This book, which results from the dramatic increase in interest in the control mechanism employed in gene expression and the importance of the regulated proteins, presents new information not covered in Translational Regulation of Gene Expression, which was published in 1987. It is not a revision of the earlier book but, rather, an extension of that volume witl, special emphasis on mecha nIsm. As the reader will discover, there is enormous diversity in the systems employing genes for translational regulation in order to regulate the appearance of the final product-the protein. Thus, we find that important proteins such as protooncogenes, growth factors, stress proteins, cytokines, lymphokines, iron storage and iron-uptake proteins, and a panorama of prokaryotic proteins, as well as eukaryotic viral proteins, are translationally regulated. Since for some gene products the degree of control is greater by a few orders of magnitude than their transcription, we can state that for these genes, at least, the expression is translationall y controlled. Translational regulation of gene expression in eukaryotes has emerged in the last few years as a major research field. The present book describes mechanisms of translational regulation in bacteria, yeast, and eukaryotic viruses, as well as in eukaryotic genes. In this book we try to provide in-depth coverage by including important examples from each group rather than systematically including all additional systems not described in the previous volume.

Proceedings of the XIIIth International Symposium, held in Santiago, Chile, March 25-29, 1996

While advances in modem medicine largely parallel our understanding of morphology, discoveries in morphology are propelled by developments of new tools and means to visualize and measure tissue elements. The invention of dissecting, light, fluorescence and electron microscopes together with advances in labeling and staining techniques are among the stepping stones of morphological progress. Today, we are in an exciting new era when classical morphology is being combined with developments from other disciplines. The combination of morphology and immunology resulted in immunocytochemistry; morphology and molecular biology led to in situ hybridization and in situ PCR. Adding computer science to morphology gave birth to image analysis. Combining laser technology and the microsope evolved into confocal microscope. For more than a decade, modem morphology has continued to develop by merging with other disciplines at a rate that is still gathering momentum, providing exciting and dynamic new frontiers for other biological fields. "Modem Methods in Analytical Morphology," based largely on the "First International Workshop on Modem Methods in Analytical Histochemistry, "is an updated review of the current trends in the field. It covers an extensive array of new technical developments in major disciplines of modem morphology. The authors are not only leaders in their fields but also have extensive "hands on" experience with "bench work. " Their chapters are written in a comprehensive manner including discussion of both theoretical considerations and practical applications to give the readers a broad view of the topics covered.

Acute lung injury (ALI) impacts patient care in every ICU in the world. Our collective understanding of this condition has grown immensely over the past decade but morbidity and mortality remain unacceptably high. To enhance the understanding of clinicians and researchers, this book addresses the pathophysiology of acute lung injury from a molecular and cellular standpoint; includes animal models of acute lung injury and points to potential therapeutic advances based on scientific findings. It is a concise compendium of the multiple pathways, mechanisms and molecules involved in the pathophysiology of acute lung injury and is intended to help caregivers understand the process and thus care for patients more effectively.

As we assume the editorship of Current Ornithology, it seems useful to review the objectives of the series. We cannot improve on the state ments of our predecessors when they began their service as editors. In his preface to Volume 1 (1983), Richard F. Johnston wrote: The appearance of the first volume of a projected series is the occasion for comment on scope, aims, and genesis of the work. The scope of Current Or nithology is all of the biology of birds. Ornithology, as a whole-organism sci ence, is concerned with birds at every level of biological organization, from the molecular to the community, at least from the Jurassic to the present time, and over every scholarly discipline in which bird biology is done; to say this is merely to expand a dictionary definition of "ornithology. " The aim of the work, to be realized over several volumes, is to present reviews or position statements concerning the active fields of ornithological research. Dennis M. Power, who edited Volumes 6-12 (1989-1995), began his preface to Volume 6 (1989) as follows: This edited series has three principal goals. The first is to provide information in a relatively concise way for researchers needing an overview of specific disciplines. The second is to provide an update on specific schools of thought, bringing together ideas from colleagues whose works often appear in a variety of journals. And the third is to stimul&te and suggest directions for new re search."

