This is the most comprehensive, up-to-date reference on this post-translational modification of proteins, which is intimately linked with DNA repair, maintenance of genomic stability, transcriptional regulation, cell death and a variety of other cellular phenomena as well as with a variety of pathophysiological conditions, including ischemia-reperfusion damage, Parkinson's disease, Type I diabetes mellitus, hemorrhagic and septic shock and other inflammatory conditions. Richly illustrated, it offers 19 chapters written by international experts.

A compendium of readily reproducible and novel methods to manipulate DNA viruses and characterize their varied biological properties. The authors emphasize techniques for viral detection and genetics, but also include methods for structure determination, gene expression, replication, pathogenesis, complex cellular models, recombinant genetics, and computational/systems approaches. Wide-ranging and highly practical, DNA Viruses: Methods and Protocols will stimulate new directions in virology research with its novel strategies for engineering viral vectors in gene therapy, and its advanced approaches for detecting viruses in human disease.

Why another book about vaccines? There are already a few extremely well-written medical textbooks that provide comprehensive, state-of-the-art technical reviews regarding vaccine science. Additionally, in the past decade alone, a number of engrossing, provocative books have been published on various related issues ra- ing from vaccines against specific diseases to vaccine safety and policy. Yet there remains a significant gap in the literature - the history of vaccines. Vaccines: A Biography seeks to fill a void in the extant literature by focusing on the history of vaccines and in so doing, recounts the social, cultural, and scientific history of vaccines; it places them within their natural, historical context. The book traces the lineage - the "biography" - of individual vaccines, originating with deeply rooted medical problems and evolving to an eventual conclusion. Nonetheless, these are not "biographies" in the traditional sense; they do not trace an individual's growth and development. Instead, they follow an idea as it is conceived and dev- oped, through the contributions of many. These are epic stories of discovery, of risk-takers, of individuals advancing medical science, in the words of the famous physical scientist Isaac Newton, "by standing on the shoulders of giants. " One grant reviewer described the book's concept as "triumphalist"; although meant as an indictment, this is only partially inaccurate.

The OHOLO conferences are sponsored by the Israel Institute for Biological Research and take their name from the site of the ?rst meeting on the shores of Lake Kinnereth. The purpose of these meetings is, as it was at their inception over 50 years ago, "to foster interdisciplinary communication between scientists in Israel, and to provide added stimulus by the participation of invited scientists from abroad". The core of the organizers of the OHOLO conferences are scientists from the Israel Institute for Biological Research. From time to time a particular OHOLO conference cooperates with an international scienti?c organization. The present 46th OHOLO Conference marks the resumption of the OHOLO tradition after 8 years of interruption caused by events beyond our control. It is my belief that our uncomp- mising commitment to excellence in research and development in the various areas of science in Israel is essential to our survival in this troubled region. The OHOLO conference tradition is a re?ection of this conviction. The present 46th OHOLO Conference entitled: The Challenge of Highly Pathogenic Microorganisms - Mechanisms of Virulence and Novel Medical Countermeasures intends to address the unique virulence features and ho- pathogen interactions of microorganisms constituting emerging biothreat with emphasis on Y. pestis, B. anthracis, F. tularensis and Orthopox viruses. Accordingly we selected classical microbiological as well as genomic, proteomic & transcr- tomic approaches towards developments of novel prophylactic and post-exposure treatment, as well as updated strategies of diagnostics and bioforensics.

Paris is a cosmopolitan city where roaring life, wonderful museums and excellent science can be found. It was during the XI IUMS conference held in this city that the Pseudomonas book series was ?rst envisaged. On the ?rst row of the auditorium sat a group of outstanding scientists in the ?eld, who after devoting much of their valuable time, contributed in an exceptional manner to the ?rst three volumes of the series, which saw the light simultaneously. The volumes were grouped under the generic titles of "Vol. I. Pseudomonas: Genomics, Life Style and Molecular Architecture", Vol. II. Pseudomonas: Virulence and gene regulation; Vol. III. Pseudomonas: Biosynthesis of Macromolecules and Molecular Metabolism. Soon after the completion of the ?rst three volumes, a rapid search for ar- cles containing the word Pseudomonas in the title in the last 10 years produced over 6,000 articles! Consequently, not all possible topics relevant to this genus were covered in the three ?rst volumes. Since then two other volumes were p- lished: Pseudomonas volume IV edited by Roger Levesque and Juan L. Ramos that came to being with the intention of collecting some of the most relevant emerging new issues that had not been dealt with in the three previous volumes. This v- ume was arranged after the Pseudomonas meeting organized by Roger Levesque in Quebec (Canada). It dealt with various topics grouped under a common heading: "Pseudomonas: Molecular Biology of Emerging Issues".

