As our understanding of apoptotic pathway expands, we are coming to realize the great potential of utilizing this pathway to treat diseases such as cancer. The book attempts to review, summarize, and speculate on the apoptotic pathways, how are they regulated and how targeted therapies are being used to treat a wide variety of diseases. Special emphasis is placed on cancer since new treatments either being developed or currently in the clinical setting are showing great promise to increase survival rates for cancer patients. Chapters will address the biology behind regulating the apoptotic pathways and what goes wrong in disease states whereas other chapters will concentrate on new therapies targeting apoptotic pathways. The reader by the end of the book should have greater insight into the understanding and utilization of apoptotic pathways to fight diseases such as cancer.

Lasso peptides form a growing family of fascinating ribosomally-synthesized and post-translationally modified peptides produced by bacteria. They contain 15 to 24 residues and share a unique interlocked topology that involves an N-terminal 7 to 9-residue macrolactam ring where the C-terminal tail is threaded and irreversibly trapped. The ring results from the condensation of the N-terminal amino group with a side-chain carboxylate of a glutamate at position 8 or 9, or an aspartate at position 7, 8 or 9. The trapping of the tail involves bulky amino acids located in the tail below and above the ring and/or disulfide bridges connecting the ring and the tail. Lasso peptides are subdivided into three subtypes depending on the absence (class II) or presence of one (class III) or two (class I) disulfide bridges. The lasso topology results in highly compact structures that give to lasso peptides an extraordinary stability towards both protease degradation and denaturing conditions. Lasso peptides are generally receptor antagonists, enzyme inhibitors and/or antibacterial or antiviral (anti-HIV) agents. The lasso scaffold and the associated biological activities shown by lasso peptides on different key targets make them promising molecules with high therapeutic potential. Their application in drug design has been exemplified by the development of an integrin antagonist based on a lasso peptide scaffold. The biosynthesis machinery of lasso peptides is therefore of high biotechnological interest, especially since such highly compact and stable structures have to date revealed inaccessible by peptide synthesis. Lasso peptides are produced from a linear precursor LasA, which undergoes a maturation process involving several steps, in particular cleavage of the leader peptide and cyclization. The post-translational modifications are ensured by a dedicated enzymatic machinery, which is composed of an ATP-dependent cysteine protease (LasB) and a lactam synthetase (LasC) that form an enzymatic complex called lasso synthetase. Microcin J25, produced by Escherichia coli AY25, is the archetype of lasso peptides and the most extensively studied. To date only around forty lasso peptides have been isolated, but genome mining approaches have revealed that they are widely distributed among Proteobacteria and Actinobacteria, particularly in Streptomyces, making available a rich resource of novel lasso peptides and enzyme machineries towards lasso topologies.

In contrast to existing books on immunoinformatics, this volume presents a cross-section of immunoinformatics research. The contributions highlight the interdisciplinary nature of the field and how collaborative efforts among bioinformaticians and bench scientists result in innovative strategies for understanding the immune system. Immunoinformatics is ideal for scientists and students in immunology, bioinformatics, microbiology, and many other disciplines.

Bioinformation Discovery illustrates the power of biological data in knowledge discovery. It describes biological data types and representations with examples for creating a workflow in Bioinformation discovery. The concepts in knowledge discovery from data are illustrated using line diagrams. The principles and concepts in knowledge discovery are used for the development of prediction models for simulations of biological reactions and events. Advanced topics in molecular evolution and cellular & molecular biology are addressed using Bioinformation gleaned through discovery. Each chapter contains approximately 10 exercises for practice. This will help students to expand their problem solving skills in Bioinformation Discovery. Each chapter concludes with a number of good problem sets to test mastery of the material.

