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This book provides a molecular view of membrane transport by means of numerous biochemical and biophysical techniques. The rapidly growing numbers of atomic structures of transporters in different conformations and the constant progress in bioinformatics have recently added deeper insights. The unifying mechanism of energized solute transport across membranes is assumed to consist of the conformational cycling of a carrier protein to provide access to substrate binding sites from either side of a cellular membrane. Due to the central role of active membrane transport there is considerable interest in deciphering the principles of one of the most fundamental processes in nature: the alternating access mechanism. This book brings together particularly significant structure-function studies on a variety of carrier systems from different transporter families: Glutamate symporters, LeuT-like fold transporters, MFS transporters and SMR (RND) exporters, as well as ABC-type importers. The selected examples impressively demonstrate how the combination of functional analysis, crystallography, investigation of dynamics and computational studies has made it possible to create a conclusive picture or more precisely, “a molecular movie”. Although we are still far from a complete molecular description of the alternating access mechanism, remarkable progress has been made from static snapshots towards membrane transport dynamics.

Reasoning in terms of molecular recognition may be traced back to Emil Fischer, who practiced the art of chemistry at Humboldt University in Prussian Berlin a century ago. Today, it is clearly recognized that molecular recognition impacts and determines all life processes. It has become a key research field in both chemistry and biology and the emerging interface of what now is being called'chemical biology'. The technological advances derived from this knowledge are particularly important, diverse, and directly evident in the pharmaceutical industry. Under the auspices of the Ernst Schering Research Foundation, a workshop held in Berlin in February 1998 addressed novel basic developments of potential relevance to drug research efforts. A balance of timely research topics in molecular recognition is presented in the lectures delivered by a multidisciplinary international panel of renowned scholars and documented in this volume.

It is hardly necessary to define the concept of receptors to readers of this series, but it should be born in mind that in several instances receptors are undefined entities, whose molecular details remain to be established. On the other hand the ligand, which reco~izes the receptors, has been identified and characterized in most cases. The current interest in the structure and function of biological membranes gives great expectations that in the near future we may understand the details of ligand-receptor interaction. This interaction involves two defined steps: the first, usually referred to as recognition, is followed by the second step, transduction, in which the ligand-receptor interaction is translated by the cell into a biochemical action. The present two volumes which cover prokaryotic and eukaryotic virus receptors, have been published together in order to illustrate the specificity of virus­ receptor recognition which appears to be a guiding principle for both bacteria and higher cells. The identification and characterization of the receptors for phages of gram-negative bacteria has to a large extent relied on the genetic techniques available for these organisms. In a similar way the availability of genetic systems has also clarified the interrelationship between animal retrovirus receptors even if the molecular structure remains to be determined. The paucity of defined genetic systems may therefore explain part of our ignorance concerning the molecular details of virus receptors on human cells and possibly also on gram­ positive bacteria.

The value of studies of monotypic populations is constantly argued in bacterial ecology. The controversy itself is evidenceofthe strong awareness that bacterial activities in natural sites are not determined by the bacteria alone. At the same time, the best evidence that bacteria are influenced by environmental factors is the contrast between their behavior in laboratory cultures and their relatively subdued influence when in the presence of com­ petitors, predators, and fluctuating-often stressful-environmental conditions. Monotypic populations are admittedly reductionist, but are not therefore irrelevant to bacterial ecology. Quite the contrary. Without pure culture studies, our understanding of important and applicable bacterial activities-N fixation, for example-would still be z limited to what we could discern from a comparison of events in steamed vis-a-vis un­ heated soil. As was evident throughout the previous volume in this treatise, practically any method of studying natural bacterial communities upsets them while permitting only limited assessment of the respective qualities and quantitative contributions to total com­ munity activity of each type of bacterium present. Total activity itself is difficult to assess and is not dependably accomplished by any single method. This third volume comprises information regarding the properties of bacteria as they have been learned largely from pure culture studies. Its purpose is twofold: to provide readers with fundamental information regarding the cellular organization, physiological capabilities, and genetic systems of bacteria; and to connect known bacterial properties with environmental influences on them and with their influences on natural processes.

