Genetics (non-medical) Books

Book SynopsisThe genetic information being unlocked by advances in genomic and high throughput technologies is rapidly revolutionizing our understanding of developmental processes in bovine species. This information is allowing researchers unprecedented insight into the genetic basis of key traits.Trade Review“As the book assumes a degree of prior understanding of the subject, it will be of particular interest to advanced students and researchers but, likewise, can provide a comprehensive overview for all those interested in the history and state of affairs in the understanding of the bovine genome and its application in breeding.” (International Journal of Dairy Technology, 3 August 2013) Table of ContentsList of Contributors Foreword Chapter 1. The Origins of Cattle Matthew D. Teasdale and Daniel G. Bradley Chapter 2. Mendelian Inheritance in Cattle Frank Nicholas Chapter 3. Genetics of Coat Color in Cattle Sheila M. Schmutz Chapter 4. From Quantitative Genetics to Quantitative Genomics: A Personal Odyssey Morris Soller Chapter 5. Cartography of the Bovine Genome James E. Womack Chapter 6. History of Linkage Mapping the Bovine Genome Stephanie D. McKay and Robert D. Schnabel Chapter 7. Bovine X and Y Chromosomes F. Abel Ponce de Le´on and Wansheng Liu Chapter 8. Cattle Comparative Genomics and Chromosomal Evolution Denis M. Larkin Chapter 9. Sequencing the Bovine Genome Kim Worley and Richard Gibbs Chapter 10. Bovine Genome Architecture David L. Adelson Chapter 11. Bovine Epigenetics and Epigenomics Xiuchun (Cindy) Tian Chapter 12. Mapping Quantitative Trait Loci Joel I. Weller Chapter 13. Genome-Wide Association Studies and Linkage Disequilibrium in Cattle M. E. Goddard and B. J. Hayes Chapter 14. Genomic Selection in Beef Cattle Jeremy F. Taylor, Stephanie D. McKay, Megan M. Rolf, Holly R. Ramey, Jared E. Decker, and Robert D. Schnabel Chapter 15. Impact of High-Throughput Genotyping and Sequencing on the Identification of Genes and Variants Underlying Phenotypic Variation in Domestic Cattle Michel Georges Index

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

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Book SynopsisThis book describes cutting-edge molecular technologies to unravel epigenetic changes, the use of in vivo and in vitro models, as well as the potential use of toxicological epigenetics in regulatory environments.Trade Review“Despite some of the issues with the structure, Toxicology and Epigenetics is an important, timely book that provides world-class, expert opinion on a broad range of topics in a fast moving highly relevant branch of toxicology.” (British Toxicology Society, 1 July 2013) Table of ContentsPreface xxi Acknowledgments xxiii List of Contributors xxv 1 Introduction 1 Saura C. Sahu References 2 2 Environment, Epigenetics, and Diseases 5 Robert Y.S. Cheng and Wan-yee Tang 2.1 Perceptions of epigenetics 5 2.2 Environmental epigenetics and human diseases 8 2.3 Implications of environmental epigenetics and future prospects 16 2.4 Key questions to be answered 17 Acknowledgments 17 References 17 3 DNA Methylation and Toxicogenomics 25 Deepti Deobagkar 3.1 Introduction 25 3.2 Toxicology 26 3.3 Toxicogenomics 27 3.4 Epigenetics 29 3.5 DNA methylation 30 3.6 DNA methyltransferases 34 3.7 DNA methylation is alteres upon exposure to chemicals and toxins 35 3.8 Toxicogenomics and epigenetics 40 3.9 Hydroxymethyl cytosine and toxicogenomics 42 3.10 MicroRNAs 42 3.11 DNA methylation in cancer 42 3.12 Bioinformatics approach 44 3.13 Summary 45 Acknowledgments 46 References 46 4 Chromatin at the Intersection of Disease and Therapy 51 Delphine Quénet, Marcin Walkiewicz, and Yamini Dalal 4.1 Epigenetic marks on chromatin: a complex pathway with high flexibility 51 4.2 Epigenetic approaches to treatment of cancer 55 4.3 Epigenetic modifications and potential therapy in other diseases 60 4.4 Conclusion 66 References 66 5 Molecular Epigenetic Changes Caused by Environmental Pollutants 73 Solange S. Lewis, Gregory J. Weber, Jennifer L. Freeman, and Maria S. Sepúlveda 5.1 Introduction 73 5.2 Mechanisms of molecular epigenetic changes 74 5.3 Epigenetic assays 76 5.4 Epigenetic changes induced by organic chemicals 78 5.5 Epigenetic changes induced by metals 90 5.6 Concluding remarks 101 References 102 6 Epigenetic Mediation of Environmental Exposures to Polycyclic Aromatic Hydrocarbons 111 Bekim Sadikovic and David I. Rodenhiser 6.1 Introduction 111 6.2 Epigenetic modifications: DNA methylation 112 6.3 DNA methylation and cancer 113 6.4 Epigenetic histone modifications 114 6.5 Benzo(a)pyrene – a prototype PAH and environmental carcinogen 115 6.6 Molecular mechanisms of benzopyrene carcinogenicity: geno- and epigeno-toxicity 115 6.7 Epigenetic effects of multiple/synergistic carcinogen exposures 120 6.8 Summary and future considerations 122 Acknowledgments 123 References 123 7 Epigenomic Actions of Environmental Arsenicals 129 Paul L. Severson and Bernard W. Futscher 7.1 Introduction 129 7.2 Arsenicals in relation to human health 130 7.3 Arsenical mechanisms of action 131 7.4 Models to study arsenical action 133 7.5 Models used to study epigenetic action 134 7.6 Epigenetic effects of