Chemical biology Books

Book SynopsisVery Short Introductions: Brilliant, Sharp, Inspiring From the simplest bacteria to humans, all living things are composed of cells of one type or another, all of which have fundamentally the same chemistry. This chemistry must provide mechanisms that allow cells to interact with the external world, a means to power the cell, machinery to carry out varied processes within the cell, a structure within which everything runs, and also governance through a web of interlocking chemical reactions. Biochemistry is the study of those reactions, the molecules that are created, manipulated, and destroyed as a result of them, and the massive macromolecules (such as DNA, cytoskeletons, proteins and carbohydrates) that form the chemical machinery and structures on which these biochemical reactions take place. It didn''t take long for an understanding of the chemistry of life to turn into a desire to manipulate it. Drugs and therapies all aim to modify biochemical processes for good or ill: Penicillin, derived from mould, stops bacteria making their cell walls. Aspirin, with its origins in willow bark, inhibits enzymes involved in inflammatory responses. A few nanograms of botulinum toxin (botox), can kill by preventing the release of neurotransmitters from the ends of nerves and so leads to paralysis and death, or give a wrinkle free forehead (if administered in very tiny quantities).This Very Short Introduction discusses the key concepts of biochemistry, as well as the historical figures in the field and the molecules they studied, before considering the current science and innovations in the field, and the interaction between biochemistry, biotechnology, and synthetic biology. ABOUT THE SERIES: The Very Short Introductions series from Oxford University Press contains hundreds of titles in almost every subject area. These pocket-sized books are the perfect way to get ahead in a new subject quickly. Our expert authors combine facts, analysis, perspective, new ideas, and enthusiasm to make interesting and challenging topics highly readable.Table of ContentsPreface 1: The roots of biochemistry 2: Water, lipids and carbohydrates 3: Proteins: Nature's nano-machines 4: Nucleic acids: Life's blueprints 5: Powering a cell: Bioenergetics 6: Manufacturing and maintaining DNA 7: Following biochemistry within the cell 8: Biotechnology and synthetic biology Further reading References

Read more less

Book SynopsisA balanced presentation of the concepts of physical chemistry, and their applications to biology and biochemistry. Written to straddle the worlds of physical chemistry and the life sciences, it shows how the tools of physical chemistry can elucidate biological questions.Table of ContentsFocus 1: Biochemical Thermodynamics: The First Law Focus 2: Biochemical Thermodynamics: The Second Law Focus 3: Water and Aqueous solutions Focus 4: Chemical equilibrium Focus 5: Ion and Electron Transport Focus 6: The Rates of Reactions Focus 7: Biochemical kinetics Focus 8: Atoms Focus 9: Molecules Focus 10: Macromolecules and self-assembly Focus 11: Biochemical spectroscopy Focus 12: Scattering techniques Focus 13: Gravimetric methods

Read more less

Book SynopsisSynthetic biology is the technique that enables us not just to read and edit but also write DNA to program living biological structures as though they were tiny computers. Unlike cloning Dolly the sheep-which cut and copied existing genetic material-the future of synthetic biology might be something like an app store, where you could download and add new capabilities into any cell, microbe, plant, or animal.This breakthrough science has the potential to mitigate, perhaps solve, humanity's immediate and longer-term existential challenges: climate change; the feeding, clothing, housing, and caring for billions of humans; fighting the next viral outbreak before it becomes a global pandemic; old age as a treatable pathology; bringing back extinct animals.It could also be anarchic and socially destructive. With our governing structures created in an era before startling advances in technology, we are not prepared for a future in which life could be manipulated or programmed.As futurist Amy Webb and synthetic biologist Andrew Hessel show in this book, within the next decade, we will need to make important decisions: whether to program novel viruses to fight diseases, what genetic privacy will look like, who will "own" living organisms, how companies should earn revenue from engineered cells, and how to contain a synthetic organism in a lab. The Genesis Machine? provides the background for us to understand and grapple with these issues, and think through the religious, philosophical, and ethical implications for the future.

Read more less

Book SynopsisAuthored by leading experts in the enzymology of natural product biosynthesis, this completely revised and updated edition provides a description of the types of natural products, the biosynthetic pathways that enable the production of these molecules, and an update on the discovery of novel products in the post-genomic era. Although some 500 000 – 600 000 natural products have been isolated and characterized over the past two centuries, there may be a 10-fold greater inventory awaiting immediate exploration based on biosynthetic gene cluster predictions. The approach of this book is to codify the chemical logic that underlies each natural product structural class as they are assembled from building blocks of primary metabolism. This second edition integrates many new findings into the sets of principles of the first edition that parsed categories of natural product chemistries into the underlying enzymatic mechanisms and the catalytic machinery for building the varied and complex end product metabolites. New chapters include evaluation of a core set of thermodynamically activated but kinetically stable metabolites that power both primary and secondary metabolic pathways. Also, after decades of uncertainty about the existence of various pericyclase classes, a series of genome mining, heterologous expression, and enzymatic activity characterization have validated a plethora of pericyclases over the past decade. The several types of pericyclases are involved in biosynthetic complexity generation of almost every major category of natural products. This text will serve as a reference point for chemists of every subdiscipline, including synthetic organic chemists and medicinal chemists. It will also be valuable to bioinformatic and computational biologists, pharmacognocists and chemical ecologists, and bioengineers and synthetic biologists.Table of ContentsMajor Classes of Natural Product Scaffolds and Enzymatic Biosynthetic Machinery; The Chemical Logic for Major Reaction Types; Polyketide Natural Products; Peptide Natural Products I: RiPPs; Peptide Natural Products II: Nonribosomal Peptides; Isoprenoids/Terpenes; Alkaloids I; Purine- and Pyrimidine-derived Natural Products; Phenylpropanoid Natural Product Biosynthesis; Alkaloids II: Indole Terpenes; Natural Product Oligosaccharides and Glycosides; Oxygenases, Thwarted Oxygenases, and Oxygen-dependent Halogenases; S-Adenosylmethionine; Pericyclases in Natural Product Biosynthesis; Natural Products Isolation and Characterization: Gene-independent Approaches; Natural Products in the Post Genomic Era

Read more less

Book SynopsisA concise and authoritative introduction to scanning electron microscopy in the biological sciences In A Practical Guide to Scanning Electron Microscopy distinguished electron microscopist Gerhard Wanner delivers a practical handbook for biological scientists working with microbial, plant, and animal cells and tissues, enabling them to successfully apply scanning electron microscopy (SEM) to their object of study. The book begins with an introduction to the principles of electron microscopy and the operation of electron microscopes before moving on to describe the preparation and mounting of specimens. It also explores the process of recoding images and their subsequent analysis, along with a wide range of advanced microscopy techniques, including cryo-SEM, FIB-SEM tomography, and stereo-SEM. Scanning Electron Microscopy in the Biosciences contains hundreds of carefully selected microscopic images, as well as hands-on, step-by-step guidance required to perform a successful TEM experiment. Readers will also find: Thorough introductions to optics, electron microscopy, electrons, and the components of electron microscopes In-depth examinations of the preparation of biological specimens and specimen mounting for scanning electron microscopy A comparison of different SEM modes and their strengths and weaknesses An introduction to novel techniques such as correlative light and electron microscopy (CLEM), array tomography, and cryo-scanning electron microscopy Perfect for cell biologists and microbiologists, A Practical Guide to Scanning Electron Microscopy in the Biosciences also belongs in the libraries of neurobiologists and biophysicists.Table of ContentsIntroduction Optics Electron Microscopy The Electrons Components of the Electron Microscope Preparation of Biological Specimens Specimen Mounting for SEM Microscopy Resolution Analytics X-Rays FIB/SEM Serial Block Face SEM Array Tomography Cryo-SEM VP-SEM Stereo-SEM

Read more less

Book SynopsisEcotoxicology offers a comprehensive overview of the science underpinning the recognition and management of environmental contamination. It describes the toxicology of environmental contaminants, the methods used for assessing their toxicity and ecological impacts, and approaches employed to mitigate pollution and ecological health risks globally. Chapters cover the latest advances in research, including genomics, natural toxins, endocrine disruption and the toxicology of radioactive substances. The second half of the book focuses on applications, such as cradle-to-grave effects of selected industries, legal and economic approaches to environmental regulation, ecological risk assessment, and contaminated site remediation. With short capsules written by invited experts, numerous case studies from around the world and further reading lists, this textbook is designed for advanced undergraduate and graduate one-semester courses. It is also a valuable reference for graduate students and professionals. Online resources for instructors and students are also available.Table of ContentsPreamble; Preface; Part I. Approaches and Methods: 1. The history and emergence of ecotoxicology as a science Pamela Welbourn and Peter V. Hodson; 2. Measuring toxicity Peter V. Hodson and David A. Wright; 3. Contaminant uptake and bioaccumulation: mechanisms, kinetics and modelling Peter G. C. Campbell, Peter V. Hodson, Pamela M. Welbourn, David A. Wright; 4. Methods in ecotoxicology Peter. V. Hodson and David W. Wright; 5 Ecotoxicogenomics Valérie S. Langlois and Christopher J. Martyniuk; Part II. Toxicology of Individual Substances: 6. Metals and metalloids Peter G. C. Campbell, Pamela M. Welbourn and Christopher D. Metcalfe; 7. Organic compounds Christopher D. Metcalfe, David A. Wright, Peter V. Hodson; 8. Endocrine disrupting chemicals Christopher D. Metcalfe, Christopher J. Martyniuk, Valérie S. Langlois, and David A. Wright; 9. Natural toxins David A. Wright and Pamela M. Welbourn; 10. Ionising radiation Louise Winn; Part III. Complex Issues: 11. Complex issues, multiple stressors and lessons learned Pamela M. Welbourn, Peter G. C. Campbell, Peter V. Hodson and Christopher D. Metcalfe) 12. Regulatory toxicology and ecological risk assessment Peter V. Hodson, Pamela Welbourn and Peter G. C. Campbell; 13. Recovery of contaminated sites Pamela M. Welbourn and Peter V. Hodson; 14. Emerging concerns and future visions David A. Wright and Peter G. C. Campbell; Index.

Read more less

Book SynopsisScience can do much good for mankind or can cause a catastrophe for mankind if it is handled by terrorists, (even aircraft can be turned into weapons of destruction as we have seen on September 11 2001 in New York City and Washington DC) This volume deals with science for the sake of mankind. Chemical physics, which combines chemistry and physics, and biochemical physics, which combines chemistry, physics and biology, have been developing quite radically recently. This holds true for pure and applied science as well. Some examples of such success are given in this book. Included in this volume are papers from Russian scientists, scientists from the republics of the former USSR and papers from scientists in western countries.

Read more less

Book SynopsisAmino acid receptors and cell surface proteins that bind amino acids and trigger changes which influence the behaviour of cells. Glutamate receptors are the most common receptors for fast excitatory synaptic transmission in the vertebrate central nervous system, and GAMMA-AMINOBUTYRIC ACID and glycine receptors are the most common receptors for fast inhibition. This book presents the latest research in the field.

Read more less

Book SynopsisThe modern synthetic chemist applies all the tools available to identify the drug-like molecules with the best chances of becoming novel drugs. This book will act as a primer for graduates and postgraduates interested in a career in drug discovery. It covers both synthetic technologies currently impacting medicinal chemistry and emerging areas. The chapters focus on topics including: parallel medicinal chemistry; solid supported reagents; microwave assisted chemistry; flow synthesis, and high throughput reaction screening.Trade Review" Elizabeth Farrant, a very experienced medicinal chemist, has collected six chapters written by experts in the field to create the book "New Synthetic Technologies in Medicinal Chemistry" ""...is well suited as an introductory course in to current trends of developing and employing enabling technologies in synthetic medicinal chemistry." * ChemMedChem 2012, 7, 1295 - 1298, Prof. Andreas Kirchning, *Table of ContentsIntroduction; Parallel Medicinal Chemistry; Solid Supported Reagents; Microwave Assisted Chemistry; Flow Synthesis; High Throughput Reaction Screening; Emerging Technologies

Read more less

Book SynopsisComplex carbohydrates such as high molecular weight polysaccharides like starch and cellulose, are well known for their importance in foodstuffs, paper and wood, but their importance extends far beyond that into the biopharmaceutical, healthcare, oil and printing industries. This book, based on a discussion meeting organised by RSC Biotechnology and Carbohydrate Groups, brings together leading experts from the polysaccharide and glycoconjugate communities to review, discuss and assess in detail one specific topic, namely the importance of the stability and degradation of carbohydrate structures. Coverage includes applications as diverse as food, biopharmaceuticals, vaccines, biofuels and preservation of Viking boats. Providing essential reading for anyone interested in these structures and the diversity of their applications, it will appeal to a broad, multidisciplinary group from industry, academia and research institutions.Table of ContentsCarbohydrates: First cousins of Water; Enzymic degradation of cell wall polysaccharides; Dietary Fibre: Functional Components and Mechanisms of Action in the Gastrointestinal Tract; Enzymatic treatment of polysaccharides; Stability of polysaccharide encapsulates; Polysaccharide and glycoconjugate vaccines; Mucin turnover; Some advances in hydrodynamic stability probes; Stability of chitosan and pectin as nasal and intestinal mucoadhesives; Cellulose crystallinity: perspectives from spectroscopy and diffraction; Cellulose; Cellulose de-construction: what can be learned from molecular modeling and dissolution experiments?; Lignin; Observations on bacterial degradation of historical wood timbers found in near anaerobic waterlogged environments; Subject Index

Read more less

a huge range and FREE tracked UK delivery on ALL orders.

