David Kuter and a host of leading international researchers summarize in one volume all the knowledge of thrombopoietins (TPO) available today. The distinguished experts review the history of the search to discover TPO, describe the molecular and biological characteristics of this new molecule, and present the results of the preclinical animal experiments that will guide clinical use of this new hormone. Along the way they provide the most recent and comprehensive guide to the biology of megakaryocytes and platelets.

This is the first in a series of volumes concerning the properties of the eukaryotic nucleus. Contributions from several of the most active laboratories are brought together to present a focused overview of a selected aspect of nuclear structure and function.

This book addresses the most recent advances in the transport of proteins across a variety of biological membranes. In addressing this topic, this volume includes several new twists not previously addressed in the literature. In the last few years, the study of protein translocation has been revolutionized by the availability of structural information on many of the components and complexes involved in the process. Unlike earlier books written on protein translocation, this volume considers these advances. In addition, several chapters discuss facets of protein translocation from a systems biology perspective, considered by many to be the next paradigm for biological study. Readers of this book will come away with a deeper understanding of the problems facing researchers of protein translocation and see how the most modern biological techniques and approaches are being recruited to answer those questions. The chapters are also written such that problems awaiting future investigation are clearly presented.

Nanoscale structures and materials have been explored in many biological applications because of their novel and impressive physical and chemical properties. Such properties allow remarkable opportunities to study and interact with complex biological processes. This book analyses the state of the art of piezoelectric nanomaterials and introduces their applications in the biomedical field. Despite their impressive potentials, piezoelectric materials have not yet received significant attention for bio-applications. This book shows that the exploitation of piezoelectric nanoparticles in nanomedicine is possible and realistic, and their impressive physical properties can be useful for several applications, ranging from sensors and transducers for the detection of biomolecules to sensible substrates for tissue engineering or cell stimulation. The book also focuses on the preparation, characterization and bio-applications of piezoelectric nanoparticles.

The latest edition in this continuing series includes the newest advances in the rapidly evolving field of animal cell culture, genetic manipulations for heterologous gene expression, cell line enhancements, improved bioreactor designs and separations, gene therapy manufacturing, tissue engineering, anti-apoptosis strategies and cell cycle research. The contents include new research articles as well as critical reviews on emerging topics such as viral and viral-like agent contamination of animal cell culture components. These papers were carefully selected from contributions by leading academic and industrial experts in the biotechnology community at the recent Cell Culture Engineering VI Meeting in San Diego, USA, 1998. However, the book is not merely a proceedings. Audience: Biochemical engineers, cell biologists, biochemists, molecular biologists, immunologists and other disciplines related to cell culture engineering, working in the academic environment and the biotechnology or pharmaceutical industry.

MicroRNA research and development is the billion-dollar baby and most lucrative option for drug discovery in gene therapy industries worldwide. Personalized microRNA treatments are in many cases the only remedy for viral diseases that have no cure in conventional drugs and offer to bring us closer than ever to "personalized medicine." They also counteract cancer and other infectious and neuro-diseases. Early diagnosis, prognosis, staging, and sub-classification of various cancers can easily be facilitated by microRNA-based biomarkers. MicroRNA surveys recent advances in RNA and RNA-protein components that highlight RNA delivery, its stability, and applications of RNA-based drugs for the modulation of gene/protein expression and gene editing. The book not only focuses on the modern medicines of microRNA-based early diagnostic and therapy development, but also works as a hidden treasure for drug discovery of multiple rare diseases worldwide. It offers indispensable learning materials for academic researchers, graduate, and medical students, and offers a powerful practical guide for RNA-Pharma and gene therapy industries.

One of the mysteries of mammalian reproduction is the physiologic process that determines the length of gestation. The proper timing of birth ensures that the young individual is sufficiently developed to survive and adapt in the extrauterine environment, and that the mother is capable to provide nutrition and protection to the newborn. This volume summarizes new knowledge obtained by many researchers seeking to unravel the compile mechanisms that contribute to the maintenance and termination of pregnancy. The most important common goal of these efforts is to reduce the incidence of preterm birth, which is the leading cause of perinatal morbidity and mortality in numerous countries.
Separate chapters are devoted to the best-studied animal models of parturition. In sheep, the fetus is in control of the timing of its own birth, while in avian species, oviposition is evidently determined by the female laying the feritlized egg. In humans and non-human primates, the roles of the fetus and the mother are more balanced, and involve a complicated and poorly understood interplay between the mother, the fetus, and the placenta. Some major aspects of these interactions, such as trophoblast function, myometrial contractility, and the endocrine-paracrine systems, are discussed in further chapters.

