Strategies of Bacterial Interaction with Eukaryotic Cells *Tobias A. Oelschlaeger and Jorg Hacker 1. BENEFICIAL BACTERIAL-HOST INTERACTIONS Already during birth and soon thereafter mammals are colonized by bacte- ria belonging to the resident microbial flora. Cutaneous and mucosal sur- faces and the gastrointestinal tract are the areas which become colonized. These indigenous or autochthonous bacteria have a variety of beneficial effects on their hosts. They play a protective role by bacterial antagonism in fighting infections (Hoszowski and Truszczynski, 1997; Hentges, 1979). Pro- duction of vitamin K is another essential contribution of the resident microbial flora to the health of the host (Hill, 1997). Even more important, studies with germ-free animals demonstrated the involvement of the microbial flora on the development of the immune system. Such animals have underdeveloped and relatively undifferentiated lymphoid tissues and low concentrations of serum immune globulins ( Cebra et at., 1998). They TOBIAS A. OELSCHLAEGER and JORG HACKER Institut filr Molekulare lnfektionsbiologie, Universitiit Wiirzburg, 97070 Wiirzburg, Germany. *Corresponding author; Phone: (0)931-312150; FAX: (0)931-312578; E-mail: [email protected] xxix Tobias A. Oelschlaeger and Jorg Hacker also show defects in specific immune responsiveness and in nonspecific resistance induced by endotoxin, which may account for their lowered resis- tance. A more typical example of symbiotic interaction of bacteria with a host are bacteria like Ruminococcus in the gut of ruminants, essential for degradation of cellulose (Hobson, 1988). The closest benefical bacterial-host interactions are those of intracellular symbiotic bacteria and their host cells.

The root is the organ that functions as the interface between the plant and the earth environment. Many human management practices involving crops, forests and natural vegetation also affect plant growth through the soil and roots. Understanding the morphology and function of roots from the cellular level to the level of the whole root system is required for both plant production and environmental protection. This book is at the forefront of plant root science (rhizology), catering to professional plant scientists and graduate students. It covers root development, stress physiology, ecology, and associations with microorganisms. The chapters are selected papers originally presented at the 6th Symposium of the International Society of Root Research, where plant biologists, ecologists, soil microbiologists, crop scientists, forestry scientists, and environmental scientists, among others, gathered to discuss current research results and to establish rhizology as a newly integrated research area.

With the invitation to edit this volume, I wanted to take the opportunity to assemble reviews on different aspects of circadian clocks and rhythms. Although most c- tributions in this volume focus on mammalian circadian clocks, the historical int- duction and comparative clocks section illustrate the importance of various other organisms in deciphering the mechanisms and principles of circadian biology. Circadian rhythms have been studied for centuries, but only recently, a mole- lar understanding of this process has emerged. This has taken research on circadian clocks from mystic phenomenology to a mechanistic level; chains of molecular events can describe phenomena with remarkable accuracy. Nevertheless, current models of the functioning of circadian clocks are still rudimentary. This is not due to the faultiness of discovered mechanisms, but due to the lack of undiscovered processes involved in contributing to circadian rhythmicity. We know for example, that the general circadian mechanism is not regulated equally in all tissues of m- mals. Hence, a lot still needs to be discovered to get a full understanding of cir- dian rhythms at the systems level. In this respect, technology has advanced at high speed in the last years and provided us with data illustrating the sheer complexity of regulation of physiological processes in organisms. To handle this information, computer aided integration of the results is of utmost importance in order to d- cover novel concepts that ultimately need to be tested experimentally.

Since its first discovery in the early 90 s, the NF-kB/Rel transcription factor family has drawn the attention of experimental biologists, medical profession, and biotech/pharmaceutical industries for its broad and diverse roles in all aspects of human biology and disease. NF-kB/Rel Transcription Factor Family intends to provide an up-to-date guide to the ever-expanding knowledge in the field of NF-kB/Rel transcription factor family.

Every cell in our bodies contains a great variety and number of permeability pathways for various organic and inorganic ions, water, metabolites, nutrients, and signalling molecules. Maintenance and precise control of gating within these pathways are fundamental principles of life as these underlie basic cellular functions such as communication, contractility, and metabolism. In Ion Channels: Methods and Protocols, Second Edition, experts in the field contribute chapters that focus on the strategies, approaches, methods, and protocols for studying a large family of proteins that form ionic channels in the plasma membrane and intracellular membranes of cells. Using practical examples from the cutting-edge current research, this volume will take a look back at the major methods and approaches that aided the progress toward the current understanding of ion channel function, structural design, and biological roles. The volume also aims to look forward and identify approaches that will lead us to future discoveries. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Ion Channels: Methods and Protocols, Second Edition will greatly assist researchers searching for specific methodology in studying ion channels on the path toward a greater understanding of these key biological features.

