Biochemistry Books

Book SynopsisWhen a biomaterial is placed inside the body, a biological response is triggered almost instantaneously. With devices that need to remain in the body for long periods, such interactions can cause encrustation, plaque formation and aseptic loosening on the surface. These problems contribute to the patient's trauma and increase the risk of death. Electrical properties, such as local electrostatic charge distribution, play a significant role in defining biological interactions, although this is often masked by other factors. This book describes the fundamental principles of this phenomenon before providing a more detailed scientific background. It covers the development of the relevant technologies and their applications in therapeutic devices such as MRSA-resistant fabrics, cardiovascular and urological stents, orthopaedic implants, and grafts. Academic and graduate students interested in producing a selective biological response at the surface of a given biomaterial will find the detailed coverage of interactions at the nanometre scale useful. Practitioners will also benefit from guidance on how to pre-screen many inappropriate designs of biomedical devices long before any expensive, animal or potentially risky clinical trials. Enhanced by the use of case studies, the book is divided in to four topical sections. The final section is dedicated to the application of related topics making the book unique in its pragmatic approach to combining high end interdisciplinary scientific knowledge with commercially viable new technologies. Contributing to the newly emerging discipline of 'nanomedicine', the book is written not only by experts from each relevant specialty but also by practitioners such as clinicians and device engineers from industry.Trade ReviewThe book originates from the activity of a BioElectricSurface consortium, funded by the European Commission under the FP-7 Nanosciences, Nanotechnologies, Materials and New Production Technologies (NMP) program and discusses the crucial role surface charge plays in the interaction between materials in biological and medical applications. The first part of the book covers new findings in biology, e.g. bone growth by charged hydroxyapatite and photocatalytic effect in doped titania and includes useful explanations of the many modern techniques used to create and measure electric charges at surfaces and intersurfaces. The first part of the book contains some very useful information, such as discussion of the polarization of hydroxyapatite, which increased bone growth on the negative surface while no growth was observed on the positive surface, and commentary on the increased photocatalytic activity of doped titania . This section also concisely, but thoroughly, analyses thermally stimulated depolarization current methods, the laser intensity modulation method of charge measurements, scanning probe, Kelvin probe force and electrostatic force microscopy, and the streaming potential measurement techniques used for wet cases. The techniques utilized for interfacial measurements, such as confocal laser scanning microscopy, are also covered in chapter 4. Part 2 describes many practical examples in which the surface interactions play an essential role. For example, chapter 5 discusses immobilized enzymes on porous surfaces in biocatalysts, drug delivery, and biosensors, while chapter 6 goes on to describe improvement of the extracellular matrix (ECM) by the interactions of host tissue cells with the implant surface Chapters 7, 8 and 9 discuss antibody immobilization on solid surfaces, adhesion, proliferation and differentiation of bone-forming cells with electrostatic charge at biomaterials surfaces and interactions of biofilm-forming bacteria with abiotic surfaces. Endothelial cells and smooth muscle cells on the biomaterials surfaces, interactions of bacteria and fungi on biofilms in hospital acquired infections and immunological response of electrostatic charge at the surface of biomaterials are covered in chapters 10, 11 and 12. Such elaborate discussions show the relevance of surface charge in biological interactions at and with non-biological surfaces and, I strongly believe, will provide a solid foundation for interested readers who are willing to bring innovative ideas of surface modifications to generate or control a specific biological response on implantable therapeutic devices. Part 3 of the book is a logical progression from parts 1 and 2, and describes some of the important applications where surface charge is believed to play a significant role. These include: Community and hospital acquired infections of methicillin-resistant staphylococcus aureus (MRSA), MRSA-resistant textiles, inhibition of encrustation in urological devices and the reduction of restenosis in cardiovascular stents. The book finishes with a general overview of a new class of materials, named as vector materials, where the interfaces between biomaterial and biological environment can be manipulated by the application of vectorial effects induced by electrical polarization. Surface charges are frequently experienced by the frictional electricity in textiles. The infection of bacteria and the restenosis of implanted stenosis are broadly concerned matters in the society. As a basic research, it is noteworthy that negatively charged hydroxyapatite induces new bone. The book shows that the study of electric charge in surfaces is important to understand the basic mechanism of all these matters. The many topics introduced in this book promises more rapid progress in future research. The abbreviation of technical words sometime hinders the understanding of sentences, but the subject index at the end of the book helps greatly to solve this difficulty. The arrangement of chapters is also well ordered. The Editor’s kind efforts are appreciated. -- Eiichi Fukada, Kobayasi Institute of Physical Research, Tokyo, Japan and Emeritus Scientist, RIKEN, Wako, JapanTable of ContentsElectrostatic Charge on Biomaterials Surface; Electrical modifications of biomaterials' surfaces: Beyond hydrophobicity and hydrophilicity; Photocatalytic effects in doped and undoped titania; Surface charge measurements on biomaterials in dry and wet conditions Measurements of surface and interfacial charge and morphology in electrically modified materials; Protein Interactions at the surface; Immobilisation of enzymes on porous surface; Fibrous proteins interactions with modified surfaces of biomaterials; Antibody immobilisation on solid surfaces: methods and applications; Cellular Interactions with Abiotic Surfaces; Interactions of bone forming cells with electrostatic charge at biomaterials surface; Interactions of biofilm-forming bacteria with abiotic surfaces; Endothelial cells and smooth muscle cells (SMC) interactions at biomaterials surfaces; Interactions of Bacteria and fungi at the surface; Immunological response of electrostatic charge at the surface of biomaterials; IV. Applications; Community and hospital acquired Staphylococcal infections; MRSA resistant textiles; Inhibition of urological devices; Encrustation; Reduction of restenosis in cardiovascular stents; Regulatory and safety issues related to biomedical devices

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Book SynopsisVitamin C (ascorbic acid) is a key vitamin to animals and plants. This book looks at all aspects of vitamin C; its chemical and biochemical properties, its role in various plants and animals and its effect on our health. Written by an international team of experts, together they represent much of the expertise on vitamin C throughout the world.Table of Contents1. Ascorbate Biosynthesis in Plants, Fungi and Animals. 2. Ascorbic Acid Catabolism- Breakdown Pathways and Products in Plants and Animals. 3. Application of Biotechnology to Ascorbic Acid Manufacture. 4. Ascorbic Acid and Oxidative Stress/ Photoprotection in Plants. 5. Ascorbic Acid and Plant Growth. 6. Ascorbic Acid Uptake and Transport. 7. Membrane Redox Proteins involved in Ascorbate-Mediated Reactions. 8. Ascorbic Acid Recycling. 9. How does Ascorbic Acid Prevent Scurvy? 10. Function of Ascorbic Acid as an Antioxidant. 11. Ascorbic Acid and DNA Damage/ Antioxidant Pro-oxidant Effects of Ascorbate. 12. Ascorbic Acid and Aging. 13. Ascorbic Acid in the Central Nervous System.14. Ascorbic Acid and Inflammation. 15. Ascorbic Acid as an Antioxidant in Atherosclerosis. 16. What Intake of Vitamin C is Required for Optimal Human Health?

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Book SynopsisThis brilliant new text by John Straub (Boston University) is designed to bridge the “mathematics knowledge gap” between what is commonly known by students after completing a year of introductory calculus, and what is required for success in the physical sciences and in physical chemistry courses. Key concepts from the introductory calculus sequence are reviewed and carefully selected topics in multivariate calculus, probability and statistics, ordinary differential equations, and linear algebra are explored. Additional chapters cover advanced topics, including partial differential equations, Fourier analysis, and group theory. Engaging narratives, fully worked examples, hundreds of colourful visualizations, and ample end-of-chapter problems with complete answers combine to make this stunning new text an excellent choice for a one-semester course on mathematical methods, as a supplement for courses in physical chemistry, or as a self-study guide. Ancillaries for adopting faculty include in-class worksheets, sample exams, and an answer manual. Key features: Abundant end-of-chapter exercises, including three difficulty levels, with answers at the back of the book Ample worked examples throughout, with clearly explained steps to guide problem solving Reviews of all basic introductory calculus concepts before the introduction of new topics Over 400 original color figures to help visualize problem solving and interpretation of results Margin notes offering historical context and additional mathematical details Key ancillaries including in-class worksheets, sample exams, and an answer guide for adopting instructors Table of ContentsIntroduction 1 Functions and coordinate systems 2 Complex numbers and logarithms 3 Differentiation in one and many dimensions 4 Scalars, vectors, and vector algebra 5 Scalar and vector operators 6 Extremizing functions of many variables 7 Integration in one and many dimensions 8 Sequences, series, and expansions 9 Fundamentals of probability and statistics 10 Ordinary differential equations 11 More ordinary differential equations 12 Partial differential equations 13 Fourier series, Fourier transforms, and harmonic analysis 14 Matrices and matrix algebra 15 Eigenvalues and eigenvectors 16 Geometric transforms and molecular symmetry Bibliography; Index; Colophon

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Book SynopsisElectrochemical Analysis of Proteins and Cells presents the remarkable progress made over the years in the electrochemical analysis of proteins and cells, due to the rapid development of protein electrochemistry together with related technologies such as surface modification, molecular recognition, molecular assembly, and nanotechnology. As an interdisciplinary field combining electrochemistry, analytical chemistry, biochemistry, biophysics, biomedicine and material science, the electrochemical analysis of proteins and cells has attracted broad and extensive research interest. The main emphasis of this book is on the principles of electrochemical strategies and the practical utility of related detection systems, which is of great importance in all biological sciences, such as cell biology and molecular biology, as well as in biomedical fields like cancer research. This brief offers an up-to-date, easy-to-follow presentation of recent advances on the subject and can serve as a supplement for graduate-level courses in analytical chemistry, biochemistry, biophysics, biotechnology, biomedical engineering, etc. It may also help young scientists get an overview of this topic.Table of ContentsIntroduction.- Theoretical Background of Electrochemical Analysis.- Electrochemical Analysis of Proteins.- Electrochemical Analysis of Cells

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Book SynopsisInfectious fungal diseases continue to take their toll in terms of human suffering and enormous economic losses. Invasive infections by opportunistic fungal pathogens are a major cause of morbidity and mortality in immuno-compromised individuals. At the same time, plant pathogenic fungi have devastating effects on crop production and human health. New strategies for antifungal control are required to meet the challenges posed by these agents, and such approaches can only be developed through the identification of novel biochemical and molecular targets. However, in contrast to bacterial pathogens, fungi display a wealth of “lifestyles” and modes of infection. This diversity makes it extremely difficult to identify individual, evolutionarily conserved virulence determinants and represents a major stumbling block in the search for common antifungal targets. In order to activate the infection programme, all fungal pathogens must undergo appropriate developmental transitions that involve cellular differentiation and the introduction of a new morphogenetic programme. How growth, cell cycle progression and morphogenesis are co-ordinately regulated during development has been an active area of research in fungal model systems such as budding and fission yeast. By contrast, we have only limited knowledge of how these developmental processes shape fungal pathogenicity, or of the role of the cell cycle and morphogenesis regulators as true virulence factors. This book combines state-of-the-art expertise from diverse pathogen model systems to update our current understanding of the regulation of fungal morphogenesis as a key determinant of pathogenicity in fungi. Trade ReviewFrom the reviews:“This book describes the molecular basis of morphogenesis and pathogenicity in the fungi and highlights new approaches. … All the chapters are well organized and each chapter contains an introduction at the beginning and a conclusion at the last that can be very useful for the reader. … This book is very important to scientists, researchers and teachers as well as students who are interested in fungal morphogenesis and pathogenicity. Therefore this book should be available in all schools, research laboratories, community and university libraries.” (Kasun M. Thambugala, Fungal Diversity, Vol. 57 (1), November, 2012)Table of ContentsMolecular basis of morphogenesis in fungi.- Tropic orientation responses of pathogenic fungi.- Hyphal fusion.- Signalling of infectious growth in Fusarium oxysporum.- Integrating Cdk signaling in Candida albicans environmental sensing networks.- Cell cycle and morphogenesis connections during the formation of the infective filament in Ustilago maydis.- Appressorium Function in Colletotrichum orbiculare and Prospect for Genome Based Analysis.- Morphogenesis in Candida albicans: How to stay focused.- Morphogenesis in Paracoccidioides brasiliensi.- Morphogenesis of Cryptococcus neoformans.- Morphogenesis and infection in Botrytis cinere.- Morphogenesis, growth and development of the grass symbiont Epichlöe festucae.- Cryptococcus-neutrophil interaction.-

