In March 2000 leading scientists gathered at the Centro Seminariale Monte Verita, Ascona, Switzerland, for the Third International Symposium on "Fractals 2000 in Biology and Medicine." This interdisciplinary conference was held over a four-day period and provided stimulating contributions from the very topical field Fractals in Biology and Medicine. This Volume III in the MBI series highlights the growing power and efficacy of the fractal geometry in understanding how to analyze living phenomena and complex shapes. Many biological objects, previously considered as hopelessly far from any quantitative description, are now being investigated by means of fractal methods. Researchers currently used fractals both as theoretical tools, to shed light on living systems self-organization and evolution, and as useful techniques, capable of quantitatively analyzing physiological and pathological cell states, shapes and ultrastructures. The book should be of interest to researchers and students from Molecular and C"

Continuous cell lines derived from human cancers are the mostwidely used resource in laboratory-based cancer research. The first 3 volumes of this series on Human Cell Culture are devoted to these cancer cell lines. The chapters in these first 3 volumes have a common aim. Their purpose is to address 3 questions offundamental importance to the relevanceof human cancer cell lines as model systems of each type of cancer: 1. Do the cell lines available accurately represent the clinical presentation? 2. Do the cell lines accurately represent the histopathology of the original tumors? 3. Do the cell lines accurately represent the molecular genetics of this type of cancer? The cancer cell lines available are derived, in most cases, from the more aggressive and advanced cancers. There are few cell lines derived from low grade organ-confined cancers. This gap can be filled with conditionally immortalized human cancer cell lines. We do not know why the success rate for establishing cell lines is so low for some types of cancer and so high for others. The histopathology of the tumor of origin and the extent to which the derived cell line retains the differentiated features of that tumor are critical. The concept that a single cell line derived from a tumor at a particular site is representative oftumors at that site is naive and misleading."

Cell biologists have recently come to understand that asymmetry of division is an important regulatory phenomenon in the fate of a cell. In adult organisms asymmetric divisions regulate the stem cell reservoir and are a source of the drift that contributes to aging. This book describes the phenomenon in different organisms and addresses its implications for the development of the organism, cell differentiation, human aging and the biology of cancers.

The book is structured in nine sections, each containing several chapters. The volume starts with an overview of analytical techniques and progresses through purification of proteins; protein modification and inactivation; protein size, shape, and structure; enzyme kinetics; protein-ligand interactions; industrial enzymology; and laboratory quality control. The book is targeted at all scientists interested in protein research.

Writing or editing a book on a very topical field of science is always a great challenge,since by the time the book is published some of the newest and latest findings might be obsolete compared with results reported in the most current issues of various high-level journals. Nevertheless,stimulating good books describe complicated systems and int- relationships and provide a broad spectrum of material for talented researchers who may find new inspiration from a joint presentation of correlated data. Of course,an editor cannot rank his own book. However,in this case,the contrib- ing authors have high scientific standards and well-known achievements which speak for themselves. Transmembrane signaling has many different forms and biochemical and biophysical details. However,the final outcome of transmembrane signaling at the cellular level elucidates some cellular functions, which are at the center of se- defense, alimentation, escape reactions, etc. Transmembrane signaling can be studied best in the immune system,in particular in lymphocytes,the main cel- lar carriers of immune defense. The different chapters are independent studies, written by well-known experts in their particular fields. Some chapters include the authors' very recent data, generalized, on the one hand, to provide und- standable material for those who are interested in the field but not experts. On the other hand,the current data and novel efforts to unify biochemical and bioph- ical events in a physiological description provide interesting reading for experts as well.

Exocytosis is a fundamental cellular process that is used by eukaryotic cells to release a variety of biological compounds including peptide hormones and neurotransmitters or to insert specific lipids and proteins in the plasma membrane. In recent years, a multidisciplinary approach promoted an extraordinary progress in the understanding of the molecular mechanisms regulating exocytosis. This led to the discovery of a large number of components belonging to the machinery that governs the fusion of secretory vesicles with plasma membranes in different cell systems, including neuronal and endocrine cells. The basic machinery required for vesicle fusion turned out to be well conserved through evolution from yeast to man. So far, because of the large number of components involved, understanding of the molecular basis of exocytosis has remained the privilege of a relatively small group of specialists. This book, written by recognized experts in the field aims at clarifying for a non-specialist audience the role of the key players in the exocytotic process not only in neuronal and endocrine cells but also in a variety of other relevant cell systems. introduce researchers and students to the forefront of this rapidly moving and fascinating field.