A NATO Advanced Study Institute on "New Developments in Lipid-Protein Interactions and Receptor Function" was held on the Island of Spetsai, Greece, from August 16-27, 1992. This Institute was organized to bring together researchers in the field of membrane organization and dynamics with those actively involved in studies on receptor function, signal transduction mechanisms and gene regulation. 2 Presentations and discussions focussed on the regulation of intracellular Ca +-levels, on the second messengers derived from inositol lipids and on the specific phospholipase C isozymes involved in these processes. A major focus was on G-proteins and the effect of lipid anchors on their function. These principles of regulation were further discussed in the context of receptors for acetylcholine, lysophosphatidic acid and low-density lipoproteins. In addition, various aspects of the genomic regulation of cell growth and differentiation by transcription factors were presented. These topics were put into perspective by discussing the most recent developments in lipid-protein interactions, protein insertion into membranes, membrane lipid organization and lipid dynamics as mediated by phospholipid transfer proteins. This book presents the content of the major lectures and a selection of the most relevant of the most important topics posters. These proceedings offer a comprehensive account presented during the course of the Institute. The book is intended to make these proceedings accessible to a large audience.

In the ten-year interval since the first edition of this volume went to press, our knowledge of extracellular matrix (ECM) function and structure has enor mously increased. Extracellular matrix and cell-matrix interaction are now routine topics in the meetings and annual reviews sponsored by cell biology societies. Research in molecular biology has so advanced the number of known matrix molecules and the topic of gene structure and regulation that we won dered how best to incorporate the new material. For example, we deliberated over the inclusion of chapters on molecular genetics. We decided that with judicious editing we could present the recent findings in molecular biology within the same cell biology framework that was used for the first edition, using three broad headings: what is extracellular matrix, how is it made, and what does it do for cells? Maintaining control over the review of literature on the subject of ECM was not always an easy task, but we felt it was essential to production of a highly readable volume, one compact enough to serve the the student as an introduction and the investigator as a quick update on graduate the important recent discoveries. The first edition of this volume enjoyed con hope the reader finds this edition equally useful. siderable success; we D. Hay Elizabeth vii Contents Introductory Remarks 1 Elizabeth D. Hay PART I. WHAT IS EXTRACELLULAR MATRIX? Chapter 1 Collagen T. F. Linsenmayer 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2. The Collagen Molecule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2. 1. Triple-Helical Domain(s) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Progress in Cell Cycle Research is a new annual series designed to be the source for up-to-date research on this rapidly expanding field. Review articles by international experts examine various aspects of cell division regulation from fundamental perspectives to potential medical applications. Researchers as well as advanced undergraduate and graduate students in cell biology, biochemistry, and molecular biology will benefit from this series.

The National Institute of Dental Research sponsored a workshop on "Genetically Engineered Vaccines: Prospects for Oral Disease Prevention," held at the National Institutes of Health (NIH) on November 6-8, 1991. The purpose of the workshop was to convene molecular biologists and immunologists to address the state of the science in vaccine development and to explore the potential of developing vaccines for prevention of oral diseases. The goal was to elicit new research initiatives and recommendations for vaccine development with emphasis on the prevention of oral diseases and diseases affecting the orofacial tissues. The workshop was attended by more than 100 persons who heard 30 presentations, and the speakers provided the papers for this volume. The workshop focused on the following topics: oral diseases and host immune responses, update on vaccines and vaccine development, vaccines and the mucosal immune system, optimizing mucosal and systemic immune responses, delivery systems and immune analysis, target antigen selection and vaccine development, immunological correlates of protection and future direc tions/recommendations. Three key areas were identified: Optimizing the Mucosal Immune Response, Antigen Delivery Systems, and Target Antigens and Immunological Correlates of Protection. The summary and recommendations from these deliberations is included at the end of this volume."

In the ten years since the first publication on PCR (Saiki et al. , 1985), this in vitro method of nucleic acid replication and modification has grown to rival in popularity traditional microbiological, genetical und technical procedures for cloning, sequencing, gene detecting and related procedures. To date the PCR literature has emphasized six main areas of application: genetic mapping, detection of mutations, genetic polymorphism, transcriptional splicing and regulation, molecular virology and quantitative procedures. The overwhelming focus of quantification of DNA or RNA by PCR has been on human microbiology and oncological problems. The exquisite sensitivity of PCR gives this method the ability to detect extremely rare DNAs, mRNAs, mRNAs in small numbers of cells or in small amounts of tissue, and mRNAs expressed in mixed-cell populations. However, the exact and accurate quantification of specific nucleic acids in biological samples is in spite of numerous publications in that field still a general problem: during the peR process, an unknown initial number of target sequences are used as a template from which a large quantity of specific product can be obtained. Although the amount of product formed is easy to determine, it is difficult to deduce the initial copy number of the target molecule because the efficiency of the peR is largely unknown.