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Book SynopsisAdvances in Comparative and Environmental Physiology provides comprehensive, integrated reviews giving sound, critical, and provocative summaries of our present knowledge in environmental and comparative physiology, from the molecular to the organismic level. The field has now gained the international status it deserves and the organization of a series devoted to it is very timely in view of its actual rapid development. Biologists, physiologists, and biochemists, independently of their basic scientific orientation, will find this new series of major interest.Table of Contents1 Mammalian Hibernation: An Escape from the Cold.- 1 Introduction.- 2 Ecological Significance of Mammalian Hibernation.- 3 Organ System and Organ/Tissue Adaptations.- 4 Cellular, Subcellular, and Membrane Adaptations.- 5 Antimetabolic Peptides, the “Hibernation Induction Trigger”, and the Opioids.- References.- 2 Water Vapor Absorption by Terrestrial Organisms.- 1 Introduction.- 2 General Features of Absorption Systems: Sites, Structures, and Mechanisms.- 3 Functional Classification of Absorption Mechanisms.- 4 Concluding Remarks.- References.- 3 Nutrient Transport by the Invertebrate Gut.- 1 Introduction.- 2 Annelida.- 3 Echinodermata.- 4 Mollusca.- 5 Arthropoda.- 6 Overview of Invertebrate Nutrient Absorption.- References.- 4 Nutrient Transport Across Vertebrate Intestine.- 1 Introduction.- 2 Where Sugar and Amino Acid Absorption Occurs.- 3 Pathways for Sugar and Amino Acid Absorption and Mechanisms of Regulation.- 4 Patterns of Adaptation.- References.- 5 Nutrient Transport Across the Integument of Marine Invertebrates.- 1 Introduction.- 2 Background Information.- 3 Integumental Transport in Marine Mollusks.- 4 Integumental DOM Transport in Echinoderms.- 5 Integumental Uptake of DOM in Annelids.- 6 On the Mechanism of Integumental Transport.- 7 Conclusions.- References.- 6 The Fate of Stable Pollutants — Heavy Metals and Organochlorines — in Marine Organisms.- 1 Introduction.- 2 Spatial and Temporal Variations of the Contamination Level of Marine Organisms.- 3 Fate of Pollutants in Marine Organisms.- 4 Stable Pollutants at the Ecosystem Level, Biological Indicators and Monitoring.- References.

