This book features a special subsection of Nanomedicine, an application of nanotech nology to achieve breakthroughs in healthcare. It exploits the improved and often novel physical, chemical and biological properties of materials only existent at the nanometer scale. As a consequence of small scale, nanosystems in most cases are efficiently uptaken by cells and appear to act at the intracellular level. Nanotechnology has the potential to improve diagnosis, treatment and follow-up of diseases, and includes targeted drug delivery and regenerative medicine; it creates new tools and methods that impact sig nificantly upon existing conservative practices. This volume is a collection of authoritative reviews. In the introductory section we define the field (intracellular delivery). Then, the fundamental routes of nanode livery devices, cellular uptake, types of delivery devices, particularly in terms of localized cellular delivery, both for small drug molecules, macromolecular drugs and genes; at the academic and applied levels, are covered. The following section is dedicated to enhancing delivery via special targeting motifs followed by the introduction of different types of intracellular nanodelivery devices (e.g. a brief description of their chemistry) and ways of producing these different devices. Finally, we put special emphasis on particular disease states and on other biomedical applications, whilst diagnostic and sensing issues are also included. Intracellular delivery / therapy is a highly topical which will stir great inter est. Intracellular delivery enables much more efficient drug delivery since the impact (on different organelles and sites) is intracellular as the drug is not supplied externally within the blood stream. There is great potential for targeted delivery with improved localized delivery and efficacy.

The goal of Biological Aging: Methods and Protocols is to present some of the most promising and important tools that are currently used in biological aging research. These tools include established protocols such as aging cell culture as well as many more contemporary approaches such as nuclear transfer, microarray and proteomics technologies and the use of ribozymes in aging research. Collectively, these powerful tools combined with the many other techniques that are presented are rapidly advancing the exciting and expanding field of biological aging.

In aerobic tissues such as heart, brain, kidney, liver and brown fat, mitochon- dria account for more than 20% of cell protein and play an essential role in res- piration, ATP formation, ketogenesis, gluconeogenesis, amino acid metabolism, ureagenesis, thermogenesis and a variety of other metabolic activities. The mecha- nisms by which these activities are integrated and regulated within the overall context of cellular physiology is of much current research interest. In order to bring together scientists examining the various diverse aspects of this overall pro- blem, an International Conference on INTEGRATION OF MITOCHONDRIAL FUNC- TION was held June 4-7, 1987 at the Hanes Art Center on the campus of the Uni- versity of North Carolina at Chapel Hill. The chapters of this volume derive from presentations made at this conference. The focus of INTEGRATION OF MITOCHONDRIAL FUNCTION is on signifi- cant new experimental and theoretical advances concerning integration of mito- chondrial function at the organelle, cell, tissue and whole organism levels of organization.

Lysosomes are membrane-surrounded organelles which are present in all animal cells. The importance of this organelle is underlined by an increasing number of human diseases, which are associated with an impaired function of the lysosomal compartment.

This book summarizes the current state-of-the art knowledge about this unique organelle. It addresses the biogenesis of this compartment, the transport of lysosomal proteins, the role of the lysosomal membrane in lysosomal stability and transport, the function of lysosomal proteases and hydrolases, lysosomal storage disorders, and new concepts on how to treat these diseases. In addition to these classical topics, new insights into lysosomal functions are covered by chapters dealing with specialized lysosomes involved in bone resorption and plasma membrane repair, the lysosomal transciptome, and proteome and the emerging role of lysosomes in special forms of autophagy.

This book will provide readers with a comprehensive overview into how this fascinating organelle works and how research in the field is developing.

This volume illustrates how microfluidic approaches can meet the requirement of clinical diagnosis based on molecular or cellular biomarkers. Microchip Diagnostics: Methods and Protocols is divided into four sections describing the business aspects of the microfluidic-based systems for diagnosis, demonstrating how versatile microfluidics can be regarding to protein bioassay integration, presenting microfluidic approaches for nucleic analysis based on mono or diphasic format, and highlighting recent contributions. 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.

