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.

A comprehensive review of all known immune mechanisms for medically important fungal pathogens from the organ perspectives of the human body. This authoritative guide is organized by organ system, as one particular fungus can have several different effects.

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.

Henipaviruses form a new genus of emerging paramyxoviruses that are the deadliest human pathogens within the Paramyxoviridae family. This volume deals with the many facets of henipavirus biology, and covers our current understanding regarding the ecology, molecular virology, and pathogenesis of henipavirus infections. It is an international effort written by a multidisciplinary panel of experts at the front lines of research into this lethal emerging group of paramyxoviruses. The first section introduces the epidemiology and ecology of Nipah and Hendra viruses in their respective endemic areas, including a first-hand account of the discovery of Nipah virus during its initial outbreak in Malaysia; the next section documents the molecular virology of henipaviruses, and the substantial advances made towards understanding the unique features of henipavirus entry and tropism; and this is followed by accounts of the clinical and pathologic features of henipavirus infections in their human and naturally infected animal hosts. The next sections on pathogenesis provide a comprehensive reference on how henipaviruses counteract the innate immune system, and the relevant pathogenic features in animal challenge models developed to test potential therapeutic strategies. The final sections describe our current and future capabilities for diagnosis and control, including an account of potentially effective immunization strategies that are currently being tested. This book will not only serve as a useful reference for the henipavirus field; it will be useful to basic and animal virologists, ecologists, epidemiologists, physicians, and others interested in emerging infectious viral diseases, as it showcases the multidisciplinary efforts required to understand the genesis, spread and hopefully, control, of a group of lethal emerging zoonotic pathogens.

The genome of retroviruses contains three major coding regions for virion proteins, gag, pol and env. Gag encompasses information for nonglycosylated viral proteins that form the matrix, the capsid and the nucleoprotein structures. From pol derive reverse transcriptase and integrase, and env codes for the surface glycoproteins of the virion which consist of a transmembrane and a surface domain, linked by disulfide bonds. A viral protease is derived eitherfrom the gagorfrom the pol coding region, depending on the virus. Simple retroviruses contain only this elementary gag, pol, and env coding information. Once integrated, they are able to multiply efficiently, using the cellular transcriptional and replication machineries without intervention of viral transacting factors. Most oncogenic retroviruses belong in this category. Complex retroviruses, on the other hand, encode additional nonstructural proteins from multiply spliced messages. These proteins play important regulatory roles in the life cycle of the virus. They function as transacting factors that, in concert with cellular regulatory proteins, control viral gene expression and function and are essential components in the replication of complex retroviruses. To this category belong the lentiviruses, the spumaviruses and a group of oncogenic retroviruses that includes human T cell leukemia virus (HTLV) and bovine leukosis virus(BLV).

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.

Organs and tissues that can tolerate little or no inflammation have developed multiple overlapping mechanisms of immune protection in the absence of inflammation. These areas have been designated "immune-privileged sites" by Peter Medawar and include the central nervous system, eye, reproductive tract, testis and possibly the liver. Mechanisms of immune homeostasis found in less immune-regulated organs are often evident in the immune privileged sites and vice versa. It is important that the non-inflammatory mechanisms that contribute to immune privilege allow host defense against infectious organisms. This volume highlights the mechanisms leading to immune privilege in tissues and organs, the deviation of immune responses and the modification of the behavior of the immune cells that manage to cross the blood barriers of tissues, in the context of infection.

