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Book SynopsisAn authoritative review of the latest developments in the chemical biology of enzymes In the first decade of the twenty-first century, enzymes and their multiple applications have played a critical role in the discovery and development of many new therapeutic agents.This book is a coordinated compilation of research expertise and current opinion uniquely focused on enzymes and their properties and applications. Compiled by editors with a combined pharmaceutical experience of over sixty years, the text provides in-depth reviews of recent developments in selective topics on biosynthesis, biocatalysis, and chemical biology of enzymes as it applies to drug discovery, development, and manufacture. The first in a multi-part series on enzymes, this volume features three sections: New Approaches to Find and Modify Enzymes describes the emerging field of metagenomics, presents the practical applications of directed evolution to enzymes and pathways, andTrade Review"This book is a coordinated compilation of research expertise and current opinion uniquely focused on enzymes and their properties and applications." (Book Circle, 1 September 2011) "It provides a good starting point and gives all the necessary information to go from the overview of one of the fields described into the details of the broad list of original literature cited." (ChemBioChem, 11 February 2011) Table of ContentsContributors. Preface. PART A NEW APPROACHES TO FINDING AND MODIFYING ENZYMES. 1 Functional Metagenomics as a Technique for the Discovery of Novel Enzymes and Natural Products (Luke A. Moe, Matthew D. McMahon, and Michael G. Thomas). 2 Directed Enzyme and Pathway Evolution (Jacob Vick and Claudia Schmidt-Dannert). 3 Combining Natural Biodiversity and Molecular-Directed Evolution to Develop New Industrial Biocatalysts and Drugs (Laurent Fourage, Celine Ayrinhac, Johann Brot, Christophe Ullmann, Denis Wahler, and Jean-Marie Sonet). 4 Principles of Enzyme Optimization for the Rapid Creation of Industrial Biocatalysts (Richard J. Fox and Lori Giver). PART B BIOCATALYTIC APPLICATIONS. 5 Enzyme Catalysis in the Synthesis of Active Pharmaceutical Ingredients (Animesh Goswami). 6 Enzymatic Processes for the Production of Pharmaceutical Intermediates (David Rozzell and Jim Lalonde). 7 Novel Developments Employing Redox Enzymes: Old Enzymes in New Clothes (Kurt Faber, Silvia M. Glueck, Birgit Seisser, and Wolfgang Kroutil). PART C BIOSYNTHETIC APPLICATIONS. 8 Drug Discovery and Development by Combinatorial Biosynthesis (Matthew A. DeSieno, Carl A. Denard, and Huimin Zhao). 9 Reprogramming Daptomycin and A54145 Biosynthesis to Produce Novel Lipopeptide Antibiotics (Richard H. Baltz, Kien T. Nguyen, and Dylan C. Alexander). 10 Pathway and Enzyme Engineering and Applications for Glycodiversification (Lishan Zhao and Hung-wen Liu). Index.

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Book SynopsisHighlighting the critical importance of enzymes in pharmaceutical and biotechnology research, Enzyme Technologies presents thorough discussions on chemical biology of enzymes, redesigning binding and catalytic specificities of enzymes, and applications of enzymes to biotechnology research in the post-genomic era.Trade Review“The book serves as a valuable desk reference volume and describes well the key concepts of the standard and emerging enzyme technologies that together constitute some of the fundamental principles and knowledge on which drug discovery research is based.” (ChemMedChem, 1 August 2015)Table of ContentsContributors vii Preface ix Part A _Enzymes – essential workhorses in pharmaceutical research 1 1 Assay Technologies for Proteases 3 Anuradha Roy, Gerald H. Lushington, James McGee, and Rathnam Chaguturu 2 Discovery and Development of Isozyme-Selective Inhibitors Involved in Lipid Metabolism 55 Taichi Ohshiro and Hiroshi Tomoda 3 Covalent Enzyme Inhibition in Drug Discovery and Development 81 Shujaath Mehdi 4 Preclinomics: Enzyme Assays and Rodent Models for Metabolic diseases 131 Wu-Kuang Yeh and Richard G. Peterson Part B _Enzymes – indispensable tools for improving druggability 163 5 Enzymes and Targeted Activation of Prodrugs 165 Yanhui Yang, Yu Chen, Herve Aloysius, Daigo Inoyama, and Longqin Hu 6 Evolution of an Orally Active Prodrug of Gemcitabine 237 James R. McCarthy 7 Enzymatically Activated Phosphate and Phosphonate Prodrugs 253 Ivan S. Krylov and Charles E. McKenna Part C E nzymes – powerful weapons for correcting Nature’s errors 301 8 Treatment Options for Mucopolysaccharidosis Type II (Hunter’s Syndrome) 303 Michael Beck 9 Enzyme Replacement Therapy for Fabry Disease 321 Ley Nadine Lacbawan, Wei Zheng, and Ozlem Goker-Alpan 10 Methods and Principles of Pancreatic Function Tests 335 Henrike von Schassen, Jutta Keller, and Peter Layer Index 341

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Book SynopsisPharmaceutical and Biomedical Portfolio Management in a Changing Global Environment explores some of the critical forces at work today in the complex endeavour of pharmaceutical and medical product development. Written by experienced professionals, and including real-world approaches and best practice examples, this new title addresses three key areas small molecules, large molecules, and medical devices - and provides hard-to-find, consolidated information relevant to and needed by pharmaceutical, biotech, and medical device company managers.Table of ContentsFOREWORD. PREFACE. ACKNOWLEDGEMENTS. CONTRIBUTORS. ABBREVIATIONS. PART I: OVERVIEW. 1: Project Leadership for Biomedical Industries (Scott D. Babler). PART II: MANAGING MEDICAL AND PHARMACEUTICAL PROJECTS. 2: Medical Devices – Components, Systems, and their Integration (Dennis F. Marr). 3: The Role of Project Management in the Development of In Vitro Diagnostics (David Kern and Diane M. Ward). 4: Drug Development Project Management (Dirk L. Raemdonck and Bradford A. Burns). PART III: EFFECT OF BUSINESS RELATIONSHIPS ON MANAGING LARGE PROJECTS. 5: Outsourcing of Project Activities (Jonathan D. Lee and Trisha Dobson). 6: The Unique Aspects of Alliance Projects (Andrew S. Eibling). Case Study: Management of Outsourcing for Biomedical Companies (Jeffery W. Frazier, Jennifer A. Hewitt and Andy Myslicki). 7: A Roadmap for Successful Technology Transfers (Nipun Davar, Sangita Ghosh, Nandan Oza). 8: Challenges for the Team Leader of Multifunctional Product Teams in an International Environment (Hartwig Hennekes). 9: Lessons Learned from Inter-Organizational Collaboration Projects (Andrea Jahn). Case Study: Project Management in Non-Profit Drug Development (Autumn Ehnow). PART IV: MANAGING UNIQUE PROJECT COMPLEXITIES. 10: Clinical Trials and Project Management (Scott E. Smith, Carol A. Connell and Dirk L. Raemdonck). 11: Role of Project Management in Quality Planning and Functions Throughout the Product Lifecycle (Thomas Dzierozynski and Ian Fleming). 12: Regulatory Strategies and Submissions in an International Product Environment (Louise Johnson). 13: Risk Management - A Practical Approach (Courtland R. LaVallee). PART V: PORTFOLIO MANAGEMENT AND RESOURCE PLANNING. 14: Managing Successful Product Portfolio Creation and R&D Pipelines (Sue E. Steven). 15: Effective Strategies for Project Resource Planning and Utilization (Eduardo Rojas and Scott D. Babler). 16: Stage Gate Product Development Processes and Lifecycle Management (Karen E. Coulson). PART VI: TRENDS IN BMI PROJECT MANAGEMENT. 17: The Future of Medical Devices (Ronald L. Kirschner). 18: The Next Wave of Managing Biomedical Projects (Scott D. Babler). INDEX.

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Book Synopsis* Covering a wide range of receptors and molecular targets, this book provides a comprehensive resource for neuro-drug discovery and molecular targets for schizophrenia.Trade Review“In summary, this book provides a timely and convenient reflection on schizophrenia drug discovery and development, which has been a major component of psychiatric drug research for several decades.” (ChemMedChem, 1 March 2013) Table of ContentsPreface vii Contributors xi Introduction 1 Alan J. Cross 1 Dopaminergic Hypothesis of Schizophrenia: A Historical Perspective 5 Aurelija Jucaite and Svante Nyberg 2 Dopamine D2/D3 Partial Agonists as Antipsychotics 37 Philip G. Strange 3 D1/D5 Dopamine Agonists as Pharmacotherapy for Schizophrenia 51 Kevin N. Boyd and Richard B. Mailman 4 Phosphodiesterase Inhibitors as a Novel Therapeutic Approach for Schizophrenia 85 Judith A. Siuciak and William J. Pitts 5 Glutamatergic Synaptic Dysregulation in Schizophrenia 115 Joseph T. Coyle, Alo Basu, and Michael Benneyworth 6 Metabotropic Glutamate 2/3 Receptor Agonists and Positive Allosteric Modulators of Metabotropic Glutamate Receptor 2 as Novel Agents for the Treatment of Schizophrenia 143 Gerard J. Marek, Bruce J. Kinon, David L. McKinzie, Jeffrey M. Schkeryantz, and James A. Monn 7 AMPA Receptor Positive Modulators 187 John A. Morrow, John K.F. Maclean, and Craig Jamieson 8 Progress in the Exploration and Development of GlyT1 Inhibitors for Schizophrenia 233 Jeffrey S. Albert and Michael W. Wood 9 Combined Dopamine D2 and 5-Hydroxytryptamine (5-HT)1A Receptor Strategies for the Treatment of Schizophrenia: A Pharmacological and Chemical Perspective 255 Andrew C. McCreary, Roelof W. Feenstra, and Caitlin A. Jones 10 5-HT2C and 5-HT6 Receptor Targeted Emerging Approaches in Schizophrenia 273 Sharon Rosenzweig-Lipson, John Dunlop, Lee E. Schechter, Thomas A. Comery, Jonathan Gross, and Karen L. Marquis 11 The Cholinergic Hypothesis: An Introduction to the Hypothesis and a Short History 295 Joseph I. Friedman, Isabella Kanellopoulou, and Vladan Novakovic 12 α7 Nicotinic Acetylcholine Receptors in the Treatment of Schizophrenia 319 Mihály Hajós and Bruce N. Rogers 13 Muscarinic Acetylcholine Receptors as Novel Targets for the Development of Therapeutics for Schizophrenia 355 Christian C. Felder, David L. McKinzie, Richard C. Thompson, and Bin Liu 14 Will Modulation of Neuropeptide Receptors Produce the Next Generation of Antipsychotic Drugs? A Focus on the Neurokinin and Neurotensin Systems 381 Lee A. Dawson, Paul W. Smith, and Jeannette M. Watson 15 GABA and Schizophrenia 425 John H. Kehne and George D. Maynard Index 469

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Book SynopsisPresents the latest research and applications for a new, promising approach to fighting infectious diseases Enzybiotics is a promising way of fighting bacterial or fungal infectious diseases by using viruses or viral-derived lysins. Drawing from the fields of medicinal chemistry, microbiology, genetics, and biochemistry, this book presents the state of the science in enzybiotics research, fully exploring its emerging therapeutic applications. The book begins with four chapters that review the potential applications, possible advantages, and phylogeny of enzybiotics. Next, the book explores: A new approach to controlling infections using Gram-negative bacteria Bacteriophage holins and their membrane-disrupting activity Anti-staphylococcal lytic enzymes Membrane-targeted enzybiotics Design of phage cocktails for therapy from a host-range point of view Novel methods Table of ContentsPREFACE. CONTRIBUTORS. 1 ENZYBIOTICS AND THEIR POTENTIAL APPLICATIONS IN MEDICINE (Jan Borysowski and Andrzej Górski). 2 ADVANTAGES AND DISADVANTAGES IN THE USE OF ANTIBIOTICS OR PHAGES AS THERAPEUTIC AGENTS (Patricia Veiga-Crespo and Tomas G. Villa). 3 ENZYBIOTICS AS SELECTIVE KILLERS OF TARGET BACTERIA (Juan C. Alonso and Marcelo E. Tolmasky). 4 PHYLOGENY OF ENZYBIOTICS (Patricia Veiga-Crespo and Tomas G. Villa). 5 BACTERIOPHAGE LYSINS: THE ULTIMATE ENZYBIOTIC (Vincent A. Fischetti). 6 BACTERIOPHAGE HOLINS AND THEIR MEMBRANEDISRUPTING ACTIVITY (María Gasset). 7 ANTI-STAPHYLOCOCCAL LYTIC ENZYMES (Jan Borysowski and Andrzej Górski). 8 MEMBRANE-TARGETED ENZYBIOTICS (María Gasset). 9 DESIGN OF PHAGE COCKTAILS FOR THERAPY FROM A HOST RANGE POINT OF VIEW (Lawrence D. Goodridge). 10 IDENTIFYING PHAGE LYTIC ENZYMES: PAST, PRESENT, AND FUTURE (Jonathan E. Schmitz, Raymond Schuch, and Vincent A. Fischetti). 11 USE OF GENETICALLY MODIFIED PHAGES TO DELIVER SUICIDAL GENES TO TARGET BACTERIA (Lawrence D. Goodridge). CONCLUDING REMARKS: THE FUTURE OF ENZYBIOTICS (Patricia Veiga-Crespo and Tomas G. Villa). INDEX.

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Book SynopsisProviding a broad overview of the microbial pathogens associated with hospital-acquired human illness, Techniques for the Study of Hospital Acquired Infection examines the cost-effective use of laboratory techniques in nosocomial infectious disease epidemiology and control.Table of ContentsContributors. Forword. Preface. Dedication. I. Introduction to Healthcare Associated Infections and Their Control. 1. The Hospital and Ambulatory Care Environment (Anne Y. Chen and Hiren Pokharma). 2. Pathogen Transmission in the Healthcare Setting (Sonja Hansen and Ralf-Peter Vonberg). 3. Infection Control Basics (Louise-Marie Dembry and Carlos Torres-Viera). 4. Cost-Effectiveness of IC Program (Marc-Oliver Wright and Eli N. Perencevich). 5. Outbreak Investigations (Importance of the Healthcare Epidemiologist) (Marcus J. Zervos). 6. Pathogen Elimination: Antibiotic and Disinfectant Use and the Development of Resistance (Steven L. Foley, Beilei Ge, Carl M. Schroeder, and Arron M. Lynne). II. Techniques to Characterize Nosocomial Pathogens. 7. Rapid PCR Screening Methods (Ngolela Esther Babady, Frankling Cockerill and Robin Patel). 8. Restriction Analysis Techniques (Richard V. Goering, Mary Stemper, SanjayShukla and Steven Foley). 9. Pulsed-field Gel Electrophoresis (Mary Stemper, Steven Foley Richard V. Goering, and Sanjay Shukla). III. Application of Techniques to Characterize Predominant Nosocomial Pathogens. 10. Staphylococcus aureus (Vanthida Huang). 11. Escherichia coli (Johann D. D. Pitout). 12. Fungal Infections (Jose A. Vazquez). Index.

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Book SynopsisThis book is a unique synthesis of the major concepts and methods in bacterial population genetics in infectious disease, a field that is now about 35 yrs old. Emphasis is given to explaining population-level processes that shape genetic variation in bacterial populations and statistical methods of analysis of bacterial genetic data.Trade Review"I enjoyed reading Chapters 9, 12, and 15 because these topics interested me. Other chapters can be recommended as sources of citations for specialists interested in those particular bacteria." (The Quarterly Review of Biology, 1 December 2011) "On the whole, this book is of general interest for teachers of microbiology, who need to explain bacteriology in the genomic age, and it may also help clinical microbiologists choose tools for identifying circulating clones. Finally, it can be useful to specialists in the field of emerging bacteria for whom the need to synthesize genomic data is part of their professional routine. I recommend this book most strongly for all of these bacteriology specialists." (Emerging Infectious Diseases Journal, 1 March 2011) Table of ContentsForeword. Preface. Contributors. Part I Concepts and Methods in Bacterial Population Genetics. 1 The Coalescent of Bacterial Populations. 1.1 Background and Motivation. 1.2 Population Reproduction Models. 1.3 Time and the Effective Population Size. 1.4 The Genealogy of a Sample of Size n. 1.5 From Coalescent Time to Real Time. 1.6 Mutations. 1.7 Demography. 1.8 Recombination and Gene Conversion. 1.9 Summary. 2 Linkage, Selection, and the Clonal Complex. 2.1 Introduction—Historical Overview. 2.2 Recombination, Linkage, and Substructure. 2.3 Neutrality versus Selection. 2.4 Clustering Techniques. 3 Sequence-Based Analysis of Bacterial Population Structures. 3.1 Introduction. 3.2 Alignments. 3.3 Phylogenetic Methods. 3.4 Measures of Uncertainty. 3.5 Beyond the Tree Model. 4 Genetic Recombination and Bacterial Population Structure. 4.1 Introduction. 4.2 Constraints on LGT. 4.3 Infl uences of LGT on Sequence Analyses. 4.4 The Detection of Individual LGT Events. 4.5 The Estimation of Homologous Recombination Rates. 4.6 Properly Accounting for LGT During Sequence Analyses. 4.7 Questions Relating Directly to LGT. 5 Statistical Methods for Detecting the Presence of Natural Selection in Bacterial Populations. 5.1 Introduction. 5.2 Natural Selection. 5.3 Statistical Methods for Detecting the Presence of Natural Selection. 5.4 Statistical Methods for Bacterial Populations. 5.5 An Example. 5.6 Discussion and Perspective. 6 Demographic Infl uences on Bacterial Population Structure. 6.1 Bacterial Population Size. 6.2 Measures of Genetic Diversity. 6.3 The Concept of Effective Population Size. 6.4 Inferring Past Demography from Genetic Sequence Data. 6.5 Population Subdivision. 6.6 What is a Bacterial Population? 6.7 Conclusion. 7 Population Genomics of Bacteria. 7.1 Introduction. 7.2 Classical Bacterial Population Genetics. 7.3 The Genomics Era. 7.4 Bacterial Population Genomics. 7.5 Next-Gen Bacterial Population Genomics. 7.6 Next-Gen Genomics Technology. 7.7 Next-Gen Genomic Data Analysis. 7.8 Conclusions/Future Prospects. 8 The Use of MLVA and SNP Analysis to Study the Population Genetics of Pathogenic Bacteria. 8.1 Introduction. 8.2 MLVA and Other DNA Fragment-Based Methods. 8.3 SNP and DNA Sequence-Based Methods. 8.4 Conclusion. Part II Population Genetics of Select Bacterial Pathogens. 9 Population Genetics of Bacillus: Phylogeography of Anthrax in North America. 9.1 Introduction. 9.2 History of Anthrax in North America. 9.3 The Anthrax Districts after 1944. 9.4 Molecular Genotyping of B. anthracis. 9.5 Genotypes within the Anthrax Districts in North America. 9.6 Phylogenetic Resolution within the WNA Lineage. 9.7 Phylogeographic Resolution within the Ames Lineage. 9.8 Additional B. anthracis Genotypes in North America. 9.9 Conclusions. 10 Population Genetics of Campylobacter. 10.1 Introduction. 10.2 Human Infection. 10.3 Genetic Structure. 10.4 Models of Campylobacter Evolution. 10.5 Clades and Species. 10.6 Conclusion. 11 Population Genetics of Enterococcus. 11.1 Introduction. 11.2 Antibiotic Resistance. 11.3 Vancomycin Resistance. 11.4 VRE: A Zoonosis or Not? 11.5 Population Structure and Genetic Evolution: Similarities and Differences Between E. faecium and E. faecalis. 11.6 What Is Driving GD in E. faecium and E. faecalis? 11.7 The Accessory Genome of E. faecium and E. faecalis. 11.8 Summary, Conclusions, and Future Perspectives. 12 Population Biology of Lyme Borreliosis Spirochetes. 12.1 Introduction. 12.2 Genome Organization of LB Spirochetes. 12.3 Genotyping of LB Spirochetes and Phylogenetic Tools. 12.4 Population Biology and Evolution of LB Spirochetes. 12.5 Do LB Species Exist? 12.6 Future Research Avenues. 13 Population Genetics of Neisseria meningitidis. 13.1 Introduction. 13.2 A Brief History of Typing of Meningococci. 13.3 Species Separation. 13.4 Sampling Strategies. 13.5 The Clonal Complexes of Meningococci. 13.6 Forces Shaping the Meningococcal Metalineage. 13.7 Virulence, a Mysterious Trait. 13.8 Population Effect of Meningococcal Vaccines. 13.9 Antibiotic Resistance and Meningococcal Lineages. 13.10 Concluding Remarks. 14 Population Genetics of Pathogenic Escherichia coli. 14.1 Introduction. 14.2 E. coli Population Genetics: Clonal or not Clonal? 14.3 The E. coli Phylogenetic Structure. 14.4 The Evolutionary History of a Host-Specifi c Obligate Pathogen: The Shigella and EIEC Case Study. 14.5 What Makes You an Opportunistic Pathogen? 14.6 The Virulence Resistance Trade-off. 14.7 Concluding Remarks. 15 Population Genetics of Salmonella: Selection for Antigenic Diversity. 15.1 Introduction. 15.2 Generation Timescale Diversifi cation. 15.3 Antigenic Diversity in Salmonella. 15.4 Why Are Diverse H and O Antigens Maintained in Salmonella? 15.5 Conclusions. 16 Population Genetics of Staphylococcus. 16.1 Introduction. 16.2 Overview of The Staphylococcal Population Structure. 16.3 Staphylococcal Population Structure in Specific Disease Contexts. 16.4 Origin and Maintenance of Staphylococcal Genetic Variation. 16.5 Macroevolutionary Considerations and Concluding Remarks. Appendix 1—Diversity and Differentiation. 17 Population Genetics of Streptococcus. 17.1 Habitats, Transmission, and Disease. 17.2 Classical Strain Typing. 17.3 Multilocus Sequence Typing (MLST) Based on Housekeeping Genes. 17.4 Species Boundaries and Gene Flow. 17.5 Niche-driving Genes. 17.6 Bacterial Population Dynamics and Selection. 17.7 Machinery of Genetic Change, Revisited. 18 Population Genetics of Vibrios. 18.1 Introduction. 18.2 V. cholerae. 18.3 V. parahaemolyticus . 18.4 V. vulnificus. 18.5 Conclusions. References. Index.

