Search

Now in its 2nd edition, this manual describes laboratory methodology for the diagnosis of inherited metabolic diseases. The book describes a spectrum of tests, from simple screening methods via classical methods that are operational in most (if not all) biochemical laboratories, to analytical methods that depend on technologies that very few are currently employing in their labs, but are certainly the functional techniques in a biochemical laboratory in this post-genomics era. Each chapter is sufficiently detailed to be self-contained, thus enabling laboratory specialists to adopt the method in their own laboratory and obviating the need for additional methods or references. The second updated edition of the book is unique in that it is the first of its kind to be published in the last 13 years, and individual chapters have been developed by experts in the field citing both established and cutting-edge (omics) technology. Thus, it is an indispensable resource for researchers and clinicians working on the field of inherited metabolic diseases and those interested in laboratory diagnoses.

This book presents the latest cutting-edge research on phase separation. It discusses the benefits and risks of phase separation for living cells from the perspectives of physics, chemistry, biology, and medicine.Phase separation is a physico-chemical process that induces a single solution of solvent and intrinsically disordered proteins (IDPs) to separate into two phases, one phase containing only solvent and the other containing IDPs in the solvent. A key molecule in phase separation is the intrinsically disordered region (IDR) proteins (IDPs), mostly comprised of RNA-binding proteins (RBPs). One of the major roles of phase separation is to generate condensates, membrane-less organelles including stress granule, Cajal body, and nucleolus.Biological actions of phase separation in various aspects of science have received increasing attention in recent years. The book consists of four parts; Part I on physics and chemistry includes topics on structural biology of RBP FUS/TLS and chaperone for phase separation, computational approach of phase separation, and chemistry of G-quadruplex of DNA and RNA. Part II on molecular biology presents molecular mechanism of IDR sequence phase separation and potential cellular function of these labile fibers, formation of membrane-less organelles, and roles of noncoding RNAs in phase separation. Part III on biology covers topics from nuclear pore complex, developmental biology regarding force-dependent remodeling, and neurobiology and higher order brain functions. Finally, Part IV on medicine presents condensates and cancer therapy, pathogenesis of neurodegenerative diseases based on IDPs, and responses of microglia to amyloid. The last chapter highlights the latest topic on how the SARS-Cov-2 virus takes advantage of phase separation for its infections.This book brings together the studies of phase separation in each area in a single volume. The comprehensive approach provides new insights to the research andwill benefit the readers by responding to the emerging needs for understanding phase separation.

This book follows up the debate on the future of science and technology at the Curious2022 – Future Insight Conference, the second event in this conference series initiated on the occasion of Merck's 350th anniversary. In the chapters, some of the world's top scientists, managers and entrepreneurs explore breakthrough technologies and how they can be applied to make a better world for humanity. The book begins with an introduction to the vision of the conference “United by science for a better tomorrow” and the impacts caused by the pandemic, highlighting the importance of gathering like-minded people to discuss and support the advancement of science and technology for the benefit of humanity. In the first part of the book, readers will also find a chapter written by the Executive Board of Merck KGaA discussing the importance of curiosity for innovation and an overview of the company's contribution in the areas of life sciences, healthcare andelectronics forward-moving the scientific discovery. The second part of the book offers insights of some of the scientific topics discussed at the conference, and particular attention is given to new therapies and sustainability. In the final part of the book, readers will find some thoughts on ethical principles guiding our application of science and technology to create a bright future for humanity, and diverse perspectives on topics such as health, life sciences, nutrition, material sciences, digitalization, AI, energy, mobility, space flight, robotics, the secrets of the human mind and new ways of working together. Given its interdisciplinary appeal, the book will inspire curiosity in a wide readership, from scholars and researchers to professionals with an interest in exploring the future of science and technology, solving the problems of today, and paving the way for a better tomorrow. Chapters “From a 350th Anniversary to a Global Movement: United by Science for a Better Tomorrow” and “ Advancing Human Progress as a Twenty-First-Century Science and Technology Pioneer” are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book provides detailed and updated knowledge about medically important ‘Big Four'venomous snakes of India (Indian spectacled cobra, Indian common krait, Indian Russell's viper, and Indian saw-scaled viper). This book essentially covers the snakebite problem in the world with particular reference to Asia and India. It discusses the evolution and systematics of venomous snakes, emphasizing ‘Big Four'venomous snakes of India; the evolution and composition of venoms determined by traditional biochemical and modern proteomic analyses. It also describes the pharmacological properties of enzymatic and non-enzymatic toxins of ‘Big Four'venomous snakes of India. Different chapters discuss exciting topics such as species-specific and geographical differences in venom composition and its impact on pathophysiology and clinical manifestations of snakebite envenomation in India, biomedical application of Indian snake venom toxins; production and quality assessment of commercial antivenom,prevention, and treatment of snakebite in India, adverse effects of antivenom including strategies to combat antivenom reactions inpatient.This book caters to toxinologists, pharmacologists, zoologists, antivenom manufacturers, biochemists, clinicians, evolutionary biologists, herpetologists, and informed non-specialists interested to know about the Indian snake venoms.