Scientific reviews are now of two complementary types: short, very up-to-date articles, as are found in the Trends series, and the more traditional longer re views, which are more comprehensive but take longer to publish. The Subcellu lar Biochemistry series belongs to the latter category where a number of reviews on a broad topic are collected together in the one volume. It has been the aim of this volume to summarize the present state of knowledge of membrane assembly. It is appreciated that some relevant topics have not been included, and an editor's selection is restricted by the many calls on potential authors who are unable to meet all requests made to them. The absence of a discussion of the roles of lipids is," however, a reflection of the fact that a recent volume in this series, edited by Dr. H. 1. Hilderson, has been devoted to this subject (Vol. 16, Intracellular Transfer of Lipid Molecules), and readers are recommended to this source.

Corona- and related viruses are important human and animal pathogens that also serve as models for other viral-mediated diseases. Interest in these pathogens has grown tremendously since the First International Symposium was held at the Institute of Virology and Immunobiology of the University of Wiirzburg, Germany. The Sixth International Symposium was held in Quebec City from August 27 to September I, 1994, and provided further understanding of the molecular biology, immunology, and pathogenesis of corona-, toro-, and arterivirus infections. Lectures were given on the molecular biology, pathogenesis, immune responses, and development of vaccines. Studies on the pathogenesis of coronavirus infections have been focused mainly on murine coronavirus, and mouse hepatitis virus. Neurotropic strains ofMHV (e.g., JHM, A59) cause a demyelinating disease that has served as an animal model for human multiple sclerosis. Dr. Samuel Dales, of the University of Western Ontario, London, Canada, gave a state-of-the-art lecture on our current under standing of the pathogenesis of JHM-induced disease.

The success of vaccination in controlling infectious diseases is well documented. However, low profitability, expense and liability have hindered research and development of vaccines. Recently, increasing realization (enhanced by the AIDS pandemic) of the need to overcome such difficulties has led to steps being taken by national authorities, non-profit and commercial organizations to resolve them. This has been facilitated by developments in recombinant DNA techniques, the advent of monoclonal anti bodies and progress in the understanding of the immunological structure of proteins which have laid the foundation of a new generation of vaccines. Such vaccines are defined at the molecular level, can elicit immune responses controlling infectious organisms and are therefore potentially free of the problems encountered in conventional ones. Unfortunately, subunit and synthetic peptide vaccines are often only weakly or non inmunogenic. However, developments in both antigen production and immuno potentiation of weak antigens have opened new avenues with exciting prospects for vaccine design.

Forty years after the discovery of the helix nature of DNA and more than twenty after the first applications of recombinant DNA technology to the pharmaceutical industry, the Pandora's vase of biotechnology seems far from being empty. New products for agriculture and the food industry are constantly being placed on the market, and powerful monitoring techniques have been developed to track non-modified and genetically modified vaccines, viruses, microbes and plants released into the environment. Molecular approaches for taxonomic purposes, which might also be useful for quality control and assurance, have been successfully developed and used for taxonomic purposes in the last decade for both prokaryotic and eukaryotic cells, including yeasts and filamentous fungi. Mycorrhizae are one example of a traditional biotechnology that can greatly benefit from the latest molecular approaches. These universal symbioses between soil fungi and plant roots playa central role in most of the natural and agricultural ecosystems in such key processes as nutrient cycling, soil structural conservation and plant health. For these reasons, mycorrhizae have been successfully used to improve the quality of forest and agricultural seedlings, to produce high-quality micropropagated plants and to increase the production of edible mushrooms of high economic value, such as truffles. However, although controlled inoculation of oak and hazel seedlings with ectomycorrhizal truffles has been carried out for decades in France and Italy, and is still expanding commercially, several technological gaps remain to be filled.

The genus Aspergillus has a worldwide distribution and is one of the most common of all groups of fungi. They are possibly the greatest contami nants of natural and man-made organic products, and a few species can cause infections in man and animals. The aspergilli are also one of the most important mycotoxin-producing groups of fungi when growing as contaminants of cereals, oil seeds, and other foods. Not all aspergilli are viewed as troublesome contaminants, however, as several species have had their metabolic capabilities harnessed for commercial use. The aspergilli have long been associated in the Far East with the koji stage of several food fermentations, particularly soy sauce and miso, and subsequently as a source of useful enzymes. The ability of these fungi to produce several organic acids, especially citric acid, has created major industrial complexes worldwide. Traditional methods of strain develop ment have been extensively studied with the industrial strains, while more recently, recombinant DNA technology has been applied to the aspergilli with emphasis on heterologous protein production. In compiling this book, I have been fortunate to have the full enthu siastic involvement of the authors, and to them I extend my very grateful thanks for mostly being on time and for producing such readable and authoritative chapters. Collectively, we hope that our efforts will strengthen the scientific understanding of this intriguing group of filamentous fungi and further their use in the field of biotechnology.