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Book SynopsisModern Methods of Plant Analysis When the handbook Modern Methods of Plant Analysis was first introduced in 1954 the considerations were 1. the dependence of scientific progress in biology on the improvement of existing and the introduction of new methods; 2. the inavailability of many new analytical methods concealed in specialized journals not normally accessible to experimental plant biologists; 3. the fact that in the methods sections of papers the description of methods is frequently so compact, or even sometimes so incomplete, that experiments are difficult to reproduce. These considerations still stand today. The series was highly successful, seven volumes appearing between 1956 and 1964. Since today there is still a demand for the old series, the publisher has decided to resume publication of Modern Methods of Plant Analysis. It is hoped that the New Series will be as acceptable to those working in plant sciences and related fields as the early volumes undoubtedly were. It is difficult to single out the major reasons for success of any publication, but we believe that the methods published in the first series were up-to-date at the time and the descriptions as applied to plant material so complete in themselves that there was little need to consult other publications.Table of ContentsCell-Wall-Isolation, General Growth Aspects.- 1 Introduction.- 2 Isolation Procedures.- 2.1 Cell Breakage.- 2.2 Cell-Wall Recovery.- 2.3 Removal of Contaminants.- 3 Composition and Ultrastructure of Plant Cell Walls.- 3.1 Chemical Composition of Plant Cell Walls.- 3.1.1 Standard Extraction Procedures.- 3.1.2 Analysis of Polysaccharide Fractions.- 3.1.2.1 Chemical Methods.- 3.1.2.2 Physical Methods.- 3.2 Supramolecular Organization of Plant Cell Walls.- 3.2.1 Morphological Observations.- 3.2.2 Selective Staining of Polysaccharides.- 3.2.2.1 Visualization of Esterified Carboxyl Groups.- 3.2.2.2 Detection of Acidic Functions.- 3.2.2.3 Periodic Oxidation of Glycol Groups.- 3.2.3 Visualization of Lignin.- 3.2.4 Identification of Wall Components by Means of Affinity Methods.- 3.2.5 Detection and Estimation of Cations.- 3.2.6 Ultracryotomy.- 4 Properties of Plant Cell Walls.- 4.1 Exchange Properties of Plant Cell Walls.- 4.2 Enzymatic Properties.- 4.2.1 Cytochemical Investigations.- 4.2.1.1 Cell-Wall Phosphatase Activities.- 4.2.1.2 Cell-Wall Peroxidase Activities.- 4.2.2 Biochemical Investigations.- 4.2.2.1 Properties of Immobilized and Solubilized Cell-Wall Enzymes.- 4.2.2.2 Biological Functions.- 4.3 Mechanical Properties.- 5 Growth Aspects.- 5.1 Cell-Wall Loosening.- 5.1.1 Wall-Loosening-Inducing Agents.- 5.1.2 Nature of the Broken Bonds.- 5.2 Deposition of Wall Material.- 5.3 Growth Direction.- References.- Cell-Wall Chemistry, Structure and Components.- 1 Introduction.- 2 Histochemical Analysis of Cell Walls.- 2.1 Specific Stainings.- 2.2 Staining with Fluorescent Brightener.- 2.3 Anisotropy Test.- 2.4 Selective Dissolution.- 2.4.1 Alkali Treatment.- 2.4.2 Cuprammonium Solution (Schweitzer’s Reagent) Treatment.- 2.4.3 Enzymatic Digestion.- 3 Quantitative Analysis of Cell Walls.- 3.1 Plant Materials.- 3.1.1 Pure Culture.- 3.1.2 Synchronous Culture.- 3.1.3 Harvesting of Cells.- 3.2 Measurement of Cell Growth.- 3.3 Preparation and Fractionation of Cell Walls.- 3.3.1 Disruption of Cells.- 3.3.2 Separation and Purification of Cell Walls.- 3.3.3 Fractionation of Cell Walls.- 3.4 Quantitative Analysis of Whole Cell Walls.- 3.4.1 Gravimetry.- 3.4.2 Turbidimetry.- 3.4.3 Colorimetry.- 4 Qualitative Analysis of Cell-Wall Materials.- 4.1 Acid Hydrolysis.- 4.2 Enzymatic Hydrolysis.- 5 Chromatographic Analysis of Cell-Wall Constituents.- 5.1 Thin-Layer Chromatography.- 5.1.1 Neutral Sugars and Uronic Acids.- 5.1.2 Amino Acids and Amino Sugars.- 5.1.3 Thin-Layer Chromatographic Analyses of the Constituents of Chlorella Cell Walls.- 5.2 Liquid Chromatography.- 5.2.1 Amino Acids and Amino Sugars.- 5.2.2 Neutral Sugars.- References.- Protoplasts—for Compartmentation Studies.- 1 Introduction.- 2 Advantages of the Use of Protoplasts for Compartmentation Studies.- 3 Protoplast Isolation and Its Effect on Cellular Metabolism.- 3.1 Isolation Procedures.- 3.2 Effect of Isolation pH.- 3.3 Effect of Plasmolysis.- 3.4 Effect of Enzyme Contaminants.- 4 Protoplast Lysis.- 5 Protoplast Fractionation.- 5.1 Density Gradient Fractionation.- 5.2 Rapid Fractionation Procedures.- 6 Methods to Relate Protoplast Activity to That of Intact Tissue.- 7 Concluding Remarks.- References.- The Marker Concept in Cell Fractionation.- 1 Introduction.- 2 The Marker Concept.- 2.1 Basic Concepts.- 2.2 Types of Marker.- 2.2.1 Morphological.- 2.2.2 Cytochemical.- 2.2.3 Biochemical.- 3 Preservation of Marker Enzyme Activity During Cell Disruption.- 3.1 Choice of Material.- 3.2 Homogenization Procedure.- 3.3 Use of Additives in the Homogenization Medium.- 3.4 Gel Filtration to Remove Soluble Hydrolytic Activity.- 4 Methods Used to Separate Markers.- 4.1 General Approaches to Cell Fractionation.- 4.2 Differential Centrifugation.- 4.2.1 Preparative vs. Analytical Cell Fractionation.- 4.2.2 Need for Quantitation.- 4.2.3 Problems with Complete Quantitation and Interpretation of Data.- 4.3 Linear Density Gradient Centrifugation.- 4.3.1 Density Gradient Material.- 4.3.2 Pelleted vs. Unpelleted Overlays.- 4.3.3 Soluble Enzyme Contamination in Gradients.- 4.3.4 Equilibrium Density Centrifugation (Isopycnic Conditions).- 4.3.5 Other Factors Which Influence Marker Enzyme Profiles Across a Gradient.- 4.3.6 Need for Quantitation and Lack of Negative Marker Activity.- 5 Concluding Remarks.- References.- Plasma Membranes.- 1 Introduction.- 2 Theory of Phase Partition.- 2.1 The Phase System.- 2.2 Partitition of Membrane Particles.- 2.3 Effects of Polymer Concentrations.- 2.4 Effects of Salts.- 2.5 Multistep Procedures.- 3 Experimentals.- 3.1 Chemicals.- 3.2 Preparation Procedure.- 4 Purity of the Preparations.- 4.1 Specific Staining.- 4.2 K+-Stimulated, Mg2+-Dependent ATPase.- 4.3 Glucan Synthetase II.- 4.4 Light-Reducible b-Cytochrome.- 4.5 Markers for Contaminants.- 5 Protein and Lipid Composition.- 6 Surface Properties of the Isolated Vesicles.- References.- Vacuoles.- 1 Introduction.- 2 Methods of Isolation.- 2.1 Isolation of Vacuoles from Meristematic Tissues.- 2.2 Isolation of Vacuoles from Mature Plant Tissue.- 2.2.1 Isolation of Mature Vacuoles from Protoplasts—Methods pre 1981.- 2.2.2 Isolation of Mature Vacuoles from Protoplasts—Methods post 1981.- 2.2.3 Isolation of Mature Vacuoles Directly from Tissue—Methods pre 1981.- 2.2.4 Isolation of Mature Vacuoles Directly from Tissue—Methods post 1981.- 2.2.5 Preparation of Lutoids from Hevea Latex.- 2.2.6 Comments on Methods for Isolating Vacuoles from Higher Plants.- 2.2.7 Isolation of Proton-Pumping Vesicles.- 2.2.8 Preparation of Vacuoles from Yeast Neurospora.- 3 Isolation of Tonoplast and Tonoplast Markers.- 4 Comments on Physiological Functions.- 5 Concluding Remarks.- References.- Protein Bodies.- 1 Introduction.- 2 Special Consideration in Isolation of Protein Bodies.- 3 Nonaqueous Preparation in Glycerol.- 4 Nonaqueous Preparation in Hexane and Carbon Tetrachloride.- 5 Aqueous Preparation in Sources Gradients.- 6 Subfractionation of Isolated Protein Bodies.- 7 Analyses.- References.- Lipid Bodies.- 1 Introduction.- 2 Ontogeny.- 3 Isolation.- 4 Markers of Lipid Bodies.- 5 Assays.- 5.1 Fluorometric Assay.- 5.2 Colorimetrie Assay.- References.- Chloroplasts as a Whole.- 1 Introduction.- 2 Considerations of Integrity and Purity.- 3 Chloroplasts from Protoplasts.- 4 The Use of Silica Sols in Density Gradient Purification of Chloroplasts.- 5 General Notes on Isolation Procedures.- 6 Specific Isolation Protocols.- 6.1 Higher Plants.- 6.1.1 C3 Plants.- 6.1.2 C4 Plants.- 6.1.3 CAM Plants.- 6.2 Algae.- 6.2.1 Volvocales.- 6.2.2 (Ceramiaceae, Rhodophyta)—Griffithsiamonilis.- 6.2.3 Siphonales.- 6.2.4 (Xanthophyceae) Bumilleriopsisfiliformis.- 6.2.5 (Euglenophyceae) Euglenagracilis.- 7 Additional Comments on Chloroplast Isolation.- 8 Abbreviations.- References.- Purification of Inner and Outer Chloroplast Envelope Membranes.- 1 Introduction.- 2 General Considerations.- 3 The Procedure.- 3.1 Reagents and Equipment.- 3.1.1 Solutions.- 3.1.2 Materials.- 3.2 Growth of Peas and Purification of Intact Chloroplasts.- 3.3 Purification of Inner and Outer Envelope Membranes.- 4 Properties of the Isolated Membranes.- 4.1 Purity.- 4.1.1 Cross-Contamination by Envelope Membranes.- 4.1.2 Contamination by Thylakoids.- 4.1.3 Contamination by Stroma.- 4.2 Other Properties.- 5 Modifications of the Procedure.- 5.1 Alternate Methods of Chloroplast Rupture.- 5.2 Purification Subsequent to Rupture.- 5.3 Application to Other Tissues.- 6 Other Procedures.- References.- The Major Protein of Chloroplast Stroma, Ribulosebisphosphate Carboxylase.- 1 Introduction.- 2 Characteristics of RuBP Carboxylase.- 2.1 Molecular Arrangement and Physical Structure of Subunits.- 2.2 Molecular Structure.- 2.3 Biosynthesis and Assembly of Subunits.- 2.3.1 Large Subunit.- 2.3.2 Small Subunit.- 2.3.3 Subunit Heterogeneity.- 2.3.4 Coordinate Control of Subunit Synthesis.- 2.4 Catalytic Mechanism.- 2.4.1 Activation and Role of Mg2 +.- 2.4.2 Carboxylation of RuBP.- 2.4.3 Oxygenation of RuBP.- 2.4.4 Localization of Catalytic and Activator Site.- 3 Practical Aspects.- 3.1 Purification.- 3.1.1 Summary of Techniques.- 3.1.2 Interfering Compounds.- 3.1.3 Choice of Extraction Buffer and Grinding Procedures.- 3.1.4 Protein Determination.- 3.1.5 Example: RuBP Carboxylase from Soybean Leaves.- 3.2 Assay.- 3.2.1 Substrates.- 3.2.2 Activation of RuBP Carboxylase.- 3.2.3 Continuous Spectrophotometry Assay for RuBP Carboxylase Activity.- 3.2.4 Discontinuous Assays for RuBP Carboxylase Activity.- 3.2.4.1 Radiochemical Assay with [14C]NaHCO3.- 3.2.4.2 Radiochemical Assay Using [14C]NaHCO3 and [l-3H]RuBP.- 3.2.4.3 Discontinuous Assay Using Nonlabeled Substrates.- 3.2.5 Assays for RuBP Oxygenase.- 3.2.6 Kinetic Parameters of RuBP Carboxylase and RuBP Oxygenase.- 4 Conclusion.- References.- The Chloroplast Thylakoid Membrane—Isolation, Subfractionation and Purification of Its Supramolecular Complexes.- 1 Introduction.- 2 Function and Organization of the Thylakoid Membrane.- 3 Isolation of Thylakoid Membranes.- 4 Thylakoid Membrane Subfractionation.- 4.1 Photosystem I Stroma Lamellae Thylakoids.- 4.2 Photosystem II Oxygen Evolving Thylakoid Preparations.- 4.2.1 Isolation by Press Treatment and Phase Partition.- 4.2.2 Isolation by Detergent Fractionation.- 4.2.3 Choice of Preparation.- 4.3 Separation of Inside-Out and Right-Side-Out Thylakoid Vesicles with the Same Composition.- 5 Isolation of Thylakoid Supramolecular Complexes.- 5.1 The Photosystem I Complex and the Light-Harvesting Complex of Photosystem II (LHC II).- 5.2 The Light-Harvesting Complex of Photosystem I (LHC I).- 5.3 The Inner Core Complex of Photosystem II (CC II).- 5.4 The Cytochrome b/f Complex.- 5.5 The ATP Synthase (CF0-CF1).- References.- The Isolation and Characterization of Nongreen Plastids.- 1 Introduction.- 2 The Terminology of Nongreen Plastids.- 2.1 Proplastids.- 2.2 Etioplasts.- 2.3 Chromoplasts.- 2.4 Amyloplasts.- 2.5 Leucoplasts.- 2.6 Other Nongreen Plastids.- 3 Basics of Plastid Isolation and Separation.- 3.1 Experimental Design.- 3.2 Isolation Medium.- 3.3 Tissue Disruption.- 3.4 General Methods of Chloroplast Isolation.- 4 Isolation of Nongreen Plastids from Developing Ricinus Endosperm.- 4.1 Rate-Zonal Sedimentation.- 4.1.1 Protocol.- 4.1.2 Analysis.- 4.1.3 Comments.- 4.2 Isopycnic Banding on Linear Sucrose Gradients.- 4.2.1 Protocol.- 4.2.2 Comments.- 4.3 Rate-Zonal Sedimentation on Linear Sucrose-Magnesium Co-Gradients.- 4.3.1 Protocol.- 4.3.2 Comments.- 4.4 Rate-Zonal Sedimentation on Discontinuous Sucrose Gradients.- 4.4.1 Protocol.- 4.4.2 Comments.- 4.5 Rate-Zonal Sedimentation on Discontinuous Percoll Gradients.- 4.5.1 Protocol.- 4.5.2 Comments.- 4.6 Nonaqueous Methods.- 4.6.1 Isopycnic Banding on Linear Hexane-CCl Gradients.- 4.6.2 Silicon Oil Centrifuged Filtration.- 4.7 Noncentrifugal Methods.- 4.7.1 Gel Permeation.- 4.7.1.1 Materials.- 4.7.1.2 Protocol.- 4.7.1.3 Comments.- 4.7.2 Phase Partition.- 4.7.3 Unit-Gravity Sedimentation.- 5 Metabolic Capabilities of Ricinus Endosperm Plastids.- 5.1 Glycolysis, the Pentose-Phosphate Pathway and Fatty Acid Synthesis.- 5.2 The Calvin Cycle.- 5.3 Nitrogen Metabolism.- 5.4 Terpenoid Metabolism.- 6 Composition and Biochemical Properties.- 6.1 Structure.- 6.2 Protein Composition.- 6.3 Membranes.- 6.4 Nucleic Acids.- 7 Future Prospects.- References.- Mitochondria.- 1 Introduction.- 2 Preparation for DNA Analysis.- 2.1 Cytoplasmic Male Sterility and Structure ot Mitochondrial DNA.- 2.2 Isolation of Mitochondria for DNA Preparation.- 2.3 Preparation of Mitochondrial DNA.- 2.4 Electrophoresis of Mitochondrial DNA.- 2.5 Restriction Analysis of Mitochondrial DNA.- 2.6 Notes on Mitochondrial DNA Studies.- 3 Preparation of Intact Mitochondria for Oxidative Studies.- 3.1 Introduction.- 3.2 Mitochondrial Preparation and Purification.- 3.3 Tests for Integrity of Mitochondria.- 3.3.1 Succinate: Cytochrome c Reductase.- 3.4 Tests for Integrity.- 3.4.1 Measurement for Oxygen Consumption for Respiratory Control and P/O Ratios.- 3.5 Notes on the Methods.- References.- Endoplasmic Reticulum.- 1 Introduction.- 2 Structure and Organization of the ER.- 3 Interactions Between Tubular and Cisternal ER.- 3.1 Role in Protein Transport.- 3.2 Role in Cell Division.- 4 Synthesis and Degradation of ER.- 4.1 Membrane Proteins.- 4.2 Membrane Lipids.- 5 Isolation and Characterization of ER.- 5.1 Isolation Media.- 5.2 Tissue Homogenization.- 5.3 Organelle Isolation.- 5.3.1 Molecular Sieve Chromatography.- 5.3.2 Differential Centrifugation.- 5.3.3 Density Gradient Centrifugation.- 5.4 Identification of ER Membranes.- 5.4.1 Magnesium Shift.- 5.4.2 Marker Enzymes.- 5.4.3 Auxin Binding.- 5.4.4 Calcium Transport.- 5.4.5 Structural Proteins.- 5.5 Concluding Remarks.- References.- Polyribosomes.- 1 Introduction.- 2 Isolation of Polysomes from Plant Cells.- 2.1 Factors that Affect the Stability and Recovery of Polyribosomes.- 2.2 Tissue Preparation.- 2.3 Subcellular Fractionation and Polysome Isolation.- 3 Purification and Analysis of Polyribosomes.- 3.1 Sucrose Gradient Centrifugation.- 3.2 Purification of Polysomes with Discontinuous Sucrose Gradients.- 3.3 Analysis of Polyribosome Profiles.- 4 Polyribosome Extraction Buffers.- 4.1 pH.- 4.2 Potassium Chloride.- 4.3 Magnesium Chloride.- 4.4 Reducing Agents.- 4.5 Chelation of Divalent Metals.- 4.6 Proteinase K.- 4.7 Other Ribonuclease Inhibitors.- 5 Uses of Purified Polyribosomes.- 5.1 Changes in Protein Synthetic Activity.- 5.2 In Vitro Protein Synthesis.- 5.3 Purification of mRNA’s.- 5.4 Subcellular Distribution of mRNA’s.- References.- The Nucleus—Cytological Methods and Isolation for Biochemical Studies.- 1 Introduction.- 2 Structure of the Plant Nucleus and Implications for Nuclear Isolation and Staining.- 3 Cytology.- 3.1 Nuclei of Whole Cells.- 3.1.1 Feulgen Microspectrophotometric Methods.- 3.1.2 Microfluorometry DNA Determination.- 3.2 Staining Nuclei During Isolation.- 3.3 Nucleolus Staining.- 3.4 Chromosome Staining.- 3.5 Other Nuclear Stains.- 4 Isolation of Plant Nuclei—General.- 4.1 Isolation of Plant Nuclei—Methods.- 4.1.1 Nuclei from Tobacco Callus Cultures for RNA Synthesis Studies.- 4.1.2 Nuclei from Tobacco Cells in Culture—for General Purpose Studies.- 4.1.3 Nuclei from Soybean Cells—for DNA Studies.- 4.1.4 Plant-Root Nuclei—for DNA Analysis.- 5 Summary.- References.- Microtubules.- 1 Introduction.- 2 Extraction of Microtubule Proteins.- 3 Purification of Tubulin and MAP’s.- 3.1 DEAE-Sephadex Ion Exchange Chromatography.- 3.2 Phosphocellulose Chromatography.- 3.3 Affinity Chromatography.- 3.4 Cycles of Polymerisation and Depolymerisation.- 3.4.1 Pre-Conditions for Microtubule Assembly.- 3.4.2 Microtubule Assembly in the Presence or Absence of Glycerol.- 3.4.3 The Dynamics of Polymerisation and the Use of Taxol.- 3.4.4 Co-Polymerisation.- 4 Fractionation and Identification of Tubulin by SDS-PAGE.- 5 Colchicine-Binding Assay for Tubulin.- 6 Immunochemical Methods of Analysis.- 6.1 Radioimmunoassay.- 6.2 Enzyme-Linked Immunosorbent Assay (ELISA).- 6.3 Antibody Purification of Antigen-Affinity Column.- 6.4 Western Blots.- 7 Concluding Remarks.- References.