This book provides a comprehensive description of sterols and their novel biological roles in mammalian signaling, the book covers their biosynthesis and structure, describes sterol receptor -mediated actions, their tissue distribution and their role in disease. It offers insight into new research findings, focusing specifically on novel discoveries in bile acid and oxysterol signaling, including the lanosterol-to-cholesterol intermediates. Special attention is paid on the sex distribution of these sterols (male or female) and their sexually dimorphic roles in mammalian species, such as human, rat and mouse. Since sterols and drugs (xenobiotics) use many identical receptor-mediated signaling pathways, the book will be interesting for researchers working on the cross-road of endogenous and xenobiotic metabolism, it is intended for advanced students and scientists in molecular biology and biochemistry as well as for medical doctors in hepatology.

This book serves as an introduction to protein structure and function. Starting with their makeup from simple building blocks, called amino acids, the 3-dimensional structure of proteins is explained. This leads to a discussion how misfolding of proteins causes diseases like cancer, various encephalopathies, or diabetes. Enzymology and modern concepts of enzyme kinetics are then introduced, taking into account the physiological, pharmacological and medical significance of this often neglected topic. This is followed by thorough coverage of hæmoglobin and myoglobin, immunoproteins, motor proteins and movement, cell-cell interactions, molecular chaperones and chaperonins, transport of proteins to various cell compartments and solute transport across biological membranes. Proteins in the laboratory are also covered, including a detailed description of the purification and determination of proteins, as well as their characterisation for size and shape, structure and molecular interactions. The book emphasises the link between protein structure, physiological function and medical significance.This book can be used for graduate and advanced undergraduate classes covering protein structure and function and as an introductory text for researchers in protein biochemistry, molecular and cell biology, chemistry, biophysics, biomedicine and related courses.About the author:Dr. Buxbaum is a biochemist with interest in enzymology and protein science. He has been working on the biochemistry of membrane transport proteins for nearly thirty years and has taught courses in biochemistry and biomedicine at several universities.

The series Structure and Bonding publishes critical reviews on topics of research concerned with chemical structure and bonding. The scope of the series spans the entire Periodic Table and addresses structure and bonding issues associated with all of the elements. It also focuses attention on new and developing areas of modern structural and theoretical chemistry such as nanostructures, molecular electronics, designed molecular solids, surfaces, metal clusters and supramolecular structures. Physical and spectroscopic techniques used to determine, examine and model structures fall within the purview of Structure and Bonding to the extent that the focus is on the scientific results obtained and not on specialist information concerning the techniques themselves. Issues associated with the development of bonding models and generalizations that illuminate the reactivity pathways and rates of chemical processes are also relevant.The individual volumes in the series are thematic. The goal of each volume is to give the reader, whether at a university or in industry, a comprehensive overview of an area where new insights are emerging that are of interest to a larger scientific audience. Thus each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years should be presented using selected examples to illustrate the principles discussed. A description of the physical basis of the experimental techniques that have been used to provide the primary data may also be appropriate, if it has not been covered in detail elsewhere. The coverage need not be exhaustive in data, but should rather be conceptual, concentrating on the new principles being developed that will allow the reader, who is not a specialist in the area covered, to understand the data presented. Discussion of possible future research directions in the area is welcomed. Review articles for the individual volumes are invited by the volume editors.Readership: research scientists at universities or in industry, graduate studentsSpecial offer for all customers who have a standing order to the print version of Structure and Bonding, we offer free access to the electronic volumes of the Series published in the current year via SpringerLink.

With contributions by numerous experts

Two-dimensional electrophoresis is the central methodology in proteome research, and the state of the art is described in detail in this text, together with extensive coverage of the detection methods available. Sufficient detail is given to allow the readers to apply these technologies to their own particular requirements.

