The Subcellular Biochemistry series has recently embarked upon an almost encyclopaedic coverage of topics relating to the structure and function of macromolecular complexes (Volumes 82, 83 and 87). The present multi-author text covers numerous aspects of current research into molecular virology, with emphasis upon viral protein and nucleoprotein structure and function. Structural data from cryo-electron microscopy and X-ray crystallography is displayed throughout the book. The 17 chapters in the book cover diverse interesting topics, all currently under investigation, contributed by authors who are active actively involved in present-day research. Whilst structural aspects predominate, there is much consideration of the structure-function relationship. In addition, the book correlates with and extends from Volume 68 of the series "Structure and Physics of Viruses: An Integrated Textbook". This book is directed primarily at professionals that work in the broad field of Structural Biology and will be of particular interest to Structural Virologists. The editors, David Bhella and Robin Harris, have much experience in virology and protein structure, respectively. Dr Bhella is Director of the Scottish Macromolecular Imaging Centre. Professor Robin Harris is the long-standing Series Editor of the Subcellular Biochemistry series. He has edited and contributed to several books in the series.

This book contains a broad survey on the peroxiredoxins. It involves almost all groups that contributed significant insights into the emerging field. Coverage discusses the diverse biological roles of the new protein family in the context of other antioxidant systems like those based on heme or selenium catalysis. In addition, the book highlights related future perspectives.

This book provides an up-to-date overview of key areas of ageing research and bridges the gap between the subcellular events and the reality of ageing as seen in clinical practice. To this end, the reader learns about the historical development and progression of clinical ageing research. All chapters address the biochemistry or cell biology of various ageing events (to the extent that the data are available) and work their way to the clinical understanding we have of ageing. The focus of this volume is on how dietary restriction, virus infection and chronic inflammation affect the ageing process. Additionally, this book discusses how phosphate metabolism and metabolic dysfunction contribute to ageing events and how various organs and tissues (e.g. tendons, ears, heart muscle, and the endocrine system) age. This book follows on from Parts I, II and III of Biochemistry and Cell Biology of Ageing within the Subcellular Biochemistry book series and aims to bring the subcellular and clinical areas into closer contact by including interesting and significant biomedical ageing topics that were not included in the earlier volumes. Comprehensive and cutting-edge, this book is a valuable resource for experienced researchers and early career scientist alike, who are interested in learning more about the fascinating and challenging question of why and how our cells age.

Volume 18 of the Subcellular Biochemistry series, which specializes in various aspects of the biochemistry of the intracellular parasites, was initially proposed by Jose Luis Avila and strongly supported by myself, as Series Editor of Sub cellular Biochemistry. Considerable assistance was received from Professor Frank Wunderlich (University of Dusseldorf) and more particularly from Dr. Michael Miles (London School of Hygiene and Tropical Medicine) during the compilation of the list of possible chapters. Our initial aim was to present a comprehensive survey of this broad field of study. Although some interesting topics have been lost due to authors backing out late in the production schedule of the book, the manuscripts that were submitted have provided a useful over view of the subject, with notable strength within the field of Leishmania. The 13 chapters of the book have been grouped according to subject. The first five chapters deal with Leishmania and are followed by two chapters on Try ponosoma cruzi, two on the malarial parasites, and two on the Coccidia. The fmal two chapters cover the Microsporidia and chemotherapy, respectively."

This text looks at subcellular chemistry, particularly at intermediate filaments. Topics include fish intermediate filament proteins in structure, evolution, and function, and lessons from keratin transgenic and knockout mice.

This series of books, devoted to aspects of blood cell biochemistry, development, immu nology, and ultrastructure, has evolved and separated from the long-established Plenum series Subcellular Biochemistry. It is the intention of these volumes to draw together related areas of investigation and to provide, in the fullness of time, complete coverage of this rapidly advancing important biomedical discipline. Both fundamental and medically applied topics, dealing with normal and pathological cells, will be included. This, the first volume of the series, contains a diverse collection of chapters, all of which relate to erythroid cells. The range of material included is extremely broad and the authors have used contrasting technical approaches, both within their personal experimen tal studies and within their manuscripts. This has led to the production of a very interest ing compilation, which does, nevertheless, possess a strong overall thematic unity. As with all edited volumes, some topics of importance and interest are not included. This may be because of oversight on my part, as editor, or because the authors originally selected failed to submit their manuscript by the agreed-upon submission date. For these omissions I take full responsibility and trust that at least some of the topics omitted, for instance membrane cation transport systems, will be covered within a future volume of the series. This book commences with two chapters of a developmental nature."

