This volume is based on a FEMS Symposium entitled "Bacterial Growth and Lysis: Metabolism and Structure of the Bacterial Sacculus" held at the Monastery of Lluc (Mallorca, Spain) on 5-10 April, 1992. The goals of the symposium were to assess the present state of knowledge on the structure and physiology of the bacterial murein sacculus, and to develop new hypotheses and strategies to promote further development of the field. Consequently, the contributions compiled in this volume include broadly different approaches, from the introduction of new analytical methods to the presentation of provocative models for cell wall growth and division. Structural, biochemical, and genetic aspects are widely covered with special emphasis on the enzymology and regulation of murein hydrolases (autolysins). Comprehensive reviews on bacterial S layers and yeast cell walls are included to stimulate conceptual cross-feeding with these closely related topics. We believe that this book will provide the reader with a useful and up-to-date review of the topic. We would feel deeply rewarded by any positive influence this book may have on the future progress of the field, whereby all the scientific credit for it should be given to the authors of the excellent contributions presented.

North American Parasitic Zoonoses provides a concise and useful review of essential information about parasitic zoonotic diseases. North American Parasitic Zoonoses, volume six of "World Class Parasites", is written for researchers, students, veterinarians, physicians and scholars who enjoy reading research that has a major impact on human health, or agricultural productivity, and against which we have no satisfactory defense. It is intended to supplement more formal texts that cover taxonomy, life cycles, morphology, vector distribution, symptoms and treatment. It integrates vector, pathogen and host biology and celebrates the diversity of approach that comprises modern parasitological research.

Although there are a number of excellent current reviews on one or another aspect of cytomegalovirus, the last comprehensive treatment of this subject was that of Krech et al. (1971a). In view of the amazing advances in the virological, epidemiologic, and clinical knowledge of cytomegaloviruses, an up-to-date book is needed. Such a work should cover many areas of expertise and a voluminous technical literature. Each area might have been reviewed and analyzed by workers more expert than myself. However, I have embarked on the entire venture alone in order to attain unity and continuity in this book, characteristics that are not easily achieved in the more popular multiauthored works. I have tried to review the literature and to provide a critical summary for each area discussed. To do this, I provide as much of the primary data of the relevant works as needed and not just the qualitative conclusions. Inevitably, the flow of the narrative may be interrupted by dry facts and figures. However, such information is essential to make this a meaningful reference work. But for those not interested in such details, I have provided at what I hope are crucial points critiques and summaries. This book is not an exhaustive review of all the literature. This is probably no longer possible or even desirable. By selection, however, one runs the risk of having missed or ignored important papers. I am keenly aware of this, and I wish to apologize for such oversight, if that is possible.

Leishmania parasites cause a diverse group of diseases endemic to many tropical and subtropical regions of the world. This volume seeks to bring together recent research on cell and molecular biology of Leishmania with chapters on the host response to infection, the current epidemiology of leishmaniasis, explanations of the many different species, vector control, and strategies for vaccine development and drug treatment. Leishmania, volume four of World Class Parasites, is written for researchers, students and scholars who enjoy reading research that has a major impact on human health, or agricultural productivity, and against which we have no satisfactory defense. It is intended to supplement more formal texts that cover taxonomy, life cycles, morphology, vector distribution, symptoms and treatment. It integrates vector, pathogen and host biology and celebrates the diversity of approach that comprises modern parasitological research.

The articles in this volume provide a comprehensive overview of our current understanding of the roles played by cellular factors in the early steps of retroviral replication. A better understanding of these functions will provide critical new insights into retrovirus-host cell interactions and is likely to prove useful for the future development of effective antiretroviral therapies.