arsenicals 135 7.7 Perspectives 140 References 141 8 Arsenic-Induced Changes to the Epigenome 149 Kathryn A. Bailey and Rebecca C. Fry 8.1 Introduction 149 8.2 Arsenic exposure and DNA methylation 152 8.3 DNA methylation changes associated with arsenic exposure 154 8.4 Histone modifications associated with arsenic exposure 173 8.5 MicroRNA (miRNA) alterations associated with arsenic exposure 180 8.6 Conclusions and future directions 182 Acknowledgments 183 References 183 9 Environmental Epigenetics, Asthma, and Allergy: Our Environment’s Molecular Footprints 191 Stephanie Lovinsky-Desir and Rachel L. Miller 9.1 Introduction 191 9.2 Asthma environmental toxicants associated with epigenetic regulation 193 9.3 Epigenetic changes and asthma phenotype 197 9.4 ‘Pharmacoepigenetics’ 200 9.5 Conclusion 200 References 201 10 miRNAs in Human Prostate Cancer 205 Ernest K. Amankwah and Jong Y. Park 10.1 Introduction 205 10.2 Biogenesis, function, and target of miRNA 206 10.3 miRNA and human cancer 208 10.4 miRNAs as oncogenes and tumor suppressors 209 10.5 Expression profile of miRNA in prostate cancer 210 10.6 miRNA as therapeutic targets for prostate cancer 213 10.7 Conclusion and future directions 213 References 213 11 Environment, Epigenetics, and Cardiovascular Health 219 Sanjukta Ghosh and Andrea Baccarelli 11.1 Introduction 219 11.2 Epidemiological evidence of environmental factors affecting cardiovascular health 220 11.3 Cause and effect relation between environmental exposure and cardiovascular diseases 222 11.4 Cardiovascular epigenetic signatures as risk factors and biomarkers for environmental exposure 232 11.5 Conclusion 233 References 233 12 Toxicology, Epigenetics, and Autoimmunity 241 Craig A. Cooney and Kathleen M. Gilbert 12.1 Introduction 241 12.2 Drugs and toxicants in epigenetics 243 12.3 Metabolic requirements for epigenetics 244 12.4 Autoimmunity and epigenetics 245 12.5 Conclusion 251 References 252 13 Toxicoepigenomics in Lupus 261 Donna Ray and Bruce C. Richardson 13.1 Introduction 261 13.2 Etiology of lupus 262 13.3 Epigenetics and lupus 264 13.4 Environmental contributions to lupus 267 13.5 Summary 270 References 270 14 Ocular Epigenomics: Potential Sites of Environmental Impact in Development and Disease 275 Kenneth P. Mitton 14.1 Introduction 275 14.2 Gene expression in ocular development 277 14.3 Epigenetic regulation in ocular development 280 14.4 DNA-methylation changes in ocular disease 283 14.5 Inherited and age-related diseases of the eye 286 14.6 Pharmacological effects on retinal function 287 14.7 Future research 289 References 289 15 Nuclear RNA Silencing and Related Phenomena in Animals 297 Radek Malik and Petr Svoboda 15.1 Introduction 297 15.2 Conclusion 310 Acknowledgments 310 References 310 16 Epigenetic Biomarkers in Cancer Detection and Diagnosis 317 Ashley G. Rivenbark and William B. Coleman 16.1 DNA methylation 317 16.2 Epigenetics of cancer 319 16.3 Epigenetic biomarkers for cancer diagnostics: DNA methylation 320 16.4 Application of aberrant DNA methylation to cancer diagnostics 323 16.5 Epigenetic biomarkers in breast cancer 323 16.6 Epigenetic biomarkers in prostate cancer 324 16.7 Epigenetic biomarkers in lung cancer 325 16.8 Epigenetic biomarkers in colorectal cancer 326 16.9 Epigenetic biomarkers in liver cancer 328 16.10 Cancer detection and diagnosis 330 References 332 17 Epigenetic Histone Changes in the Toxicologic Mode of Action of Arsenic 339 John F. Reichard and Alvaro Puga 17.1 Introduction 339 17.2 Epigenetics and cancer 340 17.3 Epigenetics effects of arsenic 341 17.4 Conclusions 348 References 350 18 Irreversible Effects of Diethylstilbestrol on Reproductive Organs and a Current Approach for Epigenetic Effects of Endocrine Disrupting Chemicals 357 Shinichi Miyagawa, Ryohei Yatsu, Tamotsu Sudo, Katsuhide Igarashi, Jun Kanno, and Taisen Iguchi 18.1 Introduction 357 18.2 Adverse effects of perinatally-exposed DES on the mouse vagina 358 18.3 MeDIP-ChIP 359 18.4 Future research needs 362 Acknowledgments 363 References 363 19 Epigenomics – Impact for Drug Safety Sciences 365 Harri Lempiäinen, Raphaëlle Luisier, Arne Müller, Philippe Marc, David Heard, Federico Bolognani, Pierre Moulin, Philippe Couttet, Olivier Grenet, Jennifer Marlowe, Jonathan Moggs, and Rémi Terranova 19.1 Introduction – the dynamic epigenome and perturbations in disease 365 19.2 Relevance of epigenetics for toxicology 370 19.3 Towards identifying epigenetic biomarkers of drug-induced toxicity 371 19.4 Challenges of integrating epigenetic analysis into toxicity testing 373 19.5 Practical considerations 374 19.6 Bioinformatics and modeling of epigenomic data 376 19.7 Case study: identification of early mechanism and biomarkers for non-genotoxic carcinogenesis (NGC) 378 19.8 Conclusions 379 Acknowledgments 380 References 380 20 Archival Toxicoepigenetics: Molecular Analysis of Modified DNA from Preserved Tissues in Toxicology Studies 387 B. Alex Merrick 20.1 Introduction 387 20.2 Preservation of tissue: effects on protein and nucleic acids 388 20.3 Extraction of nucleic acids from fixed or embedded tissues 391 20.4 Analysis of methylated DNA for epigenetics 394 20.5 Survey of epigenetic studies using formalin preserved