptomics 98 6.5.7 Proteomics 99 6.5.8 Metabolomics 99 6.6 Rhizosphere Components Amenable to Engineering 100 6.6.1 Soil Modification 100 6.6.2 Plant Amendment 100 6.6.2.1 Root Exudate Modification 100 6.6.2.2 Root Architecture Modification 101 6.6.2.3 Enhancing Abiotic Stress Tolerance in Plants 101 6.6.2.4 Enhancing Biotic Stress Tolerance in Plants 103 6.6.2.5 Engineering Metabolic Pathways in Plants 105 6.6.3 Engineering Microbial Populations 107 6.7 Conclusion and Future Prospects 107 Acknowledgment 108 References 108 7 Plant Communication with Associated: Its Components, Composition and Role in Maintaining Plant Homeostasis 118Dibyajit Lahiri, Moupriya Nag, Sayantani Garai, Bandita Dutta, and Rina Rani Ray 7.1 Introduction 118 7.2 Biofilm and Rhizospheric Interactions 119 7.3 Biofilm Formation at the Root Rhizosphere 120 7.3.1 The Components of Biofilm Matrix 121 7.3.2 Bacterial Quorum Sensing 122 7.4 Genetic Features Responsible for Bacterial Cell Adhesion to Plant System 125 7.4.1 Chemotaxis Motility 125 7.4.2 Substrate Utilization and Transport 125 7.4.3 Lipopolysaccharide and Membrane Proteins 126 7.4.4 Plant Cell Wall Modification 127 7.4.5 Adhesion and Biofilm Formation 128 7.4.6 Stress Protection 128 7.4.7 Bacterial Secretion System 129 7.4.8 Transcriptional Regulators and Sensor Proteins 130 7.5 Nutrient Interactions 138 7.5.1 Release and Activation of Minerals 138 7.5.2 Nutrient Recycling 138 7.5.3 Nitrogen Dynamics 138 7.5.4 Ionic Modification 139 7.6 Biotic Interaction 140 7.6.1 Symbiosis 140 7.6.2 Synergy 140 7.6.3 Competition 140 7.6.4 Antagonism 141 7.6.5 Pathogenesis 142 7.7 Conclusion and Future Prospects 142 References 143 8 Phytomicrobiome: Synergistic Relationship in Bioremediation of Soil for Sustainable Agriculture 150Nimmy Srivastava 8.1 Introduction 150 8.2 Phytoremediation 151 8.2.1 Process of Phytoremediation 151 8.2.2 Strategies for Phytoremediation 151 8.3 Phytomicrobe Interactions and Rhizomediation 152 8.3.1 Principle of Phytomicrobiome Interaction During Rhizomediation 152 8.3.2 Removal of Inorganic Contaminants 154 8.3.3 Removal of Organic Pollutants 154 8.3.4 Factors Affecting Rhizomediation 157 8.4 Conclusion and Future Prospects 157 References 158 9 Rhizospheric Biology: Alternate Tactics for Enhancing Sustainable Agriculture 164Kalpana Bhatt and Pankaj Bhatt 9.1 Introduction 164 9.2 Engineering the Rhizosphere 165 9.2.1 Rhizosphere and Rhizobia 165 9.2.2 Root Exudates: Chemical Nature and Types 167 9.2.3 Factors Affecting Root Exudate 168 9.3 Engineering Soil Microbial Populations and Plant–Microbe Interactions 169 9.3.1 Microorganisms in Soil 169 9.3.2 Soil Modification: Altering Microbial Populations 170 9.4 Plant Growth-Promoting Rhizobacteria: Mechanisms, Potential, and Usages 170 9.4.1 Direct Mechanisms 171 9.4.1.1 Biological N2 Fixation 171 9.4.1.2 Phosphate Solubilization 173 9.4.1.3 Zinc Solubilization 174 9.4.1.4 Siderophore Production 174 9.4.1.5 Production of Phytohormones 174 9.4.1.6 ACC (1-Aminocyclopropane-1-Carboxylate) Deaminase Activity 175 9.4.2 Indirect Mechanisms 175 9.5 Plant–Microbe Interaction 176 9.6 Biofertilizers and its Applications 177 9.7 Plant Genetic Engineering 177 9.8 Conclusion and Future Prospects 178 Acknowledgments 178 References 179 10 Application of Inorganic Amendments to Improve Soil Fertility 187Sunita Chauhan and Shweta Kulshreshtha 10.1 Introduction 187 10.2 Impact of Bhoochetna Movement in Southern India 188 10.3 Sustainable Agriculture 188 10.3.1 Healthy Soil and Soil Quality 189 10.3.2 Soil Quality 189 10.3.3 Soil Quality Indicator 190 10.3.4 Soil Quality Index 191 10.4 Factors to Be Considered While Selecting a Soil Amendment 192 10.5 Advantages of Soil Amendments 194 10.6 Land Modeling 194 10.7 Major Applications of Soil Amendments 195 10.7.1 Phyto-Stabilization in Polluted or Contaminated Soils 195 10.7.2 Restoration of Soil 196 10.7.2.1 Soil Acidity/pH Soil Amendments 196 10.7.2.2 Mineral Soil Amendments and Conditioners 196 10.7.2.3 Different Types of Inorganic Amendments 197 10.8 Combination Strategy for Soil Quality Improvement 202 10.9 Conclusion and Future Prospects 203 References 203 11 Improved Plant Resistance by Phytomicrobiome Community Towards Biotic and Abiotic Stresses 207Neha Trivedi 11.1 Introduction 207 11.2 Microbes and Plants 207 11.2.1 Abiotic Stress Responses and Microbe-Mediated Mitigation in Plants 208 11.2.2 Microbial-Induced Response to Stresses 208 11.3 Response of Abiotic Response on Plant 209 11.3.1 Induced Systemic Tolerance (IST) 209 11.3.2 Metabolic Changes in Plants Induced by Microbes During Stress 209 11.3.2.1 Metabolic Cross-Talk in Plants After Stress Induction 210 11.3.2.2 Activation of Antioxidant Mechanism 210 11.3.2.3 Activation of Systemically Induced Resistance 210 11.4 Role of Phytohormones in Increasing Abiotic and Biotic Stress Tolerance 211 11.5 Gene Transfer in Plants 212 11.6 Conclusion and Future Prospects 212 References 212 12 Bioprospecting: At the Interface of Plant and Microbial Communities 217Madan L. Verma, Varsha Rani, Reena Kumari, Deepka Sharma, Sanjeev Kumar, and Rekha Kushwaha 12.1 Introduction 217 12.2 Plant-Associated Microbial Communities 218 12.3 Beneficial Effects of Plant-Associated Microbial Communities 222 12.3.1 Rhizoremediation 223 12.3.2 Plant Growth–Promoting Rhizobacteria (PGPR) 223 12.3.3 Biotic and Abiotic Stress Resistance 224 12.3.4 Signalomics 226 12.4 Role of Microbial Processing (Signals) in Facilitating Plant Growth 226 12.5 Conclusion and Future Prospects 230 Acknowledgments 230 References 231 13 Advances in Omics and Bioinformatics Tools for Phyllosphere Studies 240Hina Bansal 13.1 Introduction 240 13.2 Recent Trends and Approaches 241 13.3 Computing for Biology 243 13.4 Bioinformatics in Microbial Research 243 13.5 Phyllosphere Microbiome Studies Based on Genome-Wide Association 245 13.6 Omics Strategies and Their Integration 246 13.6.1 Metagenomics 246 13.6.2 Metatranscriptomics 246 13.6.3 Metabolomics 247 13.6.4 Proteomics 247 13.7 Conclusion and Future Prospects 248 References 248 14 Microbial Mediated Zinc Solubilization in Legumes for Sustainable Agriculture 254Pawan Saini, Sharon Nagpal, Pooja Saini, Arun Kumar, and Mudasir Gani 14.1 Introduction 254 14.2 Chronological Events of Zinc Biology 255 14.3 Role of Zinc in Living System 256 14.3.1 Essentiality of Zinc in Humans 256 14.3.2 Essentiality of Zinc in Plants 257 14.4 Zinc Deficiency vs. Zinc Toxicity in Crop Plants 259 14.5 Availability of Zinc in Soil Environment 260 14.6 Factors Affecting Zinc Availability to Plants 261 14.7 Response of Legume Crops to Zinc 262 14.8 Microbial Mediated Zinc Solubilization in Legume Crops 263 14.8.1 Zinc-Solubilizing Bacteria (ZnSB) 264 14.8.2 Zinc-Solubilizing Fungi (ZnSF) 265 14.9 Conclusion and Future Prospects 266 References 266 15 Composition and Interconnections in Phyllomicrobiome 277Meghmala Waghmode, Aparna Gunjal, Neha Patil, and Sonali Shinde 15.1 Introduction 277 15.2 Significance of Phyllospheremicrobiota 279 15.3 Phyllosphere Microorganisms as Plant Growth Regulator 280 15.3.1 Plant Growth Hormones Production by Phyllosphere Microorganisms 280 15.3.2 Phosphorus Solubilization by Phyllosphere Microorganisms 280 15.3.3 Siderophores Production by Phyllosphere Microorganisms 280 15.3.4 Phyllosphere Microorganisms as Biocontrol Agents Against the Phytopathogens 280 15.3.5 Phyllosphere Microorganisms to Reduce Biotic and Abiotic Stress 281 15.3.6 Synthesis of 1-Aminocyclopropane-1-Carboxylate Deaminase (ACC) 282 15.3.7 Phyllosphere Microorganisms in Nitrogen-Fixation 282 15.3.8 Frost Injury and Frost Control by Altering the Phyllosphere Microbiota 282 15.3.9 Remediation of Toxic Pollutants 283 15.3.10 Plant Probiotics 283 15.3.11 Role of Phyllosphere Microorganisms in Climate Change 284 15.3.12 Phyllosphere Microorganisms in Nutrient Yield and Increase of Plant Growth 284 15.3.13 Plant Hormones as Colonization Mediators of the Plant Leaves 284 15.4 Plant–Pathogen Interactions Mediated by Phyllosphere Microbiome 285 15.4.1 Interaction Dependent on the Ionome 285 15.4.2 Role of Secretory Systems and Secretory Products 285 15.4.3 Quorum Sensing 286 15.5 Conclusion and Future Prospects 286 References 286

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Book SynopsisX-Ray Fluorescence in Biological Sciences Discover a comprehensive exploration of X-ray fluorescence in chemical biology and the clinical and plant sciences In X-Ray Fluorescence in Biological Sciences: Principles, Instrumentation, and Applications, a team of accomplished researchers delivers extensive coverage of the application of X-ray fluorescence (XRF) in the biological sciences, including chemical biology, clinical science, and plant science. The book also explores recent advances in XRF imaging techniques in these fields. The authors focus on understanding and investigating the intercellular structures and metals in plant cells, with advanced discussions of recently developed micro-analytical methods, like energy dispersive X-ray fluorescence spectrometry (EDXRF), total reflection X-ray fluorescence spectrometry (TXRF), micro-proton induced X-ray emission (micro-PIXE), electron probe X-ray microanalysis (EPXMA), synchrotron-based X-ray fluorescence Table of ContentsChapter No. Primary Author Contact Authors Chapter Title 1 Kanishka Rawat Kanishka Rawat X-ray Fluorescence and Comparison with Other Analytical Methods (AAS, ICP-AES, LA-ICP-MS, IC, LIBS, SEM-EDS, and XRD) 2 Eva Marguí Eva Marguí X-ray Fluorescence for Multi-elemental Analysis of Vegetation Samples 3 А.G. Revenko А.G. Revenko X-ray Fluorescence Studies of Tea and Coffee 4 Nand Lal Mishra Nand Lal Mishra Total Reflection X-ray Fluorescence Analysis of Biological Samples 5 Changling Lao Changling Lao Micro X-ray Fluorescence and X-ray Absorption Near Edge Structure Analysis of Heavy Metals in Microorganism 6 Yeasmin Nahar Jolly Yeasmin Nahar Jolly Use of Energy Dispersive X-ray Fluorescence for Clinical Diagnosis 7 Nuray Kup Aylikci Nuray Kup Aylikci Preparation of Sample for X-ray Fluorescence Analysis 8 M.K. Tiwari M.K. Tiwari Elemental Analysis Using Synchrotron Radiation X-ray Fluorescence 9 KatarinaVogel Mikuš KatarinaVogel Mikuš Synchrotron Radiation Based Micro X-ray Fluorescence Spectroscopy of Plant Materials 10 Jian Liu Jian Liu Micro X-ray Fluorescence Analysis of Toxic Elements in Plants 11 Jing Yuan Jing Yuan Micro X-ray Fluorescence Studies of Earthworm (Benthonic fauna) in Soils and Sediments 12 V.A.Trunova V.A.Trunova Synchronous Radiation X-ray Fluorescence Analysis of Microelements in Biopsy Tissues 13 Nand Lal Mishra Nand Lal Mishra Total Reflection X-ray Fluorescence Analysis of Marine Organisms, Blood, Oral Fluids, Hairs, Nails, Kidney Stones, Urine and Cancerous Tissues 14 M.K. Tiwari M.K. Tiwari Recent Developments in X-ray Fluorescence for Characterization of Nano-Structured Materials 15 Artem S. Maltsev Artem S. Maltsev Total-Reflection X-ray Fluorescence Analysis of Alcoholic and Non-Alcoholic Beverages 16 Tsenddavaa Amartaivan Tsenddavaa Amartaivan Trace Elements Analysis of Blood Samples and Serum using Total Reflection X-ray Fluorescence 17 Navgeet Kaur Navgeet Kaur Basics and Fundamentals of X-rays 18 Rakesh K. Sindhu Rakesh K. Sindhu General Principle, Procedures and Detectors of X-ray Fluorescence 19 Neslihan Ekinci Neslihan Ekinci Quantitative Analysis in X-ray Fluorescence System 20 Marco Carminati Marco Carminati Electronics and Instrumentation for X-ray Fluorescence 21 Marijan Nečemer Katarina Vogel-Mikuš Energy Dispersive X-ray Fluorescence Analysis of Biological Materials 22 Galina Pashkova Artem S. Maltsev X-ray Fluorescence Analysis of Milk and Dairy Products 23 E.V. Chuparina E.V. Chuparina X-ray Fluorescence Analysis of Medicinal Plants 24 Neera Yadav Neera Yadav X-ray Fluorescence Studies of Animal and Human Cell Biology 25 Kamya Goyal Anju Goyal Toxic and Essential Elemental Studies of Human Organs using X-ray Fluorescence 26 Hiroshi Yoshii Hiroshi Yoshii X-ray Fluorescence for Rapid Detection of Uranium in Blood Extracted from Wounds 27 D. Bolortuya D. Bolortuya X-ray Fluorescence Analysis of Human Hair 28 Vivek K. Singh Vivek K. Singh X-ray Fluorescence Spectrometry to Study Gallstones, Kidney Stones, Hair, Nails, Bones, Teeth and Cancerous Tissues 29 Dra. Mónica Orduña Cordero Dra. Mónica Orduña Cordero Sampling and Sample Preparation for Chemical Analysis of Plants by Wavelength Dispersive X-ray Fluorescence 30 Harinderjit Singh Harinderjit Singh X-ray Fluorescence Analysis in Medical Biology 31 А.G. Revenko А.G. Revenko X-ray Fluorescence Analysis in Pharmacology 32 Héctor Jorge Sánchez Héctor Jorge Sánchez X-ray Fluorescence and State-of-the-Art Related Techniques to the Study of Teeth, Tartar and Oral Tissues 33 Harpreet Singh Kainth Harpreet Singh Kainth Recent Advances in Wavelength Dispersive X-ray Fluorescence Techniques 34 Vitaly Panchuk Dmitry Kirsanov Chemometric Processing of X-ray Fluorescence Data 35 Shilpa Chakrabarti Neera Yadav X-ray Crystallography in Medicinal Biology 36 Kanishka Rawat Kanishka Rawat Historical Fundamentals of X-ray Instruments and Present Trends in Biological Science 37 P. Zuzaan D. Bolortuya X-ray Fluorescence Studies of Biological Objects in Mongolia 38 Jun Kawai Jun Kawai Arsenic Analysis 39 Rakesh K. Sindhu Rakesh K. Sindhu X-ray Fluorescence: Current Trends and Future Scope

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Book SynopsisFocusing on phytochemicals and their potential for drug discovery, this book offers a comprehensive resource on poisonous plants and their applications in chemistry and in pharmacology. Provides a comprehensive resource on phytotoxins, covering historical perspectives, modern applications, and their potential in drug discoveryCovers the mechanisms, benefits, risks and management protocols of phytotoxins in a scientific laboratory and the usefulness in drug discoveryPresents chapters in a carefully designed, clear order, making it an ideal resource for the academic researcher or the industry professional at any stage in their careerTable of ContentsList of Contributors xvii List of Figures xxi List of Tables xxiii Preface xxv Editors xxvii 1 Historical Use of Toxic Plants 1Godwin Anywar 1.1 Introduction to Toxic Plants 1 1.2 Poisonous Plants as Sources of Traditional and Modern Medicines 2 1.3 Toxic Plants and Justice 4 1.3.1 Toxic Plants in Capital Punishment 4 1.3.2 Trial by Ordeal 4 1.4 Toxic Plants in Poisoned Weapons 6 1.4.1 Arrow Poisons 6 1.5 Plant Fishing Poisons/Piscicides/Ichthyotoxins 6 1.6 Poisonous Plants as Food 7 1.7 Poisonous Plants as Biopesticides 9 1.8 Toxic Psychoactive Plants for Recreational and Religious Purposes 9 1.9 Poisonous Plants in Warfare and Bioterrorism 10 1.10 Poisonous Plants as Carcinogens and Teratogens 11 1.11 Conclusion 12 References 12 2 Classification of Phytotoxins and their Mechanisms of Action 19Andrew G. Mtewa, Chukwuebuka Egbuna, Kennedy J. Ngwira, Fanuel Lampiao, Umang Shah, and Thokozani Kachulu Mtewa 2.1 Introduction 20 2.1.1 Endophytic Phytotoxins 20 2.1.2 Secondary Metabolites 21 2.2 Possible Categorization 21 2.2.1 Biological Characteristics 21 2.2.2 Chemical Characteristics 22 2.3 Currently Available Classification Tools 24 2.4 Role of Phytotoxin Classification 25 2.4.1 Drug Discovery 25 2.4.2 Environmental Monitoring 25 2.4.3 Phytotoxins, Aquatic Life, and Water Quality 26 2.4.4 Air Contamination 26 2.4.5 Food Contamination 26 2.4.6 Security and Safety Services 27 2.4.7 Agricultural 27 2.5 Brief Mechanisms of Action 27 2.6 Conclusion 28 References 28 3 Poisonous Plants as Sources of Anticancer and Other Drugs 31Félicien Mushagalusa Kasali, Andrew G. Mtewa, and Gaétan Tabakam 3.1 Introduction 31 3.2 Poisonous Plants in the Treatment of Cancer and Other Diseases 32 3.3 Poisonous Plant-Based Anticancer Drugs that are on the Market 33 3.4 Poisonous Plant-Based Drugs Against Other Diseases that are on the Market 33 3.5 Conclusion 33 References 75 4 Drugs in Clinical Practice from Toxic Plants and Phytochemicals 79Tadele Mekuriya Yadesa, Patrick Engeu Ogwang, and Casim Umba Tolo 4.1 Introduction 80 4.2 Drugs in Clinical Practice from Toxic Plants 81 4.2.1 Curare 81 4.2.2 Drugs Acting on the Central Nervous System 81 4.2.2.1 Morphine 81 4.2.2.2 Cocaine 82 4.2.2.3 Ergot Alkaloids 83 4.2.3 Atropine, Scopolamine, and Hyoscyamine 84 4.2.4 Physostigmine and Other Acetylcholinesterase Inhibitors 85 4.2.5 Antitumor Agents 85 4.2.5.1 Podophyllotoxin and Etoposide 85 4.2.5.2 Taxanes 86 4.2.5.3 Vincristine and Vinblastine 87 4.2.6 Other Drugs 88 4.2.6.1 Cardiac Glycosides 88 4.2.6.2 Colchicine 89 4.2.6.3 Coumarins 89 4.2.6.4 Nicotine and the Neonicotinoids 90 References 90 5 Toxicology and Health Benefits of Plant Alkaloids 95Ibrahim Chikowe, Andrew G. Mtewa, and Duncan C. Sesaazi 5.1 Introduction 95 5.2 Pharmacological Properties of Alkaloids 97 5.3 Toxicological Properties of Alkaloids 100 5.4 Acute and Chronic Toxicities 100 5.4.1 Genotoxicity and Tumorigenicity 101 5.4.2 Lung Toxicity, Neurotoxicity, and Teratogenicity 102 5.5 Factors that Influence the Toxicological Profile of Alkaloids 102 5.6 Conclusion 103 References 103 6 Chemical and Pharmacological Mechanisms of Plant-Derived Neurotoxins 109Amanjot Annu, Reuben S. Maghembe, Andrew G. Mtewa, and G.M. Narasimha Rao 6.1 Introduction 110 6.2 Nerve Agents 110 6.3 Chemical Mechanisms of Neurotoxicity Induced by Organophosphate Nerve Agents 111 6.4 Mustards 112 6.4.1 Effect of HD on Skin 113 6.4.2 Effect of HD on Other Organs 113 6.4.3 The Activation of HD 114 6.4.4 Mechanism of Action 115 6.5 Plant Natural Neurotoxins 116 6.6 Plant Glycosides 118 6.7 Conclusion 119 References 119 7 Phytosedatives for Drug Discovery 123Shahira M. Ezzat, Ahmed Zayed, and Mohamed A. Salem 7.1 Introduction 123 7.2 Treatment of Neuropsychological Disorders: The Current Scenario 124 7.3 Phytosedatives: Desirable Alternatives to Synthesized Drugs 125 7.4 Different Classes of Phytosedatives 125 7.4.1 Flavonoids 126 7.4.2 Alkaloids 128 7.4.3 Essential Oils 129 7.4.4 Other Classes of Phytosedatives 130 7.5 Plants with Reported Sedative Actions 130 7.6 Conclusion 152 References 152 8 Mushroom Species and Classification: Bioactives in Poisonous and Edible Mushrooms 163Sadia Zafar, Farhat Jabeen, Muhammad Akram, Zarfishan Riaz, and Naveed Munir 8.1 Introduction 163 8.2 Classification of Mushrooms 164 8.2.1 Edible Mushrooms 165 8.2.2 Non-Edible Mushrooms 165 8.3 Bioactive Agents in Mushroom Species 165 8.4 Bioactive Agents in Non-Edible Mushroom Species 166 8.4.1 Polysaccharides 166 8.4.2 Glucans 166 8.4.3 Polysaccharide–Protein Complexes 174 8.4.4 Terpenes 174 8.4.5 Phenolic Compounds 175 8.4.6 Peptides and Proteins 176 8.5 Other Bioactive Compounds of Mushroom Species 176 8.6 Conclusion 176 References 177 9 Toxicity Protocols for Natural Products in the Drug Development Process 189Tamirat Bekele Beressa, Amanjot Annu, and Andrew G. Mtewa 9.1 Introduction 190 9.2 In Vitro Toxicity Testing for Natural Products 190 9.2.1 Cell Culture Method for Toxicity Testing 191 9.2.2 Cell Culture for Acute Toxicology Testing 192 9.3 Methods Used for In Vitro Toxicity Studies 193 9.3.1 MTT Assay 193 9.3.2 Neutral Red Uptake Assay 193 9.3.3 Lactate Dehydrogenase Assay 194 9.4 In Vitro Models for Liver Toxicity 194 9.5 In Vitro Models for Nephrotoxicity Studies 194 9.6 In Vitro Model for Dermal Toxicity Testing 195 9.7 Mutagenicity Testing In Vitro 195 9.7.1 Bacterial Cell System 196 9.8 Reproductive and Teratogenicity Studies In Vitro 196 9.8.1 H295R Steroidogenesis Assay 197 9.8.2 Embryonic Stem Cell Test 197 9.8.3 Whole Rat Embryo Cultures 197 9.9 In Vivo Toxicity Testing of Natural Products 198 9.9.1 Acute Toxicity Testing 198 9.9.2 Subchronic Toxicity Testing 200 9.9.3 Chronic Toxicity Testing 201 9.9.4 Dermal and Ocular Toxicity 203 9.9.5 Toxicity Testing for Fertility and Reproduction 204 9.9.6 Combined Repeated Dose Toxicity Study with Reproduction/Developmental Testing 206 9.9.7 In Vivo Carcinogenicity Testing 207 9.10 Conclusion 208 References 208 10 Quality Control for the Safety of Natural Products 213Tadele Mekuriya Yadesa, Patrick Engeu Ogwang, and Casim Umba Tolo 10.1 Introduction 214 10.2 Quality Assurance of Herbal Products 215 10.3 Methods of Quality Control for Herbal Products 216 10.3.1 DNA-Based Technologies 216 10.3.2 Good Practice Guidelines 216 10.3.3 Chemoprofiling 217 10.3.4 Toxicology 217 10.3.5 Monographs and Pharmacopeias 217 10.3.6 Preclinical Evidence of Safety and Efficacy 217 10.3.7 Systems Biology 218 10.3.8 Animal Experimentation 218 10.3.9 Clinical Evidence of Safety and Efficacy 218 10.4 WHO Guidelines for Quality Standardization of Herbal Formulations 219 10.4.1 Quality Control of Crude Material 219 10.4.2 Identity of Plant Material 219 10.4.3 Safety Assessment and Documentation 220 10.5 Concept of Validation in Herbal Products 220 10.6 Challenges Related to Quality Control and Monitoring the Safety of Herbal Products 221 References 222 11 Secondary Metabolites and Toxins of Microbial Origin for the Treatment of Diseases 225Dharmandra Baria, Umang Shah, Chukwuebuka Egbuna, and Andrew G. Mtewa 11.1 Introduction 226 11.2 Antimicrobial Agents from Microbial Sources 227 11.3 Antifungal Agents from Microbial Sources 229 11.4 Anticancer Agents from Microbial Sources 230 11.5 Hypocholesterolemic Agents from Microbial Sources 235 11.6 Immunosuppressants from Microbial Sources 237 11.7 Enzyme Inhibitors from Microbial Sources 239 11.8 Antiparasitic Agents from Microbial Sources 240 11.9 Recent Advances in Drug Discovery from Microbial Sources 241 References 243 12 Development of Phyto-Antidotes Against Adverse Chemical Agents 249Roman Lysiuk, Petro Oliynyk, Halyna Antonyak, and Dmytro Voronenko 12.1 Introduction 249 12.2 Heavy Metals and their Effects on the Body 251 12.3 Detoxification Properties of Biologically Active Substances of Plant-Based Foods 253 12.3.1 Pectins 253 12.3.2 Phytin 254 12.3.3 Betalains 255 12.3.4 Phytochelatins 256 12.3.5 Ellagic Acid 257 12.3.6 Miscellaneous 258 12.4 Current State of Clinical Application of Phyto-Antidotes 259 12.5 Further Prospects in the Search for Promising Phyto-Antidotes 260 12.6 Conclusions 261 References 262 13 Nanoformulated Herbal Drug Delivery as Efficient Antidotes Against Systemic Poisons 269Prabir Kumar Kulabhusan, Shailaja Agrawal, Jaison Jeevanandam, and Michael K. Danquah 13.1 Introduction 269 13.2 Herbal Phytochemicals as Antidotes for Systemic Poisons 271 13.2.1 Herbal Phytochemicals as Antidotes for Heavy Metal Poisoning 272 13.2.2 Herbal Phytochemicals as Antidotes for Snake Venom Poisoning 275 13.3 Nanoformulated Herbal Phytochemicals as Antidotes 276 13.3.1 Inorganic Nanoparticles 278 13.3.2 Micelles and Liposomes 279 13.3.3 Polymeric Nanoparticles 281 13.4 Mechanism of Nanoformulated Herbal Phytochemicals against Systemic Poisoning 281 13.5 Future Perspectives 283 13.6 Conclusion 285 References 285 14 Phytochemical-Based Nanoparticles as Foes and Friends 295Charles Oluwaseun Adetunji, Oluwaseyi Olaniyan, Juliana Bunmi Adetunji, and Itoan Roli 14.1 Introduction 295 14.2 Phytochemicals Used in the Synthesis of Nanoparticles 297 14.3 Anti-Inflammatory Effects of Nanoparticles 297 14.4 Wound-Healing Effects of Nanoparticles 299 14.5 Antiparasitic, Antifungal, and Antibacterial Activities of Nanoparticles 300 14.6 Neuroprotective Effects of Nanoparticles 304 14.7 Cardioprotective Effects of Nanoparticles 307 14.8 Anticancer Effects of Nanoparticles 308 14.9 Advantages of Nanoparticles 311 14.10 Disadvantages of Nanoparticles 311 14.11 Conclusion and Future Directions 312 References 313 15 Application of Metabolomics in Emergency Phytochemical Poisoning and Remediation 323Mohamed A. Salem, Ahmed Zayed, and Shahira M. Ezzat 15.1 Introduction 324 15.2 Traditional Use of Medicinal Plants 325 15.3 Natural Products: Safety and Toxicity 328 15.3.1 Safety 328 15.3.2 Toxicity and Natural Killers 329 15.4 Biological Systems in Phytochemical Poisoning and Remediation 330 15.5 Metabolomics: An Important Functional Genomics Tool 332 15.5.1 Essential Components of a Metabolomics Workflow 333 15.5.2 Sample Preparation 334 15.5.3 Analytical Methods in Metabolomics 334 15.5.4 Metabolite Identification 335 15.5.5 Data Processing and Analysis 335 15.5.6 Pathway Analysis 335 15.6 Assessment of Toxicity of Herbal Medicines Using Metabolomics 335 15.7 Application of Metabolomics in Emergency Phytochemical Poisoning and Remediation 336 15.7.1 Hepatotoxicity of Triptolide 337 15.7.2 Hepatotoxicity of Noscapine 337 15.8 Conclusion 338 References 338 16 Methods for the Detection and Identification of Phytotoxins 349Senyo Botchie and Andrew G. Mtewa 16.1 Introduction 350 16.2 Phytotoxins 350 16.2.1 Importance of Toxins 351 16.3 Methods Generally Used for Phytotoxin Detection 352 16.3.1 Biological Method Review of Detecting Phytotoxins 352 16.3.2 Chemical and Microbiological Reagents 352 16.4 Protease Inhibition Detection Protocol 354 16.4.1 Exposure of the Protease Detection Plate to a Protease Inhibitor or Bacterial Growth (Step 1) 354 16.4.2 Exposure to a Protease-Containing Solution (Step 2) 355 16.4.3 Detecting Zones of Protease Inhibition (Step 3) 355 16.5 Isolation of Phytotoxins from Microorganisms 355 16.5.1 Detection of Phytotoxins Isolated from Fungi 356 16.5.2 Purification of the Extracted Phytotoxins 356 16.6 Conclusion 356 References 357 17 Categorization, Management, and Regulation of Potentially Weaponizable Toxic Plants 359Muhammad Akram and Rabia Zahid 17.1 Introduction 359 17.2 Management of Weaponized Natural Food Agents 360 17.3 Techniques Used for Extraction, Segregation, and Decontamination of Phytochemicals 361 17.3.1 Solvent-Based Extraction of Phenolic Compounds 361 17.3.2 Microwave-Associated Extraction 361 17.3.3 Ultrasound-Assisted Extraction 362 17.4 Techniques for Identification of Bioactive Compounds 362 17.4.1 Ultraviolet–Visible Spectroscopy 362 17.4.2 Infrared Spectroscopy 363 17.4.3 Nuclear Magnetic Resonance Spectroscopy 363 17.4.4 Mass Spectrometry 363 17.5 Types of Natural Phytotoxins 363 17.5.1 Aquatic Biotoxins 363 17.5.2 Glycosides 364 17.5.3 Other Common Phytotoxins 364 17.6 Conclusion 365 References 365 18 In Silico Modeling as a Tool to Predict and Characterize Plant Toxicity 367Charles Oluwaseun Adetunji, William Peter Mitembo, Chukwuebuka Egbuna, and G.M. Narasimha Rao 18.1 Introduction 368 18.2 Components of In Silico Toxicity Methods 368 18.2.1 Databases 369 18.2.2 Molecular Descriptors 369 18.2.3 Toxicity Models and Modeling Software 369 18.2.4 Simulation Packages 369 18.3 Modeling Methods 371 18.4 Structural Alerts/Rule Based 371 18.5 Statistical Structure-Based Activity Relationship Models 373 18.5.1 Read-Across 373 18.6 Conclusion 374 References 375 Index 379

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Book SynopsisVeterinary Microbiology Comprehensive reference work on the bacterial, fungal, and viral pathogens that cause animal diseases Veterinary Microbiology, Fourth Edition presents comprehensive information based on the most recent research, diagnostic, and clinical publications for bacterial, fungal, and viral animal diseases. The information provided is intended to be most relevant for veterinary students and practitioners. The text is supported throughout by high-quality and full-color images to aid learning. A companion website offers chapter content, supplemental information, and figures from the book in PowerPoint format. Sample topics discussed within the book include: Pathogenic bacteriology: includes major classifications and genera of bacteria associated with veterinary infectious disease Pathogenic mycology: dermatophytes, agents of subcutaneous mycoses, and agents of systemic mycoses Pathogenic virology: includes RNA and DTable of ContentsList of Contributors xii Acknowledgments xviii Preface xix About the Companion Website xx Part I Introduction 1 1 Microbial Infections of Animals 3D. Scott McVey, Melissa Kennedy, and Charles Czuprynski 2 Basic Bacteriology 11Tiruvoor G. Nagaraja 3 Basic Mycology 29Charles Czuprynski and M.M. Chengappa 4 Basic Virology 35Mohamed A. Abouelkhair and Melissa Kennedy Part II Bacteriology 41 5 Family Enterobacteriaceae 43Rodney A. Moxley 6 Enterobacteriaceae: Escherichia 56Rodney A. Moxley 7 Enterobacteriaceae: Salmonella 75Rodney A. Moxley 8 Family Yersiniaceae 88Rodney A. Moxley 9 Enterobacteriaceae: Shigella 100Rodney A. Moxley 10 Pasteurellaceae: Avibacterium, Bibersteinia, Mannheimia, and Pasteurella 108William B. Crosby and Amelia R. Woolums 11 Pasteurellaceae: Actinobacillus 118Bradley W. Fenwick and Andrew N. Rycroft 12 Pasteurellaceae: Glaesserella, Haemophilus, and Histophilus 129Amelia R. Woolums 13 Bordetella 136Bradley W. Fenwick 14 Brucella 151S.C. Olsen and P. Boggiatto 15 Burkholderia mallei and Burkholderia pseudomallei 162Sanjeev Narayanan 16 Francisella tularensis 168Marilynn A. Larson and Peter C. Iwen 17 Moraxella 176John Dustin Loy and Gabriele Maier 18 Pseudomonas 183Deepti Pillai 19 Taylorella 187Megan E. Jacob 20 Spirilla I: Borrelia 192Roman R. Ganta 21 Spiral-Curved Organisms II: Brachyspira and Lawsonia 196Gerald E. Duhamel 22 Spiral-Curved Organisms III: Campylobacter and Arcobacter 207Gerald E. Duhamel 23 Spirilla IV: Helicobacter– the Spiral Microorganisms of the Gastrointestinal Tract and Liver 219Megan E. Jacob 24 Spirochetes V: Leptospira 225Sreekumari Rajeev 25 Staphylococcus 231George C. Stewart 26 Streptococcus and Enterococcus 240George C. Stewart 27 Trueperella 252Tiruvoor G. Nagaraja 28 Bacillus 257George C. Stewart 29 Corynebacterium 265Tiruvoor G. Nagaraja 30 Erysipelothrix 273Timothy Frana and Axel Neubauer 31 Listeria 280Sanjeev Narayanan 32 Rhodococcus 286Seth P. Harris and Joshua Daniels 33 Gram-Negative, Non-Spore-Forming Anaerobes 294Tiruvoor G. Nagaraja 34 Clostridium 309Iman Mehdizadeh Gohari and John F. Prescott 35 Filamentous Bacteria: Actinomyces, Nocardia, Dermatophilus, and Streptobacillus 335Megan E. Jacob 36 Mycobacteria 345Raul G. Barletta and David J. Steffen 37 Chlamydiaceae: Chlamydia 360Roman R. Ganta 38 Mollicutes 364Bonto Faburay and D. Scott McVey 39 Rickettsiaceae and Coxiellaceae: Rickettsia and Coxiella 377Roman R. Ganta 40 Anaplasmataceae: Anaplasma 381Roman R. Ganta 41 Anaplasmataceae: Ehrlichia and Neorickettsia 386Roman R. Ganta 42 Bartonellaceae 392Kathryn E. Reif Part III Fungi 405 43 Yeasts: Cryptococcus, Malassezia, and Candida 407Lisa M. Pohlman and M.M. Chengappa 44 Dermatophytes 418M.M. Chengappa and Lisa M. Pohlman 45 Agents of Subcutaneous Mycoses 425Lisa M. Pohlman and M.M. Chengappa 46 Agents of Systemic Mycoses 433Lisa M. Pohlman and M.M. Chengappa Part IV Viruses 449 47 Parvoviridae 451Rebecca P. Wilkes 48 Circoviridae 469Pablo Piñeyro and Sheela Ramamoorthy 49 Asfarviridae and Iridoviridae 478Melissa Kennedy, Gustavo Delhon, D. Scott McVey, Hiep Vu, and Manuel Borca 50 Papillomaviridae and Polyomaviridae 484Mohamed A. Abouelkhair and Melissa Kennedy 51 Adenoviridae 489Yunjeong Kim and Kyeong-Ok Chang 52 Herpesviridae 496Rebecca P. Wilkes and Jobin Kattoor 53 Poxviridae 522Gustavo Delhon 54 Picornaviridae 533Luis L. Rodriguez and Jonathan Arzt 55 Caliciviridae 543Mohamed A. Abouelkhair and Melissa Kennedy 56 Togaviridae and Flaviviridae 552Christopher C.L. Chase 57 Orthomyxoviridae 573Wenjun Ma 58 Bunyavirales 589William C. Wilson, Dana Mitzel, Lee W. Cohnstaedt, Leela Noronha, Barbara S. Drolet, and D. Scott McVey 59 Paramyxoviridae, Pneumoviridae, Filoviridae, and Bornaviridae 596Stefan Niewiesk and Michael Oglesbee 60 Rhabdoviridae 609Susan M. Moore and D. Scott McVey 61 Coronaviridae and Tobaniviridae 622Udeni B.R. Balasuriya, Yun Young Go, and Mariano Carossino 62 Arteriviridae and Roniviridae 659Udeni B. R. Balasuriya, Mariano Carossino, and Yun Young Go 63 Reoviridae 679Barbara S. Drolet, Bethany L. McGregor, Lee W. Cohnstaedt, William C. Wilson, and D. Scott McVey 64 Birnaviridae 693Melissa Kennedy and Donald L. Reynolds 65 Retroviridae 698Jean-Pierre Frossard 66 Transmissible Spongiform Encephalopathies 728Jürgen A. Richt and Nicholas Haley Part V Control of Infectious Diseases 743 67 Immune Responses to Infectious Agents 745Laurel J. Gershwin 68 Laboratory Diagnosis 760D. Scott McVey, Bruce Brodersen, Duan Loy, and John Dustin Loy 69 Antimicrobial Chemotherapy and Antimicrobial Resistance 771Michael D. Apley 70 Vaccines 803D. Scott McVey, Jishu Shi, and Donald Reynolds 71 Disinfection and Sterilization 813John Dustin Loy, D. Scott McVey, and M.M. Chengappa 72 Epidemiology of Infectious Diseases 818Natalia Cernicchiaro, Ana R.S. Oliveira, and Lee W. Cohnstaedt Index 829

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Book SynopsisExplore the past, present, and future of cancer cytogeneticsIn Abnormal Chromosomes: The Past, Present, and Future of Cancer Cytogenetics, globally renowned researchers Drs. Sverre Heim and Felix Mitelman deliver a state-of-the-art review of how cancer cytogenetic analyses have contributed to an improved understanding of tumorigenesis as well as to the diagnosis and treatment of cancer patients. The book also discusses how cytogenetics the study of chromosomes - meets, interacts with, and cross-fertilizes other investigative technologies, including molecular somatic cell genetics.The book provides an impetus to think more deeply about the role chromosomes, and their abnormalities, play in health and disease, especially in neoplastic disorders. From which origins did cytogenetics develop? How did the finding of acquired chromosomal abnormalities in cells of leukemias and solid tumors influence our understanding of cancer as a biological process? HoTable of ContentsPreface vii Part I Past 1 Chapter 1 Understanding Disease: Ancient Theories 3 Chapter 2 The Advent of Cellular Pathology 7 Chapter 3 The Colored Bodies of Cell Nuclei: Chromosomes and Heredity 15 Chapter 4 Boveri and the Somatic Mutation Theory of Cancer 23 Chapter 5 Cytogenetics from 1914 to 1960: Slow Progress Followed by Serendipitous Methodological Breakthroughs Leading to Important Discoveries 29 Chapter 6 The First Cancer-Specific Chromosome Aberrations: Ph1 and Others 41 Part II Present 57 Chapter 7 The Banding Revolution: Cancer Cytogenetics in the 1970s 59 Chapter 8 Chasing Correlations: Chromosomes and Oncogenes in Leukemias and Lymphomas 75 Chapter 9 Solid Tumor Cytogenetics 87 Chapter 10 Gains, Losses, and Rearrangements of Genomic Material: Pathogenetic Considerations 105 Chapter 11 Morphology Meets Chemistry: Integration of Molecular Genetics into the Cytogenetic Search for Cancer-Specific Chromosome Aberrations 117 Chapter 12 Unraveling the Clonal Evolution of Neoplastic Cell Populations 125 Chapter 13 Clinical Usefulness 137 Part III Future 149 Chapter 14 Toward a Pathogenetic Classification of Cancer 151 Chapter 15 Where There is Structure, There is Function 161 Chapter 16 Which Resolution Level is Optimally Suited to Answer Which Questions? Seeing Never Goes Out of Fashion . . . 169 Chapter 17 Are New Technical Breakthroughs on the Horizon? 179 Afterthoughts 189 Index 195

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Book SynopsisMANAGING PLANT STRESS USING SALICYLIC ACID Enables readers to understand the ability of salicylic acid in reducing the effects of abiotic stresses in different crop species Salicylic acid is an important plant hormone which acts as a multifunctional molecule and regulates key physiological and biochemical processes in plants. This book highlights the tremendous potential of treating plants with salicylic acid, either prior to or during stress. It focuses on the specific challenges and opportunities related to exogenous application or priming technology, such as the mode of application, new methodologies, and the potential impacts of salicylic acid on the environment. Sample topics covered in the book include: The latest research on the ability of salicylic acid in reducing the effects of abiotic stresses in different crop speciesThe mechanism of action of salicylic acid at the biochemical and molecular levelSalicylic acid and its crosstalk with other plant hormones under stressful enviTable of Contents1. Salicylic acid: A regulator of plant growth and development. 2. Salicylic acid mediated regulation of plant biology: An omics approach. 3. Regulation of plant primary metabolism by salicylic acid under abiotic stress. 4. Regulation of plant secondary metabolism by salicylic acid under abiotic stress. 5. How does salicylic acid regulate mineral nutrition in plants under stress? An update. 6. Seed germination to fruit maturation under stressful environment: Roles of salicylic acid. 7. Role of salicylic acid on post-harvest physiology of plants. 8. Salicylic acid mediated physiological and molecular mechanisms in plants under heavy metal stress. 9. Salicylic acid mediated physiological and molecular mechanisms in plants under heat stress. 10. Salicylic acid mediated physiological and molecular mechanisms in plants under chilling stress. 11. Salicylic acid mediated physiological and molecular mechanisms in plants under salt stress. 12. Salicylic acid mediated physiological and molecular mechanisms in plants under pesticide stress. 13. Salicylic acid mediated physiological and molecular mechanisms in plants under drought stress. 14. Salicylic acid mediated physiological and molecular mechanisms in plants under high light and UV exposure. 15. ROS regulation by salicylic acid. 16. Regulation of photosynthesis by salicylic acid under optimal and suboptimal conditions. 17. Regulation of abiotic stress by salicylic acid at gene level: an update. 18. Salicylic acid and its crosstalk with other plant hormones under stressful environments. 19. Regulation of non-enzymatic antioxidants by salicylic acid under abiotic stress: biochemical and molecular aspects. 20. Response of plant proteins under abiotic stress and their regulation by salicylic acid.

