Excess of homocysteine, a product of the metabolism of the essential amino acid methionine, is associated with poor health, is linked to heart and brain diseases in general human populations, and accelerates mortality in heart disease patients. Neurological and cardiovascular abnormalities occur in patients with severe genetic hyperhomocysteinemia and lead to premature death due to vascular complications. Although it is considered a non-protein amino acid, studies over the past dozen years have discovered mechanisms by which homocysteine becomes a component of proteins. Homocysteine-containing proteins lose their normal biological function and become auto-immunogenic and pro-thrombotic. In this book, the author, a pioneer and a leading contributor to the field, describes up-to date studies of the biological chemistry of homocysteine-containing proteins, as well as pathological consequences and clinical implications of their formation. This is a comprehensive account of the broad range of basic science and medical implications of homocysteine-containing proteins for health and disease.

This snapshot volume is designed to provide a smooth entry into the field of protein folding. Presented in a concise manner, each section introduces key concepts while providing a brief overview of the relevant literature. Outlook subsections will pinpoint specific aspects related to emerging methodologies, concepts and trends.

Endocytosis and vesicular trafficking determine the landscape of the cell's exterior, namely the density of surface molecules, such as receptors for growth factors and cytokines, adhesion molecules like integrins and cadherins, and a plethora of nutrient carriers. Hence, endocytosis is involved in signal transduction, cell adhesion and migration, as well as metabolism. To exploit these fundamental processes, malignancies subtly and multiply manipulate the endocytosis and the subsequent trafficking of protein cargoes. This is achieved by simultaneously altering the cytoskeleton, vesicle budding, cargo sorting and intracellular degradation. By highlighting the underlying molecular processes and concentrating on specific examples, this book reviews the recent emergence of derailed endocytosis and vesicular trafficking as a landmark of cancer. In-depth understanding of this common feature of tumors might lead the way to drug-induced strategies, able to rectify intracellular trafficking in cancer.

Here, renowned researchers in bioanalysis present in-depth reviews of recent trends in the field. Coverage includes topics such as aptamers, bioelectroanalysis, nanoparticles, quantitative NMR, mass spectrometry, immunosensors and -assays, or chiral electromigration techniques. Originally published in the journal Bioanalytical Reviews, these outstanding contributions are now available in a hardcover print format. This volume benefits in particular those research groups and libraries that have chosen to have only electronic access to the journal. It also provides valuable content for all researchers in bioanalytical science.

This book contains 14 original review chapters each yielding new, exciting and intriguing data about the emerging understanding of nucleolar structure and function in normal, stressed and diseased cells. The goal of this work is to provide special insight into the nucleolus of the past, present and future, as well its regulation, translocation, and biomedical function. A multitude of topics are introduced and discussed in detail, including nucleologenesis, nucleolar architecture, nucleolar targeting, retention, anchoring, translocation, and the relationship between the nucleolus and cancer. This book also brings together work from several different species, from human to Drosophila to Dictyostelium and other eukaryotic microbes. The final chapter summarizes some of the issues brought up in the various chapters with a view to future research. This book supports the continued emergence of the nucleolus as a dynamic intranuclear region that oversees a vast diversity of events.

This book contains an extensive collection of critical reviews, from leading researchers in the field of regulated protein degradation. It covers the role of regulated proteolysis in a range of microorganisms (from Gram positive, Gram negative and pathogenic bacteria to Archaea and the Baker's yeast Saccharomyces cerevisiae).

All three peroxisome proliferator-activated receptor (PPAR) subtypes share a high degree of structural homology while exhibiting differences in function, tissue distribution, and ligand specificity. In Peroxisome Proliferator-Activated Receptors: Discovery and Recent Advances, the authors trace the history of PPAR discovery and detail the receptor structure and its posttranslational modifications. Furthermore, endogenous ligands as well as various classes of exogenous ligands, subtype-selective, dual and pan agonists as well as antagonists, are discussed. In addition, the tissue distribution and versatile functions of PPAR subtypes in major organs are described. As PPARs play critical roles as regulators of numerous physiological as well as pathophysiological pathways, Peroxisome Proliferator-Activated Receptors: Discovery and Recent Advances aims to help researchers to develop safer and more effective PPAR modulators as therapeutic agents to treat a myriad of diseases and conditions.

