Bringing together a wide variety of examples of functional amyloid in a single volume, this book explores the importance of amyloid fibrils in fungi, bacteria, algae, invertebrate, and vertebrate animals for providing environmental protection, structural integrity, and regulating biochemical processes. It highlights many of the extraordinary examples of functional amyloid found to date. It, therefore, provides an exciting perspective for the study of amyloid deposits as important and useful protein structures widespread in nature.

The Ottawa '88 meeting of the International Society for Oxygen Transport to Tissue attracted a record number of participants and presentations. We were able to avoid simultaneous sessions and still keep the scientific program to four days by using poster sessions followed by plenary debate on each poster. To paraphrase the British physicist David Bohm, we tried to avoid an ordinary discussion, in which people usually stick to a relatively fixed position and try to convince others to change. This situation does not give rise to anything creative. So, we attempted instead to establish a true dialogue in which a person may prefer and support a certain point of view, but does not hold it nonnegotiab1y. He or she is ready to listen to others with sufficient sympathy, and is also ready to change his or her own view if there is a good reason to do so. Our Society is in its "teen" years, and there are even some arguments about its exact age. Many newer members have raised questions concerning the history of the Society. For this reason, I have asked one of the "founding fathers," D. Bruley, to prepare a brief account of the birth and early history of the Society which appears on the following page.

Trying to address the entire field of presynaptic modulation of neurotransmitter release is a rather daunting undertaking, one that is well beyond the scope of this book. In addition, studies of release modulation, particularly from a biochemical standpoint, have been the subjects of several extensive reviews, meetings, and books (Langer, 1978; Chesselet, 1984; Wessler, 1989; Kalsner and Westfall, 1990), which provide an essential introduction to this subject. What we have focused on, however, are several specific aspects of release modulation that perhaps have not been as extensively discussed. First, we felt that it was important to focus on modulation in the central nervous system; much of the work that has been done in the past has emphasized the peripheral nervous system (e. g. , the autonomic nervous system and the neuromuscular junction), in part because such preparations are more amenable to study. However, it is becoming clear that modulation of release is, if anything, more important in the central nervous system than in the periphery, and that virtually every transmitter system that has been studied shows some type of release modulation. The other way in which we have restricted the scope of this volume has been to try to emphasize studies in which functional (primarily electrophysiological) measures of transmitter release have been used rather than direct biochemical measures of release, and to explore the ways in which release modulation affects the normal physiological function at synapses.

Recent publications have addressed specific aspects of the endothelins, such as their roles in disease or the importance of endothelin receptors. However, in this book the entire field of endothelins is covered. This includes the pathways of endothelin production and their regulation, the local and systemic actions of endothelins, receptors for the endothelins and the signalling pathways employed, and the involvement of endothelins in a range of diseases. Attention is also paid to the development through chemistry, pharmacology and toxicology of endothelin antagonists and endothelin-converting enzyme inhibitors, with mention of all the important members of these drug classes. This leads to well-rounded discussions of the potential therapeutic benefit of endothelin inhibitors.

A complete account of the theory of the diffraction of x-rays by crystals with particular reference to the processes of determining the structures of protein molecules, this book is aimed primarily at structural biologists and biochemists but will also be valuable to those entering the field with a background in physical sciences or chemistry. It may be used at any post-school level, and develops from first principles all relevant mathematics, diffraction and wave theory, assuming no mathematical knowledge beyond integral calculus.
The book covers a host of important topics in the area, including:
- The practical aspects of sample preparation and x-ray data collection, using both laboratory and synchrotron sources
- Data analysis at both theoretical and practical levels
- The important role played by the Patterson function in structure analysis by both molecular replacement and experimental phasing approaches
- Methods for improving the resulting electron density map
- The theoretical basis of methods used in refinement of protein crystal structures
- In-depth explanation of the crucial task of defining the binding sites of ligands and drug molecules
- The complementary roles of other diffraction methods which reveal further detail of great functional importance in a crystal structure.

A century has already passed since FRIEDRICH MIESCHER, working at Strasbourg and Basel, began his study of protamine, one of the basic nuclear proteins of cells. It was first established by KOSSEL that protamine represents the simplest known protein. In the conviction that research into the nature of protamine would shed light on that of other typical proteins, a group of researchers in Germany followed MIESCHER and laid the foundations of protein chemistry. A general view of prot amines was thus built up by KOSSEL, working at Strasbourg, Berlin, Marburg an der Lahn, and Heidelberg, FELIX at Heidelberg, Munich, and Frankfurt am Main, and WALDSCHMIDT-LEITZ at Prague and Munich. Concepts and techniques established by these studies have been widely utilized for research on other typical proteins. The revolutionary advances in chemical and physical techniques after W orId War II extended the sphere of research to Tokyo in the Far East. Prof. FELIX' visit in 1955 greatly encouraged our research group in Tokyo. His death in August 1960 constituted a sad loss to protein chemistry and stimulated our group to assume responsibility for carrying on the studies. In the following decade we in Tokyo have been able to add a new development to the results on the chemical structure of protamines accumulated by the Eurqpean researchers over a period of about fifty years."