The last several years have been a landmark period in the ubiquitin field. The breadth of ubiquitin's roles in cell biology was first sketched, and the importance of ubiquitin-dependent proteolysis as a regulatory mechanism gained general acceptance. The many strands of work that led to this new perception are re counted in this book. A consequence of this progress is that the field has grown dramatically since the first book on ubiquitin was published almost a decade ago M. Rechsteiner (ed. ), Ubiquitin, Plenum Press, 1988]. In this span, students of the cell cycle, transcription, signal transduction, protein sorting, neuropathology, cancer, virology, and immunology have attempted to chart the role of ubi quit in in their particular experimental systems, and this integration of the field into cell biology as a whole continues at a remarkable pace. We hope that for active researchers in the field as well as for newcomers and those on the fence, this book will prove helpful for its breadth, historical perspective, and practical tips. Structural data are now available on many of the components of the ubiquitin pathway. The structures have provided basic insights into the unusual biochemical mechanisms of ubiquitination and proteasome-mediated proteolysis. Because high-speed computer graphics can convey structures more effectively than print media, we have supplemented the figures of the book with a Worldwide Web site that can display the structures in a flexible, viewer-controlled format."

This book covers the latest findings of a wide variety of viral, prokaryotic and eukaryotic macromolecular protein complexes and builds upon the solid macromolecular foundations established by previous volumes of the Subcellular Biochemistry series. Thus, an almost encyclopaedic coverage of the broad field of protein complex structure and function has been established. The 17 interesting chapters included in this book have been organised into four sections: Soluble Protein Complexes, Membrane Protein Complexes, Fibrous Protein Complexes and Viral Protein Complexes. Significant topics present here are: Fatty Acid Synthase, the Fork Protection Complex, Ribonucleotide Reductase, the Kinetochore, G proteins, the FtsEX Complex, the Kainate Receptor, the Photosystem I-antenna, the Mycobacterial Arabinofuranosyltransferases, the the Bacterial Flagellum, the Actomyosin Complex, Motile Cilia, SLS Collagen Polymorphic Structures, and the Reovirus Capsid and Polymerase. Up-dates/expansion of chapter topics present in earlier volumes are now included in chapters here, e.g., those on Ferritin-like proteins and the Multi-tRNA Synthetase. The book is richly illustrated throughout, the result of an impressive integration of structural data from X-ray crystallography and cryo-electron microscopy. The functional aspects of protein-protein interactions are also given a high priority.

Blood Cell Biochemistry was initially conceived as part of the Plenum series Subcellular Biochemistry, from which it has developed into a separate series. The present volume is devoted primarily to contributions on megakaryocytes and platelets and, to a lesser extent, to macrophages and eosinophils. The book does not attempt a rigorous or total coverage of the particular topics; it represents the areas of current scientific activity and interest that were selected by the editor at the commencement of this project. In general, the approach has been similar to that adopted for Volume 1 of the series (Erythroid Cells); the same approach will be followed subsequently in Volume 3 (Lymphocytes and Granulocytes). This book opens with a developmentally oriented chapter by Janine Breton-Gorius on megakaryocyte maturation and platelet release in normal conditions, which serves to set the scene ultrastructurally for much of the data that follow. The biosynthesis and process ing of platelet glycoproteins in megakaryocytes is dealt with by Alain Duperray and his colleagues, and thereby provides an in-depth biochemical survey of the megakaryocyte. The applications and strengths of crossed immunoelectrophoresis for the study of platelet membrane proteins is then covered by Simon Karpatkin, and a detailed account of the heredity disorders of platelet function is provided by Francine Rendu and Evelyne Dupuy."