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Book SynopsisTable of ContentsList of Contributors x Preface xvii About the Editor xix Acknowledgments xxi 1 An Overview of Genome-Engineering Methods 1Sushmita, Gurminder Kaur, Santosh Kumar Upadhyay, and Praveen Chandra Verma 2 Distribution of Nutritional and Mineral Components in Important Crop Plants 22Katarina Vogel-Mikuš, Paula Pongrac, Ivan Kreft, Primož Pelicon, Primož Vavpetič, Boštjan Jenčič, Johannes Teun van Elteren, Peter Kump, Sudhir P. Singh, and Marjana Regvar 3 Application of Genome Engineering Methods for Quality Improvement in Important Crops 43Sajid Fiaz, Sher Aslam Khan, Galal Bakr Anis, Habib Ali, Mohsin Ali, Kazim Ali, Mehmood Ali Noor, Sibtain Ahmad, and Bilal Ahmad Asad 4 Genome Engineering for Enriching Fe and Zn in Rice Grain and Increasing Micronutrient Bioavailability 69Conrado Dueñas, Jr., Gela Myan B. Mota, Norman Oliva, and Inez H. Slamet-Loedin 5 Development of Carotenoids Rich Grains by Genome Engineering 83Vikrant Gautam, Gurwinder Singh Rana, Pankaj Kumar, and Santosh Watpade 6 CRISPR-Cas9 System for Agriculture Crop Improvement 97Ashish Sharma, Poorwa Kamal Badola, and Prabodh Kumar Trivedi 7 Contribution of Crop Biofortification in Mitigating Vitamin Deficiency Globally 112Siddhant Chaturvedi, Roni Chaudhary, and Siddharth Tiwari 8 Genome Editing Approaches for Trait Improvement in the Hairy Root Cultures of the Economically Important Plants 131Pravin Prakash, Rakesh Srivastava, Ajay Kumar, Gurminder Kaur, and Praveen Chandra Verma 9 Phytic Acid Reduction in Cereal Grains by Genome Engineering: Potential Targets to Achieve Low Phytate Wheat 146Ajay K. Pandey, Sipla Aggarwal, Varsha Meena, and Anil Kumar 10 Genome Engineering for Nutritional Improvement in Pulses 157Chirag Uppal, Ajinder Kaur, and Chhaya Sharma 11 The Survey of Genetic Engineering Approaches for Oil/Fatty Acid Content Improvement in Oilseed Crops 181Kaushal Kumar Bhati, Riyazuddin Riyazuddin, Ashish Kumar Pathak, and Anuradha Singh 12 Genome-Editing Mediated Improvement of Biotic Tolerance in Crop Plants 199Krishan Mohan Rai and Harpal Singh 13 Genome Engineering and Essential Mineral Enrichment of Crops 210Erum Shoeb, Uzma Badar, Srividhya Venkataraman, Ghyda Murad Hashim, and Kathleen Hefferon 14 Genome Editing to Develop Disease Resistance in Crops 224Kashaf Zafar, Azka Noureen, Muhammad Jawad Akbar Awan, Naveed Anjum, Muhammad Qasim Aslam, Muhammad Zuhaib Khan, Imran Amin, and Shahid Mansoor 15 Biotechnological Approaches for Nutritional Improvement in Potato (Solanum tuberosum L.) 253Chandrama Prakash Upadhyaya and Deepak Singh Bagri 16 Genome Engineering Strategies for Quality Improvement in Tomato 281Tian Wang, Hongyan Zhang, and Hongliang Zhu 17 Genome Editing for Biofortification of Rice: Current Implications and Future Aspects 297Suchismita Roy and Praveen Soni 18 Genome Editing for Improving Abiotic Stress Tolerance in Rice 314Shweta Roy, Nirbhay Kumar Kushwaha, Hasthi Ram, and Praveen Soni 19 Role of Genome Engineering for the Development of Resistant Starch-Rich, Allergen-Free and Processing Quality Improved Cereal Crops 333Anuradha Singh, Amit Yadav, Joy K. Roy, and Kaushal Kumar Bhati 20 Engineering of Plant Metabolic Pathway for Nutritional Improvement: Recent Advances and Challenges 351Sameer Dixit, Akanchha Shukla, Vinayak Singh, and Santosh Kumar Upadhyay 21 Genome Engineering for Food Security 380Sajid Fiaz, Sher Aslam Khan, Mehmood Ali Noor, Afifa Younas, Habib Ali, Kazim Ali, Mahmoud Mohamed Gaballah, and Galal Bakr Anis Index 391

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Book SynopsisEssentials of Cognitive Neuroscience ntroduces and explicates key principles and concepts in cognitive neuroscience in such a way that the reader will be equipped to critically evaluate the ever-growing body of findings that the field is generating. For some students this knowledge will be needed for subsequent formal study, and for all readers it will be needed to evaluate and interpret reports about cognitive neuroscience research that make their way daily into the news media and popular culture. The book seeks to do so in a style that will give the student a sense of what it''s like to be a cognitive neuroscientist: when confronted with a problem, how does one proceed? How does one read and interpret research that''s outside of one''s sub-area of specialization? How do two scientists advancing mutually incompatible models interrelate? Most importantly, what does it feel like to partake in the wonder and excitement of this most dynamic and fundamental of sciences?Table of ContentsPreface Acknowledgments Methodology Boxes Walkthrough of Pedagogical Features Companion Website Section I: The Neurobiology of Thinking 1 Introduction and History 2 The Brain Section II: Sensation, Perception, Attention, and Action 3 Methods for Cognitive Neuroscience 4 Sensation and Perception of Visual Signals 5 Audition and Somatosensation 6 The Visual System 7 Spatial Cognition and Attention 8 Skeletomotor Control 9 Oculomotor Control and the Control of Attention Section III: Mental Representation 10 Visual Object Recognition and Knowledge 11 Neural Bases of Memory 12 Declarative Long-Term Memory 13 Semantic Long-Term Memory 14 Working Memory Section IV: High-Level Cognition 15 Cognitive Control 16 Decision-Making 17 Social Behavior 18 Emotion 19 Language 20 Consciousness Glossary 562 Index 571

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Book SynopsisDNA ORIGAMI Discover the impact and multidisciplinary applications of this subfield of DNA nanotechnology DNA origami refers to the technique of assembling single-stranded DNA template molecules into target two- and three-dimensional shapes at the nanoscale. This is accomplished by annealing templates with hundreds of DNA strands and then binding them through the specific base-pairing of complementary bases. The inherent properties of these DNA moleculesmolecular recognition, self-assembly, programmability, and structural predictabilityhas given rise to intriguing applications from drug delivery systems to uses in circuitry in plasmonic devices. The first book to examine this important subfield, DNA Origami brings together leading experts from all fields to explain the current state and future directions of this cutting-edge avenue of study. The book begins by providing a detailed examination of structural design and assembly systems and their applicatioTable of ContentsList of Contributors xiii Preface xvii 1 DNA Origami Technology: Achievements in the Initial 10 Years 1 Masayuki Endo 1.1 Introduction 1 1.1.1 DNA Nanotechnology Before the Emergence of DNA Origami 3 1.2 Two- Dimensional DNA Origami 3 1.3 Programmed Arrangement of Multiple DNA Origami Components 6 1.4 Three- Dimensional DNA Origami Structures 9 1.5 Modification and Functionalization of 2D DNA Origami Structures 11 1.5.1 Selective Placement of Functional Nanomaterials 11 1.5.2 Selective Placement of Functional Molecules and Proteins via Ligands 13 1.5.3 Distance- Controlled Enzyme Reactions and Photoreactions 13 1.6 Single- Molecule Detection and Sensing using DNA Origami Structures 14 1.6.1 Single- Molecule RNA Detection 14 1.6.2 Single- Molecule Detection of Chemical Reactions 14 1.6.3 Single- Molecule Detection using Mechanical DNA Origami 14 1.6.4 Single- Molecule Sensing using Mechanical DNA Origami 14 1.7 Application to Single Biomolecule AFM Imaging 16 1.7.1 High- Speed AFM- Based Observation of Biomolecules 16 1.7.2 Visualization of DNA Structural Changes in the DNA Nanospace 18 1.7.3 Visualization of the Reaction Events of Enzymes and Proteins in the DNA Nanospace 18 1.8 Single- Molecule Fluorescence Studies 19 1.8.1 Nanoscopic Ruler for Single- Molecule Imaging 19 1.8.2 Kinetics of Binding and Unbinding Events and DNA- PAINT 21 1.8.3 DNA Barcode Imaged by DNA- PAINT 21 1.9 DNA Molecular Machines 22 1.9.1 DNA Assembly Line Constructed on the DNA Origami 22 1.9.2 DNA Spider System Constructed on the DNA Origami 22 1.9.3 DNA Motor System Constructed on the DNA Origami 24 1.10 Selective Incorporation of Nanomaterials and the Applications 24 1.10.1 DNA Origami Plasmonic Structure with Chirality 24 1.10.2 Surface- Enhanced Fluorescence by Gold Nanoparticles and DNA Origami Structure 26 1.10.3 Placement of DNA Origami onto a Fabricated Solid Surface 26 1.11 Dynamic DNA Origami Structures Responsive to External Stimuli 27 1.11.1 DNA Origami Structures Responsive to External Stimuli 27 1.11.2 Stimuli- Responsive DNA Origami Plasmonic Structures 27 1.11.3 Photo- Controlled DNA Origami Plasmonic Structures 27 1.12 Conjugation of DNA Origami to Lipid 29 1.12.1 DNA Origami Channel with Gating 29 1.12.2 DNA Origami Templated Synthesis of Liposomes 29 1.13 DNA Origami for Biological Applications 29 1.13.1 Introduction of DNA Origami into Cells and Functional Expression 29 1.13.2 Drug Release Using the Properties Characteristic for DNA Origami 31 1.13.3 DNA Origami Structures Coated with Lipids and Polymers 32 1.13.4 Nanorobot with Dynamic Mechanism 32 1.13.5 Nanorobot Targeting Tumor In Vivo 32 1.14 Conclusions 33 References 34 2 Wireframe DNA Origami and Its Application as Tools for Molecular Force Generation 41 Marco Lolaico and Björn Högberg 2.1 Introduction 41 2.2 Pre- Origami Wireframe DNA Nanostructures 42 2.3 Hierarchical DNA Origami Wireframe 43 2.4 Entire DNA Origami Design 45 2.5 DNA Origami Wireframe as Tools for Molecular Force Application 50 2.5.1 Introduction 50 2.5.2 Results and Discussion 51 2.6 Conclusions 54 2.6.1 Materials and Methods 54 References 55 3 Capturing Structural Switching and Self- Assembly Events Using High- Speed Atomic Force Microscopy 59 Yuki Suzuki 3.1 Introduction 59 3.2 DNA Origami Nanomachines 60 3.3 Ion- Responsive Mechanical DNA Origami Devices 60 3.4 Photoresponsive Devices 62 3.5 Two- Dimensional Self- Assembly Processes 64 3.6 Sequential Self- Assembly 66 3.7 Photostimulated Assembly and Disassembly 67 3.8 Conclusions and Perspectives 69 References 69 4 Advancement of Computer- Aided Design Software and Simulation Tools for Nucleic Acid Nanostructures and DNA Origami 75 Ibuki Kawamata 4.1 Introduction 75 4.2 General- Purpose Software 76 4.3 Software for Designing Small DNA Nanostructures 78 4.4 Software for Designing DNA Origami 81 4.5 Software for Designing RNA Nanostructures 84 4.6 Software for Designing Base Sequence 84 4.7 Software for Simulating Nucleic Acid Nanostructures 85 4.8 Summary and Future Perspective 86 References 87 5 Dynamic and Mechanical Applications of DNA Nanostructures in Biophysics 101 Melika Shahhosseini, Anjelica Kucinic, Peter Beshay, Wolfgang Pfeifer, and Carlos Castro 5.1 Introduction 101 5.1.1 What Makes DNA a Good Material for Dynamic Applications 101 5.1.2 Rupture Forces 103 5.2 Applications 105 5.2.1 Force Spectroscopy 105 5.2.1.1 Utilizing the Stiffness of DNA for Force Spectroscopy 105 5.2.1.2 Applications that Utilize Rupture Forces 107 5.2.2 DNA Devices that Probe and Control DNA–DNA Interactions 108 5.2.2.1 Detection 108 5.2.2.2 Modulation 111 5.2.3 DNA Devices that Respond to Biomolecules 111 5.2.4 DNA Devices to Study Biological Molecular Motors 116 5.2.5 DNA Walkers 116 5.2.6 DNA Computing 119 5.3 Tools for Quantifying DNA Devices and their Functions 120 5.4 Modeling and Analysis 123 5.5 Conclusion 124 References 124 6 Plasmonic Nanostructures Assembled by DNA Origami 135 Sergio Kogikoski, Jr, Anushree Dutta, and Ilko Bald 6.1 Introduction 135 6.2 Optical Properties of the DNA Origami- Based Plasmonic Nanostructures 135 6.3 Nanoparticle Functionalization with DNA 138 6.4 DNA Origami- Based Plasmonic Assemblies 140 6.5 Surface- Enhanced Raman Scattering (SERS) and Other Plasmonic Effects 143 6.6 Conclusion 152 Acknowledgments 152 References 152 7 Assembly of Nanoparticle Superlattices Using DNA Origami as a Template 155 Sofia Julin, Petteri Piskunen, Mauri A. Kostiainen, and Veikko Linko 7.1 Introduction 155 7.2 Gold Nanoparticles 156 7.2.1 Oligonucleotide- Modified AuNPs 156 7.2.2 Cationic AuNPs 158 7.3 Formation of DNA Origami- Assisted Superlattices 158 7.3.1 Superlattices Formed by Oligonucleotide- Functionalized AuNPs 159 7.3.2 Superlattice Formed by Cationic AuNPs 160 7.4 Characterization of Assemblies 160 7.4.1 Electron Microscopy 161 7.4.2 Small- Angle X- ray Scattering 161 7.5 Conclusions and Future Perspectives 162 Acknowledgments 164 References 164 8 Mechanics of DNA Origami Nanoassemblies 167 Deepak Karna, Jiahao Ji, and Hanbin Mao 8.1 Introduction 167 8.2 Analytical Tools to Investigate Mechanical Properties of Nanoassemblies 168 8.2.1 Optical Tweezers 168 8.2.2 Magnetic Tweezers 169 8.2.3 Atomic Force Microscopy (AFM) 169 8.3 Mechanical Strength of DNA Origami Structures 171 8.4 Applications of Origami Nanostructures by Exploiting their Mechanical Strength 173 8.5 Mechanochemical Properties of DNA Origami 175 8.6 Conclusions 177 References 177 9 3D DNA Origami as Single- Molecule Biophysical Tools for Dissecting Molecular Motor Functions 181 Mitsuhiro Iwaki 9.1 Introduction 181 9.2 DNA Origami Nanospring 181 9.2.1 Design of DNA Origami Nanospring 181 9.2.2 Nanospring Mechanical Properties 182 9.2.3 Application to a Myosin VI Processive Motor 183 9.3 DNA Origami Thick Filament Mimicking Muscle Structure 187 9.3.1 Mystery of Muscle Contraction 187 9.3.2 Design of a DNA Origami- Based Thick Filament 188 9.3.3 High- speed AFM Observation of Force Generation by Myosin 189 9.3.4 High- Speed Darkfield Imaging of Force Generation by Myosin 189 9.4 Perspective 193 References 193 10 Switchable DNA Origami Nanostructures and Their Applications 197 Jianbang Wang, Michael P. O’Hagan, Verena Wulf, and Itamar Willner 10.1 Introduction 197 10.2 Switchable Machines Constructed from DNA Origami Scaffolds 198 10.2.1 Chemical Triggers for Origami Scaffolds 198 10.2.1.1 Triggering Origami Devices with Strand Displacement Reactions 198 10.2.1.2 Triggering Origami with Ion Concentration 200 10.2.1.3 Triggering Origami with Molecular Species 202 10.2.2 Physical Triggers for Origami Scaffolds 204 10.2.2.1 Triggering Origami with Temperature 204 10.2.2.2 Triggering Origami with Electric Fields 206 10.2.2.3 Triggering Origami with Magnetic Fields 206 10.2.2.4 Triggering Origami with Light 208 10.3 DNA Origami Scaffolds for Defined Mechanical Operations 210 10.3.1 Origami Scaffolds that Dictate the Motility of Elements 212 10.3.2 Engineering Mechanical Functions of Origami Tiles 218 10.4 Switchable Interconnected 2D Origami Assemblies 218 10.5 Dynamic Triggered Switching of Origami for Controlled Release 223 10.6 Switchable Plasmonic Phenomena with DNA Origami Scaffolds 227 10.7 Origami- Guided Organization of Nanoparticles and Proteins 234 10.8 Conclusions and Perspectives 238 References 239 11 The Effect of DNA Boundaries on Enzymatic Reactions 241 Richard Kosinski and Barbara Saccà 11.1 Introduction 241 11.2 DNA- Scaffolded Single Enzymes 242 11.3 DNA- Scaffolded Enzyme Cascades 247 11.4 On the Proximity Model and Other Hypotheses 250 11.5 Conclusions 254 Acknowledgments 256 References 256 12 The Methods to Assemble Functional Proteins on DNA Scaffold and their Applications 261 Eiji Nakata, Shiwei Zhang, Huyen Dinh, Peng Lin, and Takashi Morii 12.1 Introduction 261 12.2 Overview of the Methods for Arranging Proteins on DNA Scaffolds 262 12.2.1 Reversible Conjugation between Protein and DNA 263 12.2.1.1 Biotin- Avidin 264 12.2.1.2 Antibody- Antigen 264 12.2.1.3 Ni- NTA- Hexahistidine 266 12.2.1.4 Aptamers 266 12.2.1.5 Apo- Protein Reconstitution by the Prosthetic Group 266 12.2.2 Irreversible Conjugation between Protein and DNA 266 12.2.2.1 Chemical Crosslinking of Protein and DNA via Cross- Linker 267 12.2.2.2 Crosslinking of Genetically Fused Protein with Chemically Modified DNA 267 12.2.2.3 Covalent Conjugation of Genetically Modified Proteins to Unmodified DNA 269 12.2.2.4 Applications of the Enzyme Assembled DNA Scaffolds 269 12.3 DNA- Binding Adaptor for Assembling Proteins on DNA Scaffold and its Application 270 12.3.1 DNA- Binding Adaptor for Reversible Assembly of Proteins via Noncovalent Interactions 270 12.3.2 Modular Adaptors for Covalent Conjugation of Genetically Modified Proteins to Chemically Modified DNA 272 12.3.3 Application of DNA- Binding Adaptors for Assembling Proteins on DNA Scaffolds 275 12.3.3.1 Assembling Protein of Interest on DNA Scaffold in Cell 275 12.3.3.2 Enzymatic Reaction System on a DNA Scaffold 275 12.4 Summary 278 References 278 13 DNA Origami for Synthetic Biology: An Integrated Gene Logic- Chip 281 Hisashi Tadakuma 13.1 Introduction 281 13.2 Biomolecule Integration on DNA Nanostructure 281 13.2.1 Nature Uses “Reaction Field” to Overcome the Cross- Talk Problem 281 13.2.2 Synthetic Biology Approach 282 13.2.3 DNA–Protein Complex 282 13.2.4 Enzymatic Reaction on DNA Origami for Low- Molecular- Weight Substrate 284 13.3 Gene Expression Control Using DNA Nanostructure 285 13.3.1 Enzymatic Reaction on DNA Origami for High- Molecular- Weight Substrate 285 13.3.2 Resolving Synthetic Biology Limitation by DNA Origami- Based Nano- Chip 286 13.3.3 Unique Characters of the Nano- Chip 288 13.3.4 Limitation of the Nano- Chip 292 13.4 Summary and Perspective 292 Acknowledgments 293 References 293 14 DNA Origami for Molecular Robotics 297 Akinori Kuzuya 14.1 DNA Origami as a Stage for DNA Walkers and Robotic Arms 297 14.2 Nanomechanical DNA Origami 298 14.3 DNA Origami Used in Combination with Molecular Motors 300 14.4 Future Perspective 301 References 303 15 DNA origami Nanotechnology for the Visualization, Analysis, and Control of Molecular Events with Nanoscale Precision 305 Xiwen Xing and Masayuki Endo 15.1 Introduction 305 15.2 Designing of DNA Origami Frames for the Direct Observation of DNA Conformational Changes 308 15.3 Direct Observation of DNA Structural Changes in the DNA Origami Frame 308 15.3.1 G- Quadruplex Formation and Disruption 308 15.3.2 G- Quadruplex Formation by the Assembly of Four DNA Strands 309 15.3.3 Light- Induced Hybridization and Dehybridization of the Photoswitchable DNA Strands 309 15.3.4 Direct Observation of B–Z Transition in the Equilibrium State 312 15.3.5 Topological Control of G- Quadruplex and I- Motif Formation in the dsDNA 314 15.4 Direct Observation and Regulation of Enzyme Reactions in the DNA Origami Frame 315 15.4.1 Direct Observation and Regulation of Cre- Mediated DNA Recombination in the DNA Origami Frame 315 15.4.2 Holiday- Junction Resolution Mediated by DNA Resolvase 317 15.4.3 DNA Oxidation in the DNA Demethylation Process Mediated by TET Enzyme 317 15.4.4 Searching and Recognition of Target Sites by using Photoresponsive Transcription Factor GAL 4 319 15.5 Direct Observation of a Mobile DNA Nanomachine using DNA Origami 321 15.5.1 A DNA Linear Motor System Created on a DNA Origami System 321 15.5.2 Single- Molecule Operation of DNA Motor by using Programmed Instructions 321 15.5.3 Photo- Controlled DNA Motor System Constructed on DNA Origami 324 15.5.4 Photo- Controlled DNA Rotator System Constructed on DNA Origami 324 15.6 Limitations of AFM Imaging and Comparison with other Imaging Techniques 326 15.7 Conclusions and Perspectives 326 References 327 16 Stability and Stabilization of DNA Nanostructures in Biomedical Applications 333 Soumya Chandrasekhar, Praneetha Sundar Prakash, and Thorsten- Lars Schmidt 16.1 Threats for DNA Nanostructures 333 16.1.1 Errors from Nanostructure Synthesis 334 16.1.1.1 Missing Strands 334 16.1.1.2 Oligonucleotide Synthesis Errors 335 16.1.2 Denaturation of DNA Duplexes 336 16.1.2.1 Melting 336 16.1.2.2 The Role of Cations 336 16.1.2.3 Influence of pH on Duplex Stability 337 16.1.3 Backbone Cleavage 337 16.1.3.1 Acid- Induced Depurination 337 16.1.3.2 Base- Induced Cleavage of RNA 338 16.1.3.3 Enzymatic Digest 338 16.1.4 Chemical Damage at the Nucleobases 339 16.1.4.1 Ultraviolet Radiation 339 16.1.4.2 Radiative and Oxidative DNA Damage 340 16.1.4.3 Deamination 340 16.1.5 DNA Structures for Biological Applications 341 16.1.5.1 Bioimaging 341 16.1.5.2 Biosensing 341 16.1.5.3 Computing 341 16.1.5.4 Single- Molecule Biophysics and Mechanobiology 343 16.1.5.5 Drug Delivery and Gene Therapy 343 16.1.6 In vitro and In vivo Degradation and Clearance of DNA Structures 343 16.1.6.1 Common in vitro and in vivo Stability Assays 344 16.1.6.2 Degradation of DN in in vitro and in vivo 344 16.1.6.3 Low Mg2+ Conditions 346 16.1.6.4 Presence of Nucleases 346 16.1.6.5 Cellular Uptake and Clearance of DNs 347 16.1.6.6 Immune Response 348 16.2 Strategies to Protect DNA Origami Structures 349 16.2.1 Stabilization by Design 349 16.2.2 Stabilization by Covalent Strategies 351 16.2.2.1 Enzymatic Ligation 351 16.2.2.2 Chemical Crosslinking 352 16.2.2.3 Photo Crosslinking 354 16.2.2.4 Base Analogues and Backbone Modification 356 16.2.3 Stabilization by Non- Covalent Strategies and Additives 356 16.2.3.1 Inorganic Materials 356 16.2.3.2 Proteins 358 16.2.3.3 Polymer, Peptides, and Polycation Coatings 358 References 362 17 DNA Nanostructures for Cancer Diagnosis and Therapy 379 Zhe Li and Yonggang Ke 17.1 Introduction 379 17.2 DNA Nanostructure- Based Diagnostics 380 17.2.1 Nucleic Acid Detection 380 17.2.2 Protein and Exosome Detection 382 17.2.3 Tumor Cell Detection 384 17.2.4 Imaging 385 17.3 DNA Nanostructure- Based Drug Delivery 386 17.3.1 Small Molecules 386 17.3.1.1 Doxorubicin 386 17.3.1.2 Platinum- Based Drugs 387 17.3.2 Biologics 389 17.3.2.1 CpG 389 17.3.2.2 RNA 390 17.3.2.3 Protein 392 17.3.3 Inorganic Nanoparticles 393 17.4 Challenges and Prospects 394 17.4.1 Stability 394 17.4.1.1 Nucleases 395 17.4.1.2 Mg2+ 395 17.4.1.3 Shape and Superstructure of DNA Nanostructures 396 17.4.2 Drug Loading Efficiency 396 17.4.3 Drug releasing efficiency 397 17.4.4 Cell Internalization 398 References 400 Index 411

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Book SynopsisTable of Contents1 The Beginnings of Biomimetics 1 1.1 Early Attempts at Biomimicry: The Influence of Birds on the Development of Aircraft 3 1.2 The Fathers of Modern Biomimetics: Percy Shaw and George de Mestral 4 Relevant Innovations Described in Other Chapters 6 Note 6 Suggested Reading 7 2 Transport, Motion, and Energy 9 2.1 Birds and Bullet Trains 9 2.2 More Owl-Inspired Noise Reduction 13 2.3 Humpback Whales and Wind Turbines 14 2.4 Fish Shoals and Wind Farms 16 2.5 Liquid Movement in Nature: The Importance of Spirals 17 2.6 A Tree-Inspired Wind Turbine 20 2.7 More Fishy Developments 22 2.8 A Fishy Failure: The Boxfish Car 22 2.9 Fuel Efficiency Inspired by Sharks 24 2.10 Using Biology to Counteract Biofouling 25 2.11 The New Generation of Ornithopters 28 Relevant Innovations Described in Other Chapters 30 Note 30 Suggested Reading 30 3 Colour and Light 31 3.1 Photonic Biomimicry 36 3.2 Structure Can Influence Light Output 38 3.3 Cephalopods and Camouflage 39 3.4 Photonic Cooling 43 3.5 Biomimetic Antireflective Coatings 46 3.6 A Novel Glass Inspired by Spiders 47 Relevant Innovations Described in Other Chapters 49 Suggested Reading 49 4 The Built Environment 51 4.1 Cooling Buildings the Termite Way 51 4.2 Functional Structures Inspired by Nature 55 4.3 Self-Cleaning Surfaces 59 4.4 Self-Healing Concrete 63 4.5 New Building Materials 64 4.6 A Sunshade Modelled on Trees 65 4.7 Solar Ivy 66 4.8 The Future: Fully Responsive Buildings 67 Relevant Innovations Described in Other Chapters 68 Note 68 Suggested Reading 68 5 Smart Materials 71 5.1 Self-Cleaning Materials 71 5.1.1 Reducing Bacterial Growth Without Disinfectants 71 5.1.2 Pitcher Plants and Non-stick Surfaces 74 5.2 Novel Adhesives 76 5.2.1 Novel Glues Inspired by Marine Animals 76 5.2.2 Hierarchical Steels Modelled on Byssal Threads 78 5.2.3 Glues from Terrestrial Slugs 79 5.2.4 Gecko-Inspired Dry Adhesives 81 5.3 Self-Healing Materials 83 5.4 Novel Textiles 85 5.4.1 Smart Textiles that Respond to their Surroundings 85 5.4.2 A Polar Bear-Inspired Material for Heat Insulation 86 5.4.3 Safety Helmets Inspired by Woodpeckers 86 Relevant Material in Other Chapters 87 Note 87 Suggested Reading 88 6 Smart Devices 91 6.1 Burrowing Robots Based on Razor Clams 91 6.2 Novel Sensors 92 6.2.1 Bioinspired Underwater Pressure Sensors 92 6.2.2 Crack-Based Strain Sensors 93 6.2.3 Ice Plants and Actuators 94 6.3 Passive Water Collection 96 6.3.1 Inspiration from the Namib Desert Beetle 96 6.3.2 Collecting Water with Spiders’ Webs 98 6.3.3 Cactus-Inspired Water Collection 100 6.4 Insects and Origami 100 6.5 Mosquito Bites and Injection Needles 103 Suggested Reading 104 7 The Influence of Biology on Computer Science 107 7.1 Genetic Algorithms 108 7.2 Swarm Intelligence 110 7.3 Human Swarming 112 Suggested Reading 113 8 The Future of Biomimetics 115 Suggested Reading 116 Index 117

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Book SynopsisTable of ContentsPreface xiii List of Contributors xv 1 Beneficial Elements in Plant Life Under A Changing Environment 1 Misbah Naz, Muhammad Ammar Raza, Muhammad Adnan Bodlah, Sarah Bouzroud, Muhammad Imran Ghani, Muhammad Riaz, Tariq Shah, Akmal Zubair, Imran Bodlah, and Xiaorong Fan Introduction 1 Beneficial Element Interaction with Environment 2 Aluminium (Al) in Plants 3 Aluminium (Al) in Soil – Aluminium, a Friend or Foe of Higher Plants in Acidic Soils 4 Cobalt (Co) in Plants 5 Cobalt (Co) in Soil 6 Silicon (Si) 9 Function of Silicon 10 Silicon in Soil 11 Sodium in Plants 12 Sodium in Soil 12 Selenium (Se) 13 Selenium in Environment 13 Physiological Functions of Beneficial Elements Under A Changing Environment 13 5-Beneficial Elements Against Stresses 14 Conclusion 15 References 15 2 Role of Beneficial Elements in Epigenetic Regulation of Plants in Response to Abiotic Stress Factors 22 Muhittin Kulak and Adnan Aydin Introduction 22 Beneficial Elements for Crop and Non-Crop Plants 22 Selenium 22 Silicon 23 Aluminium 23 Sodium 23 Cobalt 23 Abiotic Stress Factors 23 Epigenetic Modifications Under Stressful Conditions 24 Studies Regarding the Effect of Beneficial Elements on Epigenetic Changes in the Genome of Plants 28 Selenium 28 Cobalt 28 Sodium 29 Aluminium 29 Silicon 30 Conclusion 30 References 30 3 Beneficial Elements and Status of ROS and RNS in Plants: Current Evidence and Future Prospects 38 Biswajita Pradhan, Rabindra Nayak, Srimanta Patra, Chhandashree Behera, Soumya Ranjan Dash, and Mrutyunjay Jena Introduction 38 Essential and Beneficial Elements in Plant Physiology: A Pleasant Dilemma 39 Aluminium 40 Cobalt 41 Sodium 42 Selenium 42 Silicon 44 ROS and RNS Production Sites in Plant Cells: Cellular Redox Compartments with Regards to Essential Elements 45 ROS and RNS Production and Their Function in Plants: Connecting Physiology to Stress Physiology 47 Conclusion and Future Perspectives 48 Acknowledgments 49 Conflicts of Interest 49 References 49 4 Biostimulant Effects and Concentration Patterns of Beneficial Elements in Plants 58 Libia I. Trejo- Téllez, Libia F. Gómez- Trejo, and Fernando C. Gómez- Merino Introduction 58 Aluminium 59 Cerium 69 Cobalt 70 Iodine 72 Lanthanum 73 Selenium 75 Silicon 77 Sodium 79 Titanium 80 Vanadium 82 Conclusions and Perspectives 83 References 84 5 Targeted Effects of Beneficial Elements in Plant Photosynthetic Process 103 Costanza Ceccanti, Ermes Lo Piccolo, Lucia Guidi, and Marco Landi Introduction 103 Effect of Metal Beneficial Elements 104 Effect of Non-metal Beneficial Elements 114 Conclusion 116 References 116 6 Aluminium Stress in Plants: Consequences and Mitigation Mechanisms 123 Akbar Hossain, Sagar Maitra, Sukamal Sarker, Abdullah Al Mahmud, Zahoor Ahmad, Reza Mohammad Emon, Hindu Vemuri, Md Abdul Malek, M. Ashraful Alam, Md Atikur Rahman, Md Jahangir Alam, Nasrin Jahan, Preetha Bhadra, Debojyoti Moulick, Saikat Saha, Milan Skalicky, and Marian Brestic Introduction 123 An Overview of Al Toxicity in Plants 124 Effect on Root Growth 124 Oxidative Stress 126 Nutrient Imbalances 127 Mechanisms for Al Stress Tolerance in Plants 127 Phenotyping for Al-toxicity Tolerance in Plants 128 Physiological Mechanisms of Al Tolerance in Plants 128 Morpho-physiological Mechanisms 129 Biochemical Mechanisms 130 Cellular Mechanisms 130 Phytohormones-based Aluminium Stress Tolerance in Plants 133 Antioxidants-based Aluminium Stress Tolerance in Plants 134 Potential Transgenic Approach for Aluminium Toxicity Improvement 134 Genes Responsive Under Aluminium Toxicity 135 Gene Family Variation 136 Interference in the Resistance Mechanism 136 Expression and Regulation of Gene Families 136 Genetic Engineering 138 Pyramiding of Genes 138 Phytoremediation of Al Stress in Plants 139 Microorganism-mediated Aluminium Stress Tolerance in Plants 142 Agronomic Management for Mitigating Aluminium Stress in Plants 143 Role of Inorganic Amendments for Mitigating Al Toxicity in Plants 144 Calcium (Ca) as a Mitigator of Al Toxicity 144 Phosphorus (P) as a Mitigator of Al Toxicity 146 Magnesium (Mg) as a Mitigator of Al Toxicity 146 Boron (B) as a Mitigator of Al Toxicity 147 Sulphur (S) as a Mitigator of Al Toxicity 147 Silicon (Si) as a Mitigator of Al Toxicity 147 Role of Organic Amendments for Mitigating Al Toxicity in Plants 147 Biochar as a Mitigator of Al Toxicity 147 Compost or Organic Matter as a Mitigator of Al Toxicity 148 Conclusion 148 Conflict of Interest 149 References 149 7 Mechanisms of Cobalt Uptake, Transport, and Beneficial Aspects in Plants 169 Zaid Ulhassan, Aamir Mehmood Shah, Ali Raza Khan, Wardah Azhar, Yasir Hamid, and Weijun Zhou Introduction 169 Mechanisms of Cobalt Uptake and Transport in Plants 170 Beneficial Aspects of Cobalt in Plants 172 Growth and Yield 172 Nitrogen Fixation and Nodule Formation 173 Alterations in Nutrient Status 173 Alterations in Physiological and Biochemical Constituents 174 Antioxidant Enzyme Activities and Synthesis of Hormones 175 Protective Roles of Cobalt Against Abiotic Stresses 175 Conclusions and Future Prospects 176 Acknowledgments 177 References 177 8 Cobalt in Plant Life: Responses and Deficiency Symptoms 182 Xiu Hu, Xiangying Wei, Jie Ling, and Jianjun Chen Introduction 182 Cobalt in Lower Plants 184 Bryophytes 184 Algae 185 Cobalt in Higher Plants 186 Root Absorption of Cobalt 186 Cobalt Transport in Plants 187 Cobalt Effects on Plant Growth 188 Cobalt is Essential for N 2 Fixation in Nodulated Legumes 188 Cobalt Enhances Growth of Non-Leguminous Crops 190 Possible Mechanisms 190 Other Beneficial Effects on Plants 192 Cobalt Deficiency in Plants 192 Cobalt Toxicity in Plants 194 Conclusions and Future Perspectives 196 References 197 9 Silicon Uptake, Transport, and Accumulation in Plants 205 Shivani Sharma, Muntazir Mushtaq, Sreeja Sudhakaran, Vandana Thakral, Gaurav Raturi, Ruchi Bansal, Virender Kumar, Sanskriti Vats, S. M. Shivaraj, and Rupesh Deshmukh Introduction 205 Molecular Mechanism Involved in Silicon Uptake 206 Seminal Studies Defining Uptake of Silicon in Different Plant Species 206 Silicon Influx Transporter 207 Silicon Efflux Transporter 209 Cordial Activity of Silicon Influx and Efflux Transporter 211 Other Homologs of Silicon Influx and Efflux Transporter 213 Silicon Transporters yet to be Discovered 213 Silicon Deposition in Different Tissues 214 Silicon Deposition in Roots 214 Silicon Deposition in Shoot 214 Silicon Deposition in Leaves 216 Phytoliths: Biochemical Composition and Deposition Patterns 217 Silicon Deposition and the Phytolith Formation 218 Role of Phytoliths in the Silicon Biogeochemical Cycle 220 References 222 10 Silicon in Soil, Plants, and Environment 227 Mujahid Ali, Muhammad Zia Ur Rehman, Asad Jamil, Muhammad Ashar Ayub, and Muhammad Tahir Shehzad Introduction 227 Sources of Silicon in Soil, Plants and Environment 228 Natural Sources 228 Artificial/Synthetic Sources 228 Uses of Silicon 229 Industrial Use 229 Application in Agro-ecosystems 229 Role of Silicon in Plant Nutrition-Growth Responses 230 Nutrient Acquisition 230 Plant Growth Promotion 230 Gas Exchange Attributes Modulation 230 Plant Water Balance 230 Antioxidant Enzymes Activities 231 Uptake and Translocation Mechanisms of Silicon 231 Role of Silicon in Agriculture 232 Role of Silicon in Abiotic Stress Management 232 Heavy Metals 232 Salinity 232 Water Stress 234 Temperature Stress 234 Role of Silicon in Biotic Stress Management 237 Pest Attack 237 Role of Silicon in Disease Management 237 Silicon-Mediated Endogenous Modifications in Plants 238 C. Mechanism of Silicon-Mediated Abiotic Stress Management 238 D. Mechanism of Silicon-Mediated Biotic Stress Management 241 Source of Silicon for Agricultural Application 241 Recommendations for Exogenous Silicon Applications 242 Conclusion and Future Perspectives 242 References 242 11 Silicon- Mediated Alleviation of Heavy Metal Stress in Plants 256 Sana Rana, Muhammad Zia ur Rehman, Muhammad Umair, Muhammad Ashar Ayub, and Muhammad Arif Introduction 256 Heavy Metal (HM) Sources in Agro-ecosystem 257 The Response of Plants Towards HM Stress 257 Sources of Silicon in Soil 258 Role of Silicon in HM Stress Management 258 Silicon Role in Plant Nutrition 259 Silicon-Mediated HM Management Mechanisms 259 Reduction of HM Uptake 259 Modification of Rhizosphere Chemistry/Making Si Complexes with Metals 260 Stimulation of Antioxidants 260 Help in Compartmentation of HM Inside Plants 260 Gene Expression Modification 261 Structural and Physiological Modification 261 Exogenous Application of Silicon to Manage HM Toxicity 261 Silicon Fertilizer 262 Biogenic Si Sources (Organic Amendments Enriched in Si) 262 Silicon Nanoparticles 265 Summary 266 References 266 12 How Does Sodium Content in Growing Media Affect the Chemical Content of Medicinal and Aromatic Plants? Two Sides of the Coin 277 Ahmet Metin Kumlay, Muhittin Kulak, Mehmet Zeki Kocak, Ferdi Celikcan, and Mehmet Hakki Alma Introduction 277 What Kinds of Functions Have Been Attributed to Sodium for Proper Metabolism of the Plant? 278 What Kind of Perturbations Might Emerge in Case of Deficiency or Excessive Accumulation of Sodium in Growing Media and in Turn, in Plants? 279 What Are the Major Mechanisms Associated with the Damage Caused by High Salinity? 279 Compartmentalization of Sodium Through Plant Parts 280 Why Is the Sodium/Potassium Ratio Important for Plant Metabolism? 280 How Do Priming or Osmo-Conditioning Seeds Using NaCl Solutions Imprint the Sequential Growth Performance or Stage of the Plants? An Approach Regarding Imprint Memory with Low Concentration versus Higher Subsequent Concentration of NaCl 281 What Are Medicinal and Aromatic Plants and Metabolites of Those Plants? How Do Those Metabolites Respond to Higher Content of Na in Media Regarding Total Content and Their Specific Compounds? 281 The Growth, Development, and Yield are Adversely Affected Under High Sodium Concentration of Growing Media, but What Can We Say for Contents of Total Metabolites or Specific Compounds? 282 Alkaloids 282 Terpenoids 283 Phenolics 286 What Kinds of Explanations Have Been Postulated for Changes Concerned with Defence-Related Metabolites in Those Plants Exposed to Higher Levels of Sodium in Growing Media? 297 Do Lower or Higher Concentration of the Sodium Favour Metabolites? 297 Two Sides of the Coin: Is a Third Probability Possible for Plant Production Versus Secondary Metabolite Production? 298 Conclusion 298 References 299 13 Sodium and Abiotic Stress Tolerance in Plants 307 Misbah Naz, Muhammad Imran Ghani, Muhammad Jawaad Atif, Muhammad Ammar Raza, Sarah Bouzroud, Muhammad Rahil Afzal, Muhammad Riaz, Maratab Ali, Muhammad Tariq, and Xiaorong Fan Introduction 307 Relationship Between Salinity and Plant 309 Salinity and the Ideal Sustainable Agricultural System 310 Relationship Between Salinity and Sodicity and Soil 311 Salt Stress Effects on Plants 311 Management Strategies to Mitigate Salt Injury 312 Salt Sensitivity 313 Genetic Engineering and Salt-Tolerant Transgenic Plants 316 Role of Sodium in Plants 317 Osmotic Tolerance 318 Proteomics Study in Plant Responses and Tolerance to Salt Stress 318 Ion Uptake/Homeostasis 319 Role of Phytohormones for Abiotic Stress Tolerance 320 Interaction Between Na + and K + in Plants 321 Interactions Between Na + and Mg 2+ in Plants 322 Interactions Between Na + and Ca 2+ in Plants 322 Conclusion 323 References 323 14 Selenium Species in Plant Life: Uptake, Transport, Metabolism, and Biochemistry 331 Zaid Ulhassan, Ali Raza Khan, Wardah Azhar, Yasir Hamid, Durgesh Kumar Tripathi, and Weijun Zhou Selenium Speciation in the Soil-Plant System 331 Accumulation and Uptake of Selenium Species by Plants 331 Transport Mechanisms of Selenium Species within Plants 333 Selenium Metabolism in Plants 333 Step 1: Conversion of Selenate into Selenite and Selenide 333 Step 2: Selenide to Selenocysteine (SeCys) Transformation 334 Step 3: Transformation of Selenocysteine (SeCys) into Elemental Se 0 and Alanine (Ala) 335 Step 4: Metabolic Pathways of Methyl Selenomethionine (MeSeMet) 335 Biochemistry of Selenium 335 Is Selenium an Essential Trace Element for Plants? 335 Conversion of Inorganic to Organic Selenium Forms (The First Step of the Se-Assimilation Pathway) 336 Adaptive Mechanisms by Plants to Evade Selenium Toxicity Participation of Se-Amino Acids 338 Volatilization of Selenium Organic Compounds 338 Involvement of Selenocysteine Lyase 339 Sequestration of Selenium Organic Compounds 339 Antioxidant Defense Mechanisms 340 Involvement of Phytohormones or Signalling Molecules 340 General Conclusions and Future Prospects 341 Acknowledgments 342 References 342 15 Lanthanides as Beneficial Elements for Plants 349 Fernando C. Gómez- Merino, Libia F. Gómez- Trejo, Rubén Ruvalcaba- Ramírez, and Libia I. Trejo- Téllez Introduction 349 Lanthanides in Biological Systems 353 Lanthanides in Plants 355 Beneficial Effects of Lanthanides in Plants 356 Conclusions and Future Research Needs 360 References 360 Index 370

