Aging is loosely defined as the accumulation of changes in an organism over time. At the cellular level such changes are distinct and multidimensional: DNA replication ceases, cells stop dividing, they become senescent and eventually die. DNA metabolism and chromosomal maintenance, together with protein metabolism are critical in the aging process. The focus of this book is on the role of protein metabolism and homeostasis in aging. An overview is provided of the current knowledge in the area, including protein synthesis, accuracy and repair, post-translational modifications, degradation and turnover, and how they define and influence aging. The chapters mainly focus on well-characterised factors and pathways, but new areas are also presented, where associations with aging are just being elucidated by current experimental data. Protein turnover, the balance between protein synthesis and protein degradation are carefully maintained in healthy cells. Chapters 1 and 2 illustrate that aging cells are characterised by alterations in the rate, level and accuracy of protein synthesis compared to young ones, and that mRNA translation, essential for cell growth and survival, is controlled at multiple levels. The theory that growth and somatic maintenance are believed to be antagonistic processes is described in Chapter 3: inhibition of protein synthesis results in decreased rates of growth and development, but also confers an extension of lifespan, as shown for example by the effects of dietary restriction in various models organisms.

Cell Adhesion Molecules: Implications in Neurological Diseases contains review articles on recent developments in the field of neural cell adhesion molecules (CAMs). The main focus is on the role of cell adhesion molecules in various neurological and neurodegenerative diseases. This perspective has been essentially overlooked in recently published books on neural CAMs. In addition, the contributors cover many newly identified cell adhesion molecules and some that have not received much attention in recent years. This books fills an important gap in the currently available literature.

The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized - and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes.

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.

This volume presents key topics of current interest with regard to several pathophysiological conditions including (a) the basic and clinical aspects of bradykinin receptor antagonists, (b) the kallikrein-kinin pathways in hypertension and diabetes, (c) tissue kallikrein-kinin therapy for hypertension and organ damage, (d) the renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs for salt-sensitive hypertension, (e) the kallikrein-kinin system in diabetes retinopathy, and (f) genetic manipulation and genetic variation of the kallikrein-kinin system and their impacts on cardiovascular and renal disease. Written by internationally reputed scientists, the book provides an essential overview of the latest developments in the field of kinin research, making it a valuable asset for endocrinologists, nephrologists, cardiologists, pharmacologists, physiologists, ophthalmologists and rheumatologists. Furthermore, it is also intended for postgraduate students in the fields of medicine, pharmacy, physiology and pharmacology, and those working at research organizations.

Leading researchers are specially invited to provide a complete understanding of the key topics in these archetypal multidisciplinary fields. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.

The aim of this book is to provide the target audience, specifically students of Medicine, Biology, Systems Biology and Bioinformatics, as well as experienced researchers in research fields relevant to metabolic syndrome (MetS) with an overview of the challenges and opportunities in systems biology and how it can be used to tackle MetS. In particular, the aims are: (1) to provide an introduction to the key biological processes involved in the pathophysiology of MetS; (2) through the use of specific examples, provide an introduction to the latest technologies that use a systems biology approach to study MetS; and (3) to give an overview of the mathematical modeling approaches for studying MetS. The clearly written chapters by leading experts in the field provides detailed descriptions crucial for the unique position of this book and its focus on the application of systems biology to tackle specific pathophysiologically relevant aspects of MetS and provides a valuable practical guide to this research community.

T. Buch, E. Schafer, D. Steinritz, A. Dietrich, T. Gudermann: Chemosensory TRP Channels in the Respiratory Tract: Role in Toxic Lung Injury and Potential as "Sweet Spots" for Targeted Therapies. D.C. Zebrowski and F. B. Engel: The Cardiomyocyte Cell Cycle in Hypertrophy, Tissue Homeostasis, and Regeneration. P. Hegyi and O.H. Petersen: The Exocrine Pancreas: The Acinar -Ductal Tango in Physiology and Pathophysiology.

This multidisciplinary book covers all aspects of oxygen delivery to tissue, including blood flow and its regulation as well as oxygen metabolism as discussed at the 33rd Annual Meeting of the International Society on Oxygen Transport to Tissue (ISOTT) held in Australia in 2005. Special attention is paid to methods of oxygen measurement in living tissue and the application of these technologies to understanding the physiological and biochemical basis for pathology related to tissue oxygenation.