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Book SynopsisThis resource provides thorough coverage of pharmacogenetics and its impact on pharmaceuticals, therapeutics, and clinical practice. It opens with the basics of pharmacogenetics, including drug disposition and pharmacodynamics.Trade Review“This is a well-written book that I highly recommend to anyone interested in any aspect of personalized medicine.” (Doody’s, 24 August 2012)Table of ContentsPreface vii Contributors ix 1. Pharmacogenetics: A Historical Perspective 1Ann K. Daly Part I Pharmacogenetics: Relationship to Pharmacokinetics and Pharmacodynamics 2. Pharmacogenetics in Drug Metabolism: Role of Phase I Enzymes 15Vita Dolžan 3. Pharmacogenetics of Phase II Drug Metabolizing Enzymes 81Ingolf Cascorbi 4. Pharmacogenetics of Drug Transporters 101Henriette E. Meyer zu Schwabedissen, Markus Grube, and Heyo K. Kroemer 5. Pharmacogenetics of Drug Targets 149Ann K. Daly and Maria Arranz Part II Pharmacogenetics: Therapeutic Areas 6. Cardiovascular Pharmacogenetics 185Bas J. M. Peters, Anthonius de Boer, Tom Schalekamp, Olaf H. Klungel, and Anke-Hilse Maitland-van der Zee 7. Pharmacogenetics in Psychiatry 215Evangelia M. Tsapakis, Sarah Curran, Ruth I. Ohlsen, Nora S. Vyas, Katherine J. Aitchison, and Ann K. Daly 8. Pharmacogenetics in Cancer 251Sharon Marsh 9. Pharmacogenetics of Asthma and COPD 271Ellen S. Koster, Jan A. M. Raaijmakers, Anke-Hilse Maitland-van der Zee, and Gerard H. Koppelman 10. Pharmacogenetics of Adverse Drug Reactions 295Ann K. Daly, Martin Armstrong, and Munir Pirmohamed 11. Pharmacogenomics of Inflammatory Bowel Diseases 323Alexander Teml, Susanne Karner, Elke Schaeffeler, and Matthias Schwab 12. Pharmacogenetics of Pain Medication 353Jörn Lötsch Part III Pharmacogenetics: Implementation in Clinical Practice 13. Ethical and Social Issues in Pharmacogenomics Testing 377Susanne Vijverberg, Toine Pieters, and Martina Cornel Part IV Developments in Pharmacogenetic Research 14. High-Throughput Genotyping Technologies for Pharmacogenetics 403Beatriz Sobrino and Angel Carracedo 15. Developments in Analyses in Pharmacogenetic Datasets 415Alison A. Motsinger-Reif Part V Pharmacogenetics: Industry and Regulatory Affairs 16. Applications of Pharmacogenetics in Pharmaceutical Research and Development 439Daniel K. Burns and Scott S. Sundseth 17. Role of Pharmacogenetics in Registration Processes 461Myong-Jin Kim, Issam Zineh, Shiew-Mei Huang, and Lawrence J. Lesko Part VI Conclusions 18. Pharmacogenetics: Possibilities and Pitfalls 479Anke-Hilse Maitland-van der Zee and Ann K. Daly Index 485

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Book SynopsisAntibiotic resistance is an ever-increasing problem in modern times, as resistant strains of bacteria become more prevalent. This book teaches about the different types of antibiotics and the bacteria they are used on individually, while, at the same time, maintaining a specific focus on the issue of resistance.Trade Review“This is a good book with good information about antibiotics. It fits nicely in the pocket of a laboratory coat and could be carried around by physicians. It concludes with a serious message -- that we have enjoyed the use of antibiotics on a "loan from nature," and this loan is expiring with a "threat of foreclosure.” (Doody’s, 6 April 2012)“This is a good book with good information about antibiotics. It fits nicely in the pocket of a laboratory coat and could be carried around by physicians. It concludes with a serious message -- that we have enjoyed the use of antibiotics on a "loan from nature," and this loan is expiring with a "threat of foreclosure.” (Doody’s, 6 April 2012) Table of Contents1. Antibiotics, the Greatest Triumph of Scientific Medicine. 2. Distribution of Antibiotics. 3. Sulfonamides and Trimethoprim. 4. Betalactams. 5. Glycopeptides. 6. Aminoglycosides. 7. Further Antibiotics Interfering with Bacterial Protein Synthesis. 8. Quinolones. 9. Antibacterial Agents that are not Related to the Large Antibiotic Families. 10. Mechanisms for the Horizontal Spread of Antibiotic Resistance Among Bacterial. 11. How to Handle Resistance Against Antibiotics?

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Book SynopsisThe purpose of the book is to introduce platelets, and their functional role in thrombotic and cardiovascular disease, justifying the relevance of platelet proteomics research. Focus then shifts to the recent developments on mass spectrometry (MS)-based proteomics. This chapter shows potential applications for platelet proteomics not yet carried out. It includes examples of post-translational modifications (PTMs) analysis in platelets. The second part of the book focuses on the main research done so far on platelet proteomics. This includes general proteome mapping by non-gel based separation methods (MudPit), analysis of the general platelet proteome and signaling cascades by gel-based separation methods (2-DE), sub-proteome analyses (secretome/releasate, membrane proteins, organelles). Finally, the last section links the platelet transcriptome and application to disease. This section is highly relevant and includes chapters on proteomics, transcriptomics, functional genomics, sysTrade Review"Experienced researchers looking for an up-to-date and comprehensive review of this rapidly developing field will find this book a valuable resource.” (American Society for Mass Spectrometry, 13 December 2011)Table of ContentsForeword xiii Preface xv Acronyms xvii Part I General Overview: Platelets, Sample Preparation, and Mass Spectrometry-Based Proteomics 1 Platelets and Their Role in Thrombotic and Cardiovascular Disease: The Impact of Proteomic Analysis 3 Ronald G. Stanley, Katherine L. Tucker, Natasha E. Barrett, and Jonathan M. Gibbins 2 Mass-Spectrometry-Based Proteomics: General Overview and Posttranslational Modification Analysis in the Context of Platelet Research 27 Julia Maria Burkhart and Albert Sickmann 3 Sample Preparation Variables in Platelet Proteomics for Biomarker Research 67 Maria Zellner and Rudolf Oehler Part II Analysis of The Platelet Proteome: Global Approaches and Subproteomes 4 Two-Dimensional Gel Electrophoresis: Basic Principles and Application to Platelet Signaling Studies 89 Ángel García 5 The Platelet Membrane Proteome 111 Yotis A. Senis 6 Proteomics of Platelet Granules, Organelles, and Releasate 139 James P. McRedmond 7 The Platelet Microparticle Proteome 159 David M. Smalley 8 N-Terminal Combined Fractional Diagonal Chromatographic (COFRADIC) Analysis of the Human Platelet Proteome 185 Francis Impens, Kenny Helsens, Niklaas Colaert, Lennart Martens, Joël Vandekerckhove, and Kris Gevaert Part III Integrated “Omics” and Application to Disease 9 Serial Analysis of Gene Expression (SAGE) For Studying the Platelet and Megakaryocyte Transcriptome 209 Michael G. Tomlinson 10 The Application of Microarray Analysis and Its Integration with Proteomics for Study of Platelet-Associated Disorders 231 Dmitri V. Gnatenko and Wadie F. Bahou 11 Platelet Functional Genomics 253 Isabelle I. Salles, Marie N. O’Connor, Daphne C. Thijssen-Timmer, Katleen Broos, and Hans Deckmyn 12 Systems Biology to Study Platelet-Related Bleeding Disorders 285 Jan-Willem N. Akkerman and Bernard De Bono 13 Platelet Proteomics in Transfusion Medicine 321 Thomas Thiele, Leif Steil, Uwe Völker, and Andreas Greinacher 14 Cardiovascular Proteomics 341 Fernando Vivanco, Fernando de la Cuesta, Maria G. Barderas, Irene Zubiri, and Gloria Álvarez-Llamas Index 381

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Book SynopsisHuman Population Genetics will provide an introduction to mathematical population genetics, along with relevant examples from human (and some non-human primate) populations, and will also present concepts and methods of population genetics that are specific to the study of human populations.Trade Review“Relethford’s Human Population Geneticsis a superb attempt at facing the challenges of explaining the basics of population genetics to those with a limited background in evolutionary theory and a fear of the quantitative.” (The Quarterly Review of Biology, 1 September 2014) “For many students, and likely some instructors, who have found the mathematical underpinnings of evolutionary genetics daunting, this new volume will be a welcome addition to the bookshelf. It is an easy book to recommend either as a primary text in anthropological genetics courses, or as a recommended or adjunct text in upper division/beginning graduate courses in human biology, human genetics, or human evolution.” (American Journal of Physical Anthropology, 19 September 2013) Table of ContentsForeword vii Preface ix 1 Genetic, Mathematical, and Anthropological Background 1 I. The Scope of Population Genetics 2 II. Genetics Background 5 III. Principles of Probability 14 IV. The Anthropological Connection 17 V. A Closing Thought 21 2 Hardy–Weinberg Equilibrium 23 I. Genotype and Allele Frequencies 24 II. What is Hardy–Weinberg Equilibrium? 30 III. The Mathematics of Hardy–Weinberg Equilibrium 31 IV. Using Hardy–Weinberg Equilibrium 37 V. Extensions of Hardy–Weinberg Equilibrium 40 VI. Hardy–Weinberg Equilibrium and Evolution 44 VII. Summary 45 3 Inbreeding 49 I. Quantifying Inbreeding 51 II. Population Genetics and Inbreeding 62 III. Inbreeding in Human Populations 65 IV. Summary 75 4 Mutation 77 I. The Nature of Mutations 77 II. Models of Mutation 81 III. Mutational History and Anthropological Questions 88 IV. Summary 96 5 Genetic Drift 101 I. What is Genetic Drift? 102 II. Genetic Drift and Population Size 112 III. Effects on Genetic Variation 120 IV. Mutation and Genetic Drift 121 V. Coalescent Theory 125 VI. Summary 131 6 Models of Natural Selection 139 I. How Does Natural Selection Work? 140 II. A General Model of Natural Selection 145 III. Types of Natural Selection 147 IV. Other Aspects of Selection 160 V. Summary 167 7 Natural Selection in Human Populations 181 I. Case Studies of Natural Selection in Human Populations 182 II. Are Humans Still EvolVIng? 198 III. Summary 203 8 Gene Flow 205 I. The Evolutionary Impact of Gene Flow 206 II. Models of Gene Flow 208 III. Gene Flow and Genetic Drift 213 IV. Estimating Admixture in Human Populations 226 V. Summary 230 9 Human Population Structure and History 237 I. Case Studies of Human Population Structure 238 II. The Origin of Modern Humans 242 III. Case Studies of Population Origins 247 IV. Summary 255 Glossary 257 References 267 Index 279

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Book SynopsisThe Human Microbiota offers a comprehensive review of all human-associated microbial niches in a single volume, focusing on what modern tools in molecular microbiology are revealing about human microbiota, and how specific microbial communities can be associated with either beneficial effects or diseases. An excellent resource for microbiologists, physicians, infectious disease specialists, and others in the field, the book describes the latest research findings and evaluates the most innovative research approaches and technologies. Perspectives from pioneers in human microbial ecology are provided throughout.Trade Review“Overall, this book provides a concise overview of the human microbiota in and on different body sites, a bit too concise for me. It fulfils the intention to discuss many different body sites but in doing so neglects to get to the detailed description of the human microbiota, let alone to give a good overview of their role in health and disease.” (Beneficial Microbes, 1 March 2014) “Having said that, I’m sure the book will be of interest to all those studying the effects of micro-organisms on the human body.” (Microbiology Today, 30 August 2013) Table of ContentsPREFACE vii CONTRIBUTORS xi 1 THE NIH HUMAN MICROBIOME PROJECT 1 Lita M. Proctor, Shaila Chhibba, Jean McEwen, Jane Peterson, Chris Wellington, Carl Baker, Maria Giovanni, Pamela McInnes, and R. Dwayne Lunsford 2 METHODS FOR CHARACTERIZING MICROBIAL COMMUNITIES ASSOCIATED WITH THE HUMAN BODY 51 Christine Bassis, Vincent Young, and Thomas Schmidt 3 PHYLOARRAYS 75 Eoin L. Brodie and Susan V. Lynch 4 MATHEMATICAL APPROACHES FOR DESCRIBING MICROBIAL POPULATIONS: PRACTICE AND THEORY FOR EXTRAPOLATION OF RICH ENVIRONMENTS 85 Manuel E. Lladser and Rob Knight 5 TENSION AT THE BORDER: HOW HOST GENETICS AND THE ENTERIC MICROBIOTA CONSPIRE TO PROMOTE CROHN’S DISEASE 105 Daniel N. Frank and Ellen Li 6 THE HUMAN AIRWAY MICROBIOME 119 Edith T. Zemanick and J. Kirk Harris 7 MICROBIOTA OF THE MOUTH: A BLESSING OR A CURSE? 135 Angela H. Nobbs, David Dymock, and Howard F. Jenkinson 8 MICROBIOTA OF THE GENITOURINARY TRACT 167 Laura K. Sycuro and David N. Fredricks 9 FUNCTIONAL STRUCTURE OF INTESTINAL MICROBIOTA IN HEALTH AND DISEASE 211 Alexander Swidsinski and Vera Loening-Baucke 10 FROM FLY TO HUMAN: UNDERSTANDING HOW COMMENSAL MICROORGANISMS INFLUENCE HOST IMMUNITY AND HEALTH 255 June L. Round 11 INSIGHTS INTO THE HUMAN MICROBIOME FROM ANIMAL MODELS 273 Bethany A. Rader and Karen Guillemin 12 TO GROW OR NOT TO GROW: ISOLATION AND CULTIVATION PROCEDURES IN THE GENOMIC AGE 289 Karsten Zengler 13 NEW APPROACHES TO CULTIVATION OF HUMAN MICROBIOTA 303 Slava S. Epstein, Maria Sizova, and Amanda Hazen 14 MANIPULATING THE INDIGENOUS MICROBIOTA IN HUMANS: PREBIOTICS, PROBIOTICS, AND SYNBIOTICS 315 George T. Macfarlane and Sandra Macfarlane INDEX 339

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Book SynopsisThis book provides readers with new paradigms on the mutation discovery in the post-genome era. The completion of human and other genome sequencing, along with other new technologies, such as mutation analysis and microarray, has dramatically accelerated the progress in positional cloning of genes from mutated models.Table of ContentsPreface. Acknowledgments. Contributors. 1. Gene Discovery: From Positional Cloning to Genomic Cloning (Weikuan Gu and Daniel Goldowitz). 2. High-Throughput Gene Expression Analysis and the Identification of Expression QTLs (Rudi Alberts and Klaus Schughart). 3. DNA Methylation in the Pathogenesis of Autoimmunity (Xueqing Xu, Ping Yang, Zhang Shu, Yun Bai, and Cong-Yi Wang). 4. Cell-Based Analysis with Microfl uidic Chip (Wang Qi and Zhao Long). 5. Missing Dimension: Protein Turnover Rate Measurement in Gene Discovery (Gary Guishan Xiao). 6. Bioinformatics Tools for Gene Function Prediction (Yan Cui). 7. Determination of Genomic Locations of Target Genetic Loci (Bo Chang). 8. Mutation Discovery Using High-Throughput Mutation Screening Technology (Kai Li, Hanlin Gao, Hong-Guang Xie, Wanping Sun, and Jia Zhang). 9. Candidate Screening through Gene Expression Profile (Michal Korostynski). 10. Candidate Screening through High-Density SNP Array (Ching-Wan Lam and Kin-Chong Lau). 11. Gene Discovery by Direct Genome Sequencing (Kunal Ray, Arijit Mukhopadhyay, and Mainak Sengupta). 12. Candidate Screening through Bioinformatics Tools (Song Wu and Wei Zhao). 13. Using an Integrative Strategy to Identify Mutations (Yan Jiao and Weikuan Gu). 14. Determination of the Function of a Mutation (Bouchra Edderkaoui). 15. Confi rmation of a Mutation by Multiple Molecular Approaches (Hector Martinez-Valdez and Blanca Ortiz-Quintero). 16. Confi rmation of a Mutation by MicroRNA (Hongwei Zheng and Yongjun Wang). 17. Confi rmation of Gene Function Using Translational Approaches (Caroline J. Zeiss). 18. Confi rmation of Single Nucleotide Mutations (Jochen Graw). 19. Initial Identifi cation and Confi rmation of a QTL Gene (David C. Airey and Chun Li). 20. Gene Discovery of Crop Disease in the Postgenome Era (Yulin Jia). 21. Impact of Genomewide Structural Variation on Gene Discovery (Lisenka E.L.M. Vissers and Joris A. Veltman). 22. Impact of Whole Genome Protein Analysis on Gene Discovery of Disease Models (Sheng Zhang, Yong Yang, and Theodore W. Thannhauser). Index.

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Book SynopsisA Research-Driven Resource on Building Biochemical Systems to Perform Information Processing Functions Information Processing by Biochemical Systems describes fully delineated biochemical systems, organized as neural networktype assemblies. It explains the relationship between these two apparently unrelated fields, revealing how biochemical systems have the advantage of using the language of the physiological processes and, therefore, can be organized into the neural networktype assemblies, much in the way that natural biosystems are. A wealth of information is included concerning both the experimental aspects (such as materials and equipment used) and the computational procedures involved. This authoritative reference: Addresses network-type connectivity, considered to be a key feature underlying the information processing ability of the brain Describes novel scientific achievements, and serves as an aid for those interested in furtTrade Review "A wealth of information is included concerning both the experimental aspects (such as materials and equipment used) and the computational procedures involved." (Zentralblatt MATH 2016) Table of ContentsPreface. Terminology. List of Symbols and Acronyms. 1 Introduction and Literature Survey. 1.1 Introduction. 1.2 Computational Processes Based on Biological Principles. 1.2.1 Modeling Biological Processes. 1.2.2 Artificial Neural Networks. 1.3 Molecular and Biomolecular Electronics. 1.3.1 Motivation. 1.3.2 Molecular Electronics. 1.3.3 Biomolecular Electronics. 1.4 Biochemical Devices Based on Enzymic Reactions. 1.5 Oscillations in Biochemical Systems. 1.6 Kinetic Characteristics of Cyclic Enzyme Systems. 2 Background and Goals of This Study. 3 Materials and Methods. 3.1 Materials. 3.2 Instruments. 3.3 Experimental Methods. 3.3.1 Determination of Kinetic Constants. 3.3.2 Determination of the Inhibition Constant for Inhibition of Glutathione Reductase by Glucose-6-Phosphate. 3.3.3 Immobilization on Affi-Gel 10. 3.3.4 Assay for Glucose-6-Phosphate Dehydrogenase. 3.3.5 Assay for Glutathione Reductase. 3.4 Computational Methods. 4 Results. 4.1 The Basic System: Theoretical Considerations and Results. 4.1.1 Characteristics of the Basic System. 4.1.2 The Basic System as an Information-Processing Unit. 4.1.3 Analytical Models for the Basic System. 4.1.4 Results of Numerical Simulations for the Basic System. 4.2 Neural Network–Type Biochemical Systems for Information Processing. 4.2.1 Network A. 4.2.2 Network B. 4.2.3 Network C. 4.3 The Basic System: Experimental Results. 4.3.1 Deciding on the Experimental System. 4.3.2 Kinetic Study of the Experimental System. 4.3.3 Control of the Input Signal. 4.3.4 The Basic System in a Fed-Batch Reactor. 4.3.5 Internal Inhibition in the Basic System. 4.3.6 Prediction of the Analytical Model Considering Internal Inhibition in a Fed-Batch Reactor. 4.3.7 Immobilization of G6PDH and GR. 4.3.8 The Basic System in a Packed Bed Reactor. 4.4 The Extended Basic System: Theoretical Considerations and Results. 4.4.1 Characteristics of the Extended Basic System. 4.4.2 The Extended Basic System as an Information-Processing Unit. 4.4.3 Analytical Model for the Extended Basic System. 4.4.4 Results of Numerical Simulations for the Extended Basic System. 5 Discussion. 5.1 The Basic System. 5.1.1 Fed-Batch Reactor: Numerical Simulations. 5.1.2 Continuous Reactor: Numerical Simulations. 5.1.3 Assessment of Experimental Results. 5.2 The Extended Basic System. 5.3 Biochemical Networks. 5.4 Comparing Artificial Neural Networks with Biochemical Networks. 5.5 Comparing Biochemical Networks to Computational Models. 6 Conclusions. References. Index.

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Book SynopsisThe only book available in the area of forward-time population genetics simulationsapplicable to both biomedical and evolutionary studies The rapid increase of the power of personal computers has led to the use of serious forward-time simulation programs in genetic studies. Forward-Time Population Genetics Simulations presents both new and commonly used methods, and introduces simuPOP, a powerful and flexible new program that can be used to simulate arbitrary evolutionary processes with unique features like customized chromosome types, arbitrary nonrandom mating schemes, virtual subpopulations, information fields, and Python operators. The book begins with an overview of important concepts and models, then goes on to show how simuPOP can simulate a number of standard population genetics modelswith the goal of demonstrating the impact of genetic factors such as mutation, selection, and recombination on standard Wright-Fisher models. The rest of the book is devoted to aTable of ContentsPreface ix Acknowledgments xiii List of examples xxiii 1. Basic concepts and models 1 1.1 Biological and genetic concepts 2 1.2 Population and evolutionary genetics 6 1.3 Statistical genetics and genetic epidemiology 17 2. Simulation of population genetics models 25 2.1 Random genetic drift 25 2.2 Demographic models 29 2.3 Mutation 31 2.4 Migration 34 2.5 Recombination and linkage disequilibrium 36 2.6 Natural selection 37 2.7 Genealogy of forward-time simulations 41 3. Ascertainment bias in population genetics 47 3.1 Introduction 47 3.2 Methods 49 3.3 Results 54 3.4 Discussion and Conclusions 58 4. Observing properties of evolving populations 63 4.1 Introduction 64 4.2 Simulation of the evolution of allele spectra 66 4.3 Extensions to the basic model 78 5. Simulating populations with complex human diseases 89 5.1 Introduction 89 5.2 Controlling disease allele frequencies at the present generation 91 5.3 Forward-time simulation of realistic samples 102 5.4 Discussion 119 6. Nonrandom mating and its applications 125 6.1 Assortative mating 126 6.2 More complex non-random mating schemes 132 6.3 Hetergeneous mating schemes 140 6.4 Simulation of age structured populations 145 Appendix: Forward-time simulations using stimulPOP 157 A.1 Introduction 157 A.2 Population 160 A.3 Operators 172 A.4 Evolve on or more populations 181 A.5 A complete stimuPOP script 185

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Book SynopsisPharmacology for the Health Care Professions is an accessible introduction to the pharmacology necessary for health care professionals training to be non-medical prescribers looking for an overview of the subject.Table of ContentsForeword. Preface. Acknowledgements. 1. Introduction. Part I: Principles of Pharmacology. 2. Drug disposition. 3. Effects of drugs on the body. Part II: Systemic Pharmacology. 4. Cardiovascular and blood disorders. 5. Respiratory Disorders. 6. Disorders of the endocrine system. 7. Disorders of the musculoskeletal system. 8. Disorders of the skin. 9. Chemotherapy of infectious diseases. 10. Cancer chemotherapy. 11. Disorders of the central nervous system. 12. Anaesthesia and analgesia. 13. Contrast agents and adjuncts to radiography. Part III: Prescribing and the Law. 14. Medicines, the law and health care professionals. 15. prescribing in practice. Appendices. Appendix A. Drug Names. Appendix B. Glossary. Appendix C. Examples of Patient Group Directions. bibliography. Useful websites. Index.