7th Jenner Glycobiology and Medicine Symposium Sunday5-W Wednesday 8 September 2004 John S. Axford StGeorge's, University of London, UK The potential for glycobiology to improve the practice of medicine has been well recognised, which is why biannual meetings concerning the association have been taking place for the last 14 years. The science of glycobiology has matured rapidly, and with it the far reaching clinical implications are becoming understood. The next decade is going to see this ?nal frontier of science conquered. The impact this understanding of glycobiology will have upon our practice of medicine is going to be exciting. The 7th Jenner Glycobiology and Medicine Symposium was designed tore?ecttheseadvances.Allthemajorclinicalareaswereinvolved,withcontributions from pivotal players in science and medicine. As with our previous meetings, junior scientists were involved as we recognise that at the end of the next decade they will be in the driving seat. This introduction serves as a taster to whet your appetite. From embryogenesis to pathogenesis, glycosylation plays a pivotal role. Complex and hybrid N-glyans and O-fucose glycans are critical in oocyte devel- ment and function. This area must surely be a fertile ground for glycosylation research.

2004 marks the 100th anniversary of the first description of the autoimmune disease paroxysmal cold hemoglobinuria, a rare hemolytic disorder, by Julius Donath and Karl Landsteiner. After a century of research, the list of autoimmune diseases has become impressive. With a prevalence of approximately 5% of the world-wide population, these chronic, debilitating conditions affect almost every major organ of the body and, for reasons that remain unclear, are much more prevalent in woman than in men. Despite our rapidly expanding knowledge of the cellular and molecular pathways that govern a normal immune response, deciphering the precise etiology of autoimmune diseases remains an important challenge. Over the last few years, our understanding of the pathogenesis of autoimmune diseases has improved rapidly, leading to the emergence of elegant immunointervention strategies. Molecular Autoimmunity illustrates how cutting-edge research is continuing to advance our understanding of autoimmune disease mechanisms and identifies novel therapeutic targets that provide a hope for effective future treatments. This volume contains a selected number of exciting advances in unraveling autoimmune reactions, and the resulting new armory of experimental immunotherapies that may lead to new ways of controlling autoimmune reactions.

The idea that the microbial communities within the GI tract have a profound influence on general human health actually originated with Russian scientist Elie Metchnikov at the turn ofthe last century. Also known as the "fatherofimmunol- ogy", Metchnikovbelievedthat putrefactivebacteriain the gut were responsible for enhancing the aging process. He theorized that ingestion ofhealthy bacteria found in fermented foods could counteract toxic bacteria and was the key to good health. His theories concerning good bacteria and health can be found in his treatise "The ProlongationofLife: Optimistic Studies".Thesewritings promptedJapanesescientist Minoru Shirotatobegin investigationofhow fermentative bacteriaimprove health. He succeededin isolating astrainofLactobacillusthat could survive passage through the intestine, while promoting a healthy balance ofmicrobes. The "Shirota strain" is still used today in the fermented beverage Yakult.It is clear from a commercial standpoint that these ideas have inspired the development of a probiotic industry, which has expanded greatly in the U.S. over the past 5-10 years.

According to the Autoimmune Diseases Coordinating Committee (ADCC), between 14.7 and 23.5 million people in the USA - up to eight percent of the population are affected by autoimmune disease. Autoimmune diseases are a family of more than 100 chronic, and often disabling, illnesses that develop when underlying defects in the immune system lead the body to attack its own organs, tissues, and cells. In Handbook of Autoimmune Disease, the editors have gathered in a comprehensive handbook a critical review, by renowned experts, of more than 100 autoimmune diseases, divided into two main groups, namely systemic and organ-specific autoimmune diseases. A contemporary overview of these conditions with special emphasis on diagnosis is presented. Each chapter contains the essential information required by attending physicians as well as bench scientists to understand the definition of a specific autoimmune disease, the diagnostic criteria, and the treatment.

The American Peptide Society (APS) provides a forum for advancing and promoting knowledge of the chemistry and biology of peptides. The approximately one thousand members of the Society come from North America and from more than thirty other countries throughout the world. Establishment of the APS was a result of the rapid worldwide growth that has occurred in peptide-related research, and of the increasing interaction of peptide scientists with virtually all fields of science. Peptides for Youth: The Proceedings of the the 20th American Peptide Symposium will highlight many of the recent developments in peptide science, with a particular emphasis on how these advances are being applied to basic problems in biology and medicine. The 20th American Peptide Symposium will take place June 26 - 30, 2007 in Montreal, Canada.