tissues 395 20.6 Prospects for toxicoepigenetics in preserved tissues 401 20.7 Conclusion 402 References 403 21 Nanoparticles and Toxicoepigenomics 409 Manasi P. Jain, Angela O. Choi, and Dusica Maysinger 21.1 Nanoparticles 409 21.2 Particles and the environment 410 21.3 Nanoparticles in soil 412 21.4 Nanoparticles in water 412 21.5 Nanoparticles in air 413 21.6 Nanoparticles in medicine 414 21.7 Nanotoxicology 414 21.8 Nanotoxicology in humans and experimental animals 414 21.9 Complications with nanotoxicological studies 416 21.10 Molecular mechanisms of nanoparticle toxicity and cellular defense mechanisms 417 21.11 Molecular mechanisms of nanoparticle-induced cytotoxicity 418 21.12 Nano-epigenomcs and epigenetics 419 21.13 Conclusion 421 References 422 22 Methods of Global Epigenomic Profiling 427 Michael W.Y. Chan, Zhengang Peng, Jennifer Chao Weber, Ying-Wei Li, Matthew T. Zuzolo, and Huey-Jen L. Lin 22.1 Introduction 427 22.2 DNA methylation 428 22.3 Histone modifications and chromatin remodeling 435 22.4 Noncoding RNA 439 22.5 Summary and discussion 440 Acknowledgments 440 References 440 23 Transcriptomics: Applications in Epigenetic Toxicology 445 Pius Joseph 23.1 Introduction 445 23.2 Microarray analysis of gene expression profiles 446 23.3 Gene expression studies – challenges 453 23.4 Conclusions 456 Acknowledgments 456 Disclaimer 457 References 457 24 Carcinogenic Metals Alter Histone Tail Modifications 459 Yana Chervona and Max Costa 24.1 Introduction 459 24.2 Epigenetics and histone tail modifications 460 24.3 Arsenic 462 24.4 Nickel 463 24.5 Hexavalent chromium (Cr [VI]) 466 24.6 Cadmium 468 24.7 Summary 470 References 470 25 Prediction of Epigenetic and Stochastic Gene Expression Profiles of Late Effects after Radiation Exposure 475 Yoko Hirabayashi and Tohru Inoue 25.1 Introduction – pathological profiling (diagnostic endpoint) and toxicological profiling (probabilistic endpoint) 475 25.2 Radiation exposure and dosimetric quantum biology 477 25.3 Common gene expression profiles after subacute and prolonged effects after radiation exposure 478 25.4 Stochastic expression gene profiles after radiation exposure 483 25.5 Conclusions 492 Appendix A 494 Appendix B 495 Appendix C 496 References 509 26 Modulation of Developmentally Regulated Gene Expression Programs through Targeting of Polycomb and Trithorax Group Proteins 511 Marjorie Brand and F.J. Dilworth 26.1 Introduction 511 26.2 Polycomb group (PcG) proteins 512 26.3 Trithorax group genes 516 26.4 Model for the transcriptional regulation of developmentally regulated genes by PcG and TrxG 526 26.5 PcG and TrxG proteins in disease 527 26.6 Targeting PcG and TrxG proteins in disease 528 References 529 27 Chromatin Insulators and Epigenetic Inheritance in Health and Disease 539 Jingping Yang and Victor G. Corces 27.1 Introduction 539 27.2 Structure and organization of insulators 540 27.3 Insulators and chromatin architecture 543 27.4 Regulation of insulator function 552 27.5 Insulators and the external/internal cellular environment 555 27.6 Insulators and disease 557 27.7 Concluding remarks 560 Acknowledgments 561 References 561 28 Bioinformatics for High-Throughput Toxico-Epigenomics Studies 569 Maureen A. Sartor, Dana C. Dolinoy, Laura S. Rozek, and Gilbert S. Omenn 28.1 Introduction 569 28.2 Evaluating environmental influences on the epigenome 570 28.3 Establishment of the field of environmental epigenomics 570 28.4 An evolutionary perspective: the case of genomic imprinting 571 28.5 Transitioning from epigenetics to epigenomics and related bioinformatics 572 28.6 Observational studies in epigenomics 576 28.7 Integrative analyses with epigenomics data 577 28.8 Gene set enrichment and concept tools for pathway analyses 578 28.9 Databases and resources 580 28.10 Illustrative applications from environmental exposures/perturbations 581 28.11 University of Michigan NIEHS center approach to Lifestage Exposures and Adult Disease (LEAD) 583 28.12 Future directions 584 Acknowledgments 584 References 584 29 Computational Methods in Toxicoepigenomics 589 Joo Chuan Tong 29.1 Introduction 589 29.2 Data sources 589 29.3 Computational tools 591 29.4 Conclusion 592 References 592 30 Databases and Tools for Computational Epigenomics 595 V. Umashankar and S. Gurunathan 30.1 Introduction 595 30.2 Epigenetics and computational epigenetics 596 30.3 Epigenomics and computational epigenomics 596 30.4 Human epigenome project (HEP) 596 30.5 Epigenome prediction mechanism 597 30.6 Epigenomics databases 599 30.7 Tools employed in computational epigenomics 606 30.8 Sophisticated algorithms 611 30.9 Conclusion 612 References 613 Website references 613 31 Interface of Epigenetics and Carcinogenic Risk Assessment 615 Paul Nioi 31.1 Introduction 615 31.2 Key epigenetic changes implicated in carcinogenesis 616 31.3 DNA methylation changes in chemical carcinogenesis 617 31.4 Methods of detecting alterations in the genomic methylome 623 31.5 Conclusions 624 References 627 32 Epigenetic Modifications in Chemical Carcinogenesis 631 Igor P. Pogribny, Igor Koturbash, and Frederick A. Beland 32.1 Introduction 631 32.2 Epigenetic alterations in cancer cells 632 32.3 Role of epigenetic alterations in chemical carcinogenesis 634 32.4 Future perspectives: epigenetic alterations and cancer risk assessment 638 References 638 33 Application of Cancer Toxicoepigenomics in Identifying High-Risk Populations 645 Mukesh Verma and Krishna K. Banaudha 33.1 Introduction: epigenetic mechanisms and cancer 645 33.2 Toxicity and cancer epigenetics 646 33.3 Advantages of using a cohort consortia approach to studying toxicoepigenomics in cancer 649 33.4 Data integration 650 33.5 Challenges and future directions 650 References 651 Author Index 653 Subject Index 655