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Book SynopsisUnique in-depth investigation of the relationship between physical exercise and brain function. Covers theoretical approaches and experimental results and includes chapters on the latest developments in research design. Examines the effects of both acute and chronic exercise on brain function.Trade Review"A text brimming with new research in the field and practical suggestions for application and future research. … Discussion of the methodologies and protocols presented should generate considerable interest. … I found the text to be a worthwhile addition to my library." (PsycCRITIQUES, February 2010) Table of ContentsPreface ix Contributors xi PART 1 THEORETICAL AND METHODOLOGICAL ISSUES 1 1 Acute exercise and psychological functions: a cognitive-energetic approach 3Michel Audiffren 1.1 Varieties of exercise effects on psychological variables 4 1.2 The cognitive psychology approach 9 1.3 The energetic approach 11 1.4 Exercise effects and cognitive-energetic models 14 1.5 Sensorimotor and cognitive functions affected by exercise 24 1.6 Limits of the cognitive-energetic approach and future perspectives 33 1.7 Conclusion 39 2 Exercise and cognitive function: a neuroendocrinological explanation 41Terry McMorris 2.1 Catecholamines and 5-hydroxytryptamine as brain neurotransmitters 41 2.2 How exercise induces increases in brain concentrations of noradrenaline, dopamine, cortisol and 5-hydroxytryptamine 43 2.3 Exercise, catecholamines, cortisol and cognition: research 50 2.4 Task type 59 2.5 Discussion 63 2.6 Developing a neuroendocrinological model for an interaction between exercise and cognition 67 3 The transient hypofrontality theory and its implications for emotion and cognition 69Arne Dietrich 3.1 Clearing the ground 71 3.2 Exercise-induced transient hypofrontality 73 3.3 Implications for emotion 79 3.4 Implications for cognition 81 3.5 Reconceptualizing the existing data in the field 87 4 Methodological issues: research approaches, research design, and task selection 91Phillip D. Tomporowski 4.1 Research approaches 92 4.2 Research design issues 99 4.3 Task selection issues 106 4.4 Conclusions and recommendations 112 PART 2 ACUTE EXERCISE AND COGNITION 115 5 Exercise, dehydration and cognitive function 117Terry McMorris 5.1 Exercise-induced dehydration and cognitive function 119 5.2 Discussion 128 5.3 Conclusions 134 6 Exercise, nutrition and cognition 135Adam David Cunliffe and Gulshanara Begum 6.1 Fatigue and limits to human performance 136 6.2 Assessing the effects of exercise and nutrition on cognitive performance 138 6.3 Nutrition, exercise and cognitive performance 142 6.4 Micronutrients, exercise and cognitive performance 145 6.5 Nutritional ergogenic aids and cognitive performance 147 6.6 Integration of research observations 148 6.7 Challenges in research 150 6.8 Conclusion 151 7 A chronometric and electromyographic approach to the effect of exercise on reaction time 153Karen Davranche and Michel Audiffren 7.1 Research 156 7.2 Conclusion 159 8 Acute aerobic exercise effects on event-related brain potentials 161Charles H. Hillman, Matthew Pontifex and Jason R. Themanson 8.1 Executive control 163 8.2 Neuroelectric measurement 164 8.3 Event-related brain potentials during exercise 165 8.4 Event-related brain potentials following exercise 170 8.5 Future directions and conclusions 177 9 Exercise and decision-making in team games 179Terry McMorris 9.1 Designing a decision-making test 180 9.2 Research results 183 9.3 Ecological validity and future research 189 9.4 Implications for team games players and coaches 192 10 Blood glucose and brain metabolism in exercise 193Niels H. Secher, Thomas Seifert, Henning B. Nielsen and Bjørn Quistorff 10.1 Cerebral metabolism during exercise 194 10.2 Cerebral oxygenation 202 10.3 Cerebral metabolism 203 10.4 Acute hypoglycemia 209 10.5 Conclusions 209 10.6 Future research 210 Acknowledgements 210 PART 3 CHRONIC EXERCISE AND COGNITION 211 11 An integrated approach to the effect of acute and chronic exercise on cognition: the linked role of individual and task constraints 213Caterina Pesce 11.1 The gap between acute and chronic exercise research 213 11.2 Individual constraints on the acute exercise–cognition relationship: the role of chronic exercise effects 215 11.3 Effect of physical fitness: links to exercise intensity and to the time relation between physical exercise and cognitive task 218 11.4 Effect of cognitive expertise: links to cognitive task complexity, exercise intensity and duration, and age 219 11.5 Effect of motor coordination skills: links to physical exercise complexity, intensity and duration 223 11.6 Bridging the gap between acute and chronic exercise studies 225 12 Chronic exercise and cognition in older adults 227Jennifer Etnier 12.1 Theoretical underpinnings 228 12.2 Empirical evidence 230 12.3 Moderators of the relationship 245 12.4 Practical conclusions 245 12.5 Challenges 246 12.6 Future research 247 13 Exercise and cognition in children 249Catherine L. Davis and Kate Lambourne 13.1 Definition of terms 249 13.2 Literature review 250 13.3 The Medical College of Georgia study 254 13.4 Potential mechanisms 262 13.5 Summary and recommendations for future research 266 14 Chronic exercise and developmental disabilities 269James Zagrodnik and Michael Horvat 14.1 Defining terms 269 14.2 Research investigating the effects of exercise on cognition among the developmentally disabled 272 14.3 Problems to address and future research considerations 279 14.4 Practical applications and conclusions 282 15 Chronic exercise in brain diseases 285Laura Eggermont and Erik Scherder 15.1 Observational studies of physical activity 286 15.2 Physical activity intervention studies 288 15.3 Physical activity, cognition and different types of dementia 298 15.4 Role of vascular disease 302 15.5 Neurodegenerative disease, nitric oxide, vascular disease and physical activity 305 15.6 Final conclusion 305 PART 4 DISCUSSION AND CONCLUSION 307 16 Summary and direction for future research 309Terry McMorris, Phillip D. Tomporowski, and Michel Audiffren 16.1 Summary: emerging theoretical approaches 309 16.2 Summary of research results 312 16.3 Future theoretically driven research 314 16.4 Future applied research 316 16.5 General summary 317 References 319 Index 375

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Book SynopsisAT LAST - A comprehensive, accessible textbook on glial neurobiology! Authored by leading experts in the field, Glial Neurobiology provides a concise, thorough and up-do-date overview of glial cells function, the role of glial cells in various neural processes and their involvement in nervous system pathology.Trade Review"This is a good book for neurosciences libraries." (Doody's Book Reviews)Table of ContentsPreface. List of abbreviations. PART I: Physiology of Glia. 1. Introduction to Glia. 2. General Overview of Signalling in the Nervous System. 3. Morphology of Glial Cells. 4. Glial Development. 5. General Physiology of Glial Cells. 6. Neuronal-Glial Interactions. PART II: Glial Cells and Nervous System Function. 7. Astrocytes. 8. Oligodendrocytes, Schwann Cells and Myelination. PART III: Glia and Nervous System Pathology. 9. General Pathophysiology of Glia. 10. Gila and Diseases of the Nervous System. Conclusions. Recommended Literature. Author Index. Subject Index.

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Book SynopsisIt is said if you take care of the pennies, the pounds will take care of themselves. Richard Burton''s excellent book takes this approach to calculations applied to the biomedical sciencesThis is certainly interesting and engaging but it avoids being complicated. Journal of Biological Education, April 2009 Biomedical Calculations: Principles and Practice is an accessible, student-friendly introduction to calculating, applying formulae and solving quantitative problems within these subjects. This book targets a problem area for many students and aims to give them the confidence which they are so often lacking when undertaking scientific calculations. It takes a unique approach to the subject and uses unit analysis as a central theme throughout the book to enhance student understanding. Clearly structured throughout, little basic knowledge of mathematics is assumed, but even the most numerate readers will be interested in the sometimes-novel biological detTrade Review?I really liked this book and the approach the author has taken. It will certainly be useful for biomedical scientists and for those teaching potential biomedical scientists, either at university or during training in the laboratory.? ( British J of Biomedical Science, 2008) "It is said if you take care of the pennies, the pounds will take care of themselves. Richard Burton's excellent book takes this approach to calculations applied to the biomedical sciences?This is certainly interesting and engaging but it avoids being complicated." ?Journal of Biological Education, April 2009Table of ContentsPreface. Acknowledgements. This book, and how to use it. PART I. 1. Unit analysis: the neglected key to confidence. 1.1 Calculating with units. 1.2 Ways of writing composite units. 1.3 How unit analysis can guide thinking and help solve problems. 1.4 When to specify substances along with units. 1.5 The need to use appropriate and compatible units in formulae. 1.6 Checking and deriving formulae. 1.7 When unit analysis raises questions about formulae. 1.8 Dimensional analysis. PART II. 2. Units: length, area, volume, mass, moles and equivalents. 2.1 The Système International and unit prefixes. 2.2 Length and distance. 2.3 Area. 2.4 Volume. 2.5 Mass. 2.6 Moles. 2.7 Equivalents. 2.8 Conversion between units. Problems. 3. Percentages. 3.1 When percentages mislead: human body fat and fat in milk. 3.2 Heat loss from the body: further questionable percentages. Problems. 4. Composite units I - density. 4.1 Specific gravity. 4.2 Specific volume. 4.3 Two definitions of body density. 4.4 Thinking about a formula. Problems. 5. Composite units II - concentration. 5.1 Concentrations: kilograms of water vs litres of solution. 5.2 Simple protein-free salt solutions. 5.3 Millimolar and millimolal concentrations in blood plasma. 5.4 Some quite different uses for Eq. (5.1). Problems. 6. Aspects of problem solving. 6.1 Letting unit analysis solve the problem. 6.2 ‘Let x be the unknown’. Problems. 7. Making up and diluting solutions. 7.1 Preparing 250 mL of 150 mM NaCl from the dry salt. 7.2 Preparing dilutions from stock solutions. Problems. 8. Calculating drug doses. Problems. 9. More about solutions - electroneutrality, osmotic pressure and activity. 9.1 The principle of electroneutrality. 9.2 But what about membrane potentials and short-circuit currents? 9.3 Anion gap. 9.4 Osmoles and osmolality. 9.5 Osmolar gap. 9.6 Osmosity. 9.7 Cell contents. 9.8 Effective osmolality, effective osmotic pressure. 9.9 Osmotic shifts of water between cells and extracellular fluid. 9.10 Free and bound concentrations, activities. PART III. 10. Graphs, straight lines and equations. 10.1 Graphs: some terminology. 10.2 Advice on drawing graphs. 10.3 The equation of a straight line. 10.4 Finding the equation of a line that passes through two specified points. 10.5 Drawing a line that is defined by a specified equation. 10.6 Finding the equation of a line from its gradient and the coordinates of a single point on it. 10.7 Finding the line that best fits a number of points when these lie only roughly in a straight line. 10.8 ‘Proportional’ and ‘inversely proportional’. 10.9 Gradients of curves. 10.10 A note on units. 10.11 On the different kinds of formulae and equations. Problems. 11. On shapes and sizes. 11.1 Areas and volumes of simple shapes. 11.2 Erythrocytes, cylinders and spheres. 11.3 The swelling of erythrocytes in hypo-osmotic solutions. 11.4 Distortion of erythrocytes in passing along narrow blood vessels. 11.5 An exercise in rearranging equations to eliminate an unwanted term. 11.6 Easy and general ways to check algebraic working. 11.7 Solving the equation by trial and error in a spreadsheet. 11.8 Why do we not have naturally spherical erythrocytes? 11.9 General properties of simple geometrical shapes. 11.10 Replacing volumes with masses in these equations. 11.11 A digression on graphs. 11.12 Calculating surface area from volume and height: another exercise in re-arranging equations and eliminating unwanted terms. 11.13 Another digression to check algebraic working. 11.14 Generalizing the formula to include the human body. 11.15 Surface/volume and surface/mass ratios. 11.16 The surface area of the human body. 11.17 Standard formulae for body surface area. 11.18 An exercise in comparing formulae containing exponents. Problems. 12. Body size, body build, fatness and muscularity: unit analysis as an aid to discovery. 12.1 Variations in fat-free mass with height and age. 12.2 The Rohrer index, or ‘height-weight index of build’. 12.3 The body mass index; estimating body fat from body mass and height. 12.4 Upper arm muscle: how its cross-sectional area varies with body height. 12.5 Weightlifting - and the cross-sectional area of muscle. 12.6 Estimating body fat from skinfold thickness measurements. 12.7 Postscript. PART IV. 13. Introducing time. 13.1 Frequency. 13.2 Speed and velocity. 13.3 Acceleration. 13.4 Rates of flow of substances carried in fluids. 13.5 Thinking about a formula. 13.6 The concept of renal clearance. 13.7 Relating the clearance formula for renal plasma flow to the Fick Principle. 13.8 Creatinine clearance as a measure of GFR, and a convenient formula for estimating it. Problems. PART V. 14. Force, pressure, energy, work and power. 14.1 Force and weight. 14.2 Pressure. 14.3 Columns of water, columns of blood. 14.4 Osmotic pressure and colloid osmotic pressure (oncotic pressure). 14.5 Energy and work. 14.6 Power. 14.7 An overview of units - from mass to pressure and power. Problems. 15. Lessons from another formula. 15.1 Poiseuille’s equation and viscosity. 15.2 Peripheral resistance. Problems. 16. Heat and temperature. 16.1 Temperature scales. 16.2 The temperature coefficient, Q10. 16.3 Heat capacity and specific heat. Problems. 17. Gases: dry and wet gas mixtures, partial pressures, gases in solution. 17.1 A reminder of units. 17.2 Natural variations in atmospheric pressure. 17.3 The gas laws. 17.4 A closer look at Eq. (17.1) and the universal gas constant, with attention to units. 17.5 Treatment of gas mixtures - percentages. 17.6 Treatment of gas mixtures - partial pressures, tensions. 17.7 Water vapour pressure. 17.8 ‘Standard temperature and pressure, dry’. 17.9 Dissolved O2 and CO2 in blood plasma and other fluids. Problems. PART VI. 18. Introduction to logarithms. 18.1 Definitions. 18.2 Rules for working with logarithms. 18.3 The usefulness of remembering log102. 18.4 Logarithmic scales on graphs. 18.5 What about units? 18.6 Natural logarithms. Problems. 19. Exponential time courses. 19.1 Use of semi-logarithmic plots. 19.2 Common complications. Problems. 20. Nernst equations in physiology and biochemistry: logarithms and ‘RT/zF’. 20.1 More on RT/zF. Problems. 21. pH - two definitions and a possible dilemma for teachers. 21.1 pH as -log[H+]. 21.2 The true definition of pH: pH as a number on a conventional scale. 21.3 The meaning of 10-pH. 21.4 Final comments. Problems. 22. Equilibrium constants, the Henderson-Hasselbalch equation, dose-response curves. 22.1 Equilibrium constants. 22.2 Concentrations or activities? 22.3 The Henderson-Hasselbalch equation. 22.4 Application of the Henderson-Hasselbalch equation to drugs. 22.5 The dependence of [AB] on [A] when ([B] + [AB]) is constant. 22.6 Concentration-response curves, dose-response curves. Problems. 23. Buffering and acid-base balance. 23.1 Non-bicarbonate buffering. 23.2 A link with dose-response curves. 23.3 Bicarbonate buffering. 23.4 CO2/HCO3- and non-bicarbonate buffers together. 23.5 The whole body: diet and the titratable acidity of urine. 23.6 Other aspects of acid-base balance. Problems. References. Appendix A. Basic mathematics and mathematical language. Appendix B. Some non-metric units. Appendix C. Notes. Appendix D. Solutions to problems. Index.

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Book SynopsisDecision-making is an integral part of our daily lives. Researchers seek a complete understanding of the decision-making process, including the biological and social basis and the impact of our decisions.Trade Review“But, on the whole, readers will come away with an appreciation for the complexities and potential rewards inherent in this still-growing field.” (The Quarterly Review of Biology, 1 December 2012) Table of ContentsContributors vii Introduction 1 Richard P. Ebstein, Mikhail Monakhov, Poh San Lai, and Simone G. Shamay-Tsoory PART 1 EMPATHY: NEURAL BASES AND GENETIC CORRELATES 19 1.1 Genes Related to Autistic Traits and Empathy 21 Bhismadev Chakrabarti and Simon Baron-Cohen 1.2 The Behavioral Genetics of Human Pair Bonding 37 Hasse Walum and Lars Westberg 1.3 Brain Networks Supporting Empathy 47 Martin Schulte-Rüther and Ellen Greimel 1.4 The Human Mirror Neuron System and Social Cognition 63 Sook-Lei Liew and Lisa Aziz-Zadeh 1.5 Motivational Aspects of Future Thinking in the Ventromedial Prefrontal Cortex 81 Arnaud D'Argembeau PART 2 MORAL NEUROSCIENCE AND EMOTION 91 2.1 Contributions of the Prefrontal Cortex to Social Cognition and Moral Judgment Processes 93 Chad E. Forbes, Joshua C. Poore, and Jordan Grafman 2.2 Emotion and Moral Cognition 111 Michael Koenigs 2.3 The Neuroanatomical Basis of Moral Cognition and Emotion 123 Roland Zahn, Ricardo de Oliveira-Souza, and Jorge Moll 2.4 Envy and Schadenfreude: The Neural Correlates of Competitive Emotions 139 Jonathan Dvash and Simone G. Shamay-Tsoory PART 3 Genes and Decision Making 157 3.1 The Somatic Marker Framework and the Neurological Basis of Decision Making 159 Antoine Bechara 3.2 A Model of the Initial Stages of Drug Abuse: From Reinforcement Learning to Social Contagion 185 Gilly Koritzky, Adi Luria, and Eldad Yechiam 3.3 Extrinsic Effects and Models of Dominance Hierarchy Formation 203 Matthew Druen and Lee Alan Dugatkin 3.4 Complex Social Cognition and the Appreciation of Social Norms in Psychiatric Disorders: Insights from Evolutionary Game Theory 215 Martin Brüne and Julia Wischniewski 3.5 From Neuroeconomics to Genetics: The Intertemporal Choices Case as an Example 233 Itzhak Aharon and Sacha Bourgeois-Gironde Index 245

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Book SynopsisThe diversity of animal signals has been widely documented, and the generality of animal signals also tantalizingly suggests that there are common mechanisms that have selected for their origin.Trade Review“Though it covers a variety of topics (e.g., deception, biomechanics, condition) important for understanding this research area, the book is definitely a resource for specialists. It will be useful only to those interested in the most current research on particular aspects of animal communication . . . Summing Up: Recommended. Graduate students, researchers”. (Choice, 1 January 2015) Table of ContentsContributors ix 1 INTRODUCTION 1Duncan J. Irschick, Mark Briffa, and Jeffrey Podos References 7 2 EARLY LIFE-HISTORY EFFECTS, OXIDATIVE STRESS, AND THE EVOLUTION AND EXPRESSION OF ANIMAL SIGNALS 11Nick J. Royle, Josephine M. Orledge, and Jonathan D. Blount Introduction 11 Signaling 12 Early Life-History Effects and Resource Allocation Trade-Offs 13 Oxidative Stress as a Mediator of Resource Allocation Trade-Offs 15 Signals Expressed During Development 20 Signals Expressed During Adulthood 25 Competition-Dependent Sexual Signals 32 Conclusions 34 Acknowledgments 36 References 36 3 A PERFORMANCE-BASED APPROACH TO STUDYING COSTS OF RELIABLE SIGNALS 47Jerry F. Husak, Justin P. Henningsen, Bieke Vanhooydonck, and Duncan J. Irschick Introduction 47 Receiver-Independent Costs 51 Receiver-Dependent Costs 55 Compensatory Traits 59 Conclusions 63 Acknowledgments 64 References 65 4 COGNITIVELY DRIVEN CO-OPTION AND THE EVOLUTION OF COMPLEX SEXUAL DISPLAYS IN BOWERBIRDS 75Gerald Borgia and Jason Keagy Introduction 75 Cognition, Co-Option, and Complex Display 78 Delayed Male Maturity, Male–Male Courtship, and Display Trait Acquisition 81 Female Signaling to Affect Male Display Intensity: An Innovation that Improves Courtship Success 82 Mate Searching and Flexibility in Adaptive Decision-Making 83 Female Uncertainty and Flexibility in Active Mate Assessment 84 Long-Term Age-Related Improvement in Decoration Display: Symmetrical Decoration Displays on Older Males’ Bowers 84 Anticipation of Male Routes during Courtship: Paths on Display Courts of Spotted Bowerbirds 86 Some Other Possible Cognitive Display-Related Behaviors of Bowerbirds 87 Construction of Successive Scenes for Females Visiting the Bower 88 Cognitive Aspects of Bower Building: Age-Related Improvement in Construction and Novel Techniques for Maintaining Symmetry 90 Cognitive Flexibility and Innovation in Display 93 Decoration Stealing: An Innovation for Display Trait Acquisition 94 Cooperating with Relatives for Display: An Innovation to Reduce Sexual Competition 95 Vocal Mimicry: Learning and Innovation in Use of Co-Opted Displays 96 Co-Option Mechanism 98 Cognition in Display Trait Acquisition 100 References 101 5 INTEGRATING FUNCTIONAL AND EVOLUTIONARY APPROACHES TO THE STUDY OF COLOR-BASED ANIMAL SIGNALS 111Darrell J. Kemp and Gregory F. Grether Introduction 111 Color Signal Production in More Detail 115 Signals, Honesty, and Condition-Dependence 116 Coloration as an Honest Advertisement 117 Trinidadian Guppies (Poecilia Reticulata) 118 Pierid Butterflies (Subfamily Coliadinae) 122 Birds 127 Discussion/Conclusion/Future Work 129 Acknowledgments 131 References 131 6 AGONISTIC SIGNALS: INTEGRATING ANALYSIS OF FUNCTIONS AND MECHANISMS 141Mark Briffa Animal Contests and the Evolution of Agonistic Signals 141 Empirical Approaches to Testing Theory: “Physiological Costs,” “Stamina,” and “Performance” 154 Energy Status and Agonistic Signals 156 Whole Body Performance and Agonistic Signals 159 Conclusions 164 References 167 7 ACOUSTIC SIGNAL EVOLUTION: BIOMECHANICS, SIZE, AND PERFORMANCE 175Jeffrey Podos and S.N. Patek Introduction 175 Biomechanics 178 Body Size 183 Performance 187 Concluding Remarks 194 Acknowledgments 195 References 195 8 DISHONEST SIGNALING DURING AGGRESSIVE INTERACTIONS: THEORY AND EMPIRICAL EVIDENCE 205Robbie S. Wilson and Michael J. Angilletta Jr. Introduction 205 The Evolution of Signaling 206 The Theory of Dishonesty 208 Dishonest Signaling in Aggressive Interactions between Conspecifics 209 Conclusions 223 References 223 9 FUNCTIONAL APPROACH TO CONDITION 229Dustin J. Wilgers and Eileen A. Hebets Introduction 229 Practical Approaches to Condition 230 Condition and Animal Performance 235 Condition and Mate Choice 239 Summary 241 References 242 Index 253

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Book SynopsisThe current state of the science supporting new research in lysophospholipids The study of lysophospholipids exploded with the discovery of cell surface receptors on both lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). Since then, thousands of original research reports?ranging from fundamental cell signaling to the physiology and pathophysiology of individual organ systems?have centered on lysophospholipids. This book draws together and analyzes the current literature to provide readers with a state-of-the-science review as well as current techniques that support research in all aspects of the field of lysophospholipid signaling. Lysophospholipid Receptors is divided into three sections: Receptors and other possible effectors Enzymes Physiology and pathophysiology Within each section, the authors explain the similarities and differences between LPA and S1P signaling. Examples are provided that deTable of ContentsPREFACE ix CONTRIBUTORS xi 1 LYSOPHOSPHATIDIC ACID (LPA) RECEPTOR SIGNALING 1 Hope Mirendil, Mu-En Lin, and Jerold Chun 2 SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTORS 41 Bongnam Jung and Timothy Hla 3 GLOBAL GENE EXPRESSION PROGRAM OF LYSOPHOSPHATIDIC ACID (LPA)-STIMULATED FIBROBLASTS 61 Catelijne Stortelers and Wouter H. Moolenaar 4 IDENTIFICATION OF DIRECT INTRACELLULAR TARGETS OF SPHINGOSINE 1-PHOSPHATE (S1P) 71 Nitai C. Hait, Sheldon Milstien, and Sarah Spiegel 5 LYSOPHOSPHOLIPID RECEPTOR SIGNALING PLATFORMS: THE RECEPTOR TYROSINE KINASE–G PROTEIN-COUPLED RECEPTOR SIGNALING COMPLEX 85 Nigel J. Pyne and Susan Pyne 6 AUTOTAXIN: A UNIQUE ECTO-TYPE PYROPHOSPHODIESTERASE WITH DIVERSE FUNCTIONS 103 Hiroshi Yukiura and Junken Aoki 7 STUDIES ON AUTOTAXIN SIGNALING IN ENDOCYTIC VESICLE BIOGENESIS AND EMBRYONIC DEVELOPMENT USING WHOLE EMBRYO CULTURE AND ELECTROPORATION 121 Masayuki Masu, Seiichi Koike, Takuya Okada, and Kazuko Keino-Masu 8 STANDARDIZATION AND QUANTIFICATION OF LYSOPHOSPHATIDIC ACID COMPOUNDS BY NORMAL-PHASE AND REVERSED-PHASE CHROMATOGRAPHY–TANDEM MASS SPECTROMETRY 137 Jeff D. Moore, Shengrong Li, David S. Myers, Stephen B. Milne, H. Alex Brown, and Walter A. Shaw 9 SPHINGOSINE KINASES: BIOCHEMISTRY, REGULATION, AND ROLES 153 Melissa R. Pitman, Kate E. Jarman, Tamara M. Leclercq, Duyen H. Pham, and Stuart M. Pitson 10 FUNCTIONAL AND PHYSIOLOGICAL ROLES OF SPHINGOSINE 1-PHOSPHATE TRANSPORTERS 185 Atsuo Kawahara and Tsuyoshi Nishi 11 LIPID PHOSPHATE PHOSPHATASES AND SIGNALING BY LYSOPHOSPHOLIPID RECEPTORS 201 Ganesh Venkatraman and David N. Brindley 12 LIPID PHOSPHATE PHOSPHATASES: RECENT PROGRESS AND ASSAY METHODS 229 Andrew J. Morris, Susan S. Smyth, Abdel K. Salous, and Andrew D. Renault 13 LYSOPHOSPHATIDIC ACID (LPA) SIGNALING AND CARDIOVASCULAR PATHOLOGY 265 Susan S. Smyth, Anping Dong, Jessica Wheeler, Manikandan Panchatcharam, and Andrew J. Morris 14 SPHINGOSINE 1-PHOSPHATE (S1P) SIGNALING IN CARDIOVASCULAR PHYSIOLOGY AND DISEASE 283 Bodo Levkau 15 SPHINGOSINE 1-PHOSPHATE (S1P) SIGNALING AND THE VASCULATURE 313 Christian Waeber 16 REGULATION OF THE NUCLEAR HORMONE RECEPTOR PPARγ BY ENDOGENOUS LYSOPHOSPHATIDIC ACIDS (LPAS) 349 Ryoko Tsukahara, Tamotsu Tsukahara, and Gabor Tigyi 17 MECHANISMS AND MODELS FOR ELUCIDATING THE CARDIAC EFFECTS OF SPHINGOSINE 1-PHOSPHATE (S1P) 373 Shigeki Miyamoto, Sunny Yang Xiang, Nicole H. Purcell, and Joan Heller Brown 18 NEURAL EFFECTS OF LYSOPHOSPHATIDIC ACID (LPA) SIGNALING 399 Nobuyuki Fukushima 19 WIDESPREAD EXPRESSION OF SPHINGOSINE KINASES AND SPHINGOSINE 1-PHOSPHATE (S1P) LYASE SUGGESTS DIVERSE FUNCTIONS IN THE VERTEBRATE NERVOUS SYSTEM 419 H. Meng and V.M. Lee 20 LYSOPHOSPHATIDIC ACID AND NEUROPATHIC PAIN: DEMYELINATION AND LPA BIOSYNTHESIS 433 Hiroshi Ueda 21 ROLE OF LYSOPHOSPHATIDIC ACID (LPA) IN BEHAVIORAL PROCESSES: IMPLICATIONS FOR PSYCHIATRIC DISORDERS 451 Guillermo Estivill-Torrús, Luis Javier Santín, Carmen Pedraza, Estela Castilla-Ortega, and Fernando Rodríguez de Fonseca 22 SPHINGOSINE 1-PHOSPHATE (S1P) SIGNALING AND LYMPHOCYTE EGRESS 475 Alejandra Mendoza, Lauren A. Pitt, and Susan R. Schwab 23 BIOLOGY REVEALED BY SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTOR GENE-ALTERED MICE 489 Maria L. Allende, Mari Kono, Aikaterini Alexaki, Christina Giannouli, Jiman Kang, Catherine C. Theisen, Eleanor L. Koerner, and Richard L. Proia 24 ROLE OF LYSOPHOSPHATIDIC ACID (LPA) IN THE INTESTINE 507 C. Chris Yun and Peijian He 25 LYSOPHOSPHOLIPID SIGNALING IN FEMALE AND MALE REPRODUCTIVE SYSTEMS 529 Xiaoqin Ye 26 THE GONADS AND THEIR MAGIC BULLET, LYSOPHOSPHATIDIC ACID: PHYSIOLOGICAL AND TOXICOLOGICAL FUNCTIONS OF LYSOPHOSPHATIDIC ACID (LPA) IN FEMALE AND MALE REPRODUCTIVE SYSTEMS 569 Lygia Therese Budnik, Bärbel Brunswig-Spickenheier, and Dieter Müller 27 LYSOPHOSPHOLIPID REGULATION OF LUNG FIBROSIS 587 Barry S. Shea and Andrew M. Tager 28 LYSOPHOSPHATIDIC ACID (LPA) SIGNALING AND BONE 609 Jean Pierre Salles, Sara Laurencin-Dalicieux, Françoise Conte-Auriol, Fabienne Briand-Mésange, and Isabelle Gennero 29 LYSOPHOSPHATIDIC ACID (LPA) SIGNALING AND BONE CANCER 627 Olivier Peyruchaud, Marion David, Timothy L. Macdonald, and Kevin R. Lynch 30 UNDERSTANDING THE FUNCTIONS OF LYSOPHOSPHATIDIC ACID RECEPTORS IN CANCER 641 Nattapon Panupinthu and Gordon B. Mills 31 LYSOPHOSPHATIDIC ACID RECEPTORS IN CANCER 661 Abir Mukherjee, Jinhua Wu, Yongling Gong, and Xianjun Fang 32 LPA RECEPTOR SUBTYPES LPA1 AND LPA2 AS POTENTIAL DRUG TARGETS 681 Gretchen Bain and T. Jon Seiders 33 CLINICAL INTRODUCTION OF LYSOPHOSPHATIDIC ACID (LPA) AND AUTOTAXIN ASSAYS 709 Yutaka Yatomi, Koji Igarashi, Kazuhiro Nakamura, Ryunosuke Ohkawa, Akiko Masuda, Akiko Suzuki, Tatsuya Kishimoto, Hitoshi Ikeda, and Junken Aoki 34 ANTIBODIES TO BIOACTIVE LYSOPHOSPHOLIPIDS 737 Roger A. Sabbadini, Jonathan M. Wojciak, Kelli Moreno, James S. Swaney, and Barbara Visentin INDEX 753