This detailed volume encompasses new technological developments that specifically address questions related to adenosine 3',5'-monophosphate (cAMP) compartmentalization, that probe relevant protein-protein interactions, that increase the spatial and temporal resolution of cAMP signal detection, and that can facilitate integration of the mounting complexity of the information that is becoming available on this signaling system. cAMP, the prototypical intracellular second messenger, regulates a large variety of cellular functions and biological processes, including gene transcription, cell metabolism, proliferation, development, as well as more specialized functions depending on the cell type, so the realization of its extremely complex spatial organization and local regulation is providing novel mechanistic insight into cell physiology and is producing a novel framework for the identification of disease mechanisms. Written in the highly successful Methods in Molecular Biology series format, chapters include introduction 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. Practical and authoritative, cAMP Signaling: Methods and Protocols serves as a vital resource for researchers working in this expanding, complex field.

The plant' is often the most neglected part of plant-based medicine. Throughout time, humans have searched, collected, and effectively used plants for healing. Currently, the medicinal plant-based business is flourishing at a dramatic pace and at the expense of an already declining population of plant species, many of which are on the verge of extinction. In spite of this history and popularity, the mystery of what transforms a plant into a medicinal plant persists, and there are chronic problems with ensuring the safety and efficacy of medicinal plant products. Therefore, there is a real need for a full characterization of medicinal plant species and for the development and application of novel technologies for the production of plant-based medicines. This book highlights some of the recent advances and new approaches to the development of technologies for plant-based medicines and is intended to stimulate new discussions among researchers, regulatory authorities, and pharmaceutical organizations, leading to significant advancements in the field.

Products from Cells - Cells as Products This book ist he "lasting" product, a resource ofup to date information in the scientific literature fort he field ofanimal cell tec hnology, as it was presented during a pleasant and s timulating mee ting that was held in Lugano Switzerland in April 1999. "Products" appeartwice int he title oft he conference. This clearly indicates the fact that the focus oft he papers presented during this meeting was really the application ofn ew technologies (novel reactors or novel vectors, for example for the preparation and/ort he more efficient generation ofproducts ) that could be used, mainly, int he medical field. Classical approaches forthe use ofa nimal cells, for example forthe p r oduction of virus vaccines for human and animal health, still remain an important technology and still have, surprisingly, quite significant potential for further development and improvement. How ever, it appears that major technological advances an d major growth from an economical point ofview are occurring in other areas. Most importantly, protein production on the basis of recombinant DNA molecules transferred into a nimal cells, appears to be an ever increasing field of interest and innovation, even though the first production scheme with this technology was approved more than 15 years ago.

Sodium channels confer excitability on neurons in nociceptive pathways and exhibit neuronal tissue specific and injury regulated expression. This volume provides recent insights into the control of expression, functioning and membrane trafficking of nervous system sodium channels and reviews why sodium channel sub-types are potentially important drug targets in the treatment of pain. The roles of sodium channels in dental and visceral pain are also addressed. The emerging role of sodium channel Nav1.3 in neuropathic states is another important theme.

Authors from the pharmaceutical industry discuss pharmacological approaches to the drug targeting of sodium channels, and in particular Nav1.8, exclusively expressed in nociceptive neurons. The final chapter highlights the functional diversity of sodium channels in part provided by post-transcriptional processing and the insights into sodium channel function that are being provided by tissue specific and inducible gene knock-out technology.

Recent work has revealed that stabilizing G-quadruplexes in telomeric DNA inhibits telomerase activity, providing impetus for the development of G-quartet-interacting drugs, while G-quartet-containing oligonucleotides have been recognized as a potent class of aptamers effective against STAT3 and other transcription factors implicated in oncogenesis, proving these guanine-quartets to be a vital and rich area for future study. In "G-Quadruplex DNA: Methods and Protocols", experts in the field present a collection of detailed techniques for studying G-quartet formation, dynamics, and molecular recognition. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, "G-Quadruplex DNA: Methods and Protocols "promises to be a useful resource for those familiar with G-quartets as well as an easy entry point for those researchers from diverse fields who are just developing an interest in the exciting implications of G-quadruplex DNA.