During the last few years, an explosion of infonnation has come from human genetics and molecular and cell biological studies as to the genetic basis for a number of fonns of inherited retinal degenerations. These disorders have plagued mankind for millennia because they take from otherwise healthy individuals the precious gift of sight. The fundamental advances in recent years have identified a number of genes involved in the groups of diseases which hopefully will lead to discoveries that may, in the not too distant future, allow the prevention and possible cure of some of these blinding eye disorders. To foster a forum for discussions of studies on degenerative retinal disorders, we convened a symposium on retinal degenerations in 1984, at the VIth International Congress of Eye Research Meeting, held in Alicante, Spain. Because of the success of this meeting and the subsequent publication, we have since organized a series of biennial satellite meetings on retinal degenerations for the ISER congresses held in Nagoya, Japan (1986), San Francisco (1988) and Helsinki (1990). Each of these satellite symposium on retinal degenerations was accompanied by a published proceedings volume. This volume is the fifth in this series and contains the proceedings of the Sardinia Symposium on Retinal Degeneration held September 15-20, 1992, as a satellite meeting of the 10th International Congress of Eye Research.

Mycobacteria is divided into two volumes. The first volume deals with the basic biology of mycobacteria. With its emphasis on the state of the art outlook, this volume includes taxonomy and molecular biology of mycobacteria, modern approaches for detection of mycobacteria, and immunology and immunization against tuberculosis. The second volume covers drug trestments for mycobacteria anad tuberculosis. It outlines trends of discovery and development of chemotherapy, starting from the mid-50's to present day uses of chemotherapy in treating AIDS, drug-resistant tuberculosis, and other non-tuberculosis mycobacterial diseases.

Alcohol abuse and alcoholism are international problems whose costs economical ly, psychologically and medically have been well documented. Alcohol is a unique drug in that the effects of excessive use can have a deleterious effect on most if not all organs of the body. The brain is one of the organs most affected by excessive alcohol consumption. Effects on the brain can be seen in cognitive function, brain structure and neurochemistry. Over the past few years, there have been significant advances made in understanding how alcohol affects brain neurochemistry. This book examines four major areas, i. e. , membrane lipids, receptors and ion channels, second messengers, and gene expression, where significant advancements have been made. The book is divided into four sections based on the four major areas. In each section, data are examined that cover a range of approaches from in vitro to in vivo studies. The section on membrane lipids includes recent developments in how ethanol affects membrane cholesterol domains, polyunsaturated fatty acids, the cause and consequences of phosphatidylethanol formation, and the modulation of membrane protein function by lipid-protein interaction. The second section comprises chapters on NMDA and 5-HT3 receptors, including new aspects on alcohol neurotoxicity and the molecular heterogeneity that may underlie differences in alcohol sensitivity as well as chapters on GABA-gated chloride flux, and calcium channels.

We have considered it to be a demanding assignment to provide a complete exposition dealing with the nature of radiation, its effects, and protection against it to workers in health-related activities. "Radiation" (and more precisely "ionizing radiation") is emitted by X-ray machines, nuclear reactors, and nuclear weapons, but also comes from natural sources to which we are all exposed. It would have been easier to deal with this subject area with the terminology and mathematics employed by specialists. However, although most of the potential readers probably have obtained further pertinent knowledge, we assume no more than a high school education in science and mathematics and the challenge was to provide maximum information within this constraint. This book contains five sections: (A) Radiation Physics, (B) Radiological Physics, (C) Radiation Biology, (D) Radiation Effects on Human Populations, and (E) Radiation Protection. Each section is preceded by a synopsis covering its essential features. It provides sufficient information to enable readers to obtain a general under standing of the subject of the section and an adequate background for comprehension of other sections. The more detailed presentation in the bulk of each section is followed by appendixes that generally contain more advanced topics. This scheme necessarily involves some repetition but permits a more flexible approach for readers who are especially interested in the contents of particular sections.

