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This book provides an accessible introduction to the principles and tools for modeling, analyzing, and synthesizing biomolecular systems. It begins with modeling tools such as reaction-rate equations, reduced-order models, stochastic models, and specific models of important core processes. It then describes in detail the control and dynamical systems tools used to analyze these models. These include tools for analyzing stability of equilibria, limit cycles, robustness, and parameter uncertainty. Modeling and analysis techniques are then applied to design examples from both natural systems and synthetic biomolecular circuits. In addition, the book addresses the problem of modular composition of synthetic circuits, the tools for analyzing the extent of modularity, and the design techniques for ensuring modular behavior. It also looks at design trade-offs, focusing on perturbations due to noise and competition for shared cellular resources. Featuring numerous exercises and illustrations throughout, the book is the ideal textbook for advanced undergraduates and graduate students. For researchers, it can also serve as a self-contained reference on the feedback control techniques that can be applied to biomolecular systems.

This book provides an introduction to three of the main tools used in the development of bioinformatics software — Perl, R, and MySQL — and explains how these can be used together to tackle the complex data-driven challenges that typify modern biology. The book is intended to provide the reader with the knowledge and confidence needed to create databases, to write programs to analyse and visualise data, and to develop interactive web-based applications. Platform-independent examples are provided throughout, making the book suitable for users of Windows, Mac OS or Linux.

Epigenetics is the study of heritable changes in gene function that do not involve changes in the DNA sequence. Epigenetic changes, consisting principally of DNA methylation, histone modifications and non-coding RNAs, maintain and modulate the initial impact of regulatory factors that recognize and associate with particular genomic sequences. This book’s primary goal is to establish a framework that can be used to understand the basis of epigenetic regulation and to appreciate both its derivation from genetics and its interdependence with genetic mechanisms. A further aim is to highlight the role played by the three-dimensional organization of the genetic material itself (the complex of DNA, histones and non-histone proteins referred to as chromatin) and its distribution within a functionally compartmentalized nucleus. Dysfunctions at any level of genetic regulation have the potential to result in an increased susceptibility to disease or actually give rise to overt pathologies. As illustrated in this book, research is continuously uncovering the role of epigenetics in a variety of human disorders, providing new avenues for therapeutic interventions and advances in regenerative medicine.

Quantitative traits—be they morphological or physiological characters, aspects of behavior, or genome-level features such as the amount of RNA or protein expression for a specific gene—usually show considerable variation within and among populations. Quantitative genetics, also referred to as the genetics of complex traits, is the study of such characters and is based on mathematical models of evolution in which many genes influence the trait and in which non-genetic factors may also be important. Evolution and Selection of Quantitative Traits presents a holistic treatment of the subject, showing the interplay between theory and data with extensive discussions on statistical issues relating to the estimation of the biologically relevant parameters for these models. Quantitative genetics is viewed as the bridge between complex mathematical models of trait evolution and real-world data, and the authors have clearly framed their treatment as such. This is the second volume in a planned trilogy that summarizes the modern field of quantitative genetics, informed by empirical observations from wide-ranging fields (agriculture, evolution, ecology, and human biology) as well as population genetics, statistical theory, mathematical modeling, genetics, and genomics. Whilst volume 1 (1998) dealt with the genetics of such traits, the main focus of volume 2 is on their evolution, with a special emphasis on detecting selection (ranging from the use of genomic and historical data through to ecological field data) and examining its consequences. This extensive work of reference is suitable for graduate level students as well as professional researchers (both empiricists and theoreticians) in the fields of evolutionary biology, genetics, and genomics. It will also be of particular relevance and use to plant and animal breeders, human geneticists, and statisticians.