There are probably few people who do not dream of the good old times, when do ing science often meant fascination, excitement, even adventure. In our time, do ing science involves often technology and, perhaps, even business. But there are still niches where curiosity and fascination have their place. The subject of this book, technological as its title may sound, is one of the fortunate examples. It will report on lasers generating the coldest places in the Universe, and on table top laser microtools which can produce a heat "inferno" as it prevails in the interior of the Sun, or simulate, for specific plant cells, microgravity of the space around our plan et Earth. There will be some real surprises for the reader. The applications range from basic studies of the driving forces of cell division (and thus life) via genetic modification of cells (for example, for plant breeding) to medical applications such as blood cell analysis and finally in vitro fertilization. What are these instruments: laser microbeams and optical tweezers? Both are lasers coupled with a fluorescence microscope. The laser microbeam uses a pulsed ultraviolet laser. Light is focused, as well as possible, in space and time, in order to obtain extremely high light intensities - high enough to generate, for a very short instant, extremely hot spots which can be used to cut, fuse or perforate biological material."

The discovery of adult neurogenesis caused a paradigm shift in the neurosciences. For more than 100 years, it was believed that adult neurons do not regenerate. Joseph Altman and Fernando Nottebohm found proof to the contrary and changed the course of history. Their research, included here, provides the foundations of the field. Today, adult neurogenesis is a rapidly expanding discipline applicable to the study of brain development and diseases, learning and memory, aging, and neuropsychiatric disorders. With multiple authors, the 27 chapters of this book contain the latest work in two volumes. The first presents the basic biology of adult neurogenesis in non-mammalian vertebrates and in the mammalian hippocampus and olfactory bulb, and the second discusses clinical implications and delves into adult neurogenesis and brain injury as well as neurodegenerative and neuropsychiatric pathologies. With details of the anatomy, physiology, and molecular biology of the two neurogenic brain regions, this book provides indispensable knowledge for many areas of neuroscience and for experimental and clinical applications of adult neurogenesis to brain therapy.

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.

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."

The migration of stem cells has been found to be critical during early development for the organization of the embryonic body as well as during adult life with tissue homeostasis and regeneration of organ function. Due to the low frequency of these cells in vivo, problems in identifying and prospectively purifying tissue specific stem cells near homogeneity, and, most importantly, a lack of adequate technologies and protocols to study stem cell migration in vivo, this vital research has been quite difficult until recently. In "Stem Cell Migration: Methods and Protocols," experts in the field compile and highlight the standard and novel techniques that allow the studying of the migration of stem cells in one succinct manual. Including protocols on germ, neuronal, and hematopoietic stem cells, during development and adulthood with a clear emphasis on in vivo technologies, the volume also extends its coverage to in vitro approaches toward several developmentally-conserved signaling pathways. 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.

Practical and convenient, "Stem Cell Migration: Methods and Protocols" provides key, state-of the art information on experimental techniques for studying stem cell migration both at a cellular and molecular level in development, regeneration, and disease.

This detailed volume provides thorough protocols describing how to use genetics to study mouse and zebrafish erythropoiesis in whole animal models and for genetically manipulating cultured mouse and human erythroid cells. Protocols include strategies to analyze circulating red blood cell parameters, as well as progenitor cell status, stage of differentiation, and enucleation. Methods for the study of erythroid cell gene regulation using chromatin immunoprecipitation and chromatin conformation capture are detailed. Furthermore, protocols are provided to examine stress erythropoiesis, erythroblastic islands, and erythroblast structure. The collection also includes reviews on the available mouse models of erythropoiesis, as well as on future considerations for good manufacturing practice in order to translate the manufacture of erythrocytes to the clinic. Written for the highly successful Methods in Molecular Biology series, 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 practical, Erythropoiesis: Methods and Protocols provides a definitive source for molecular and cellular biology protocols to study erythropoiesis and to move this vital field forward.

This volume covers data describing the role of free radicals and antioxidants that deal with clinical and pre-clinical trials, as well as basic research in the area of women's health. There is increasing evidence that oxidative stress is a causative, or at least a supporting factor in female pathology and infertility. During advancing gestational age, oxidative stress biomakers rise. Oxidative stress plays a regulatory role in transcription, signal transduction, gene expression and membrane trafficking. A search on Pub Med shows 449 papers have been published to date related to women's health disorders and use of antioxidants in a variety of disease that are prevalent in women, such as hypertension and cardiovascular disease, osteoporosis, obesity and restless leg syndrome.

In Neuronal Cell Culture: Methods and Protocols, the latest aspects of the culture of neural cells are explored by experts in the field who also explain the practical and theoretical considerations of the techniques involved. Starting with a general overview of the neuronal culturing principles that are described, this detailed volume covers cell line models for neural cells, the isolation and propagation of primary cultures, stem cells, transfection and transduction of neural cultures, and other more advanced techniques. Written for the Methods in Molecular Biology series, 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. Practical and easy to use, Neuronal Cell Culture: Methods and Protocols will be of interest to scientists at all levels developing cell culture models for neuroscientific studies.

