Mammalian reovirus had been the major focus for molecular understanding of the Reoviridae and has served as a model system for the other members of the family. Indeed, most of our initial understanding of molecular biology and processes involved in virus replication and pathogenesis for the members of the family was generated from reovirus studies. With this platform two other members of the family causing disease in human and/or animals have gained in prominence and the molecular interactions from a structural level through to host-virus interactions as well as the function of the structural and non-structural proteins in the virus life cycle has been investigated in detail.

This book reviews our current understanding of Reoviridae entry, disassembly/assembly and egress in addition to updating high resolution structures of virus proteins and capsids from three different genera of the family.

Over the past decade, we have made great advances in the field of multiple sclerosis (MS) research, and this book focuses on those advances in MS pathogenesis and treatment. While some of these advances have been through new approaches and ideas that have emerged in the last decade such as the newly identified protective role that amyloid proteins may play in MS or the use of helminths to treat autoimmune diseases, others have evolved from previous theories and ideas that have only now gained momentum and a deeper understanding such as the role of HLA or gender in MS susceptibility. This book covers these emerging and evolving topics and highlights the substantial advancements made in elucidation of the factors regulating susceptibility or disease progression, identification of new ways to monitor or predict MS pathology, and development of new strategies for treating MS.

This book is a direct result of 10 years of the well-known "Autoimmunity Days" in Israel, which are increasingly becoming an international focal point for autoimmunity scientists. Top researchers provide coverage of the most important knowledge generated during the last decade. The volume can therefore be seen almost as a textbook on autoimmunity, projecting from the last decade to the next millennium.
A variety of different subjects in autoimmunity, from etiology to pathogenesis, from postulated mechanisms to innovative therapeutic modalities, is handled by noted contributors, while additional authors contribute top papers which significantly enhance a better understanding of autoimmunity.
An excellent treatise on the subject, and a worthwhile addition to both clinical and research libraries.

As the research has continued, it has become increasingly clear that natural killer (NK) cells are critical sentinels of the innate immune response, playing important roles in protecting the body from numerous pathogens and cancer in addition to contributing to normal pregnancy and impacting the outcomes of transplantation. While the first edition provided a valuable collection of classical cellular and in vivo techniques to study NK cell functions, the Second Edition of "Natural Killer Cell Protocols: Cellular and Molecular Methods" brings together more recently developed methods, more refined techniques, and detailed protocols designed to study NK cells within specialized tissue sites in both mice and humans. In this collection of methods, international leaders in the field cover topics ranging from the analysis of the various stages of NK cell development and maturation to specialized techniques for the identification of ligands for NK cell receptors. This volume also includes an appendix, providing a rich resource summarizing available reagents to study NK cells, cross-referencing KIR nomenclature, and detailing the many HLA ligands for various KIR family members. As a volume in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and thorough notes sections, highlighting tips on troubleshooting and avoiding known pitfalls.

Comprehensive and cutting-edge, "Natural Killer Cell Protocols: Cellular and Molecular Methods, Second Edition" seeks to aid researchers and further advance our understanding of the functions, maturation, and regulation of these fascinating and dynamic cells."

From small beginnings in the early 1970s, the study of complement regulatory proteins has grown in the last decade to the point where it dominates the complement field. This growth has been fueled by the discovery of new regulators, the cloning of old and new regulators, the discovery that many of the regulators are structurally and evolutionarily related to each other and the development of recombinant forms for use in therapy. There are now more proteins known to be involved in controlling the complement system than there are components of the system and the list continues to grow. The time is ripe for a comprehensive review of our current knowledge of these intriguing proteins. This book does just that. The first few chapters discuss the "nuts-and-bolts" of the complement regulators, describing their structures, functional roles and modes of action. The roles of the complement regulators "in vivo" are then described, focusing on the consequences of deficiency, roles in the reproductive system, interactions with pathogens and exploitation for therapy. The interesting developments in defining the complement regulators expressed in other species are also discussed. The book is written as a monograph, albeit by two people. The text is as readable as possible without compromising on scientific accuracy and completeness. The conversational style very evident in some sections is deliberate Placing all references in a single bibliography at the end of the text further improves readability. The reader will go to the book to discover a specific fact but be persuaded to read more and derive pleasure from the process. The authors' enthusiasm for the subject comes over strongly in the text, and this enthusiasm proves infectious.
Key Features
* Complement regulators--structure, functional roles and mode of action
* Comprehensive reviews of each of the individual regulators
* Roles of Complement regulators "in vivo, "in health and disease:
* Consequences of deficiency
* Roles in the reproductive system
* Interactions with pathogens
* Exploitation for therapy
* Complement regulators in other species