Read more less

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

Read more less

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

Read more less

Book SynopsisProtein Homeostasis in Drug Discovery Comprehensive resource on all aspects of protein homeostasis, covering both historical perspectives and emerging technologies that are revolutionizing the field Protein Homeostasis in Drug Discovery highlights drug discovery and development efforts targeting protein homeostasis and considers the emerging appreciation that a protein's activity may not be the only factor to consider when developing therapeutic agents. The chapters cover various aspects of protein homeostasis such as cellular localization, abundance, interactions, and more. Moreover, the text contains up-to-date information regarding targeted protein degradation, an emerging drug discovery modality. Readers interested in targeting different regulatory events that control protein homeostasis or modulating protein abundance will find this book an excellent resource. Furthermore, those interested in the link between biological function and regulating prTable of ContentsList of Contributors ix Preface xv Section I Protein Folding and Quality Control in Drug Discovery 1 1 Epichaperomes as a Gateway to Understanding, Diagnosing, and Treating Disease Through Rebalancing Protein–Protein Interaction Networks 3Chander S. Digwal, Sahil Sharma, Anand R. Santhaseela, Stephen D. Ginsberg, and Gabriela Chiosis 2 Stability of Steroid Hormone Receptors: The Intersection of Proteostasis and Selective Degradation 27Zachary J. Gale-Day and Jason E. Gestwicki 3 Pharmacological Chaperones: Therapeutic Potential for Diseases Resulting from GPCR Misfolding 65Suli-Anne Laurin, Sajjad Ahrari, and Michel Bouvier Section II Protein Degradation and Clearance as Drug Targeting Opportunities 135 4 Exploiting the Proteasome for Disease Treatment: From Dynamic Architecture to Vast Functions 137Gwen R. Buel, Xiuxiu Lu, and Kylie J. Walters 5 Targeting the Ubiquitination Cascade for Drug Discovery 179Qi Liu, Gabriel LaPlante, and Wei Zhang 6 Understanding, Targeting, and Hijacking Autophagy 227Hongguang Xia, Xiaoyan Xu, Mengxin Zhou, Manke Zhang, and Lingzhi Ye 7 Deubiquitinating Enzymes: From Undruggable Targets to Emerging Opportunities 249Xiaoxi Liu, Laura Doherty, Alejandra Felix, and Sara Buhrlage Section III Redirecting Protein Degradation Processes for Drug Development 283 8 History of IMiDs and Protein Degradation as a Pharmacological Modality 285Junichi Yamamoto, Tomoko Asatsuma-Okumura, Takumi Ito, Yuki Yamaguchi, and Hiroshi Handa 9 PROTAC Degraders: Mechanism, Recent Advances, and Future Challenges 317Alessio Ciulli and Oliver Hsia 10 Biochemical Principles of Targeted Protein Degradation 357Roman V. Agafonov, Richard W. Deibler, William A. Elam, Joe S. Patel, and Stewart L. Fisher 11 Pharmacology of PROTAC Degrader Molecules: Optimizing for In Vivo Performance 385Andy Pike, Sofia Guzzetti, Pablo M. Morentin Gutierrez, and James S. Scott Section IV Emerging Technologies and Future Opportunities 419 12 Proximity-Inducing Bifunctional Molecules Beyond PROTACs 421Sophia Lai, Ashley E. Modell, and Amit Choudhary 13 Strategies for Tag-Based Protein Control 447Behnam Nabet, Nathanael S. Gray, and Fleur M. Ferguson 14 Targeted Protein Degradation in Antiviral Drug Discovery 465Mélissanne de Wispelaere and Priscilla L. Yang 15 Beyond Inhibition: Ligand-Based Pharmacological Exploration as a Strategy Toward New Targets and Modalities 491Milka Kostic and Lyn H. Jones Index 519

Read more less

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

Read more less

Book SynopsisTable of ContentsPreface xvii About the Authors xix Part I Introduction to Viruses 1 1 Overview of Molecular Biology 3 Contributing Author: Sarah Forster 1.1 Cell Basics 4 1.1.1 Cytoplasm 5 1.1.2 Ribosomes 5 1.1.3 Nucleus 6 1.2 Cell Replication 6 1.2.1 Nucleic Acids 6 1.2.2 DNA Replication 7 1.2.3 RNA Structure and Role 9 1.2.4 Protein Synthesis 9 1.3 Cellular Transport 11 1.3.1 Plasma Membrane 11 1.3.2 Cell Signaling 11 1.4 Immune Defense 12 1.4.1 Innate Immunity 12 1.4.2 Adaptive Immunity 13 1.4.2.1 Humoral Immunity 13 1.4.2.2 Cellular Immunity 14 1.5 Applications 14 1.6 Chapter Summary 16 1.7 Problems 16 References 16 2 Basics of Virology 19 2.1 Viral Basics and Terminology 19 2.2 Viral Life Cycle 21 2.2.1 Attachment (Connection) 21 2.2.2 Penetration (Entry) 22 2.2.3 Uncoating 22 2.2.4 Replication 23 2.2.5 Assembly 23 2.2.6 Maturation and Release 23 2.3 Virus Structure and Classification 24 2.3.1 DNA Viruses 25 2.3.2 RNA Viruses 25 2.3.3 Reverse Transcription Viruses (Retroviruses) 27 2.4 Viruses in Context of the Tree of Life 27 2.5 Viral Genetics 28 2.5.1 Antigenic Shift 28 2.5.2 Antigenic Drift 29 2.5.3 Phenotypic Mixing 29 2.5.4 Complementation 29 2.6 Applications 29 2.7 Chapter Summary 31 2.8 Problems 31 References 32 3 Pandemics, Epidemics, and Outbreaks 33 3.1 Human Viral Diseases 34 3.2 Ebola and Marburg Viruses 35 3.2.1 Symptoms 36 3.2.2 Diagnosis 37 3.2.3 Prevention and Treatment 37 3.3 Human Immunodeficiency Disease (HIV) 38 3.3.1 HIV Symptoms 39 3.3.1.1 Stage 1: Acute Infection 39 3.3.1.2 Stage 2: Chronic HIV Infection (Latent Phase) 39 3.3.1.3 Stage 3: Acquired Immunodeficiency Syndrome (AIDS) 39 3.3.2 Diagnosis 40 3.3.3 HIV Prevention and Treatment 40 3.4 Influenza 41 3.4.1 Influenza Symptoms 41 3.4.2 Influenza Diagnosis 42 3.4.3 Influenza Prevention and Treatment 42 3.4.4 Influenza Pandemics 43 3.5 Coronaviruses 44 3.5.1 Symptoms 45 3.5.1.1 Typical Acute Symptoms 45 3.5.1.2 Post-COVID Conditions 46 3.5.1.3 COVID-19 Multiorgan System Effects (MIS) 46 3.5.2 COVID-19 Diagnosis 47 3.5.3 COVID-19 Prevention and treatment 48 3.6 Current and Emerging Viral Threats 48 3.7 Applications 51 3.8 Chapter Summary 52 3.9 Problems 53 References 53 4 Virus Prevention, Diagnosis, and Treatment 57 4.1 Vaccination Successes and Challenges 58 4.2 Current Vaccine Technology 59 4.2.1 Live-attenuated vaccines 60 4.2.2 Inactivated vaccines 61 4.2.3 Recombinant Subunit Vaccines 61 4.2.4 Viral Vector Vaccines 62 4.2.5 Messenger RNA (mRNA) Vaccines 62 4.3 U.S.-Approved Vaccines and Requirements 63 4.3.1 Commercially Available Viral Vaccines 63 4.3.2 Vaccination Requirements 63 4.4 Viral Testing and Diagnosis 64 4.4.1 Viral Testing 65 4.4.2 Antibody Testing 66 4.5 Antiviral Treatment Options 66 4.5.1 HIV 67 4.5.1.1 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) 67 4.5.1.2 Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 67 4.5.1.3 Protease Inhibitors (PIs) 67 4.5.1.4 Fusion Inhibitors (FIs) 67 4.5.1.5 Integrase Strand Transfer Inhibitors (INSTIs) 67 4.5.1.6 CCR5 Antagonists 67 4.5.1.7 Attachment Inhibitors 68 4.5.1.8 Post-Attachment Inhibitors 68 4.5.1.9 Pharmacokinetic Enhancers 68 4.5.2 Influenza 68 4.5.3 Hepatitis C virus (HCV) 68 4.5.4 Other Treatment Options 69 4.6 Applications 70 4.7 Chapter Summary 71 4.8 Problems 72 References 72 5 Safety Protocols and Personal Protection Equipment 75 Contributing Author: Emma Parente 5.1 Regulations and Oversight of Safety Protocols 76 5.2 Protective and Safety Systems 76 5.2.1 Personal Protective Devices and Practices 76 5.2.2 Antimicrobial Suppression And Eradication 77 5.3 Disinfection Categories and Procedures 78 5.4 Occupational Health and Safety Administration Hazmat Regulations 79 5.4.1 HAZMAT Level A Protection 80 5.4.2 HAZMAT Level B Protection 81 5.4.3 Level C Protection 82 5.4.4 Level D Protection 83 5.5 Bio Level Safety and Security 83 5.6 COVID-Related Safety Precautions 84 5.6.1 Personal Protective Equipment 84 5.6.2 Transmission Control 85 5.7 Applications 85 5.8 Summary 87 5.9 Problems 87 References 88 6 Epidemiology and Virus Transmission 91 6.1 Overview of Epidemiology 92 6.2 Government Agencies’ Contributions to Public Health 94 6.2.1 The Role of the Centers for Disease Control and Prevention (CDC) 94 6.2.2 The World Health Organization (WHO): Successes and Challenges 95 6.3 Epidemiologic Study Design 96 6.3.1 Outbreak Case Example 98 6.3.2 Clinical Trials 99 6.4 Virus Transmission 100 6.4.1 Modes of Transmission 101 6.5 Applications 102 6.6 Chapter Summary 104 6.7 Problems 105 References 105 Part II Practical and Technical Considerations 109 7 Engineering Principles and Fundamentals 111 Contributing Author: Vishal Bhatty 7.1 History of Engineering 112 7.2 Problem Solving: The Engineering Approach 113 7.2.1 Problem-Solving Methodology 114 7.2.2 Engineering and Scientific Sources 115 7.3 Units and Conversion Constants 115 7.3.1 The Metric System 115 7.3.2 The SI System 117 7.4 Dimensional Analysis 117 7.5 Process Variables 119 7.6 The Conservation Laws 121 7.7 Thermodynamics and Kinetics 125 7.8 Applications 126 7.9 Chapter Summary 130 7.10 Problems 130 References 131 8 Legal and Regulatory Considerations 133 8.1 The Regulatory System 134 8.1.1 Laws, Regulations, Plans and policy: The Differences 135 8.1.2 Policies and Plans 137 8.2 The Role of Individual States 138 8.3 Key Government Agencies 140 8.3.1 Environmental Protection Agency (EPA) 140 8.3.2 Centers for Disease Control and Prevention (CDC) 141 8.3.3 Food and Drug Administration (FDA) 141 8.3.4 Occupational Health and Safety Administration (OSHA) 141 8.3.5 Legal Considerations during a Public Health Crisis 142 8.4 Public Health Emergency Declarations 143 8.5 Key Environmental Acts 145 8.6 The Clean Air Act 145 8.7 Regulation of Toxic Substances 147 8.7.1 Toxic Water Pollutants: Control and Classification 150 8.7.2 Drinking Water 150 8.7.3 Surface Water Treatment Rules (SWTR) 151 8.8 Regulations Governing Infectious Diseases 153 8.8.1 Vaccination Laws 155 8.8.2 State Healthcare Worker and Patient Vaccination Laws 155 8.8.3 State-Mandated Childhood Vaccinations 155 8.9 Applications 155 8.10 Chapter Summary 159 8.11 Problems 159 References 160 9 Emergency Planning and Response 163 9.1 The Importance of Emergency Planning and Response 164 9.2 Planning for Emergencies 166 9.2.1 Preparedness Training 166 9.3 Plan Implementation 167 9.3.1 Notification of Public and Regulatory Officials 168 9.4 EP&R for Epidemics and Pandemics 169 9.4.1 Federal Public Health and Medical Emergency Preparedness 170 9.4.2 Emergency Operations Center 170 9.4.3 Disease Containment 172 9.4.4 Public Notification of Pandemic Quarantines and Lockdowns 173 9.4.5 The National Strategy for Pandemic Influenza (NSPI) 173 9.5 EP&R for Industrial Accidents 174 9.5.1 Emergency Planning and Community Right-to-Know Act (epcra) 175 9.5.2 The Planning Committee 177 9.6 EP&R for Natural Disasters 179 9.7 Current and Future Trends 181 9.8 Applications 181 9.9 Chapter Summary 184 9.10 Problems 184 References 185 10 Ethical Considerations within Virology 189 Contributing Author: Paul DiGaetano, Jr. 10.1 Core Ethics Principles 190 10.2 Important Tenets of Ethical Research 191 10.2.1 Conducting Research During a Health Crisis 192 10.2.2 Scientific Cooperation During a Health Crisis 192 10.2.3 Fair and Ethical Study Design and Implementation 193 10.3 Ethical Dilemmas in Public Health 193 10.3.1 Public Health Surveillance 193 10.3.2 Ethical Evaluation of Nonpharmaceutical Interventions 195 10.3.3 Ethical Consideration Involving Restrictions of Movement 197 10.4 Ethical Considerations Regarding Medical Interventions 199 10.4.1 Emergency Use Of Medical Interventions 200 10.5 Applications 201 10.6 Chapter Summary 202 10.7 Problems 203 References 203 11 Health and Hazard Risk Assessment 205 11.1 Introduction to Risk Assessment 207 11.2 The Health Risk Assessment Process 209 11.3 Dose–Response Assessment 211 11.4 The Hazard Risk Assessment Process 213 11.5 Hazard Risk Versus Health Risk 214 11.5.1 Health Risk Assessment (HRA) Example 215 11.5.2 Hazard Risk Assessment (HRZA) Example 215 11.6 COVID-19 Pandemic Hazard Risk 216 11.7 The Uncertainty Factor 217 11.8 Applications 218 11.9 Chapter Summary 220 11.10 Problems 220 References 221 Part III Engineering Considerations 223 12 Introduction to Mathematical Methods 225 Contributing Author: Julian Theodore 12.1 Differentiation 226 12.2 Integration 228 12.2.1 The Trapezoidal Rule 228 12.2.2 Simpson’s Rule 229 12.3 Simultaneous Linear Algebraic Equations 230 12.3.1 Gauss–Jordan Reduction 231 12.3.2 Gauss Elimination 232 12.3.3 Gauss–Seidel Approach 232 12.4 Nonlinear Algebraic Equations 233 12.5 Ordinary Differential Equations 234 12.6 Partial Differential Equations 237 12.7 Applications 237 12.8 Chapter Summary 240 12.9 Problems 240 References 241 13 Probability and Statistical Principles 243 13.1 Probability Definitions and Interpretations 244 13.2 Introduction to Probability Distributions 246 13.3 Discrete Probability Distributions 247 13.3.1 The Binomial Distribution 248 13.3.2 Multinomial Distribution 248 13.3.3 Hypergeometric Distribution 249 13.3.4 Poisson Distribution 250 13.4 Continuous Probability Distributions 250 13.4.1 Measures of Central Tendency and Scatter 251 13.4.2 The Normal Distribution 252 13.4.3 The Lognormal Distribution 256 13.4.4 The Exponential Distribution 257 13.4.5 The Weibull Distribution 258 13.5 Contemporary Statistics 259 13.5.1 Confidence Intervals for Means 260 13.5.2 Confidence Intervals for Proportions 260 13.5.3 Hypothesis Testing 261 13.5.4 Hypothesis Test for Means and Proportions 261 13.5.5 The F Distribution 262 13.5.6 Analysis of Variance (ANOVA) 262 13.5.7 Nonparametric Tests 264 13.6 Applications 264 13.7 Chapter Summary 268 13.8 Problems 268 References 269 14 Linear Regression 271 14.1 Rectangular Coordinates 272 14.2 Logarithmic Coordinates 273 14.3 Methods of Plotting Data 275 14.4 Scatter Diagrams 275 14.5 Curve Fitting 278 14.6 Method of Least Squares 280 14.7 Applications 284 14.8 Chapter Summary 287 14.9 Problems 288 References 288 15 Ventilation 289 15.1 Introduction to Industrial Ventilation Systems 290 15.2 Components of Ventilation Systems 291 15.3 Fans, Valves and Fittings, and Ductwork 293 15.3.1 Fans 293 15.3.2 Valves and Fittings 295 15.4 Selecting Ventilation Systems 296 15.5 Key Process Equations 298 15.5.1 Regarding Friction Losses 299 15.6 Ventilation Models 300 15.7 Model Limitations 302 15.8 Infection Control Implications 303 15.9 Applications 305 15.10 Chapter Summary 309 15.11 Problems 310 References 310 16 Pandemic Health Data Modeling 313 16.1 COVID-19: A Rude Awakening 315 16.2 Earlier Work 316 16.3 Planning for Pandemics 318 16.4 Generating Mathematical Models 319 16.5 Pandemic Health Data Models 324 16.6 In Review 329 16.7 Applications 331 16.8 Chapter Summary 338 16.9 Problems 338 References 339 17 Optimization Procedures 341 17.1 The History of Optimization 342 17.2 The Scope of Optimization 344 17.3 Conventional Optimization Procedures 346 17.4 Analytical Fomulation of the Optimum 347 17.5 Contemporary Optimization: Concepts in Linear Programming 350 17.6 Applied Concepts in Linear Programming 351 17.7 Applications 355 17.8 Chapter Summary 357 17.9 Problems 358 References 359 Index 361

