Mammalian Toll-like receptors (TLRs) were first identified in 1997 based on their homology with Drosophila Toll, which mediates innate immunity in the fly. In recent years, the number of studies describing TLR expression and function in the nervous system has been increasing steadily and expanding beyond their traditional roles in infectious diseases to neurodegenerative disorders and injury. Interest in the field serves as the impetus for this volume in the Current Topics in Microbiology and Immunology series entitled "Toll-like receptors: Roles in Infection and Neuropathology." The first five chapters highlight more traditional roles for TLRs in infectious diseases of the CNS. The second half of the volume discusses recently emerging roles for TLRs in non-infectious neurodegenerative diseases and the challenges faced in these models with identifying endogenous ligands. Several conceptual theories are introduced in various chapters that deal with the dual nature of TLR engagement and whether these signals favor neuroprotective versus neurodegenerative outcomes. This volume should be informative for both experts as well as newcomers to the field of TLRs in the nervous system based on its coverage of basic TLR biology as well as specialization to discuss specific diseases of the nervous system where TLR function has been implicated. A must read for researchers interested in the dual role of these receptors in neuroinfection and neurodegeneration.

The emergence of H5N1 avian influenza in 1997 and of the influenza A H1N1 of swine origin in 2009 calls for new, rapid and sustainable solutions for both seasonal and pandemic influenza viruses. During the last ten years, science and technology have made enormous progress, and we are now able to monitor in real time the genetics of viruses while they spread globally, to make more powerful vaccines using novel adjuvants, and to generate viruses in the laboratory using reverse genetics. This volume not only provides state-of-the-art information on the biology of influenza viruses and on influenza vaccines, but is also designed to be a resource to face the present H1N1 pandemic and to plan for long-term global and sustainable solutions.

In recent years, biotechnology research and development (R&D) in China has been receiving increasing attention from the world. With the open-door policy of the Chinese government, many international publications (for academia) and large market potential (for industry) constitute the two big reasons for the above phen- enon. Biotechnology has become one of the priorities in Mainland China for so- ing many important problems, such as food supply, health care, environment protection, and even energy. The central government has been implementing a c- ple of programs which cover a wide spectrum in basic research, high-tech devel- ment and industrialization, such as Basic Research Program (973 Plan), Hi-Tech R&D Program (863 Plan), Key Science & Technology Problem Solving Program (Gong-guan Plan), as well as the establishment of centers of excellence - Key Laboratories and Engineering Centers, etc. The funding from various local gove- ments and industry for R&D has also been increasing continuously. Biotechnology centers in Shenzhen, Shanghai and Beijing have been established. There are more than 400 universities, research institutes and companies and a total of over 20,000 researchers involved in biotechnology in the Mainland. The number of research papers published internationally and patent applications is also increasing rapidly. In addition, the huge market potential with about 1. 4 billion population, which is already open to the outside world, has provided numerous opportunities for int- national and domestic companies to invest in biotechnology, which pushes forward the biotechnology industrialization in China.

The Parvoviridae have been of increasing interest to reseachers in the past decade. Their small size and simple structure have made them ame- nable to detailed physiochemical analysis, and from this work relatively detailed information has resulted that has signficantly increased our un- derstanding of the biology of these viruses. It has become clear that the Parvoviridae are of interest not only for their own sake, but also because their relative simplicity renders them useful probes in the study of the biology of host cells and of other DNA viruses with which they interact. The Dependovirus genus, for instance, contains the defective adeno-as- sociated viruses (AA V), which require a coinfection with either an ad- enovirus or a herpesvirus for productive multiplication. Studies of AA V, therefore, necessarily impinge on our understanding of the control of macromolecular synthesis by the helper virus. Similarly AA V has been reported to inhibit the oncogenicity of both adeno-and herpesviruses and has been used as a probe of mechanism in these instances as well. Finally, AA V establishes latent infections in vivo and is the only mammalian DNA virus where a comparable model system has been established in cell culture. This system has allowed study of the mechanism of latent infection at the molecular level.

In the past half century, filamentous fungi have grown in commercial importance not only in the food industry but also as sources of pharmaceutical agents for the treatment of infectious and metabolic diseases and of specialty proteins and enzymes used to process foods, fortify detergents, and perform biotransformations. The commercial impact of molds is also measured on a negative scale since some of these organisms are significant as pathogens of crop plants, agents of food spoilage, and sources of toxic and carcinogenic compounds. Recent advances in the molecular genetics of filamentous fungi are finding increased application in the pharmaceutical, agricultural, and enzyme industries, and this trend promises to continue as the genomics of fungi is explored and new techniques to speed genetic manipulation become available. This volume focuses on the filamentous fungi and highlights the advances of the past decade, both in methodology and in the understanding of genomic organization and regulation of gene and pathway expression.