Humans have been "manually" extracting patterns from data for centuries, but the increasing volume of data in modern times has called for more automatic approaches. Early methods of identifying patterns in data include Bayes' theorem (1700s) and Regression analysis (1800s). The proliferation, ubiquity and incre- ing power of computer technology has increased data collection and storage. As data sets have grown in size and complexity, direct hands-on data analysis has - creasingly been augmented with indirect, automatic data processing. Data mining has been developed as the tool for extracting hidden patterns from data, by using computing power and applying new techniques and methodologies for knowledge discovery. This has been aided by other discoveries in computer science, such as Neural networks, Clustering, Genetic algorithms (1950s), Decision trees (1960s) and Support vector machines (1980s). Data mining commonlyinvolves four classes of tasks: * Classi cation: Arranges the data into prede ned groups. For example, an e-mail program might attempt to classify an e-mail as legitimate or spam. Common algorithmsinclude Nearest neighbor,Naive Bayes classi er and Neural network. * Clustering: Is like classi cation but the groups are not prede ned, so the algorithm will try to group similar items together. * Regression: Attempts to nd a function which models the data with the least error. A common method is to use Genetic Programming. * Association rule learning: Searches for relationships between variables. For example, a supermarket might gather data of what each customer buys.

The First European Symposium on Calcium-Binding Proteins in Normal and Transformed Cells was held at the Faculty of Medicine of the "Universit6 Libre de Bruxelles" in Brussels, Belgium, April 20-22, 1989. Delegates from seventeen countries attended. This Symposium was initiated through an EEC Stimulation Program. The formal program included forty verbal presentations by invited speakers and sixty miniposter presentations, and was formulated by the Organizing and Scientific Committee: E. Carmeliet (Leuven), J. P. Collin (Poitiers), S. Forsen (Lund), C. W. Heizmann (Ziirich), D. E. M. Lawson (Cambridge), P. Miroir (Brussels), J. L. Pasteels (Brussels) and R. Pochet (Brussels). This volume contains the papers prepared by the invited speakers. The contributions are grouped according to their general subject matter: Genes of Calcium-Binding Protein Family, Structure/Function Relationships, The Cytoskeleton and Calcium-Binding Proteins, Calcium-Binding Proteins in TransforlIled Cells, Calcium/Lipid-Binding Proteins, Calcium-Binding Proteins Substrates and Immunohistochemistry of Calbindin and Calretinin. The highlights of the symposium are numerous. Among the items to be noted are the growing number of abundant proteins which interact with calcium and sometimes with other second messenger sys- tems; specifically pH associated with the tyrosine kinase calpactin, calcYclin, p9Ka induced by growth fac- tors, MRP-8 and MRP-14 (also called cystic fibrosis antigen, L1 or calgranulins) forming half the soluble protein of granulocytes. New structure/function relationships on calbindin D9K and calmodulin have emerged from nuclear magnetic resonance and site-directed mutagenesis studies.

This volume contains the proceedings of the International Conference on Prostaglandins and Lipid Metabolism in Radiation Injury held in Rockville, Maryland, on October 2-3, 1986. Over 200 persons from eight countries attended the program, which consisted of 24 oral presentations and 38 poster presentations. Forty-two of those presentations have been included in this volume. The conference was sponsored by the Armed Forces Radiobiology Research Institute, located in Bethesda, Maryland. The effects of radiation on lipid synthesis and membrane damage are aptly summarized in the first five chapters. These chapters describe the effects of radiation on lipid peroxidation of model membranes, and the role of lipid composition in mammalian cell death and in bacterial radio- and thermosensitivity. In bacteria, lipid peroxidation is not essential for radiation-induced cell death. One of the key points of the conference was the paradoxical nature of the radiobiology of eicosanoids. On the one hand, eicosanoids are mediators of damage; on the other, they are radioprotective agents. It is clear from the literature and from the data presented at the conference that both of these properties may also be observed as a consequence of radiotherapy. Some studies indicate that nonsteroidal anti-inflammatory drugs may minimize or prevent certain radiation induced damage, but other studies show no positive effect."

