Biochemistry Books

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 SynopsisG protein-coupled receptors (GPCRs) are a large protein family of transmembrane receptors vital in dictating cellular responses. GPCRs are involved in many diseases, but are also the target of around half of all modern medicinal drugs. Shifting Paradigms in G Protein Coupled Receptors takes a look at the way GPCRs are examined today, how they react, how their mutations lead to disease, and the many ways in which they can be screened for compounds that modulate them. Chemists, pharmacologists, and biologists will find essential information in this comprehensive reference.Trade Review"Additionally, the presentation of the fundamental concepts of GPCR biology by the authors, who are recognized experts in the GPCR field, is likely to be appreciated by students of pharmacology. . . This is a unique resource for navigating the field of GPCR research." (Doody's, 23 September 2011) ". . . scientists whose area of research is (or will be) connected with GPCRs ... will get a comprehensive overview of current state-of-the-art research in this broad and rapidly developing field." (ChemMedChem, 1 February 2011)Table of ContentsPreface. Contributors. 1. The Evolution of Receptors: From On–Off Switches to Microprocessors (Terry Kenakin). 1.1. Introduction. 1.2. The Receptor as an On–Off Switch. 1.3. Historical Background and Classical Receptor Theory. 1.4. The Operational Model of Drug Action. 1.5. Receptor Antagonism. 1.6. Specific Models of GPCRs (7TM Receptors). 1.7. The Receptor as Microprocessor: Ternary Complex Models. 1.8. Receptors as Basic Drug Recognition Units. 1.9. Receptor Structure. 1.10. Future Considerations. References. 2. The Evolving Pharmacology of GPCRs 27 (Lauren T. May, Nicholas D. Holliday, and Stephen J. Hill). 2.1. Agonists, Neutral Antagonists, and Inverse Agonists. 2.2. LDTRS/Protean Agonism. 2.3. Molecular Mechanisms of GPCR Ligand Binding. 2.4. Two GPCR Ligands Binding at Once—Concept of Allosterism. 2.5. GPCR Dimerization. 2.6. Future Perspectives. Acknowledgments. References. 3. The Emergence of Allosteric Modulators for G Protein-Coupled Receptors (Karen J. Gregory, Celine Valant, John Simms, Patrick M. Sexton, and Arthur Christopoulos). 3.1. Introduction. 3.2. Foundations of Allosteric Receptor Theory. 3.3. Models for Understanding the Effects of Allosteric Modulators. 3.4. Types of Allosteric Modulators and Their Properties. 3.5. Detection and Quantification of Allosteric Interactions. 3.6. Some Examples of GPCR Allosteric Modulators. 3.7. Concluding Remarks. References. 4. Receptor-Mediated G Protein Activation: How, How Many, and Where? (Ingrid Gsandtner, Christian W. Gruber, and Michael Freissmuth). 4.1. The Mechanical Problem—Three Different Solutions. 4.2. Receptor Monomers–Dimers–Oligomers: One Size Fits All? 4.3. Corrals, Fences, Rafts—Are There Privileged Places for GPCR Activation? Acknowledgments. References. 5. Molecular Pharmacology of Frizzleds—with Implications for Possible Therapy (Gunnar Schulte). 5.1. Introduction. 5.2. Frizzleds as WNT Receptors. 5.3. Frizzled Signaling 120. 5.4. Frizzleds—Physiology and Possible Therapy. Acknowledgments. References. 6. Secretin Receptor Dimerization: A Possible Functionally Important Paradigm for Family B G Protein-Coupled Receptors (Kaleeckal G. Harikumar, Maoqing Dong, and Laurence J. Miller). 6.1. Methodological Approaches to GPCR Oligomerization. 6.2. Structural Themes for GPCR Oligomerization. 6.3. Functional Effects of GPCR Oligomerization. 6.4. Secretin Receptor Oligomerization. References. 7. Past and Future Strategies for GPCR Deorphanization (Angélique Levoye, Nathalie Clement, Elodie Tenconi and Ralf Jockers). 7.1. Introduction. 7.2. Current Strategies to Identify the Ligand and Function of Orphan 7TM Proteins. 7.3. Functional Assays for Deorphanization. 7.4. Future Directions and New Concepts. 7.5. Controversial Issues. Acknowledgments. References. 8. High-Throughput GPCR Screening Technologies and the Emerging Importance of the Cell Phenotype (Terry Reisine and Richard M. Eglen). 8.1. Introduction. 8.2. How Are GPCR Drugs Discovered? 8.3. GPCR Dependence on G Proteins. 8.4. Technologies for GPCR Compound Screening and Drug Discovery. 8.5. Importance of Target Cells in GPCR HTS Assays. 8.6. Summary. References. 9. Are "Traditional" Biochemical Techniques Out of Fashion in the New Era of GPCR Pharmacology? (Maria Teresa Dell’anno and Maria Rosa Mazzoni). 9.1. Overview. 9.2. Receptor Binding Assays. 9.3. Methods for Measurement of cAMP. 9.4. Conclusions. References. 10. Fluorescence and Resonance Energy Transfer Shine New Light on GPCR Function (Carsten Hoffmann and Moritz Bünemann). 10.1. Overview. 10.2. Introduction. 10.3. Labeling GPCRs with Fluorescent Tags. 10.4. Detection of Fluorescence and Bioluminescence. 10.5. Fluorescence-Based Assays to Study Receptor Localization, Trafficking and Receptor Function. 10.6. Resonance Energy Transfer, a Tool to Get New Insights into GPCR Function. 10.7. Analysis of Steady-State Protein–Protein Interaction by Means of RET. 10.8. Kinetic Analysis of Protein–Protein Interactions by Means of FRET. 10.9. Detection of Receptor Function by Fluorescence Resonance Energy. References. 11. Integration of Label-Free Detection Methods in GPCR Drug Discovery (Oliver Nayler, Magdalena Birker-Robaczewska, and John Gatfield). 11.1. Overview. 11.2. Introduction. 11.3. Label-Free Technologies—Past and Present. 11.4. Discussion. Acknowledgments. References. 12. Screening for Allosteric Modulators of G Protein-Coupled Receptors (Christopher Langmead). 12.1. Introduction. 12.2. The Allosteric Ternary Complex Model, Radioligand Binding, and Affinity. 12.3. Beyond Affinity—Functional Assays, Efficacy, and Allosteric Agonism. 12.4. Allosteric Modulator Titration Curves. 12.5. The Impact of Functional Assay Format on Allosteric Modulator Screening. 12.6. Taking Advantage of Structural Understanding of Allosteric Binding Sites. 12.7. Summary and Future Directions. References. 13. Ultra-High-Throughput Screening Assays for GPCRs (Priya Kunapuli). 13.1. Introduction. 13.2. Assay Types for GPCRs in uHTS. 13.3. Summary. Acknowledgments. References. 14. New Techniques to Express and Crystallize G Protein-Coupled Receptors (James C. Errey and Fiona H. Marshall). 14.1. Introduction. 14.2. Key Problems Limiting Production of 3D GPCR Structures. 14.3. History of GPCR Structures. 14.4. The Search for Other GPCR Structures. 14.5. Protein Purification and Solubilization. 14.6. In Cubo Crystallization. 14.7. Engineering Receptor Stability. 14.8. Structures of the â2AR. 14.9. The Adenosine A2a Receptor. 14.10. Conclusions and Future Developments. Acknowledgments. References. 15. Structure and Modeling of GPCRs: Implications for Drug Discovery (Kimberly A. Reynolds, Vsevolod Katritch, and Ruben Abagyan). 15.1. Introduction. 15.2. High-Resolution GPCR Modeling. 15.3. Constructing and Evaluating Homology Models of Other Receptor Types. 15.4. Modeling GPCR Functional Features—Analysis of Activation and Signaling. 15.5. Beyond Class A: Modeling of Other GPCR Families. 15.6. Summary and Conclusions. Acknowledgments. References. 16. X-Ray Structure Developments for GPCR Drug Targets (Michael Sabio and Sidney W. Topiol). 16.1. Overview. 16.2. Introduction. 16.3. Class A GPCRs. 16.4. Class C GPCRs. 16.5. Conclusions. References. 17. Pharmacological Chaperones: Potential for the Treatment of Hereditary Diseases Caused by Mutations in G Protein-Coupled Receptors (Kenneth J. Valenzano, Elfrida R. Benjamin,Patricia René, and Michel Bouvier). 17.1. Overview. 17.2. Introduction. 17.3. NDI and the V2R. 17.4. RP and the Rhodopsin Receptor. 17.5. IHH and the Gonadotropin-Releasing Hormone Receptor. 17.6. Other Human Diseases Caused by Inactivating Mutations in GPCRs. 17.7. Considerations for the Therapeutic Use of Pharmacological Chaperones. 17.8. Concluding Remarks. Acknowledgments. References. Index.

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Book SynopsisInstrumental techniques for analyzing intrinsically disordered proteins The recently recognized phenomenon of protein intrinsic disorder is gaining significant interest among researchers, especially as the number of proteins and protein domains that have been shown to be intrinsically disordered rapidly grows. The first reference to tackle this little-documented area, Instrumental Analysis of Intrinsically Disordered Proteins: Assessing Structure and Conformation provides researchers with a much-needed, comprehensive summary of recent achievements in the methods for structural characterization of intrinsically disordered proteins (IDPs). Chapters discuss: Assessment of IDPs in the living cell Spectroscopic techniques for the analysis of IDPs, including NMR and EPR spectroscopies, FTIR, circular dichroism, fluorescence spectroscopy, vibrational methods, and single-molecule analysis Single-molecule techniques aTrade Review"With contributions from an international selection of leading researchers, this book fills an important need in a rapidly growing field. It is required reading for biochemists, biophysicists, molecular biologists, geneticists, cell biologists, physiologists, and specialists in drug design and development, proteomics, and molecular medicine with an interest in proteins and peptides." (Anticancer Research, 1 August 2010)Table of ContentsPREFACE. INTRODUCTION TO THE WILEY SERIES ON PROTEIN AND PEPTIDE SCIENCE. LIST OF CONTRIBUTORS. LIST OF ABBREVIATIONS. PART I ASSESSING IDPs IN THE LIVING CELL. 1 IDPs and Protein Degradation in The Cell (Yosef Shaul, Peter Tsvetkov, and Nina Reuven). 2 The Structural Biology of IDPs Inside Cells (Philipp Selenko). PART II SPECTROSCOPIC TECHNIQUES. 3 Nuclear Magnetic Resonance Spectroscopy Applied to (Intrinsically) Disordered Proteins (Frans A. A. Mulder, Martin Lundqvist, and Ruud M. Scheek). 4 Atomic-Level Characterization of Disordered Protein Ensembles Using NMR Residual Dipolar Couplings (Martin Blackledge, Pau Bernadó, and Malene Ringkjøbing Jensen). 5 Determining Structural Ensembles for Intrinsically Disordered Proteins (Gary W. Daughdrill). 6 Site-Directed Spin Labeling EPR Spectroscopy (Valérie Belle,, Sabrina Rouger, Stéphanie Costanzo, Sonia Longhi, and André Fournel). 7 The Structure of Unfolded Peptides and Proteins Explored by Vibrational Spectroscopy (Reinhard Schweitzer-Stenner, Thomas J. Measey, Andrew M. Hagarman, and Isabelle C. Dragomir). 8 Intrinsically Disordered Proteins and Induced Folding Studied by Fourier Transform Infrared Spectroscopy (Antonino Natalello and Silvia Maria Doglia). 9 Genetically Engineered Polypeptides as a Model of Intrinsically Disordered Fibrillogenic Proteins: Deep UV Resonance Raman Spectroscopic Study (Natalya I. Topilina, Vitali Sikirzhytski, Seiichiro Higashiya, Vladimir V. Ermolenkov, John T. Welch, and Igor K. Lednev). 10 Circular Dichroism of Intrinsically Disordered Proteins (Robert W. Woody). 11 Fluorescence Spectroscopy of Intrinsically Disordered Proteins (Eugene A. Permyakov and Vladimir N. Uversky). 12 Hydration of Intrinsically Disordered Proteins From Wide-Line NMR (Kálmán Tompa, Monika Bokor, and Peter Tompa). PART III SINGLE-MOLECULE TECHNIQUES. 13 Single-Molecule Spectroscopy of Unfolded Proteins (Benjamin Schuler). 14 Monitoring the Conformational Equilibria of Monomeric Intrinsically Disordered Proteins by Single-Molecule Force Spectroscopy (Massimo Sandal, Marco Brucale, and Bruno Samorì). PART IV METHODS TO ASSESS PROTEIN SIZE AND SHAPE. 15 Analytical Ultracentrifugation, a Useful Tool to Probe Intrinsically Disordered Proteins (Florence Manon and Christine Ebel). 16 Structural Insights into Intrinsically Disordered Proteins by Small-Angle X-Ray Scattering (Pau Bernadó and Dmitri I. Svergun). 17 Dynamic and Static Light Scattering (Klaus Gast). 18 Analyzing Intrinsically Disordered Proteins by Size Exclusion Chromatography (Vladimir N. Uversky). PART V CONFORMATIONAL STABILITY 545 19 Conformational Behavior of Intrinsically Disordered Proteins: Effects of Strong Denaturants, Temperature, PH, Counterions, and Macromolecular Crowding (Vladimir N. Uversky). 20 Detecting Disordered Regions in Proteins by Limited Proteolysis (Angelo Fontana, Patrizia Polverino de Laureto, Barbara Spolaore, Erica Frare, and Marcello Zambonin). PART VI MASS SPECTROMETRY. 21 Mass Spectrometry Tools for the Investigation of Structural Disorder and Conformational Transitions in Proteins (Mária Šamalíková, Carlo Santambrogio, and Rita Grandori). PART VII EXPRESSION AND PURIFICATION OF IDPS. 22 Recombinant Production of Intrinsically Disordered Proteins for Biophysical and Structural Characterization (Dmitri Tolkatchev, Josee Plamondon, Richard Gingras, Zhengding Su, and Feng Ni). 23 Large-Scale Identifi cation of Intrinsically Disordered Proteins (Vladimir N. Uversky, Marc S. Cortese, Peter Tompa, Veronika Csizmok, and A. Keith Dunker). 24 Purification of Intrinsically Disordered Proteins (Aviv Paz, Tzviya Zeev-Ben-Mordehai, Joel L. Sussman, and Israel Silman). INDEX.

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Book SynopsisThe book provides an account of the totality of fragrance chemistry in one volume. It describes the chemistry of odorous materials, how and why they are produced in nature, how they are produced and used commercially, how they are analyzed and characterized, the chemistry of how we perceive them, and their role in our everyday lives.Trade Review“I cannot recommend this fascinating book highly enough.” (Simon Cotton, Chemistry & Industry, September 2014) “In conclusion: A comprehensive introduction to the world of odours, not only for chemists.” (review in German: Monika Paduch, Gefahrstoffe - Reinhaltung Luft, October 2014)Table of ContentsPreface vii Acknowledgments ix Introduction 1 1 Why Do We Have a Sense of Smell? 4 2 The Mechanism of Olfaction 32 3 Analysis and Characterisation of Odour 188 4 The Sense of Smell in Our Lives 209 5 The Scents of Nature 237 6 Manufacture of Fragrance Ingredients 296 7 The Design of New Fragrance Ingredients 357 8 The Relationship Between Molecular Structure and Odour 388 9 Intellectual Challenges in Fragrance Chemistry and the Future 420 Glossary 428 Index 437

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Book SynopsisThis book reviews advances in understanding phosphodiesterases within the central nervous system and theirtherapeutic applications. A range of expert authors from both academia and industry describe these, then focus on the areas of greatest scientific and medical interest to provide more detailed coverage. Therapeutic and drug discovery applications are covered for diseasesincluding Alzheimer''s, Parkinson''s, schizophrenia, erectile dysfunction, and spinal cord injuries. There is also a chapter on drug discovery tools such as in vitro assays and X-ray structures for medicinal chemistry studies.Table of ContentsPREFACE vii CONTRIBUTORS ix 1 PHOSPHODIESTERASES AND CYCLIC NUCLEOTIDE SIGNALING IN THE CNS 1 Marco Conti and Wito Richter 2 PUTTING TOGETHER THE PIECES OF PHOSPHODIESTERASE DISTRIBUTION PATTERNS IN THE BRAIN: A JIGSAW PUZZLE OF CYCLIC NUCLEOTIDE REGULATION 47 Michy P. Kelly 3 COMPARTMENTALIZATION AND REGULATION OF CYCLIC NUCLEOTIDE SIGNALING IN THE CNS 59 Manuela Zaccolo and Alessandra Stangherlin 4 PHARMACOLOGICAL MANIPULATION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE SIGNALING FOR THE TREATMENT OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS IN THE BRAIN 77 Frank S. Menniti, Niels Plath, Niels Svenstrup, and Christopher J. Schmidt 5 RECENT RESULTS IN PHOSPHODIESTERASE INHIBITOR DEVELOPMENT AND CNS APPLICATIONS 115 David P. Rotella 6 CRYSTAL STRUCTURES OF PHOSPHODIESTERASES AND IMPLICATION ON DISCOVERY OF INHIBITORS 145 Hengming Ke, Huanchen Wang, Mengchun Ye, and Yingchun Huang 7 INHIBITION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASES TO REGULATE MEMORY 171 Han-Ting Zhang, Ying Xu, and James O’Donnell 8 EMERGING ROLE FOR PDE4 IN NEUROPSYCHIATRIC DISORDERS: TRANSLATING ADVANCES FROM GENETIC STUDIES INTO RELEVANT THERAPEUTIC STRATEGIES 211 Sandra P. Zoubovsky, Nicholas J. Brandon, and Akira Sawa 9 BEYOND ERECTILE DYSFUNCTION: UNDERSTANDING PDE5 ACTIVITY IN THE CENTRAL NERVOUS SYSTEM 223 Eva P.P. Bollen, Kris Rutten, Olga A.H. Reneerkens, Harry M.W. Steinbusch, and Jos Prickaerts 10 MOLECULAR AND CELLULAR UNDERSTANDING OF PDE10A: A DUAL-SUBSTRATE PHOSPHODIESTERASE WITH THERAPEUTIC POTENTIAL TO MODULATE BASAL GANGLIA FUNCTION 247 Erik I. Charych and Nicholas J. Brandon 11 ROLE OF CYCLIC NUCLEOTIDE SIGNALING AND PHOSPHODIESTERASE ACTIVATION IN THE MODULATION OF ELECTROPHYSIOLOGICAL ACTIVITY OF CENTRAL NEURONS 269 Sarah Threlfell and Anthony R. West 12 THE ROLE OF PHOSPHODIESTERASES IN DOPAMINE SYSTEMS GOVERNING MOTIVATED BEHAVIOR 303 Gretchen L. Snyder, Joseph P. Hendrick, and Akinori Nishi 13 INHIBITION OF PHOSPHODIESTERASES AS A STRATEGY FOR TREATMENT OF SPINAL CORD INJURY 353 Elena Nikulina and Marie T. Filbin INDEX 375

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Book SynopsisAn overview of the new technologies that have revolutionized organic chemistry and allowed easy access to complex bioactives, this book brings modern synthetic techniques and bioactives together. The synthesis of structurally complex molecules has become a real challenge for the synthetic community.Table of ContentsFOREWORD vii PREFACE ix CONTRIBUTORS xi CHAPTER 1 C–H FUNCTIONALIZATION: A NEW STRATEGY FOR THE SYNTHESIS OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS 1 Sophie Rousseaux, Benoýˆt Lie´gault, and Keith Fagnou CHAPTER 2 THE NEGISHI CROSS-COUPLING IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOACTIVE MOLECULES 33 Evelina Colacino, Jean Martinez, and Fre´de´ric Lamaty CHAPTER 3 METAL-CATALYZED C–HETEROATOM CROSS-COUPLING REACTIONS 77 Renata Marcia de Figueiredo, Jean Marc Campagne, and Damien Prim CHAPTER 4 GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS 111 Fabien Gagosz CHAPTER 5 METATHESIS-BASED SYNTHESIS OF COMPLEX BIOACTIVES 155 Jean-Alexandre Richard, Sin Yee Ng, and David Y.-K. Chen CHAPTER 6 ENANTIOSELECTIVE ORGANOCATALYSIS: A POWERFUL TOOL FOR THE SYNTHESIS OF BIOACTIVE MOLECULES 189 Mitsuru Shoji and Yujiro Hayashi CHAPTER 7 ASYMMETRIC PHASE-TRANSFER CATALYSIS 213 Seiji Shirakawa, Shin A. Moteki, and Keiji Maruoka CHAPTER 8 REARRANGEMENTS IN NATURAL PRODUCT SYNTHESIS 243 Jose´ Marco-Contelles and Elena Soriano CHAPTER 9 DOMINO REACTIONS IN THE ENANTIOSELECTIVE SYNTHESIS OF BIOACTIVE NATURAL PRODUCTS 271 Lutz F. Tietze, Scott G. Stewart, and Alexander Du¨fert CHAPTER 10 FLUOROUS LINKER-FACILITATED SYNTHESIS OF BIOLOGICALLY INTERESTING MOLECULES 335 Wei Zhang CHAPTER 11 THE EVOLUTION OF IMMOBILIZED REAGENTS AND THEIR APPLICATION IN FLOW CHEMISTRY FOR THE SYNTHESIS OF NATURAL PRODUCTS AND PHARMACEUTICAL COMPOUNDS 359 Rebecca M. Myers, Kimberley A. Roper, Ian R. Baxendale, and Steven V. Ley CHAPTER 12 SYNTHETIC APPROACHES TO BIOACTIVE CARBOHYDRATES 395 Xavier Guinchard, Se´bastien Picard, and David Crich CHAPTER 13 AMMONIUM YLIDES AS BUILDING BLOCKS FOR ALKALOID SYNTHESIS 433 Scott Bur and Albert Padwa CHAPTER 14 PRECURSOR-DIRECTED BIOSYNTHESIS OF POLYKETIDE AND NONRIBOSOMAL PEPTIDE NATURAL PRODUCTS 485 Colin J. B. Harvey and Chaitan Khosla CHAPTER 15 TARGET-ORIENTED AND DIVERSITY-ORIENTED ORGANIC SYNTHESIS 513 Raphae¨l Rodriguez CHAPTER 16 DNA AS A TOOL FOR MOLECULAR DISCOVERY 539 Michael Smietana, Jean-Jacques Vasseur, Janine Cossy, and Stellios Arseniyadis INDEX 557

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Book SynopsisThis book provides up-to-date information on experimental and computational characterization of the structural and functional properties of viral proteins, which are widely involved in regulatory and signaling processes. With chapters by leading research groups, it features current information on the structural and functional roles of intrinsic disorders in viral proteomes. It systematically addresses the measles, HIV, influenza, potato virus, forest virus, bovine virus, hepatitis, and rotavirus as well as viral genomics. After analyzing the unique features of each class of viral proteins, future directions for research and disease management are presented.Table of ContentsPreface. 1. Do viral proteins possess unique features? (Vladimir Uversky). 2. Functional role of structural disorder in capsid proteins (Lars Liljas). 3. Structural disorder within the nucleoproteins and phosphoproteins of measles, Nipah and Hendra viruses (Johnny Habchi and Sonia Longhi). 4. Structural disorder within the Sendai virus nucleoprotein and phosphoprotein (Rob Ruigrok and Martin Blackledge). 5. Structural disorder in Rhabdoviridae phosphoproteins (Marc Jamin). 6. Structural disorder in matrix proteins from HiV-related viruses (Vladimir Uversky and Keith Dunker). 7. Structural disorder in proteins from influenza virus (Vladmir Uversky and Keith Dunker). 8. Structural disorder in the HIV-1 Vif protein and oilgomerization-dependent gain of structure (Assaf Friedler). 9. Order from Disorder: Structure, Function and Dynamics of the HIV-1 Transactivator of Transcription (Joe D. O’Neil). 10. Intrinsically disordered protein domains of the non structural proteins of Sesbania mosaic virus and their functional role (Handanahal S. Savithri). 11. Intrinsic disorder in genome-linked viral proteins VPgs of potyviruses (Jadwiga Chroboczek, Eugénie Hébrard, Kristiina Mäkinen, Thierry Michon and Kimmo Rantalainen). 12. Intrinsic disorder in HPV 16 E7 protein (Gonzalo de Prat-Gay). 13. The Semiliki forest virus serine protease is disordered and yet displays catalytic activity (Manuel Morillas). 14. Intrinsic disorder in the core proteins of Flaviviridae (Jean-Luc Darlix). 15. Domains 2 and 3 of non-structural protein 5A (NS5A) of hepatitis C virus is natively unfolded (Ho Sup Yoon). 16. Intrinsic disorder within phage λ N protein and interaction with the E. coli NusA protein (Kristian Schweimer). 17. The N-terminal extension region of Hordeivirus movement TGB1 protein consists of two domains with different content of disordered structure (V.V. Makarov, M.E. Tailansky, E.N. Dobrov, N.O. Kalinina).