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Book SynopsisCommonly used by researchers to develop technologies for modifying and studying genetic process, RNA interference (RNAi) has many potential uses in medicine, biotechnology, and functional genomics.Table of ContentsPreface xvii Contributors xix About the Editors xxiii Part 1 Introduction and Basics of RNAi 1 1 Mechanisms and Barriers to RNAi Delivery 3 Jiehua Zhou and John J. Rossi 1.1 Introduction 3 1.2 Barriers to Systemic RNAi Delivery 5 1.3 Rational Design to Improve RNAi Efficacy 6 1.4 Chemical Modifications to Enhance siRNA Stability and Reduce Immune Response 7 1.5 Cellular Uptake and Intracellular Release of siRNA 7 1.6 Combinatorial Targeting for Targeted RNAi Delivery 8 1.7 Cell-Specific Aptamer-Functionalized Nanocarriers for RNAi Delivery 9 1.8 The Clinical Development and Challenges of siRNAs Therapeutics 10 1.9 Conclusion and Perspectives 12 References 12 2 Analysis of siRNA Delivery Using Various Methodologies 19 Yi Pei 2.1 Introduction 19 2.2 Checkpoints for Analyzing siRNA Delivery 20 2.3 Methods for Analysis of siRNA 26 2.4 Case Study for siRNA Delivery Analysis 38 References 39 3 Challenges and Opportunities in Bringing RNAi Technologies from Bench to Bed 45 Sandesh Subramanya and Lance Ford 3.1 Introduction 45 3.2 RNAi Mediator (siRNA or shRNA) 45 3.3 Safety Issues of RNAi Mediators 50 3.4 Efficacy of RNAi Mediators 52 3.5 RNAi Mediators in Clinical Trials 53 3.6 Conclusion 54 References 55 Nonclinical Safety Assessments and Clinical Pharmacokinetics for Oligonucleotide Therapeutics: A Regulatory Perspective 63 Shwu-Luan Lee, Paul Brown, Jian Wang and Robert T. Dorsam 4.1 Introduction 63 4.2 Unique Properties of Oligonucleotide-based Therapeutics 63 4.3 Regulation of Oligonucleotide-Based Therapeutics 65 4.4 Conclusion 79 Disclaimer 79 Appendix 79 References 80 Role of Promoters and MicroRNA Backbone for Efficient Gene Silencing 83 Feng Li and Ram I. Mahato 5.1 Introduction 83 5.2 Promoters for shRNA Expression 84 5.3 miRNA-based shRNAs 96 5.4 Concluding Remarks 100 References 101 Part 2 RNAi Delivery Strategies 109 6 Bioconjugation of siRNA for Site-specific Delivery 111 Bin Qin, Wei Jin and Kun Cheng 6.1 Introduction 111 6.2 Conjugation Strategy 112 6.3 Bioconjugates for Site-specific Delivery 120 6.4 Conclusion 129 References 129 7 Multifunctional RNAi Delivery Systems 137 China Malakondaiah Kummitha, Anthony S. Malamas and Zheng-Rong Lu 7.1 Introduction 137 7.1.1 Chapter Objectives 139 7.2 Lipid-Based Delivery Systems 139 7.3 Polymeric Multifunctional siRNA Delivery Systems 150 7.4 Conclusion 157 References 157 8 Dendrimers in RNAi Delivery 163 Jose Luis Jimenez Fuentes, Paula Ortega, Sara Ferrando-Martýnez, Rafael Gomez, Manuel Leal, Javier de la Mata and MaAngeles Munoz-Fernandez 8.1 Introduction 163 8.2 Challenges in RNAi Delivery 164 8.3 Dendrimers as Non Viral Vectors 166 9 Development of Pharmaceutically Adapted Mesoporous Silica Nanoparticles for siRNA Delivery 187 Wilson X. Mai, Tian Xia and Huan Meng 9.1 Introduction 187 9.2 Mesoporous Silica Nanoparticles as Novel Inorganic Nanocarriers for siRNA Delivery 188 9.3 Safety Assessment of Nanocarrier and Design of Safe MSNP Carrier 199 References 179 9.4 Summary References 202 10 Environmentally-Responsive Nanogels for siRNA Delivery 207 Atsushi Tamura and Yukio Nagasaki 10.1 Introduction 207 10.2 Reductive Environment-Responsive Disulfide Crosslinked Nanogels 209 10.3 Temperature-Responsive Nanogels 211 10.4 pH-Responsive Nanogels 212 10.5 PEGylated and Partially Quaternized Polyamine Nanogels 216 10.6 Conclusions 220 References 220 11 Viral-Mediated Delivery of shRNA and miRNA 225 Fredric P. Manfredsson 11.1 Introduction 225 11.2 RNAi – A Brief Overview 226 11.3 shRNA or miRNA? 226 11.4 Rational Design 227 11.5 Viral Vectors 227 11.6 Tissue-specific Transduction 233 11.7 Applications of Virally Expressed shRNAs 241 11.8 Viral Gene Therapy in the Clinic 241 11.9 Conclusion 242 References 242 12 The Control of RNA Interference with Light 255 Simon H. Friedman 12.1 Introduction 255 12.2 The Importance of Gene Expression 255 12.3 Light Control of Gene Expression 257 12.4 Why Use RNA Interference as a Basis for Light Control of Gene Expression? 