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The second edition of this book presents the role of osmolytes in human health and diseases. Some of the chapters deal about the possibility of the use of osmolytes as diagnostic biomarkers and potential drug design for neurodegenerative and other human diseases. Other chapters also include reviews on the role of osmolytes in cancer, metastasis, infectious diseases, metabolic disorders, immunological disorders, and tissue regeneration. Importantly, the book also contain recent updates on the role of naturally occurring osmolytes in protein folding pathway, protein stability, and their underlying mechanisms. The book also covers the aspects that osmolytes could promote conformational alterations of transcription factors that favor metastatic behavior. Potential of the osmolytes in the various process of vaccine development, including enhancing the efficacy, production, and purification steps are also succintly described. Towards the end, the book also elucidates the use of specific molecules for the prevention of toxic gain of functions and restoration of function to disease-causing mutant protein. This book is an invaluable asset for the researchers especially working in osmolyte biology and scientists involved in basic and clinical research particularly neurodegeneration, diabetes, cancer, and metabolic disorders.

Aging: Oxidative Stress and Dietary Antioxidants, Second Edition, bridges the trans-disciplinary divide and covers the science of oxidative stress in aging and the therapeutic use of natural antioxidants in the food matrix in a single volume. The second edition covers new trials and investigations used to determine the comprehensive properties of antioxidants, food items and extracts, as well as any adverse properties they may have. It has been updated to include new clinical human trials and a new section dedicated to animal models of aging. Throughtout the book the processes within the science of oxidative stress are described in concert with other processes, such as apoptosis, cell signaling, and receptor mediated responses. This approach recognizes that diseases are often multifactorial, and oxidative stress is a single component of this. Gerontologists, geriatricians, nutritionists, and dieticians are separated by divergent skills and professional disciplines that need to be bridged to advance preventative as well as treatment strategies. While gerontologists and geriatricians may study the underlying processes of aging, they are less likely to be conversant in the science of nutrition and dietetics. On the other hand, nutritionists and dietitians are less conversant with the detailed clinical background and science of gerontology. This book addresses this gap and brings each of these disciplines to bear on the processes inherent in the oxidative stress of aging. This will aid in better research, treatment and outcome for patients. - Compares information related to mitochondrial oxidative stress in one disease to diet-related strategies in other unrelated diseases - Provides an understanding of cell signalling leading to new suggestions of preventative or therapeutic strategies - Includes a new section dedicated to animal models of aging

This book includes a series of reviews on general aspects of biomarker use in the study of psychiatric and neurodegenerative diseases and the development of medications involved in their treatment. It describes the pros and cons of the various approaches and covers the successes and failures in this research field. It is only by a thorough understanding of the shortcomings that progress can be made. The overall goal is to facilitate the understanding and treatment of these disorders, by providing a viable mechanism of catching up with other areas of modern medicine, such as diabetes and heart disease. Finally, it is anticipated that the development and application of valid biomarker tests and the leveraging of novel drug targets will help the fields of psychiatry on neurodegenerative disorders move into the area of personalized medicine where the right patients can receive the right medication at the right time for the best possible outcome.

The purpose of this book is to introduce the readers on the perspective of the role that unsaturated fatty acids and complex lipids play on health and disease. Bioactive lipids can be modified affecting membrane composition, structure and fluidity in addition to changes in cell signaling associated to lipid-protein (membrane receptors) interactions, issues that are addressed by the authors. This book analyzes key topics involving bioactive lipids and their role in normal signaling and the mechanisms of disease. The book navigates from structural studies of oxidized and non-oxidized lipids to the reactions and cell signaling processes that bioactive lipids play in cardiovascular and neurodegenerative diseases. The book contains the recent advances reported in the literature about lipidomics as well as the role that lipid-derived compounds exert on unfolded protein response and lipid metabolism and disease. This book represents a state of the art introduction to lipid metabolism from a biochemical to an in vivo overview being an useful tool for students and investigators. We hope the mechanistic observations on the role of bioactive lipids in health and disease serve a perspective to improve the existing treatments or propose new lipid-based pharmacology

