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In 1957 two young scientists, Matthew Meselson and Frank Stahl, produced a landmark experiment confirming that DNA replicates as predicted by the double helix structure Watson and Crick had recently proposed. It also gained immediate renown as a "most beautiful" experiment whose beauty was tied to its simplicity. Yet the investigative path that led to the experiment was anything but simple, Frederic L. Holmes shows in this masterful account of Meselson and Stahl's quest. This book vividly reconstructs the complex route that led to the Meselson-Stahl experiment and provides an inside view of day-to-day scientific research--its unpredictability, excitement, intellectual challenge, and serendipitous windfalls, as well as its frustrations, unexpected diversions away from original plans, and chronic uncertainty. Holmes uses research logs, experimental films, correspondence, and interviews with the participants to record the history of Meselson and Stahl's research, from their first thinking about the problem through the publication of their dramatic results. Holmes also reviews the scientific community's reception of the experiment, the experiment's influence on later investigations, and the reasons for its reputation as an exceptionally beautiful experiment.
Proteomics is an introduction to the exciting new field of proteomics, an interdisciplinary science that includes biology, bioinformatics, and protein chemistry. The purpose of this book is to provide the active researcher with an overview of the types of questions being addressed in proteomics studies and the technologies used to address those questions. Key subjects covered in this book include: an assessment of the limitations of this approach and outlines new developments in mass spectrometry that will advance future research high-throughput recombinant DNA cloning methods used to systematically clone all of the open reading frames of an organism into plasmid vectors for large scale protein expression and functional studies such as protein-protein interactions with the two-hybrid system protein structure an overview of large-scale experimental attempts to determine the three-dimensional structures of representative sets of proteins computational approaches to determining the three-dimensional structure of proteins. Proteomics provides a starting point for researchers who would like a theoretical understanding of the new technologies in the field, and obtain a solid grasp of the fundamentals before integrating new tools into their experiments. Written with attention to detail, but without being overwhelmingly technical, Proteomics is a user-friendly guide needed by most biologists today.
A principal architect and visionary of the new biology, a Nobel Prize-winner at 34 and best-selling author at 40 (The Double Helix), James D. Watson had the authority, flair, and courage to take an early and prominent role as commentator on the march of DNA science and its implications for society. In essays for publications large and small, and in lectures around the world, he delivered what were, in effect, dispatches from the front lines of the revolution. Outspoken and sparkling with ideas and opinions, a selection of them is collected for the first time in this volume. Their resonance with today's headlines is striking. All orders from the UK and Australia must be directed to Oxford University Press, [email protected]
Genome Stability: DNA Repair and Recombination describes the various mechanisms of repairing DNA damage by recombination, most notably the repair of chromosomal breaks. The text presents a definitive history of the evolution of molecular models of DNA repair, emphasizing current research. The book introduces the central players in recombination. An overview of the four major pathways of homologous recombinational repair is followed by a description of the several mechanisms of nonhomologous end-joining. Designed as a textbook for advanced undergraduate and graduate students with a molecular biology and genetics background, researchers and practitioners, especially in cancer biology, will also appreciate the book as a reference.
This book introduces the reader to modern computational and statistical tools for translational epigenomics research. Over the last decade, epigenomics has emerged as a key area of molecular biology, epidemiology and genome medicine. Epigenomics not only offers us a deeper understanding of fundamental cellular biology, but also provides us with the basis for an improved understanding and management of complex diseases. From novel biomarkers for risk prediction, early detection, diagnosis and prognosis of common diseases, to novel therapeutic strategies, epigenomics is set to play a key role in the personalized medicine of the future. In this book we introduce the reader to some of the most important computational and statistical methods for analyzing epigenomic data, with a special focus on DNA methylation. Topics include normalization, correction for cellular heterogeneity, batch effects, clustering, supervised analysis and integrative methods for systems epigenomics. This book will be of interest to students and researchers in bioinformatics, biostatistics, biologists and clinicians alike. Dr. Andrew E. Teschendorff is Head of the Computational Systems Genomics Lab at the CAS-MPG Partner Institute for Computational Biology, Shanghai, China, as well as an Honorary Research Fellow at the UCL Cancer Institute, University College London, UK.