This volume contains the papers presented at the International Symposium on "Cirrhosis, Hyperammonemia and Hepatic Encephalopathy," held in Valencia, Spain, January 24th-27th, 1994. Liver cirrhosis and other hepatic dysfunctions such as fulminant hepatic failure and congenital defects of urea cycle enzymes can lead to hepatic encephalopathy, coma and death. Hepatic encephalopathy is one of the main causes of death in western countries. The ability to detoxify ammonia by its incorporation into urea is diminished by impaired liver function, resulting in increased ammonia levels in blood and brain. Hyperammonemia is considered one of the main factors in the mediation of hepatic encephalopathy and the classical clinical treatments are directed towards reducing blood ammonia levels. However, the molecular bases of the pathogenesis of hepatic encephalopathy and the role of hyperammonemia in this process remain unclear and several hypotheses have been proposed. To clarify the mechanisms involved in hepatic encephalopathy and hyperammonemia suitable animal models are necessary. The animal models available and the ideal features of an animal model are presented in the initial part of the book.

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.

Sponges (phylum Porifera) are known to be very rich sources for bioactive compounds, mainly secondary metabolites. Main efforts are devoted to cell- and mariculture of sponges to assure a sustainable exploitation of bioactive compounds from biological starting material. These activities are flanked by improved technologies to cultivate bacteria and fungi which are associated with the sponges. It is the hope that by elucidating the strategies of interaction between microorganisms and their host (sponge), by modern cell and molecular biological methods, a more comprehensive cultivation of the symbiotic organisms will be possible. The next step in the transfer of knowledge to biotechnological applications is the isolation, characterization and structural determination of the bioactive compounds by sophisticated chemical approaches.

The mycoplasmas, a trivial name used to denote organisms included in the class Mollicutes, are a group of prokaryotic organisms comprising more than 120 species distinguished from ordinary bacteria by their small size and the total lack of cell walls. The absence of a cell wall in mycoplasmas is a characteristic of outstanding importance to which the mycoplasmas owe many of their pecu liarities, for example, their morphological instability, osmotic sensitivity, unique ion pumping systems, resistance to antibiotics that interfere with cell wall bio synthesis, and susceptibility to lysis by detergents and alcohols. The fact that the mycoplasma cells contain only one membrane type, the plasma membrane, constitutes one of their most useful properties for membrane studies; once the membrane is isolated, it is uncontaminated with other mem brane types. Another advantage in using mycoplasmas as models for membrane studies stems from the fact that their membrane lipid composition can be altered in a controlled manner. This characteristic results from the partial or total inabili ty of the mycoplasmas to synthesize long-chain fatty acids and cholesterol, making mycoplasmas dependent on the supply of fatty acids from the growth medium. The ability to introduce controlled alterations in the fatty acid composi tion and cholesterol content of mycoplasma membranes has been utilized in studying the molecular organization and physical properties of biological mem branes.

In the past two decades, the importance of animal cell technology has increased enormously. First, useful proteins can be produced by cultured animal cells, in which the desired product can be modified and organized so as to retain its biological function. Second, studies of cultured cells can provide information needed to understand molecular mechanisms that govern what happens in tissues, organs, and even entire organisms. For this second purpose, biochemists and molecular biologists may need a large number of such cells. Third, cultured cells can be used instead of tissues and organs clinically. The Third Annual Meeting of the Japanese Association for Animal Cell Technology (JAACT), at which participants from abroad were warmly welcomed, was held in Kyoto on December 11-13, 1990. It was organized around the idea of providing a place for the review of much new data on such applications of cultured cells and for exchanges of the views of the participants about progress in the field. This volume, divided into seven sections, contains the proceedings of the meeting. The first section reviews the molecular basis of the control of animal cell growth. In the following sections, physicochemical and biochemical factors for cell growth and production of biologicals, cell culture systems including serum-free culture, new cell lines, specific products and their characteristics, and in vitro assays for toxic, carcinogenic, and pharmacological effects are taken up in their tum.

This book contains a collection of papers dealing with various aspects of the biology and aquaculture of the large branchiopod crustacea; the Anostraca, Conchostraca, and Notostraca. Included are many of the papers presented at the Second International Large Branchiopod Symposium convened in Ulm, Germany, 30 July--3 August 1993. Additional manuscripts contributed by colleagues who were unable to attend are also included. A special feature of this volume is a checklist of the Anostraca, including information on distribution, location of type material, taxonomic problems, and literature references.