Epithelia are one of the commonest tissue types in the animal kingdom. Chapters from leading scientists in the major international research laboratories use examples from different systems to illustrate the form and function of epithelia. An important theme is the way in which epithelial cells differentiate to specialized tissue - reversal of this process occurs when cells become tumorigenic.

Systematic investigations of the structure, mechanics, and dynamics of biological surfaces help us understand more about biological processes taking place at cell and bacteria surfaces. Presented here is a study of the role membrane-bound saccharides play in the modulation of interactions between cells/bacteria and their environments. In this thesis, membrane structures were probed perpendicular and parallel to the surface, and sophisticated planar models of biomembranes composed of glycolipids of various structural complexities were designed. Furthermore, specular and off-specular X-ray and neutron scattering experiments were carried out. This research has led to the development of several new methods for extracting information on the structure and mechanics of saccharide-rendered biomembranes from the measured scattering signals. In fact, more is now known about the influence of the saccharide structure. These results demonstrate that the study of planar model systems with X-ray and neutron scattering techniques can provide comprehensive insight into the structure and mechanics of complex biological surfaces.

This essential volume explores mesenchymal stem cells (MSCs) and their potential to suppress immune-mediated inflammation. The chapters examine applications in autoimmune diseases such as lupus, rheumatoid arthritis and multiple sclerosis; blood cancers such as leukemia and lymphoma; and reproductive complications, specifically pre-term labor and use of MSCs in vitro and in animal models to discover methods of suppressing the causal inflammatory response. It also further defines the methodologies required to develop research on MSCs in vitro into established preclinical animal models including those which are proven replicas of autoimmunity and pre-term labor, to name but two. Mesenchymal Stem Cells and Immunomodulation, part of Springer's Stem Cell Biology and Regenerative Medicine, is an invaluable resource for researchers and clinicians working with stem cells, autoimmune disease, oncology, and reproductive medicine.

Despite many technological challenges faced by the xenotransplantation field, many major advances have been made in the last two decades. The field seeks to overcome the limitations and difficulties in organ procurement, which also apply to human cells and tissues, and facilitate the development of new therapies based on cell and engineered-tissue. Xenogeneic cells are simpler than solid organs and seem to pose less hurdles to attain long-term graft survival. In, Xenotransplantation: Methods and Protocols expert researchers study characterizations of xenogeneic interactions at the cellular and molecular levels and describe the use of relevant small-animal and pig-to-primate models. Related ethical and legal considerations are also covered. Written in the highly successful Methods in Molecular Biology (TM) series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Xenotransplantation: Methods and Protocols aids scientists in continuing to study xenotransplantation and its multiple aspects.

Investigation of the mechanisms of cellular response to different mechanical stimuli, as well as mechano-electrical feedback (MEF) in the intact heart is one of the main topics in fundamental and clinical cardiology. The present volume of "Mechanosensitivity in Cells and Tissues: Mechanosensitivity of the Heart" c- bines excellent reviews written by worldwide leaders in this ?eld. The 3rd volume is a great addition to this excellent series of books edited by Andre Kamkin and Irina Kiseleva. This volume successfully combines reviews, aimed at academic, physiology and clinical cardiology communities, devoted to mechanosensitivity of the normal and diseased heart at the ion channel, cell, tissue and organ levels. Kamkin and Kiseleva have made signi?cant contributions to the investigation of mechanosentive ion channels in cardiomyocytes and ?broblasts. Their ba- ground, in addition to extensive collaborations helped them to ?nd and consolidate valuable research ?ndings from prominent specialists in the ?eld of cardiac mechanosensitivity. In the last decade, interest in the role of MEF in the heart has increased sign- cantly. MEF within cardiac tissue is a complex phenomenon in which electroph- iological changes are triggered by myocardial stretch. This phenomenon has been studiedintheclinicalcommunityforoveracenturyandmayhavebothpro-rhythmic and arrhythmogenic consequences. While signi?cant advances have been made in understanding of the effects of mechanical forces on cardiac cells, many questions remain regarding the mechanisms whereby mechanical forces are transduced into changes which alter the behavior of various cardiac cells.