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Book SynopsisAn invaluable tool in Bioinformatics, this unique volume provides both theoretical and experimental results, and describes basic principles of computational intelligence and pattern analysis while deepening the reader''s understanding of the ways in which these principles can be used for analyzing biological data in an efficient manner. This book synthesizes current research in the integration of computational intelligence and pattern analysis techniques, either individually or in a hybridized manner. The purpose is to analyze biological data and enable extraction of more meaningful information and insight from it. Biological data for analysis include sequence data, secondary and tertiary structure data, and microarray data. These data types are complex and advanced methods are required, including the use of domain-specific knowledge for reducing search space, dealing with uncertainty, partial truth and imprecision, efficient linear and/or sub-linear scalability, incremental approaTrade Review"This collection of 16 papers, edited by Maulik (computer science and engineering, Jadavpur U., India), Bandyopadhyay (Indian Statistical Institute, India), and Wang (data and knowledge engineering, New Jersey Institute of Technology, US), brings together contributions from practitioners integrating computational intelligence and pattern analysis techniques for analyzing biological data, including sequence, structure, and microarray data. The material is organized into five sections that explore basic principles and methodologies of computational techniques, applications of computational intelligence and pattern analysis for biological sequence analysis, structural analysis; microarray data analysis, and systems biology." (Reference and Research Book News, February 2011)Table of ContentsPreface. Contributors. PART 1 INTRODUCTION. 1 Computational Intelligence: Foundations, Perspectives, and Recent Trends (Swagatam Das, Ajith Abraham, and B. K. Panigrahi). 2 Fundamentals of Pattern Analysis: A Brief Overview (Basabi Chakraborty). 3 Biological Informatics: Data, Tools, and Applications (Kevin Byron, Miguel Cervantes-Cervantes, and Jason T. L. Wang). PART II SEQUENCE ANALYSIS. 4 Promoter Recognition Using Neural Network Approaches (T. Sobha Rani, S. Durga Bhavani, and S. Bapi Raju). 5 Predicting microRNA Prostate Cancer Target Genes (Francesco Masulli, Stefano Rovetta, and Giuseppe Russo). PART III STRUCTURE ANALYSIS. 6 Structural Search in RNA Motif Databases (Dongrong Wen and Jason T. L. Wang). 7 Kernels on Protein Structures (Sourangshu Bhattacharya, Chiranjib Bhattacharyya, and Nagasuma R. Chandra). 8 Characterization of Conformational Patterns in Active and Inactive Forms of Kinases using Protein Blocks Approach (G. Agarwal, D. C. Dinesh, N. Srinivasan, and Alexandre G. de Brevern). 9 Kernel Function Applications in Cheminformatics (Aaron Smalter and Jun Huan). 10 In Silico Drug Design Using a Computational Intelligence Technique (Soumi Sengupta and Sanghamitra Bandyopadhyay). PART IV MICROARRAY DATA ANALYSIS. 11 Integrated Differential Fuzzy Clustering for Analysis of Microarray Data (Indrajit Saha and Ujjwal Maulik). 12 Identifying Potential Gene Markers Using SVM Classifier Ensemble (Anirban Mukhopadhyay, Ujjwal Maulik, and Sanghamitra Bandyopadhyay). 13 Gene Microarray Data Analysis Using Parallel Point Symmetry-Based Clustering (Ujjwal Maulik and Anasua Sarkar). PART V SYSTEMS BIOLOGY. 14 Techniques for Prioritization of Candidate Disease Genes (Jieun Jeong and Jake Y. Chen). 15 Prediction of Protein–Protein Interactions (Angshuman Bagchi). 16 Analyzing Topological Properties of Protein–Protein Interaction Networks: A Perspective Toward Systems Biology (Malay Bhattacharyya and Sanghamitra Bandyopadhyay). Index.

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Book SynopsisThis latest volume in the Harvey Lectures Series reflects the evolution of physiology and physiological chemistry into biochemistry and the development of molecular biology from the roots of bacteriology and biochemistry in the 20th and 21st centuries. This lecture series, collected and published annually, provides a series of distinguished lectures in the life sciences by world-renowned scientists in all areas of biomedicine. These lectures occur in New York City throughout the course of each academic year.Table of ContentsCONSTITUTION OF THE HARVEY SOCIETY. BY-LAWS OF THE HARVEY SOCIETY, INC. OFFICERS OF THE HARVEY SOCIETY. CORPORATE SPONSORS. PREFACE: A BRIEF HISTORY OF THE HARVEY SOCIETY, NEW YORK. HARVEY LECTURES 2006–2007. DRUGGING THE "UNDRUGGABLE" (Gregory L. Verdine, Ph.D., Erving Professor of Chemistry, Department of Stem Cell and Regenerative Biology, Chemistry and Chemical Biology, and Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts; Director, Chemical Biology Initiative and Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, Massachusetts). BASAL BODIES: THEIR ROLES IN GENERATING ASYMMETRY (Susan K. Dutcher, Ph.D., Professor of Genetics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri). PROTEIN TRANSPORT IN AND OUT OF THE ENDOPLASMIC RETICULUM (Tom A. Rapoport, Ph.D., Professor, Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts). SIGNALING NETWORKS THAT CONTROL SYNAPSE DEVELOPMENT AND COGNITIVE FUNCTION (Michael E. Greenberg, Ph.D., Professor of Neurology, Professor of Neurobiology, Children’s Hospital Boston, Program in Neurobiology, Harvard Medical School, Department of Neurobiology, Boston, Massachusetts). CILIA AND HEDGEHOG SIGNALING IN THE MOUSE EMBRYO (Kathryn V. Anderson, Ph.D., Program Chair, Developmental Biology Program, Sloan-Kettering Institute, New York, New York). DERIVATION OF ADULT STEM CELLS DURING EMBRYOGENESIS (Leonard I. Zon, M.D., Grousbeck Professor of Pediatrics, Children’s Hospital Boston, Howard Hughes Medical Institute, Boston, Massachusetts). TRACKING THE ROAD FROM INFLAMMATION TO CANCER: THE CRITICAL ROLE OF IκB KINASE (IKK) (Michael Karin, Ph.D., Distinguished Professor of Pharmacology, Laboratory of gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology Cancer Center, School of Medicine, University of California, San Diego, La Jolla, California). FORMER OFFICERS OF THE HARVEY SOCIETY. CUMULATIVE AUTHOR INDEX. ACTIVE MEMBERS.

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Book Synopsis* Comprehensively and systematically covers cellular membrane domains * Each chapter focuses on a different domain and is supported by figures defining the domains * A concluding chapter compares the protein composition of each domain, highlighting differences and similarities .Table of ContentsPREFACE. CONTRIBUTORS. PART I MEMBRANE DOMAINS. CHAPTER 1 CYTOSKELETON-INDUCED MESOSCALE DOMAINS (Ziya Kalay, Takahiro K. Fujiwara, and Akihiro Kusumi). CHAPTER 2 CLATHRIN-COATED PITS (James R. Thieman and Linton M. Traub). CHAPTER 3 CAVEOLAE (Dan Tse and Radu V. Stan). CHAPTER 4 LIPID RAFTS (Leonard J. Foster). CHAPTER 5 MODELING MEMBRANE DOMAINS (Daniel Coombs, Raibatak Das, and Jennifer S. Morrison). PART II ORGANELLAR DOMAINS. CHAPTER 6 MITOCHONDRIA (Michael Zick and Andreas S. Reichert). CHAPTER 7 THE ENDOPLASMIC RETICULUM (Jody Groenendyk and Marek Michalak). CHAPTER 8 THE GOLGI APPARATUS (James W. Dennis and Ivan R. Nabi). CHAPTER 9 ENDOSOMES (Thierry Galvez and Marino Zerial). CHAPTER 10 LYSOSOMES AND PHAGOSOMES (Guillaume Goyette and Michel Desjardins). CHAPTER 11 ENDOPLASMIC RETICULUM JUNCTIONS (Jesse T. Chao and Christopher J.R. Loewen). PART III CYTOSKELETAL DOMAINS. CHAPTER 12 THE ACTIN CYTOSKELETON (Jonathan A. Kelber and Richard L. Klemke). CHAPTER 13 MICROVILLI (Florent Ubelmann, Sylvie Robine, and Daniel Louvard). CHAPTER 14 MICROTUBULES (Geoffrey O. Wasteneys and Bettina Lechner). CHAPTER 15 CILIA (Laura K. Hilton and Lynne M. Quarmby). CHAPTER 16 INTERMEDIATE FILAMENTS (Normand Marceau, Anne Loranger, Stéphane Gilbert, and François Bordeleau). PART IV ADHESIVE AND COMMUNICATING DOMAINS. CHAPTER 17 FOCAL ADHESIONS (Caitlin Tolbert and Keith Burridge). CHAPTER 18 THE ADHERENS JUNCTION (Christopher P. Toret and W. James Nelson). CHAPTER 19 SPECIALIZED INTERCELLULAR JUNCTIONS IN EPITHELIAL CELLS: THE TIGHT JUNCTION AND DESMOSOME (Keli Kolegraff, Porfi rio Nava, and Asma Nusrat). CHAPTER 20 GAP JUNCTIONS (Jared M. Churko and Dale W. Laird). PART V POLARIZED CELLULAR DOMAINS. CHAPTER 21 EPITHELIAL DOMAINS (Nancy Philp, Liora Shoshani, Marcelino Cereijido, and Enrique Rodriguez-Boulan). CHAPTER 22 NEURONAL DOMAINS (Jennifer S. Goldman and Timothy E. Kennedy). PART VI DOMAINS REGULATING GENE EXPRESSION. CHAPTER 23 NUCLEAR DOMAINS (Dale Corkery, Kendra L. Cann, and Graham Dellaire). CHAPTER 24 THE NUCLEAR PORE (Richard W. Wozniak, Christopher Ptak, and John D. Aitchison). CHAPTER 25 CYTOPLASMIC RNA DOMAINS (Henry Parker and Tom C. Hobman). INDEX.

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Book SynopsisWritten by esteemed experts in the field, Models and Algorithms for Biomolecules and Molecular Networks provides readers with a global perspectives on the relevant biological phenomena, modeling frameworks, technical challenges, and algorithms.Table of ContentsList of Figures xiii List of Tables xix Foreword xxi Acknowledgments xxiii 1 Geometric Models of Protein Structure and Function Prediction 1 1.1 Introduction 1 1.2 Theory and Model 2 1.2.1 Idealized Ball Model 2 1.2.2 Surface Models of Proteins 3 1.2.3 Geometric Constructs 4 1.2.4 Topological Structures 6 1.2.5 Metric Measurements 9 1.3 Algorithm and Computation 13 1.4 Applications 15 1.4.1 Protein Packing 15 1.4.2 Predicting Protein Functions from Structures 17 1.5 Discussion and Summary 20 References 22 Exercises 25 2 Scoring Functions for Predicting Structure and Binding of Proteins 29 2.1 Introduction 29 2.2 General Framework of Scoring Function and Potential Function 31 2.2.1 Protein Representation and Descriptors 31 2.2.2 Functional Form 32 2.2.3 Deriving Parameters of Potential Functions 32 2.3 Statistical Method 32 2.3.1 Background 32 2.3.2 Theoretical Model 33 2.3.3 Miyazawa--Jernigan Contact Potential 34 2.3.4 Distance-Dependent Potential Function 41 2.3.5 Geometric Potential Functions 45 2.4 Optimization Method 49 2.4.1 Geometric Nature of Discrimination 50 2.4.2 Optimal Linear Potential Function 52 2.4.3 Optimal Nonlinear Potential Function 53 2.4.4 Deriving Optimal Nonlinear Scoring Function 55 2.4.5 Optimization Techniques 55 2.5 Applications 55 2.5.1 Protein Structure Prediction 56 2.5.2 Protein--Protein Docking Prediction 56 2.5.3 Protein Design 58 2.5.4 Protein Stability and Binding Affinity 59 2.6 Discussion and Summary 60 2.6.1 Knowledge-Based Statistical Potential Functions 60 2.6.2 Relationship of Knowledge-Based Energy Functions and Further Development 64 2.6.3 Optimized Potential Function 65 2.6.4 Data Dependency of Knowledge-Based Potentials 66 References 67 Exercises 75 3 Sampling Techniques: Estimating Evolutionary Rates and Generating Molecular Structures 79 3.1 Introduction 79 3.2 Principles of Monte Carlo Sampling 81 3.2.1 Estimation Through Sampling from Target Distribution 81 3.2.2 Rejection Sampling 82 3.3 Markov Chains and Metropolis Monte Carlo Sampling 83 3.3.1 Properties of Markov Chains 83 3.3.2 Markov Chain Monte Carlo Sampling 85 3.4 Sequential Monte Carlo Sampling 87 3.4.1 Importance Sampling 87 3.4.2 Sequential Importance Sampling 87 3.4.3 Resampling 91 3.5 Applications 92 3.5.1 Markov Chain Monte Carlo for Evolutionary Rate Estimation 92 3.5.2 Sequentail Chain Growth Monte Carlo for Estimating Conformational Entropy of RNA Loops 95 3.6 Discussion and Summary 96 References 97 Exercises 99 4 Stochastic Molecular Networks 103 4.1 Introduction 103 4.2 Reaction System and Discrete Chemical Master Equation 104 4.3 Direct Solution of Chemical Master Equation 106 4.3.1 State Enumeration with Finite Buffer 106 4.3.2 Generalization and Multi-Buffer dCME Method 108 4.3.3 Calculation of Steady-State Probability Landscape 108 4.3.4 Calculation of Dynamically Evolving Probability Landscape 108 4.3.5 Methods for State Space Truncation for Simplification 109 4.4 Quantifying and Controlling Errors from State Space Truncation 111 4.5 Approximating Discrete Chemical Master Equation 114 4.5.1 Continuous Chemical Master Equation 114 4.5.2 Stochastic Differential Equation: Fokker—Planck Approach 114 4.5.3 Stochastic Differential Equation: Langevin Approach 116 4.5.4 Other Approximations 117 4.6 Stochastic Simulation 118 4.6.1 Reaction Probability 118 4.6.2 Reaction Trajectory 118 4.6.3 Probability of Reaction Trajectory 119 4.6.4 Stochastic Simulation Algorithm 119 4.7 Applications 121 4.7.1 Probability Landscape of a Stochastic Toggle Switch 121 4.7.2 Epigenetic Decision Network of Cellular Fate in Phage Lambda 123 4.8 Discussions and Summary 127 References 128 Exercises 131 5 Cellular Interaction Networks 135 5.1 Basic Definitions and Graph-Theoretic Notions 136 5.1.1 Topological Representation 136 5.1.2 Dynamical Representation 138 5.1.3 Topological Representation of Dynamical Models 139 5.2 Boolean Interaction Networks 139 5.3 Signal Transduction Networks 141 5.3.1 Synthesizing Signal Transduction Networks 142 5.3.2 Collecting Data for Network Synthesis 146 5.3.3 Transitive Reduction and Pseudo-node Collapse 147 5.3.4 Redundancy and Degeneracy of Networks 153 5.3.5 Random Interaction Networks and Statistical Evaluations 157 5.4 Reverse Engineering of Biological Networks 159 5.4.1 Modular Response Analysis Approach 160 5.4.2 Parsimonious Combinatorial Approaches 166 5.4.3 Evaluation of Quality of the Reconstructed Network 171 References 173 Exercises 178 6 Dynamical Systems and Interaction Networks 183 6.1 Some Basic Control-Theoretic Concepts 185 6.2 Discrete-Time Boolean Network Models 186 6.3 Artificial Neural Network Models 188 6.3.1 Computational Powers of ANNs 189 6.3.2 Reverse Engineering of ANNs 190 6.3.3 Applications of ANN Models in Studying Biological Networks 192 6.4 Piecewise Linear Models 192 6.4.1 Dynamics of PL Models 194 6.4.2 Biological Application of PL Models 195 6.5 Monotone Systems 200 6.5.1 Definition of Monotonicity 201 6.5.2 Combinatorial Characterizations and Measure of Monotonicity 203 6.5.3 Algorithmic Issues in Computing the Degree of Monotonicity 𝖬 207 References 209 Exercises 214 7 Case Study of Biological Models 217 7.1 Segment Polarity Network Models 217 7.1.1 Boolean Network Model 218 7.1.2 Signal Transduction Network Model 218 7.2 ABA-Induced Stomatal Closure Network 219 7.3 Epidermal Growth Factor Receptor Signaling Network 220 7.4 C. elegans Metabolic Network 223 7.5 Network for T-Cell Survival and Death in Large Granular Lymphocyte Leukemia 223 References 224 Exercises 225 Glossary 227 Index 229

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Book Synopsis With addiction a key target for drug discovery efforts, this book fills an important and timely need for medicinal chemists who need to understand complex neuroscience issues. The author illustrates medicinal chemistry''s prominent role in treating addiction and covers specific drugs of abuse including narcotics, stimulants, depressants, nicotine, and marijuana. Interprets complex neuro- biological and pharmacological information, like the drug-reward system, for medicinal chemists Emphasizes neurotransmitters and neurochemical mechanisms of addictive drugs Pulls together information on the many potential drug targets for treating addiction Stresses unique medicinal chemistry problems when describing pharmacology testing methods and drug developmentTable of ContentsPreface xiii 1 What Is Drug Addiction? 1 1.1 Definitions 2 1.2 The Drugs of Abuse 4 1.3 Schedule of Controlled Substances 5 1.4 Some Facts From 2012 NSDUH Study 6 1.5 The Addictive State 8 1.6 Theories of Addiction 12 1.7 Comorbidity 13 1.8 Genetic Aspects of Addiction 13 1.9 Approved Medications for the Treatment of Substance Abuse and Addiction 16 2 Physiological Basis of Addiction—A Chemist's Interpretation 18 2.1 The Reward System 19 2.2 Neuroanatomy of the Reward System 21 2.3 Brief Review of the Central Nervous System and Addiction 22 2.4 Neurotransmitters and Their Targets 25 2.5 Neurocircuitry and Neurotransmitters in Addiction 32 2.6 Location of Receptors 62 2.7 An Example 64 2.8 Use of Biological Markers 65 2.9 Memories and Addiction 68 2.10 Stress the HPA Axis and Addiction 72 3 Behavioral Pharmacology and Addiction 76 3.1 Animal Models of Addiction 76 3.2 Self-Administration 80 3.3 Conditioned Place Preference 85 3.4 Tolerance 86 3.5 Extinction/Withdrawal 87 3.6 Reinstatement (Animal Models of Relapse) 87 3.7 Drug Discrimination 89 3.8 Operant Sensation Seeking Model 92 3.9 Use of Animal Behavioral Models 92 Acknowledgments 93 4 Medication Development for the Treatment of Drug Addiction 94 4.1 Lead Discovery 95 4.1.1 NIDA Addiction Treatment Discovery Program 96 4.2 Pharmacological Assays 103 4.3 Partial Agonist Approach 110 4.4 Allosteric Modulators 110 4.5 Functional Interactions Between Receptors 114 4.6 Multi-Target Drugs 121 4.7 Physicochemical Properties of CNS Drugs and Blood-Brain Barrier 124 4.8 Brain Imaging Agents 131 4.9 QT Prolongation 135 5 Medication Development for Narcotic Addiction 137 5.1 Pharmacology of Narcotic Addiction and Pain 138 5.2 Prescription Drug Addiction 139 5.3 Approved Medications 140 5.4 Medication Development 151 6 Medication Development for Stimulant Addiction 160 6.1 Pharmacology of Cocaine Addiction 160 6.2 Pharmacology of Methamphetamine Addiction 163 6.3 Medication Development 166 7 Medication Development for Depressant Addiction 213 7.1 Pharmacology of Alcohol Addiction 213 7.2 Approved Medications 214 7.3 Medication Development 219 7.4 Benzodiazepines 228 7.5 Barbiturates 229 8 Medication Development for Nicotine Addiction 230 8.1 Pharmacology of Nicotine Addiction 230 8.2 Approved Medications 232 8.3 Medication Development 237 9 Medication Development for Marijuana Addiction 240 9.1 Pharmacology of Marijuana Addiction 241 9.2 CB1 Antagonist: Rimonabant 243 9.3 Medication Development 244 10 Designer Drugs 252 10.1 Cathinone Drugs 253 10.2 MDMA—ECSTASY 256 10.3 Cannabinoid Designer Drugs 257 Conclusion 259 Appendix A Further Reading for Chemists Interested in a More Detailed Understanding of Addiction and the Central Nervous System 261 Appendix B Public Databases and Sources of Information of Interest to Medicinal Chemistry Addiction Researchers 262 Appendix C Glossary of Terms Used in Addiction Research 263 Appendix D Glossary of Terms Used in Medicinal Chemistry 271 References 290 Index 335

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Book SynopsisThis first edition text developed and evolved to meet three pedagogical goals we deemed essential for those studying allied health and are pre-professional. The use of microbiology case studies were modified to maintain their value as tools that result in critical thinking and knowledge retention while providing a more realistic context for preparing future health care professionals. Consequently, the text has real life, personally-oriented microbiology cases appropriate for those in nursing, pharmacy, and other allied health disciplines (pre-med, pre-PA, CLS, etc.). This format presents material as a story about the patient as well as information regarding their family circumstances, personal characteristics, and individual motivations.Table of ContentsPreface ix I. Community-Acquired Infections 1 A. Infections of the Skin, Eyes, and Underlying Tissues 2 1. A Homeless Hazard 3 2. "The Funk" 6 3. Hats Off to MRSA 8 4. Trouble Is Afoot 12 5. Down on the Farm 14 6. My, What Pretty Eyes You Have! 20 7. He Did It His Way 22 8. The "Tat" Is Where It’s At! 24 9. A Persistent Pimple 26 B. Nervous System Infections 29 1. Life in the Meningitis Belt 30 2. The Flying Mouse 31 3. Vacation Headaches 34 C. Infections of the Cardiovascular and Lymphatic Systems 36 1. A Common Opportunistic Pathogen 37 2. Unhappy Returns 39 3. Bunny Bits! 40 4. The Black Measles 44 5. Pucker Up! 47 6. Toxoplasmosis …Don’t Blame Fluffy! 50 D. Infections of the Respiratory System 53 1. Strawberry Red 54 2. An Evolving Situation 56 3. Q Fever …An Occupational Hazard 58 4. Swimming Pool Blues 61 E. Digestive System Infections 62 1. Hand Washing ABCs 63 2. A Distressing Side Effect 65 3. Hold the Onions 67 4. Diarrhea 101 69 5. An Uninvited Party Guest 70 F. Infections of the Urogenital Tract 72 1. The Honeymoon Is Over 73 2. Sex, Drugs, and Rock and Roll 77 3. A Bad First Impression 78 4. The Domino Effect 80 5. An Ongoing Problem 83 6. An Infectious New Lifestyle 87 II. Nosocomial Infections 89 1. A Nose for Trouble 91 2. A "Hep C" History Lesson 93 3. The "Superbug" 99 III. Family Health Care 103 A. Pediatric Infections 104 1. A New Twist on a Childhood Disease 105 2. Why Did the Chicken Pox Cross the Road? 106 3. Hand, Foot, and Mouth Disease 108 4. Seeing Red! 110 5. ‘Tis the Season 115 6. Splash! 117 B. Childbearing-Related Infections 119 1. Special Delivery 120 2. Cookout Concerns 122 C. Geriatric Infections 126 1. The Second Time Around 127 2. An Unexpected Outbreak 129 IV. Food Safety 131 1. No, Thanks, I Think I’ll Have the Turkey 132 2. Danger in the NICU 134 V. Regionally Acquired Infections 137 1. An Infectious Vacation 138 2. Rain, Rain, Go Away 141 ??