Microbiology has undergone a number of metamorphoses in its relatively brief existence. It has been in approximate succession, morphology, epidemiology, biochemistry, genetics, and molecular biology. It is also becoming a significant parcel of cell surface studies. The one embodiment which has remained elusiv- particularly for bacteriology - is the taxonomic one. This may have been a blessing in disguise because it encouraged microbiologists to deal with the general rather than the particular; promoting a search for unitary explanations, in the manner of Kluyver and van Niel, long before anyone knew about the universality of the genetic code, or could trace the genealogy of enzymes from the study of amino acid substitutions.. This volume is predicated on the idea that deep analogies underly the mech­ anisms of cellular interaction, and therefore belongs in the unitary tradition of microbiology. It occupies itself with a wide variety of micro-organisms, considering them from vantage points of considerable diversity, ranging from taxonomic irreverence to keen evolutionary awareness, and is concerned with areas which have developed independently of each other.

Less than a year before this writing, a Nobel Prize was shared by Albert Claude, Christian de Duve, and George Palade, pioneers in the development of modern cell biology, of which membrane biology is an integral part. For many years, a seemingly unbridgeable gap separated the physiologist working at the organ level from the biochemist studying the molecular composition of cell constituents and the chemical reactions that occur in water-soluble extracts of cells. Physiology has a long history, and the disciplines epitomized by intermediary metabolism and molecular biology progressed rapidly during the 1950s and 1960s. Meanwhile, electron micros­ copists painstakingly mapped the newly discovered intracellular world of membranes, organelles, microtubules, and microfilaments, and other scien­ tists developed techniques for the quantitative separation and characteriza­ tion of these intracellular structures. Thus it finally became possible to localize the many enzymes, and the metabolic activities they catalyze, to recognizable structures whose composition and organization can be studied. We are now well on our way to bridging that gap between biochemistry and physiology-to understanding how the cell functions.

It is perhaps obvious to any student of Biology that the discovery of chemical processes in whole organisms has usually preceded the elucidation of the compo­ nent steps. However, it is perhaps less obvious that the unravelling of the se­ quences in which those chemical steps occur in living matter, of the precise mechanisms involved, and of the manner in which they are regulated, would have been achieved neither by the study of intact plants and animals nor even of extracts derived from them. Our ability to understand the nature and regulation of metabolism rests on two main premises: the postulate that life processes can indeed be validly investigated with individual cells and cell-free extracts, and the thesis that there is an essential'unity in biochemistry'(as Kluyver put it, 60 years ago) that enables events in one organism to be legitimately studied in another. Of particular utility in this latter respect has been the use of cultures of single-celled organisms, growing in defined media-especially prokaryotes, such as Escherichia coli, and eukaryotes, such as Neurospora and Sac­ charomyces sp., to which both biochemical and genetical techniques could be applied. It was, of course, Pasteur's observations of bacterial fermentations that first overthrew the belief that oxygen was essential for all energy-yielding pro­ cesses: his recognition that'La fermentation..... c'est La vie sans air'laid the foundations of our knowledge of glycolysis.

This volume of Advances in Microbial Ecology marks a change in the editor­ ship of the series. The Editorial Board wishes to take this opportunity to express its gratitude to Martin Alexander, the founding editor and editor of the first five volumes, for his enterprise in establishing the series and in ensuring that Advances has become an outstanding focal point for the identification of new developments in the rapidly expanding field of microbial ecology. With the publication of this volume, we welcome Howard Slater to the Editorial Board. The policies of the Editorial Board remain the same as before. Most con­ tributions to Advances in Microbial Ecology will be solicited by the Board. However, individuals are encouraged to submit outlines of unsolicited contri­ butions to the Board for consideration for inclusion in the series. Advances is designed to serve an international audience and to provide critical reviews on basic and applied aspects of microbial ecology. Contributions in the present volume are predominantly concerned with the ecology of aquatic microorganisms, but encompass a variety of approaches to this area. The exception is the chapter by J. W. Doran on the role of micro­ organisms in the cycling of selenium. G-Y. Rhee discusses the effects of envi­ ronmental factors on phytoplankton growth. The factors limiting the produc­ tivity of freshwater microbial ecosystems are considered by H. W. Paerl.