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Book SynopsisMechanistische Überlegungen nehmen heute einen festen Platz in der Organischen Chemie ein: Welche Faktoren beeinflussen die Reaktivität eines Moleküls? Welche typischen Reaktionsprinzipien und -muster gibt es, und in welchen Schritten verlaufen organisch-chemische Reaktionen? Wie lassen sich Reaktionen steuern? Anhand moderner und präparativ nützlicher Reaktionen erläutert der Autor die Reaktionsprinzipien; klar und verständlich werden Konzepte herausgearbeitet, stets auch stereochemische Konsequenzen abgeleitet. Der Autor bietet Faustregeln zur Reaktivitätsabschätzung sowie Tips und Tricks für die Praxis. Die zweifarbige Gestaltung erhöht die Übersichtlichkeit und erleichtert das Verfolgen der Mechanismen. In der vorliegenden 3. Auflage wurden nach dem überwältigenden Verkaufserfolg der 2. Auflage die Fehler in Text und Grafiken korrigiert und die Literatur nochmals aktualisiert. Der Index eignet sich nun für eine detaillierte Stichwortsuche.Table of ContentsRadikalische Substitutionsreaktionen am gesättigten C-Atom.- Nucleophile Substitutionsreaktionen am gesättigten C-Atom.- Additionen an die olefinische C=C-Doppelbindung.- beta-Eliminierungen.- Substitutionsreaktionen an Aromaten.- Nucleophile Substitutionsreaktionen (außer durch Enolate) am Carboxyl-Kohlenstoff.- Carboxylverbindungen und Nitrile und deren Umwandlung ineinander.- Kohlensäurederivate und Heterocumulene und deren Umwandlung ineinander.- Additionen von Heteroatom-Nucleophilen an Carbonylverbindungen und Folgereaktionen - Kondensationen von Heteroatom-Nucleophilen mit Carbonylverbindungen.- Addition von H-Nucleophilen und von Metallorganylen an Carbonylverbindungen.- Umsetzung von Phosphor- oder Schwefel-stabilisierten C-Nucleophilen mit C-Carbonylverbindungen: durch Additionen eingeleitete Kondensationen.- Chemie der Enole und Enamine.- Chemie der Alkalimetall-Enolate.- Umlagerungen.- Thermische Cycloadditionen.- Übergangsmetall-vermittelte Alkenylierungen, Arylierungen und Alkinylierungen.- Oxidationen und Reduktionen.- Index.

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Book SynopsisTable of ContentsG Proteins and G Protein–Coupled Receptors.- Traditional GPCR Pharmacology and Beyond.- Regulation of Intraneuronal Trafficking of G-Protein-Coupled Receptors by Neurotransmitters In Vivo.- Small GTPases and Their Role in Regulating G Protein-Coupled Receptor Signal Transduction.- Regulation of G Protein Receptor Coupling, Mood Disorders and Mechanism of Action of Antidepressants.- Dysregulation of G Protein-Coupled Receptor Signaling in Cancer.- Growth Factors.- Insulin Signaling in Normal and Diabetic Conditions.- Epidermal Growth Factor (EGF) Receptor Signaling and Cancer.- Leptin Signaling Pathway.- Signaling in Normal and Pathological Angiogenesis.- Signaling Platforms.- Spatial and Temporal Control of Cell Signaling by A-Kinase Anchoring Proteins.- Mitochondria, a Platform for Diverse Signaling Pathways.- Mitogen-Activated Protein Kinases and Their Scaffolding Proteins.- Molecular and Functional Determinants of Ca2+ Signaling Microdomains.- Nuclear Receptors / Transcription.- Eukaryotic Gene Transcription.- Estrogen Signaling Mechanisms.- Signal Transduction Pathways Involved in Glucocorticoid Actions.- Reactive Signaling Molecules.- Cellular Signaling by Reactive Oxygen Species: Biochemical Basis and Physiological Scope.- Soluble Guanylyl Cyclase: The Nitric Oxide Receptor.- Cell Cycle, Cell Death and Cancer.- Distinct Roles of the Pocket Proteins in the Control of Cell Cycle.- Activation of the p53 Tumor Suppressor and its Multiple Roles in Cell Cycle and Apoptosis.- Aging and Cancer: Caretakers and Gatekeepers.- Signal Transduction in Embryonic Stem Cells and the Rise of iPS Cells.- Erratum to.

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Book SynopsisDie technischen Fortschritte und neuen Möglichkeiten der molekularen Biologie – Genomanalysen, Expressionsanalysen, konfokale Lasermikroskopie, Proteomics – lassen die Physiologie von Wirbeltieren, genauso wie die von Nicht-Wirbeltieren, in einem neuen Licht erscheinen. Bei der Darstellung der Endokrinologie von Mensch und Tier wird dieser Entwicklung Rechnung getragen: Die Schwerpunkte liegen auf Hormonbiochemie, Hormonphysiologie, Hormonrezeptoren, endokrinen Organen und Regelkreisen und der Regelung endokriner Rhythmen. Die Betrachtung des Hormonsystems reicht von seinen Ursprüngen bei Invertebraten, seiner Evolution, den Wechselwirkungen mit Nerven- oder Immunsystem bis zu Stoffwechselstörungen bei menschlichen Gen-Defekten. Die 4. Auflage ist deutlich erweitert. Das Thema Stoffwechsel nimmt, verteilt über mehrere Kapitel, eine wesentlich größeren Raum ein. Komplett neu ist auch die Embryologie der endokrinen Organe.Trade Review“... Zusammenfassend handelt es sich beim „Kleine/Rossmanith" um ein kompaktes Lehrbuch, das die wesentlichen Bereiche der Endokrinologie abdeckt und für den Einstieg in dieses spannende Fach zu empfehlen ist.” (Jan Tuckermann, in: BIOspektrum, Jg. 28, Heft 4, 2022) “… Das Buch stellt eine immense Fleißarbeit dar, alleine die bei den einzelnen' Kapiteln angeführten Literaturverzeichnisse haben einen Umfang, den man in den üblichen Lehrbüchern nur noch selten findet. Das macht dieses Lehrbuch aber zu einem nützlichen Nachschlagewerk für jeden, der sich über spezielle Probleme der Endokrinologie auch unter evolutionären und vergleichenden Aspekten informieren will.” (Prof. Dr. L. Wildt, in: Der Gynäkologe, Heft 8, August 2021)Table of ContentsEinführung.- Zur Geschichte der Endokrinologie.- Hormone – eine Definition.- Protein- und Peptid-Hormone von Vertebraten.- Protein- und Peptide-Hormone von Invertebraten.- Juvenil- and Steroid-Hormone.- Produkte von Aminosäuren.- Hormonrezeptoren.- Bildung, Freisetzung und Wirkung.- Organe des Hormonsystems.- Regulationsmuster.- Endokrine Musik: Sekretionsrhythmen.- Evolution der Hormonbildung.- Krankheiten des endokrinen Systems.-Leistungssteigerung – legal und Illegal.- Anhang.

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Book SynopsisDu hast dein Studium der Biologie begonnen, aber hast leichten oder großen Respekt vor der damit verknüpften Chemie? Schätzt du dein Vorwissen in Chemie als unzureichend ein oder hast gar kein Vorwissen? Keine Sorge! In diesem Buch erklären wir dir die Grundlagen der Chemie – ausführlich und zugeschnitten auf die Bedürfnisse von Biolog*innen. Wir erinnern uns gut an so manche gedankliche Hürde beim Chemielernen. Diese Hürden möchten wir für dich einreißen und führen dich somit von den grundlegenden Anfängen bis hin zu einem soliden Verständnis durch die Welt der Chemie – egal für wie ahnungslos du dich jetzt noch halten magst. Mit zahlreichen Beispielen aus dem Fach Biologie zeigen wir dir, warum Chemie so wichtig ist. Wir möchten, dass du Chemie verstehen lernst und nach der Lektüre dieses Buches Spaß daran hast, tiefergehenden Fragestellungen aus der Chemie auf den Grund zu gehen. Denn mit einem guten Verständnis für Chemie wird jede Beschäftigung mit der Biologie erst besonders spannend – egal ob du ein Fach in den Life Sciences studierst oder ob du eine Ausbildung mit biowissenschaftlichen Inhalten absolvierst. Wirf einen Blick ins Buch und finde heraus, was es alles zu entdecken gibt.Table of ContentsChemie verstehen – der Weg zum Ziel.- I Chemische Grundbegriffe und physikalische Grundlagen.- Grundbegriffe der Chemie.- Materie und ihre Eigenschaften.- Stoffgemische und Stofftrennung.- II Aufbau der Atome, chemische Bindungen und Eigenschaften der Moleküle.- Aufbau der Atome.- Chemische Bindungen.- Struktur von Molekülen.- Zusammenhang zwischen Aufbau und Eigenschaften chemischer Verbindungen – anorganische und organische Stoffgruppen.- Die wichtigsten bioorganischen Moleküle.- III Chemische Reaktionen.- Chemische Reaktionen im Überblick.- Energieumsatz chemischer Reaktionen.- Geschwindigkeit chemischer Reaktionen.- Säuren und Basen.- Redox-Reaktionen und Elektrochemie.- IV Die Bedeutung der Chemie für die Biologie.- Das biologische Abschlusskapitel.- Anhang: Lösungen der Übungsaufgaben.- Index.

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Book SynopsisFor centuries preparations containing resin from the root of Thapsia garganica L. (Fig. 1) have been used in Arabian and European medicine for treatment of pulmonary diseases, catarrh and as counterirritants for relief of rheumatic pains (1). The properties of the resin were described already by Theophrastos (372-287 B. C. ), Dioscorides (approximately A. D. 50), and Plinius (A. D. 24-79) (2). Radix Thapsiae and Resina Thapsiae have been included in several pharmacopoeias, the latest in the French pharmacopoeia from 1937. The two major active principles were about Fig. I. Thapsia garganica References, pp. 163-167 Sesquiterpenoids from Thapsia Species 131 Thapsigargin (1), Rl: Oct, R2= But Thapsigargicin (2), Rl= Hex, R2 = But Thapsitranstagin (3), Rl: iVai, R2= 2-MeBut Thapsivillosin A (4), Rl= Ang, R2= Sen Thapsivillosin B ( 5), Rl: Ang, R2= 2-MeBut Thapsivillosin C ( 6), Rl= Oct, R2= 2-MeBut Thapsivillosin D ( 7), Rl: 6-MeOct, R2= Sen Thapsivillosin E ( 8), Rl: 6-MeOct, R2= 2-MeBut Thapsivillosin G ( 9), Rl= 6-MeHcp, R2= 2-MeBut Thapsivillosin H ( 10), Rl or R2= Ang or Sen Thapsivillosin I ( 11), Rl= Ang, R2= But Thapsivillosin J ( 12), Rl: iVai, R2= But Thapsivillosin K ( 13), Rl: Sen, R2= 2-MeBut Chart 1. Hexaoxygenated thapsigargins found in Thapsia two decades ago found to be the sesquiterpene lactones thapsigargin (1) and thapsigargicin (2) (3).Table of ContentsThe Explosion of Structural Information on Insect Neuropeptides.- 1. Introduction.- 2. General Methods Used for Isolation, Identification and Characterization of Insect Neuropeptides.- 2.1. Biological Assays.- 2.1.1. Adipokinetic Bioassay.- 2.1.2. Myotropic Bioassay.- 2.2. Liquid Chromatography.- 2.3. Edman Degradation Sequencing, Mass Spectrometry and Peptide Synthesis.- 2.4. Immunological Techniques (RIA, ELISA, Immunocytochemistry).- 2.5. Molecular Biological Techniques.- 3. The Insect Neuropeptides.- 3.1. Peptides Involved in Homeostasis and Metabolism.- 3.1.1. Adipokinetic and Hypertrehalosaemic Peptides.- 3.1.2. Diuretic and Antidiuretic Peptides.- 3.2. Peptides Regulating Reproduction, Growth and Development.- 3.2.1. Pheromone Biosynthesis Activating Neuropeptides.- 3.2.2. Allatotropins and Allatostatins.- 3.2.2.1. Allatotropins.- 3.2.2.2. Allatostatins.- 3.2.3. Prothoracicotropic Hormone, Bombyxin and Other Insulin-Related Neuropeptides.- 3.2.3.1. Prothoracicotropic Hormone.- 3.2.3.2. Bombyxin.- 3.2.3.3. Locusta Insulin-Related Peptide.- 3.2.4. Eclosion Hormones.- 3.2.5. Peptides Affecting Gonad Activity.- 3.2.5.1. Ovary Maturating Peptide and Neuroparsin of Locusta migratoria.- 3.2.5.2. Oostatic Hormones of Diptera.- 3.2.6. Diapause Hormones.- 3.3. Peptides Modifying Spontaneous Muscle Contractions:Mytropic Peptides.- 3.3.1. Proctolin and Cardiostimulatory Peptides.- 3.3.2. Myokinins.- 3.3.3. Sulfakinins.- 3.3.4. Pyrokinins/Myotropins.- 3.3.5. Tachykinins.- 3.3.6. Periviscerokinin.- 3.3.7. Accessory Glands- and Midgut Myotropins and Others.- 3.3.8. Myoinhibitory Peptides and Other FMRF amide Related Peptides (FaRPs).- 3.4. Chromatotropic Factors in Insects.- 4. Conclusions.- Acknowledgments.- References.- Sesquiterpenoids from Thapsia Species and Medicinal Chemistry of the Thapsigargins.- 1. Introduction.- 2. Taxonomy of Thapsia.- 2.1. Thapsia garganica and Thapsia transtagana.- 2.2. Thapsia maxima.- 2.3. Thapsia villosa.- 2.4. Thapsia gymnesica.- 3. Elucidation of the Structure of Thapsigargin.- 4. Proazulenic Slovanolides.- 5. Non-lactonic Sesquiterpenoids from Thapsia.- 6. Pharmacological Activity of the Thapsigargins.- 7. Molecular Pharmacology.- 8. Chemistry of Thapsigargin.- 8.1. Changes at C(8).- 8.2. Changes at C(3).- 8.3. Changes of the Vicinal Diol.- 8.4. Changes of Lactone Carbonyl Group.- 8.5. Changes at O(10).- 9. Structure Activity Relationships.- 10. Metabolic Catabolism of Thapsigargin.- References.- Pregnane Glycosides.- 1. Introduction.- 2. Isolation and Identification.- 2.1. Thin Layer and Column Chromatography.- 2.2. Sephadex LH-20 Chromatography.- 2.3. Flash Chromatography.- 2.4. Low Pressure Liquid Chromatography (LPLC).- 2.5. High Performance Liquid Chromatography (HPLC).- 3. Structure Elucidation.- 3.1. One-Dimensional NMR Spectroscopy.- 3.2. Two-Dimensional NMR Spectroscopy.- 3.3. Mass Spectrometry.- 3.4. I.R. Spectroscopy.- 3.5. U.V. Spectroscopy.- 3.6. Optical Rotatory Dispersion.- 3.7. Hydrolysis of Pregnane Glycosides.- 4. Pregnane Aglycons.- 5. Sugars of Pregnane Glycosides.- 5.1. General and Monosaccharides.- 5.2. Disaccharides from Pregnane Glycosides.- 5.3. Trisaccharides from Pregnane Glycosides.- 6. Biosynthesis of Pregnane Glycosides.- 7. Biological Activity.- Acknowledgement.- References.- Author Index.