Stem Cell Biology in Health and Disease presents an up-to-date overview about the dual role of stem cells in health and disease. The Editors have drawn together an international team of experts providing chapters which, in this fully-illustrated volume, discuss: - the controversial debate on the great expectations concerning stem cell based regeneration therapies raised by the pluripotency of various stem cells. - the advantages and concerns about embryonic stem cells (ES cells), induced pluripotent stem cells (iPS cells) and adult stem cells, such as bone marrow-derived stem cells (BMDCs). - the type of stem cells, which has become of interest in the past decade, namely so-called cancer stem cells (CSCs). CSCs are now in the focus of cancer research since the eradication of tumour initiating cells would raise the changes of definitely cure cancer. Professor Dittmar and Professor Zanker have edited a must-read book for researchers and professionals working in the field of regenerative medicine and/or cancer.

Biomaterials associated infection (BAI) is one of the most common complications associated with implantation of any biomaterial regardless of form or function. These infections usually involve bacterial colonization and biofilm formation on the biomaterial itself, rendering the infection impervious to antimicrobials and host defenses. In addition, it is becoming increasingly clear that infection of the surrounding tissues also plays an important role in BAI, and that the infection may be influenced by the composition and design of the implanted biomaterial. In this book, worldwide leaders in the field address this critical problem in the translation of biomaterials research into clinical practice. The book begins with an emphasis on the latest research in the pathogenesis of BAI from microbiological, immunological, and materials science perspectives. The current state of the art in antimicrobial activation of biomaterials through surface modification and the incorporation of antimicrobial agents is then discussed. In the concluding chapters, successful translation of a selection of antimicrobial technologies from preclinical research into clinical use is described alongside a discussion of the utility of these devices and perspectives for future development. This book is essential reading for researchers and clinicians who are interested in understanding the fundamentals of BAI, the latest in antimicrobial materials research, and the state of the art in clinically available antimicrobial containing medical devices.

Cancer still remains a most important killer and even though synthetic chemotherapeutic agents are currently used, they are cost-intensive and do not always meet the expectations. In parallel, there is increasing evidence for the potential of nature-derived compounds on the inhibition of different steps of cancer initiation, promotion and progression. We believe that all diseases can be found in Nature but that Nature also provides the efficient cures as said the Prophet of Allah: "Allah did not create any illness without also creating the remedy". The content of this book gives a multi-disciplinary approach into the anti-cancer research field related to natural products and dietary compounds. Mainly, it covers the area of antitumor activity through an in-depth description of the cytotoxic, anti-inflammatory and anti-oxidant properties in cancer, inflammatory and cardio-vascular diseases. The cell death inducing mechanisms (apoptosis, anti-proliferative activity, angiogenesis, cell cycle control, cytostatic property and autophagy) give an overview of how natural products are able to target cancer cells. We believe that all diseases can be found in Nature but that Nature also provides the efficient cures as said the Prophet of Allah: "Allah did not create any illness without also creating the remedy". The content of this book gives a multi-disciplinary approach into the anti-cancer research field related to natural products and dietary compounds. Mainly, it covers the area of antitumor activity through an in-depth description of the cytotoxic, anti-inflammatory and anti-oxidant properties in cancer, inflammatory and cardio-vascular diseases. The cell death inducing mechanisms (apoptosis, anti-proliferative activity, angiogenesis, cell cycle control, cytostatic property and autophagy) give an overview of how natural products are able to target cancer cells.

Whole new areas of immunological research are emerging from the analysis of experimental data, going beyond statistics and parameter estimation into what an applied mathematician would recognise as modelling of dynamical systems. Stochastic methods are increasingly important, because stochastic models are closer to the Brownian reality of the cellular and sub-cellular world.

The bacterial lipopolysaccharide also known as endotoxin is exhaustively covered in the present work. Central emphasis is placed upon the fine chemical structure of the lipopolysaccharide and its significance for understanding their activity and function. In particular, the role it plays in the interaction of bacteria with other biological systems is examined. New aspects of their physicochemical biology are introduced and updates to the current knowledge concerning the lipopolysaccharide are provided. This important class of biomolecules has recently attracted the attention of many investigators, in particular for understanding its involvement in innate immunity, toll-like receptor recognition and intracellular signaling.