Fungal dimorphism is a topic that sounds inherently too rarified to attract more than a specialist audience. Yet some 230 individuals representing an eclectic mixture of interests, from basic science to medical practice, gathered in Churchill College, Cambridge in Semptember 1992 for a meeting devoted only to this subject. The symposium was the fourth in a series "Topics in Mycology" to be jointly organized by the Janssen Research Foundation and the International Society for Human and Animal Mycology. The participants enjoyed a rich and varied diet of oral presentations and poster displays in the field of fungal morphogenesis. This book sets down in print the material presented at the dimorphism symposium. We think that the high quality of these papers conveys very well the flavor of what was an excellent meeting. The selection of contributions in this volume covers very wide ground indeed. Chapters devoted to some non-pathogenic fungi are included, because the scientific basis of morphological development belongs to the fields of cellular and molecular biology: it does not recognize the boundary imposed by considerations of virulence of a fungus for a human host. Yet morphogenetic change in those fungi that do cause human disease frequently appears to be a component of the pathological process: many important pathogens change from a hyphal form in the external environment to a round form in infected tissues. This relationship between dimorphism and pathogenicity is the point of contact between pure biology and medicine.

The aberrant replication pathway of foamy viruses distinguishes them from all other retroviruses. Many details have been accumulated over the past ten or so years. Most of the findings on foamy viruses were obtained by research on a single virus isolate previously called "human foamy virus," which appeared to be the first to be investigated on a molecular level. However, to the editor's knowledge, genuine human foamy viruses do not exist, but several trans-species transmissions of different simian foamy viruses from monkeys and apes to human hosts.

P. Doherty...VB Introduction D. Dobbelaere and D. McKeever...IX Theileria Development and Host Cell Invasion Michael K. Shaw...1 Genomic Polymorphism, Sexual Recombination and Molecular Epidemiology af Theileria Parva R. Bishop, D. Geysen, R. Skilton, D. Odongo, V. Nene, B. Allsopp, S. Mbogo, P. Spooner and S. Morzaria...23 Epidemiological Significance of Strain-Specific Immunity to Theileria Parva D. J. McKeever and W. I. Morrison...41 Virulence and Attenuation in Theileria Annulata R. Adamson and R. Hall...55 Theileria Survival Strategies and Host Cell Transformation V. T. Heussler...69 Genomics of Theileria Parva V. Nene, R. Bishop, J. Quackenbush, M. Pertea, S. L. Salzberg, E. Taracha, S. Morzaria, C. M. Fraser and M. Gardner...85 Non-Transforming Theileria Parasites of Ruminants C. Sugimoto and K. Fujisaki 93 Index...107 FOREWORD The apicomplexan protozoal parasites continue to provide major challenges for human and animal health. While most of us have some familiarity with the ravages of malaria, there is relatively little awareness of diseases caused by parasites of the Theileria species. The reason is that these tick-borne organisms are problematic only in cattle and small ruminants. This does not mean, however, that the various manifestations of Theileriosis are of little interest to those concerned principally with human health. The economic loss and diminished food production associated with East Coast Fever (ECF, caused by T. parva) continues to be a major problem in East Africa.

As discussed in this book, a large body of evidence indicates that selenium is a cancer chemopreventive agent. Further evidence points to a role of this element in reducing viral expression, in preventing heart disease, and other cardiovascular and muscle disorders, and in delaying the progression of AIDS in HIV infected patients. Selenium may also have a role in mammalian development, in male fertility, in immune function and in slowing the aging process. The mechanism by which selenium exerts its beneficial effects on health may be through selenium-containing proteins. Selenium is incorporated into protein as the amino acid selenocysteine. Selenocysteine utilizes a specific tRNA, a specific elongation factor, a specific set of signals, and the codeword, UGA, for its cotranslational insertion into protein. It is indeed the 21st naturally occurring amino acid to be incorporated into protein and marks the first and only expansion of the genetic code since the code was deciphered in the mid 1960s.