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Book SynopsisMedical Biochemistry at a Glance is a concise, illustrated summary of biochemistry and its relevance to clinical medicine. It is intended for students of medicine and the biomedical sciences such as nutrition, biochemistry, sports science, medical laboratory sciences, physiotherapy, pharmacy, physiology, pharmacology and veterinary science.Trade ReviewI have taught biochemistry to medical students and to undergraduates and graduate students, at both Temple University School of Medicine and at Case Western Reserve University, since 1968, so that I have had a great deal of experience in the field and have a feel for what works well for medical students. Medical Biochemistry at a Glance would be an excellent book for USMLE Step 1. In my experience, medical students (and pre-medical students) would greatly benefit from reading it in preparation for the exam. This compares very well with Lippincott’s Biochemistry - this has the right price and approach to compete with Lippincott for a less expensive and more accessible alternative to the larger text books that are out there. I like the way it combines the metabolic pathways and principles in such a creative fashion, and the metabolism sections are among the best I have read and the easiest to understand. Metabolism is a very complicated subject and, in my experience, most teachers of the subject would really benefit from your text. (Richard W. Hanson, Case Western Reserve University School of Medicine)Table of ContentsPreface to the third edition 7 Acknowledgements to the third edition 7 Figure key 8 SI/mass unit conversions 9 Part 1 Acids, bases and pH 1 Acids, bases and hydrogen ions (protons) 10 2 Understanding pH 12 3 Production and removal of protons into and from the blood 14 4 Metabolic alkalosis and metabolic acidosis 16 5 Respiratory alkalosis and respiratory acidosis 18 Part 2 Structure of amino acids and proteins 6 Amino acids and the primary structure of proteins 20 7 Secondary structure of proteins 22 8 Tertiary and quaternary structure and collagen 24 Part 3 Formation of ATP: oxidation and reduction reactions 9 Oxidation/reduction reactions, coenzymes and prosthetic groups 26 10 Anaerobic production of ATP by substrate-level phosphorylation, from phosphocreatine and by the adenylate kinase (myokinase) reaction 28 11 Aerobic production of ATP 30 12 Biosynthesis of ATP by oxidative phosphorylation I 32 13 Biosynthesis of ATP by oxidative phosphorylation II 34 14 What happens when protons or electrons leak from the respiratory chain? 36 15 Free radicals, reactive oxygen species and oxidative damage 38 16 Aerobic oxidation of glucose to provide energy as ATP 40 17 Anaerobic oxidation of glucose by glycolysis to form ATP and lactate 42 18 Anaerobic glycolysis in red blood cells, 2,3-BPG (2,3-DPG) and the Bohr effect 44 Part 4 Carbohydrates 19 Carbohydrates 46 20 Absorption of carbohydrates and metabolism of galactose 48 21 Fate of glucose in liver: glycogenesis and lipogenesis 50 22 Fructose metabolism 52 23 Glucose homeostasis 54 24 Glucose-stimulated secretion of insulin from β-cells 56 25 Regulation of glycogen metabolism 58 26 Glycogen breakdown (glycogenolysis) and glycogen storage diseases 60 27 Insulin signal transduction and diabetes mellitus 62 28 Diabetes mellitus 64 29 Alcohol metabolism: hypoglycaemia, hyperlactataemia and steatosis 66 Part 5 Enzymes and regulation of pathways 30 Enzymes: nomenclature, kinetics and inhibitors 68 31 Regulation of enzyme activity 70 32 Regulation of glycolysis and Krebs cycle 72 33 Oxidation of fatty acids to produce ATP in muscle and ketone bodies in liver 74 34 Regulation of lipolysis, β-oxidation, ketogenesis and gluconeogenesis 76 Part 6 Lipids and lipid metabolism 35 Structure of lipids 78 36 Phospholipids I: phospholipids and sphingolipids 80 37 Phospholipids II: micelles, liposomes, lipoproteins and membranes 82 38 Metabolism of carbohydrate to cholesterol 84 39 VLDL and LDL metabolism I: “forward” cholesterol transport 86 40 VLDL and LDL metabolism II: endogenous triacylglycerol transport 88 41 HDL metabolism: “reverse” cholesterol transport 90 42 Absorption and disposal of dietary triacylglycerols and cholesterol by chylomicrons 92 43 Steroid hormones: aldosterone, cortisol, androgens and oestrogens 94 Part 7 Metabolism of amino acids and porphyrins 44 Urea cycle and overview of amino acid catabolism 96 45 Non-essential and essential amino acids 98 46 Amino acid metabolism: to energy as ATP; to glucose and ketone bodies 100 47 Amino acid disorders: maple syrup urine disease, homocystinuria, cystinuria, alkaptonuria and albinism 102 48 Phenylalanine and tyrosine metabolism in health and disease 104 49 Products of tryptophan and histidine metabolism 106 50 Haem, bilirubin and porphyria 108 Part 8 Vitamins 51 Fat-soluble vitamins I: vitamins A and D 110 52 Fat-soluble vitamins II: vitamins E and K 112 53 Water-soluble vitamins I: thiamin, riboflavin, niacin and pantothenate 114 54 Water-soluble vitamins II: pyridoxal phosphate (B6) 116 55 Water-soluble vitamins III: folate and vitamin B12 118 56 Water-soluble vitamins IV: biotin and vitamin C 120 Part 9 Molecular biology 57 The cell cycle 122 58 Pyrimidine metabolism 124 59 Purine metabolism 126 60 Structure of DNA 128 61 The “central dogma” of molecular biology 130 62 Organisation of DNA in chromosomes 132 63 Replication of DNA (part 1) 134 64 Replication of DNA (part 2) 136 65 DNA damage and repair 138 66 Transcription of DNA to make messenger RNA (part 1) 140 67 Transcription of DNA to make messenger RNA (part 2) 142 68 Transcription of DNA to make transfer RNA 144 69 Transcription of DNA to make ribosomal RNA 146 70 Translation and protein synthesis 148 71 Comparison of DNA replication, DNA transcription and protein synthesis in eukaryotes and prokaryotes 150 Part 10 Diagnostic clinical biochemistry 72 Diagnostic clinical biochemistry (with Dr J. W. Wright FRCP, MRCPath) 152 Index 154

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Book SynopsisHuman blood performs many important functions including defence against disease and transport of biomolecules, but perhaps the most important is to carry oxygen the fundamental biochemical fuel - and other blood gases around the cardiovascular system. Traditional therapies for the impairment of this function, or the rapid replacement of lost blood, have centred around blood transfusions. However scientists are developing chemicals (oxygen therapeutics, or blood substitutes) which have the same oxygen-carrying capability as blood and can be used as replacements for blood transfusion or to treat diseases where oxygen transport is impaired. Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood links the underlying biochemical principles of the field with chemical and biotechnological innovations and pre-clinical development. The first part of the book deals with the chemistry, biochemistry, physiology and toxicity of oxygen, including cTable of ContentsList of Contributors xvii Preface xxiii 1. Introduction 1 Richard B. Weiskopf References 5 Part I. Oxygen: Chemistry, Biochemistry, Physiology and Toxicity 9 2. Hemoglobin Reactivity and Regulation 11 Stefano Bettati and Andrea Mozzarelli 2.1 Introduction 11 2.2 Oxygen Loading and Transport 11 2.3 NO Reactivity with Hb 15 2.4 Hb Oxidation 16 2.5 Nitrite Reactivity with Hb 16 2.6 Amino-acid Determinants of Hb Reactivity: Natural and Engineered Hbs 17 2.6.1 Modulation of Oxygen Affinity and Cooperativity 17 2.6.2 NO Reactivity and Oxidation 18 2.7 Conclusion 18 Acknowledgments 19 References 19 3. The Major Physiological Control Mechanisms of Blood Flow and Oxygen Delivery 23 Raymond C. Koehler 3.1 Introduction 23 3.2 Autoregulation of Blood Flow to Changes in Perfusion Pressure 23 3.3 Metabolic Regulation of Blood Flow 26 3.4 O2 Transport 27 3.5 O2 Delivery 27 3.6 Endothelial Control of Vasomotor Tone 29 3.7 Effect of Cell-free Hb on Endothelial Function 31 3.8 Hypoxic Hypoxia 33 3.9 Carbon Monoxide Hypoxia 36 3.10 Anemia 36 3.11 Conclusion 39 References 39 4. The Main Players: Hemoglobin and Myoglobin; Nitric Oxide and Oxygen 47 Tim J. McMahon and Joseph Bonaventura 4.1 Introduction 47 4.2 Role of Mammalian Mb in O2 Homeostasis 47 4.3 What’s Missing in the Mb Knockout Mouse 48 4.4 Evolutionary Origins of Mb and the Nitrogen Cycle 49 4.5 Human Hb: Evolved Sensor of pO2 and Redox 49 4.6 Broad Reactivity and Influence of NO: Lessons from the Microcosm Hb 49 4.7 Some Fish Demonstrate a Fundamental “Need” for Hb-dependent NO Cycling, as in Humans 50 4.8 Reactions of NO with Hb that Preserve NO Bioactivity 52 4.9 Mammalian RBC/Hb–NO Interactions 52 4.10 A Mutant Mouse Challenges the SNO-Hb Hypothesis, but does not Overthrow it 54 4.11 Signaling by Hb-derived SNO: A Metabolically Responsive, Regulated Pathway 54 4.12 Signaling by Hb-derived SNO: Pathway Complexity Revealed by Multiple Defects in Disease States 55 4.13 Therapeutic Implications of the Hb–NO Signaling System 56 4.14 HBOCs, NO, and SNO 56 4.15 Other Gaseous Hb Ligands of Potential Therapeutic Significance 57 4.16 NO-related Enzymatic Activities of Hb: Reconciling Nitrite Reductase and SNO Synthase Functions 57 4.17 Measuring Biologically Relevant Hb–NO Adducts 58 4.18 Conclusion 58 Acknowledgments 58 References 59 5. The Role of Reactive Oxygen and Nitrogen Species in Ischemia/Reperfusion Injury 63 Ester Spagnolli and Warren M. Zapol 5.1 Introduction 63 5.2 Redox System and Free Radicals in Biological Systems 64 5.3 Pathophysiology of Ischemia/Reperfusion Injury 65 5.3.1 Cell Death 65 5.3.2 The Inflammatory Response 67 5.4 Protection Against I/R Injury 67 5.4.1 Ischemic Pre- and Post-conditioning 67 5.4.2 Pharmacological Conditioning 68 5.4.2.1 The Protective Role of ROS and Antioxidants 68 5.4.2.2 The Protective Role of NO 69 5.4.2.3 NO-based Therapies for I/R Injury 70 5.5 Conclusion 72 Acknowledgments 72 References 72 Part II. Medical Needs for Oxygen Supply 79 6. Acute Traumatic Hemorrhage and Anemia 81 Lena M. Napolitano 6.1 Introduction 81 6.2 Blood Transfusion in Trauma 83 6.2.1 Massive Transfusion 83 6.2.2 Massive Transfusion and Coagulopathy 83 6.2.3 Hypotensive or Delayed Resuscitation 84 6.2.4 Hemostatic Resuscitation 84 6.2.5 Massive Transfusion Protocols 86 6.2.6 Transfusion after Hemorrhage Control 86 6.2.7 Efficacy of RBC Transfusion in Trauma and Associated Risks 86 6.3 Oxygen Therapeutics in Trauma 88 6.3.1 Diaspirin Crosslinked Hb 90 6.3.2 Hemopure 90 6.3.3 PolyHeme 91 6.3.4 MP4OX 93 6.3.5 Recombinant Human Hb 95 6.3.6 Adverse Effects of HBOCs 95 6.3.7 HBOCs in Trauma: A Way Forward? 96 6.4 Conclusion 97 References 97 7. Diagnosis and Treatment of Haemorrhages in ‘Nonsurgical’ Patients 107 Umberto Rossi and Rosa Chianese 7.1 Introduction 107 7.1.1 Aetiopathogenetic Classification 107 7.1.2 Multifactorial Pathogenesis 108 7.1.3 Haemorrhagic Syndromes from Antithrombotic Treatment or Prophylaxis 108 7.2 Clinical Assessment 111 7.2.1 Medical History 111 7.2.2 Physical Examination 112 7.3 Laboratory Tests 113 7.3.1 Screening Tests 113 7.3.2 Second-level Laboratory Tests 113 7.3.3 Other Tests 114 7.4 Haemorrhagic Syndromes Clinically Indicative of Systemic Defects with Normal Screening Tests 117 7.5 Blood and Blood Components in the Treatment of Haemorrhagic Syndromes 118 Further Reading 118 8. Management of Perioperative Bleeding 121 Sibylle A. Kozek-Langenecker 8.1 Introduction 121 8.2 Pathomechanisms of Coagulopathy in Massive Bleeding 121 8.3 Perioperative Coagulation Monitoring 122 8.4 Limitations of Routine Coagulation Tests in the Perioperative Setting 123 8.5 Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM) 124 8.6 Procoagulant Interventions 124 8.7 Algorithm for Coagulation Management 126 References 127 9. Oxygenation in the Preterm Neonate 131 Vidheya Venkatesh, Priya Muthukumar, Anna Curley and Simon Stanworth 9.1 Introduction 131 9.2 Physiology of Oxygen Transport in Fetal and Postnatal Life 132 9.2.1 Oxygenation of the Fetus 132 9.2.2 Measuring Oxygenation in the Neonate 133 9.3 Oxygen Therapy in the Postnatal Period 133 9.3.1 Oxidative Stresses in the Newborn Period 134 9.3.2 Clinical Sequelae of Hyperoxia 134 9.3.2.1 Retinopathy of Prematurity 134 9.3.2.2 Oxygen and Chronic Lung Disease 135 9.3.2.3 Oxygen and Periventricular Leukomalacia 136 9.4 Oxygen and Resuscitation of the Newborn Infant 136 9.5 Transfusion in the Newborn 137 9.6 ROP and Transfusions 137 9.7 Conclusion 137 References 138 10. Ischemia 145 Hooman Mirzakhani and Ala Nozari 10.1 Introduction 145 10.2 Pathophysiology 145 10.2.1 Energy Failure 145 10.2.2 Cell Membrane Damage 146 10.2.3 Increased Cytosolic Calcium 146 10.2.4 Inflammation 148 10.2.5 The No-reflow Phenomenon 149 10.2.6 Free Radicals and Reactive Oxygen Species 149 10.2.7 Excitotoxicity 150 10.3 Therapeutic Potentials 150 10.3.1 Preconditioning 150 10.3.2 Antioxidants 151 10.3.3 Anti-inflammation Therapy 151 10.3.4 Therapeutic Hypothermia 151 10.3.5 Hydrogen Sulfide 152 10.3.6 Hyperoxia and Hyperbaric Oxygen 152 10.3.7 Hemoglobin-based Oxygen Carriers 152 10.4 Conclusion 153 References 153 11. Normobaric and Hyperbaric Oxygen Therapy for Ischemic Stroke and Other Neurological Conditions 159 Ari Moskowitz, Yu-Feng Yvonne Chan and Aneesh B. Singhal 11.1 Introduction 159 11.2 Rationale of Oxygen Therapy in AIS 160 11.3 Hyperbaric Oxygen Therapy 162 11.4 Normobaric Oxygen Therapy 164 11.5 The Status of Supplemental Oxygen Delivery 165 11.6 Comparison of HBO and NBO in AIS 165 11.7 Safety Concerns 168 11.8 HBO and NBO in Other Conditions 169 11.9 Conclusion 169 References 170 12. Transfusion Therapy in β Thalassemia and Sickle Cell Disease 179 Carlo Brugnara and Lucia De Franceschi 12.1 Introduction 179 12.2 β Thalassemia and Transfusion 179 12.3 Sickle Cell Disease and Transfusion 182 12.4 Iron Chelation Tools 185 12.5 Conclusion 186 References 186 Part III. “Old” and New Strategies for Oxygen Supply 193 13. Transfusion: Political, Administrative and Logistic Issues 195 John R. Hess and Giuliano Grazzini Disclaimer 195 13.1 Introduction 195 13.2 Blood Safety 196 13.3 Blood Availability 198 13.4 Cost and Fairness 200 13.5 Transfusion Medicine 201 References 202 14. Conscientious Objection in Patient Blood Management 205 Kenneth E. Nollet and Hitoshi Ohto 14.1 Introduction 205 14.2 Conscientious Objection 205 14.3 Patient Blood Management 206 14.4 Jehovah’s Witnesses 207 14.5 Will the Real Objection Please Stand Up? 208 14.6 Conscientious Objection in Relation to Oxygen Therapeutics and Other Innovations 208 Acknowledgements 209 References 210 15. Red-cell Transfusion in Clinical Practice 213 Harvey G. Klein 15.1 Introduction 213 15.2 Red-cell Use 214 15.3 The Red-cell-transfusion Trigger 215 15.4 Risks of Red-cell Transfusion 216 15.5 Conclusion 218 Disclaimer 218 References 218 16. Causes and Consequences of Red Cell Incompatibility 221 Chisa Yamada and Robertson Davenport 16.1 Introduction 221 16.2 Red Cell Antigens 221 16.2.1 ABO and the H System 221 16.2.2 The Lewis System and Structurally Related Antigens 222 16.2.3 The Rh System 222 16.2.4 Other Blood Group Systems 222 16.3 Red Cell Antibodies 223 16.3.1 Naturally Occurring Antibodies and Immune Antibodies 223 16.3.2 Autoantibodies 224 16.3.3 Drug Induced Antibodies 224 16.4 Compatibility Testing 224 16.4.1 ABO and Rh D Typing 224 16.4.2 Antibody Screening and Identification 224 16.4.3 Selection of Appropriate Blood 225 16.4.4 Crossmatch Testing 225 16.5 Hemolytic Transfusion Reactions 225 16.5.1 Pathophysiology 226 16.5.2 Prevention 228 References 228 17. Biochemistry of Storage of Red Blood Cells 231 Ryan Stapley, Dario A. Vitturi and Rakesh P. Patel 17.1 Introduction 231 17.2 Pathologic Consequences of Transfusion with Aged RBCs 232 17.3 Changes in Oxygen Affinity During RBC Storage 232 17.4 Role of Oxidative Damage During RBC Storage 233 17.5 Changes in the Physical Properties of RBCs During Storage 234 17.6 RBCs as Modulators of Vascular Flow 234 17.6.1 ATP Release Hypothesis 234 17.6.2 SNO-hemoglobin Hypothesis 235 17.6.3 Nitrite Reductase/Anhydrase Hypothesis 236 17.7 RBC-dependent Modulation of Inflammation 237 17.8 Conclusion 237 Acknowledgements 238 References 238 18. Proteomic Investigations of Stored Red Blood Cells 243 Lello Zolla and Angelo D’Alessandro 18.1 Introduction 243 18.2 RBC Ageing and Metabolism in vivo 244 18.3 RBC Storage Lesions Through Proteomics 248 18.4 Conclusion 252 References 252 19. Red Blood Cells from Stem Cells 257 Anna Rita Migliaccio, Carolyn Whitsett and Giovanni Migliaccio 19.1 Introduction 257 19.2 Stem-cell Sources for ex vivo Generation of Erythroid Cells as a Transfusion Product 258 19.3 Conditions that Favor ex vivo Erythroid Cell Expansion 260 19.4 A Clinical-grade Production Process for ex vivo Generation of Red-cell Transfusion Products 261 19.4.1 The Nature of the Production Process 261 19.4.2 Cellular Composition of the Product 263 19.4.3 Functional Status of Product 264 19.4.4 Safety Considerations 265 19.5 Time Line of the Clinical Application of ex vivo-generated Erythroid Cells 266 19.5.1 Drug Discovery 266 19.5.2 Drug Delivery 267 19.5.3 Ex vivo-expanded EBs for Alloimmunized Patients 268 References 268 20. The Universal Red Blood Cell 273 Luca Ronda and Serena Faggiano 20.1 Introduction 273 20.1.1 ABO Antigens 274 20.1.2 The Rh System 274 20.2 Enzymatic Removal of A and B Antigens 275 20.2.1 Conversion of B RBCs to Group O 275 20.2.2 Conversion of A RBCs to Group O 277 20.3 RBC Camouflage Through PEGylation 277 20.3.1 Functionalized Methoxy PEG 278 20.3.2 Cyanuric Chloride PEG 279 20.3.3 Extension Arm-facilitated RBC PEGylation 279 20.3.4 Increasing the Degree of RBC PEGylation 280 20.4 Conclusion 280 References 280 21. Allosteric Effectors of Hemoglobin: Past, Present and Future 285 Martin K. Safo and Stefano Bruno 21.1 Introduction 285 21.2 Natural and Synthetic Allosteric Effectors 288 21.2.1 Organic Phosphates 288 21.2.2 Synthetic Aromatic Propionate Right-shifters 289 21.2.3 Aromatic Aldehyde Left-shifters 290 21.3 Molecular Mechanism of Action of Allosteric Effectors 293 21.3.1 Oxygen Binding Curve and Hb Structural Changes 293 21.3.2 How Allosteric Effectors can Bind to the Same Site and Have Opposite Allosteric Properties 294 21.3.3 Decreasing Subunit Mobility and Changes in Allosteric Properties: Molecular Ratchets 294 21.4 The First Visualization of an Important Pharmacological Theory via Hb Allosteric Effector Binding 295 21.5 The Clinical Importance of Hemoglobin Allosteric Effectors 295 References 296 22. Hemoglobin-based Oxygen Carriers: History, Limits, Brief Summary of the State of the Art, Including Clinical Trials 301 Jonathan S. Jahr, Arezou Sadighi, Linzy Doherty, Alvin Li and Hae Won Kim 22.1 Introduction 301 22.2 American Society of Anesthesiologists Guidelines and Risks of Blood Transfusion 302 22.3 Limitations of Blood Transfusion 302 22.4 History 302 22.5 Development 303 22.6 Definitive Clinical Trials 304 22.6.1 Diaspirin Crosslinked Hemoglobin (DCLHb, HemeAssist, Baxter Laboratories, Deerfield, IL) 304 22.6.2 Hemoglobin Raffimer (HR, Hemolink, Hemosol Inc., Ontario, Canada) 306 22.6.3 Human Polymerized Hemoglobin (PolyHeme, Northfield Laboratories, Evanston, IL) 307 22.6.4 Hemoglobin Glutamer-250 (Bovine) (HBOC-201, Hemopure, Biopure Corp., Cambridge, MA) 308 22.6.5 Maleimide-polyethylene Glycol-modified Hemoglobin (MP4, Hemospan, Sangart Inc., San Diego, CA) 309 22.7 Current Status and Future Directions of HBOCs 311 References 314 23. Oxygen Delivery by Natural and Artificial Oxygen Carriers 317 Enrico Bucci 23.1 Introduction 317 23.2 The Role of Oxygen Carriers 317 23.3 The Role of Natural Cell-bound Oxygen Carriers 318 23.4 Matching the Rate of Oxygen Delivery with the Rate of Oxygen Consumption 320 23.4.1 The Imbalance 320 23.4.2 The Rate of Oxygen Release from the Red Cells 320 23.4.3 Matching the Delivery/Consumption Rates 321 23.4.4 The Hematocrit is a Critical Parameter 321 23.5 The Role of Artificial Cell-free Oxygen Carriers 321 23.5.1 Facilitated Diffusion 321 23.5.2 Toxicity 322 23.6 Other Parameters 322 23.7 Clinical Use? 323 Acknowledgments 324 References 324 24. Crosslinked and Polymerized Hemoglobins as Potential Blood Substitutes 327 Kenneth W. Olsen and Eugene Tarasov 24.1 Introduction 327 24.2 Crosslinking the Hb Tetramer 328 24.3 Hb Polymers 332 24.4 Conclusion 337 References 338 25. Engineering the Molecular Shape of PEG-Hemoglobin Adducts for Supraperfusion 345 Seetharama A. Acharya, Marcos Intaglietta, Amy G. Tsai, Kulal Ananda and Fantao Meng 25.1 Introduction 345 25.2 Enzon DecaPEGylated Bovine Hb is Nonhypertensive 346 25.3 EAF HexaPEGylated Hb (EAF P5K6-Hb) is Nonhypertensive 347 25.4 Molecular and Solution Properties of EAF HexaPEGylated Human Hb (EAF-P5K6-Hb) 347 25.5 High O2 Affinity of EAF HexaPEGylated Hb and Tissue Oxygenation in Extreme Hemodilution 349 25.6 Influence of Total PEG Mass Conjugated to Hb on O2 Affinity and Tissue Oxygenation by PEG-Hbs 350 25.7 Influence of PEGylation Chemistry on Structural, Functional, and Solution Properties of HexaPEGylated Hb 351 25.8 Reductive PEGylation-induced Weakening of Interdimeric Interactions of Tetrameric Hbs 352 25.9 PEGylation-promoted Dissociation of Hb Tetramer is Attenuated by the Extension Arms of EAF PEGylated Hbs 353 25.10 Does Urethane-linkage-mediated PEGylation of Hb Promote its Dissociation? 354 25.11 Hemospan: Prototype of EAF HexaPEGylated Hb Designed at Einstein 354 25.12 EAF HexaPEGylated Hb Compared to other Blood Substitutes of Earlier Designs 355 25.13 Reversible Protection of Cys-93(β) during EAF PEGylation of Hb and Crosslinked Hbs: A Structural Requirement to Generate Medium- and Low-O2-affinity PEG-Hbs 355 25.14 Engineering Extension Arms between the Protein Core and PEG Shell Attenuates PEGylation-promoted Tetramer Dissociation 356 25.15 Attenuation of Direct HexaPEGylation-promoted Dissociation of Hb Tetramers by Increasing the Tetramer Stability Through Chemical Modification 359 25.16 Influence of the Extension Arm on the HexaPEGylation-enhanced Thermal Stability of Hb 359 25.17 PEGylation of Hb Induces a Hydrostatic Molecular Drag to the PEG-Hb Conjugate 360 25.18 EAF HexaPEGylated Hb is a Superperfusion Agent 360 25.19 EAF PEG-Hb-induced Vasodilation 361 25.20 In vivo Vasodilation by EAF PEG-Hb through its Enhanced Nitrite Reductase Activity 361 25.21 EAF PEG-Hbs as Mechanotransducers of e-NOS Activity 363 25.22 The Pattern of PEGylation of Intramolecularly Crosslinked Hbs Influences the Viscosity of the PEG-Hb Solution 364 25.23 Conclusion 364 Acknowledgments 366 References 367 26. Hb Octamers by Introduction of Surface Cysteines 371 V´eronique Baudin-Creuza, Chien Ho and Michael C. Marden 26.1 Introduction 371 26.2 Genetic Engineering of Proteins with Cysteines 373 26.2.1 Protein Expression 373 26.2.2 Oligomer Size 374 26.2.3 Disulfide Bond Formation 375 26.2.4 Functional Properties of the Octamers 376 26.2.5 Octamer Properties 378 26.2.6 Octamer Constraint 378 26.3 Conclusion 378 References 378 27. Hemoglobin Vesicles as a Cellular-type Hemoglobin-based Oxygen Carrier 381 Hiromi Sakai, Hirohisa Horinouchi, Eishun Tsuchida and Koichi Kobayashi 27.1 Introduction 381 27.2 The Concept of Hb Encapsulation in Liposomes 382 27.3 Hb Encapsulation Retards Gas Reactions 383 27.4 HBOCs as a Carrier of not only O2 but also CO 385 27.5 Conclusion 387 Acknowledgments 387 References 387 28. Animal Models and Oxidative Biomarkers to Evaluate Preclinical Safety of Extracellular Hemoglobins 391 Paul W. Buehler and Felice D’Agnillo Disclaimer 391 28.1 Introduction 391 28.2 HBOC Safety and Efficacy 392 28.2.1 Proposed Mechanisms of Toxicity 392 28.2.1.1 Hypertension 392 28.2.1.2 Oxidative Stress 392 28.2.2 Safety Pharmacology and Toxicology Studies 393 28.2.3 In vivo Models of Efficacy “Proof of Concept” 395 28.2.3.1 Tissue Blood Flow and Oxygenation 395 28.2.3.2 Traumatic Hemorrhage 396 28.2.3.3 Local Ischemia 397 28.2.3.4 Sickle Cell Disease 397 28.2.4 Experimental Approaches to Assessing Preclinical Safety of HBOCs 398 28.2.4.1 Species Antioxidant Status (Natural Evolution) 398 28.2.4.2 Chemically Induced Antioxidant Depletion 398 28.2.4.3 Endothelial Dysfunction 399 28.2.4.4 Sepsis and Endotoxemia 400 28.3 Experimental Oxidative Biomarkers and Extracellular Hb Exposure 400 28.3.1 Heme Iron Oxidation 400 28.3.2 Amino-acid Oxidation 401 28.3.3 Heme Catabolism and Iron Sequestration 401 28.4 Markers of in vivo Oxidative Stress and Tissue Damage 403 28.4.1 4-hydroxy-2-nonenal (4-HNE) Protein Adducts 403 28.4.2 8-hydroxy-2-deoxyguanosine (8-OHdG) 403 28.5 Conclusion 404 References 405 29. Academia–Industry Collaboration in Blood Substitute Development: Issues, Case Histories and a Proposal 413 Hae Won Kim, Andrea Mozzarelli, Hiromi Sakai and Jonathan S. Jahr 29.1 Introduction 413 29.2 Generic Issues in Academia–Industry Collaboration 414 29.3 Academia–Industry Collaboration in HBOC Development 415 29.4 Proposal for a New Academia–Industry Collaboration Model in HBOC Development: an HBOC Research Consortium (a Conceptual Model) 417 29.4.1 Mission 417 29.4.2 Guiding Principles 417 29.4.3 Key Objectives 417 29.4.4 Structure 418 29.4.5 Operation 419 29.5 Discussion 420 29.6 Conclusions 421 Appendix: Successful Academia–Industry Collaboration Cases in HBOC Development 422 Case A: Waseda–Keio–Industry Research Collaboration 422 Case B: EuroBloodSubstitutes Consortium 424 References 426 Index 429