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Table of ContentsChemistry of Synthetic Immunomodulant Muramyl Peptides.- I. From Freund’s Adjuvant to MDP.- II. Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP).- 1. Protected Dipeptide Derivatives.- 2. Protected N-acetyl-muramyl Derivatives.- 3. Coupling of Protected Muramic Acid and Dipeptide Derivatives.- 4. Deprotecting Procedures.- 5. Synthesis of Labelled MDP.- III. Synthesis of Other N-acetyl-muramyl-dipeptides, Analogues and Derivatives of MDP.- 1. Modifications of the Peptide Moiety.- 2. Modifications of the Carbohydrate Moiety.- IV. Synthesis of N-acetyl-muramyl-tri-, tetra-, and -pentapeptides, and of Some Analogs Bearing a Lipophilic Group at the C-terminal End.- 1. Substitution of the ?-amide Group of MDP by a Free or Amidated Amino Acid.- 2. Lengthening of the Peptide Chain at the Carboxyl Function of MDP.- 3. Lipophilic Derivatives of N-acetyl-muramyl-L-alanyl-D-isoglutaminyl-L-alanine.- V. Synthesis of N-acetyl-?-D-glucosaminyl-(1–4)-N-acetyl-muramyl-peptides.- VI. Synthesis of Oligomers and Conjugates of MDP.- 1. Synthesis of Oligomers of MDP.- 2. Synthesis of Conjugates of MDP.- VII. Mass Spectrometry of MDP and Analogues.- VIII. 13C-NMR Spectrometry of MDP and Derivatives.- IX. Analysis of MDP.- Addendum.- References.- Appendix: Leading References on Biological Activities of MDP and Derivatives.- The Chemistry of Longifolene and Its Derivatives..- I. Introduction.- II. Isolation, Occurrence.- III. Structure.- IV. Synthesis.- V. Isolongifolene.- 1. Structure.- 2. Synthesis.- 3. Mechanism of Rearrangement.- VI. Reactions of Longifolene.- 1. “Normal” Reactions.- a) Addition Reactions.- b) Substitution Reactions.- 2. Skeletal Rearrangements.- a) Simple Wagner-Meerwein Rearrangements.- b) Deep-Seated Rearrangements.- 3. Steric Diversion.- a) Electrophilic Additions.- b) Oxidations.- 4. Transannular Reactions.- a) Radical Reactions.- b) Ionic Reactions.- c) Lead Tetraacetate Oxidation of Longifolols.- 5. Conversions into Other Sesquiterpene Skeletons.- 6. Miscellaneous Transformations.- VII. Reactions of Isolongifolene.- 1. Epoxidation and Reactions of Epoxide.- 2. Addition of Halogens and Pseudo-Halogens.- VIII. Ultraviolet Absorption of Some Longifolene Derivatives.- IX. Biosynthesis.- X. Longifolene in Industry.- References.- Homoisoflavanones and Biogenetically Related Compounds..- 1. Introduction.- 2. Isolation and Identification.- 2.1. Isolation.- 2.2. Chromatography.- 3. Structure and Nomenclature.- 3.1. General Aspects and Nomenclature.- 3.2. Ultraviolet-Visible Spectroscopy.- 3.3. Infrared Spectroscopy.- 3.4. Nuclear Magnetic Resonance Spectroscopy.- 3.4.1. 1H-NMR Spectra.- 3.4.2. 13C-NMR Spectra.- 3.5. Mass Spectrometry.- 3.6. Optical Activity and Absolute Configuration.- 4. Chemical Transformations and Syntheses.- 4.1. Synthesis of the Skeleton.- 4.2. Routes to Eucomol.- 4.3. Isomerization and Hydrogenation Reactions of the 3(9)-Double Bond.- 4.4. Deuterium Exchange Reactions.- 4.5. Acylation and Deacylation Reactions.- 4.6. Alkylation and Dealkylation Reactions.- 4.7. Further Reactions of Eucomol.- 4.8. Chemistry of Brazilin and Hematoxylin.- 5. Biosynthesis.- 6. Biological Activity.- 7. Chemotaxonomy.- References.- Naturally Occurring Phenalenones and Related Compounds..- I. Introduction.- II. Phenalenones and Related Metabolites from Fungi.- A. Occurrence.- B. Structure and Chemistry.- C. Synthesis.- D. Biosynthesis.- E. Biological Activity.- III. Phenalenones and Related Metabolites in Higher Plants.- A. Occurrence.- B. Structure Determination.- C. Spectroscopic Methods.- D. Synthesis.- E. Biological Activity.- F. Biosynthesis.- References.- Molecular Mechanisms of Enzyme-Catalyzed Dioxygenation. (An Interdisciplinary Review.).- I. Introduction.- II. Some Basic Chemistry of Molecular Oxygen.- III. Precedents for Metal-Activation of Dioxygen.- 1. How Would an Iron- or Copper-Protein Interact with Molecular Oxygen?.- 2. Precedents for the Transfer of Dioxygen Within the Co-ordination Sphere.- 3. Precedents for the Reaction of Co-ordinated Dioxygen with Free Substrates.- 4. Free Forms of Activated Dioxygen Generated by Metals.- IV. Precedents for Metal Activation of Organic Substrates.- V. The Double Bond-Cleaving Dioxygenases.- 1. Ene-diol Cleaving Dioxygenases.- 2. Extradiol-Cleaving Dioxygenases.- 3. Other Double Bond-Cleaving Dioxygenases.- VI. The Luciferases.- VII. Peroxidizing Dioxygenases.- VIII. Miscellaneous Dioxygenases.- 1. External Flavoprotein Dioxygenases.- 2. Sulfur Oxidizing Dioxygenases.- 3. Inositol Dioxygenase.- 4. Nitropropane Dioxygenase.- 5. Carotene Dioxygenase.- 6. Ribulose Bisphosphate Carboxylate/Oxygenase.- IX. ?-Keto Carboxylic Acid Decarboxylating Dioxygenases.- X. Summary.- Acknowledgments.- References.- Author Index.

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Book SynopsisRadionuclide distribution and transport in terrestrial and aquatic ecosystems is Volume 5 of a critical review of data (Prepared for the Commission of the European Communities) in 1984.

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Book SynopsisWe are at a critical point in human history and that of the planet. In this book, a world leader in agricultural research, Professor Sayed Azam-Ali, proposes a radical transformation of our agrifood system. He argues that agriculture must be understood as part of global biodiversity and that food systems have cultural, nutritional, and social values beyond market price alone. He describes the perilous risks of relying on just four staple crops for most of our food and the consequences of our current agrifood model on human and planetary health.In plain language for the wider public, students, researchers, and policy makers, Azam-Ali envisions the agrifood system as a global public good in which its practitioners include a new and different generation of farmers, its production systems link novel and traditional technologies, and its activities encompass landscapes, urban spaces, and controlled environments. The book concludes with a call to action in which diversification of species, systems, knowledge, cultures, and products all contribute to The Ninth Revolution that will transform food systems for good.Related Link(s)

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Book SynopsisThis book focuses on the advantages and disadvantages of each of the commonly used quantitative proteomic methods in terms of accuracy, sensitivity, and reproducibility. It also concentrates on the effective applications of these methods that resulted in many discoveries of the role of the proteins expressed in living cells and biological fluids. The book focuses on the description of advantages and disadvantages of each of the commonly used quantitative proteomic methods, and provides concise descriptions of the effective applications of these methods.Table of ContentsFD-LC-MS/MS. 2-D DIGE. Mass Spectrometry Utilizing ICAT. Proteomic Analyses of Post-translational Modifications. Cardiovascular Proteomic Analysis. Proteome in Neurodegenerative Diseases. Liver Disease-Related Proteome. Respiratory Disease Related Proteome. Renal Disease-Related Proteome. Aging-Related Proteome. Phosphoproteomics of Tumor Cell Lines. HCV Infection and Mitochondria Proteomics. Infectious Disease by SELDI. Quantitative Proteomic Analysis of HIV Infection.

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Book SynopsisThis book describes the design and the use of bioluminescent biosensors. It introduces beginners and experienced researchers starting in the microbiological biosensor domain to the practical aspects of building a luminescent microbial biosensor. It is also a source of information about other applications that use microbial cells. Each chapter focuses as far as possible on the technological conception of the presented biosensor with a clear demonstration of the issues in the design and how to reach the proof of concept. The book is divided into three practical sections facilitating the reader to easily access the information.Table of ContentsLuminescent Biosensors with Free Suspended Cells. Fully Automated Fluidic Analyzer for Food Quality Assessment Using Bioluminescent Biosensors. Technological Design of Optical Bacterial Biosensors for the Online Environmental Monitoring of Water Pollutants. Luminescent Biosensors with Immobilized Cells. Fiber Optic Biosensors for Environmental Monitoring. Non-Fiber Optic Bioluminescent Biosensors. Biosensor with Immobilized Cells and Lensless Imaging Detection Luca CeveniniaA biosensor with Genetically Modified Bacteria Immobilized on a Fiber and a Glass Slide. Development and Characterization of a Living-Cell Bioluminescent Bioreporter Integrated Circuit (BBIC). BOD Sensor with Immobilized Luminous Cells on ChipBioluminescent Whole-Cell Sensors: Integration of Bacterial Reporter Cells onto Hardware Platforms. Luminescent Biosensors with Bioluminescent Sporulated Cells ("Sporosensor"). Luminescent Biosensing Systems Based on Genetically Engineered Spore-Forming Bacteria.

