This volume contains the lectures given at the NATO Advanced Study Institute on "Biophysics of Photoreceptors and Photomovements in Microorganisms" held in Tir renia (Pisa), Italy, in September 1990. The Institute was sponsored and mainly funded by the Scientific Affairs Division of NATO; the Physical Science Committee and the Institute of Biophysics of National Research Council of Italy also supported the School and substantially contributed to its success. It is our pleasant duty to thank these institu tions. Scientists from very different backgrounds contributed to the understanding of this fast developing field of research, which has seen considerable progress during the last years. The areas of expertise ranged from behavioral sciences, supported by sophi sticated techniques such as image analysis or laser light scattering, to spectroscopy, ap plied, in different time domains, to the study of the primary photoreactions, to electro physiology, biochemistry or molecular biology, with the aim of analyzing the various steps of the transduction chains and how they control the motor apparatus of the cells. The organisms studied covered a wide range, from bacteria to algae, fungi and other eukaryotes. Thus, the ASI represented a successful opportunity for carrying on and imple menting an interdisciplinary approach to the study of the biophysical basis of photore ception and photosensory transduction in aneural organisms, with special attention to the basic phenomena and the underlying molecular events. We hope that this book has caught the spirit in which the ASI was conceived."

Lyme Borreliosis is a worldwide infectious disease causing a multisystem illness with considerable morbidity, particularly in North America and Europe. The causative agent is the spirochaete Borrelia burgdorferi, which is usually transmitted by the ixodid tick from animal reservoirs. This book is formed by contributions from the Second European Symposium on Lyme Borreliosis, held at St George's Hospital Medical School, London in 1993, which reviewed the current state of knowledge of the condition with regard to clinical manifestations, diagnosis, treatment, ecology, epidemiology, biology and immunopathogenesis. In this book, important data is reviewed concerning the clinical manifestations of Lyme Borreliosis. It seems that strain variation of the spirochaete is the main cause of regional differences seen in the clinical presentation of patients. One striking example of this, is the relatively high incidence of Lyme arthritis in the USA and apparent rarity of this manifestion in some areas of Europe. These important studies open the way for exciting new research that focuses on the immunological and molecular mechanisms that result in disease. A full insight into the ecology of Borrelia burgdorferi is essential to a balanced understanding of the disease and a number of excellent reviews on this subject are included. Significant advances with regard to the biology of Borrelia burgdorjeri and the immunopathogenic mechanisms that result in disease have been made, enabling the role of the Band T lymphocytes in disease to be established and the development of sophisticated phenotyping methods, improved diagnostic tests and effective vaccines.

Advances in genetics, molecular biology and gene delivery technologies in recent years have led to new gene therapy strategies for treatment of a variety of diseases. This book gives a comprehensive overview of the present status and future directions of gene delivery systems and therapeutic strategies for the clinical application of gene therapy in cancer, cardiovascular and central nervous system diseases. Stem cell-based therapies and gene expression regulatory systems as novel platform technologies for various gene therapy applications are also discussed. Leading experts give excellent overviews of basic molecular aspects and clinical applications in this new emerging biomedical field.

A very early step in microbial colonization and pathogenesis is that involving recog nition of the host by the microbe. In the final analysis such recognition is due to interaction between specific molecules on the two sides, without which host and microbe would ignore each other. It is therefore exciting to learn the rules that govern host-microbe interaction at to a large extent determines whether or not we are infected by the molecular level, which influenza virus, leishmanias, staphylococci and other pathogens. This book is a compendium of the addresses delivered at a symposium on molecular interaction at Porvoo, Finland in August 1991. Realizing that there are no a priori differ ences in receptor recognition in viruses, eukaryotic parasites and bacteria, we freely inter mingled these microbes at the symposium, and in this book. We found the interdisciplinary discussions and comparisons both educative and stimulating. Thus the book is divided into parts that focus on host cell receptors, on microbial recognition molecules and molecules that mediate microbial interaction with a host cell receptor and, briefly, on the molecular events that follow. Although many microbes and many cellular receptors are missing from the book -owing to the limited duration and size of the symposium -the articles presented here constitute an impressive body of examples of how initial host-microbe interaction can come about. We believe that as such the book is a useful and interesting overview of the mechanisms and principles involved in these interactions.