Volume 11 provides in an authoritative and timely manner in 16 stimulating chapters, written by 40 internationally recognized experts from 11 nations, and supported by more than 2600 references, 35 tables, and over 100 illustrations, many in color, a most up-to-date view on the role of cadmium for life, presently a vibrant research area. MILS-11 covers the bioinorganic chemistry of Cd(II), its biogeochemistry, anthropogenic release into the environment, and speciation in the atmosphere, waters, soils, and sediments. The analytical tools for Cd determination, its imaging in cells, and the use of 113Cd NMR to probe Zn(II) and Ca(II) proteins are summarized, as are Cd(II) interactions with nucleotides, nucleic acids, amino acids, and proteins including metallothioneins. The phytoremediation by Cd(II)-accumulating plants, etc., the toxicology of Cd(II), its damage to mammalian organs, and its role as a carcinogen for humans, are highlighted.

Taurine 8 represents the combined efforts of investigators on the roles of the amino acid taurine on human health and disease. The chapters covered in this book are directly derived from presentations of the contributors at the 18th International Taurine Meeting held in Marrakech, Morocco in April 2012. The purpose of this book is to disseminate current findings on taurine's contribution in several organ systems. This book covers the following topics: Taurine in the Nervous System, Taurine in the Immune System, Taurine and Diabetes, and Taurine and the Cardiovascular System. Dr. Abdeslem El Idrissi, College of Staten Island and Dr. William L'Amoreaux, College of Staten Island, were co-chairs of the Organizing Committee for the meeting. Data presented at this meeting provided compelling evidence that taurine is not only cytoprotective in cardiomyocytes, but also is a potent GABA agonist, whereby it can facilitate vasodilation of conducting arteries. Taurine conjugates, such as taurine chloramine, may protect cells from oxidative stress via increased HO-1 expression. In adult rodents, taurine has a potent effect on plasma glucose levels, likely through the release of insulin in pancreatic beta cells. As a potential neurotransmitter, taurine is known to work via the GABAergic system, but current research presented at this meeting suggest that taurine may interact with glutamate and serotonin receptors as well. Data are also presented to demonstrate the protective roles of taurine on neurons in neuroblastoma. Perhaps the most important and exciting presentation is the role of taurine and alcohol: the combination may be lethal. Data are also presented at this meeting of the potential role taurine may have as an adjuvant treatment with cisplatin in chemotherapy.

Taurine 8 represents the combined efforts of investigators on the roles of the amino acid taurine on human health and disease. The chapters covered in this book are directly derived from presentations of the contributors at the 18th International Taurine Meeting held in Marrakech, Morocco in April 2012. The purpose of this book is to disseminate current findings on taurine's contribution in several organ systems. This book covers the following topics: Taurine in Nutrition and Metabolism, the Protective Role of Taurine, and the Role of Taurine in Reproduction, Development, and Differentiation. Dr. Abdeslem El Idrissi, College of Staten Island and Dr. William L'Amoreaux, College of Staten Island, were co-chairs of the Organizing Committee for the meeting. Data presented at this meeting provided compelling evidence that taurine is not only cytoprotective in cardiomyocytes, but also is a potent GABA agonist, whereby it can facilitate vasodilation of conducting arteries. Taurine conjugates, such as taurine chloramine, may protect cells from oxidative stress via increased HO-1 expression. In adult rodents, taurine has a potent effect on plasma glucose levels, likely through the release of insulin in pancreatic beta cells. As a potential neurotransmitter, taurine is known to work via the GABAergic system, but current research presented at this meeting suggest that taurine may interact with glutamate and serotonin receptors as well. Data are also presented to demonstrate the protective roles of taurine on neurons in neuroblastoma. Perhaps the most important and exciting presentation is the role of taurine and alcohol: the combination may be lethal. Data are also presented at this meeting of the potential role taurine may have as an adjuvant treatment with cisplatin in chemotherapy.