What justifies the size of this compendium of reviews on the paramyxoviruses? As intracellular parasites that reproduce with almost complete indifference to nuclear activities, paramyxoviruses have not been providing insights about genes that regulate cellular activities and development, topics that account for much of the excitement in modem biology. For contributions of virus research to those topics, we must look to the retroviruses, which have the propensity to steal developmentally important genes and subvert them to malignant pur poses, and to the nuclear DNA viruses, whose gene expression depends heavily upon cellular transcription machinery, making them exceptionally useful tools for identifying and characterizing components of that machinery. From this perspective, it may appear that purely lytic viruses like the paramyxoviruses are sitting on the sidelines of contemporary biology. But there is plenty of action on the sidelines. Paramyxoviruses remain unconquered, devastating agents of disease. Human deaths attributable to paramyxoviruses worldwide, especially in children, are numbered in the mil lions annually. There are many pathogenic paramyxoviruses and too few effec tive vaccines, and those vaccines (against measles and mumps) are affordable only by relatively affluent nations. Moreover, the paramyxoviruses are intrin sically interesting organisms, presenting the challenge of understanding the self-replication of RNA and many other challenges peculiar to the structures and functions of their proteins, not only as individual entities, but also as they act in concert during virus reproduction and interact with vital functions of the cells they infect and often (but not always) destroy."

Marek's disease virus (MDV) is a herpesvirus which causes a lymphoproliferative disorder of the domestic chicken worldwide. This serious economical problem caused by MDV was mostly solved by development of an effective vaccine against MDV. The development of live vaccines against the disease is remarkable as it has led to the first example of a commercially available vaccine against cancer as well as against diseases caused by herpesviruses.
This volume gives an overview on many aspects of MDV research and summarizes recent advances in the field. The topics include the history, biology, and molecular biology of MDV, pathogenesis, vaccinal immunity, immune response, genetic resistance and development of recombinant polyvalent vaccines. It is hoped that this volume will make an important contribution towards the control of infectious diseases.

There is considerable interest in thermophile microorganisms, in their environments, their ability to survive at temperatures which normally denature proteins, but more importantly, as a valuable resource for bio technology. The first reported isolation of Thermus by Tom Brock was in 1969. This initiated the present era of thermophilic research with the realization that where liquid water is available, there may be no limits to the temper ature at which microorganisms can grow. Considerable research into the ecology, physiology, metabolism, and thermostable enzymes of thermo philes has led to their evaluation for a range of industrial and commercial processes. The past fifteen years have been an explosive period of dis covery of many new genera and species, including the descriptions of a new fundamental kingdom-the Archaea. Much of the current research has been focused on the Archaea; but it is significant that during this period, the original type strain YT-l of Thermus aquaticus described by Brock has provided a major step forward in molecular biology. DNA polymerase from strain YT-I has proved to be the major success in the commercialization of enzymes from thermophilic microorganisms to date. The ease with which Thermus strains can be handled in laboratories without specialized equipment, together with the large investment in de scribing their structure, metabolism, and genetics, should ensure a con tinuing effort in Thermus research.

Much research over the past 30 to 40 years has shown that the inflammatory response, while critical for host defense during microbial infection, may itself play a central role in the pathogenesis of sepsis. Although key mediators responsible for this injury have been identified, efforts clinically to augment our conventional antimicrobial and supportive therapies during sepsis with agents modulating the inflammatory response have been unsuccessful. As a result, the mortality associated with this lethal syndrome, especially when complicated by shock, has remained persistently high. Unfortunately, during this same period of time, the incidence of sepsis has accelerated as other fields of medicine have relied increasingly on therapies that predispose to infection. While frustrating, overall this experience in the field of sepsis has not been without value. Most importantly, it has helped define on several different levels the complexity of the septic patient. Recognizing and addressing this complexity as discussed by each of the contributors to Evolving Concepts in Sepsis and Septic Shock may now provide new inroads into the treatment of sepsis.

This volume is based on the program of the Second International Conference on Drugs of Abuse, Immunity and AIDS, held in Clearwater Beach, FL in June 1992. The Conference was supported in part by the University of South Florida College of MediCine with financial assistance from the National Institute on Drug Abuse. The focus of this conference was the effects of drugs of abuse on immunity. It is now widely recognized that psychoactive drugs of abuse, including marijuana, cocaine, and opiates, as well as alcohol, have marked effects in an individual, including effects on their nervous system and behavior. In the past two decades, the scope of studies concerning the effects of some drugs of abuse have also involved investigations of alterations of various physiologic parameters including effects on the immune system. and the influence of such immune alterations on normal physiological responses. In this regard, participants in this Second International Conference provided newer information concerning both basic and clinical aspects of drugs of abuse and immunity, especially immunodeficiencies. In this regard, advances have been made in recent years concerning the nature and mechanisms whereby the immune system is regulated and the possible mechanisms by which drugs of abuse influence such immune systems. In particular, the emergence of psychoneuroimmunology as a new discipline the last decade has heightened interest in the immune responses influenced by psychoactive drugs. This has resulted in interdisciplinary investigations involving both clinical and basic scientists, including microbiologists, immunologists, physiologists, psychiatrists, oncologists, psychologists, etc.