Congenital cytomegalovirus (CMV) infection is the most common intrauterine transmitted viral infection, with a tremendous impact on fetuses and newborns. In this book the history of this disease, its pathophysiological background, epidemiology and symptoms, as well as diagnostic and therapeutic strategies, will be discussed. Since economic aspects are gaining more and more importance in health politics, one chapter is dedicated to this issue in the context of congenital CMV infection. The content is based on the latest scientific findings and written in an understandable manner, allowing persons not working in the field of congenital CMV to also profit from it. Thus, this book is of interest for medical doctors, nurses, midwives, economists, but also for men and women who want to inform themselves about this topic.

This teaching monograph on systems approaches to cancer research and clinical applications provides a unique synthesis, by world-class scientists and doctors, of laboratory, computational, and clinical methods, thereby establishing the foundations for major advances not possible with current methods. Specifically, the book: 1) Sets the stage by describing the basis of systems biology and bioinformatics approaches, and the clinical background of cancer in a systems context; 2) Summarizes the laboratory, clinical, data systems analysis and bioinformatics tools, along with infrastructure and resources required; 3) Demonstrates the application of these tools to cancer research; 4) Extends these tools and methods to clinical diagnosis, drug development and treatment applications; and 5) Finishes by exploring longer term perspectives and providing conclusions. This book reviews the state-of-the-art, and goes beyond into new applications. It is written and highly referenced as a textbook and practical guide aimed at students, academics, doctors, clinicians, industrialists and managers in cancer research and therapeutic applications. Ideally, it will set the stage for integration of available knowledge to optimize communication between basic and clinical researchers involved in the ultimate fight against cancer, whatever the field of specific interest, whatever the area of activity within translational 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.

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.

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.

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.

This book describes antibiotic resistance amongst pathogenic bacteria. It starts with an overview of the erosion of the efficacy of antibiotics by resistance and the decrease in the rate of replacement of redundant compounds. The origins of antibiotic resistance are then described. It is proposed that there is a large bacterial resistome which is a collection of all resistance genes and their precursors in both pathogenic and non-pathogenic bacteria. Ongoing resistance surveillance programs are also discussed, together with the perspective of a clinical microbiologist. The book then turns to specific themes such as the most serious area of resistance in pathogens, namely in Gram-negative organisms. The role of combinations of antibiotics in combating resistance emergence is discussed, particularly in the tuberculosis field, and then the importance of non-multiplying and persistent bacteria which are phenotypically resistant to antibiotics and prolong the duration of therapy of antibiotics which leads to poor compliance and resistance emergence. The role of anti-microbial compounds in textiles is covered, with its potential to exacerbate the spread of resistance. Then, efflux pumps are discussed. The final chapter describes the compounds which are in late stage clinical development, illustrating the paucity of the antibiotic pipeline, especially for Gram-negative bacteria.

Prokaryotic Toxins - Antitoxins gives the first overview of an exciting and rapidly expanding research field. Toxin - antitoxin (TA) genes were discovered on plasmids 30 years ago. Since then it has become evident that TA genes are highly abundant in bacterial and archaeal chromosomes. TA genes code for an antitoxin that combine with and neutralize a cognate toxin. When activated, the toxins inhibit protein synthesis and cell growth and thereby induce dormancy and multidrug tolerance (persistence). Remarkably, in some species, the TA gene families have undergone dramatic expansions. For example, the highly persistent major human pathogen Mycobacterium tuberculosis has "100 TA loci. The large expansion of TA genes by some organisms is a biological mystery. However, recent observations indicate that TA genes contribute cumulatively to the persistence of bacteria. This medically important phenomenon may thus for the first time become experimentally tractable at the molecular level.