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Book SynopsisThis book applies systems biology methods to analyze Traditional Chinese Medicine (TCM), providing a comprehensive resource for modernization of TCM research and drug discovery.Table of ContentsForeword ix Preface xiii Abbreviations xvii 1 Introduction of Systems Biology in Traditional Chinese Medicine (tcm) 1 1.1 Characteristics and Compatibility Principles of Traditional Chinese Medicine (TCM) 1 1.2 Key Scientific Issues in TCM Modernization 9 1.3 Development of Systems Biology 16 1.4 Chemomics Integrated Systems Biology 19 1.5 Research Strategy and Prospective of Systems Biology in Tcm 25 References 34 2 Chemomics of Traditional Chinese Medicine 38 2.1 Characteristics and Research Difficulties in TCM 39 2.2 Background of TCM Chemomics’ Proposal and Development 45 2.3 Chemomics 52 2.4 Chemomics and the Research of Formulas 58 References 63 3 Technological Platform of Tcm Chemomics 66 3.1 Acquisition Methods and Techniques for TCM Chemomics 66 3.2 Characterization Techniques of Chemome-TCM Fingerprinting 73 3.3 Information Processing for the Study of TCM Chemomics 107 3.4 Development of an Intelligent Quality Control System in the Process of Chinese Medicine Production 119 References 127 4 Pharmacokinetic Investigation on Tcm Formulas Based on Global Systems Biology 131 4.1 Pharmacokinetic Characteristics of TCM Formulas 131 4.2 Methodology of Pharmacokinetics of TCM Formulas 133 4.3 Application of PK-PD Model in the Toxicological Research of Liushen Pills (LSP) 138 4.4 Prospect 143 References 144 5 Application of Genomics in the Research of Tcm 146 5.1 Genomics and TCM System Research 146 5.2 Prospect of Genomics in TCM Research 148 5.3 Cases of the Application of Genomics in TCM Research 148 References 168 6 Proteomics Study of Tcm 171 6.1 Proteomics in TCM Research 171 6.2 A Case Study of Proteomics in TCM 174 6.3 The Application of High Content Screening in TCM Research 182 6.4 Limitations and Prospect of TCM Proteomics 186 References 187 7 Application of Metabonomics in Research on Tcm 191 7.1 Current Research Situation of Metabonomics 191 7.2 Integration of Quantitative Metabonomics Platform Technology (qmpt) 191 7.3 Application of Metabonomics in the Field of Medicine 194 7.4 Examples of Metabonomic Research on TCM 198 References 206 8 Application of Chemometrics and Bioinformatics in Tcm Research 210 8.1 Introduction of Chemometrics 210 8.2 Chemometric Techniques and Their Applications in TCM Research 211 8.3 Introduction of Bioinformatics 216 8.4 Bioinformatics Techniques and Their Applications in the Research of TCM 219 8.5 Conclusions 222 References 224 9 Study of Integrated Biomarker System of Diabetic Nephropathy 228 9.1 Introduction of Diabetic Nephropathy 228 9.2 Mogensen Staging and TCM Typing of DN 234 9.3 The Metabonomics Study of DN 244 9.4 Condition of Metabolism after Treatment with TangShen Formula (TSF) 278 9.5 Genomics Study of Diabetic Neuropathy 286 9.6 The Integrated Biomarker System of DN 301 9.7 Conclusions 311 References 312 10 Chemomics Research on the Tcm Formula of The Qingkailing Injection 317 10.1 Chemomics Research of Qingkailing Injection 318 10.2 Pharmacodynamic Evaluation of Qingkailing Injection 330 10.3 Research on the Qingkailing Derived Formula 335 10.4 Conclusions 368 References 369 11 Integrated Global Systems Biology for the Research and Development of Chinese Medicine Shuanglong Formula 371 11.1 Brief Introduction to the Shuanglong Formula 371 11.2 Chemomics Study of the Shuanglong Formula 374 11.3 Pharmacodynamic Evaluation of SLF Effective Ingredients 384 11.4 Systems Biology Study of the Mechanism of Directed Differentiation of Stem Cells Induced by NSLF6 402 11.5 Anti-Myocardial Infarction Effect of NSLF6 426 11.6 Conclusions 429 References 430 12 Demonstrative Research on the Safety Evaluation of Liushen Pills 437 12.1 Introduction 437 12.2 Toxicity Study of Chansu 438 12.3 Chemomics Study of LSP 446 12.4 Assessment of Effectiveness and Safety of LSP 457 12.5 In Vivo Distribution and Metabonomics of LSP and Xionghuang 462 12.6 Metabonomic Research of LSP 467 12.7 Conclusions 477 References 478 Index 481

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Book SynopsisThe premiere two-volume reference on revelations from studying complex microbial communities in many distinct habitats Metagenomics is an emerging field that has changed the way microbiologists study microorganisms. It involves the genomic analysis of microorganisms by extraction and cloning of DNA from a group of microorganisms, or the direct use of the purified DNA or RNA for sequencing, which allows scientists to bypass the usual protocol of isolating and culturing individual microbial species. This method is now used in laboratories across the globe to study microorganism diversity and for isolating novel medical and industrial compounds. Handbook of Molecular Microbial Ecology is the first comprehensive two-volume reference to cover unculturable microorganisms in a large variety of habitats, which could not previously have been analyzed without metagenomic methodology. It features review articles as well as a large number of case studies, based largely on oTrade Review“Handbook of Molecular Microbial Ecology I is an invaluable reference for researchers in metagenomics, microbiology, and environmental microbiology; those working on the Human Microbiome Project; microbial geneticists; molecular microbial ecologists; and professionals in molecular microbiology and bioinformatics.” (Bois et Forets des Tropiques, 2011) "Handbook of Molecular Microbial Ecology I is an invaluable reference for researchers in metagenomics, microbiology, and environmental microbiology; those working on the Human Microbiome Project; microbial geneticists; molecular microbial ecologists; and professionals in molecular microbiology and bioinformatics." (TMCnet.com, 8 November 2011) Table of ContentsPreface. Contributors. 1. Introduction (Frans J. de Bruijn). Background Chapters. 2. DNA reassociation yields broad-scale information on metagenome complexity and microbial diversity (V. Torsvik). 3. Diversity of 23S rRNA genes within individual prokaryotic genomes (Zhiheng Pei). 4. Use of the rRNA operon and genomic repetitive sequences for the identification of bacteria (A. Nascimento). 5. Use of different PCR primer-based strategies for characterization of natural microbial communities (James Prosser). 6. Horizontal gene transfer and recombination shape mesorhizobial populations in the gene center of the host plants Astragalus luteolus and Astragalus ernestii in Sichuan, China (Xiaoping Zhang). 7. Amplified rDNA restriction analysis (ARDRA)for identification and phylogenetic placement of 16S-rDNA clones (Menachim Sklarz). 8. Clustering-based peak alignment algorithm for objective and quantitative analysis of DNA fingerprinting data (Satoshi Ishii). The Species Concept. 9. Population genomics informs our understanding of the bacterial species concept (Margaret Riley). 10. Genome analysis of Streptococcus agalactiae: Implication for the microbial “pan-genome” (R. Rappuoli). 11. Metagenomic insights into bacterial species (Kostas Konstantinidis). 12. Report of the ad hoc committee for the re-evaluation of the species definition in bacteriology (E. Stackebrandt). 13. Metagenomic Approaches for the Identification of Microbial Species (David Ward). Metagenomics. 14. Microbial Ecology in the age of metagenomics (Jianping Xu). 15. The enduring legacy of small rRNA in microbiology (Susan Tringe). 16. Pitfalls of PCR-based rRNA gene sequence analysis: an update on some parameters (Stackebrandt). 17. Empirical testing of 16S rRNA gene PCR primer pairs reveals variance in target specificity and efficacy not suggested by in silico analysis (Sergio Morales and Bill Holben). 18. The impact of next-generation sequencing technologies on (meta)genomics (George Weinstock). 19. Accuracy and quality of massively parallel DNA pyrosequencing (Susan Huse and David Mark Welch). 20. Environmental shotgun sequencing: Its potential and challenges for studying the hidden world of microbes (Jonathan Eisen). 21. Comparison of random sequence reads versus 16S rDNA sequences for estimating the biodiversity of a metagenomic library (C. Manischan). 22. Metagenomic libraries for functional screeing (Svein Valla). 23. GC Fractionation Allows Comparative Total Microbial Community Analysis, Enhances Diversity Assessment, and Facilitates of Minority Populations of Bacteria (Bill Holben). 24. Enriching plant microbiota for a metagenomic library construction (Ying Zeng). 25. Towards Automated Phylogenomic Inference (Wu and Eisen). 26. Integron first gene cassettes: a target to find adaptive genes in metagenomes (Christine Cagnon). 27. High-resolution metagenomics: assessing specific functional types in complex microbial communities (Christoserdova). 28. Gene-targeted –metagenomics (GT-metagenomics) to explore the extensive diversity of genes of interest in microbial communities (J. Tiedje). 29. Phylogenetic screening of metagenomic libraries using homing endonuclease restriction and marker insertion (Torsten Thomas). 30. ArrayOme- & tRNAcc-facilitated mobilome discovery: comparative genomics approaches for identifying rich veins of novel bacterial DNA sequences (Hong-Yu OU). 31. Sequence-Based Characterization of Microbiomes by Serial Analysis of Ribosomal Sequence Tags (SARST) (Zhongtang Yu). Consortia and Databases. 32. The metagenomics of plant pathogen-suppressive soils (J.D. Van Elsas). 33. Soil Metagenomic Exploration of the Rare Biosphere (Pascal Simonet and Timothy Vogel). 34. The BIOSPAS consortium: Soil Biology and agricultural production (Luis Wall). 35. The Human Microbiome Project (George Weinstock). 36. The Ribosomal Database Project: sequences and Software for high-throughput rRNA analysis (J. R. Cole, G. M. Garrity and Jim Tiedje). 37. The metagenomics RAST server- a public resource for the automatic phylogenetic and functional analysis of metagenomes (Folker Meyer). 38. The EBI Metagenomics Archive, Integration and Analysis resource (Apweiler). Computer Assisted Analysis. 39. Comparative metagenome analysis using MEGAN (Suparna Mitra and Daniel Huson). 40. Phylogenetic binning of metagenome sequence samples (Alice C. McHardy). 41. Gene prediction in metagenomic fragments with Orphelia: A large scale machine learning approach (Katharina Hoff). 42. Binning metagenomic sequences using seeded GSOm (Sen-Lin Tang). 43. Iterative read mapping and assembly allows the use of a more distant reference in metagenomic assembly (Bas E. Dutilh). 44. Ribosomal RNA identification in metagenomic and metatranscriptomic datasets (Li). 45. SILVA: comprehensive databases for quality checked and aligned ribosomal RNA sequence data compatible with ARB (Frank Gloeckner). 46. ARB; a software environment for sequence data (Wolfgang Ludwig). 47. The Phyloware Project: A software framework for phylogenomic virtue (Daniel Frank). 48. Metasim- A sequencing simulator for genomics and metagenomics (Daniel Richter). 49. ClustScan: an integrated program package for the detection and semi-automatic annotation of secondary metabolite clusters in genomic and metagenomic DNA datasets (Daslav Hranueli). 50. MetaGene; Prediction of prokaryotic and phage genes in metagenomic sequences (Noguchi). 51. primers4clades, a web server to design lineage-specific PCR primers for gene-targeted metagenomics (Pablo Vinuesa). 52. A parsimony approach to biological pathway reconstruction/inference for genomes and metagenomes (Y. Ye). 53. ESPRIT: estimating species richness using large collections of 16S rRNA data (Yijun Sun). Complementary Approaches. 54. (Meta) genomics approaches in systems biology (Manuel Ferrer). 55. Towards “focused metagenomics”: a case study combining DNA stable-isotope probing, multiple displacement amplification and metagenomics (J. Colin Murrell). 56. Galbraith, E. A., D. A. Antonopoulos, K. E. Nelson, and B. A. White . Suppressive subtractive hybridization reveals extensive horizontal transfer in the rumen metagenome (Bryan White). Microarrays. 57. GeoChip: A high throughout metagenomics technology for dissecting microbial community functional structure (J. Zhou). 58. Phylogenetic microarrays (PhyloChips) for analysis of complex microbial communities (Eoin Brodie). 59. Phenomics and Phenotype MicroArrays: Applications Complementing Metagenomics (Barry Bochner). 60. Microbial persistence in low biomass, extreme environments: The great unknown (Kasthuri Venkateswaran). 61. Application of phylogenetic oligonucleotide microarrays in microbial analysis (Nian Wang). Metatranscriptomics. 62. Isolation of mRNA from environmental microbial communities for metatranscriptomic analyses (P. Schenk). 63. Comparative day/night metatrancriptomic analysis of microbial communities in the North Pacific subtropical gyre (Rachel Poretski). 64. The “double RNA” approach to simultaneously assess the structure and function of environmental microbial communities by meta-transcriptomics (Tim Urich and Christa Schleper). 65. Soil eukaryotic diversity, a metatranscriptomic approach (Marmeisse). Metaproteomics. 66. Proteomics for the analysis of environmental stress responses in prokaryotes (Mark Suter). 67. Microbial community proteomics (Paul Wilmes). 68. Synchronicity between population structure and proteome profiles: A metaproteomic analysis of Chesapeake Bay bacterial communities (Feng Chen). 69. High-Throughput Cyanobacterial Proteomics: Systems-level Proteome Identification and Quantitation (Phillip Wright). 70. Protein Expression Profile of an Environmentally Important Bacterial Strain: the Chromate Response of Arthrobacter sp. strain FB24 (K. Henne). Metabolomics. 71. The small molecule dimension: Mass spectrometry based metabolomics, enzyme assays, and imaging (Trent R. Northen). 72. Metabolomics: high resolution tools offer to follow bacterial growth on a molecular level (Lucio Marianna and Philipp Schmitt-Kopplin). 73. Metabolic profiling of plant tissues by electrospray mass spectrometry (Heather Walker). 74. Metabolite identification, pathways and omic integration using online databases and tools (Matthew Davey). Single cell analysis. 75. Application of cytomics to separate natural microbial communities by their physiological properties (Susann Müller). 76. Capturing microbial populations for environmental genomics (A. Pernthaler/Wendeberg). 77. Microscopic single-cell isolation and multiple displacement amplification of genomes from uncultured prokaryotes (Peter Westermann).

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Book SynopsisThe late Navjot Sodhi conceived this book as a way of bringing to the forefront of our conservation planning for the tropics the views of people who were actually working and living there. In its 31 chapters, 55 authors present their views on the conservation problems they face and how they deal with them. Effective long term conservation in the tropics requires the full participation of local people, organizations and governments. The human population of tropical countries is expected to grow by more than 2.5 billion people over the next several decades, with expectations of increased consumption levels growing even more rapidly than population levels; clearly there will be a need for more trained conservationists and biologists. Significant levels of local involvement are essential to conservation success, with the rights of local people fully recognized, protected and fostered by governmental and international assistance. Overarching conservation plans are necessary, but cannot in themselves lead to success. The individual experiences presented in the pages of this book will provide useful models that may serve to build better and more sustainable lives for the people who live in the tropics and lead to the continued survival of as many species and functioning ecosystems as possible.Trade Review“Those involved in funding or planning programmes and projects in the tropics are sure to find this instructive.” (Biodivers Conserv, 1 October 2015) “Highly recommended. Upper-division undergraduates, graduate students, and researchers/faculty. (Choice, 1 May 2014)Table of ContentsList of Contributors vii Notes on Contributors xi Acknowledgments xx Remembering Navjot Sodhi: An Inspiring Mentor, Scholar, and Friend xxi Maharaj K. Pandit 1 INTRODUCTION: GIVING A VOICE TO THE TROPICS, 1 Luke Gibson and Peter H. Raven PART 1: FROM WITHIN THE REGION, 5 SECTION 1: AFRICA, 5 2 CONSERVATION PARADIGMS SEEN THROUGH THE EYES OF BONOBOS IN THE DEMOCRATIC REPUBLIC OF CONGO, 7 Bila-Isia Inogwabini and Nigel Leader-Williams 3 GOVERNANCE FOR EFFECTIVE AND EFFICIENT CONSERVATION IN ETHIOPIA, 19 Fikirte Gebresenbet, Wondmagegne Daniel, Amleset Haile and Hans Bauer 4 WILDLIFE IN JEOPARDY INSIDE AND OUTSIDE PROTECTED AREAS IN CÔTE D’IVOIRE: THE COMBINED EFFECTS OF DISORGANIZATION, LACK OF AWARENESS, AND INSTITUTIONAL WEAKNESS, 26 Inza Koné 5 CONSERVATION CHALLENGES FOR MADAGASCAR IN THE NEXT DECADE, 33 Hajanirina Rakotomanana, Richard K.B. Jenkins and Jonah Ratsimbazafy 6 CONSERVATION IN MAURITIUS AND RODRIGUES: CHALLENGES AND ACHIEVEMENTS FROM TWO ECOLOGICALLY DEVASTATED OCEANIC ISLANDS, 40 F.B. Vincent Florens 7 DESIGN AND OUTCOMES OF COMMUNITY FOREST CONSERVATION INITIATIVES IN CROSS RIVER STATE OF NIGERIA: A FOUNDATION FOR REDD+?, 51 Sylvanus Abua, Robert Spencer and Dimitrina Spencer 8 SHADES OF GREEN: CONSERVATION IN THE DEVELOPING ENVIRONMENT OF TANZANIA, 59 Flora I. Tibazarwa and Roy E. Gereau 9 SUSTAINABLE CONSERVATION: TIME FOR AFRICA TO RETHINK THE FOUNDATION, 65 Mwangi Githiru SECTION 2: AMERICAS, 75 10 CHALLENGES AND OPPORTUNITIES FOR BRIDGING THE RESEARCH–IMPLEMENTATION GAP IN ECOLOGICAL SCIENCE AND MANAGEMENT IN BRAZIL, 77 Renata Pardini, Pedro L.B. da Rocha, Charbel El-Hani and Flavia Pardini 11 CONSERVING BIODIVERSITY IN A COMPLEX BIOLOGICAL AND SOCIAL SETTING: THE CASE OF COLOMBIA, 86 Carolina Murcia, Gustavo H. Kattan, and Germán Ignacio Andrade-Pérez 12 INDIGENOUS RIGHTS, CONSERVATION, AND CLIMATE CHANGE STRATEGIES IN GUYANA, 97 Michelle Kalamandeen 13 CHALLENGES AND OPPORTUNITIES FOR CONSERVATION OF MEXICAN BIODIVERSITY, 105 Gerardo Ceballos and Andrés García 14 PARAGUAY’S CHALLENGE OF CONSERVING NATURAL HABITATS AND BIODIVERSITY WITH GLOBAL MARKETS DEMANDING FOR PRODUCTS, 113 Alberto Yanosky SECTION 3: ASIA, 121 15 LAND-USE CHANGE AND CONSERVATION CHALLENGES IN THE INDIAN HIMALAYA: PAST, PRESENT, AND FUTURE, 123 Maharaj K. Pandit and Virendra Kumar 16 CONSERVATION CHALLENGES IN INDONESIA, 134 Dewi M. Prawiradilaga and Herwasono Soedjito 17 SINGAPORE: HALF FULL OR HALF EMPTY?, 142 Richard T. Corlett 18 WANT TO AVERT EXTINCTIONS IN SRI LANKA? EMPOWER THE CITIZENRY!, 148 Rohan Pethiyagoda 19 CONSERVATION OF HORNBILLS IN THAILAND, 157 Pilai Poonswad, Vijak Chimchome, Narong Mahannop and Sittichai Mudsri SECTION 4: OCEANIA, 167 20 TIPPING POINTS AND THE VULNERABILITY OF AUSTRALIA’S TROPICAL ECOSYSTEMS, 169 William F. Laurance 21 BIODIVERSITY AND CONSERVATION IN THE PACIFIC ISLANDS: WHY ARE WE NOT SUCCEEDING?, 181 Gilianne Brodie, Patrick Pikacha and Marika Tuiwawa 22 WHEN WORLDS COLLIDE: CHALLENGES AND OPPORTUNITIES FOR CONSERVATION OF BIODIVERSITY IN THE HAWAIIAN ISLANDS, 188 Carter T. Atkinson, Thane K. Pratt, Paul C. Banko, James D. Jacobi and Bethany L. Woodworth 23 THE CHIMERA OF CONSERVATION IN PAPUA NEW GUINEA AND THE CHALLENGE OF CHANGING TRAJECTORIES, 197 Phil Shearman PART 2 THOUGHTS FROM DIASPORA, 205 24 COMPLEX FORCES AFFECT CHINA’S BIODIVERSITY, 207 Jianguo Liu 25 GOVERNANCE AND CONSERVATION IN THE TROPICAL DEVELOPING WORLD, 216 Kelvin S.-H. Peh 26 KNOWLEDGE, INSTITUTIONS, AND HUMAN RESOURCES FOR CONSERVATION OF BIODIVERSITY, 226 Kamaljit S. Bawa 27 PEOPLE, PLANTS AND POLLINATORS: UNITING CONSERVATION, FOOD SECURITY, AND SUSTAINABLE AGRICULTURE IN EAST AFRICA, 232 Dino J. Martins 28 BALANCING SOCIETIES’ PRIORITIES: A SCIENCE-BASED APPROACH TO SUSTAINABLE DEVELOPMENT IN THE TROPICS, 239 Lian Pin Koh 29 BIODIVERSITY CONSERVATION PERFORMANCE OF SUSTAINABLE-USE TROPICAL FOREST RESERVES, 245 Carlos A. Peres 30 CONCLUDING REMARKS: LESSONS FROM THE TROPICS, 254 Luke Gibson and Peter H. Raven Index 259

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Book SynopsisEffective Learning in the Life Sciences is intended to help ensure that each student achieves his or her true potential by learning how to solve problems creatively in laboratory, field or other workplace setting. Each chapter describes state of the art approaches to learning and teaching and will include case studies, worked examples and a section that lists additional online and other resources. All of the chapters are written from the perspective both of students and academics and emphasize and embrace effective scientific method throughout. This title also draws on experience from a major project conducted by the Centre for Bioscience, with a wide range of collaborators, designed to identify and implement creative teaching in bioscience laboratories and field settings. With a strong emphasis on students thinking for themselves and actively learning about their chosen subject Effective Learning in the Life Sciences provides an invaluable guide to makiTrade Review"I highly recommend the essential and student potential developing book Effective Learning in the Life Sciences: How Students Can Achieve Their Full Potential, edited by David J. Adams, Ph.D., to any students, educators, bioscience practitioners, business leaders, or policy makers seeking a useful and accessible guide to learning, instructing, and understanding the wide array of concepts and issues within the fields of biology, bioscience, and the life sciences. This book is a must read for anyone involved with the biosciences in education, policy making, or a business environment." (Blog Business World, 9 December 2011) Table of ContentsChapter 1: Creativity (David J. Adams & Kevin Byron). Chapter 2: Problem solving: developing critical, evaluative and analytical thinking skills (Tina L. Overton). Chapter 3: In the Laboratory )Pauline Millican & David J. Adams). Chapter 4: Fieldwork (Julie Peacock, Julian R. Park & Alice Mauchline). Chapter 5: In vivo work (Dave Lewis). Chapter 6: Research projects (Martin Luck). Chapter 7: Maths and Stats for Biologists (Dawn Hawkins). Chapter 8: E-learning for biologists (Jo Badge, Jon Scott, Terry McAndrew). Chapter 9: Bioethics (Chris Willmott). Chapter 10: Assessment, Feedback and Review (Stephen Maw & Paul Orsmond). Chapter 11: Communication in the Biosciences (Maureen Dawson & Joanna Verran). Chapter 12: Bioenterprise (Lee J. Beniston, David J. Adams & Carol Wakeford).