Investigations involving incisive mechanistic dissection of various types of synaptic plasticity have revealed that it plays key roles in neural development, sensory information processing, cortical remapping following brain injury, perception, and behavioral learning and memory. Disruptions of synaptic plasticity may underlie neurological and behavioral disorders such as Alzheimer disease, Fragile-X syndrome, autism, and drug addiction. Multidisciplinary Tools for Investigating Synaptic Plasticity, therefore, assembles expert contributions that highlight techniques and strategies used in probing the cellular and molecular mechanisms of synaptic plasticity in the nervous systems of vertebrate and invertebrate species. Divided into three sections, this meticulous volume describes biochemical and genetic strategies for studying synaptic plasticity, behavior, neural development, and synaptogenesis, and also includes cellular electrophysiological and optical methods for interrogating a diverse array of mechanistic issues. As part of the Neuromethods series, this book contains the kind of detail and key implementation advice that maximizes successful results. Authoritative and invaluable, Multidisciplinary Tools for Investigating Synaptic Plasticity serves as an ideal primer for introducing researchers to specific techniques that will enhance their success at addressing novel questions in synaptic plasticity at the lab bench.

Functional selectivity refers to the ability of different ligands acting at one receptor subtype to activate multiple signaling pathways in unique combinations; that is, one drug can be an agonist at pathway A and an antagonist or partial agonist at pathway B, and another drug can have the reverse profile. Functional selectivity has profound implications for drug development, for chemical biology, and for the design of experiments to characterize receptor function. In Functional Selectivity of G Protein-Coupled Receptors expert neuroscientists and pharmacologists review the work that demonstrated the existence of functional selectivity, placed it within a theoretical framework, and provided a mechanistic basis for the phenomenon. This exciting, comprehensive, and future-oriented volume includes chapters that focus on theoretical and mechanistic aspects of functional selectivity and that cut across subfamilies of GPCRs. Additional chapters focus on subfamilies of therapeutically relevant receptors where there is considerable evidence of ligand functional selectivity. Accessible and authoritative, Functional Selectivity of G Protein-Coupled Receptors is a valuable educational tool and reference source for students and scientists interested in drug development, chemical biology, and GPCR function.

Calcium ions represent Mother Nature's 'ion-of-choice' for regulating fundamental physiological functions, as they initiate a new life at the time of fertilization and guide subsequent developmental and physiological functions of the human body. Calcium channels, which act as gated pathways for the movement of calcium ions across the membranes, play a central part in the initiation of calcium signals, and defects in calcium channel function have been found to result in a plethora of human diseases, referred to as the calcium channelopathies. Pathologies of Calcium Channels brings together leading international experts to discuss our current understanding of human diseases associated with the various calcium channels, from their molecular basis to potential future therapeutic targeting of calcium channels.

Hepatocytes account for approximately 80% of the liver mass and play a significant role in various aspects of liver physiopathology, exhibiting unrivaled complexity and diversity of functions. In Hepatocytes: Methods and Protocols, expert researchers provide the reader with methods, technical protocols, and review chapters focusing on selected areas of hepatocyte biology including isolation, culture, differentiation and stem cells, and hepatocyte use in clinical, basic, and applied research. With a specific emphasis on human hepatocytes, the volume presents chapters covering subjects including hepatocyte culture models, cryopreservation methods, differentiation assessment, liver ontogenesis, production of hepatocytes from stem cells, drug/xenobiotic metabolism, toxicity and transport, bile acid and blood coagulation factor production, infection by HBV and HCV, humanized animals, biortificial liver devices, hepatocyte transplantation. As a volume in the highly successful Methods in Molecular Biology (TM) series, protocol chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Hepatocytes: Methods and Protocols will be useful to all those who are currently using or planning to use human, or animal, hepatocytes to investigate any aspect of liver physiopathology or who are interested in liver development or liver stem cells and liver biotherapy.

1 a a 4 17 10 15 ubiquitin; and of 16 VCP 17 18 20 33 34 34 36 p domain. 41 42 42 43 P U 42 47 binding. C. elegans 16 In 21 22 50 51 52 53 13 and UFD 4 10 of Cdc48. 18 30 of Ufd2. COFACTORS 47 23 13 47 47 47 72 15 15 and of Spt23 p90. Ufd2 and Cdc48. In C. elegans 74 16 75 75 76 76 Ufd2 25 54 54 7 56 p47 7 7 80 30 30 81 82 82 but and CD3 26 DUB COFACTORS 30 UFD3 OTU1 4 Cdc48 30 4 OLE1. 15 27 87 REFERENCES 30 REGULATION OF UBIQUITIN MONOUBIQUITINATION UBIQUITINATION 1 32 7 S) d 33 12 13 14 15 18 19 15 20 21 35 15 15 27 15 31 32 31 33 36 monoubiquitination of pol pol 34 37 34 monoubiquitination. 20 35 trans 3 15 REFERENCES by monoubiquitination. Mol Cell; 2009. UBIQUITIN LIGASE ACTIVITY BY Nedd 1 2 of 41 5 6 8 fold. 9 13 14 edd 43 18 18 K M and k 18 22 23 K M 24 25 K M 26 edd 45 18 27 K M K D 18 25 . 8 10 M 21 28 MECHANISM AND REGULATION OF CRLs 34 41 34 edd 47 48 S. pombe 49 51 p27 and I by SCF and SCF 57 58 59 60 CTD CTD CTD CTD in Cul5 CTD CTD CTD 60 18