Burgeoning research into marine natural products during the past two decades has in no small measure been due to an heightened and world-wide interest in the ocean, to the development of new sophisticated computer-driven instrumentation, and to major advances in separation science. Organic chemists have been fully aware that processes in living systems occur in an aqueous medium. Nevertheless, the chemists who have specialized in the study of small molecules have found it expedient to use organic rather than aqueous solvents for the isolation and manipulation of secondary metabolites. The emergence of new chromatographic techniques, the promise of rewarding results, not to mention the relevance of polar molecules to life itself, have contributed to a new awareness of the importance of organic chemistry in an aqueous medium. The first chapter in Volume 2 of Bioorganic Marine Chemistry reflects the growing interest and concern with water-soluble com­ pounds. Quinn, who pioneered the separation of such molecules, has contributed a review which closely links techniques with results and is based on practical experience. The second chapter, by Stonik and Elyakov, examines the vast chemical literature of the phylum Echinodermata - over one fourth of it in difficulty accessible Russian language publications. The Soviet authors evaluate the data for their suitability as chemotaxonomic markers.

The first three chapters of Vol. 3 of Bio-organic Marine Chemistry deal with the chemistry and function of peptides. Chapter 1 by Ireland and coworkers serves as an introduction to marine-derived peptides. It is arranged phyletically and encompasses the entire range from dipeptides to a compound with 95 amino acid residues. Peptides involved in primary metabolism and hence belonging to the realm of macromolecular biochemistry are excluded. However, it might be mentioned in passing that the dividing line between large and small molecule chemistry is continually becoming less distinct. Not only are more compounds of intermediate size, from 1,000 to 10,000 dalton, being discovered, but instruments and techniques, particularly in mass spectrometry and nuclear magnetic resonance have been developed for their structural elucidation by what is considered small molecule methodology. Two groups of peptides are discussed in separate chapters. Biologists who have observed and described the mating behavior of diverse species of marine invertebrates have long surmised that a chemical mechanism might be operating in many cases of individual as well as mass fertilization. The chemical activators of sea urchin sperm prove to be a series of peptides, whose structures and activity are discussed by Suzuki.

Biological inorganic chemistry is a field of research at the interface of inorganic and biological chemistry. The rapidly developing insights into the role of metals in biological systems has far-reaching implications not only for biological science but also for related disciplines, ranging from molecular medicine to the environment. In each volume the reader, whether engaged in chemistry, biochemistry, biology or molecular medicine, receives a comprehensive summary and critical overview of a topic of high current interest written by leading international experts.

Many human genetic diseases associated with blood, brain, colon, ear, eye, heart, kidney, liver, muscle, and pancreas are caused by mutations in mitochondrial DNA. Mutations in DNA can result in defects of the electron transport complexes, intermediates of the tricarboxylic acid cycle and substrate transport. The clinical manifestation of these diseases often involves muscle and the nervous system. Mitochondrial DNA mutations have now been associated with aging as well as age-related degenerative diseases such as Parkinson's, Alzheimer's, and Huntington's diseases. Changes in structure, function, and a number of mitochondria play an important role in carcinogenesis. Furthermore, the role of mitochondria in the execution of programmed cell death or apoptosis has been recognized recently.

This monograph explores the relationships between cell signaling and the cytoplasmic cytoskeleton in fundamental cell processes, thus bridging the gap between two very active aspects of molecular cell biology. It covers the two main - and reciprocal - questions of these relationships: How are structure and function of the cytoskeleton affected by external signals which impinge on the cell? How does the cytoskeleton influence the cellular signaling processes which determine cell behavior?

Proceedings of the NATO Study Institute on Molecular Mechanisms of Signalling and Targeting, held on the Island of Spetsai, Greece, August 18-30, 1996

Restriction Landmark Genomic Scanning (RLGS) is a new multiplex method for simultaneous analysis of over 3,000 genome loci. Written by the inventor of RLGS, Yoshihide Hayashizaki, and his co-workers, this is the first manual on this method. RLGS is a powerful technique with enormous potential for biological (animal and plant sciences), and biomedical research. Yielding results much faster than conventional techniques, RLGS is particularly suited to the identification of the chromosomal location of the genes implicated in inherited diseases, and for the genetic disturbances present in cancerous tissue.