Course covers topics in infectious diseases in children and is intended for Pediatric Infectious disease trainees, trainers, and all those who manage children with infections.

Development of new-generation vaccines is now more challenging than ever, as identifying, purifying and evaluating vaccine antigens is a complex undertaking. Most importantly, once the relevant antigens have been identified, key focus then shifts to the development of suitable delivery systems and formulations to achieve maximum in vivo potency with minimum potential side effects. These novel formulations-many of which will be nanoparticulates-can deliver the antigens to the desired site, to the relevant antigen presenting cells, and prevent systemic exposure of the immune potentiators. The proposed book will outline all the critical steps that need to be considered for successful development of various types of nanoparticulate delivery systems for vaccine antigens. These contributions from leading experts in the area of vaccine formulation and delivery systems will tie in what is the most current status, including clinical evaluations with these novel vaccine technologies.

"HPV and Cancer" is a concise read that covers all aspects of the Human Papilloma Virus as it relates to human cancers. While written by professionals, it design to be understandable by those that are not in the field, yet it has the technical details that professionals want to stay abreast of this changing field. The book starts out the history of HPV and progresses into the molecular biology of the virus and our current understand of the structure and functions of the proteins and genes it encodes. We then look at the dynamic trends of this infectious agent in the human population, how it interacts with human cells, and the role it plays with other organisms to produce both benign and malignant tumors. Lastly, there is a discussion about a new vaccine for HPV and the hopes that are held by many to change the trends with this virus and the associated cancers it produces.

The stages of Blastocystis have been known for 101 years. However, many facts are still disputed, e.g. even the question whether it is a true pathogen or a commensal present in sometimes life- threatening diarrheas. The present book evaluates in chapters contributed by renowned researchers the latest findings on: * Landmarks in the discovery of Blastocystis * Epidemiology, transmission and zoonotic potential * Morphology of human and animal Blastocystis isolates * Clinical aspects of Blastocystis infections * Behavioral decision analysis: what makes us sick? * Blastocystis-host interactions * Molecular approaches on the systematical position * Genetic polymorphism * Blastocystis from a statistical point of view * Diarrheas due to different agents of disease * Zoonotic diseases in comparison As such, this book provides a broad range of information for people working in this field, for physicians and veterinarians who are confronted with clinical cases, teachers, students and technical staff members in the fields of microbiology, parasitology and diagnostic methods.

CRISPR/Cas is a recently described defense system that protects bacteria and archaea against invasion by mobile genetic elements such as viruses and plasmids. A wide spectrum of distinct CRISPR/Cas systems has been identified in at least half of the available prokaryotic genomes. On-going structural and functional analyses have resulted in a far greater insight into the functions and possible applications of these systems, although many secrets remain to be discovered.

In this book, experts summarize the state of the art in this exciting field.

Deficiencies in any of the defense mechanisms of the host can lead to severe microbial infections; these are of clinical relevance. Broad up-to-date knowledge in this field allows identification of many unspecific as well as highly specific defense reactions involved in the struggle against infectious diseases. On the other hand, protective structures on the microbial cell surfaces have been adapted and improve the counterpart's chances of survival. In particular, it has been considered that the great diversity of the bacterial envelopes not only determines the anatomical location of the tissue injury but also induces activation of distinct parts of the complex defense system. The specific defense mechanism, whose most prominent constituent is provided by the antibo

It has been known for a long time that the majority of plant viruses contain RNA and in the past decade and a half it has been realized that many have genomes consisting of three molecules of single-stranded RNA with positive polarity. Among these are viruses belonging to four groups recognized by the International Committee for Virus Taxonomy: the Bromovirus and Cucumovirus groups whose genomes are encapsi dated in small icosahedral particles or the Ilarvirus and alfalfa mosaic virus groups with spheroidal or bacilliform particles. In addition to their tripartite genomes, these viruses share a number of other properties and it has been proposed that they should perhaps be grouped in a single virus family for which the name Tricornaviridae has been suggested, the tri indicating the tripartite nature of the genome, the co emphasizing the cooperation of the three genome parts required to initiate infection, and the rna indicating that the genome is composed of RNA. Viruses of this "family" are less uniform in their biological proper ties. A number of them are widespread, causing very destructive plant diseases. Viruses such as those of cucumber mosaic and alfalfa mosaic have very extensive host ranges and are responsible for serious crop losses in many parts of the world. Others such as prunus necrotic ringspot or prune dwarf viruses are more restricted in their host ranges but never theless infect important perennial hosts such as stone fruits and reduce productivity considerably."