Knowledge of cholesterol and its interaction with protein molecules is of fundamental importance in both animal and human biology. This book contains 22 chapters, dealing in depth with structural and functional aspects of the currently known and extremely diverse unrelated families of cholesterol-binding and cholesterol transport proteins. By drawing together this range of topics the Editor has attempted to correlate this broad field of study for the first time. Technical aspects are given considerable emphasis, particularly in relation cholesterol reporter molecules and to the isolation and study of membrane cholesterol- and sphingomyelin-rich "raft" domains. Cell biological, biochemical and clinical topics are included in this book, which serve to emphasize the acknowledged and important benefits to be gained from the study of cholesterol and cholesterol-binding proteins within the biomedical sciences and the involvement of cholesterol in several clinical disorders. It is hoped that by presenting this topic in this integrated manner that an appreciation of the fact that there is much more that needs to be taken into account, studied and understood than the widely discussed "bad and good cholesterol" associated, respectively, with the low- and high-density lipoproteins, LDL and HDL. Content Level Professional/practitioner

Preface:

To understand Alzheimera (TM)s disease (AD) is one of the major thrusts of present-day clinical research, strongly supported by more fundamental cellular, biochemical, immunological and structural studies. It is these latter that receive attention within this book. This compilation of 20 chapters indicates the diversity of work currently in progress and summarizes the current state of knowledge. Experienced authors who are scientifically active in their fields of study have been selected as contributors to this book, in an attempt to present a reasonably complete survey of the field. Inevitably, some exciting topics for one reason or another have not been included, for which we can only apologize.

Standardization of terminology is often a problem in science, not least in the Alzheimer field; editorial effort has been made to achieve standardazation between the Chapters, but some minor yet acceptable personal / author variation is still present, i.e. A-amyloid/amyloid-A; AA42/AA1-42/AA1-42!

The book commences with a broad survey of the contribution that the range of available microscopical techniques has made to the study of Alzheimera (TM)s amyloid plaques and amyloid fibrillogenesis. This chapter also serves as an Introduction to the book, since several of the topics introduced here are expanded upon in later chapters. Also, it is significant to the presence of this chapter that the initial discovery of brain plaques, by Alois Alzheimer, utilized light microscopy, a technique that continues to be extremely valuable in present-day AD research. Then follow 19 further chapters dealing with interesting areas of research that have a bearing upon Alzheimera (TM)sdisease. The authors present their own data within the context of a review of related work from others in their field of study.

Transgenic mouse models for AD are increasingly important and widely used, as is the understanding of the enzymology and biochemistry of amyloid A production from the amyloid precursor protein (APP) by the A- and g -secretases, and the non-amyloidogenic APP cleavage products due to a -secreatases. Similarly, discussion of the enzymes responsible for the natural degradation of amyloid-A is included. Oxidative stress in AD and the possible protective role of vitamin E have emerged as highly significant topics. Likewise, the role of the metals, aluminium copper and zinc in AD is thoroughly addressed, along with the possible value of metal chelation. Current concepts as to the fundamental importance of amyloid-A oligomers versus AA fibrillar deposits (diffuse and senile plaques) in the pathogenesis of AD is presented, along with the likely role of tissue and cellular cholesterol in the promotion of AA fibrillogenesis, and Congo red binding to AA fibrils.

Several naturally occurring human proteins have the ability to bind to AA and are found in AD diffuse and senile plaques. Apolipoprotein E4, clusterin (ApoJ) and acetylcholinesterase are considered in depth. The direct effects of AA on neuronal membranes, in terms of neuronal membrane fluidity changes and calcium ion transport are dealt with, then the role of amyloid inhibitors and A-sheet breaking drugs is included. The likely important beneficial effects of the cholesterol-lowering drugs, the statins, in lowering brain AA and consequently the therapeutic prevention of AD by reducing AA deposition in plaquesis discussed thoroughly. Finally, an exciting new concept is advanced, namely the possible significance of phosphorylated AA in Alzheimera (TM)s disease. From in vitro experiments AA phosphorylation appears to increase the proportion of AA oligomeric forms, an observation which correlates with a the higher cytotoxicity of this species, compared to non-phosphorylated AA.

The editors hope that this book will be of interest and value to both medical and scientific research communities working on AD, and to others with a more general interest in the understanding of this devastating neurodegenerative disorder of the elderly.