Investigations of the oxygen carriers range from the characterization of natural populations to measurements of tenths of nanometer distances between atoms. The scope is so great that few biologists and biochemists can fully comprehend the primary literature in its entirety. In addition, the findings of the past two or three decades have advanced the field so rapidly that a truly current account is not readily accessible to a general audience. In recognition of the problem a symposium was held and its proceedings published in the American Zoologist in 1980. Although it included several research reports, most of the contributions were intended to summarize then state-of-the-art information on molecular structure and respiratory function at a level that could be understood by biologists and biochemists who are not experts on our subject. Judging from the reprint requests with which the authors were inundated, the assessment of need had been accurate. I believe that the need for an update, which is wholly focused on communication to the general audience, is even greater in 1992. I therefore asked the authors of this volume to address individuals who might otherwise turn in vain to an advanced textbook of physiology or biochemistry. I have, of course, requested a more comprehensive coverage than would be possible in a general text, but one that is not more parochial. Just as textbooks differ vastly in the level at which their subject matter is presented, so the level of non-expertise was conceived differently by the contributors to this volume.

Eukaryotic cells contain a plurality of organelles distinguished by their specific membranes and contents. Their biogenesis occurs by growth and division of preexisting structures rather than de novo. Mitochondria and chloroplasts, which appear to be descended from prokaryotic ancestors, have retained some DNA and the biosynthetic capability for its expression. They synthesize, however, only a few of their proteins themselves. Most of their proteins are synthesized on free ribosomes in the cytoplasm and are only assembled in the correct membrane after synthesis is complete. The biogenesis of peroxisomes and glyoxysomes also appears to occur by an incorporation of proteins synthesized first in the cytoplasm. Other organelles, the Golgi complex, lysosomes, secretory vesicles, and the plasma membrane, are formed in a different manner. Their proteins are assembled in the membrane of the endoplasmic reticulum during trans­ lation by bound ribosomes and they must then be transported to the correct membrane. The 1980 Mosbach Colloquium was one of the first attempts to discuss the biogenesis of the various organelles in biochemical terms. This was appropriate since the crucial problems now center on the search for signals and receptors that dictate the site of assembly, the route taken, and the final location of a particular organelle protein. The assembly of prokaryotic membranes and the membrane of an animal virus were also discussed, since these simpler systems might shed light on the biogenesis of organelles in eukaryotes.

In the first edition of The Enzymes of Biological Membranes. published in four volumes in 1976, we collected the mass of widely scattered information on membrane-linked enzymes and metabolic processes up to about 1975. This was a period of transition from the romantic phase of membrane biochemistry, preoccupied with conceptual developments and the general properties of membranes, to an era of mounting interest in the specific properties of membrane-linked enzymes analyzed from the viewpoints of modem enzymology. The level of sophistication in various areas of membrane research varied widely; the structures of cytochrome c and cytochrome b were known 5 to atomic detail, while the majority of membrane-linked enzymes had not even been isolated. In the intervening eight years our knowledge of membrane-linked enzymes ex­ panded beyond the wildest expectations. The purpose of the second edition of The Enzymes of Biological Membranes is to record these developments. The first volume describesthe physical and chemical techniques used in the analysis of the structure and dynamics of biological membranes. In the second volume the enzymes and met­ abolic systems that participate in the biosynthesis of cell and membrane components are discussed. The third and fourth volumes review recent developments in active transport, oxidative phosphorylation and photosynthesis.