The Bunyaviridae represent an extremely diverse family of viruses, whichuntilrecentlywererelativelypoorlyunderstood. These viruses have become increasingly important in both human and veterinary medicine, and, most recently, bunyaviruses have been recognized as plant pathogens as well. This book attemptsto treat all aspectsof their biology, including their natural history, genetics, virion structure, unusual pathway of intracellular assembly, gene structure and the mechanisms of its expression, antigenicity, and pathogenesis, inasinglevolume. Assuch, itfillsavoid inthe virologyliterature.Thisvolumeisalsotimely, asthemolecular descriptionofthisfamilyisnowalmostcomplete. Thereader can expect to find the present state of the art on how bunyavirusesaremaintainedinnature, andhowtheyreplicate and sometimescausedisease. Iwould like tothank myco-contributorsfor the time and efforttheyhaveinvestedtomaketheirchaptersascompleteas possible, and notleastofall, for byand largerespectingthe deadline. Iam alsogratefulto DickCompansforsuggesting this volume and helping to design its contents, and for the manydiscussionsduring hisstayin Geneva. DANIEL KOLAKOFSKY ListofContents C. R. PRINGLE: TheBunyaviridaeandTheirGenetics An Overview . . . . . . . . . . . . . . . . . . . . . B.J. BEATYand C. H. CALISHER: Bunyaviridae- Natural History. . . . . . . . . . . . . . . . . . 27 M.J. HEWLETTand W. CHIU: Virion Structure . . 79 R. M. ELLIOTT, C. S. SCHMALJOHN.and M. S. COLLETT: BunyaviridaeGenomeStructureandGeneExpression 91 D. KOLAKOFSKYand D. HACKER: BunyavirusRNA Synthesis: GenomeTranscriptionand Replication. 143 Y. MATSUOKA, S. Y. CHEN, and R. W. COMPANS: BunyavirusProteinTransportandAssembly. 161 L. KINGSFORD: AntigenicVariance. . . . . . . . 181 F.GONZALEZ-SCARANO, M. J. ENDRES.and N. NATHANSON: Pathogenesis. . . . . . . . . . . . . . . . . . . . . . ... 217 ListofContributors BEATY, B. J.... 27 HACKER. D.... 143 CALISHER, C. H.. 27 HEWLETT, M. J. 79 CHEN, S.Y . 161 KINGSFORD, L.. 181 CHIU, w. . 79 KOLAKOFSKY D.. 143 COLLETT, M.S. . 91 MATSUOKA, Y.. 161 COMPANS, R. W.. 161 NATHANSON, N.. 217 ELLIOTT, R. M.. . 91 PRINGLE, C. R.. . 1 ENDRES. M. J. . . 217 SCHMALJOHN. C.S.. 91 GONZALEZ-S

The data summarized in this chapter show that morphological transformation and oncogenesis by adenoviruses are brought about by the coordinated activity of regions E1A and E1B. Gene products of each of these subregions appear to fulfill distinct roles in oncogenic transformation, with the possible exception of the product(s) encoded by the O. 9-kb E1A mRNA. Also unclear is the func- tion of the 20-kd E1B protein, which has a small role, if any, in morphological transformation, but appears to be essential for the development of the oncogenic phenotype, as defined by the ability of transformed cells to grow in immuno- deficient nude mice. The differences in biological properties of oncogenic and nononcogenic adenoviruses must be attributed to differences in the primary structure of the respective E1A and E1B gene products, in particular of the product(s) of the 1. 0-kb E1A mRNA and of the 55-kd protein encoded by the 2. 2-kb EiB mRNA. The availability of cold-sensitive adenovirus mutants has enabled us to conclude that the transformed phenotype is maintained as a result of continuous expression of at least region E1A gene products, and is therefore not the result of a hit-and-run mechanism. Despite the progress in our understanding of adenovirus transformation and oncogenesis, virtually nothing is known about the precise mechanism by which the viral gene products bring about the neoplastic changes in cells. The only exception is the demonstration that Ad12 region E1A (1.