This volume focuses on the structure, function and regulation of plant signaling G proteins and their function in hormonal pathways, polarity, differentiation, morphogenesis and responses to biotic and abiotic stresses.

Plants are sessile organisms that need to continuously coordinate between external and internal cues. This coordination requires the existence of hubs to allow cross-talk between different signaling pathways. A single family of Rho GTPases, termed either ROPS or RACs, and heterotrimeric G proteins have emerged as the major molecular switches in a multitude of signal transduction pathway in plants.

The initial identification of the Adenomatous polyposis eoli (Ape) gene as the site of mutations in familial adenomatous polyposis (FAP) was described in 1 1992. ,2 A causal relationship between Ape mutations and intestinal tract tumours was confirmed three years later with the establishment ofthe Min mouse model) These mice are heterozygous forApe and develop numerous intestinal tumours that mimic FAP. Subsequently, Ape has emerged as the most commonly mutated gene in colorectal cancerwith reports varying between 50-80% ofsporadic tumours car- rying such mutations. The search for how mutations in Ape initiate and/or support progression oftumours in the intestinal tract has revealed that the Ape protein is a multifunctionalparticipant in a diverse array ofcellular functions. By collecting and assembling the chapters inthisbook, we aimed toprovide an overview of the diverse functions performed by the Ape protein. As summarised in a short final chapter by Trainer,heterozygosityofApe leads to a number ofextracolonic manifestations that further support this emerging picture ofthe Ape protein as an active contributor to many different cellular functions. The first recognised function of Ape was its role in Wnt signalling. o This function is one of the driving forces for how mutations in Ape ensure that cells remain proliferative. Many of the molecular details of this pathway have been discovered and are described in the first chapter by Kennell and Cadigan.

Researchers in structural genomics continue to search for biochemical and cellular functions of proteins as well as the ways in which proteins assemble into functional pathways and networks using either experimental or computational approaches. Based on the experience of leading international experts, Structural Genomics and High Throughput Structural Biology details state-of-the-art analytical and computational methods used to reveal the three-dimensional structure and function of proteins. A historical perspective and a detailed guide to the production of protein material for structural determination, a key step in the process, lay the necessary foundation for discussing the most effective structure determination technologies, such as X-ray crystallography and NMR spectroscopy. Encouraging the study of genes and proteins of unknown structure in order to discover new information about folding, specific structural features, or function, Structural Genomics and High Throughput Structural Biology presents the methods used to interpret the sequences of proteins in a structural context, giving insight into their function. It also explains how to extract information from public data repositories and how to account for variability and accuracy in the quality of this data. The book concludes with a discussion of practical applications of therapeutically driven structural genomics, and presents future directions in the field. Structural Genomics and High Throughput Structural Biology offers a comprehensive guide to the theoretical, technological, and experimental methodologies used to derive structural information from encoded proteins by renowned and world leading scientists in the field.

Haemocyanin was first recognised as a respiratory pigment by P. Bert in 1867. Over the years the haemocyanins have attracted attention as macromolecules and copper-contain- ing respiratory proteins. The early functional studies of A.C. Redfield (Biol. Rev. 9, 176, 1934) and the ultracen- trifuge work of I.B. Ericksson-Quensel and T. Svedberg (Biol. Bull. 21, 498, 1936) come easily to mind. In recent years haemocyanin studies have come to the forefront with the work of the Ghirettis (Padova), R. Lontie (Louven), E.F.J. Van Bruggen (Groningen) and Joe and Celia Bonaven- tura (Beaufort) to mention but a few of the number of able investigators coming to this field from diverse disciplines. It is hoped that this book presents a fair cross section of current workers and work on haemocyanin. It is the sec- ond collection of haemocyanin studies to be published after a Workshop on the Structure and Function of Haemocyanin. The first haemocyanin meeting was held by Professors F. "Ghiro" Ghiretti and Anna Ghiretti-Magaldi in Naples in 1966. Subsequent meetings have been held at Groningen (1970), Louven (1971) and Padova (1974). Current interest in haemocyanin can be judged by the scope and breadth of the papers from the Malta meeting and pre- sented here. In organising the Malta meeting I would like to thank Dr. John Tooze of the European Molecular Biology Organisation and my friend and colleague, Professor Mauri- zio Brunori for their continuous help and support.

Epithelial mucins are large complex cell surface and secreted glycoproteins produced by mucosal epithelial cells. In, Mucins: Methods and Protocols expert researchers in the field detail many of the methods which are now commonly used to study Mucins. These include methods and techniques for the best approaches to analysing each specific area of mucin biochemistry, physiology and biophysics before providing individual detailed experimental protocols together with troubleshooting and interpretation tips. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Mucins: Methods and Protocols is designed to be a useful resource for those entering the mucin field and to facilitate those already studying mucins to broaden their experimental approaches to understanding mucosal biology.