Etwa 3 Milliarden Genbausteine umfaßt das Erbgut des Menschen, an dessen Entschlüsselung Forscher in aller Welt arbeiten. Verständlich und aktuell informiert dieses Buch über die wichtigsten Forschungsprojekte und ihre Ergebnisse. Es zeigt, welche Hoffnungen in die medizinische Anwendung der Genforschung sich bislang erfüllt haben, wo Gentests und Gentherapien heute möglich sind oder wo sie in naher Zukunft entwickelt werden können. Eine kritische Diskussion gilt der Frage nach der Patentierung von Genen und der möglichen Diskriminierung von Personen und Volksgruppen durch Gentests. An ausgewählten Beispielen wird schließlich gezeigt, wie sich mit Hilfe der Gene ein Blick zurück in die Evolution tun läßt. Ein ausführliches Glossar mit der Erklärung wichtiger Fachbegriffe schließt das Buch ab.

This book provides a comprehensive, up-to-date review of the distribution, pharmacology and physiology of central 5-hydroxytryptamine (5-HT)4 receptors. The 5-HT receptor subtypes exhibit a unique pharmacology, distribution and function, of which the 5-HT4 receptor has been one of the most intensively studied in recent years, both from a basic research standpoint and as a target for novel therapeutics.

Recombinant proteins, produced in cells or microorganisms, play an important role in basic research, medical science and the biotechnology industry. Many foreign gene expression systems using mammalian cells, E. coli, insect cells, yeast and other organisms as hosts have been developed. However, only recently has the expression system of Schizosaccharomyces pombe as a host become a subject of focus, as it is expected to be profitable for expressing foreign genes. The reason for this is that S. pombe is evolutionarily more advanced than other types of yeast. This book describes the use of S. pombe in basic research and industrial applications.

This monograph reviews and summarizes the substantial body of work that has been published on the transcription by polymerase III over the past 5 years. Progress in this field has been very rapid since 1993, and this new edition incorporates all the recent developments and offers the reader a highly detailed analysis of the current state of research on this largest and most complex of the eukaryotic RNA polymerases.

In recent years, because of advances in karyological techniques, we have witnessed a remarkable renewal of interest in studies of mammalian chromosomes. These techniques, generally involving the use of tissue culture, colchicine and hypotonic solution pretreatments, allow for a much clearer display of metaphase chromosomes of mammalian cells than the classic direct squash or tissue section methods. Consequently, what was known about the chromosome complement of most mammals must be revised. The most astonishing revision, of course, was that made by Tjio and Levan in 1956, who demonstrated that the diploid number of man is 46, not 48 as previously believed. Similar revisions will have to be made for many other mammalian species, either in number or in karyotype structure. Many animals are being examined cytologically for the first time. The findings are now extensive and scattered; they appear in numer­ ous periodicals and newsletters, or they are kept in cytologists'file drawers without being published. It is difficult to have access to perti­ nent data for comparison among related species or for evaluation of various karyological characteristics within a karyotype. Such evaluations can be done only when reasonably uniform material is collected and placed side by side for comparison, accompanied by relative references. We considered that probably an Atlas of Mammalian Chromosomes would fulfill such a need. Needless to say, it is impossible to present karyotypes of all mam­ malian species at one time.

We are extremely pleased that all of the chapters in this volume provide up-to-date information on a variety of topics of interest to scientists working on membrane biology. As in the past, we have attempted to expedite the transition from submission of the manuscripts to publication in order to make the reviews as timely as possible. Cell biology and molecular biology are increasingly be­ coming concerned with the study of structural elements in cells and their assem­ bly. The rules which govern membrane synthesis, assembly and interaction of membrane components with other cellular elements, notably the cytoskeleton, are at the center of research in these fields. We will continue in subsequent volumes of this series to focus on these areas. We would welcome suggestions of topics which would benefit from a review at the present time. We thank all of the contributors for providing these very excellent reviews and for doing so in a timely fashion. Elliot L. Elson William A. Frazier Luis Glaser St. Louis, Missouri vii CONTENTS Chapter 1 Chemotactic Transduction in the Cellular Slime Molds William A. Frazier, Beth L. Meyers-Hutchins, Gordon A. Jamieson, Jr., and Nancy J. Galvin 1. Introduction-Chemotaxis in the Cellular Slime Molds........... 2. Receptors for Chemoattractants of the Cellular Slime Molds....... 4 2. 1. The Folate Receptor of Vegetative D. discoideum........... 4 2. 2. The cAMP Receptor of Aggregating D. discoideum......... 6 3. Putative Transduction Events in D. discoideum................. 10 3. 1. cGMP and Guanylate Cyclase...........................