attempted to cover metabolic matters already reviewed in Volumes I and II of The Biochemistry and Physiology of Protozoa (eds. Lwoff, and Lwoff and Hutner). To those interested in the broader aspects of photo- synthesis and photoreception, reference is made to Photosynthesis and Related Processes, Volume I, and parts I and 2 of Volume II, by E. Rabinowitch; the Brookhaven Symposium on The Photochemical Ap- paratus: Its Structure and Function (1959); the New York Academy of Sciences conference on Photoreception (1958), and to the many recent symposia, reviews, and current journal literature. This book is primarily concerned with the use of Euglena in study- ing photoreception; it is also hoped that biologists, biochemists, and biophysicists will find in Euglena a remarkably versatile research tool for attacking some of their problems. I would like to thank Drs. S. H. Hutner and L. Provasoli of the Haskins Laboratories for introducing me to Euglena as an exceptional experimental "animal," as well as for many stimulating discussions and continued enthusiasm. I am indebted to Drs. G. E. Palade and K. R.

There has been a tremendous increase in interest in the neuropathogenicity of viruses during the past decade as we have come to recognize that the human immunodeficiency virus, which causes the acquired immunodeficiency syndrome (AIDS), can infect glial cells and cause neurological disease. Yet this increase has not been limited to AIDS but has extended to viruses that infect either or both the central and peripheral nervous systems. The changes examined here include both neurological and psychological diseases or syndromes. Moreover, the chapters in this volume review the interaction of the host immune system with the viruses examined and how such interactions may increase or decrease the neuropatho genicity of the viruses. Questions regarding viral neuropathogenesis include: (I) What is the mode of transmission of virus to the nervous system? (2) What types of cells are infected, and do they contain receptors for the virus? (3) What is the extent of damage that results from viral infection? (4) What are the immunologic mecha nisms by which damage is mediated or limited? Many of these questions remain unanswered, but this volume delves into efforts to provide some answers.

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having passed only recently through its descriptive phase of naming and num bering, has probably reached that stage at which relatively few new truly new-viruses will be discovered. Triggered by the intellectual probes and techniques of molecular biology, genetics, biochemical cytology, and high-resolution microscopy and spectroscopy, the field has experienced a genuine information explosion. Few serious attempts have been made to chronicle these events. This comprehensive series, which will comprise some 6000 pages in a total of about 22 volumes, represents a commitment by a large group of active investigators to analyze, digest, and expostulate on the great mass of data relating to viruses, much of which is now amorphous and disjointed, and scattered throughout a wide literature. In this way, we hope to place the entire field in perspective, and to develop an invaluable reference and sourcebook for researchers and students at all levels. This series is designed as a continuum that can be entered anywhere, but which also provides a logical progression of developing facts and integrated concepts."

Mter the discoveryof the tobacco mosaic virus by D. I. Ivanov skU in 1892 14], the new science of virology was born and began to develop rapidly. The number of viruses now known is enormous and they can infect nearly all animal and plant organisms. Microorganisms themselves are no exception to this rule. Despite intensive study of Vlruses, their origin and nature are still a subject for speculation and hypothesis. The general concept of viruses embraces a wide group of biologically active structures occupying an intermediate position between living and nonliving matter. The dual character of viruses is determined by the fact that, while they do not possess an inde pendent system of metabolism, which is a characteristic feature of every living being, they nevertheless carry within themselves all the necessary information for autoreproduction. A striking feature of the virus is that it consists essentially of two components: a protein envelope and the nucleic acid con tained within it. In contrast to the elementary structural unit of the living or ganism, the cell, which contains two types of nucleic acid (DNA and RNA), the virus particle contains only one type of nucleic acid - either DNA or RNA. It is perhaps this which is responsible for the imperfection of the virus as a living organism."

The study of viruses necessarily involves dissecting the intimate details of cellular pathways. Viruses have often been employed as tools in studying cellular pathways, as was done by early retrovirologists such as Peyton Rous in attempting to understand the mechanism of cellular transformation and oncogenesis. On the other side of the coin, virologists seek to de?ne those cellular elements interacting intimatelywiththeir virus ofinterestinorder to better understand viral replication itself, and in some cases to develop antiviral strategies. It is in the intersection of virology and cell biology that many of us ?nd the most rewarding aspects of our research. When a new discovery yields insights into basic cellular mechanisms and presents new targets for int- vention to ?ght a serious pathogen, the impact can be high and the excitement intense. HIV has been no exception to the rule that viruses reveal many basic aspects of cellular biology. In recent years, in part because of the importance of HIV as a major cause of human suffering, numerous cellular processes have been elucidated through work on processes or proteins of this human retrovirus. The excitement in this ?eld is especially well illustrated by the discovery of new innate means of resisting viral replication, such as the work on APOBEC3G, TRIM5a, and BST-2/ tetherin presented in this volume.