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Book SynopsisWetlands Conservation An up-to-date overview of approaches for addressing wetlands degradation and its effects on ecosystem services, human health, and other ecosystems Wetlands are essential sources of biodiversity, water purification, groundwater replenishment, flood control, storm protection, sediment retention, recreation and tourism, and more. Human exploitation of natural resources over the past 200 years has caused significant wetlands degradation and loss. Although the Ramsar Convention of 1971 drafted polices for wetland conservation and responsible use, many wetland sites remain inadequately conserved or managed. Maintaining the ecological balance and equilibrium of wetlands requires a clear understanding of the vital role of wetlands, the difficulties they face, and the policies enacted for their protection. Wetlands Conservation: Current Challenges and Future Strategies summarizes both current and emerging management strategies, trends, and policies regarding wetlands proteTable of ContentsPreface xiii List of Contributors xvii 1 Global Wetlands: Categorization, Distribution and Global Scenario 1 1.1 Wetlands Definition, Categorization and Classification Criteria 1 1.1.1 Wetlands- Categorization and Classification 3 1.1.2 Human- Made Wetlands 5 1.2 Importance of Wetland Ecosystem 5 1.3 Spatial Distribution and Potential of Global Wetlands 7 1.4 Status and Impacts on the Wetlands Ecosystem 8 1.4.1 Conservation Measures and Future Strategies 10 1.4.2 Conclusion and Recommendation 11 Acknowledgements 13 References 13 2 Ramsar Convention: History, Structure, Operations, and Relevance 17 2.1 Background 17 2.2 The Ramsar Convention 18 2.3 The Convention Text 19 2.4 Wetland Definition and Classification 19 2.5 Mission of the Convention 22 2.6 Structural Framework of the Convention 22 2.7 Operational Framework of the Convention 25 2.7.1 Convention Membership 25 2.7.2 Ramsar Regions 26 2.7.3 National Ramsar Committees 30 2.7.4 The Montreux Record 31 2.7.5 Ramsar Strategic Plan 31 2.7.6 Three Pillars of Ramsar Convention 31 2.7.7 The Convention Budget 32 2.8 External Partnerships and Synergies 33 2.9 Education and Outreach 35 2.9.1 Communication, Education, Participation, and Awareness (CEPA) 35 2.9.2 World Wetlands Day 36 2.10 Legal Status 36 2.11 Effectiveness of the Convention 37 References 38 3 Ecological Importance of Wetland Systems 40 3.1 Introduction 40 3.2 Importance of Wetlands in Flood Control 40 3.3 Role of Wetlands in Groundwater Replenishment 41 3.4 Role of Wetlands in Stabilization and Storm Protection of Shorelines 42 3.5 Role of Wetlands in Sediment and Nutrient Retention 43 3.6 Role of Wetlands in Water Purification 44 3.7 Biodiversity of Wetlands 45 3.8 Wetland Products 46 3.9 Sociocultural Values of Wetlands 46 3.10 Wetlands in Relation to Recreation and Tourism 47 3.11 Wetland and Climate Change 48 3.12 Summary 49 Acknowledgments 50 References 50 4 Ecological and Societal Importance of Wetlands: A Case Study of North Bihar (India) 55 4.1 Introduction 55 4.2 Geographical and District-Wise Distribution of Wetlands in North Bihar 58 4.2.1 Kabartal 60 4.2.2 Baraila Jheel 60 4.2.3 Kusheshwar Asthan 62 4.2.4 Jagatpur Wetland 62 4.2.5 Moti Jheel 63 4.2.6 Gogabeel Pakshi Vihar 64 4.3 Wetlands: Promoters of Sustainable Livelihood and Services 64 4.4 North Bihar Wetland Biodiversity: Status and Role 65 4.5 Urbanization, Pollution, and Climate Change Impacts 71 4.6 Legal Framework, Policies, and Challenges 77 4.7 Conclusion 79 Acknowledgments 80 References 80 5 Recognizing Economic Values of Wetland Ecosystem Services: A Study of Emerging Role of Monetary Evaluation of Chandubi Ecosystem and Biodiversity 87 5.1 Introduction 87 5.2 Methodology of Ecosystem Valuation 90 5.2.1 Market Prices – Revealed Willingness to Pay 90 5.2.1.1 Market Price Method 91 5.2.1.2 Productivity Method 91 5.2.1.3 Hedonic Pricing Method 92 5.2.1.4 Travel Cost Method 93 5.2.2 Circumstantial Evidence – Imputed Willingness to Pay 94 5.2.2.1 Damage Cost Avoided, Replacement Cost, and Substitute Cost Methods 94 5.2.3 Surveys – Expressed Willingness to Pay 95 5.2.3.1 Contingent Valuation Method 95 5.2.3.2 Contingent Choice Method 96 5.3 Ecosystem Services of Wetland 97 5.4 Chandubi Wetland: Introduction, Impact, and Introspection 97 5.5 Scaling up Wetland Conservation, Wise Use, and Restoration for Achieving Sustainable Development Goals 103 5.6 Wetlands’ Role in Achieving SDGs 104 5.7 Conclusion 108 Acknowledgments 109 References 109 6 Ecosystem Services of Lagoon Wetlands System in India 111 6.1 Introduction 111 6.2 Chilika Lagoon 112 6.3 Ecosystem Services Provided by Chilika Lagoon 112 6.3.1 Provisioning Services 114 6.3.1.1 Commercial Fisheries 114 6.3.1.2 Other Flora and Fauna of Chilika Lagoon 114 6.3.1.3 Navigation 115 6.3.2 Regulating Services 115 6.3.3 Cultural Services 116 6.3.4 Supporting Services 116 6.4 Threats and Management of Chilika Lagoon 117 6.5 Pulicat Lagoon 118 6.6 Ecosystem Services Provided by Pulicat Lagoon 119 6.6.1 Provisioning Services 119 6.6.1.1 Fisheries in Pulicat 119 6.6.2 Aquatic Flora and Fauna of Pulicat 120 6.6.3 Regulatory Services Provided by Pulicat Lagoon 120 6.6.4 Historical and Cultural Importance of Pulicat Lagoon 120 6.6.5 Supporting Services Provided by Pulicat Lagoon 121 6.6.6 Threats and Management of Pulicat Lagoon 121 6.7 Conclusion 123 Acknowledgments 124 References 124 7 Sustainable Practices for Conservation of Wetland Ecosystem 129 7.1 Introduction 129 7.2 Role of Wetlands in the Ecosystem 130 7.3 Challenges to Conserve Wetlands 133 7.4 Wetland Management and Sustainable Development 134 7.5 Future Strategies for Wetland Conservation 135 7.6 Development of the Legal Framework 135 7.7 Technology Intervention with Baseline Data for Wetland Conservation 136 7.8 Development of National Action Plans 136 7.9 Promotion of Research for Conservation Setup 136 7.10 Conclusion 136 References 137 8 Assessing the Benefits, Threats and Conservation of Reservoir-Based Wetlands in the Eastern Himalayan River Basin 140 8.1 Introduction 140 8.1.1 RBWs’ Significance and Ignorance 141 8.1.2 RBWs in India 142 8.1.3 The RBWs in the Eastern Himalayas 143 8.2 The RBWs in the Tista Basin 144 8.3 Benefits of Reservoirs as Wetland 145 8.3.1 Ecosystem Services Provided by the RBWs 145 8.4 Assessment of Ecosystem Services in the Tista Basin Provided by the RBWs 147 8.5 Adverse Impact of RBWs 149 8.5.1 Construction and Function of RBWs Across the World 149 8.5.2 Adverse Impact of RBWs in the Eastern Himalayas 149 8.6 Assessment of Impact on the Tista basin 150 8.7 Potential Challenges and Threats to RBW 152 8.7.1 Anthropogenic Activities 152 8.7.2 Variations in Water Level 153 8.8 Climate Change 153 8.9 Management and Conservation of RBWs 154 8.10 Conclusion 155 References 156 9 Spatiotemporal Evaluation of Causes and Consequences of Wetland Degradation 162 9.1 Introduction 162 9.2 Classification of Wetlands 162 9.3 Causes of and Consequence of Wetland Degradation 164 9.3.1 Natural Causes 164 9.3.1.1 Storms Surge 165 9.3.1.2 Disintegration of Barrier Islands 165 9.3.1.3 Flooding and Salinization 165 9.3.1.4 Herbivory 166 9.3.1.5 Climate Change 166 9.3.1.6 Major Shifts in a River’s Course 166 9.3.2 Anthropogenic Causes of Wetland Loss 166 9.3.2.1 Infrastructure Development 167 9.3.2.2 Land Conversion 167 9.3.2.3 Water Withdrawal 168 9.3.2.4 Eutrophication and Pollution 168 9.3.2.5 Overharvesting and Overexploitation 168 9.3.2.6 Introduction of Invasive Species 168 9.3.2.7 Others 169 9.4 Consequences of Wetland Loss 170 9.4.1 Loss of Biodiversity 170 9.4.2 Decrease in Water Level 171 9.4.3 Loss of Habitat 171 9.4.4 Climate Change 171 9.4.5 Emission of Greenhouse Gases 171 9.4.6 Erosion of River Delta 172 References 172 10 The Status of Current Knowledge, Distribution, and Conservation Challenges of Wetland Ecosystems in Kashmir Himalaya, India 175 10.1 Introduction 175 10.2 Wetlands Over North-Western Kashmir Himalaya 176 10.2.1 Current Status 176 10.2.2 Wetland Classification 178 10.2.2.1 High Altitude Wetlands (HAWs) 182 10.2.2.2 Mid-Altitude Wetlands (MAWs) 182 10.2.3 Wetland Distribution and Extent in Kashmir Himalaya 182 10.3 Wetland Functions and Values 184 10.3.1 Regulatory functions 184 10.3.1.1 Regulation of Global Climate 184 10.3.1.2 Groundwater Recharge and Discharge 184 10.3.1.3 Water Purification 185 10.3.1.4 Natural Hazard and Flood Control 185 10.3.1.5 Sediment Retention 185 10.3.2 Provisioning Functions 185 10.3.2.1 Food Resources 185 10.3.2.2 Raw Materials 186 10.3.2.3 Medicinal Resources 186 10.3.3 Cultural Functions 186 10.3.3.1 Tourism, Aesthetics, and Recreation 186 10.3.3.2 Scientific and Educational Information 186 10.3.4 Supporting Functions 187 10.3.4.1 Biodiversity Habitats 187 10.3.4.2 Nutrient Cycling 187 10.3.5 Economic Values 187 10.4 Drivers of Wetland Degradation 187 10.4.1 Land System Changes 188 10.4.2 Pollution 189 10.4.3 Floating Agriculture 190 10.4.4 Siltation 190 10.4.5 Roads and Railways 190 10.4.6 Plantations 190 10.4.7 Overexploitation 191 10.4.8 Weed Infestation 191 10.4.9 Hunting and Poaching 191 10.4.10 Land Reclamation 191 10.5 Wetland Conservation in Kashmir Himalaya 191 10.5.1 Legal Framework 192 10.5.2 Conservation Challenges 193 10.5.3 Conservation Strategies 193 10.5.4 Knowledge Gaps 193 10.6 Conclusion 195 Acknowledgments 195 References 195 11 Heavy Metal Pollution in Coastal Environment and Its Remediation Using Mangroves: An Eco-sustainable Approach 201 11.1 Introduction 201 11.2 Pollution in Mangrove Habitats: A Global Concern 202 11.3 Heavy Metal Cycling in the Mangrove Ecosystem 203 11.4 Heavy Metal Transport, Uptake, and Release 204 11.5 Bioavailability and Concentration of Heavy Metals in the Sediments 204 11.6 Factors Affecting Heavy Metals in the Sediment 205 11.7 Heavy Metal Accumulation in Mangrove Plants 210 11.8 Heavy Metal Remediation Potential of Mangroves 210 11.9 Distribution of Heavy Metals in Different Plant Tissues of Mangrove Species 214 11.10 Application of Phytoremediation to Coastal Pollution Remediation 214 11.10.1 Phytoremediation Using Constructed Wetlands (CWs) Technology 214 11.10.2 Phytoremediation Using Constructed Floating Bed 216 11.11 Eco-remediation Technologies as Sustainable Natural Treatment Systems for Waste Water Treatment 217 11.12 Conclusion and Future Prospects 217 References 218 12 Mangrove Forests: Distribution, Species Diversity, Roles, Threats and Conservation Strategies 229 12.1 Introduction 229 12.2 Mangrove Species Diversity 230 12.3 Geographical Distribution of Mangroves Across the Globe and India 237 12.4 Important Roles of Mangroves 237 12.4.1 Mangrove Forests are the Richest and Most Biodiverse Ecosystems on Earth 241 12.4.2 Aquaculture: Shrimp and Fish Cultivation 242 12.4.3 Protection from Natural Disasters: Mangroves Act as Natural Bioshields Against Natural Disasters 242 12.4.4 Medicinal Value of Mangroves 243 12.5 Threats to Mangroves 243 12.5.1 Human Settlements and Other Developmental Activities 244 12.5.2 Excessive Extraction of Wood 245 12.5.3 Conversion of Mangrove Forests for Farming and Related Activities 245 12.5.4 Conversion of Mangrove Forests for Aquaculture 245 12.5.5 Global Warming, Climate Change, and Sea Level Rise 246 12.5.6 Limits to Landward Movement 246 12.5.7 El Niño and La Niña Events 247 12.6 Strategies for the Conservation of Mangroves 247 12.6.1 Increased and Focused Research on Understanding Mangroves 247 12.6.2 Implementation of Mangrove Conservation‐Related Laws, Guidelines, and Other Initiatives 247 12.6.3 Strengthening Conservation Mechanisms 251 12.6.4 Targeting Land Ownership‐Related Issues 251 12.6.5 Involvement of Local Communities 251 12.7 Conclusion 252 Acknowledgments 253 References 253 13 Wetland Conservation and Restoration 272 13.1 Introduction 272 13.2 Wetlands: Role and Importance 274 13.3 Wetland Loss Leading to Ecological Imbalance 275 13.4 Wetland Management Strategies: Current Status 277 13.5 Wetland Restoration and Sustainability 280 13.5.1 4th Ramsar Strategic Plan 2016–2024 (Source: Ramsar Secretariat 2016) 280 13.6 Conclusion 281 Acknowledgments 281 References 281 Index 285

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Book SynopsisALGORITHMS IN BIOINFORMATICS Explore a comprehensive and insightful treatment of the practical application of bioinformatic algorithms in a variety of fields Algorithms in Bioinformatics: Theory and Implementation delivers a fulsome treatment of some of the main algorithms used to explain biological functions and relationships. It introduces readers to the art of algorithms in a practical manner which is linked with biological theory and interpretation. The book covers many key areas of bioinformatics, including global and local sequence alignment, forced alignment, detection of motifs, Sequence logos, Markov chains or information entropy. Other novel approaches are also described, such as Self-Sequence alignment, Objective Digital Stains (ODSs) or Spectral Forecast and the Discrete Probability Detector (DPD) algorithm. The text incorporates graphical illustrations to highlight and emphasize the technical details oTable of ContentsPreface xv About the Companion Website xvii 1 The Tree of Life (I) 1 1.1 Introduction 1 1.2 Emergence of Life 1 1.2.1 Timeline Disagreements 3 1.3 Classifications and Mechanisms 4 1.4 Chromatin Structure 5 1.5 Molecular Mechanisms 9 1.5.1 Precursor Messenger RNA 9 1.5.2 Precursor Messenger RNA to Messenger RNA 10 1.5.3 Classes of Introns 10 1.5.4 Messenger RNA 10 1.5.5 mRNA to Proteins 11 1.5.6 Transfer RNA 12 1.5.7 Small RNA 12 1.5.8 The Transcriptome 13 1.5.9 Gene Networks and Information Processing 13 1.5.10 Eukaryotic vs. Prokaryotic Regulation 14 1.5.11 What Is Life? 14 1.6 Known Species 14 1.7 Approaches for Compartmentalization 15 1.7.1 Two Main Approaches for Organism Formation 16 1.7.2 Size and Metabolism 16 1.8 Sizes in Eukaryotes 16 1.8.1 Sizes in Unicellular Eukaryotes 17 1.8.2 Sizes in Multicellular Eukaryotes 17 1.9 Sizes in Prokaryotes 17 1.10 Virus Sizes 18 1.10.1 Viruses vs. the Spark of Metabolism 20 1.11 The Diffusion Coefficient 20 1.12 The Origins of Eukaryotic Cells 21 1.12.1 Endosymbiosis Theory 21 1.12.2 DNA and Organelles 22 1.12.3 Membrane-bound Organelles with DNA 23 1.12.4 Membrane-bound Organelles Without DNA 23 1.12.5 Control and Division of Organelles 24 1.12.6 The Horizontal Gene Transfer 24 1.12.7 On the Mechanisms of Horizontal Gene Transfer 25 1.13 Origins of Eukaryotic Multicellularity 26 1.13.1 Colonies Inside an Early Unicellular Common Ancestor 26 1.13.2 Colonies of Early Unicellular Common Ancestors 26 1.13.3 Colonies of Inseparable Early Unicellular Common Ancestors 1.13.4 Chimerism and Mosaicism 28 1.14 Conclusions 29 2 Tree of Life: Genomes (II) 31 2.1 Introduction 31 2.2 Rules of Engagement 31 2.3 Genome Sizes in the Tree of Life 32 2.3.1 Alternative Methods 33 2.3.2 The Weaving of Scales 33 2.3.3 Computations on the Average Genome Size 36 2.3.4 Observations on Data 38 2.4 Organellar Genomes 40 2.4.1 Chloroplasts 40 2.4.2 Apicoplasts 40 2.4.3 Chromatophores 42 2.4.4 Cyanelles 42 2.4.5 Kinetoplasts 42 2.4.6 Mitochondria 43 2.5 Plasmids 43 2.6 Virus Genomes 44 2.7 Viroids and Their Implications 46 2.8 Genes vs. Proteins in the Tree of Life 47 2.9 Conclusions 49 3 Sequence Alignment (I) 51 3.1 Introduction 51 3.2 Style and Visualization 51 3.3 Initialization of the Score Matrix 54 3.4 Calculation of Scores 57 3.4.1 Initialization of the Score Matrix for Global Alignment 57 3.4.2 Initialization of the Score Matrix for Local Alignment 62 3.4.3 Optimization of the Initialization Steps 65 3.4.4 Curiosities 66 3.5 Traceback 71 3.6 Global Alignment 75 3.7 Local Alignment 79 3.8 Alignment Layout 84 3.9 Local Sequence Alignment – The Final Version 87 3.10 Complementarity 91 3.11 Conclusions 97 4 Forced Alignment (II) 99 4.1 Introduction 99 4.2 Global and Local Sequence Alignment 100 4.2.1 Short Notes 100 4.2.2 Understanding the Technology 101 4.2.3 Main Objectives 102 4.3 Experiments and Discussions 102 4.3.1 Alignment Layout 106 4.3.2 Forced Alignment Regime 106 4.3.3 Alignment Scores and Significance 109 4.3.4 Optimal Alignments 110 4.3.5 The Main Significance Scores 110 4.3.6 The Information Content 110 4.3.7 The Match Percentage 112 4.3.8 Significance vs. Chance 113 4.3.9 The Importance of Randomness 113 4.3.10 Sequence Quality and the Score Matrix 114 4.3.11 The Significance Threshold 115 4.3.12 Optimal Alignments by Numbers 116 4.3.13 Chaos Theory on Sequence Alignment 116 4.3.14 Image-Encoding Possibilities 116 4.4 Advanced Features and Methods 117 4.4.1 Sequence Detector 117 4.4.2 Parameters 117 4.4.3 Heatmap 118 4.4.4 Text Visualization 123 4.4.5 Graphics for Manuscript Figures and Didactic Presentations 124 4.4.6 Dynamics 124 4.4.7 Independence 125 4.4.8 Limits 125 4.4.9 Local Storage 125 4.5 Conclusions 128 5 Self-Sequence Alignment (I) 129 5.1 Introduction 129 5.2 True Randomness 130 5.3 Information and Compression Algorithms 130 5.4 White Noise and Biological Sequences 131 5.5 The Mathematical Model 131 5.5.1 A Concrete Example 132 5.5.2 Model Dissection 133 5.5.3 Conditions for Maxima and Minima 136 5.6 Noise vs. Redundancy 137 5.7 Global and Local Information Content 137 5.8 Signal Sensitivity 138 5.9 Implementation 140 5.9.1 Global Self-Sequence Alignment 140 5.9.2 Local Self-Sequence Alignment 144 5.10 A Complete Scanner for Information Content 147 5.11 Conclusions 149 6 Frequencies and Percentages (II) 151 6.1 Introduction 151 6.2 Base Composition 152 6.3 Percentage of Nucleotide Combinations 152 6.4 Implementation 153 6.5 A Frequency Scanner 156 6.6 Examples of Known Significance 158 6.7 Observation vs. Expectation 160 6.8 A Frequency Scanner with a Threshold 161 6.9 Conclusions 163 7 Objective Digital Stains (III) 165 7.1 Introduction 165 7.2 Information and Frequency 166 7.3 The Objective Digital Stain 169 7.3.1 A 3D Representation Over a 2D Plane 173 7.3.2 ODSs Relative to the Background 177 7.4 Interpretation of ODSs 181 7.5 The Significance of the Areas in the ODS 183 7.6 Discussions 184 7.6.1 A Similarity Between Dissimilar Sequences 186 7.7 Conclusions 186 8 Detection of Motifs (I) 187 8.1 Introduction 187 8.2 DNA Motifs 187 8.2.1 DNA-binding Proteins vs. Motifs and Degeneracy 188 8.2.2 Concrete Examples of DNA Motifs 188 8.3 Major Functions of DNA Motifs 191 8.3.1 RNA Splicing and DNA Motifs 191 8.4 Conclusions 195 9 Representation of Motifs (II) 197 9.1 Introduction 197 9.2 The Training Data 197 9.3 A Visualization Function 198 9.4 The Alignment Matrix 200 9.5 Alphabet Detection 203 9.6 The Position-Specific Scoring Matrix (PSSM) Initialization 206 9.7 The Position Frequency Matrix (PFM) 207 9.8 The Position Probability Matrix (PPM) 208 9.8.1 A Kind of PPM Pseudo-Scanner 209 9.9 The Position Weight Matrix (PWM) 212 9.10 The Background Model 215 9.11 The Consensus Sequence 218 9.11.1 The Consensus – Not Necessarily Functional 219 9.12 Mutational Intolerance 221 9.13 From Motifs to PWMs 222 9.14 Pseudo-Counts and Negative Infinity 226 9.15 Conclusions 229 10 The Motif Scanner (III) 231 10.1 Introduction 231 10.2 Looking for Signals 232 10.3 A Functional Scanner 235 10.4 The Meaning of Scores 239 10.4.1 A Score Value Above Zero 239 10.4.2 A Score Value Below Zero 241 10.4.3 A Score Value of Zero 241 10.5 Conclusions 242 11 Understanding the Parameters (IV) 243 11.1 Introduction 243 11.2 Experimentation 243 11.2.1 A Scanner Implementation Based on Pseudo-Counts 244 11.2.2 A Scanner Implementation Based on Propagation of Zero Counts 246 11.3 Signal Discrimination 249 11.4 False-Positive Results 250 11.5 Sensitivity Adjustments 251 11.6 Beyond Bioinformatics 252 11.7 A Scanner That Uses a Known PWM 253 11.8 Signal Thresholds 256 11.8.1 Implementation and Filter Testing 258 11.9 Conclusions 262 12 Dynamic Backgrounds (V) 263 12.1 Introduction 263 12.2 Toward a Scanner with Two PFMs 263 12.2.1 The Implementation of Dynamic PWMs 264 12.2.2 Issues and Corrections for Dynamic PWMs 271 12.2.3 Solutions for Aberrant Positive Likelihood Values 274 12.3 A Scanner with Two PFMs 280 12.4 Information and Background Frequencies on Score Values 283 12.5 Dynamic Background vs. Null Model 285 12.6 Conclusions 285 13 Markov Chains: The Machine (I) 287 13.1 Introduction 287 13.2 Transition Matrices 287 13.3 Discrete Probability Detector 292 13.3.1 Alphabet Detection 292 13.3.2 Matrix Initialization 293 13.3.3 Frequency Detection 295 13.3.4 Calculation of Transition Probabilities 297 13.3.5 Particularities in Calculating the Transition Probabilities 306 13.4 Markov Chains Generators 307 13.4.1 The Experiment 308 13.4.2 The Implementation 312 13.4.3 Simulation of Transition Probabilities 315 13.4.4 The Markov machine 315 13.4.5 Result Verification 317 13.5 Conclusions 318 14 Markov Chains: Log Likelihood (II) 319 14.1 Introduction 319 14.2 The Log-Likelihood Matrix 319 14.2.1 A Log-Likelihood Matrix Based on the Null Model 320 14.2.2 A Log-Likelihood Matrix Based on Two Models 322 14.3 Interpretation and Use of the Log-Likelihood Matrix 326 14.4 Construction of a Markov Scanner 328 14.5 A Scanner That Uses a Known LLM 337 14.6 The Meaning of Scores 340 14.7 Beyond Bioinformatics 344 14.8 Conclusions 345 15 Spectral Forecast (I) 347 15.1 Introduction 347 15.2 The Spectral Forecast Model 347 15.3 The Spectral Forecast Equation 349 15.4 The Spectral Forecast Inner Workings 350 15.4.1 Each Part on a Single Matrix 351 15.4.2 Both Parts on a Single Matrix 352 15.4.3 Both Parts on Separate Matrices 353 15.4.4 Concrete Example 1 354 15.4.5 Concrete Example 2 357 15.4.6 Concrete Example 3 359 15.5 Implementations 360 15.5.1 Spectral Forecast for Signals 362 15.5.2 What Does the Value of d Mean? 364 15.5.3 Spectral Forecast for Matrices 368 15.6 The Spectral Forecast Model for Predictions 372 15.6.1 The Spectral Forecast Model for Signals 372 15.6.2 Experiments on the Similarity Index Values 381 15.6.3 The Spectral Forecast Model for Matrices 384 15.7 Conclusions 389 16 Entropy vs. Content (I) 391 16.1 Introduction 391 16.2 Information Entropy 391 16.3 Implementation 395 16.4 Information Content vs. Information Entropy 400 16.4.1 Implementation 403 16.4.2 Additional Considerations 409 16.5 Conclusions 409 17 Philosophical Transactions 411 17.1 Introduction 411 17.2 The Frame of Reference 411 17.2.1 The Fundamental Layer of Complexity 412 17.2.2 On the Complexity of Life 414 17.3 Random vs. Pseudo-random 415 17.4 Random Numbers and Noise 418 17.5 Determinism and Chaos 419 17.5.1 Chaos Without Noise 420 17.5.2 Chaos with Noise 427 17.5.3 Limits of Prediction 430 17.5.4 On the Wings of Chaos 431 17.6 Free Will and Determinism 431 17.6.1 The Greatest Disappointment 432 17.6.2 The Most Powerful Processor in Existence 433 17.6.3 Certainty vs. Interpretation 435 17.6.4 A Wisdom that Applies 436 17.7 Conclusions 439 Appendix A 441 A.1 Association of Numerical Values with Letters 441 A.2 Sorting Values on Columns 443 A.3 The Implementation of a Sequence Logo 446 A.4 Sequence Logos Based on Maximum Values 451 A.5 Using Logarithms to Build Sequence Logos 455 A.6 From a Motif Set to a Sequence Logo 459 References 467 Index 489

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Book SynopsisProvides an interdisciplinary introduction to peptide science, covering their properties and synthesis, as well as many contemporary applications Peptides are biomolecules comprised of amino acids which play an important role in modulating many physiological processes in our body. This book presents an interdisciplinary approach and general introduction to peptide science, covering contemporary topics including their applicability in therapeutics, peptide hormones, amyloid structures, self-assembled structures, hydrogels, and peptide conjugates including lipopeptides and polymer-peptide conjugates. In addition, it discusses basic properties and synthesis clearly and concisely. Taking a logical approach to the subject, Introduction to Peptide Science gives readers the fundamental knowledge that is required to understand the cutting-edge material which comes later in the book. It offers readers in-depth chapter coverage of the basic properties of peptides; synthesis; amyloid and peptTable of ContentsPreface vii 1 Basic Properties 1 1.1 Introduction 1 1.2 Properties of Amino Acids 2 1.3 The Peptide Bond 22 1.4 Secondary Structures 24 1.5 Peptide Structure and Conformation Characterization Methods 32 1.6 Peptide Databases and Web Software 39 Bibliography 43 2 Synthesis 45 2.1 Introduction 45 2.2 Solid-Phase Peptide Synthesis 46 2.3 Solution-Phase Peptide Synthesis 58 2.4 Methods to Prepare Longer Peptides 59 2.5 Peptide Library Synthesis 62 2.6 Synthesis of Cyclic Peptides 65 2.7 Peptidomimetics 69 2.8 Post-Translational Modifications 70 2.9 Lipidation 71 2.10 Glycosylation 73 2.11 Polypeptide Polymers and Conjugates of Peptides and Polymers 74 2.12 Non-Ribosomal Peptide Synthesis 80 2.13 Purification and Analysis Methods 80 Bibliography 84 3 Amyloid and Other Peptide Aggregate Structures 87 3.1 Introduction 87 3.2 Amyloid 90 3.3 Amyloid β 93 3.4 Mechanisms and Kinetics of Amyloid Aggregation 100 3.5 Toxicity and Relevance to Disease 105 3.6 Fibrillization of Small Peptides 108 3.7 Biological Functional Amyloid and Bioengineering Applications of Amyloid Materials 110 3.8 Fibrils From α-Helices 111 3.9 Peptide Hydrogels and Tissue Scaffolds 112 3.10 Peptide Nanotubes 116 3.11 Peptide and Peptide Conjugate Assemblies 119 3.12 Characterization Methods for Peptide Assemblies 124 Bibliography 130 4 Antimicrobial and Cell-penetrating Peptides 133 4.1 Introduction 133 4.2 Bacterial Pathogens, Targets of Antibacterial Agents, and Antimicrobial Resistance Pathways 134 4.3 Testing Antimicrobial Activity 139 4.4 Bacterial Biofilms 140 4.5 Design of Antimicrobial Peptides 144 4.6 Classes of Antibacterial Peptides 146 4.7 Antifungal Peptides 155 4.8 Antiviral Peptides 159 4.9 Antiparasitic Peptides 160 4.10 Mechanisms of Activity 160 4.11 Cell-Penetrating Peptides 164 Bibliography 167 5 Peptide Hormones and Peptide Therapeutics 169 5.1 Introduction 169 5.2 General Principles of Peptide Therapeutics 170 5.3 Peptide Hormones 176 5.4 Neuropeptides and other Peptides In vivo 202 5.5 Venom-Derived Peptides 204 5.6 Anticancer Peptides 207 5.7 Miscellaneous Peptide Therapeutics 212 5.8 Cosmetic Peptides and Lipopeptides 214 Bibliography 216 Index 219

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Book SynopsisNow in its second edition, Practical Statistics for Nursing and Health Care provides a sound foundation for nursing, midwifery and other health care students and early career professionals, guiding readers through the often daunting subject of statistics ''from scratch''. Making no assumptions about one''s existing knowledge, the text develops in complexity as the material and concepts become more familiar, allowing readers to build the confidence and skills to apply various formula and techniques to their own data. The authors explain common methods of interpreting data sets and explore basic statistical principles that enable nurses and health care professionals to decide on suitable treatment, as well as equipping readers with the tools to critically appraise clinical trials and epidemiology journals. Offers information on statistics presented in a clear, straightforward manner Covers all basic statistical concepts and tests, and includes workeTrade Review"The language is friendly and puts the reader at ease ....This book provides comprehensive coverage of an area that is important to all health care professionals. (Nursing Times, 28 March 2002) "...a plain English guide...to facilitate both learning and reference..." (Nurse Education Today, No.23,2003) "...helpful in enabling nurses to appraise empirical research and utilise research in their practice..." (Primary Health Care, October 2003) "...provides clear explanations of the statistical concepts and illustrates these using relevant nursing scenarios..." (Practice Nurse, Friday 16 January, 2004) "...provides a basic foundation of statistics...good resource for nurses...very user friendly..." (Oncology Nursing Forum, Vol31(2), 2004) Table of ContentsPreface xi Foreword to Students xv 1 Introduction 1 1.1 What Do we Mean by Statistics? 1 1.2 Why Is Statistics Necessary? 1 1.3 The Limitations of Statistics 2 1.4 Performing Statistical Calculations 2 1.5 The Purpose of this Text 2 2 Health Care Investigations: Measurement and Sampling Concepts 5 2.1 Introduction 5 2.2 Populations, Samples and Observations 5 2.3 Counting Things – The Sampling Unit 6 2.4 Sampling Strategy 6 2.5 Target and Study Populations 7 2.6 Sample Designs 7 2.7 Simple Random Sampling 8 2.8 Systematic Sampling 9 2.9 Stratified Sampling 9 2.10 Quota Sampling 10 2.11 Cluster Sampling 11 2.12 Sampling Designs – Summary 11 2.13 Statistics and Parameters 11 2.14 Descriptive and Inferential Statistics 12 2.15 Parametric and Non-Parametric Statistics 12 3 Processing Data 13 3.1 Scales of Measurement 13 3.2 The Nominal Scale 13 3.3 The Ordinal Scale 14 3.4 The Interval Scale 14 3.5 The Ratio Scale 15 3.6 Conversion of Interval Observations to an Ordinal Scale 15 3.7 Derived Variables 16 3.8 Logarithms 17 3.9 The Precision of Observations 18 3.10 How Precise Should We Be? 19 3.11 The Frequency Table 19 3.12 Aggregating Frequency Classes 21 3.13 Frequency Distribution of Count Observations 23 3.14 Bivariate Data 23 4 Presenting Data 25 4.1 Introduction 25 4.2 Dot Plot or Line Plot 25 4.3 Bar Graph 26 4.4 Histogram 28 4.5 Frequency Polygon and Frequency Curve 29 4.6 Centiles and Growth Charts 29 4.7 Scattergram 32 4.8 Circle or Pie Graph 32 5 Clinical Trials 35 5.1 Introduction 35 5.2 The Nature of Clinical Trials 35 5.3 Clinical Trial Designs 36 5.4 Psychological Effects and Blind Trials 37 5.5 Historical Controls 38 5.6 Ethical Issues 38 5.7 Case Study: Leicestershire Electroconvulsive Therapy Study 38 5.8 Summary 40 6 Introduction to Epidemiology 41 6.1 Introduction 41 6.2 Measuring Disease 42 6.3 Study Designs – Cohort Studies 43 6.4 Study Designs – Case-Control Studies 45 6.5 Cohort or Case-Control Study? 46 6.6 Choice of Comparison Group 46 6.7 Confounding 47 6.8 Summary 48 7 Measuring the Average 49 7.1 What Is an Average? 49 7.2 The Mean 49 7.3 Calculating the Mean of Grouped Data 51 7.4 The Median – A Resistant Statistic 52 7.5 The Median of a Frequency Distribution 53 7.6 The Mode 54 7.7 Relationship between Mean, Median and Mode 55 8 Measuring Variability 57 8.1 Variability 57 8.2 The Range 57 8.3 The Standard Deviation 58 8.4 Calculating the Standard Deviation 59 8.5 Calculating the Standard Deviation from Grouped Data 60 8.6 Variance 61 8.7 An Alternative Formula for Calculating the Variance and Standard Deviation 61 8.8 Degrees of Freedom 62 8.9 The Coefficient of Variation 63 9 Probability and the Normal Curve 65 9.1 The Meaning of Probability 65 9.2 Compound Probabilities 66 9.3 Critical Probability 67 9.4 Probability Distribution 68 9.5 The Normal Curve 69 9.6 Some Properties of the Normal Curve 70 9.7 Standardizing the Normal Curve 71 9.8 Two-Tailed or One-Tailed? 72 9.9 Small Samples: The t-Distribution 74 9.10 Are our Data Normally Distributed? 75 9.11 Dealing with ‘Non-normal’ Data 77 10 How Good Are our Estimates? 81 10.1 Sampling Error 81 10.2 The Distribution of a Sample Mean 81 10.3 The Confidence Interval of a Mean of a Large Sample 83 10.4 The Confidence Interval of a Mean of a Small Sample 85 10.5 The Difference between the Means of Two Large Samples 86 10.6 The Difference between the Means of Two Small Samples 88 10.7 Estimating a Proportion 89 10.8 The Finite Population Correction 90 11 The Basis of Statistical Testing 91 11.1 Introduction 91 11.2 The Experimental Hypothesis 91 11.3 The Statistical Hypothesis 92 11.4 Test Statistics 93 11.5 One-Tailed and Two-Tailed Tests 93 11.6 Hypothesis Testing and the Normal Curve 94 11.7 Type 1 and Type 2 Errors 95 11.8 Parametric and Non-parametric Statistics: Some Further Observations 96 11.9 The Power of a Test 97 12 Analysing Frequencies 99 12.1 The Chi-Square Test 99 12.2 Calculating the Test Statistic 99 12.3 A Practical Example of a Test for Homogeneous Frequencies 102 12.4 One Degree of Freedom – Yates’ Correction 103 12.5 Goodness of Fit Tests 104 12.6 The Contingency Table – Tests for Association 105 12.7 The ‘Rows by Columns’ (r × c) Contingency Table 108 12.8 Larger Contingency Tables 109 12.9 Advice on Analysing Frequencies 111 13 Measuring Correlations 113 13.1 The Meaning of Correlation 113 13.2 Investigating Correlation 113 13.3 The Strength and Significance of a Correlation 115 13.4 The Product Moment Correlation Coefficient 116 13.5 The Coefficient of Determination r2 118 13.6 The Spearman Rank Correlation Coefficient rs 118 13.7 Advice on Measuring Correlations 120 14 Regression Analysis 121 14.1 Introduction 121 14.2 Gradients and Triangles 121 14.3 Dependent and Independent Variables 122 14.4 A Perfect Rectilinear Relationship 123 14.5 The Line of Least Squares 125 14.6 Simple Linear Regression 126 14.7 Fitting the Regression Line to the Scattergram 128 14.8 Regression for Estimation 128 14.9 The Coefficient of Determination in Regression 129 14.10 Dealing with Curved Relationships 129 14.11 How Can We ‘Straighten Up’ Curved Relationships? 132 14.12 Advice on Using Regression Analysis 133 15 Comparing Averages 135 15.1 Introduction 135 15.2 Matched and Unmatched Observations 136 15.3 The Mann–Whitney U-Test for Unmatched Samples 136 15.4 Advice on Using the Mann–Whitney U-Test 137 15.5 More than Two Samples – The Kruskal–Wallis Test 138 15.6 Advice on Using the Kruskal–Wallis Test 140 15.7 The Wilcoxon Test for Matched Pairs 140 15.8 Advice on Using the Wilcoxon Test for Matched Pairs 143 15.9 Comparing Means – Parametric Tests 143 15.10 The z-Test for Comparing the Means of Two Large Samples 144 15.11 The t-Test for Comparing the Means of Two Small Samples 145 15.12 The t-Test for Matched Pairs 146 15.13 Advice on Comparing Means 147 16 Analysis of Variance – ANOVA 149 16.1 Why Do We Need ANOVA? 149 16.2 How ANOVA Works 149 16.3 Procedure for Computing ANOVA 151 16.4 The Tukey Test 154 16.5 Further Applications of ANOVA 155 16.6 Advice on Using ANOVA 157 Appendices Appendix A: Table of Random Numbers 159 Appendix B: t-Distribution 160 Appendix C: χ2-Distribution 162 Appendix D: Critical Values of Spearman’s Rank Correlation Coefficient 164 Appendix E: Critical Values of the Product Moment Correlation Coefficient 166 Appendix F: Mann–Whitney U-test Values (Two-Tailed Test) P =0.05 169 Appendix G: Critical Values of T in the Wilcoxon Test for Matched Pairs 170 Appendix H: F-Distribution 173 Appendix I: Tukey Test 178 Appendix J: Symbols 180 Appendix K: Leicestershire ECT Study Data: Subgroup with Depressive Illness 183 Appendix L: How Large Should Our Samples Be? 187 Bibliography 193 Index 195

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Book SynopsisDive into the most common statistical tests andsoftwarepackagesused for scientific data analysis and interpretation In Essential Statistics For Bioscientists, experienced university and bioscientist Dr Mohammed Meah delivers easyaccesstostatistical analysisand data presentation.It is a great resource for students in the field of life and health sciences to conceptualize, analyze, and presentdata. Thisbook usesthree popularand commonly usedstatisticssoftwaresMicrosoft Excel,GraphpadPrism, and SPSSand offers clear, step-by-step instructions foressentialdata analysis andgraphical/tabular display of data. Beginning withfundamentalstatistics terminology and concepts,including data types,descriptive statistics (central and spread of data), exploratory statistics (graphical display) and inferential statistics (hypothesis testing and correlation),the contentgraduallybuilds in complexity,explainingwhich statistical test is best suited and how to perform it. A thorough introduction tobasic staTable of ContentsAcknowledgements vi List of Worked Examples of Statistical Tests vii Introduction 1 1 Basic Statistics 4 2 Displaying and Exploring Sample Data Graphically 35 3 Choosing The Appropriate Statistical Test For Analysis 65 4 Inferential Statistics: Parametric Tests 79 5 Inferential Statistics: Non-parametric Tests 91 6 Using Excel: Descriptive and Inferential Statistics 101 7 Using Prism: Descriptive and Inferential Statistics 138 8 Using SPSS: Descriptive and Inferential Statistics 170 9 Misuse and Misinterpretations of Statistics 202 Appendix 1 Historical Landmarks in Statistics 208 Appendix 2 Common Statistical Terms 210 Appendix 3 Common Symbols Used in Statistics 214 Appendix 4 Standard Formulas 216 Appendix 5 How to Calculate Sample Size 218 Appendix 6 Familiarisation with GraphPad Prism 220 Appendix 7 Answers to Sample Problems 224 Appendix 8 Standard Critical Tables 229 References 243 Index 245