The study of bacterial plasmids has not always been as popular as it is today. For many years, the molecular biology of pro cary- otes was focused heavily on bacteriophage and plasmid investigations which were carried out in only a few laboratories. Whatever inter- est existed in plasmids concerned the role of these extrachromosomal elements in bacterial conjugation, genetic exchanges, and antibiotic resistance, as well as in the structure of plasmids themselves. Gradually, however, it became increasingly evident that many of the special characteristics displayed by bacteria of medical, agricul- tural, industrial, and environmental importance are determined by genes carried by plasmids, and this interest in plasmid-encoded functions, such as bacterial virulence properties (exotoxin produc- tion, serum resistance, adhesiveness), metabolism of organic com- pounds, plant tumor formation, and biological nitrogen fixation, led to increasing study of. the plasmids that carry these genes. Inves- tigations of other plasmid-related properties such as replication and recombination have yielded much information about fundamental biological processes; information having implications that extend far beyond the particular plasmids under study. Concurrently, plas- mids were playing a key role in the discovery of bacterial transpos- able elements and were proving to be increasingly useful in the elu- cidation of mechanisms responsible for a variety of chromosomal rearrangement events in bacteria and plants. Their status as "mini- chromosomes" that could be isolated easily from bacterial cells and then reintroduced into other cells by transformation is of fundamen- tal importance in this regard.

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 time seems ripe for a critical compendum 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 numbering, 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 invalua ble 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."

During the two years since the publication of the first edition of this book, the global spread of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has continued. HIV was estimated by the World Health Organization (WHO) in 1993 to have at least 13 million individuals worldwide, with 1 million infected infected in the United States. HIV/AIDS in the United States has become the leading cause of death among men 25 to 44 years of age and the fifth leading cause of death among women of the same age group. Prevention of HIV infection remains a global challenge. Testing for HIV is the cornerstone for surveillance and prevention programs and for the provision of appropriate medical care for those who are infected. Such testing is equally essential to the search for effective antivirus drugs and vaccines. This second edition of AIDS Testing incorporates the most current thinking on test methodology and interpretation, some of which has changed considerably over the past two years. This edition also has been expanded to include a section consisting of six chapters on test applica tions and a section consisting of four chapters on management issues. This edition, like the first, describes in clear terms all the complex ele ments of testing, including applications, scientific principles, quality assurance, safety, and medical, ethical, and legal considerations.

Nearly thirty years ago, in 1974, the volume on Angiotensin edited by Irvine H.Page and F. Merlin Bumpus expanded the Handbook of Experimental Pharmacology. Even after two decades the multiplicity of its actions appears not to have been fully discovered. To call attention to its many functions is one of the purposes of this book. This new edition of the volume on Angiotensin attempts to provide an updated account of the knowledge and findings accumulated since the complexity of angiotensin was so accurately recognized.

Herpesviruses, classified in the family Herpesviridae, are important human and animal pathogens that can cause primary, latent or recurrent infections and even cancer. The major interest in research on herpesviruses today focuses on understanding the organization of the DNA genome, as well as on characterizing the viral genes in regard to their control and function. Modern techniques have allowed the viral DNA to become a molecular tool in the study of gene function, since it is now possible to implant the DNA into eukaryotic cells. This book contains original studies on the structure and organization of the DNA of human and animal herpes viruses. The various chapters acquaint the reader with the organization of the viral DNA, the mRNA transcripts, the replicative intermediates of the viral DNA, defective DNA genomes and their mode of synthesis, analyses of the viral DNA sequences in transformed cells, and the relationship between the presence of viral DNA fragments in the cancer cells and the transformed state of the cells."