Prof. J. Robin Harris

Prof. Falk Fahrenholz

University of Mainz

August, 2004

Cellular virology has made tremendous advances in the past decade due to the availability and application of new immunological techniques together with the vast range of biochemical techniques and the continued impact of transmission electron microscopy. The chapters contained in this volume provide significant coverage of the subject of cellular virology as a whole. Considerable overall emphasis is placed upon the membrane biochemistry of viral proteins and glycoproteins within the infected cell. In the opening chapter Edouard Kurstak and his colleagues provide a useful survey on the detection of viral antigens and antibodies by immunoassays. This chapter, with its emphasis on the important role of immunology in present-day virology, sets the scene for the volume. Following this is an exciting presentation from Stefan Hoglund and his colleagues on ISCOMs and immunostimulation with viral antigens. This unique approach is already proving to be of value, particularly in animal virology. A somewhat pharmacological diversion appears in Chapter 3, by Kazukiyo Onodera and his colleagues, in which the biological activity of the damavaricin C derivatives is discussed. This chapter provides a link between the biochemical and the chemotherapeutic approach in cellular virology. Yet another specialist area is covered in Chapter 4 by Otto Schmidt and hnke Schuchmann-Feddersen, who discuss the role of virus-like particles in para site-host interactions of insects. Contributing a strong biomedical emphasis to the volume is the provocative chapter by Abraham Karpas on human leukemia and retroviruses."

This volume of the Subcellular Biochemistry series is the result of the long-standing research interest of the editor in the molecular mechanism underlying Alzheimer's disease and other amyloid diseases, indicated also by the earlier book in the series (Volume 38), devoted to Alzheimer's disease. The broad coverage within the present amyloidogenesis book represents an attempt to collate current knowledge relating to the proteins and peptides involved in most of the known amyloid diseases, together with some amyloid/fibril-forming proteins and peptides that are not involved in diseases. Thus, the range of topics included is comprehensive and furthermore it was thought appropriate to include both basic science and clinical presentation of the subjects under discussion.

This volume and future ones in the series, which is now under new editorship. depart from the pattern established by previous volumes in containing chapters loosely related to one another. It is thus appropriate that each volume should have a relevant subtitle. In the present volume the underlying theme is immu nology and its application to the study of a number of different biochemical systems. Almost inevitably, the study of the cell-surface antigens and glycoproteins of a number of different tissues tends to dominate the contents, but considerable emphasis is also placed on subcellular organelles and enzymes. Undoubtedly, it is the impact of readily available monoclonal antibodies that dominates work in the field. The epitope specificity provided by monoclonal antibodies gives the biochemist a powerful lever with which to probe the location, structure, and function of cellular protein and glycoprotein antigens. A number of the chapters included in this volume have a strong biomedical emphasis. This is indeed intentional, as it is now the policy of the series to cover the more applied aspects ofthe subject, while in no way neglecting more fundamentaltopics in subcellular biochemistry."

The Subcellular Biochemistry series has recently embarked upon an almost encyclopaedic coverage of topics relating to the structure and function of macromolecular complexes (Volumes 82, 83 and 87). The present multi-author text covers numerous aspects of current research into molecular virology, with emphasis upon viral protein and nucleoprotein structure and function. Structural data from cryo-electron microscopy and X-ray crystallography is displayed throughout the book. The 17 chapters in the book cover diverse interesting topics, all currently under investigation, contributed by authors who are active actively involved in present-day research. Whilst structural aspects predominate, there is much consideration of the structure-function relationship. In addition, the book correlates with and extends from Volume 68 of the series "Structure and Physics of Viruses: An Integrated Textbook". This book is directed primarily at professionals that work in the broad field of Structural Biology and will be of particular interest to Structural Virologists. The editors, David Bhella and Robin Harris, have much experience in virology and protein structure, respectively. Dr Bhella is Director of the Scottish Macromolecular Imaging Centre. Professor Robin Harris is the long-standing Series Editor of the Subcellular Biochemistry series. He has edited and contributed to several books in the series.

This volume of the Subcellular Biochemistry series is the result of the long-standing research interest of the editor in the molecular mechanism underlying Alzheimer's disease and other amyloid diseases, indicated also by the earlier book in the series (Volume 38), devoted to Alzheimer's disease. The broad coverage within the present amyloidogenesis book represents an attempt to collate current knowledge relating to the proteins and peptides involved in most of the known amyloid diseases, together with some amyloid/fibril-forming proteins and peptides that are not involved in diseases. Thus, the range of topics included is comprehensive and furthermore it was thought appropriate to include both basic science and clinical presentation of the subjects under discussion.