258 12.5 Light Activated RNA Interference (LARI), the work of Friedman and Co-Workers 259 12.6 Work of McMaster and Co-Workers, 50 Antisense Phosphate Block 262 12.7 Work of Heckel and Co-Workers, Nucleobase Block 263 12.8 Use of 20 FsiRNA, work of Monroe and Co-Workers 264 12.9 Photochemical Internalization 265 12.10 Future Directions and Conclusions 266 Acknowledgments 267 References 267 Part 3 Applications of RNAi in Various Diseases 269 13 RNAi in Cancer Therapy 271 Cristian Rodriguez-Aguayo, Arturo Chavez-Reyes, Gabriel Lopez-Berestein and Anil K. Sood 13.1 Introduction 271 13.2 Therapeutic Opportunities for Noncoding RNAs 274 13.3 RNAs as Drugs 277 13.4 Overcoming Anatomical and Physiologic Barriers 278 13.5 Advanced Delivery 283 13.6 Clinical Experience 294 13.7 The Next Steps 298 Acknowledgments 298 References 298 14 Adenovirus-mediated siRNA Delivery to Cancer 309 Chae-Ok Yun 14.1 Introduction 309 14.2 shRNA-expressing Adenoviruses: Cancer Biological Studies and Therapeutic Implications 312 14.3 Exploiting Oncolytic Adenovirus for siRNA Expression 315 14.4 Current Limitations of Adenovirus-mediated siRNA Therapy and Future Directions: Smart Adenovirus Nanocomplexes Expressing siRNA for Systemic Administration 318 14.5 Conclusion 320 References 321 15 RNAi in Liver Diseases 327 Jiang Li, Jianqin Lu, Yifei Zhang, Mohammed Ghazwani, Peng Zhang, Xiang Gao and Song Li 15.1 Introduction 327 15.2 RNAi in Viral Hepatitis 327 15.3 RNAi in Hepatocellular Carcinoma 336 15.4 RNAi in Liver Fibrosis 340 15.5 Delivery Systems in RNAi 345 15.6 Conclusion 352 Acknowledgments 353 References 353 16 Approaches to Delivering RNAi Therapeutics that Target Hepatitis B Virus 367 Carol Crowther, Mohube Betty Mowa, Abdullah Ely and Patrick Arbuthnot 16.1 Introduction 367 16.2 Vectors Suitable for Hepatic Delivery of HBV Gene Silencers 369 16.3 Conclusions 381 Acknowledgments 382 References 382 17 RNAi in Respiratory Diseases 391 Ciara Kelly, Awadh B. Yadav, Paul J. McKiernan, Catherine M. Greene and Sally-Ann Cryan 17.1 Introduction 391 17.2 Respiratory Disease and RNA Interference 392 17.3 Delivery and Development of RNAi Therapies for Respiratory Disease 397 17.4 Conclusions 408 Acknowledgements 408 References 408 18 RNAi in Ocular Diseases 417 Andrey Turchinovich, Georg Zoidl and Rolf Dermietzel 18.1 Introduction 417 18.2 The Principle of RNAi 418 18.3 In vivo Delivery of siRNA 419 18.4 Delivery of siRNA into the Eye 420 18.5 Conclusions 431 Abbreviations 432 References 432 19 micro RNAs as Therapeutic Agents and Targets 439 D.S. Karolina and K. Jeyaseelan 19.1 Introduction 439 19.2 miRNA Therapeutics 440 19.3 MicroRNAs and Cancer 447 19.4 MicroRNAs in Stroke 450 19.5 MicroRNAs in Heart Diseases 452 19.6 MicroRNAs in Diabetes Mellitus 454 19.7 MicroRNAs in Liver Diseases 457 19.8 MicroRNAs and Ocular Diseases 461 19.9 MicroRNAs and Respiratory Diseases 462 19.10 MicroRNAs and Stem Cell Research 465 19.11 Conclusion 468 References 469 20 Delivery of Micro RNA Sponges for Interrogation of MicroRNA Function In Vitro and In Vivo 483 Jiakai Lin and Shu Wang 20.1 MicroRNA Loss-of-Function Studies 483 20.2 Considerations in MicroRNA Sponge Design 486 20.3 Advantages and Limitations of MicroRNA Sponge over Other MicroRNA Loss-of-Function Strategies 489 20.4 Interrogating MicroRNA Function via Transient MicroRNA Sponge Expression 493 20.5 Interrogating MicroRNA Function via Stable MicroRNA Sponge Expression 494 20.6 Utility of MicroRNA Sponge in Living Organisms 496 20.7 Future Perspectives 498 References 499 Index 505

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Book SynopsisPlant Genes, Genomes and Genetics provides a comprehensive treatment of all aspects of plant gene expression. Unique in explaining the subject from a plant perspective, it highlights the importance of key processes, many first discovered in plants, that impact how plants develop and interact with the environment.Table of ContentsAcknowledgements xi Introduction xiii About the Companion Website xix PART I: PLANT GENOMES AND GENES Chapter 1 Plant genetic material 3 1.1 DNA is the genetic material of all living organisms, including plants 3 1.2 The plant cell contains three independent genomes 8 1.3 A gene is a complete set of instructions for building an RNA molecule 10 1.4 Genes include coding sequences and regulatory sequences 11 1.5 Nuclear genome size in plants is variable but the numbers of protein-coding, non-transposable element genes are roughly the same 12 1.6 Genomic DNA is packaged in chromosomes 15 1.7 Summary 15 1.8 Problems 15 References 16 Chapter 2 The shifting genomic landscape 17 2.1 The genomes of individual plants can differ in many ways 17 2.2 Differences in sequences between plants provide clues about gene function 20 2.3 SNPs and lengthmutations in simple sequence repeats are useful tools for genome mapping and marker assisted selection 22 2.4 Genome size and chromosome number are variable 28 2.5 Segments of DNA are often duplicated and can recombine 30 2.6 Some genes are copied nearby in the genome 31 2.7 Whole genome duplications are common in plants 34 2.8 Whole genome duplication has many effects on the genome and on gene function 37 2.9 Summary 41 2.10 Problems 42 Further reading 42 References 42 Chapter 3 Transposable elements 45 3.1 Transposable elements are common in genomes of all organisms 45 3.2 Retrotransposons are mainly responsible for increases in genome size 46 3.3 DNA transposons create small mutations when they insert and excise 52 3.4 Transposable elements move genes and change their regulation 57 3.5 How are transposable elements controlled? 