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Book SynopsisThe ABC of Acid-Base Chemistry provides physiologists, medical students, and physicians with an intelligible outline of the elements of physiological acid-base chemistry. This new edition of Horace W. Davenport's standard text takes into account different ways of looking at the problems of acid-base derived from new instrumentation. The exposition has been modified to allow the student to apply his understanding to other systems of description of the acid-base status. Although the pH system has been retained, there is increasing emphasis on the use of hydrogen ion concentration. Topics discussed include: partial pressure of gases, composition of alveolar gas, transport of oxygen and carbon dioxide in the blood, buffer action of hemoglobin and seperated plasma, oxygenated whole blood and reduced blood, concepts of base excess and base deficit, and chemical regulation of respiration. Any reader who clearly understands the subject matter of this book will have a firm grounding in the prin

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Book SynopsisBefore the hydrogen bomb indelibly associated radioactivity with death, many chemists, physicians, botanists, and geneticists believed that radium might hold the secret to life. This book recovers a forgotten history of the connections between radioactivity and the life sciences that existed long before the dawn of molecular biology.Trade Review"Radium and the Secret of Life probes the experimental and metaphorical connections between transmutation and mutation. As that coupling makes clear, it was a book waiting to be written. Campos provides a deeply researched, engagingly written, and provocatively argued history of this potent conjunction and how it disintegrated so fully as to be nearly forgotten." (Angela N. H. Creager, author of Life Atomic)

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Book SynopsisToday's science tells us that our bodies are filled with molecular machinery that orchestrates all sorts of life processes. When we think, microscopic channelsopen and close in our brain cell membranes; when we run, tiny motorsspin in our muscle cell membranes; and when we see, light operates molecular switchesin our eyes and nerves. A molecular-mechanical vision of life has become commonplace in both the halls of philosophy and the offices of drug companies, where researchers are developing proton pump inhibitors or medicines similar to Prozac. Membranes to Molecular Machines explores just how late twentieth-century science came to think of our cells and bodies this way. This story is told through the lens of membrane research, an unwritten history at the crossroads of molecular biology, biochemistry, physiology, and the neurosciences, that directly feeds into today's synthetic biology as well as nano- and biotechnology. Mathias Grote shows how these sciences not only have made us think differently about life, they have, by reworking what membranes and proteins represent in laboratories, allowed us to manipulate life as active matterin new ways. Covering the science of biological membranes in the United States and Europe from the mid-1960s to the 1990s, this book connects that history to contemporary work with optogenetics, a method for stimulating individual neurons using light, and will enlighten and provoke anyone interested in the intersection of chemical research and the life sciencesfrom practitioner to historian to philosopher. The research described in the book and its central actor, Dieter Oesterhelt, were honored with the 2021 Albert Lasker Basic Medical Research Awardfor his contribution to the development of optogenetics.

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Book SynopsisTrade ReviewThe dearth of promising new treatments for many a serious disease remains a major challenge not just for the pharmaceutical industry but for all of society. In this exhaustively researched book, Brent R. Stockwell surveys the history of drug development and offers insightful suggestions for innovative new approaches. This is critical reading for the many involved in and concerned about this urgent issue. -- Robert Bazell, chief science correspondent, NBC News, and author of Her-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer This is a terrific book! Stockwell's writing is clear and engaging as he presents a thoughtful analysis of drug development that can be understood and appreciated by a diverse readership. Stockwell beautifully combines scientific history and personal anecdotes with clear explanations of the principles and practices of chemical biology to make a fascinating story of the past, present, and future of drug discovery. His book is informative, accurate, and a good read all put together. -- Geoffrey Cooper, Boston University, author of The Cell: A Molecular Approach and Oncogenes This is a truly wonderful book. Stockwell's writing will open the door to a universe that many readers may know little about. Drugs are born, biotech companies are created, scientists' careers are made and unmade, egos are raised and dashed. This book is so readable, it is an absolute page-turner. Yet it is also authoritative and scientifically sophisticated, managing to distill a complex, changing field into a beautifully written, well-crafted story. -- Siddhartha Mukherjee, Columbia University, author of The Emperor of All Maladies: A Biography of Cancer By providing accessible explanations for the underlying biological and chemical principles that apply to the complex solutions he describes, Stockwell enables even the scientifically unsophisticated reader to gain a wider perspective on what future disease treatment might entail. Publishers Weekly This very readable, even exciting work takes us through the medical breakthroughs of the past century. Globe and Mail This book deserves a readership, and there is certainly a need for it. As a drug companyresearcher, I have often wished that more people understood what the field was likeand how simultaneously fascinating and frustrating it can be. -- Derek B. Lowe Cell In this well-researched look into the complexities of making medicines, a chemical biologist gives a history of drug making and details innovative methods of drug discovery. Science News Despite our current political paralysis, government leaders should listen to Stockwell and be certain to advance our capacity to generate the drugs that our society and the world need. Harvard Magazine The book is well organized and includes many interesting, clever analogies to explain what can be complicated scientific problems. Choice An engaging and rewarding read... -- Donald C. Lo Journal of Clinical Investigation The reader is not only left with a satisfying overview of the proud history and future challenges of finding new medicines but also encouragement that Stockwell and his contemporaries are creatively committed to academic drug discovery. -- David Kroll Nature Chemistry Stockwell writes well-his prose is accessible to the educated reader, irrespective of his or her background. All of the personalities, errors and successes in contemporary drug discovery are presented. Stockwell enlivens their stories with anecdotes... -- Garrett A. FitzGerald Nature Medicine It is impossible to read this relatively short book...without being captured by the author's optimism about the future of drug development. -- Robert C. Young, M.D. Oncology TimesTable of ContentsList of Illustrations Preface Acknowledgments Abbreviations Part I. The Vanishing Cures 1. The Drug Discovery Crisis 2. A New Science of Molecules 3. The Birth of the First Cancer Drugs 4. A New Company Creating Drug Combinations 5. The Undruggable RAS Protein 6. The Druggable Genome Part II. The Path to the Next Generation of Medicines 7. Peering Inside Proteins 8. The Nature of Interactions Between Proteins 9. From Protein-Protein Interactions to Personalized Medicines 10. A Revolution in Peptide Synthesis 11. A Vast Array of Drug Candidates 12. Moving Outside the Small Molecule Box 13. Accelerating the Arrival of Next-Generation Drugs Notes Glossary Index

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Book SynopsisFoundations of Confocal Scanned Imaging in Light Microscopy.- Fundamental Limits in Confocal Microscopy.- Special Optical Elements.- Points, Pixels, and Gray Levels: Digitizing Image Data.- Laser Sources for Confocal Microscopy.- Non-Laser Light Sources for Three-Dimensional Microscopy.- Objective Lenses for Confocal Microscopy.- The Contrast Formation in Optical Microscopy.- The Intermediate Optical System of Laser-Scanning Confocal Microscopes.- Disk-Scanning Confocal Microscopy.- Measuring the Real Point Spread Function of High Numerical Aperture Microscope Objective Lenses.- Photon Detectors for Confocal Microscopy.- Structured Illumination Methods.- Visualization Systems for Multi-Dimensional Microscopy Images.- Automated Three-Dimensional Image Analysis Methods for Confocal Microscopy.- Fluorophores for Confocal Microscopy: Photophysics and Photochemistry.- Practical Considerations in the Selection and Application of Fluorescent Probes.- Guiding Principles of Specimen PreservatioTable of ContentsFoundations of Confocal Scanned Imaging in Light Microscopy.- Fundamental Limits in Confocal Microscopy.- Special Optical Elements.- Points, Pixels, and Gray Levels: Digitizing Image Data.- Laser Sources for Confocal Microscopy.- Non-Laser Light Sources for Three-Dimensional Microscopy.- Objective Lenses for Confocal Microscopy.- The Contrast Formation in Optical Microscopy.- The Intermediate Optical System of Laser-Scanning Confocal Microscopes.- Disk-Scanning Confocal Microscopy.- Measuring the Real Point Spread Function of High Numerical Aperture Microscope Objective Lenses.- Photon Detectors for Confocal Microscopy.- Structured Illumination Methods.- Visualization Systems for Multi-Dimensional Microscopy Images.- Automated Three-Dimensional Image Analysis Methods for Confocal Microscopy.- Fluorophores for Confocal Microscopy: Photophysics and Photochemistry.- Practical Considerations in the Selection and Application of Fluorescent Probes.- Guiding Principles of Specimen Preservation for Confocal Fluorescence Microscopy.- Confocal Microscopy of Living Cells.- Aberrations in Confocal and Multi-Photon Fluorescence Microscopy Induced by Refractive Index Mismatch.- Interaction of Light with Botanical Specimens.- Signal-to-Noise Ratio in Confocal Microscopes.- Comparison of Widefield/Deconvolution and Confocal Microscopy for Three-Dimensional Imaging.- Blind Deconvolution.- Image Enhancement by Deconvolution.- Fiber-Optics in Scanning Optical Microscopy.- Fluorescence Lifetime Imaging in Scanning Microscopy.- Multi-Photon Molecular Excitation in Laser-Scanning Microscopy.- Multifocal Multi-Photon Microscopy.- 4Pi Microscopy.- Nanoscale Resolution with Focused Light: Stimulated Emission Depletion and Other Reversible Saturable Optical Fluorescence Transitions Microscopy Concepts.- Mass Storage, Display, and Hard Copy.- Coherent Anti-Stokes Raman Scattering Microscopy.- Related Methods for Three-Dimensional Imaging.- Tutorial on Practical Confocal Microscopy and Use of the Confocal Test Specimen.- Practical Confocal Microscopy.- Selective Plane Illumination Microscopy.- Cell Damage During Multi-Photon Microscopy.- Photobleaching.- Nonlinear (Harmonic Generation) Optical Microscopy.- Imaging Brain Slices.- Fluorescent Ion Measurement.- Confocal and Multi-Photon Imaging of Living Embryos.- Imaging Plant Cells.- Practical Fluorescence Resonance Energy Transfer or Molecular Nanobioscopy of Living Cells.- Automated Confocal Imaging and High-Content Screening for Cytomics.- Automated Interpretation of Subcellular Location Patterns from Three-Dimensional Confocal Microscopy.- Display and Presentation Software.- When Light Microscope Resolution Is Not Enough:Correlational Light Microscopy and Electron Microscopy.- Databases for Two- and Three-Dimensional Microscopical Images in Biology.- Confocal Microscopy of Biofilms — Spatiotemporal Approaches.- Bibliography of Confocal Microscopy.