Read more less

Book SynopsisParasitic Infections Understand and defeat a scourge of public health with this cutting-edge guide Parasitic diseases are considered as an important public health problem due to the high morbidity and mortality rates, particularly in countries where climate and level of economic development create serious challenges to the creation of public health infrastructure, thus can make parasitic infections both graver and more difficult to contain. As we come to understand the global ramifications of public health, there has never been a more crucial time to understand these infections and the processes by which they can be managed and defeated. Parasitic Infections is a comprehensive overview of parasitic immunopathology, including the fundamentals of parasite biology, mechanisms and processes of infection, and the key steps of drug discovery and treatment. In addition to detailed coverage of the most commonly encountered infectious parasites, analysis of the immTable of ContentsList of Contributors ix Preface xv Acknowledgments xviii 1 Introduction: Back to the Future ‒ Solutions for Parasitic Problems 1 Rahime Şimşek, Aqsa Farooqui, Salah-Ud-Din Khan, and Shahanavaj Khan 2 Induction of Immune Responses and Inflammation to Parasitic Infections 47 Gurdeep Singh, Abhishek Tiwari, Varsha Tiwari, and Mukesh Kr Singh 3 Animal Parasites: Insight into Natural Resistance 60 Nasib Zaman, Muhammad Rizwan, Kishawar Sultana, Abdur Rauf, Yahya S. Al-Awthan, and Omar Bahattab 4 Immune Response against Protozoan Parasites 73 Ahmed Olatunde, Olalekan Ogunro, Habibu Tijjani, Shakir Mayowa Obidola, Mustapha Abdullahi Akpaki, Archana Yadav, Manisha Nigam, and Abhay Prakash Mishra 5 Immune Response against Helminths 100 Varsha Tiwari, Abhishek Tiwari, Gurdeep Singh, and Mukesh Kr Singh 6 Ectoparasites Host Resistance and Tolerance 124 Jacob Kehinde Akintunde and Ayodeji Mathias Adegoke 7 Microorganisms as Drivers of Host‒Parasite Interactions 141 Rahul Negi, Munni Bhandari, Rahul Kunwar Singh, and Tribhuvan Mohan Mohapatra 8 Neglected Parasitic Infections: History to Current Status 156 Sarmistha Debbarma, Jupi Talukdar, Prabhakar Maurya, Luit Moni Barkalita, and Anupam Brahma 9 Molecular Techniques for the Study and Diagnosis of Parasite Infection 176 Syed Muhammad Mukarram Shah, Saira, and Fida Hussain 10 Drugs for the Control of Parasitic Diseases: Current Status and Case Studies 205 Pratichi Singh, Swetanshu, Shikha Yadav, Adeline Lum Nde, and Vijay Jyoti Kumar 11 Opportunities and Challenges in the Development of Antiparasitic Drugs 227 Maryam Bello-Akinosho, Kayode Olayinka Afolabi, Harish Chandra, Dearikha Karina Mayashinta, Yulia Dwi Setia, and Carolina Pohl-Albertyn 12 Phytopharmaceuticals as an Alternative Treatment against Parasites 251 Rajesh Kumar, Seetha Harilal, Arti Gautam, Manisha Nigam, and Abhay Prakash Mishra 13 Nanoparticles for Antiparasitic Drug Delivery 303 Abdulkadir Mohammed Danyaro, Habibu Tijjani, Swinder Jeet Singh Kalra, and Ahmed Olatunde 14 Vaccination Against Parasitic Infection: From Past to Current Approaches in the Development of a Vaccine 328 Mukesh Kr Singh, Gurdeep Singh, Varsha Tiwari, and Abhishek Tiwari 15 Current Trends in Parasitic Diseases and Precautionary Measures 356 Nisha Singh Index 382

Read more less

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

Read more less

Book SynopsisCHEMISTRY AND BIOLOGICAL ACTIVITIES OF IVERMECTIN The book focuses on the biological activities of ivermectin as well as the significant global utility of IVM since it was first used about 35 years ago. Ivermectin (IVM) is a wonder drug containing a 16-membered macrocyclic lactone ring system in its structure and derived from the family of avermectins. It was isolated by the fermentation of the soil microorganism Streptomyces avermitilis by Satoshi Omura in 1960 and studied by William C. Campbell in 1981, which allowed for its treatment of onchocerciasis (River Blindness) in Africa. Both scientists subsequently received the 2015 Nobel Prize in Physiology or Medicine. It was approved by the FDA in 1997 for the treatment of Strongyloidiasis and crusted scabies in AIDS patients. After that, IVM has attracted the tremendous attention of the scientific community and has been used for diverse purposes, including as an inhibitor of the causative virus (SARS-CoV-2). The chief purpose of this vTable of ContentsPreface xi 1 Introduction to Ivermectin 1Aeyaz Ahmad Bhat, Atif Khurshid Wani, Tahir ul Gani Mir and Nahid Akther 1.1 Introduction 1 1.2 Sources and Synthesis 3 1.3 Pharmacological Potential of Ivermectin 4 1.4 Ivermectin's Beneficial Role in Cattle 8 1.5 Ivermectin in the Treatment of COVID-19 8 1.6 Toxicity of Ivermectin 10 1.7 Conclusion 13 2 Historical Background of and Synthetic Approaches to Ivermectin (IVM) and its Homologues 23Shakeel Alvi, Mohd Kamil Hussain and Rashid Ali 2.1 Introduction 24 2.2 Synthetic Approaches Towards the Construction of IVM and Analogues 29 2.3 Biosynthesis 29 2.4 Chemical Synthetic Pathway 33 2.5 Crystal Structure 42 2.6 Conclusion and Outlook 42 3 Ivermectin as a Repurposed Drug for COVID-19 47Hari Madhav, Mohammad Rehan, Nasimul Hoda and Ehtesham Jameel 3.1 Introduction 47 3.2 Symptoms of COVID-19 50 3.3 Repurposing of the Drugs 52 3.4 Repurposed Drugs for COVID-19 52 3.5 Repurposing of Ivermectin for COVID-19 53 3.6 Proposed Possible Mechanism of Action 54 3.7 SARS COVID-19 Clinical Studies with Ivermectin 55 3.8 Conclusions 59 3.9 Acknowledgments 60 4 Ivermectin as an Anti-Parasitic Agent 69Areeba Rahman, Abdulaziz S. Alouffi, Mohammad Husain and Abdur Rub 4.1 Introduction 70 4.2 Use of Ivermectin Against Various Human Parasitic Infections 76 4.3 Mode of Action Against Various Parasites 83 4.4 Conclusions 83 4.5 Acknowledgements 84 5 Emerging Paradigm of Ivermectin and its Hybrids in Elimination of Malaria 93Iram Irfan, Diksha Shahi, Mukesh C. Joshi, Shailja Singh and Mohammad Abid 5.1 Introduction 94 5.2 Malaria 95 5.3 Life Cycle of Malaria 100 5.4 Drug Against Hepatic Malarial Stage 105 5.5 About Ivermectin 106 5.6 Designing and Synthesis of Ivermectin Inhibitors 107 5.7 Conclusions 112 5.8 Acknowledgments 113 6 Ivermectin: A Potential Repurposed Anti-Cancer Therapeutic 121Mohd Kamil Hussain, Rashid Ali, Shakir Ahamad, Mohammad Faheem Khan and Mohammad Saquib 6.1 Introduction 122 6.2 Mechanism of Anti-Carcinogenesis 124 6.3 Activation of Chloride Ion Channels 125 6.4 Anti-Mitotic Effect and Inhibition of Angiogenesis 127 6.5 Inhibition of Mitochondrial Respiration 127 6.6 Inhibitor of Cancer Stem Cells (CSCs) 128 6.7 Induction of Immunogenic Cell Death (ICD) 128 6.8 Epigenetic Modulator 129 6.9 Induction PAK1-Mediated Cytostatic Autophagy 129 6.10 Inhibition of P-glycoprotein (P-gp) 130 6.11 Inhibition of Yes-Associated Protein 1 (YAP1) 130 6.12 Inhibition of RNA Helicase 131 6.13 Caspase-Dependent Apoptosis 132 6.14 Activation of Transcription Factor E3 (TFE3) 132 6.15 Inhibition of Wnt-TCF Pathway Responses 132 6.16 Conclusions 133 7 Ivermectin as an Anti-Inflammatory Agent 141Mudasir Nabi Peerzada and Saurabh Verma 7.1 Introduction 141 7.2 Ant-Inflammatory Action of Ivermectin 147 7.3 Conclusions 155 8 Ivermectin: An Anthelminthic and Insecticide 163Manisha Arora Pandit and Tarkeshwar 8.1 Introduction 164 8.2 Ivermectin as an Anthelmintic 165 8.3 Insecticidal Activity of Ivermectin 176 9 Potential Applications of Ivermectin (IVM) in Dermatology 199Vikrant Jayant and Rashid Ali 9.1 Introduction 200 9.2 Mechanism of Action, Toxicity, and Side Effects of IVM 203 9.3 Motivational Approach of IVM in the Treatment of Skin 206 9.4 Role of IVM with Good Anti-Parasitic Properties Against the Infection of Skin 212 9.5 Importance of IVM as an Anti-Cancer or Anti-Tumor Agent in Curing the Skin 219 9.6 Social Value of IVM in the Medical Care of Red Scrotum Syndrome (RSS) 220 9.7 Utility of IVM as an Anti-Inflammatory Drug in the Treatment of Skin-Related Issues 221 9.8 Conclusions 224 10 Antiviral Uses of Ivermectin 231Shabnam Kawoosa, Rabiah Bashir, Sheeba Nazir, Zubaid-ul-Khazir Rather, Gulam Nabi Yatoo and Nisar Ahmad Khan 10.1 Introduction 231 10.2 Mechanism of Action of Ivermectin 233 10.3 Anti-Viral Effects Against Various DNA and RNA Viruses 236 10.4 Conclusion 242 11 Toxicology, Safety, and Environmental Aspects of Ivermectin 247Ayesha Akhtar, Nasreen A. Mazumdar and Afreen Inam 11.1 Introduction 247 11.2 Ivermectin’s Antiparasitic Activity 249 11.3 Pharmacology 250 11.4 Adverse Effects in Humans and Animals 251 11.5 Ivermectin and Ectoparasites 255 11.6 Environmental Impact and Biodegradation of Ivermectin 258 11.7 Conclusion 259 References 259 Index 265