This unique work compiles the latest knowledge around veterinary nutraceuticals, commonly referred to as dietary supplements, from ingredients to final products in a single source. More than sixty chapters organized in seven sections collate all related aspects of nutraceutical research in animal health and disease, among them many novel topics: common nutraceutical ingredients (Section-I), prebiotics, probiotics, synbiotics, enzymes and antibacterial alternatives (Section-II), applications of nutraceuticals in prevention and treatment of various diseases such as arthritis, periodontitis, diabetes, cognitive dysfunctions, mastitis, wounds, immune disorders, and cancer (Section-III), utilization of nutraceuticals in specific animal species (Section-IV), safety and toxicity evaluation of nutraceuticals and functional foods (Section-V), recent trends in nutraceutical research and product development (Section-VI), as well as regulatory aspects for nutraceuticals (Section-VII). The future of nutraceuticals and functional foods in veterinary medicine seems bright, as novel nutraceuticals will emerge and new uses of old agents will be discovered. International contributors to this book cover a variety of specialties in veterinary medicine, pharmacology, pharmacognosy, toxicology, chemistry, medicinal chemistry, biochemistry, physiology, nutrition, drug development, regulatory frameworks, and the nutraceutical industry. This is a highly informative and carefully presented book, providing scientific insight for academia, veterinarians, governmental and regulatory agencies with an interest in animal nutrition, complementary veterinary medicine, nutraceutical product development and research.

The book Heat Shock Proteins and Stress provides the most comprehensive review on contemporary knowledge on the role of HSP in Stress. Using an integrative approach to understanding the regulation of HSP responses, the contributors provide a synopsis of novel mechanisms by which HSP responses are regulated under normal physiological and pathophysiological conditions. Key basic and clinical research laboratories from major universities and academic medical hospitals around the world contribute chapters that review present research activity and importantly project the field into the future. The book is a must read for researchers, postdoctoral fellows and graduate students in the fields of Translational Medicine, Clinical Psychologists, Human Physiology, Zoologists, Botanists, Biotechnology, Molecular Medicine, Infectious Diseases Experts and Pathologists.

This book presents an overview of lipid peroxidation: inhibition, effects and mechanisms. The topics analyzed, cover a broad spectrum of functions played by lipid peroxidation and presents new information in this area of research. The topics analyzed include: progress in the knowledge of lipid peroxidation, from the first evidences issued by Nicolas Theodore de Saussure in Paris 1804; fighting against lipid peroxidation: the unique story of docosahexaenoic acid in the brain; protective effects of melatonin and structurally-related molecules in reducing membrane rigidity due to lipid peroxidation; synergistic effects of antioxidant compositions during inhibited lipid autoxidation; lipid peroxidation and animal longevity; free radicals in health and disease; lipid peroxidation in autoimmune diseases; aldehydes derived from lipid peroxidation in cancer and autoimmunity; the role of reactive oxygen species and lipid peroxidation in the neurodegenerative process after spinal cord injury; kinetics and mechanisms of inhibited lipid autoxidation in presence of 4-substituted-coumarins; hypoxia and oxidative stress: cell signaling mechanisms and protective role of vitamin C and cilnidipine; characterization of oxidative stress and antioxidant potency; paying attention to time and location; lipid peroxidation in aquatic organisms: ontogenetic, phylogenetic and ecological aspects; chemistry of lipid oxidation in edible oils; and menopause progression and oxidative stress: associated mechanisms and the importance of physical exercise.

This book summarizes the most recent progress in the studies of lipid mediators from the molecular to clinical level and introduces newly created tools for analysis including imaging mass spectrometry. Comprising 29 chapters divided into four major parts, the book describes the molecular natures of enzymes, transporters, and receptors for lipid mediators (Part I), the function of lipid mediators in Drosophila and Zebrafish (Part II), the relationships between lipid mediators and various diseases (Part III), and detailed procedures of extraction, preparation, and quantification of lipid mediators (Part IV). Research on lipid mediators initially started with analysis of the action of aspirin, and subsequent biochemical experiments identified many enzymes and receptors responsible for the biosynthesis and signal transduction of individual lipid mediators. Through the phenotypic analyses of transgenic and knockout mice, it has been shown that the dysregulation of some lipid mediators causes inflammatory, immune, or oncogenic disorders. Lipid mediators have attracted increased attention because their structures are conserved among different species, and their biosynthetic and signaling pathways have been deciphered at the molecular level. Many drugs that target lipid mediators are already being used in hospitals, and this book suggests further possibilities for development of a wide variety of such drugs. Very recently, highly sensitive mass spectrometry has begun to be used to identify novel lipid mediators that are present only in trace amounts in tissues but with robust biological activity. Written by international experts, this book provides readers a comprehensive view of lipid mediators and related topics and helps in the process of determining research targets for the near future.