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Book SynopsisChromatographic Methods in Clinical Chemistry and Toxicology fills the gap that exists between theoretical treatments of chromatography, and clinical chemistry and toxicology texts that focus almost exclusively on clinical relevance and applications.Table of ContentsPreface xi List of Contributors xiii 1. Quality Assurance, Quality Control and Method Validation in Chromatographic Applications 1Michele L. Merves and Bruce A. Goldberger 1.1 Introduction 1 1.2 History 1 1.3 Definition of Quality Assurance and Quality Control 3 1.4 Professional Organizations 4 1.5 Internal Quality Assurance and Control 5 1.5.1 Standard operating procedure manual 5 1.5.2 Method development 5 1.5.3 Method validation 6 1.5.4 Accuracy 7 1.5.5 Precision 7 1.5.6 Recovery 7 1.5.7 Lower limits of detection (sensitivity) and quantitation 8 1.5.8 Range of linearity 8 1.5.9 Specificity 9 1.5.10 Stability 9 1.5.11 Carryover 9 1.5.12 Ruggedness 9 1.5.13 Selection of a reference standard 10 1.5.14 Selection of an internal standard and standard addition 10 1.5.15 Selection of derivatization agent 10 1.5.16 Selection of ions for selected-ion monitoring or full-scan analysis 11 1.5.17 Chromatographic performance 11 1.5.18 Statistical evaluation of quality control 11 1.6 External Quality Assurance 13 References 13 2. Liquid Chromatographic-Mass Spectrometric Measurement of Anabolic Steroids 15Don H. Catlin, Yu-Chen Chang, Borislav Starcevic and Caroline K. Hatton 2.1 Introduction 15 2.2 LC-MS Analysis of Synthetic Steroids or Animal Samples 16 2.3 LC-MS Analysis of Natural Androgens in Human Samples 19 2.4 Conclusion 29 References 29 3. High-performance Liquid Chromatography in the Analysis of Active Ingredients in Herbal Nutritional Supplements 33Amitava Dasgupta 3.1 Introduction 33 3.2 St John’s Wort 35 3.2.1 Drug interactions with St John’s wort 35 3.2.2 Measurement of active ingredients of St John’s wort using HPLC 36 3.2.3 Analysis of St John’s wort extract with other analytical techniques 38 3.2.4 Measurement of hypericin and hyperforin in human plasma using HPLC 38 3.3 Herbal Supplements with Digoxin-like Immunoreactivity 39 3.3.1 Use of HPLC for the determination of chan su, danshen and ginsengs 40 3.4 Herbal Remedies and Abnormal Liver Function Tests 41 3.4.1 Use of GC-MS and HPLC for the measurement of active components 43 3.5 Ginkgo Biloba 43 3.5.1 Analysis of components of ginkgo biloba by HPLC 44 3.6 Echinacea 45 3.6.1 Analysis of active components of echinacea by HPLC 45 3.7 Valerian 46 3.7.1 Analysis of components of valerian by HPLC 46 3.8 Feverfew 46 3.8.1 Analysis of parthenolide by HPLC 47 3.9 Garlic 47 3.9.1 Measurement of components of garlic by HPLC 48 3.10 Ephedra (Ma Huang) and Related Drugs 48 3.10.1 Analysis of active components of ephedra-containing products 49 3.11 Conclusions 50 References 50 4. Measurement of Plasma L-DOPA and L-Tyrosine by High-Performance Liquid Chromatography as a Tumor Marker in Melanoma 56Thierry Le Bricon, Sabine Letellier, Konstantin Stoitchkov and Jean-Pierre Garnier 4.1 Introduction 56 4.2 Melanogenesis 57 4.2.1 Overview of the pathway 57 4.2.2 Potential tumor markers 58 4.3 L-DOPA Alone 59 4.3.1 Urine analysis 59 4.3.2 Blood (plasma or serum) analysis 59 4.4 L-DOPA/L-Tyrosine Ratio 60 4.4.1 Technical aspects 60 4.4.2 Clinical results 61 4.4.3 Future directions 63 4.5 Conclusion 64 References 65 5. Hypersensitive Measurement of Proteins by Capillary Isoelectric Focusing and Liquid Chromatography-Mass Spectrometry 67Feng Zhou and Murray Johnston 5.1 Introduction 67 5.2 A Robust CIEF-RPLC Interface 69 5.3 First-Generation CIEF-RPLC-MS System for Proteins 71 5.4 Second-Generation CIEF-RPLC-MS System 76 5.5 Future Improvements 83 Acknowledgment 83 References 83 6. Chromatographic Measurement of Transferrin Glycoforms for Detecting Alcohol Abuse and Congenital Disorders of Glycosylation 87Anders Helander 6.1 Introduction 87 6.2 Transferrin Microheterogeneity 88 6.3 Carbohydrate-deficient Transferrin (CDT) 89 6.4 Congenital Disorders of Glycosylation (CDG) 89 6.5 Analytical Methods for Transferrin Microheterogeneity 90 6.6 Chromatographic Methods for CDT 91 6.6.1 HPLC conditions and potential interferences 91 6.6.2 Chromatographic separation of transferrin glycoforms 92 6.6.3 Genetic transferrin variants and glycoform types 94 6.6.4 Sensitivity and reproducibility 94 6.7 Chromatographic Methods for CDG 94 6.7.1 HPLC testing for CDG 95 6.7.2 LC-MS testing for CDG 95 6.8 Summary and Conclusions 96 References 97 7. Chromatographic Measurements of Catecholamines and Metanephrines 101Eric C. Y. Chan and Paul C. L. Ho 7.1 Background 101 7.1.1 Total or individual assays 104 7.2 Analytical Measurements of Catecholamines and Metanephrines 105 7.3 Early Methods 105 7.3.1 Catecholamines 105 7.3.2 Metanephrines 106 7.4 Current Chromatographic Methods 106 7.4.1 Chemistry of catecholamines 106 7.4.2 Specimen preparation 107 7.4.3 Fluorescence detection 109 7.4.4 Electrochemical detection 110 7.4.5 Chemiluminescence detection 112 7.4.6 Mass spectrometry 115 7.5 Practical Considerations for the Stability of Urinary Catecholamines and Metanephrines During Storage 117 7.6 Future Developments 118 Dedication 119 References 119 8. Chromatographic Measurement of Volatile Organic Compounds (VOCs) 127Larry A. Broussard 8.1 Introduction 127 8.2 General Considerations 127 8.3 Intended Use 128 8.4 Volatility of Compounds 128 8.5 Sample Collection, Handling and Storage 129 8.6 Headspace Gas Chromatographic Methods 129 8.7 Columns and Detectors 130 8.8 Identification, Quantitation and Confirmation 130 8.9 Ethanol and Other Volatile Alcohols 131 8.10 Inhalants and Screening for Multiple VOCs 132 8.11 Interpretation 134 8.12 Conclusion 136 References 136 9. Chromatographic Techniques for Measuring Organophosphorus Pesticides 139H. Wollersen and F. Musshoff 9.1 Introduction 139 9.2 Organophosphorus Pesticides (OPs) 141 9.2.1 Mechanism of action 141 9.2.2 Intoxication 141 9.2.3 Progression of intoxication and longer term risks 145 9.2.4 Therapy 146 9.2.5 Analytical procedures 146 9.3 Conclusion 163 References 164 10. Chromatographic Analysis of Nerve Agents 170Jeri D. Ropero-Miller 10.1 Introduction 170 10.2 Neuromuscular Blockers 170 10.2.1 Background and uses 170 10.2.2 Classification, mechanism and duration of action 171 10.2.3 Effects and toxicity 173 10.2.4 Analysis 173 10.3 Paralytic Shellfish Poisoning: Saxitoxin 185 10.3.1 Background 185 10.3.2 Toxicity 187 10.3.3 Analysis 188 10.4 Summary 191 References 195 11. History and Pharmacology of c-Hydroxybutyric Acid 197Laureen Marinetti 11.1 Introduction 197 11.2 History of Illicit Use of GHB 198 11.3 Clinical Use of GHB in Humans 200 11.4 History of Illicit Use of GBL and 1,4BD 200 11.5 Distribution and Pharmacokinetics of GHB, GBL and 1,4BD 202 11.6 GHB Interpretation Issues and Post-mortem Production 204 11.7 Analysis for GHB, GBL and 1,4BD 208 References 213 12. Liquid Chromatography with Inductively Coupled Plasma Mass Spectrometric Detection for Element Speciation: Clinical and Toxicological Applications 217Katarzyna Wrobel, Kazimierz Wrobel and Joseph A. Caruso 12.1 Introduction 217 12.2 Liquid Chromatography with Inductively Coupled Plasma Mass Spectrometric Detection 218 12.3 Analytical Applications of Clinical and Toxicological Relevance 219 12.3.1 Arsenic 219 12.3.2 Iodine 234 12.3.3 Mercury 234 12.3.4 Platinum 240 12.3.5 Selenium 245 12.4 Conclusions and Future Trends 260 12.5 Abbreviations 260 References 262 13. Applications of Gas Chromatography-Mass Spectrometry to the Determination of Toxic Metals 274Suresh K. Aggarwal, Robert L. Fitzgerald and David A. Herold 13.1 Introduction 274 13.2 Instrumentation 275 13.3 Experimental Procedure 276 13.3.1 Preparation of internal standard solutions 276 13.3.2 Digestion of biological sample 276 13.3.3 Preparation of metal chelate 277 13.4 GC-MS Studies 278 13.4.1 Memory effect evaluation 278 13.4.2 Precision and accuracy in measuring isotope ratios 281 13.4.3 Results of concentration determination of toxic metals in biological samples 283 13.5 Conclusions 284 References 284 Index 287

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Book SynopsisAn accessible engaging biochemistry primer with short, 'bite sized' chapters that gently lead the reader through the essential chemistry and biochemistry they need to know without going into unnecessary and intimidating detail. Assumes only a basic understanding of chemistry and focuses on helping the reader to understand key concepts.Trade Review"For students embarking on careers in the health sciences, it is an essential academic companion and, retailing at approximately £28, it is excellent value for money". (The Biochemist, 1 June 2011) "It's not every day that one picks up a textbook that can claim to occupy a unique niche, given the multitude of scientific textbooks that are vying for a medical readership. However, with the recent publication of Pain-Free Biochemistry: An Essential Guide for the Health Sciences, which is specifically aimed at students of medicine and nursing, one could be left wondering just why nobody thought of this sooner." (Irish Medical News, September 08, 2010)Table of ContentsPreface x Section 1 Foundations 1 Topic 1 Why biochemistry? 3 Topic 2 Remarkableness of life 9 Chemistry I The basic structure of substances: atoms, molecules, elements and compounds 13 Chemistry II Atomic structure, valency and bonding 16 Chemistry III Protons, acids, bases, concentration and the pH scale 25 Topic 3 Shape, molecular recognition and proteins: an example 32 Topic 4 Proteins: molecular necklaces 38 Topic 5 Chemical transformations in the living organism: metabolism 43 Topic 6 Reactions, catalysts and enzymes 46 Topic 7 Specificity, saturation and active sites 49 Topic 8 Structure of metabolism: anabolism and catabolism 54 Chemistry IV Equilibrium 56 Topic 9 Catabolism: degradation vs energy metabolism 60 Chemistry V Oxidation and reduction 63 Topic 10 Oxidation and reduction in metabolism 67 Section 2 Catabolism 71 Chemistry VI Aldehydes, ketones and sugars 73 Topic 11 Carbohydrates: sugars and polysaccharides in metabolism 81 Topic 12 Glucose inside the body 85 Topic 13 Breakdown of sugar: glycolysis 88 Topic 14 Aerobic oxidation of pyruvate: Krebs cycle 94 Topic 15 Respiratory chain, oxidative phosphorylation and overall ATP yields 98 Topic 16 Mobilising the carbohydrate store: glycogenolysis 103 Chemistry VII Alcohols, esters, glycerol, fatty acids and triglycerides 106 Chemistry VIII Hydrophobic, hydrophilic and amphiphilic 109 Topic 17 Phospholipids and membranes 111 Chemistry IX Saturated and unsaturated 114 Topic 18 Fats as an energy source 119 Topic 19 Fats: digestion, transport, storage and mobilisation 122 Topic 20 Fats: oxidation of fatty acids 126 Topic 21 Ketone bodies in health and disease 133 Topic 22 Dietary fat: essential fatty acids 137 Topic 23 Protein and amino acid breakdown 140 Topic 24 Shedding excess amino groups: urea cycle 147 Section 3 Anabolism and Control 151 Topic 25 Is anabolism just catabolism backwards? 153 Topic 26 Making new glucose: gluconeogenesis 156 Topic 27 Fatty acid biosynthesis 161 Topic 28 Providing reducing power: NADPH and the pentose phosphate pathway 164 Chemistry X Isotopes 168 Topic 29 Red cells and white cells: defence against reactive oxygen and reactive oxygen as defence! 172 Topic 30 The need for metabolic control 176 Topic 31 Relationship of fats and carbohydrates: use by different tissues 179 Section 4 Genes and Protein Synthesis 181 Topic 32 The idea of genes 183 Topic 33 The chemistry of genes: DNA and the double helix 186 Topic 34 The genetic code and mRNA 190 Topic 35 Protein synthesis, ribosomes and tRNA 193 Topic 36 Genetic differences and disease 197 Topic 37 Genetic variability: drug metabolism and disease susceptibility 203 Topic 38 Mutation, radiation and ageing 205 Topic 39 Switching genes on and off: development, tissue specificity, adaptation and tolerance 207 Topic 40 DNA and protein synthesis as targets: chemotherapy, antibiotics, etc. 210 Section 5 Physiological Systems and Clinical Issues 217 Topic 41 Hormones and second messengers 219 Topic 42 Switching enzymes on and off: coarse and fine control 222 Topic 43 Insulin, glucagon and adrenaline 224 Topic 44 Diabetes 229 Topic 45 Steroid hormones and receptors: fertility control, pregnancy testing, etc. 233 Topic 46 Pituitary hormones and feedback loops 238 Topic 47 Thyroid hormones 240 Topic 48 Adrenal cortex 244 Topic 49 Prostaglandins and inflammation: aspirin 246 Topic 50 Membrane transport 250 Topic 51 Nerve and muscle 255 Topic 52 pH homeostasis 258 Topic 53 Diagnostic markers: biochemical tests 261 Topic 54 Blood, bleeding and clotting 265 Section 6 Appendices 271 Appendix 1 pH and neutrality 273 Appendix 2 Crystallography 274 Appendix 3 Protein forces, secondary structure and folding 277 Appendix 4 Equilibrium constant 281 Appendix 5 Phosphorus, phosphoric acid and phosphate esters 283 Appendix 6 Coenzymes, cofactors and prosthetic groups 285 Appendix 7 Coenzyme A 287 Appendix 8 Krebs cycle and evidence for a catalytic reaction sequence 289 Appendix 9 Knoop’s experiment pointing to β-oxidation of fatty acids 291 Appendix 10 Isoenzymes 293 Appendix 11 Genetic code 295 Appendix 12 Different kinds of mutation 297 Appendix 13 Restriction enzymes 299 Appendix 14 Enzyme inhibition 301 Appendix 15 Electrophoresis to separate proteins 304 Appendix 16 Chromatography and mass spectrometry to separate and identify metabolites 308 Glossary 313 MCQ answers 322 Index 323