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Book SynopsisTable of ContentsAbout the Editors xvi List of Contributors xviii Preface xxiii Acknowledgments xxiv 1 An Introduction to Microbial Biodiversity and Bioprospection 1 Tomoya Shintani, Santosh Kumar Upadhyay, and Sudhir P. Singh 1.1 Introduction 1 1.1.1 Microorganisms 1 1.1.2 Bioprospecting 1 1.1.3 Bioprospection of Microorganisms 2 1.2 Conclusions and Perspectives 3 Acknowledgment 4 References 4 2 Application of Microorganisms in Biosurfactant Production 6 Lorena Pedraza- Segura, Luis V. Rodríguez- Durán, Gerardo Saucedo- Castañeda, and José de Jesús Cázares- Marinero 2.1 Biosurfactants Nature and Classification 6 2.2 Biosynthesis of BS by Archaea and Bacteria 12 2.3 Biosynthesis of BS by Yeasts and Molds 14 2.4 Screening for BS Producers 15 2.5 A Case Study: SL by Solid- State Fermentation (SSF), Kinetics, and Reactor Size Estimation 16 2.6 Conclusions and Perspectives 23 References 24 3 Microbial Gums: Current Trends and Applications 31 Rwivoo Baruah and Prakash M. Halami 3.1 Introduction 31 3.2 Biosynthesis of Microbial Gums 32 3.3 Production of Microbial Gums 33 3.4 Structure and Properties of Microbial Gums 34 3.5 Types of Microbial Gums 34 3.5.1 Xanthan Gum 36 3.5.2 Sphingans 36 3.5.2.1 Gellan Gum 36 3.5.2.2 Welan Gum 37 3.5.2.3 Rhamsan Gum 37 3.5.2.4 Diutan Gum 38 3.5.3 Pullulan 38 3.5.4 Other Microbial Gums 38 3.6 Applications of Microbial Gums 39 3.6.1 Food Applications 40 3.6.2 Biomedical Applications 41 3.6.3 Applications in Nanotechnology 42 3.7 Conclusions and Perspectives 42 Acknowledgments 43 References 43 4 Antiaging and Skin Lightening Microbial Products 47 Prabuddha Gupta, Ujwalkumar Trivedi, Mahendrapalsingh Rajput, Tejas Oza, Jasmita Chauhan, and Gaurav Sanghvi 4.1 Introduction 47 4.2 Aging 48 4.2.1 Structure of Skin 48 4.2.2 Skin Aging Factors 50 4.2.3 Intrinsic Skin Aging Factors 50 4.2.3.1 Anatomical and Histological Changes 50 4.2.3.2 Telomere Shortening 50 4.2.3.3 Metabolic ROS Production 51 4.2.3.4 Upregulation of Matrix Metalloproteinases 51 4.2.3.5 Mitochondrial Dysfunction 51 4.2.3.6 Mutations and Oncogenesis 51 4.3 Extrinsic Skin Aging Factors 52 4.3.1 Photoaging 52 4.3.2 Tobacco Smoking 52 4.3.3 Air Pollution 53 4.4 Why Microbes 53 4.4.1 Bacterial Compounds 54 4.4.2 Polysaccharides and Oligosaccharides 54 4.4.2.1 Hyaluronic Acid 54 4.4.2.2 Bacterial Cellulose 55 4.4.2.3 Astaxanthin and Equol 55 4.4.3 Fungi Compounds 56 4.4.3.1 Tyrosinase Inhibition 56 4.4.3.2 Hyaluronidase Inhibition 56 4.4.3.3 Collagenase and Elastase Inhibition 57 4.4.4 Algae Compounds 57 4.4.4.1 Carbohydrates from Algae 58 4.4.4.2 Fucoidan 60 4.4.4.3 Laminaran 60 4.4.4.4 Ulvans 60 4.4.4.5 Porphyran 61 4.4.4.6 Carrageenan 61 4.4.4.7 Agar 61 4.4.4.8 Alginic Acids 62 4.4.5 Pigments from Algae 62 4.4.5.1 Phycobiliproteins 62 4.4.5.2 Chlorophylls 64 4.4.5.3 Carotenoids 64 4.4.5.4 β- carotene 64 4.4.5.5 Canthaxanthins 66 4.4.5.6 Astaxanthin 66 4.4.5.7 Fucoxanthin 66 4.4.5.8 Zeaxanthin 66 4.4.5.9 Violaxanthin 66 4.4.6 Secondary Metabolites 67 4.5 Conclusions and Perspectives 67 References 68 5 Application of Microorganisms in Bioremediation 77 Himani Thakkar and Vinnyfred Vincent 5.1 Introduction 77 5.2 Microbial Bioremediation 78 5.3 Microbial Bioremediation of Organic Pollutants 79 5.3.1 Bioremediation of Alkanes 79 5.3.2 Bioremediation of Benzene, Toluene, Ethylbenzene, and Xylenes (BTEX) 80 5.3.3 Bioremediation of Polyaromatic Hydrocarbons 80 5.3.3.1 Degradation of High- Molecular- Weight Polyaromatic Hydrocarbons 83 5.3.4 Fungal Degradation of Polyaromatic Hydrocarbons 83 5.3.4.1 Bioremediation of PAHs by Ligninolytic Fungi 84 5.3.4.2 Catabolism of PAHs by Non- Ligninolytic Fungi 84 5.3.5 Bioremediation of Pesticides by Microbes 84 5.4 Microbial Degradation of Heavy Metals 87 5.5 Factors Affecting Bioremediation 89 5.5.1 Abiotic Factors 90 5.5.2 Biotic Factors 91 5.6 Advances in Bioremediation 91 5.7 Conclusions and Perspectives 94 References 95 6 Microbial Applications in Organic Acid Production 104 Jyoti Singh Jadaun, Amit K. Rai, and Sudhir P. Singh 6.1 Introduction 104 6.2 Glycolic acid (2C) 105 6.3 Acetic Acid (2C) 108 6.4 Pyruvic Acid (3C) 108 6.5 Lactic Acid (3C) 109 6.6 Succinic Acid (4C) 109 6.7 Fumaric Acid (4C) 110 6.8 Malic Acid (4C) 111 6.9 Itaconic Acid (5C) 112 6.10 Gluconic Acid (6C) 113 6.11 Citric Acid (6C) 114 6.12 Kojic Acid (6C) 114 6.13 Muconic and Adipic Acid (C6) 115 6.14 Conclusions and Perspectives 117 Acknowledgments 117 References 117 7 Production of Bioactive Compounds vs. Recombinant Proteins 125 Maria F. Salazar Affonso, Débora Bublitz Anton, Daniel Kuhn, Bruno Dahmer, Camile Wünsch, Verônica Contini, Luís F. Saraiva Macedo Timmers, Claucia F. Volken de Souza, Márcia I. Goettert, and Rodrigo G. Ducati 7.1 Introduction 125 7.2 In vitro Cell-Based Assays 126 7.3 Cell Viability Assays 127 7.4 Cell Metabolic Assays 127 7.5 Cell Survival Assays 128 7.6 Cell Transformation Assays 129 7.7 Cell Irritation Assays 129 7.8 Heterologous Expression of Recombinant Proteins of Biomedical Relevance 130 7.9 Lactic Acid Bacteria and the Production of Metabolites with Therapeutic Roles 132 7.10 Preclinical Studies 134 7.10.1 Acute Toxicity 135 7.10.2 Repeated Dose Toxicity 136 7.10.3 Genotoxicity 136 7.10.4 Carcinogenicity 136 7.10.5 Reproductive Toxicity 137 7.11 Computer-aided Drug Design 137 7.12 Conclusions and Perspectives 140 References 140 8 Microbial Production of Antimicrobial and Anticancerous Biomolecules 147 M. Indira, T. C. Venkateswarulu, S. Krupanidhi, and K. Abraham Peele 8.1 Introduction 147 8.2 Microbial Sources 148 8.2.1 Bacteria 148 8.2.2 Fungi 149 8.2.3 Actinomycetes 150 8.2.4 Extremophiles 150 8.3 Microbial Bioprospecting Methods 151 8.3.1 Cultural Bioprospecting 151 8.3.2 Nonculturable Microorganism’s Bioprospecting 152 8.3.3 In Silico Bioprospecting of Microorganisms 152 8.4 Bioactive Compounds 153 8.4.1 Antibiotics 155 8.4.2 Bacteriocins 155 8.4.3 Biosurfactants 156 8.4.4 Exopolysaccharides 156 8.4.5 Enzymes 157 8.4.6 Biopolymers 158 8.4.7 Bioenergy Compounds 158 8.4.8 Anticancer Compounds 158 8.5 Future Prospects 160 8.6 Conclusions and Perspectives 160 Acknowledgments 161 References 161 9 Microbial Fuel Cells and Plant Microbial Fuel Cells to Degradation of Polluted Contaminants in Soil and Water 170 Chung-Yu Guan and Chang-Ping Yu 9.1 Introduction 170 9.2 History 172 9.3 Electricigens 173 9.3.1 Electricigens of Bacteria 173 9.3.2 Electrocigens of Fungi 175 9.4 Electron Generation and Transfer Mechanisms of Electricigens 175 9.4.1 Electron Generation Mechanism 175 9.4.2 Electron Transfer Mechanism 175 9.4.3 Biofilm Mechanism 176 9.4.4 Electron Shuttle Mechanism 176 9.4.5 Electron Transfer by Exogenous Mediators 176 9.4.6 Microbial Secondary Metabolites for Electron Transfer 177 9.4.7 Oxidation of Reduced Primary Metabolites 177 9.5 Materials 177 9.5.1 Anode Materials 177 9.5.2 Base Materials of the Anode 177 9.5.3 The Modification of Anode Materials 178 9.5.4 Cathode Materials 179 9.5.5 Carbon-Based Materials of Cathodes 179 9.5.6 Non-Carbon-Based Materials 179 9.5.7 Cathode Catalyst 180 9.5.8 Biocathode 181 9.5.9 Separator Materials 181 9.5.9.1 Conventional Separator Materials 181 9.5.9.2 New Separator Materials 181 9.6 Design and Operation of Bioelectrochemical Systems 182 9.6.1 MFC Configuration 182 9.6.1.1 Two-Compartment MFCs 182 9.6.1.2 Air Cathode MFC 184 9.6.1.3 Other Configurations 185 9.6.2 Soil MFC and PMFC Configurations 185 9.6.2.1 Dual-Chamber of Soil MFCs and PMFCs 185 9.6.2.2 Single-Chamber MFCs 186 9.6.2.3 Air-Diffusion Cathode System 186 9.6.2.4 Other Configuration of PMFCs 187 9.7 Performances of the MFCs in Actual Wastewater Treatment 187 9.7.1 Industrial Wastewater 187 9.7.2 Domestic and Livestock Wastewater 188 9.8 Soil MFCs for Soil Remediation 189 9.8.1 Remediation of Organic Contaminated Soils 189 9.8.2 Remediation of Heavy Metal Contaminated Soils 189 9.9 PMFCs for Environmental Remediation 190 9.9.1 PMFCs for Wastewater Treatment 190 9.9.2 PMFCs for Soil Remediation 190 9.10 Prospectives 191 9.11 Conclusions 191 References 192 10 Microalgae- Based UV Protection Compounds 201 Jorge Alberto Vieira Costa, Juliana Botelho Moreira, Gabrielle Guimarães Izaguirres, Liliane Martins Teixeira, and Michele Greque de Morais 10.1 Introduction 201 10.2 UV Radiation 202 10.3 Protection Compounds Induced by UV Radiation 202 10.3.1 Mycosporine- Like Amino Acids 203 10.3.2 Phenolic Compounds 203 10.3.3 Carotenoids 203 10.3.4 Phycocyanin 204 10.3.5 Polyamines 204 10.3.6 Scytonemin 205 10.4 Microalgal Biotechnology for the Production of Photoprotective Compounds 206 10.5 Effects of UV Radiation on the Growth, Morphology, and Production of Lipids, Proteins, and Carbohydrates 209 10.6 Extraction Methods of Photoprotective Compounds 211 10.7 Prospects for Commercial Applications 213 10.8 Conclusion and Perspectives 215 References 215 11 Microorganisms as a Potential Source of Antioxidants 225 Ayerim Hernández-Almanza, Nathiely Ramírez-Guzman, Gloria A. Martínez-Medina, Araceli Loredo-Treviño, Deepak Kumar Verma, and Cristobal N. Aguilar 11.1 Introduction 225 11.2 Antioxidant-Producing Microorganisms 225 11.3 Production of Some Microbial Antioxidants and Their Action Mechanisms 226 11.3.1 Peptides 226 11.3.2 Pigments 227 11.3.3 Polyphenols 229 11.4 Extraction and Purification of Microbial Antioxidants 230 11.4.1 Extraction of Microbial Antioxidants 230 11.4.2 Purification of Microbial Antioxidants 231 11.5 Evaluation of Antioxidant Activity 231 11.5.1 Classical Methods 232 11.5.2 Cellular Methods 234 11.6 Conclusions and Perspectives 235 References 236 12 Microbial Production of Biomethane from Digested Waste and Its Significance 242 Arun Kumar Pal, Vijay Tripathi, Prashant Kumar, and Pradeep Kumar 12.1 Introduction 242 12.2 Methane 243 12.2.1 Source of Methane 243 12.2.1.1 Industry 244 12.2.1.2 Agriculture 244 12.2.1.3 Waste 244 12.2.2 Biomethane 245 12.3 Types of Waste 245 12.3.1 Biological Waste 247 12.3.2 Household Waste 247 12.3.3 Agricultural Waste 248 12.4 Digestion Processes of Organic Wastes 248 12.4.1 Hydrolysis of Organic Waste 248 12.4.2 Acidogenesis of Hydrolyzed Matter 249 12.4.3 Acetogenesis 249 12.4.3.1 Methanogenesis 250 12.5 Conclusions and Perspectives 250 Acknowledgments 250 Conflicts of Interest 250 References 250 13 Enzymatic Biosynthesis of Carbohydrate Biopolymers and Uses Thereof 254 Manisha Sharma, Jyoti Singh Jadaun, Santosh Kumar Upadhyay, and Sudhir P. Singh 13.1 Introduction 254 13.2 Dextran 255 13.2.1 Mechanism of Dextran Production 255 13.2.2 Production of Dextran at Industrial Level 255 13.2.3 Applications of Dextran 256 13.3 Chitin and Chitosan 256 13.3.1 Biological Extraction of Chitin 257 13.3.1.1 Biosynthesis of Chitin and Chitosan 257 13.3.1.2 Chitin and Chitosan- Producing Fungi 257 13.3.1.3 Enzymatic Deproteinization 257 13.3.1.4 Fermentation 259 13.3.1.5 Enzymatic Deacetylation 259 13.3.2 Applications of Chitin and Chitosan 259 13.4 Xanthan Gum 260 13.4.1 Xanthan Gum Production 260 13.4.2 Microbial Production 261 13.4.3 Applications of Xanthan Gum 261 13.5 Bacterial Cellulose 261 13.5.1 Biosynthetic Pathway for Cellulose Production 261 13.5.2 Cellulose Precursor 262 13.5.3 Microbial Source for Cellulose Production 262 13.5.4 Applications of Cellulose 263 13.6 Levan 263 13.6.1 Levan Producing Organism 264 13.6.2 Mechanism for Levan Biosynthesis 264 13.6.3 Strategies for Levan Production 265 13.6.4 Applications of Levan 265 13.7 Conclusions and Perspectives 266 Acknowledgments 266 References 266 14 Polysaccharides from Marine Microalgal Sources 278 Ratih Pangestuti, Evi Amelia Siahaan, Yanuariska Putra, and Puji Rahmadi 14.1 Introduction 278 14.2 Polysaccharides from Marine Microalgae 279 14.2.1 Subcritical Water Hydrolysis 280 14.2.2 Ultrasonic- Aided Extraction 281 14.2.3 Microwave- Assisted Extraction 282 14.2.4 Enzyme- Assisted Extraction 282 14.3 Optimization of Microalgae Culture Conditions 282 14.4 Bioactivities and Potential Health Benefits 285 14.4.1 Antiviral Activity 285 14.4.2 Antioxidant 286 14.4.3 Anticancer 287 14.4.4 Immunomodulatory 288 14.5 Conclusions and Perspectives 288 Acknowledgment 288 References 289 15 Microbial Production of Bioplastic: Current Status and Future Prospects 295 Karishma Seem 15.1 Introduction 295 15.2 General Structure of PHA 297 15.3 Physical Properties 298 15.4 Biodegradability of PHA 298 15.5 Biosynthesis of PHA 299 15.6 Challenges of Scaling Up of PHA Production on an Industrial Scale 300 15.6.1 Renewable Sources as Feedstock for PHA Production 300 15.6.1.1 Food Processing and Agricultural Industries Discharge 300 15.6.1.2 Glycerol 301 15.6.1.3 Agro- Industrial Oily Wastes 301 15.6.2 Cyanobacteria 302 15.6.3 Bacteria from Extreme Niches 303 15.6.3.1 Halophilic Bacteria 303 15.6.3.2 Thermophiles for PHA 304 15.6.3.3 Psycrophiles for PHA 304 15.7 Co- synthesis of PHA with Value- Added Products 304 15.8 Blends of PHA 305 15.9 Applications of PHA 306 15.9.1 Biomedical Applications 306 15.9.2 Soft Tissue Implants 307 15.9.3 Esophagus, Pericardial Patches 307 15.9.4 Heart Valve Tissue Engineering 307 15.9.5 Nerve Regeneration 308 15.9.6 Drug Delivery System 308 15.10 Conclusions and Perspectives 309 References 309 16 Microbial Enzymes for the Mineralization of Xenobiotic Compounds 319 Ankita Chatterjee, Pritha Chakraborty, and Jayanthi Abraham 16.1 Introduction 319 16.2 Major Pollutants and Their Removal with White- Rot Fungi 320 16.2.1 Pesticides 320 16.2.2 Polychlorinated Biphenyls 321 16.2.3 Polycyclic Aromatic Hydrocarbons 321 16.2.4 Synthetic Dyes 322 16.2.5 Synthetic Polymers 322 16.2.6 Phenolic Compounds 322 16.2.7 Petroleum Hydrocarbons 323 16.3 Enzyme System of White- Rot Fungi 323 16.3.1 Laccase 323 16.3.1.1 Mechanisms 327 16.3.2 Lignin Peroxidase 328 16.3.3 Manganese Peroxidase 329 16.3.3.1 Mechanism 329 16.3.4 Other Enzymes 330 16.4 Molecular Aspect 330 16.5 Conclusions and Perspectives 331 Acknowledgement 331 Compliance with Ethical Guidelines 332 References 332 17 Functional Oligosaccharides and Microbial Sources 337 SA Belorkar 17.1 Introduction 337 17.1.1 What Are Functional Foods? All You Need to Know 338 17.2 Inulin and Oligofructose: The Preliminary Functional Oligosaccharides 339 17.3 GRAS and FOSHU Status 339 17.4 Conventional and Upcoming Oligosaccharides 339 17.5 Microbes and Functional Oligosaccharides 340 17.6 Arabinoxylo- Oligosaccharides 340 17.7 Sources and Properties 341 17.8 Approaches for AXOS Production 341 17.9 Isomaltooligosaccharides 342 17.10 Sources and Properties 343 17.11 Production of IMO 344 17.12 Approaches to Improve IMO Production 344 17.13 Lactosucrose 345 17.14 Novel Approaches in Lactosucrose Preparation 347 17.15 Xylooligosaccharides 347 17.16 Occurrence and Properties 348 17.17 Approaches to Improve the Efficiency of XOS 349 17.18 Conclusions and Perspectives 349 References 350 18 Algal Biomass and Biofuel Production 357 Suman Sanju, Aditi Thakur, Pragati Misra, and Pradeep Kumar Shukla 18.1 Introduction 357 18.2 Biofuels 357 18.2.1 First-Generation Biofuels 358 18.2.2 Second-Generation Biofuels 358 18.2.3 Third-Generation Biofuels 359 18.3 Algae: The Biomass 359 18.4 Microalgae as Biofuel Biomass 360 18.5 Microalgae Culture Systems 362 18.5.1 Open Algal Systems 362 18.5.2 Closed Algal Systems 363 18.5.3 Hybrid Algal Systems 363 18.6 Microalgae Harvesting 364 18.7 Processing and Extraction of Components 364 18.8 Biofuel Conversion Processes 364 18.8.1 Transesterification 365 18.8.2 Biochemical Methods 366 18.8.2.1 Fermentation 366 18.8.2.2 Anaerobic Digestion 366 18.8.3 Thermochemical Conversions 367 18.8.3.1 Gasification 367 18.8.3.2 Pyrolysis 367 18.8.3.3 Liquefaction 368 18.8.4 Direct Combustion 368 18.9 Microalgal Biofuels 368 18.9.1 Biodiesel 368 18.9.2 Bioethanol 369 18.9.3 Biogas 370 18.9.4 Bio-Oil and Bio-Syngas 370 18.9.5 Biohydrogen 371 18.10 Conclusions and Perspectives 371 References 371 19 Microbial Source of Insect- Toxic Proteins 377 Tripti Yadav and Geetanjali Mishra 19.1 Introduction 377 19.2 Fungi 378 19.3 Bacteria 384 19.4 Virus 386 19.5 Conclusions and Perspectives 387 References 388 20 Recent Trends in Conventional and Nonconventional Bioprocessing 404 Saswata Goswami, Keyur Raval, Anjana, and Priyanka Bhat 20.1 Advances in Conventional Bioprocessing 404 20.1.1 The Stirred- Tank Bioreactor Systems 407 20.2 Nonconventional Bioprocessing 409 20.2.1 Wave Bioreactors 409 20.2.2 Orbital Shaken Bioreactors 410 20.2.3 Stirred Tank Bioreactors 411 20.3 Brief Note on the Recent Trends in Downstream Bioprocessing 413 20.4 Perfusion Culture for Bioprocess Intensification 413 20.5 Conclusions and Perspectives 416 References 416 Index 418

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Book SynopsisDENTAL NEUROIMAGING Provides the latest neuroimaging-based evidence on the brain mechanisms of oral functions Dental Neuroimaging: The Role of the Brain in Oral Functions provides an up-to-date overview of neuroimaging research on the neural mechanisms underlying mastication, swallowing, sensory processing, and other oral topics. Divided into three parts, the book first introduces the theoretical framework of the brain-stomatognathic axis, clinical assessments for oral function, and neuroimaging methods. The second part presents recent neuroimaging findings of oral sensory and motor functions such as somatosensation, gustation, and orofacial pain and anxiety. The book concludes with a review of recent translational research and discussion of the application of neuroimaging in clinical management. Throughout the text, boxed sections highlight key information about cognitive neuroscience, imaging techniques, interpreting neuroimaging results, and relating reTable of ContentsList of Figures x List of Tables xviii List of Boxes xx List of Abbreviations xxi Preface xxiii Introduction to Students and Instructors xxiv Acknowledgements xxv About the Companion Website xxvi Part I Methods of Neuroimaging and Assessment of Oral Functions 1 1 Introduction to Neuroimaging and the Brain–Stomatognathic Axis 3 1.1 Why Do Dentists Need to Understand the Brain? 3 1.2 What Is Neuroimaging? 6 1.3 How Does Neuroimaging Contribute to Clinical Practice? 15 1.4 The Brain–Stomatognathic Axis 17 Further Readings 21 References 22 2 Assessment of Human Brain Using MRI 25 2.1 Advantages and Limitations of Magnetic Resonance Imaging of the Brain 25 2.2 Research of Task- based Functional Activation 30 2.3 Research of Structural Features of the Brain 39 2.4 Research of Brain Connectivity 45 Further Readings 56 References 56 3 Assessment of Oral Functions 59 3.1 Assessment of Masticatory and Swallowing Performance 59 3.2 Assessment of Orofacial Pain and Somatosensory Experience 68 3.3 Assessment of Cognitive Functions and Emotional Experience 77 Further Readings 81 References 81 Part II Neuroimaging Research of Brain Mechanisms of Oral Functions 89 4 Brain Mechanisms of Oral Motor Functions 91 4.1 Introduction of Brain Mechanisms of Motor Control 91 4.2 Brain Mechanisms of Human Mastication 98 4.3 Brain Mechanisms of Human Swallowing 109 4.4 Cognitive Processing and Motor Learning of Oromotor Movement 116 Further Readings 120 References 121 5 Brain Mechanisms of Oral Sensory Functions 128 5.1 Brain Mechanisms of Oral Somatosensory Processing 128 5.2 Brain Mechanisms of Gustation 136 5.3 Cognitive–Affective Issues of Oral Sensory Functions 141 5.4 Brain Mechanisms of Multisensory Integration 149 Further Readings 154 References 154 6 Brain Mechanisms of Pain and Anxiety of Dental Patients 161 6.1 Brain Mechanisms Related to Pain 161 6.2 Chronic Pain, Neural Plasticity and Central Sensitization 170 6.3 Brain Mechanisms of Chronic Orofacial Pain 178 6.4 Brain Mechanisms of Dental Fear and Anxiety 191 Further Readings 199 References 200 Part III Translational Research of Dental Neuroimaging 213 7 Age- related Differences in the Brain–Stomatognathic Axis 215 7.1 Age- related Differences in Brain Mechanisms 215 7.2 Age- related Changes in Oral Sensorimotor Functions 220 7.3 Association Between the Brain and Oral Functions in Older People 229 7.4 Association Between Oral Conditions and Neurodegenerative Disorders 235 Further Readings 245 References 245 8 Brain Mechanisms of Adaptation of Oral Sensorimotor Functions 254 8.1 Brain Plasticity and Adaptation 254 8.2 Adaptation of Pain and Oral Sensory Functions 260 8.3 Functional Adaptation of Mastication and Swallowing 266 8.4 Brain Plasticity Associated with Oral Functional Training 271 Further Readings 275 References 275 9 A Synthesis Between Neuroimaging and Oral Healthcare 281 9.1 Assessment of Individual Differences in Brain–Stomatognathic Axis 281 9.2 Future Direction of Neuroimaging in Oral Neuroscience 287 Further Readings 290 References 290 Index 292

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Book SynopsisMolecular Fluorescent Sensors for Cellular Studies Enables readers to fully understand the fundamentals and chemical principles of fluorescent sensing and the design of fluorescent sensors Fluorescent sensors are able to provide specific chemical information about cells and can be invaluable in understanding processes that underpin health and disease. Molecular Fluorescent Sensors for Cellular Studies provides an avenue into and overview of currently available fluorescent sensing technology and its application to biological imaging. This book aims to help the reader understand the principles of fluorescence and the mechanisms by which fluorescent sensors operate in order to ensure appropriate and optimal use of sensors. Key applications of fluorescent sensing are presented, with explanations not only of how new sensors can be designed, but also how existing sensors can be applied to various biological settings and conditions. Clear and engaging schematics throughout the book explainTable of ContentsList of Contributors ix 1 An Introduction to Small Molecule Fluorescent Sensors 1 Liam D. Adair, Kylie Yang, and Elizabeth J. New 1.1 What is Fluorescence? 1 1.2 Why Is Fluorescence Useful? 3 1.3 What Is a Fluorescent Sensor? 4 1.4 General Types of Fluorescent Sensors 5 1.5 Important Parameters 7 1.5.1 Excitation Maxima 7 1.5.2 Emission Maxima 8 1.5.3 Stokes Shift 8 1.5.4 Quantum Yield 9 1.5.5 Molar Extinction Coefficient 9 1.5.6 Brightness 10 1.5.7 Lifetime 10 1.5.8 Photobleaching 11 1.5.9 Anisotropy 12 1.5.10 Quenching 12 1.6 Fluorescence Mechanisms Used in Fluorescent Sensors 13 1.6.1 Photoinduced Electron Transfer 13 1.6.2 Internal Charge Transfer 14 1.6.3 Förster Resonance Energy Transfer 15 1.6.4 Through Bond Energy Transfer 17 1.6.5 Excited- State Intramolecular Proton Transfer 18 1.6.6 Aggregation- Induced Emission 19 1.6.7 Excimer Formation 21 1.7 Commonly Used Fluorophores 21 1.7.1 Fluorescein 22 1.7.2 Rhodamine 24 1.7.3 Coumarin 26 1.7.4 Naphthalimide 26 1.7.5 BODIPY (4,4- Difluoro4- bora- 3a,4a- diaza- s- indacene) 27 1.7.6 Cyanine 28 1.8 Summary 30 References 30 2 The Applications of Responsive Fluorescent Sensors to Biological Systems 37 Jia Hao Yeo and Elizabeth J. New 2.1 Criteria for Biologically Relevant Fluorescent Sensors 37 2.2 Microscopy for Visualising Fluorescent Sensors 39 2.2.1 Important Considerations in Microscopy 39 2.2.1.1 Resolution in Microscopy 39 2.2.1.2 Understanding the Competition Between True Signal and Noise 41 2.2.1.3 Phototoxicity in Cells 42 2.2.2 Common Microscopy Techniques 43 2.2.2.1 Fluorescence Microscopy 43 2.2.2.2 Confocal Microscopy 44 2.2.2.3 Multiphoton Microscopy 45 2.2.2.4 Fluorescence Lifetime Imaging Microscopy 45 2.2.2.5 Other Advanced Microscopy Techniques 47 2.3 Other Instrumental Techniques for Studying Cells Treated with Fluorescent Sensors 49 2.3.1 Flow Cytometry 49 2.3.1.1 Principles of Flow Cytometry 49 2.3.1.2 Understanding Flow Cytometry Data with Small- molecule Sensors 50 2.3.1.3 Recent Advances in Flow Cytometry 51 2.3.2 Fluorescence Plate- readers 51 2.3.2.1 Standard Plate- reader Assays 51 2.3.2.2 High- content Imaging (HCI) Plate- readers 52 2.4 Biological Samples to Which Fluorescent Sensors Can Be Applied 52 2.4.1 Cultured Mammalian Cells 52 2.4.1.1 Adherent Mammalian Cells 53 2.4.1.2 Non- adherent Cells 53 2.4.1.3 Multi- cellular Models 54 2.4.2 Bacteria 54 2.4.3 Plants 54 2.4.4 Multi- cellular Organisms 55 2.4.5 Towards In Vivo Imaging 55 2.5 Common Challenges and Misconceptions in the Applications of Fluorescent Sensors 56 2.5.1 Important Considerations in Applying Sensors 56 2.5.2 Common Misconceptions About the Use of Sensors – The Bridge Between Multiple Disciplines 57 2.6 Conclusions 60 References 60 3 Methods to Control the Subcellular Localisation of Fluorescent Sensors 63 Jiarun Lin, Kylie Yang, and Elizabeth J. New 3.1 Introduction 63 3.2 Targeting the Nucleus 64 3.3 Targeting Mitochondria 66 3.4 Targeting Lysosomes 67 3.5 Targeting Endosomes 69 3.6 Targeting Autophagic Compartments 70 3.7 Targeting Peroxisomes 70 3.8 Targeting the Endoplasmic Reticulum 71 3.9 Targeting the Golgi Apparatus 72 3.10 Targeting Lipid Droplets 73 3.11 Targeting the Plasma Membrane 74 3.12 Targeting the Cytoskeleton 75 3.13 Targeting the Cytosol 76 3.14 Trapping and Accumulation of Sensors 76 References 77 4 Recognition- based Sensors for Cellular Imaging 83 Amy A. Bowyer, Jianping Zhu, and Elizabeth J. New 4.1 Considerations for Recognition- based Sensing 83 4.1.1 Receptor–Analyte Recognition and Binding Affinity 84 4.1.1.1 Defining Binding Affinity 85 4.1.1.2 Measuring Binding Stoichiometries and Binding Affinity 85 4.1.2 Key Considerations to Enhance Selective Receptor to Analyte Recognition 87 4.1.2.1 Size 88 4.1.2.2 The Chelate Effect 88 4.1.2.3 Hard–Soft Acid–Base Theory 89 4.1.2.4 Crystal and Ligand Field Theory 89 4.2 Recognition- based Cation Sensing 91 4.2.1 Group I and II Metal Sensing 92 4.2.1.1 The Biological Significance of Group I and II Metals 92 4.2.1.2 Receptor Group Design for Group I and II Metals 93 4.2.2 Essential Transition Metal Sensing 98 4.2.2.1 The Biological Significance of Essential Transition Metals 98 4.2.2.2 Receptor Group Design for Essential Transition Metals 99 4.2.3 Toxic Metal Sensing 107 4.2.3.1 The Biological Significance of Toxic Metals 107 4.2.3.2 Receptor Group Design for Toxic Metals 108 4.3 Recognition- based Anion Sensing 110 4.3.1 Anion Sensing Approaches 110 4.3.1.1 Hydrogen Bonding 110 4.3.1.2 Displacement Approach 111 4.3.1.3 Metal Coordination 112 4.3.2 Halogen Ions Sensing 113 4.3.2.1 The Biological Role of Halogen Ions 113 4.3.2.2 Recognition- based Fluorescent Sensors for Halogen Ions 113 4.3.3 Inorganic Phosphates and Pyrophosphates 114 4.3.3.1 The Biological Role of Inorganic Phosphates and Pyrophosphates 114 4.3.3.2 Sensors for Inorganic Phosphates 115 4.3.3.3 Sensors for Inorganic Pyrophosphate 116 4.3.4 Bicarbonate, Hydrogen Sulfate, and Nitrate 120 4.3.4.1 The Biological Roles of Bicarbonate, Hydrogen Sulfate, and Nitrate 120 4.3.4.2 Sensors for Bicarbonate, Hydrogen Sulfate, and Nitrate 121 4.4 Conclusions 123 References 123 5 Activity- based Fluorescent Sensors and Their Applications in Biological Studies 129 Liam D. Adair, Nian Kee Tan, and Elizabeth J. New 5.1 Introduction 129 5.1.1 Design Principles 130 5.2 Oxidation Reactions for Sensing Oxidative Species 131 5.2.1 Fluorescent Sensors for Hydrogen Peroxide 131 5.2.2 Fluorescent Sensors for Peroxynitrite 134 5.2.3 Fluorescent Sensors for Hypochlorous Acid 136 5.2.4 Fluorescent Sensors for Nitric Oxide 137 5.2.5 Fluorescent Sensors for Singlet Oxygen 138 5.3 Reduction Reactions for Sensing Reductive Species 140 5.3.1 Fluorescent Sensors for Hydrogen Sulfides 140 5.3.2 Fluorescent Sensors for Glutathione, Cysteine, and Homocysteine 141 5.3.3 Fluorescent Sensors for Selenocysteine 144 5.4 Reactions for Sensing Carbonyl Species 145 5.4.1 Fluorescent Sensors for Formaldehyde 145 5.4.2 Fluorescent Sensors for Methylglyoxal 146 5.5 Metal- mediated Reactions 148 5.6 Metal- sensing Reactions 149 5.7 Enzymatic Reactions 155 5.8 Reversible Reactions 159 5.8.1 Nucleophilic Conjugate Additions 159 5.8.2 Nucleophilic Addition 162 5.8.3 Imine Formation 162 5.8.4 Oxidation–Reduction Reactions 163 5.9 Analyte Regeneration 164 5.10 Summary 166 References 166 6 Fluorescent Sensors of the Cellular Environment 173 Nian Kee Tan, Jianping Zhu, and Elizabeth J. New 6.1 Fluorescent Sensors for Polarity and Viscosity 173 6.1.1 The Biological Significance of Polarity and Viscosity 173 6.1.2 Twisted Intramolecular Charge Transfer as a Mechanism for Polarity and Viscosity Sensing 174 6.1.2.1 TICT- based Viscosity Sensors 176 6.1.2.2 TICT- based Polarity Sensors 178 6.1.3 Polarity Sensors Based on Other Mechanisms 178 6.1.3.1 Polarity Sensors Based on Intramolecular Charge Transfer Mechanism 178 6.1.3.2 Polarity Sensors Based on Excited- state Intramolecular Proton Transfer Mechanism 180 6.1.3.3 Polarity Sensors Based on Photoinduced Electron Transfer Mechanism 180 6.2 Fluorescent Sensors for pH 181 6.2.1 The Regulation of pH in Health and Disease 181 6.2.2 Considerations and Design Strategies for the Preparation of pH Sensors 182 6.2.2.1 Methods to Control pK a 183 6.2.3 Examples of pH Sensors 185 6.2.3.1 Photoinduced Electron Transfer as a Mechanism for Sensing 185 6.2.3.2 The Ring Opening of Rhodamines as a Mechanism for pH Sensing 187 6.2.3.3 Intramolecular Charge Transfer as a Mechanism for Ratiometric pH Sensing 188 6.2.3.4 pH Sensors Based on Addition Reactions 189 6.3 Fluorescent Redox Sensors for Biological Studies 190 6.3.1 The Regulation of Redox State in Health and Disease 190 6.3.2 Design Strategies of Fluorescent Redox Sensors and Key Examples 191 6.3.2.1 Redox Sensors Based on the Nitroxyl Radical/Hydroxylamine Redox Couple 191 6.3.2.2 Redox Sensors Based on the Quinone/Hydroquinone Redox Couple 192 6.3.2.3 Redox Sensors Based on Chalcogens 193 6.3.2.4 Redox Sensors Based on Flavins and Nicotinamides 194 6.4 Conclusions 196 References 197 7 Labelling Proteins and Biomolecules with Small Fluorescent Sensors 201 Joy Ghrayche, Marcus E. Graziotto, Paris I. Jeffcoat, and Elizabeth J. New 7.1 Labelling Biomolecules in Cells with Fluorescent Sensors 201 7.2 Small- molecule Modifications and Bioorthogonal Reactions 204 7.2.1 Polar Ketone and Aldehyde Condensations 204 7.2.2 Azide Bioorthogonal Chemistry 205 7.2.2.1 Staudinger Ligations 206 7.2.2.2 Copper Azide–Alkyne Cycloadditions 208 7.2.2.3 Strain- promoted Cycloadditions 208 7.2.2.4 Fluorogenic Dyes for Azide–Alkyne Labelling 209 7.2.3 Tetrazine Ligation 210 7.2.4 Commercial Fluorescent Labels 215 7.3 Short peptide Recognition Sequences 215 7.4 Fusion Protein Tagging Systems 218 7.4.1 FKBP Tag 219 7.4.2 eDHFR Tag 220 7.4.3 PYP Tag 223 7.4.4 SNAP- Tag and CLIP- Tag 225 7.4.5 HaloTag 229 7.5 Enzymatic Modifications for Labelling Proteins 230 7.5.1 The LAP- tag System 230 7.5.2 Protein Trans- splicing 233 7.6 Future Developments 235 References 235 8 Future Directions of Fluorescence Sensors for Cellular Studies 241 Jiarun Lin, Natalie Trinh, and Elizabeth New 8.1 Fluorescence Lifetime Imaging Microscopy 241 8.1.1 Introduction 241 8.1.2 Advantages of Fluorescence Lifetime Imaging Microscopy 242 8.1.3 Examples of Sensors for FLIM 242 8.1.3.1 Endogenous Sensors 242 8.1.3.2 Exogenous Sensors 243 8.1.4 Future Directions 245 8.2 Near- infrared Sensors 246 8.2.1 Strategies to Make NIR Sensors 247 8.2.2 NIR Fluorophore Scaffolds 247 8.2.2.1 Cyanine Dyes and Their Derivatives 247 8.2.2.2 BODIPY Dyes 250 8.2.2.3 Squaraine Dyes 250 8.2.2.4 Other Dye Scaffolds 251 8.2.3 Future Directions 252 8.3 Dual- analyte Sensing 252 8.3.1 Introduction 252 8.3.2 Reversible Dual- analyte Sensors 254 8.3.3 Reaction Dual- analyte Sensors 255 8.3.4 Mixed Dual- analyte Sensors 255 8.3.5 Sequence- specific Reactions 256 8.3.6 Conclusions and Future Directions 257 8.4 Super- resolution Microscopy 258 8.4.1 Introduction 258 8.4.2 Super- resolution Microscopy Techniques 258 8.4.3 Considerations for Use of Super Resolution Microscopy 262 8.4.4 Fluorescent Sensors for Super- resolution Microscopy 263 8.4.5 Future Directions 265 8.5 Multimodality 267 8.5.1 Introduction 267 8.5.2 Radioisotope Techniques 267 8.5.3 Computed Tomography 269 8.5.4 Magnetic Resonance Imaging 269 8.5.5 Photoacoustic Imaging 271 8.5.6 Vibrational Spectroscopy 271 8.5.7 Synchrotron X- ray Techniques 273 8.5.8 Mass Spectrometry 273 8.5.9 Electron Microscopy 274 8.5.10 Three or More Modalities 276 8.5.11 Future Directions 277 References 278 Index 285