In 1996 the International Committee for Taxonomy of Viruses (ICTV) recognized the name Nidovirales, as the formal name for Coronaviridae and A rteriviridae. In recognition of this change, and in response to the wishes of our colleagues we named this meeting for the first time "The International Symposium of Nidoviruses". The meeting in the wooded environment of Lake Harmony, Pennsylvania, provided a stimulating opportunity for assessing the progress made in the field since the last meeting in Segovia Spain in 1997. Over 150 scientists from academia and industry attended the meeting. The meeting hosted senior members of the Nidovirus community, some of whom have been studying the subject for over 20 years, as well as younger scientists, the next generation of Nidoviro10gists. The traditional informal format, the shared meals, the social activities and the relatively inexpensive venue made the meeting a popular adventure. In her opening remarks Susan Weiss showed pictures from previous meetings, reminding us how young we used to look. Neal Nathanson was our keynote speaker at the opening night, giving an overview on how viral pathogenesis studies helped in shaping the evolution of viral research and vaccine development. The scientific program of the meeting was divided into 9 sessions including lO keynote presentations. The meeting opened with a session on epidemiology, evolution and genome structure. Sasha Gorbalenya shared with us insights gained from comparative sequence analysis, emphasizing the unifying traits among nidovriuses, but also pointed out the remaining "black holes".

Heat shock proteins (HSP) have received ample interest by immunologists over recent years. Initially they were found to be dominantly immunogenic microbial antigens. The connection with inflammation was established when it was uncovered that T cells specific for these antigens have a crucial role in the induction and regulation of experimental arthritis. Since then, the raised presence of immunity to HSPs in virtually all conditions of inflammation, including autoimmune diseases, transplant rejection and atherosclerosis, has emphasised the critical significance of immunity to HSPs in inflammatory diseases.

The tendency of fungi pathogenic for humans to have shapes in tissue distinct from their usual saprophytic morphologies has fascinated the pathologist and medical mycologist for almost a century. A primary rea son for this fascination is the possibility that fungal duality of form, or dimorphism, may be an important virulence factor that allows the zoo pathogenic fungus to survive host defenses. A second reason relates to the desire to gain basic insights into the regulation of cellular develop ment and morphogenesis among the etiological agents of human mycoses. Many excellent treatises have appeared within the recent past dealing with fungal dimorphism. However, it is becoming increasingly clear that it may be beyond the capability of one or a few authors to review this subject adequately. Instead, the ever-increasing volume ofliterature asso ciated with fungal dimorphism and the diversity offungi now recognized to exhibit a type of dimorphism suggest that a volume comprised of con tributions by numerous researchers may be more appropriate. This per ception provided me with the motivation to compile a multiauthor volume."

Integrating Population Outcomes, Biological Mechanisms and Research Methods in the Study of Human Milk and Lactation is the product of the 10th Conference of the International Society for Research on Human Milk and Lactation, held on September 15-19, 2000, in Tucson, Arizona. The presented sessions at the meeting are as diverse as the volume itself. These sessions include the impact of micronutrient deficiencies during lactation on maternal and infant health, the premature infant, developmental immunology, breastfeeding in the industrialized world, and viral transmission in milk. Whenever possible, the sessions were organized to include human population research, research showing the biological underpinnings of the effects on human health, and important methodological issues. This volume is a contemporary and influential tool for human milk biologists, breastfeeding epidemiologists, biochemists, immunologists, clinical specialists, and all professionals and researchers in the field.