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Book SynopsisThis is a comprehensive research guide that describes both the key new techniques and more established methods. Every chapter discusses the merits and limitations of the various approaches and then provides selected tried-and-tested protocols, as well as a plethora of good practical advice, for immediate use at the bench.Trade Review"It will be a great resource for students and established researchers who want to learn more about modern cell culture techniques." (Doody's, 13 January 2012)Table of ContentsContributors. Preface. Abbreviations. Protocols. 1 The Cell Culture Laboratory (Sue Clarke and Janette Dillon). 2 Sterilization (Peter L. Roberts). 3 Microscopy of Living Cells (Colin Gray and Daniel Zicha). 4 Basic Techniques and Media, the Maintenance of Cell Lines, and Safety (John M. Davis). 5 Development and Optimization of Serum- and Protein-free Culture Media (Stephen F. Gorfien and David W. Jayme). 6 Cryopreservation and Banking of Cell Lines (Glyn N. Stacey, Ross Hawkins and Roland A. Fleck). 7 Primary Culture of Specific Cell Types and the Establishment of Cell Lines (Kee Woei Ng, Mohan Chothirakottu Abraham, David Tai Wei Leong, Chris Morris and Jan-Thorsten Schantz). 8 Cloning (John Clarke, Alison Porter and John M. Davis). 9 The Quality Control of Animal Cell Lines and the Prevention, Detection and Cure of Contamination (Peter Thraves and Cathy Rowe). 10 Systems for Cell Culture Scale-up (Jennifer Halsall and John M. Davis). 11 Good Laboratory Practice in the Cell Culture Laboratory (Barbara Orton). Index. Colour plates.

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Book SynopsisOne of the first textbooks in this emerging important field of ecology. Most of ecology is about metabolism: the ways that organisms use energy and materials. The energy requirements of individuals their metabolic rates vary predictably with their body size and temperature.Trade Review“If you want a thorough, up-to-date coverage of research based upon the MTE and its many applications, this book is a must-read.” (Ecology, 1 January 2013) “Intended to be accessible to upper-level undergraduates, the book should be widely-read by anyone who seeks a more powerful science of ecology.” (British Ecological Society Bulletin, 1 December 2012) “The book is copiously illustrated, and the complex mathematics limited and treated discreetly so the nonmathematician can follow the logic. A necessary read for ecologists. Summing Up: Highly recommended. Upper-division undergraduates and above.” (Choice, 1 November 2012) Table of ContentsNotes on contributors vii Preface xiv Introduction: Metabolism as the basis for a theoretical unification of ecology 1James H. Brown, Richard M. Sibly, and Astrid Kodric-Brown Part I Foundations 7 1 Methodological tools 9Ethan P. White, Xiao Xiao, Nick J. B. Isaac, and Richard M. Sibly 2 The metabolic theory of ecology and its central equation 21James H. Brown and Richard M. Sibly 3 Stoichiometry 34Michael Kaspari 4 Modeling metazoan growth and ontogeny 48Andrew J. Kerkhoff 5 Life history 57Richard M. Sibly 6 Behavior 67April Hayward, James F. Gillooly, and Astrid Kodric-Brown 7 Population and community ecology 77Nick J.B. Isaac, Chris Carbone, and Brian Mcgill 8 Predator–prey relations and food webs 86Owen L. Petchey and Jennifer A. Dunne 9 Ecosystems 99Kristina J. Anderson-Teixeira and Peter M. Vitousek 10 Rates of metabolism and evolution 112John L. Gittleman and Patrick R. Stephens 11 Biodiversity and its energetic and thermal controls 120David Storch Part II Selected Organisms and Topics 133 12 Microorganisms 135Jordan G. Okie 13 Phytoplankton 154Elena Litchman 14 Land plants: new theoretical directions and empirical prospects 164Brian J. Enquist and Lisa Patrick Bentley 15 Marine invertebrates 188Mary I. O’connor and John F. Bruno 16 Insect metabolic rates 198James S. Waters and Jon F. Harrison 17 Terrestrial vertebrates 212William Karasov 18 Seabirds and marine mammals 225Daniel P. Costa and Scott A. Shaffer 19 Parasites 234Ryan F. Hechinger, Kevin D. Lafferty, and Armand M. Kuris 20 Human ecology 248Marcus J. Hamilton, Oskar Burger, and Robert S. Walker Part III Practical Applications 259 21 Marine ecology and fisheries 261Simon Jennings, Ken H. Andersen, and Julia L. Blanchard 22 Conservation biology 271Alison G. Boyer and Walter Jetz 23 Climate change 280Kristina J. Anderson-Teixeira, Felisa A. Smith, and S. K. Morgan Ernest 24 Beyond biology 293Melanie E. Moses and Stephanie Forrest 25 Synthesis and prospect 302James H. Brown, Richard M. Sibly, and Astrid Kodric-Brown Glossary 306 References 309 Index 361

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Book SynopsisIn Alternative Ecological Risk Assessment the author, Lawrence V. Tannenbaum, provides a critical review of current practices in the ecological risk assessment field and proposes alternatives that are supported by established science and keen observation. It is hoped that this approach will pave the way to a greater understanding of what appropriate and useful ecological assessment for contaminated sites should entail. He demonstrates that in most cases current practices do not provide for an assessment of ecological risk, and moreover, that endeavoring to assess ecological risk is actually an unnecessary undertaking at conventional hazardous waste sites. (He states, for example, that the concept of scale is often ignored by practitioners, questions why animals like deer are routinely assessed at 5-acre sites, and challenges the ecotoxicology data currently used.) The book is aimed at students and professionals in the fields of environmental science, ecology, ecTable of ContentsPreface ixAcknowledgments xi1 An introduction and overview 12 Facing the music: understanding what ERA is . . . and is not 143 Alternative exposure assessment 284 Toxicology and toxicity assessment in ERA revisited 565 Risk characterization versus site ecological assessment: Old and new 996 Case study: Problem formulation versus making problems for yourself 1137 Getting beyond ERA 1378 A new ecological assessment paradigm for historically contaminated sites: Direct health status assessment 1609 Is RSA the answer to ERA? 179Index 201

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Book SynopsisIn 1837 a young Charles Darwin took his notebook, wrote I think and then sketched a rudimentary, stick-like tree. Each branch of Darwin's tree of life told a story of survival and adaptation adaptation of animals and plants not just to the environment but also to life with other living things.Trade Review“In summary, The Evolutionary Strategies that Shape Ecosystemsis well-written and stimulating, and encourages its readers to think about how all the pieces of ecology might fit together, from the scale of an individual organism to entire ecosystems. It would make a valuable addition to the library of any scientist interested in ecological and evolutionary strategies.” (Austral Ecology, 1 October 2013) “Certainly I have found this a useful way to think about conservation Management.” (British Ecological Society, 1 April 2013) “The case studies range from microbes to animals, and even palaeontology is included in the mix, making the book a very comprehensive resource for those interested in eco-evolutionary dynamics.” (Teaching Biology, 20 December 2012) “I recommend this book to people interested in evolutionary and ecological strategies in ecosystems, to those who think about universal patterns in organism life history tactics and also to those who love the challenge of linking ecology and evolution.” (Basic and Applied Ecology, 1 November 2012) “A significant contribution to the field and a must read for ecologists. Summing Up: Highly recommended. Upper-division undergraduates and above.” (Choice, 1 October 2012)Table of ContentsPreface x Chapter Summaries xii Acknowledgements xviii Introduction 1 1 Evolution and Ecology: a Janus Perspective? 3 Evolutionary biology 3 Ecology 4 The emergence of a science of adaptive strategies 6 Summary 7 2 Primary Strategies: the Ideas 8 MacArthur's 'blurred vision' 9 The mechanism of convergence; trade-offs 10 The theory of r- and K-selection 11 CSR Theory 12 Summary 23 3 Primary Adaptive Strategies in Plants 25 The search for adaptive strategies 26 Theoretical work 26 Measuring variation in plant traits: screening programmes 28 Screening of plant growth rates 29 The Integrated Screening Programme 29 Further trait screening 34 The application of CSR theory 34 Virtual plant strategies 36 Summary 38 4 Primary Adaptive Strategies in Organisms Other Than Plants 40 The architecture of the tree of life 41 r, K and beyond K 42 Empirical evidence for three primary strategies in animals 43 The universal three-way trade-off 44 Mammalia (mammals) 46 Aves (avian therapods) 53 Squamata (snakes and lizards) (with notes on other extant reptile clades) 56 Amphibia (amphibians) 60 Osteichthyes (bony fi shes) 61 Chondrichthyes (cartilaginous fi shes) 65 Insecta (insects) 68 Aracnida (spiders, scorpions, mites and ticks) 72 Crustacea (crustaceans) 74 Echinodermata (sea urchins, starfi sh, crinoids, sea cucumbers) 75 Mollusca (snails, clams, squids) 77 Annelida (segmented worms) 79 Cnidaria (corals, sea anemones, jellyfi sh, hydras, sea pens) 81 Eumycota (fungi) (including notes on lichens) 83 Archaea 84 Proteobacteria 86 Firmicutes 87 Cyanobacteria 88 Viruses 90 Extinct groups 94 Universal adaptive strategy theory – the evolution of CSR and beyond K theories 99 First steps towards a universal methodology 100 Summary 103 5 From Adaptive Strategies to Communities 105 Plant communities 106 Productive disturbed communities 107 Productive undisturbed communities 108 Unproductive relatively undisturbed communities 111 Plant community composition 111 The humped-back model 114 Origins 114 Formulation 115 Independent confi rmation and compatibility with new research 116 Species-pools, fi lters and community composition 121 Evidence for the action of twin fi lters 128 Additional mechanisms promoting diversity 132 Genetic diversity, intraspecifi c functional diversity and species diversity 132 Microbial communities 136 The effects of plant strategies on soil microbial communities 139 Facilitation in bacterial communities 141 Coexistence in marine surface waters 142 Novel techniques for investigating microbial adaptive strategies 142 Animal communities 144 Primary producers delimit animal diversity/productivity relationships 145 Twin fi lters and animal community assembly 150 Adaptive radiation and community assembly 154 Summary 160 6 From Strategies to Ecosystems 163 Back to Bayreuth 164 The Darwinian basis of ecosystem assembly 167 How do primary adaptive strategies drive ecosystem functioning? 168 The plant traits that drive ecosystems 169 The propagation of trait infl uences through food chains 176 Complicating factors 178 Ecosystem processes 180 Dominance and mass ratio effects 180 Fluxes and feedbacks between communities 181 Top-down control by herbivores 187 Top-down control by carnivores 189 The key role of eco-evolutionary dynamics 190 Summary 192 7 The Path from Evolution to Ecology 194 What has been learned? 194 What are the implications for conservation and management? 198 Research priorities for the next decade 199 References 202 Organism Index 235 Subject Index 241

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Book SynopsisThe latest edition of this highly successful textbook introduces the key techniques and concepts involved in cloning genes and in studying their expression and variation. The new edition features: Increased coverage of whole-genome sequencing technologies and enhanced treatment of bioinformatics. Clear, two-colour diagrams throughout. A dedicated website including all figures. Noted for its outstanding balance between clarity of coverage and level of detail, this book provides an excellent introduction to the fast moving world of molecular genetics.Trade Review“This third edition is absolutely necessary to incorporate the recent advances, such as genome sequencing, polymerase chain reaction, and microarray technology, in this field.” (Doody’s, 19 October 2012)Table of ContentsPreface xiii 1 From Genes to Genomes 1 1.1 Introduction 1 1.2 Basic molecular biology 4 1.2.1 The DNA backbone 4 1.2.2 The base pairs 6 1.2.3 RNA structure 10 1.2.4 Nucleic acid synthesis 11 1.2.5 Coiling and supercoilin 11 1.3 What is a gene? 13 1.4 Information flow: gene expression 15 1.4.1 Transcription 16 1.4.2 Translation 19 1.5 Gene structure and organisation 20 1.5.1 Operons 20 1.5.2 Exons and introns 21 1.6 Refinements of the model 22 2 How to Clone a Gene 25 2.1 What is cloning? 25 2.2 Overview of the procedures 26 2.3 Extraction and purification of nucleic acids 29 2.3.1 Breaking up cells and tissues 29 2.3.2 Alkaline denaturation 31 2.3.3 Column purification 31 2.4 Detection and quantitation of nucleic acids 32 2.5 Gel electrophoresis 33 2.5.1 Analytical gel electrophoresis 33 2.5.2 Preparative gel electrophoresis 36 2.6 Restriction endonucleases 36 2.6.1 Specificity 37 2.6.2 Sticky and blunt ends 40 2.7 Ligation 42 2.7.1 Optimising ligation conditions 44 2.7.2 Preventing unwanted ligation: alkaline phosphatase and double digests 46 2.7.3 Other ways of joining DNA fragments 48 2.8 Modification of restriction fragment ends 49 2.8.1 Linkers and adaptors 50 2.8.2 Homopolymer tailing 52 2.9 Plasmid vectors 53 2.9.1 Plasmid replication 54 2.9.2 Cloning sites 55 2.9.3 Selectable markers 57 2.9.4 Insertional inactivation 58 2.9.5 Transformation 59 2.10 Vectors based on the lambda bacteriophage 61 2.10.1 Lambda biology 61 2.10.2 In vitro packaging 65 2.10.3 Insertion vectors 66 2.10.4 Replacement vectors 68 2.11 Cosmids 71 2.12 Supervectors: YACs and BACs 72 2.13 Summary 73 3 Genomic and cDNA Libraries 75 3.1 Genomic libraries 77 3.1.1 Partial digests 77 3.1.2 Choice of vectors 80 3.1.3 Construction and evaluation of a genomic library 83 3.2 Growing and storing libraries 86 3.3 cDNA libraries 87 3.3.1 Isolation of mRNA 88 3.3.2 cDNA synthesis 89 3.3.3 Bacterial cDNA 93 3.4 Screening libraries with gene probes 94 3.4.1 Hybridization 94 3.4.2 Labelling probes 98 3.4.3 Steps in a hybridization experiment 99 3.4.4 Screening procedure 100 3.4.5 Probe selection and generation 101 3.5 Screening expression libraries with antibodies 103 3.6 Characterization of plasmid clones 106 3.6.1 Southern blots 107 3.6.2 PCR and sequence analysis 108 4 Polymerase Chain Reaction (PCR) 109 4.1 The PCR reaction 110 4.2 PCR in practice 114 4.2.1 Optimisation of the PCR reaction 114 4.2.2 Primer design 115 4.2.3 Analysis of PCR products 117 4.2.4 Contamination 118 4.3 Cloning PCR products 119 4.4 Long-range PCR 121 4.5 Reverse-transcription PCR 123 4.6 Quantitative and real-time PCR 123 4.6.1 SYBR Green 123 4.6.2 TaqMan 125 4.6.3 Molecular beacons 125 4.7 Applications of PCR 127 4.7.1 Probes and other modified products 127 4.7.2 PCR cloning strategies 128 4.7.3 Analysis of recombinant clones and rare events 129 4.7.4 Diagnostic applications 130 5 Sequencing a Cloned Gene 131 5.1 DNA sequencing 131 5.1.1 Principles of DNA sequencing 131 5.1.2 Automated sequencing 136 5.1.3 Extending the sequence 137 5.1.4 Shotgun sequencing; contig assembly 138 5.2 Databank entries and annotation 140 5.3 Sequence analysis 146 5.3.1 Identification of coding region 146 5.3.2 Expression signals 147 5.4 Sequence comparisons 148 5.4.1 DNA sequences 148 5.4.2 Protein sequence comparisons 151 5.4.3 Sequence alignments: Clustal 157 5.5 Protein structure 160 5.5.1 Structure predictions 160 5.5.2 Protein motifs and domains 162 5.6 Confirming gene function 165 5.6.1 Allelic replacement and gene knockouts 166 5.6.2 Complementation 168 6 Analysis of Gene Expression 169 6.1 Analysing transcription 169 6.1.1 Northern blots 170 6.1.2 Reverse transcription-PCR 171 6.1.3 In situ hybridization 174 6.2 Methods for studying the promoter 174 6.2.1 Locating the promoter 175 6.2.2 Reporter genes 177 6.3 Regulatory elements and DNA-binding proteins 179 6.3.1 Yeast one-hybrid assays 179 6.3.2 DNase I footprinting 181 6.3.3 Gel retardation assays 181 6.3.4 Chromatin immunoprecipitation (ChIP) 183 6.4 Translational analysis 185 6.4.1 Western blots 185 6.4.2 Immunocytochemistry and immunohistochemistry 187 7 Products from Native and Manipulated Cloned Genes 189 7.1 Factors affecting expression of cloned genes 190 7.1.1 Transcription 190 7.1.2 Translation initiation 192 7.1.3 Codon usage 193 7.1.4 Nature of the protein product 194 7.2 Expression of cloned genes in bacteria 195 7.2.1 Transcriptional fusions 195 7.2.2 Stability: conditional expression 198 7.2.3 Expression of lethal genes 201 7.2.4 Translational fusions 201 7.3 Yeast systems 204 7.3.1 Cloning vectors for yeasts 204 7.3.2 Yeast expression systems 206 7.4 Expression in insect cells: baculovirus systems 208 7.5 Mammalian cells 209 7.5.1 Cloning vectors for mammalian cells 210 7.5.2 Expression in mammalian cells 213 7.6 Adding tags and signals 215 7.6.1 Tagged proteins 215 7.6.2 Secretion signals 217 7.7 In vitro mutagenesis 218 7.7.1 Site-directed mutagenesis 218 7.7.2 Synthetic genes 223 7.7.3 Assembly PCR 223 7.7.4 Synthetic genomes 224 7.7.5 Protein engineering 224 7.8 Vaccines 225 7.8.1 Subunit vaccines 225 7.8.2 DNA vaccines 226 8 Genomic Analysis 229 8.1 Overview of genome sequencing 229 8.1.1 Strategies 230 8.2 Next generation sequencing (NGS) 231 8.2.1 Pyrosequencing (454) 232 8.2.2 SOLiD sequencing (Applied Biosystems) 235 8.2.3 Bridge amplification sequencing (Solexa/Ilumina) 237 8.2.4 Other technologies 239 8.3 De novo sequence assembly 239 8.3.1 Repetitive elements and gaps 240 8.4 Analysis and annotation 242 8.4.1 Identification of ORFs 243 8.4.2 Identification of the function of genes and their products 250 8.4.3 Other features of nucleic acid sequences 251 8.5 Comparing genomes 256 8.5.1 BLAST 256 8.5.2 Synteny 257 8.6 Genome browsers 258 8.7 Relating genes and functions: genetic and physical maps 260 8.7.1 Linkage analysis 261 8.7.2 Ordered libraries and chromosome walking 262 8.8 Transposon mutagenesis and other screening techniques 263 8.8.1 Transposition in bacteria 263 8.8.2 Transposition in Drosophila 266 8.8.3 Transposition in other organisms 268 8.8.4 Signature-tagged mutagenesis 269 8.9 Gene knockouts, gene knockdowns and gene silencing 271 8.10 Metagenomics 273 8.11 Conclusion 274 9 Analysis of Genetic Variation 275 9.1 Single nucleotide polymorphisms 276 9.1.1 Direct sequencing 278 9.1.2 SNP arrays 279 9.2 Larger scale variations 280 9.2.1 Microarrays and indels 281 9.3 Other methods for studying variation 282 9.3.1 Genomic Southern blot analysis: restriction fragment length polymorphisms (RFLPs) 282 9.3.2 VNTR and microsatellites 285 9.3.3 Pulsed-field gel electrophoresis 287 9.4 Human genetic variation: relating phenotype to genotype 289 9.4.1 Linkage analysis 289 9.4.2 Genome-wide association studies (GWAS) 292 9.4.3 Database resources 294 9.4.4 Genetic diagnosis 294 9.5 Molecular phylogeny 295 9.5.1 Methods for constructing trees 298 10 Post-Genomic Analysis 305 10.1 Analysing transcription: transcriptomes 305 10.1.1 Differential screening 306 10.1.2 Other methods: transposons and reporters 308 10.2 Array-based methods 308 10.2.1 Expressed sequence tag (EST) arrays 309 10.2.2 PCR product arrays 310 10.2.3 Synthetic oligonucleotide arrays 312 10.2.4 Important factors in array hybridization 313 10.3 Transcriptome sequencing 315 10.4 Translational analysis: proteomics 316 10.4.1 Two-dimensional electrophoresis 317 10.4.2 Mass spectrometry 318 10.5 Post-translational analysis: protein interactions 320 10.5.1 Two-hybrid screening 320 10.5.2 Phage display libraries 321 10.6 Epigenetics 323 10.7 Integrative studies: systems biology 324 10.7.1 Metabolomic analysis 324 10.7.2 Pathway analysis and systems biology 325 11 Modifying Organisms: Transgenics 327 11.1 Transgenesis and cloning 327 11.1.1 Common species used for transgenesis 328 11.1.2 Control of transgene expression 330 11.2 Animal transgenesis 333 11.2.1 Basic methods 333 11.2.2 Direct injection 333 11.2.3 Retroviral vectors 335 11.2.4 Embryonic stem cell technology 336 11.2.5 Gene knockouts 339 11.2.6 Gene knock-down technology: RNA interference 340 11.2.7 Gene knock-in technology 341 11.3 Applications of transgenic animals 342 11.4 Disease prevention and treatment 343 11.4.1 Live vaccine production: modification of bacteria and viruses 343 11.4.2 Gene therapy 346 11.4.3 Viral vectors for gene therapy 347 11.5 Transgenic plants and their applications 349 11.5.1 Introducing foreign genes 349 11.5.2 Gene subtraction 351 11.5.3 Applications 352 11.6 Transgenics: a coda 353 Glossary 355 Bibliography 375 Index 379

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Book SynopsisEnvironmental Biotechnology: Theory and Applications, 2nd Edition is designed to draw together the microscopic, functional level and the macroscopic, practical applications of biotechnology and to explain how the two relate within an environmental context. It presents the practical biological approaches currently employed to address environmental problems and provides the reader with a working knowledge of the science that underpins them. Biotechnology has now become a realistic alternative to many established approaches for manufacturing, land remediation, pollution control and waste management and is therefore an essential aspect of environmental studies. Fully updated to reflect new developments in the field and with numerous new case studies throughout this edition will be essential reading for undergraduates and masters students taking modules in Biotechnology or Pollution Control as part of Environmental Science, Environmental Management or Environmental BiologyTable of ContentsForeword. Preface. Acknowledgements. Chapter 1 Introduction to Environmental Biotechnology. Chapter 2 Microbes and Metabolism. Chapter 3 Fundamentals of Biological Intervention. Chapter 4 Pollution and Pollution Control. Chapter 5 Contaminated Land and Bio-Remediation. Chapter 6 Aerobes and Effluents. Chapter 7 Phytotechnology and Photosynthesis. Chapter 8 Biotechnology and Waste. Chapter 9 Genetic Manipulation. Chapter 10 Integrated Environmental Biotechnology. Bibliography and Suggested Further Reading. Index.