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Book SynopsisA guide to thescientificinterpretation of blood traces Blood Tracesprovides anauthoritative resource that reviews many of the aspects of the interpretation of blood traces that have not been treated with the thoroughness they deserve. With strict adherence to the scientific method, the authorsnoted experts on the topicaddressthe complexitiesencountered wheninterpretingblood trace configurations. The bookprovides an understanding of the scientific basis for the use of blood trace deposits,i.e.bloodstain patterns,at crime scenes to betterreconstructa criminal event. The authors define eightoverarchingprinciples for the comprehensive analysis and interpretation of blood trace configurations.Three of theseprinciplesare:blood tracesmayreveal a great deal of useful information;extensive blood traces, although present,may notalwaysyieldinformation relevant toquestions that may arise in a given case;and acollection of a few seemingly related dried blood dropletdeTable of ContentsDEDICATION v EPIGRAPH vii TABLE OF CONTENTS ix FOREWORD xvii ACKNOWLEDGEMENTS xix PREFACE TO BLOOD TRACES: INTERPRETATION OF DEPOSITION AND DISTRIBUTION xxi 1 Physical Evidence Record 1 1.1 Generation of Physical Evidence Record 1 1.1.1 Scene as a Recording Medium 1 1.1.2 Creation of Blood Traces 5 1.2 Capturing the Physical Evidence Record: Crime Scene Analysis 5 1.2.1 The Stages of Crime Scene Investigation 6 1.2.1.1 Scene Protection and Security 6 1.2.1.2 Evidence Recognition 8 1.2.1.3 Evidence Documentation 10 1.2.1.4 Evidence Recovery, Packaging, and Transportation 14 1.3 Reconstruction of Past Incidents from the Physical Evidence Record 17 1.3.1 Definition 17 1.3.2 Art or Science, or Both? 17 1.3.3 Importance of the Scientific Method 18 1.3.4 Reconstruction vs. Reenactment 18 1.3.5 Holistic Philosophy: Blood Trace Configuration Interpretation Is Only One Aspect of Reconstruction 19 References 20 2 Historical Perspective 21 2.1 Edgar Allen Poe and Sir Arthur Conan Doyle: History in Fiction 21 2.2 Hans Gross 22 2.3 History of Research in Blood Traces 22 2.4 Detective Charlie Chan: History in Film 23 2.5 Paul Kirk 23 2.6 Herbert MacDonell 25 2.7 Bloodstain Pattern Analysis Committees and Organizations 26 References 26 3 Characteristics of Liquids Including Blood 29 3.1 Physical Properties and Fluid Mechanics of Liquids 29 3.1.1 Surface Tension and Weber Number 29 3.1.2 Density 31 3.1.3 Newtonian and Non-Newtonian Fluids 31 3.1.4 Viscosity and Poiseuille’s Equation 32 3.1.5 Flow Stability, Reynolds Number, and Rayleigh Number 33 3.1.6 Viscoelasticity 34 3.1.7 Caveats 34 3.2 Physical Characteristics of Blood 35 3.2.1 Definition and Description of Blood 35 3.2.2 Factors that Influence Droplet Deposit Periphery 37 3.2.3 Factors that Influence Droplet and Deposit Size 38 3.2.4 Sedimentation and Hematocrit 40 3.3 Optical Properties of Blood Deposits 40 3.4 Physiological Characteristics of Blood 41 3.4.1 Hemostasis and Clotting 41 3.4.1.1 Postmortem Clotting 42 3.4.1.2 Lack of Clotting 42 3.5 Use of Blood Substitutes in Training and Simulations 43 References 44 4 Detection, Visual Enhancement, Identification, and Source Attribution of Blood Deposits and Configurations 47 4.1 Optical Visualization of Blood Trace Deposits 48 4.2 Catalytic Tests 52 4.3 Protein Stains 53 4.4 Blood Typing and DNA Technology 53 4.5 A Limitation of Laboratory SOPs 54 4.6 Ongoing and Future Research 55 4.7 Conclusion 58 References 58 5 Terminology, Typology, and Taxonomy 61 5.1 History of Terminologies Applied to Blood Trace Configurations 61 5.2 A Typology for Blood Trace Deposits 63 5.2.1 Contact Transfers 64 5.2.1.1 Figure(s): Static Contact Transfers 66 5.2.2 Noncontact Deposit Configurations 69 5.2.3 Arc (“Cast-off”) Deposit Configurations 69 5.2.4 Arterial Deposit Configurations 70 5.2.5 Droplet Trail Deposit Configurations 71 5.2.6 Airborne Droplets in Respiratory Airstreams 72 5.2.7 Radial (“Impact”) Spatter (Include Close-Up) 73 5.2.8 Secondary Spatter 74 5.2.8.1 Dropping Height Experiments 75 5.2.8.2 Dropping Volume Experiments 76 5.2.8.3 Various Substrates 77 5.2.8.4 Secondary Spatter Discussion 77 5.2.9 Spatter Associated with Gunshot Wounds 78 5.2.9.1 Patterns from Perforating (Through-and-through) Wounds 78 5.2.9.2 Backspatter from Entrance Wounds with No Exit (Penetrating Wounds) 80 5.2.9.3 Blood Traces from Blowback 80 5.2.10 Other Configurations 82 5.2.10.1 Flow Configurations 82 5.2.10.2 Pooling Configurations 82 5.2.10.2.1 Clotting, Serum Separation and its Significance 82 5.2.10.3 Diluted Blood Deposits 83 5.2.10.4 Significance of Voids 86 5.2.11 Post-Incident Events (“Artifacts”) 87 5.2.11.1 Human Attempts at Clean-Up 87 5.2.11.1.1 Inhibiting and Obscuring Cleaning Agents 87 5.2.11.1.2 Luminol and Investigative Leads 88 5.2.11.2 Animals and Insects 88 5.2.11.3 Unavoidable Environmental Events (i.e., Rain, Wind…) 90 References 92 6 Blood Droplet Dynamics and Deposit Formation 95 6.1 Blood Droplet Motion and Velocity Vectors 95 6.2 Angle of Impact 96 6.3 Blood Droplet Trajectory and Resulting Impact Geometry 98 6.4 Region of Convergence and Region of Origin 101 6.5 Equivalence of Relativistic Motion 104 6.6 Impact Mechanism and Blood Trace Deposit Formation 110 6.6.1 Impacts of Falling Droplets with Sessile Blood 114 6.7 Conclusion 116 References 116 7 Blood Trace Interpretation and Crime Scene/Incident Reconstruction 119 7.1 Principles of Blood Trace Reconstruction 119 7.2 Utility 126 7.2.1 Associative 126 7.2.2 Action 126 7.2.3 Positional 128 7.2.4 Directional 129 7.2.5 Temporal 129 7.2.6 Pattern Directed Sampling 130 7.3 Limitations, Problems, and Common Acceptance of the Status Quo 130 7.3.1 Lack of Teamwork and Potential Synergism Between Criminal and Scientist Investigator 130 7.3.1.1 Lack of Appreciation for the Contributions of the Scientist (or Undervaluing of the Scientist) 131 7.3.2 Potential Failures of the Scientist Investigator 132 7.3.2.1 Investigator Inexperience 132 7.3.2.2 Neglect of Scientific Principles 132 7.3.2.2.1 Misunderstanding and/or Misuse of the Scientific Method 132 7.3.2.2.2 Over-Interpretation 136 7.3.2.2.3 Opinion of a Scientist vs. Scientific Opinion 139 7.3.2.3 Deficiency in Scientific Integrity 139 7.3.2.4 Cognitive Biases 140 7.3.3 Pre- and Post-Event Artifacts 140 7.3.4 Risks Engendered by Limited or Erroneous Information 141 7.3.5 Problems with “Patterns” 142 7.3.5.1 General Problems 142 7.3.5.2 Patterns Involving a Limited Number or Detail of Traces 143 7.3.5.3 Chronological Sequencing 144 7.3.5.4 Effects Caused by Interaction of Blood and Target Surface 144 7.3.5.5 Configurations Observed after Application of Blood Presumptive and Enhancement Reagents 147 7.3.6 Problems with the Interpretation of Specific Blood Trace Configurations 148 7.3.6.1 False Expectation of Airborne Blood Droplets from the First Wounding 148 7.3.6.2 Limitations in Determining the Origin with the Radial Spatter Configurations 149 7.3.6.3 Measurement Uncertainty and Significant Figures 150 7.3.6.4 “Height of Fall” Estimations 151 7.3.6.5 Crude Age Estimations of Dried Blood Traces Based on Appearance 152 7.3.7 Experimental Design 152 7.4 Blood Trace Configuration Analysis as Part of a Holistic Approach to Reconstruction 154 References 155 8 Science and Pseudoscience 157 8.1 Science 157 8.1.1 The Need for a Generalist-Scientist in Crime Scene Investigation 157 8.2 Pseudoscience 158 8.2.1 The Pernicious Consequences with Respect to Reconstructions 158 8.2.2 Pseudoscience Characteristics 158 8.2.2.1 Isolation 159 8.2.2.2 Nonfalsifiability 159 8.2.2.3 Misuse of Data 160 8.2.2.4 Lack of Replicability 160 8.2.2.5 Claims of Unusually High Precision, Sensitivity of Detection, or Accuracy of Measurement 160 8.2.3 Hallmarks of a Pseudoscientist 160 8.2.3.1 Impenetrability 161 8.2.3.2 Ulterior Motives (Financial Gain/Recognition) 161 8.2.3.3 Lack of Formal Science Education 162 8.2.3.4 Unwillingness to Self-Correct 162 8.3 Bad Science 163 8.4 Conclusions 164 References 164 9 Modes of Practice and Practitioner Preparation and Qualification 167 9.1 Existing Modes of Crime Scene Investigation Practice 167 9.1.1 The Folly of Casting Technicians into the Roles of Scientists 169 9.2 Preparations and Qualifications of Practitioners 170 9.2.1 Education and Training 172 9.2.2 Experience 173 9.2.3 Mentoring 174 9.2.4 Professional Development 174 9.2.5 Peer or Technical Review 174 9.2.6 Certification & Qualification Standards 176 References 177 10 Interesting and Illustrative Cases 179 10.1 The Sam Sheppard Case 180 10.1.1 Case Scenario/Background Information 180 10.1.2 The Physical Evidence and Its Interpretation 180 10.1.3 Conclusions 182 10.1.4 Lessons 184 10.2 Knife in the Gift Bag 185 10.2.1 Case Scenario/Background Information 185 10.2.2 The Physical Evidence and Its Interpretation 185 10.2.3 Conclusions 186 10.2.4 Lessons 186 10.3 The Farhan Nassar Case 186 10.3.1 Case Scenario/Background Information 186 10.3.2 The Physical Evidence and Its Interpretation 187 10.3.3 Conclusions 190 10.3.4 Lessons 191 10.4 Passive Documentation 191 10.4.1 Case Scenario/Background Information 191 10.4.2 The Physical Evidence and Its Interpretation 192 10.4.3 Conclusions 193 10.4.4 Lessons 193 10.5 The British Island Holiday Case 194 10.5.1 Case Scenario/Background Information 194 10.5.2 The Physical Evidence and Its Interpretation 195 10.5.3 Conclusions 198 10.5.4 Lessons 198 10.6 Absence of Evidence is Not Evidence of Absence 199 10.6.1 Case Scenario/Background Information 199 10.6.2 The Physical Evidence and Its Interpretation 200 10.6.3 Conclusions 201 10.6.4 Lessons 201 10.7 Triple Homicide 202 10.7.1 Case Scenario/Background Information 202 10.7.2 The Physical Evidence and Its Interpretation 202 10.7.3 Conclusions 204 10.7.4 Lessons 204 10.8 The O.J. Simpson Case 205 10.8.1 Case Scenario/Background Information 205 10.8.2 The Physical Evidence and Its Interpretation 207 10.8.2.1 Trails of Blood Droplets and Footwear 207 10.8.2.2 The Blood on and in the Bronco 213 10.8.2.3 The Socks and EDTA Testing 214 10.8.2.4 The Envelope 218 10.8.2.5 The Hat and Gloves 220 10.8.3 Conclusions 221 10.8.4 Lessons 223 10.9 A Vertical Crime Scene 223 10.9.1 Case Scenario/Background Information 223 10.9.2 The Physical Evidence and Its Interpretation 224 10.9.3 Conclusions 228 10.9.4 Lessons 229 10.10 Tissue Spatter from a Large Caliber Gunshot 229 10.10.1 Case Scenario/Background Information 229 10.10.2 The Physical Evidence and Its Interpretation 229 10.10.3 Conclusions 230 10.10.4 Lessons 230 10.11 Shooting of a Driver 230 10.11.1 Case Scenario/Background Information 230 10.11.2 The Physical Evidence and Its Interpretation 231 10.11.3 Conclusions 233 10.11.4 Lessons 233 10.12 A Contested Fratricide 235 10.12.1 Case Scenario/Background Information 235 10.12.2 The Physical Evidence and Its Interpretation 236 10.12.3 Conclusions 238 10.12.4 Lessons 238 References 240 11 “Bad” Cases – Misleading or Incompetent Interpretations 241 11.1 David Camm 242 11.1.1 Case Scenario/Background Information 242 11.1.2 The Physical Evidence and Its Interpretation 242 11.1.3 Conclusions 250 11.1.4 Lessons 251 11.2 Dew Theory 252 11.2.1 Case Scenario/Background Information 252 11.2.2 The Physical Evidence and Its Interpretation 252 11.2.3 Conclusions 253 11.2.4 Lessons 254 11.3 Murder of an Off-Duty Police Officer 254 11.3.1 Case Scenario/Background Information 254 11.3.2 The Physical Evidence and Its Interpretation 255 11.3.3 Conclusions 261 11.3.4 Lessons 261 11.4 The Imagined Mist Pattern 262 11.4.1 Case Scenario/Background Information 262 11.4.2 The Physical Evidence and Its Interpretation 262 11.4.3 Conclusions 263 11.4.4 Lessons 263 11.5 Concealed Blood Traces 264 11.5.1 Case Scenario/Background Information 264 11.5.2 The Physical Evidence and Its Interpretation 264 11.5.3 Conclusions 265 11.5.4 Lessons 265 11.6 A Stomping Homicide – Misuse of Enhancement Reagents 266 11.6.1 Case Scenario/Background Information 266 11.6.2 The Physical Evidence and Its Interpretation 266 11.6.3 Conclusions 268 11.6.4 Lessons 268 References 268 12 More Broadly Assessed Cases: Going Beyond the Request 269 12.1 Gunshot to the Forehead and the Runaway Car 270 12.1.1 Case Scenario/Background Information 270 12.1.2 The Physical Evidence and Its Interpretation 270 12.1.3 Conclusions 271 12.1.4 Lessons 271 12.2 The Obscured Bloody Imprint 273 12.2.1 Case Scenario/Background Information 273 12.2.2 The Physical Evidence and Its Interpretation 274 12.2.3 Conclusions 278 12.2.4 Lessons 278 12.3 The Murder of a Deputy: Shooting in a Hospital Room 279 12.3.1 Case Scenario/Background Information 279 12.3.2 The Physical Evidence and Its Interpretation 280 12.3.3 Conclusions 281 12.3.4 Lessons 281 13 Widely Held Misconceptions 283 13.1 Blood Traces Produced by Gunshot Wounds 283 13.1.1 Introduction to Firearms and Wounding 283 13.1.2 Microvascularization and Experimental Laboratory Models 285 13.1.3 Proposed Models and Their Failure to Consider Microvascular Structures 288 13.2 The “Normal Drop” Claim 295 13.3 MacDonell Priority Claims Relative to the Seminal 1939 Balthazard et al. Paper 296 13.4 The Claimed Equivalence of Deposits Diameters and Drop Diameters 296 13.5 Ambiguous Trace Configurations 297 13.5.1 Configuration Issues 297 13.5.2 Fabric Issues 298 13.6 Issues with Interpretation of Asymmetrical Blood Projections from Impacts 302 References 302 14 Resources 305 14.1 Bloodstain Pattern Analysis Groups 305 14.1.1 SWGSTAIN 306 14.1.2 NIST OSAC Bloodstain Pattern Analysis Subcommittee 308 14.1.3 Organizations 309 14.2 Publications and Other Information Sources 310 14.2.1 Journals 310 14.2.2 Newsletters 311 14.2.3 Books 311 14.2.4 Internet Resources 311 14.3 Training and Education 311 14.3.1 Continuing Education 312 14.4 Proficiency Tests 312 References 312 15 Concluding Remarks and Looking to the Future 315 15.1 Importance of Science on the Front End 315 15.2 The Integration of Physical Evidence with Police Investigations 316 15.3 Troubling Developments and Perceptions 317 15.4 Testing Facilities & the Creeping Inversion 318 15.5 The Pernicious Effects and Fallout from Bloodstain Workshops 319 15.6 Future Directions 320 References 323 BIBLIOGRAPHY 325 APPENDIX1: FUNDAMENTALS REVISITED 341

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Book SynopsisBiomolecules from Natural Sources An up-to-date exploration of new and novel biomolecules In Biomolecules from Natural Sources: Advances and Applications, a team of accomplished researchers delivers up-to-date information on various bioresources, bioprocessing, production, mechanisms of action for selective bioactivity, biochemistry, targeted therapeutic roles and the advancements made on their bioactive potentials of new and novel biomolecules. The book presents recent trends in new and novel biomolecules and their identification, characterization, and potential applications. The selected contributions canvas a variety of breakthroughs in the understanding and applications of naturally derived biomolecules. Biomolecules from Natural Sources: Advances and Applications is an exhaustive collection of research and information, as well as an insightful and interdisciplinary treatment of a rapidly developing field. Readers will also find: A thorTable of ContentsPreface vii List of Contributors ix 1 Glycolipids: From Biosynthesis to Biological Activity toward Therapeutic Application 1Maria H. Ribeiro, Eva Fahr, and Sara Lopes 2 Natural Polymer Types and Applications 31Amro Abd Al Fattah Amara 3 Mushroom Pigments and Their Applications 82Maura Téllez-Téllez and Gerardo Díaz-Godínez 4 Pharmacological Potential of Pigments 101M. C. Pagano, E. J. A. Corrêa, N. F. Duarte, and B. K. Yelikbayev 5 Bioactive Compounds: Encapsulation, Delivery, and Applications Using Albumins as Carriers 113Flavia F. Visentini, Adrian A. Perez, Joana B. Ferrado, María Laura Deseta, and Liliana G. Santiago 6 The Protein Structure, Function and Specificity: PhaC Synthases Type I, II, III and IV as a Model 181Amro Abd Al Fattah Amara 7 Extremozyme-Based Technology for Biofuel Generation: Bioactivity and Stability Performances 214Amal Souii, Afwa Ghorrab, Khouloud Hammami, Ahmed Slaheddine Masmoudi, Ameur Cherif, and Mohamed Neifar 8 The Role of Divalent Cations in Antibiotic Sensitivity: A Molecular Aspect 252Amro Abd Al Fattah Amara 9 Biomolecules from Vegetable Wastes 278Begoña de Ancos and Concepción Sánchez-Moreno 10 Retention of Natural Bioactive Compounds of Berry Fruits during Surface Decontamination Using an Eco-friendly Sanitizer 309María P. Méndez-Galarraga, Franco Van de Velde, Andrea M. Piagentini, and María Elida Pirovani 11 Biomolecules from Basil – Pharmacological Significance 322Ivayla Dincheva and Ilian Badjakov 12 Himalayan Peony (Paeonia emodi Royle): Enlightening Bioactive Compounds and Biological Applications towards Sustainable Use 345Prabhakar Semwal, Sakshi Painuli, Natália Cruz-Martins, and Ashish Thapliyal 13 Health Properties of Dietary Monoterpenes 362Rafael Chelala Moreira, Kele A.C. Vespermann, Gustavo Molina, Juliano Lemos Bicas, and Mario Roberto Marostica Junior 14 Biomolecules Derived from Whey: Strategies for Production and Biological Properties 390M. C. Perotti, C. I. Vénica, I. V. Wolf, M. A. Vélez, G. H. Peralta, A. Quiberoni, and C. V. Bergamini 15 EPS from Lactobacilli and Bifidobacteria: Microbial Metabolites with Both Technological and Health-Promoting Properties 433Elisa C. Ale, Melisa A. Puntillo, María F. Rojas, and Ana G. Binetti 16 Characterization of Bacteriocins Produced by Lactic Acid Bacteria of Industrial Interest 458Silvina Alicia Pujato, Andrea del Luján Quiberoni, and Daniela Marta Guglielmotti Index 470

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Book SynopsisTable of ContentsList of Contributors Foreword Preface Chapter 1 Climate change and Agriculture: State of the Art, Challenges, and Perspectives Imran, Noureddine Benkeblia, Amanullah, and Abdel Rehman Altawaha Chapter 2 Climate-Smart Plants Combat Climate Change and Liable for Food Security Imran, Amanullah, and Abdel- Rehman Altawaha Chapter 3 Adapting Crops to Climate Change Abdel Rahman M.S. Al-Tawaaha, Samia Khanum, Noureddine Benkeblia, Amanullah, Imran, Shah Khaled, Abdel Razzaq Al- Tawaha, Mousumi Mondal, Nidal Odat, Abhijit Dey, Nujoud Alimad, Devarajan Thangadurai, Jeyabalan Sangeetha , Saher Islam, and Mohammad Shatnawi Chapter 4 Role of Biotechnology in Climate-Resilient Agriculture Abdel Rahman M.S. Al-Tawaaha, Rachid Mrabet, Mina Bayanati, Banothu Santhosh, Noureddine Benkeblia, Imran, Amanullah, Shah Khaled, Abdel Razzaq Al- Tawaha, Hiba Alatrash, Yaman Jabbour, Abhijit Dey, Devarajan Thangadurai, Jeyabalan Sangeetha and Saher Islam Chapter 5 Breeding Crops for Tolerance to Salinity, Heat and Drought Abdel Rahman M.S. Al-Tawaha*, Nidal Odat, Noureddine Benkeblia, Naila Kerkoub, ZinebLabidi, Mahyeddine Boumendjel,Hichem Nasri,Imran, Amanullah, Shah Khaled, Abdel Razzaq Al- Tawaha, Mina Bayanati, Hiba Alatrash, Abhijit Dey, Devarajan Thangadurai, Jeyabalan Sangeethaand Saher Islam Chapter 6 Innovative approaches in breeding of climate-resilient crops Sandra Cvejić, Siniša Jocić, Goran Bekavac, Milan Mirosavljević, Ana Marjanović Jeromela, Miroslav Zorić, Aleksandra Radanović, Ankica Kondić-Špika, Dragana Miladinović Chapter 7 Challenges of Soil Fertility under Changing Climate and its opposing components Imran, Amanullah, Ibrahim Ortas, Tariq Mahmood, Muhammad Arif, Abdel- Rehman Altawaha and Mohammad Ilyas Chapter 8 The declining trend of Soil Fertility with Climate Change and its solution Imran, Amanullah and Ibrahim Ortas Chapter 9 Nano-Black Carbon is an Organic Tool for the Alleviation of Abiotic Stresses and its Certain Damages under Changing Climate Imran, Amanullah, Muhammad Arif, Abdel-Rehman Altawaha, and Tariq Mahmood Chapter 10 Biological Nitrogen Fixation in Non-Legume Plant and Changing Climate Abdel Rahman M.S. Al Tawaaha, Pratibha Vyas, Arun Karnwalc Noureddine Benkeblia, Swapnil Ganesh Sanmukh, Eduard Torrents Serra, Imran, Amanullah, Shah Khaled, Abdel Razzaq Al- Tawaha, Abhijit Dey, Nujoud Alimad, , Devarajan Thangadurai, Jeyabalan Sangeetha, Saher Islam, Mohammad Shatnawi, Chapter 11 Role of Phosphorus in Imparting Abiotic Stress Tolerance to Plants Bhaswati Baroowa, Sreyashi Paul and Nirmali Gogoi Chapter 12 Climate Change and Cereal Production Abdel Rahman M.S. Al-Tawaha, Javeid Ahmed Dar, Amreena Sultan, Noureddine Benkeblia, Amanullah, Imran, Shah Khaled, Abdel Razzaq Al- Tawaha, Nidal Odat, Hiba Alatrash Chapter 13 Impact of climate change on tea cultivation and adaptation strategies: Special emphasis on tea pests in North East India Azariah Babu, Somnath Roy, Rupanjali Deb Baruah, Bhabesh Deka, Kamruza Z. Ahmed , Sourajit Bayen and Suman Sarkar Chapter 14 Impact of Climate Change on Integrated Pest Management Strategies Sonja Gvozdenac, Boško Dedić, Sanja Mikić, Jelena Ovuka, Dragana Miladinović Chapter 15 Climate Change and its Effects on Plant Viruses Aarshi Srivastava, Vineeta Pandey and R.K.Gaur Chapter 16 Green chemistry in sustainable use of agrowaste Pratibha Deka, Mayuree Gohain, Nilutpal Bhuyan, Nirmali Gogoi, Rupam Kataki2 Chapter 17 Assessing Satellite-Based Products in Characterizing Agricultural Drought Under Climate Change in Northeast Brazil Franklin Paredes-Trejo, Humberto Alves Barbosa, Jason Giovannettone, T.V. Lakshmi Kumar, Manoj Kumar Thakur, Catarina de Oliveira Buriti and José Prieto Chapter 18 Understanding smallholder farmers’ perceptions of and adaptations to climate change: The case of the Zambezi region, Namibia. Lee-Ann Steenkamp and Winnie Thebuho Index

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Book SynopsisTable of ContentsAbout the editors, xiii About the contributors, xv Foreword, xix Preface, xxiii Series preface, xxvii Acknowledgments, xxix 1 The anthropology of violent death and the treatment of the bodies: an introduction, 1Roberto C. Parra and Douglas H. Ubelaker 2 The posthumous dignity of dead persons, 1Antoon De Baets 2.1 Introduction: generations and posthumous dignity, 15 2.2 The dead and posthumous dignity, 17 2.3 Evidence for posthumous dignity, 18 2.4 Duties flowing from posthumous dignity, 19 2.5 The nature of posthumous dignity, 23 2.6 Semantic debates about posthumous dignity, 25 2.7 Breaches of posthumous dignity, 26 2.8 Restoration of posthumous dignity, 28 2.9 Conclusion: the impact of posthumous dignity, 31 3 Continuing bonds and social memory: absence--presence, 39Avril Maddrell 3.1 What are continuing bonds and how are they experienced and expressed?, 39 3.2 Continuing bonds and the well-being of mourners, 43 3.3 Implications for professional service providers, 46 4 The archaeology of disappearance, 49Alfredo González-Ruibal 4.1 Introduction, 49 4.2 Disappearance and power: concealment, dispersal, and virtualization, 51 4.3 Material disappearance, human disappearance, 55 4.4 The disappearance of disappearance, 58 4.5 Concluding Remarks, 62 5 Bioarchaeology of violent death, 67Anna Osterholtz, Debra Martin and Ryan Harrod 5.1 Introduction and background, 67 5.2 Categories of group-level violent death, 70 5.2.1 Bioarchaeology of Massacres, 70 5.3 Case studies illustrating integrative approaches to massacres in the past, 70 5.4 Differentiating between kratophanous violence and ritualized death, 77 5.5 Conclusions, 81 6 Destruction, mass violence, and human remains: Dealing with dead bodies as a "total social phenomenon", 91Élisabeth Anstett 6.1 Introduction, 91 6.2 Understanding the forms taken by the Forensic Turn, and its effects, 93 6.3 Understanding the genealogy of professional practices of disinterment, 98 6.4 The blind spots of a total social phenomenon of great complexity, 102 6.5 Conclusion, 103 7 Kill, kill again and destroy: when death is not enough, 109Roberto C. Parra, Digna M. Vigo-Corea and Pierre Perich 7.1 Introduction, 109 7.2 Dehumanizing, 111 7.3 When death is not enough, 114 7.4 Dismembering/mutilating: the perspective from culture, 121 7.5 Conclusions, 126 8 Mourning violent deaths and disappearances, 133Antonius C. G. M. Robben 8.1 Introduction, 133 8.2 The conflictive mourning of the dead and missing after the First World War, 134 8.3 Enduring bonds of the living, the dead, and the disappeared in Argentina, 138 8.4 Oscillatory mourning of the dead and the disappeared by the bereaved, 142 8.5 Conclusion, 147 9 Whose humanitarianism, whose forensic anthropology?, 153Jaymelee J. Kim and Adam Rosenblatt 9.1 Introduction, 153 9.2 Positionality of the authors, 155 9.3 Reconceptualizing violent deaths, 156 9.4 The dead as articipants in forensic anthropology, 158 9.5 What's missing from human rights, 166 9.6 The continued expansion of forensic anthropology, 169 10 Battlefields and killed in action: tombs of the unknown soldier and commemoration, 177Laura Wittman 10.1 Introduction, 177 10.2 Tomb of the unknown soldier, 178 10.3 Mutilated victory, 182 10.4 As an Epilogue, 190 11 Mass grave protection and missing persons, 197Melanie Klinkner 11.1 Introduction, 197 11.2 Missing persons in mass graves: a worldwide phenomenon, 198 11.3 The legal framework for mass grave protection, 201 11.4 Practicalities of protection, 208 11.5 Protection on a global scale, 210 11.6 Conclusion: the need to do better, 213 12 Respect for the dead under international law and Islamic law in armed conflicts, 219Ahmed Al-Dawoody and Alexandra Ortiz Signoret 12.1 Introduction, 219 12.2 The Legal Framework, 220 12.3 Search for, Collect, and Evacuate the Dead without Adverse Distinction, 221 12.4 Identification and Recording of Information on the Dead, 224 12.5 Respecting the Dead and Dignified Treatment, 226 12.6 Respectful Disposal of the Dead, 229 12.7 Gravesites and Other Locations of Mortal Remains, 233 12.8 Exhumations, 234 12.9 Return of Human Remains and Personal Effects of the Dead, 236 12.10 Conclusion, 239 13 Unmaking forgotten mass graves and honorable burial: engaging with the spanish civil war legacy, 251Francisco Ferrándiz 13.1 Overture, 251 13.2 On Funerary Militarism, 252 13.3 Franco's Militarist Imprint Under Siege, 256 13.4 Unmaking the Generalissimo's Burial, 262 13.5 Military disassemblage, 269 14 Dealing with bad death in post-conflict societies: forensic devices, burials of exhumed remains, and mourning processes in Peru, 277Valérie Robin-Azevedo 14.1 Models for dealing with death: morphologies of "good death" and "bad death", 277 14.2 Contexts of mass violence through the lens of bad death, 278 14.3 Transitional justice, the forensic turn, and the "dignified burial": can we reverse bad death?, 280 14.4 From the necropolitics to the necrogovernamentality of the Peruvian state, 281 14.5 Exhumation of mass graves and the reactivation of bad death in the Andes, 284 14.6 The task of identification or the process of rehumanization of ill-treated bodies, 287 14.7 The uncertain dates and stretched time of bad death, 291 14.8 Body substitutes in the absence of any trace of remains, 293 14.9 Conclusion, 295 15 Migrant death and the ethics of visual documentation in forensic anthropology, 303Krista E. Latham, Alyson J. O'Daniel and Tanya Ramos 15.1 Introduction, 303 15.2 Disciplinary ethics and social change: contextualizingforensic anthropology practices, 304 15.3 Methods and scope, 309 15.4 Making the case for a more socially aware practice of forensic anthropology, 318 15.5 Closing, 320 16 Bedeviling binaries: an integrated and dialectical approach to forensicanthropology in northern Uganda, 327Tricia Redeker Hepner and Dawnie W. Steadman 16.1 Introduction, 327 16.2 Restless spirits and human remains in Acholiland, Uganda, 329 16.3 The integrated approach, 336 16.4 To excavate or not to excavate?, 340 16.5 Conclusion: from binary to dialectical relationships, 344 17 Guiding principles for the dignified management of the dead in humanitarian emergencies and to prevent them from becoming missing persons, 351Stephen Cordner and Morris Tidball-Binz 17.1 Why the need for these principles?, 351 17.2 To whom are the guiding principles addressed?, 354 17.3 Setting the scene, 355 17.4 The preamble to the Guiding Principles, 360 17.5 The Guiding Principles, 362 17.6 The process of producing the Guiding Principles, 369 17.7 Conclusions, 369 18 Epilog: Anthropology of violent death and forensic humanitarian action, 375Douglas H. Ubelaker and Roberto C. Parra 18.1 Humanity and its less violent reactions?, 375 18.2 Anthropology applied to forensic sciences and the notion of anthropology of violent death in the humanitarian context, 377 Note 382 References 383 Index, 385

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Book SynopsisHandbook of Natural Colorants Second Edition A detailed survey of a variety of natural colorants and their different applications including textiles, polymers, and cosmetics Colorants describe a wide range of materials such as dyes, pigments, inks, paint, or chemicals, which are used in small quantities but play an important role in many products such as textiles, polymers, food, and cosmetics. As the effects of climate change begin to be felt, there has been a shift in focus in the field to renewable resources and sustainability, and an interest in the replacement of oil-based products with greener substitutions. As the push to adopt natural resources grows, there have been significant developments in the research and application of natural colorants as a step in the transition to a bio-based economy. The second edition of Handbook of Natural Colorants provides a detailed introduction to natural colorants in a marriage of theory and practice, from Table of ContentsList of Contributors xxi Series Preface xxv Preface xxvii I Historical Development 1 1 History of Natural Dyes in the Ancient Mediterranean Civilization 3 Maria J. Melo 1.1 Introduction 3 1.1.1 Ancient Mediterranean World 3 1.1.2 Dyes from Antiquity 4 1.1.3 Unveiling the Secrets of Ancient Dyes with Modern Science 7 1.2 Ancient Reds 7 1.2.1 Anthraquinone Reds 7 1.2.2 Redwoods 10 1.2.3 Flavylium/Anthocyanin Reds 12 1.2.3.1 Equilibria in solution 13 1.3 Ancient Blues 14 1.3.1 Indigo Blues 14 1.3.2 Anthocyanin Blues 15 1.4 Ancient Purples 16 1.4.1 Tyrian Purple: Real Purple from Sea Snails 16 1.4.2 Orchil Purples 18 1.4.3 Folium 18 1.5 Ancient Yellows 20 1.5.1 Flavonoid Yellows 20 1.5.2 Carotenoid Yellows 21 1.5.3 Chalcone and Aurone Yellows 22 Acknowledgements 22 References 22 2 Colors in Civilizations of the World and Natural Colorants: History under Tension 27 Dominique Cardon 2.1 Introduction 27 2.2 The Triumph of Mauveine: Synthetic Fulfillment of the Antique Purplemania 28 2.3 Blue: From Kingly Regional to Globally Democratic 29 2.4 Red and Yellow: From Micro to Macro Scales 29 2.5 What Is the Future for Natural Colorants in the Dawning Era of Renewable Resources? 30 Acknowledgement 31 References 31 3 History of Natural Dyes in North Africa_Egypt 33 Harby Ezzeldeen Ahmed 3.1 Introduction 33 3.2 Natural Dyes in Pharaonic Textiles 34 3.3 Dyeing Techniques 34 3.4 Dye Sources 34 3.4.1 Woad 35 3.4.2 Indigo 35 3.4.3 Red 35 3.4.4 Yellow 36 3.4.5 Black 36 3.4.6 Brown 36 3.4.7 Green 36 3.4.8 Purple 36 3.5 Dyeing in Coptic Textiles 36 3.6 Wool- Dyed Fabric with Natural Dye 38 3.7 Dyes in Islamic Textiles 38 3.8 Mordants 40 References 40 II Natural Colorants in Different Regions of the World 43 4 Sources for Natural Colorants in Europe 45 Thomas Bechtold, Tung Pham and Avinash P. Manian 4.1 Introduction 45 4.2 Cultivation 46 4.2.1 Potential European Dye Plants Yesterday and Now 46 4.2.2 Modern Cultivation Methods— General Facts 47 4.2.3 Blue- Dye Plants 48 4.2.4 Red- Dye Plants 49 4.2.5 Yellow- Dye Plants 49 4.2.6 Brown- Dye Plants 52 4.2.7 Production of Dye Extracts 54 4.3 Natural Colorants from Agro- Food Residues 55 4.4 Natural Colorants from Forestry and Timber Industry 56 4.5 Relevant Examples for the Application 57 4.6 Conclusions, Discussion, and Summary 58 Acknowledgement 58 References 59 5 Dyes in South America 63 Veridiana Vera de Rosso and Adriana Zerlotti Mercadante 5.1 Introduction 63 5.2 Annatto 65 5.3 Turmeric 67 5.4 Marigold 68 5.5 Cochineal and Carmine 69 Acknowledgements 71 References 71 6 Natural Dyes in Eastern Asia (Vietnam and Neighboring Countries) 75 Tung Pham and Thomas Bechtold 6.1 Introduction 75 6.2 Annatto (Bixa orellana L., Family Bixaceae) 75 6.3 Tea (Camellia sinensis (L.) Kuntze, Family Theaceae) 77 6.4 Umbrella Tree (Terminalia catappa L., Family Combretaceae) 77 6.5 Mackloeur (Diospyros mollis L. Griff, Family Ebenaceae) 78 6.6 Indigo (Indigofera L., Family Fabaceae) 79 6.6.1 Indigofera tinctoria L. 79 6.6.2 Indigofera galegoides dc 80 6.6.3 Strobilanthes cusia (Baphicacanthus) 80 6.7 Henna (Kok Khan or Khao Youak in Laos) (Lawsonia spinosa L., Family Lythraceae) 80 6.8 Nacre (African Mahogany, Khaya senegalensis, Family Meliaceae) 81 6.9 Sappan Wood (Caesalpinia sappan L., Family Fabaceae) 81 6.10 Japanese Pagoda Tree Flowers (Sophora japonica L., Family Leguminosae) 82 6.11 Turmeric (Curcuma longa L., Family Zingiberaceae) 82 6.12 Sapodilla (Manilkara zapota L. or Achras zapota, Family Sapotaceae) 82 6.13 Betel (Piper betel L., Family Piperaceae) 83 6.14 Eucalyptus (Eucalyptus, Family Myrtaceae) 83 6.15 Caesalpinia Yellow (Caesalpinia pulcherrima L., Family Fabaceae) 83 6.16 Brow- Tuber; Yam (Dioscorea cirrhosa Lour, Family Dioscoreaceae) 83 6.17 Others 84 Acknowledgement 84 References 84 7 Sources for Natural Colorants in China 89 Ren-Cheng Tang 7.1 Introduction 89 7.2 Sophora japonica Yellow 92 7.3 Turmeric 93 7.4 Gardenia Yellow 93 7.5 Emodin 93 7.6 Baicalin 94 7.7 Berberine 94 7.8 Henna 94 7.9 Monascus Red 95 7.10 Madder 95 7.11 Sorghum Red 95 7.12 Mulberry Red 96 7.13 Shikonin 96 7.14 Indigo 96 7.15 Condensed Tannins 97 7.16 Tea Polyphenols 98 7.17 Gallnut 99 References 99 8 Sources, Application, and Analysis of Natural Colorants: An Indian Perspective 103 Prof. (Dr.) Ashis Kumar Samanta and Prof. (Dr.) Deepali Singhee 8.1 Introduction 103 8.2 Natural Dyes in India 104 8.2.1 History 104 8.2.2 Traditional Processes of Dyeing with Natural Dyes in Different Parts of India 105 8.2.3 Sources of Natural Dyes in India 106 8.2.4 Use of Some Natural Dyes in Traditional Textiles of India 107 8.3 Details of Some Dye Sources and Their Application in India 109 8.3.1 Turmeric 109 8.3.2 Pomegranate 111 8.3.3 Flame of Forest 114 8.3.4 Marigold 116 8.3.5 Safflower 118 8.3.6 Annatto 120 8.3.7 Madder 123 8.3.8 Indian Mulberry 125 8.3.9 Arjuna 127 8.3.10 Sappanwood 130 8.3.11 Eucalyptus 132 8.3.12 Catechu 134 8.3.13 Gallnut 137 8.3.14 Myrobolan 140 8.3.15 Lac 142 8.3.16 Indigo 145 References 147 9 Natural Dye Gardens in North America 161 Wendy Weiss and Thomas Bechtold 9.1 Introduction 161 9.2 Participants 162 9.3 Education 163 9.4 Motivation to Work with Natural Dye 166 9.5 Plant List— Cultivated Plants 166 9.6 Chemical Background of Most Relevant Plants 168 9.7 Plant List— Foraged Plants 172 9.8 Plants with Indigotin 172 9.9 Importance of the Fibershed Movement 173 9.10 Educational and Community Gardens 174 9.11 Mexico 177 9.12 Canada 177 9.13 Future Research 178 References 178 Notes 179 III Colorant Production and Properties 181 10 Chlorophylls 183 María Roca 10.1 Introduction 183 10.2 Chemical Structures and Physicochemical Properties 184 10.3 Chlorophylls as Colorants 187 10.4 New Trends in the Use of Chlorophylls as Colorants 189 10.5 Stability and Analysis 190 10.6 Toxicological and Safety Aspects 191 References 192 11 Indigo— Production and Properties 195 Philip John and Luciana Gabriella Angelini 11.1 Introduction 195 11.2 Agronomy 196 11.2.1 Isatis 196 11.2.1.1 Developmental Stages and Climate and Soil Crop Requirements 197 11.2.1.2 Rotation 201 11.2.1.3 Soil Tillage and Seed Sowing 202 11.2.1.4 Weeds, Pests, and Diseases 203 11.2.1.5 Fertilizers and Irrigation 204 11.2.1.6 Harvesting and Yields 205 11.2.1.7 Seed Production 207 11.2.1.8 Isatis indigotica Compared with Isatis tinctoria 208 11.2.2 Persicaria 209 11.2.2.1 Introduction 209 11.2.2.2 Developmental Stages 211 11.2.2.3 Sowing, Harvesting, and Yield 211 11.2.2.4 Weeds, Pests, and Diseases 216 11.2.2.5 Fertilizer and Irrigation Requirement 216 11.2.2.6 Seed Production 217 11.2.3 Indigofera 217 11.3 Methods of Determining Indigo 219 11.4 Precursors in the Plants 222 11.5 Direct Dyeing with Indican 227 11.6 Indigo Formation 227 11.7 Extraction Procedures 229 11.7.1 Traditional Process Using Crushed Leaf Material 229 11.7.1.1 Isatis 229 11.7.1.2 Persicaria 230 11.7.2 Steeping in Water 231 11.7.2.1 Indigofera 232 11.7.2.2 Isatis 234 11.7.2.3 Persicaria 239 11.8 Purity of Natural Indigo 240 11.8.1 Purification by Sublimation 241 11.8.2 Impurities in Natural Indigo 242 Acknowledgements 245 References 245 12 Anthocyanins: Revisiting Nature’s Glamorous Palette 251 Maria J. Melo, Fernando Pina, Natércia Teixeira and Claude Andary 12.1 Chemical Basis 251 12.1.1 Chemical Structures 251 12.1.2 Equilibria in Solution 253 12.1.3 Kinetics 254 12.1.4 Color and Color Stability 254 12.1.5 Anthocyanins as Antioxidants 258 12.2 Natural Sources and Applications for Anthocyanins 259 12.2.1 Plants Sources, Content, Influencing Parameters 259 12.2.2 Food Colorants 260 12.2.3 Other Uses 261 12.2.4 Examples of Commercial Products and Processing 262 References 263 Appendix 1 267 A1.1 Multi-Equilibria in Acidic and Basic Media 267 A1.2 Measuring the Equilibria Constants 269 13 Natural Colorants— Quinoid, Naphthoquinoid, and Anthraquinoid Dyes 271 Goverdina C. H. Derksen and Thomas Bechtold 13.1 Introduction 271 13.2 Benzoquinone Dyes 271 13.3 Diaryloylmethane Dyes 273 13.4 Naphthoquinone Dyes 273 13.4.1 Lawson (2- hydroxy- 1,4- naphthoquinone, CI Natural Orange 6) 274 13.4.1.1 Properties and Use 274 13.4.1.2 Agricultural Aspects 276 13.4.2 Juglone (5- hydroxy- 1,4- naphthoquinone, CI Natural Brown 7) 278 13.5 Anthraquinone Dyes 279 13.5.1 Main Components Emodin and Chrysophanol— Rheum and Rumex Species 279 13.5.2 Main Components Alizarin and/or Pseudopurpurin/Purpurin 281 13.5.2.1 Plant Sources 281 13.5.2.2 Madder CI Natural Red 8 282 References 294 14 Natural Colorants from Lichens and Mushrooms 317 Riikka Räisänen 14.1 Use of Lichen and Mushroom Colorants in History 317 14.2 Cultivation of Lichens and Mushrooms 318 14.3 Colorant Structures in Lichens and Mushrooms 319 14.3.1 Lichen Dyes: Orchils and Litmus 321 14.3.2 Yellowish, Brownish, and Reddish Colorants from Lichen 322 14.3.3 Blue Terphenylquinones from Mushrooms 322 14.3.4 Anthraquinones 324 14.3.4.1 Bloodred Webcap (Cortinarius sanguineus) 324 14.3.5 Other Colorants of Fungi 326 14.3.5.1 Yellows from Grevillines 326 14.3.5.2 Yellow and Orange Colors from Pulvinic Acid Derivatives 326 14.3.5.3 Brown from Badiones 326 14.4 Stability of Lichen and Mushroom Colorants 326 14.5 New Approaches to Lichen and Fungal Colorants 327 References 328 15 Focus on Tannins 333 Riitta Julkunen-Tiitto and Hely Häggman 15.1 Introduction 333 15.2 Chemical Structure, Biosynthesis, and Degradation 335 15.3 Properties of Tannins 338 15.4 Chemical Activities of Tannins 340 15.5 Analysis of Tannins 340 15.5.1 Sample Preservation 340 15.5.2 Extraction and Purification 340 15.5.3 Quantification of Tannins 341 15.6 Use, Toxicology, and Safety Aspects of Tannins 342 References 345 16 Carotenoid Dyes— Properties and Production 351 U. Gamage Chandrika 16.1 Introduction 351 16.1.1 Occurrence of Carotenoids 351 16.1.2 Chemistry of Carotenoids 351 16.1.3 Chemical Characteristics of Natural Carotenoids 352 16.2 Properties and Functions of Carotenoids 354 16.2.1 Carotenoids’ Role as Pro- vitamin A 354 16.2.2 Use of Carotenoids as Markers of Dietary Practices 356 16.2.3 Carotenoids as Antioxidants 356 16.2.4 Carotenoids in the Macular Region of the Retina 357 16.2.5 Carotenoids as Anticancer Agents 357 16.2.6 Carotenoids as Natural Colorants 357 16.3 General Procedure for Carotenoid Analysis 357 16.3.1 Sampling 359 16.3.2 Extraction 359 16.3.3 Saponification of Carotenoids 359 16.3.4 Chromatographic Separation 359 16.3.5 Chemical Tests 361 16.3.6 Detection and Identification of Carotenoids 361 16.3.7 Quantification of Carotenoids 362 16.4 Problems in Carotenoid Analysis 362 16.5 Factors Influencing Carotenoid Composition in Plant Sources 363 16.5.1 Stage of Maturity 363 16.5.2 Cultivar or Varietal Differences 363 16.5.3 Climatic or Geographic Effects 364 16.5.4 Post- Harvest Storage and Packing 364 16.5.5 Changes in Processing/Cooking 364 16.5.6 Effect of Agrochemicals 366 References 366 17 Flavonoids as Natural Pigments 371 M. Monica Giusti, Gonzalo Miyagusuku-Cruzado and Taylor C. Wallace 17.1 Introduction 371 17.2 Role of Localized Flavonoids in the Plant 372 17.3 General Flavonoid Chemical Structure 372 17.4 Biosynthesis of Flavonoids 373 17.5 Anthocyanins as Natural Colorants 373 17.5.1 Structure 375 17.5.2 Structural Transformation and pH 376 17.5.3 Temperature 377 17.5.4 Oxygen and Ascorbic Acid 377 17.5.5 Light 378 17.5.6 Enzymes and Sugars 379 17.5.7 Sulfur Dioxide 379 17.5.8 Co- Pigmentation and Metal Complexation 380 17.6 Other Flavonoids as Natural Colorants 381 17.6.1 Yellow Flavonoid Pigments 381 17.6.2 Tannins 381 17.6.3 Anthocyanin- Derived Pigments: Pyranoanthocyanins 382 17.7 Therapeutic Effects of Flavonoids in the Diet 382 17.8 The Use of Flavonoids as Food Colors in the US and EU 383 References 384 18 Natural Colorants from Fungi 391 Cassamo U. Mussagy, Fernanda de Oliveira and Valeria C. Santos-Ebinuma 18.1 Introduction 391 18.2 Types of Fungi Colorants 392 18.3 Fungal Producer of Colorants 394 18.4 Bioprocess 395 18.4.1 Biosynthesis Pathway 395 18.4.2 Production and Extraction Process 400 18.5 Toxicity 404 18.6 Industrial Application of Fungi Colorants 406 18.7 Conclusion 407 References 407 19 Natural Colorants from Cyanobacteria and Algae 417 Laurent Dufossé 19.1 Introduction 417 19.2 Phycobiliproteins from Cyanobacteria 418 19.2.1 Structural Characteristics of Phycobiliproteins 420 19.2.2 Food Grade Phycobiliproteins 422 19.2.3 Future Trends 422 19.3 Pigments from Microalgae 422 19.3.1 β- Carotene from the Microalga Dunaliella, Salty but Effective! 423 19.3.1.1 β- Carotene from Microalgae 423 19.3.1.2 Dunaliella Species for Carotenoids 424 19.3.2 Why Carotenoids from Dunaliella? 424 19.3.2.1 Natural vs. Synthetic β- Carotene 424 19.3.2.2 Applications of β- Carotene 424 19.3.2.3 Advantages of Carotenoids Production from Dunaliella 425 19.3.2.4 Process for Production of β- Carotene from Dunaliella 425 19.3.2.5 Companies Producing Dunaliella 425 19.3.2.6 Marketed Products of β- Carotene 426 19.3.3 Haematococcus for Astaxanthin, the Red Gold Rush 426 19.3.3.1 Advantages of Astaxanthin over Other Carotenoids 427 19.3.3.2 Astaxanthin as Nutraceutical 427 19.3.3.3 Astaxanthin as Antioxidant 427 19.3.3.4 Astaxanthin for Health 428 19.3.3.5 Astaxanthin for Salmon and Trout Feeds 428 19.3.3.6 Astaxanthin for Humans 429 19.3.3.7 Production System for Haematococcus 429 19.3.3.8 Companies Producing Astaxanthin from Haematococcus 430 19.3.3.9 Astaxanthin- Containing Formulations 431 19.4 Natural Colorants from Macroalgae (e.g., Seaweeds) 431 19.4.1 Biodiversity of Seaweeds 431 19.4.2 Seasonal Variations and Environmental Threats 432 19.4.3 Major Classes of Seaweed Pigments 433 19.4.3.1 Chlorophylls 433 19.4.3.2 Carotenoids 433 19.4.3.3 Phycobiliproteins 434 19.5 Conclusion 434 References 434 20 Biotechnological Production of Microbial Pigments: Recent Findings 439 Vivian Katherine Colorado Gómez, Juan Pablo Ruiz-Sánchez, Alejandro Méndez-Zavala, Lourdes Morales-Oyervides and Julio Montañez 20.1 Introduction 439 20.2 Microbial Pigments Market 440 20.3 Production Strategies 440 20.4 Novel Extraction Technologies for Pigments Recovery 441 20.5 Regulation and Biosynthesis of Microbial Pigments 443 20.6 Strain Engineering Strategies for Pigment Production 446 20.7 Trends in New Microbial Sources of Pigments 448 20.8 Microbial Pigments Applications 449 20.8.1 Solar Cells 449 20.8.2 Therapeutic Application 450 20.8.3 Other Applications 450 20.9 Regulations on Microbial Pigments Use 451 20.10 Conclusions and Future Perspectives 452 References 452 21 Analytical Methods for Characterization and Standardization of Natural Dyes and Pigments 459 Tung Pham, Avinash Manian and Thomas Bechtold 21.1 Introduction 459 21.2 Chemical Analysis— Identification 460 21.3 Quantification by Sum Parameters 463 21.4 Applicatory Tests 464 21.5 Product Performance 465 References 466 22 Wood— From Natural Color Patterns Toward Naturally Altered Color Impressions 469 Martin Weigl-Kuska, Andreas Kandelbauer, Christian Hansmann and Ulrich Müller 22.1 The Color of Wood 469 22.1.1 Wood Chemical Composition 470 22.1.2 Wood Anatomical Appearance 471 22.1.3 Physical Properties of the Wood Surface 472 22.2 Coatings 473 22.3 Dyes 477 22.3.1 Impregnation 477 22.3.1.1 Technology 477 22.3.1.2 Color 479 22.3.1.3 Products 480 22.4 Color Modification 481 22.4.1 Drying 482 22.4.1.1 Basics 482 22.4.1.2 Technology 483 22.4.1.3 Color 484 22.4.2 Steaming 485 22.4.2.1 Basics 485 22.4.2.2 Technology 485 22.4.2.3 Color 486 22.4.3 Thermal Treatment 487 22.4.3.1 Technology 487 22.4.3.2 Color 487 22.4.4 Ammoniation 488 22.4.4.1 Basics 488 22.4.4.2 Color 489 22.4.5 Bleaching 491 22.4.5.1 Basics 491 22.4.5.2 Color 491 22.4.6 Enzymatic Treatment 492 22.4.6.1 Basics 492 22.4.6.2 Laccases 493 22.4.7 Radiation 495 22.4.7.1 Basics 495 22.4.7.2 Color 495 22.4.7.3 Technology 497 22.5 Outlook 498 References 498 23 The Role of Mordants in Fixation of Natural Dyes 507 Avinash P. Manian 23.1 Introduction 507 23.2 Metal Salts 508 23.3 Biomordants 508 23.4 Substrate Pretreatments 508 23.5 No Mordant 509 References 509 24 Textile Coloration with Natural Dyes and Pigments 517 Thomas Bechtold, Tung Pham and Avinash P. Manian 24.1 Introduction 517 24.2 Reasons for Natural Coloration 518 24.3 The Dyestuff–Fiber Interaction 520 24.4 Design of a Dyeing Process 521 24.5 Transfer of a Dyeing Process into Technical Scale 523 24.6 Processes and Resources 524 24.7 Technical Requirements for a Natural Dyestuff 526 24.7.1 Gamut and Color Shade 526 24.7.2 Fastness Criteria 528 24.8 Handling of Natural Dyes in a Technical Dyehouse 530 24.9 Mordanting 531 24.10 Natural Dyes on an Industrial Scale 533 24.10.1 Dyeing Technology— Exhaust Process 533 24.10.2 Hank Dyeing of Woolen Yarn and Production of Woolen Caps 534 24.10.3 Dyeing of Cones in a Yarn Dyeing Machine 534 24.10.4 Dyeing of Cotton Fabric on a Jet Dyeing Machine 535 24.10.5 Fabric Dyeing on a Garment Dyeing Machine 536 24.10.6 Dyeing of Polyamide Tights in a Paddle Dyeing Machine 536 24.10.7 Dyeing Technology— Continuous Dyeing 536 24.11 Conclusion 537 Acknowledgement 538 References 538 25 Hair Coloration with Natural Dyes and Pigments 543 Thomas Bechtold 25.1 Introduction 543 25.2 Human Hair 544 25.3 General Requirements on Hair Dyeing Concepts 544 25.4 Chemical Principles of Dyestuff Binding 546 25.5 Relevant Natural Dyes for Hair Dyeing 546 25.5.1 Naphthoquinone Dyes— Henna and Walnut 546 25.5.1.1 Henna, CI (Color Index) Natural Orange 6 546 25.5.1.2 Juglon, CI Natural Brown 7 547 25.5.2 Indigo 548 25.5.3 Metal Complexes 548 25.5.4 Metal Reaction Dyes 550 25.5.5 Anthraquinoid Dyes 551 25.6 Specialties 551 25.7 Regulations 552 References 552 26 Natural Colorants in the Mass Coloration of Plastics 557 Thomas Bechtold and Tung Pham 26.1 Introduction 557 26.2 Representative Examples 559 Acknowledgement 561 References 561 27 Natural Colorants in Printing/Packaging 563 Thomas Bechtold and Tung Pham 27.1 Introduction 563 27.2 Packaging Films 564 27.3 Film Coloration 567 27.4 Paper Dyeing 568 27.5 Paints 568 Acknowledgement 569 References 569 28 Technical Aspects and Requirements to Produce Natural Colorants— Processes and Product Standardization 573 Thomas Bechtold and Avinash Manian 28.1 Introduction 573 28.2 Sources of Plant Material— Product I 576 28.2.1 Organic Farming 576 28.2.2 Sustainable Farming 576 28.2.3 Native Species 577 28.2.4 Farming for Food or/and Natural Colorants 577 28.2.5 Residual Materials and By- Products 577 28.3 Processing to Dyestuff— Product II 579 28.4 Quality Control and Standardization of a Dye (Product II) 583 28.4.1 Anthocyanins 584 28.4.2 Flavonoids 584 28.4.3 Dye Lakes 585 28.5 Challenges for the Industrial Use of Natural Colorants 585 28.6 Dealing with Sustainability 586 28.7 Conclusions 587 References 587 29 Environmental and Economic Position of Natural Colorants— Energy and Resources Balances, Sustainability, Ecology, and Costs 591 Susanne Geissler and Thomas Bechtold 29.1 Introduction 591 29.2 Dye Plant Production 592 29.3 Dye Extraction and Dyestuff Production 595 29.4 Transportation 596 29.5 Textile Dyeing 596 29.6 Commercial Aspects— Costs 597 29.6.1 Basic Requirements for the Industrial Use of Natural Colorants 598 29.6.1.1 Precondition 1: acceptable costs of natural colorants and dyeing processes 599 29.6.1.2 Precondition 2: feasible cost of process engineering 599 29.6.1.3 Precondition 3: compliance with requested colorfastness properties 599 29.6.1.4 Precondition 4: competitive cost of naturally dyed products 600 29.6.1.5 Precondition 5: security of natural colorant supply 600 29.6.2 Consumer Expectations 600 29.6.3 Market Research for Naturally Dyed Products 601 29.7 Production Costs of Natural Colorant Products 602 29.7.1 Cost Categories 603 29.7.2 Aspects Influencing Production Costs 603 29.8 Prices of Synthetic Dyes— How Much Are Textile Companies Prepared to Pay for Dyes? 605 29.9 Acceptable Production Costs through a Mixed Portfolio (Agricultural Primary Production and Residues from Other Production Processes) 606 29.10 Closed- Loop Economy: Toward a Zero- Emission and Zero- Waste Society 607 29.11 Considerations Concerning the Life Cycle 609 29.12 Conclusion: Aspects Influencing Market Development for Natural Colorants 609 References 610 30 Aspects of Human Toxicology and Consumer Safety 613 Judith Büttler, Thomas Bechtold and Tung Pham 30.1 Introduction 613 30.2 Basic Aspects of Xenobiotic- Induced Toxicity 614 30.3 Toxicological Aspects of Natural Colorants in Food and Medical Applications 615 30.3.1 Risk Assessment 617 30.3.2 Therapeutic Effects (= Risk) 618 30.4 Toxicological Aspects of Natural Colorants in Cosmetics 618 30.4.1 Risk Assessment 619 30.5 Toxicological Aspects of Natural Colorants in Textile Dyeing 619 30.5.1 Plant Extracts 620 30.5.2 Pretreatment Agents and Mordants 621 30.5.3 Wastewater and Antimicrobial Compounds 621 30.5.4 Dyed Products 622 30.6 Test Methods for Toxicity Screening 622 30.6.1 Extract Preparation 624 30.6.2 Cytotoxicity 624 30.6.3 Mutagenicity and Carcinogenicity 625 30.6.4 Antimicrobial Activity 625 30.6.5 Metabolism and In Vivo Animal Bioassays 626 Acknowledgement 626 References 626 Index 629