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Book Synopsis* A major new edition of this highly successful, authoritative, superbly illustrated text * Distinguished, internationally renowned Editors * Completely revised with over half of the chapters having a major rewrite * Includes two new chapters on signal transduction and responses to pathogens .Trade Review“Biochemistry and Molecular Biology of Plants, 2nd edi­tion is a beast, but it’s a user-friendly one that should be wel­comed into one’s life to provide much-appreciated com­pan­ion­ship to fur­ther one’s plant bio­logy studies.” (AoB Blog, 1 November 2015) Table of ContentsThe Editors xi List of Contributors xii Preface xv About the Companion Website xvi COMPARTMENTS 1 Membrane Structure and Membranous Organelles 2 Introduction 2 1.1 Common properties and inheritance of cell membranes 2 1.2 The fluid-mosaic membrane model 4 1.3 Plasma membrane 10 1.4 Endoplasmic reticulum 13 1.5 Golgi apparatus 18 1.6 Exocytosis and endocytosis 23 1.7 Vacuoles 27 1.8 The nucleus 28 1.9 Peroxisomes 31 1.10 Plastids 32 1.11 Mitochondria 39 Summary 44 2 The Cell Wall 45 Introduction 45 2.1 Sugars are building blocks of the cell wall 45 2.2 Macromolecules of the cell wall 51 2.3 Cell wall architecture 73 2.4 Cell wall biosynthesis and assembly 80 2.5 Growth and cell walls 90 2.6 Cell differentiation 99 2.7 Cell walls as sources of food, feed, fiber, and fuel, and their genetic improvement 108 Summary 110 3 Membrane Transport 111 Introduction 111 3.1 Overview of plant membrane transport systems 111 3.2 Pumps 120 3.3 Ion channels 128 3.4 Cotransporters 142 3.5 Water transport through aquaporins 146 Summary 148 4 Protein Sorting and Vesicle Traffic 151 Introduction 151 4.1 The cellular machinery of protein sorting 151 4.2 Targeting proteins to the plastids 153 4.3 Targeting proteins to mitochondria 157 4.4 Targeting proteins to peroxisomes 159 4.5 Transport in and out of the nucleus 160 4.6 ER is the secretory pathway port of entry and a protein nursery 161 4.7 Protein traffic and sorting in the secretory pathway: the ER 175 4.8 Protein traffic and sorting in the secretory pathway: the Golgi apparatus and beyond 182 4.9 Endocytosis and endosomal compartments 188 Summary 189 5 The Cytoskeleton 191 Introduction 191 5.1 Introduction to the cytoskeleton 191 5.2 Actin and tubulin gene families 194 5.3 Characteristics of actin filaments and microtubules 196 5.4 Cytoskeletal accessory proteins 202 5.5 Observing the cytoskeleton: Statics and dynamics 207 5.6 Role of actin filaments in directed intracellular movement 210 5.7 Cortical microtubules and expansion 216 5.8 The cytoskeleton and signal transduction 219 5.9 Mitosis and cytokinesis 222 Summary 238 CELL REPRODUCTION 6 Nucleic Acids 240 Introduction 240 6.1 Composition of nucleic acids and synthesis of nucleotides 240 6.2 Replication of nuclear DNA 245 6.3 DNA repair 250 6.4 DNA recombination 255 6.5 Organellar DNA 260 6.6 DNA transcription 268 6.7 Characteristics and functions of RNA 270 6.8 RNA processing 278 Summary 288 7 Amino Acids 289 Introduction 289 7.1 Amino acid biosynthesis in plants: research and prospects 289 7.2 Assimilation of inorganic nitrogen into N-transport amino acids 292 7.3 Aromatic amino acids 302 7.4 Aspartate-derived amino acids 318 7.5 Branched-chain amino acids 326 7.6 Glutamate-derived amino acids 330 7.7 Histidine 333 Summary 336 8 Lipids 336 Introduction 337 8.1 Structure and function of lipids 337 8.2 Fatty acid biosynthesis 344 8.3 Acetyl-CoA carboxylase 348 8.4 Fatty acid synthase 350 8.5 Desaturation and elongation of C16 and C18 fatty acids 352 8.6 Synthesis of unusual fatty acids 360 8.7 Synthesis of membrane lipids 365 8.8 Function of membrane lipids 373 8.9 Synthesis and function of extracellular lipids 382 8.10 Synthesis and catabolism of storage lipids 389 8.11 Genetic engineering of lipids 395 Summary 400 9 Genome Structure and Organization 401 Introduction 401 9.1 Genome structure: a 21st]century perspective 401 9.2 Genome organization 404 9.3 Transposable elements 416 9.4 Gene expression 422 9.5 Chromatin and the epigenetic regulation of gene expression 430 Summary 436 10 Protein Synthesis, Folding, and Degradation 438 Introduction 438 10.1 Organellar compartmentalization of protein synthesis 438 10.2 From RNA to protein 439 10.3 Mechanisms of plant viral translation 447 10.4 Protein synthesis in plastids 450 10.5 Post-translational modification of proteins 457 10.6 Protein degradation 463 Summary 475 11 Cell Division 476 Introduction 476 11.1 Animal and plant cell cycles 476 11.2 Historical perspective on cell cycle research 477 11.3 Mechanisms of cell cycle control 482 11.4 The cell cycle in action 488 11.5 Cell cycle control during development 497 Summary 506 ENERGY FLOW 12 Photosynthesis 508 Introduction 508 12.1 Overview of photosynthesis 508 12.2 Light absorption and energy conversion 511 12.3 Photosystem structure and function 519 12.4 Electron transport pathways in chloroplast membranes 529 12.5 ATP synthesis in chloroplasts 537 12.6 Organization and regulation of photosynthetic complexes 540 12.7 Carbon reactions: the Calvin-Benson cycle 542 12.8 Rubisco 548 12.9 Regulation of the Calvin-Benson cycle by light 551 12.10 Variations in mechanisms of CO 2 fixation 557 Summary 565 13 Carbohydrate Metabolism 567 Introduction 567 13.1 The concept of metabolite pools 570 13.2 The hexose phosphate pool: a major crossroads in plant metabolism 571 13.3 Sucrose biosynthesis 573 13.4 Sucrose metabolism 577 13.5 Starch biosynthesis 580 13.6 Partitioning of photoassimilates between sucrose and starch 587 13.7 Starch degradation 593 13.8 The pentose phosphate/triose phosphate pool 597 13.9 Energy and reducing power for biosynthesis 601 13.10 Sugar-regulated gene expression 606 Summary 608 14 Respiration and Photorespiration 610 Introduction 610 14.1 Overview of respiration 610 14.2 Citric acid cycle 613 14.3 Plant mitochondrial electron transport 620 14.4 Plant mitochondrial ATP synthesis 632 14.5 Regulation of the citric acid cycle and the cytochrome pathway 634 14.6 Integration of the cytochrome pathway and nonphosphorylating pathways 635 14.7 Interactions between mitochondria and other cellular compartments 639 14.8 Biochemical basis of photorespiration 646 14.9 The photorespiratory pathway 648 14.10 Role of photorespiration in plants 652 Summary 655 METABOLIC AND DEVELOPMENTAL INTEGRATION 15 Long]Distance Transport 658 Introduction 658 15.1 Selection pressures and long-distance transport systems 658 15.2 Cell biology of transport modules 664 15.3 Short-distance transport events between xylem and nonvascular cells 668 15.4 Short-]distance transport events between phloem and nonvascular cells 673 15.5 Whole-plant organization of xylem transport 691 15.6 Whole-plant organization of phloem transport 696 15.7 Communication and regulation controlling phloem transport events 705 Summary 710 16 Nitrogen and Sulfur 711 Introduction 711 16.1 Overview of nitrogen in the biosphere and in plants 711 16.2 Overview of biological nitrogen fixation 715 16.3 Enzymology of nitrogen fixation 715 16.4 Symbiotic nitrogen fixation 718 16.5 Ammonia uptake and transport 735 16.6 Nitrate uptake and transport 735 16.7 Nitrate reduction 739 16.8 Nitrite reduction 744 16.9 Nitrate signaling 745 16.10 Interaction between nitrate assimilation and carbon metabolism 745 16.11 Overview of sulfur in the biosphere and plants 746 16.12 Sulfur chemistry and function 747 16.13 Sulfate uptake and transport 750 16.14 The reductive sulfate assimilation pathway 752 16.15 Cysteine synthesis 755 16.16 Synthesis and function of glutathione and its derivatives 758 16.17 Sulfated compounds 763 16.18 Regulation of sulfate assimilation and interaction with nitrogen and carbon metabolism 764 Summary 767 17 Biosynthesis of Hormones 769 Introduction 769 17.1 Gibberellins 769 17.2 Abscisic acid 777 17.3 Cytokinins 785 17.4 Auxins 795 17.5 Ethylene 806 17.6 Brassinosteroids 810 17.7 Polyamines 818 17.8 Jasmonic acid 821 17.9 Salicylic acid 826 17.10 Strigolactones 830 Summary 833 18 Signal Transduction 834 Introduction 834 18.1 Characteristics of signal perception, transduction, and integration in plants 834 18.2 Overview of signal perception at the plasma membrane 838 18.3 Intracellular signal transduction, amplification, and integration via second messengers and MAPK cascades 843 18.4 Ethylene signal transduction 847 18.5 Cytokinin signal transduction 850 18.6 Integration of auxin signaling and transport 852 18.7 Signal transduction from phytochromes 857 18.8 Gibberellin signal transduction and its integration with phytochrome signaling during seedling development 861 18.9 Integration of light, ABA, and CO2 signals in the regulation of stomatal aperture 866 18.10 Prospects 870 Summary 870 19 Molecular Regulation of Reproductive Development 872 Introduction 872 19.1 The transition from vegetative to reproductive development 872 19.2 The molecular basis of flower development 881 19.3 The formation of male gametes 889 19.4 The formation of female gametes 897 19.5 Pollination and fertilization 902 19.6 The molecular basis of self]incompatibility 908 19.7 Seed development 913 Summary 923 20 Senescence and Cell Death 925 Introduction 925 20.1 Types of cell death 925 20.2 PCD during seed development and germination 930 20.3 Cell death during the development of secretory bodies, defensive structures and organ shapes 932 20.4 PCD during reproductive development 937 20.5 Senescence and PCD in the terminal development of leaves and other lateral organs 940 20.6 Pigment metabolism in senescence 948 20.7 Macromolecule breakdown and salvage of nutrients in senescence 951 20.8 Energy and oxidative metabolism during senescence 957 20.9 Environmental influences on senescence and cell death I: Abiotic interactions 961 20.10 Environmental influences on senescence and cell death II: PCD responses to pathogen attack 964 20.11 Plant hormones in senescence and defense-related PCD 974 Summary 982 PLANT ENVIRONMENT AND AGRICULTURE 21 Responses to Plant Pathogens 984 Introduction 984 21.1 Pathogens, pests, and disease 984 21.2 An overview of immunity and defense 985 21.3 How pathogens and pests cause disease 989 21.4 Preformed defenses 1009 21.5 Induced defense 1012 21.6 Effector-triggered immunity, a second level of induced defense 1022 21.7 Other sources of genetic variation for resistance 1032 21.8 Local and systemic defense signaling 1033 21.9 Plant gene silencing confers virus resistance, tolerance, and attenuation 1042 21.10 Control of plant pathogens by genetic engineering 1044 Summary 1050 22 Responses to Abiotic Stress 1051 Introduction 1051 22.1 Plant responses to abiotic stress 1051 22.2 Physiological and cellular responses to water deficit 1054 22.3 Gene expression and signal transduction in response to dehydration 1061 22.4 Freezing and chilling stress 1068 22.5 Flooding and oxygen deficit 1076 22.6 Oxidative stress 1085 22.7 Heat stress 1094 22.8 Crosstalk in stress responses 1097 Summary 1099 23 Mineral Nutrient Acquisition, Transport, and Utilization 1101 Introduction 1101 23.1 Overview of essential mineral elements 1102 23.2 Mechanisms and regulation of plant K+ transport 1103 23.3 Phosphorus nutrition and transport 1113 23.4 The molecular physiology of micronutrient acquisition 1118 23.5 Plant responses to mineral toxicity 1127 Summary 1131 24 Natural Products 1132 Introduction 1132 24.1 Terpenoids 1133 24.2 Biosynthesis of the basic five-carbon unit 1135 24.3 Repetitive additions of C5 units 1138 24.4 Formation of parent carbon skeletons 1141 24.5 Modification of terpenoid skeletons 1143 24.6 Metabolic engineering of terpenoid production 1145 24.7 Cyanogenic glycosides 1146 24.8 Cyanogenic glycoside biosynthesis 1152 24.9 Functions of cyanogenic glycosides 1157 24.10 Glucosinolates 1158 24.11 Alkaloids 1159 24.12 Alkaloid biosynthesis 1164 24.13 Biotechnological application of alkaloid biosynthesis research 1171 24.14 Phenolic compounds 1178 24.15 Phenolic biosynthesis 1185 24.16 The phenylpropanoid-acetate pathway 1188 24.17 The phenylpropanoid pathway 1195 24.18 Universal features of phenolic biosynthesis 1202 24.19 Evolution of secondary pathways 1205 Summary 1206 Further reading 1207 Index 1222