In situ hybridization has developed as a means of localizing specific DNA and RNA sequences within tissues. The great strength of this approach is the ability to relate the distribution of specific nucleic acids with cell structures and the protein products of the target gene by means of immunohistochemistry. Complementary DNA, RNA or oligonucleotide probes, suitably labelled, are hybridized to specific DNA or RNA targets within tissues. The spatial information thus obtained has contributed greatly to our understanding of such diverse areas of research as gene mapping, viral infection, cytogenetics, protein synthesis, prenatal diagnosis and tissue grafting. This book is not intended as another recipe book, although it does describe theoretical and practical aspects of the technology. Rather, the authors critically describe the contribution made by in situ hybridization to specific areas of medical research.

The current explosive progress in molecular biological research can be definitively traced to the development of molecular cloning technology. The ability to insert specific gene sequences into cloning vectors and their subse quent expansion is the cornerstone of modem molecular biology. A direct practical outcome of molecular cloning technology is its application to ex press specific recombinant genes. Currently, recombinant gene products are used in a wide spectrum of applications, including gene therapy, production of bioactive pharmaceuticals, synthesis of novel biopolymers, in agriculture and animal husbandry, and so on. A fundamental requirement for successful recombinant gene expression is the design of the cloning vector and the choice of the host organism for expression. Recombinant Gene Expression Protocols grows out of the need for a laboratory manual that provides the reader the background and rationale, as well as the practical protocols for the preparation of "expression constructs" and their introduction into appropriate host cells and/or organisms. The chap ters in this book are grouped by their expression hosts, including E. coli, yeast, mammalian cells, nonmammalian eukaryotes such as plants, Xenopus, and insects, as well as in transgenic organisms. In-depth information is presented on the important characteristics of expression cloning vectors and the various methods for efficiently introducing expression constructs into target cells and/ or organisms. Throughout Recombinant Gene Expression Protocols, the authors have consistently striven for a balanced presentation of both background informa tion and actual laboratory details.

Since the initial establishment of Robert Koch's postulates in the nineteenth century, microbial protein toxins have been recognized as a major factor of bacterial and fungal virulence. An increasing number of proteins produced and secreted by various bacteria, yeasts and plants are extremely toxic and most of them developed remarkably "intelligent" strategies to enter, to penetrate and to finally kill a eukaryotic target cell by modifying or blocking essential cellular components.

This book describes the strategies employed by protein toxins to render their pro- and eukaryotic producers a selective growth advantage over competitors. In providing an up-to-date overview on the mode of protein toxin actions, it accommodates biomedically and biologically relevant toxin model systems. As a result, it significantly broadens our perspective on biochemical architecture and molecular ploy behind the lethal principles of pro- and eukaryotic toxins.

Koval provides an interdisciplinary forum for the diverse studies involved in the stress biology of eukaryotic cells. Readers gain access to the most recent information available for eukaryotic systems ranging from plants to humans. For the student, this format introduces a source of potentially unifying concepts and hypotheses. Scientists will find a unique opportunity to conveniently examine the similarities among inducible responses initiated by a variety of agents.

This book is a broadly historical account of a remarkable and very exciting scientific story-the search for the number of human chromosomes. It covers the processes and people, culminating in the realization that discovering the number of human chromosomes brought as much benefit as unraveling the genetic code itself. With the exception of red blood cells, which have no nucleus and therefore no DNA, and sex cells, humans have 46 chromosomes in every single cell. Not only do chromosomes carry all of the genes that code our inheritance, they also carry them in a specific order. It is essential that the number and structure of chromosomes remains intact, in order to pass on the correct amount of DNA to succeeding generations and for the cells to survive. Knowing the number of human chromosomes has provided a vital diagnostic tool in the prenatal diagnosis of genetic disorders, and the search for this number and developing an understanding of what it means are the focus of this book.

