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In December 1992, the Department of Pure and Applied Biochemistry at the Chemical Center in Lund, Sweden, organized an international meeting, the Mosbach Symposium on Biochemical Technology, to celebrate the 60th birthday of professor Klaus Mosbach, one of the founders of modern biotechnology. The history of Pure and Applied Biochemistry had its start in 1970, a couple of years after the foundation of the Chemical Center. Klaus Mosbach has been its professor and head of Pure and Applied Biochemistry since its start. During the 1980's he also maintained a professorship at the ETH in Zurich, Switzerland. Professor Mosbach is internationally well-known and he has world-leading position within the field of immobilization of bioactive substances and cells as well as affinity chromatography. In 1990, Professor Mosbach was awarded the gold medal by the Royal Swedish Academy of Engineering Sciences for his contributions to biotechnology, especially on the immobilization of bioactive substances.The research activities of the Department of Pure and Applied Biochemistry cover a broad area, such as affinity and separation techniques, bioprocess control, biosensors, development of new carriers and new immobilization procedures for small molecules as well as proteins and cells, including animal and plant cells, gene technology, processes based on immobilized biocatalysts, and construction of organic polymers with enzyme-like properties. The hallmark of the department is its diversified research that generates considerable synergistic effects that are manifested by many new techniques and concepts emanating from the laboratory during the last 20 years. Several of these are marketed by various biotechnology companies. At this meeting we therefore arranged for some of the world's leading experts in biochemistry and biotechnology to give lectures. The topics covered comprise enzyme technology, immobilization of enzymes and cells, abzymes, metabolic engineering, biosensors, and molecular recognition. The official gift from the symposium committee and the participants is this "Festschrift" which covers several important fields of research within the area of biochemical technology. We have made a very unusual approach and have let the "hero of the occasion" present the history of his research.

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Advances in Developmental Biology was launched as a series by JAI Press in 1992 with the appearance of Volume 1. This series is inextricably linked to the companion series, Advances in Developmental Biochemistry, that was launched at the same time. As stated in the Preface to Volume 1: "Together the two series will provide annual reviews of research topics in developmental biology/biochemistry, written from the perspectives of leading investigators in these fields. It is intended that each review draw heavily form the author's own research contributions and perspective. Thus, the presentations are not necessarily encyclopedic in coverage, nor do they necessarily reflect all opposing views of the subject." Volume 2 of the series follows these same guidelines.

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Both eukaryotic and prokaryotic cells depend strongly on the function of ion pumps present in their membranes. The term ion pump, synonymous with active ion-transport system, refers to a membrane-associated protein that translocates ions uphill against an electrochemical potential gradient. Primary ion pumps utilize energy derived from chemical reactions or from the absorption of light, while secondary ion pumps derive the energy for uphill movement of one ionic species from the downhill movement of another species.

In the present volume, various aspects of ion pump structure, mechanism, and regulation are treated using mostly the ion-transporting ATPases as examples. One chapter has been devoted to a secondary ion pump, the Na+-Ca2+ exchanger, not only because of the vital role played by this transport system in regulation of cardiac contractility, but also because it exemplifies the interesting mechanistic and structural similarities between primary and secondary pumps.

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Protein Structural Biology in Biomedical Research, Part A

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Recent advances in protein structural biology, coupled with new developments in human genetics, have opened the door to understanding the molecular basis of many metabolic, physiological, and developmental processes in human biology. Medical pathologies, and their chemical therapies, are increasingly being described at the molecular level. For single-gene diseases, and some multi-gene conditions, identification of highly correlated genes immediately leads to identification of covalent structures of the actual chemical agents of the disease, namely the protein gene products. Once the primary sequence of a protein is ascertained, structural biologists work to determine its three-dimensional, biologically active structure, or to predict its probable fold and/or function by comparison to the data base of known protein structures. Similarly, three-dimensional structures of proteins produced by microbiological pathogens are the subject of intense study, for example, the proteins necessary for maturation of the human HIV virus. Once the three-dimensional structure of a protein is known or predicted, its function, as well as potential binding sites for drugs that inhibit its function, become tractable questions. The medical ramifications of the burgeoning results of protein structural biology, from gene replacement therapy to "rational" drug design, are well recognized by researchers in biomedical areas, and by a significant proportion of the general population. The purpose of this book is to introduce biomedical scientists to important areas of protein structural biology, and to provide an insightful orientation to the primary literature that shapes the field in each subject.