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Book SynopsisA Companion to Biological Anthropology The discipline of biological anthropologythe study of the variation and evolution of human beings and their evolutionary relationships with past and living hominin and primate relativeshas undergone enormous growth in recent years. Advances in DNA research, behavioral anthropology, nutrition science, and other fields are transforming our understanding of what makes us human. A Companion to Biological Anthropology provides a timely and comprehensive account of the foundational concepts, historical development, current trends, and future directions of the discipline. Authoritative yet accessible, this field-defining reference work brings together 37 chapters by established and younger scholars on the biological and evolutionary components of the study of human development. The authors discuss all facets of contemporary biological anthropology including systematics and taxonomy, population and molecular genetics, human biology and functional adaptation, early primate evolution, paleoanthropology, paleopathology, bioarchaeology, forensic anthropology, and paleogenetics. Updated and expanded throughout, this second edition explores new topics, revisits key issues, and examines recent innovations and discoveries in biological anthropology such as race and human variation, epidemiology and catastrophic disease outbreaks, global inequalities, migration and health, resource access and population growth, recent primate behavior research, the fossil record of primates and humans, and much more. A Companion to Biological Anthropology, Second Edition is an indispensable guide for researchers and advanced students in biological anthropology, geosciences, ancient and modern disease, bone biology, biogeochemistry, behavioral ecology, forensic anthropology, systematics and taxonomy, nutritional anthropology, and related disciplines.Table of ContentsNotes on Contributors x Acknowledgments xx Foreword xxii 1 The Breadth and Vision of Biological Anthropology 1 Clark Spencer Larsen Part I: History 13 2 Foundation and History of Biological Anthropology 15 Michael A. Little and Jane E. Buikstra Part II: The Present and the Living 39 3 Evolution: What It Means and How We Know 41 Kenneth M. Weiss and Anne V. Buchanan 4 Systematics, Taxonomy, and Phylogenetics: Ordering Life, Past and Present 55 Alexis Uluutku and Bernard Wood 5 Diversity, Ancestry, and Evolution: The Genetics of Human Populations 73 John H. Relethford 6 Human Population Genomics: Diversity and Adaptation 87 Dennis H. O’Rourke 7 Race, Racism, and Racial Thinking: Implications for Biological Anthropology 103 Rachel Caspari 8 Human Life History Evolution: Growth, Development, and Senescence 122 Douglas E. Crews and Barry Bogin 9 Climate-Related Human Biological Variation 140 Cynthia M. Beall 10 Infectious Disease and Epidemiology: Dealing with the Present and Preparing for Future New Epidemics 167 Lisa Sattenspiel and Carolyn Orbann 11 Evolutionary Insights into the Social and Environmental Drivers of Health Inequality: The Example of theGlobal Epidemic of Overweight and Cardiovascular Diseases 184 Christopher W. Kuzawa and Melissa B. Manus 12 Ancient DNA and Disease 199 Anne Stone 13 Paleogenomics: Ancient DNA in Biological Anthropology 210 C. Eduardo Guerra Amorim 14 Demography, Including Paleodemography 223 Lyle W. Konigsberg George R. Milner, and Jesper L. Boldsen 15 Nutritional Anthropology: Contemporary Themes in Food, Diet, and Nutrition 244 Darna L. Dufour and Barbara A. Piperata 16 Ongoing Evolution: Are We Still Evolving? 262 Fabian Crespo 17 Primates Defined 277 W. Scott McGraw 18 Primate Behavior, Social Flexibility, and Conservation 300 Karen B. Strier 19 Behavioral Ecology: Background and Illustrative Example 314 James F. O’Connell and Kristen Hawkes 20 Brain, Cognition, and Behavior in Humans and Other Primates 329 Elaine N. Miller and Chet C. Sherwood Part III: The Past and the Dead 345 21 Taphonomy and Biological Anthropology 347 Luis L. Cabo, Dennis C. Dirkmaat, and Andrea M. Zurek-Ost 22 Primate Origins: The Earliest Primates and Euprimates and Their Role in the Evolution of the Order 365 Mary T. Silcox and Sergi López-Torres 23 Catarrhine Origins and Evolution 381 David R. Begun 24 The Human Journey Begins: Origins and Diversity in Early Hominins 400 Scott W. Simpson 25 Early Homo: Systematics, Paleobiology, and the First Out-of-Africa Dispersals 421 G. Philip Rightmire 26 Panmixis in Middle and Late Pleistocene Human Subspecies: The Genetic/Genomic Revolution inPaleoanthropology 440 Fred H. Smith and Whitney M. Karriger 27 Bioarchaeology: Transformations in Lifestyle, Morbidity, and Mortality 458 George R. Milner and Clark Spencer Larsen 28 Paleopathology: A Twenty-first Century Perspective 474 Jane E. Buikstra 29 Forensic Anthropology: Current Issues 494 Douglas H. Ubelaker 30 Diet reconstruction and Ecology 510 Margaret J. Schoeninger and Laurie J. Reitsema 31 Current Concepts in Bone Biology 527 Mary E. Cole, James H. Gosman, and Samuel D. Stout 32 Deducing Attributes of Dental Growth and Development from Fossil Hominin Teeth 544 Debbie Guatelli-Steinberg 33 Skull: Function – New Directions 559 Qian Wang and Rachel A. Menegaz 34 Dental Microwear Analysis: Wear We Are Going, Wear We Have Been 572 Christopher W. Schmidt and Peter S. Ungar 35 Primate Locomotion: A Comparative and Developmental Perspective 587 Michael C. Granatosky and Jesse W. Young 36 Teaching Biological Anthropology: Pedagogy of Human Evolution and Human Variation 603 Briana Pobiner Index 622

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Book SynopsisFluorescent Dye Labels and Stains The only comprehensive database of fluorophores and their physical and photochemical properties Fluorophores are chemical compounds that strongly absorb in the ultraviolet, visible, and/or near-infrared and with bright emission in these ranges. As a result, they are exceptionally valuable as dyes for various analytical processes, capable of labelling and staining particular targets for purposes of fluorescent imaging, sensitive detection, and quantification (exhibiting linear responses over very wide concentration ranges). These compounds are many and varied, and panoramic views of their options, physical properties and their reactions to light excitations can be critical to their successful integration into chemical analysis, pharmaceutical analysis, clinical analysis, microscopies, optical bioimaging, cancer imaging, real-time PCR, flow cytometry, multiplexing in proteomics, life sciences in general, and many other high-tech fieldTable of ContentsPreface x Acronyms xii Symbols and Conventionsxiii 1 Introduction 1 2 Basic Definitions and Fundamentals 5 2.1 Introduction 5 2.2 Light Sources 5 2.3 Filtering and Dispersing Light 6 2.3.1 Absorber Filters 6 2.3.2 Interference Filters 8 2.3.3 Polarizers 8 2.3.4 Prisms 9 2.3.5 Grating 9 2.4 Light Detectors 10 2.5 Light Beams 12 2.5.1 Radiant Power and Radiance in Space: Divergent and Collimated Beams 12 2.5.2 Radiant Power and Radiance in Time: Continuous, Modulated, and Pulsed 13 2.5.3 Spectral Radiant Power (Emission Spectra) of Lamps, LEDs, and Lasers 14 2.5.4 Light Wavelength, Transmittance, and Absorbance 14 2.5.5 Spontaneous Decay and Stimulated Emission in Lasers and STED Nanoscopy 16 2.5.6 Energy, Momentum, Polarization, Spin, and Angular Momentum 17 2.6 Light Collection Set-Ups 17 2.6.1 Microscope Objectives 17 2.6.2 Fluorescence Detection Set-Ups 18 2.6.3 Fluorescence Imaging Set-Ups 18 2.7 Fundamentals of Fluorescence 21 2.7.1 Fluorescence: Fields of Application 22 2.7.2 Molar Absorption Coefficient 23 2.7.3 Excitation Spectra 24 2.7.4 Emission Spectra 25 2.7.5 Stokes Shift 25 2.7.6 Fluorescence Quantum Yield 27 2.7.7 Brightness 27 2.7.8 Effective Brightness 27 2.7.9 Fluorescence Mean-Lifetime 28 2.7.10 Factors Affecting Fluorescence 29 2.7.10.1 Effect of Microenvironment 29 2.7.10.2 Influence of Liquid Viscosity on Fluorescence Quantum Yield and Fluorescence Mean-Lifetime 30 2.7.10.3 Influence of Electric Permittivity and Hydrogen Bonding 30 2.7.10.4 Effects of Temperature 31 2.7.10.5 Quenching 31 2.7.10.6 Self-Quenching 32 2.7.10.7 Singlet Oxygen Production by Sensitizer Dyes 32 2.8 Photostability 32 3 Target-Fluorophore Binding 37 3.1 Introduction 37 3.2 Choosing the Right Solvent 37 3.2.1 Water and PBS 37 3.2.2 Water Miscible Organic Solvents 39 3.3 Fluorogenic Reactions 45 3.3.1 Primary Amines 45 3.3.1.1 Fluorogenic Reactions of Primary Amines With Homocyclic o-Phthaldihaldehydes 45 3.3.1.2 Fluorogenic Reactions of Primary Amines With Heterocyclic o-Dicarboxaldehydes 49 3.3.1.3 Fluorogenic Reactions of Primary Amines With Other Reagents 49 3.3.2 Secondary Amines 52 3.3.3 Thiols 53 3.3.4 Cyanide 53 3.3.5 α-Dicarbonylic Compounds 53 3.4 Labeling Reactions 54 3.4.1 Covalent Labeling of Amines 56 3.4.2 Covalent Labeling of Thiols 57 3.4.3 Covalent Labeling of Carboxylic Acids 57 3.4.4 Covalent Labeling of Alcohols 58 3.4.5 Covalent Labeling of Reducing Saccharides 58 3.4.6 Others 60 3.5 Immunofluorescence 61 4 Classes and Molecular Structures 65 4.1 Introduction 65 4.2 Rhodamines 73 4.2.1 Rhodamines With Absorption Maximum Below 500 nm 73 4.2.2 Rhodamines With Absorption Maximum Between 500 and 550 nm 73 4.2.3 Rhodamines With Absorption Maximum Between 550 and 600 nm 73 4.2.4 Rhodamines With Absorption Maximum Above 600 nm 75 4.2.5 Rhodamines With a High Net Charge 78 4.3 HAS-Rhodamines 79 4.3.1 Carbo-Rhodamines 79 4.3.2 Silico-Rhodamines 79 4.3.3 Other HAS-Rhodamines 79 4.4 Pyronines 79 4.5 HAS-Pyronines 82 4.6 Sulforhodamines 84 4.7 HAS-Sulforhodamines 84 4.8 Fluoresceins 84 4.8.1 Non-Halogenated Fluoresceins 88 4.8.2 Halogenated Fluoresceines 89 4.8.3 Mercaptofluoresceins 91 4.8.4 Fluorescein-Analogs 91 4.9 HAS-Fluoresceins 91 4.10 Sulfofluoresceins 91 4.11 Fluorones 92 4.12 HAS-Fluorones 93 4.13 Cyanines 93 4.13.1 Trimethine Cyanines 95 4.13.2 Pentamethine Cyanines 95 4.13.3 Heptamethine Cyanines 97 4.14 Borondipyrromethenes 97 4.14.1 Small Water-Soluble Borondipyrromethenes 100 4.14.2 Medium-Sized, Water-Soluble Borondipyrromethenes 104 4.14.3 Large Water-Soluble Borondipyrromethenes 106 4.14.4 Other Classes Derived From Borondipyrromethene 108 4.15 Rhodols 109 4.15.1 The First Rhodols Synthesized 109 4.15.2 Rhodols Synthesized More Recently 109 4.15.3 Rhodol Analogs 112 4.16 HAS-Rhodols 113 4.17 Rosamines 114 4.18 HAS-Rosamines 114 4.18.1 Silico-Rosamines 114 4.18.2 Phospha-Rosamines 115 4.18.3 Other HAS-Rosamines 115 4.19 Rosols 118 4.20 HAS-Rosols 118 4.21 Pyrodols and Pyrodones 119 4.22 Trianguleniums 120 4.23 Acridines 120 4.23.1 Simple Acridines 121 4.23.2 Acridones 122 4.24 Merocyanines 122 4.25 Phenoxazines 122 4.26 Coumarins 125 4.26.1 7-Hydroxy Coumarins 125 4.26.2 Small 7-Amino Coumarins 125 4.26.3 More Elaborated 7-Amino Coumarins 126 4.27 Sulforhodols 128 4.28 Pyrenes 128 4.29 Quinolines 129 4.30 Benzothiazoles 132 4.31 Chromones 133 4.32 Naphthalimides 133 4.33 Indoles 134 4.34 Naphthalenes 135 4.35 Squaraines 137 4.36 Pteridines 137 4.37 Isoquinolines 139 4.38 Benzene Derivatives 140 4.39 Other Single Structures 140 4.39.1 Small Structures 140 4.39.2 Medium-Sized Structures 142 4.39.3 Large Structures (Na > 80) 142 4.40 Hybrid Structures 145 4.40.1 Hybrid Structures: Fusion of Two Existing Dyes 146 4.40.2 Hybrid Structures: Single Bond Connected Dyes 146 4.40.3 Hybrid Structures: Polymethine Bridged Dyes 147 4.41 Non-Disclosed Structures 148 4.42 Fluorescent Structures Other Than Small-Molecule Organic Dyes 149 5 Scattergrams of the Photophysical Properties 163 5.1 Introduction 163 5.2 Photophysical Properties Along the Spectrum 164 5.2.1 Molecular Sizes vs. λa,max 164 5.2.2 Molar Absorption Coefficients vs. λa,max169 5.2.3 Fluorescence Quantum Yield vs. λa,max 169 5.2.4 Brightness vs. λa,max 172 5.2.5 Stokes Shift vs. λa,max 173 5.2.6 Stokes Shift vs. Brightness 174 5.2.7 Fluorescence Mean-Lifetime vs. λa,max 177 5.2.8 Fluorescence Mean-Lifetime vs. Brightness 178 5.3 Fluorophore Charges 180 6 Band Shapes and Excitation and Emission Ranges 185 6.1 Introduction 185 6.2 Typical Absorption and Emission Spectra of Some Classes 187 6.3 Coarse Prediction of Excitation and Emission Ranges 191 7 Measuring Photostability and Mitigating Photobleaching 195 7.1 Introduction 195 7.2 Measuring Photostability 196 7.3 Mitigating Photobleaching 202 Appendix A A1. Short Name, Name, Class, Molecular Formula, and References 207 Appendix B B1. Ranked by Excitation Maximum 253 Appendix C C1. Ranked by Emission Maximum 297 Appendix D D1. Ranked by Stokes Shifts 335 Appendix E E1. Ranked by Brightness 371 Appendix F F1. Ranked by Fluorescence Mean-Lifetime 419 Appendix G G1. Ranked by Molecular Net Charge 433 Index 479

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Book SynopsisPlant polyphenols are specialized metabolites that constitute one of the most common and widespread groups of natural products. They are essential plant components for adaptation to the environment and possess a large and diverse range of biological functions that provide many benefits to both plants and humans. Polyphenols, from their structurally simplest forms to their oligo/polymeric versions (i.e. tannins and lignins), are phytoestrogens, plant pigments, antioxidants, and structural components of the plant cell wall. The interactions between tannins and proteins are involved in plant defense against predation, cause astringency in foods and beverages, and affect the nutritional and health properties of human and animal food plants. This eighth volume of the highly regarded Recent Advances in Polyphenol Research series is edited by Juha-Pekka Salminen, Kristiina Wahala, Victor de Freitas, and Stephane Quideau, and brings together chapters written by some of the leading experts workTable of ContentsContributors Preface Acknowledgements 1 Lignins and Lignification: New Developments and Emerging ConceptsJohn Ralph, Hoon Kim, Fachuang Lu, Rebecca A. Smith, Steven D. Karlen, Nuoendagula, Koichi Yoshioka, Alexis Eugene, Sarah Liu, Canan Sener, Daisuke Ando, Mingjie Chen, Yanding Li, Leta L. Landucci, Sally A. Ralph, Vitaliy I. Timokhin, Wu Lan, Jorge Rencoret, José C. del Río 1.1 Introduction 1.2 The monolignol pathway and interacting pathways -- New lignins 1.3 Lignin conjugates, 'clip-offs' -- new discoveries, and enhancing levels 1.4 Features of lignification, and the possibility of new polymerization pathways 1.5 The value of model studies and synthesis -- a reminder 1.6 New or improved analytics 1.7 Conclusions and Opportunities 2 Synthesis of epigallocatechin gallate, nobiletin and their derivatives for chemical-biology studiesTomohiro Asakawa, Makoto Inai and Toshiyuki Kan 2.1 Synthetic investigations of catechin derivatives 2.2 Synthesis and application of fluorescent catechin probes 2.3 Generation of catechin antibody 2.4 PET imaging of biodistribution of catechin 2.5 Practical synthesis of nobiletin 2.6 Derivatization of desmethyl nobiletins 2.7 PET imaging of biodistribution of nobiletin 2.8 Synthesis and application of fluorescent nobiletin probe 2.9 Conclusions 3 Procyanidins in the Onset and Progression of Colorectal Cancer: Recent Advances and Open QuestionsWei Zhu, Gerardo G. Mackenzie and Patricia I. Oteiza 3.1 Introduction 3.2 Procyanidins:chemistry and metabolism 3.3 Procyanidins and CRC: epidemiological evidence 3.4 Procyanidins and CRC: rodent studies 3.5 Procyanidins and CRC: mechanisms of actions 3.6 Conclusions and open questions 3.7 Acknowledgements 4 The Potential of Low Molecular Weight (Poly)phenol Metabolites for Attenuating Neuroinflammation and Treatment of Neurodegenerative DiseasesDaniela Marques, Rafael Carecho, Diogo Carregosa and Cláudia Nunes dos Santos 4.1 Introduction - Neurodegenerative disorders, dietary (poly)phenols and neuroinflammation 4.2 (Poly)phenols metabolism and distribution 4.3 (Poly)phenol metabolites and their brain permeability 4.4 LMW (poly)phenols metabolites as effectors for attenuating neuroinflammation 4.5 Concluding remarks 5 Deciphering Complex Natural Mixtures through Metabolome Mining of Mass Spectrometry Data: the Plant Specialized Metabolome as a Case StudyJustin J.J. van der Hooft, Madeleine Ernst, Daniel Papenberg, Kyo Bin Kang, Iris F. Kappers, Marnix H. Medema, Pieter C. Dorrestein, and Simon Rogers 5.1 Introduction 5.2 Materials and methods 5.3 Results and discussion 5.4 Current limitations 5.5 Conclusions 5.6 Outlook 5.7 Acknowledgements 6 Application of MS-based Metabolomics to Investigate Biomarkers of Apple Consumption Resulting from Microbiota and Host Metabolism InteractionsFulvio Mattivi and Maria M. Ulaszewska 6.1 Introduction 6.2 Materials and methods 6.3 Results and discussion 6.4 Conclusions 7 Non-extractable polyphenols should be systematically included in polyphenols analysisEnrique Báez-García, Sonia G. Sáyago-Ayerdi and Jara Pérez-Jiménez 7.1 Introduction: the concept of non-extractable polyphenols 7.2 Analysis of non-extractable polyphenols 7.3 Why should non-extractable polyphenols be systematically included in polyphenol analysis? 7.4 Relevance of the determination of non-extractable polyphenols in quality control 7.5. Perspectives 8 Template-mediated engineering of functional metal--phenolic complex coatingsSteve Spoljaric, J.J. Richardson, Yi Ju, Frank Caruso 8.1 Introduction 8.2 Template-mediated techniques to deposit MPNs 8.3 MPN film properties 8.4 MPN surface interactions and applications 8.5 Upscaling considerations and challenges 8.6 Method automation: possibilities and outlook 8.7 Conclusions 9 Highly Efficient Production of Dihydroflavonol 4-Reductases in Tobacco Cells and Refinement of the BuOH-HCl Enzymatic AssayLingping Zhu, Saku Mattila, Roosa Matomäki, Lorenzo Mollo, Sharmin Ahamed, Sara M. Abdou, Hany Bashandy and Teemu H. Teeri 9.1 Introduction 9.2 Results 9.3 Materials and methods 9.4 Discussion 10 A long and winding road: the evolution of transcriptional regulation of polyphenol biosynthesisCathie Martin, Jie Li and Nick W. Albert 10.1 Introduction 10.2 The importance of R2R3Myb transcription factors (TFs) in the regulation of phenylpropanoid metabolism in plants 10.3 The role of bHLH proteins in the regulation of phenylpropanoid metabolism 10.4 The role of the WDR in the MBW complex in the regulation of polyphenol metabolism 10.5 Additional factors regulating transcriptional control of the MBW complex 10.6 Conclusions 10.7 Acknowledgements 11 Analysis of Proanthocyanidins in Food Ingredients by the 4-(Dimethylamino)cinnamaldehyde ReactionDaniel Esquivel-Alvarado, Emilia Alfaro-Viquez, Andrew Birmingham, Abigail Kramschuster, Christian G. Krueger, and Jess D. Reed 11.1. Introduction 11.2. Background on the 4-(dimethylamino)cinnalmaldehyde (DMAC) reaction with PACs 11.3. Mechanism of the acid catalyzed DMAC reaction with PACs 11.4 Absorption and emission spectra of the DMAC reaction products 11.5 Standards for the DMAC reaction and accuracy of the method 11.6 Interaction of PAC-DMAC reaction products with Extra-Intestinal Pathogenic Escherichia coli 11.7 Conclusions 12 Reactions of Ellagitannins Related to their Metabolism in Higher PlantsTakashi Tanaka 12.1 Introduction 12.2 Structural variety of ellagitannin acyl groups 12.3 Reactions of the DHHDP group 12.4 Decomposition of 1,4-DHHDP-α-D-glucose 12.5 Amariin as a precursor of geraniin 12.6 Triterpene HHDP esters in Castanopsis sieboldii 12.7 Highly-oxidized ellagitannins in Carpinus japonica 12.8 Similarity of catechin oxidation to oxidation of methyl gallate 12.9 Production mechanism of DHHDP and HHDP 12.10 Oxidative degradation of ellagitannins 12.11 Conclusions References Index

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Book SynopsisMICROBIAL FERMENTATIONS IN NATURE AND AS DESIGNED PROCESSES Fermentation is one of the most important metabolic tools that biology has developed and microorganisms in many ways seem to have become the true masters of fermentative metabolism. Each of the fermentative microbial functions evolved to fit an energetic opportunity, and each function has ecological value. This book provides its readers with: Understanding regarding the commonalities and distinctions between aerobic and anaerobic fermentations as performed by microorganisms. A summary of knowledge regarding the ways in which animals and plants depend upon symbiotic interactions with their fermenting microbial partners including the deconstruction of complex polysaccharides. Information is also included about how those natural technologies constitute adaptation into designed processes for anaerobic degradation of lignocellulosic materials. The important role of rhizosphere microbes that facilitate availability of inorganicTable of ContentsLIST OF FIGURES ix LIST OF CONTRIBUTORS xv PREFACE xix SECTION I AN INTRODUCTION TO MICROBIAL FERMENTATION 1 1 Microbial Fermentation: Understanding and Using One of Nature’s Tools 3Christon J. Hurst 2 Rhodotorula Toruloides as a Biofactory of Carotenoids, Lipids, and Enzymes 103Nayra Ochoa Viñals, Dania Alonso Estrada, Evelyn Faife Pérez, Lourdes Georgina Michelena Álvarez, José Luis Martínez-Hernández, Roberto Arredondo Valdés, Arianna Núñez Caraballo, and Anna Iliná SECTION II THE ROLE OF MICROBIAL FERMENTATION IN DIGESTION PROCESSES 121 3 Gut Microbial Ecology 123Erin A. McKenney 4 Fermentation in the Rumen 133Emilio M. Ungerfeld, Nathaly Cancino-Padilla, and Nelson Vera-Aguilera 5 Microbial Degradation of Lignocellulose in Natural and Engineered Systems -- From the Smallest to the Biggest Bioreactor 167Xavier Goux, Tong Liu, Maria Westerholm, and Magdalena Calusinska SECTION III USING MICROBIAL FERMENTATION TO PRODUCE BEER AND WINE 207 6 Archeological Evidence for Fermented Alcoholic Beverages In Ritual Feasts of Neolithic China 209Li Liu 7 Brews of the Past: Bioarchaeology of Microbial Fermentation 225Keith Thomas 8 An Accidental Art Form: Spontaneous Fermentation of Beer 245Cassandra Suther 9 Japanese Traditional Fermentation Uses Solid-State Fungal Cultivation to Produce Sake 255Norio Takeshita and Ken Oda SECTION IV USING MICROBIAL FERMENTATION TO PRODUCE FOOD AND FODDER 261 10 Safety Demonstration of Food and Feed Cultures 263François Bourdichon, Alessandra Fontana, Vania Patrone, and Lorenzo Morelli 11 Starter Cultures and Their Role in Fermented Foods 281Marta Laranjo 12 African Fermented Foods and Beverages. Potential Impact on Health 293Victoria Bell, José Guina, and Tito H. Fernandes 13 Fermented Foods of South Asia 323Gomathy M, Sabarinathan K.G, Rajakumar D, Manoj M, Bhimani H.D, Priya John, Tharanee Wijayaratne, Sagarika Ekanayake, Uma Maheswari, Anu S. Rajan, Dilip Saikia, Dilip Tamang, Simana Bora, Theradimani M, and Ramya P 14 The Ensiling Fermentation of Forage Crops 353Zwi G. Weinberg SECTION V A CLOSING PERSPECTIVE OF MICROBIAL FERMENTATION 373 15 The Intersection of Microbial Fermentation and Evolutionary Ecology: We Provide the Habitat, You Provide the Fermentation 375Christon J. Hurst INDEX 381

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Book SynopsisBiosurfactants and Sustainability A timely and authoritative collection of resources on the sustainable production of biosurfactants In Biosurfactants and Sustainability, a team of distinguished researchers presents emerging themes in the rapidly evolving field of biosurfactants. The editors have chosen work that focuses on biosurfactants as eco-friendly and versatile compounds of interest in societies seeking sustainable forms of development. The book examines biosurfactants in the context of biorefineries and in the exploration of extremophilic microorganisms for biosurfactant production. The included works discuss biosurfactant production from different lignocellulosic and amylaceous raw materials, as well as oilseeds and other agro-industrial byproducts. Readers will also find: A thorough introduction to microorganisms producing biosurfactants, as well as sustainable biosurfactant production in biorefineries Comprehensive explorations Table of ContentsList of Contributors xi Foreword xv Introduction 1 Paulo Ricardo Franco Marcelino, Carlos Augusto Ramos, Guilherme de Oliveira Silva, Ramiro Reyes Guzman, Silvio Silverio da Silva, and Antonio Ortiz Lopez Biosurfactants: Concept, Biological Functions, Classification, General Properties and Applications 1 1 Microorganisms Producing Biosurfactants in the Current Scenario 11 Fernanda Palladino, Rita C.L.B. Rodrigues, Yasmim Senden dos Santos, and Carlos A. Rosa 1.1 Introduction 11 1.2 Microbial Biosurfactants 12 1.2.1 Structure and Classification of Biosurfactants 12 1.2.2 Biosurfactants Producing Yeasts 14 1.2.3 Biosurfactants Produced by Extremophile Microorganisms 17 1.3 Industrial Applications of Biosurfactants 18 References 20 2 Selection of Biosurfactant-Producing Microorganisms 29 Julio Bonilla Jaime, Luis Galarza Romero, and Jonathan Coronel León 2.1 Introduction 29 2.2 Traditional Methods of Detection 30 2.2.1 Direct Measure of Surface/interfacial Activity 31 2.2.2 Indirect Measure of Surface/interfacial Activity 32 2.2.3 EffectsofCultureMediaBasedonAgro-industrialBy-productsonProperties of BS 34 2.3 High-throughputAnalysisMethodfortheScreeningofPotentialBiosurfactants Producers 35 2.4 Screening of Microorganisms Biosurfactants and Lipases Producers 40 2.5 Conclusion and Future Perspectives 45 References 46 3 Metabolic Engineering as a Tool for Biosurfactant Production by Microorganisms 61 Roberta Barros Lovaglio, Vinícius Luiz da Silva, and Jonas Contiero 3.1 Metabolic Engineering and Biosurfactants 61 3.2 Regulation and Heterologous Production of Biosurfactants 63 3.3 Extension of Substrate Range for Biosurfactant Production 67 3.4 Improvement of Overall Cellular Physiology 68 3.5 Elimination or Reduction of By-product 69 3.6 Future Perspectives 69 3.7 Conclusions 70 References 71 4 Biosurfactant Production in the Context of Biorefineries 77 Paulo Ricardo Franco Marcelino, Carlos Augusto Ramos, Maria Teresa Ramos, Renan Murbach Pereira, Rafael Rodrigues Philippini, Emily Emy Matsumura, and Silvio Silvério da Silva 4.1 Biorefineries in Contemporary Society 77 4.2 Biomass and Biorefineries: Industrial By-products as Raw Materials for Biorefineries 78 4.3 Biosurfactant Production in the Context of Lignocellulosic Biorefineries 80 4.4 Biosurfactant Production in the Context of Oleaginous Biorefineries 85 4.5 Biosurfactant Production in the Context of Starchy and Biodiesel Biorefineries 87 4.6 Conclusion 88 References 88 5 Biosurfactant Production by Solid-state Fermentation in Biorefineries 95 Daylin Rubio-Ribeaux, Rogger Alessandro Mata da Costa, Dayana Montero Rodríguez, Nathália Sá Alencar do Amaral Marques, Gilda Mariano Silva, and Silvio Silvério da Silva 5.1 Introduction 95 5.2 Advantages of Biosurfactant Production by Solid-State Fermentation 96 5.3 Suitable Biomasses for Biosurfactant Production in Biorefineries 96 5.4 Microorganisms Used in Biosurfactant Production by Solid-state Fermentation 98 5.5 Raw Materials Used in Solid-state Fermentation for Biosurfactant Production 99 5.6 Pretreatment of Raw Materials for the Production of Biosurfactants in Solid-state Fermentation 101 5.7 Physicochemical Factors of Solid-state Fermentation 103 5.8 Strategies for Scaling-up of Solid-state Fermentation for Biosurfactant Production 105 5.9 Conclusion 108 References 108 6 An Overview of Developments and Challenges in the Production of Biosurfactant by Fermentation Processes 117 F.G. Barbosa, M.J. Castro-Alonso, T.M. Rocha, S. Sánchez-Muñoz, G.L. de Arruda, M.C.A. Viana, C.A. Prado, P.R.F. Marcelino, J.C. Santos, and Silvio S. Da Silva 6.1 Introduction 117 6.2 Current Market and Potential Applications of Biosurfactants 118 6.3 Biosurfactant as a Sustainable Alternative: Factors Influencing its Production 118 6.3.1 Factors Involved in the Biosurfactant Production 119 6.4 Strategies and Main Challenges for Biosurfactant Production 122 6.4.1 Process Configurations as Strategies for Biosurfactant Production 123 6.4.2 Bioreactors Used in the Biosurfactants Production: Types, Advantages, and Disadvantages 125 6.4.3 Biosurfactant Separation Processes 128 6.5 Future Perspectives and Conclusion 132 References 132 7 Enzymatic Production of Biosurfactants 143 Ana Karine F. de Carvalho, Heitor B.S. Bento, Felipe R. Carlos, Vitor B. Hidalgo, Cintia M. Romero, Bruno C. Gambarato, and Patrícia C.M. Da Rós 7.1 Introduction 143 7.2 What are the Biosurfactants Produced Enzymatically? Esterification Reactions of Sugars and Fatty Acids Catalyzed by Enzymes 144 7.2.1 Esterification Reactions of Sugars and Fatty Acids Catalyzed by Enzymes 144 7.3 Enzymes and Methods for Biosurfactant Production: Bioreactors and Ways of Conducting Enzymatic Processes 145 7.4 Advantages and Disadvantages of Enzymatic Biosurfactant Production 148 7.5 Potential Use of Enzymes for the Production of Biosurfactants 149 7.6 Production of Biosurfactants by the Enzymatic Route in Biorefineries: Demand for More Modern Production Processes 150 7.7 Conclusion 153 References 153 8 Co-production of Biosurfactants and Other Bioproducts in Biorefineries 157 Martha Inés Vélez-Mercado, Carlos Antonio Espinosa-Lavenant, Juan Gerardo Flores-Iga, Fernando Hernández Teran, María de Lourdes Froto Madariaga, and Nagamani Balagurusamy 8.1 Introduction 157 8.2 Microbial Surfactant Production 158 8.3 Co-production of Biosurfactants in a Biorefinery 160 8.3.1 Co-production of Biosurfactants and Polyhydroxyalkanoates 161 8.3.2 Co-production of Biosurfactants and Enzymes 162 8.3.3 Co-production of Biosurfactants and Lipids 164 8.3.4 Co-production of Biosurfactants and Ethanol 165 8.4 Conclusions 166 References 166 9 Biosurfactants in Nanotechnology: Recent Advances and Applications 173 Avinash P. Ingle, Shreshtha Saxena, Mangesh Moharil, Mahendra Rai, and Silvio S. Da Silva 9.1 Introduction 173 9.2 Biosurfactants and their Types 174 9.2.1 Glycolipid Biosurfactants 174 9.2.2 Rhamnolipids 174 9.2.3 Trehalolipids 175 9.2.4 Sophorolipids 175 9.2.5 Mannosylerythritol Lipids 175 9.2.6 Lipopeptide Biosurfactants 175 9.2.7 Phospholipid Biosurfactants 176 9.2.8 Polymeric Biosurfactants 176 9.3 Properties of Biosurfactants 178 9.3.1 Surface and Interface Activity 178 9.3.2 Efficiency 179 9.3.3 Foaming Capacity 179 9.3.4 Emulsification/Emulsion Forming and Emulsion Breaking 179 9.3.5 Tolerance for Temperature and pH Tolerance 180 9.3.6 Low Toxicity 180 9.3.7 Biodegradability 180 9.4 Conventional Methods for Biosurfactant Production 180 9.5 Commercial Applications of Biosurfactants 182 9.5.1 Application of Biosurfactants in Agriculture 182 9.5.2 Application of Biosurfactants in Nanotechnology 183 9.5.3 Applications of Biosurfactants in Commercial Laundry Detergents 184 9.5.4 Application of Biosurfactants in Medicine 184 9.5.5 Application of Biosurfactants in the Food Processing Industry 185 9.5.6 Application of Biosurfactants in the Cosmetic Industry 185 9.5.7 Application of Biosurfactants in Petroleum 185 9.5.8 Application of Biosurfactant in Microbial-enhanced Oil Recovery 186 9.6 Biosurfactants in Nanotechnology (Biosurfactant Mediated Synthesis of Nanoparticles) 186 9.6.1 Glycolipids Biosurfactants Produced Nanoparticles 186 9.6.2 Lipopeptides Biosurfactants Produced Nanoparticles 187 9.7 Conclusions 188 References 188 10 Interaction of Glycolipid Biosurfactants with Model Membranes and Proteins 195 Francisco J. Aranda, Antonio Ortiz, and José A. Teruel 10.1 Introduction 195 10.2 Interaction of Glycolipid Biosurfactants with Model Membranes 196 10.2.1 Rhamnolipids 197 10.2.2 Trehalose Lipids 206 10.2.3 Other Glycolipids 209 10.3 Interaction of Glycolipid Biosurfactants with Proteins 211 10.3.1 Rhamnolipids 211 10.3.2 Trehalose Lipids 211 10.3.3 Mannosylerythritol Lipids 212 10.4 Conclusions 212 References 213 11 Biosurfactants: Properties and Current Therapeutic Applications 221 Cristiani Baldo, Maria Ines Rezende, and Fabiana Guillen Moreira Gasparin 11.1 Production of Microbial Biosurfactants 221 11.2 Anti-tumoral Activity of Biosurfactants 223 11.3 Anti-inflammatory Activity of Biosurfactants 226 11.4 Anti-microbial Activity of Biosurfactant 228 11.4.1 Biosurfactants as Anti-bacterial Agents 229 11.4.2 Biosurfactants as Anti-viral Agents 231 11.4.3 Biosurfactants as Anti-fungal Agents 232 11.5 Other Therapeutic Applications of Biosurfactants 233 11.6 Concluding Remarks 234 References 234 12 Fungal Biosurfactants: Applications in Agriculture and Environmental Bioremediation Processes 243 Láuren Machado Drumond de Souza, Débora Luiza Costa Barreto, Lívia da Costa Coelho, Elisa Amorim Amâncio Teixeira, Vívian Nicolau Gonçalves, Júlia de Paula Muzetti Ribeiro, Natana Gontijo Rabelo, Stephanie Evelinde Oliveira Alves, Mayanne Karla da Silva, Laura Beatriz Miranda Martins, Charles Lowell Cantrell, Stephen Oscar Duke, and Luiz Henrique Rosa 12.1 Biosurfactants as Agrochemicals 243 12.1.1 Biosurfactants as Herbicide Adjuvants 244 12.1.2 Biosurfactants and Antifungal Activity 245 12.1.3 Biosurfactants as Insecticidal Adjuvants 246 12.2 Insecticidal Biosurfactants for Use against Disease Vector Insects 246 12.3 Fungal Biosurfactants in Bioremediation Processes 248 References 249 13 New Formulations Based on Biosurfactants and Their Potential Applications 255 Maria Jose Castro-Alonso, Fernanda G. Barbosa, Thiago A. Vieira, Diana A. Sanchez, Monica C. Santos, Thércia R. Balbino, Salvador S. Muñoz, and Talita M. Lacerda 13.1 Introduction 255 13.2 General Chemical and Biochemical Aspects 258 13.3 Downstream Processing 259 13.4 Biosurfactants in Cosmetics and Personal Care 259 13.5 Biosurfactants in Medicine and Pharmaceutics 261 13.6 Biosurfactants in Food and Feed 262 13.7 Biosurfactants in Pesticides, Insecticides, and Herbicide Formulations 264 13.8 Biosurfactants in Civil Engineering 265 13.9 Miscellaneous 266 13.9.1 Detergent Formulations 266 13.9.2 Bioremediation Purposes 267 13.9.3 Nanoparticle Synthesis 267 13.9.4 Polymer Synthesis 268 13.10 Overview of the Biosurfactant Market 268 13.11 Conclusions and Future Perspectives 270 References 270 14 Techno-economic-environmental Analysis of the Production of Biosurfactants in the Context of Biorefineries 281 Andreza Aparecida Longati, Andrew Milli Elias, Felipe Fernando, Furlan Everson Alves Miranda, and Roberto de Campos Giordano 14.1 Introduction 281 14.1.1 Background 281 14.1.2 Surfactant Versus Biosurfactant 282 14.1.3 Biosurfactant Market, Producers, and Patents 282 14.1.4 Biosurfactant Production Routes 283 14.2 Economic Aspects of the BS Production 286 14.3 Environmental Aspects 288 14.4 Biosurfactant Production Synergies in the Brazilian Biorefineries Context 290 14.5 Conclusion 293 References 294 Index 301