The main purpose of this book is to unify approaches and ideas in the field of aneural sensory transduction. This field has recently come to the attention of several research groups in various disciplines, and their number seems to be growing. Unfortunately, because of the diverse scientific backgrounds of the researchers in the field, the apparent heterogeneity of experimental techniques (i. e., behavioral response analysis, sophisticated biochemical and genetic manipulations, conventional and pulsed laser spectroscopy) and theoretical approaches may be discouraging, for both the experienced worker and the new­ comer. Actually, this heterogeneity is more apparent than real, and unifying concepts, approaches, and ideas already exist, particularly with respect to all the questions concerning the role of membranes and their properties (such as ion permeability, electric potentials, and active transport) in the various steps of sensory perception and transduction processes. It is currently accepted that most, if not all, the fundamental facts in molecular sensory physiology of aneural organisms, be they chemosensory, photosensory, or geosensory, can ultimately be understood in terms of a few basic ideas. Each chapter of this book emphasizes and clarifies the role of mem­ brane properties and phenomena in the particular sensory response examined. Of course, in some cases, this task has been rather complex because of the limited amount of experimental data clearly supporting a membrane-based model of sensory transduction.

In 1968 when Cell Walls and Membranes was published it was still reasonable to attempt to write a book covering the whole subject. Accordingly this edition of the book had something to say about walls from micro-organisms and plants as well as about membranes from bacteria and animal cells. A decade later this is manifestly impossible. Knowledge about almost all the subjects has grown explosively, par­ ticularly about membranes and the biosynthesis of macromolecules. Moreover aspects of the subject that were still in a relatively primitive state ten years ago have grown into highly sophisticated subjects worthy of extended treatment. The result is that the present book has had to be confined to structures and functions relating to only one division of the biological kingdom, namely micro-organisms. Even then severe limitations have had to be made to keep the task within the time available to the authors and their expertise. A few of the titles of chapters such as those on the isolation of walls and membranes, the structure of the components of bacterial and micro-fungal walls and their biosynthesis remain from the earlier book. These chapters have been almost completely rewritten and a number of quite new chapters added on topics such as the action of the antibiotics that inhibit bacterial wall syn­ thesis, on the function of bacterial membranes, and the bacterial autolysins.

Much of the information currently available on the transport systems of bacterial and animal cell membranes and their mode of coupling to metabolic supply of energy can be found in this volume. Consideration of the participating enzymes dictated the choice of topics: Several transport systems where little information is available on the enzymology of the process are not included, while separate chapters deal with y-glutamyl transpeptidase and intestinal disaccharidases which meet many of the requirements of transport enzymes. The volume also includes two chapters on photosynthetic membranes as a general introduction to the topic. Other aspects of biological transport and photosynthesis will be developed in detail in a forthcoming volume now in preparation. These chapters reveal the excitement and rapid advance of the field, the daily reports of new concepts, new techniques, and new experimental findings which instantly interact to generate further progress. Our aim was to provide a starting point for those who are just beginning, and an opportunity for others to stop, take stock, and start in a new direction. My warmest thanks to all who contributed to this volume.

This volume contains the proceedings of the FEBS Sym­ posium on the Biochemistry of Membrane Transport, which was held at the Swiss Institute of Technology, Zlirich, July 18-23, 1976. Of the speakers invited or­ iginally, only five could not attend the meeting, and of the lectures given, all but one of the texts are published here. Thus, this volume gives a faithful ac­ count of the way the meeting was originally conceived and actually took place. This Symposium on Biochemistry of Membrane Transport was the first Symposium sponsored by the FEBS outside the yearly FEBS-Meetings, after the Special Meeting on Industrial Biochemistry, which took place in Dublin in 1973, and it reflects the interest and the trend for gatherings of smaller size than the official FEBS Meetings. The topic of the Symposium was an easy choice, not only because membrane transport is becom­ ing more and more important to biochemistry every year, but also because of the long-standing interest of Swiss Science in the field. In the choice of the topics and of the speakers, efforts were made to achieve as balanced a coverage of the area as possible. However, since some aspects of membrane biochemistry were dealt with extensively at the parallel 10th Inter­ national Congress of Biochemistry in Hamburg, GFR, cer­ tain topics were given less emphasis than others. The Symposium was attended by about 400 participants (we expected 200-250); among them 48 were invited speakers, and some 200 contributed posters.