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Book SynopsisComing to a conclusion, this wonderful, informative and very interesting book presents an excellent overview of small volatile organic compounds and their role in our life and environment. Really fascinating is the entirety of scientific disciplines which were addressed by this book.Trade Review"Coming to a conclusion, this wonderful, informative and very interesting book presents an excellent overview of small volatile organic compounds and their role in our life and environment. Really fascinating is the entirety of scientific disciplines which were addressed by this book." (Flavour and Fragrance Journal, 2011) "In spite of its few shortcomings, this book deserves to be a well-used reference in the library of any laboratory specialising in VOC". (Chemistry World, 1 May 2011) "The Chemistry and Biology of Volatiles takes an interdisciplinary approach to volatile molecules". (Small Business VoIP, 14 December 2010)Table of ContentsForeword xiii List of Contributors xv Acknowledgements xvii Abbreviations xix 1 Volatiles – An Interdisciplinary Approach 1 Andreas Herrmann 1.1 Introduction 1 1.2 Geraniol – A Typical Example 2 1.3 Conclusion 8 References 8 2 Biosynthesis and Emission of Isoprene, Methylbutanol and Other Volatile Plant Isoprenoids 11 Hartmut K. Lichtenthaler 2.1 Introduction 11 2.2 Plant Isoprenoids 12 2.3 Two IPP-Yielding Pathways in Plants 15 2.4 Prenyl Chain Formation and Elongation 16 2.5 Compartmentation of Plant Isoprenoid Biosynthesis 16 2.6 The Enzyme Steps of the Plastidic DOXP/MEP Pathway of IPP Formation 17 2.7 Cross-Talk Between the Two IPP Biosynthesis Pathways 19 2.8 Biosynthesis and Emission of Volatile Isoprene at High Irradiance 22 2.8.1 Regulation of Isoprene Emission 25 2.9 Inhibition of Isoprene Biosynthesis 26 2.9.1 Fosmidomycin and 5-Ketoclomazone 26 2.9.2 Diuron 27 2.10 Inhibition of Carotenoid and Chlorophyll Biosynthesis by Fosmidomycin and 5-Ketoclomazone 27 2.11 Biosynthesis and Emission of Methylbutenol at High Irradiance 28 2.12 Source of Pyruvate for Isoprene and Methylbutenol Biosynthesis 29 2.13 Branching Point of DOXP/MEP Pathway with Other Metabolic Chloroplast Pathways 30 2.14 Is There a Physiological Function of Isoprene and MBO Emission? 31 2.15 Biosynthesis and Emission of Monoterpenes, Sesquiterpenes and Diterpenes 33 2.15.1 Monoterpenes 35 2.15.2 Diterpenes 36 2.15.3 Sesquiterpenes 36 2.16 Some General Remarks on the Regulation of Terpene Biosynthesis in Plants 36 2.17 Volatile Terpenoids as Aroma Compounds of Wine 37 2.18 Function of Terpenes in Plant Defence 38 2.19 Conclusion 38 Acknowledgements 39 References 40 3 Analysis of the Plant Volatile Fraction 49 Patrizia Rubiolo, Barbara Sgorbini, Erica Liberto, Chiara Cordero and Carlo Bicchi 3.1 Introduction 49 3.2 Sample Preparation 50 3.2.1 ‘Liquid’ Phase Sampling 51 3.2.2 Headspace Sampling 51 3.2.3 Headspace–Solid Phase Microextraction 52 3.2.4 In-Tube Sorptive Extraction 54 3.2.5 Headspace Sorptive Extraction 55 3.2.6 Static and Trapped Headspace 56 3.2.7 Solid-Phase Aroma Concentrate Extraction 56 3.2.8 Headspace Liquid-Phase Microextraction 56 3.2.9 Large Surface Area High Concentration Capacity Headspace Sampling 59 3.3 Analysis 59 3.3.1 Fast-GC and Fast-GC-qMS EO Analysis 61 3.3.2 Qualitative Analysis 65 3.3.3 Quantitative Analysis 66 3.3.4 Enantioselective GC 70 3.3.5 Multidimensional GC Techniques 75 3.4 Further Developments 76 3.5 Conclusion 85 Acknowledgements 87 References 87 4 Plant Volatile Signalling: Multitrophic Interactions in the Headspace 95 Andre Kessler and Kimberly Morrell 4.1 Introduction 95 4.2 The Specificity and Complexity of Herbivore-Induced VOC Production 97 4.2.1 Plant Endogenous Wound Signalling 99 4.2.2 Herbivore-Derived Elicitors of VOC Emission 102 4.3 Ecological Consequences of VOC Emission 104 4.3.1 Within-Plant Defence Signalling 104 4.3.2 Herbivore-Induced VOC Emission as Part of a Metabolic Reconfiguration of the Plant 105 4.3.3 Herbivores Use VOCs to Select Host Plants 107 4.3.4 VOCs as Indirect Defences Against Herbivores 108 4.3.5 VOCs in Plant–Plant Interactions 111 4.4 Conclusion 112 Acknowledgements 114 References 114 5 Pheromones in Chemical Communication 123 Kenji Mori 5.1 Introduction 123 5.1.1 Definition of Pheromones 123 5.1.2 Classification of Pheromones 123 5.2 History of Pheromone Research 125 5.3 Research Techniques in Pheromone Science 127 5.3.1 The Collecting of Pheromones 127 5.3.2 Bioassay-Guided Purification 128 5.3.3 Structure Determination and Synthesis 128 5.3.4 Field Bioassay 129 5.3.5 Structure Elucidation of the Male-Produced Aggregation Pheromone of the Stink Bug Eysarcoris lewisi – A Case Study 129 5.4 Structural Diversity Among Pheromones 132 5.5 Complexity of Multicomponent Pheromones 137 5.6 Stereochemistry and Pheromone Activity 139 5.6.1 Only a Single Enantiomer is Bioactive and its Opposite Enantiomer Does Not Inhibit the Response to the Active Isomer 139 5.6.2 Only One Enantiomer is Bioactive, and its Opposite Enantiomer Inhibits the Response to the Pheromone 139 5.6.3 Only One Enantiomer is Bioactive, and its Diastereomer Inhibits the Response to the Pheromone 139 5.6.4 The Natural Pheromone is a Single Enantiomer, and its Opposite Enantiomer or Diastereomer is Also Active 140 5.6.5 The Natural Pheromone is a Mixture of Enantiomers or Diastereomers, and Both of the Enantiomers, or All of the Diastereomers are Separately Active 141 5.6.6 Different Enantiomers or Diastereomers are Employed by Different Species 141 5.6.7 Both Enantiomers are Necessary for Bioactivity 141 5.6.8 One Enantiomer is More Active Than the Other, but an Enantiomeric or Diastereomeric Mixture is More Active Than the Enantiomer Alone 141 5.6.9 One Enantiomer is Active on Males, While the Other is Active on Females 142 5.6.10 Only the meso-Isomer is Active 142 5.7 Pheromones With Kairomonal Activities 142 5.8 Mammalian Pheromones 143 5.9 Invention of Pheromone Mimics 145 5.10 Conclusion 147 Acknowledgements 147 References 147 6 Use of Volatiles in Pest Control 151 J. Richard M. Thacker and Margaret R. Train 6.1 Introduction 151 6.2 Repellents (DEET, Neem, Essential Oils) 151 6.3 Volatile Synthetic Chemicals and Fumigants 154 6.4 Pheromones 158 6.5 Volatile Allelochemicals 165 6.6 Plant Volatiles and Behavioural Modification of Beneficial Insects 166 6.7 Concluding Comments 167 References 168 7 Challenges in the Synthesis of Natural and Non-Natural Volatiles 173 Anthony A. Birkbeck 7.1 Introduction – The Art of Organic Synthesis 173 7.2 Overcoming Challenges in the Small-Scale Synthesis of Natural Volatile Compounds 174 7.2.1 D,L-Caryophyllene (1964) 174 7.2.2 b-Vetivone (1973) 175 7.3 Overcoming Challenges in the Large-Scale Synthesis of Nature Identical and Non-Natural Molecules 176 7.3.1 (Z)-3-Hexenol 176 7.3.2 Citral 177 7.3.3 (–)-Menthol 179 7.3.4 Habanolide 180 7.4 Remaining Challenges in the Large-Scale Synthesis of Natural and Non-Natural Volatiles 180 7.5 Design and Synthesis of Novel Odorants and Potential Industrial Routes to a Natural Product 182 7.5.1 Cassis (Blackcurrant) 182 7.5.2 Patchouli 184 7.5.3 Musk 187 7.5.4 Sandalwood 189 7.6 Other Challenges 193 7.7 Conclusion 193 Acknowledgements 194 Dedication 195 References 195 8 The Biosynthesis of Volatile Sulfur Flavour Compounds 203 Meriel G. Jones 8.1 Introduction: Flavours as Secondary Metabolites 203 8.2 Sulfur in Plant Biology 204 8.3 Sulfur Compounds as Flavour Volatiles 205 8.4 The Alk(en)yl Cysteine Sulfoxide Flavour Precursors 206 8.5 Biosynthesis of the Flavour Precursors of Allium 207 8.5.1 The Biosynthesis of Allium Flavour Precursors via g-Glutamyl Peptides 208 8.5.2 The Biosynthesis of Allium Flavour Precursors via Cysteine Synthases 209 8.6 Formation of Volatiles from CSOs 210 8.6.1 S-Methyl-L-cysteine sulfoxide 210 8.6.2 Release of the Allium CSOs 211 8.7 The Allium Flavour Volatiles 212 8.8 The Enzyme Alliinase 213 8.9 The Enzyme Lachrymatory Factor Synthase 214 8.10 The Biological Roles of the Flavour Precursors 215 8.11 The Glucosinolate Flavour Precursors 216 8.12 GS and Their Biosynthetic Pathways 216 8.13 Release of Volatile GS Hydrolysis Products 218 8.14 The Biological Role of Glucosinolates 220 8.15 Application of Transgenic Technology to Applied Aspects of GS Biosynthesis 222 8.16 Volatile Sulfur Compounds from Other Plants 222 8.16.1 Complex Organic Sulfur Volatiles 222 8.16.2 Simple Sulfur Volatiles 223 8.16.3 Hydrogen Sulfide 223 8.16.4 Methanethiol 224 8.17 Conclusion 224 References 224 9 Thermal Generation of Aroma-Active Volatiles in Food 231 Christoph Cerny 9.1 Introduction 231 9.2 The Maillard Reaction 233 9.2.1 The Amadori Rearrangement 234 9.2.2 Deoxyosones 235 9.2.3 Retro-Aldolization 235 9.3 Formation of Aroma Compounds in the Later Stages of the Maillard Reaction 237 9.3.1 2-Furfurylthiol 237 9.3.2 4-Hydroxy-2,5-dimethyl-3(2H)-furanone 239 9.3.3 Alkyl and Alkenylpyrazines 239 9.3.4 2-Acetyl-1-pyrroline 241 9.4 The Strecker Degradation 241 9.5 Caramelization 244 9.6 Thiamin Degradation 246 9.7 Ferulic Acid Degradation 246 9.8 Fat Oxidation 247 9.9 Conclusion 250 References 250 10 Human Olfactory Perception 253 Alan Gelperin 10.1 Introduction 253 10.2 Historical Perspective on Olfactory Perception 254 10.3 Human Olfactory Pathway 255 10.4 Functional Studies in Human Subjects 256 10.5 Functional Studies in Brain-Damaged Subjects 259 10.6 Single Odorants, Binary Mixtures and Complex Odour Objects 259 10.7 Olfactory Versus Trigeminal Odorant Identification 262 10.8 Orthonasal Versus Retronasal Odour Perception 263 10.9 Specific Anosmias 264 10.10 MHC-Correlated Odour Preferences in Human Subjects 265 10.11 Odour Deprivation and Odour Perception 266 10.12 Age-Related Decline in Olfactory Perception 267 10.13 New Neurons in Adult Brains 268 10.14 Epidemiological Studies of Human Olfaction 268 10.15 Active Sampling and Olfactory Perception 269 10.16 Human Olfactory Imagery 270 10.17 Top-Down Influences on Olfactory Perception 271 10.18 Reproductive State and Olfactory Sensitivity 272 10.19 Olfaction, Hunger and Satiety 273 10.20 Odour Perception Bias by Odour Names 274 10.21 Olfaction and Disease States 275 10.22 Prenatal and Postnatal Influences on Infant Odour/Flavour Preferences 276 10.23 Future Directions 277 Acknowledgements 277 References 278 11 Perfumery – The Wizardry of Volatile Molecules 291 Christophe Laudamiel 11.1 The Big Picture 291 11.2 Wizardry No. 1: Full Holograms Create Real Emotions 292 11.3 Volatiles Need a Language Wizard 296 11.4 Wizardry No. 2: The Perfumer in the Jungle of Volatiles to Create Emotions 298 11.5 Wizardry No. 3: End Results Are Music to the Nose 303 References 304 12 Microencapsulation Techniques for Food Flavour 307 Youngjae Byun, Young Teck Kim, Kashappa Goud H. Desai and Hyun Jin Park 12.1 Demands 307 12.2 Microencapsulation in the Food Industry 307 12.3 Techniques and Materials for Flavour Microencapsulation 308 12.3.1 Spray Drying 308 12.3.2 Extrusion 312 12.3.3 Cyclodextrin Inclusion Complexes 314 12.3.4 Helical Inclusion Complexes 316 12.3.5 Fluidized Bed Coating 318 12.3.6 Top Spray Fluidized Bed Coating 318 12.3.7 Bottom Spray System 318 12.3.8 Wurster System 320 12.3.9 Tangential Spray or Rotary Fluidized Bed Coating 320 12.3.10 Coacervation 320 12.3.11 Double or Multiple Emulsion with Freeze Drying 321 12.3.12 Co-Crystallization 322 12.3.13 Spray Chilling and Spray Cooling 322 12.3.14 Supercritical Fluids 323 12.3.15 Other Techniques 323 12.4 Conclusion and Future Trends 325 References 326 13 Profragrances and Properfumes 333 Andreas Herrmann 13.1 Introduction 333 13.2 Release of Alcohols 335 13.2.1 Enzymatic Hydrolysis 335 13.2.2 Neighbouring-Group-Assisted, Non-Enzymatic Hydrolysis 340 13.3 Release of Carbonyl Derivatives 346 13.3.1 Oxidations 346 13.3.2 Reversible Systems 350 13.3.3 Retro 1,4-Additions 354 13.4 Profragrance and Properfume Strategies 356 13.4.1 Performance and Cost Efficiency 356 13.4.2 Stability 357 13.5 Conclusion 357 Acknowledgements 358 References 358 14 Reactions of Biogenic Volatile Organic Compounds in the Atmosphere 363 Russell K. Monson 14.1 Introduction 363 14.2 The Relative Importance of Anthropogenic Versus Biogenic VOC Emissions to Atmospheric Chemistry 364 14.3 Overview of BVOC Oxidation 365 14.4 The Types of Emitted BVOCs and General Roles in Atmospheric Chemistry 370 14.5 Gas Phase Oxidation of BVOCs 372 14.6 Gas Phase Chemistry of BVOCs in Urban and Suburban Airsheds 374 14.7 Gas Phase Chemistry Within and Above Forests 375 14.8 BVOC Emissions and SOA Formation 377 14.9 Conclusion 381 References 381 Index 389