Food proteomics is one of the most dynamic and fast-developing areas in food science. The goal of this book is to be a reference guide on the principles and the current and future potential applications of proteomics in food science and technology. More specifically, the book will discuss recent developments and the expected trends of the near future in food proteomics. The book will be divided into two parts. The first part (7 chapters) will focus on the basic principles for proteomics, e.g., sample preparation, such as extraction and separation techniques, analytical instrumentation currently in use, and available databases for peptide and protein identification. The second part of the book (26 chapters) will focus on applications in foods. It will deal with quality issues related to post-mortem processes in animal foods and quality traits for all foods in general, as well as the identification of bioactive peptides and proteins, which are very important from the nutritional point of view. Furthermore, consumers are now extremely susceptible to food safety issues, and proteomics can provide reassurance with different safety aspects, such as food authenticity, detection of animal species in the food, and identification of food allergens. All of these issues will be covered in this book. It is also worth noting that both editors are internationally recognized experts in the field of food science, and both have edited numerous food science books and handbooks.

This book can be used to provide insight into this important application of biophysics for those who are planning a career in protein therapeutic development, and for those outside this area who are interested in understanding it better. The initial chapters describe the underlying theory, and strengths and weaknesses of the different techniques commonly used during therapeutic development. The majority of the chapters discuss the applications of these techniques, including case studies, across the product lifecycle from early discovery, where the focus is on identifying targets, and screening for potential drug product candidates, through expression and purification, large scale production, formulation development, lot-to-lot comparability studies, and commercial support including investigations.

Many physiological conditions such as host defense or aging and pathological conditions such as neurodegenerative diseases, and diabetes are associated with the accumulation of high levels of reactive oxygen species and reactive nitrogen species. This generates a condition called oxidative stress. Low levels of reactive oxygen species, however, which are continuously produced during aerobic metabolism, function as important signaling molecules, setting the metabolic pace of cells and regulating processes ranging from gene expression to apoptosis. For this book we would like to recruit the experts in the field of redox chemistry, bioinformatics and proteomics, redox signaling and oxidative stress biology to discuss how organisms achieve the appropriate redox balance, the mechanisms that lead to oxidative stress conditions and the physiological consequences that contribute to aging and disease.

"Bioinformatics of Human Proteomics" discusses the development of methods, techniques and applications in the field of protein bioinformatics, an important direction in bioinformatics. It collects contributions from expert researchers in order to provide a practical guide to this complex field of study. The book covers the protein interaction network, drug discovery and development, the relationship between translational medicine and bioinformatics, and advances in proteomic methods, while also demonstrating important bioinformatics tools and methods available today for protein analysis, interpretation and predication. It is intended for experts or senior researchers in the fields of clinical research-related biostatistics, bioinformatics, computational biology, medicine, statistics, system biology, molecular diagnostics, biomarkers, or drug discovery and development. Dr.Xiangdong Wang works as a distinguished professor of Respiratory Medicine at Fudan University, Shanghai, China. He serves as Director of Biomedical Research Center, Fudan University Zhongshan Hospital and adjunct professor of Clinical Bioinformatics at Lund University, Sweden. His main research is focused on the role of clinical bioinformatics in the development of disease-specific biomarkers and dynamic network biomarkers, the molecular mechanism of organ dysfunction and potential therapies.

Tetraspanin proteins have recently emerged as a new class of modulators of various processes involving cell surface receptors, including cell migration and invasion, host immune responses, cell-cell fusion, and viral infection. The book summarises recent advances in the fields of biology in which the role of tetraspanins have been established and also covers the molecular evolution of the tetraspanin superfamily and structural aspects of the organisation of tetraspanin microdomains.

The knowledge of Th17 cells and other cell populations which secrete IL-17A, and/or IL-22 has expanded tremendously since the publication of the first edition "Th17 Cells: Role in Inflammation and Autoimmune Disease" in 2008. The present volume has been completely revised with the addition of new chapters on the IL-17 receptor family and signaling, and an in-depth review of IL-22 and innate lymphoid cells. The differentiation of naive T cells into regulatory T cells and Th17 cells as well as the plasticity of Th17 cells is discussed. The role of IL-22 in cutaneous inflammation including psoriasis has been reviewed. In addition, the volume contains critical updates on autoimmunity, organ transplantation, tumor immunology and genetic mouse models for mechanistic studies. Lastly, the latest clinical progress in neutralizing antibodies to IL-17A, IL-17RA not only confirms the therapeutic promise foreseen in 2008, but also improves our knowledge of the pathogenesis of autoimmune diseases. In summary, this is a timely update and important review of the clinical and experimental aspects of IL-17, IL-22 and their producing cells.