Cell-free protein synthesis is coming of age! Motivated by an escalating need for efficient protein synthesis and empowered by readily accessible cell-free protein synthesis kits, the technology is expanding both in the range of feasible proteins and in the ways that proteins can be labeled and modified. This volume follows'Cell-Free Translation Systems', edited by Professor Alexander S. Spirin in 2002. Since then, an impressive collection of new work has emerged that demonstrates a substantial expansion of capability. In this volume, we show that proteins now can be efficiently produced using PCR products as DNA templates and that even membrane proteins and proteins with multiple disulfide proteins are obtained at high yields. Many additional advances are also presented. It is an exciting time for protein synthesis technology.

This book, written by the leading experts in the field of plant electrophysiology, provides a comprehensive and up-to-date overview of the current state of knowledge on electrical signaling and responses in plant physiology. It covers a significant interdisciplinary area for a broad range of researchers, emphasizing the physical, chemical, biological, and technological aspects of plant electrophysiology, while also demonstrating the role of electrochemical processes and ion channels in plant life cycles. Separate chapters describe the electrophysiology of the Venus flytrap, the Telegraph plant, Mimosa pudica, and other interesting plant species. Subsequent sections focus on mechanisms of plant movement, the role of ion channels, morphing structures, and the effects of electrical signal transduction on photosynthesis and respiration. Further topics include the electrophysiology of plant-insect interactions, how plants sense different environmental stresses and stimuli, and how phytoactuators respond to them. All chapters analyze the generation and transmission of electrical signals in plants.

The NATO Advanced Study Institute entitled'Surface Membrane Receptors: Interface Between Cells and Environment'was held in Bellagio, Italy September 13-21, 1975. This meeting was an attempt to bring together in an international and interdisci­ plinary forum scientists who are studying recognitive phenomona which take place at the surface membrane of cells. While an attempt was made to restrict the subject areas covered at the meeting to those experimental systems which have been biochemi­ cally characterized to some extent, it will also be noted that some contributions to this volume represent a preliminary iden­ tification of interesting regulatory substances which might reasonably be expected to act at the cell surface. This book is divided into four sections reflecting the subject areas covered during the course of the meeting. The first section entitled'Membrane Structure and Receptor Function'is intended as an overview of the role of membrane structure in determining the regulatory properties, physical state, structure and location of cell surface receptors. It should be noted that the plasma membrane itself provided the unifying theme for the intention­ ally diverse contributions to this volume. The following three sections represent an arbitrary division into three levels of structural complexity of the things in their external environ­ ment with which cells must specifically interact.

Proceedings of a NATO ASI held in Cape Sounion Beach, Greece, June 24-July 5, 1991

Salmonella infections of man and animals continue to be a distressing health problem worldwide. Far from disappearing, the incidence of typhoid fever in developing countries may be far higher than we had imagined. Salmonella food poisoning has increased to one of the major causes of gastroenteritis in the developed world, in itself also an indication that animal salmonellosis is still a major cause for concern. The situation requires a concerted multidisciplinary research effort in order to generate the new information and technology needed to assist in the control of these diseases. This concept was the driving force behind the NATO Advanced Research Workshop on'Biology of Salmonella'held at Portorosa, Messina, Italy, May 11-15, 1992. With additional support from the University of Messina, Medeva Group Research (UK) and the Swiss Serum and Vaccine Research Institute, the meeting brought together epidemiologists, microbiologists, molecular biologists, immunologists and clinicians. All the participants were actively working on different but related aspects of Salmonella and salmonellosis, with most of the leading laboratories worldwide being represented. The workshop provided an excellent opportunity for interdisciplinary consultation; it is not often that the topic of Salmonella and salmonellosis is covered to such breadth and depth in one extended meeting. Keynote addresses by invited speakers were interspersed with offered papers, many by younger members of the scientific community, and this volume presents the collated manuscripts of the lectures and extended summaries of the offered papers.