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Book SynopsisThe latest edition of this highly acclaimed textbook, provides a comprehensive and up--to--date overview of the science and medical applications of biopharmaceutical products.Trade Review"…contains just about everything that anyone would want to know about the subject…It's all here in this easy-to-read textbook.” (Biochemistry and Molecular Education, March/April 2004) "...well written… (and) copiously illustrated..." (Chemistry & Industry, 17th January 2005) “This book should be recommended reading for all under-graduate course in pharmacy and the pharmaceutical sciences …”. (Cell Biochemistry & Function, March-April 2005)Table of ContentsPreface xvii Chapter 1 Pharmaceuticals, biologics and biopharmaceuticals 1 Introduction to pharmaceutical products 1 Biopharmaceuticals and pharmaceutical biotechnology 1 History of the pharmaceutical industry 3 The age of biopharmaceuticals 5 Biopharmaceuticals: current status and future prospects 8 Traditional pharmaceuticals of biological origin 12 Pharmaceuticals of animal origin 13 The sex hormones 14 The androgens 14 Oestrogens 15 Progesterone and progestogens 17 Corticosteroids 19 Catecholamines 21 Prostaglandins 23 Pharmaceutical substances of plant origin 27 Alkaloids 28 Atropine and scopalamine 28 Morphine and cocaine 29 Additional plant alkaloids 30 Ergot alkaloids 30 Flavonoids, xanthines and terpenoids 30 Cardiac glycosides and coumarins 33 Aspirin 33 Pharmaceutical substances of microbial origin 33 The macrolides and ansamycins 38 Peptide and other antibiotics 39 Conclusion 39 Further reading 40 Chapter 2 The drug development process 43 Drug discovery 44 The impact of genomics and related technologies upon drug discovery 45 Gene chips 47 Proteomics 49 Structural genomics 50 Pharmacogenetics 51 Plants as a source of drugs 52 Microbial drugs 53 Rational drug design 54 Combinatorial approaches to drug discovery 56 Initial product characterization 57 Patenting 57 What is a patent and what is patentable? 57 Patent types 62 The patent application 63 Patenting in biotechnology 64 Delivery of biopharmaceuticals 66 Oral delivery systems 66 Pulmonary delivery 67 Nasal, transmucosal and transdermal delivery systems 68 Pre-clinical trials 69 Pharmacokinetics and pharmacodynamics 69 Toxicity studies 71 Reproductive toxicity and teratogenicity 71 Mutagenicity, carcinogenicity and other tests 72 Clinical trials 73 Clinical trial design 75 Trial size and study population 75 Randomized control studies 76 Additional trial designs 76 The role and remit of regulatory authorities 78 The Food and Drug Administration 78 The investigational new drug application 80 The new drug application 82 European regulations 84 National regulatory authorities 84 The EMEA and the new EU drug approval systems 85 The centralized procedure 86 Mutual recognition 88 Drug registration in Japan 88 World harmonization of drug approvals 89 Conclusion 89 Further reading 89 Chapter 3 The drug manufacturing process 93 International pharmacopoeia 93 Martindale, the Extra Pharmacopoeia 94 Guides to good manufacturing practice 94 The manufacturing facility 97 Clean rooms 98 Cleaning, decontamination and sanitation (CDS) 101 CDS of the general manufacturing area 102 CDS of process equipment 102 Water for biopharmaceutical processing 104 Generation of purified water and water for injections (WFI) 105 Distribution system for WFI 107 Documentation 109 Specifications 110 Manufacturing formulae, processing and packaging instructions 110 Records 111 Generation of manufacturing records 111 Sources of biopharmaceuticals 112 E. coli as a source of recombinant, therapeutic proteins 112 Expression of recombinant proteins in animal cell culture systems 116 Additional production systems: yeasts 116 Fungal production systems 117 Transgenic animals 118 Transgenic plants 122 Insect cell-based systems 123 Production of final product 124 Cell banking systems 127 Upstream processing 128 Microbial cell fermentation 129 Mammalian cell culture systems 133 Downstream processing 134 Final product formulation 140 Some influences that can alter the biological activity of proteins 142 Proteolytic degradation 143 Protein deamidation 144 Oxidation and disulphide exchange 145 Alteration of glycoprotein glycosylation patterns 147 Stabilizing excipients used in final product formulations 150 Final product fill 153 Freeze-drying 155 Labelling and packing 158 Analysis of the final product 159 Protein-based contaminants 159 Removal of altered forms of the protein of interest from the product stream 160 Product potency 161 Determination of protein concentration 163 Detection of protein-based product impurities 164 Capillary electrophoresis 166 High-pressure liquid chromatography (HPLC) 167 Mass spectrometry 168 Immunological approaches to detection of contaminants 168 Amino acid analysis 169 Peptide mapping 170 N-terminal sequencing 171 Analysis of secondary and tertiary structure 173 Endotoxin and other pyrogenic contaminants 173 Endotoxin, the molecule 174 Pyrogen detection 176 Dna 179 Microbial and viral contaminants 180 Viral assays 181 Miscellaneous contaminants 182 Validation studies 183 Further reading 185 Chapter 4 The cytokines —the interferon family 189 Cytokines 189 Cytokine receptors 194 Cytokines as biopharmaceuticals 195 The interferons 196 The biochemistry of interferon-a 197 Interferon-b 198 Interferon-g 198 Interferon signal transduction 198 The interferon receptors 199 The JAK–STAT pathway 199 The interferon JAK–STAT pathway 202 The biological effects of interferons 203 The eIF-2a protein kinase system 207 Interferon biotechnology 207 Production and medical uses of IFN-a 210 Medical uses of IFN-b 213 Medical applications of IFN-g 214 Interferon toxicity 216 Additional interferons 218 Conclusion 219 Further reading 219 Chapter 5 Cytokines: interleukins and tumour necrosis factor 223 Interleukin-2 (IL-2) 225 IL-2 production 228 IL-2 and cancer treatment 228 IL-2 and infectious diseases 230 Safety issues 231 Inhibition of IL-2 activity 231 Interleukin-1 (IL-1) 232 The biological activities of IL- 1 233 IL-1 biotechnology 234 Interleukin-3: biochemistry and biotechnology 235 Interleukin- 4 236 Interleukin- 6 238 Interleukin- 11 240 Interleukin- 5 241 Interleukin- 12 244 Tumour necrosis factors (TNFs) 246 TNF biochemistry 246 Biological activities of TNF-a 247 Immunity and inflammation 248 TNF receptors 249 TNF: therapeutic aspects 250 Further reading 252 Chapter 6 Haemopoietic growth factors 255 The interleukins as haemopoietic growth factors 257 Granulocyte colony stimulating factor (G-CSF) 258 Macrophage colony-stimulating factor (M-CSF) 259 Granulocyte-macrophage colony stimulating factor (GM-CSF) 259 Clinical application of CSFs 261 Leukaemia inhibitory factor (LIF) 263 Erythropoietin (EPO) 264 The EPO receptor and signal transduction 267 Regulation of EPO production 267 Therapeutic applications of EPO 268 Chronic disease and cancer chemotherapy 271 Additional non-renal applications 272 Tolerability 273 Thrombopoietin 273 Further reading 275 Chapter 7 Growth factors 277 Growth factors and wound healing 277 Insulin-like growth factors (IGFs) 279 IGF biochemistry 280 IGF receptors 280 IGF-binding proteins 282 Biological effects 282 IGF and fetal development 283 IGFs and growth 283 Renal and reproductive effects 284 Neuronal and other effects 285 Epidermal growth factor (EGF) 285 The EGF receptor 286 Platelet-derived growth factor (PDGF) 287 The PDGF receptor and signal transduction 288 PDGF and wound healing 289 Fibroblast growth factors (FGFs) 289 Transforming growth factors (TGFs) 290 TGF-a 290 TGF-b 292 Neurotrophic factors 293 The neurotrophins 294 Neurotrophin receptors 296 The neurotrophin low-affinity receptor 297 Ciliary neurotrophic factor and glial cell line-derived neurotrophic factor 297 Neurotrophic factors and neurodegenerative disease 298 Amyotrophic lateral sclerosis (ALS) and peripheral neuropathy 298 Neurotrophic factors and neurodegenerative diseases of the brain 298 Further reading 300 Chapter 8 Hormones of therapeutic interest 303 Insulin 303 Diabetes mellitus 304 The insulin molecule 304 The insulin receptor and signal transduction 307 Insulin production 307 Enzymatic conversion of porcine insulin 311 Production of human insulin by recombinant DNA technology 312 Formulation of insulin products 314 Engineered insulins 317 Additional means of insulin administration 320 Treating diabetics with insulin-producing cells 321 Glucagon 321 Human growth hormone (hGH) 324 Growth hormone releasing factor (GHRF) and inhibitory factor (GHRIF) 325 The GH receptor 325 Biological effects of GH 327 Therapeutic uses of GH 328 Recombinant hGH (rhGH) and pituitary dwarfism 328 Idiopathic short stature and Turner’s syndrome 330 Metabolic effects of hGH 330 GH, lactation and ovulation 331 The gonadotrophins 331 Follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) 331 Pregnant mare serum gonadotrophin (PMSG) 335 The inhibins and activins 337 LHRH and regulation of gonadotrophin production 338 Medical and veterinary applications of gonadotrophins 339 Sources and medical uses of FSH, LHand hCG 340 Recombinant gonadotrophins 342 Veterinary uses of gonadotrophins 344 Gonadotrophin releasing hormone (GnRH) 345 Additional recombinant hormones now approved 345 Conclusions 348 Further reading 348 Chapter 9 Blood products and therapeutic enzymes 351 Disease transmission 351 Whole blood 353 Platelets and red blood cells 353 Blood substitutes 353 Dextrans 354 Albumin 355 Gelatin 357 Oxygen-carrying blood substitutes 357 Haemostasis 358 The coagulation pathway 358 Terminal steps of coagulation pathway 361 Clotting disorders 365 Factor VIII and haemophilia 366 Production of Factor VIII 368 Factors IX, VII a and XIII 371 Anticoagulants 372 Heparin 372 Vitamin Kantimetabolites 375 Hirudin 375 Antithrombin 379 Thrombolytic agents 380 Tissue plasminogen activator (tPA) 381 First-generation tPA 383 Engineered tPA 383 Streptokinase 385 Urokinase 386 Staphylokinase 386 a1 -Antitrypsin 388 Enzymes of therapeutic value 389 Asparaginase 390 DNase 392 Glucocerebrosidase 393 a-Galactosidase and urate oxidase 395 Superoxide dismutase 397 Debriding agents 397 Digestive aids 398 Lactase 400 Further reading 400 Chapter 10 Antibodies, vaccines and adjuvants 403 Polyclonal antibody preparations 403 Anti-D immunoglobulin 406 Normal immunoglobulins 407 Hepatitis Band tetanus immunoglobulin 407 Snake and spider antivenins 408 Monoclonal antibodies 409 Production of monoclonals via hybridoma technology 411 Antibody screening: phage display technology 412 Therapeutic application of monoclonal antibodies 414 Tumour immunology 415 Antibody-based strategies for tumour detection/destruction 417 Drug-based tumour immunotherapy 424 First-generation anti-tumour antibodies: clinical disappointment 426 Tumour-associated antigens 426 Antigenicity of murine monoclonals 428 Chimaeric and humanized antibodies 429 Antibody fragments 432 Additional therapeutic applications of monoclonal antibodies 433 Cardiovascular and related disease 433 Infectious diseases 433 Autoimmune disease 434 Transplantation 434 Vaccine technology 435 Traditional vaccine preparations 436 Attenuated, dead or inactivated bacteria 438 Attenuated and inactivated viral vaccines 439 Toxoids, antigen-based and other vaccine preparations 440 The impact of genetic engineering on vaccine technology 441 Peptide vaccines 444 Vaccine vectors 445 Development of an AIDS vaccine 447 Difficulties associated with vaccine development 450 AIDS vaccines in clinical trials 450 Cancer vaccines 452 Recombinant veterinary vaccines 452 Adjuvant technology 453 Adjuvant mode of action 455 Mineral-based adjuvants 455 Oil-based emulsion adjuvants 455 Bacteria/bacterial products as adjuvants 457 Additional adjuvants 458 Further reading 460 Chapter 11 Nucleic acid therapeutics 463 Gene therapy 463 Basic approach to gene therapy 464 Some additional questions 467 Vectors used in gene therapy 468 Retroviral vectors 468 Additional viral-based vectors 472 Manufacture of viral vectors 474 Non-viral vectors 476 Manufacture of plasmid DNA 480 Gene therapy and genetic disease 482 Gene therapy and cancer 485 Gene therapy and AIDS 486 Gene-based vaccines 488 Gene therapy: some additional considerations 488 Anti-sense technology 488 Anti-sense oligonucleotides 490 Uses, advantages and disadvantages of ‘oligos’ 491 Delivery and cellular uptake of oligonucleotides 493 Manufacture of oligonucleotides 493 Vitravene, an approved antisense agent 494 Antigene sequences and ribozymes 494 Conclusion 495 Further reading 496 Appendix 1 Biopharmaceuticals thus far approved in the USA or European Union 499 Appendix 2 Some Internet addresses relevant to the biopharmaceutical sector 509 Appendix 3 Two selected monographs reproduced from the European Pharmacopoeia with permission from the European Commission: I. Products of recombinant DNA technology 515 II. Interferon a-2 concentrated solution 520 Appendix 4 Manufacture of biological medicinal products for human use. (Annex 2 from The Rules Governing Medicinal Products in the European Community, Vol. 4, Good Manufacturing Practice for Medicinal Products) 527 Index 533

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Book SynopsisThe advances made in molecular biology have allowed scientists to manipulate DNA. This means that molecular biology has become a tool for answering scientific questions that may be quite unrelated to genetics and cell biology. The techniques have become a means to an end, rather than an end in themselves. This work deals with this area.Table of ContentsPreface Introduction and Background Part 1 Molecular Biology Experiment 1 Instructions for Pipetman Use Experiment 2 Preparation of Plasmid Template DNA Experiment 3 Estimation of Plasmid DNA Concentration PCR Amplification of LTB Gene from Plasmid DNA Experiment 4 Agarose Gel Eletrophoresis Recovery of PCR Product Experiment 5 Restriction Digest of LTB Insert Plate Preparation Experiment 6 Purification of Digested Insert and Vector by Agarose Gel Eletrophoresis Recovery of Digested Insert and Vector Experiment 7 Determination of DNA Concentrations Ligation of Insert into Vector Experiment 8 Transformation of Host Cells by Construct Experiment 9 Colony-pick PCR to Check for Presence of Insert Streak Plates with Potential Constructs Inoculate Cultures/Run PCR Experiment 10 Agarose Gel Electrophoresis to Verify Presence of Insert Purification of the Plasmid Construct using a Plasmid Miniprep Kit Experiment 11 DNA Concentration Determination Ethanol Precipitation of Plasmid DNA Sequencing Reaction Experiment 12 Purification of Extension Reaction Products Sequencing Gel Demonstration Experiment 13 Analysis of Sequencing Data Verification of Insert Sequence Experiment 14 Gene Expression Transformation into Expression Host Experiment 15 Induction of LTB Gene Expression Part 2 Protein Chemistry Experiment 16 SDS-PAGE of Induction Time Course Transfer of Protein to Membrane for Western Blot Experiment 17 Visualization of Western Blot Experiment 18 Large Scale Culture Preparation Experiment 19 Isolation of LTB by Affinity Chromatography Experiment 20 SDS-PAGE of Column Fractions Immunoblot to verify Presence of LTB Experiment 21 Protein Concentration Protein Crystallization Experiment 22 Setting up an ELISA Microtiter Plate Experiment 23 ELISA of a Panel of Ganglioside Ligands Experiment 24 Protein Structure Determination: X-ray Diffraction Techniques Experiment 25 Characterization of a Protein Crystal Experiment 26 Primer Design

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Book SynopsisThe astounding diversity of the immune system and the complexity of its regulatory pathways makes immunology a combinatorial science. Computational analysis has therefore become an essential element of immunology research and this has led to the creation of the emerging field of immunoinformatics. This book is the first to feature thorough coverage of this new field. Immunoinformatics facilitates the understanding of immune function by modelling the interactions among immunological components. Biological research provides ever deeper insights into the complexity of living organisms while computer science provides an effective means to store and analyse large volumes of complex data. Combining the two fields increases the efficiency of biological research and offers the potential for major advances in the study of biological systems. This book encompasses key developments in immunoinformatics, including immunological databases, sequence analysis, structure modelling, mathematiTable of ContentsChair's Introduction (H. Rammensee). Immunoinformatics - the new kid in town (V. Brusic & N. Petrovsky). The fututre of computational modelling and prediction systems in clinical immunology (N. Petrovsky, et al.). Immunoinformatics in personalized medicine (K. Gulukota). From immunome to vaccine: epitope mapping and vaccine design tools (A. De Groot & W. Martin). Insights from MHC-bound peptides (H. Margalit & Y. Altuvia). General discussion I. Computation vaccinology: quanitative approaches (D. Flower, et al). IMGT, the international ImMunoGeneTics information System®, http://imgt.cines.fr (M. Lefranc). Generating data for databases—the peptide repertoire of HLA molecules (S. Stevanovic, et al.). HLA nomenclature and the IMGT/HLA Sequence Database (S. Marsh). From immunogenetics to immunomics: functional prospecting of genes and transcripts (C. Schönbach). Mathematical models of HIV and the immune system (D. Wodarz). General discussion II. Immunogenomics: towards a digital immune system (S. Beck). Viral bioinformatics: computational views of host and pathogen (P. Kellam, et al.). Final general discussion Closing remarks (H. Rammensee). Index of Contributors. Subject Index.

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Book Synopsis* Offers textbook level introductions into basic microbiology as it relates to human and ecological risk assessment of antibiotics and antibiotic resistance genes. * The unique multidisciplinary platform is intended to integrate environmental microbiology into human and ecological risk assessment.Trade Review“This is an excellent publication, including primary data and detailed explanations of specific studies and techniques as well as review chapters. As both an introduction to a research area and a call for greater study and thought into how we regulate antimicrobial use in all spheres of society to limit further resistance, I highly recommend Antimicrobial resistance in the environment.” (Phenotype, 1 February 2013) “This book will be an ideal read for anyone seeking a comprehensive introduction to the many reservoirs and routes a resistance gene may pass through before or after its appearance in a clinical setting. Even experts in the field stand to gain knowledge regarding the complex web that is the issue of antibiotic resistance in the environment.” (The Quarterly Review of Biology, 1 December 2012) Table of ContentsPREFACE xi CONTRIBUTORS xv PART I SOURCES 1 Chapter 1 Introduction 3 Stuart B. Levy Chapter 2 Path to Resistance 7 Vivian Miao, Dorothy Davies, and Julian Davies Chapter 3 Antibiotic Resistome: A Framework Linking the Clinic and the Environment 15 Gerard D. Wright Chapter 4 Ecological and Clinical Consequences of Antibiotic Subsistence by Environmental Microbes 29 Gautam Dantas and Morten O. A. Sommer Chapter 5 Importance of Adaptive and Stepwise Changes in the Rise and Spread of Antimicrobial Resistance 43 Lucia Fernandez, Elena B. M. Breidenstein, and Robert E. W. Hancock Chapter 6 Environmental Reservoirs of Resistance Genes in Antibiotic-Producing Bacteria and Their Possible Impact on the Evolution of Antibiotic Resistance 73 Paris Laskaris, William H. Gaze and Elizabeth M. H. Wellington Chapter 7 Mechanisms of Bacterial Antibiotic Resistance and Lessons Learned from Environmental Tetracycline-Resistant Bacteria 93 Marilyn C. Roberts Chapter 8 Environmental Antibiotic Resistome: New Insights from Culture-Independent Approaches 123 Isabel S. Henriques, Artur Alves, Maria Jose´ Saavedra, Mark H. M. M. Montforts, and Anto´nio Correia PART II FATE 149 Chapter 9 Environmental Pollution by Antibiotic Resistance Genes 151 Jose Luis Martinez and Jorge Olivares Chapter 10 Quantifying Anthropogenic Impacts on Environmental Reservoirs of Antibiotic Resistance 173 Amy Pruden and Mazdak Arabi Chapter 11 Antibiotic Resistance in Swine-Manure-Impacted Environments 203 Joanne Chee-Sanford, Scott Maxwell, Kristy Tsau, Kelly Merrick, and Rustam Aminov Chapter 12 Antimicrobial-Resistant Indicator Bacteria in Manure and the Tracking of Indicator Resistance Genes 225 Christina S. Ho¨lzel and Karin Schwaiger Chapter 13 Municipal Wastewater as a Reservoir of Antibiotic Resistance 241 Timothy Lapara and Tucker Burch Chapter 14 Strategies to Assess and Minimize the Biological Risk of Antibiotic Resistance in the Environment 251 Thomas Schwartz Chapter 15 Antibiotic Resistance in Animals—The Australian Perspective 265 Olasumbo Ndi and Mary Barton PART III ANTIMICROBIAL SUBSTANCES AND RESISTANCE 291 Chapter 16 Detection and Occurrence of Antibiotics and Their Metabolites in Pig Manure in Bavaria (Germany) 293 Katrin Harms and Johann Bauer Chapter 17 Fate and Transport of Antibiotics in Soil Systems 309 Alistair B. A. Boxall Chapter 18 Antibiotics in the Aquatic Environment 325 Klaus Ku¨mmerer Chapter 19 Residues of Veterinary Drugs in Wild Fish 337 Thomas Heberer Chapter 20 Role of Quaternary Ammonium Compounds on Antimicrobial Resistance in the Environment 349 Ulas Tezel and Spyros G. Pavlostathis PART IV EFFECTS AND RISKS 389 Chapter 21 Human Health Importance of use of Antimicrobials in Animals and Its Selection of Antimicrobial Resistance 391 Scott A. McEwen Chapter 22 Antimicrobial Resistance Associated with Salmonid Farming 423 Claudio D. Miranda Chapter 23 Effect of Veterinary Medicines Introduced via Manure into Soil on the Abundance and Diversity of Antibiotic Resistance Genes on Their Transferability 453 Holger Heuer, Christoph Kopmann, Ute Zimmerling, Ellen Kro¨gerrecklenfort, Kristina Kleineidamm, Michael Schloter, Eva M. Top and Kornelia Smalla Chapter 24 Tracking Antibiotics and Antibiotic Resistance Genes through the Composting Process and Field Distribution of Poultry Waste: Lessons Learned 465 Patricia L. Keen and Nancy De With Chapter 25 Environmental Microbial Communities Living Under Very High Antibiotic Selection Pressure 483 Anders Janzon, Erik Kristiansson, and D. G. Joakim Larsson Chapter 26 Antibiotic Use During an Influenza Pandemic: Downstream Ecological Effects and Antibiotic Resistance 503 Andrew C. Singer and Heike Schmitt Chapter 27 Use of Veterinary Antibacterial Agents in Europe and the United States 539 Ingeborg M. van Geijlswijk, Nico Bondt, Linda F. Puister-Jansen, and Dik J. Mevius Chapter 28 Regulatory Research on Antimicrobial Resistance in the Environment 549 Emily A. McVey and Mark H. M. M. Montforts INDEX 569

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Book SynopsisThe application of plant chemical biology is currently limited to specialized subfields of plant research.Table of ContentsPreface vii Contributors ix part one Introduction 1 1.1 From Herbal Remedies to Cutting-Edge Science: A Historical Perspective of Plant Chemical Biology 3 Michelle Q. Brown, Abel Rosado, and Natasha V. Raikhel part Two Sources of small molecules 19 2.1 Compound Collections 21 Reg Richardson 2.2 Combinatorial Chemistry Library Design 40 Robert Klein and Stephen D. Lindell 2.3 Natural Product-Based Libraries 64 Alan L. Harvey part three Identification of new chemical tools by High-Throughput Screening 73 3.1 Assay Design for High-Throughput Screening 75 Frank W. An and Jose R. Perez part four Use of chemical biology to study plant physiology 93 4.1 Use of Chemical Biology to Understand Auxin Metabolism, Signaling, and Polar Transport 95 Ken-ichiro Hayashi and Paul Overvoorde 4.2 Brassinosteroids Signaling and Biosynthesis 128 Takeshi Nakano and Tadao Asami 4.3 Chemical Genetic Approaches on ABA Signal Transduction 145 Eunjoo Park and Tae-Houn Kim 4.4 Jasmonic Acid 160 Christian Meesters and Erich Kombrink 4.5 Chemical Genetics as a Tool to Study Ethylene Biology in Plants 184 Yuming Hu, Filip Vandenbussche, and Dominique Van Der Straeten part five Use of chemical biology to study plant cellular processes 203 5.1 The Use of Small Molecules to Dissect Cell Wall Biosynthesis and Manipulate the Cortical Cytoskeleton 205 Darby Harris and Seth DeBolt 5.2 The Use of Chemical Biology to Study Plant Cellular Processes: Subcellular Trafficking 218 Ash Haeger, Malgorzata £angowska, and Stéphanie Robert part six Target identification 233 6.1 Target Identification of Biologically Active Small Molecules 235 Paul Overvoorde and Dominique Audenaert part seven Translation of plant chemical biology from the lab to the field 247 7.1 Prospects and Challenges for Translating Emerging Insights in Plant Chemical Biology into New Agrochemicals 249 Terence A. Walsh 7.2 In Vitro Propagation 263 Hans Motte, Stefaan Werbrouck, and Danny Geelen Index 289

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Book SynopsisProteins in solution and at interfaces are increasingly used in exciting new applications, from biomimetic materials to nanoparticle patterning.Table of ContentsPREFACE ix CONTRIBUTORS xiii PART I 1 X-Ray Crystallography of Biological Macromolecules: Fundamentals and Applications 3 Antonio L. Llamas-Saiz and Mark J. van Raaij 2 Nuclear Magnetic Resonance Methods for Studying Soluble, Fibrous, and Membrane-Embedded Proteins 23 Victoria A. Higman 3 Small-Angle X-Ray Scattering Applied to Proteins in Solution 49 Leandro Ramos Souza Barbosa, Francesco Spinozzi, Paolo Mariani, and Rosangela Itri 4 Analyzing the Solution State of Protein Structure, Interactions, and Ligands by Spectroscopic Methods 73 Veronica I. Dodero and Paula V. Messina 5 Resolving Membrane-Bound Protein Orientation and Conformation by Neutron Reflectivity 99 Hirsh Nanda 6 Investigating Protein Interactions at Solid Surfaces—In Situ, Nonlabeling Techniques 113 Olof Svensson, Javier Sotres, and Alejandro Barrantes 7 Calorimetric Methods to Characterize the Forces Driving Macromolecular Association and Folding Processes 139 Conceic¸ ˜ao A.S.A. Minetti, Peter L. Privalov, and David P. Remeta 8 Virtual Ligand Screening Against Comparative Models of Proteins 179 Hao Fan 9 Atomistic and Coarse-Grained Molecular Dynamics Simulations of Membrane Proteins 193 Thomas J. Piggot, Peter J. Bond, and Syma Khalid PART II 10 Preparation of Nanomaterials Based on Peptides and Proteins 209 Yujing Sun and Zhuang Li 11 Natural Fibrous Proteins: Structural Analysis, Assembly, and Applications 219 Mark J. van Raaij and Anna Mitraki 12 Amyloid-Like Fibrils: Origin, Structure, Properties, and Potential Technological Applications 233 Pablo Taboada, Silvia Barbosa, Josue Juarez, Manuel-Alatorre Meda, and Výctor Mosquera 13 Proteins and Peptides in Biomimetic Polymeric Membranes 283 Alfredo Gonzalez-Perez 14 Study of Proteins and Peptides at Interfaces By Molecular Dynamics Simulation Techniques 291 David Poger and Alan E. Mark 15 A Single-Molecule Approach to Explore the Role of the Solvent Environment in Protein Folding 315 Katarzyna Tych and Lorna Dougan 16 Enhanced Functionality of Peroxidases By Its Immobilization at The Solid–Liquid Interface of Mesoporous Materials and Nanoparticles 335 Jose Campos-Teran, Iker Inarritu, Jorge Aburto, and Eduardo Torres 17 Superactivity of Enzymes in Supramolecular Hydrogels 353 Ye Zhang and Bing Xu 18 Surfactant Proteins and Natural Biofoams 365 Malcolm W. Kennedy and Alan Cooper 19 Promiscuous Enzymes 379 Luis F. Olguin 20 Thermodynamics and Kinetics of Mixed Protein/Surfactant Adsorption Layers at Liquid Interfaces 389 Reinhard Miller, E.V. Aksenenko, V.S. Alahverdjieva, V.B. Fainerman, C.S. Kotsmar, J. Kragel, M.E. Leser, J. Maldonado-Valderrama, V. Pradines, C. Stefaniu, A. Stocco, and R. Wustneck 21 Application of Force Spectroscopy Methods to the Study of Biomaterials 429 Chuan Xu and Erika F. Merschrod S. 22 Protein Gel Rheology 437 Katie Weigandt and Danilo Pozzo 23 Exploring Biomolecular Thermodynamics in Aqueous and Nonaqueous Environments using Time-Resolved Photothermal Methods 449 Randy W. Larsen, Carissa M. Vetromile, William A. Maza, Khoa Pham, Jaroslava Miksovska INDEX 473

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Book SynopsisThis edited volume spans the latest developments and applications in a new and exciting field of spectroscopy - Fourier Transform Infra-Red (FTIR) spectroscopy.Table of ContentsTheoretical Analyses of the Amide I Infrared Bands of GlobularProteins (H. Torii & M. Tasumi). Fourier Transform Infrared Spectroscopy of Enzyme Systems (J.Alben). Light-Induced Fourier Transform Infrared Difference Spectroscopy ofthe Primary Electron Donor in Photosynthetic Reaction Centers (E.Nabedryk). Equipment: Slow and Fast Infrared Kinetic Studies (F.Siebert). Ultrafast Infrared Spectroscopy of Biomolecules (B. Cohen & R.Hochstrasser). Infrared Spectroscopy of Nucleic Acids (J. Liquier & E.Taillandier). Fourier Transform Infrared Spectroscopy in the Study of HydratedLipids and Lipid Bilayer Membranes (R. Lewis & R.McElhaney). Fourier Transform Infrared Spectroscopic Studies of Cell SurfacePolysaccharides (K. Brandenburg & U. Seydel). Fourier Transform Infrared Spectroscopy of Biomembrane Systems (P.Haris & D. Chapman). What Can Infrared Spectroscopy Tell Us About the Structure andComposition of Intact Bacterial Cells? (D. Naumann, et al.). Biomedical Infrared Spectroscopy (M. Jackson & H.Mantsch). New Trends in Isotope-Edited Infrared Spectroscopy (H. Fabian, etal.). Index.