The chapters in this volume cover aspects of protein structural biology which have led to the recognition of fundamental relationships between protein structure and function.

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The rapid expansion of the area of free radical biology in the last 25 years has occurred within a framework of assumptions and preconceived notions that has at times directed the course of this movement. The most dominant of these notions has been the view that free radical production is without exception a bad thing, and that the more efficient our elimination of these toxic substances, the better off we will be. The very important observation by Bernard Babior and colleagues in 1973 that activated phagocytes produce superoxide in order to kill micro organisms, served to illustrate that constructive roles are possible for free radicals. For many in the field, however, this merely underscored the deadly nature of oxygen-derived radicals, both from the microbe's point of view and from the host's as well. (Phagocyte-produced superoxide is responsible in part for the tissue injury manifested as inflammation. See Harris and Granger, Chapter 5, and Leff, Hybertson and Repine, Chapter 6.)
Mother Nature, however, has a penchant for being able to make a silk purse from a sow's ear. If one is dealt a bad hand, one must simply make the best of it. After two decades of focusing on the destructive side of free radicals, the last few years have begun to reveal a new and finer perspective on free radical metabolism - a role in regulation of cellular function (see Schulze-Osthoff and Baeuerle, Chapter 2). Evidence from a number of sources suggests that an increase in the oxidative status of cell encourages that cell to grow and divide. Increasing the expression of mangnese superoxide dismutase can suppress the malignant phenotype of melanon cells (see Oberley and Oberley, Chapter 3). Oxidative stress beyond a certain poitosis (from the Greek, literally "to fall apart"). Is this suicide response an evolutionary fail-safe device to curtail tumorogenesis? Does oxidative stress-induced apoptosis account for the loss of immune cells in AIDS (see Flores and McCor Chapter 4)?
This volume attempts to present the spectrum of roles, both good and bad played by active oxygen species as understood at this point in the evolution of this field of free radical biology.

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This series provides annual reviews of research topics in developmental biology/biochemistry, written from the perspectives of leading investigators in these fields. This volume of Advances in Developmental Biochemistry consists of seven chapters that review specific aspects of development in several different organisms including mollusks, flies and mice.

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One of the mysteries of mammalian reproduction is the physiologic process that determines the length of gestation. The proper timing of birth ensures that the young individual is sufficiently developed to survive and adapt in the extrauterine environment, and that the mother is capable to provide nutrition and protection to the newborn. This volume summarizes new knowledge obtained by many researchers seeking to unravel the compile mechanisms that contribute to the maintenance and termination of pregnancy. The most important common goal of these efforts is to reduce the incidence of preterm birth, which is the leading cause of perinatal morbidity and mortality in numerous countries.

Separate chapters are devoted to the best-studied animal models of parturition. In sheep, the fetus is in control of the timing of its own birth, while in avian species, oviposition is evidently determined by the female laying the feritlized egg. In humans and non-human primates, the roles of the fetus and the mother are more balanced, and involve a complicated and poorly understood interplay between the mother, the fetus, and the placenta. Some major aspects of these interactions, such as trophoblast function, myometrial contractility, and the endocrine-paracrine systems, are discussed in further chapters.