The most practical and clinical reasons for attempting to understand the immunology of infections and disease revolves around the CD137 and CD137/41BB receptor and ligand molecules. This book covers all aspects of CD137/4-1BB pathway research from microbiology, infectious disease, molecular biology, biochemistry, and genetics to immune responses and potential applications in the diagnosis and treatment of human diseases. This pathway is emerging as one of the most important targets for manipulation of immune responses for disease diagnosis and treatment. This book is written by the man who discovered the CD-137 and B7H1 molecules in 1999.

Every day many people suffer from intestinal diseases. These disorders can result from pathogens like bacteria, fungi, parasites and viruses, but the causes of non-infectious intestinal disorders and colorectal cancers remain to be elucidated. Disturbances to the normal gut flora (the microbiota) are central to the development of many, if not all, of these disorders. Disturbed gut microbiota is a prelude to public health issues like traveller's-, antibiotic- and Clostridium difficile-associated diarrhoea, irritable bowel syndrome, inflammatory bowel disease, and colorectal cancers. This book discusses the way intestinal disorders affect the microbiota, how the disturbed microbiotal balance leads to enteric disorders and the ways to prevent these disorders. Further his book explores the potential of probiotics (live microorganisms that when ingested bring a health benefit) in treating enteric disorders by analysing the probiotic genome through proteomics, metabolomics and functional assays. Discussed is how the ingestion of specific microorganisms repairs the disturbed microbiota and subsequently ameliorates enteric disorders. Finally this book addresses how genetic engineering and biotechnology will contribute to the development of effective and safe designer probiotics.

Microbial cell wall structures play a significant role in maintaining cells' shape, as protecting layers against harmful agents, in cell adhesion and in positive and negative biological activities with host cells. All prokaryotes, whether they are bacteria or archaea, rely on their surface polymers for these multiple functions. Their surfaces serve as the indispensable primary interfaces between the cell and its surroundings, often mediating or catalyzing important interactions. Prokaryotic Cell Wall Compounds summarizes the current state of knowledge on the prokaryotic cell wall. Topics concerning bacterial and archaeal polymeric cell wall structures, biological activities, growth and inhibition, cell wall interactions and the applications of cell wall components, especially in the field of nanobiotechnology, are presented.

Innate immunity is one the most evolutionally conserved systems, designed to protect the organism from viruses and bacterial infections, stress and many other types of attacks from the outside world. During the past decade, the capacity of molecular biology and information technology to produce and analyse data have grown exponentially, rapidly reforming many aspects of immunology research in the post-genomics era. As a result, scientific understanding of signalling networks governing the innate immunity response in human tissues and other organisms has evolved beyond recognition, compared to even just a decade ago. Many strategies have been designed over the years to identify novel proteins, which have a crucial role in innate immunity responses by regulating particular signalling pathways. These projects had many advantages, including the definition of novel drug targets, as exemplified by the recent success of anti-TNF therapy, as well as leading to a better, system-wide understanding of the molecular control of innate immunity. In the past few years, a new concept, Immunomics, has been adopted to define an emerging, multidisciplinary field of research (Schonbach, 2003). Although rapid progress has been made to identify the proteins playing pivotal roles in the innate immunity-related signalling pathways (for example, TIR signalling pathways), the catalogue of proteins with a key regulatory function identified and studied is far from completed. Novel proteins need to be char- terised to gain a more comprehensive picture of how signalling networks are regulated.

This volume throws light on the Sick Building Syndrome in Libraries and other public buildings, and the extent to which it is influenced by the internal environment of libraries. One of the signs of this disease is that the person suffers from a set of symptoms closely related to his/her presence in the building, without the identification of any clear causes, and his/her relief of these symptoms when he/she are out of the building. Hence, the book sheds on the extent to which the interior environment impacts upon the health of the people, and the extent to which this is reflected in their performance. The book can be used for teaching, research, and professional reference. It concludes with the recommendation that is essential to observe environmental dimensions when designing library and public buildings, taking into consideration the expected impact of SBS in library and public buildings on people. The significance of the book derives from the fact that it is the first of its kind to examine the issue of the interior environment and SBS of library and public building worldwide.