60 3.6 Summary 60 3.7 Problems 61 References 61 Chapter 4 Chromatin, centromeres and telomeres 63 4.1 Chromosomes are made up of chromatin, a complex of DNA and protein 63 4.2 Telomeres make up the ends of chromosomes 67 4.3 The chromosome middles–centromeres 71 4.4 Summary 77 4.5 Problems 77 Further reading 77 References 77 Chapter 5 Genomes of organelles 79 5.1 Plastids and mitochondria are descendants of free-living bacteria 79 5.2 Organellar genes have been transferred to the nuclear genome 80 5.3 Organellar genes sometimes include introns 82 5.4 Organellar mRNA is often edited 82 5.5 Mitochondrial genomes contain fewer genes than chloroplasts 84 5.6 Plant mitochondrial genomes are large and undergo frequent recombination 87 5.7 All plastid genomes in a cell are identical 91 5.8 Plastid genomes are similar among land plants but contain some structural rearrangements 93 5.9 Summary 95 5.10 Problems 95 Further reading 95 References 95 PART II: TRANSCRIBING PLANT GENES Chapter 6 RNA 99 6.1 RNA links components of the Central Dogma 99 6.2 Structure provides RNA with unique properties 102 6.3 RNA has multiple regulatory activities 105 6.4 Summary 108 6.5 Problems 108 References 109 Chapter 7 The plant RNA polymerases 111 7.1 Transcription makes RNA from DNA 111 7.2 Varying numbers of RNA polymerases in the different kingdoms 112 7.3 RNA polymerase I transcribes rRNAs 114 7.4 RNA polymerase III recruitment to upstream and internal promoters 116 7.5 Plant-specific RNP-IV and RNP-V participate in transcriptional gene silencing 117 7.6 Organelles have their own set of RNA polymerases 117 7.7 Summary 118 7.8 Problems 118 References 118 Chapter 8 Making mRNAs – Control of transcription by RNA polymerase II 121 8.1 RNA polymerase II transcribes protein-coding genes 121 8.2 The structure of RNA polymerase II reveals how it functions 121 8.3 The core promoter 123 8.4 Initiation of transcription 125 8.5 The mediator complex 127 8.6 Transcription elongation: the role of RNP-II phosphorylation 128 8.7 RNP-II pausing and termination 129 8.8 Transcription re-initiation 130 8.9 Summary 130 8.10 Problems 130 References 130 Chapter 9 Transcription factors interpret cis-regulatory information 133 9.1 Information on when, where and how much a gene is expressed is codified by the gene’s regulatory regions 133 9.2 Identifying regulatory regions requires the use of reporter genes 134 9.3 Gene regulatory regions have a modular structure 135 9.4 Enhancers: Cis-regulatory elements or modules that function at a distance 137 9.5 Transcription factors interpret the gene regulatory code 138 9.6 Transcription factors can be classified in families 138 9.7 How transcription factors bind DNA 139 9.8 Modular structure of transcription factors 143 9.9 Organization of transcription factors into gene regulatory grids and networks 146 9.10 Summary 146 9.11 Problems 146 More challenging problems 147 References 147 Chapter 10 Control of transcription factor activity 149 10.1 Transcription factor phosphorylation 149 10.2 Protein–protein interactions 151 10.3 Preventing transcription factors from access to the nucleus 155 10.4 Movement of transcription factors between cells 156 10.5 Summary 158 10.6 Problems 158 References 158 Chapter 11 Small RNAs 161 11.1 The phenomenon of cosuppression or gene silencing 161 11.2 Discovery of small RNAs 162 11.3 Pathways for miRNA formation and function 163 11.4 Plant siRNAs originate from different types of double-stranded RNAs 166 11.5 Intercellular and systemic movement of small RNAs 168 11.6 Role of miRNAs in plant physiology and development 170 11.7 Summary 171 11.8 Problems 171 References 172 Chapter 12 Chromatin and gene expression 173 12.1 Packing long DNA molecules in a small space: the function of chromatin 173 12.2 Heterochromatin and euchromatin 173 12.3 Histone modifications 174 12.4 Histone modifications affect gene expression 175 12.5 Introducing and removing histone marks: writers and erasers 175 12.6 ‘Readers’ recognize histone modifications 177 12.7 Nucleosome positioning 177 12.8 DNA methylation 178 12.9 RNA-directed DNA methylation 179 12.10 Control of flowering by histone modifications 180 12.11 Summary 181 12.12 Problems 181 References 181 PART III: FROM RNA TO PROTEINS Chapter 13 RNA processing and transport 185 13.1 RNA processing can be thought of as steps 185 13.2 RNA capping provides a distinctive 5’ end to mRNAs 185 13.3 Transcription termination consists of mRNA 3’-end formation and polyadenylation 189 13.4 RNA splicing is another major source of genetic variation 192 13.5 Export of mRNA from the nucleus is a gateway for regulating which mRNAs actually get translated 194 13.6 Summary 196 13.7 Problems 196 References 196 Chapter 14 Fate of RNA 199 14.1 Regulation of RNA continues upon export from nucleus 199 14.2 Mechanisms for RNA turnover 199 14.3 RNA surveillance mechanisms 201 14.4 RNA sorting 202 14.5 RNA movement 203 14.6 Summary 204 14.7 Problems 204 Further reading 205 References 205 Chapter 15 Translation of RNA 207 15.1 Translation: a key aspect of gene expression 207 15.2 Initiation 209 15.3 Elongation 209 15.4 Termination 210 15.5 Tools for studying the regulation of translation 211 15.6 Specific