The book covers areas of cellular physiology and metabolism that are of interest to scientists involved in research in diabetes and metabolic diseases. Some chapters of the book are specifically research-oriented, as all the authors are actively practicing either bench or clinical research in the area. Nonetheless, since the work is fully comprehensive of the discipline, it is also suitable for university classes of graduate and undergraduate students. In particular, the book discusses classical aspects of cellular physiology and the metabolism of physical exercise, as well as novel topics like exercise in transplantation and exercise in beta-cell failure, which mark the frontiers of research in sport-related sciences and research. Exercise physiologists, biologists and physicians are the specific professional and academic targets of this work. The team of authors together with the editor are world-renowned experts in the field of physiology and metabolism applied to sport sciences.

Darwinian medicine looks at the ecological and evolutionary roots of disease. A disease is an interaction between a genome and its biotic or abiotic environment and therefore a disease is essentially an ecological process. Good understanding of ecology and a Darwinian way of thinking can give us novel and useful perspectives on health and disease. If we understand the disease process better, we can certainly prevent, control as well as treat diseases in a better way. Although the thought that the origins of obesity and type 2 diabetes (T2D) might lie in our hunter gatherer adaptations is not new, research over the last decade makes us rethink many of the classical concepts. Brain and behavior is increasingly being recognized as central to all the endocrine, metabolic and immunological changes that earmark type 2 diabetes and other metabolic syndrome disorders. A major change in paradigm appears to be on the horizon and the proposed book intends to speed up the paradigm shift by raising important questions, pointing out flaws and inadequacies in the prevalent paradigm and stimulating radical rethinking which would redirect and refine the line of research as well as bring some fundamental changes in drug discovery and clinical practice.

Recent Advances in Prolactin Research summarizes the current knowledge of prolactin (PRL), PRL receptor, PRL-dependent signaling pathways, the role of PRL in oncogenesis and PRL crosstalk with other oncogenic factors. The chapters are written by experts in these fields and focus on identifying and reviewing timely experimental findings that provide new insights into the expanding role of PRL in the pathophysiology associated with a variety of human conditions. Prolactin is a peptide hormone that is best known for its role in lactation. Prolactin also has an influence on hematopoiesis and angiogenesis, and is involved in the regulation of blood clotting through several pathways. Although PRL was discovered more than 80 years ago, the understanding of PRL signaling and its relationship to various pathologies is still very incomplete. PRL is not only a pituitary hormone with an important role in reproduction, but PRL also acts as a cytokine, modulating a wide variety of physiological processes. For example, data gathered during the last decade have demonstrated that locally produced PRL acts as the autocrine/paracrine factor and plays a contributory role during breast oncogenesis. In fact, the scientific and clinical communities have suggested that the manipulation of the PRL axis may lead to the successful treatment of breast cancer. However, recent work has demonstrated that the role of the PRL axis is much more complex than first envisaged.

This book provides a detailed review of state of the art knowledge on critical care topics as well as the latest research findings. It covers the core aspects in excellent detail, but is not so comprehensive as to make its daily use unfeasible. For each condition considered, discussion of the pathophysiology is integrated with observations on diagnosis and treatment in order to allow a deeper understanding. The book is scientifically based, with extensive references to published research. This will allow readers to investigate their individual interests further and will enable physicians to justify measures by providing a coherent, evidence-based strategy and relevant citations where needed. Core Knowledge in Critical Care Medicine will appeal to experienced practitioners as an aide-memoire, but will also be of great value to a wide range of more junior staff wishing to complement their background knowledge with important facts applicable to everyday practice.

A host of neurotransmitters and neuroactive substances underlies respiratory regulation in health and disease. The centerpiece of investigations regarding adaptation to hypoxia and sensorial perception has been the dopaminergic system. It is now clear that a complex interaction among various neuroactive substances, rather than a single one, forms the basis of respiratory changes. The research on neurotransmitter interactions provides the knowledge of how the brain functions and a new level of understanding of mind-to-body connection, which opens up avenues for novel therapeutic interventions.