Epigenetic modifications act on DNA and its packaging proteins, the histones, to regulate genome function. Manifest as the heritable methylation of DNA and as post-translational histone modifications, these molecular flags influence the architecture and integrity of the chromosome, the accessibility of DNA to gene regulatory components and the ability of chromatin to interact within nuclear complexes. While a multicellular individual has only one genome, it has multiple epigenomes reflecting the diversity of cell types and their properties at different times of life; in health and in disease. Relationships are emerging between the underlying DNA sequence and dynamic epigenetic states and their consequences,such as the role of RNA interference and non-coding RNA. These integrated approaches go hand-in-hand with studies describing the genomic locations of epigenetic modifications in different cell types at different times. The excitement and curiosity surrounding epigenomics is driven by a growing community of researchers in a burgeoning field and the development of new technologies built on the backbone of genome sequencing projects. Research has shown that the adaptability and vulnerability of epigenetic states has profound effects on natural variation, the response of the genome to its environment and on health and disease. The aim of this volume is not to describe epigenomes, but rather to explore how understanding epigenomes tells us more about how biological systems work and the challenges and approaches taken to accomplish this. These contributions have attempted to integrate epigenomics into our understanding of genomes in wider context, and to communicate some of the wonders of epigenetics illustrated through examples across the biological spectrum.
In the past four years, many genetic loci have been implicated for BMI from the outcomes of genome-wide association studies (GWAS), primarily in adults. Insulin-induced gene 2 (INSIG2) was the first locus to be reported by this method to have a role in obesity but replication attempts have yielded inconsistent outcomes. The identification of the second locus, the fat mass- and obesity-associated gene (FTO), h has been more robustly observed by others. Studies from both FTO knock out and FTO overexpression mouse model support the fact that FTO is directly involved in the regulation of energy intake and metabolism in mice, where the lack of FTO expression leads to leanness while enhanced expression of FTO leads to obesity. Along with numerous other studies, a number of genetic variants have been established robustly in the context of obesity, giving us fresh insights into the pathogenesis of the disease. This book will give a comprehensive overview of efforts aimed at uncovering genetic variants associated with obesity, which have been particularly successful in the past 5 years with the advent of genome-wide association studies (GWAS). This book will cover this state of the art technology and its application to obesity in great detail. Topics covered will include genetics of childhood obesity, genetics of syndromic obesity, copy number variants and extreme obesity, co-morbidities of obesity genetics, and functional follow-up of genetic variants. "
This authoritative text/reference presents a review of the history, current status, and potential future directions of computational biology in molecular evolution. Gathering together the unique insights of an international selection of prestigious researchers, this must-read volume examines the latest developments in the field, the challenges that remain, and the new avenues emerging from the growing influx of sequence data. These viewpoints build upon the pioneering work of David Sankoff, one of the founding fathers of computational biology, and mark the 50th anniversary of his first scientific article. The broad spectrum of rich contributions in this essential collection will appeal to all computer scientists, mathematicians and biologists involved in comparative genomics, phylogenetics and related areas.
In Tiling Arrays: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to study tiling microarrays in genomic discovery . These include methods and applications for transcriptional regulation, expression, genetic and epigenetic regulation, as well as techniques and skills on tiling microarray data analysis. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Tiling Arrays: Methods and Protocols seeks to provide scientists with a comprehensive and down to earth approach to maximize results.