This book is a direct result of 10 years of the well-known "Autoimmunity Days" in Israel, which are increasingly becoming an international focal point for autoimmunity scientists. Top researchers provide coverage of the most important knowledge generated during the last decade. The volume can therefore be seen almost as a textbook on autoimmunity, projecting from the last decade to the next millennium.
A variety of different subjects in autoimmunity, from etiology to pathogenesis, from postulated mechanisms to innovative therapeutic modalities, is handled by noted contributors, while additional authors contribute top papers which significantly enhance a better understanding of autoimmunity.
An excellent treatise on the subject, and a worthwhile addition to both clinical and research libraries.

As the research has continued, it has become increasingly clear that natural killer (NK) cells are critical sentinels of the innate immune response, playing important roles in protecting the body from numerous pathogens and cancer in addition to contributing to normal pregnancy and impacting the outcomes of transplantation. While the first edition provided a valuable collection of classical cellular and in vivo techniques to study NK cell functions, the Second Edition of "Natural Killer Cell Protocols: Cellular and Molecular Methods" brings together more recently developed methods, more refined techniques, and detailed protocols designed to study NK cells within specialized tissue sites in both mice and humans. In this collection of methods, international leaders in the field cover topics ranging from the analysis of the various stages of NK cell development and maturation to specialized techniques for the identification of ligands for NK cell receptors. This volume also includes an appendix, providing a rich resource summarizing available reagents to study NK cells, cross-referencing KIR nomenclature, and detailing the many HLA ligands for various KIR family members. As a volume in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and thorough notes sections, highlighting tips on troubleshooting and avoiding known pitfalls.

Comprehensive and cutting-edge, "Natural Killer Cell Protocols: Cellular and Molecular Methods, Second Edition" seeks to aid researchers and further advance our understanding of the functions, maturation, and regulation of these fascinating and dynamic cells."

This book mainly focuses on key aspects of biomembranes that have emerged over the past 15 years. It covers static and dynamic descriptions, as well as modeling for membrane organization and shape at the local and global (at the cell level) scale. It also discusses several new developments in non-equilibrium aspects that have not yet been covered elsewhere. Biological membranes are the seat of interactions between cells and the rest of the world, and internally, they are at the core of complex dynamic reorganizations and chemical reactions. Despite the long tradition of membrane research in biophysics, the physics of cell membranes as well as of biomimetic or synthetic membranes is a rapidly developing field. Though successful books have already been published on this topic over the past decades, none include the most recent advances. Additionally, in this domain, the traditional distinction between biological and physical approaches tends to blur. This book gathers the most recent advances in this area, and will benefit biologists and physicists alike.

This book delves into the recent developments in the microscale and microfluidic technologies that allow manipulation at the single and cell aggregate level. Expert authors review the dominant mechanisms that manipulate and sort biological structures, making this a state-of-the-art overview of conventional cell sorting techniques, the principles of microfluidics, and of microfluidic devices. All chapters highlight the benefits and drawbacks of each technique they discuss, which include magnetic, electrical, optical, acoustic, gravity/sedimentation, inertial, deformability, and aqueous two-phase systems as the dominant mechanisms utilized by microfluidic devices to handle biological samples. Each chapter explains the physics of the mechanism at work, and reviews common geometries and devices to help readers decide the type of style of device required for various applications. This book is appropriate for graduate-level biomedical engineering and analytical chemistry students, as well as engineers and scientists working in the biotechnology industry.

This second edition volume expands on the previous edition with chapters discussing the latest developments and research initiatives in mitochondrial functions. The chapters in this book explore topics such as high-resolution fluorespirometry and OXPHOS protocols in human cells, analysis of mitochondrial oxygen consumption, mitochondrial bioenergetics, and mitochondrial dynamics in mammalian cells. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and practical, Mitochondrial Bioenergetics: Methods and Protocols, Second Edition is a valuable resource for students, and practitioners in the pharmaceutical sciences, environmental sciences, and mitochondrial genetics industries.

Kidney Development and Disease brings together established and young investigators who are leading authorities in nephrology to describe recent advances in three primary areas of research. The first section describes the use of animal models as powerful tools for the discovery of numerous molecular mechanisms regulating kidney development. The second section focuses on nephric cell renewal and differentiation, which lead to diverse cell fates within the developing kidney, and discusses diseases resulting from the aberrant regulation of the balance between cell fate decisions. The final section concentrates on morphogenesis of the developing kidney and its maintenance after formation as well as the diseases resulting from failures in these processes. Kidney form and function have been extensively studied for centuries, leading to discoveries related to their development and disease. Recent scientific advances in molecular and imaging techniques have broadened our understanding of nephron development and maintenance as well as the diseases related to these processes.