Scientists often look askance at their colleagues whose research appears too strongly focused on a single gene or gene product. We are supposed to be interested in the "big picture" and excessive zeal in pursuit of a single pixel might seem to border on an obsession that is likely to yield only details. However as this volume of Current Topics in Microbiology and Immunology demonstrates, this is certainly not the case for myc. Intense study of this en- matic proto-oncogene over the last twenty years has only broadened our view of its functions and led to insights into mechanisms relating to transcriptional regulation as well as to cell growth, proliferation, differentiation, apoptosis and organismal development. The myc gene originally came to light as a retroviral oncogene (v-myc) associated with a wide range of acute neoplasms. It was later shown to be a virally transduced cellular gene (c-myc) which is a member of family of on- genes (c-myc,N-myc,L-myc). These family members are themselves subject to a bewildering assortment of genetic rearrangements associated with many different types of tumors derived from many different types of cells. These rearrangements (including chromosomal translocation, viral integration, and gene ampli?cation) act to uncouple expression of the myc family genes from their normal physiological regulators. The chapter by LIU and LEVENS - scribes the key pathways leading to regulation of myc expression, showing that such regulation occurs at several different levels and through multiple mechanisms.

TwentyyearshavegonebysinceJackSokatch?rstpublishedhisoutsta- ingTheBiologyofPseudomonasbackin1986.Thiswasfollowedbytwobooks published by the ASM that contained the presentations of the Pseudomonas meetings held in Chicago in 1989 and Trieste in 1991. The earlier volume of these two was edited by Simon Silver, Al Chakrabarty, Barbara Iglewski, and Sam Kaplan, and the later one by Enrica Galli, Simon Silver, and Bernard Witholt. The time was ripe for a series of books on Pseudomonas because of its importance in human and plant pathogenesis, bio?lms, soil and rhizosphere colonization, etc. Efforts were devoted to produce the ?rst three volumes of the series on the biology of Pseudomonas after a meeting with Kluwer staff members in August 2002 during the XI IUMS conference in Paris (France). In less than a year a group of outstanding scientists in the ?eld, after devoting much of their valuable time, managed to complete their chapters for the three volumes of the series. To ensure the high standard of each chapter, renowned scientists participated in the reviewing process. The three books collected part of the "explosion" of new vital information on the genus Pseudomonas.

This book will assemble the views of many of the world's experts in the field of viruses and diabetes. It will look critically at some unanswered questions, in the field. Among these, How do viruses destroy or modify the pancreatic islet? Which viruses are involved? What is the role of virus-induced cytokines> Could vaccines prevent virus-induced diabetes? Until recent technological advances, progress in the understanding of the relationship between viruses and diabetes has been hampered. New technologies are helping shed new light on these mysteries. This will be the first comprehensive volume on this topic.

Muscle disease represents an important health threat to the general population. There is essentially no cure. Gene therapy holds great promise to correct the genetic defects and eventually achieve full recovery in these diseases. Significant progresses have been made in the field of muscle gene therapy over the last few years. The development of novel gene delivery vectors has substantially enhanced specificity and efficiency of muscle gene delivery. The new knowledge on the immune response to viral vectors has added new insight in overcoming the immune obstacles. Most importantly, the field has finally moved from small experimental animal models to human patients. This book will bring together the leaders in the field of muscle gene transfer to provide an updated overview on the progress of muscle gene therapy. It will also highlight important clinical applications of muscle gene therapy.

1 Fleas are wingless insects with a laterally compressed body of about 1.5-4 mm length. Like all insects they possess six legs and three body segments. Taxonomically they belong to the order Siphonaptera (Eckert et al. 2000) (Table 1). This family contains several species and subspecies. Fleas represent one of the most important ectoparasites (Mehl- horn 2000; Mehlhorn et al. 2001b). At the moment there are more than 2000 described species and subspecies throughout the world (Borror et al. 1981). These species belong to the families Pulicidae, including Pulex spp., Ctenocephalides spp., Spilopsyllus spp. and Archaeopsyllus spp., or the familia Ceratophyllidae with the genuses Ceratophyllus or Nosopsyllus to mention only some of the most important veterinary and human representatives. Fleas have a history of about 60 million years and were already found on prehistoric mammals. While becoming parasitic the original exterior of the two-wing insects, also designated as the order Diptera, has changed by losing the wings in the adults, whereas the larval form still has similarity with the larva of the order Diptera (Strenger 1973). About 95% of the -2000 different flea species parasitize on mammals, 5% live on birds. Table 1. Taxonomy of fleas Systematic Taxonomy Phylum Arthropoda Tracheata (=Antennata) Subphylum Classis Insecta (Hexapoda) Ordo Siphonapterida Familia Pulicidae Familia CeratophyUidae Genus Ctenocephalides. Genus Ceratophyllus. Nosopsyllus Pulex.