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A large number of newly-synthesized polypeptides must cross one or several intracellular membranes to reach their functional locations in the eukaryotic cell. The mechanisms of protein trafficking, in particular the post-translational targeting and membrane translocation of proteins, are of fundamental biological importance and are the focus of intensive research world-wide. For more than 15 years, mitochondria have served as the paradigm organelle system to study these processes. Although key questions, such as how precisely proteins cross a membrane, still remain to be answered, exciting progress has been made in understanding the basic pathways of protein import into mitochondria and the components involved. In addition to a fascinating richness and complexity in detail, the analysis of mitochondrial protein import has revealed mechanistic principles of general significance: Major discoveries include the demonstration of the requirement of an unfolded state for translocation and of the essential role of molecular chaperones on both sides of the membranes in maintaining a translocation-competent conformation and in protein folding after import. It is becoming clear how a polypeptide chain is "reeled" across the membrane in  an ATP-dependent process by the functional cooperation of membrane proteins, presumably constituting part of a transmembrane channel, with peripheral components at the trans-side of the membrane.In this volume, eminent experts in the field take the time to review the central aspects of mitochondrial biogenesis. The logical order of the 16 chapters is determined by the sequence of steps during protein import, starting with the events taking place in the cytosol, followed by the recognition of targeting signals, the translocation of precursor proteins across the outer and inner membranes, their proteolytic processing and intramitochondrial sorting, and finally their folding and oligomeric assembly. In addition, the mechanisms involved in the export of mitochondrially encoded proteins as well as recent advances in understanding the division and inheritance of mitochondria will be discussed.

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Molecular and Cellular Biology of Bone, Part A

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These volumes differ from the current conventional texts on bone cell biology. Biology itself is advancing at breakneck speed and many presentations completely fail to present the field in a truly modern context. This text does not attempt to present detailed clinical descriptions. Rather, after discussion of basic concepts, there is a concentration on recently developed findings equally relevant to basic research and a modern understanding of metabolic bone disease. The book will afford productive new insights into the intimate inter-relation of experimental findings and clinical understanding. Modern medicine is founded in the laboratory and demands of its practitioners a broad scientific understanding: these volumes are written to exemplify this approach. This book is likely to become essential reading equally for laboratory and clinical scientists.

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Heart failure continues to be a major public health problem in the United States with close to half a million new cases diagnosed each year. Moreover, deaths from heart failure are on the increase, in part because of advances in the treatment of other fatal diseases, and in part from the prevalence of lifestyles indifferent to the risk factors for heart disease. This is not to say that no progress has been made in the treatment of heart failure. While for many years treatment was confined to the management of the symptoms, in recent years with the advent of ACE inhibitor and  blacker therapies, real improvements in cardiac function and life expectancy have been achieved (Volume 4B, Leier). On a more basic level, enormous advances have been made in describing many of the changes in structure and function of the heart and the parallel neurohumoral and circulatory adaptations that occur during the onset of failure. These advances have been made not only by using various animal models of heart failure, but also using fresh failing human heart tissue, which has become readily available for experimental investigation since the advent of cardiac transplantation.Understanding the significance of many of these changes that occur during the transition to failure and the role they play in the etiology of failure is, however, a much more difficult task. These are exciting times in heart failure research. It is as though many of the pieces of the jigsaw puzzle are available but the puzzle has yet to be assembled. The objective of these volumes is to bring together some advances that have been made in recent years in defining one aspect of the failing heart, that is, the role of altered metabolism, in order to facilitate assembly of the puzzle.

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Volume 3 of Advances in Developmental Biology and Biochemistry consists of five chapters that review specific aspects of mammalian, fly, and ascidian development. In Chapter 1, J. Campos-Ortega discusses mechanisms of neurogenesis in Drosophila, with special attention given to the process of separation of epidermal and neural progenitor cells. In Chapter 2, D. Rappolee and Z. Werb discuss the role of growth factors in early mammalian embryos and compare genes used in mouse with those used in Xenopus and chick. In Chapter 3, E. Linney and A.-S. LaMantia discuss the range of malformations resulting from retinoid teratogenesis, the molecular biology of retinoids, the use of transgenic mice to study retinoid signaling, and differentiation of the CNS in the context of retinoid signaling. In Chapter 4, E. Gavis and R. Lehmann discuss pathways and components involved in RNA localization and targeting in Drosophila oocytes. In Chapter 5, W. Jeffery discusses the use of actin as a tissue-specific marker in studies of ascidian development and evolution

