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This book discusses a broad range of basic and advanced topics in the field of protein structure, function, folding, flexibility, and dynamics. Starting with a basic introduction to protein purification, estimation, storage, and its effect on the protein structure, function, and dynamics, it also discusses various experimental and computational structure determination approaches; the importance of molecular interactions and water in protein stability, folding and dynamics; kinetic and thermodynamic parameters associated with protein-ligand binding; single molecule techniques and their applications in studying protein folding and aggregation; protein quality control; the role of amino acid sequence in protein aggregation; muscarinic acetylcholine receptors, antimuscarinic drugs, and their clinical significances. Further, the book explains the current understanding on the therapeutic importance of the enzyme dopamine beta hydroxylase; structural dynamics and motions in molecularmotors; role of cathepsins in controlling degradation of extracellular matrix during disease states; and the important structure-function relationship of iron-binding proteins, ferritins. Overall, the book is an important guide and a comprehensive resource for understanding protein structure, function, dynamics, and interaction.

This book addresses the design of emerging conceptual tools, technologies and systems including novel synthetic parts, devices, circuits, oscillators, biological gates, and small regulatory RNAs (riboregulators and riboswitches), which serve as versatile control elements for regulating gene expression. Synthetic biology, a rapidly growing field that involves the application of engineering principles in biology, is now being used to develop novel systems for a wide range of applications including diagnostics, cell reprogramming, therapeutics, enzymes, vaccines, biomaterials, biofuels, fine chemicals and many more. The book subsequently summarizes recent developments in technologies for assembling synthetic genomes, minimal genomes, synthetic biology toolboxes, CRISPR-Cas systems, cell-free protein synthesis systems and microfluidics. Accordingly, it offers a valuable resource not only for beginners in synthetic biology, but also for researchers, students, scientists, clinicians, stakeholders and policymakers interested in the potential held by synthetic biology.

This book provides a comprehensive summary of the latest developments in the field of the genomics of cardiac disease. Written and edited by leading clinicians and scientists involved in the analysis and therapy of genetic cardiac disorders, it discusses the genetic causes of a variety of cardiac diseases, such as the complex genetics and etiology of congenital heart diseases. It also explores sex differences in prevalent diseases, genetics-based therapeutic strategies and the use of various animal models and alternatives. The book is intended for research scientists and clinical scientists in the cardiovascular field, human geneticists and cardiologists.

Most biological pathways, physical and neurological properties are highly conserved between humans and Drosophila and nearly 75% of human disease-causing genes have a functional homologue in Drosophila. This volume provides recent advances in Drosophila models for various human diseases, with each chapter providing a review of studies involving Drosophila models, as well as detailed protocols commonly used in laboratories. Starting with a review of Drosophila's value as a highly tractable model organism for studying human diseases, subsequent chapters present Drosophila models for specific human diseases. The book provides a useful resource for all scientists who are starting to use the Drosophila model in their studies, and for researchers working in the pharmaceutical industry and using new screening models to develop new medicines for various diseases.

Ribonucleic acid (RNA) binding proteins currently number in the thousands and defects in their function are at the heart of diseases such as cancer and neurodegeneration. RNA binding proteins have become implicated in the intricate control of surprisingly diverse biological settings, such as circadian rhythm, stem cell self-renewal, oncogenesis and germ cell development. This book surveys a range of genome-wide and systems approaches to studying RNA binding proteins, the importance of RNA binding proteins in development, cancer and circadian rhythm.

G protein-coupled receptors (GPCRs) are heptahelical transmembrane receptors that convert extra-cellular stimuli into intra-cellular signaling, and ultimately into biological responses. Since GPCRs are natural targets for approximately 40% of all modern medicines, it is not surprising that they have been the subject of intense research. Notwithstanding the amount of data generated over the years, discovering ligands of these receptors with optimal therapeutic properties is not straightforward and has certainly been hampered for years by the lack of high-resolution structural information about these receptors. Luckily, there has been a steady increase of high-resolution crystal structures of these receptors since 2007, and this information, integrated with dynamic inferences from computational and experimental methods, holds great potential for the discovery of new, improved drugs. This book, which provides, for the first time, state-of-the-art views on modeling and simulation of GPCRs, is divided into 4 parts. In the first part, the impact of currently available GPCR crystal structures on structural modeling is discussed extensively as are critical insights from simulations in the second part of the book. The third part reports recent progress in rational ligand discovery and mathematical modeling, whereas the fourth part provides an overview of bioinformatics tools and resources that are available for GPCRs.

This volume contains 29 engrossing chapters contributed by worldwide, leading research groups in the field of chemical biology. Topics include pre-biology; the establishment of the genetic code; isomerization of RNA; damage of nucleobases in RNA; the dynamic structure of nucleic acids and their analogs in DNA replication, extra- and intra-cellular transport; molecular crowding by the use of ionic liquids; new technologies enabling the modification of gene expression via editing of therapeutic genes; the use of riboswitches; the modification of mRNA cap regions; new approaches to detect appropriately modified RNAs with EPR spectroscopy and the use of parallel and high-throughput techniques for the analysis of the structure and new functions of nucleic acids. This volume discusses how chemistry can add new frontiers to the field of nucleic acids in molecular medicine, biotechnology and nanotechnology and is not only an invaluable source of information to chemists, biochemists and life scientists but will also stimulate future research.