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Book SynopsisAnimal Welfare An Accessible Overview of the Concept of Sentience Throughout the Animal Kingdom and Why It Matters to Humans Animal Welfare explores the concept of sentience and the development of sentient minds throughout the animal kingdom. The work provides improved definitions and analysis of the ideas of sentience, cognition, and consciousness, along with evidence of advanced mental formulation in birds, fish, and invertebrates. Considerations between humans and animals are also discussed, such as outcome-based ethics in relation to humans' duties of care and the rights and wrongs of domestication. The work is divided into three parts and covers key topics such as: Specifics of animal sentience, from pain and suffering, to fear and dread, all the way to animals' social life and the comfort/joy/hope/despair they experience What we know about the sentience of different classes of animals in the waters, air, savannah/plains, and forests<Table of ContentsAbout the Author xi Preface xiii Acknowledgements and Apologies xv Part 1 The Sentient Mind: Skills and Strategies 1 1 Setting the Scene 3 Human Attitudes to Animals 5 Animal Behaviour Science 7 Rules of Engagement 9 2 Sentience and the Sentient Mind 13 Sentience, Consciousness and the Mind 14 The Five Skandhas of Sentience 14 Understanding the Sentient Mind 17 Pain and Suffering 21 Fear and Dread 23 Coping with Challenge: Stress and Boredom 24 Social Life 26 Comfort and Joy 28 Hope and Despair 29 Sex and Love 29 Summary 30 3 Special Senses and Their Interpretation 32 Vision 33 Hearing 35 Smell and Taste 36 Cutaneous Sensation, Touch 37 Magnetoreception 38 Interpreting the Special Senses 38 Theory of Mind, or Metarepresentation 40 Summary 41 4 Survival Strategies 42 Foraging 43 Hunting Behaviour: The Predator and the Prey 48 Spatial Awareness and Navigation 50 Breeding Behaviour and Parental Care 52 5 Social Strategies 55 Sentient Social Life 57 Social Hierarchies: The Pecking Order 58 Communication 59 Cooperation and Empathy 60 Social Learning, Education and Culture 61 Territorial Behaviour and Tribalism 62 Part 2 Shaping Sentient Minds: Adaptation to the Environment 65 6 Animals of the Waters 67 Pain and Fear 69 Survival Skills: Hunting, Hiding and Problem Solving 71 Migration 72 Communication and Social Behaviour 74 7 Animals of the Air 77 Feeding Strategies 78 Migration 80 Sentience and Breeding Behaviour 82 Social Behaviour, Culture and Education 83 Bats 84 8 Animals of the Savannah and Plains 86 Environmental Challenges 87 Animals of the Open Plains 88 Sheep 88 Goats 90 Cattle 91 Wild Bovidae 92 Feral Horses 93 Elephants 93 Predators 96 9 Animals of the Forest 97 The Boreal Forest 97 Cervidae 98 Beavers 100 Bears 101 The Tropical Rain Forests 102 Snakes 103 Primates 104 10 Close Neighbours 106 History of Domestication 107 Artificial Selection and Unnatural Breeding 108 Domestication, Sentience and Wellbeing 109 Pigs 110 Dogs 113 Cats 114 Dairy Cows 115 Horses and Donkeys 118 Chickens 121 Opportunist Neighbours: Rats and Urban Foxes 123 Coda 124 Part 3 Why it matters: Nature’s Social Union 125 11 Our Duty of Care 127 Sentience Revisited 128 Outcome-based Ethics 131 Death and Killing 133 Farms, Farmed Animals and Food 135 Animals in Laboratories 136 Wild Animals in Captivity 138 Animals in Sport and Entertainment 140 Pets 143 What can We Learn from the Animals? 144 Further Reading 147 General Reading 151 Index 152

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Book SynopsisTable of ContentsCortical Progenitors and Germinal Zones 1 Neural stem cells as glia. 2 Diversity and evolution of human cortical progenitor cell types. 3 Intermediate progenitors in neocortical development and evolution. 4 Area V1 development, a model system to link corticogenesis to adult cortex structure and function? 5 Neocortical neurogenesis in amniote evolution. 6 Dynamic transcriptional control of neural stem cells. 7 Mechanical and physical interactions involving neocortical progenitor cells. 8 The role of human-specific genes and amino acid substitutions for neocortex expansion and modern human vs. Neanderthal differences in neocortical neurogenesis. Progenitor Lineages 9 Temporal scaling: a link between conserved neurogenic processes and differential size in mammalian cortical development. 10 Interplay of cell-autonomous gene function and tissue-wide mechanisms regulating radial glial progenitor lineage progression. Generation of Neuron Types 11 Generation of projection neuron diversity in the neocortex: from embryos to organoids. 12 Development of cortical neuron heterogeneity and impact of neurodevelopmental disorders. 13 Developmental and evolutionary origins of cortical projection neuron identity and connectivity. 14 Intrinsic and input-dependent development of cortical neuron types. 15 Corpus callosum evolution and development. 16 Towards the transcriptionally-based classification of L6b in the adult mouse brain. Neuron Migration 17 Cortical neuron migration in health and disease. 18 The emerging roles of LIS1 biomechanics in cellular and cortical homeostasis. Neural Patterning, Specification of Cortical Regions 19 Understanding human forebrain morphogenesis and early expansion using organoids. 20 Early neuronal differentiation/patterning of the human pallium, modeling by in vitro systems, and disruption in developmental disorders. 21 Mammalian cortical regional specification. 22 Development of the neocortical area map. Cortical Folding 23 Old models know wrinkles best -- A critical review on the mechanisms of cortical gyrification 24 Investigation of the mechanisms underlying the development and evolution of the cerebral cortex using gyrencephalic ferrets. Cortical Development: Variations, Disorders and Malformations 25 Genetic variation altering cortical progenitor function leads to human brain evolution and interindividual differences in human brain structure. 26 Human neocortical evolution and neurological disorders 27 Clinical and molecular overview of cortical malformations. Overarching Topics 28 Post-transcriptional control of brain development. 29 Regulation of mRNA localization and translation in brain development: Implications for the mechanism leading to the brain evolution and pathogenesis. 30 The roles of signal transduction during cortical neurogenesis. 31 Centrosome regulation and function in the developing neocortex. 32 Keeping the cortex afloat: Cerebrospinal fluid contributions to cerebral cortical development. 33 Comparative cognitive neuroscience and dorsal and ventral streams in primates.

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Book SynopsisMicrobial Bioreactors for Industrial Molecules Harness the planet's most numerous resources with this comprehensive guide Microorganisms constitute the invisible majority of all living creatures on Earth. They are found virtually everywhere on the planet, including in environments too extreme for any larger organisms to exist. They form a hugely significant resource whose potential value for human society cannot be overlooked. The creation of microorganism- based bioreactors for the industrial production of valuable biomolecules has the potential to revolutionize a range of industries and fields. Microbial Bioreactors for Industrial Molecules provides a comprehensive introduction to these bioresources. It covers all potential approaches to the use of microbial technology and the production of high-value biomolecules for the pharmaceutical, cosmetic, and agricultural industries, among others. The book's rigorous detail and global, holistic approach to harnessing the power of the planetary microbiome make it an invaluable introduction to this growing area of research and production. Readers will also find: Detailed coverage of basic, applied, biosynthetic, and translational approaches to the use of microbial technologyDiscussion of industrially produced microbe-borne enzymes including invertase, lipase, keratinase, protease, and moreApproaches for using microbial bioreactors to generate biofuels Microbial Bioreactors for Industrial Molecules is essential for scientists and researchers in microbiology and biotechnology, as well as for professionals in the biotech industries and graduate students studying the applications of the life sciences.Table of ContentsList of Contributors xv Preface xxii 1 Microbial Bioreactors: An Introduction 1 Ashish Kumar Singh, Santosh Kumar Upadhyay, and Sudhir P. Singh 1.1 Microbial Bioresources 1 1.2 Microbial Bioresources for the Production of Enzymes 2 1.3 Microbial Bioresources for Therapeutic Application 3 1.4 Microbial Bioresources for Biogenesis 4 1.5 Microbial Fermentation 5 1.6 Microbial Biodegradation 6 1.7 Microbioresources for High- Value Metabolites 7 Acknowledgments 8 References 9 2 Microbial Bioresource for the Production of Marine Enzymes 17 Lorena Pedraza- Segura, Karina Maldonado- Ruiz Esparza, and Ruth Pedroza- Islas 2.1 Introduction 17 2.2 Prokaryotes 17 2.2.1 Amylases 19 2.2.2 Proteases 19 2.2.3 Bactericide 19 2.2.4 l- Asparaginase 19 2.2.5 Carbohydrases 20 2.3 Marine Archaea 20 2.4 Eukaryotes 23 2.4.1 Yeasts 23 2.4.2 Enzymes from Marine- Derived Fungi 24 References 30 3 Lactic Acid Production Using Microbial Bioreactors 39 Juliana Botelho Moreira, Ana Luiza Machado Terra, Whyara Karoline Almeida da Costa, Marciane Magnani, Michele Greque de Morais, and Jorge Alberto Vieira Costa 3.1 Introduction 39 3.2 Microbial Lactic Acid Producers 40 3.2.1 Bacteria 40 3.2.2 Fungi and Yeast 41 3.2.3 Microalgae 41 3.3 Alternative Substrates for Lactic Acid Production 42 3.4 Fermentation Process Parameters 42 3.5 Mode Improvement of Lactic Acid and Reactor Configuration 43 3.6 Challenges 47 3.7 Conclusions 49 Acknowledgments 50 References 50 4 Advancement in the Research and Development of Synbiotic Products 55 Anna María Polanía, Alexis García, and Liliana Londoño 4.1 Introduction 55 4.2 Probiotics, Prebiotics, and Synbiotics 56 4.2.1 Probiotics 56 4.2.2 Requirements and Selection Criteria for Probiotic Strains 57 4.3 Prebiotics 57 4.3.1 Requirements and Selection Criteria for Prebiotic Strains 59 4.4 Synbiotics 60 4.4.1 Synbiotic Selection Criteria 61 4.4.2 Mechanism of Action of Synbiotics 61 4.5 Health Benefits from Synbiotics 63 4.6 Bioreactor Design for Synbiotic Production 65 4.7 Microencapsulation and Nanotechnology to Ensure Their Viability 67 4.8 Nanoparticles 68 4.9 Applications in Various Fields such as Dermatological Diseases, Animal Feed, and Functional Foods 68 4.9.1 Dermatological Diseases 68 4.9.2 Functional Foods 70 4.9.3 Animal Feed 71 4.10 Conclusions 72 References 73 5 Microbial Asparaginase and Its Bioprocessing Significance 81 Susana Calderón- Toledo, Amparo Iris Zavaleta, and Adalberto Pessoa- Junior 5.1 Introduction 81 5.2 Classification of l- Asparaginase 82 5.3 Bioprocessing 82 5.3.1 Sources of microbial l- Asparaginase 82 5.3.2 Upstream Bioprocessing 83 5.3.3 Downstream Bioprocessing 87 5.3.3.1 Protein Concentration 87 5.3.3.2 l- Asparaginase Release 88 5.3.3.3 Chromatography 88 5.4 Scaled Up to Bioreactor 89 5.5 Characterization of l- Asparaginase 90 5.6 Applications of l- Asparaginase 92 5.6.1 Pharmaceutical Industry 92 5.6.2 Food Industry 92 5.7 Conclusions 93 References 93 6 Bioreactor- Scale Strategy for Pectinase Production 103 Javier Ulises Hernández- Beltrán, Carlos Alberto Acosta- Saldívar, Genesis Escobedo- Morales, Nagamani Balagurusamy, and Miriam Paulina Luévanos- Escareño 6.1 Introduction 103 6.2 Pectinase Classification and Origin Sources 104 6.2.1 Pectinases 104 6.2.2 Origin Source of Production of Microbial Pectinase 106 6.3 Substrates Used for Pectinase Production 107 6.4 Fermentation Strategies 107 6.4.1 Solid- State Fermentation 107 6.4.2 Submerged Fermentation 113 6.5 Bioreactor- Scale Strategies 116 6.6 Conclusions 121 References 124 7 Microbes as a Bio- Factory for Polyhydroxyalkanoate Biopolymer Production 131 Daniel Tobías- Soria, Julio Montañez, Iván Salmerón, Alejandro Mendez- Zavala, James Winterburn, and Lourdes Morales- Oyervides 7.1 Introduction 131 7.2 Microbial Polyhydroxyalkanoates as a Novel Alternative to Substitute Petroleum- Derived Plastics 132 7.3 Microbial PHAs Classification, Synthesis, and Producing Microorganisms 133 7.3.1 PHAs Classification 133 7.3.2 Biosynthetic Pathways for PHAs Production 134 7.3.3 PHAs Producing Strains 137 7.3.4 Bacteria as the Main Species for the PHA Production 139 7.3.5 Algae as a Feasible Alternative for PHA Production 140 7.4 Trends and Challenges in the PHAs Synthesis Process 141 7.4.1 Upstream Processing Trends and Challenges 142 7.4.2 Downstream Processing, Trends and Challenges 144 7.5 Process Economics and Perspectives Toward Industrial Implementation 145 7.6 Concluding Remarks 151 References 151 8 Microbial Production of Critical Enzymes of Lignolytic Functions 161 M. Indira, S. Krupanidhi, K. Vidya Prabhakar, T. C. Venkateswarulu, and K. Abraham Peele 8.1 Introduction 161 8.2 Sources of Lignolytic Enzymes 162 8.2.1 Plants 164 8.2.2 Insects 164 8.2.3 Bacteria 165 8.2.4 Fungi 165 8.2.5 Actinomycetes 166 8.2.6 Extremophiles 166 8.3 Lignolytic Enzymes 167 8.3.1 Lignin Peroxidase (EC 1.11.1.14) 167 8.3.2 Manganese Peroxidase (EC 1.11.1.13) 168 8.3.3 Versatile Peroxidase (EC 1.11.1.16) 168 8.3.4 Dye Decolorizing Peroxidases (DyPs) (EC 1.11.1.19) 169 8.3.5 Laccases (EC 1.10.3.2) 169 8.3.6 Feruloyl Esterase (EC.3.1.1.73) 170 8.3.7 Aryl Alcohol Oxidase (EC 1.1.3.7) 170 8.3.8 Pyranose- 2- Oxidase (EC 1.1.3.10) 171 8.3.9 Vanillyl Alcohol Oxidase (EC 1.1.3.38) 171 8.3.10 Quinone Reductase (EC 1.6.5.5) 171 8.4 Microbial Production of Lignolytic Enzymes 171 8.5 Mechanism of Action of Lignolytic Enzymes 175 8.6 Conclusions 177 Acknowledgments 177 References 178 9 Microbial Bioreactors for Biofuels 189 Paulo Renato Souza de Oliveira, Allana Katiussya Silva Pereira, Iara Nobre Carmona, and Ananias Francisco Dias Júnior 9.1 Introduction 189 9.2 General Classification of Bioreactor 190 9.3 Liquid- Phase Bioreactor 190 9.3.1 Cell- Free 190 9.3.1.1 Mechanically Stirred 190 9.3.1.2 Pneumatically Stirred 190 9.3.2 Immobilized Cell 191 9.4 Reactors for Solid- State Cultures 192 9.5 Bioreactor Operation Mode 193 9.6 Biofuels 194 9.6.1 Bioethanol 194 9.6.2 Biodiesel 196 9.6.3 Butanol 197 9.6.4 Biogas and Methane 198 9.6.5 Hydrogen 199 9.6.6 Biohythane 200 9.7 Considerations and Future Perspectives 201 References 201 10 Potential Microbial Bioresources for Functional Sugar Molecules 211 Satya Narayan Patel, Sweety Sharma, Ashish Kumar Singh, and Sudhir P. Singh 10.1 Introduction 211 10.2 D- Allulose 212 10.3 D- Tagatose 215 10.4 Trehalose 217 10.5 Turanose 218 10.6 Trehalulose 221 10.7 D- Allose 222 10.8 D- Talose 224 10.9 Conclusions 224 Acknowledgment 225 References 225 11 Microbial Production of Bioactive Peptides 237 Adriano Gennari, Fernanda Leonhardt, Graziela Barbosa Paludo, Daniel Neutzling Lehn, Gaby Renard, Giandra Volpato, and Claucia Fernanda Volken de Souza 11.1 Introduction 237 11.2 Microbial Production of Peptides with Antioxidant Activity 238 11.3 Microbial Production of Peptides with Antimicrobial Activity 239 11.4 Microbial Production of Peptides with Antihypertensive Activity 240 11.5 Microbial Production of Peptides with Antidiabetic Activity 242 11.6 Microbial Production of Peptides with Immunomodulatory Activities 243 11.7 Microbial Production of Peptides with Antitumoral Activity 243 11.8 Microbial Production of Peptides with Opioid Activity 247 11.9 Microbial Production of Peptides with Antithrombotic Activity 248 11.10 Production of Recombinant Peptides in Microbial Expression Systems 249 11.11 Purification and Identification of Microbial Bioactive Peptides 251 11.12 Conclusions and Perspectives 252 References 253 12 Trends in Microbial Sources of Oils, Fats, and Fatty Acids for Industrial Use 261 Alaa Kareem Niamah, Deepak Kumar Verma, Shayma Thyab Gddoa Al- Sahlany, Soubhagya Tripathy, Smita Singh, Nihir Shah, Ami R. Patel, Mamta Thakur, Gemilang Lara Utama, Mónica L. Chávez- González, and Cristobal Noe Aguilar 12.1 Introduction 261 12.2 Microbial Sources 263 12.2.1 Microalgal Sources 264 12.2.2 Bacterial Sources 266 12.2.3 Fungal and Yeast Sources 267 12.3 Application in Food and Health 269 12.4 Opportunities and Prospective Future 270 12.5 Conclusion 271 References 271 13 Microbial Bioreactors for Secondary Metabolite Production 275 Luis V. Rodríguez- Durán, Mariela R. Michel, Alejandra Pichardo, and Pedro Aguilar- Zárate 13.1 Introduction 275 13.2 Design of Bioreactors 276 13.3 Types of Bioreactors for Secondary Metabolite Production 278 13.3.1 Stirred Tank Bioreactor (STB) 278 13.3.2 Bubble Column 280 13.3.3 Air- Lift 282 13.3.4 Biofilm Bioreactor 283 13.3.5 Solid- State Fermentation (SSF) Bioreactors 285 13.3.6 Tray Bioreactor 286 13.3.7 Packed Bed Bioreactor 287 13.3.8 Stirred and Rotating Drum Bioreactor 288 13.4 Conclusion 289 Acknowledgment 289 References 289 14 Microbial Cell Factories for Nitrilase Production and Its Applications 297 Neerja Thakur, Vinay Kumar, and Shashi Kant Bhatia 14.1 Introduction 297 14.2 Nitrilase Categorization, Sources, Metabolism, and Production Process 298 14.2.1 Nitrilase Categorization 298 14.2.2 Nitrilase Sources 298 14.2.3 Nitrilase in the Metabolism of Nitriles 298 14.2.4 Isolation and Screening of Nitrilase- Producing Microorganisms 299 14.2.5 Cultivation of Nitrilase- Producing Microbes 299 14.2.6 Nitrilase Production in Bioreactor 301 14.2.6.1 Factors Affecting Nitrilase Production in a Bioreactor 301 14.3 Nitrilase in the Biotransformation of Nitriles 302 14.3.1 Aliphatic Acids 305 14.3.1.1 Acrylic Acid 305 14.3.1.2 Glycolic Acid 305 14.3.2 Aromatic Acids 305 14.3.2.1 Nicotinic Acid 305 14.3.2.2 Isonicotinic Acid 306 14.3.2.3 Benzoic Acid 306 14.3.3 Arylacetic Acids 306 14.3.3.1 Mandelic Acid 306 14.3.3.2 Phenylacetic Acid 307 14.4 Conclusion 307 References 307 15 Chemistry and Sources of Lactase Enzyme with an Emphasis on Microbial Biotransformation in Milk 315 Alaa Kareem Niamah, Shayma Thyab Gddoa Al- Sahlany, Deepak Kumar Verma, Smita Singh, Soubhagya Tripathy, Deepika Baranwal, Nihir Shah, Ami R. Patel, Mamta Thakur, Gemilang Lara Utama, Mónica L. Chávez- González, and Cristobal Noe Aguilar 15.1 Introduction 315 15.2 Lactase Enzyme 316 15.3 Sources of Lactase 318 15.3.1 Plants 318 15.3.2 Bacteria 319 15.3.3 Yeasts 321 15.3.4 Molds 322 15.4 Microbial Biotransformation of Lactase Enzyme 322 15.4.1 Improvement of Microbial Strains 322 15.4.2 Galactooligosaccharide Synthesis and Transglycosylation 324 15.4.3 Lactose Intolerance 325 15.5 Conclusion 326 References 327 16 Microbial Biogas Production: Challenges and Opportunities 333 Diana B. Muñiz- Márquez, Christian Iván Cano- Gómez, Jorge Enrique Wong- Paz, Victor Emmanuel Balderas- Hernández, and Fabiola Veana 16.1 Introduction 333 16.2 Generalities of Biogas Production: the Process and Its Yields 334 16.3 Feedstocks Used in Biogas Production and Their Characteristics 336 16.4 Microbial Biodiversity in Biogas Production 337 16.4.1 Generalities 337 16.4.2 Anaerobic Fungi in Biogas Production 338 16.4.3 Anaerobic Bacteria in Biogas Production 340 16.4.4 Methanogenic Archaeal and Algae in Biogas Production 340 16.5 The Role of the Enzymes in Biogas Production 341 16.6 Challenges and Opportunities in Biogas Production 344 16.6.1 Challenges for Biogas Production 344 16.6.2 Opportunities for Biogas Production 346 References 347 17 Molecular Farming and Anticancer Vaccine: Current Opportunities and Openings 355 Yashwant Kumar Ratre, Arundhati Mehta, Sapnita Shinde, Vibha Sinha, Vivek Kumar Soni, Subash Chandra Sonkar, Dhananjay Shukla, and Naveen Kumar Vishvakarma 17.1 Introduction 355 17.2 Vaccines and the Possibility in Noncommunicable Diseases 356 17.3 Vaccine Production 357 17.3.1 Cancer Vaccine 358 17.4 Types of Cancer Vaccine 359 17.5 Microbial Production of Anticancer Vaccine: Challenges and Opportunities 361 17.5.1 Yeast- Based Cancer Vaccine (YBCV) 362 17.5.2 Bacteria- Based Cancer Vaccine (BBCV) 364 17.6 Conclusion 365 References 366 18 Microbial Bioreactors at Different Scales for the Alginate Production by Azotobacter vinelandii 375 Belén Ponce, Viviana Urtuvia, Tania Castillo, Daniel Segura, Carlos Peña, and Alvaro Díaz- Barrera 18.1 Introduction 375 18.2 Bacterial Alginate 376 18.2.1 Compositions and Structures 376 18.2.2 Applications 376 18.3 Alginate Biosynthesis and Genetic Regulation 376 18.4 Production of Bacterial Alginate on a Bioreactor Scale 380 18.4.1 Cultivation Modality for Alginate Production 380 18.4.2 Influence of Oxygen on Alginate Production 382 18.4.3 Influence of Cultivation Modality on the Molecular Weight of Alginate 384 18.5 Chemical Characterization of Alginate Quality 384 18.5.1 Scale- up of Alginate Production 385 18.6 Prospects and Conclusions 388 Acknowledgment 390 References 390 19 Environment- Friendly Microbial Bioremediation 397 Areej Shahbaz, Nazim Hussain, Tehreem Mahmood, Mubeen Ashraf, and Nida Khaliq 19.1 Introduction 397 19.2 Principle of Bioremediation 400 19.3 Types of Bioremediations 402 19.3.1 Biostimulation 402 19.3.2 Bioattenuation 402 19.3.3 Bioaugmentation 403 19.3.4 Genetically Engineered Microorganisms (GEMs) 403 19.4 Factors Affecting Microbial Bioremediation 404 19.4.1 Biological Factors 405 19.4.2 Environmental Factors 405 19.4.2.1 Availability of Nutrients 405 19.4.2.2 Temperature and pH 406 19.4.2.3 Concentration of Oxygen and Moisture Content 406 19.4.2.4 Site Characterization and Selection 406 19.4.2.5 Metal Ions and Toxic Compounds 407 19.5 Bioremediation Techniques 407 19.6 Methods for Ex Situ Bioremediation 408 19.6.1 Solid Phase Treatment 408 19.6.1.1 Slurry Phase Bioremediation 409 19.6.1.2 In Situ Bioremediation 409 19.6.2 Engineered Bioremediation 409 19.6.3 Intrinsic Bioremediation 410 19.7 Bioremediation Using Microbial Enzymes 410 19.7.1 Laccases 411 19.7.2 Lipases 411 19.7.3 Proteases 411 19.7.4 Peroxidases 411 19.7.5 Hydrolytic Enzymes 412 19.7.6 Oxidoreductases 412 19.8 Bioremediation Prospects 412 19.9 Future Prospective 414 19.10 Conclusion 415 References 415 20 Microbial Bioresource for Plastic- Degrading Enzymes 421 Ayodeji Amobonye, Christiana Eleojo Aruwa, and Santhosh Pillai 20.1 Introduction 421 20.2 Classification of Plastics: Biobased, Biodegradable, and Fossil- Based Plastics 423 20.2.1 Fossil- Based Plastics 423 20.2.2 Biobased Plastics 423 20.2.3 Biodegradable Plastics 424 20.3 General Mechanism of Plastic Biodegradation 424 20.4 Microbial Sources of Plastic- Degrading Enzymes 426 20.4.1 Actinomycetes 426 20.4.2 Algae 427 20.4.3 Bacteria 427 20.4.4 Fungi 428 20.5 Biotechnological Strategies for Identifying/Improving Microbial Enzymes and Their Sources for Plastic Biodegradation 429 20.5.1 Conventional Culturing Approach 429 20.5.2 Metagenomics 430 20.5.3 Recombinant Technology 431 20.5.4 Protein Engineering 431 20.6 Conclusion and Future Perspectives 432 References 434 21 Strategies, Trends, and Technological Advancements in Microbial Bioreactor System for Probiotic Products 443 Soubhagya Tripathy, Ami R. Patel, Deepak Kumar Verma, Smita Singh, Gemilang Lara Utama, Mamta Thakur, Alaa Kareem Niamah, Nihir Shah, Shayma Thyab Gddoa Al- Sahlany, Prem Prakash Srivastav, Mónica L. Chávez- González, and Cristobal Noe Aguilar 21.1 Introduction 443 21.2 Bioreactors and Production of Probiotics 444 21.2.1 Conventional Batch Bioreactor System 447 21.2.2 Membrane Bioreactor System 449 21.2.3 Co- culture Fermentation 452 21.2.4 Recent Methods for Producing Multiple Probiotic Strains 454 21.3 Strategies Employed for Harvesting and Drying Probiotic Cells 455 21.4 Final Remarks and Possible Directions for the Future 456 Abbreviations 457 References 457 22 Microbial Bioproduction of Antiaging Molecules 465 Ankita Dua, Aeshna Nigam, Anjali Saxena, Gauri Garg Dhingra, and Roshan Kumar 22.1 Introduction 465 22.2 The Aging Process: An Overview 466 22.3 Human Health and the Aging Gut Microbiome 468 22.4 The Antiaging Bioproducts from Microbes 469 22.4.1 Bacteria 469 22.4.2 Fungi 471 22.4.3 Algae 471 22.5 The Impact of Microbial Bioproducts on Gut Diversity 472 22.6 Microbial Bioproduction of Extremolytes 472 22.7 The Role of Antiaging and Antioxidant Molecules 473 22.8 Conclusions 480 References 480 Index 487

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Book SynopsisUnravelling Long COVID An authoritative medical reference on the various ways in which Long-COVID presents and an in-depth discussion of its mechanisms and potential therapeutic options. Unravelling Long COVID aims to provide a better awareness and understanding of the persistent health problems that can arise following SARS-CoV-2 infection. Variously described as Long-COVID, Long-Haulers' Syndrome, and Post-Acute Sequelae of SARS-CoV-2, this newly-designated disorder is estimated to have affected somewhere between 50 to 250 million people. It is in fact considered by many as the next global public health disaster. With such a broad and important topic, the authors of Unravelling Long COVID have focused primarily on two major problems in the current understanding of Long-COVID: 1.) the failure to distinguish patients with organ damagehere called Long-COVID Disease and those with unexplained, persistent symptomswhat is termed Long-COVID syndrome, and 2.) the failure of current medical approaches to comprehend and treat those persistent unexplained symptoms. Unravelling Long COVID is: One of the first books focused specifically on defining and understanding Long-COVID with the goal of establishing optimal managementA unique reference to distinguish patients with organ damage caused by Long-COVID disease from those with unexplained, persistent symptoms that manifest as Long-COVID syndromeAn in-depth exploration of neuroimmune pathways to help clarify the previously unexplained symptoms of Long-COVID Unravelling Long COVID isan essential reference for anyone interested in Long-COVID and the impact that this condition has had on the population. It will be a useful resource for both patients suffering from the Long-Covid syndrome, their physicians and for the growing number of Long-COVID clinics that have been established across the US, the UK, and other countries. This book is paired with a long-COVID blog, updated regularly by the authors, so the reader will be kept up to date with new clinical and research findings, in real time. To visit this site, follow this link:unravellinglongcovid.com providing the latest information on long-COVIDTable of ContentsIntroduction Section 1: Long-COVID Disease Chapter 1. Long-COVID Disease or Long-COVID Syndrome? Chapter 2. Lung, Heart Disease, and Other Organ Damage Chapter 3. COVID-19 Direct Effects on the Central Nervous System Section 2: Long-COVID Syndrome and Unexplained Symptoms Chapter 4. Unexplained Symptoms: Medicine’s Blind Spot Chapter 5. Historical Perspectives, Including Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Fibromyalgia Section 3. Mechanisms and Pathways Chapter 6. Brain Homeostasis Run Amok Chapter 7. Neuroimmune Dysfunction Section 4. Evaluation and Management Chapter 8. Patient Evaluation and Research Chapter 9. Patient Management and Rethinking Healthcare Amid Long COVID Chapter 10. The Way Forward: For Patients, Healthcare Providers, and Research Appendix A. Long-COVID Clinics in the US and Europe Appendix B. Suggestions for Future Research Focused on the Cellular and Molecular Basis of Long-COVID Syndrome Index

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Book SynopsisImpact of Engineered Nanomaterials in Genomics and Epigenomics Overview of current research and technologies in nanomaterial science as applied to omics science at the single cell level Impact of Engineered Nanomaterials in Genomics and Epigenomics is a comprehensive and authoritative compilation of the genetic processes and instructions that specifically direct individual genes to turn on or off, focusing on the developing technologies of engineering nanomaterials and their role in cell engineering which have become important research tools for pharmaceutical, biological, medical, and toxicological studies. Combining state-of-the art information on the impact of engineered nanomaterials in genomics and epigenomics, from a range of internationally recognized investigators from around the world, this edited volume offers unique insights into the current trends and future directions of research in this scientific field. Impact of Engineered NanomateriTable of ContentsContents List of Contributors xv Preface xix Acknowledgments xxi 1 Impact of Engineered Nanomaterials in Genomics and Epigenomics 1 Saura C. Sahu Contents Nanotechnology: A Technological Advancement of the Twenty-First Century 1 Genomics and Epigenomics 1 Beneficial Impacts of Engineered Nanomaterials on Human Life 2 Potential Adverse Health Effects of Engineered Nanomaterials 2 Conclusions 3 References 3 2 Molecular Impacts of Advanced Nanomaterials at Genomic and Epigenomic Levels 5 Kamran Shekh, Rais A Ansari, Yadollah Omidi, and Saghir A. Shakil Introduction 5 Classification of NMs 6 Absorption and Distribution of NMs 6 Major Adverse Effects of NMs 8 Known Cellular and Nuclear Uptake Mechanisms for Nanoparticles 10 Epigenetic Mechanisms and the Effect of NMs 11 DNA Methylation 12 Genetic and Genomic Effects of NMs 20 Conclusion 25 References 26 3 Endocrine Disruptors: Genetic, Epigenetic, and Related Pathways 41 Rais A. Ansari, Saleh Alfuraih, Kamran Shekh, Yadollah Omidi, Saleem Javed, and Saghir A. Shakil Introduction 41 Toxic Effects of EDCs on Wildlife and Humans 47 Effects During Development 48 Delayed Effects 48 Transgenerational Effects 49 Identification of EDC: Methods 49 Genetic Pathways 50 Phosphorylation-Mediated Signaling Pathways of Nuclear Receptors and Other Transcription Factors: Link to EDC 53 ER-Signaling Pathways 53 Xenoandrogens and Metabolic Syndrome 54 AR Signaling Pathways 54 Mechanism of ED 55 Methylation and Gene Regulation 55 Role of Noncoding RNAs 59 Transgenerational Inheritance of Epigenetics Induced by EDCs 59 Anti-Thyroids 60 Organotin 62 Epigenetic Effects of Organotin 63 TCDD and Related Compounds 63 TCDD and Genetic Response 64 TCDD-Mediated Epigenetic Response 65 Conclusions 65 References 66 4 Nanoplastics in Agroecosystem and Phytotoxicity: An Evaluation of Cytogenotoxicity and Epigenetic Regulation 83 Piyoosh Kumar Babele and Ravi Kant Bhatia Introduction 83 Fate and Behavior of NPs in Agroecosystem and Soil Environment 85 Uptake and Accumulation of NPs in Plants 87 NPs and Phytotoxicity 88 Can NPs Cause Cytogenotoxicity and Dysregulate Epigenetic Markers in Plants? 89 NPs and Epigenetic Regulation 91 Conclusion and Perspectives 92 References 93 5 Metal Oxide Nanoparticles and Graphene-Based Nanomaterials: Genotoxic, Oxidative, and Epigenetic Effects 99 Delia Cavallo, Pieranna Chiarella, Anna Maria Fresegna, Aureliano Ciervo, Valentina Del Frate, and Cinzia Lucia Ursini Introduction 99 Physicochemical Properties of NMs and Toxicity 100 Mechanism of NM Genotoxicity 101 Epigenetic Effects of Nanomaterials 102 Studies on Genotoxic and Oxidative Effects of Metal Oxides and Graphene-Based Nanomaterials 104 Graphene-Based NMs 120 Studies on Epigenetic Effects of Metal Oxides and Graphene-Based Nanomaterials 123 Studies on Workers – Genotoxic and Oxidative Effects of Occupational Exposure to Metal Oxides Nanoparticles, SiO2 NPs, and Graphene-Based Nanomaterials 127 Conclusions 132 References 132 6 Epigenotoxicity of Titanium Dioxide Nanoparticles 145 Carlos Wells, Marta Pogribna, Beverly Lyn-Cook, and George Hammons Introduction 145 Cellular Uptake and Biodistribution 147 DNA Methylation and TiO2 Nanoparticles 151 Histone Modifications and TiO2 Nanoparticles 157 MicroRNAs and TiO2 Nanoparticles 161 Risk Assessment 167 Conclusion 173 Disclaimer 174 References 174 7 Toxicogenomics of Multi-Walled Carbon Nanotubes 187 Pius Joseph Introduction 187 MWCNTs 188 Lung Injury 190 Inflammation 190 Oxidative Stress 192 Fibrosis 193 Mesothelioma 195 Lung Cancer 196 Genotoxicity 197 Toxicogenomics of ENMs 198 Transcriptomics – Technical Aspects 199 Toxicogenomics of MWCNTs – Animal Studies 201 Toxicogenomics of MWCNT – Human Studies 206 Disclaimer 207 References 207 8 Nano-Engineering in Traumatic Brain Injury 217 Najlaa Al-Thani, Mohammad Z. Haider , Maryam Al-Mansoob, Stuti Patel, Salma M.S. Ahmad, Firas Kobeissy, and Abdullah Shaito Introduction 217 Nanoparticles in the Treatment of TBI 218 Conclusion 222 References 223 9 Application of Nanoemulsions in Food Industries: Recent Progress, Challenges, and Opportunities 229 Ramesh Chaudhari, Vishva Patel, and Ashutosh Kumar Introduction 229 Components of Nanoemulsions 231 Approaches for Nanoemulsion Production 232 Applications of Food-Grade Nanoemulsions 235 Comparison of Nanoemulsion from Conventional Methods 241 Problems and Probable Solutions of Nanoemulsions 242 Future Trends and Challenges 243 Regulations and Safety Aspects 243 Conclusion 244 Conflict of Interest 245 Acknowledgments 245 References 245 10 Adverse Epigenetic Effects of Environmental Engineered Nanoparticles as Drug Carriers 251 Yingxue Zhang, Eid Alshammari, Nouran Yonis, and Zhe Yang Introduction 251 ENP-Based Drug-Delivery Systems 252 Adverse Epigenetic Effects of ENPs 257 ENP-Induced Epigenetic Toxicity Likely Mediated by ROS 269 Conclusion 271 References 271 11 Engineered Nanoparticles Adversely Impact Glucose Energy Metabolism 283 Yingxue Zhang, Alexander Yang, and Zhe Yang Introduction 283 Biological Toxicity of Engineered Nanoparticles 284 Engineered Nanoparticles Alter Glucose Metabolism 285 Engineered Nanoparticles Alter TCA Cycle 288 Engineered Nanoparticles Alter Oxidative Phosphorylation 289 Conclusion 291 References 291 12 Artificial Intelligence and Machine Learning of Single-Cell Transcriptomics of Engineered Nanoparticles 295 Alexander Yang, Yingxue Zhang, and Zhe Yang Introduction 295 Impact of Nanoparticles on Single-Cell Transcriptomics and Response Heterogeneity 297 AI and ML in scRNA-Seq Data Analysis 301 Determining Cell Differentiation and Lineage Based on Single-Cell Entropy 303 Conclusion 304 References 305 13 Toxicogenomics and Toxicological Mechanisms of Engineered Nanomaterials 309 Eid Alshammari, Yingxue Zhang, Alexander Yang, and Zhe Yang Introduction 309 Genomic Responses to ENMs 310 Transcriptomic Responses to ENMs 313 Conclusion 314 References 315 14 Carbon Nanotubes Alter Metabolomics Pathways Leading to Broad Ecological Toxicity 319 Nouran Yonis, Eid Alshammari, and Zhe Yang Introduction 319 Biomedical Application and Toxicity of Carbon Nanotubes 321 Metabolomics Toxicity of Carbon Nanotubes 323 Conclusion 326 References 326 15 Assessment of the Biological Impact of Engineered Nanomaterials Using Mass Spectrometry-Based MultiOmics Approaches 331 Nicholas Day, Tong Zhang, Matthew J. Gaffrey, Brian D. Thrall, and Wei-Jun Qian Introduction 331 Applications of MS for the Measurements of Proteins, PTMs, Lipids, and Metabolites 332 Multiomics Investigation of ENM Exposure to Microorganisms 335 Multiomics Investigation of ENM Exposure Using In Vitro Cell Culture Models 337 Multiomics Studies Reveal Organ-Specific Toxicity at the Organismal Level 340 Conclusions and Perspectives 344 Acknowledgments 347 Compliance with Ethical Standards 347 References 347 16 Current Scenario and Future Trends of Plant Nano-Interaction to Mitigate Abiotic Stresses: A Review 355 Farhat Yasmeen, Ghazala Mustafa, Hafiz Muhammad Jhanzab, and Setsuko Komatsu Abbreviations 355 Introduction 355 Synthesis of Nanoparticles 356 Morphophysiological Effects of Nanoparticles on Plant 364 Molecular Mechanism Altered by Nanoparticles 370 Nanoparticles Interaction with Plants 374 Conclusion and Future Prospects 375 References 376 17 Latest Insights on Genomic and Epigenomic Mechanisms of Nanotoxicity 397 Vratko Himič, Nikolaos Syrmos, Gianfranco K.I. Ligarotti, and Mario Ganau Introduction 397 Mechanisms of Genotoxicity 397 Genomic Consequences of ENM Exposure 400 A Primer on Epigenetic Processes 403 Epigenomic Consequences of ENM Exposure 404 Importance of Properties of ENMs 409 Future Perspectives 411 References 411 Index 419