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Book SynopsisThe book fills the void between rigorous theoretical discussions of ligand binding for physical chemists (often beyond the needs of bench experimentalists in the life sciences) and compilations of experimental recipes that offer scant regard for the appropriateness of the protocol for the particular ligand interaction under investigation.Table of ContentsIntroduction: The Analysis of Simple Binding Responses. Experimental Methods Based on Phase Separation. Spectral Studies of Ligand Binding. Other Direct Procedures for Characterizing Ligand Binding. Binding Constants from Competitive Binding Assays. Sigmoidal Binding Curves: Analysis and Interpretation. Complicating Factors in the Analysis of Binding Curves. Studies of DNA-Ligand Interactions. Concluding Remarks. Glossary of Symbols. References. Index.

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Book SynopsisProvides a lot of reading pleasure and many new insights. -Journal of Molecular Structure This is the most entertaining, stimulating and useful book which can be thoroughly recommended to anyone with an interest in computer simulation. -Contemporary Physics A very useful introduction . . . more interesting to read than the often dry equation-based texts. -Journal of the American Chemical Society Written especially for the novice, Molecular Dynamics Simulation demonstrates how molecular dynamics simulations work and how to perform them, focusing on how to devise a model for specific molecules and then how to simulate their movements using a computer. This book provides a collection of methods that until now have been scattered through the literature of the last 25 years. It reviews elements of sampling theory and discusses how modern notions of chaos and nonlinear dynamics explain the workings of molecular dynamics. Stresses easy-to-use molecules Table of ContentsFundamentals. Hard Spheres. Finite-Difference Methods. Soft Spheres. Static Properties. Dynamic Properties. Appendices. Notation. Bibliography. Index.

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Book SynopsisChemical and biochemical Laboratories are full of potentially dangerous chemicals and equipment. 'Safety in the Chemistry and Biochemistry Laboratory' provides the necessary information needed for working with these chemicals and apparatus to avoid: fires, explosions, toxic fumes, skin burns, poisoning and other hazards.Table of ContentsFrom the Contents: Chemical Risks: The Handling of Chemical Substances, Neutralization and Destruction of Chemical Substances/ Other Risks in the Chemistry Laboratory: Biological Risks, Laboratory Risks Associated with Non-Ionizing Radiation, Laboratory Risk Associated with Radioelements/ Bibliography/ Index/ Appendices

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Book SynopsisThis is the first book to present a topical overview of the research and development of microbial polyesters. Comprehensive and amply illustrated, it covers the * biosynthesis * structure * properties * applications of these biodegradable and biocompatible thermoplastics. The book provides the reader with the necessary background to understand the nature and mechanism of biological polymerization. It unites aspects from both the biological and polymer sciences and is a typical modern example of the analysis of biological macromolecules.Table of ContentsChapter 1 Introduction 1.1 Microbial Poly(3-hydroxybutyrate) 1.2 Microbial Poly(hydroxyalkanoates) 1.3 Environmentally Degradable Polyesters References Chapter 2 Fermentation and Analysis of Microbial Polyesters 2.1 Fermentation Production 2.1.1 Poly(3-hydroxybutyrate) 2.1.2 Poly(hydroxyalkanoates) 2.2 Polymer Isolation 2.2.1 Solvent Extraction 2.2.2 Alkaline Hypochlorite Treatment 2.2.3 Enzyme Treatment 2.3 Analysis 2.3.1 Polyester Content of Cells 2.3.2 Composition of Copolymers 2.3.3 Molecular Weight References Chapter 3 Microorganisms and Poly(3-hydroxyalkanoates) 3.1 Poly(3-hydroxybutyrate) in Microorganisms 3.1.1 Functions of Poly(3-hydroxybutyrate) 3.1.2 Structure of Native P(3HB) Granules 3.2 Biosynthesis of Poly(3-hydroxyalkanoates) 3.2.1 Alcaligenes eutrophus 3.2.2 Pseudomonas oleovorans 3.2.3 Other Bacterial Strains 3.3 Molecular Structures of Poly(3-hydroxyalkanoates) 3.3.1 Poly(3-hydroxybutyrate-co-3-hydroxyalerate) 3.3.2 Poly(3-hydroxyalkanoates-co-3-hydroxy--chloroalkanoates) References Chapter 4 Poly(3-hydroxyalkanoates) Metabolism 4.1 Pathways of Poly(3-hydroxybutyrate) Synthesis 4.2 Pathways of Poly(3-hydroxyalkanoates) Synthesis 4.3 Enzymology of Poly(3-hydroxyalkanoates) Synthesis 4.3.1 3-Ketothiolase 4.3.2 Acetoacetyl-CoA Reductase 4.3.3 P(3HB) Synthase 4.4 Pathways of P(3-hydroxybutyrate) Degradation 4.5 Cyclic Nature of Poly(3-hydroxyalkanoates) Metabolism 4.5.1 Replacement of P(3HB) by P(3HB-co-3HV) 4.5.2 Replacement of P(3HB-co-3HV) by P(3HB) 4.5.3 Application to PHA Fermentation References Chapter 5 Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) 5.1 Alcaligenes eutrophus and Carbon Substrates 5.2 Molecular Structure 5.3 Biosynthetic Pathway References Chapter 6 Structure and Properties of Poly(3-hydroxybutyrate) 6.1 Crystal Structure and Properties 6.1.1 Crystal Structure 6.1.2 Solid-State Properties 6.2 Solution Properties References Chapter 7 Solid-State Properties of Copolyesters 7.1 Composition and Physical Properties 7.1.1 X-Ray Diffraction Analysis 7.1.2 Solid-State CP/MAS 13C-NMR Analysis 7.1.3 Mechanical Properties 7.2 Thermal Properties 7.2.1 Melting Temperatures 7.2.2 Glass-Transition Temperatures 7.2.3 Thermal Stability 7.3 Kinetics of Crystallization References Chapter 8 Biodegradation of Microbial Polyesters 8.1 Extracellular P(3HB) Depolymerase 8.1.1 Pseudomonas lemoignei 8.1.2 Alcaligenes faecalis 8.2 Enzymatic Hydrolysis of Copolyesters 8.3 Simple Hydrolysis of Polyesters 8.4 Applications and Prospects 8.4.1 Environmentally Degradable Plastics 8.4.2 Medical Applications References Index

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Book SynopsisThe text will provide a set of problems covering mechanistic, structural and spectroscopic issues in inorganic chemistry. Specific areas to be covered include coordination chemistry, physiochemical aspects of solution chemistry, inorganic chemistry of biological systems (both natural biomolecules and bioinorganic models). Illustrative worked examples will be included. The problems will be categorized by topic chapters for ease of reference and use in courses. They will provide a valuable resource for instructors, providing a means of testing and developing the many principles covered in texts and advanced courses. Often students find it difficult to find practical problems to test the principles they have learned in class. This text will provide a series of questions to test understanding and worked examples as a pedagogical aid.Table of ContentsFundamentals of Inorganic Biochemistry. Experimental Methods. Transport and Storage. Metalloproteins and Metalloenzymes: (I) Oxygen Carriers and Hydrolases. Metalloproteins and Metalloenzymes: (II) Redox Chemistry. Alkali and Alkaline Earth Metals. Metals in the Regulation of Biochemical Events. Cell Toxicity and Chemotherapeutics. Metal Complexes as Probes of Structure and Reactivity. Case Studies. Appendices. Index.

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Book SynopsisThese two volumes provide a comprehensive look into one of chemistry's fastest growing specialities - sesquiterpene synthesis. They provide a useful and practical tool for researchers interested in locating any of the major classes of sesquiterpene compounds.Table of ContentsAcknowledgments Introduction Reagent Glossary III. Bicyclic Sesquiterpenes A. Eudesmanes 1. β-Eudesmol, α-Eudesmol, Intermediol, Neointermediol, Amiteol, Cycloeudesmol, Maaliol, α-Selinene, β-Selinene, γ-Selinene, Selinadiene, AE 1, Vetiselinene 2. β-Dictyopterol, Selin-4(15)-ene-1β, 11-diol, Balanitol, Occidentalol, Isochamaecynone, Chamaecynone, Emmotin-G, Occidol 3. Amitermes Defensive Substance, Isocelorbicol 4. α-Cyperone, β-Cyperone, Carissone 5. Eudesma-4(14),7(11)-diene-8-one, Arctiol, β-Costol, β-Costal, Isocostic Acid, 3-Oxoisocostic Acid, 1-Oxocostic Acid 6. α-Costal, 7-Hydroxycostol, 7-Hydroxycostal 7. 3-Oxoeudesmatrienoic Acid, 12,15-Dioxaselina-4,11-diene 8. Junenol, Acolamone 9. Atractylon, Lindestrene, Tubipofuran 10. Glutinosone 11. Dehydroasterolide, Dihydrocallitrisin, Isoalantolactone, Septuplinolide, Ivalin, Oxodiplophyllin, Yomogin 12. Frullanolide, Tuberiferin, Deoxybrachylaenolide, Gazanolide, Arbusculin D, 3-Oxo-11-hydroxy-eudesmadienolide, Magnolialide, Maritimin, Dihydrosantamarine, α-Santonin B. Cadinanes 1. Calamenene, Hydroxycalamenenes, Methoxycalamenenes 2. Mansonones, Perezinone 3. 7,8-Dihydroxy-11,12-dehydrocalamenene, Heritol 4. Lacinilene C 5. α-Cadinene, γ2-Cadinene, ε-Cadinene, ε-Muurolene, β-Cadinene, δ-Cadinene 6. Zonarene, Dihydropernetic Acid B, Veticadinol, Torreyol, Isocalamenediol, Cubenol, Epicubenol 7. 1,4-Epoxycadinane, Verboccidentafuran, Hibiscone, Arteannuin B 8. Halipanicine, Sclerosporin, Sclerosporal, Khusilal C. Drimanes 1. Bicyclofarnesic Acid, Drimenol, Albicanyl Acetate, Albicanol, Farnesiferol A 2. Euryfuran, Valdiviolide, Confertifolin, Isodrimenin, Cinnamolide, Polygodial, Drimenin 3. Fragrolide, Cinnamodial, Warburganal, Isotadeonal, Muzigidial, Colorata-4(13),8-dienolide, 3β-Acetoxydrimenin, Pereniporin A, Pereniporin B 4. Driman-8,11-diol, Drim-9(11)-en-8-ol, 7-Oxo-11-nordrimen-8-en-12-oic Acid, 1,1,5,6-Tetramethyltetralin D. Eremophilanes 1. Nootkatone, Valencene, Isovalencenic Acid, Isovalencenol, Eremoligenol, Eremophilene, Valerianol, Eremophilone, Dehydrofukinone, Aristolone, Isopetasol, Petasol, Petasitolone 2. Phomenone, Eremofortin B, Sporogen-AO 1 3. Ligularenolide, Ligularone, Petasalbine, Eremophilenolide, Furanoeremophilone, Furanoeremophilan-14,6a-olide E. Miscellaneous Hydronaphthalenes 1. Acetyldehydrorishitinol, Cinalbicol, 4-Methoxyisocadalene, 4-Hydroxyisocadalene, 1-Hydroxyisocadal-4-one, 2-Methoxy-7-norcalamenene, Maturone, Platyphyllide 2. Ambrox, Pallescensin A 3. Furodysin, Furodysinin 4. Lemnal-5a-en-2-one, Kanshone A, Nardosinone 5. Valerane, Valeranone, Cryptofauronol, Fauronyl Acetate 6. Isoacanthodoral, Nanaiomoal 7. Thujopsene F. Fused Ring Compounds: 6,3 1. Sirenin, Sesquicarene, Isosesquicarene G. Fused Ring Compounds: 6,5 1. Pterosins 2. Pacifigorgiol, Tamariscol 3. Brasilenol, Conocephalenol 4. Axamide-1, Axisonitrile-1, Axamide-4, Axisonitrile-4, Axisothiocyanate-4, Oppositol 5. Pinguisone, Deoxopinguisone 6. Alliacolide 7. Chiloscyphone 8. Coriamyrtin, Asteromurin, Picrotoxinin, Picrotin 9. Oplopanone, Anhydrooplopanone 10. Bakkenolide A, Homogynolide A, Homogynolide B, Palmosalide C 11. Thapsane 12. Valerenal 13. 8-Deoxyanisatin, Anisatin, Neoanisatin, Noranisatin 14. Isovelleral, Stearoylvelutinal 15. Marmalerin H. Fused Ring Compounds: 6,7 1. ar-Himachalene, α-Himachalene, β-Himachalene, γ-Himachalene 2. Perforenone, Guadalupol, Epiguadalupol, Perforene 3. Widdrol 4. Pallescensin E, Pallescensin F, Pallescensin G I. Fused Ring Compounds: 6,8 1. Neolemnane, Neolemnanyl Acetate, Parvifolin J. Fused Ring Compounds: 5,7 1. Lettucenin A 2. β-Bulnesene, α-Bulnesol 3. Gnididione 4. Curcumenol, Curcumol 5. Liguloxide, Kessane 6. Alismol 7. Guaianolides: Compressanolide, Estafiatin 8. Guaianolides: Arborescin, 3-Epizaluzanin C, Zaluzanin C, Mokko Lactone, Dehydrocostus Lactone, Eremanthin 9. Guaianolides: Grosshemin, Oxoisodehydroleucodin, Jalcagauianolide 10. Pseudoguaianolides: Ambrosanolides-Confertin, Rudmollin 11. Pseudoguaianolides: Helananolides-Aromatin, Aromaticin, Graveolide, Fastigilin C, Carpesiolin 12. Daucene, Aspterric Acid 13. Mintsulfide, Aphanamol-I, 2-Oxoisodauc-5-en-12-al 14. Furanol, Furanether A, Furanether B, Furandiol, Lactarorufin A, Furoscrobiculin B 15. Africanol 16. Spathulenol, Alloaromadendrane-4α,10α-diol, Cyclocolorenone, Didehydroaromadendrane 17. Clavukerin A, Clavukerin C, Clavularin A and B K. Fused Ring Compounds: 5,8 1. Precapnelladiene 2. Poitediol 3. Dactylol 4. Asteriscanolide L. Fused Ring Compounds: 4,9 1. Isocaryophyllene, Caryophyllene 2. Punctaporonin B M. Fused Ring Compounds: 5,5 1. Pentalenolactone E 2. Pentalenolactone, Pentalenolactone G, Pentalenolactone H, Pentalenolactone P N. Isolated Rings 1. Cuparene, Herbertene, Tochuinol 2. α-Cuparenone, β-Cuparenone 3. Laurene, Epilaurene, Isolaurene 4. Allolaurinterol, Cyclolaurene 5. Aplysin, Filiformin, Aplysinol, Isoaplysin 6. Trichodiene, Bazzanene 7. Trichodermol, Verrucarol 8. Calonectrin, Anguidine 9. 12,13-Epoxytrichothec-9-ene, 15-Hydroxytrichothec-9,12-diene 10. Neosporol, Sporol 11. Dihydrofomannosin Acetate, Fomannosin O. Spirocyclic Systems 1. Acoradiene, α-Acoradiene, Acoratriene, β-Acorenol, β-Acoradiene 2. Acorone, Acorenone, Acorenone B 3. Hinesol, Agarospirol, α-Vetispirene, β-Vetispirene 4. β-Vetivone, Anhydro-β-rotunol 5. Solavetivone, 15-nor-Solavetivone, 3-Hydroxysolavetivone, Aglycone A3, Lubimin, Oxylubimin, Isolubimin, Lubiminol 6. Vitrenal 7. Spirolaurenone 8. Erythrodiene 9. Cinera-5,7,11-trien-9-one 10. α-Chamigrene, β-Chamigrene, Bromomethylenechamigrenone P. Bridged Systems 1. β-Santalol, β-Santalene, epi-β-Santalene, α-Santalol, α-Santalene 2. α-cis-Bergamotene, β-cis-Bergamotene, β-trans-Bergamotene, (E)-endo-α-Bergamoten-12-oic acid, (E)-endo-β-Bergamoten-12-oic acid, Pinthunamide 3. Helminthosporal 4. Upial 5. Nakafuran-8, Nakafuran-9, Dihydropallescensin 6. Dihydrospiniferin-1, Spiniferin-1 IV. Tricyclic Sesquiterpenes A. Angular Triquinanes 1. Isocomene 2. Silphinene, 8-Oxo-silphinene 3. Pentalenene, Pentalenic Acid 4. Silphiperfolenes, Methyl Cantabrenonate, Subergorgic Acid B. Propellanes 1. Modhephene C. Linear Triquinanes 1. Hirsutene 2. Capnellenes 3. Coriolin, Hypnophilin 4. Hirsutic Acid C, Cerotopicanol D. Miscellaneous Fused Tricyclic Sesquiterpenes 1. β-Bourbonene, Panasinsene, Italicene 2. Protoillud-6-ene, 8-Hydroxy-protoillud-6-ene, Illudol 3. Punctatin A, Ptaquilosin, Illudin M 4. Sterpuric Acid, Sterpurene-3,12,14-triol, Sterpurene E. Bridged Tricyclic Sesquiterpenes 1. Khusimone, Zizaene, Zizanoic acid, Prezizaene, Prezizanol, Jinkohol 2. Patchouli alcohol, Norpatchoulenol, Seychellene, Cycloseychellene 3. Longifolene, Culmorin, Longiborneol 4. Copacamphor, Ylangocamphor, Cyclosativene, Sativene, cis-Sativenediol, Sinularene, Acetoxysinularene 5. Quadrone 6. Cedrene, Isocedrenes, 8,14-Cedranoxide, 8,14-Cedranediol, Biotol, Pipitzols 7. α-Copaene, β-Copaene, β-Ylangene, Lemnalol, Longipinene 8. 9-Isocyanopupukeanane 9. Gymnomitrol 10. Secoishwaranol, Ishwarane 11. Rhodolauradiol, Khusiol Epilogue References Skeleton Index Author Index Subject Index

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Book SynopsisThe detection of neurotransmitter receptor locations and distribution densities within the central nervous system and peripheral tissues is receiving intense attention within the neuroscience research community. Neurotransmitter receptors, which receive the chemical signals sent from one neuron to another, are critical links in a highly complex information-processing chain. Pinpointing receptor sites and systems is crucial for understanding neurological function as well as dysfunction. It is also essential for understanding how receptors process information when impacted by such substances as heroin or nicotine, or when affected by neurodegenerative disease. Receptor Localization: Laboratory Methods and Procedures is the first user-friendly guide to the latest techniques and approaches being employed to examine the localization of neurotransmitter receptors in the central nervous system and peripheral tissues. It covers detection methods that are applicable to a wide varieTrade Review"…an excellent handbook for the budding neuroscientist and should deserve attention for its conciseness and clarity." (Yale Journal of Biology and Medicine, May 2003) "This book is the first in a newly launched series of text dedicated to receptor biochemistry and methodology." (Annals of Clinical Biochemistry).Table of ContentsAutoradiography of Irreversible Ligands/Toxins: Nicotinic Acetylcholine Receptors (E. Sorenson & V. Chiappinelli). Autoradiography of Reversible Ligands (J. Maggio & P. Mantyh). Fluorescent Ligand Binding in Slices and Culture Systems (M. Ray & M. Ariano). Glutamate Receptor Antibodies: Production and Immunocytochemistry (R. Petralia & R. Wenthold). Receptor Fusion Proteins and Analysis (M. Gilmor, et al.). Immunochemical Analysis of Neurotransmitter Receptors (T. Swanson & S. Rivkees). Subcellular Localization of Receptors Using Electron Microscopy (H. Yi & S. Hersch). Infrared Video Microscopy: Visualization and Manipulation of Neurons in Neostriatal Slices (M. Levine, et al.). Localization of mRNAs Encoding Receptors with In Situ Hybridization Histochemistry (M.-F. Chesselet). The Application of RT-PCR Techniques to the Analysis of mRNA in Tissue and Single Cells (Z. Yan, et al.). Detection of Receptor mRNA Using Fluorescent In Situ Transcription (K. Noblett & M. Ariano). Imaging Dopamine Receptors on Living Neurons in Culture (S. Rayport). Receptor Measurements Using PET and SPECT (S. Gatley, et al.). Index.