Mechanics plays a central role in determining form and function in biology. This holds at the cellular, molecular and tissue scales. At the cellular scale, mechanics in?uences cell adhesion, cytoskeletal dynamics and the traction that the cell can generate on a given substrate. All of these in turn - fect the cellular functions of migration, mitosis, phagocytosis, endocytosis and stem cell differentiation among others. Indeed, if cells do not develop the appropriate stresses, they are unviable and die. These aspects of cell mechanics are frequently used by mainstream biologists, as traditional mechanicians may be surprised to learn. There is a growing view that many functions of the cell are mechanical in nature even though chemical signals play crucial roles in the processes. Free energy barriers control transitions between different conformations of vir- ally every macromolecule including DNA, RNA, the adhesion protein integrin, the motor protein myosin, and the proteins vinculin and talin that link the cytoskeleton to focal adhesions. The strain energy can be a signi?cant component of the total free energy barrier. For binding to take place, the macromolecules need to be in conf- mational states that expose chemical groups without steric hinderance. The kinetics of chemical reactions are therefore strongly in?uenced by the conformational strain energy.

This book outlines the interaction of cadmium with the proteome and signalling molecules of mammalian cells. Chapters from expert contributors cover topics such as cadmium chemical biology, membrane receptors and transporters for cadmium and cadmium complexes, and targets of cadmium toxicity. Students and researchers working in bioinorganic chemistry will find this book an important account.

This volume describes the state-of-knowledge in the study of the relationships between mechanical loading states in tissues and common pathophysiologies related to increase in mass of adipose tissues and/or hyperglycemia which eventually lead to obesity, diabetes, insulin resistance, hyperlipidemia, metabolic inflammations, certain types of cancer and other related diseases. There appears to be an interaction between the loading states in tissues and cells and these chronic conditions, as well as with factors such as age, gender and genetics of the individual. Bioengineering has made key contributions to this research field in providing technologies for cell biomechanics experimentation, microscopy and image processing, tissue engineering and multi-scale, multi-physics computational modeling. Topics at the frontier of this field of study include: the continuous monitoring of cell growth, proliferation and differentiation in response to mechanical factors such as stiffness of the extracellular matrix (ECM) and mechanical loads transferred through the ECM; mechanically-activated signaling pathways and molecular mechanisms; effects of different loading regimes and mechanical environments on differentiation fates of mesenchymal stem cells (MSCs) into myogenic and osteogenic versus adipogenic lineages; the interactions between nutrition and mechanotransduction; cell morphology, focal adhesion patterns and cytoskeletal remodeling changes in adipogenesis; activation of receptors related to diabetes by mechanical forces; brown and white adipose plasticity and its regulation by mechanical factors.

Plant protoplasts have proved to be an excellent tool for in vitro manipulation, somatic hybridization, DNA uptake and genetic trans- formation, and for the induction of somac1onal variation. These studies reflect the far-reaching impact of protoplast research in agriculture and forest biotechnology. Taking these aspects into consideration, the series of books on Plant Protoplasts and Genetic Engineering provides a survey of the literature, focusing on recent information and the state of the art in protoplast manipulation and genetic transformation. This book, Plant Protoplasts and Genetic Engineering VII, like the previous six volumes published in 1989, 1993, 1994, and 1995, is unique in its approach. It comprises 27 chapters dealing with the regeneration of plants from protoplasts, and genetic transformation in various species of Agrostis, Allium, Anthriscus, Asparagus, Avena, Boehmeria, Carthamus, Coffea, Funaria, Geranium, Ginkgo, Gladiolus, Helianthus, Hordeum, Lilium, Lithospermum, Mentha, Panax, Papaver, Passiflora, Petunia, Physcomi- trella, Pinus, Poa, Populus, Rubus, Saintpaulia, and Swertia. This book may be of special interest to advanced students, teachers, and research scientists in the field of plant tissue culture, molecular biology, genetic engineering, plant breeding, and general biotechnology. New Delhi, June 1996 Professor y. P. S. BAJAJ Series Editor Contents Section I Regeneration of Plants from Protoplasts 1. 1 Regeneration of Plantlets from Protoplasts of Allium cepa (Onion) E. E. HANSEN, J. F. HUBSTENBERGER, and G. C. PHILLIPS (With 3 Figures) 1 Introduction ...3 2 Protoplast Isolation ...4 3 Protoplast Culture ...8 4 Regeneration of Plantlets ...9 5 Summary...