Read more less

Book SynopsisMicroalgae are a diverse set of eukaryotic photosynthetic organisms with great potential for being used to produce various high-value molecules. Using synthetic biology to manipulate and control the metabolic processes of microalgae, scientists hope to find economical and sustainable alternatives for commercial production of high value biochemicals and other metabolites for diverse applications. Highlighting the immense potential of microalgae as a renewable and sustainable source of commercially important, high-value biomolecules, this book covers the recent advances in the resources, tools, and techniques used for genetic engineering of microalgae. Also discussed are the legislative challenges associated with genetically engineered microalgae, their derived products and their uses, as well as socio-economic and environmental acceptance. Written to be accessible to a wide audience, this book will be a useful reference to students and researchers from both academia and industry, as well as policy makers, for understanding the current status, trends and future possibilities of using microalgae for biotechnological applications.Table of ContentsMicroalgae as a Renewable and Sustainable Source of High Value Metabolites;Recent Advances and Challenges in Establishing Commercial Scale Multi-product Microalgal Biorefineries;Understanding Metabolic Pathways and Their Network to Augment Microalgal Strain Performance for Industrially Important Metabolite Production;Advances in the Resources to Augment Microalgal Genetic Engineering: Omics-based Resources, Mutant Libraries, and High-throughput Screening Techniques;Recent Advances in Microalgal Genome Editing with Special Emphasis on CRISPR Mediated Modification Systems;Microalgae as a Sustainable Synthetic-biology Platform for the Production of Recombinant Proteins: Advantages, Bottlenecks and Case Studies;Genetic Engineering of Microalgae for Enhanced Photosynthetic Efficiency, CO2 Fixation, and Fuel-based Products;Genetic Engineering of Microalgae for Non-fuel, High-value Biochemicals of Industrial Significance;Use of Genetically Modified Algae: Consumption Safety Challenges, Current Legislations, and Socio-economic and Environmental Concerns;Microalgal Product Basket: Portfolio Positioning Across Food, Feed, and Fuel Segments with Industrial Growth Projections

Read more less

Book SynopsisDas bewährte Standardwerk Bioanalytik beschreibt und erläutert alle analytischen Methoden, die heute in der Biochemie und Molekularbiologie eingesetzt werden - in fünf großen Abschnitten: Proteinanalytik, 3D-Strukturaufklärung, Spezielle Stoffgruppen, Nucleinsäureanalytik, Systematische Funktionsanalytik. Die komplett überarbeitete 3. Auflage berücksichtigt zahlreiche methodische Weiterentwicklungen und greift auch hochaktuelle Trends in der Forschung auf. Großer Wert wurde auf eine kritische, praxisbezogene Darstellung der Methoden und auf eine Vernetzung der verschiedenen Kapitel untereinander gelegt. So wird die Neuauflage dieses kompetenten und informationsreichen Lehr- und Handbuches wieder all jenen, die sich in der Vielfalt der biologisch-chemischen Labormethoden zurechtfinden müssen, als zuverlässiger Wegweiser dienen.Table of Contents1 Bioanalytik - eine eigenständige Wissenschaft.- Teil I Proteinanalytik.- 2 Proteinreinigung.- 3 Proteinbestimmungen.- 4 Enzymatische Aktivitätstests.- 5 Mikrokalorimetrie.- 6 Immunologische Techniken.- 7 Chemische Modifikation von Proteinen und Proteinkomplexen.- 8 Spektroskopie.- 9 Lichtmikroskopische Verfahren – Imaging.- 10 Spaltung von Proteinen .- 11 Chromatographische Trennmethoden.- 12 Elektrophoretische Verfahren.- 13 Kapillarelektrophorese.- 14 Aminosäureanalyse.- 15 Proteinsequenzanalyse.- 16 Massenspektrometrie.- 17 Massenspektrometriebasierte Immunassays.- 18 Bildgebende Massenspektrometrie.- 19 Protein-Protein-Wechselwirkungen.- 20 Bio- und biomimetische Sensoren.- Teil II 3D-Strukturaufklärung.- 21 Magnetische Resonanzspektroskopie von Biomolekülen.- 22 EPR-Spektroskopie an biologischen Systemen.- 23 Elektronenmikroskopie.- 24 Rasterkraftmikroskopie.- 25 Röntgenstrukturanalyse.- Teil III Spezielle Stoffgruppen.- 26 Analytik synthetischer Peptide.- 27 Kohlenhydratanalytik.- 28 Lipidanalytik.- 29 Analytik posttranslationaler Modifikationen: Phosphorylierung und oxidative Cysteinmodifikation von Proteinen.- Teil IV Nucleinsäureanalytik.- 30 Isolierung und Reinigung von Nucleinsäuren.- 31 Aufarbeitung und chemische Analytik von Nucleinsäuren.- 32 RNA-Strukturaufklärung durch chemische Modifikation.- 33 Polymerasekettenreaktion.- 34 DNA-Sequenzierung.- 35 Analyse der epigenetischen Modifikationen.- 36 Protein-Nucleinsäure-Wechselwirkungen.- Teil V Systematische Funktionsanalytik.- 37 Sequenzanalyse.- 38 Hybridisierung fluoreszenzmarkierter DNA zur Genomanalyse in der molekularen Cytogenetik.- 39 Physikalische, genetische und funktionelle Kartierung des Genoms.- 40 DNA-Microarray-Technologie.- 41 Silencing-Technologien zur Analyse von Genfunktionen.- 42 Proteomanalyse.- 43 Metabolomics- 44 Interactomics - systematische Protein-Protein-Wechselwirkungen.- 45 Chemische Biologie.- 46 Toponomanalyse.- 47 Organ-on-Chip.- 48 Systembiologie.- Anhang

Read more less

Book SynopsisThe field of plant biochemistry is of great significance in the agricultural sciences, and it is essential to have a solid understanding of the biochemical mechanisms involved in the synthesis of various plant components. This knowledge is crucial for advancements in other areas of agriculture such as plant breeding, plant protection, and plant production. In recent times, biotechnology and biochemistry have been working together to address various problems faced by humans and other living beings. This book is specifically designed to provide valuable information to graduate and post-graduate students in agriculture and biology. Additionally, it will serve as a useful reference book for researchers in plant breeding, agronomy, plant physiology, and plant protection. This book will be instrumental in solving many global problems faced by present and future generations.

Read more less

Book SynopsisA comprehensive explanation of drug metabolism concepts and applications in drug development and cancer treatment In the newly revised second edition of Drug Metabolism Handbook: Concepts and Applications in Cancer Research, a distinguished team of researchers delivers an incisive and robust exploration of the drug metabolism system and a well-illustrated and detailed explanation of the latest tools and techniques used in the research, pharmacology, and medicine. The book discusses the creation of new molecular entities, drug development, troubleshooting, and other highly relevant concepts, guiding readers through new applications in pharmaceutical research, development, and assessment. The latest edition offers updated content on metabolism basics and the application of a variety of new techniques to cancer treatment, including mass spectrometry, imaging, metabolomics, and immunotherapy. It also offers in-depth case studies highlighting the role of metabolism in drug development. ReadTable of ContentsVolume 1 Preface xiii List of contributors xv Part I. Introduction 1 1. Historical Perspective 3 Roberta S. King 1.1 Controversies Spanning Past, Present, and Future 3 1.2 1800s: Discovery of Major Drug Metabolism Pathways (Conti and Bickel, 1977) 5 1.3 1900–1950s: Confirmation of Major Pathways and Mechanistic Studies 8 1.4 1950s–1980: Modern Drug Metabolism Emerges, with Enzymatic Basis 9 1.5 1980–2005: Field Driven by Improved Technologies 10 1.6 2005+: High Technology 10 References 10 2. Factors Affecting Metabolism 13 Roberta S. King References 16 3. Biotransformations in Drug Metabolism 17 Roberta S. King 3.1 Drug Metabolism in Drug Development and Drug Therapy 17 3.2 Prediction of Metabolite and Enzyme Responsible 20 3.3 Functional Group Biotransformations: Phase I, Phase II, and Catalysis 21 3.4 Oxidations and Cytochrome P450 23 3.5 Enzymology and Modifiers of Cytochrome P450s 34 References 39 4. A Comprehensive Picture of Biotransformation in Drug Discovery 41 Joe R. Cannon, Prakash Vachaspati, and Yang Yuan 4.1 Introduction 41 4.2 Rate of Metabolism 43 4.3 Metabolism of Small Molecules 46 4.4 Analytical Technologies in Drug Metabolism 65 4.5 Biotransformation for Novel Modalities – Peptides and Protein Degraders 79 4.6 Conclusion 93 References 93 5. In Vivo Drug Metabolite Kinetics 103 Zheng Yang 5.1 Introduction 103 5.2 In Vivo Drug Metabolite Kinetic Concepts and Principles 105 5.3 Effect of Inhibition and Induction on Metabolite Kinetics 122 5.4 Determination of Formation and Elimination Clearance of Metabolite 127 5.5 Incorporation of Pharmacologically Active Metabolite(s) in Pharmacokinetic/Pharmacodynamic Modeling 130 5.6 Summary 135 Abbreviations 135 References 137 6. LC-MS/MS-Based Proteomics Methods for Quantifying Drug-Metabolizing Enzymes and Transporters 143 Logan S. Smith, Sun Min Jung, Jiapeng Li, and Hao-Jie Zhu 6.1 Introduction 143 6.2 Mass Spectrometry Versus Alternative Protein Quantification Methods 144 6.3 Mass Spectrometry Data Acquisition Methods for Proteomics Analysis 145 6.4 Targeted Approaches 146 6.5 Untargeted Proteomics Approaches 147 6.6 Relative Quantification Versus Absolute Quantification 150 6.7 Label-Based Proteomics 152 6.8 Label-Free Proteomics 155 6.9 DMET Protein Quantification Using LC-MS/MS-Based Proteomics 158 6.10 Potential Application of DMET Expression Studies 160 6.11 Considerations of DMET Protein Quantification Utilizing LC-MS/MS Methods 163 6.12 Conclusion 164 References 164 Part II. Technologies for in vitro and in vivo studies 177 7. Mass Spectrometry 179 Thomas R. Sharp 7.1 Introduction 179 7.2 A Brief History 180 7.3 The Mass Spectrometry Literature 182 7.4 Mass Spectrometry Instrumentation 183 7.5 Interpretation:What Does it Mean 211 7.6 Conclusions 254 References 255 8. Accelerating Metabolite Identification Mass Spectrometry Technology Drives Metabolite Identification Studies Forward 267 Ala F. Nassar 8.1 Introduction 267 8.2 Criteria for LC-MS Methods 269 8.3 Matrices Effect 269 8.4 Tool of Choice for Metabolite Characterization 270 8.5 Strategies for Identifying Unknown Metabolites 274 8.6 Online HD-LC-MS 275 8.7 “All-in-One” Radioactivity Detector, Stop Flow, and Dynamic Flow for Metabolite Identification 282 8.8 Metabolic Activation Studies by Mass Spectrometry 287 8.9 Strategies to Screen for Reactive Metabolites 288 8.10 Summary 289 Abbreviations and Glossary 290 References 299 9. Role of Structural Modifications of Drug Candidates to Enhance Metabolic Stability 303 Ala F. Nassar 9.1 Background 303 9.2 Introduction 304 9.3 Significance of Metabolite Characterization and Structure Modification 305 9.4 Enhance Metabolic Stability 305 9.5 Metabolic Stability and Intrinsic Metabolic Clearance 306 9.6 Advantages of Enhancing Metabolic Stability 307 9.7 Strategies to Enhance Metabolic Stability 307 9.8 Analytical Tools 317 9.9 Case Studies 318 9.10 Conclusions 320 References 320 10. Drug Design Strategies: Role of Structural Modifications of Drug Candidates to Improve PK Parameters of New Drugs 323 Ala F. Nassar 10.1 Active Metabolites 323 10.2 Oral Absorption and Intravenous Dose 333 10.3 PK Analysis 333 10.4 Case Studies 334 10.5 Prodrugs to IncreaseWater Solubility 338 10.6 Conclusion 339 References 340 11. Chemical Structural Alert and Reactive Metabolite Concept as Applied in Medicinal Chemistry to Minimize the Toxicity of Drug Candidates 345 Ala F. Nassar 11.1 Importance of Reactive Intermediates in Drug Discovery and Development 345 11.2 Idiosyncratic Drug Toxicity and Molecular Mechanisms 349 11.3 Key Tools and Strategies to Improve Drug Safety 352 11.4 Peroxidases 357 11.5 Acyl Glucuronidation and S-Acyl-CoA Thioesters 358 11.6 Covalent Binding 359 11.7 Mechanistic Studies 360 11.8 Preclinical Development 363 11.9 Clinical Development: Strategy 364 11.10 Case Studies 364 11.11 Conclusion and Future Possibilities 366 References 367 12. Studies of Reactive Metabolites using Genotoxicity Arrays and Enzyme/DNA Biocolloids – 2021 373 James F. Rusling and Eli G. Hvastkovs 12.1 Introduction 373 12.2 On Demand Metabolic Reactions 374 12.3 Arrays with Electrochemical Detection 376 12.4 Electrochemiluminescent Arrays 379 12.5 ECL Arrays can Measure Both DNA Oxidation and Nucleobase Adduction 388 12.6 Detecting Site-Specific Damage to TUMOR SUPPRESSORGenes 392 12.7 Emerging Technologies and Methods 394 12.8 Conclusions and Future Outlook 398 Acknowledgments 399 Biographies 399 References 399 Part III. Drug interactions 407 13. Enzyme Inhibition 409 Paul F. Hollenberg 13.1 Introduction 409 13.2 Mechanisms of Enzyme Inhibition 411 13.3 Competitive Inhibition 412 13.4 Noncompetitive Inhibition 413 13.5 Uncompetitive Inhibition 414 13.6 Product Inhibition 414 13.7 Transition-State Analogs 415 13.8 Slow, Tight-Binding Inhibitors 415 13.9 Mechanism-Based Inactivators 415 13.10 Inhibitors that are Metabolized to Reactive Products that Covalently Attach to the Enzyme 418 13.11 Substrate Inhibition 419 13.12 Partial Inhibition 419 13.13 Inhibition of Cytochrome P450 Enzymes 420 13.14 Reversible Inhibitors 421 13.15 Quasi-Irreversible Inhibitors 421 13.16 Mechanism-Based Inactivators 422 References 424 14. Xenobiotic Receptor-Mediated Gene Regulation in Drug Metabolism and Disposition 427 Hongbing Wang and Wen Xie 14.1 Introduction 427 14.2 Pregnane X Receptor 429 14.3 Constitutive Androstane/Activated Receptor (CAR) 441 14.4 Closing Remarks and Perspectives 452 Acknowledgments 453 References 453 15. Characterization of Cytochrome P450 Mechanism Based Inhibition 465 Dan A. Rock and Larry C. Wienkers 15.1 Introduction 465 15.2 Inhibitors that Upon Activation Bind Covalently to the P450 Apoprotein 475 15.3 Inhibitors that Interact in a Pseudoirreversible Manner with Heme Iron 478 15.4 Inactivation that Cause Destruction of the Prosthetic Heme Group, Often Times Leading to Heme-Derived Products that Covalently Modify the Apoprotein 480 References 515 16. An Introduction to Metabolic Reaction-Phenotyping 527 Carl Davis 16.1 Introduction 527 16.2 Significant Drug-Metabolizing Enzymes 528 16.3 Common In VitroMethods to Assess Drug Metabolism 534 16.4 In Vitroto In VivoExtrapolation of Metabolic Clearance 539 16.5 Summary 546 References 546 17. Epigenetic Regulation of Drug-Metabolizing Enzymes in Cancer 553 Jiaqi Wang, Xiaoli Zheng, and Su Zeng 17.1 Introduction 553 17.2 DNA Methylation of DMEs 554 17.3 Histone Modification 558 17.4 Noncoding RNA 559 17.5 RNA Methylation 561 17.6 Closing Remarks and Perspectives 563 Acknowledgments 564 References 564 18. Epigenetic Regulation of Drug Transporters in Cancer 573 Yingying Wang, Ying Zhou, Yu Wang, Lushan Yu, and Su Zeng 18.1 Introduction 573 18.2 DNA Methylation 575 18.3 Histone Modifications 579 18.4 Noncoding RNAs 581 18.5 Closing Remarks and Perspectives 591 Acknowledgments 592 References 592 Volume 2 Preface xi List of contributors xiii Part IV. Toxicity 605 19. The Role of Drug Metabolism in Toxicity 607 Umesh M. Hanumegowda and Carl Davis 20. Allergic Reactions to Drugs 677 Mark P. Grillo 21. Chemical Mechanisms in Toxicology 703 Mark P. Grillo 22. Role of Bioactivation Reactions in Chemically Induced Nephrotoxicity 745 Lawrence H. Lash Part V. Applications 773 23. Mapping the Heterogeneous Distribution of Cancer Drugs by Imaging Mass Spectrometry 775 Purva S. Damale and Shibdas Banerjee 24. Systemic Metabolomic Changes Associated with Chemotherapy: Role in Personalized Therapy 811 Bhargab Kalita, Ganesh K. Barik, Tanisha Sharma, Khushman Taunk, Praneeta P. Bhavsar, Manas K. Santra, and Srikanth Rapole 25. Metabolic Reprogramming in Cancer 841 Debasish Prusty and Soumen Kanti Manna 26. Case Study: Metabolism and Reactions of Alkylating Agents in Cancer Therapy 893 Ala F. Nassar, Adam V. Wisnewski, and Ivan King 27. Rewiring of Drug Metabolism and Its Cross-talk with Metabolic Reprogramming in Cancer 923 Subhabrata Majumder and Soumen Kanti Manna 28. Principles of Drug Metabolism and Interactions in Cardio-Oncology 967Sherry-Ann Brown, Craig Beavers, Sailaja Kamaraju, Meera Mohan, Olubadewa Fatunde, Gift Echefu, Svetlana Zaharova, Brianna Wallace, and Carolyn Oxencis Index 993