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Book SynopsisWith chapters provided by international leading experts, this book covers the recent advances in protein and peptide mass spectrometry.Trade Review"This book will be a valuable reference as it contains plenty of depth and substance to be of interest to experienced practitioners of mass spectrometry and related techniques, but is still accessible to pharmaceutical researchers who want to learn more about MS technologies and its applications." (American Society for Mass Spectrometry, 1 July 2012) Table of ContentsPREFACE xv CONTRIBUTORS xvii PART I METHODOLOGY 1 1 Ionization Methods in Protein Mass Spectrometry 3 Ismael Cotte-Rodriguez, Yun Zhang, Zhixin Miao, and Hao Chen 1.1 History of the Development of Protein Mass Spectrometry 4 1.2 Laser-Based Ionization Methods for Proteins 5 1.3 Spray-Based Ionization Methods for Proteins 13 1.4 Ambient Ionization Methods 20 1.5 Conclusions 30 Acknowledgments 30 References 30 2 Ion Activation and Mass Analysis in Protein Mass Spectrometry 43 Cheng Lin and Peter O’Connor 2.1 Introduction 43 2.2 Ion Activation and Tandem MS Analysis 46 2.3 Mass Analyzers 59 References 81 3 Target Proteins: Bottom-up and Top-down Proteomics 89 Michael Boyne and Ron Bose 3.1 Mass Spectral Approaches to Targeted Protein Identification 89 3.2 Bottom-up Proteomics 90 3.3 Top-down Approaches 96 3.4 Next-Generation Approaches 98 References 99 4 Quantitative Proteomics by Mass Spectrometry 101 Jacob Galan, Anton Iliuk, and W. Andy Tao 4.1 Introduction 101 4.2 In-Cell Labeling 105 4.3 Quantitation via Isotopic Labeling of Proteins 107 4.4 Quantitation via Isotopic Labeling on Peptides 112 4.5 Label-Free Quantitation 116 4.6 Conclusions 119 Acknowledgment 120 References 120 5 Comparative Proteomics by Direct Tissue Analysis Using Imaging Mass Spectrometry 129 Michelle L. Reyzer and Richard M. Caprioli 5.1 Introduction 129 5.2 Conventional Comparative Proteomics 130 5.3 Comparative Proteomics Using Imaging MS 131 5.4 Conclusions 136 Acknowledgments 137 References 137 6 Peptide and Protein Analysis Using Ion Mobility–Mass Spectrometry 139 Jeffrey R. Enders, Michal Kliman, Sevugarajan Sundarapandian, and John A. McLean 6.1 Ion Mobility–Mass Spectrometry: Instrumentation and Separation Selectivity 139 6.2 Characterizing and Interpreting Peptide and Protein Structures 147 6.3 Applications of IM-MS to Peptide and Protein Characterizations 152 6.4 Future Directions 158 Acknowledgments 159 References 160 7 Chemical Footprinting for Determining Protein Properties and Interactions 175 Sandra A. Kerfoot and Michael L. Gross 7.1 Introduction to Hydrogen–Deuterium Exchange 175 7.2 Experimental Procedures 178 7.3 Mass Spectrometry-Based HDX in Practice 182 7.4 Protein Footprinting via Free-Radical Oxidation 193 7.5 Chemical Crosslinking 198 7.6 Selective and Irreversible Chemical Modification 201 7.7 Conclusion 205 References 206 8 Microwave Technology to Accelerate Protein Analysis 213 Urooj A. Mirza, Birendra N. Pramanik, and Ajay K. Bose 8.1 Introduction 213 8.2 Microwave Technology 215 8.3 Summary 224 Acknowledgments 224 References 224 9 Bioinformatics and Database Searching 231 Surendra Dasari and David L. Tabb 9.1 Overview 231 9.2 Introduction to Tandem Mass Spectrometry 231 9.3 Overview of Peptide Identification with Database Searching 234 9.4 MyriMatch-IDPicker Protein Identification Pipeline 235 9.5 Results of a Shotgun Proteomics Study 246 9.6 Improvements to MyriMatch Database Search Engine 248 9.7 Applications of MyriMatch-IDPicker Pipeline 250 9.8 Conclusions 251 Acknowledgments 251 References 251 PART II Applications 253 10 Mass Spectrometry-Based Screening and Characterization of Protein–Ligand Complexes in Drug Discovery 255 Christine L. Andrews, Michael R. Ziebell, Elliott Nickbarg, and Xianshu Yang 10.1 Introduction 255 10.2 Affinity Selection Mass Spectrometry (AS-MS) 256 10.3 Solution-Based AS-MS as Screening Technologies 258 10.4 Gas-Phase Interactions 267 10.5 Enzyme Activity Assays Using MS for Screening or Confirming Drug Candidates 271 10.6 Conclusions and Future Directions 276 References 277 11 Utilization of Mass Spectrometry for the Structural Characterization of Biopharmaceutical Protein Products 287 Amareth Lim and Catherine A. Srebalus Barnes 11.1 Introduction 287 11.2 MS-Based Approach for the Characterization of Recombinant Therapeutic Proteins 288 11.3 Cell Culture Development 290 11.4 Purification Development 294 11.5 Formulation Development 300 11.6 Analytical Method Development 304 11.7 Confirmation of Structure/Product Comparability Assessment 311 11.8 Conclusions 313 Acknowledgments 315 References 315 12 Post-translationally Modified Proteins: Glycosylation, Phosphorylation, and Disulfide Bond Formation 321 Anthony Tsarbopoulos and Fotini N. Bazoti 12.1 Introduction 321 12.2 Glycosylation 322 12.3 Phosphorylation 338 12.4 Disulfide Bond Detection and Mapping 347 12.5 Future Perspectives 350 Acknowledgments 352 Abbreviations 353 References 354 13 Mass Spectrometry of Antigenic Peptides 371 Henry Rohrs 13.1 Introduction 371 13.2 Analysis of Antigenic Peptides 374 13.3 Examples of the Application of Mass Spectrometry to Antigenic Peptide Study 381 13.4 Future Work 385 Acknowledgments 386 Abbreviations 387 References 387 14 Neuropeptidomics 393 Jonathan V. Sweedler, Fang Xie, and Adriana Bora 14.1 Introduction 393 14.2 Neuropeptidomics: Characterizing Peptides in the Brain 394 14.3 Sample Preparation for Mass Spectrometry 395 14.4 Separations 405 14.5 Peptide Characterization via Mass Spectrometry 407 14.6 Conclusions 419 14.7 Future Perspectives 419 Acknowledgments 420 References 420 15 Mass Spectrometry for the Study of Peptide Drug Metabolism 435 Patrick J. Rudewicz 15.1 Introduction 435 15.2 Peptide Drug Metabolism 436 15.3 LC-MS/MS for Metabolite Identification 437 15.4 Quantitative Analysis 439 15.5 Case Study: IL-1b Protease Inhibitors 440 15.6 Future Directions 445 References 445 INDEX 449

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Book SynopsisThis book presents a clear and precise discussion of the biochemistry of eukaryotic cells, particularly those of mammalian tissues, relates biochemical events at a cellular level to the subsequent physiological processes in the whole animal, and cites examples of abnormal biochemical processes in human disease.Table of ContentsPART I STRUCTURE OF MACROMOLECULES. Chapter 1 Eukaryotic Cell Structure (Thomas M. Devlin). Chapter 2 DNA and RNA: Composition and Structure (Stephen A. Woski and Francis J. Schmidt). Chapter 3 Proteins I: Composition and Structure (Richard M. Schultz). PART II TRANSMISSION OF INFORMATION Chapter 4 DNA Replication, Recombination, and Repair (Howard J. Edenberg). Chapter 5 RNA: Transcription and RNA Processing (Frank J. Schmidt and David R. Setzer). Chapter 6 Protein Synthesis: Translation and Posttranslational Modifications (Dohn Glitz). Chapter 7 Recombinant DNA and Biotechnology (Gerald Soslau). Chapter 8 Regulation of Gene Expression (Daniel L. Weeks and John E. Donelson). PART III FUNCTIONS OF PROTEINS. Chapter 9 Proteins II: Structure-Function Relationships in Protein Families (Richard M. Schultz). Chapter 10 Enzymes: Classification, Kinetics, and Control (Henry Weiner). Chapter 11 The Cytochromes P450 and Nitric Oxide Synthases (Linda J. Roman and Bettie Sue Siler Masters). Chapter 12 Biological Membranes: Structure, Receptors, and Solute Transport (Thomas M. Devlin). Chapter 13: Fundamentals of Signal Transduction (George R. Dubyak). PART IV METABOLIC PATHWAYS AND THEIR CONTROL. Chapter 14 Bioenergetics, Mitochondria, and Oxidative Metabolism (Diana S. Beattie). Chapter 15 Carbohydrate Metabolism I: Major Metabolic Pathways and Their Control (Robert A. Harris). Chapter 16 Carbohydrate Metabolism II: Special Pathways and Glycoconjugates (Nancy B Schwartz). Chapter 17 Lipid Metabolism I: Synthesis, Storage, and Utilization of Fatty Acids and Triacylglycerols (Martin D. Snider, J. Denis McGarry, and Richard W. Hanson). Chapter 18 Lipid Metabolism II: Pathways of Metabolism of Special Lipids (Robert H. Glew). Chapter 19 Amino Acid and Heme Metabolism (Marguerite W. Coomes). Chapter 20 Purine and Pyrimidine Nucleotide Metabolism (Joseph G. Cory and Ann H. Cory). Chapter 21 Metabolic Interrelationships (Robert A. Harris and David W. Crabb). Chapter 22 Biochemistry of Hormones (Thomas J. Schmidt). PART V PHYSIOLOGICAL PROCESSES Chapter 23 Molecular Cell Biology (Thomas E. Smith). Chapter 24 Cell Cycle, Programmed Cell Death and Cancer (Richard M. Schultz). Chapter 25 Digestion and Absorption of Basic Nutritional Constituents (Ulrich Hopfer). Chapter 26 Vitamins and Minerals: Requirements and Function (Stephen G. Chaney). Chapter 27 Macronutrients: Metabolic Effects and Health Implications (Stephen G. Chaney). Appendix: Review of Organic Chemistry (Carol N. Angstadt). Glossary (Francis Vella). Index.

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

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Book 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 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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