Volume II features a variety of animal and human prion diseases, including the newly-identified atypical forms of bovine spongiform encephalopathy and scrapie in animals, and variably protease-sensitive prionopathy in humans, prions in the environment, Tau pathology in human prion disease, transmission of the disease by blood transfusion, mammalian and non-mammalian models, conventional and advanced diagnoses, prion-specific antibodies, as well as decontamination of prions and development of therapeutics of prion diseases, such as the application of immunomodulation. This volume provides up-to-date knowledge about the etiology, pathogenesis, classification, histopathological, and clinical aspects of the highly publicized animal and human prion diseases.

Six decades after the serendipitous discovery of chlorpromazine as an antipsychotic and four decades after the launch of clozapine, the first atypical or second generation antipsychotic, psychopharmacology has arrived at an important crossroad. It is clear that pharmacological research and pharmaceutical development must now focus on complementary or even alternative mechanisms of action to address unmet medical needs, i.e. poorly treated domains of schizophrenia, improved acceptance by patients, better adherence to medication, safety in psychoses in demented patients, and avoiding cardiac and metabolic adverse effects. The first completely novel mechanisms evolving from our insights into the pathophysiology of psychotic disorders, especially the role of glutamatergic mechanisms in schizophrenia, are now under development, and further principles are on the horizon. This situation, in many respects similar to that when the initial second-generation antipsychotics became available, can be rewarding for all. Preclinical and clinical researchers now have the opportunity to confirm their hypotheses and the pharmaceutical industry may be able to develop really novel classes of therapeutics. When we were approached by the publishers of the Handbook of Experimental Pharmacology to prepare a new volume on antipsychotics, our intention was to capture both, the accumulated preclinical and clinical knowledge about current antipsychotics as well as prospects for new and potentially more specific antischizophrenia principles. These efforts should be based on the pathophysiology of the diseases and the affected neurotransmitter systems. Since preclinical research on antipsychotic compounds is only reliable when intimately linked through translational aspects to clinical results, we decided to include clinical science as well. It turned out that that this endeavor could not be covered by a single volume. We thank the editorial board and the publishers for supporting our decision to prepare two volumes: Current Antipsychotics and Novel Antischizophrenia Treatments. These topics cannot really be separated from one another and should be seen as a composite entity despite the somewhat arbitrary separation of contributions into two volumes. The continuing challenges of developing improved and safer antipsychotic medications remain of concern and are discussed in the first volume. The new opportunities for the field to develop and license adjunctive treatments for the negative symptoms and cognitive deficits that are treated inadequately by existing compounds have been incentivized recently and provide the focus for the second volume. We hope these collective contributions will facilitate the development of improved treatments for the full range of symptomatology seen in the group of schizophrenias and other major psychotic disorders. Gerhard Gross, Ludwigshafen, Germany Mark A. Geyer, La Jolla, CA This volume will try to put current therapy - achievements, shortcomings, remaining medical needs - and emerging new targets into the context of increasing knowledge regarding the genetic and neurodevelopmental contributions to the pathophysiology of schizophrenia. Some of the chapters will also deal with respective experimental and clinical methodology, biomarkers, and translational aspects of drug development. Non-schizophrenia indications will be covered to some extent, but not exhaustively.

The book will discuss classes of proteins and their folding, as well as the involvement of bioinformatics in solving the protein folding problem. In vivo and in vitro folding mechanisms are examined, as well as the failures of in vitro folding, a mechanism helpful in understanding disease caused by misfolding. The role of energy landscapes is also discussed and the computational approaches to these landscapes.

Volume I highlights the association of the cellular prion protein (PrPC) with copper and zinc, the potential roles of PrPC in Alzheimer's disease and cancers, insoluble PrPC, PMCA, molecular and cellular mechanisms of PrPSc formation and clearance, possible co-factors involved in the conversion of PrPC into PrPSc, infectious and pathogenic forms of PrP, cell biology of prions, prion strains and their interference, as well as yeast prions and their inheritable and structural traits. This unique volume will take you through the fascinating chronicle of prions in mammals, yeast, and fungi.