Haploid plants have the gametophytic number of chromosomes. They are of great importance, especially in studies on the induction of muta tions and also for the production of homozygous plants, they are needed in large numbers. The conventional methods employed by plant breeders for their production are cumbersome, time-consuming, laborious and rather inefficient. Sometimes it may take years to produce a pure line. However, with the introduction of in vitro techniques, especially anther culture for the induction of androgenesis, it has become increasingly evi dent that these methods considerably accelerate the production of haploids for plant breeding programs. During the last decade, in vitro-produced haploids have been incor porated into breeding programs of many agricultural crops, and positive results have been obtained especially with rice, wheat, potato, barley, maize, asparagus, sunflower, brassica, tobacco, etc. Among these, rice and wheat are the best examples in which a number of improved varieties have been released. In wheat, the breeding cycle can be shortened by three or four generations when the pollen haploid breeding method is used instead of conventional cross-breeding. The release of the wheat varieties Jinghua 1 and Florin is a typical example of what can be achieved with other crops. Taking these developments into considera tion, the present volume, Haploids in Crop Improvement I, was compil ed."

A collection of standard and cutting-edge techniques for using Xenopus oocytes and oocytes/egg extracts to reconstitute biological and cellular processes. These readily reproducible methods take advantage of the oocyte's impressive protein abundance, its striking protein translation capacity, and its breathtaking possibilities for the assembly of infectious viral particles by single cell injection of multiple RNAs. The authors focus on the versatility of frog oocytes and egg extracts in cell biology and signal transduction, and cover all the major uses of oocytes/extracts as experimental models.

Human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, are a key focus of current biomedical research. The emergence of state of the art culturing techniques is promoting the realization of the full potential of pluripotent stem cells in basic and translational research and in cell-based therapies. This comprehensive and authoritative atlas summarizes more than a decade of experience accumulated by a leading research team in this field. Hands-on step-by-step guidance for the derivation and culturing of human pluripotent stem cells in defined conditions (animal product-free, serum-free, feeder-free) and in non-adhesion suspension culture are provided, as well as methods for examining pluripotency (embryoid body and teratoma formation) and karyotype stability. The Atlas of Human Pluripotent Stem Cells - Derivation and Culturing will serve as a reference and guide to established researchers and those wishing to enter the promising field of pluripotent stem cell research.

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.

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.

Animal cell technology is a growing discipline of cell biology, which aims not only to understand structures, functions, and behaviours of differentiated animal cells but also to ascertain their ability to be used for industrial and medical purposes. The goal of animal cell technology includes accomplishments of clonal expansion of differentiated cells with useful ability, optimisation of their culture conditions, modulation of their ability for production of medically and pharmaceutically important proteins, and the application of animal cells to gene therapy, artificial organs, and functional foods. This volume gives the reader a complete review of the present state of the art in Japan and other countries where this field is well advanced. The Proceedings will be useful for cell biologists, biochemists, molecular biologists, immunologists, biochemical engineers, and other disciplines related to animal cell culture, working in either academic environments or in industries of biotechnology and pharmacy.

Theodosius Dobzhansky's statement that nothing in biology makes sense except in the light of evolution, also applies to the major histocompatibility complex (MHC). This book presents up-to-date, state-of-the-art reviews on diverse topics pertinent to MHC evolution, including the organization of the MHC in humans and other model vertebrates, the nature and origin of MHC polymorphism, MHC-parasite co-evolution, and the origin of the adaptive immune system. The book will be of interest not only for immunologists, geneticists, and evolutionary biologists, but also for other specialists who want to keep abreast of the latest developments in this rapidly expanding field.

Research into and interest in the role of stromal cells in immunology has exploded over the past 15 years. The conventional view that placed non-hematopoietic stromal cells as passive, structural, and supportive entities has now been replaced with an appreciation that these cells have active, dynamic roles during immune responses, and thus impact on the pathophysiology of multiple immune-mediated diseases. This book serves to provide solid grounding in the fundamentals of stromal immunology, focusing on the biological aspects of their function in addition to highlighting key areas for the development of the field in the future. The book is also a unique source of information on emerging concepts that place stromal cells from outside lymphoid organs as major contributors to the biology of diverse conditions, such as rheumatoid arthritis, chronic parasitic infection, inflammatory bowel disease, and cancer.

This volume looks at the latest methodologies used to study cellular metabolism with in silico approaches. The chapters in this book are divided into 3 parts: part I discusses tools and methods used for metabolic reconstructions and basic constraint-based metabolic modeling (CBMM); Part II explores protocols for the generation of experimental data for metabolic reconstruction and modeling, including transcriptomics, proteomics, and mutant generations; and Part III cover advanced techniques for quantitative modeling of cellular metabolism, including dynamic Flux Balance Analysis and multi-objective optimization. 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 thorough, Metabolic Network Reconstruction and Modeling: Methods and Protocols is a valuable resource for qualified investigators studying cellular metabolism, and novice researchers who want to start working with CBMM.