From the first detailed clinical description of the disease in the Midwestern United States in 1918, to the isolation of the causative agent, the first of any influenza virus, in 1930 to its role in the genesis of the 2009 human pandemic, swine have played a central role in the ecology of influenza. Although not considered the major natural reservoir for influenza A viruses, swine are host to a limited but dynamic assortment of viruses. A number of subtypes of influenza A viruses of human and avian origin, including H1, H2, H3, H4, H5, H7, and H9, have been isolated from global swine populations. Most of these isolations have, however, been limited in number and it is only H1 and H3 influenza viruses that are known to have formed stable lineages in swine. In this respect, swine influenza viruses (SIV) are similar to their counterparts in humans where H1 and H3 viruses have also been maintained. The nature of these H1 and H3 viruses differ between the two host populations, however, and, as discussed throughout this book, are even different in swine populations in different geographic regions of the world due to multiple introductions of avian and human influenza viruses.

A review of 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. 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. This book will interest researchers and scientists in the field of virology.

The present volume of Current Topics in Microbiology and Immunology c- tains seven chapters that illuminate various aspects of a protein's genesis and terminal fate in the endoplasmic reticulum (ER). This area is of immediate medical relevance and has blossomed, to no small extent, because of the study of molecules central to the function of the immune system [immunogl- ulins, T cell receptors, major histocompatibility complex (MHC)-encoded products]. Similarly, the clever strategies used by bacteria or viruses to gain a foothold in the host and ensure their continued survival have uncovered altogether new cell biological principles. It is therefore ?tting that a special volume be devoted to the interplay between pathways of protein degradation in the ER and a wide variety of pathogens. The concept of quality control emerged with the appreciation that, in the case of multimeric glycoproteins, any unpaired glycoprotein subunit had great dif?culties leaving its site of synthesis-the ER-and was destroyed instead. Free immunoglobulin heavy chains were probably the earliest documented example of this kind, and were long known to cause pathology when their accumulation went unchecked. Increased knowledge of the biosynthetic pathways of glycoproteins allowed the identi?cation of the ER as an important site where such quality control decisions were made. The T cell receptor for antigen, long considered the paradigm of this mode of degradation, led the way in these early explorations.

This volume reviews the unique and common features of rhabdoviruses, which have a very wide host range and are associated with human diseases and also infect domestic livestock and agricultural plants, causing enormous economic loss.

Viral infections of the nervous system are important because they are associated with high morbidity and mortality. A variety of pathogenetic mechanisms are involved in these infections and an understanding of the pathogenesis is essential in understanding the diagnostic and clinical management aspects of the disease. Specialized investigations are often necessary for definitive diagnosis, although a presumptive diagnosis should often be suspected on the basis of the clinical features. Many of the chapters in this book are written by neurologists who are experts in basic science research of their topic in addition to active clinical practice in their specialty.

Metabolic engineering has been developed over the past 20 years to become an important tool for the rational engineering of industrial microorganisms. This book has a particular interest in the methods and applications of metabolic engineering to improve the production and yield of a variety of different metabolites. The overall goal is to achieve a better understanding of the metabolism in different microorganisms, and provide a rational basis to reprogram microorganisms for improved biochemical production.

The Reverse Transcriptase (RT) of Human Immunodeficiency Virus Type 1 (HIV-1) arguably ranks amongst one of the most extensively studied retroviral enzymes. Heterologous expression and purification of HIV-1 RT in the early eighties, approval of the first nucleoside analogue RT inhibitor (NRTI) in 1987, discovery of resistance to RT inhibitors, approval of the first non-nucleoside analogue RT inhibitor (NNRTI) in 1996 and the various crystal structures of RT with and without bound substrate(s) and/or inhibitors represent only a few of the important milestones that describe the a bench-to-bedside success in the continuing effort to combat HIV-1 infection and its consequences. Nucleoside and nonnucleoside RT inhibitors remain important components in frequently used drug regimens to treat the infection. RT inhibitors also play important roles in recently validated strategies to prevent transmission of the virus. The relevance of HIV-1 RT as a drug target has simultaneously triggered interest in basic research studies aimed at providing a more detailed understanding of interactions between proteins, nucleic acids, and small molecule ligands in general terms. In light of the ever-growing knowledge on structure and function of HIV-1 RT, this enzyme serves as a valuable "model system" in efforts to develop novel experimental tools and to explain biochemical processes. This monograph is designed to provide an overview of important aspects in past and current HIV-1 RT research, with focus on mechanistic aspects and translation of knowledge into drug discovery and development. The first section includes chapters with emphasis placed on the coordination of the RT-associated DNA polymerase and ribonuclease H (RNase H) activities. The second covers mechanisms of action and future perspectives associated with NRTIs and NNRTIs, while the third section includes chapters focusing on novel strategies to target the RT enzyme. Chapters of the final part are intended to discuss mechanisms involved in HIV variability and the development of drug resistance. We hope that these contributions will stimulate interest, and encourage research aimed at the development of novel RT inhibitors. The lack of bona fide RNase H inhibitors with potent antiviral activity provides an example for challenges and opportunities in the field.