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Book SynopsisEnzymes are the primary catalysts of life processes. This book covers the latest advances in enzymology, explaining the behaviour of enzymes and how they can be utilized to develop novel drugs, synthesize known and novel compounds, and understand evolutionary processes.Table of ContentsContributors. Preface. Abstracts. Molecular Paleoscience: Systems Biology from the Past (Steven A. Benner, Slim O. Sassi, and Eric A. Gaucher). A Structure-Centric View of Protein Evolution, Design, and Adaptation (Eric J. Deeds and Eugene I. Shakhnovich). Mechanisms of Protein Evolution and Their Application to Protein Engineering (Margaret E. Glasner, John A. Gerlt, and Patricia C. Babbitt). Novel Enzymes Through Design and Evolution (Kenneth J. Woycechowsky, Katherina Vamvaca, and Donald Hilvert). Author Index. Subject Index.

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Book SynopsisThermodynamics of Biochemical Reactions emphasizes the fundamental equations of thermodynamics and the application of these equations to systems of biochemical reactions. This emphasis leads to new thermodynamic potentials that provide criteria for spontaneous change and equilibrium under the conditions in a living cell.Trade Review"Through the writing of his new book, Professor Alberty has performed a great service to future textbook authors and to their readers, as well as to the biochemical community in general.” (Biochemistry and Molecular Education, Nov/Dec 2003) "...a useful learning device...through the writing of his new book, Professor Alberty has performed a great service to future textbook authors and their readers, as well as to the biochemical community in general." (Biochemistry and Molecular Biology Education,Vol. 31, No. 6) "...this book will prove useful for students and working biochemists...highly recommended..." (Choice, September 2003) "...emphasizes the application of the fundamental equations of thermodynamics to systems of enzyme-catalyzed reactions making up the metabolism of living organisms." (Pharmaceutical Research, Vol. 20, No. 9, September 2003) "...written by the most experienced authority in this field...well-written and -organized, and nicely produced..." (Angewandte Chemie International Edition, Vol 42(37), 2003) "...the authors are to be congratulated on producing an updated, valuable and comprehensive review of the field..." (ChemPhysChem, Vol 5, 2004)Table of ContentsPreface. Chapter 1. Introduction to Apparent Equilibrium Constants. Chapter 2. Structure of Thermodynamics. Chapter 3. Chemical Equilibrium in Aqueous Solutions. Chapter 4. Thermodynamics of Biochemical Reactions at Specified pH. Chapter 5. Matrices in Chemical and Biochemical Thermodynamics. Chapter 6. Systems of Biochemical Reactions. Chapter 7. Thermodynamics of Binding of the Ligands by Proteins. Chapter 8. Phase Equilibrium in Aqueous Systems. Chapter 9. Oxidation-Reduction Reactions. Chapter 10. Calorimetry of Biochemical Reactions. Chapter 11. Use of Semigrand Partition Functions. Glossary. References.

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Book SynopsisBioseparations engineering is the "multidisciplinary application of fundamental engineering and biological principles to the design of adsorbents, systems, and processes for the separation of biological molecules.Trade Review"a comprehensive text that has brought together the theory and practice of bioseperations in an intelligent and well-presented fashion." (Bioseperations Engineering (Food & Bioproducts Processing, December 2001) "...Ladish reviews the techniques that have been developed over the past couple decades...in the hope that the explanations will apply to bioproducts not yet invented and biological molecules not yet produced...as well as to those currently being used." (SciTech Book News, Vol. 25, No. 4, December 2001)Table of ContentsPreface. Acknowledgements. Bioseparations. Sedimentation, Centrifugation, and Filtration. Membrane Separations. Precipitation, Crystallization, and Extraction. Principles of Liquid Chromatography. Liquid Chromatography Scale-Up. Principles of Gradient Elution Chromatography. Principles of Bioseparations for Biopharmaceuticals and Recombinant Protein Products. Affinity Chromatography: Bridge Between Molecular Biology, Combinatorial Methods, and Separations Science. Author Index. Subject Index.

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Book SynopsisBiological catalysis plays a dominant role both in fermentation and industrial process chemistry. This collection of chapters, written by a well-known biochemist and enzymologist, should serve as an invaluable reference to those investigators seeking to optimize the application of enzymatic catalysis for commercial purposes.Table of ContentsClassics in Enzymology: The Kinetics of the Enzyme-SubstrateCompound of Peroxidase (B. Chance). Rethinking Fundamentals of Enzyme Action (D. Northrop). Adenylosuccinate Synthetase: Recent Developments (R. Honzatko, etal.). Nucleoside Monophosphate Kinases: Structure, Mechanism, andSubstrate Specificity (H. Yan & M.-D. Tsai). Enzymology of NAD?+ Synthesis (G. Magni, et al.). Solution Structure and Mechanism of MutT Pyrophosphohydrolase ( A.Mildvan, et al.). The Enzymes of Glutathione Synthesis: gamma-GlutamylcysteineSynthetase (O. Griffith & R. Mulcahy). Indexes.

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Book SynopsisG protein-coupled receptors (GPCRs) are the largest single class of receptors in biology, often playing key roles in a remarkably large number of physiological and pathophysiological conditions. GPCRs or GPCR-dependent signalling pathways are the targets of a very large number of therapeutically useful drugs. Detailed knowledge about the molecular structure of GPCRs should therefore pave the way for the design of novel drugs with increased efficacy and specificity. This volume provides a concise, up-to-date presentation of methods (including molecular genetic, biochemical, and biophysical) which have been used successfully in studying the structure and function of GPCRs. With contributions from international leaders in the field, the editor provides overviews of various techniques, followed by in-depth descriptions of basic procedures and discussions of critical experimental parameters. Divided into specific, accessible sections, Structure-Function Analysis of G ProteTable of ContentsPartial table of contents: Overview of Mutagenesis Techniques (T. Fong). The Substituted-Cysteine Accessibility Method (J. Javitch). Metal-Ions as Atomic Scale Probes of G Protein-Coupled Receptor Structure (J. Schetz & D. Sibley). Genetic Approaches for Studying the Structure and Function of G Protein-Coupled Receptors in Yeast (C. Sommers & M. Dumont). Electron-Crystallographic Analysis of Two-Dimensional Rhodopsin Crystals (G. Schertler). Site-Directed Spin-Labeling (SDSL) Studies of the G Protein-Coupled Receptor Rhodopsin (D. Farrens). Lead Discovery and Development for G Protein-Coupled Receptors (D. Underwood & M. Cascieri). Index.

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Book SynopsisThere have been dramatic advances in the field of researching Vitamin B12, and those advances have served to revitalize interest in Vitamin B12 among biochemists, organic and inorganic chemists, microbiologists, structural biologists, and many other science professions.Table of ContentsCHEMISTRY OF B_12. B_12 History (H. Hogenkamp). X-ray Crystallography of B_12 (B. Kräutler & C. Kratky). X-Ray Absorption Spectorscopy of B_12: Structural Changes of Intermediate States (M. Chance). Electronic Structure and Spectra of B_12: From Trans Effects to Protein Conformation I (J. Pratt). Electronic Structure and Spectra of B_12: From Trans Effects to Protein Conformation II (J. Pratt). EPR Spectroscopy of B_12-Dependent Enzymes (G. Gerfen). NMR Spectroscopy of B_12 (K. Brown). Vibrational Spectroscopy of B_12 and Related Compounds (L. Marzilli & S. Hirota). Magnetic Field Dependence of Cobalamin Photochemistry and Enzymes (C. Grissom). Stereospecificity of the Coenzyme B_12 Catalyzed Rearrangements and the Role of Negative Catalysis (J. Retey). Modeling the Structure of Cobalt Corrins by Molecular Mechanics and Molecular Dynamics Methods (H. Marques). B_12 Electrochemistry and Organometallic Electrochemical Synthesis (B. Kräutler). BIOCHEMISTRY AND BIOLOGY OF B_12. B_12 and Nutrition (S. Stabler). Inborn Errors of Cobalamin Metabolism (D. Rosenblatt & W. Fenton). Diagnostic and Therapeutic Analogs of Cobalamin (H. Hogenkamp, et al.). Intrinsic Factor and Haptocorrin and Their Receptors (D. Alpers & G. Russell-Jones). Transcobalamin II (S. Rothenberg, et al.). Mammalian Receptors of Vitamin B_12-Binding Proteins (S. Moestrup & P. Verroust). Cobalamin Transport in Bacteria (C. Bradbeer). Biosynthesis of B_12 in the Aerobic Organism Pseudomonas denitrificans (A. Battersby & F. Leeper). B_12 Biosynthesis: The Anaerobic Pathway (A. Scott, et al.). Biosynthesis of the 5-6 Dimethylbenzimidazole Moiety of Cobalamin and of the Other Bases Found in Natural Corrinoids (P. Renz). Regulation of Adenosylcobalamin Biosynthesis in Salmonella typhimurium (J. Semerena). X-ray Crystallography of B_12 Enzymes: Methylmalonyl-CoA Mutase and Methionine Synthase (M. Ludwig & P. Evans). The Acetogenic Corriniod Proteins (S. Ragsdale). The Role of Corrinoids in Methanogenesis (K. Sauer & R. Thauer). Methionine Synthase (R. Matthews). Methylmalonyl-CoA Mutase (R. Banerjee & S. Chowdhury). Ribonucleotide Reductases (M. Fontecave & E. Mulliez). Glutamate Mutase and 2-Methyleneglutarate Mutase (W. Buckel, et al.). Diol Dehydrase and Glycerol Dehydrase (T. Toraya). Ethanolamine Ammonia-Lyase (V. Bandarian & G. Reed). Anomutases (P. Frey). Isobutyryl-CoA Mutase (K. Zerbe-Burkhardt, et al.). Reductive Dehalogenases (G. Wohlfarth & G. Diekert).

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Book SynopsisToxicology--the scientific study of environmental factors that are harmful to living organisms--was established more than 400 years ago by the Swiss physician Paracelsus.Table of ContentsIntroduction to Toxicology. Epidemiological and Toxicological Studies. Routes of Exposure. The Dose-Response Relationship. Absorption, Distribution, Metabolism, and Elimination of Toxics. Target Organ Effects. Survey of Toxic Substances. Radiation, Pathogens, and Naturally Occurring Toxins. Mutagens, Teratogens, and Carcinogens. Risk Assessment and Acute Exposure Treatment. Glossary. Bibliography. Index.

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Book SynopsisThis volume describes the complete process of analyzing protein sequences by mass spectrometry including sample preparation, analysis, and data interpretation at a practical level. It provides sufficient experimental detail to carry out the experiments and consistently achieve good results.Trade Review"[the authors] present their own laboratory-tested protocols for the analysis of a wide variety of samples, providing sufficient detail for duplication of their methods..." (SciTech Book News Vol. 25, No. 2 June 2001) "...an informative, well-written and well-illustrated book with a large number of useful references.... It should prove invaluable to anyone working in the field of protein sequencing." (Spectroscopyeurope.com)Table of ContentsAn Introduction to Protein Sequencing Using Tandem Mass Spectrometry. The Primary Structure of Proteins and a Historical Overview of Protein Sequencing. Fundamental Mass Spectrometry. Collisionally Induced Dissociation of Protonated Peptide Ions and the Interpretation of Product Ion Spectra. Basic Polyacrylamide Gel Electrophoresis. The Preparation of Protein Digests for Mass Spectrometric Sequencing Experiments. Mass Spectrometric Analysis of Tryptic Digests. Protein Identification by Database Searching. Sequence Analysis of Novel Proteins. The Characterization of Post-Translationally Modified Proteins Using Tandem Mass Spectrometry. Index.

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Book SynopsisThis work provides a comprehensive and critical overview of all the main classes of theoretical molecular descriptors. It reviews computational methods that can be employed in the development of QSAR and QSPR equations.Trade Review"This text for academic and industrial chemists covers empirical and molecular descriptors, and methods for QSAR/QSPR development." (SciTech Book News, Vol. 24, No. 4, December 2000)Table of ContentsEmpirical Molecular Descriptors. Theoretical Molecular Descriptors. Methods for the Development of QSAR/QSPR. Appendix. Index.

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Book SynopsisProvides a comprehensive overview of direct and indirect effects of air pollutants on plant life. This book covers both physiological and biochemical impacts as well as effects at the whole plant/ecological level.Trade Review"...should be studied by many, whose interest lies in the preservation of air quality..." (International Journal of Environment Studies, Vol.60, No.2, 2003) "...Bell and Treshow have produced what I suspect will be a classic. (Times Higher Educational Supplement, 30 May 2003)Table of ContentsIntroduction (Nigel Bell & Michael Treshaw) Historical Perspective (Michael Treshaw & Nigel Bell) Emissions, Dispersion, Atmospheric Transformation (Roy Colville) Deposition and Uptake by Vegetation (David Fowler) Effects of Oxidants at the Biochemical, Cell and Physiological Levels with Particular Reference to Ozone (Stephen Long and Shawna Naidu) Effects of Oxidants at the Whole Plant and Community level (Michael Ashmore) Nitrogen Oxides: Old Problems and new Challenges (Terry Mansfield) Effects of Sulphur Dioxide (Allan Legge & Sagar Krupa) Effects of Fluorides (Len Weinstein & Del McCune) Effects of Volatile Organic Compounds (Christopher Collins & Nigel Bell) Effects of Particulates (Andrew Farmer) Effects of Increased Nitrogen Deposition (Roland Bobbink & Leon Laners) Effects of Wet Deposited Acidity (Trevor Ashenden) Effects of Pollutant Mixtures (Andreas Fangmeier, Juergen Bender, Hans-Joachim Weigel & Hans-Juergen Jager) Forest Decline and Air Pollution: An Assessment of "Forest Health" in the Forests of Europe, the Northeastern United States and Southeastern Canada (John Innes & John Skelly) Effects of Acidic Deposition on Aquatic Ecosystems (Ronald Harriman, Richard Batterbee & Don Monteith) Effects on Bryophytes and Lichens (Jeffrey Bates) Modification of Plant Response by Environmental Conditions (Gina Mills) Air Pollutant - Abiotic Stress Interactions (Alan Davison & Jeremy Barnes) Effects of Air pollutants on Biotic Stresses (Walter Fluckiger, Sabine Braun & Erika Hiltbrunner) Effects of Air Pollutants in Developing Countries (Fiona Marshall) Air Quality Guidelines and their Role in Pollution Control Policy (Michael Ashmore) Air Pollution and Climate Change (Victor Runeckles) Future Research Priorities and Directions (Nigel Bell)

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Book SynopsisProvides a comprehensive overview of the direct and indirect effects of air pollutants on plant life. This book also covers both physiological and biochemical impacts as well as larger-scale effects at the whole plant/ecological level. It is useful for students in Environmental Science, and Biological Science and Agriculture.Trade Review"...should be studied by many, whose interest lies in the preservation of air quality..." (International Journal of Environment Studies, Vol.60, No.2, 2003) "...Bell and Treshow have produced what I suspect will be a classic. (Times Higher Educational Supplement, 30 May 2003)Table of ContentsIntroduction (Nigel Bell & Michael Treshaw) Historical Perspectives (Michael Treshaw & Nigel Bell) Emissions, Dispersion and Atmospheric Transformation (Roy Colville) Deposition and Uptake by Vegetation (David Fowler) Effects of Oxidants at the Biochemical, Cell and Physiological Levels with Particular Reference to Ozone (Stephen Long and Shawna Naidu) Effects of Oxidants at the Whole Plant and Community Level (Michael Ashmore) Nitrogen Oxides: Old Problems and New Challenges (Terry Mansfield) Effects of Sulphur Dioxide (Allan Legge & Sagar Krupa) Effects of Fluorides (Len Weinstein & Del McCune) Effects of Volatile Organic Compounds (Christopher Collins & Nigel Bell) Effects of Particulates (Andrew Farmer) Effects of Increased Nitrogen Deposition (Roland Bobbink & Leon Laners) Effects of Wet Deposited Acidity (Trevor Ashenden) Effects of Pollutant mixtures (Andreas Fangmeier, Juergen Bender, Hand-Joachim Weigel & Hans-Juergen Jager) Forest Decline and Air Pollution: An Assessment of "Forest Health" in the Forests of Europe, the Northeastern United States and Southeastern Canada (John Innes & John Skelly) Effects of Acidic Deposition on Aquatic Ecosystems (Ronald Harriman, Ricahrd Battarbee & Don Monteith) Effects on Bryophytes and Lichens (Jeffrey Bates) Modifications of Plant Response by Environmental Conditions (Gina Mills) Air Pollutant - Abiotic Stress Interactions (Alan Davison & Jeremy Barnes) Effects of Air Pollutants on Biotic Stresses (Walter Fluckiger, Sabine Braun & Erika Hiltbrunner) Effects of Air Pollutants in Developing Countries (Fiona Marshall) Air Quality Guidelines and their Role in Pollution Control Policy (Michael Ashmore) Air Pollution and Climate Change (Victor Runeckles) Future Research Priorities and Directions (Nigel Bell)

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Book SynopsisExplores the latest findings for both selective and efficient separation devices in the field of kidney research. It is divided into three major sections. Part one deals with the ``biochemistry'''' part of the problem, including how to identify ligands of interest, how to link them to synthetic membranes, and some kinetic limitations of frontal elution chromatography. The second part comprehensively discusses the various substrata used in affinity separations and the formation processes of semi-permeable membranes. The final section explores the filtration processes using membranes and the kinetics of separations based on affinity membranes.Table of ContentsAffinity Adsorption. Substrates. Binding Chemistries. Ligand Types. Capacity of Affinity Matrices. Membrane Formation. Characterization. Microfiltration. Applications for Affinity Microfiltration Membranes. Appendix. Index.

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Book SynopsisBuprenorphine: Combatting Drug Abuse with a Unique Opioid Editors: Alan Cowan and John W. Lewis Scientists involved in the study of opioid pharmacology and drug abuse have long included among their goals the development of effective analgesics with reduced potential for abuse and dependence, and the development of effective pharmacological agents for the treatment of opioid abuse and dependence. Buprenorphine appears to have made an important scientific and clinical contribution on both of these fronts. In this timely volume, international experts describe the unusual chemical and biological characteristics which make this agent unique, from the opiate receptor, through animal pharmacology, to clinical uses, culminating in a discussion of the use of buprenorphine as a medication in the treatment of opioid abuse. Buprenorphine holds great promise as a significant addition to the therapeutic menu available to drug abuse therapists. Buprenorphine: CombaTable of ContentsPartial table of contents: CHEMISTRY. Buprenorphine-Medicinal Chemistry (J. Lewis). PRECLINICAL PHARMACOLOGY. Update on the General Pharmacology of Buprenorphine (A. Cowan). ASSAY, METABOLISM, AND PHARMACOKINETICS. Analysis (R. Moore). CLINICAL PHARMACOLOGY AND EVALUATION. Buprenorphine in Psychiatric Disorders (D. Nutt, et al.). STUDIES RELATING TO TREATMENT OF SUBSTANCE ABUSE. Detoxification and Induction Onto Naltrexone (M. Rosen & T. Kosten). PERSPECTIVE. Buprenorphine: What Interests the National Institute on Drug Abuse? (D. Segal & C. Schuster). Index.

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Book SynopsisA comprehensive, up-to-date treatment of the biochemistry essential for an understanding of molecular and cellular biological processes. This third edition offers new units covering the chemistry of life, bioenergetics, energy transfer molecules, regulation of enzymes and reaction sequences, lab techniques for purification of proteins and nucleic acids, and lab techniques of molecular genetics. Also, each unit contains more applications to biological systems. The text provides a well-organized and rigorous approach suitable for classroom use or self-instruction. Each unit begins with a 1- to 2-page presentation of basic concepts, followed by about 20 questions and problems with sample responses. Self-tests appear after every 2 to 3 units and there is a cumulative self-test at the end of the book.Table of ContentsIntroduction to the Chemistry of Life. Particles, Atoms, and Molecules. Chemical Groups. Ions, Ionic Bonds, and Crystals. Polarity, Hydrogen Bonds, Solubility, and HydrophobicInteractions. Chemical Equilibrium. Carbohydrates I: Monosaccharides and Related Molecules. Carbohydrates II: Disaccharides, and Polysaccharides. Amino Acids. Proteins I: Peptide Bonding and Polypeptides. Proteins II: Levels of Structure and Conjugated Proteins. Lipids: Fats, Phospholipids, Sterols, and Prostaglandins. Nucleic Acids. Bioenergetics. Energy Transfer Molecules. Enzymes. Regulation of Enzymes and Reaction Sequences. Molecular Weight and Molar, Percent, Mg Percent, and ppmSolutions. pH and H?+ Concentration. Weak Acids, Dissociation Constants, and Buffers. Self-Test. Laboratory Methods. Cumulative Self-Test. Index.