This volume is a collection of the contributions presented at the 42nd Erice Crystallographic Course whose main objective was to train the younger generation on advanced methods and techniques for examining structural and dynamic aspects of biological macromolecules. The papers review the techniques used to study protein assemblies and their dynamics, including X-ray diffraction and scattering, electron cryo-electron microscopy, electro nanospray mass spectrometry, NMR, protein docking and molecular dynamics. A key theme throughout the book is the dependence of modern structural science on multiple experimental and computational techniques, and it is the development of these techniques and their integration that will take us forward in the future.

Amino acids are featured in course syllabuses and in project and research work over a wide spectrum of subject areas in chemistry and biology. Chemists and biochemists using amino acids have many common needs when they turn to the literature for comprehensive information. Among these common interests, analytical studies, in particular, have undergone rapid development in recent years. All other chemical and biochemical aspects of amino acids - synthesis, properties and reactions, preparation of derivatives for use in peptide synthesis, racemization and other fundamental mechanistic knowledge - have been the subject of vigorous progress. This book offers a thorough treatment of all these developing areas, and is structured in the belief that biochemists, physiologists and others will profit from access to information on topics such as the physical chemistry of amino acid solutions, as well as from thorough coverage of amino acid metabolism, biosynthesis and enzyme inhibition; and that chemists will find relevant material in biological areas as well as in the analysis, synthesis and reactions of amino acids.

Strictly speaking, the term regulatory peptides may include any peptide which has a regulatory function in any organism. In recent years, how ever, the term has come to mean those originally classified as brain-gut peptides. The peptides initially defined as those belonging to the brain gut axis had a dual location in neurones of the brain and endocrine cells of the gut. We now include a number of neuropeptides found in the autonomic nervous system of the gut, the cardiovascular system and other systems. To many scientists comparative physiology means comparison of the mechanisms of certain functions in the rat, the guinea-pig, the cat and maybe some other mammal. If the philosophy is that man is the centre of the universe and other mammals can be used as 'models' of man, this may well be the most useful way to study the functions of the human being, without actually chopping somebody up. However, with a some what wider perspective on life, it is easy to see the importance of a full understanding of the function of all living organisms, in its own right as well as a link in the evolution towards individuals able to survive and reproduce in very different environments. The importance of com parative studies in all living organisms cannot be emphasized too much. It has been the ambition with this book to treat all animals as equally important."

This volume presents the proceedings of the Fourth Annual Symposium on the Molecular Biology of Hemopoiesis, held in Reno, Nevada, November 1 and 2, 1988. Its focus on erythropoiesis represents an attempt to cover a rapidly expanding field, which has gone from elegant studies of erythro poietin physiology, to molecular biology, to clinical applications and again to physiology. The rapid development has been made possible by cloning of erythropoietin gene and the availability of recombinant hormone. The regulation of heme and its derivatives has also been aided by techniques of molecular biology; there is now a concerted effort to better understand how these enzymes contribute to proliferation, differentiation and maturation of the erythron. Globin gene derrangements have been targets of recent research in an attempt to correct the defect by genetic engineering. In the chapters of this book, several groups "expressed" their views on this subject. Finally, we analyze various regulators of erythropoiesis, both in vivo and in vitro. Dr. Richard Levere was a pioneer in many studies of heme metabolism and of erythropoiesis. He has been a generous supporter of research in this field and of our past meetings. It is only. fitting that this volume should be dedicated to him."

The present volume contains the proceedings of the 23rd Mos bach Colloquium on "Protein-Protein Interactions." It includes the paper by Prof. S. LIFSON who unfortunately was unable to attend. Discussions were included whenever possible in order to make the complete proceedings accessible to the future reader. The colloquium was generously supported by the firms who are corporate members of the Gesellschaft fur Biologische Chemie. Dr. W. B. GRATZER and Dr. L. JAENICKE, as weIl as some of the invited speakers, were a tremendous help in preparing the program and we wish to thank them for their helpfuI suggestions and advice. Our appreciation extends to Prof. E. AUHAGEN and Prof. H. GIBIAN, and their secretaries, who shared the burden of organizing the colloquium. In addition, we wish to express our gratitude to Springer-Ver Iag, and especially to Dr. H. MAYER-KAUPP for editoriaI help and for the rapid publication of this volume. We hope that the reader, Iike the audience in the Mosbach market hall, will gain an impression of the present state of protein research and of the way in which intermolecular interactions hold specific implications for the structure and function of proteins. Regensburg and Wurzburg, autumn 1972 R. JAENICKE E. HELMREICH Contents Introduction. R. JAENICKE (Regensburg) 1 Molecular Forees. S. LIFSON (Rehovot) ................... 3 Structure, Function and Dynamics of a ReguIatory Enzyme: Aspartate Transcarbamylase. H. K. SCHACHMAN (Berkeley) 17 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 . . . . . . . . . . . . . ."