Well known experts in the field of Chronobiology from around the world, provide an integrative view of the state of the art of circadian biology. At present, genetic and epigenetic interaction of regulatory pathways among circadian oscillators, metabolic networks, cellular differentiation and neuronal communication are subject of intense scrutiny. The book is organized in three sections: The first includes selected examples of the circadian systems of crustaceans, insects, fish, birds and mammals. The second is a detailed view of the physiological mechanisms underlying the circadian clocks in mammals. Finally, in the third section some examples of the relevance of circadian biology and circadian misalignment to health and disease are provided including nutrition and metabolism, obesity, cancer, cardiovascular and pulmonary diseases, Huntington and affective diseases. This section concludes with a brief review on gene therapy and its potential use as a therapeutic tool to correct "clock genes" pathologies. This book is aimed at all those interested in contemporary aspects of physiology, biochemistry and molecular biology applied to the study and characterization of timing systems.. It could be used as an initial approach to this field, but it also provides updated information for those already familiar with the fascinating field of Chronobiology.

The mechanisms and physiological functions of urea transporters across biological membranes are subjects of long-standing interests. Although urea represents roughly 40% of all urinary solutes in normal human urine, the handling of urea in the tissues has been largely neglected in the past and few clinical or experimental studies now report data on urea. Most recent physiological text books include chapters on water and electrolyte physiology but no chapter on urea. Our aim in writing this book is to stimulate further research in new directions by providing novel and provocative insights into the further mechanisms and physiological significance of urea metabolism and transport in mammals. This book offers a state-of-the-art report on recent discoveries concerning urea transport and where the field is going. It mainly focuses on advances made over the past 20 years on the biophysics, genetics, protein structure, molecular biology, physiology, pathophysiology and pharmacology of urea transport in mammalian cell membranes. It will help graduate students and researchers to get an overall picture of mammalian urea transporters and may also yield benefits for pharmaceutical companies with regard to drug discovery based on the urea transporter. Baoxue Yang is a professor and vice chairman of the Department of Pharmacology, Peking University. He is also an adjunct professor of Jilin University and a visiting professor of Northeast Normal University. Prof. Yang has been researching urea transporters for nearly 20 years and has published more than 70 original research articles in this field.

To celebrate the Center for Perinatal Biology's 40th Anniversary, an illustrious group gathered at Loma Linda University in February 2013. That gathering of experts and this volume of the proceedings are a tribute to the founder of the Center, Lawrence D. Longo, M.D. These chapters present contributions from individuals who in some way or another were influenced by Dr. Longo. Covering a wide range of topics, and illustrating the diversity of thinking and scientific interests, these proceedings address basic science through to clinical problems in the developmental programming of health and disease.

Defining and understanding cellular and molecular mechanisms that are relevant to women's health has become a critical area of scientific pursuit. Until recently, very little effort has been place on defining or understanding critical differences between women and men that may be critical to the overall health of the woman. In 1990, the National Institutes of Health recognized this gap in knowledge resulting in the creation of the Office of Research on Women's Health. One of the purposes of this office was to advance the understanding of health issues from the women's perspective from both a basic and clinical scientific perspective. From a scientific evolution of understanding, the existence of this office is new and thus there has not been enough time for new information to integrate itself in our current scientific thought process. This book will seek to capture and disseminate our current understanding of scientific advancements relevant to women's health and provide the information to a broad audience. The purpose of this work is to discuss recent advancements in basic science across three areas of concern for women's health. In addition, the book will provide "translational" chapters that attempt to place the basic science work in context within our current understanding of the human. Although it is well acknowledge that gender differences exist across organ function which translates into differences in whole body function, until recently little effort has been made to define basic mechanisms within various tissues within the woman. This work will focus on recent scientific findings that are relevant to women's health and to provide novel and relevant information to interested scientists and clinicians.

The highly successful Reviews of Physiology, Biochemistry and Pharmacology continue to offer high-quality, in-depth reviews covering the full range of modern physiology, biochemistry and pharmacology. Leading researchers are specially invited to provide a complete understanding of the key topics in these archetypal multidisciplinary fields. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.

This book describes the evolution of ideas relating to the mechanism of muscular contraction since the discovery of sliding filaments in 1954. An amazing variety of experimental techniques have been employed to investigate the mechanism of muscular contraction and relaxation. Some background of these various techniques is presented in order to gain a fuller appreciation of their strengths and weaknesses. Controversies in the muscle field are discussed along with some missed opportunities and false trails. The pathway to ATP and the high energy phosphate bond will be discussed, as well as the discovery of myosin, contraction coupling and the emergence of cell and molecular biology in the muscle field. Numerous figures from original papers are also included for readers to see the data that led to important conclusions. This book is published on behalf of the American Physiological Society by Springer. Access to APS books published with Springer is free to APS members.