Will address an important, yet underrepresented, topic. The correlation between viruses and atherosclerosis has been a focal point of the authors work, for a number of years. This volume will explore the relationship between different viral strains and atherosclerosis. It will begin by describing the hypothesis and denoting the mechanisms of virus-driven atherosclerosis, then expanding on the subject by focusing on different virus strains from Herpes, to Epstein-Barr, to the triad of Hepatitis viruses, et al on a chapter-by-chapter basis. While there are books, albeit few, that cover particular viral strains and their relationship to cardiovascular diseases, this work will be unique in its scope by considering multiple strains of viruses, making it a repository of information on the topic; a truly comprehensive volume. "

Alternative Sources of Adult Stem Cells: Human Amniotic Membrane, by S. Wolbank, M. van Griensven, R. Grillari-Voglauer, and A. Peterbauer-Scherb;
*
Mesenchymal Stromal Cells Derived from Human Umbilical Cord Tissues: Primitive Cells with Potential for Clinical and Tissue Engineering Applications, by P. Moretti, T. Hatlapatka, D. Marten, A. Lavrentieva, I. Majore, R. Hass and C. Kasper;
*
Isolation, Characterization, Differentiation, and Application of Adipose-Derived Stem Cells, by J. W. Kuhbier, B. Weyand, C. Radtke, P. M. Vogt, C. Kasper and K. Reimers;
*
Induced Pluripotent Stem Cells: Characteristics and Perspectives, by T. Cantz and U. Martin;
*
Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology, by D. Pei, J. Xu, Q. Zhuang, H.-F. Tse and M. A. Esteban;
*
Production Process for Stem Cell Based Therapeutic Implants: Expansion of the Production Cell Line and Cultivation of Encapsulated Cells, by C. Weber, S. Pohl, R. Poertner, P. Pino-Grace, D. Freimark, C. Wallrapp, P. Geigle and P. Czermak;
*
Cartilage Engineering from Mesenchymal Stem Cells, by C. Goepfert, A. Slobodianski, A.F. Schilling, P. Adamietz and R. Poertner;
*
Outgrowth Endothelial Cells: Sources, Characteristics and Potential Applications in Tissue Engineering and Regenerative Medicine, by S. Fuchs, E. Dohle, M. Kolbe, C. J. Kirkpatrick;
*
Basic Science and Clinical Application of Stem Cells in Veterinary Medicine, by I. Ribitsch, J. Burk, U. Delling, C. Geissler, C. Gittel, H. Julke, W. Brehm;
*
Bone Marrow Stem Cells in ClinicalApplication: Harnessing Paracrine Roles and Niche Mechanisms, by R. M. El Backly, R. Cancedda;
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Clinical Application of Stem Cellsin the Cardiovascular System, C. Stamm, K. Klose, Y.-H. Choi"

For over 30 years I have been engaged as a parasitolo nitz, Springer-Verlag, Heidelberg, was arranged in the pres gist in research on endemic diseases in our land. However, ence of Professor Jusatz. lt was indeed a great honor for I have been somewhat dissatisfied within my heart of me, but I also felt a very heavy responsibility; how to set hearts from the point of view of a medical person. Most of up the scheme, how to collect the materials, how to di gest, analyze and compile them in accordance with the us, myself included, handle disease sectionally, not com prehensively. Clinicians pay more attention to finding ef original goals. I frankly confess to realizing how limited fective drugs, medical scientists concentrate more effort my knowledge was at the same time. Poor editing would on clarifying pathologic etiology, and public health work result in dishonor not only to myself, but to my country ers are more concerned with environmental sanitation. as well. Now at this juncture, the point of editing, I am filled Thus, most of us generally neglect to search out the with deep emotion. In spite of limited time and knowl causal relation of a certain disease. For a disease to be established various factors must be involved: agent, ecolo edge, this manuscript will be prepared for edition at all gy, hosts, carriers, transmitters, habits, geographic and events.