This volume assembles protocols for chromosome engineering and genome editing in two recently developed approaches for manipulating chromosomal and genomic DNA in plants. The first approach is a "plant chromosome vector" system, which allows the introduction of desired genes or DNA into target sites on the chromosome vector, particularly by sequence-specific recombination. The second approach is "genome-editing," which makes it possible to introduce mutations into any of the genes of DNA that we wish to change. In addition, this book also covers other related techniques used to accelerate progress in plant chromosome and genome engineering. 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, Chromosome and Genomic Engineering in Plants: Methods and Protocols provides a comprehensive source of protocols and other necessary information to anyone interested in this field of study.

In Neuroprotective Signal Transduction prominent researchers and clinicians focus on how inter- and intracellular signaling mechanisms prevent the degeneration and death of neurons occurring in both acute and chronic neurodegenerative disorders. Authoritative contributions dissect the signaling pathways of an array of neuroprotective factors-ranging from neurotrophins (NGF, BDNF, NT-3, and NT-4/5), to growth factors (bFGF, IGF-1, GDNF), to cytokines (TNF, IL-1b, and TGFb), to secreted amyloid precursor proteins, to protease nexin-1. Also treated are cytoprotective signaling events that occur within injured neurons independently of intercellular signals. Neuroprotective Signal Transduction presents fundamental, cutting-edge treatment of the cellular and molecular signal transduction pathways found in human neurodegenerative conditions. The book's elucidation of the molecular cascades evolved by the nervous system to protect itself is now lead to effective strategies for preventing neuronal degeneration in such conditions as stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and will form the basis for powerful new drug discovery and gene therapy strategies.

An innovative theory proposes a new therapeutic strategy to break the stalemate in the war on cancer. It is called cancer stem cell (CSC) theory, and Lucie Laplane offers a comprehensive analysis, based on an original interdisciplinary approach that combines biology, biomedical history, and philosophy. Rather than treat cancer by aggressively trying to eliminate all cancerous cells-with harmful side effects for patients-CSC theory suggests the possibility of targeting the CSCs, a small fraction of cells that lie at the root of cancers. CSCs are cancer cells that also have the defining properties of stem cells-the abilities to self-renew and to differentiate. According to this theory, only CSCs and no other cancer cells can induce tumor formation. To date, researchers have not agreed on the defining feature of CSCs-their stemness. Drawing from a philosophical perspective, Laplane shows that there are four possible ways to understand this property: stemness can be categorical (an intrinsic property of stem cells), dispositional (an intrinsic property whose expression depends on external stimuli), relational (an extrinsic property determined by a cell's relationship with the microenvironment), or systemic (an extrinsic property controlled at the system level). Our ability to cure cancers may well depend upon determining how these definitions apply to different types of cancers.

This book focuses on issues in clinical practice and research that are of general interest. The articles primarily focus on understanding the pathogenic mechanisms of diseases, their prevention, and therapy. The topics addressed include cardiovascular regulation with regard to blood pressure and heart rate variability, and to coupling blood pressure changes with subarachnoid fluid oscillations. In addition, the book discusses recent advances in the diagnostics of and targeted molecular therapy for renal and pancreatic malignancies, growth disorders, vitamin D and calcium homeostasis in children in the context of neonatal urolithiasis, and neurosurgical interventions in multifarious age-related diseases of the vertebrae. Neuropsychological aspects of patients' quality of life and of shaping medical staff's attitude toward patients are also addressed. The respective articles are intended to build a bridge between basic and clinical research. Further, the book enhances the current body of knowledge on diagnostics and patient treatment and offers valuable new perspectives on practical clinical issues. As such, it offers a unique resource for clinicians, family physicians, medical scholars, and professionals engaged in patient management.

In the summer of 1988, my developmental biology professor announced to the class that hematopoietic stem cells (HSCs) had finally been purified. Somehow, I never forgot the professor's words. When I started working in Dr. Irv Weissman's labo- tory at Stanford as a postdoctoral fellow, I realized that the findings mentioned by the professor were from Weissman's laboratory and had been published in a 1988 edition of the journal Science. It has been over 20 years since the publication of that seminal paper, and since then tremendous advances in understanding the biology and maturation of HSCs, namely the process of hematopoiesis, which includes lymphocyte development, have been made. These discoveries were made possible in part by advancements in technology. For example, recent availability of user friendly fluorescence activated cell sorting (FACS) machines and monoclonal an- bodies with a variety of fluorescent labels has allowed more scientists to sort and analyze rare populations in the bone marrow, such as HSCs. All classes of hematopoietic cells are derived from HSCs. Stem cell biology draws enormous attention not only from scientists, but also from ordinary people because of the tremendous potential for development of new therapeutic application to diseases that currently lack any type of effective therapy. Thus, this type of "regenerative medicine" is a relatively new and attractive field in both basic science and clinical medicine.