Fas Signaling is focused on the signaling mechanisms and biology of the prototypic death receptor Fas, also called CD95 or APO-1. The chapters of this book cover, besides the well recognized apoptosis-related functions of Fas, its emerging role as a proinflammatory cytokine and as an inducer of alternative forms of cell death. Fas Signaling aims to provide the reader with an up-to-date survey of the various aspects of Fas biology and the open questions of the field are addressed. This title is intended for Ph.D and post-doctoral students starting to work in the field, but is also useful for everyone with an interest in the biology of this exciting molecule.

Stem Cells and CNS Development critically reviews recent findings on stem cells, their involvement in neurogenesis and gliogenesis, and the therapeutic implications of these findings. It defines by consensus the classes of stem cells in the nervous system, compares their similarities and differences, discusses the gains made in identifying human homologs of neural stem cells, and describes how these cells are beginning to be used
for therapeutic purposes. Comprehensive and cutting-edge, this book provides all developmental scientists and neurobiologists not only an authoritative account of the current results in neural stem cell research, but also an incisive review of the rapidly emerging therapeutic uses of stem cells.

The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. More than 285 volumes have been published (all of them still in print) and much of the material is relevant even today-truly an essential publication for researchersin all fields of life sciences.
Key Features
* Prokaryotic ABC Transporters
* Eukaryotic ABC Transporters
* Nonmammalian ABC Transport Systems
* Mammalian P-Glycoproteins
* Multidrug Resistance Associated Protein
* Cystic Fibrosis Transmembrane Conductance Regulator
* Sulfonylurea Receptor
* Intracellular ABC Transporters

The last few years have witnessed an explosion of both interest and knowledge about apoptosis, the process by which a cell actively commits suicide. The number of publications on the topic has increased from nothing in the early 1980s to more than 10,000 papers annually today. It is now well recognized that apoptosis is essential in many aspects of normal development and is required for maintaining tissue homeostasis. The idea that life requires death seems somewhat paradoxical, but cell suicide is essential for an animal to survive. For example, without selective destruction of "non-self" T cells, an animal would lack immunity. Similarly, meaningful neural connections in the brain are whittled from a mass of cells. Further, developmental cell remodeling during tissue maturation involves programmed cell death as the major mechanism for functional and structural safe transition of undifferentiated cells to more specialized counterparts. Apoptosis research, with roots in biochemistry, developmental and cell biology, genetics, and immunology, embraces this long-ignored natural law. Failure to properly regulate apoptosis can have catastrophic consequences. Cancer and many diseases (AIDS, Alzheimer's disease, Parkinson's disease, heart attack, stroke, etc. ) are thought to arise from deregulation of apoptosis. As apoptosis emerges as a key biological regulatory mechanism, it has become harder and harder to keep up with new developments in this field.

Most organisms and populations have to cope with hostile environments, threatening their existence. Their ability to respond phenotypically and genetically to these challenges and to evolve adaptive mechanisms is, therefore, crucial. The contributions to this book aim at understanding, from a evolutionary perspective, the impact of stress on biological systems. Scientists, applying different approaches spanning from the molecular and the protein level to individuals, populations and ecosystems, explore how organisms adapt to extreme environments, how stress changes genetic structure and affects life histories, how organisms cope with thermal stress through acclimation, and how environmental and genetic stress induce fluctuating asymmetry, shape selection pressure and cause extinction of populations. Finally, it discusses the role of stress in evolutionary change, from stress induced mutations and selection to speciation and evolution at the geological time scale. The book contains reviews and novel scientific results on the subject. It will be of interest to both researchers and graduate students and may serve as a text for graduate courses.

The development of liposomes as a drug delivery system has fluctuated since its introduction in the late 1960's by A.D. Bangham. While academic research of liposomes as a model membrane system has always flourished, as the exponential growth of papers can testify, the application of these findings to medically useful products has gone through several crises. Following the original optimism in the 70's and early 80's, a period of severe skepticism ensued at the end of the 80's and beginning of the 90's, culminating in a moderate but real optimism in the mid 90's, as a result of a successful launch of the first products in the US and Europe.

In this collection of papers, the editors have gathered the most promising ideas, approaches, applications and commercial developments, thereby presenting an up-to-date compilation of the present status of the field. This includes such broad areas as anti-cancer chemotherapy immune stimulation and infectious diseases. Currently, the major areas of progress are in delivery of anti-fungal agents by conventional liposomes or lipid-based carriers and systemic anticancer therapy using long-circulating liposomes. The future applications as characterized by the direction of present day research is in specific targeting and delivery of informational molecules such as DNA plasmids (genes), antisense oligonucleotides or ribozymes. Other future developments may be in topical delivery, vaccination and in diagnostics.

Features of this book:

Contributions from almost all the leading labs in the field

Up-to-date, critical reviews bridged by editors' introductions

Organized into a logical framework."