The genomes of humans, as well as many other species, are interspersed with hundreds of thousands of tandem repeats of DNA sequences. Those tandem repeats located as codons within open reading frames encode amino acid runs, such as polyglutamine and polyalanine. Tandem repeats have not only been implicated in biological evolution, development and function but also in a large collection of human disorders. In Tandem Repeats in Genes, Proteins, and Disease: Methods and Protocols, expert researchers in the field detail many methods covering the analysis of tandem repeats in DNA, RNA and protein, in healthy and diseased states. This will include molecular genetics, molecular biology, biochemistry, proteomics, biophysics, cell biology, and molecular and cellular approaches to animal models of tandem repeat disorders. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoratative and Practical, Tandem Repeats in Genes, Proteins, and Disease: Methods and Protocols aids scientists in continuing to study the unique methodological challenges that come from repetitive DNA and poly-amino acid sequences.
Using genome sequencing, one can predict possible interactions among proteins. There are very few titles that focus on protein-protein interaction predictions in bacteria. The authors will describe these methods and further highlight its use to predict various biological pathways and complexity of the cellular response to various environmental conditions. Topics include analysis of complex genome-scale protein-protein interaction networks, effects of reference genome selection on prediction accuracy, and genome sequence templates to predict protein function.
The goal of this volume is to provide a comprehensive
mechanistic and quantitative view of the processes that mediate or
influence the quality control in translation. In addition to
discussing processes with direct contribution to translation
fidelity, such as aminoacylation of tRNAs and translation
elongation itself, special attention is given to other processes
with impact on quality control: detection and elimination of
defective mRNAs, recycling and translation re-initiation, mRNA
editing, and translational recoding through programmed
Provides a comprehensive mechanistic and quantitative view of the processes that mediate or influence the quality control in translation.
Special attention is given to other processes with impact on quality control: detection and elimination of defective mRNAs, recycling and translation re-initiation, mRNA editing, and translational recoding through programmed frame-shifting.
Colin Graham and a team of leading investigators and expert clinical scientists update the acclaimed first edition with a collection of powerful, up-to-date PCR-based methods for DNA sequencing, many suitable for human genome sequencing and mutation detection in human disease. This second edition offers new material on automated DNA sequencers, capillary DNA sequencers, heterozygote mutation detection, web-based sequencing databases and genome sequencing sites, and the human genome project. State-of-the-art and highly practical, DNA Sequencing Protocols, 2nd Edn. constitutes an essential laboratory handbook for geneticists and molecular biologists, offering concise, easy-to-follow methods that will work and impact today's genome sequencing projects.
DNA Repair, Volume 115, the latest release in the Advances in Protein Chemistry and Structural Biology series, provides an overview of current developments in mechanisms underlying DNA repair, their involvement in maintaining chromatin repair, the balance between chromosome breaks repair pathways, tumorigenesis, immune signaling and infection-induced inflammation. Specific chapters cover the Structure and function of the multi-subunit TFIIH with insights into nucleotide excision repair, Chromatin repair: how DNA packaging controls double-strand break repair, Controlling the balance between chromosome breaks repair pathways, The targeting of DNA repair pathways in the era of precision oncology, and much more.
A comprehensive treatment of the characterisation techniques used in investigating inorganic and organic molecules that interact with biomolecules is presented to the reader in a clear fashion. The work consists of two parts: (i) synthetic aspects of metallointercalators along with targeting and improving transport and (ii) the various techniques that are used for probing their interactions, such as; DNA-NMR, PGSE-NMR, DNA ESI-MS, Linear and Circular Dichroism, Fluorescence Spectroscopy, Confocal Microscopy, Viscosity, TGA and dialysis, Microarrays, biological analysis. Chapters are devoted to the synthesis and the techniques used to study the interactions of inorganic complexes with biomolecules. Considerably detailed examples are used to help illustrate the application of these techniques. This book is a useful resource for an array of inorganic and organic advanced undergraduate and graduate courses and for researchers in drug discovery.