Proteostasis is central to the development of various human diseases caused due to excessive protein misfolding and the disregulation of the protein quality control system. In this book, respected researchers from many leading institutions contribute their insights on proteostasis maintenance. The coverage mainly focuses on the basics of maintaining proteostasis, the consequences of proteostatic system failure, and how chaperone systems constantly maintain proteostasis. In addition, the book presents in detail different treatment strategies for diseases caused by proteostatic system failure, as well as the inhibition of proteostatic failure using small molecule compounds. It examines advances in the modulation of proteopathies, providing a comprehensive source of key mechanistic insights on these diseases. As such, the book offers a valuable resource for beginners and more experienced investigators alike who are looking for detailed and reliable information on protein homeostasis, the diseases that can develop due to related imbalances and the essential role of molecular and chemical chaperones.

This book, for the first time, comprehensively assembles and analyzes a large body of information on the role of the fundamental mechanism of the protein biosynthesis pathway, translation, in cancer biology. It systematically explores the function of the translation machinery and its regulation, including cell signaling, in the development, maintenance and progression of human cancer. The work presented here unveils the tremendous potential and applications of this vast and exciting branch of genetic, biochemical and molecular science in cancer medicine and drug development.Chapters contributed by experts in the field take the reader on a journey that starts with a dissection of the translation machinery and its regulation in norm and cancer. Later chapters characterize etiological and pathogenetic roles that translation plays in specific cancer types. Various aspects of diagnostic, prognostic and therapeutic significance of the translation machinery and its control in cancer are discussed. Readers will discover the importance of the process of translation and its regulatory mechanisms in physiology and cancer biology.The chapters and the numerous illustrations included here were contributed by expert scientists and clinicians from renowned academic and clinical establishments in Canada, the United States of America, the United Kingdom, Italy, France, Belgium, Spain, Germany and Australia.The book conveys information and knowledge that may interest a broad range of students and scholars ranging from basic scientists to clinicians and drug developers seeking to better understand the protein synthesis and its aberrations in cancer biology and cancer medicine.

This volume presents the response of the eukaryotic translational apparatus to cellular stress and apoptosis, including kinases activated through both the ERK and stress-activated pathways. It further explores two agents that inhibit protein synthesis, calcium and the immunosuppressant rapamycin. Six chapters written by leading experts in the field provide both new data and comprehensive literature reviews. Both the regulation of initiation and elongation are discussed, and the mechanisms of apoptosis are related to changes in the protein synthesis machinery.

Proceedings of the NATO Advanced Study Institute on Cellular Regulation by Protein Phosphorylation held at Chateau La Londe les Maures (France), September 5-15, 1990

The articles in the present volume are by major contributors to our under­ standing of signaling pathways affecting protein synthesis. They focus pri­ marily on two extracellular anabolic signals, although others are included as well. Insulin is one of the best-studied extracellular regulators of protein syn­ thesis. Several of the known pathways for regulation of protein synthesis were elucidated using insulin-dependent systems. Regulation of protein synthesis by amino acids, by contrast, is an emerging field that has recently received a great deal of attention. The dual role of amino acids as substrates for protein syn­ thesis and regulators of the overall process has only recently been recognized. Since amino acids serve as precursors for proteins, one might expect that with­ holding an essential amino acid would inhibit the elongation phase. Surpris­ ingly, research has shown that it is the initiation phase of protein synthesis that is restricted during amino acid starvation. Understanding the mechanisms by which the biosynthesis of proteins is reg­ ulated is important for several reasons. Protein synthesis consumes a major portion of the cellular ATP that is generated. Therefore, small changes in protein synthesis can have great consequences for cellular energy metabolism. Translation is also a major site for control of gene expression, since messenger RNAs differ widely in translational efficiency, and changes to the protein syn­ thesis machinery can differentially affect recruitment of individual mRNAs.