Influenza continues to be an ongoing problem despite the existence of vaccines and drugs. Disease outbreaks can occur relatively quickly as witnessed with the recent emergence of the influenza virus A/H1N1 pandemic. The development of new anti-influenza drugs is thus a major challenge. This volume describes all aspects of the virus structure and function relevant to infection. The focus is on drug discovery of inhibitors to the enzyme sialidase, which plays a key role in the infectious lifecycle of the virus. Following an overview of the influenza virus, the haemagglutinin, the interactions with the cell receptors and the enzymology of virus sialidase, recent results in drug design are presented. These include a full coverage of the design, synthesis and evaluation of carbohydrate as well as non-carbohydrate influenza virus sialidase inhibitors. Further reviews of the clinical experience with influenza virus sialidase inhibitors and of the development of resistance to these inhibitor drugs complement the topic.

Vaccinology, the concept of a science ranging from the study of immunology to the development and distribution of vaccines, was a word invented by Jonas Salk. This book covers the history of the methodological progress in vaccine development and to the social and ethical issues raised by vaccination. Chapters include "Jenner and the Vaccination against Smallpox," "Viral Vaccines," and "Ethical and Social Aspects of vaccines." Contributing authors include pioneers in the field, such as Samuel L. Katz and Hilary Koprowski. This history of vaccines is relatively short and many of its protagonists are still alive. This book was written by some of the chief actors in the drama whose subject matter is the conquest of epidemic disease.

Given rapid research progress and advance of the techniques in studying HIV interactions with host cells and factors, there is a critical need for a book on HIV interactions with DCs. The proposed book will aim for a broad readership to facilitate HIV/AIDS research and provide a practical tool for HIV researchers to continuously address novel questions. Specifically, the editors will summarize the literature in this field and provide critical analysis and future directions. International researchers will be invited as contributors of the book, highlighting authors who have contributed significantly to the field from different angles and aspects of virology, cell biology and immunology, etc.

The purpose of this monograph is to bring together under one cover results of research on phenomena drawn from the fields of chemistry, biochemistry, bio physics, virology,and cell biology. The processes and reactions considered have one important feature in common: they are endothermic and, therefore, entropy driven. They are, in the main, reversible reactions leading to the formation of large structures, some of which play critical roles in life processes. If one thinks only of the subunits and of the structures they form upon poly merization, it seems to be a contradiction that such reactions can be driven by an increase in entropy; entropy is a measure of disorder. The increase in entropy must come from some other source, usually from the release of something coincidental to polymerization. That something has been shown to be water for the case of the polymerization of tobacco mosaic virus protein. Because of the remarkable similarity of the other processes to this one, it is a permissable inference that the release of water is the source of the entropy increase and therefore the driving force for all of them. The reactions and processes brought together in this book are still the sub jects of active research. ;~ny of the detailed interpretations presented here must be regarded as tentative, subject to modification as new information becomes available. However, the main characteristic of each reaction or pro cess, its endothermic or entropy-driven nature, is well established in all but one or two instances.

and the development of resistance such recommenda The aim of this atlas is to provide clear guidance and a source of quick and easy reference for all physicians tions can, of course, only be of a general nature in an dealing with patients suffering from exotic skin diseases atlas such as this. The practising physician is therefore and for medical staff working in tropical and sub recommended to consult pertinent standard texts and guidelines on the respective diseases. Synonyms do tropical regions. It is not designed to replace the numerous excellent textbooks on tropical diseases and not change as rapidly as recommended treatments, and dermatology, but rather to supplement and com in an atlas of tropical dermatology and venerology are plement them in a practical way. indispensable to those readers whose first language is not the same as that used in the text: Thus, in addition The text and illustrations are the result of the per sonal experience gained from around the world in the to the English names, Spanish, French, German, Latin last forty years, and thus provide the reader with easy and local names as far as they are known are quoted to understand practical information on tropical and for each condition. Finally, for some infectious skin diseases, the distribution and life cycles of the parasites venereal diseases and ubiquitous dermatoses of the tropics and subtropics. are shown in maps and diagrams.