The revolution in biological research initiated by the demonstration that particular DNA molecules could be isolated, recombined in novel ways, and conveniently replicated to high copy number in vivo for further study, that is, the recombinant DNA era, has spawned many additional advances, both methodological and intellectual, that have enhanced our understanding of cellular processes to an astonishing degree. As part of the subsequent outpouring of information, research exploring the mechanisms of gene regulation, both in prokaryotes and eukaryotes (but particularly the latter), has been particularly well represented. Although no one technical approach can be said to have brought the filed to its current level of sophistication, the ability to map the interactions of trans-acting factors with their DNA recognition sequences to a high level of precision has certainly been one of the more important advances. This "footprinting" approach has become almost ubiquitous in gene regulatory studies; however, it is in its ""in vivo"" application that ambiguities, confusions, and inconsistencies that may arise from a purely ""in vitro""-based approach can often be resolved and placed in their proper perspective. Put more simply, that an interaction can be demonstrated to occur between purified factors and a particular piece of DNA in a test tube does not, of course, say anything regarding whether such interactions are occurring "in vivo." The ability to probe for such interactions as they occur inside cells, with due attention paid to the relevant developmental stage, or to the tissue specificity of the interaction being probed, has made "in vivo" footprinting approach an invaluable adjunct to the "gene jockey's" arsenal of weapons.

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

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.

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.

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.

This book covers the origins and subsequent history of research results in which attempts have been made to clarify issues related to cellular ageing, senescence, and age-related pathologies including cancer. Cellular Ageing and Replicative Senescence revisits more than fifty-five years of research based on the discovery that cultured normal cells are mortal and the interpretation that this phenomenon is associated with the origins of ageing. The mortality of normal cells and the immortality of cancer cells were also reported to have in vivo counterparts. Thus began the field of cytogerontology. Cellular Ageing and Replicative Senescence is organized into five sections: history and origins; serial passaging and progressive ageing; cell cycle arrest and senescence; system modulation; and recapitulation and future expectations. These issues are discussed by leading thinkers and researchers in biogerontology and cytogerontology. This collection of articles provides state-of-the-art information, and will encourage students, teachers, health care professionals and others interested in the biology of ageing to explore the fascinating and challenging question of why and how our cells age, and what can and cannot be done about it.

How do you keep track of basic information on the proteins you work with? Where do you find details of their physicochemical properties, amino acid sequences, and structure? Are you tired of scanning review articles, primary papers, and databases to locate that elusive fact?
The Academic Press FactsBook Series has established itself as the best source of easily-accessible and accurate facts about protein groups. Described as "a growing series of excellent manuals" by "Molecular Medicine Today" and "essential works of reference" by "Trends in Biochemical Sciences," the FactsBooks have become the most popular comprehensive data resources available. Using an easy-to-follow format, the FactsBooks will keep you up-to-date with the latest advances in structure, amino acid sequences, physicochemical properties, and biological activity. Meticulously researched and compiled by experts in the field, keeping abreast of developments has never been so easy
The Transporter FactsBook contains entries covering almost 800 transporters. Organized into 55 families of structurally related transporters, this volume includes ATPases, ABC transporters, H+-dependent antiporters and symporters, Na+-dependent antiporters and symporters, and other transporters such as mitochondrial transporters.
Key Features
* Nomenclature, biological sources and substrates
* Phylogenetic relationships
* Predicted structures
* Physical and genetic characteristics
* Multiple amino acid sequence alignments
* Database accession numbers
* Key references

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

mRNA Formation and Function presents a compendium of techniques geared exclusively toward the understanding of RNA metabolism. It will be particularly useful because a number of different organisms and systems are employed.
Key Features
* Isolation and characterization of specific RNA binding proteins
* RNA metabolism and associated regulatory proteins
* RNA detection and localization
* A genetic approach to RNA function

The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ER stress . Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases."

This comprehensive volume discusses the current scope of umbilical cord blood transplantation (UCBT), including recent controversies and future developments for improving clinical outcomes. Its twenty chapters introduce new applications in regenerative medicine and discuss the latest scientific, regulatory, clinical and investigational aspects of cord blood banking. Physicians from around the world provide a global collaboration which explores strategies for umbilical cord blood expansion, homing, unit selection, and combining of graft sources to improve patient outcomes. Umbilical Cord Blood Banking and Transplantation also reviews advances in pediatric UCBT for hematologic and non-hematologic disorders as well as immune recovery, which is critical to preventing infection. Finally, it compares UCBT with other graft sources in an attempt to understand the optimal graft source for the individual patient. UCBT is an important option for many patients who need a transplant but do not have a family donor or a matched unrelated donor. The collective and timely knowledge presented here is essential reading for any regenerative medicine investigator, cord blood banker, transplant laboratory scientist or clinical physician interested in improving and expanding the applications of umbilical cord blood.

As mass spectrometric methods now offer a level of specificity and sensitivity unrealized by spectrophotometric- and immunoassay-based methods, mass spectrometry has entered the clinical laboratory where it is being used for a wide range of applications. In Clinical Applications of Mass Spectrometry: Methods and Protocols, expert researchers provide detailed step-by-step procedures for the analysis of number of analytes of clinical importance. This versatile and expansive volume covers mass spectrometry methods for analytes including a variety of drugs, hormones, and metabolic compounds spanning the disciplines of toxicology, therapeutic drug monitoring, endocrinology, and pediatric metabolism. Written in the highly successful Methods in Molecular BiologyT series format, chapters include brief introductions to the analytes, lists of the necessary materials and reagents, readily reproducible analytical protocols, and detailed notes on troubleshooting and avoiding known pitfalls. Comprehensive and dependable, Clinical Applications of Mass Spectrometry: Methods and Protocols offers its readers a wide array of valuable methods for experienced mass spectrometric labs that are looking to introduce new analyses as well as for those laboratories currently considering the addition of this resourceful and vital technology. Written for: Biochemists, laboratory scientists, pharmacologists, toxicologists, and endocrinologists