translational control mechanisms 211 15.7 Summary 213 15.8 Problems 214 Further reading 214 References 214 Chapter 16 Protein folding and transport 215 16.1 The pathway to a protein’s function is a complicated matter 215 16.2 Protein folding and assembly 215 16.3 Protein targeting 218 16.4 Co-translational targeting 218 16.5 Post-translational targeting 219 16.6 Post-translational modifications regulating function 220 16.7 Summary 222 16.8 Problems 223 Further reading 223 References 224 Chapter 17 Protein degradation 225 17.1 Two sides of gene expression–synthesis and degradation 225 17.2 Autophagy, senescence and programmed cell death 225 17.3 Protein-tagging mechanisms 226 17.4 The ubiquitin proteasome system rivals gene transcription 228 17.5 Summary 231 17.6 Problems 231 Further reading 231 Reference 231 Index 233

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Book SynopsisInside the quest to unlock the mysteries of development—and how this knowledge can transform our future

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Book SynopsisFrom a witty new voice in popular science comes a life-changing look at what makes you you. Trade Review“I would have read this book on the information about coffee alone, but I’m going to really love explaining to people why it’s not my fault I don’t like bacon and my love of hot sauce is actually my way of thrill seeking. So, go grab this book if you want to learn some amazing things while being thoroughly amused.” –Amy’s Book-et List “There are so many interesting tidbits that you could use as cocktail party conversation- the study of nursery schoolers personality traits that predicts political affiliation 20 years later, acetaminophen has been shown to decrease empathy, birds are better at multitasking than people...(Why do smokers drink a lot of coffee?)” –Bookchickdi “Just know that the writing is top notch and the content will keep you interested long after you put the book down. Its funny, interesting, and unforgettable - what more could you want, right? I know I loved it.” –A Bookish Way of LIfe “There is so much to unpack in this book. First, I need to mention that it’s written with a lot of humor to make it more readable, especially the first half or so. Second, any book that tells of the Kenny Rogers Seinfeld episode has already won me over. “ –Stacy’s Books “Sullivan delivers the science behind these concepts with humor and approachability.” –JulzReads “I laughed out loud more than once as the author described gene therapy “as easy as a Matchbox Twenty guitar solo…” and comparing religion to duct tape “despite the monumental discoveries driven by science, some people still really love the duct tape.” --Orange County Readers “This is accessible genetics the way you wish your high school biology teacher would have taught things and is filled with pop-culture references and engaging language that will appeal to science buffs and curious minds alike.” –Stephanie’s Book Reviews “Pleased to Meet Me…may very possibly give you a case of the goosebumps as you have one epiphany after another as Sullivan teaches us to take a long hard look at all the things that miraculously came together to make us truly unique. Whether you’re interested in science or simply the human condition, this should be mandatory reading.” –Jathan & Heather “Honestly, this book is sort of mind-blowing. I feel like I have a whole new grasp on a lot of concepts that I had never even thought of before. I’m really just hoping this helps me with a pub quiz soon.” –The Desert Bibliophile “There are constant gems of information that are either fascinating all on their own or feel highly applicable to day-to-day life.” –Sara Ames-Foley “It’s a quick read that I was able to step away from feeling quite a bit smarter than when I started.” –Paul’s Picks “I’ve been thinking of this book often since finishing it, and I think I’ll be returning to it often as well, because there are so many times that the topics it covers arise — whether in the news, conversation, other reading — everywhere, really.” –What’s Nonfiction?“In equal parts approachable and mind-blowing. Sullivan gives us a whistle-stop tour of the myriad factors that make you who you are”—David Eagleman, host of PBS’s The Brain with David Eagleman “From microbes that make you intoxicated to the genetic demons hiding within your DNA, Pleased to Meet Me is a whirlwind journey through human biology. Deftly weaving cutting-edge science with popular culture, this accessible book will leave you wanting more.” —Sharon Moalem, PhD, author of Survival of the Sickest “A rare treat: A book that’s fun to read from cover to cover, while leaving you wiser and better-informed about who you really are.” —Adam Alter, New York Times bestselling author of Drunk Tank Pink and Irresistible “Bill Sullivan is a sympathetic guide who understands your dislike of exercise and most things healthy. This wide-ranging tome puts a new light on human pursuits, including eating, drinking, thinking, sex, free will, even politics and religion, all presented with topical humor and wit.” —Scott Anderson, co-author of The Psychobiotic Revolution “Bill Sullivan artfully reports on how our genes