Read more less

Book SynopsisThis fully updated and expanded second edition of a highly popular text book focuses on the structure and mechanism in carbohydrate chemistry and biochemistry. Carbohydrates play important roles in biological systems as energy sources, as structural materials, and as informational structures (when they are often attached to proteins or lipids). Their chemical reactivity and conformational behaviour is governed by mechanistic and stereochemical rules, which apply as much to enzymic as to non-enzymic reactivity. The same principles of reactivity and conformation govern changes brought about in the process industries, such as pulp, paper and food. Extensively referenced with citations and a detailed index, the book contains everything the reader needs to know to start a carbohydrate research project with one of the real strengths being the treatment and integration of the important physical-chemical principles and methods (though lead references only are given to the finer points of carbohydrate synthesis). The book is suitable for both researchers who are new to the subject and those more established as well as a readership from diverse backgrounds and interests, including chemists, biochemists, food scientists and technologists involved with the processing of polysaccharides in the paper, textile, cosmetics, biofuels and other industries.Trade Review"...the book provides an excellent and authoritative reference resource for beginning and established researchers interested in structural and mechanistic aspects of carbohydrate (biochemistry)""useful addition to the library of individuals with interests in theglycoscience field, as well as students wishing to learn moreabout this area.""the overall view of the text is favorable, since it covers so many varied topics, some perhaps unfamiliar to even the most seasoned glycoscientists""...this is an excellent treatment of carbohydrate chemistry. It belongs in libraries and on the bookshelves of carbohydrate chemists and biochemists.""..an invaluable companion and introduction to the primary literature of the field."Table of ContentsStructures of the open-chain forms of reducing sugars and related molecules. Mechanistic probes of sugar carbonyl group additions; Conformations of Sugar Rings and Glycosidic Linkages; Nucleophilic Substitution a the Anomeric Centre; Enzymic Glycoside Hydrolysis and Transglycosylation: Kinetics and Mechanism; Primary Structure and Conformation of Oligosaccharides and Polysaccharides; Heterolytic Reactions of OH Groups; Heterolytic Chemistry of the Carbon Chain; Glycosyl Transferases and Oligosaccharide and Polysaccharide Biosynthesis; Glycoconjugates: Biosynthesis and Properties; One-electron Chemistry of Carbohydrates; Appendix; Subject Index

Read more less

Book SynopsisThe pharmaceutical industry has become increasingly interested in biologics from animal venoms as a potential source for therapeutic agents in recent years, with a particularly emphasis on peptides. To date six drugs derived from venom peptides or proteins have been approved by the FDA, with nine further agents currently being investigated in clinical trials. In addition to these drugs in approved or advanced stages of development, many more peptides and proteins are being studied in varying stages of preclinical development. This unique book provides an up to date and comprehensive account of the potential of peptides and proteins from animal venoms as possible therapeutics. Topics covered include chemistry and structural biology of animal venoms, proteomic and transcriptomic approaches to drug discovery, bioassays, high-throughput screens and target identification, and reptile, scorpion, spider and cone snail venoms as a platform for drug development. Case studies are used to illustrate methods and successes and highlight issues surrounding administration and other important lessons that have been learnt from the development of approved therapeutics based on venoms. The first text to focus on this fascinating area and bridging an important gap, this book provides the reader with essential and current knowledge on this fast-developing area. Venoms to Drugs will find wide readership with researchers working in academia and industry working in all medicinal and pharmaceutical areas.Trade ReviewBelonging to the RSC’s Drug Discovery series, Venoms to Drugs is a welcome addition to the bookshelf designed to guide the reader through the opportunities and challenges to be found in Nature’s treasure chest in the efforts to develop new therapeutic solutions to human maladies. Venoms have evolved to assist numerous animals with matters of defence or in catching prey—if you’ve been stung by a bee you’ll have felt the power of a venom at work—and here we explore a little-tapped natural resource which could help provide the chemical foundations for the next big painkiller, antihypertensive or anti-inflammatory. Turning venom, consisting of a cocktail of toxins, from a potentially deadly secretion into a relatively safe, efficacious medicine is not simple. This book does not shy away from this fact, but embraces the problems and examines methods afforded by recent scientific advances through which the many challenges may be overcome. The book begins by introducing the drug-development opportunities provided by these natural resources, with an overview of the evolution of venoms across species and how many venom toxins retain a similar basic template upon which to pin their more specific functional flourishes for various targets and effects. We are given a detailed introduction to the obstacles met when turning these natural products into medicines, from the problems of retaining functionality to producing stable formulations. What stands out here in particular is that there are groups of animals whose venoms remain completely unexplored in terms of their therapeutic potential, and thus the scene is set for the rest of the book. The structure of the book is logical and the contents detailed, well-written and informative throughout. Chapters on approaches to drug discovery, taking into account advantages provided by recent technological advances, are followed by an examination of venoms as lead compounds from various animal orders in four further chapters. Later on, Chapters 9 and 10 describe the development of analgesic drugs and anti-inflammatory/autoimmune compounds from some extraordinary sea creatures, demonstrating good examples of the possibilities that may be found. The technical detail in the writing has not been lost or brushed over, which makes the book all-the-better as a useful resource. One aspect that is particularly good is the inclusion of case studies, to demonstrate how a carefully nurtured project can bear fruit. As always, there are chemical puzzles to solve, pharmacological mechanisms to pick apart and regulatory hurdles to jump, but from deadly cone-snail venom used to paralyse its prey comes the analgesic ziconatide, and from pit viper venom comes the ACE inhibitor captopril—one wonders what next might be found from a jellyfish’s tentacles or a spider’s jaws. If there is a sting in the tail in this particular story, then it is certainly to be extracted, analysed and put to good use! This book is, of course, targeted towards chemists as is clear from the detail and style throughout, but others with an interest in this subject (pharmacologists, electrophysiologists, formulation scientists and their kin) will certainly find this a useful, interesting and perhaps even thought-provoking resource to have at hand. -- Neil C. Henny, Liverpool John Moores University * Chromatographia (2015) 78:1507-1508 *Table of ContentsVenomous animals: evolution and ecology; Chemistry and structural biology of animal venoms; Venoms-based drug discovery: proteomic and transcriptomic approaches; Venoms-based drug discovery: bioassays, high-throughput screens, and target identification; Reptile venoms as a platform for drug development; Cone snail venoms as a platform for drug development; Scorpion venoms as a platform for drug development; Spider-venom peptides as a platform for drug development; Case study 1: development of the analgesic drugs Prialt® and Xen2174; Case study 2: development of exenatide for treatment of type 2 diabetes; Case study 3: development of ShK for the treatment of autoimmune diseases; Development of venom natriuretic peptides for treating congestive heart failure; Engineering venom peptides to improve their stability and bioavailability; Manufacturing of venom-derived therapeutic peptides; Venoms to drugs: prospects and pitfalls

Read more less

Book SynopsisUnderstanding and quantifying the effects of membrane transporters within the human body is essential for modulating drug safety and drug efficacy. In this first volume on Drug Transporters, the current knowledge and techniques in the transporter sciences and their relations to drug metabolism and pharmacokinetics are comprehensively reviewed. The second volume of the book is specifically dedicated to emerging science and technologies, highlighting potential areas for future advances within the drug transporter field. The topics covered in both volumes ensure that all relevant aspects of transporters are described across the drug development process, from in silico models and preclinical tools through to the potential impact of transporters in the clinic. Contributions are included from expert leaders in the field, at-the-bench industrial scientists, renowned academics and international regulators. Case studies and emerging developments are highlighted, together with the merits and limitations of the available methods and tools, and extensive references to reviews on specific in-depth topics are also included for those wishing to pursue their knowledge further. As such, this text serves as an essential handbook of information for postgraduate students, academics, industrial scientists and regulators who wish to understand the role of transporters in absorption, distribution, metabolism, and excretion processes. In addition, it is also a useful reference tool on the models and calculations necessary to predict their effect on human pharmacokinetics and pharmacodynamics.Table of ContentsOverview of drug transporter families and their role in drug development; Liver transporters and their involvement in the hepatocellular uptake and export systems of organic anions; Intestinal transporters; Kidney transporters; CNS transporters; Lung transporters; The use of in vitro and in silico systems for investigating transporter interactions; The use of transgenic and knockout in vivo systems for investigating transporter interactions; Modelling and simulation of transporter interactions; Clinical Drug-Drug Interactions: An industrial Pharmaceutical Perspective; Regulatory requirements, Labelling and Drug Transporters; Recent Advances and Emerging Technologies; Bioinformatics; Regulation of transporters; Transporter Pharmacogenomics; Transporter Imaging; Transporters and Proteomics