This volume is a practical biochemical guide to the Enzyme-Linked Immunosorbent Assay (ELISA), used to detect a target substance in a liquid sample. The ELISA is an important and widely used diagnostic tool in medicine, animal health, botany and quality assurance processes in food and beverage production. An introductory chapter orients the reader on the basic structure and function of immunoglobulins and their fragments while subsequent chapters outline the methodology to generate monoclonal antibodies using hybridoma technology and the general methods used to purify antibodies. Multiple chapters demonstrate how to creatively use the properties of the antibody to identify, localize and quantify target analytes to answer questions and resolve problems. The reader will learn how to use a variety of immunoassay strategies, reporters and detection systems that will undoubtedly facilitate their efforts to gain answers to their own questions. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, ELISA: Methods and Protocols seeks to provide both professionals and novices with the technical information necessary for the reader to successfully use the immunoassay as part of the discovery process.

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.

Engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials and their total worldwide sales continue to increase significantly. The importance of antibody applications is reflected in their increasing clinical and industrial applications as well as in the progression of established and emerging production strategies. This volume provides detailed coverage of the generation, optimization, characterization, production and applications of antibody. It provides the necessary theoretical background and description of methods for the expression of antibody in microbial and animal cell cultures and in transgenic animals and plants. There is a strong focus on those issues related to the production of intrabodies, bispecific antibody and antibody fragments and also to novel applications in cancer immunotherapy.

The book covers recent developments in research and practice of allergy and immunology. Special emphasis has been given to epidemiology and the relation of genetic and environmental factors in allergic diseases. Occupational aspects and the pathophysiology are additionally covered and an overview of the current pharmacotherapy and immunotherapy is provided.

Hepatobiliary cancer refers to primary malignant tumors originating in cells of the liver, bile ducts, and gallbladder. Globally, primary liver cancer, which includes hepatocellular carcinoma (~75 % of all cases) and intrahepatic biliary cancer or cholangiocarcinoma (~10-15 % 0f all cases) is the 6th most commonly diagnosed cancer and 3rd leading cause of cancer deaths worldwide. The vast majority of these highly malignant cancers are diagnosed at an advanced stage where treatment options are limited and patient survival outcomes are poor. The biological and therapeutic challenges posed by hepatobililiary cancers such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are daunting, emphasizing a critical need to review and assess current and evolving basic, translational, and clinical research focused on addressing the critical obstacles that continue to limit progress towards achieving significant improvements in HCC and CCA clinical management and patient survival outcomes. Towards this goal, this special edition of Advances in Cancer Research is focused on providing a comprehensive, timely and authoritative reviews covering such topics of significant scientific and clinical relevance, including hepatobiliary cancer risk mechanisms and risk-predictive molecular biomarkers; causes and functional intricacies of inter- and intratumor heterogeneity; novel insights into the role of tumor microenvironment and key signaling pathways in promoting hepatobiliary cancer progression, therapeutic resistance and immunosuppression; emerging biomarkers of HCC and CCA prognosis; advances in molecular genomics for personalizing tumor classification and targeted therapies; innovative preclinical cell culture modeling for hepatobiliary cancer drug discovery; and current and emerging trends in hepatobiliary cancer molecular therapeutic targeting and immunotherapies.