To understand Alzheimer's disease (AD) is one of the major thrusts of present-day clinical research, strongly supported by more fimdamental cellular, biochemical, immunological and structural studies. It is these latter that receive attention within this book. This compilation of 20 chapters indicates the diversity of work currently in progress and summarizes the current state of knowledge. Experienced authors who are scientifically active in their fields of study have been selected as contributors to this book, in an attempt to present a reasonably complete survey of the field. Inevitably, some exciting topics for one reason or another have not been included, for which we can only apologize. Standardization of terminology is often a problem in science, not least in the Alzheimer field; editorial effort has been made to achieve standardization between the Chapters, but some minor yet acceptable personal / author variation is still present, i. e. P-amyloid/amyloid-P; Ap42/Apl-42/APi. 42! The book commences with a broad survey of the contribution that the range of available microscopical techniques has made to the study of Alzheimer's amyloid plaques and amyloid fibrillogenesis. This chapter also serves as an Introduction to the book, since several of the topics introduced here are expanded upon in later chapters. Also, it is significant to the presence of this chapter that the initial discovery of brain plaques, by Alois Alzheimer, utilized light microscopy, a technique that continues to be extremely valuable in present-day AD research.

In step with the rapid growth of research into the biochemical and functional characterization of the endosome, Volume 19 surveys the recent advances in the methodological aspects of this field. Coverage includes the use of free flow electrophoresis to define endosome subpopulations, the endosomal compartments in rat hepatocytes, the role of endosomes in transmembrane signalling, and six additional articles.

This volume and future ones in the series, which is now under new editorship. depart from the pattern established by previous volumes in containing chapters loosely related to one another. It is thus appropriate that each volume should have a relevant subtitle. In the present volume the underlying theme is immu nology and its application to the study of a number of different biochemical systems. Almost inevitably, the study of the cell-surface antigens and glycoproteins of a number of different tissues tends to dominate the contents, but considerable emphasis is also placed on subcellular organelles and enzymes. Undoubtedly, it is the impact of readily available monoclonal antibodies that dominates work in the field. The epitope specificity provided by monoclonal antibodies gives the biochemist a powerful lever with which to probe the location, structure, and function of cellular protein and glycoprotein antigens. A number of the chapters included in this volume have a strong biomedical emphasis. This is indeed intentional, as it is now the policy of the series to cover the more applied aspects ofthe subject, while in no way neglecting more fundamentaltopics in subcellular biochemistry."

Volume 18 of the Subcellular Biochemistry series, which specializes in various aspects of the biochemistry of the intracellular parasites, was initially proposed by Jose Luis Avila and strongly supported by myself, as Series Editor of Sub cellular Biochemistry. Considerable assistance was received from Professor Frank Wunderlich (University of Dusseldorf) and more particularly from Dr. Michael Miles (London School of Hygiene and Tropical Medicine) during the compilation of the list of possible chapters. Our initial aim was to present a comprehensive survey of this broad field of study. Although some interesting topics have been lost due to authors backing out late in the production schedule of the book, the manuscripts that were submitted have provided a useful over view of the subject, with notable strength within the field of Leishmania. The 13 chapters of the book have been grouped according to subject. The first five chapters deal with Leishmania and are followed by two chapters on Try ponosoma cruzi, two on the malarial parasites, and two on the Coccidia. The fmal two chapters cover the Microsporidia and chemotherapy, respectively.

Cellular virology has made tremendous advances in the past decade due to the availability and application of new immunological techniques together with the vast range of biochemical techniques and the continued impact of transmission electron microscopy. The chapters contained in this volume provide significant coverage of the subject of cellular virology as a whole. Considerable overall emphasis is placed upon the membrane biochemistry of viral proteins and glycoproteins within the infected cell. In the opening chapter Edouard Kurstak and his colleagues provide a useful survey on the detection of viral antigens and antibodies by immunoassays. This chapter, with its emphasis on the important role of immunology in present-day virology, sets the scene for the volume. Following this is an exciting presentation from Stefan Hoglund and his colleagues on ISCOMs and immunostimulation with viral antigens. This unique approach is already proving to be of value, particularly in animal virology. A somewhat pharmacological diversion appears in Chapter 3, by Kazukiyo Onodera and his colleagues, in which the biological activity of the damavaricin C derivatives is discussed. This chapter provides a link between the biochemical and the chemotherapeutic approach in cellular virology. Yet another specialist area is covered in Chapter 4 by Otto Schmidt and hnke Schuchmann-Feddersen, who discuss the role of virus-like particles in para site-host interactions of insects. Contributing a strong biomedical emphasis to the volume is the provocative chapter by Abraham Karpas on human leukemia and retroviruses."