In Vivo EPR (ESR) is a textbook on this relatively new subject in biomedical electron spin resonance. While a few chapters have appeared in special topics volumes in this series, this book covers the principles and theory, instrumentation as well as the latest applications at the time of its writing. The authors are world-renowned experts and pioneers in their fields. This book is divided into two major sections dealing with theory and instrumentation, and aspects of biochemistry, in vitro and in vivo applications. A significant amount of detail is devoted to clinical applications and the problems and pitfalls encountered in in vivo spectroscopy and imaging.
Key Features:

-History of In Vivo EPR,
-Principles of Imaging-Theory and Instrumentation,
-Time-domain Radio Frequency EPR Imaging,
-The Measurement of Oxygen In Vivo Using In Vivo EPR Techniques,
-Potential Medical (Clinical) Applications of EPR,
-Combining NMR and EPR/ESR for In Vivo Experiments.

Technological advances, together with a better understanding of the molecular biology of infectious microorganisms, are creating exciting possibilities for a new generation of replicating vaccines. Historically, live vaccines have been either directly derived from a natural source or attenuated by empirical approaches using serial passages and host cell adaptation. Currently, we are witnessing a quantum leap in our technological capabilities to specifically modify the genetic make-up of viruses and bacteria, making it possible to generate improved live vaccines and to develop completely new types of replicating vaccines, such as vectored vaccines, single-round infectious vaccines and replicon vaccines. This book highlights some of the most exciting recent developments towards a new generation of replicating vaccines.

This compendium is the result of the FEMS Workshop on "Rapid Diagnosis of Mycoplasmas" which I organized and which took place in Jerusalem, Israel, August 11-23, 1991. The first week's sessions were held at a resort on the outskirts of Jerusalem and consisted of lectures and discussions. This part was modelled along the lines of the Gordon Conference in the USA, i.e., in an intimate atmo sphere in which everyone could mix and exchange ideas, and was very benefi cial. About 100 scientists from around the world attended the first week. Dur ing the first week, the biology, molecular biology and pathophysiology of myco plasmas, as well as all the main diagnostic methods were covered, including both conventional and the newer technologies. The session on mycoplasmas in the human urogenital tracts was held in conjunction with the Israel Society for the Study and Prevention of Sexually Transmitted Disease. The second week was a laboratory session and was held at the Hebrew University-Hadassah Medical School campus in Ein Karem, Jerusalem. All ex periments were conducted by eminent specialists in their field. The lab session had 36 participants from 19 countries who used the most modern techniques for the diagnosis of mycoplasmas in medicine, veterinary medicine and agri culture. The efficacy of several commercial kits were also tested at this time. I want to again thank everyone who helped and supported this work shop, as well as the authors of the various chapters.

Severe Infections Caused by Pseudomonas aeruginosa emphasizes controversies worldwide in the diagnosis, treatment, prevention and pathogenesis of pseudomonas aeruginosa infections. By including both chapters written by European authors and chapters written by North American experts, the reader is ensured of receiving a broad spectrum of opinions on controversial topics. Special attention is paid to such topics as the diagnosis of hospital-acquired pneumonia caused by p. aeruginosa, scheduled antibiotic therapy for patients with cystic fibrosis, empiric therapy for febrile neurotropenic patients, combination vs. single agent antibiotic therapy for severely ill patients, and alternatives to conventional antibiotic therapies.

This excellent overview of our current understanding of pseudomonas aeruginosa pathogenesis will prove useful to clinicians and microbiologists around the globe.

During recent years the subject of extreme environments and extremophiles has become a central topic in modern Biology. The capability of some microorganisms to withstand, and often prefer, the harsh conditions found in such environments is helping to define the physicho-chemicallimits of life and in consequence its essential nature. Halophiles are one of the most representative types of extremophiles, requiring high concentrations of inorganic salts, mostly sodium chloride, to grow and survive. They inhabit hypersaline environments, the distribution and abundance of which dur ing geological eras are attested by the vast amounts of evaporite rocks present in the Earth crust and by their role in the generation of petroleum deposits. The corditions of high osmolarity and ionic strength that are concomitant with concentrated salt solutions challenge the stability of lipid bilayers and the structure of proteins forcing halophilic microbes to develop specialized molecules and physiological me;;hanisms to cope with this environmental stress. Even so, halophilism is a widespread trait in the microbial world. All the major groups of eucaryotic microbes, two groups of archaeobacteria and most phylogenetic branches of eubacteria have halophilic representatives. Therefore, the study of halophilic microorganisms is indeed a highly heterogeneous and extense topic. The present volume contains the contributions to the FEMS-NATO Advanced Research Workshop on "General and Applied Aspects of Halophilic Microorganisms" held at Alicante, Spain, September 17-22, 1989.