Amyloid-forming proteins are implicated in over 30 human diseases. The proteins involved in each disease have unrelated sequences and dissimilar native structures, but they all undergo conformational alterations to form fibrillar polymers. The fibrillar assemblies accumulate progressively into disease-specific lesions in vivo. Substantial evidence suggests these lesions are the end state of aberrant protein folding whereas the actual disease-causing culprits likely are soluble, non-fibrillar assemblies preceding the aggregates. The non-fibrillar protein assemblies range from small, low-order oligomers to spherical, annular, and protofibrillar species. Oligomeric species are believed to mediate various pathogenic mechanisms that lead to cellular dysfunction, cytotoxicity, and cell loss, eventuating in disease-specific degeneration and systemic morbidity. The particular pathologies thus are determined by the afflicted cell types, organs, systems, and the proteins involved. Evidence suggests that the oligomeric species may share structural features and possibly common mechanisms of action. In many cases, the structure–function interrelationships amongst the various protein assemblies described in vitro are still elusive. Deciphering these intricate structure–function correlations will help understanding a complex array of pathogenic mechanisms, some of which may be common across different diseases albeit affecting different cell types and systems.

Among all cellular RNA species of the three main types, ribosomal RNA, transfer RNA or messenger RNA, be they from prokaryotic or eukaryotic organisms, the prokaryotic mRNA is unique in that it has no precursor and is synthesized in the same mature form as it is translated into proteins. In fact, ribosomes join the nascent mRNA chain and engage in protein synthesis long before its transcription is complete. Provisions are even made for slowing down the ribo­ somes at some sites to prevent them from catching up with the RNA-polymerase. Of course, such a situation is only possible in the prokaryotic world where there is no such thing as a nuclear mem­ brane physically secluding the transcription process from the cy­ toplasm where translation is restricted. Quite in the opposite extreme, the eukaryotic pre-messenger RNA has to suffer many and sometimes drastic steps of maturation (capping, polyadenylation, splicing, edition) before the decision is made to export it to the cytoplasm. That is where it enters the scope of this book. Once in the cytoplasm, many options are still open to it: its entrance into polysomes may be delayed (as it is in unfertilized eggs) or merely prohibited (ferritin mRNA in iron-starved cells), directed to specific locations within the cytoplasm or be more or less rapidly degraded. During gametogenesis and early development, translational control is probably the most significant level of gene expression.

Recent advances in molecular biology have shown GTPases and phosphoproteins to be the paramount molecular switches utilized intracellularly in biological systems. The origins of the GTPase switch appear to be almost as ancient as life itself, and through evolution nature has adapted this switch to a variety of purposes. In this two-volume work a broad survey of the major classes of GTPases is presented. The role of GTPases in ensuring accuracy during protein translation, a new look at the trimeric G-protein cycle, the molecular function of ARF in vesicle coating, the emerging role of the dynamin family in vesicle transfer, GTPases which activate GTPases during nascent protein translocation, and the many roles of ras-related proteins in growth, cytoskeletal polymerization, and vesicle transfer, are all described in 80 chapters by the leading authorities in their fields. Both detailed knowledge of specific systems or proteins and general principles of structure and function are offered. Much of this information has never been published before. At the rate the extended family of GTPases is growing it becomes increasingly unlikely that we will again get it to sit for a group portrait such as this. Therefore, the volume has the chance to become the reference work for GTPases.