The last several years have been a landmark period in the ubiquitin field. The breadth of ubiquitin's roles in cell biology was first sketched, and the importance of ubiquitin-dependent proteolysis as a regulatory mechanism gained general acceptance. The many strands of work that led to this new perception are re counted in this book. A consequence of this progress is that the field has grown dramatically since the first book on ubiquitin was published almost a decade ago M. Rechsteiner (ed. ), Ubiquitin, Plenum Press, 1988]. In this span, students of the cell cycle, transcription, signal transduction, protein sorting, neuropathology, cancer, virology, and immunology have attempted to chart the role of ubi quit in in their particular experimental systems, and this integration of the field into cell biology as a whole continues at a remarkable pace. We hope that for active researchers in the field as well as for newcomers and those on the fence, this book will prove helpful for its breadth, historical perspective, and practical tips. Structural data are now available on many of the components of the ubiquitin pathway. The structures have provided basic insights into the unusual biochemical mechanisms of ubiquitination and proteasome-mediated proteolysis. Because high-speed computer graphics can convey structures more effectively than print media, we have supplemented the figures of the book with a Worldwide Web site that can display the structures in a flexible, viewer-controlled format."

This series of books, devoted to aspects of blood cell biochemistry, development, immu nology, and ultrastructure, has evolved and separated from the long-established Plenum series Subcellular Biochemistry. It is the intention of these volumes to draw together related areas of investigation and to provide, in the fullness of time, complete coverage of this rapidly advancing important biomedical discipline. Both fundamental and medically applied topics, dealing with normal and pathological cells, will be included. This, the first volume of the series, contains a diverse collection of chapters, all of which relate to erythroid cells. The range of material included is extremely broad and the authors have used contrasting technical approaches, both within their personal experimen tal studies and within their manuscripts. This has led to the production of a very interest ing compilation, which does, nevertheless, possess a strong overall thematic unity. As with all edited volumes, some topics of importance and interest are not included. This may be because of oversight on my part, as editor, or because the authors originally selected failed to submit their manuscript by the agreed-upon submission date. For these omissions I take full responsibility and trust that at least some of the topics omitted, for instance membrane cation transport systems, will be covered within a future volume of the series. This book commences with two chapters of a developmental nature."

Blood Cell Biochemistry was initially conceived as part of the Plenum series Subcellular Biochemistry, from which it has developed into a separate series. The present volume is devoted primarily to contributions on megakaryocytes and platelets and, to a lesser extent, to macrophages and eosinophils. The book does not attempt a rigorous or total coverage of the particular topics; it represents the areas of current scientific activity and interest that were selected by the editor at the commencement of this project. In general, the approach has been similar to that adopted for Volume 1 of the series (Erythroid Cells); the same approach will be followed subsequently in Volume 3 (Lymphocytes and Granulocytes). This book opens with a developmentally oriented chapter by Janine Breton-Gorius on megakaryocyte maturation and platelet release in normal conditions, which serves to set the scene ultrastructurally for much of the data that follow. The biosynthesis and process ing of platelet glycoproteins in megakaryocytes is dealt with by Alain Duperray and his colleagues, and thereby provides an in-depth biochemical survey of the megakaryocyte. The applications and strengths of crossed immunoelectrophoresis for the study of platelet membrane proteins is then covered by Simon Karpatkin, and a detailed account of the heredity disorders of platelet function is provided by Francine Rendu and Evelyne Dupuy."

In step with the surge of interest in the endoplasmic reticulum, the current volume takes an integrated look at this functionally diverse organelle. Coverage includes protein translocation and export, lipid metabolism, antigen presentation, and many other subjects, gleaned from such diverse fields as cell biology, enzymology and membrane biochemistry, immunology, and signal transduction.