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This 2nd revised edition equals the popular 1st edition in providing a clear and detailed overview of cell culture. It presents information on:
characteristics of cultured cells; culture vessels; glassware preparation and sterilisation techniques; subculturing; primary cells; cell culture media; techniques; contamination; the cell cycle; cell synchronisation; use of radioactive isotopes in cell culture; cell mutants and cell hybrids; viruses; and differentiation in cell cultures.

Reviews on the 1st edition:

``.. the book provides an excellent insight into the way cell culture techniques can be employed in the analytical study of cellular biology.'' - Trends in Biochemical Sciences

``It is well written in a concise, easy-to-read style which stimulates the interest of the reader....'' - Science Tools

``A useful handbook on principles and practice.'' - Immunology Today

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Volume 4 of Advances in Developmental Biology and Biochemistry consists of five chapters that review specific aspects of fly and mammalian development. In Chapter 1, Y. Mishina and R. Behringer discuss various aspects of Mullerian-inhibiting substance (MIS) in mammals, from a brief history of its discovery to recent studies of the MIS gene in transgenic and knock-out animals. In Chapter 2, C. Rushlow and S. Roth discuss the role of the dpp-group genes in dorsoventral patterning of the Drosophila embryo. In Chapter 3, M. Yip and H. Lipshitz discuss the terminal (asegmental termini) gene hierarchy of Drosophila and the genetic control of tissue specification and morphogenesis. In Chapter 4, R. Bachvarova discusses induction of mesoderm and the origin of anterior-posterior polarity in the mouse embryo, using the frog embryo as a paradigm. In Chapter 5, P. Vogt discusses human Y chromosome function in male germ cell development.  <br>

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Genetic Aberrancies and Neurodegenerative Disorders presents critical reviews and emerging findings concerning the roles of genetic mutations and polymorphisms in the pathogenesis of a range of neurological disorders including Alzheimer's and Parkinson's diseases, trinucleotide repeat disorders, stroke, epilepsy and others.  This volume, written by leading experts, brings together fundamental information concerning the roles of inherited traits in the pathogenesis of different neurodegenerative disorders.  In addition to providing a catalogue of the known genetic alterations that are linked to specific neurodegenerative disorders, the chapters detail the current state of understanding of the cellular and biochemical mechanisms whereby the genetic aberrancies lead to neuronal dysfunction and degeneration.   The emerging picture of each disorder, painted by pathological, biochemical and molecular brushes, suggests that they share key mechanisms including increased levels of oxidative stress, perturbed ion homeostasis, mitochondrial dysfunction and apoptotic proteolytic cascades.  The existence of specific molecular defects  provides the opportunity to design experiments that can establish the precise pathogenic mechanism of a specific mutation or genetic risk factor.   The value of this approach is exemplified by recent studies of how mutations in Cu/Zn-superoxide dismutase cause amyotrophic lateral sclerosis and how presenilin mutations result in early-onset Alzheimer's disease.  A theme developed among the different chapters is that events that occur during aging predispose neurons to genetic aberrancies that promote degenerative cascades, and that specific genetic defects exert their influence on particular populations of neurons in a disorder-specific manner.  The chapters in this volume will stimulate readers to generate new hypotheses concerning the pathogenic mechanisms of genetic aberrancies that can be experimentally tested.<br>

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One prerequisite for the evolution of multicellular organisms was the invention of mechanisms by which cells could adhere to one another. At some point in our history, dividing cells no longer went their separate protozoic ways in the primordial oceans, but instead found that by maintaining an association, by sticking together but not fusing, numerous evolutionary advantages became possible. The subsequent development of specialized tissues and organs depended on the elaboration of incredibly sophisticated, regulatable cell-to-cell adhesion mechanisms which are known to operate in biological processes as diverse as the growth of the embryo, the immune response, the establishment of connections between nerve cells, and arteriosclerosis, to name just a few. Although we can only guess at the ancestral mechanisms that fostered the first primitive intercellular unions, some one billion years ago, we now recognize contemporary molecular "themes" with presumably ancient origins that mediate cell-cell interactions.