Read more less

Book SynopsisVom Eiswürfelkran zum selbst gemachten Christbaumschmuck: mehr als 50 originelle Versuche zu den Grundlagen der Chemie mit Bildanleitung und kindgerechter Erklärung wecken auf spielerische Weise das Interesse an der Natur und an der Wissenschaft.Trade ReviewDNA-Extraktion aus Tomaten, wachsende Kristalle, Bau eines Handspektroskopes und Analyse künstlicher Lichtquellen, Deko-Anhänger aus recyceltem Polyethylen, Kartoffelbatterien, Rakete mit Backpulver antrieb - Beispiele aus 54 zumeist unkompliziert und überwiegend gefahrlos durchzuführenden Experimenten aus 12 thematischen Abschnitten, u.a. Gase, Wasser, Kristalle, Kunststoffe, Bestandteile von Lebensmitteln. "Ideal für das gemeinsame Experimentieren mit Kindern der Altersstufen 8 bis 12". Wichtig ist "gemeinsam", die erläuternden Texte sind sehr ausführlich und sehr gut verständlich, allerdings schon Schulbuch-Niveau (u.a. Reaktions- und Strukturformeln). Chemisches Grundverständnis/Grundkenntnisse ratsam. Vor Gefahren wird gewarnt; bei einem bestimmten Experiment wird auf eventuell entstehendes Chlorgas hingewiesen - "Wenn ihr ein Labor habt, arbeitet am Abzug, sonst am besten im Freien". Das Buch vermittelt über Spielereien hinaus auch für "Nur-Leser*innen" bereits ein gediegenes Grundwissen zu Chemie im Alltag. Gerne empfohlen auch neben Georg Schwedt (ID-A 25/22, ID-A 48/19, IDG 41/15). (2 S) Rolf Becker-Friedrich, ekz-Publikation ID bzw. IN 2023/20Table of ContentsVorwort ix So Experimentiert Ihr Sicher xi 1 Feuer, Plasma und die chemische Reaktion 1 1.1 Wo Moleküle zerbrechen 2 1.1.1 Experiment: Kerzenflammen werfen Schatten! 2 1.2 Aus Stoffen entstehen neue Stoffe 3 1.2.1 Paraffin verbrennt: die chemische Reaktion in der Kerzenflamme 3 1.2.2 Experimente: Die chemische Reaktion wird „sichtbar“ 4 1.3 Was die Reaktion am Laufen hält 5 1.3.1 Warum sind Flammen heiß? – Was ist eigentlich Wärme? 5 1.3.2 Wie heiß muss Paraffin werden, damit es brennt? 6 1.3.3 Ein Metallsieb als Feuersperre 7 2 Licht und Materie 9 2.1 Warum Stoffe farbig sind 10 2.1.1 Wie unsere Augen Farben sehen 10 2.1.2 Was Stoffe mit Licht anstellen 11 2.2 Was Licht uns über Stoffe verrät 12 2.2.1 Wir können Licht zerlegen 12 2.2.2 Was das Licht über seine Quelle preisgibt 14 2.3 Farbstoffe in der Natur entdecken 16 2.3.1 Papierchromatografie von Blattfarbstoffen 16 2.4 Mysteriöse Lichterscheinungen 19 2.4.1 Ein Stoff – verschiedene Farben? 19 2.4.2 Licht aus dem Dunklen: Fluoreszenz 20 2.4.3 Glow-in-the-dark-Effekte: Phosphoreszenz 21 3 Mit der Kraft des Lichtes: Photochemie 23 3.1 Dank Chemie können wir sehen 24 3.1.1 Viele Sehzellen ergeben ein Bild 24 3.2 Moleküle gebaut mit Lichtenergie 25 3.2.1 Photosynthese 26 3.3 Chemie für Nostalgiker: Fotografie 28 3.3.1 Wie man mit Chemie Fotos macht 28 3.3.2 Euer eigenes Fotolabor 29 3.4 Unerwünschte Fotochemie 30 3.4.1 Licht zerstört Moleküle 30 3.4.2 Sonnencreme schützt unsere Haut 31 4 Gase: flüchtig und voluminös 33 4.1 Inertgas für die Sicherheit 34 4.2 Gase brauchen Platz, viel Platz 35 4.2.1 Woher das Gas im Airbag kommt 35 4.2.2 Gase als Raketentreibstoff 35 4.3 Sprengstoffe: Viel Gas in kurzer Zeit 38 4.3.1 Welche Stoffe haben Sprengkraft? 38 4.3.2 Explosiv und spektakulär: Vulkanausbruch daheim 38 4.4 Beweglichkeit macht gefährlich 39 5 Wasser – ein ganz besonderer Stoff 41 5.1 Woraus bestehen Wassermoleküle? 42 5.1.1 Analyse: Wie ihr einen Stoff auseinandernehmt 42 5.2 Warum ist Wasser nass? 45 5.2.1 Das Geheimnis des krummen Wasserstrahls 45 5.2.2 Wenn Atome Tauziehen machen 46 5.2.3 Wie stark Moleküle zusammenhalten 47 5.3 Was passiert, wenn Wasser fest wird 47 5.3.1 Experiment im Winter: Schnee mikroskopieren 48 5.3.2 Wie Salze die Entstehung von Eis verhindern 49 5.3.3 Kann es belebtes Wasser geben? 52 5.4 Echt merkwürdig: die Dichteanomalie des Wassers 53 5.4.1 Warum können Eiswürfel schwimmen? 53 5.4.2 Schlittschuhlaufen – Druck machts möglich 55 6 Kristalle – die Chemie der Schönheit 57 6.1 Mineralien und Würze: Ionenkristalle 58 6.1.1 Wie Ionenkristalle entstehen 58 6.1.2 Wasser im Gitter: Können Kristalle nass sein? 60 6.2 Kristalle aus Molekülen 62 6.2.1 Das Rätsel um den Eiswürfelkran 63 6.3 Diamant: ein Riesenmolekülkristall und der härteste Naturstoff der Welt 64 7 Elektronen auf Wanderschaft: Redox-Reaktionen 65 7.1 Wie Ionen entstehen und vergehen 66 7.1.1 Von Hochhäusern und vollen Etagen 66 7.1.2 Oxidation, Reduktion, Redox-Chemie 67 7.1.3 Aus Salzen lassen sich Metalle gewinnen 68 7.2 Redox-Reaktionen dank Elektrizität 71 7.2.1 Redox-Reaktionen im Stromkreis 71 7.3 Wirklich lästige Chemie: Korrosion 74 7.3.1 Unedle Metalle korrodieren an Luft und Wasser. 74 7.3.2 Redox-Reaktionen mit Edelmetall 76 7.4 Das Wandern ist der Ionen Lust: Stofftransport dank Redox-Potentialen 78 7.5 Wie eine Batterie funktioniert 80 8 Gar nicht so komplex: Koordinationsverbindungen 83 8.1 Wie Unlösliches löslich wird 84 8.1.1 Nachweis von Kupfer mit bunten Komplexen 85 8.1.2 Komplex-Verbindungen als Haushaltshelfer 87 8.2 Wie man Schwermetalle loswird 88 8.3 Ein Platz für nützliche Metallionen 89 9 Reaktionen leicht gemacht: Katalysatoren 91 9.1 Kfz-Katalysator: mit Edelmetall gegen Abgase 92 9.1.1 Wie giftige Abgase entstehen 92 9.1.2 Was ein Katalysator mit den Abgasen tut 92 9.2 Enzyme – Katalysatoren in der Natur 94 9.2.1 Enzyme verdauen Nahrung 94 9.2.2 Enzyme beseitigen Giftstoffe 96 9.2.3 Medikamente blockieren Enzyme 97 9.3 Wie Reaktionen wirtschaftlich werden 98 10 Tenside – Moleküle mit Superwaschkraft 101 10.1 Seife –eines der ältesten Chemieprodukte der Welt 102 10.2 Die Superkräfte der Tenside 105 10.2.1 Mischbar oder nicht mischbar, das ist hier die Frage 105 10.2.2 Januskopf-Moleküle 105 10.3 Was haben Seifenblasen mit Körperzellen gemeinsam? 106 10.3.1 Wie Seifenblasen aufgebaut sind 107 10.3.2 Und der Aufbau der Hülle von Körperzellen 108 10.4 Tenside und die Oberflächenspannung 109 10.5 Tenside in der Umwelt 110 11 Unsere Nahrung: Makromoleküle 113 11.1 Struktur und Ordnung: Stärke und Zellulose 114 11.1.1 Aufgeräumt: Stärke als Nährstofflager 114 11.1.2 Wie wir Makromoleküle verwerten: Verdauung 115 11.2 Nukleinsäuren: Moleküle als Datenspeicher 117 11.3 Proteine: vielfältige Helferlein 118 12 Natur nachgeahmt: Kunststoffe 121 12.1 Kunststoffe: Designermaterialien aus Makromolekülen 122 12.1.1 Ein Musterbeispiel für Thermoplaste: Polyethylen 122 12.2 Festigkeit durch Vernetzung – Warum selbstgemachter Slime nur im Labor gut gelingt 125 12.3 Wunscheigenschaften durch Additive 126 12.4 Wunderpolymere als Wasserspeicher 129 A Anhang 133 A.1 Chemikalienverzeichnis 133 A.1 Lebensmittel und Lebensmittelbestandteile 134 A.1. 2 Alltagschemikalien 135 A.1. 3 Besondere Chemikalien 137 A. 2 Wortlaut der H- und P-Sätze des EU-GHS-Systems 140 A.2. 1 H-Sätze 140 A. 2 P-Sätze 141 Bildquellen 143 Literatur 145 Stichwortverzeichnis 147

Read more less

Book SynopsisWith the increase in volume, velocity and variety of information, researchers can find it difficult to keep up to date with the literature in the field. As the synthesis of novel carbohydrates and carbohydrate mimetics continues to be a major challenge for organic chemists, not least because of the increasingly interdisciplinary nature of carbohydrate science, Carbohydrate Chemistry Volume 41 will prove invaluable. Covering both chemical and biological science, this series collates modern carbohydrate research from theory to application and will be of great benefit to any researcher who wishes to learn about the latest developments in the carbohydrate field.Table of ContentsPreface; Design and synthesis of glycomimetics; Pyranose glycals in the generation of skeletal diversity; Recent developments in the stereoselective synthesis of deoxy glycosides; Lewis acid promoted anomerisation: recent developments and applications; Progress in the synthesis of mycothiol, its biosynthetic precursors and analogues; Synthetic receptors for molecular recognition of carbohydrates; Contribution of carbohydrate chemistry to assessment of the biological role of natural alpha-glycosides; Carbohydrate-carbohydrate interation: from hypothesis to confirmation

Read more less

Book SynopsisMetal ions play key roles in biology. Many are essential for catalysis, for electron transfer and for the fixation, sensing, and metabolism of gases. Others compete with those essential metal ions or have toxic or pharmacological effects. This book is structured around the periodic table and focuses on the control of metal ions in cells. It addresses the molecular aspects of binding, transport and storage that ensure balanced levels of the essential elements. Organisms have also developed mechanisms to deal with the non-essential metal ions. However, through new uses and manufacturing processes, organisms are increasingly exposed to changing levels of both essential and non-essential ions in new chemical forms. They may not have developed defenses against some of these forms (such as nanoparticles). Many diseases such as cancer, diabetes and neurodegeneration are associated with metal ion imbalance. There may be a deficiency of the essential metals, overload of either essential or non-essential metals or perturbation of the overall natural balance. This book is the first to comprehensively survey the molecular nature of the overall natural balance of metal ions in nutrition, toxicology and pharmacology. It is written as an introduction to research for students and researchers in academia and industry and begins with a chapter by Professor R J P Williams FRS.Table of ContentsIntroduction to the Biological Chemistry of Nickel; Oceanic Nickel Biogeochemistry and the Evolution of Nickel Use; Nickel Toxicity and Carcinogenesis; Nickel Binding Sites - Coordination Modes and Thermodynamics; Urease; Crystallographic Analyses of the Active Site Chemistry and Oxygen Sensitivity of [NiFe(Se)]-Hydrogenases; One-Carbon Chemistry of Nickel-Containing Carbon Monoxide Dehydrogenase and Acetyl-CoA Synthase; Biochemistry of Methyl-Coenzyme M Reductase; Reinventing the Wheel: The NiSOD Story; Nickel Glyoxalase I; Lactate Racemase and Its Niacin-Derived, Covalently-Tethered, Nickel Cofactor; Nickel in Microbial Physiology - from Single Proteins to Complex Trafficking Systems: Nickel Import/Export; Nickel Regulation; Nickel Metallochaperones: Structure, Function, and Nickel-Binding Properties; Cross-Talk Between Nickel and Other Metals in Microbial Systems; Nickel and Virulence in Bacterial Pathogens; Application of Ni(II)-Binding Proteins

Read more less

Book SynopsisComprehensive Biomarker Discovery and Validation for Clinical Application provides the reader with an extensive introduction into all aspects of proteomics biomarker discovery, validation and development. It discusses the current status of science and technology, its limitations, bottlenecks as well as future development trends to improve the success rate of translating biomarker discovery into useful clinical tests. The most important feature of the book is to provide an overview of current technologies and the challenges encountered during biomarker discovery and validation, such as patient selection, sample handling, data processing, statistical analysis and registration and approval of validated biomarkers through European and US regulatory authorities. The authors introduce the reader to each of these topics in significant detail and provide examples or guidelines for best practice. There are prominent chapters included on biomarkers in translational and personalised medicine; an introduction to regulatory affairs and bring biomarkers to the market; biomarker discovery and the use of mass spectrometry based profiling platforms; MALDI imaging techniques in tissue-based biomarkers discovery and a clinical application study on the use of diagnostic assays for early diagnosis of heart failure using various proteomic methods. The book concludes with a final chapter on future trends in biomarker discovery and validation. The book targets a readership of industrial and academic researchers that are involved in biomarker discovery and validation or that manage biobanks, develop sample preparation methods, analytical profiling systems and bioinformatics tools. Common pitfalls and success stories in biomarker discovery are highlighted and guidelines for best practice are provided for the different parts of the procedure. The book will be an essential information resource for scientists working in the field.Table of ContentsIntroduction to biomarker discovery and validation; Clinical context of proteomics biomarker discovery and validation, authority regulations; Biomarker discovery: Patient selection; Biomarker discovery: Experimental design and biobanking; Biomarker discovery: body fluids; Biomarker discovery: tissues; Biomarker discovery: mass spectrometry based profiling platforms; Biomarker discovery: array based profiling platforms; Biomarker discovery: data preprocessing for LC-MS data; Biomarker discovery: data preprocessing for Maldi imaging, and 2D electrophoresis and protein arrays data; Biomarker discovery: statistical analysis and validation; Biomarker validation: biomarker validation methods; Functional biomarker validation; Clinical application: case studies Clinical application: summary and future technology development trends