It is now just 40 years since coxsackieviruses were first isolated by Dalldorf and Sickles in the "eponymous" town of Coxsackie, New York. Yet the overall contribution of coxsackieviruses to clinically evident dis ease of humans is still largely an open problem. Following their discov ery, coxsackieviruses were under intense clinical and laboratory scrutiny for a long time. Because of their relationship to polioviruses, the under standing of their structure, biochemistry, biology, and epidemiology ad vanced rapidly as a result of the formidable efforts that eventually led to the defeat of poliomyelitis. The ability of these viruses to infect mice permitted dissection of their pathogenicity in an experimental host and elucidation of conditions that influence its expression. Coxsackieviruses have been progressively associated with an increasing array of widely diverse human diseases. However, only some of the suggested causal correlations have been substantiated with satisfactory certainty. For others, conclusive evidence has so far resisted investigation. Most impor tant, among the latter are chronic maladies, such as dilated car diomyopathy and juvenile diabetes, that demand consideration. In recent times, there has been a partial eclipse of the subject of coxsackieviruses in the medical literature. In addition to the difficulties encountered in pinpointing their pathogenic potential, possible reasons include the general decline of interest in enteroviruses, which ensued after the conquest of poliomyelitis, and the continuous appearance in the limelight of new, more esoteric, and therefore more "appealing" viruses."

Kevin Marshall is a hard act to follow. Volume 13 of Advances in Microbial Ecology has been produced by a new editorial board, and we, the members of that board, are delighted to have the opportunity to pay tribute to Kevin's achievements. In his time as Series Editor, the quality of the chapters submitted and the range of subject matter covered have ensured an expanding and more stimulated readership. This represents a considerable achievement, given the growth in the number of review volumes and the increasing tendency for journals to publish review articles. The achievement was reached not only through metic ulous attention to quality and detail but also by providing a forum for the expression of views, information, and results that would stimulate discussion. Advances in Microbial Ecology will continue to provide such a focus, although, because of the frequency of publication, it would not be practicable to introduce a "reply" or "comment" section. Although we do not deliberately aim to provide a forum for controversy, we encourage speculation based on sound scientific arguments. In addition, we would like to encourage authors to offer chapters for consideration. In the past, the volumes have largely comprised invited chapters. With the best will in the world, an editorial board of four cannot claim adequate coverage of such a vast and rapidly developing research area. We would there fore welcome submission of outline plans for chapters, which should be sent to the Editor.

In 1898 Camillo Golgi reported his newly observed intracellular structure, the apparato reticolare interno, now universally known as the Golgi Apparatus. The method he used was an ingenious histological technique (La reazione nera) which brought him fame for the discovery of neuronal networks and culminated in the award of the Nobel Prize for Physiology and Medicine in 1906. This technique, however, was not easily reproducible and led to a long-lasting controversy about the reality of the Golgi apparatus. Its identification as a ubiquitous organelle by electron microscopy turned out to be the breakthrough and incited an enormous wave of interest in this organelle at the end of the sixties. In recent years immunochemical techniques and molecular cloning approaches opened up new avenues and led to an ongoing resurgence of interest. The role of the Golgi apparatus in modifying, broadening and refining the structural information conferred by transcription/translation is now generally accepted but still incompletely understood. During the coming years, this topic certainly will remain center stage in the field of cell biology. The centennial of the discovery of this fascinating organelle prompted us to edit a new comprehensive book on the Golgi apparatus whose complexity necessitated the contributions of leading specialists in this field. This book is aimed at a broad readership of glycobiologists as well as cell and molecular biologists and may also be interesting for advanced students of biology and life sciences.