Depite the rapid expansion of the field of biophysics, there are very few books that comprehensively treat specific topics in this area. Recently, the field of single molecule biophysics has developed very quickly, and a few books specifically treating single molecule methods are beginning to appear. However, the promise of single molecule biophysics is to contribute to the understanding of specific fields of biology using new methods. This book would focus on the specific topic of the biophysics of DNA-protein interactions, and would include the use of new approaches, including both bulk methods as well as single molecule methods. This would make the book attractive to anyone working in the general area of DNA-protein interactions, which is of course a much wider market than just single molecule biophysicists or even biophysicists. The subject of the book will be the biophysics of DNA-protein interactions, and will include new methods and results that describe the physical mechanism by which proteins interact with DNA. For example, there has been much recent work on the mechanism by which proteins search for specific binding sites on DNA. A few chapters will be devoted to experiments and theory that shed light on this important problem. We will also cover proteins that alter DNA properties to facilitate interactions important for transcription or replication. Another section of the book will cover the biophysical mechanism by which motor proteins interact with DNA. Finally, we will cover larger protein-DNA complexes, such as replication forks, recombination complexes, DNA repair interactions, and their chromatin context.
Nutritional Epigenomics offers a comprehensive overview of nutritional epigenomics as a mode of study, along with nutrition's role in the epigenomic regulation of disease, health and developmental processes. Here, an expert team of international contributors introduces readers to nutritional epigenomic regulators of gene expression, our diet's role in epigenomic regulation of disease and disease inheritance, caloric restriction and exercise as they relate to recent epigenomic findings, and the influence of nutritional epigenomics over circadian rhythms, aging and longevity, and fetal health and development, among other processes. Disease specific chapters address metabolic disease (obesity and diabetes), cancer, and neurodegeneration, among other disorders. Diet-gut microbiome interactions in the epigenomic regulation of disease are also discussed, as is the role of micronutrients and milk miRNAs in epigenetic regulation. Finally, chapter authors examine ongoing discussions of race and ethnicity in the social-epigenomic regulation of health and disease.
* Comprehensive and an easily accessible reference volume for developing, running, and analyzing biomedical research using the rat as model system Grown exponentially by the genomic revolution, the use of the rat as a model of choice for physiological studies continues in popularity and at a much greater depth of understanding. In Rat Genomics: Methods and Protocols, world-wide experts provide both practical information for researchers involved in genomic research in the rat along with a more contextual discussion about the usefulness of the rat in physiological or translational research in different organs and systems. The volume extensively covers topics including genome sequencing, quantitative trait loci mapping, and the identification of single nucleotide polymorphisms as well as the development of transgenic technologies such as nuclear cloning, lentiviral-mediated transgenesis, gene knock-down using RNA interference, gene knock-out by mutagenesis, and zinc finger nucleases plus exciting advances in the obtention of rat embryonic cell lines. As a volume in the highly successful Methods in Molecular BiologyT series, this work provides the kind of detailed description and implementation advice that is crucial for getting optimal results. Comprehensive and up-to-date, Rat Genomics: Methods and Protocols thoroughly covers the current techniques used in labs around the world and overviews the applications of the data obtained, making it certain to be useful to the scientific community as a key source of references and methods.
Significant advancements have been made in the study of chromatin structure and function over the past fifty years but none as spectacular as those made in the last decade due to the development of novel techniques and the ability to sequence large stretches of DNA. In Chromatin Protocols, Second Edition, expert researchers delineate these cutting-edge techniques via step-by-step laboratory methods and protocols, which encompass a wide array of topics from the isolation of nucleosomes, assembly of nucleosomes and study of the basic chromatin structure to detailed analysis of histone modifications and chromatin function. Written in the highly successful Methods in Molecular Biology (TM) series style, chapters include brief introductions to the subjects, lists of the necessary materials and reagents, readily reproducible protocols, and Notes sections which highlight tips on troubleshooting and avoiding known pitfalls. Comprehensive and up-to-date, Chromatin Protocols, Second Edition is a valuable tool for scientists studying various aspects of chromatin function and an ideal guide to aid in the development of new techniques as well as new ideas in the field of chromatin biology.