The new edition of this well-established book is thoroughly revised and gives a comprehensive account of the role of free radicals, other reactive species (RS), and antioxidants in life, health, and disease. Chapter 1 reviews how oxygen (O₂) is used by living organisms, why it can be toxic, and introduces the concept of oxygen radicals and other RS; their chemistry is detailed in Chapter 2, especially for superoxide, hydroxyl radical (including Fenton chemistry), peroxynitrite, nitric oxide, ozone, and singlet O₂, with emphasis on their redox properties. Subsequent chapters detail what antioxidants can be made in vivo (e.g. superoxide dismutases, peroxiredoxins) and which can come from diet (e.g. vitamins E and C, carotenoids, and polyphenols such as the flavonoids) and how they work in vivo. The role of RS in cell proliferation, senescence, and death (e.g. by apoptosis, necrosis, or intermediate forms) is presented. Methods for measuring RS are described in detail, including electron paramagnetic resonance and biomarker determination. Useful roles for RS (e.g. cell signalling, phagocyte action), as well as systems in which they cause particular problems (e.g. premature babies, the eye, the ear) are presented. Acute and chronic inflammation are used to illustrate both roles There is a comprehensive description of the role of RS in human diseases, from cancer to heart disease to dementia, in the ageing process, and in the toxicity of many agents, from ethanol to carbon tetrachloride to paraquat. Therapeutic agents active against RS are reviewed in detail, including NADPH oxidase inhibitors, N-acetylcysteine, and Ebselen.

The aims of this book are to provide a synthesis of our current understanding of hemoglobin structure, function, and evolution, and to illustrate how research on this paradigmatic protein has provided general insights into mechanisms of molecular evolution and biochemical adaptation. The book promotes an appreciation of how mechanistic insights into protein function can enrich our understanding of how evolution works and, reciprocally, it highlights how approaches in evolutionary genetics (such as phylogenetic comparative methods and ancestral sequence reconstruction) can be brought to bear on questions about the functional evolution of proteins. This treatise on the functional evolution of hemoglobin illustrates how research on a single, well-chosen model system can enhance our investigative acuity and bring key conceptual questions into sharp focus. Hemoglobin: Insights into Protein Structure, Function, and Evolution is suitable for a wide range of graduate level students taking interdisciplinary courses in biochemical physiology and protein evolution, and will serve as a key reference for researchers in molecular evolution, biochemistry, and comparative physiology.

The discovery of how the machinery of life works, and how it is constructed, is one of the glories of 20th century science. By contrast, we know little of the origin and evolution of cells and their parts, and what we have learned is in dispute. This book surveys ongoing efforts to make cell evolution intelligible. The text revolves around a small set of fundamental questions: 1. How many kinds of cellular designs does our world hold, and how are they related? 2. Is the traditional metaphor of a tree of life still useful, or has it been superseded? 3. What are viruses, and how are they related to cells? 4 Can one construct a timeline for the origin and early history of life? 5. Do all living things share a common ancestor, and what was its nature? 6. Why are eukaryotic organisms so much more complex than prokaryotic ones, and how did they arise? 7. Has functional, adaptive organization increased over time, and if so, why? 8. Is there a way to generate functional organization that does not depend on heredity, and selection? 9. How did life emerge from the lifeless world of chemistry and physics? 10. Can a generalized theory of evolution explain the origin of life? 11. Is the history of life a succession of contingent events, or does it have direction and meaning?

Macromolecular crystallography is the study of macromolecules (proteins and nucleic acids) using X-ray crystallographic techniques in order to determine their molecular structure. The knowledge of accurate molecular structures is a pre-requisite for rational drug design, and for structure-based function studies to aid the development of effective therapeutic agents and drugs. The successful determination of the complete genome (genetic sequence) of several species (including humans) has recently directed scientific attention towards identifying the structure and function of the complete complement of proteins that make up that species; a new and rapidly growing field of study called ‘structural genomics’. There are now several important and well-funded global initiatives in operation to identify all of the proteins of key model species. One of the main requirements for these initiatives is a high-throughput crystallization facility to speed-up the protein identification process. The extent to which these technologies have advanced calls for an updated review of current crystallographic theory and practice. This book features the latest conventional and high-throughput methods, and includes contributions from a team of internationally recognized leaders and experts.