Proteins interacting with diverse ligands - proteins, peptides or DNA - are the basic principles underlying many biological processes, such as antigen-antibody binding, signal transduction or receptor binding.The technique of oligopeptide synthesis on a cellulose membrane and the subsequent binding assays allow the investigation of protein interactions. A particular advantage of these peptide arrays (SPOT - technology) is the high number of oligopeptide probes that can be tested in parallel. Detailed protocols for peptide synthesis, and the analysis of protein-protein, protein-DNA interactions as well as epitope mapping are presented in this manual. It is ideally suited not only for basic research laboratories but also for diagnostic and therapeutic applications since many diseases are related to dysfunctions in protein recognition and binding.

This volume describes high-throughput approaches to a series of robust, established methodologies in molecular genetic studies of population samples. Such developments have been essential not only to linkage and association studies of single-gene and complex traits in humans, animals and plants, but also to the characterisation of clone banks, for example in mapping of genomes. Chapters have been written by developers or highly experienced end-users concerned with a diverse array of biological applications. The book should appeal to any researcher for whom costs and throughput in their genetics laboratory have become an issue.

In recent years remarkable progress has been accomplished with respect to our knowledge about bacterial protein toxins. This refers especially to structural aspects of protein toxins but also holds true for genetics, molecular biology and biochemical mechanisms underlying the action of toxins. This volume covers the very current and exciting aspects of up-to-date bacterial toxicology and comprehensively reviews the most important bacterial protein toxins such as the intracellular acting toxins which exhibit enzyme activity, as well as those toxins that interact with cell plasma membranes by damaging the membranes (pore formation) or stimulating cell receptors (superantigens). This is the most current reference work on these important bacterial protein toxins, which are presented from the point of view of different disciplines such as pharmacology, microbiology, cell biology and protein chemistry.

This is now the fourth time that protein phosphorylation has been the focus of a NATO Advanced Study Institute. The first meeting with the topic'Signal Trans­ duction and Protein Phosphorylation'was held on the island of Spezai, Greece, in September 1986. The second one took place in Chateau La Londe, France, in September 1989 on'Cellular Regulation by Protein Phosphorylation', the third one on'Tyrosine Phosphorylation/Dephosphorylation and Downstream Signaling'was in September 1992 in Maratea, Italy. The titles of these books clearly mirror the developments that have taken place in the last decade. Beginning with the recognition that protein phosphorylation is at the center of signaling -clearly established in 1990 -it became apparent that many cellular processes are regulated by this mode. A new focus then emerged when it was recognized that growth factors are bound to corresponding receptors trigger protein tyrosine phosphorylation which controls cell prolifera­ tion. This was the topic of the third meeting in this series. It is now evident that further progress depends on understanding the three dimensional structure of the proteins involved. It goes without saying, for example, that understanding the location of proteins by adaptor proteins is only possible on the basis of the three dimensional protein structure. Therefore, the fourth meeting in this series concentrated on the protein structure of signaling molecules as well as on the elucidation of the principles of protein domain interactions.

The aim of this monograph is to summarize the essential features which characterize the behavior of regulatory systems. Firstly we discuss the laws which govern ligand binding in thermodynamic terms. The basic cooperative and allosteric phenomena are des­ cribed in thermodynamic terms without assuming any particular mo­ del. Then the molecular models developed by Monod, Wyman and Changeux and by Koshland, Nemethy and Filmer are presented in detail. Special emphasis has been given to the analysis of the Hill coefficient and its meaning both in thermodynamic terms and in terms of the two allosteric models: the concerted model of Monod, Wyman and Changeux and the sequential model of Koshland, Nemethy and Filmer. Special types of cooperativities are dis­ cussed in some detail namely, cooperativity stemming from ligand­ coupled protein association or dissociation, negative cooperati­ vity and half-of-the-sites reactivity. A slightly extended space was devoted to the discussion of negative cooperativity and half­ of-the-sites reactivity, since the existence of these phenomena and their possible biological importance is less of a common knowledge than positive cooperativity. This monograph does not attempt to be a review of specific examples analyzed according to one model or another. Rather, an attempt is made to provide the reader with the quantitative tools to analyze any specific regulatory system. Last but not least, I would like to thank Prof. F. W. Dahlquist from the Institute of Molecular Biology, the University of Oregon (Eugene) and Prof. D. E. Koshland, Jr.

This book provides an introduction to and an overview of the field of regulatory RNA, focusing on the identification of regulatory elements and motifs in such RNA molecules. Central to the book is the use of appropriate techniques to identify regulatory RNA and regulatory motifs. The prospects for this new and expanding research field - understanding regulatory RNA elements and motifs - are also explored, including new developments, medical applications, and applications in other fields.