Scientists can use molecular profiling microarrays to compare healthy cells with their diseased counterparts and develop gene-specific treatments. Finding the best way to interpret original profiling data into accurate trends, however, continues to drive the development of normalization algorithms and software tools. Methods in Microarray Normalization compiles the most useful and novel techniques for the first time into a single, organized source. Experts in the field provide a diverse view of the mathematical processes that are important in normalizing data and avoiding inherent systematic biases. They also review useful software, including discussions on key algorithms, comparative data, and download locations. The book discusses the use of early normalization techniques for new profiling methods and includes strategies for assessing the utility of various normalization algorithms. It presents the latest microarray innovations from companies such as Agilent, Affymetrix, and GeneGo as well as new normalization methods for protein and CGH arrays, many of which are applicable for antibody, microRNA, methylation, and siRNA arrays. Methods in Microarray Normalization provides scientists with a complete resource on the most effective tools available for maximizing microarray data in biochemical research. Daniel E. Levy, editor of the Drug Discovery Series, is the founder of DEL BioPharma, a consulting service for drug discovery programs. He also maintains a blog that explores organic chemistry.
One of the most important topics in evolutionary biology concerns the origin and evolution of sex-determining systems and sex chromosomes. Certain plant species display younger sex-chromosome systems in different evolutionary stages. It is thought that the same evolutionary forces described for animals are operating in plants. However, in opposition to the situation in animals, sex-determining mechanisms seem to be more flexible, and most species with separate sexes have evolved directly from ancestors with both sex functions. These features make plants excellent models for studies on sex determination. In this context, early evolved plant-sex chromosomes have given rise to many studies in recent years. In this book, the most recent findings are highlighted and reviewed, focusing specifically on model species, including Carica papaya, Fragaria virginiana, Silene latifolia and Rumex acetosa
This book contains a broad survey on the peroxiredoxins. It involves almost all groups that contributed significant insights into the emerging field. Coverage discusses the diverse biological roles of the new protein family in the context of other antioxidant systems like those based on heme or selenium catalysis. In addition, the book highlights related future perspectives.
Plants are sessile organisms and their only alternative to a rapidly changing environment is a fast adaptation to abiotic and biotic stresses. Among the several known species of flowering plants, Arabidopsis thaliana is the only plant that has been most thoroughly studied. This angiosperm with dicotyledonous seeds belonging to the family Brassicaceae was known to botanists for at least four centuries and has been used since then for experimental studies for about half a century, until it was Friedrich Laibach who had outlined the advantages of using it in genetic experiments and had also suggested that it could be used as a plant model system in 1943. Its unique features favors genetic experiments, which include its small size, a rapid generation time, the ability to grow well under controlled conditions, high fecundity of up to 10,000 seeds per plant. Like the peas that Mendel studied, it reproduces mainly by self-fertilisation. Arabidopsis is considered a model plant for many studies as its genomic sequence was completely identified and its mechanisms in genomic, transcriptomic and proteomic regulation are often similar to other plant species. The aim of this book is to give an up-to-date overview on the recent breakthroughs in the area of responses and adaptations of Arabidopsis, particularly those regarding its cultivation, life cycle and functional genomics. The chapters are focused on the most exciting and innovative researches on this species, involving authors with strong research experience. The present volume would definitely be an ideal source of scientific information to the advanced students, junior researchers, faculty and scientists involved in the ecology, agriculture, environmental microbiology, genetics, molecular biology, biochemistry, biotechnology and other areas involving Arabidopsis studies and plant sciences in general.
In the post-genomic age, much biomedical research looks at when, where, and at what level genes are expressed. Measuring Gene Expression is an all-in-one introduction to the main methods of measuring gene expression, including RT-PCR, differential display, RNA interference, reporter genes, microarrays, and proteomics, as well as a section on RNA isolation and analysis. There is an overview of each method: its pros and cons, sample preparation, sources of error, and data interpretation.
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