The chapters in this book serve as useful, thought-provoking, but not exhaustive, commentaries on contemporary topics within the broad field of cell adhesion. If the reader detects a slight tilt toward those adhesion molecules that function in the nervous system, this is merely a reflection of this editor's interests, biases, and of course, limitations.

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The aim of "The Adhesive Interaction of Cells" has been to assemble a series of reviews by leading international experts embracing many of the most important recent developments in this rapidly expanding field. The purpose of all biological research is to understand the form and function of living organisms and, by comprehending the normal, to find explanations and remedies for the abnormal and for disease conditions. The molecules involved in cell adhesion are of fundamental importance to the structure and function of all multicellular organisms. In this book, the contributors focus on the systems of vertebrates, especially mammals, since these are most relevant to human disease. It would have been equally possible to concentrate on developmental processes and adhesion in lower organisms.
A major function of adhesion molecules is to bind cells to each other or to the extracellular matrix, but they are much more than "glue". Adhesions in animal tissues must be dynamic-forming, persisting, or declining in regulated fashion- to facilitate the mobility and turnover of tissue cells. Moreover, the majority of adhesion molecules are transmembrane molecules and thus provide links between the cells and their surroundings. This gives rise to another major function of adhesion molecules, the capacity to transduce signals across the hydrophobic barrier imposed by the plasma membrane. Such signal transduction is crucially important to many aspects of cellular function including the regulation of cell motility, gene expression, and differentiation.
The work in this book progresses through four sections. Part I discusses the four major families of adhesion molecules themselves, the integrins (Green and Humphries), the cadherins (Stappert and Kemler), the selectins (Tedder et al.) and the immunoglobulin superfamily (Simmons); part 2 considers junctional complexes involved in cell interactions: focal adhesions and adherens junctions (Ben Ze'ev), desmosomes (Garrod et al.), and tight junctions (Citi and Cordenonsi). The signaling role of adhesion molecules is the focus of part 3, through integrins and the extracellular matrix (Edwards and Streuli), through platelet adhesion (Du and Ginsberg), and in the nervous system (Hemperley). In part 4, the aim is to show how adhesive phenomena contribute to important aspects of cell behavior and human health. Leukocyte trafficking (Haskard et al.), cancer metastasis (Marshall and Hart), cell migration (Paleck et al.), and implantation and placentation (Damsky et al.) are the topics considered in depth.
The different sections are, of course, not mutually exclusive: it is both undesirable and impossible to separate structure from function when considering cell adhesion. Each chapter has its unique features, but some overlap is both invevitable and valuable since it provides different perspectives on closely related topics. We hope that the whole contributes a valuable and stimulating consideration of this important topic.

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David Garrod, A.J. North, M.A.J. Chidgey

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Myocardial Preservation and Cellular Adaptation

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Living organisms exhibit specific responses when confronted with sudden changes in their environmental conditions. The ability of the cells to acclimate to their new environment is the integral driving force for adaptive modification of the cells. Such adaptation involves a number of cellular and biochemical alteration including metabolic homeostasis and reprogramming of gene expression. Changes in metabolic pathways are generally short-lived and reversible, while the consequences of gene expression are a long-term process and may lead to permanent alternation in the pattern of adaptive responses.