Fluorescence in situ hybridization (FISH) has been developed as a powerful technology which allows direct visualisation or localisation of genomic alterations. The technique has been adopted to a range of applications in both medicine, especially in the areas of diagnostic cytogenetics, and biology. Topics described in this manual include: FISH on native human tissues, such as blood, bone marrow, epithelial cells, hair root cells, amniotic fluid cells, human sperm cells; FISH on archival human tissues, such as formalin fixed and paraffin embedded tissue sections, cryofixed tissue; simultaneous detection of apoptosis and xpression of apoptosis-related genes; comparative genomic ybridization; and special FISH techniques.

For those like me who witnessed the beginning of the adventure of human mitochon­ drial pathology, one can only be astounded by the extent and unexpectedness of what the field has come to offer. Extent because nobody could have imagined the sheer size of the domain. Unexpectedness because hitherto it was impossible to imagine the clinical polymorphism that this pathology would represent. The starting point was clear. Initially, there was the exceptional, and for a long time unique, observation of euthyroidian hypermetabolism that Luft and colleagues analyzed remarkably in biochemical and clinical terms. Thereafter, there was the support provided by the electron microscopy studies of Afzelius, and the very first visualization of mitochondrial abnormalities. That was way back in 1958. A few years later, progress in the cytology and cytochemistry of skeletal muscle tissue was to provide the means of detecting such abnormalities by examining sections with light microscopy. The colorful term'ragged red fibers', coined by W. K. Engel, became uni­ versally accepted, and this typical aspect with Gomori trichrome stain was to throw light on the frequency with which these mitochondrial abnormalities could occur under pathological conditions which, until then, had remained a total mystery regard­ ing their mechanism: syndromes such as the ocular myopathies with their descending evolution and the oculocraniosomatic syndromes. We were at the beginning of the 1970s.

This volume represents the proceedings of the 24th Mos­ bach Colloquium on'Regulation of Transcription and Trans­ lation in Eukaryotes'which was held April 26-28, 1973, in Mosbach, Germany, under the auspices of the Gesellschaft fiir Biologische Chemie. To the three of us (H. KERSTEN, P. KARLSON and myself) who were commissioned with the invitation of speakers, it was a difficult decision as to whether we should attempt to cover with some twenty contributions as many aspects of this broad topic as possible, or to sacrifice the intellectually perhaps more pleasing but more specula­ tive concepts and to concentrate on a few aspects of gene expression in reasonable detail. We unanimously decided on the latter course, leaving such important and timely topics as for example, hormone action, cyclic AMP and reverse transcription to the proceedings of other symposia, and con­ centrating on the four questions which are most basic to an understanding of the mechanisms of transcription and trans­ lation and for which fragmentary but nonetheless reliable experimental results have become available within the last few years. These are the structure of chromatin, the syn­ thesis of messenger RNA, the structure of the active ribo­ some, and the role of initiation factors in protein synthesis.

Biological inorganic chemistry is a field of research at the interface of inorganic and biological chemistry. The rapidly developing insights into the role of metals in biological systems has far-reaching implications not only for biological science but also for related disciplines, ranging from molecular medicine to the environment. In each volume the reader, whether engaged in chemistry, biochemistry, biology or molecular medicine, receives a comprehensive summary and critical overview of a topic of hight current interest written by leading international experts.

18. 2 Principle of FACE/Gel Retardation Assay.................................. 349 18. 3 Labelling of Oligosaccharides with ANTS................................. 350 18. 4 Screening of Carbohydrate Ligands for Proteins........................... 352 18. 5 Measurement of Binding Constant for the Interaction Between Protein and ANTS-Labelled Carbohydrate....................................... 355 18. 6 Measurement of Binding Constant for the Interaction Between Protein and Native Carbohydrate................................................... 357 References............................................................ 360 ~ The Application of Capillary Affinity Electrophoresis to the Analysis _ of Carbohydrate-Protein Interactions.................................... 361 19. 1 Introduction........................................................... 361 19. 2 Principle of CAE....................................................... 363 19. 3 Determination of Association Constants.................................. 364 19. 4 Technical Procedures................................................... 366 General considerations................................................. 366 19. 5 Limitations of the Technique............................................ 370 19. 6 Application of CAE to the Analysis of Carbohydrate-Protein Interactions...... 371 19. 7 Conclusions........................................................... 375 References............................................................ 377 20. 1 Introduction........................................................... 379 Definitions............................................................ 380 20. 2 Technical Procedures................................................... 381 20. 3 Sample Detection and Sample Recovery.................................. 389 Autoradiography and staining............................................ 389 Sample detection by blotting............................................ 389 Semipreparative ACE.................................................. 390 20. 4 Analysis of Data....................................................... 391 Measuring sample mobilities - calculating a retardation coefficient............ 391 Graphical analysis of data............................................... 392 Interpreting ACE patterns............................................... 393 Reverse ACE.......................................................... 395 20. 5 Summary............................................................. 397 Acknowledgements.................................................... 398 References.......