The decline of infections, starvation, heart attack, and stroke has allowed people to reach extreme old age--and ushered in disability, dementia, and degenerative disease, with profound consequences for the self and society. In chapters echoing Dante's nine circles of hell, Dr. Guy Brown explores these vital issues at various levels, from the cell, to the whole body, to society and how all this new medical technology affects the meaning of death. He tracks the seismic shifts in the causes and character of death that are rocking medicine and reveals how technological innovations, such as cloning and electronic interfaces, hint at new modes of "survival" after death.

This thoughtful and provocative book provides a concise, up-to-date presentation of how current and projected future phosphorus scarcity will affect legume growth and their symbiotic nitrogen-fixing capabilities. It is a timely examination of the physiological and molecular responses of nodules to phosphorous deficiency in attempt to identify common principles. Students and researchers in the many disciplines related to crop productivity will find this title an exciting contribution in the area of plant stress physiology. The knowledge in this volume can also aid plant breeders, particularly through new methods of genetic engineering, in developing unique and adaptive cultivars with higher symbiotic efficiency. The awareness of the rapidly rising world population must translate into a parallel increase in agricultural production in order to sustain the growing population both now and in the future. Hence, the demand for food crops to produce proteins and vegetable oil for human consumption is going to increase considerably during the coming years. The essential role of legumes in agriculture is well-recognized, given the abundant levels of proteins and oils found in plants along with their enormous contribution to the sustainability of agricultural systems and human health. The capacity of legumes to fix nitrogen (N2) in partnership with rhizobia provides an input-saving and resource-conserving alternative, thereby reducing the need for chemical fertilizers while enhancing overall crop productivity. The use of N2-fixing legumes to produce plant proteins results in a substantial decrease in the consumption of fossil fuels and therefore also in the agricultural effects to global warming. However, a major constraint to legume production is low soil phosphorus (P) availability, considering that an overwhelming majority of the world's soils are classified as P-deficient. Low-P availability is especially problematic for legumes, since legume nodules responsible for N2 fixation have a high P requirement. Therefore, this book explains how nodule N2 fixation responds to low P availability, which is crucial for improving legume production and maintaining agricultural sustainability in the context of the global P crisis.

''Interesting with many useful ideas and references. It covers a broad range and it is a good introduction to this field.'' ---Analyst

The receptor-associated JAK protein kinases and their substrates, the STAT transcriptional activators, transmit signals following cytokine and growth factor binding to receptors expressed on the cell surface, to result in specific transcriptional and cellular responses. Over the last two decades, the field has progressed from identification of the individual components through to an understanding of the activation and deactivation mechanisms, and the complex structural detail of the proteins involved. We now know that these pathways are important in many biological processes, including growth and development, hematopoiesis, and the innate and adaptive immune response. JAK-STAT Signalling: Methods and Protocols provides detailed methodologies for examining many aspects of the pathway. Divided into four sections, topics include JAK and STAT specific approaches, the negative regulators of the pathway (SOCS proteins), and the production and crystallization of JAK and STAT proteins, among others. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, JAK-STAT Signalling: Methods and Protocols will be of use not only to those working in the area but also to new investigators who are led to delve into the complexities of JAK and STAT responses.

Transposable elements are short lengths of DNA with the capacity to move between different points within a genome. This process can affect the function of genes at or near the insertion site. The present book gives an overview of the impact of transposable elements on plant genomes and explains how to recognize and study transposable elements, e.g. by using state-of-the-art strategies like "new generation sequencing." Moreover, the impact of transposable elements on plant genome structure and function is reviewed in detail, and also illustrated in examples and case studies. The book is intended both for readers familiar with the field and for newcomers. With large-scale sequencing becoming increasingly available, more and more people will come across transposable element sequences in their data, and this volume will hopefully help to convince them that they are not just "junk DNA."