Plasma lipoproteins constitute a unique macromolecular system of lipid-protein complexes responsible for the transport of lipids from their sites of origin to their sites of utilization either as metabolic fuel or as structural components of cell membranes. Although studies on the role of lipoproteins in the mechanism of lipid transport are meritorious in their own right, the ever-increasing interest in chemical and functional properties of this remarkable class of conjugated proteins stems from the impressive evidence of their direct involvement in the genesis and develop ment of atherosclerotic lesions. The initial emphasis on neutral lipids and phospholipids as the most characteristic constituents of operationally defined lipoprotein classes has shifted in recent years to their protein moieties or apolipoproteins. The discovery of a number of apolipoproteins and characterization of familial hypolipoproteinemias as apolipoprotein deficiency disorders indicated that apolipoproteins play an essential role in maintaining the structural stability and integrity of lipoprotein particles. In addition to their role in the formation of lipoproteins, apolipoproteins were shown to perform a variety of functions in metabolic conversion of lipoproteins and their interactions with cellular surfaces. Results from several laboratories have demonstrated that the chemical and metabolic heterogeneity of operationally-defined lipoprotein classes is due to the presence of several discrete lipoprotein particles with similar physical properties but different and characteristic apolipoprotein composition. Thus, the apolipoproteins have emerged not only as essential structural and functional constituents of lipoproteins but also as unique chemical markers for identifying and classifying lipoprotein particles."

We are proud to present Volume 3 of Biological Magnetic Resonance, a series that has met with praise from the scientific community. This volume covers the new applications of various multiple irradia- tion techniques to the NMR of biomolecules; the chapter of Keller and Wuthrich describes much of the technique and its applications to hemo- proteins. The ESR of some hemoproteins in the single crystal is described by Chien and Dickinson, who also include discussions of techniques and methods for single-crystal ESR of paramagnetically intrinsic and spin- labeled protein crystals. Mims and Peisach describe the latest applications and results in electron spin echo spectroscopy of several metalloproteins. Two ESR spin probe techniques are reviewed. Chasteen describes the methods and applications of vanadyl(JV) to several systems. Ohnishi and Tokutomi describe studies of phase separations in mixed and model mem- branes by the nitroxide spin probe technique. We have been successful in continuing to provide topics that are timely and experimentally informative with a heavy emphasis on biolo- gically relevant applications. We thank our colleagues in the scientific com- munity for their suggestions on future coverage-we will remain receptive to future suggestions and comments on this series. A tentative topic list for forthcoming volumes is given on the following pages.

Published continuously since 1944, the" Advances in Protein Chemistry and Structural Biology" serial has been a continuous, essential resource for protein chemists. Covering reviews of methodology and research in all aspects of protein chemistry, including purification/expression, proteomics, modeling and structural determination and design, each volume brings forth new information about protocols and analysis of proteins while presentingthe most recent findings from leading experts in a broad range of protein-related topics. This volume features articles on Computational Chemistry methods in Structural Biology.

Essential resource for protein chemists This volume features articles on Computational Chemistry methods in Structural Biology"

Molecular farming is a biotechnological approach that includes the genetic adjustment of agricultural products to create proteins and chemicals for profitable and pharmaceutical purposes. Plant molecular farming describes the manufacture of recombinant proteins and other biologically active product in plants. This approach depends on a genetic transformation of plants that can be accomplished by the methods of stable gene transfer, such as gene transfer to nuclei and chloroplasts, and unstable transfer methods like viral vectors. The requirement for recombinant proteins in terms of quality, quantity, and diversity is increasing exponentially This demand is traditionally met by recombinant protein construction technologies and the engineering of orthodox expression systems based on bacteria or mammalian cell cultures. However, majority of developing countries cannot afford the high costs of medicine derived from such existing methods. Hence, we need to produce not only the new drugs but also the cheaper versions of those already present in the market. Plant molecular farming is considered as a cost-effective technology that has grown and advanced tremendously over the past two decades. This book summarizes the advances and challenges of plant molecular farming for all those who are working on or have an interest in this rapidly emerging area of research.