This book explains the role of simple biological model systems in the growth of molecular biology. Essentially, the whole history of molecular biology is presented here, tracing the work in bacteriophages in E. coli, the role of other prokaryotic systems, and also the protozoan and algal models — Paramecium and Chlamydomonas, primarily — and the move into eukaryotes with the fungal systems Neurospora, Aspergillus, and yeast. Each model was selected for its appropriateness for asking a given class of questions, and each spawned its own community of investigators. Some individuals made the transition to a new model over time, and remnant communities of investigators continue to pursue questions in all these models, as the cutting edge of molecular biological research flows onward from model to model, and onward into higher organisms and, ultimately, mouse and man.

Natural Products (NPs) is the term used to describe the hundreds of thousands of chemical compounds or substances that are continually produced by living organisms (plants and microbes). Hundreds of millions of tons of these chemicals are generated annually, and the trade in just a few of these has dominated human economic activity for thousands of years. Indeed, the current world geopolitical map has been shaped by attempts to control the supply of a few of these compounds. Every day of our lives each human spends time and money trying to procure the NPs of their choice. However, despite their overwhelming influence on human culture, they remain poorly understood. A knowledge of NPs can help in our search for new drugs, further the debate about GM manipulation, help us address environmental pollution, and enable a better understanding of drug trafficking. This is the first book to describe Natural Products (NPs) in an evolutionary context, distilling the few simple principles that govern the way in which organisms (including humans) have evolved to produce, cope with, or respond to NPs. It neatly synthesizes a widely dispersed literature and provides a general picture of NPs, encompassing evolution, history, ecology, and environmental issues (along with some deeper theory relevant to biochemistry), with the goal of enabling a wider section of the scientific community to fully appreciate the crucial importance of Natural Products to human culture and future survival.

Phosphorus is essential to all life. A critical component of fertilizers, Phosphorus currently has no known substitute in agriculture. Without it, crops cannot grow. With too much of it, waterways are polluted. Across the globe, social, political, and economic pressures are influencing the biogeochemical cycle of phosphorus. A better understanding of this non-renewable resource and its impacts on the environment is critical to conserving our global supply and increasing agricultural productivity. Most of the phosphorus-focused discussion within the academic community is highly fragmented. This book brings together the necessary multi-disciplinary perspectives to build a cohesive knowledge base of phosphorus sustainability. The book is a direct continuation of processes associated with the first international conference on sustainable phosphorus held in the United States, the Frontiers in Life Sciences: Sustainable Phosphorus Summit, though it is not a book of conference proceedings; rather, the book is part of an integrated, coordinated process that builds on the momentum of the Summit. The first chapter introduces the biological and chemical necessity of phosphorus. The subsequent ten chapters explore different facets of phosphorus sustainability and the role of policy on future global phosphorus supplies. The final chapter synthesizes all of the emerging views contained in the book, drawing out the leading dilemmas and opportunities for phosphorus sustainability.

This book, which discusses the major processes carried out by viruses, bacteria, fungi, protozoa, and other protists – the microbes – in freshwater, marine, and terrestrial ecosystems, focuses on biogeochemical processes, starting with primary production and the initial fixation of carbon into cellular biomass. It then discusses how that carbon is degraded in both oxygen-rich (oxic) and oxygen-deficient (anoxic) environments. These biogeochemical processes are affected by ecological interactions, including competition for limiting nutrients, viral lysis, and predation by various protists in soils and aquatic habitats. The book links up processes occurring at the micron scale to events happening at the global scale, including the carbon cycle and its connection to climate change issues, and ends with a chapter devoted to symbiosis and other relationships between microbes and large organisms. Microbes have large impacts not only on biogeochemical cycles, but also on the ecology and evolution of large organisms, including Homo sapiens.

Recent research in molecular biology has produced a remarkably detailed understanding of how living things operate. Becoming conversant with the intricacies of molecular biology and its extensive technical vocabulary can be a challenge, though, as introductory materials often seem more like a barrier than an invitation to the study of life. This text offers a concise and accessible introduction to molecular biology, requiring no previous background in science.