New Bacterial Vaccines focuses upon unfulfilled needs for bacterial vaccines. The increase in drug resistance among many bacterial species has increased the need for new bacterial vaccines. This book serves as a comprehensive reference on the major aspects of developing new bacterial vaccines. The distinctive feature of this book is that it focuses upon new vaccines now under development by reviewing key issues for each vaccine target and new technologies being applied to developing new vaccines. This book should prove useful for students in the life sciences, scientists, developers of vaccines and biotechnology products, clinicians, regulators, and health-care practitioners.

2. The Translational Machinery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Translation Initiation in Prokaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Translation Initiation in Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 14 Translation Elongation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Translation Termination in Prokaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Translation Termination in Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Error Correction in Translation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 A Structural Basis of Error Correction in Translation . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Ribosome Editing: A Failsafe Error Correction Mechanism . . . . . . . . . . . . . . . . 22 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3. Errors During Elongation Can Cause Translational 29 Frameshifting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Spontaneous Frameshifting Versus Programmed Frameshifting . . . . . . . . . . 30 Spontaneous Frameshifts Can Be Induced at Specific Codons . . . . . . . . . . . . 31 4. Programmed +1 Frameshifting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 The pifE Gene of E. coli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Using the pifE System to Study General Frameshifting in E. coli . . . . . . . . 46 Ty Retrotransposons in Yeast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Frameshifting in Retrotransposon Ty1 Occurs by tRNA Slippage . . . . . . . 48 Frameshifting in Retrotransposon Ty3 Occurs by Out-of-Frame Binding of tRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 The Rat Ornithine Decarboxylase Antizyme Gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 5. Programmed -1 Frameshifting in Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Programmed -1 Frameshifting in Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 -1 Frameshifting Occurs on a "Slippery Heptamer" . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 The Simultaneous-Slippage Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 of -1 Frameshifting by a Downstream Pseudoknot . . . . . . . . . . 77 Stimulation Does the Pseudoknot Only Block Passage of the Ribosome? . . . . . . . . . .

Molecular biology has rapidly advanced since the discovery of the basic flow of information in life, from DNA to RNA to proteins. While there are several important and interesting exceptions to this general flow of information, the importance of these biological macromolecules in dictating the phenotypic nature of living creatures in health and disease is paramount. In the last one and a half decades, and particularly after the completion of the Human Genome Project, there has been an explosion of technologies that allow the broad characterization of these macromolecules in physiology, and the perturbations to these macromolecules that occur in diseases such as cancer. In this volume, we will explore the modern approaches used to characterize these macromolecules in an unbiased, systematic way. Such technologies are rapidly advancing our knowledge of the coordinated and complicated changes that occur during carcinogenesis, and are providing vital information that, when correctly interpreted by biostatistical/bioinformatics analyses, can be exploited for the prevention, diagnosis, and treatment of human cancers. The purpose of this volume is to provide an overview of modern molecular biological approaches to unbiased discovery in cancer research. Advances in molecular biology allowing unbiased analysis of changes in cancer initiation and progression will be overviewed. These include the strategies employed in modern genomics, gene expression analysis, and proteomics.

The advantages of the baculovirus system are rooted in the properties of the virus and the host (insect, or cell lines derived from it). During the normal infection cycle, two forms of the virus are produced: an early budded virus (BY) form (Kost et al. , 2000), in which the viral DNA and structural proteins are surrounded by membrane derived from the infected cell; and a late occluded form (occlusion-derived virus, ODy), consisting of enveloped viral cores which are embedded in a crystal matrix of viral proteins. The principal component of the matrix is the abundantly expressed protein polyhedrin. The budded virus rapidly spreads the infection from cell to cell within the insect host, resulting ultimately in the complete liquefaction of the host, and release of occluded virus into the environment. The occluded form protects the released virus, allowing it to survive for long periods in the environment until ingested by another host. In the alkaline environment ofthe insect gut, the protective protein matrix is removed, and the life cycle is repeated. In insect cell cultures, only the BV form of baculovirus is required, and the polyhedrin gene may be replaced with the gene for the recombinant protein. An additional benefit of replacing or deleting polyhedrin is that it effectively makes the virus unable to survive outside the laboratory, an advantage in terms of environmental safety. The system is intrinsically safe to animals, being unable to replicate in species other than a limited range of insects.