This book explores the many mechanisms by which the most prevalent Spirochetal pathogens persist in a healthy immune-competent host. Among them are the direct and indirect suppression of host immune signals, phase and antigenic variation, escaping recognition by host complement proteins, and seclusion into immune privileged sites. We also explore antibiotic therapy for control of infection, a baffling topic that lends itself to exalted interpretation.

The book provides a comprehensive account of ticks and tick-borne diseases occurring in tropical and subtropical areas. It begins with a complete up-to-date overview of the systematics of the Ixodida (Ixodidae, Argasidae and Nutalliellidae) and is followed by a review of the problem of ticks and tick-borne diseases of domestic animals world wide. This leads on to multi-disciplinary approaches to planning tick and tick-borne disease control and to contributions on calculating the economic impact of a tick species such as Amblyomma americanum on beef production systems. Heartwater fever (cowdriosis) and dermatophilosis are endemic in Africa and pose a threat to the North American mainland. The epidemiology of these two diseases is discussed in detail as is the role of frozen vaccines to control bovine babesiosis and anaplasmosis. The book also includes chapters on tick transmitted zoonoses such as Lyme borreliosis, tick typhus and ehrlichiosis. It concludes with a review of the acaricidal treatment of tick infestation.

Organisms are constantly being bombarded by stimuli in their envi ronment (and also by internal stimuli), and a common way of responding is by movement. This is an aspect of irritability, or excitability, or behaviour. Response to stimuli by movement is found in all organisms: it represents one of the universalities of biology. Yet at the molecular level it is one of the least understood of biological phenomena. Micro-organisms are no exception. If motile, they respond to stimuli by active movement (taxis); if sessile, they respond by growth movements (tropisms). Responses by movement are known among micro-organisms to such stimuli as chemicals, electric current, gravity, light, temperature, touch, and vibrations. The behaviour of micro-organisms is an exciting subject, first of all for its own sake, but in addition because it may reveal facts and concepts that are applicable to understanding behaviour in more complicated organisms (even us) and because it may, help to understand the movement of cells and tissues during differentiation and development of higher plants and animals.

All but one* of the following articles represent comprehensive reports on a workshop held between 7 and 9 May 1981 at the Institute of Virology and Immunobiology, University of Wfuzburg, Federal Republic of Germany. The title of the workshop was "The Involvement of Endogenous Retroviruses inN ormalFunction and Pathological Growth of Lymphocytes." Rather than collecting and printing manuscripts of the individual communications, the organizers asked selected parti cipants to write, after the workshop, concise articles each compris ing several contributions and discussions on major topics. In so doing, we hope to present to a larger audience a synopsis of the various information and views exchanged at the meeting. Such a procedure seemed the more appropriate as the workshop was intended to bring together specialists from two rather diverse fields: RNA-tumor virology and immunobiology. While this created some initial problems of terminology, it was quite effective in making representatives of one field more aware of the significance and the contributions ofthe other. It also great ly contributed to realization of the complexity of the problems involved in virus-induced leukemogenesis."

of McGill University of Montreal, Canada, who talks about artifi cial cells prepared from semipermeable microcapsules. Also illustrative of this method is a contribution on microencapsulated pesticides by C. B. Desavigny and E. E. Ivy of Pennwalt Corporation. Another method of polymerization in situ is micro encapsulation by vapor deposition, the subject of W. M. Jayne of Union Carbide Corporation. The more mechanical methods of microencapsulation are represented by two techniques, one involving a fluidized bed the other involving mainly a centrifugal method. The fluidized bed method is covered in a paper by H. Hall and T. M. Hinkes of the Wisconsin Alumini Research Foundation. The centrifugal and other related methods are treated by Mr. J. E. Goodwin and Mr. Sommerville of the Southwest Research Institute of San Antoni~ Texas. Dr. G. Baxter of Moore Business Forms, studied capsules made by mechanical methods as well as by chemical methods. Mr. Russell G. Arnold of the Bureau of Veteranary Medicine of the Food and Drug Administration draws our attention to the procedures to be used for securing approval of a new animal drug application for the marketing of microencapsulated products. And last but not least, we have a contribution by Mr. G. O. Fanger on "Micro encapsulation a Brief History and Introduction, whose title speaks for itself.