These Proceedings of the Fourth International Congress on the Cornea continue a tradition of summarizing the state-of-the art basic and clinical research in cornea and ex- ternal diseases since the first Congress was held in 1964. Reflecting the emerging impor- tance of refractive surgery, two of the twelve sessions of the Congress were devoted to refractive surgery; this is reflected in an emphasis in these Proceedings. In addition, an en- tire session was devoted to the molecular and cellular biology of the cornea with impor- tant new information on the role of growth factors and cytokine modulation of corneal wound healing. Within these Proceedings an international group of expert researchers and practitioners provide the latest insights into the tear film and ocular surface, corneal trans- plantation and eyebanking, the corneal stroma and endothelium, contact lenses, microbial and nonmicrobial keratitis, keratoconus, and world corneal health. Notable subjects covered include the latest understanding of the barrier function of the ocular surface epithelium, corneal hydration control, the molecular mechanisms con- trolling gene expression in corneal wound healing, stromal~pithelial interactions in the cornea, the immunology of blepharitis, the effect of contact lenses on the conjunctiva, morphologic and functional evaluation of the human corneal endothelium, long-term fol- low-up of penetrating keratoplasty in keratoconus, the Tampa trephine penetrating kerato- plasty, and the refractive results of the Nidek EC-5000 excimer laser.

It is necessary to realize that the term "photosynthetic prokaryotes" encom- passes the widest and most diverse grouping of bacteria, but in itself has no taxonomic or phylogenetic significance. It means those organisms, other than eukaryotes, which require, obligately or facultatively, light for growth. The re cent application 16S rRNA sequencing to microbial phylogeny, asso- ciated mainly with the work of Woese, emphasizes the evolutionarily dis- persed nature of purpIe and green photosynthetic bacteria as weIl as the rather coherent phylogenetic connections of the cyanobacteria. It is not surprising, therefore, that a volume such as this which seeks to give an introduction to this collection of organisms must be highly selective; ac- cordingly, several important features are discussed only superficiaIly, e. g. , differentiation, life cycles, and biochemical aspects of nutrition. Rather, we have attempted to provide adescription of the essential features which are common and those which are characteristic, e. g. , the physiology of photo- synthesis and ecological distribution. Bearing in mind the aim of the series, we have asked our authors to emphasize aspects of the importance of these organisms in nature and their industrial applications. As will be seen from the text, these organisms have an ancient history in "biotechnology," having been used as foodstuffs by several cultures, but their exploitation has been limited to their natural patterns and products of growth.

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 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.

This concise yet comprehensive text surveys the field of bacterial metabolism in terms useful to students and researchers. Emphasis is on those metabolic reactions occurring only in bacteria. Thus, the book describes in detail the energy metabolism of the various groups of bacteria. In addition it examines pathways used by bacteria for the degradation of organic compounds, the synthesis of cellular consituents, the regulation of bacterial metabolism and the fixation of molecular nitrogen. The general arrangement of the first edition has been retained. However, it has been thoroughly revised and updated in recognition of the rapid progress of research in this field. Readers will also appreciate the increased emphasis on membrane-associated processes. From the review of the second edition: If there is a better textbook in its fields, I'm not aware of it, and I feel the book deserves a place on the shelf of any serious student of microbiology. -ASM News

This book details recent findings in the field of cave microbiology and builds on fast-paced efforts to exploit an unconventional and underexplored environment for new microorganisms which may provide an untapped source of drugs: microorganisms from caves.

The objective of this" CTMI" volume is to provide readers with a foundation for understanding what ADARs are and how they act to affect gene expression and function. It is becoming increasingly apparent that ADARs may possess roles not only as enzymes that deaminate adenosine to produce inosine in RNA substrates with double-stranded character, but also as proteins independent of their catalytic property. Because A-to-I editing may affect base-pairing and RNA structure, processes including translation, splicing, RNA replication, and miR and siRNA silencing may be affected. Future studies of ADARs no doubt will provide us with additional surprises and new insights into the modulation of biological processes by the ADAR family of proteins. "