interact with our surroundings to shape our unique personalities and the people we’ve become. A beautiful melding of science and the human experience.” —Peter Hotez, MD, PhD, author of Vaccines Did Not Cause Rachel’s Autism “Pleased to Meet Me is as close to philosophy as science books get. Infused with Sullivan’s witty voice, the book exposes us as the biological machines we really are. You’ll be quoting it to your friends.” —Dr. Alanna Collen, author of 10% Human “Pleased to Meet Me makes you see the world in a new way. We like to think we’re totally in control of how we think and act, but Sullivan makes a strong case that our beloved ‘agency’ is not what we think it is.” —Matthew Simon, Wired science writer and author of Plight of the Living Dead "Filled with surprising facts, witty anecdotes, and engaging explorations of the biological forces that make us who we are, Pleased to Meet Me is a must-read for anyone interested in an intelligent approach to self-discovery. Bill Sullivan translates cutting-edge science into practical insights about the ways that genes, germs, and environment shape our health, happiness, and relationships. This delightful book will change the way you see yourself—and will provide newfound empathy for others." —Ty Tashiro, author of Awkward and The Science of Happily Ever After “A book for everyone with an interest in human behavior, Pleased to Meet Me achieves the rare feat of presenting of scientific information that is also fun to read. Not only will your knowledge be greatly enhanced, but you’re more likely to become more compassionate as well.” —James E. Alcock, PhD, author of Belief

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Book SynopsisWhat makes someone a boy or a girl? Is it external genitalia, chromosomes, DNA, environment, or some combination of these factors? Not even doctors or scientists are entirely clear. What is clear is that sex is not girl/boy or XX/XY, switching between two poles like an on/off switch on a radio.Rather, sex is like the bass and treble knobs on that radio. In this eye-opening exploration of the science of sex, Gerald N. Callahan, PhD, challenges our notion of two opposite sexes. Human sex is more than it appears to be. Using a brief history of sex from the ancient Greeks to the geneticists of the twentieth century, he shows us how our understanding of the sexual development of human beings is constantly evolving.By sharing the extraordinary stories of people living with intersex conditions such as hermaphroditism, Klinefelter syndrome, and androgen insensitivity syndrome, Between XX and XY reveals that the path of sexual development is as varied as humans themselves

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Book SynopsisEn El origen de la vida: lo que todo el mundo necesita saber, David W. Deamer ha escrito una guÍa completa sobre el origen de la vida que estÁ organizada en tres secciones. La primera secciÓn aborda preguntas como: ¿De dÓnde provienen los Átomos de la vida? ¿QuÉ edad tiene la Tierra? ¿CÓmo era la Tierra antes de que comenzara la vida? ¿De dÓnde viene el agua? DespuÉs de que se responde cada pregunta, hay un seguimiento: ¿CÓmo lo sabemos? Esto amplÍa el horizonte del libro, explicando cÓmo los cientÍficos llegan a conclusiones y por quÉ podemos confiar en estas respuestas. La segunda secciÓn describe cÓmo ciertas molÉculas orgÁnicas pueden ensamblarse espontÁneamente en poblaciones de protocÉlulas que pueden someterse a selecciÓn y evolucionar hacia sistemas vivos primitivos. AquÍ Deamer propone un concepto verdaderamente novedoso de que la vida no comenzÓ en el ocÉano sino en fuentes termales de agua dulce en masas de tierra volcÁnica que se asemejan a Hawaii hoy. El verdadero conocimiento no es solo lo que sabemos, sino que es igualmente importante lo que aÚn no sabemos. En la tercera secciÓn, Deamer enumera las preguntas pendientes que deben abordarse antes de que podamos finalmente responder a una pregunta fundamental de la biologÍa: ¿CÓmo puede comenzar la vida? In Origin of Life: What Everyone Needs to Know , David W. Deamer has written a comprehensive guide to the origin of life that is organized in three sections. The first section addresses questions such as: Where do the atoms of life come from? How old is Earth? What was the Earth like before life began? Where does water come from? After each question is answered, there is a follow-up: How do we know? This expands the horizon of the book, explaining how scientists reach conclusions and why we can trust these answers. The second section describes how certain organic molecules can spontaneously assemble into populations of protocells that can undergo selection and evolve toward primitive living systems. Here Deamer proposes a truly novel concept that life did not begin in the ocean but instead in fresh water hot springs on volcanic land masses resembling Hawaii today. True knowledge is not just what we know, but equally important is what we don't yet know. In the third section Deamer lists the outstanding questions that must be addressed before we can finally answer a fundamental question of biology: How can life begin?

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