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Book SynopsisMediterranean Mountain Environments places its emphasis on physical geography while still adopting an integrated approach to the whole subject area. The book draws examples from a wide range of environments, demonstrating the interaction between human and physical processes responsible for shaping mountain areas.Trade Review“The diversity of contributions is well organized, making Mediterranean Mountain Environmentsuseful also as textbook, as it is presenting general concepts and detailed case-studies at the time.” (Ethology Ecology & Evolution, 1 May 2013) “This framework could be a useful starting point for a future edition of this book, which could truly be a textbook with chapters on both physical and human geography, drawing together all of the knowledge deriving from research in the mountains of all of the countries of the region, including Algeria, Cyprus, Lebanon, Turkey, and the countries of the West Balkans, which rarely feature in this book.” (Mountain Research and Development, 1 August 2013) “It will provide ideal reading for students, perhaps as the textbook for a field course.” (Frontiers of Biogeography, 1 December 2012) Table of ContentsList of contributors xi Preface xiii Acknowledgements xv 1 Introduction to the Mediterranean mountain environments 1 Ioannis N. Vogiatzakis 1.1 Introduction 1 1.2 Setting the scene 3 1.3 The character of the Mediterranean mountains 6 References 9 2 Quaternary environmental history 11 A.M. Mannion 2.1 Introduction 11 2.2 The pre-Quaternary period 12 2.3 The Quaternary period 15 2.4 The Holocene 27 2.5 Conclusion 29 References 30 3 Glacial history 35 Philip D. Hughes 3.1 Introduction 35 3.2 Pleistocene glaciations in the Mediterranean mountains 37 3.3 Modern and recent glaciers in the Mediterranean mountains 52 3.4 Conclusion 56 References 56 4 Landforms and soils 65 Maria Teresa Melis and Stefano Loddo 4.1 Introduction 65 4.2 Geomorphological processes in the Mediterranean mountain region 65 4.3 Geological setting 66 4.4 Soil characteristics of Mediterranean landscape units 67 4.5 Northern Mediterranean mountain landscapes: from the Pyrenees to the Hellenids 70 4.6 Eastern Mediterranean mountains: the Lebanon Mountains 72 4.7 Southern Mediterranean mountains: Atlas Mountains and Iberian Baetic Cordillera 74 4.8 Characteristic mountain landscapes of the Mediterranean islands 78 4.9 Conclusion 83 References 83 5 Climate and hydrology 87 Carmen de Jong, Ibrahim Gürer, Alon Rimmer, Amin Shaban and Mark Williams 5.1 Introduction 87 5.2 Climate and physical characteristics 90 5.3 Vulnerability of water resources to climate change 103 5.4 Adaptation strategies 106 5.5 Conclusion 108 References 109 6 Biogeography 115 Ioannis N. Vogiatzakis 6.1 Introduction to mountain biogeography 115 6.2 Vegetation 118 6.3 Flora 124 6.4 Fauna 127 6.5 Conservation in Mediterranean mountains 129 6.6 Conclusion 131 References 132 7 Cultural geographies 137 Veronica della Dora and Theano S. Terkenli 7.1 Introduction 137 7.2 Mythical mountains 139 7.3 Theophanic mountains 142 7.4 ‘Traditional’ mountains 148 7.5 Commodified mountains 151 7.6 Conclusion 154 References 155 8 Land use changes 159 Vasilios P. Papanastasis 8.1 Introduction 159 8.2 Drivers of land use changes 160 8.3 Major land uses and their historical evolution 162 8.4 Recent land use changes 167 8.5 Discussion 173 8.6 Conclusion 178 8.7 Acknowledgements 178 References 179 9 Climate change and its impact 185 D. Nogués-Bravo, J.I. López-Moreno and S.M. Vicente-Serrano 9.1 Introduction 185 9.2 Climate change in Mediterranean mountains 186 9.3 Cryosphere changes in the Mediterranean mountains 190 9.4 Hydrosphere changes in the Mediterranean mountains 191 9.5 Biosphere changes in the Mediterranean mountains 192 9.6 Conclusion 197 References 198 10 Conclusions 201 Ioannis N. Vogiatzakis 10.1 Introduction 201 10.2 Environmental challenges in Mediterranean mountains 202 10.3 Adaptation and protection 205 10.4 Conclusion 208 References 208 Index 211

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Book SynopsisThe ability to culture cells is fundamental for mass propagationand as a baseline for the genetic manipulation of plant nuclei andorganelles.Trade Review"In summary, this book is important for plant scientists as it thoroughly covers elementary technologies, providing the tools for comprehensive plant research." (The Quarterly Review of Biology, 1 September 2011) "For anyone working in the area of plant tissue culture, micro-propagation or transformation this book is essential reading." (The Journal of Experimental Agriculture, 1 October 2011)Table of ContentsPreface. Contributors. 1 Plant Micropropagation (Ivan Iliev, Alena Gajdosova, Gabriela Libiakova, Shri Mohan Jain). 1.1 Introduction. 1.2 Methods and approaches. 1.2.1 Explants and their surface disinfection. 1.2.2 Culture media and their preparation. 1.2.3 Stages of micropropagation. 1.2.4 Techniques of micropropagation. 1.3 Troubleshooting. References. 2 Thin Cell Layers: The Technique (Jaime A. Teixeira da Silva and Michio Tanaka). 2.1 Introduction. 2.2 Methods and approaches. 2.2.1 TCL. 2.2.2 Choice of material: Cymbidium hybrid. 2.3 Troubleshooting. 2.3.1 General comments. References. 3 Plant Regeneration – Somatic Embryogenesis (Kim E. Nolan, Ray J. Rose). 3.1 Introduction. 3.2 Methods and approaches. 3.2.1 Selection of the cultivar and type of explant. 3.2.2 Culture media. 3.2.3 Preparation of culture media. 3.2.4 Sterilization of tissues and sterile technique. 3.2.5 Culture and growth of tissue. 3.2.6 Culture and induction of somatic embryos. 3.2.7 Embryo development. 3.2.8 Transfer to soil – the final stage of regeneration. 3.3 Troubleshooting. References. 4 Haploid Plants (Sant S. Bhojwani and Prem K. Dantu). 4.1 Introduction. 4.2 Methods and approaches. 4.2.1 Androgenesis. 4.2.2 Diploidization. 4.3 Troubleshooting. References. 5 Embryo Rescue (Traud Winkelmann, Antje Doil, Sandra Reinhardt and Aloma Ewald). 5.1 Introduction. 5.2 Methods and approaches. 5.2.1 Identification of the time and type of barrier in hybridization. 5.2.2 Isolation of plant material after fertilization. 5.2.3 Culture conditions and media. 5.2.4 Confirmation of hybridity and ploidy. 5.2.5 Conditions for regeneration of embryos to plants. 5.3 Troubleshooting. References. 6 In vitro Flowering and Seed Set: Acceleration of Generation Cycles (Sergio J. Ochatt and Rajbir S. Sangwan). 6.1 Introduction. 6.2 Methods and approaches. 6.2.1 Protein legumes [7]. 6.2.2 Arabidopsis thaliana [13]. 6.3 Troubleshooting. References. 7 Induced Mutagenesis in Plants Using Physical and Chemical Agents (Chikelu Mba, Rownak Afza, Souleymane Bado and Shri Mohan Jain). 7.1 Introduction. 7.2 Methods and approaches. 7.2.1 Determination of the optimal doses of mutagens for inducing mutations. 7.3 Troubleshooting. 7.3.1 Factors influencing the outcome of mutagenesis using chemical mutagens. 7.3.2 Factors influencing the outcome of mutagenesis using physical mutagens. 7.3.3 Facts about induced mutations. References. 8 Cryopreservation of Plant Germplasm (E.R. Joachim Keller and Angelika Senula). 8.1 Introduction. 8.2 Methods and approaches. 8.2.1 Main principles. 8.2.2 Slow (two-step) freezing. 8.2.3 Vitrification. 8.2.4 Encapsulation–dehydration. 8.2.5 DMSO droplet freezing. 8.2.6 Combined methods. 8.2.7 Freezing of cold-hardened buds. 8.2.8 Freezing of orthodox seeds. 8.2.9 Freezing of pollen and spores. 8.3 Troubleshooting. References. 9 Plant Protoplasts: Isolation, Culture and Plant Regeneration (Michael R. Davey, Paul Anthony, Deval Patel and J. Brian Power). 9.1 Introduction. 9.2 Methods and approaches. 9.2.1 Protoplast isolation. 9.2.2 Protoplast culture. 9.3 Troubleshooting. References. 10 Protoplast Fusion Technology – Somatic Hybridization and Cybridization (Jude W. Grosser, Milica Calovic and Eliezer S. Louzada). 10.1 Introduction. 10.2 General applications of somatic hybridization. 10.3 Methods and approaches. 10.4 Troubleshooting. References. 11 Genetic Transformation – Agrobacterium (Ian S. Curtis). 11.1 Introduction. 11.2 Methods and approaches. 11.2.1 Agrobacterium as a natural genetic engineer. 11.2.2 Vector systems for transformation. 11.2.3 Inoculation procedures. 11.3 Troubleshooting. References. 12 Genetic Transformation – Biolistics (Fredy Altpeter and Sukhpreet Sandhu). 12.1 Introduction. 12.2 Methods and approaches. 12.2.1 Biolistic technology. 12.2.2 Optimization of gene delivery parameters. 12.2.3 Target tissues. 12.2.4 Reporter gene assays. 12.2.5 Selection and plant regeneration. 12.3 Troubleshooting. References. 13 Plastid Transformation (Bridget V. Hogg, Cilia L.C. Lelivelt, Aisling Dunne, Kim-Hong Nguyen and Jacqueline M. Nugent). 13.1 Introduction. 13.2 Methods and approaches. 13.2.1 Principles of plastid transformation. 13.2.2 Biolistic-mediated plastid transformation. 13.2.3 PEG-mediated plastid transformation. 13.2.4 Identification and characterization of transplastomic plants. 13.3 Troubleshooting. 13.3.1 Biolistic-mediated transformation. 13.3.2 PEG-mediated transformation. References. 14 Molecular Characterization of Genetically Manipulated Plants (Cristiano Lacorte, Giovanni Vianna, Francisco J.L. Aragao and El´ıbio L. Rech). 14.1 Introduction. 14.2 Methods and approaches. 14.2.1 Plant DNA extraction. 14.2.2 Polymerase chain reaction. 14.2.3 Southern blot technique. 14.2.4 Analysis of the integration site: inverse PCR (iPCR) and thermal asymmetric interlaced PCR (Tail-PCR). 14.3 Troubleshooting. References. 15 Bioreactors (Spiridon Kintzios). 15.1 Introduction. 15.2 Methods and approaches. 15.2.1 Medium scale disposable or semidisposable airlift reactors. 15.2.2 The RITA temporary immersion reactor. 15.2.3 The LifeReactor. 15.2.4 Immobilized cell bioreactors. 15.2.5 Mini-bioreactors. 15.3 Troubleshooting. References. 16 Secondary Products (Kexuan Tang, Lei Zhang, Junfeng Chen, Ying Xiao, Wansheng Chen and Xiaofen Sun). 16.1 Introduction. 16.2 Methods and approaches. 16.2.1 Plant cell cultures. 16.2.2 Scale-up and regulation of secondary metabolite production. 16.2.3 Detection of secondary products. 16.3 Troubleshooting. References. 17 Plant Cell Culture – Present and Future (Jim M. Dunwell). 17.1 Introduction. 17.2 Micropropagation. 17.3 Embryogenesis. 17.3.1 Background. 17.3.2 Commercial exploitation of somatic embryos. 17.3.3 Molecular aspects of somatic embryogenesis. 17.3.4 Microspore derived embryos. 17.4 Haploid methodology. 17.4.1 Haploids and their exploitation. 17.4.2 Induction of haploid plants. 17.4.3 Molecular aspects of haploid induction from microspores. 17.4.4 Ab initio zygotic-like embryogenesis from microspores. 17.5 Somaclonal variation. 17.6 Transgenic methods. 17.6.1 Background. 17.6.2 Regeneration and transformation techniques. 17.6.3 Chloroplast transformation. 17.6.4 Biopharming. 17.7 Protoplasts and somatic hybridization. 17.8 Bioreactors. 17.8.1 Production of plant products. 17.8.2 Production of pharmaceuticals. 17.8.3 Production of food ingredients. 17.8.4 Production of cosmetics. 17.8.5 Analytical methodology. 17.9 Cryopreservation. 17.10 Intellectual property and commercialization. 17.10.1 Background. 17.10.2 Sources of patent and other relevant information. 17.11 Conclusion. References. Index.

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Book SynopsisThis innovative textbook provides a readable, contemporary and fully integrated introduction to endocrine glands, their hormones and how their function relates to homeostasis. It explores the pathology of endocrine disease by relating the underpinning science through a wealth of clinical scenarios and examples.Table of ContentsPreface vii 1 The Molecular Basis of Hormones 1 2 The Hypothalamus and the Concept of Neurosecretion 43 3 The Pituitary Gland (1): The Anterior Lobe (Adenohypophysis) 51 4 The Pituitary Gland (2): The Posterior Lobe (Neurohypophysis) 89 5 Diseases of the Pituitary Gland 109 6 The Gonads (1): Testes 133 7 The Gonads (2): Ovaries 155 8 The Endocrine Control of Puberty 189 9 The Hormones of Pregnancy, Parturition and Lactation 199 10 The Adrenal Glands (1): Adrenal Cortex 211 11 The Adrenal Glands (2): Adrenal Medulla 247 12 The Endocrine Control of Salt and Water Balance 259 13 The Thyroid Gland and Its Iodothyronine Hormones 275 14 The Islets of Langerhans and Their Hormones 303 15 Diabetes Mellitus 325 16 The Gut–Brain Axis 337 17 Hormones, Endocrine Tumours and the Gut 343 18 The Parathyroids, the Endocrine Kidney and Calcium Regulation 349 19 The Genetics of Endocrine Tumours 375 20 Future Prospects 383 Index 387

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Book SynopsisThis innovative textbook provides a readable, contemporary and fully integrated introduction to endocrine glands, their hormones and how their function relates to homeostasis. It explores the pathology of endocrine disease by relating the underpinning science through a wealth of clinical scenarios and examples.Table of ContentsPreface vii 1 The Molecular Basis of Hormones 1 2 The Hypothalamus and the Concept of Neurosecretion 43 3 The Pituitary Gland (1): The Anterior Lobe (Adenohypophysis) 51 4 The Pituitary Gland (2): The Posterior Lobe (Neurohypophysis) 89 5 Diseases of the Pituitary Gland 109 6 The Gonads (1): Testes 133 7 The Gonads (2): Ovaries 155 8 The Endocrine Control of Puberty 189 9 The Hormones of Pregnancy, Parturition and Lactation 199 10 The Adrenal Glands (1): Adrenal Cortex 211 11 The Adrenal Glands (2): Adrenal Medulla 247 12 The Endocrine Control of Salt and Water Balance 259 13 The Thyroid Gland and Its Iodothyronine Hormones 275 14 The Islets of Langerhans and Their Hormones 303 15 Diabetes Mellitus 325 16 The Gut–Brain Axis 337 17 Hormones, Endocrine Tumours and the Gut 343 18 The Parathyroids, the Endocrine Kidney and Calcium Regulation 349 19 The Genetics of Endocrine Tumours 375 20 Future Prospects 383 Index 387

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Book SynopsisThis bookisa completely revised and updated version of this invaluable text which allows science students to extend necessary skills and techniques, with the topics being developed through examples in science which are easily understood by students from a range of disciplines. The introductory approach eases students into the subject, progressing to cover topics relevant to first and second year study and support data analysis for final year projects. The revision of the material in the book has been matched, on the accompanying website, with the extensive use of video, providing worked answers to over 200 questions in the book plus additional tutorial support. The second edition has also improved the learning approach for key topic areas to make it even more accessible and user-friendly, making it a perfect resource for students of all abilities. The expanding website provides a wide range of support material, providing a study environment within which students can develop their iTable of ContentsPreface xi On-line Learning Support xv 1 Mathematics and Statistics in Science 1 1.1 Data and Information 2 1.2 Experimental Variation and Uncertainty 2 1.3 Mathematical Models in Science 4 2 Scientific Data 7 2.1 Scientific Numbers 8 2.2 Scientific Quantities 15 2.3 Chemical Quantities 20 2.4 Angular Measurements 31 3 Equations in Science 41 3.1 Basic Techniques 41 3.2 Rearranging Simple Equations 53 3.3 Symbols 63 3.4 Further Equations 68 3.5 Quadratic and Simultaneous Equations 78 4 Linear Relationships 87 4.1 Straight Line Graph 89 4.2 Linear Regression 99 4.3 Linearization 107 5 Logarithmic and Exponential Functions 113 5.1 Mathematics of e, ln and log 114 5.2 Exponential Growth and Decay 128 6 Rates of Change 145 6.1 Rate of Change 145 6.2 Differentiation 152 7 Statistics for Science 161 7.1 Analysing Replicate Data 162 7.2 Describing and Estimating 168 7.3 Frequency Statistics 176 7.4 Probability 190 7.5 Factorials, Permutations and Combinations 203 8 Distributions and Uncertainty 211 8.1 Normal Distribution 212 8.2 Uncertainties in Measurement 217 8.3 Presenting Uncertainty 224 8.4 Binomial and Poisson Distributions 230 9 Scientific Investigation 243 9.1 Scientific Systems 243 9.2 The ‘Scientific Method’ 245 9.3 Decision Making with Statistics 246 9.4 Hypothesis Testing 250 9.5 Selecting Analyses and Tests 256 10 t-tests and F-tests 261 10.1 One-sample t-tests 262 10.2 Two-sample t-tests 267 10.3 Paired t-tests 272 10.4 F-tests 274 11 ANOVA – Analysis of Variance 279 11.1 One-way ANOVA 279 11.2 Two-way ANOVA 286 11.3 Two-way ANOVA with Replication 290 11.4 ANOVA Post Hoc Testing 296 12 Non-parametric Tests for Medians 299 12.1 One-sample Wilcoxon Test 301 12.2 Two-sample Mann–Whitney U-test 305 12.3 Paired Wilcoxon Test 308 12.4 Kruskal–Wallis and Friedman Tests 311 13 Correlation and Regression 315 13.1 Linear Correlation 316 13.2 Statistics of Correlation and Regression 320 13.3 Uncertainty in Linear Calibration 324 14 Frequency and Proportion 331 14.1 Chi-squared Contingency Table 332 14.2 Goodness of Fit 340 14.3 Tests for Proportion 343 15 Experimental Design 349 15.1 Principal Techniques 349 15.2 Planning a Research Project 357 Appendix I: Microsoft Excel 359 Appendix II: Cumulative z-areas for Standard Normal Distribution 363 Appendix III: Critical Values: t-statistic and Chi-squared, χ2 365 Appendix IV: Critical F-values at 0.05 (95 %) Significance 367 Appendix V: Critical Values at 0.05 (95 %) Significance for: Pearson’s Correlation Coefficient, r, Spearman’s Rank Correlation Coefficient, rS , and Wilcoxon Lower Limit, WL 369 Appendix VI: Mann–Whitney Lower Limit, UL, at 0.05 (95 %) Significance 371 Short Answers to ‘Q’ Questions 373 Index 379

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Book SynopsisHow to Be a Quantitative Ecologist is comprised of two equal parts on mathematics and statistics with emphasis on quantitative skills. A major component of this guide is computer implementation techniques, accompanied by computer practicals using the language R.Trade Review“For those looking through R books for something a bit more technical, this book will be an essential accomplice to mastering R.” (British Ecological Society, 1 April 2013) “The book is written in a style that is easy to read and for which one quickly forgets that the examples are essentially mathematical in nature. If you are an ecologist who has shied away from quantitative ecology in the past then this may be the text to convince you that there is much to be learnt from quantitative ecology. I thoroughly recommend this book and trust that you enjoy reading it as much as I did.” (International Statistical Review, 2012) "After a course of one or two semesters using this textbook, he says, students should have the absolute minimum of knowledge about quantitative research that ecologists need, but can provide a foundation for students who want to move further in that direction." (Book News, 1 August 2011) Table of ContentsHow I chose to write this book, and why you might choose to read it. Preface. 0. How to start a meaningful relationship with your computer. Introduction to R. 0.1 What is R? 0.2 Why use R for this book? 0.3 Computing with a scientific package like R. 0.4 Installing and interacting with R. 0.5 Style conventions. 0.6 Valuable R accessories. 0.7 Getting help. 0.8 Basic R usage. 0.9 Importing data from a spreadsheet. 0.10 Storing data in data frames. 0.11 Exporting data from R. 0.12 Quitting R. 1. How to make mathematical statements. Numbers, equations and functions. 1.1 Qualitative and quantitative scales. 1.2 Numbers. 1.3 Symbols. 1.4 Logical operations. 1.5 Algebraic operations. 1.6 Manipulating numbers. 1.7 Manipulating units. 1.8 Manipulating expressions. 1.9 Polynomials. 1.10 Equations. 1.11 First order polynomial equations. 1.12 Proportionality and scaling: a special kind of first order polynomial equation. 1.13 Second and higher order polynomial equations. 1.14 Systems of polynomial equations. 1.15 Inequalities. 1.16 Coordinate systems. 1.17 Complex numbers. 1.18 Relations and functions. 1.19 The graph of a function. 1.20 First order polynomial functions. 1.21 Higher order polynomial functions. 1.22 The relationship between equations and functions. 1.23 Other useful functions. 1.24 Inverse functions. 1.25 Functions of more than one variable. 2. How to describe regular shapes and patterns. Geometry and trigonometry. 2.1 Primitive elements. 2.2 Axioms of Euclidean geometry. 2.3 Propositions. 2.4 Distance between two points. 2.5 Areas and volumes. 2.6 Measuring angles. 2.7 The trigonometric circle. 2.8 Trigonometric functions. 2.9 Polar coordinates. 2.10 Graphs of trigonometric functions. 2.11 Trigonometric identities. 2.12 Inverses of trigonometric functions. 2.13 Trigonometric equations. 2.14 Modifying the basic trigonometric graphs. 2.15 Superimposing trigonometric functions. 2.16 Spectral analysis. 2.17 Fractal geometry. 3. How to change things, one step at a time. Sequences, difference equations and logarithms. 3.1 Sequences. 3.2 Difference equations. 3.3 Higher order difference equations. 3.4 Initial conditions and parameters. 3.5 Solutions of a difference equation. 3.6 Equilibrium solutions. 3.7 Stable and unstable equilibria. 3.8 Investigating stability. 3.9 Chaos. 3.10 Exponential function. 3.11 Logarithmic function. 3.12 Logarithmic equations. 4. How to change things, continuously. Derivatives and their applications. 4.1 Average rate of change. 4.2 Instantaneous rate of change. 4.3 Limits. 4.4 The derivative of a function. 4.5 Differentiating polynomials. 4.6 Differentiating other functions. 4.7 The chain rule. 4.8 Higher order derivatives. 4.9 Derivatives of functions of many variables. 4.10 Optimisation. 4.11 Local stability for difference equations. 4.12 Series expansions. 5. How to work with accumulated change. Integrals and their applications. 5.1 Antiderivatives. 5.2 Indefinite integrals. 5.3 Three analytical methods of integration. 5.4 Summation. 5.5 Area under a curve. 5.6 Definite integrals. 5.7 Some properties of definite integrals. 5.8 Improper integrals. 5.9 Differential equations. 5.10 Solving differential equations. 5.11 Stability analysis for differential equations. 6. How to keep stuff organised in tables. Matrices and their applications. 6.1 Matrices. 6.2 Matrix operations. 6.3 Geometric interpretation of vectors and square matrices. 6.4 Solving systems of equations with matrices. 6.5 Markov chains. 6.6 Eigenvalues and eigenvectors. 6.7 Leslie matrix models. 6.8 Analysis of linear dynamical systems. 6.9 Analysis of nonlinear dynamical systems. 7. How to visualise and summarise data. Descriptive statistics. 7.1 Overview of statistics. 7.2 Statistical variables. 7.3 Populations and samples. 7.4 Single-variable samples. 7.5 Frequency distributions. 7.6 Measures of centrality. 7.7 Measures of spread. 7.8 Skewness and kurtosis. 7.9 Graphical summaries. 7.10 Data sets with more than one variable. 7.11 Association between qualitative variables. 7.12 Association between quantitative variables. 7.13 Joint frequency distributions. 8. How to put a value on uncertainty. Probability. 8.1 Random experiments and event spaces. 8.2 Events. 8.3 Frequentist probability. 8.4 Equally likely events. 8.5 The union of events. 8.6 Conditional probability. 8.7 Independent events. 8.8 Total probability. 8.9 Bayesian probability. 9. How to identify different kinds of randomness. Probability distributions. 9.1 Probability distributions. 9.2 Discrete probability distributions. 9.3 Continuous probability distributions. 9.4 Expectation. 9.5 Named distributions. 9.6 Equally likely events: the uniform distribution. 9.7 Hit or miss: the Bernoulli distribution. 9.8 Count of occurrences in a given number of trials: the binomial distribution. 9.9 Counting different types of occurrences: the multinomial distribution. 9.10 Number of occurrences in a unit of time or space: the Poisson distribution. 9.11 The gentle art of waiting: geometric, negative binomial, exponential and gamma distributions. 9.12 Assigning probabilities to probabilities: the beta and Dirichlet distributions. 9.13 Perfect symmetry: the normal distribution. 9.14 Because it looks right: using probability distributions empirically. 9.15 Mixtures, outliers and the t-distribution. 9.16 Joint, conditional and marginal probability distributions. 9.17 The bivariate normal distribution. 9.18 Sums of random variables: the central limit theorem. 9.19 Products of random variables: the log-normal distribution. 9.20 Modelling residuals: the chi-square distribution. 9.21 Stochastic simulation. 10. How to see the forest from the trees. Estimation and testing. 10.1 Estimators and their properties. 10.2 Normal theory. 10.3 Estimating the population mean. 10.4 Estimating the variance of a normal population. 10.5 Confidence intervals. 10.6 Inference by bootstrapping. 10.7 More general estimation methods. 10.8 Estimation by least squares. 10.9 Estimation by maximum likelihood. 10.10 Bayesian estimation. 10.11 Link between maximum likelihood and Bayesian estimation. 10.12 Hypothesis testing: rationale. 10.13 Tests for the population mean. 10.14 Tests comparing two different means. 10.15 Hypotheses about qualitative data. 10.16 Hypothesis testing debunked. 11. How to separate the signal from the noise. Statistical modelling. 11.1 Comparing the means of several populations. 11.2 Simple linear regression. 11.3 Prediction. 11.4 How good is the best-fit line? 11.5 Multiple linear regression. 11.6 Model selection. 11.7 Generalised linear models. 11.8 Evaluation, diagnostics and model selection for GLMs. 11.9 Modelling dispersion. 11.10 Fitting more complicated models to data: polynomials, interactions, nonlinear regression. 11.11 Letting the data suggest more complicated models: smoothing. 11.12 Partitioning variation: mixed effects models. 12. How to measure similarity. Multivariate methods 12.1 The problem with multivariate data. 12.2 Ordination in general. 12.3 Principal components analysis. 12.4 Clustering in general. 12.5 Agglomerative hierarchical clustering. 12.6 Nonhierarchical clustering: k means analysis. 12.7 Classification in general. 12.8 Logistic regression: two classes. 12.9 Logistic regression: many classes. Further reading. References. Appendix: Formulae. R Index. Index.