Main Question: G protein coupled receptors are involved in highly efficient and specific activation of signalling pathways. How do GPCR signalling complexes get assembled to generate such specificity? In order to answer this question, we need to understand how receptors and their signalling partners are synthesized, folded and quality-controlled in order to generate functional proteins. Then, we need to understand how each partner of the signalling complex is selected to join a complex, and what makes this assembly possible. GPCRs are known to be able to function as oligomers, what drives the assembly into oligomers and what will be the effects of such organization on specificity and efficacy of signal transduction. Once the receptor complexes are assembled, they need to reach different locations in the cell; what drives and controls the trafficking of GPCR signalling complexes. Finally, defects in synthesis, maturation or trafficking can alter functionality of GPCRs signalling complexes; how can we manipulate the system to make it function normally again? Pharmacological chaperones may just be part of the answer to this question.

In Single Molecule Studies of Proteins, expert researchers discuss the successful application of single-molecule techniques to a wide range of biological events, such as the imaging and mapping of cell surface receptors, the analysis of the unfolding and folding pathways of single proteins, the analysis interaction forces between biomolecules, the study of enzyme catalysis or the visualization of molecular motors in action. The chapters are aimed at established investigators and post-doctoral researchers in the life sciences wanting to pursue research in the various areas in which single-molecule approaches are important; this volume also remains accessible to advanced graduate students seeking similar research goals.

The CCN family of genes currently comprises six secreted proteins (designated CCN16 i.e., Cyr61/CCN1; ctgf/CCN2; Nov/CCN3; WISP1/CCN4; WISP2/CCN5, and WISP3/CCN6) showing a strikingly conserved primary structure, with four modules sharing partial identity with IGF binding proteins, Von Willebrand protein, thrombospondin and several matricellular proteins and growth factors. The current view is that CCN proteins modulate signaling pathways that involve regulatory components of the extracellular matrix. As such, they likely act as a central hub in the regulation of mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration of multiple cell types. The 5th international workshop on the CCN family of genes, that was held in Toronto in 2008 brought together scientists from around the world who have an interest in the biological roles of this emerging family of proteins. On an educational point of view, the workshop was a unique place for an efficient diffusion of scientific information. The present book comprises a series of selected manuscripts that are based on the original communications that were presented at the meeting by worldwide leaders in the field of CCN biology. All major aspects of CCN proteins biology in both normal and pathological conditions are covered in this volume, from structure-functions analysis up to the involvement of CCN proteins in complex physiological functions. In addition to reports that support the Yin-Yang concept of CCN proteins driving opposite effects on the same biological process, this book also comprises several contributions that point to CCN proteins as amenable targets for therapeutic manipulation of disease processes. Together with the special issue of Journal of Cell Communication and Signaling in which authors have extended on the original data presented at the meeting, the present Proceedings provide an instant picture and unique update of the state of the art in the CCN field.

In the late 1980s, Peptide Societies were established in Europe, the United States, and Japan, and more recently, in the Asian and the Pacific Rim regions including Australia, China, and Korea. At the time of the establishment of the American, European and Japanese Peptide Societies, the International Liaison Organizing Committee representing these Peptide Societies, along with the Australian Peptide Society, began discussions for holding international confer ences which would supercede or be held in lieu of the numerous individual meetings, held by the peptide societies of each individual country or region. The representative of the Chinese Peptide Society participated in these discus sion in the International Liaison Organizing Committee at the meeting of the American Peptide Symposium in Nashville, in June 1997. After lengthy discus sions over several years, we agreed to organize and host the International Peptide Symposium in Japan. The First International Peptide Symposium (IPS'97) was held on November 30-December 5, 1997, in Kyoto, and was co sponsored by four Peptide Societies. The attendance at this Symposium was 550 participants, including representatives from 32 different countries. We were very pleased with this outcome and anticipate an even larger attendance for forthcoming Symposia in future years. The revolution and advances in science and technology during the past two decades has caused traditional peptide chemistry to expand to peptide science, spreading from physical science to biology, pharmacology, and medicine.

Starting from a comprehensive quantum mechanical description, this book introduces the optical (IR, Raman, UV/Vis, CD, fluorescence and laser spectroscopy) and magnetic resonance (1D and 2D-NMR, ESR) techniques. The book offers a timely review of the increasing interest in using spin-label ESR as an alternative structural technique for NMR or X-ray diffraction. Future aspects are treated as well, but only as an illustration of the progress of ESR in this field.