Read more less

Book SynopsisIn this volume, glycochemistry and glycobiology have been combined to demonstrate the contribution of organic chemistry, modern analytics, biological and biochemical expertise to the increasingly important field of glycomincs. A polysaccharide immunomodulator with therapeutic implications, carbohydrate vaccines, new findings emphasizing the influence of carbohydrate decoration on the regulation of inflammatory response and new therapeutic approaches in the treatment of acute and chronic inflammatory diseases, recent approachesin the treatment of acute and chronic inflammatory diseases, recent progress on glycoengineering based on a glycosylation, and key aspects of the glycosylation changes associated with bladder cancer are amongst the subjects presented in this volume. The contribution of glycochemistry to innovation in glycosciences is shown with chapters covering highly functionalized exo-glycals for the generation of molecular diversity in a chemoselective manner, imino sugar glycosidase inhibitors, carbasugars, multivalent glycoconjugates, including glycodendrimers, glyconanotubes, and glyconanoparticles, and their uses in medicinal chemistry, as well as artificial saccharide-based and saccharide functionalized gene delivery systems. Siderphores based on monosaccharides (which have proven effective for Gram-negative bacteria and mycobacteria), and the so-called smart materials, (which can modulate and control cell behaviour), complete the volume. Volume 38 of Carbohydrate Chemistry - Chemical and Biological Apporaches contains contributions ranging from glycochemistry to glycobiology. This collection demonstrates in a meaningful way how the interdisciplinary approach of an international glyconetwork can advance the field of carbohydrate research in Europe and worldwide.Table of Contents1. Applications of glycobiology: biological and immunological effects of a chemically modified amylose-derivative; 2. Lipopolysaccharide structure and biological activity of Cystic fibrosis pathogens; 3. Synthesis of inner core lipopolysaccharide structures for the development of vaccines and antibiotics against Gram-negative bacterial infections; 4. Synthetic Glycopeptides in Vaccine Development and Antibody Epitope Mapping; 5. Posttranslational sialylation and its impact on leukocyte recruitment during inflammation; 6. Glycoengineering of protein-based therapeutics; 7. Exploring CDG diagnostic tools; 8. Bladder cancer: glycosylation insights; 9. Levansucrases of Pseudomonas bacteria: novel approaches for protein expression, assay of enzymes, fructooligosaccharides and heterooligofructans; 10. Recent advances on the application of NMR methods to study the conformation, dynamics and molecular recognition features of carbohydrates; 11. Glycosidase inhibitors: versatile tools in glycobiology; 12. An overview of key routes for the transformation of sugars into carbasugars and related compounds; 13. Multivalent glycoconjugates in Medicinal Chemistry; 14. Glycotransporters for gene delivery; 15. Furanose-based templates in the chemoselective generation of molecular diversity; 16. Synthesis of carbohydrate-based artificial siderophores and their biological applications; 17. Smart biomaterials: the contribution of glycoscience

Read more less

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

Read more less

Book SynopsisGenomic and Epigenomic Biomarkers of Toxicology and Disease The latest developments in biomarker research applicable to toxicology and medicine Research on genomic and epigenomic biomarkers is developing rapidly with cutting-edge studies scattered throughout the academic literature, making the status of ongoing scientific activity in this area difficult to ascertain. Genomic and Epigenomic Biomarkers of Toxicology and Disease: Clinical and Therapeutic Actions delivers a comprehensive and authoritative compilation of up-to-date developments in the application of genomic and epigenomic biomarkers to toxicology, disease prevention, cancer detection, therapeutics, gene therapy, and other areas. With contributions from a collection of internationally recognized investigators, this edited volume offers unique insights into current trends and future directions of research in the discussed areas. Combining state-of-the-art information on genomic and epigenomTable of ContentsDedication ix Preface xi Acknowledgements xiii List of Contributors xv 1 Genomic and Epigenomic Biomarkers for Predictive Toxicity and Disease 1 Saura C. Sahu 2 MicroRNAs as Non-invasive Biomarkers of Toxicity and Chemical Hazard: Genomic and Epigenomic Biomarkers of Toxicology and Disease 7 Gail M. Nelson and Brian N. Chorley 3 EV (Extracellular Vesicle)-associated miRNAs as Biomarkers of Toxicity 37 Ryuichi Ono, Yusuke Yoshioka, Yusuke Furukawa, Mie Naruse, Makiko Kuwagata, Takahiro Ochiya, Satoshi Kitajima, and Yoko Hirabayashi 4 Circulating miRNAs as Biomarkers of Toxic Heavy Metal Exposure 63 Alexandra N. Nail, Ana P. Ferragut Cardoso, Mayukh Banerjee, and J. Christopher States 5 MicroRNA Biomarkers of Malignant Mesothelioma 89 Lijin Zhu, Fangfang Zhang, Min Zhang, Hailing Xia, Xiuyuan Yuan, and Yanan Gao 6 Role of Non-coding RNAs in Innate Immune Responses Perturbed by Environmental Arsenic Exposure 101 Liz Saavedra Perez and Benjamin L. King 7 Transcriptomics: Applications in Toxicology and Medicine 133 Pius Joseph Copyrighted Material 8 Network Biology for Biomarker Discovery and Therapy in Cancer 163 Asim Bikas Das 9 Epigenetic Biomarkers: Link to Maternal Exposure and Offspring Health Outcomes 185 Jairus Pulczinski, Moira Mccormick, Yuchen Sun, Musa Watfa, Robert YS Cheng, and Wan-Yee Tang 10 The Role of Dynamic Epigenetic Changes in Modulating Homeostasis after Exposure to Low-dose Environmental Chemicals 213 Chongli Yuan, Jennifer L. Freeman, Junkai Xie, and Han Zhao 11 Emerging Non-invasive Molecular Biomarkers for Early Cancer Detection 229 Jacob Sobota, Yingxue Zhang, Eid Alshammari,and Zhe Yang 12 Aberrant DNA Methylation of Tumor Suppressor Genes and Oncogenes as Cancer Biomarkers 251 Eid Alshammari, Yingxue Zhang, Jacob Sobota, and Zhe Yang 13 SMYD Protein Family as Promising Biomarkers for Cancer Diagnosis and Prognosis 273 Yingxue Zhang, Eid Alshammari, Jacob Sobota, and Zhe Yang 14 Toward Precision Medicine: Epigenetic Alterations in Human Melanoma 309 Carmen Elena Condrat, Elena Codruta Dobrica, Sanda Maria Cretoiu, and Dragos Cretoiu 15 Currents Trends and Future Perspectives in Our Epigenetic Signatures: What a Diet Can Trigger 333 Elena-Codruța Dobrică, Mihnea-Alexandru Găman, Matei-Alexandru Cozma, and Sanda Maria Cretoiu 16 Genetic and Epigenetic Biomarkers of Organophosphate Compounds, Dialkyl Phosphate Exposure, and Their Relation to Biological Effects 363 David S. Hernández-Toledano and Libia Vega 17 Genetic, Epigenetic, and Anatomical Factors in Agenesis and Development of Female Reproductive Tract 383 Tadaaki Nakajima, Tomomi Sato, and Taisen Iguchi 18 Cause or Consequence: Epigenomic DNA Methylation Changes in Arsenic- Mediated in Vitro Transformation of Human Prostate Cells 395 B. Alex Merrick, Dhiral P. Phadke, Ruchir R. Shah, Deepak Mav, and Erik J. Tokar 19 Epigenetic Regulation of Sex Determination and Toxicity in Nonmammalian Vertebrates 415 Genki Yamagishi, Taisen Iguchi, and Shinichi Miyagawa 20 Characterization of Genomic and Epigenomic Biomarkers of Nanoparticle Toxicity Using the Zebrafish Model System 449 Athira Sairanthry Suku, Parayanthala Valappil Mohanan, and Jennifer L. Freeman Index 477

Read more less

Book Synopsis

Read more less

Book SynopsisThe given compilation is devoted to the anniversary of Professor Gennady E Zaikov. The compilation itself has been prepared by those scientists with whom G. E. Zaikov has worked during more than half a century of his scientific career.

Read more less

Book Synopsis

Read more less

Book SynopsisThere has been enormous progress in our understanding of molybdenum and tungsten enzymes and relevant inorganic complexes of molybdenum and tungsten over the past twenty years. This set of three books provides a timely and comprehensive overview of the field and documents the latest research. The first volume in the set focusses on the enzymes themselves, and discusses active sites and substrate channels of relevant proteins. The book begins with an introductory overview of the whole field. Chapters are contributed by world leaders and topics covered include pyranopterin cofactor biosynthesis and incorporation of the mature cofactor into apoprotein. Subsequent volumes cover the bioinorganic chemistry relevant to these enzymes and the full range of spectroscopic and theoretical methods that are used to investigate their physical and electronic structure and function. This text will be a valuable reference to workers both inside and outside the field, including graduate students and young investigators interested in developing new research programs in this area.Table of ContentsPart I Molybdenum- and tungsten-containing enzymes; Abundance, ubiquity, and evolution of molybdoenzymes; Molybdenum cofactor biosynthesis; Bacterial molybdoenzymes; The prokaryotic Mo/W-bisPGD enzyme family; Enzymes of the xanthine oxidase family; The sulfite oxidase family of Mo enzymes; Nitrogenase; Tungsten-containing enzymes; Part II Introduction and overview of synthetic Mo and W chemistry; Synthesis of mono- and bisdithiolene Mo and W model compounds; Pterin‐inspired Model Compounds of Molybdenum Enzymes; Synthesis of models for the xanthine oxidase family of enzymes; Electron transfer mechanisms in Mo and W compounds; Comparative kinetics of enzymes and models; Models of the metal clusters of nitrogenase; Part III Overview of spectroscopic and electronic studies of Mo and W enzymes; Spectroscopic and electronic structure studies of Mo model compounds and enzymes; Electron paramagnetic resonance studies of molybdenum enzymes; X-ray absorption spectroscopic studies of molybdenum enzymes; Electrochemistry of molybdenum and tungsten enzymes; Computational studies of molybdenum and tungsten enzymes; Nitrogen Fixation in Nitrogenase and Related Small-Molecule Models