Volume 47 of "Progress in Drug Research" contains eight reviews and the various indexes which facilitate its use and establish the connection with the previous volumes. The articles in this volume deal with inotropic steroids, with chemokines and their involvement in a wide range of inflam matory diseases, with the subclassification and nomenclature of ul- and Uz-adrenoceptors, with Chinese traditional medicine, with drug targets in the molecular pathogenesis of asthma, with cytokines and their therapeutic application in immunosuppression and immunostimulation, with alter native medicine and with the potential use of calcium blockers in psy chiatry. These reviews and the quotations of original articles provide the reader with valuable information on several new developments in the world-wide search for new and better medicines. In 1959, when the Editor started this series of monographs, it was his intention to help disseminate informa tion on the vast and fast growing domain of drug research. Already at that time,it was not possible to follow the major individual publications in this field, and the reader was thereby provided with a tool to keep abreast of the latest developments and trends. This goal remained unchanged over the last 37 years, and I believe that the reviews in PDR are useful to the non-specialist who can obtain an overview of a particular field of drug research in a relatively short time.

The immune system is not bound by a single tissue but is instead bestowed with the challenge of warding off invading pathogens throughout the body. Constant surveillance of the body requires that the immune system be highly mobile and able to purge pathogens from all tissues. Because each tissue presents its own unique architecture and milieu, it is necessary for the immune system to be as malleable as it is dynamic. For example, how the immune system handles a pathogen in the lung can differ significantly from a pathogen encountered in the gut.

Understanding immune complexity in diverse tissue environments is a challenge for researchers. However, advances in imaging have greatly improved our ability to probe the immune system. From snap-shots in time to 4D movies, imaging systems have been used to generate stunning visualizations of immune cells in action throughout the body. These visualizations are not only aesthetically pleasing but they have yielded great advances in our understanding of immune function. This volume provides a synopsis of major insights in immunology revealed using imaging approaches. "Seeing is truly believing," and this volume was assembled to recognize past accomplishments and to provide visions of what the future holds in store in this exciting field.

The revised second edition addresses the complete range of conditions produced by this common disorder also known as APS or "sticky blood" syndrome. APS is one of the main causes of strokes (40%), leg deep vein thrombosis, and recurrent miscarriages in women. It is an important risk factor for thrombosis in women taking the oral contraceptive pill.

The effects of this syndrome were found initially in thrombosis, obstetrics (APS is the commonest treatable cause of recurrent pregnancy loss) and neurology. Its impact is now felt in a diverse range of conditions, including surgery (graft rejection), orthopedics (avascular necrosis, DVT), psychiatry (memory loss), cardiology (pulmonary hypertension, valvular disease, angina), ENT (vertigo), and pediatrics (young strokes, epilepsy).

Described as one of the major new diseases of the late 20th century, APS is a multi-specialty disease and is of increasing interest to obstetricians, rheumatologists, hematologists, dermatologists, neurologists and immunologists.

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.

Introductory Address.- The New Biology and Vaccine Research.- Keynote Presentation.- Mucosal Immunity To Vaccines: Current Concepts for Vaccine Development and Immune Response Analysis.- Session I: Oral Diseases and Host Immune Responses.- Prospects for Human Mucosal Vaccines.- Bacterial Diseases of the Oral Tissues.- Oral Virus Infections: The Potential for Gene Transfer in Treatment and Prevention.- Session II: Update on Vaccines and Vaccine Development.- Bacterial Mucosal Vaccines.- A General Overview of Viral Vaccine Development.- Session III: Vaccines and the Mucosal Immune System.- An Update on the "Jennerian" and Modified "Jennerian" Approach to Vaccination of Infants and Young Children Against Rota Virus Diarrhea.- Induction of Mucosal and Serum Immune Responses to a Specific Antigen of Peridontal Bacteria.- IgA1 Proteases and Host-Parasite Relationships in the Oral Cavity.- Transport of Iga Immune Complexes Across Epithelial Membranes: New Concepts n Mucosal Immunity.- Effect of Mucosal Microenvironment on Immune Response to Viruses.- Session IV: Optimizing Mucosal and Systemic Immune Responses.- Induction of T Helper Cells and Cytokines For Mucosal IgA Responses.- Cytokine Production and T Cell Receptor Expression by Salivary Gland T Cell and Intraepithelial T Lymphocytes for the Regulation of the IgA Response.- Immunological Adjuvants.- Session V: Delivery Systems and Immune Analysis.- M Cell-Mediated Antigen Transport and Monoclonal IgA Antibodies For MucosalImmune Protection.- A Mechanism of Passive Immunization with Monoclonal Antibodies to a 185,000Mr Streptococcal Antigen.- Delivery of Antigens by Recombinant Avirulent Salmonella Strains.- Use of Recombinant BCG as a Vaccine Delivery Vehicle.- Vaccinia Virus Recombinants as Potential Herpes Simplex Virus Vaccines.- Liposomes and Conjugate Vaccines for Antigen Delivery and Induction of Mucosal Immune Responses.- Peroral Immunization with a Cholera Toxin-Linked Bacterial Protein Antigen and Synthetic Peptide.- Peptomers as Vaccine Candidates.- Session VI: Target Antigen Selection and Vaccine Development.- Structural and Functional Studies of Herpes Simplex Virus Glycoprotein D.- Molecular, Immunological and Functional Characterization of the Major Surfae Adhesin of Streptococcus Mutans.- Reacitve Antigens of the Periodontopathic Bacterium Actinobacillus Actinmycetemcomitans.- Immunization with Fimbrial Protein and Peptide Protects Against Porphyromonas Gingivalis- Induced Periodontal Tissue Destruction.- Vaccine Development: Progression from Target Antigen to Product.- Session VII: Immunological Correlates of Protection.- Significance of Immune Responses to Oral Antigens in Dental Diseases.- Laboratory Correlates of Protection and Protective Immunity to Bordetella Pertussis.- Future Directions.- Challenges and Opportunities in Vaccine Research.- Summary and Recommendations for Future Research.- Speakers and Moderators.- Author Index.