In order to provide a functional organisation of the various biochemical processes, the intracellular environment is subdivided into compartments formed by organelles. Mitochondria serve to restore energy-rich compounds, while energy is mainly consumed in the cytosolic space. Molecules involved in these metabolic cycles have to cross the mitochondrial membrane via specialized carriers embedded in the inner mitochondrial membrane. All relevant structural and functional aspects of the Anion Carriers of Mitochondrial Membranes as well as isolation procedures, reconstitution experiments and biogenesis of the carriers, kinetics of transport as well as the metabolic regulation mechanisms are treated in this volume.

Microbial cell wall structures play a significant role in maintaining cells'shape, as protecting layers against harmful agents, in cell adhesion and in positive and negative biological activities with host cells. All prokaryotes, whether they are bacteria or archaea, rely on their surface polymers for these multiple functions. Their surfaces serve as the indispensable primary interfaces between the cell and its surroundings, often mediating or catalyzing important interactions.Prokaryotic Cell Wall Compounds summarizes the current state of knowledge on the prokaryotic cell wall. Topics concerning bacterial and archaeal polymeric cell wall structures, biological activities, growth and inhibition, cell wall interactions and the applications of cell wall components, especially in the field of nanobiotechnology, are presented.

This volume provides a comprehensive look at the biology of plastids, the multifunctional biosynthetic factories that are unique to plants and algae. Fifty-six international experts have contributed 28 chapters that cover all aspects of this large and diverse family of plant and algal organelles. The book is divided into five sections: (I): Plastid Origin and Development; (II): The Plastid Genome and Its Interaction with the Nuclear Genome; (III): Photosynthetic Metabolism in Plastids; (IV): Non-Photosynthetic Metabolism in Plastids; (V): Plastid Differentiation and Response to Environmental Factors. Each chapter includes an integrated view of plant biology from the standpoint of the plastid. The book is intended for a wide audience, but is specifically designed for advanced undergraduate and graduate students and scientists in the fields of photosynthesis, biochemistry, molecular biology, physiology, and plant biology.

Advances in science and medicine are closely linked; they are characterised by episodic imaginative leaps, often with dramatic effects on mankind and beyond. The advent of body sensor networks represents such a leap. The reason for this stems from the fact that all branches of modern medicine, ranging from prevention to complex intervention, rely heavily on early, accurate, and complete diagnosis followed by close monitoring of the results. To date, attempts at doing this consisted of intermittent contact with the individual concerned, producing a series of snapshots at personal, biochemical, mechanical, cellular, or molecular levels. This was followed by making a series of assumptions which inevitably resulted in a distortion of the real picture. Although the human genome project has shown that we are all “equal”, it confirmed the fact that each one of us has unique features at many levels, some of which include our susceptibility to disease and a particular response to many external stimuli, medicines, or procedures. This has resulted in the concept of personalised medicines or procedures promised to revolutionise our approach to healthcare. To achieve this, we need accurate individualised information obtained at many levels in a continuous fashion. This needs to be accomplished in a sensitive, respectful, non-invasive manner which does not interfere with human dignity or quality of life, and more importantly it must be affordable and cost-effective.

As a pioneering work on plant electrophysiology, this exciting reference compiles new findings from the work of internationally renowned experts in the fields of electrophysiology, bio-electrochemistry, biophysics, signal transduction, phloem transport, tropisms, ion channels, plant electrochemistry, and membrane transport. The book starts with a historical introduction to plant electrophysiology, followed by two distinct parts. The first one deals with methods in plant electrophysiology, including, amongst others, measuring membrane potentials and ion fluxes, path-clamp technique, and electrochemical sensors. The second part covers experimental results and their theoretical interpretation.