Read more less

Book SynopsisThe field of proteomics has developed rapidly over the past decade nurturing the need for a detailed introduction to the various informatics topics that underpin the main liquid chromatography tandem mass spectrometry (LC-MS/MS) protocols used for protein identification and quantitation. Proteins are a key component of any biological system, and monitoring proteins using LC-MS/MS proteomics is becoming commonplace in a wide range of biological research areas. However, many researchers treat proteomics software tools as a black box, drawing conclusions from the output of such tools without considering the nuances and limitations of the algorithms on which such software is based. This book seeks to address this situation by bringing together world experts to provide clear explanations of the key algorithms, workflows and analysis frameworks, so that users of proteomics data can be confident that they are using appropriate tools in suitable ways.Trade ReviewThis is a timely book for the proteomics researcher in guiding decision trees involved in the informatics pipelines of this rapidly developing field. The book does an excellent job in focusing on that part of the informatics discipline, both at the user interface and behind the scenes algorithms, that is of great importance to developing innovative and effective methods for protein interrogation. -- Taufika Islam Williams * Analytical and Bioanalytical Chemistry *Book’s topic: Proteomics, the comprehensive interrogation of proteins expressed by a living system, has enjoyed expeditious growth and development in recent years, as it brings together a range of informatics themes that fortify and support the everincreasing power of LC-MS/MS platforms to tackle important biological questions. Proteins are the vehicles of change in living cells and understanding them is elemental to understanding molecular biology. The complexity of the proteomics workflow, from sample preparation to LC-MS/MS to bioinformatics analyses, is such thatmore often than not, the intricacies and indeed shortcomings of the bioinformatics software are not carefully considered during data interpretation. This is an unwelcome prospect, given that comprehending the inner workings of living systems can be intimately tied to fluctuating patterns of protein expression,which can only be as thoroughly understood as the cumulative proteomics experiment allows. State-of-the-art sample preparation and LC-MS/MS will only be as biologically informative as the informatics methods with which data are interrogated. Proteome informatics is described as the ever increasing collection of bioinformatics methodologies that can be exercised in the analysis of protein expression. The book Proteome informatics, edited byConradBessant and the 5th volume of the Royal Society of Chemistry on New Developments in Mass Spectrometry, describes the bioinformatics of proteome analyses in the very context of proteomics workflows. It is an opportune discussion by leading experts on the current state of this evolving discipline, highlighting the essential fund of knowledge that will enable the proteomics expert, who may or may not be well-versed in computer science or statistics, to exploit and construct algorithms that can effectively interrogate gigabytes of data, while keeping a sharp focus on the limitations of what such software can reasonably underscore about the system being studied. Contents: This book is divided into four main sections, which follow an introductory chapter on proteome informatics. The first section describes protein identification and begins with manual de novo sequencing to more sophisticated de novo algorithms. The book steers into details of peptide spectrum matching by database search and the alternative spectral library search in use today. Despite the established advantages of the latter, the approach is only as good as the population of the library itself, which invariably limits the identification of experimental peptides and their post-translational modifications (PTMs). Discussion proceeds into peptide-spectrum match (PSM) scoring and validation, a lynchpin of proteome informatics which unequivocally dictates the “goodness of fit” in a given peptide (and subsequently protein) identification. Merits and demerits of common methods are briefly explored. This is proceeded by a chapter on protein grouping, which links identified peptides to identifying proteins. The section concludes with commentary on identification and positioning of the all-important PTMs. Indeed, the hundreds of in vivo PTMs (not to mention the many more possibilities of chemical modifications that may be artificially introduced into the system under investigation) are subject to change with changing cellular milieu, and hence are critical in a comprehensive proteomics study. The second section is dedicated to the quantification of proteins. Algorithms detailing MS1-based quantification are examined in its five components. The central point for such algorithms is the detection and quantification of peptidespecific signal patterns, called features. Peptide- and protein level identification are effected using precursor ion exact mass, charge state, and tandem MS. Chromatographic alignment fine-tunes all runs to a common retention time (RT) coordinate system such that corresponding features will display analogous RTs. -- Taufika Islam Williams * Analytical and Bioanalytical Chemistry - Review part 1 *Internal standard features are then used to derive normalization factors that correct for sample loading disparities and ionization variabilities. Protein-level differential analysis encompasses processes to quantify proteins via constituent peptide analyses, as well as approaches to determine protein regulation disparities across study samples. MS2-based quantification, which exploits abundance data of fragment ions in tandem MS spectra, is then discussed by drawing comparisons between spectral counting and reporter ion-based quantification. Discussion then veers into the bioinformatics support for selected reaction monitoring (SRM), the gold standard for accurate, unambiguous MS-based quantification. The section concludes with a chapter on dataindependent acquisition (DIA), which primarily differs from data-dependent acquisition (DDA) in that the window selection of the first mass analyzer is dynamic during DDA, whereas it is used to scan the entire spectrum during DIA. Data analysis can be tricky in DIA and the chapter does justice in surveying DIA theory, notable DIA methods employed today, and major considerations in data interrogation. The third section details the open source software landscape for bioinformatics in proteomics investigations. A key consideration is data formatting, given the breadth of academic and commercial software that is commonly exercised for proteomics data management. The section proceeds to discuss three major software platforms for proteomics data analysis pipelines: OpenMS (modular solution for proteomics and metabolomics), Galaxy (originally designed for the genomics research community), and R (programming language for statistical computing and graphics). Section 4 takes the reader into the broader territory of integrating proteomics data with that from other studies, particularly genomics and transcriptomics. Proteogenomics, the application of proteomics data to augment genome annotation, does not quite offer the sensitivities featured by RNA-Seq and does exhibit particular bioinformatics challenges. Nevertheless, a major advantage of this field is the successful interrogation of proteins whose exact sequences are missing from generic databases to which they are matched and whose function may have critical bearings on biological phenotype. The authors detail underlying theory, software platforms, data formats, current challenges, and future direction. The section, and indeed the book, concludes with a discussion of the union between proteomics and transcriptomics data or proteome informed by transcriptomics (PIT). While PIT data can be used for genome annotations, the power behind this approach lies in facilitating proteomic analyses in the absence of a reference genome, not to mention the pinpointing of sequence variation and examining such dynamic events as isoform switching. In PIT, the protein database is created from RNA-Seq data. The authors elaborate PIT applications and data management options. Comparison with the existing literature: This book is distinctive in how it frames bioinformatics strictly in its relevance to designing a proteomics experiment. The authors draw upon only that portion of knowledge from key disciplines that intersect with proteomics to better construct sophisticated and robust informatics pipelines. In the last decade, a number of books have addressed bioinformatics as it relates to the rapidly developing field of proteomics, notably Bioinformatics for comparative proteomics edited by Cathy Wu and Chuming Chen (2010), Proteome bioinformatics edited by Simon Hubbard and Andrew Jones (2010), Bioinformatics of human proteomics edited by XiagdongWang (2013), Mass spectrometry data analysis in proteomics edited by Rune Matthiesen (2013), Bioinformatics: genomics and proteomics by Ruchi Singh (2015), Proteome bioinformatics edited by Shivakumar Keerthikumar and Suresh Mathivanan (2016), Exploring genomics, proteomics and bioinformatics by Charles Malkoff (2016), Modern proteomics—sample preparation, analysis and practical applications edited by Hamid Mirzaei and Martin Carrasco (2016), Protein bioinformatics edited by Cathy Wu, Cecilia Arighi and Karen Ross (2017). Some provide a bird’s eye view of informatics as applied to proteomics. Some delve deeper into PTMs, while others focus on database searching aspects, cancer research, human proteins, or the interplay between gene expression and protein expression. Yet others center on proteomics while discussing informatics as a part of the whole experiment or explore specific MS-based methods and data analysis strategies. This book presents the advantage of elaborating important bioinformatics details, both at the user interface and behind the scenes (i.e., software algorithms), that should be carefully considered by the proteomics scientist in experimental design to better understand and interpret the data. Critical assessment: The book performs a thorough assessment of informatics processes and considerations in proteomics. Representative examples of informatics workflows are provided and discussed, but given the breadth of the subject, not all important bioinformatics software that is currently used in proteomics (i.e., Byonic™ by Protein Metrics) was able to receive attention. This is relevant because a detailed comparison of the inner workings of proteomics software in use today would better equip the proteomics researcher to build effective workflows, which is the major purpose of this book. Nevertheless, the discussions of examples that are provided do highlight the considerations of importance when selecting software and of course when using the software in the proteomics experiment. It must be mentioned that Bessant has put together a very useful body of work, harnessing the expertise of over 35 contributing authors to cover a number of very relevant topics in the informatics arena of proteomics science. Some topics are more in-depth than others perhaps not as thorough as they ought to be. There is unavoidable overlap with limited inter-chapter connections. The book would have benefited from additional chapters describing the integration of proteomics data with other metadata experiments (i.e., metabolomics, lipidomics) and the unique bioinformatics challenges they present. Mass spectrometry imaging (MSI), a rapidly emerging and developing field, is not covered in much detail in the context of this book. The particulars of open source software in proteomics, along with protein identification and quantification, are overall, quite helpful. Readership recommendation: The target audience for this book includes scientists and doctoral students using proteomics science to understand biological systems. Given the interdisciplinary nature of proteomics, this book will be of benefit to and of interest to the bioanalytical chemist, biophysicist, biomedical engineer, biologist, and indeed the biostatistician. The book is constructed in such a manner that it includes enough introductory material for those new to proteome analysis, as well as enough depth and details for experts and specialists. No doubt, it offers a very useful fund of knowledge to the proteomics researcher. Summary: Proteomics research is inherently multidisciplinary in its workflows, as it brings together concepts from chemistry, engineering, computer science, biochemistry, statistics, mathematics, and biology to understand protein expression. This is a timely book for the proteomics researcher in guiding decision trees involved in the informatics pipelines of this rapidly developing field. The book does an excellent job in focusing on that part of the informatics discipline, both at the user interface and behind the scenes algorithms, that is of great importance to developing innovative and effective methods for protein interrogation. Informatics is placed squarely within the framework of proteomics and this will be most beneficial indeed for the target audience. -- Taufika Islam Williams * Analytical and Bioanalytical Chemistry - Review part 2 *by Charles Malkoff (2016), Modern proteomics—sample preparation, analysis and practical applications edited by Hamid Mirzaei and Martin Carrasco (2016), Protein bioinformatics edited by Cathy Wu, Cecilia Arighi and Karen Ross (2017). Some provide a bird’s eye view of informatics as applied to proteomics. Some delve deeper into PTMs, while others focus on database searching aspects, cancer research, human proteins, or the interplay between gene expression and protein expression. Yet others center on proteomics while discussing informatics as a part of the whole experiment or explore specific MS-based methods and data analysis strategies. This book presents the advantage of elaborating important bioinformatics details, both at the user interface and behind the scenes (i.e., software algorithms), that should be carefully considered by the proteomics scientist in experimental design to better understand and interpret the data. Critical assessment: The book performs a thorough assessment of informatics processes and considerations in proteomics. Representative examples of informatics workflows are provided and discussed, but given the breadth of the subject, not all important bioinformatics software that is currently used in proteomics (i.e., Byonic™ by Protein Metrics) was able to receive attention. This is relevant because a detailed comparison of the inner workings of proteomics software in use today would better equip the proteomics researcher to build effective workflows, which is the major purpose of this book. Nevertheless, the discussions of examples that are provided do highlight the considerations of importance when selecting software and of course when using the software in the proteomics experiment. It must be mentioned that Bessant has put together a very useful body of work, harnessing the expertise of over 35 contributing authors to cover a number of very relevant topics in the informatics arena of proteomics science. Some topics are more in-depth than others perhaps not as thorough as they ought to be. There is unavoidable overlap with limited inter-chapter connections. The book would have benefited from additional chapters describing the integration of proteomics data with other metadata experiments (i.e., metabolomics, lipidomics) and the unique bioinformatics challenges they present. Mass spectrometry imaging (MSI), a rapidly emerging and developing field, is not covered in much detail in the context of this book. The particulars of open source software in proteomics, along with protein identification and quantification, are overall, quite helpful. Readership recommendation: The target audience for this book includes scientists and doctoral students using proteomics science to understand biological systems. Given the interdisciplinary nature of proteomics, this book will be of benefit to and of interest to the bioanalytical chemist, biophysicist, biomedical engineer, biologist, and indeed the biostatistician. The book is constructed in such a manner that it includes enough introductory material for those new to proteome analysis, as well as enough depth and details for experts and specialists. No doubt, it offers a very useful fund of knowledge to the proteomics researcher. -- Taufika Islam Williams * Analytical and Bioanalytical Chemistry - Review part 3 *Table of ContentsIntroduction to Proteome Informatics; De Novo Sequencing; Peptide-Spectrum Matching; PSM Scoring and Validation; Protein Grouping; Identification and Localisation of Post Translational Modifications; Algorithms for MS1-Based Quantitation; Algorithms for MS2-Based Quantitation; Informatics Solutions for Selected Reaction Monitoring; Data Analysis for Data Independent Acquisition; Mining Proteomics Repositories; Data Formats of the Proteomics Standards Initiative; OpenMS; Using Galaxy for Proteomics; R for Proteomics; Proteogenomics: Proteomics for Genome Annotation; Proteomics Informed by Transcriptomics; Subject Index

Read more less

Book SynopsisAlthough the concept of allosterism has been known for over half a century, its application in drug discovery has exploded in recent years. The emergence of novel technologies that enable molecular-level ligand-receptor interactions to be studied in studied in unprecedented detail has driven this trend. This book, written by the leaders in this young research area, describes the latest developments in allosterism for drug discovery. Bringing together research in a diverse range of scientific disciplines, Allosterism in Drug Discovery is a key reference for academics and industrialists interested in understanding allosteric interactions. The book provides an in-depth review of research using small molecules as chemical probes and drug candidates that interact allosterically with proteins of relevance to life sciences and human disease. Knowledge of these interactions can then be applied in the discovery of the novel therapeutics of the future. This book will be useful for people working in all disciplines associated with drug discovery in academia or industry, as well as postgraduate students who may be working in the design of allosteric modulators.Table of ContentsModulation of Biological Targets: Why Use Allosteric Ligands?; Identifying and Quantifying Allosteric Drug Function; Targeting Catalytic and Non-catalytic Functions of Protein Kinases; Molecular Biology Techniques Applied to GPCR Allosteric and Biased Ligands; Examining Allosterism in a Dimeric GPCR Context; A Unifying Approach to the Duality of "Energetic" Versus "Conformational" Formulations of Allosteric Coupling: Mechanistic Implications on GPCR Allostery; mGluR2 Positive Allosteric Modulators; Muscarinic Receptors Allosteric Modulation; Positive Allosteric Modulators of Opioid Receptors; mGluR7 allostery: up and down modulation; Allosteric Modulators of Adenosine, P2Y and P2X Receptors; Positive Allosteric Modulators of G Protein-Coupled Receptors that Act via Covalent Mechanisms of Action; mGluR4 PET ligands as enablers of target biology understanding; Mechanism of action of a GluN2C- and GluN2D-selective NMDA receptor positive allosteric modulator; Development of AMPA Receptor Modulators as Cognition Enhancers; Allosteric modulation of the neuronal nicotinic acetylcholine receptor; Allosteric Binding in the Serotonin Transporter – Pharmacology, Structure, Function and Potential Use as a Novel Drug Target; Allosteric Inhibition of Abl Kinase; Allosteric Modulators of Heat Shock Protein 90 (HSP90); A look forward;

Read more less

Book SynopsisWith the increase in volume, velocity and variety of information, researchers can find it difficult to keep up to date with the literature in their field. This invaluable volume contains analysed, evaluated and distilled information on the latest in carbohydrate research. The discovery and synthesis of novel carbohydrates and mimetics with diverse applications continues to be a major challenge for carbohydrate chemists. The understanding of the structure and function of carbohydrates and glycoconjugates remains vital in medicine and molecular biology. This volume collates modern carbohydrate research from theory to application and demonstrates the importance of carbohydrates in new lead generation. It is of benefit to any researcher who wishes to learn about the latest developments in the carbohydrate field.Table of ContentsContemporary glycoconjugation chemistry; Advances in applications of NMR methods to uncover the conformation and recognition features of glycans; Recent advances in Kdo-glycoside synthesis; Predictable and highly efficient preparation of carbohydrate-based vaccines: Squaric acid chemistry is the way to go; Synthetic Approaches to Cyclodextrins and Their Analogues; Bacterial lipopolysaccharides covalently bound to hopanoids: key molecules that favour the life of Bradyrhizobia in stressful environments; Giant dsDNA viruses taste for sugars; Glycosteroids: a specific type of glycolipids with self assembly properties; Recent examples of novel synthetic approaches to diverse amino-sugars; FimH Antagonists – Solubility vs. Oral Availability; Ferrier rearrangement. An update on recent developments; Recent advances in the synthesis of iminosugars. An insight into the cascade addition of Grignard reagents to halonitriles/cyclization;

Read more less

Book SynopsisThere has been enormous progress in our understanding of molybdenum and tungsten enzymes and relevant inorganic complexes of molybdenum and tungsten over the past twenty years. This set of three books provides a timely and comprehensive overview of the field and documents the latest research. Building on the first volume that focussed on biochemistry aspects, the second volume in the set focusses on the inorganic complexes that model the structures and reactivity of the active sites of each major group of molybdenum and tungsten enzymes. Special attention is given to synthetic strategies, reaction mechanism and chemical kinetics of these systems. The introductory chapter provides a useful overview and places the topic of the book into a wider context. This text will be a valuable reference to workers both inside and outside the field, including graduate students and young investigators interested in developing new research programs in this area.Table of ContentsPart I Molybdenum- and tungsten-containing enzymes; Abundance, ubiquity, and evolution of molybdoenzymes; Molybdenum cofactor biosynthesis; Bacterial molybdoenzymes; The prokaryotic Mo/W-bisPGD enzyme family; Enzymes of the xanthine oxidase family; The sulfite oxidase family of Mo enzymes; Nitrogenase; Tungsten-containing enzymes; Part II Introduction and overview of synthetic Mo and W chemistry; Synthesis of mono- and bisdithiolene Mo and W model compounds; Pterin‐inspired Model Compounds of Molybdenum Enzymes; Synthesis of models for the xanthine oxidase family of enzymes; Electron transfer mechanisms in Mo and W compounds; Comparative kinetics of enzymes and models; Models of the metal clusters of nitrogenase; Part III Overview of spectroscopic and electronic studies of Mo and W enzymes; Spectroscopic and electronic structure studies of Mo model compounds and enzymes; Electron paramagnetic resonance studies of molybdenum enzymes; X-ray absorption spectroscopic studies of molybdenum enzymes; Electrochemistry of molybdenum and tungsten enzymes; Computational studies of molybdenum and tungsten enzymes; Nitrogen Fixation in Nitrogenase and Related Small-Molecule Models

Read more less