It is very clear nowadays that plants offer several opportunities for basic studies, e.g. on development and embryogenesis, and that the fundamental principles laid open contribute to the development of new tools for plant breeding. Within the scope of the present publication, the editors have had to make a difficult choice from the many important subjects that have contributed to the remarkable progress of our molecular biological understanding of complex biological problems. This has resulted in review papers showing the present state of the art in genetic engineering, gene expression and its manipulation, microbe and insect interactions with plants, transposable elements and gene tagging, plant and organ development, the function and structure of the genome chloroplasts, and lipid biosynthesis. All papers have been written in such a way that they are also useful for non-experts interested in a particular field, as well as for students following courses in plant molecular biology. Besides presenting the state of the art, each paper gives some historical background to the developments in the field as well as perspectives for further basic research and applications. Because of the latter, scientists and students engaged in plant breeding will also profit from this publication.

This must-have cell signaling title will appeal to researchers across molecular biology, biochemistry, cell biology and genetics. The articles are written and edited by experts in the field and emphasize signaling to and from intracellular compartments including transcriptional responses to cytoplasmic and nuclear signaling events, chromatin remodeling and stress responses, the regulation of endoplasmic reticulum function, control of cell cycle progression and apoptosis and the modulation of the activities of mitochondria and other organelles. - Articles written and edited by experts in the field - Thematic volume covering regulation of endoplasmic reticulum function, regulation of cell cycle progression, and quality control and assurance in mitochondrion events - Up-to-date research on events in membrane proteins and proteins of intracellular matrix

Signal Transduction, 2e, is a thorough, well-illustrated study in cellular signaling processes. Beginning with the basics, this book shows how cells respond to external cues, hormones, growth factors, cytokines, cell surfaces, etc., and further instructs how these inputs are integrated. Instruction continues with up-to-date, inclusive coverage of intracellular calcium, nuclear receptors, tyrosine protein kinases and adaptive immunity, and targeting transduction pathways for research and medical intervention. Signal Transduction, 2e, serves as an invaluable resource for advanced undergraduates, graduate researchers, and established scientists working in cell biology, pharmacology, immunology, and related fields.Up-to-date, inclusive coverage of targeting transduction pathways for research and medical intervention In-depth coverage of nuclear receptors, including steps in isolation of steroid hormones and the discovery of intracellular hormone receptors; tyrosine protein kinases and adaptive immunity; and intracellular calciumExtensive conceptual color artwork to assist with comprehension of key topicsInstrumental margin notes highlight milestones in signaling mechanisms

Proceedings of the 7th International Conference on Alzheimer's Disease and Parkinson's Disease (ADPD), held March 9-13, 2005 in Sorrento, Italy. The subject matter of the ADPD conferences is unique in that it deals not only with issues related individually to Alzheimer's disease and Parkinson's disease, but also with the integration of these and other related diseases. The most up-to-date techniques and research findings are illustrated in this volume, covering topics such as immunology, neuroscience, pharmacology, genetics, molecular biology, biochemistry and the history, epidemiology, clinical phenomenology, diagnosis, imaging, treatment,and future perspectives of Alzheimer's and Parkinson's Diseases.

Proteomics is a multifaceted, interdisciplinary field which studies the complexity and dynamics of proteins in biological systems. It combines powerful separation and analytical technology with advanced informatics to understand the function of proteins in the cell and in the body. This book provides a clear conceptual description of each facet of proteomics, describes recent advances in technology and thinking in each area, and provides details of how these have been applied to a variety of biological problems. It is written by expert practitioners in the field, from industry, research institutions, and the clinic. It provides junior and experienced researchers with an invaluable proteomic reference, and gives fascinating glimpses of the future of this dynamic field.

Molecular chaperones are involved in a wide variety of essential cellular processes in living cells. A subset of molecular chaperones have been initially described as heat shock proteins protecting cells from stress damage by keeping cellular proteins in a folding competent state and preventing them from irreversible aggregation. Later it became obvious that molecular chaperones are also expressed constitutively in the cell and are involved in complex processes such as protein synthesis, intracellular protein transport, post-translational modification and secretion of proteins as well as receptor signalling. Hence, it is not surprising that molecular chaperones are implicated in the pathogenesis of many relevant diseases and could be regarded as potential pharmacological targets. Starting with the analysis of the mode of action of chaperones at the molecular, cellular and organismic level, this book will then describe specific aspects where modulation of chaperone action could be of pharmacological and therapeutic interest.