The data reference books for practicing scientists present key information for a major subject in one place. This edition has been divided into two parts, recombinant DNA and gene analysis, comprising a compendium of up-to-date methods available in molecular biology. Covering enzymes used for restriction, methylation and modification of nucleic acids, cloning vectors, hosts, genomes and genes as well as techniques such as blotting and hybridization, DNA sequencing, PCR methodology, labelling and separation of nucleic acids.;The edition also provides information on general chemicals and reagents and safety considerations.

In the eight years since the original publication of Molecular Biology Labfax, there has been a vast proliferation of molecular biology techniques. The Second Edition has been divided into two parts: Recombinant DNA, and Gene Analysis. Together they comprise a comprehensive collection of the most up-to-date methods available in molecular biology. This second volume of the two-part Second Edition provides key information on nucleic acid blotting and hybridization, DNA sequencing, PCR, labelingnucleic acids, electrophoresis, centrifugation, chemicals and reagents, and safety. Molecular Biology Labfax will be essential for scientists of all disciplines within the life sciences who use molecular biological techniques.
Key Features
* Provides most up-to-date information on techniques, sources, and equipment for anyone using molecular biological techniques
* Clearly presented information
* Divided into two parts which together comprise a complete collection of molecular biological methods

The aim of the former editions remains unchanged in the present updated version, namely to put forward a general and comprehensive review on complement. It is intended not only for individual investigators working in this specific field, but also for those who are less familiar with it. Students or younger scientists will hopefully be stimulated and attracted by the fascination of complement biology. Again, it was clear from the beginning that the field has experienced an explosive expansion in various directions and continues to accumulate data too large to be dealt with by a single author in a critical and coherent manner. The editors are grateful that the invited authors, all of them leading scientists in their field, helped again to make The Complement System a true mirror of the state of the art. Some parallels in the various chapters were accepted, as was a particular emphasis on newer developments in some chapters.

This book offers a broad collection of methods for studying the molecular biology, function, and features of mitochondria. In the past decade, mitochondrial research has elucidated the important influence of mitochondrial processes on integral cell processes. This practical guide presents a wide spectrum of mitochondrial methods, each written by specialists with solid experience and intended for implementation by novice and expert researchers alike.

Video microscopy is used extensively in many life and biomedical science disciplines today, and is a useful tool for both cell biologists and students. This book presents how to track the dynamic changes that take place in the structure of living cells and in reconstituted preparations using video and digital imaging microscopy. Basic information, principles, and applications are also covered, as well as more specialized video microscopy techniques.
Key Features
* Chapters cover the commonly used video technologies in biological research
* Nontechnical presentation of principles
* Emphasis on the practical aspects of instrument use
* Covers pitfalls in instrument uses that can lead to artifacts
* Authors are leaders in the design and application of video methods to biological microscopy
* Presentation of material tailored for the established researcher that has little experience with video methods
* Examples are extensively illustrated with photographs

Gaining an understanding of the mechanisms by which cells process and respond to extracellular cues has become a major goal in many areas of bi- ogy and has attracted the attentions of almost every traditional discipline within the biological sciences. At the heart of these divergent endeavors are common methods that can aid biochemists, physiologists, and pharmacologists in ta- ling the specific questions addressed by their research. In Receptor Signal Transduction Protocols, a diverse array of meth- ologies employed to interrogate ligand--receptor and receptor-effector int- actions are described by authors who have devised and successfully applied them. The authors blend excellent descriptions and applications of fairly well established methodologies with new technologies at the cutting-edge of signal transduction research and as such I hope the present volume will complement and extend a previous excellent volume in this series edited by David Kendall and Stephen Hill (Methods Molecular Biology, vol. 41, Signal Transd- tion Protocols).

Conditions such as oxidative stress and hypoxia, which have a generalized impact on the oxygen metabolism, have been implicated in the genesis of kidney disease. This means that deepening our understanding of the pathobiology of oxygen metabolism in such diseases could be a fruitful path towards tangible clinical benefits. Studies in Renal Disorder collects reviews from leading researchers and clinical scientists working in exactly this field, providing an overview of the latest advances. The causal role of impaired oxygen metabolism in kidney disease has numerous clinical implications. It affects our understanding of the therapeutic benefits accruing from anti-hypertensive agents; the way we control hyperglycemia/hyperinsulinemia and hyperlipidemia; and our use of dietary approaches to the correction of obesity. The defensive mechanisms against oxidative stress, such as the Nrf2-Keap1 system, and hypoxia, such as the PHD-HIF system, have recently been explored in various cells, including kidney cells. These mechanisms include intracellular sensors for oxidative stress and hypoxia. This means that novel approaches targeting these sensors may offer clinical benefits in kidney disease in which oxidative stress and/or hypoxia is a final, common pathway.