This is the first volume in a series that will be dedicated to publishing advances in immunomics particularly those focusing on systemic and integrative approaches in basic and clinical immunology, immunoinformatics, and immunologically relevant instrumentation and high-throughput screening methods.

Immunoinformatics utilizes mathematics, information science, computer engineering, genomics, proteomics and immunological methods to bridge immunology and informatics. Ten expert reviews introduce bioinformaticians and immunologists alike to successfully applied data-driven strategies in MHC, TCR, peptide-MHC and allergen research, epitope prediction, de-immunization of therapeutic proteins, host-pathogen interactions, modeling of immune responses to pathogens and large-scale chemical mutagenesis-driven genetic analyses systems. In contrast to existing books on immunoinformatics which emphasize epitope prediction this volume presents a cross-section of immunoinformatic research. The contributions show the interdisciplinarity of the field and how collaborative efforts among bioinformaticians and a oebench scientistsa result in innovative strategies towards understanding the immune system.

a oeImmunoinformaticsa is an ideal volume for scientists, researchers, students and professionals in the fields of Immunology, bioinformatics, microbiology, genetics, systems biology, biotechnology, computational biology.

Established for almost 30 years, Methods in Microbiology is the most prestigious series devoted to techniques and methodology in the field. Now totally revamped, revitalized, with a new format and expanded scope, Methods in Microbiology will continue to provide you with tried and tested, cutting-edge protocols to directly benefit your research.
Immunology of Infection, edited by two of the foremost figures in the field, presents the most appropriate, up-to-date techniques in the detail you require. The layout is structured for ease of reference, and the volume will be essential reading for all researchers working in microbiology, immunology, virology, mycology, and parasitology.
The new volume provides a carefully selected collection of immunological techniques for the microbiologist wishing to study host-pathogen relationships "in vivo" and "in vitro." This multi-authored book has succeeded in bringing together experts from various fields of molecular and cellular immunology who provide ready-to-use recipes for the "ex vivo" and "in vitro" analysis of anti-infective immunity.
Key Features
* Focuses on the methods most useful for the microbiologist interested in analysing host-pathogen relationships
* Ready-to-use, tried and tested recipes
* Lists of suppliers provided as appendices to each chapter
* Covers techniques useful for the analysis of human and murine cells
* Includes techniques for the prediction and determination of MHC ligands and T cell epitopes
* Describes the art and science of DNA vaccines
* Essential methods for measuring human cytokine responses
* Covers isolation and propagation of dendritic cells

This comprehensive book explores the role of cytokines in immunotoxicology and human health using a variety of complex methods, from basic research to highly applied therapeutic applications. It includes a basic study of cytokines and details the effects of cytokines on the immune system and in treating cancer. The book serves as both a primer and a starting point for a more detailed investigation of the role these biological regulators play.