The Meyerhof Symposium on'Molecular Bioenergetics and Macromolecular Biochemistry'took place in Heidelberg from the 5th to the 8th of July, 1970. The timing was chosen to coincide with the creation of a new chair, in the Weizmann Institute of Science in Rehovot, in memory of OTTO MEYERHOF and the location was determined by the fact that so much of MEYERHOF'S scientific work was done in Heidelberg. The historical reason for the symposium was the urgent want of many leading biochemists and physiologists active in Molecular Biology to honour the memory of one of the greatest scientists in this field and also one of the greatest biologists of the 20th century. October 1971 is the twentieth anniversary of the death of OTTO MEYERHOF and 1972 marks 50 years since he was awarded the Nobel prize (1922). With regard to the age of some of his friends and pupils it was decided the symposium to be arranged in 1970, the first of the three commemorative years.

For centuries, TK has been used almost exclusively by its creators, that is, indigenous and local communities. Access to, use of and handing down of TK has been regulated by local laws, customs and tmditions. Some TK has been freely accessible by all members of an indigenous or local community and has been freely exchanged with other communities; other TK has only been known to particular individuals within these communities such as shamans, and has been handed down only to particular individuals of thc next generation. Over many generations, indigenous and local communities have accumulated a great deal of TK which has generally been adapted, developed and improved by the generations that followed. For a long time, Western anthropologists and other scientists have generally been able to freely access TK and have documented it in their works. Still, this TK was only seldom used outside the indigenous and local communities that created it. More recently, however, Western scientists have become aware that TK is neither outdated nor valueless knowledge, but, instead, 1 can be useful to solve some of the problems facing today's world. Modem science, for example, has shown an increased interest in some fornls ofTK as knowledge that can be used in 4 research and development (R&D) activities and be integrated in modem innovations. This holds especially true for TK regarding genetic resources, which has been integrated in modem 6 phannaceuticals,s agro-chemicals and seed.

This manual collects in the form of laboratory protocols a series of experiments in the field of Membrane Transport and Membrane Bioenergetics. It represents the experience accumulated during four advanced courses held at the Depart­ ment of Biochemistry of the Swiss Federal Institute of Technology on behalf of Federation of European Biochemical Societies (FEBS) in the years 1975 through 1978. The idea of collecting the experiments into a laboratory manual developed as a response to a demand from the students who took part in the courses. Further motivation came with the fmding that, in planning the laboratory sessions, the teaching staff had no organized, modern source of information in the literature. The experiments presented cover most areas of importance in the subject mat­ ter. Their presentation has been continuously modified in the course of the four years during which the manual took shape, to accommodate to experience and various suggestions. In their present form, all of the experiments described have been repeatedly practiced to optimize their execution. Efforts have been made to combine in the manual classical experiments, and techniques which require relatively unsophisticated instrumentation and can therefore be carried out in most laboratories, with more modern experiments and relatively newer technol­ ogies. In its present form, the manual should therefore provide a usefui tool in the hands of researchers and laboratory teachers at different levels of sophisti­ cation and instrumentation.

For many years, Springer has been publishing an impressive series of textbooks of pharmacology which have set standards in medical science. Surprisingly, an extensive overview of the current state of the art in research on estrogens and anti estrogens was still lacking. The present two volumes on estrogens and antiestrogens provide a comprehensive review of a field of research in which remarkable progress has been made over the past few years. New insights into the mechanisms of steroid hormone action resulted in a tremendous number of publications from which new principles of preventive and therapeutic appli­ cations of estrogens and antiestrogens emerged. Although various electronic data bases provide easy access to this copious information, there was a clear necessity for a monograph-style textbook which assesses and summarizes current knowledge in this rapidly expanding field of research. It should be noted, however, that, due to this dynamic development, it is barely possible to comprehensively update every aspect of basic and clinical knowledge on estro­ gens and antiestrogens. Thus, the intention of the editors was to provide the reader with an overview of the'classic'and most recently explored areas of research and stimulate future interests in basic and applied endocrinology. Estrogens were among the first steroid hormones described in the scientific literature. Since they were first isolated, since the chemical, synthesic and pharmacological characterization of naturally occurring estrogens and, later on, of orally active derivatives, estrogen research has produced continu­ ously hallmark results in reproductive endocrinology worldwide.