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Book SynopsisBridging the knowledge gap between scientists that develop and apply proteomics technologies and oncologists who focus on understanding the biological basis behind cancer manifestation and progression, this title provides an account of how the multiple facets of proteomics have been applied to cancer.Trade Review“By guiding readers through the latest proteomic technologies and their applications in cancer research, “Proteomic Applications in Cancer Detection and Discovery" enhances the ability of researchers in proteomics and researchers in oncology to collaborate in order to better understand cancer and develop strategies to prevent and treat it.” (Newbooks.lib, 11 September 2014Table of ContentsPreface vii Acknowledgments ix 1 Systems Biology 1 2 Mass Spectrometry in Cancer Research 27 3 Quantitative Proteomics 59 4 Proteomic Analysis of Posttranslational Modifications 87 5 Characterization of Protein Complexes 117 6 Global Phosphorylation Analysis 145 7 the Search for Biomarkers in Biofluids 171 8 Proteomic Patterns: a New Paradigm in Diagnostics And Therapeutics? 195 9 the Emergence of Protein Arrays 215 10 the Role of Proteomics in Personalized Medicine 241 11 the Critical Role of Bioinformatics 263 12 Future Prospects of Proteomics in Cancer Research 281 Index 305

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Book SynopsisDrug Metabolism in Drug Design and Development provides a practical description of what happens during the drug design and development process and focuses on issues such as: what data are needed; what experiments and analytical methods are typically employed; and how to interpret and apply data.Trade Review"I highly recommend this book to anyone interested in drug metabolism." (Journal of Medicinal Chemistry, 2008)Table of ContentsPreface. Contributors. Part I: Basic Concepts of Drug Metabolism. 1. Overview: Drug Metabolism in the Modern Pharmaceutical Industry (Scott J. Grossman) 2. Oxidative, Reductive, and Hydrolytic Metabolism of Drugs (F. Peter Guengerich) 3. Conjugative Metabolism of Drugs (Rory Remmel, Swati Nagar and Upendra Argikar) 4. Enzyme Kinetics (Timothy S. Tracy) 5. Metabolism-Mediated Drug-Drug Interactions (Hongjian Zhang, Michael W. Sinz, and A. David Rodrigues) 6. Drug Transporters in Drug Disposition, Drug Interactions, and Drug Resistance (Cindy Q. Xia, Johnny J. Yang, and Suresh K. balani) 7. Regulatory Considerations of Drug Metabolism and Drug Interaction Studies (Xiaoxiong Wei and Mingshe Zhu) Part II: Role of Drug Metabolism in the Pharmaceutical Industry. 8. Drug Metabolism Research as an Integral Part of the Drug Discovery Process (W. Griffith Humphreys) 9. Role of Drug Metabosim in Drug Development (Ramaswamy Iyer and Donglu Zhang) Part III: Analytical techniques in Drug Metabolism. 10. Applications of Liquid Radiochromatography Techniques in Drug Metabolism Studies (Mingshe Zhu, Weiping Zhao, and W. Griffith Humphreys) 11. Application of Liquid Chromatogrpahy/Mass Spectrometry for Metabolite Identification (Shuguang Ma and Swapan K. Chowdhury) 12. Introductin to NMR and Its Application in Metabolite Structure Determination (Xiaohua Huang, Robert Powers, Adrienne Tymiak, Robert Espina, and Vikram Roongta) Part IV: Common Experimental Approaches and Protocols. 13. Determination of Metabolic Rats and Enzyme Kinetics (Zhi-Yi Zhang and Laurence S. Kaminsky) 14. Protocols for Assessment of In vitro and In vivo Bioactivation Potential of Drug Candidates (Zhoupeng Zhang and Jinping Gan) 15. Reaction Phenotyping (Susan Hurst, J. Andrew Williams, and Steven Hansel) 16. Analysis of In vitro Cytochrome P450 Inhibition in Drug Discovery and Development (Magang Shou and Renke Dai) 17. Testing Drug Candidates for CYP3A4 Induction (Gang Luo, Liang-Shang Gan, and Thomas M. Guenthner) 18. ADME Studies in Animals and Humans: Experimental Design, Metabolite Profoling and Identification, and Data Presentation (Donglu Zhang and S. Nilgun Comezoglu) Index.

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Book SynopsisTools, techniques, and progress in cancer biomarkers discovery The completion of a number of gene sequencing projects, recent advances in genomic and proteomic technologies, and the availability of powerful bioinformatics tools have led to promising new avenues and approaches in the search for cancer biomarkers.Trade ReviewVery well written and up-to-date. I recommend … to anyone interested in learning about cancer research from the basic discovery to clinical stages. (The Yale Journal of Biology and Medicine, June 2007)Table of ContentsPreface. Acknowledgments. Introduction. 1 Overview. 1.1. Introduction. 1.2. Cancer Biomarkers. 1.3. Phases of Biomarkers Development. 1.4. New Approach to Biomarkers Discovery. 1.4.1. New and Powerful Technologies. 1.4.2. Promising Sources for Biomarkers. 1.4.2.1. DNA Methylation. 1.4.2.2. Mitochondrial DNA Mutations. 1.4.2.3. Phosphatidylinositol-3 Kinases (PI3Ks). 1.4.2.4. Profi ling Tyrosine Phosphorylation. 1.4.2.5. Proteins Expression. 1.5. Initiatives Relevant to Biomarkers Discovery. 1.5.1. Initiatives of the Human Proteome Organization (HUPO). 1.5.2. Data Mining in Cancer Research. 1.6. Concluding Remarks. References. 2 Proteomic Platforms for Biomarkers Discovery. 2.1. Surface Enhanced Laser Desorption Ionization. 2.1.1. Some Basic Considerations. 2.1.2. Protein Capture Surfaces. 2.1.3. Enrichment/prefractionation Prior to SELDI Analysis. 2.1.3.1. Combinatorial Affi nity. 2.1.3.2. Magnetic Beads. 2.1.3.3. Stacked Sorbents. 2.1.3.4. Organic Solvent Extraction. 2.2. Bioinformatics in SELDI. 2.3. Some Representative SELDI Applications. 2.3.1. Addressing Reproducibility in SELDI Analysis. 2.3.2. Limitations and Other Open Questions Regarding Current SELDI. 2.3.3. Other Open Questions. 2.3.4. Outlook. 2.4. Two-dimensional Polyacrylamide Gel Electrophoresis. 2.4.1. Sample Preparation. 2.4.2. Reducing Sample Complexity. 2.4.3. Various Nomenclatures In-gel Analysis. 2.4.3.1. Multiple-gels Two-dimensional Analyses. 2.4.3.2. Two-dimensional DIGE Analysis. 2.4.3.3. Multiphoton Detection Imaging. 2.4.3.4. Stable-isotope Labeling with Amino Acids in Cell Culture (SILAC). 2.5. Laser Capture Microdissection. 2.6. MS Analysis of Gel-separated Proteins. 2.7. Representative Applications of 2-DE for Biomarkers Discovery. 2.8. Protein Microarrays. 2.8.1. Analytical Protein Microarrays. 2.8.2. Substrates and Protein Attachment Methods. 2.8.3. Detection Strategies. 2.8.3.1. Surface Plasmon Resonance (SPR). 2.8.3.2. Atomic Force Microscopy (AFM). 2.8.3.3. Enzyme-linked Immunosorbent Assay (ELISA). 2.8.3.4. Radio Isotope Labeling. 2.8.3.5. Fluorescence Detection. 2.8.4. Functional Protein Microarrays. 2.8.5. Reverse-phase Protein Microarrays. 2.8.6. Future Prospects. 2.9. Multidimensional Liquid Chromatography Coupled to MS. 2.9.1. Protein Labeling. 2.9.2. Labeling a Specifi c Amino Acid. 2.9.3. Stable Isotope Incorporation. 2.9.4. Limitations of Labeling. 2.10. Chromatographic Separation. 2.10.1. Three Dimensional Separation. 2.10.2. Two-dimensional Chromatography. 2.10.3. Basic Considerations Regarding MudPIT. 2.10.4. Mass Spectrometry and Data Analysis. 2.10.5. Data Analysis and Interpretation. 2.10.6. Application of Multidimensional Chromatography/MS. 2.10.7. Outlook for Multidimensional LC/MS. 2.11. Imaging Mass Spectrometry. 2.11.1. Tissue Preparation and Matrix Application. 2.11.2. MS Acquisition. 2.11.3. Some Representative Applications of Imaging MS. 2.11.4. Current Limitations and Potential Developments. References. 3 Some Existing Cancer Biomarkers. 3.1. Introduction. 3.2. Historic Glimpse at PSA. 3.3. Prostate-specifi c Antigen. 3.4. PSA as a Screening Marker. 3.5. Improving the Specifi city of PSA. 3.5.1. Free/Complexed PSA. 3.5.2. PSA Isoforms. 3.5.3. Impact of Age, Race, and PSA Velocity. 3.6. Looking for Other Solutions. 3.6.1. Genetic Alterations. 3.6.2. Phosphorylated Akt. 3.7. Concluding Remarks. 3.8. Existing Biomarkers for Ovarian Cancer. 3.8.1. Genetic Disorder and Increased Risk of Ovarian Cancer. 3.8.2. Association of BRCA1 and BRCA2 with Cancer-susceptibility. 3.8.3. p53 Mutations in BRCA1-linked and Sporadic Ovarian Cancer. 3.8.4. Carcinoma-associated Glycoprotein Antigen (CA-125). 3.8.5. Potential Uses of CA-125 in Prognosis and Patient Management. 3.9. Osteopontin. 3.9.1. Human Kallikrein 10. 3.9.2. Prostasin. 3.10. Combination of CA-125 with Other Potential Biomarkers. 3.11. Profi ling Proteins and Gene Expression in Ovarian Cancer. 3.12. General Observations. References. 4 Potential Cancer Biomarkers. 4.1. Introduction. 4.2. Human Tissue Kallikreins. 4.2.1. Background and Nomenclature. 4.2.2. Gene Locus and Gene Organization of Human Kallikreins. 4.2.3. Tissue Expression and Regulation. 4.2.4. Physiologic Roles. 4.2.5. Kallikreins as Potential Cancer Biomarkers. 4.2.6. Concluding Remarks. 4.3. Protein Family 14-3-3. 4.3.1. Functions Attributed to the 14-3-3 Proteins. 4.3.2. Binding of 14-3-3 Proteins to Different Partners. 4.3.3. The Role of 14-3-3 Proteins in Apoptosis. 4.3.4. The Role of 14-3-3 Proteins in Cell-cycle Regulation. 4.3.5. The Potential of Some 14-3-3 Proteins as Cancer Biomarkers. 4.3.5.1. Down-regulation of 14-3-3σ in Various Types of Cancer. 4.3.5.2. Down-regulation of 14-3-3σ in Breast Cancer. 4.3.5.3. Perspectives. 4.4. Heat Shock Proteins (HSPs). 4.4.1. Structure and Functions of HSP90. 4.4.2. Association of HSP90 with Cancer. 4.4.3. HSP90 as a Therapeutic Target. 4.5. Heat Shock Protein 27 (HSP27). 4.5.1. The Role of HSP27 in Apoptosis. 4.5.2. Expression of HSP27 in Cancer. 4.6. Heat Shock Protein 70 (HSP70). 4.6.1. Structure and Mechanism of Action. 4.6.2. Anti-apoptotic Role of HSP70. 4.6.3. Overexpression of HSP70 in Cancer. 4.7. General Remarks. 4.8. Calcium Binding Proteins. 4.8.1. Structure and Chromosomal Location of S100. 4.8.2. S100A4 Protein. 4.8.3. Association of S100A4 with Cancer. 4.8.4. Overexpression of S100A4 in Pancreatic Ductal Adenocarcinoma. 4.8.5. S100A4 in Human Breast Cancer. 4.8.6. General Considerations. 4.9. DNA Methylation. 4.9.1. Detection of DNA Methylation. 4.9.1.1. Restriction Landmark Genomic Screening (RLGS). 4.9.1.2. Methylation-specifi c PCR (MSP). 4.9.1.3. Other Variations. 4.10. DNA Methylation in Cancer. 4.10.1. CpG Island Methylation and Gene Silencing. 4.10.1.1. Proteins that Mediate DNA Methylation. 4.10.1.2. Nucleosomes. 4.10.1.3. Histone Acetylation. 4.10.2. Methylated Biomarkers in Cancer. 4.10.3. Hypermethylation as a Biomarker in Lung Cancer. 4.11. Inhibition of DNA Methylation. 4.12. Concluding Remarks. References. 5 Protein Networks and Protein Phosphorylation in Cancer. 5.1. Introduction. 5.2. Protein Interaction Networks. 5.2.1. Experimental Approaches. 5.2.2. Yeast Two Hybrid (Y2H) System. 5.2.3. Tandem Affi nity Purifi cation/Mass Spectrometry (TAP-MS). 5.2.4. Y2H and TAP-MS as Complementary Approaches. 5.2.5. DNA Microarrays. 5.2.6. Other Approaches. 5.3. Computational Approaches. 5.3.1. Phylogentic Profi les. 5.3.2. Similarity of Phylogenetic Trees (Mirrortree). 5.3.3. In Silico Two-hybrid Method. 5.4. Human Protein Intractome. 5.4.1. Human Intractome Based on Orthologs. 5.4.2. Human Interactome Based on Experimental Data. 5.5. Relationship Between Gene Expression and Protein Interaction. 5.6. Gene Signatures in Cancer Prediction/Classifi cation. 5.6.1. Breast Cancer. 5.6.2. Follicular Lymphoma. 5.6.3. Lymphocytic Leukemia. 5.6.4. Lung Adenocarcinoma. 5.7. Concluding Remarks. 5.8. Protein Phosphorylation. 5.8.1. Introduction. 5.8.2. Experimental Approaches for the Detection and Quantifi cation of Protein Phosphorylation. 5.8.3. Enrichment Strategies. 5.8.4. MS Detection of Phosphorylation. 5.8.4.1. Analyses Using Electrospray Ionization (ESI). 5.8.4.2. Liquid Chromatography/Mass Spectrometry. 5.9. Other Approaches. 5.10. The Phosphatidylinositol 3-Kinase-Akt Pathway (PI3K-Akt). 5.10.1. Phosphatidylinositol 3-Kinase (PI3K). 5.10.2. Akt (PKB) and Its Activation. 5.10.3. Biological Consequences of Akt Activation. 5.10.4. Altered PI3K-Akt Signaling in Human Cancer. 5.11. PIK3/Akt Alterations and Prognostic Biomarkers. 5.11.1. Melanoma. 5.11.2. Non-small-cell Lung Cancer (NSCLC). 5.11.3. Prostate Cancer. 5.12. General Observations. References. 6 Ethical Issues and Initiatives Relevant to Cancer Biomarkers. 6.1. Introduction. 6.2. Background. 6.3. Ethical Committees/Organizations. 6.4. Human Biobanks. 6.4.1. Ethical Issues in Biobanking. 6.5. Large Population Screening. 6.5.1. Screening for Colorectal Cancer. 6.5.2. Screening for Early Prostate Cancer. 6.5.3. Screening for Cervical Cancer. 6.6. Genetic Testing for Cancer Susceptibility. 6.7. Ethics in Phase I Oncology Trials. 6.7.1. Risks and Benefi ts of Phase I Oncology Trials. 6.8. Initiatives Relevant to Biomarkers Discovery. 6.8.1. The Human Proteome Organization (HUPO). 6.8.2. HUPO Initiative Around Biological Fluids. 6.8.3. Early Detection Research Network (EDRN). 6.8.4. Other Initiatives. 6.9. Genomic Initiatives/Resources. 6.9.1. The Cancer Genome Anatomy Project (CGAP). 6.9.2. The Human Cancer Genome Project (HCGP). 6.10. Achievements and Perspectives. 6.10.1. Molecular Biomarkers. 6.10.2. Integrative Analysis of Cancer. References. Abbreviations. Index.

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Book SynopsisRedox Biochemistry provides an excellent text and useful resource for students and practicing researches on redox biochemistry in medical biochemistry, enzyme structure and catalysis, environmental biochemistry, and nutrition.Table of ContentsContributors. List of Abbreviations. Preface. 1. Redox Metabolism and Life (Ruma Banerjee) 2. Antioxidant Molecules and Redox Cofactors (Donald Becker) 3. Antioxidant Enzymes (Vadim Gladyshev) 4. Redox Regulation of Physiological Processes (Martin Dickman) 5. Pathological Processes Related to Redox (Ruma Banerjee) 6. Specialized Methods (Stephen Ragsdale) 7. Index.

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Book SynopsisIn recent years, organo-fluorine chemistry has made a marked impacton the design and synthesis of a large variety of biologicallyactive molecules, such as steroids, carbohydrates, amines, aminoacids, peptides and other natural products. Naturally occurringamino acids play a pivotal role in living systems, and thereforesynthetic fluorine-containing amino acids have been of significantinterest to researchers working towards the understanding andmodification of physiological processes. Fluorine-containing AminoAcids: * is the first volume devoted to the synthesis and properties offluorine-containing amino acids * pays special attention to the preparation of enantiomericallypure acids (which are essential to the modern pharmaceuticalindustry) * deals with a rapidly expanding field of research * has been written by experienced researchers who are responsiblefor many developments in the field * highlights the interdisciplinary nature of this topic Fluorine-containing Table of ContentsPartial table of contents: Syntheses of Fluorine-Containing Amino Acids by Methods ofClassical Amino Acid Chemistry (V. Tolman). Preparation of Fluorine-Containing Amino Acids by Methods ofOrganofluorine Chemistry (V. Kukhar). Synthesis of Fluorine-Containing Amino Acids by Means ofHomogeneous Catalysis (I. Ojima & Q. Dong). Synthesis of beta-Fluorine-Containing Amino Acids (N. Sewald &K. Burger). Asymmetric Synthesis of Fluorine-Containing Amino Acids (V. Kukhar,et. al). Enzymatic Synthesis of Fluorine-Containing Amino Acids (Y.Matsumura & M. Urushihara). Enzymatic Resolution of Racemic Fluorine-Containing Amino Acids (T.Miyazawa). High-Performance Liquid Chromatography of Fluorine-Containing AminoAcids (S. Galushko). Renin Inhibitors with Fluorine-Containing Amino Acid Derivatives(H. Sham). Index.

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Book SynopsisImmunoassays are in use in many laboratories and across many disciplines. They involve the use of antibodies to detect and quantitate proteins. The Essential Data Series is a series of handy pocket-sized books which allow researchers to have all the key experimental facts at their fingertips.Table of ContentsHistory and Classification (R. Edwards). Antibodies and Antisera (R. Edwards). Assay Design (R. Edwards). Seperation (R. Edwards). Radiolabeled Immunoassays (R. Edwards). Enzyme-labeled Immunoassay (J. Little). Flurescent and Phosphorescent Labeled Assays (S. Blincko). Chemiluminescent and Bioluminescent Labeled Assays (S. Blincko). Precipitation and Agglutination Methods (J. Little). Dry Surface Immunoassays and Immunosensors (R. Edwards). Data Processing (I. Howes). Manufacturers and Suppliers. References. Index.

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Book SynopsisThis study explores the movement of pesticides into ground water, describing how computers can be used to model this phenomenon. It features novel approaches to the analysis of environmental samples and reviews analytical methods for the detection of agrochemical run-off.Table of ContentsEstimation of Physicochemical Properties: Theoretical andExperimental Approaches (P. Fisk). Recommended Approaches to Assess Pesticide Mobility in Soil (M.Russell). Soils and Pesticide Mobility (C. Brown, et al.). Pesticide Leaching Models and Their Use for Management Purposes (N.Jarvis, et al.). Pesticides in Run-Off and Surface Waters (B. Burgoa & R.Wauchope). The Volatization of Pesticide Residues (A. Taylor). Biosensors for Detection of Pesticides (M. Eldefrawi, etal.). Techniques and Procedures for the Determination of Pesticides inWater (C. Eadsforth & A. Woodbridge). Index.

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Book SynopsisWritten by international experts in the field, this book sets out the scientific arguments for and against the use of methyl bromide which is both naturally occurring and also a man-made product believed to have played a significant role in the depletion of the ozone layer.Trade Review"The four chapters covering the chemistry and mammalian toxicology of the compound, its effects on target organisms, uses in storage practice, uses in storage practice, and alternative method sof preventing infestation and spoilage are written by scientists with established reputations in the fields of fumigation and food storage practice from this institution. What makes the book particularly useful is the juxtaposition of these chapters with contributions from leading experts in atmospheric ozone depletion and environmental analysis (in both the chemical and political sense)." Pesticide ScienceTable of ContentsMethyl Bromide in Perspective (N. Price). Methyl Bromide in the Atmosphere (J. Butler & J.Rodriguez). Methyl Bromide and the Environment (M. Miller). Effects on Target Organisms (O. Macdonald & C.Reichmuth). Methyl Bromide as a Soil Fumigant (L. Klein). Methyl Bromide in Storage Practice and Quarantine (B.Chakrabarti). Alternatives--Chemicals (P. Annis & C. Waterford). Alternatives--Physical Methods and Emission Reduction (C.Bell). Indexes.

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Book SynopsisMetal Speciation and Bioavailability in Aquatic Systems is thefirst comprehensive review to deal with fundamental concepts andmodels, speciation measurements and field applications in metalspeciation and bioavailability in aquatic environments. This volumeprovides a thorough review of current developments concerning theinteractions between trace metals and aquatic organisms. MetalSpeciation and Bioavailability in Aquatic Systems provides: * The first comprehensive approach to the subject covering allaspects of trace metal ecotoxicology in the environment. * Essential reading for researchers and graduate students who willappreciate critical reviews of classical and modern methods ofmetal speciation. * Contributions from leading scientists from many disciplinesassessing both analytical and physical methods applied to thisgrowing field of environmental analysis. * An introduction to the use of laboratory bioassays as predictivetools for understanding trace metal organism iTable of ContentsTransport of Metals Across Membranes (K. Simkiss & M.Taylor). Interactions between Trace Metals and Aquatic Organisms: A Critiqueof the Free-Ion Activity Model (P. Campbell). Environmental Organometallic Chemistry of Mercury, Tin and Lead:Present Status and Perspectives (E. Pelletier). Problems in Trace Metal Speciation Modeling (D. Turner). Trace Metal Speciation of Labile Chemical Species in Natural Water:Electrochemical Methods (A. Mota & M. Correia dosSantos). Trace Metal Speciation of Labile Chemical Species in Natural Watersand Sediments: Non-Electrochemical Approaches (S. Apter & G.Batley). Chromatographic Approaches to Trace Element Speciation ofNon-Labile Chemical Species (W. Marshall & G.-M. Momplaisir). The Trophic Transfer of Metals in Marine Systems (N. Fisher &J. Reinfelder). Biological Factors Involved in Metal Concentrations Observed inAquatic Organisms (W. Langston & S. Spence). Metal Detoxification in Aquatic Organisms (A. Mason & K.Jenkins). Prediction of Metal Toxicity in Nature from Bioassays: Limitationsand Research Needs (S. Luoma). Index.

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