This collection of reviews and protocols provides the reader with an introduction to the current state of knowledge on how various diseases are related to mitochondrial dysfunction. Mitochondria contain their own genome, a small, circular double-stranded DNA (mtDNA), and alterations in mtDNA may play an important role in the multistep carcinogenesis of at least some types of human cancer. In addition to mutations of mtDNA, many mitochondrial syndromes are due to abnormalities in nuclear genes related to oxidative phosphorylation (OXPHOS). Mitochondrial tRNA (MTT) gene mutations are an important cause of human morbidity and are associated with a wide range of pathology, from isolated organ?]specific diseases such as myopathy or hearing loss, to multisystem disorders with encephalopathy, gastrointestinal dysmotility, and life?]threatening cardiomyopathy. The relationship of the mitochondrion organelle to aging and longevity is also discussed. Laboratory protocols describe methodology to characterize mtDNA heteroplasmy by parallel sequencing. Each eukaryotic cell contains hundreds of mitochondria with hundreds of mitochondria genomes. Mutant and wild-type mtDNA may co-exist as heteroplasmy, and cause human disease. The purpose of this protocol is to simultaneously determine mtDNA sequence and quantify the heteroplasmic level. Another protocol describes procedures for obtaining tissue sections and cell material suitable for histological evaluation of OXPHOS activity and integrity and immunodetection of the complexes in tissue from patients suspected of mitochondrial disease. Emphasis lies on the diagnostic potential of these techniques to differentiate mtDNA from nuclear mutations. This e-book — a curated collection from eLS, WIREs, and Current Protocols — offers a fantastic introduction to the field of mitochondrial diseases for students or interdisciplinary collaborators.

The last ten years have witnessed a remarkable increase in our awareness of the importance of events subsequent to transcriptional initiation in terms of the regulation and control of gene expression. In particular, the development of recombinant DNA techniques that began in the 1970s provided powerful new tools with which to study the molecular basis of control and regulation at all levels. The resulting investigations revealed a diversity of post-transcriptional mechanisms in both prokaryotes and eukaryotes. Scientists working on translation, mRNA stability, transcriptional (anti)termination or other aspects of gene expression will often have met at specialist meetings for their own research area. However, only rarely do workers in different areas of post-transcriptional control/ regulation have the opportunity to meet under one roof. We therefore thought it was time to bring together leading representatives of most of the relevant areas in a small workshop intended to encourage interaction across the usual borders of research, both in terms of the processes studied, and with respect to the evolutionary division prokaryotes/eukaryotes. Given the breadth of topics covered and the restrictions in size imposed by the NATO workshop format, it was an extraordinarily difficult task to choose the participants. However, we regarded this first attempt as an experiment on a small scale, intended to explore the possibilities of a meeting of this kind. Judging by the response of the participants during and after the workshop, the effort had been worthwhile.

For those like me who witnessed the beginning of the adventure of human mitochon­ drial pathology, one can only be astounded by the extent and unexpectedness of what the field has come to offer. Extent because nobody could have imagined the sheer size of the domain. Unexpectedness because hitherto it was impossible to imagine the clinical polymorphism that this pathology would represent. The starting point was clear. Initially, there was the exceptional, and for a long time unique, observation of euthyroidian hypermetabolism that Luft and colleagues analyzed remarkably in biochemical and clinical terms. Thereafter, there was the support provided by the electron microscopy studies of Afzelius, and the very first visualization of mitochondrial abnormalities. That was way back in 1958. A few years later, progress in the cytology and cytochemistry of skeletal muscle tissue was to provide the means of detecting such abnormalities by examining sections with light microscopy. The colorful term'ragged red fibers', coined by W. K. Engel, became uni­ versally accepted, and this typical aspect with Gomori trichrome stain was to throw light on the frequency with which these mitochondrial abnormalities could occur under pathological conditions which, until then, had remained a total mystery regard­ ing their mechanism: syndromes such as the ocular myopathies with their descending evolution and the oculocraniosomatic syndromes. We were at the beginning of the 1970s.

The 5th edition of this successful Glossary has been completely revised, updated and supplemented by up-to-date terms used in genetic engineering and molecular genetics. Where necessary a short essay explaining an entry in more detail is added to the stated definition. Wherever possible, the author of an entry is mentioned and the respective publication cited. Cross references ease the orientation within the glossary.'This excellent textbook should serve seasoned scientists as a feast for the mind and as a valuable work for graduate students. It is a true bargain...'(Quarterly Review of Biology)'By the very fact that this Glossary is now in its fifth edition, one can be assured of its usefulness... Highly recommended.'(Australasian)