Prevention of infectious diseases by vaccination is one of the most significant achievements of modern medicine. During the 20th century, the average human life span in the developed world was about 70 years and it is expected to increase, with a significant portion of this increase directly attributed to vaccination. Since the first empiric vaccination trials, knowledge and technology have enormously evolved and new vaccination strategies are emerging on the market. Indeed, in spite of the great success, conventional vaccination strategies sometimes may result ineffective and, above all, may raise safety concerns. The aim of this book is to provide an overview of some of the technology platforms that have been realized or are currently under development to try to address unsolved and new issues in the field of vaccine development. Common denominator of all thematic areas described herein is the multidisciplinary teamwork. Most of the enabling technologies have been established by putting in the "melting pot" expertise in fields that, at first glance, may appear very far apart. I hope that this collection of articles will make the readers aware that vaccinology is rapidly taking a new direction, ceasing to be an empirical science.

A renaissance of virus research is taking centre stage in biology. Empirical data from the last decade indicate the important roles of viruses, both in the evolution of all life and as symbionts of host organisms. There is increasing evidence that all cellular life is colonized by exogenous and/or endogenous viruses in a non-lytic but persistent lifestyle. Viruses and viral parts form the most numerous genetic matter on this planet.

Interface oral health science was founded on the concept that healthy oral function is maintained by biological and biomechanical harmony between three systems: oral tissues, parasitic oral microorganisms, and biomaterials. On that basis, dental caries, periodontal disease, and temporomandibular joint disorders may be regarded as interface disorders that result from a disruption in the intact interface of these systems. Interface oral health science encompasses the fields of dentistry and dental medicine, but also extends to general medicine, agriculture, biomaterials science, bioengineering, and pharmacology. This book is a compendium of the research presented at symposiums held in 2011 by the Tohoku University Graduate School of Dentistry and by the Forsyth Institute. Its publication is intended provide further impetus for the progress of oral science and health, pointing the way for dental research for future generations.

The human foetus is separated from the maternal blood by the syncytiotrophoblast induced by endogeneous human retrovirus-encoded proteins. This barrier is a highly developed one, which suppors apical-basolateral transport of maternal idiotype and anti-idiotype IgG, IgG-virus complexes. The selective maternal-fetal transport of epitope- and paratope-bearing entities can influence the developping fetal immune system during pregnancy. The bidirectional maternal-fetal transfer of cells are of even more importance during pregnancy. Maternal cells with latent viruses transport viruses without impairment of fetal development. Cells with premaligant and malignant genetic transformation are also transported to the fetus. Fetal and neonatal tumours are initiated by such cells in spite of the antitumour potential of fetal organism. On the contary, the fetal cells repair maternal tissue injouries and survive in the organisms of the recipients for decades. These possess new consequences for the neonatal immunity and organ transplatation surgery.

There is a high demand for antimicrobials for the treatment of new and emerging microbial diseases. In particular, microbes developing multidrug resistance have created a pressing need to search for a new generation of antimicrobial agents, which are effective, safe and can be used for the cure of multidrug-resistant microbial infections. Nano-antimicrobials offer effective solutions for these challenges; the details of these new technologies are presented here.

The book includes chapters by an international team of experts. Chemical, physical, electrochemical, photochemical and mechanical methods of synthesis are covered. Moreover, biological synthesis using microbes, an option that is both eco-friendly and economically viable, is presented. The antimicrobial potential of different nanoparticles is also covered, bioactivity mechanisms are elaborated on, and several applications are reviewed in separate sections. Lastly, the toxicology of nano-antimicrobials is briefly assessed."