Clinical Mycology offers a comprehensive review of this discipline. Organized by types of fungi, this volume covers microbiologic, epidemiologic and demographic aspects of fungal infections as well as diagnostic, clinical, therapeutic, and preventive approaches. Special patient populations are also detailed.

The ?eld of cellular responses to DNA damage has attained widespread recognition and interest in recent years commensurate with its fundamental role in the ma- tenance of genomic stability. These responses, which are essential to preventing cellular death or malignant transformation, are organized into a sophisticated s- tem designated the "DNA damage response". This system operates in all living organisms to maintain genomic stability in the face of constant attacks on the DNA from a variety of endogenous by-products of normal metabolism, as well as exogenous agents such as radiation and toxic chemicals in the environment. The response repairs DNA damage via an intricate cellular signal transduction network that coordinates with various processes such as regulation of DNA replication, tr- scriptional responses, and temporary cell cycle arrest to allow the repair to take place. Defects in this system result in severe genetic disorders involving tissue degeneration, sensitivity to speci?c damaging agents, immunode?ciency, genomic instability, cancer predisposition and premature aging. The ?nding that many of the crucial players involved in DNA damage response are structurally and functionally conserved in different species spurred discoveries of new players through similar analyses in yeast and mammals. We now understand the chain of events that leads to instantaneous activation of the massive cellular responses to DNA lesions. This book summarizes several new concepts in this rapidly evolving ?eld, and the advances in our understanding of the complex network of processes that respond to DNA damage.

The Third Aegean Conferences Workshop on Complement-Associated Diseases, Animal Models, and Therapeutics convened to discuss progress in complement research as it pertains to human disease pathogenesis and therapeutics. The rapid pace of research and new experimental approaches allow an integrated view of the in vivo biology of the complement system. This book collects writings on the functions of complement, pathophysiology, protein structures, design of complement inhibitors, and complement assays discussed at the conference.

Immunotherapy is now recognized as an essential component of treatment for a wide variety of cancers. It is an interdisciplinary field that is critically dependent upon an improved understanding of a vast network of cross-regulatory cellular populations and a diversity of molecular effectors; it is a leading example of translational medicine with a favorable concept-to-clinical-trial timeframe of just a few years. There are many established immunotherapies already in existence, but there are exciting new cancer immunotherapies just on the horizon, which are likely to be more potent, less toxic and more cost effective than many therapies currently in use. Experimental and Applied Immunotherapy is a state-of-the-art text offering a roadmap leading to the creation of these future cancer-fighting immunotherapies. It includes essays by leading researchers that cover a wide variety of topics including T cell and non-T cell therapy, monoclonal antibody therapy, dendritic cell-based cancer vaccines, mesenchymal stromal cells, negative regulators in cancer immunology and immunotherapy, non-cellular aspects of cancer immunotherapy, the combining of cancer vaccines with conventional therapies, the combining of oncolytic viruses with cancer immunotherapy, transplantation, and more. The field of immunotherapy holds great promise that will soon come to fruition if creative investigators can bridge seemingly disparate disciplines, such as T cell therapy, gene therapy, and transplantation therapy. This text is a vital tool in the building of that bridge.

The human immune system is a complex network of tissues and organs dispersed throughout the body. Immunology, as one of the most rapidly evolving fields in biomedical research, has to date covered the essential cellular and molecular events necessary for immune responses to occur. However, it has paid relatively little attention to important developmental processes underlying the formation of the tissues themselves that carry out immune responses in humans and other mammalians. In contrast to the thymus and bone marrow that are the sole tissues for generating mature leukocytes for antigen recognition and handling in humans and most mammalian species, the peripheral lymphoid tissues where adaptive immune responses are focused display broad tissue distribution and possess diverse architectural characteristics. These organs develop prior to the individual's exposure to external antigens, and despite their similar functions, their varied appearances indicate a substantial complexity of tissue ontogeny. This volume presents a comprehensive overview of the developmental features of the major peripheral lymphoid organs, thus examining the connection between immunological functionality and structural characteristics utilizing a developmental approach, for an audience ranging from undergraduate students to senior researchers in immunology, histology and clinical medicine.

The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as 'ER stress'. Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases.