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 invalu able 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."

No one whose opinion deserves a moment's consideration can doubt that most of the great positive evils of the world are in themselves removable, and will, if human affairs continue to improve, be in the end reduced to narrow limits. J. S. Mill, Utilitarianism, II, 1863 Mill was not writing about herpesviruses, but had he known them as we do, he would have included them among the great positive evils of the world. They cause disease and premature death, and are very costly to our society. There is no loftier aim than to cure or prevent human infections with these viruses. The objective of much of the current research on herpesviruses is directed toward an understanding of the molecular mechanisms involved in initiation of infection, establish ment and termination of latent state, virus multiplication, and the destruction of cells which ultimately is the basis of the diseases caused by these viruses. At no time during the past 80 years, since members of the herpesvirus family were first discovered, has there been so much progress in our understanding of the biology of these viruses as in the past few years. Along with the development of a greater understanding of the molecular biol ogy of the well-known herpesviruses we have witnessed the isolation of new human herpes viruses.

The Streptomycetes are industrially widely used microorganisms due to their ability to produce numerous different chemical compounds. These show very varied effects upon other living systems, and result from profound and subtle biochemical and morphological differentiation during the streptomycete life cycle. It is therefore not surprising that research on the genetics of antibiotic biosynthesis and differentiation in this group is currently progressing rapidly in many countries. Intimately connected with the production of antibiotics is resistance to them; analysis of this is giving further information about the origin and evolution of this class of genes and their hypothesized spread among other microorganisms. Another interesting feature of the Streptomyces group is their mycelial growth. Also, their ecologically important utilization of high molecular weight compounds requires enzymes to be transported outside the cell to hydrolyze non-diffusible substrates. Finally, we have as yet limited understanding of the various mechanisms of genome rearrangement observed in some of these species; deletions and/or amplifications of enormous amounts of DNA can occur without seriously affecting the viability of the organism under laboratory conditions. The present volume, which includes contributions addressing the above subjects and others, originates from a meeting on "Genetics and Product Formation in Streptomyces" sponsored by the Federation of European Microbiological Societies in Erfurt on May 1-6 1990. Compared to previous ones of this kind held in 1979, 1983 and 1987 in Weimar, one can point to impressive progress in the study and applications of Streptomyces genetics.

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 invalu able 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."

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having only recently passed 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 so far 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 as well as 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."

The fIrst reports on the tropism of the human immunodefIciency virus (HIV), then called human T-celilymphotrophic virus type ill (HTLY- ill) or lymphadenopathy associated virus (LA V), indicated an almost absolute specifIcity of the virus for T4 (helper/inducer) lymphocytes. It became apparent a few years later that macrophages were also infectable by HIV. The common cellular receptor for the virus on these cell types was CD4. A remarkable series of studies by fIve different groups, four of which were published in the same issue of~, showed that recombinant soluble CD4 could inhibit the infectivity of the virus. Subsequent studies began to reveal, however, that cells not expressing CD4 could also be infected, thus raising the possibility that almost any cell in the body could act as a latent reservoir for the virus. Recent observations that the infectivity of patient isolates is not inhibited at the low concentrations of rsCD4 that inhibit laboratory strains, also indicate the importance of CD4-independent mechanisms. The mechanisms of fusion of my with cellular membranes are under investigation by a large number of laboratories. These studies range from the determination of the oligomeric structure of the envelope glycoproteins, to the analysis of the function of various regions of the proteins by site-directed mutagenesis, to the fluorimetric monitoring of membrane fusion. This book originated as the proceedings of a Workshop on the Mechanisms and Specificity of HIV Entry into Host Cells, held at the University of California, San Francisco in June 1989.

Advances in Microbial Ecology was established by the International Com mittee on Microbial Ecology (ICOME) as a vehicle for the publication of critical reviews selected to reflect current trends in the ever-expanding field of microbial ecology. Most of the chapters found in Advances in Microbial Ecology have been solicited by the Editorial Board. Individuals are encouraged, however, to submit outlines of unsolicited contributions to any member of the Editorial Board for consideration for inclusion in a subsequent volume of Advances. Contributions are expected to be in depth, even provocative, reviews of topical interest relating to the ecology of microorganisms. With the publication of Volume 8 of Advances we welcome to the panel of contributors Martin Alexander, the founding editor of this series, who discusses the range of natural constraints on nitrogen fixation in agri cultural ecosystems. Ecological aspects of cellulose degradation are dis cussed by L. G. Ljungdahl and K. -E. Eriksson, and of heavy metal responses in microorganisms by T. Duxbury. In his chapter, A. Lee con siders the gastrointestinal tract as an ecological system, and comments on the possibility of manipulating this system. The complex interactions among aerobic and anaerobic sulfur-oxidizing bacteria are discussed in terms of natural habitats and chemostat culture by J. G. Kuenen, L. Rob ertson, and H. van Gemerden. Finally, J. A. Robinson presents the advantages and limitations in the use of nonlinear regression analysis in determining microbial kinetic parameters in ecological situations. K. C. Marshall, Editor R. M. Atlas B. B."

Virus diseases continue to represent serious health problems in most parts of the world. In spite of the fact that diseases such as polio myelitis and measles have been controlled in the industrialized countries by vaccination, vaccines now in use in tropical countries have proved not to be optimal. Further research is needed to develop new vaccines that will be effective in all countries. To do so we need to understand better the immune response to different viruses so that we may be able to maxi mize the protective response of new vaccines and minimize their potential immunopathologic effect. An exciting new discovery which is now being further developed is the possibility of being able to use some viruses (e.g. vaccinia, adenoviruses, etc.), as carriers for other antigens. This may open up the way for the production of vaccines that will be inexpensive and that will confer long lasting immunity after only one injection. This meeting has also served to review our present knowledge of virus diseases which are still of great importance such as hepatitis, dengue and influenza."

When Antibiotics I was published in 1967, the teleological view was held by some that" antibiotics" were substances elaborated by certain microorgan isms for the purpose of competing with other microorganisms for survival in mixed ecological environments. However, not only had J. EHRLICH and his associates shown 15 years earlier that chloramphenicol was produced by Strepto myces venezuelae in cultures of sterilized soils but not in parallel cultures of the same soils which were not sterilized, but operationally, the search for anti cancer antibiotics was actively under way (Antibiotics I reporting on numerous such substances), although the concept of antibiosis could not logically justify such undertakings. This editor hesitates to accept the use of the term "antibiotic" for anti microbial agents of non microbiological origins which is sometimes encountered, but neither does he subscribe to the view that antibiotics are in some fundamental manner different from chemotherapeutic substances of other origins. Modes and mechanisms of action of chemotherapeutic compounds are not systematic functions of their origins nor of the taxonomical position of the target organisms. Consequently, in the selection of topics for Antibiotics III (published in 1975), synthetic drugs and natural products of higher plants (alkaloids) were represented, along with antibiotics in the strict sense of the definition. We now present Antibiotics V, for whose assembly the same selection criteria were applied as for Antibiotics Ill. The aggregate length of the contributions rendered it impractical to place the entire text between the covers of one book."

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 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.

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.

This volume is based on the program of the International Conference on Drugs of Abuse, Immunity and Immunodeficiency held in Clearwater Beach, Florida. It was sponsored by the University of South Florida College of Medicine with the support of the National Institute on Drug Abuse. During the past few decades, drugs of abuse, including marijuana, cocaine, opiates and alcohol, have been studied by biomedical scientists in terms of the systemic effects of the drugs as well as alterations in neurophysiology and the psychology. More recently, the scope of such investigations has been broadened to include alterations within the immune system, and the influence of altered immunity on physiological and psychological consequences of drug abuse. In this regard, participants in the Clearwater Beach conference provided new information concern ing both basic and clinical aspects of drugs of abuse and immunity, especially immunodeficiency. Advances have been made in recent years in understanding the nature and mechanisms regulating the immune response and the mechanisms by which drugs may influence immune responses. In particular, the emergence of psychoneuroimmunology as a new discipline has heightened interest in immune responses influenced by psychoactive drugs. This has resulted in interdisciplinary investigations involving clinical and basic scientists including microbiologists, immu nologists, physiologists, psychiatrists, oncologists and others. The recreational use of the above mentioned drugs by large numbers of individuals has aroused serious concern about the consequences of this activity.

Scientific research on dengue has a long and rich history. The literature has been touched by famous names in medicine- Benjamin Rush, Walter Reed, and Albert Sabin, to name a very few- and has been fertile ground for medical historians . The advances made in those early investigations are all the more remarkable for the limited tools available at the time. The demonstration of a viral etiology for dengue fever, the recognition of mosquitoes as the vector for transmission to humans, and the existence of multiple viral variants (serotypes) with only partial cross-protection were all accomplished prior to the ability to culture and characterize the etiologic agent. Research on dengue in this period was typically driven by circumstances. Epidemics of dengue created public health crises, although these were relatively short-lived in any one location, as the population of susceptible individuals quickly shrank. Military considerations became as a major driving force for research. With the introduction of large numbers of non-immune individuals into endemic areas, dengue could cripple military readiness, taking more soldiers out of action than hostile fire. Dengue and dengue hemorrhagic fever, which assumed pandemic proportions during the latter half of the last century, have shown no indication of slowing their growth during this first decade of the twenty-first century. Challenges remain in understanding the basic mechanisms of viral replication and disease pathogenesis, in clinical management of patients, and in control of dengue viral transmission. Nevertheless, new tools and insights have led to major recent scientific advances. As the first candidate vaccines enter large-scale efficacy trials, there is reason to hope that we may soon "turn the corner" on this disease.

This volume in the Monographs in Evolutionary Biology series addresses issues that are part of an emerging area of research loosely called "mo lecular evolution. " Its practitioners include both molecular biologists cu rious about the evolutionary implications of their data and evolutionary biologists pushing their analyses to the molecular level. The union of these fields of molecular and organismal biology has been turbulent at times, and, as shall be seen, this dialectic has led to some very serious challenges to long-held notions about the role of natural selection in evolution and the economy of genome organization in eukaryotes. As an inevitable outgrowth of molecular biology, molecular evolution is necessarily a young discipline, but it can already point proudly to two major discoveries. The first, is the molecular clock, a concept that has emerged from the analysis of at least four data sets-amino acid sequences, immunologic data, DNA renaturation studies, and, recently, analyses of DNA sequences. The reality of a strong stochastic component in the evolution of nucleotide sequences can no longer be doubted, although the accuracy of the clock with regard to particular sequences and within particular groups of or ganisms should be independently measured each time it is used. Never theless, molecular clocks will assume increasingly important roles in phy logenetic reconstructions, especially since the fossil record is so fragmentary. The second major discovery of molecular evolution has been the incredible complexity of the eukaryotic genome."

The first volume of Antibiotics was published in 1967 and contained a series of review papers on antibiotic actions. The editors, Drs. GOTTLIEB and SHAW, were aware of the rapid development of this field of study and provided a number of addenda in an effort to keep knowledge up to date while the book was in production. One year after the publication of Antibiotics I, this editor had a conference with Dr. KONRAD F. SPRINGER in which it became clear that another volume on actions of antibiotics would be necessary. For a variety of reasons, this was delayed until 1975 and became Antibiotics III. It did not contain addenda since it was recognized by the editors, Drs. CORCORAN and HAHN, that still another volume would have to follow and that in a moving field, such as the study of the actions of antibacterial drugs, no publication can be definitive or remain current, except for a limited period of time. The editors of Volume III grouped the contributions into sections: 1. Inter ference with nucleic acid biosyntheses, 2. Interference with protein biosynthesis, and 3. Interference with cell wall/membrane biosynthesis, specific enzyme sys tems, and those in which the mode of action was not known with certainty."

Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. It has a growing spectrum of acknowledged roles in immunity, aging, development, neurodegeneration, and cancer biology. An immunological role of autophagy was first recognized with the discovery of autophagy's ability to sanitize the cellular interior by killing intracellular microbes. Since then, the repertoire of autophagy's roles in immunity has been vastly expanded to include a diverse but interconnected portfolio of regulatory and effector functions. Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it shapes central tolerance; it affects B and T cell homeostasis; it acts both as an effector and a regulator of Toll-like receptor and other innate immunity receptor signaling; and it may help ward off chronic inflammatory disease in humans. With such a multitude of innate and adaptive immunity functions, the study of autophagy in immunity is one of the most rapidly growing fields of contemporary immunological research. This book introduces the reader to the fundamentals of autophagy, guides a novice and the well-informed reader alike through different immunological aspects of autophagy as well as the countermeasures used by highly adapted pathogens to fight autophagy, and provides the expert with the latest, up-to-date information on the specifics of the leading edge of autophagy research in infection and immunity.

It has been 10 years since the Plenum Publishing Corporation printed a series of review articles on bacteriophages in Comprehensive Virology. Articles in that series contained physical-genetic maps but very little DNA sequence information. Now the complete DNA sequence is known for some phages, and others will soon follow. During the past 10 years, two phages have come into common use as reagents: A phage for cloning single copies of genes, and M13 for cloning and DNA sequencing by the dideoxy termination method. Also during this period the use of alter native sigma factors by RNA polymerase has become established for and T4. This seems to be a widely used mechanism in bacteria, SPO 1 since it has been implicated in sporulation, heat shock response, and regulation of nitrogen metabolism. The control of transcription by the binding of A phage CII protein to the -35 region of the promoter is a recent finding, and it is not known how widespread this mechanism may be. This rapid progress made me eager to solicit a new series of reviews. These chapters are of two types: each of the first type deals with an issue that is exemplified by many kinds of phages. Chapters of this type should be useful in teaching advanced courses. Chapters of the second type pro vide comprehensive pictures of individual phage families and should pro vide valuable information for use in planning experiments."

When phagocytes are exposed to a number of different stimuli, they undergo dra matic changes in the way they process oxygen. Oxygen uptake increases markedly, frequently more than 50-fold; the phagocytes begin to produce large quantities of superoxide and hydrogen peroxide; and they immediately begin to metabolize large amounts of glucose by way of the hexose monophosphate shunt. This series of changes has become known as the respiratory burst. It was first believed that the major function of this respiratory burst was to generate powerful antibacterial agents by the partial reduction of oxygen. It is becoming apparent that the respiratory burst has much wider application, and its physiological function in many different biolog ical areas is clear. In this volume, we have attempted to bring together the work of experts who have published extensively on the involvement of the respiratory burst in different physiological functions. In the first three chapters, Dr. Borregaard and Dr. Berton and co-workers and Dr. Roos and co-workers bring together what is known about the respiratory burst. They present up-to-date versions of the biochemical and metabolic activities associ ated with the burst. In Chapter 4, Dr. Styrt and Dr. Klempner discuss the respiratory burst as it affects cellular ion homeostasis. Dr. Cohen and Dr. Britigan (Chapter 5) present some interesting data on the competition between the respiratory burst and bacteria for oxygen. Dr. Dobrina and Dr."

nomenon [26]. Indeed, Krieg et al. [21] showed that the elimination of the CpG in a particular ODN invariably abolished immune stimulation, but changes in the ODN sequences that did not affect the CpG or the flanking bases did not alter the immuno- stimulatory (IS) effect. Furthermore, they extended the initial observations of the IS effects to non-palindromic CpG-enriched ODN [21]. Subsequent studies showed that CpG-enriched ODN also induce the secretion of IL-6 and IL-12 [19] and IFN-a [6, 27]. By adding or deleting various IS sequences (ISS)-ODN to or from different pDNAs, it was demonstrated that the ISS have a pivotal role in the induction of the subsequent immune response to the gene product in gene-vaccinated animals. The enhanced Thl immune response induced by gene vaccination is the consequence of the activation of the innate immune response by the ISS in the pDNA backbone [30, 31], rather than the low dose of intracellularly produced antigen. The cell activation products induced by the ISS, i. e. , IFN-a [3], IFN-~ [43], IL-12 [37], and IL-18 [25], are established inducers of IFN-y synthesis and promote the differentiation of naive T helper cells to Thl lym- phocytes. Thus, the ISS activate the precise innate cytokine network required to pro- mote Thl differentiation (see Fig. 1). In a recent study it was demonstrated that this ap- proach is also applicable to a protein antigen.

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."

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.

The use of biotechnical processes in control of environmental pollution and in haz ardous waste treatment is viewed as an advantageous alternative or adduct to phys ical chemical treatment technologies. Yet, the development and implementation of both conventional and advanced biotechnologies in predictable and efficacious field applications suffer from numerous technical, regulatory, and societal uncertainties. With the application of modern molecular biology and genetic engineering, there is clear potential for biotechnical developments that will lead to breakthroughs in controlled and optimized hazardous waste treatment for in situ and unit process use. There is, however, great concern that the development of these technologies may be needlessly hindered in their applications and that the fundamental research base may not be able to sustain continued technology development. Some of these issues have been discussed in a fragmented fashion within the research and development community. A basic research agenda has been established to promote a sustainable cross-disciplinary technology base. This agenda includes developing new and improved strains for biodegradation, improving bioanalytical methods to measure strain and biodegradation performance, and providing an in tegrated environmental and reactor systems analysis approach for process control and optimization."

JAMES L. MCGAUGH Understanding of the nature and functions of neurotransmitter systems in the brain has increased enormously in recent decades. Lack of knowledge required us, not too long ago, to use the adjective "putative" when discussing transmitters. Such caution is no longer essential (at least for a number of transmitters). Impressive progress has been achieved in understanding the pharmacology, biochemistry and anatomy of transmitter systems. There has, however, been relatively less progress in understanding the functioning of brain transmitters in regulating and mediating behavior. A simple and certainly correct explanation for this is, of course, that understanding of neurotransmitter functions requires prior detailed knowledge of basic pharmacology, biochemistry and anatomy. Beyond that, it now seems likely that progress in understanding the functions of brain neurotransmitters will proceed only as we examine the interactions of neurotransmitter systems in regulating behavioral functions. This premise is, of course, suggested by the findings of studies of the chemical neuroanatomy of the brain: Neurotransmitter systems are influenced by other neurotransmitter systems and, in tum, influence the same as well as other systems. No system works alone. The chapters in this book explicitly examine the interactions of neurotransmitter systems involved in the regulation of cognitive processes. The facts and interpretations offered provide compelling support for the premise that cognitive processes are orchestrated by interactions among neurotransmitter systems. And, they offer promise that understanding of such interactions will be of critical importance in the develop ment of treatments for brain diseases affecting cognitive functioning."