This volume brings together contributions from experts in the field of Pasteurella research. Its covers areas such as comparative genomics, pathogenic mechanisms, bacterial proteomics, as well as a detailed description and analysis of PMT and its interaction with host tissues, cells, immune system, and signalling pathways.

Oxygen-Ozone therapy is a complementary approach less known than homeopathy and acupuncture because it has come of age only three decades ago. This book clarifies that, in the often nebulous field of natural medicine, the biological bases of ozone therapy are totally in line with classical biochemistry, physiological and pharmacological knowledge. Ozone is an oxidizing molecule, a sort of super active oxygen, which, by reacting with blood components generates a number of chemical messengers responsible for activating crucial biological functions such as oxygen delivery, immune activation, release of hormones and induction of antioxidant enzymes, which is an exceptional property for correcting the chronic oxidative stress present in atherosclerosis, diabetes and cancer. Moreover, by inducing nitric oxide synthase, ozone therapy may mobilize endogenous stem cells, which will promote regeneration of ischemic tissues. The description of these phenomena offers the first comprehensive picture for understanding how ozone works and why. When properly used as a real drug within therapeutic range, ozone therapy does not only does not procure adverse effects but yields a feeling of wellness. Half the book describes the value of ozone treatment in several diseases, particularly cutanious infection and vascular diseases where ozone really behaves as a "wonder drug". The book has been written for clinical researchers, physicians and ozone therapists, but also for the layman or the patient interested in this therapy.

SARS was the ?rst new plague of the twenty-?rst century. Within months, it spread worldwide from its "birthplace" in Guangdong Province, China, affecting over 8,000 people in 25 countries and territories across ?ve continents. SARS exposed the vulnerability of our modern globalised world to the spread of a new emerging infection. SARS (or a similar new emerging disease) could neither have spread so rapidly nor had such a great global impact even 50 years ago, and arguably, it was itself a product of our global inter-connectedness. Increasing af?uence and a demand for wild-game as exotic food led to the development of large trade of live animal and game animal markets where many species of wild and domestic animals were co-housed, providing the ideal opportunities for inter-species tra- mission of viruses and other microbes. Once such a virus jumped species and attacked humans, the increased human mobility allowed the virus the opportunity for rapid spread. An infected patient from Guangdong who stayed for one day at a hotel in Hong Kong led to the transmission of the disease to 16 other guests who travelled on to seed outbreaks of the disease in Toronto, Singapore, and Vietnam, as well as within Hong Kong itself. The virus exploited the practices used in modern intensive care of patients with severe respiratory disease and the weakness in infection control practices within our health care systems to cause outbreaks within hospitals, further amplifying the spread of the disease. Health-care itself has become a two-edged sword.

An estimated 2-3 billion people in the less developed countries suffer from infections, often multiple, caused by a variety of parasitic organisms. These infections are frequently debilitat ing rather than fatal, and the toll in human misery is fearsome. To this may be added the prevalence of similar diseases in do mestic animals, which diminish supplies of animal pro tein. As the world population increases, the already enormous problem also continues to grow. The resources of the less developed nations are inadequate for solving the problem, and in the de veloped countries a lack of interest in tropical diseases has meant low priority for research. Two recent methodological advances now raise the real possibility of a systematic and effec tive attack upon these diseases - hybridoma and recombinant nucleic acid technologies. The combination ofthese with the still necessary clinical, parasitological and imrnunological in formation permits a logical, planned and realistic approach to diagnosis and treatment. The central aim ofthese modem tech niques is to define antigens with regard to diagnosis, protection and pathology. In the case of some diseases, work has already commenced along these lines; in the case of others, knowledge lags a long way behind. This volume represents a summary of current knowledge about a wide, representative spectrum of tropical diseases. There is considerable common ground between the different infections as regards objectives and the methods for achieving them."