This book is an update and major revision to Radiological Assessment: A Textbook on Environmental Dose Analysis published by the U.S. Nuclear Regulatory Commission in 1983. It focuses on risk to the public because decision makers typically use that endpoint to allocate resources and resolve issues. Chapters in the book explain the fundamental steps of radiological assessment, and they are organized in a sequence that would typically be used when undertaking an analysis of risk. The key components of radiological risk assessment discussed include source terms, atmospheric transport, surface water transport, groundwater transport, terrestrial and aquatic food chain pathways, estimating exposures, conversion of intakes and exposures to dose and risk, uncertainty analysis, environmental epidemiology, and model validation. A chapter on regulations related to environmental exposure is also included. Contributors to the book are well known experts from the various disciplines addressed.

Recent scandals and controversies—such as the falsification, fabrication, and plagiarism of data in federally funded science; the manipulation and distortion of research sponsored by private companies; human embryonic stem cell research; cloning; and the patenting of DNA and cell lines—illustrate the importance of ethics in scientific research. This book provides an introduction and overview of many of the social, ethical, and legal issues facing scientists today. The book includes chapters on research misconduct, conflicts of interest, data management, mentoring, authorship, peer review, publication, intellectual property, research with human subjects, research with animal subjects, genetic and stem cell research, international research, and ethical decision making. The book also features dozens of real and hypothetical cases for discussion and analysis and introduces the reader to important research regulations and guidelines. Now in its second edition, this book synthesizes the diverse talents and experiences. This second edition of this book includes new chapters and cases and has been brought up to date on the latest issues and problems in research ethics.

In this book, the mathematical principles and working methods of single-particle reconstruction are described; a method designed to retrieve three-dimensional structural information from electron micrographs showing thousands of “copies” of biological molecules trapped in a thin layer of ice. This technique is uniquely suited to obtain three-dimensional images of molecular machines in different functional states, as it dispenses with the need for crystals. The book starts with an introduction of image formation in the electron microscope, which includes the definition of the contrast transfer function. Next, averaging techniques and tools for image alignment, multivariate data analysis, and classification are described. An introduction into the mathematical principles underlying reconstruction of an object from its projections is followed by detailed accounts on how projection angles are determined, and how reconstruction is done in practice. The book concludes with a chapter on interpretation of density maps reconstructed, including methods for segmentation as well as fitting and docking of atomic coordinates.

Although cell biology is often considered to have arisen following World War II in tandem with certain technological developments—in particular, the electron microscope and cell fractionation—its origins actually date to the 1830s and the development of cytology, the scientific study of cells. By 1924, with the publication of Edmund Vincent Cowdry’s General Cytology, the discipline had stretched beyond the bounds of purely microscopic observation to include as well the chemical, physical, and genetic analysis of cells. Inspired by this classic, watershed work, Visions of Cell Biology collects contributions from cell biologists, historians, and philosophers of science to explore the history and current status of cell biology. Despite extraordinary advances in describing both the structure and function of cells, cell biology tends to be overshadowed by molecular biology, a field that developed contemporaneously. This book remedies that unjust disparity through an investigation of cell biology’s evolution. Contributors show that modern concepts of cell organization, mechanistic explanation, epigenetics, molecular thinking, and even computational approaches all can be placed on the continuum of cell studies from cytology to cell biology and beyond.

Knowledge of the microscopic structure of biological systems is the key to understanding their physiological properties. Most of what we now know about this subject has been generated by techniques that produce images of the materials of interest, one way or another, and there is every reason to believe that the impact of these techniques on the biological sciences will be every bit as important in the future as they are today. Thus the 21st-century biologist needs to understand how microscopic imaging techniques work, as it is likely that sooner or later he or she will have to use one or another of them, or will otherwise become dependent on the information that they provide. This book introduces readers to the many techniques now available for imaging biological materials—crystallography, optical microscopy, and electron microscopy—at a level that will enable them to use them effectively to do research. Since all of these experimental methods are best understood in terms of Fourier transformations, this book explains the relevant concepts from this branch of mathematics, and then illustrates their elegance and power by applying them to each of the techniques presented.