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Book SynopsisTable of ContentsForeword xii Preface xiv Symbols and Abbreviations xvi 1 History and Context 1 1.1 From Cells to Their Nuclei 1 1.1.1 The Cell Theory 2 1.1.2 Mitosis 3 1.1.3 The Chromosome Theory of Heredity 6 1.1.4 Deoxyribonucleic Acid (DNA) 9 1.1.5 Cell Cycles Come in Many Flavors 12 2 Cell Growth and Division 17 2.1 Balanced Growth and Cell Proliferation 17 2.2 Measures of Cell Growth 21 2.3 The Relationship Between Cell Growth and Division 24 2.4 Patterns of Growth in the Cell Cycle 27 2.4.1 Amoeba Cell Growth 28 2.4.2 Fission Yeast Growth 29 2.4.3 Budding Yeast Growth 30 2.4.4 Mammalian Cell Growth 31 2.5 Sizers vs Adders 32 3 Assaying Cell Cycle Progression 39 3.1 Measuring Cell Cycle Phases 39 3.1.1 Single- Cell Imaging 39 3.1.2 Labeled Mitoses 41 3.1.3 Frequency Distributions 43 3.2 Growth Limitations and Variations in the Duration of Cell Cycle Phases 46 3.3 Synchronous Cultures 49 3.3.1 How can One Induce Synchrony? 49 3.3.2 Selecting for Synchrony 52 3.3.2.1 Elutriation: The Mother of all Synchrony Selections 53 4 The Master Switch 57 4.1 Genetic Analyses Leading the Way 59 4.1.1 The cdc28 Mutant of Budding Yeast 59 4.1.2 From the wee1 to the cdc2 Mutant of Fission Yeast 63 4.1.3 What is True for One is True for All 66 4.2 All Roads Lead to the Same Control System 67 4.2.1 Cyclins 67 4.2.2 Maturation Promoting Factor (MPF) 70 4.3 Making Sense of it All 75 4.3.1 Cyclins Galore in Budding Yeast 76 4.3.1.1 G1 Cyclins 77 4.3.2 Back to wee1 78 5 Controlling the Master Switch 80 5.1 Cyclins in Cdk Complexes 81 5.2 Cdk as a Target of Phosphorylations 84 5.2.1 Activating Phosphorylation 84 5.2.2 Inhibitory Phosphorylation 85 5.3 Other Proteins in Cyclin/Cdk Complexes 86 5.3.1 Cdk Inhibitors 86 5.3.1.1 Cip/Kip Proteins 88 5.3.1.2 INK4 Proteins 88 5.3.2 Cks1 89 5.4 What Are Its Targets and How Cdk Phosphorylates Them 89 5.4.1 Defining the Cdk Substrate Universe 89 5.4.2 Cyclin the Recruiter 91 5.4.3 Here Comes Cks1 92 5.5 Ordering Cdk Phosphorylation in the Cell Cycle 94 5.5.1 Order from Intrinsic Cdk Activity 94 5.5.2 Precision from Specificity 96 6 A Full Circle of the Switch 99 6.1 Modeling a Cell Cycle Oscillator 99 6.2 The M- Cdk Switch 103 6.2.1 Exit from Interphase into Mitosis 103 6.2.2 The Anaphase Promoting Complex (apc) 104 6.2.3 From Metaphase to Anaphase 105 6.2.4 Flipping the M- Cdk Switch Off 106 6.2.5 Unsolved Problem: “Sizing” the M-.Cdk Switch 109 6.3 The G1/S Cdk Switch 110 6.3.1 G1- Cdk Activates G1/S Transcription 111 6.3.1.1 Doing Away with Transcriptional Inhibitors 111 6.3.2 Positive Feedback at the G1/S Switch 114 6.3.3 Negative Feedback at the G1/S Switch 115 6.3.4 Physiological Relevance of G1/S Switch in Cancer 116 6.4 Transcriptional Waves Until the End of the Cell Cycle 117 6.5 Comments on Overall Gene Expression in the Cell Cycle 119 7 Duplicating the Genome 121 7.1 DNA Replication 121 7.1.1 Setting the Stage 122 7.1.2 Origin Firing 126 7.1.3 Chromatin 128 7.1.4 Sisters Stay Together 129 7.2 Checkpoints 132 7.2.1 The General Concept 132 7.2.2 DNA Damage Checkpoint 134 8 Segregating the Chromosomes 138 8.1 Blind Men’s Riddle 138 8.2 The Mitotic Spindle 139 8.2.1 Tubulin 140 8.2.2 MTs are Dynamic 142 8.2.3 Scaling the Spindle 146 8.3 The MT Organizing Centers (MTOCs) 147 8.4 The Kinetochore 152 8.4.1 Kinetochore- MT Attachment: Stochastic or Deterministic? 154 8.4.2 May the Force Be With You 156 8.5 The Spindle Assembly Checkpoint (SAC) 159 9 Segregating Organelles and the Cytoplasm 162 9.1 The Golgi 164 9.2 Mitochondria 166 9.3 Lysosomes and Vacuoles 169 9.4 Mitotic Fragmentation of the Nuclear Envelope 170 9.5 Cytokinesis: Two from One 172 9.5.1 Position 172 9.5.2 Assemble 176 9.5.3 Contract 179 References 189 Index 209

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Book SynopsisEdited and written by leading researchers from around the world, The Ecological Genomics of Fungi covers a broad diversity of fungal systems and provides unique insight into the functions of those fungi in various ecosystems, from soil, to plant, to human.Trade Review“I think the volume may succeed in its ambition to serve as a catalyst for further studies by showing researchers venturing into ecological genomics and those already in genomics the width of the field. This may, in turn, further more integrative studies that will benefit our understanding of fungi.” (The Quarterly Review of Biology, 1 October 2015) Table of ContentsContributors vii Preface xiii Section 1 Sequencing Fungal Genomes 1 1 A Changing Landscape of Fungal Genomics 3 Igor V. Grigoriev 2 Repeated Elements in Filamentous Fungi with a Focus on Wood-Decay Fungi 21 Claude Murat, Thibaut Payen, Denis Petitpierre, and Jessy Labbé Section 2 Saprotrophic Fungi 41 3 Wood Decay 43 Dan Cullen 4 Aspergilli and Biomass-Degrading Fungi 63 Isabelle Benoit, Ronald P. de Vries, Scott E. Baker, and Sue A. Karagiosis 5 Ecological Genomics of Trichoderma 89 Irina S. Druzhinina and Christian P. Kubicek Section 3 Plant-Interacting Fungi 117 6 Dothideomycetes: Plant Pathogens, Saprobes, and Extremophiles 119 Stephen B. Goodwin 7 Biotrophic Fungi (Powdery Mildews, Rusts, and Smuts) 149 Sébastien Duplessis, Pietro D. Spanu, and Jan Schirawski 8 The Mycorrhizal Symbiosis Genomics 169 Francis Martin and Annegret Kohler 9 Lichen Genomics: Prospects and Progress 191 Martin Grube, Gabriele Berg, ólafur S. Andrésson, Oddur Vilhelmsson, Paul S. Dyer, and Vivian P.W. Miao Section 4 Animal-Interacting Fungi 213 10 Ecogenomics of Human and Animal Basidiomycetous Yeast Pathogens 215 Sheng Sun, Ferry Hagen, Jun Xu, Tom Dawson, Joseph Heitman, James Kronstad, Charles Saunders, and Teun Boekhout 11 Genomics of Entomopathogenic Fungi 243 Chengshu Wang and Raymond J. St. Leger 12 Ecological Genomics of the Microsporidia 261 Nicolas Corradi and Patrick J. Keeling Section 5 Metagenomics and Biogeography of Fungi 279 13 Metagenomics for Study of Fungal Ecology 281 Björn D. Lindahl and Cheryl R. Kuske 14 Metatranscriptomics of Soil Eukaryotic Communities 305 Laurence Fraissinet-Tachet, Roland Marmeisse, Lucie Zinger, and Patricia Luis 15 Fungi in Deep-Sea Environments and Metagenomics 325 Stéphane Mahé, Vanessa Rédou, Thomas Le Calvez, Philippe Vandenkoornhuyse, and Gaëtan Burgaud 16 The Biodiversity, Ecology, and Biogeography of Ascomycetous Yeasts 355 Marc-André Lachance Index 371

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Book SynopsisImaging Life is an accessible textbook that covers scientific imaging, from creating pictures with a wide range of instruments, to processing and analyzing them.Table of ContentsPreface xii Acknowledgments xiv About the Companion Website xv Section 1 Image Acquisition 1 1 Image Structure and Pixels 3 1.1 The Pixel Is the Smallest Discrete Unit of a Picture 3 1.2 The Resolving Power of a Camera or Display Is the Spatial Frequency of Its Pixels 6 1.3 Image Legibility Is the Ability to Recognize Text in an Image by Eye 7 1.4 Magnification Reduces Spatial Frequencies While Making Bigger Images 9 1.5 Technology Determines Scale and Resolution 11 1.6 The Nyquist Criterion: Capture at Twice the Spatial Frequency of the Smallest Object Imaged 12 1.7 Archival Time, Storage Limits, and the Resolution of the Display Medium Influence Capture and Scan Resolving Power 13 1.8 Digital Image Resizing or Scaling Match the Captured Image Resolution to the Output Resolution 14 1.9 Metadata Describes Image Content, Structure, and Conditions of Acquisition 16 2 Pixel Values and Image Contrast 20 2.1 Contrast Compares the Intensity of a Pixel with That of Its Surround 20 2.2 Pixel Values Determine Brightness and Color 21 2.3 The Histogram Is a Plot of the Number of Pixels in an Image at Each Level of Intensity 24 2.4 Tonal Range Is How Much of the Pixel Depth Is Used in an Image 25 2.5 The Image Histogram Shows Overexposure and Underexposure 26 2.6 High-Key Images Are Very Light, and Low-Key Images Are Very Dark 27 2.7 Color Images Have Various Pixel Depths 27 2.8 Contrast Analysis and Adjustment Using Histograms Are Available in Proprietary and Open-Source Software 29 2.9 The Intensity Transfer Graph Shows Adjustments of Contrast and Brightness Using Input and Output Histograms 30 2.10 Histogram Stretching Can Improve the Contrast and Tonal Range of the Image without Losing Information 32 2.11 Histogram Stretching of Color Channels Improves Color Balance 32 2.12 Software Tools for Contrast Manipulation Provide Linear, Non-linear, and Output-Visualized Adjustment 34 2.13 Different Image Formats Support Different Image Modes 36 2.14 Lossless Compression Preserves Pixel Values, and Lossy Compression Changes Them 37 3 Representation and Evaluation of Image Data 42 3.1 Image Representation Incorporates Multiple Visual Elements to Tell a Story 42 3.2 Illustrated Confections Combine the Accuracy of a Typical Specimen with a Science Story 42 3.3 Digital Confections Combine the Accuracy of Photography with a Science Story 45 3.4 The Video Storyboard Is an Explicit Visual Confection 48 3.5 Artificial Intelligence Can Generate Photorealistic Images from Text Stories 48 3.6 Making Images Believable: Show Representative Images and State the Acquisition Method 50 3.7 Making Images Understood: Clearly Identify Regions of Interest with Suitable Framing, Labels, and Image Contrast 51 3.8 Avoid Dequantification and Technical Artifacts While Not Hesitating to Take the Picture 55 3.9 Accurate, Reproducible Imaging Requires a Set of Rules and Guidelines 56 3.10 The Structural Similarity Index Measure Quantifies Image Degradation 57 4 Image Capture by Eye 61 4.1 The Anatomy of the Eye Limits Its Spatial Resolution 61 4.2 The Dynamic Range of the Eye Exceeds 11 Orders of Magnitude of Light Intensity, and Intrascene Dynamic Range Is about 3 Orders 63 4.3 The Absorption Characteristics of Photopigments of the Eye Determines Its Wavelength Sensitivity 63 4.4 Refraction and Reflection Determine the Optical Properties of Materials 67 4.5 Movement of Light Through the Eye Depends on the Refractive Index and Thickness of the Lens, the Vitreous Humor, and Other Components 69 4.6 Neural Feedback in the Brain Dictates Temporal Resolution of the Eye 69 4.7 We Sense Size and Distribution in Large Spaces Using the Rules of Perspective 70 4.8 Three-Dimensional Representation Depends on Eye Focus from Different Angles 71 4.9 Binocular Vision Relaxes the Eye and Provides a Three-Dimensional View in Stereomicroscopes 74 5 Image Capture with Digital Cameras 78 5.1 Digital Cameras are Everywhere 78 5.2 Light Interacts with Silicon Chips to Produce Electrons 78 5.3 The Anatomy of the Camera Chip Limits Its Spatial Resolution 80 5.4 Camera Chips Convert Spatial Frequencies to Temporal Frequencies with a Series of Horizontal and Vertical Clocks 82 5.5 Different Charge-Coupled Device Architectures Have Different Read-out Mechanisms 85 5.6 The Digital Camera Image Starts Out as an Analog Signal that Becomes Digital 87 5.7 Video Broadcast Uses Legacy Frequency Standards 88 5.8 Codecs Code and Decode Digital Video 89 5.9 Digital Video Playback Formats Vary Widely, Reflecting Different Means of Transmission and Display 91 5.10 The Light Absorption Characteristics of the Metal Oxide Semiconductor, Its Filters, and Its Coatings Determine the Wavelength Sensitivity of the Camera Chip 91 5.11 Camera Noise and Potential Well Size Determine the Sensitivity of the Camera to Detectable Light 93 5.12 Scientific Camera Chips Increase Light Sensitivity and Amplify the Signal 97 5.13 Cameras for Electron Microscopy Use Regular Imaging Chips after Converting Electrons to Photons or Detect the Electron Signal Directly with Modified CMOS 99 5.14 Camera Lenses Place Additional Constraints on Spatial Resolution 101 5.15 Lens Aperture Controls Resolution, the Amount of Light, the Contrast, and the Depth of Field in a Digital Camera 106 5.16 Relative Magnification with a Photographic Lens Depends on Chip Size and Lens Focal Length 107 6 Image Capture by Scanning Systems 111 6.1 Scanners Build Images Point by Point, Line by Line, and Slice by Slice 111 6.2 Consumer-Grade Flatbed Scanners Provide Calibrated Color and Relatively High Resolution Over a Wide Field of View 111 6.3 Scientific-Grade Flatbed Scanners Can Detect Chemiluminescence, Fluorescence, and Phosphorescence 114 6.4 Scientific-Grade Scanning Systems Often Use Photomultiplier Tubes and Avalanche Photodiodes as the Camera 118 6.5 X-ray Planar Radiography Uses Both Scanning and Camera Technologies 119 6.6 Medical Computed Tomography Scans Rotate the X-ray Source and Sensor in a Helical Fashion Around the Body 121 6.7 Micro-CT and Nano-CT Scanners Use Both Hard and Soft X-Rays and Can Resolve Cellular Features 123 6.8 Macro Laser Scanners Acquire Three-Dimensional Images by Time-of-Flight or Structured Light 125 6.9 Laser Scanning and Spinning Disks Generate Images for Confocal Scanning Microscopy 126 6.10 Electron Beam Scanning Generates Images for Scanning Electron Microscopy 128 6.11 Atomic Force Microscopy Scans a Force-Sensing Probe Across the Sample 128 Section 2 Image Analysis 135 7 Measuring Selected Image Features 137 7.1 Digital Image Processing and Measurements are Part of the Image Metadata 137 7.2 The Subject Matter Determines the Choice of Image Analysis and Measurement Software 140 7.3 Recorded Paths, Regions of Interest, or Masks Save Selections for Measurement in Separate Images, Channels, and Overlays 140 7.4 Stereology and Photoquadrat Sampling Measure Unsegmented Images 144 7.5 Automatic Segmentation of Images Selects Image Features for Measurement Based on Common Feature Properties 146 7.6 Segmenting by Pixel Intensity Is Thresholding 146 7.7 Color Segmentation Looks for Similarities in a Three-Dimensional Color Space 147 7.8 Morphological Image Processing Separates or Connects Features 149 7.9 Measures of Pixel Intensity Quantify Light Absorption by and Emission from the Sample 153 7.10 Morphometric Measurements Quantify the Geometric Properties of Selections 155 7.11 Multi-dimensional Measurements Require Specific Filters 156 8 Optics and Image Formation 161 8.1 Optical Mechanics Can Be Well Described Mathematically 161 8.2 A Lens Divides Space Into Image and Object Spaces 161 8.3 The Lens Aperture Determines How Well the Lens Collects Radiation 163 8.4 The Diffraction Limit and the Contrast between Two Closely Spaced Self-Luminous Spots Give Rise to the Limits of Resolution 164 8.5 The Depth of the Three-Dimensional Slice of Object Space Remaining in Focus Is the Depth of Field 167 8.6 In Electromagnetic Lenses, Focal Length Produces Focus and Magnification 170 8.7 The Axial, Z-Dimensional, Point Spread Function Is a Measure of the Axial Resolution of High Numerical Aperture Lenses 171 8.8 Numerical Aperture and Magnification Determine the Light-Gathering Properties of the Microscope Objective 172 8.9 The Modulation (Contrast) Transfer Function Relates the Relative Contrast to Resolving Power in Fourier, or Frequency, Space 172 8.10 The Point Spread Function Convolves the Object to Generate the Image 176 8.11 Problems with the Focus of the Lens Arise from Lens Aberrations 177 8.12 Refractive Index Mismatch in the Sample Produces Spherical Aberration 182 8.13 Adaptive Optics Compensate for Refractive Index Changes and Aberration Introduced by Thick Samples 183 9 Contrast and Tone Control 189 9.1 The Subject Determines the Lighting 189 9.2 Light Measurements Use Two Different Standards: Photometric and Radiometric Units 190 9.3 The Light Emission and Contrast of Small Objects Limits Their Visibility 194 9.4 Use the Image Histogram to Adjust the Trade-off Between Depth of Field and Motion Blur 194 9.5 Use the Camera’s Light Meter to Detect Intrascene Dynamic Range and Set Exposure Compensation 196 9.6 Light Sources Produce a Variety of Colors and Intensities That Determine the Quality of the Illumination 197 9.7 Lasers and LEDs Provide Lighting with Specific Color and High Intensity 199 9.8 Change Light Values with Absorption, Reflectance, Interference, and Polarizing Filters 200 9.9 Köhler-Illuminated Microscopes Produce Conjugate Planes of Collimated Light from the Source and Specimen 203 9.10 Reflectors, Diffusers, and Filters Control Lighting in Macro-imaging 207 10 Processing with Digital Filters 212 10.1 Image Processing Occurs Before, During, and After Image Acquisition 212 10.2 Near-Neighbor Operations Modify the Value of a Target Pixel 214 10.3 Rank Filters Identify Noise and Remove It from Images 215 10.4 Convolution Can Be an Arithmetic Operation with Near Neighbors 217 10.5 Deblurring and Background Subtraction Remove Out-of-Focus Features from Optical Sections 221 10.6 Convolution Operations in Frequency Space Multiply the Fourier Transform of an Image by the Fourier Transform of the Convolution Mask 222 10.7 Tomographic Operations in Frequency Space Produce Better Back-Projections 224 10.8 Deconvolution in Frequency Space Removes Blur Introduced by the Optical System But Has a Problem with Noise 224 11 Spatial Analysis 231 11.1 Affine Transforms Produce Geometric Transformations 231 11.2 Measuring Geometric Distortion Requires Grid Calibration 231 11.3 Distortion Compensation Locally Adds and Subtracts Pixels 231 11.4 Shape Analysis Starts with the Identification of Landmarks, Then Registration 232 11.5 Grid Transformations are the Basis for Morphometric Examination of Shape Change in Populations 234 11.6 Principal Component Analysis and Canonical Variates Analysis Use Measures of Similarity as Coordinates 237 11.7 Convolutional Neural Networks Can Identify Shapes and Objects Using Deep Learning 238 11.8 Boundary Morphometrics Analyzes and Mathematically Describes the Edge of the Object 240 11.9 Measurement of Object Boundaries Can Reveal Fractal Relationships 245 11.10 Pixel Intensity–Based Colocalization Analysis Reports the Spatial Correlation of Overlapping Signals 246 11.11 Distance-Based Colocalization and Cluster Analysis Analyze the Spatial Proximity of Objects 250 11.12 Fluorescence Resonance Energy Transfer Occurs Over Small (1–10 nm) Distances 252 11.13 Image Correlations Reveal Patterns in Time and Space 253 12 Temporal Analysis 260 12.1 Representations of Molecular, Cellular, Tissue, and Organism Dynamics Require Video and Motion Graphics 260 12.2 Motion Graphics Editors Use Key Frames to Specify Motion 262 12.3 Motion Estimation Uses Successive Video Frames to Analyze Motion 265 12.4 Optic Flow Compares the Intensities of Pixels, Pixel Blocks, or Regions Between Frames 266 12.5 The Kymograph Uses Time as an Axis to Make a Visual Plot of the Object Motion 268 12.6 Particle Tracking Is a Form of Feature-Based Motion Estimation 269 12.7 Fluorescence Recovery After Photobleaching Shows Compartment Connectivity and the Movement of Molecules 273 12.8 Fluorescence Switching Also Shows Connectivity and Movement 276 12.9 Fluorescence Correlation Spectroscopy and Raster Image Correlation Spectroscopy Can Distinguish between Diffusion and Advection 280 12.10 Fluorescent Protein Timers Provide Tracking of Maturing Proteins as They Move through Compartments 282 13 Three-Dimensional Imaging, Modeling, and Analysis 287 13.1 Three-Dimensional Worlds Are Scalable and Require Both Camera and Actor Views 287 13.2 Stacking Multiple Adjacent Slices Can Produce a Three-Dimensional Volume or Surface 291 13.3 Structure-from-Motion Photogrammetry Reconstructs Three-Dimensional Surfaces Using Multiple Camera Views 292 13.4 Reconstruction of Aligned Images in Fourier Space Produces Three-Dimensional Volumes or Surfaces 295 13.5 Surface Rendering Produces Isosurface Polygon Meshes Generated from Contoured Intensities 296 13.6 Texture Maps of Object Isosurfaces Are Images or Movies 299 13.7 Ray Tracing Follows a Ray of Light Backward from the Eye or Camera to Its Source 300 13.8 Ray Tracing Shows the Object Based on Internal Intensities or Nearness to the Camera 300 13.9 Transfer Functions Discriminate Objects in Ray-Traced Three Dimensions 301 13.10 Four Dimensions, a Time Series of Three-Dimensional Volumes, Can Use Either Ray-Traced or Isosurface Rendering 303 13.11 Volumes Rendered with Splats and Texture Maps Provide Realistic Object-Ordered Reconstructions 303 13.12 Analysis of Three-Dimensional Volumes Uses the Same Approaches as Two-Dimensional Area Analysis But Includes Voxel Adjacency and Connectivity 305 13.13 Head-Mounted Displays and Holograms Achieve an Immersive Three-Dimensional Experience 307 Section 3 Image Modalities 313 14 Ultrasound Imaging 315 14.1 Ultrasonography Is a Cheap, High-Resolution, Deep-Penetration, Non-invasive Imaging Modality 315 14.2 Many Species Use Ultrasound and Infrasound for Communication and Detection 315 14.3 Sound Is a Compression, or Pressure, Wave 316 14.4 The Measurement of Audible Sound Intensity Is in Decibels 317 14.5 A Piezoelectric Transducer Creates the Ultrasound Wave 318 14.6 Different Tissues Have Different Acoustic Impedances 319 14.7 Sonic Wave Scatter Generates Speckle 321 14.8 Lateral Resolution Depends on Sound Frequency and the Size and Focal Length of the Transducer Elements 322 14.9 Axial Resolution Depends on the Duration of the Ultrasound Pulse 323 14.10 Scatter and Absorption by Tissues Attenuate the Ultrasound Beam 324 14.11 Amplitude Mode, Motion Mode, Brightness Mode, and Coherent Planar Wave Mode Are the Standard Modes for Clinical Practice 324 14.12 Doppler Scans of Moving Red Blood Cells Reveal Changes in Vascular Flows with Time and Provide the Basis for Functional Ultrasound Imaging 327 14.13 Microbubbles and Gas Vesicles Provide Ultrasound Contrast and Have Therapeutic Potential 329 15 Magnetic Resonance Imaging 334 15.1 Magnetic Resonance Imaging, Like Ultrasound, Performs Non-invasive Analysis without Ionizing Radiation 334 15.2 Magnetic Resonance Imaging Is an Image of the Hydrogen Nuclei in Fat and Water 337 15.3 Magnetic Resonance Imaging Sets up a Net Magnetization in Each Voxel That Is in Dynamic Equilibrium with the Applied Field 338 15.4 The Magnetic Field Imposed by Magnetic Resonance Imaging Makes Protons Spin Like Tops with the Same Tilt and Determines the Frequency of Precession 338 15.5 Magnetic Resonance Imaging Disturbs the Net Magnetization Equilibrium and Then Follows the Relaxation Back to Equilibrium 339 15.6 T2 Relaxation, or Spin–Spin Relaxation, Causes the Disappearance of Transverse (x-y Direction) Magnetization Through Dephasing 342 15.7 T1 Relaxation, or Spin-Lattice Relaxation, Causes the Disappearance of Longitudinal (z-Direction) Magnetization Through Energy Loss 342 15.8 Faraday Induction Produces the Magnetic Resonance Imaging Signal (in Volts) with Coils in the x-y Plane 343 15.9 Magnetic Gradients and Selective Radiofrequency Frequencies Generate Slices in the x, y, and z Directions 343 15.10 Acquiring a Gradient Echo Image Is a Highly Repetitive Process, Getting Information Independently in the x, y, and z Dimensions 344 15.11 Fast Low-Angle Shot Gradient Echo Imaging Speeds Up Imaging for T1-Weighted Images 346 15.12 The Spin-Echo Image Compensates for Magnetic Heterogeneities in the Tissue in T2-Weighted Images 346 15.13 Three-Dimensional Imaging Sequences Produce Higher Axial Resolution 347 15.14 Echo Planar Imaging Is a Fast Two-Dimensional Imaging Modality But Has Limited Resolving Power 347 15.15 Magnetic Resonance Angiography Analyzes Blood Velocity 347 15.16 Diffusion Tensor Imaging Visualizes and Compares Directional (Anisotropic) Diffusion Coefficients in a Tissue 349 15.17 Functional Magnetic Resonance Imaging Provides a Map of Brain Activity 350 15.18 Magnetic Resonance Imaging Contrast Agents Detect Small Lesions That Are Otherwise Difficult to Detect 351 16 Microscopy with Transmitted and Refracted Light 355 16.1 Brightfield Microscopy of Living Cells Uses Apertures and the Absorbance of Transmitted Light to Generate Contrast 355 16.2 Staining Fixed or Frozen Tissue Can Localize Large Polymers, Such as Proteins, Carbohydrates, and Nucleic Acids, But Is Less Effective for Lipids, Diffusible Ions, and Small Metabolites 361 16.3 Darkfield Microscopy Generates Contrast by Only Collecting the Refracted Light from the Specimen 365 16.4 Rheinberg Microscopy Generates Contrast by Producing Color Differences between Refracted and Unrefracted Light 368 16.5 Wave Interference from the Object and Its Surround Generates Contrast in Polarized Light, Differential Interference Contrast, and Phase Contrast Microscopies 369 16.6 Phase Contrast Microscopy Generates Contrast by Changing the Phase Difference Between the Light Coming from the Object and Its Surround 369 16.7 Polarized Light Reveals Order within a Specimen and Differences in Object Thickness 374 16.8 The Phase Difference Between the Slow and Fast Axes of Ordered Specimens Generates Contrast in Polarized Light Microscopy 376 16.9 Compensators Cancel Out or Add to the Retardation Introduced by the Sample, Making It Possible to Measure the Sample Retardation 379 16.10 Differential Interference Contrast Microscopy Is a Form of Polarized Light Microscopy That Generates Contrast Through Differential Interference of Two Slightly Separated Beams of Light 383 17 Microscopy Using Fluoresced and Reflected Light 390 17.1 Fluorescence and Autofluorescence: Excitation of Molecules by Light Leads to Rapid Re-emission of Lower Energy Light 390 17.2 Fluorescence Properties Vary Among Molecules and Depend on Their Environment 391 17.3 Fluorescent Labels Include Fluorescent Proteins, Fluorescent Labeling Agents, and Vital and Non-vital Fluorescence Affinity Dyes 394 17.4 Fluorescence Environment Sensors Include Single-Wavelength Ion Sensors, Ratio Imaging Ion Sensors, FRET Sensors, and FRET-FLIM Sensors 399 17.5 Widefield Microscopy for Reflective or Fluorescent Samples Uses Epi-illumination 402 17.6 Epi-polarization Microscopy Detects Reflective Ordered Inorganic or Organic Crystallites and Uses Nanogold and Gold Beads as Labels 405 17.7 To Optimize the Signal from the Sample, Use Specialized and Adaptive Optics 405 17.8 Confocal Microscopes Use Accurate, Mechanical Four-Dimensional Epi-illumination and Acquisition 408 17.9 The Best Light Sources for Fluorescence Match Fluorophore Absorbance 410 17.10 Filters, Mirrors, and Computational Approaches Optimize Signal While Limiting the Crosstalk Between Fluorophores 411 17.11 The Confocal Microscope Has Higher Axial and Lateral Resolving Power Than the Widefield Epi-illuminated Microscope, Some Designs Reaching Superresolution 415 17.12 Multiphoton Microscopy and Other Forms of Non-linear Optics Create Conditions for Near-Simultaneous Excitation of Fluorophores with Two or More Photons 419 18 Extending the Resolving Power of the Light Microscope in Time and Space 427 18.1 Superresolution Microscopy Extends the Resolving Power of the Light Microscope 427 18.2 Fluorescence Lifetime Imaging Uses a Temporal Resolving Power that Extends to Gigahertz Frequencies (Nanosecond Resolution) 428 18.3 Spatial Resolving Power Extends Past the Diffraction Limit of Light 429 18.4 Light Sheet Fluorescence Microscopy Achieves Fast Acquisition Times and Low Photon Dose 432 18.5 Lattice Light Sheets Increase Axial Resolving Power 435 18.6 Total Internal Reflection Microscopy and Glancing Incident Microscopy Produce a Thin Sheet of Excitation Energy Near the Coverslip 437 18.7 Structured Illumination Microscopy Improves Resolution with Harmonic Patterns That Reveal Higher Spatial Frequencies 440 18.8 Stimulated Emission Depletion and Reversible Saturable Optical Linear Fluorescence Transitions Superresolution Approaches Use Reversibly Saturable Fluorescence to Reduce the Size of the Illumination Spot 447 18.9 Single-Molecule Excitation Microscopies, Photo-Activated Localization Microscopy, and Stochastic Optical Reconstruction Microscopy Also Rely on Switchable Fluorophores 452 18.10 MINFLUX Combines Single-Molecule Localization with Structured Illumination to Get Resolution below 10 nm 455 19 Electron Microscopy 461 19.1 Electron Microscopy Uses a Transmitted Primary Electron Beam (Transmission Electron Micrography) or Secondary and Backscattered Electrons (Scanning Electron Micrography) to Image the Sample 461 19.2 Some Forms of Scanning Electron Micrography Use Unfixed Tissue at Low Vacuums (Relatively High Pressure) 462 19.3 Both Transmission Electron Micrography and Scanning Electron Micrography Use Frozen or Fixed Tissues 465 19.4 Critical Point Drying and Surface Coating with Metal Preserves Surface Structures and Enhances Contrast for Scanning Electron Micrography 467 19.5 Glass and Diamond Knives Make Ultrathin Sections on Ultramicrotomes 468 19.6 The Filament Type and the Condenser Lenses Control Illumination in Scanning Electron Micrography and Transmission Electron Micrography 471 19.7 The Objective Lens Aperture Blocks Scattered Electrons, Producing Contrast in Transmission Electron Micrography 474 19.8 High-Resolution Transmission Electron Micrography Uses Large (or No) Objective Apertures 475 19.9 Conventional Transmission Electron Micrography Provides a Cellular Context for Visualizing Organelles and Specific Molecules 479 19.10 Serial Section Transmitted Primary Electron Analysis Can Provide Three-Dimensional Cellular Structures 482 19.11 Scanning Electron Micrography Volume Microscopy Produces Three-Dimensional Microscopy at Nanometer Scales and Includes In-Lens Detectors and In-Column Sectioning Devices 483 19.12 Correlative Electron Microscopy Provides Ultrastructural Context for Fluorescence Studies 488 19.13 Tomographic Reconstruction of Transmission Electron Micrography Images Produces Very Thin (10-nm) Virtual Sections for High-Resolution Three-Dimensional Reconstruction 490 19.14 Cryo-Electron Microscopy Achieves Molecular Resolving Power (Resolution, 0.1–0.2 Nm) Using Single-Particle Analysis 492 Index 497

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Book SynopsisOver the last ten years the subject of toxicology has changed dramatically, moving from a discipline which was once firmly wedded to traditional (some might say old-fashioned) methods to one which is keen to embrace the innovative techniques emerging from the developing fields of cell culture and molecular biology.Trade Review“Overall, we consider that this book is a useful summary of current and emerging techniques in molecular toxicology.” (BTS Newsletter, 1 March 2015) Table of ContentsForeword xiii Preface xv Acknowledgements xvii Abbreviations xix About the Companion Website xxiii 1 Background to Molecular and Cellular Toxicology 1 1.1 What do we mean by molecular and cellular toxicology? 1 1.2 Tissues and their maintenance 2 1.2.1 Stem cells 3 1.3 Tissue damage 4 1.3.1 Consequences of tissue injury 4 1.3.2 Reversible changes in cells and tissues 6 1.3.3 Irreversible changes in cells and tissues 7 1.4 Tissue responses to injury 7 1.4.1 Oxidative stress 7 1.4.2 Necrosis and apoptosis 10 1.4.3 Neoplasia 13 1.4.4 The initiation–promotion paradigm 13 1.5 Key concepts in toxicology 23 1.5.1 Risk and hazard 23 1.5.2 Variability and uncertainty 25 1.5.3 Threshold and non-threshold dose responses 26 1.5.4 The regulatory context 28 1.5.5 Limitations of whole animal studies 29 1.5.6 Use of human tissues in toxicology 31 1.6 Summing up 33 Self-assessment questions 33 Background Reading 34 References 34 2 Individual Susceptibility to Toxic Chemicals 37 2.1 Introduction 37 2.2 Toxicogenetics and toxicogenomics 38 2.3 Genotyping and phenotyping 39 2.3.1 Genotyping 40 2.3.2 Phenotyping 43 2.3.3 Correlating genotype and phenotype 44 2.4 Polymorphic xenobiotic metabolism 45 2.4.1 Polymorphic xenobiotic metabolising enzymes 49 2.4.2 The role of xenobiotic metabolising polymorphisms in susceptibility to toxic agents 50 2.5 Study numbers and effect size 60 2.6 Recent developments 62 2.6.1 Genome-wide association studies 62 2.6.2 Collaborative programmes 64 2.7 The UK Biobank 69 2.8 Conclusions 71 Self-assessment questions 72 Background Reading 72 References 73 3 ‘Omics Techniques 79 3.1 ‘Omics and bioinformatics 79 3.2 Transcriptomics 80 3.2.1 Methodology 80 3.2.2 Proof of principle 89 3.2.3 Hepatotoxicity 91 3.2.4 Extrahepatic toxicity 96 3.3 Proteomics 97 3.3.1 Methodology 98 3.4 Metabolomics/metabonomics 101 3.4.1 MS-based metabolomics 102 3.4.2 NMR-based metabolomics 106 3.5 Integrating different types of ‘omics data 107 3.5.1 ‘Omics in drug discovery 108 3.5.2 ‘Omics profiles as biomarkers of toxicity 109 3.6 Remaining issues with ‘omics approaches 111 3.7 Conclusions 112 Self-assessment questions 113 Background Reading 113 References 113 4 In Vitro Methods for Predicting In Vivo Toxicity 117 4.1 In vitro toxicology 117 4.2 Tissue culture 117 4.2.1 Primary cell cultures 122 4.2.2 Established cell lines 125 4.3 Acute toxicity in vitro 127 4.3.1 Cytotoxicity testing 127 4.3.2 Choice of cell line 129 4.3.3 Liver 131 4.3.4 Skin 133 4.3.5 Eye 141 4.4 Repeated dose toxicity 144 4.5 Reproductive toxicity 147 4.6 Stem cell-derived systems 149 4.7 Conclusions 151 Self-assessment questions 151 Background Reading 152 References 152 5 In Vitro Methods for Absorption, Distribution, Metabolism and Excretion 159 5.1 Why study ADME in vitro? 159 5.2 Absorption 160 5.2.1 Dermal penetration 160 5.2.2 Gastrointestinal absorption 164 5.3 Distribution 171 5.3.1 Protein binding 172 5.3.2 Blood-brain barrier 172 5.3.3 Other protective barriers 176 5.4 Metabolism 176 5.4.1 Skin 177 5.4.2 Gastrointestinal tract 179 5.4.3 Liver 179 5.5 Excretion 189 5.5.1 Biliary excretion 190 5.5.2 Renal clearance 191 5.6 Conclusions 191 Self-assessment questions 192 References 192 6 In Silico Methods and Structure–Activity Relationships 199 6.1 Why in silico? 199 6.2 Predicting the ADME characteristics of xenobiotics 200 6.2.1 Absorption 200 6.2.2 Distribution 206 6.2.3 Metabolism 207 6.2.4 Excretion 212 6.3 Physiologically based biokinetic modelling 212 6.4 Toxicity 221 6.4.1 Exposure modelling 222 6.4.2 Prediction of toxicity 223 6.5 Conclusions 233 Self-assessment questions 235 References 235 7 Transgenic Animal Models for ADME and Systemic Toxicity 241 7.1 Transgenic models and their use in toxicology 241 7.2 ADME models 242 7.2.1 Nuclear receptor models 244 7.2.2 Xenobiotic metabolism models 251 7.2.3 Drug transporter models 259 7.3 Reporter models 264 7.3.1 LacZ-based models 264 7.3.2 Green fluorescent protein-based models 267 7.3.3 Luciferase-based models 268 7.3.4 Evaluation 273 7.4 Conclusions 273 Self-assessment questions 274 Background Reading 274 References 274 8 Genotoxicity and its Measurement 281 8.1 Genotoxicity testing 281 8.2 Core in vitro tests 282 8.2.1 The Ames test 282 8.2.2 In vitro gene mutation tests using mammalian cells 283 8.2.3 The in vitro chromosome aberration test 284 8.2.4 The in vitro micronucleus assay 287 8.3 Assessment of genotoxicity for regulatory purposes 291 8.4 Novel in vitro methods 292 8.4.1 GreenScreen HC 292 8.4.2 The Reconstructed Skin MicroNucleus assay 293 8.5 Novel in vivo assays for gene mutations 294 8.5.1 The Pig-A assay 294 8.5.2 In vivo assays using transgenic mouse models 295 8.6 DNA damage and its repair 300 8.6.1 DNA damage 300 8.6.2 DNA repair 305 8.7 Thresholds 308 8.8 Conclusions 310 Self-assessment questions 310 References 311 9 Oncogenes and the Identification of Human Carcinogens 317 9.1 Introduction 317 9.2 Identification of human carcinogens 317 9.2.1 The lifetime carcinogenicity bioassay 317 9.2.2 The National Toxicology Program 2-year bioassay 318 9.3 Genetic changes in cancer 321 9.3.1 Methods for detecting activated oncogenes 324 9.3.2 In vitro transformation assays 324 9.3.3 Ras oncogene activation during tumour development 326 9.3.4 Non-ras oncogenes 328 9.3.5 Evaluation 329 9.4 Non-genotoxic carcinogenesis 329 9.4.1 Non-receptor-mediated mechanisms 330 9.4.2 Receptor-mediated mechanisms 331 9.4.3 When is a genotoxic carcinogen not a genotoxic carcinogen? 333 9.5 Transgenic models for short-term carcinogenicity bioassays 335 9.5.1 RasH2 335 9.5.2 Tg.AC 337 9.5.3 p53 models 338 9.5.4 XPC−¨M−, XPA−¨M− and XPA−¨M−/p53+¨M− null mouse models 340 9.5.5 Comparative evaluation of models 340 9.5.6 Regulatory status 341 9.5.7 Limitations of the assays 343 9.5.8 Evaluation 344 9.6 Conclusions 345 Self-assessment questions 346 References 346 10 Emerging Techniques 351 10.1 What’s next? 351 10.2 Novel model organisms 351 10.2.1 The zebrafish 352 10.2.2 Evaluation 358 10.3 Less invasive methods 359 10.3.1 Use of biomarkers 359 10.3.2 Liver 359 10.3.3 Kidney 367 10.3.4 Circulating mRNA biomarkers 371 10.3.5 Evaluation 373 10.4 The systems biology approach 373 10.4.1 Systems biology in toxicology 376 10.5 Collaborative programmes 381 10.5.1 Europe 381 10.5.2 USA 383 10.5.3 Evaluation 384 10.6 Final word 385 Self-assessment questions 385 References 385 Index 391

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Book SynopsisThis book is about water - in Britain, and in the world. It is about water resources, their conservation, protection of water quality for human consumption and aquatic ecosystems. Since the publication of the first edition in 1998, major political and regulatory changes have taken place; this book provides a clear and comprehensive update of conservation and water resource management issues in the UK over the past two decades, and in an expansion of its original UK perspective now includes examples of global best practice. The UK's 2003 adoption of the EU Water Framework Directive has had enormous implications for the conservation and management of our water resources. In 2016, with the UK's decision to leave the EU, the governance scene is entering upon an unpredictable future regarding its major water resource policies. The Protection and Conservation of Water Resources, Second edition provides a clear and comprehensive update of conservation and water resouTable of ContentsNotes on Author ix Preface xi Preface to the First Edition xvii Acknowledgements xix Introduction 1 1 Water, Policy and Procedure 5 2 Water Resource Availability in Britain 31 3 Institutions and Legislation for Resource Management 63 4 The Catchment Approach: Ways and Means 101 5 Sustaining Bulk Supply: Consumption and Interference 131 6 Sustaining Bulk Supply: Possible Solutions 159 7 Water Quality Background Issues 193 8 Environmental Issues of Water Quality and Quantity 231 9 Towards Solutions: Land Use and Technical Fixes 275 10 Framing Water Policies: Emerging Governance Arrangements 313 11 The USA, Australia, Europe and Lessons to be Learned: Lessons to be Learned? 357 References 385 Index 429

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