In the future'the decade of the 1990s will likely be viewed as a Golden Age for retinoid research. There have been unprecedented research gains in the understanding of retinoid actions and physiology; since the retinoid nuclear receptors were first identified and the importance of retinoic acid in develop­ mental processes was first broadly recognized in the late 1980s. Between then and now, our knowledge of retinoid action has evolved from one of a near complete lack of understanding of how retinoids act within cells to one of sophisticated understanding of the molecular processes through which retinoids modulate transcription. In this volume, we have tried to provide a comprehensive update of the present understanding of retinoid actions, with an emphasis on re­ cent advances. The initial chapters of the volume, or Section A, focus on the physicochemical properties and metabolism of naturally occurring retinoids: - N OY provides an uncommonly encountered view of retinoid effects from the perspective of the physiochemical properties of retinoids. - V AKIANI and BUCK lend a perspective on the biological occurrence and actions of retro- and anhydro-retinoids. Section B considers both the retinoid nuclear receptors and their mechanisms of action as well as synthetic retinoids that have been used exper­ imentally to provide mechanistic insights into receptor actions and have potential therapeutic use for treating disease: - PIEDRAFITA and PFAHL provide a comprehensive review of retinoid nuclear receptor biochemistry and molecular biology.

For many years, Springer has been publishing an impressive series of textbooks of pharmacology which have set standards in medical science. Surprisingly, an extensive overview of the current state of the art in research on estrogens and anti estrogens was still lacking. The present two volumes on estrogens and anti estrogens provide a comprehensive review of a field of research in which remarkable progress has been made over the past few years. New insights into the mechanisms of steroid hormone action resulted in a tremendous number of pUblications from which new principles of preventive and therapeutic appli­ cations of estrogens and anti estrogens emerged. Although various electronic data bases provide easy access to this copious information, there was a clear necessity for a monograph-style textbook which assesses and summarizes current knowledge in this rapidly expanding field of research. It should be noted, however, that, due to this dynamic development, it is barely possible to comprehensively update every aspect of basic and clinical knowledge on estro­ gens and antiestrogens. Thus, the intention of the editors was to provide the reader with an overview of the'classic'and most recently explored areas of research and stimulate future interests in basic and applied endocrinology. Estrogens were among the first steroid hormones described in the scientific literature. Since they were first isolated, since the chemical, synthesic and pharmacological characterization of naturally occurring estrogens and, later on, of orally active derivatives, estrogen research has produced continu­ ously hallmark results in reproductive endocrinology worldwide.

Improved technology for imaging living cells, specific cellular targets and organelles is having a dramatic impact on basic and applied research. By combining optical design and molecular genetics, a new series of tools is being developed and successfully applied together with classical probes. Novel labelling strategies, better software for image enhancement and analysis are now available and allow image acquisition with greater speed and precision. This lab manual, intended as for bench-top use, is suitable for both scientists and graduate students, combines an update on the most advanced imaging procedures with detailed protocols. Examples, cleverly selected from the wide repertoire of cell pyhsiology, cover different functional aspects such as distribution of multiple ions, electrical activity, exo-endocytosis, gene expression, and the cell cycle.

The synthetic chemistry of carbohydrates has advanced at a scarcely equalled rate in the last 25 years, due to the great interest of biologically active natural products coritaining sugar moieties. It suffices to note that in the review by J. D. Dutcher appearing in'Advances in Carbohydrate Chemistry'vol. 18, 1963, only the structures of less than ten aminodeoxy sugars were reported. This book deals exclusively with a single class of carbohydrates, namely the aminodeoxy sugars of antibiotics, the most popular of which is probably daunosamine, a compound for which more than 20 different synthetic approaches have been reported in the literature since the publication of its structure in 1964. No compound in the 3-amino-2-deoxY-L-hexose series had been prepared by chemical synthesis when we started our synthetic work in this field in 1972 on the wave of the successful therapeutic applications of adriamycin. The compounds with xylo stereochemistry were unknown even in the more easily accessible D-series. The size of this book documents the rapid development of the field. I wish to add that the improvements of chemical methodology reported in. the volume outspan the specific field and are of importance in the design of synthetic approaches to other carbohydrate structures. These also include compounds involved in chemical interactions of great biological interest, but hitherto un­ explained at the molecular level, such as those related with cell recognition, adhesiveness and differentiation.