The heart possesses remarkable ability to adapt itself against any stressful situation by increasing resistance to the adverse consequences. Stress composes the foundation of many degenerative heart diseases including atherosclerosis, spasm, thrombosis, cardiomyopathy, and congestive heart failure. Based on the concept that excessive stress may play a crucial role in the pathogenesis of ischemic heart disease, attempts were made to design methods for preventing of myocardial injury. Creation of stress reactions by repeated ischemia and reperfusion or subjecting the hearts to heat or oxidative stress enables them to meet the future stress challenge. Repeated stress exposures adapt the heart to withstand more severe stress reactions probably by upregulating the cellular defense and direct accumulation of intracellular mediators, which presumably constitute the material basis of increased adaptation to stress. Thus, the powerful cardioprotective effect of adaptation is likely to originate at the cellular and molecular levels that compose fundamental processes in the prophylaxis of such diseases.

Volume six of the Advances in Organ Biology series contains state-of-the-art reviews on myocardial preservation and cellular adaptation from the leading authorities in this subject.

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Volume 3 of Advances in Developmental Biology and Biochemistry consists of five chapters that review specific aspects of mammalian and fly development. In Chapter 1, D. Chapman and D. Wolgemuth discuss the role of protein kinases, especially tyrosine-and serine/threonine kinases, in regulating cell cycle events during mammalian gametogenesis. IN Chapter 2, M. Lundell and J. Hirsh discuss the regulation of the DOPA decarboxylase gene during Drosophila development. DO PA decarboxylase is a key enzyme in biogenic amine biosynthesis and its expression is subject to both transcriptional and post-transcriptional regulation. In Chapter 3, S. Potter discusses the role of homeobox genes as master switches determining the developmental destinies of groups of cells during murine development. In Chapter 4, G. Cooper discusses the expression and function of the c-mos proto-oncogene in mammalian germ cells where it plays a central role in regulating the meiotic cell cycle. In Chapter 5, F. Beermann, R. Gan, and G. Schutz discuss the regulation of pigmentation during mammalian development, with emphasis on the production of melanin in mouse melanocytes.

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Few cells conform to the stereotype of the spherical blob hastily scribbled on chalkboards and, regrettably, sometimes even displayed prominently in textbooks. Instead, real cells display a remarkable degree of structural and functional asymmetry. In modern cell biological parlance, this asymmetry has come to be lumped under the general heading of "cell polarity". Cell polarity is by no means restricted to the cells of tissues and organs, but can also be displayed by cells that lead a more solitary existence. The amazing extent to which cell morphology is correlated with function has long been a source of inspiration for biologists. Today the fascination continues unabated in the field of cell polarity, where it is fueled by an ever-deepening appreciation for the ways that fundamental cellular processes, such as membrane trafficking and cytoskeleton assembly, contribute to the establishment and maintenance of cell polarity. In the ensuing chapters, a collection of experts will summarize and interpret the findings obtained from basic research on cell polarity in a diverse array of experimental systems. <br>

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There has been an enormous advance in our understanding of the regulation of the cell division cycle in the last five years. The leap in understanding has centered on the cell cycle control protein p34cdc2 and its congeners and on the cyclins. The most important insight to emerge has been that cell cycle control mechanisms and their participating proteins are very well-conserved through evolution. This has created a spectacular growth in knowledge as data from one organism have been readily applied to another. In this volume, there are sea urchin and frog eggs, as well as mammalian cells and yeast. There is also an illustration of how fruitful the genetic approach can be in other organisms than yeast with a chapter on Aspergillus nidulans. The cell cycle kinase has been well-characterized and has also been well-exposed in numerous proceedings volumes and collections. In this issue of Advances in Molecular Cell Biology, the cell cycle kinase is ever present, but in the early chapters it has a supporting role. Center stage are the regulatory mechanisms that control the kinase. The contribution that the centrosome (the organelle of cell division) makes to cell cycle regulation are described. The part played by calcium and calcium-controlled regulatory proteins is emphasized. The importance of phosphatase as well as kinase activity to cell cycle regulation is stressed. The last words are reserved for the mitotic kinase: the last chapters describe its effects and its regulation in cell-free systems.