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Book SynopsisHow to Be a Quantitative Ecologist is comprised of two equal parts on mathematics and statistics with emphasis on quantitative skills. A major component of this guide is computer implementation techniques, accompanied by computer practicals using the language R.Trade Review“For those looking through R books for something a bit more technical, this book will be an essential accomplice to mastering R.” (British Ecological Society, 1 April 2013) “The book is written in a style that is easy to read and for which one quickly forgets that the examples are essentially mathematical in nature. If you are an ecologist who has shied away from quantitative ecology in the past then this may be the text to convince you that there is much to be learnt from quantitative ecology. I thoroughly recommend this book and trust that you enjoy reading it as much as I did.” (International Statistical Review, 2012) "After a course of one or two semesters using this textbook, he says, students should have the absolute minimum of knowledge about quantitative research that ecologists need, but can provide a foundation for students who want to move further in that direction." (Book News, 1 August 2011) Table of ContentsHow I chose to write this book, and why you might choose to read it. Preface. 0. How to start a meaningful relationship with your computer. Introduction to R. 0.1 What is R? 0.2 Why use R for this book? 0.3 Computing with a scientific package like R. 0.4 Installing and interacting with R. 0.5 Style conventions. 0.6 Valuable R accessories. 0.7 Getting help. 0.8 Basic R usage. 0.9 Importing data from a spreadsheet. 0.10 Storing data in data frames. 0.11 Exporting data from R. 0.12 Quitting R. 1. How to make mathematical statements. Numbers, equations and functions. 1.1 Qualitative and quantitative scales. 1.2 Numbers. 1.3 Symbols. 1.4 Logical operations. 1.5 Algebraic operations. 1.6 Manipulating numbers. 1.7 Manipulating units. 1.8 Manipulating expressions. 1.9 Polynomials. 1.10 Equations. 1.11 First order polynomial equations. 1.12 Proportionality and scaling: a special kind of first order polynomial equation. 1.13 Second and higher order polynomial equations. 1.14 Systems of polynomial equations. 1.15 Inequalities. 1.16 Coordinate systems. 1.17 Complex numbers. 1.18 Relations and functions. 1.19 The graph of a function. 1.20 First order polynomial functions. 1.21 Higher order polynomial functions. 1.22 The relationship between equations and functions. 1.23 Other useful functions. 1.24 Inverse functions. 1.25 Functions of more than one variable. 2. How to describe regular shapes and patterns. Geometry and trigonometry. 2.1 Primitive elements. 2.2 Axioms of Euclidean geometry. 2.3 Propositions. 2.4 Distance between two points. 2.5 Areas and volumes. 2.6 Measuring angles. 2.7 The trigonometric circle. 2.8 Trigonometric functions. 2.9 Polar coordinates. 2.10 Graphs of trigonometric functions. 2.11 Trigonometric identities. 2.12 Inverses of trigonometric functions. 2.13 Trigonometric equations. 2.14 Modifying the basic trigonometric graphs. 2.15 Superimposing trigonometric functions. 2.16 Spectral analysis. 2.17 Fractal geometry. 3. How to change things, one step at a time. Sequences, difference equations and logarithms. 3.1 Sequences. 3.2 Difference equations. 3.3 Higher order difference equations. 3.4 Initial conditions and parameters. 3.5 Solutions of a difference equation. 3.6 Equilibrium solutions. 3.7 Stable and unstable equilibria. 3.8 Investigating stability. 3.9 Chaos. 3.10 Exponential function. 3.11 Logarithmic function. 3.12 Logarithmic equations. 4. How to change things, continuously. Derivatives and their applications. 4.1 Average rate of change. 4.2 Instantaneous rate of change. 4.3 Limits. 4.4 The derivative of a function. 4.5 Differentiating polynomials. 4.6 Differentiating other functions. 4.7 The chain rule. 4.8 Higher order derivatives. 4.9 Derivatives of functions of many variables. 4.10 Optimisation. 4.11 Local stability for difference equations. 4.12 Series expansions. 5. How to work with accumulated change. Integrals and their applications. 5.1 Antiderivatives. 5.2 Indefinite integrals. 5.3 Three analytical methods of integration. 5.4 Summation. 5.5 Area under a curve. 5.6 Definite integrals. 5.7 Some properties of definite integrals. 5.8 Improper integrals. 5.9 Differential equations. 5.10 Solving differential equations. 5.11 Stability analysis for differential equations. 6. How to keep stuff organised in tables. Matrices and their applications. 6.1 Matrices. 6.2 Matrix operations. 6.3 Geometric interpretation of vectors and square matrices. 6.4 Solving systems of equations with matrices. 6.5 Markov chains. 6.6 Eigenvalues and eigenvectors. 6.7 Leslie matrix models. 6.8 Analysis of linear dynamical systems. 6.9 Analysis of nonlinear dynamical systems. 7. How to visualise and summarise data. Descriptive statistics. 7.1 Overview of statistics. 7.2 Statistical variables. 7.3 Populations and samples. 7.4 Single-variable samples. 7.5 Frequency distributions. 7.6 Measures of centrality. 7.7 Measures of spread. 7.8 Skewness and kurtosis. 7.9 Graphical summaries. 7.10 Data sets with more than one variable. 7.11 Association between qualitative variables. 7.12 Association between quantitative variables. 7.13 Joint frequency distributions. 8. How to put a value on uncertainty. Probability. 8.1 Random experiments and event spaces. 8.2 Events. 8.3 Frequentist probability. 8.4 Equally likely events. 8.5 The union of events. 8.6 Conditional probability. 8.7 Independent events. 8.8 Total probability. 8.9 Bayesian probability. 9. How to identify different kinds of randomness. Probability distributions. 9.1 Probability distributions 300 9.2 Discrete probability distributions 301 9.3 Continuous probability distributions 304 9.4 Expectation 306 9.5 Named distributions 309 9.6 Equally likely events: the uniform distribution. 9.7 Hit or miss: the Bernoulli distribution. 9.8 Count of occurrences in a given number of trials: the binomial distribution. 9.9 Counting different types of occurrences: the multinomial distribution. 9.10 Number of occurrences in a unit of time or space: the Poisson distribution. 9.11 The gentle art of waiting: geometric, negative binomial, exponential and gamma distributions. 9.12 Assigning probabilities to probabilities: the beta and Dirichlet distributions. 9.13 Perfect symmetry: the normal distribution. 9.14 Because it looks right: using probability distributions empirically. 9.15 Mixtures, outliers and the t-distribution. 9.16 Joint, conditional and marginal probability distributions. 9.17 The bivariate normal distribution. 9.18 Sums of random variables: the central limit theorem. 9.19 Products of random variables: the log-normal distribution. 9.20 Modelling residuals: the chi-square distribution. 9.21 Stochastic simulation. 10. How to see the forest from the trees. Estimation and testing. 10.1 Estimators and their properties. 10.2 Normal theory. 10.3 Estimating the population mean. 10.4 Estimating the variance of a normal population. 10.5 Confidence intervals. 10.6 Inference by bootstrapping. 10.7 More general estimation methods. 10.8 Estimation by least squares. 10.9 Estimation by maximum likelihood. 10.10 Bayesian estimation. 10.11 Link between maximum likelihood and Bayesian estimation. 10.12 Hypothesis testing: rationale. 10.13 Tests for the population mean. 10.14 Tests comparing two different means. 10.15 Hypotheses about qualitative data. 10.16 Hypothesis testing debunked. 11. How to separate the signal from the noise. Statistical modelling. 11.1 Comparing the means of several populations. 11.2 Simple linear regression. 11.3 Prediction. 11.4 How good is the best-fit line? 11.5 Multiple linear regression. 11.6 Model selection. 11.7 Generalised linear models. 11.8 Evaluation, diagnostics and model selection for GLMs. 11.9 Modelling dispersion 409 11.10 Fitting more complicated models to data: polynomials, interactions, nonlinear regression. 11.11 Letting the data suggest more complicated models: smoothing. 11.12 Partitioning variation: mixed effects models. 12. How to measure similarity. Multivariate methods 12.1 The problem with multivariate data. 12.2 Ordination in general. 12.3 Principal components analysis. 12.4 Clustering in general. 12.5 Agglomerative hierarchical clustering. 12.6 Nonhierarchical clustering: k means analysis. 12.7 Classification in general. 12.8 Logistic regression: two classes. 12.9 Logistic regression: many classes. Further reading. References. Appendix: Formulae. R Index. Index.

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Book SynopsisThis book on cell death contains 29 self-contained, peer-reviewed articles written by leading scientists in each field. It features overview articles aimed at undergraduates and non-specialists, which present basic information and provide entry into the following advanced articles.Trade Review"The book of Melino and Vaux is definitively a tremendous effort to summarize the vast amount of knowledge. It is divided into 29 chapters, which are all written by the leading experts in the field. Chapters range from basic biochemical mechanisms to therapy, from apoptosis to autophagy and from lower organisms to humans, and as such give a great overview of the research area." (Cell Death and Differentiation, December 2010) "Each chapter contains novel information ensuring that this book stands out among the numerous others centered on cell death and constitutes an extremely useful addition." (Cell Death and Disease, December 2010)Table of ContentsContributors. Preface. The Siren’s Song: This Death That Makes Life Live (Gerry Melino, Richard A Knight and Jean-Claude Ameisen). The Origin and Evolution of Programmed Cell Death (Jean Claude Ameisen). Cell Death in C. elegans (Ataman Sendoel and Michael O Hengartner). Caspases and Cell Death (Lorraine D Hernandez, Caroline Houde, Maarten Hoek, Brent Butts, Donald W Nicholson and Huseyin Mehmet). The Apoptosome: The Executioner of Mitochondria-mediated Apoptosis (Elisabetta Ferraro and Francesco Cecconi). Caspases, Substrates and Sequential Activation (John G Walsh and Seamus J Martin). Dismantling the Apoptotic Cell (Paula Deming and Sally Kornbluth). The BCL-2 Family Proteins – Key Regulators and Effectors of Apoptosis (David L Vaux). BH3-only Proteins (Lina Happo, Andreas Strasser and Clare L Scott). Mitochondrial Outer Membrane Permeabilization (Melissa J Parsons and Douglas R Green). Mitochondria Fusion and Fission (Giovanni Benard, Guihong Peng and Mariusz Karbowski). Death Receptors (Peter H Krammer and Inna N Lavrik). Death Receptors at the Molecular Level: Therapeutic Implications (Marion MacFarlane). Death Receptor-induced Necroptosis (Wim Declercq, Franky Van Herreweghe, Tom Vanden Berghe and Peter Vandenabeele). Inhibitor of Apoptosis (IAP) and BIR-containing Proteins (David L Vaux). Structures, Domains and Functions in Cell Death (DD, DED, CARD, PYD) (Hao Wu and Yu-Chih Lo). Structure and Function of IAP and Bcl-2 Proteins (Mark G Hinds, Peter D Mace and Catherine L Day). Engulfment of Apoptotic Cells and its Physiological Roles (Rikinari Hanayama, Masanori Miyanishi, Hiroshi Yamaguchi, Jun Suzuki and Shigekazu Nagata). Autophagy (María Isabel Colombo and Hans-Uwe Simon). Autophagy in Nonmammalian Systems (Jahda H Hill and Eric H Baehrecke). Apoptosis: Regulatory Genes and Disease (James E Vince and John Silke). Caspases in Inflammation and Immunity (Philippe M LeBlanc and Maya Saleh). Immunity, Granzymes and Cell Killing (Nigel J Waterhouse, Olivia Susanto, Karin A Sedelies and Joseph A Trapani). P53 and Cell Death (Kamil Wolyniec, Sue Haupt and Ygal Haupt). Cornification of the Skin: A Non-apoptotic Cell Death Mechanism (E Candi, RA Knight and G Melino). Apoptosis: Inherited Disorders (Helen C Su and Michael J Lenardo). From Reactive Oxygen and Nitrogen Species to Therapy (Scott R McKercher, Tomohiro Nakamura and Stuart A Lipton). Microbial Inhibitors of Apoptosis (Georg Häcker). Drug Discovery in Apoptosis (Tom O’Brien and Vishva M Dixit). Subject Index.

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Book Synopsis* The latest edition of this highly successful introduction tobacterial genetics covering basic concepts and latestdevelopments. * Contains more detail on sigma factors, expanded treatment of integrons and a major update of the chapter on Gene Mapping and Genomics .Table of ContentsPreface. 1 Nucleic Acid Structure and Function. 1.1 Structure of nucleic acids. 1.1.1 DNA. 1.1.2 RNA. 1.1.3 Hydrophobic interactions. 1.1.4 Different forms of the double helix. 1.1.5 Supercoiling. 1.1.6 Denaturation and hybridization. 1.1.7 Orientation of nucleic acid strands. 1.2 Replication of DNA. 1.2.1 Unwinding and rewinding. 1.2.2 Fidelity of replication; proofreading. 1.3 Chromosome replication and cell division. 1.4 DNA repair. 1.4.1 Mismatch repair. 1.4.2 Excision repair. 1.4.3 Recombination (post-replication) repair. 1.4.4 SOS repair. 1.5 Gene expression. 1.5.1 Transcription. 1.5.2 Translation. 1.5.3 Post-translational events. 1.6 Gene organization. 2 Mutation and Variation. 2.1 Variation and evolution. 2.1.1 Fluctuation test. 2.1.2 Replica plating. 2.1.3 Directed mutation in bacteria? 2.2 Types of mutation. 2.2.1 Point mutations. 2.2.2 Conditional mutants. 2.2.3 Variation due to larger-scale DNA alterations. 2.2.4 Extrachromosomal agents and horizontal gene transfer. 2.3 Recombination. 2.3.1 A model of the general (homologous) recombination process. 2.3.2 Enzymes involved in recombination. 2.4 Phenotypes. 2.4.1 Restoration of phenotype. 2.5 Mechanisms of mutation. 2.5.1 Spontaneous mutation. 2.5.2 Chemical mutagens. 2.5.3 Ultraviolet irradiation. 2.6 Isolation and identification of mutants. 2.6.1 Mutation and selection. 2.6.2 Replica plating. 2.6.3 Isolation of other mutants. 2.6.4 Molecular methods. 3 Regulation of Gene Expression. 3.1 Gene copy number. 3.2 Transcriptional control. 3.2.1 Promoters. 3.2.2 Terminators, attenuators and anti-terminators. 3.2.3 Induction and repression: regulatory proteins. 3.2.4 Two-component regulatory systems. 3.2.5 Global regulatory systems. 3.2.6 Quorum sensing. 3.3 Translational control. 3.3.1 Ribosome binding. 3.3.2 Codon usage. 3.3.3 Stringent response. 3.3.4 Regulatory RNA. 3.4 Phase variation. 4 Genetics of Bacteriophages. 4.1 Bacteriophage structure. 4.2 Single-strand DNA bacteriophages. 4.2.1 ϕX174. 4.2.2 M13. 4.3 RNA-containing phages: MS2. 4.4 Double-stranded DNA phages. 4.4.1 Bacteriophage T4. 4.4.2 Bacteriophage λ. 4.4.3 Lytic and lysogenic regulation of bacteriophage λ. 4.5 Restriction and modification. 4.6 Bacterial resistance to phage attack. 4.7 Complementation and recombination. 4.8 Why are bacteriophages important? 4.8.1 Phage typing. 4.8.2 Phage therapy. 4.8.3 Phage display. 4.8.4 Phages in the natural environment. 4.8.5 Bacterial virulence and phage conversion. 5 Plasmids. 5.1 Some bacterial characteristics are determined by plasmids. 5.1.1 Antibiotic resistance. 5.1.2 Colicins and bacteriocins. 5.1.3 Virulence determinants. 5.1.4 Plasmids in plant-associated bacteria. 5.1.5 Metabolic activities. 5.2 Molecular properties of plasmids. 5.2.1 Plasmid replication and control. 5.2.2 Partitioning. 5.2.3 Host range. 5.2.4 Plasmid incompatibility. 5.3 Plasmid stability. 5.3.1 Plasmid integrity. 5.3.2 Partitioning. 5.3.3 Differential growth rate. 5.4 Associating a plasmid with a phenotype. 6 Gene Transfer. 6.1 Transformation. 6.2 Conjugation. 6.2.1 Mechanism of conjugation. 6.2.2 The F plasmid. 6.2.3 Conjugation in other bacteria. 6.3 Transduction. 6.3.1 Specialized transduction. 6.4 Recombination. 6.4.1 Consequences of recombination. 6.4.2 Site-specific and non-homologous (illegitimate) recombination. 6.5 Mosaic genes and chromosome plasticity. 7 Genomic Plasticity: Movable Genes and Phase Variation. 7.1 Insertion sequences. 7.1.1 Structure of insertion sequences. 7.1.2 Occurrence of insertion sequences. 7.2 Transposons. 7.2.1 Structure of transposons. 7.2.2 Integrons. 7.2.3 ISCR elements. 7.3 Mechanisms of transposition. 7.3.1 Replicative transposition. 7.3.2 Non-replicative (conservative) transposition. 7.3.3 Regulation of transposition. 7.3.4 Activation of genes by transposable elements. 7.3.5 Mu: A transposable bacteriophage. 7.3.6 Conjugative transposons. 7.4 Phase variation. 7.4.1 Variation mediated by simple DNA inversion. 7.4.2 Variation mediated by nested DNA inversion. 7.4.3 Antigenic variation in the gonococcus. 7.4.4 Phase variation by slipped-strand mispairing. 7.4.5 Phase variation mediated by differential DNA methylation. 7.5 Clustered regularly interspersed short palindromic repeats. 8 Genetic Modification: Exploiting the Potential of Bacteria. 8.1 Strain development. 8.1.1 Generation of variation. 8.1.2 Selection of desired variants. 8.2 Overproduction of primary metabolites. 8.2.1 Simple pathways. 8.2.2 Branched pathways. 8.3 Overproduction of secondary metabolites. 8.4 Gene cloning. 8.4.1 Cutting and joining DNA. 8.4.2 Plasmid vectors. 8.4.3 Bacteriophage λ vectors. 8.4.4 Cloning larger fragments. 8.4.5 Bacteriophage M13 vectors. 8.5 Gene libraries. 8.5.1 Construction of genomic libraries. 8.5.2 Screening a gene library. 8.5.3 Cloning PCR products. 8.5.4 Construction of a cDNA library. 8.6 Products from cloned genes. 8.6.1 Expression vectors. 8.6.2 Making new genes. 8.6.3 Other bacterial hosts. 8.6.4 Novel vaccines. 8.7 Other uses of gene technology. 9 Genetic Methods for Investigating Bacteria. 9.1 Metabolic pathways. 9.1.1 Complementation. 9.1.2 Cross-feeding. 9.2 Microbial physiology. 9.2.1 Reporter genes. 9.2.2 Chromatin immunoprecipitation. 9.2.3 Cell division. 9.2.4 Motility and chemotaxis. 9.2.5 Cell differentiation. 9.3 Bacterial virulence. 9.3.1 Wide-range mechanisms of bacterial pathogenesis. 9.3.2 Detection of virulence genes. 9.4 Specific mutagenesis. 9.4.1 Gene replacement. 9.4.2 Antisense RNA. 9.5 Taxonomy, evolution and epidemiology. 9.5.1 Molecular taxonomy. 9.5.2 GC content. 9.5.3 16 S rRNA. 9.5.4 Denaturing-gradient gel electrophoresis and temperature-gradient gel electrophoresis. 9.5.5 Diagnostic use of PCR. 9.5.6 Molecular epidemiology. 10 Gene Mapping to Genomics and Beyond. 10.1 Gene mapping. 10.1.1 Conjugational analysis. 10.1.2 Gene libraries. 10.1.3 Restriction mapping and pulsed-field gel electrophoresis. 10.2 DNA sequence determination. 10.2.1 Sanger sequencing. 10.2.2 Dye terminator sequencing. 10.2.3 Pyrosequencing. 10.2.4 Massively parallel sequencing. 10.3 Genome sequencing. 10.3.1 Genome-sequencing strategies. 10.3.2 Relating sequence to function. 10.3.3 Metagenomics. 10.4 Comparative genomics. 10.4.1 Microarrays. 10.5 Analysis of gene expression. 10.5.1 Transcriptional analysis. 10.5.2 Translational analysis. 10.6 Metabolomics. 10.7 Systems biology and synthetic genomics. 10.7.1 Systems biology. 10.7.2 Synthetic genomics. 10.8 Conclusion. Appendix A Further Reading. Appendix B Abbreviations Used. Appendix C Glossary. Appendix D Enzymes and other Proteins. Appendix E Genes. Appendix F Standard Genetic Code. Appendix G Bacterial Species. Index.

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