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 volume presents the most current reviews on how cancer stem cells (CSCs) hypothesis dictates that the continued proliferation of a tumor is dependent on a sub-population of self-renewing and asymmetrically dividing neoplastic stem cells that supply a largely differentiated tumor. This volume provides a comprehensive overview of the characteristics of CSCs, their role in central nervous system (CNS) tumors, and the recent CSC-specific treatment modalities being used. The emerging focus on CSCs in brain tumors represents a paradigm shift in our understanding of the pathogenesis of these neoplasms. Importantly, the realization that a distinct sub-population of cells contributes disproportionately to the growth and sustenance of central nervous system tumors has important implications for the treatment of such tumors. To treat CNS tumors, there is now a growing need to treat CSCs to achieve adequate tumor control.

An understanding of the mechanisms by which plants perceive environmental cues, both physical and chemical, and transduce the signals that influence specific expression of genes, is an area of intensive scientific research. With the completion of the genome sequence of Arabidopsis it is understood now that a larger number of genes encode for proteins involved in signalling cascades and transcription factors. In this volume, different chapters deal with plant receptors, second messengers like calcium ions, phosphoinositides, salicylic acid and nitrous oxide, calcium binding proteins and kinases. In addition to dealing with the response of plants to light, hormones, pathogens, heat, etc. on cellular activity, work currently going on in apoptosis, cell division, and plastid gene expression is also covered in this book.

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.

Epigenetic Regulation of Cancer in Response to Chemotherapy, Volume 158 of the Advances in Cancer Research series, highlights new advances in the field, with this new volume presenting interesting chapters. Each chapter is written by an international board of authors.

"Notch Signaling: Methods and Protocols" focuses on molecular, biochemical and bioinformatics aspects of Notch signaling. Chapters analyze the Notch interactome, post-translational modifications of Notch, ligand binding assays, methods to assess proteolytic cleavage and transcriptional targets. 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 key tips on troubleshooting and avoiding known pitfalls.

Authoritative and practical, " Notch Signaling: Methods and Protocols" is a valuable contribution to hundreds of labs and thousands of scientists who pursue this research area with vigor.

This second edition volume expands on the first edition with new developments on Toll-Like Receptors (TLRs) controlling events such as cross-priming of associated pattern recognition receptors, post-transcriptional regulation, interaction with other cellular and biologic systems, and cancer progression. This book is divided into five sections: Part I outlines methods for TLR detection, interaction, and intracellular trafficking; Part II describes methods and assays to investigate how TLRs cross-prime other pattern recognition receptors, including intracellular DNA receptors and inflammasome formation; Part III highlights RNA regulation, detailing how TLRs can induce RNA transcripts and molecules such as lncRNAs and microRNAs; Part IV explores TLR detection and activation in systems such as epithelial barrier function, metabolism and the circadian clock, as well as cellular systems including T and B lymphocytes; and Part V describes models to delineate the role of TLRs in diseases such as dermatitis, arthritis, and gastric cancer. Written in the highly successful Methods in Molecular Biology series format, each chapter contains a summary, a list of required materials, step-by-step, readily reproducible laboratory protocols, useful notes to investigate TLRs in cell culture, systems and disease, and tips on troubleshooting and avoiding known pitfalls. Practical and cutting-edge, Toll-Like Receptors: Methods and Protocols, Second Edition is a valuable resource to any immunologist, molecular or medical biologist working in a laboratory setting. It will add skill to both students and the more advanced molecular biologist who wishes to learn a new technique or move to a different area within their current repertoire of practical knowledge.

This text covers the basic principles of mitochondrial dynamics in cardiovascular medicine, with particular emphasis on their functional roles in physiology and disease. The book will include articles pertaining to mitochondrial fitness on a global basis, providing therefore an update on the progress made in several aspects in the field. Thus, it will assist scientists and clinicians alike in furthering basic and translational research. Organized in sections focusing on: basic science, mitochondrial dysfunction in cardiac disorders, in vascular disorders, in metabolic disorders, in kidney disease, therapeutic challenges and options, this essential volume fills imperative gaps in understanding and potentially treating several cardiovascular disorders.

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.

Of all scientific instruments, probably none has had more applications in the life sciences than the light microscope. In Light Microscopy: Methods and Protocols, expert researchers explore the basics and the latest advances in microscope instrumentation, sample preparation, and imaging techniques, all of which have been producing fundamental insights into the functions of cells and tissues. Chapters cover a variety of bright field and fluorescence microscopy-based approaches that are central to the study of a range of biological questions, providing information on how to prepare cells and tissues for microscopic investigations, covering detailed staining procedures, and exploring methods to analyze images and interpret the results accurately. Composed in the highly successful Methods in Molecular Biology(TM) series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Comprehensive and current, Light Microscopy: Methods and Protocols is an essential handbook for all researchers who are exploring the intriguing microscopic world of the cell.