This book covers all aspects of oxygen delivery to tissue, including blood flow and its regulation as well as oxygen metabolism. Special attention will be paid to methods of oxygen measurement in living tissue and application of these technologies to understanding physiological and biochemical basis for pathology related to tissue oxygenation. This book is multidisciplinary and designed to bring together experts and students from a range of research fields including biochemical engineering, physiology, microcirculation, and hematology.

It has been known for a number of years that not only pathogenicity islands but also plasmids and bacteriophages are able to carry genes whose products are involved in pathogenic processes. Accordingly, such elements and their products play an important role in pathogenesis due to the intestinal E. coli as well due to Shigellae. Another interesting aspect which is reflected in different articles is that genomes evolve by acquisition of new pieces of DNA following gene transfer, but also by genome reduction. Different mechanisms include the deletion of sequences or the elimination of functions by the accumulation of point mutations or rearrangements.

Two decades have passed since the mechanisms of protein synthesis became well enough understood to permit the genetic modification oforganisms. An impressive amount of new knowledge has emerged from the new technology, but much ofthe promise of20years ago has notyet been fulfilled. In biotechnology, efforts to increase the yields of commercially valuable metabolites have been less successful than ex pected, and when they have succeeded it has often been as much from selective breeding as from new methods. The cell is more complicated than what is presented in the classical teaching of biochemistry, it contains more structure than was dreamed of 20 years ago, and the behaviour ofany systemofenzymes is more elaborate than can be explained in terms ofa single supposedly rate-limiting enzyme. Even if classical enzymology and meta bolism may have seemed rather unfashionable during the rise ofmolecular biology, they remain central to any modification ofthe metabolic behaviour oforganisms. As such modification is essential in much ofbiotechnology and drug development, bio technologists can only ignore these topics at their peril."

Antibiotics are truly miracle drugs. As a class, they are one of the only ones that actually cure disease as opposed to most drugs that only help relieve symptoms or control disease. Since bacteria that cause serious disease in humans are becoming more and more resistant to the antibiotics we have today, and because they will ultimately become resistant to any antibiotic that we use for treatment or for anything else, we need a steady supply of new antibiotics active against any resistant bacteria that arise. However, the antibiotics marketplace is no longer attractive for large pharmaceutical companies, the costs of development are skyrocketing because of ever more stringent requirements by the regulatory agencies, and finding new antibiotics active against resistant strains is getting harder and harder. These forces are all combining to deny us these miracle drugs when we need them the most. I provide a number of possible paths to shelter from this perfect storm.

A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and biotechnologist effective strategies of drug discovery and development that are producing valuable new complement inhibitors for the treatment of a wide variety of clinically important diseases.

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."

Contents. List of Contributors. Brian Henderson and Gerry Higgs: Targets for modulating cytokine responses in inflammatory and infectious diseases. Mary Lee MacKichan and Anthony L. DeFranco: Cell signalling and cytokine induction by lipopolysaccharide. Rodger A. Allen and Stephen E. Rapecki: Regulation of cytokine production by inhibitors of cell signalling. Stanley T. Crooke: Oligonucleotide-based drugs in the control of cytokine synthesis. Peter I. Croucher, Ingunn Holen and Philip G. Hargreaves: Inhibiting cytokine-processing enzymes. Amanda Suitters and Roly Foulkes: Cytokine-neutralizing therapeutic antibodies. Ravinder N. Maini: The debut of anti-TNF therapy of rheumatoid arthritis in the clinic. Anthony Meager: Blockade of cytokine activity by soluble cytokine receptors. Michael F. Smith Jr.: Interleukin-1 receptor antagonist. Raymond J. Owens and Simon Lumb: Therapeutic regulation of cytokine signalling by inhibitors of p38 mitogen-activated protein kinase. Christian Bogdan, Yoram Vodovotz and John Letterio: TGF-ss and IL-10: inhibitory cytokines regulating immunity and the response to infection. Brian Henderson: Therapeutic control of cytokines: lessons from microorganisms. Index