* Discusses cancer cell biology in relation to Genome stability and Cell cycle regulation Unique assembly of experts in these fields who wrote a comprehensive and deep up-to-date overview Discusses models for the understanding of DNA damage-dependent signal transduction and regulation in human cells Since the establishment of the DNA structure researchers have been highly interested in the molecular basis of the inheritance of genes and of genetic disorders. Scientific investigations of the last two decades have shown that, in addition to oncogenic viruses and signalling pathways alterations, genomic instability is important in the development of cancer. This view is supported by the findings that aneuploidy, which results from chromosome instability, is one of the hallmarks of cancer cells. Chromosomal instability also underpins our fundamental principles of understanding tumourigenesis: It thought that cancer arises from the sequential acquisition of genetic alterations in specific genes. In this hypothesis, these rare genetic events represent rate-limiting bottlenecks' in the clonal evolution of a cancer, and pre-cancerous cells can evolve into neoplastic cells through the acquisition of somatic mutations. This book is written by international leading scientists in the field of genome stability. Chapters are devoted to genome stability and anti-cancer drug targets, histone modifications, chromatin factors, DNA repair, apoptosis and many other key areas of research. The chapters give insights into the newest development of the genome stability and human diseases and bring the current understanding of the mechanisms leading to chromosome instability and their potential for clinical impact to the reader.

The Biogenesis of Cellular Organelles represents a comprehensive summary of recent advances in the study of the biogenesis and functional dynamics of the major organelles operating in the eukaryotic cell. This book begins by placing the study of organelle biogenesis in a historical perspective by describing past scientific strategies, theories, and findings and relating these foundations to current investigations. Reviews of protein and lipid mediators important for organelle biogenesis are then presented, and are followed by summaries focused on the endoplasmic reticulum, Golgi, lysosome, nucleus, mitochondria, and peroxisome. All chapters are written by experts in their fields and, though concentrated on particular topics, are integrated under the general themes of organelle structure, function, dynamics, and biogenesis. An understanding of these concepts is important for all researchers and students interested in general cell biology and particularly to those with interests in organelle function.

Edward B. Lewis' science is the bridge linking experimental genetics as conducted in the first half of the 20th century, and the powerful molecular genetic approaches that revolutionized the field in its last quarter. His Nobel Prize winning studies founded the field of developmental genetics and laid the groundwork for our current understanding of the universal, evolutionarily conserved strategies controlling animal development. A lesser-known aspect of Lewis' canon is the pioneering studies he carried out on ionizing radiation and human cancer. In doing so, he was propelled into a public storm over nuclear weapons testing policy. For the first time Lewis' key publications in the fields of genetics, developmental biology, radiation and cancer are compiled within one volume. commentaries on the papers placing them in their scientific and historical context and, throughout, giving insight into Lewis' approach to science and the motivations that drove Lewis' choice of subject matter. This book will be invaluable to a wide audience of professionals in the life and biomedical sciences; including geneticists, developmental biologists, molecular biologists, radiation biologists and cancer researchers. It provides source material for advanced undergraduate and graduate level courses in genetics, developmental biology, radiation and cancer. In addition, historians of science will find it to be a valuable resource both because it contains original research publications and because of the illuminating commentary.

In today's world, three great classes of non-infectious diseases - the metabolic syndromes (such as type 2 diabetes and atherosclerosis), the cancers, and the neurodegenerative disorders - have risen to the fore. These diseases, all associated with increasing age of an individual, have proven to be remarkably complex and difficult to treat. This is because, in large measure, when the cellular signaling pathways responsible for maintaining homeostasis and health of the body become dysregulated, they generate equally stable disease states. As a result the body may respond positively to a drug, but only for a while and then revert back to the disease state. Cellular Signaling in Health and Disease summarizes our current understanding of these regulatory networks in the healthy and diseased states, showing which molecular components might be prime targets for drug interventions. This is accomplished by presenting models that explain in mechanistic, molecular detail how a particular part of the cellular signaling web operates properly in health and improperly in disease.

The stability of the health- and disease-associated states is dynamic and supported by multiple feedback loops acting positively and negatively along with linkages between pathways. During the past few years an ongoing series of important discoveries have been made that advance our understanding of how the body works and may guide us on how to better deal with these diseases. These include the discovery of chronic inflammation as a causal factor in all of these disease classes, the appearance of reactive oxygen species as a messenger molecule that can act both positively and negatively, the propensity of proteins to misfold into aggregation- and disease-prone forms, and the rise of epigenetics including the emergence of small non-coding RNA with important regulatory functions out of the so-called junk RNA. Chapters are devoted to each of these classes of findings with additional details integrated into the chapters dealing directly with the diseases. The connections responsible for maintaining stability are explored in depth.

This title will focus on the study of human interphase chromosomes and its relation to health and disease. Orchestrated organization and human genome function in interphase nuclei at the chromosomal level have been repeatedly shown to play a significant role in a variety of basic biological processes involved in realization and inheritance of genetic information within and between species. Current biomedical sciences of post-genomic era refocus basic and applied studies of interphase nuclei genetics and genomics with special attention to interphase chromosome behavior in health and disease. Additionally, related processes are a target of studies elucidating the role of interphase chromosome behavior during development, chromosome/DNA replication, DNA reparation etc. Studies of interphase nuclei have an appreciable impact on different areas of biomedical sciences such as cell biology, neurobiology, cancer research, developmental biology, epigenetics, cytogenetics, and medical genetics, as a whole. Moreover, development of innovative and emergent technologies to analyze interphase nuclei are closely associated with application of these techniques in clinical, diagnostic and research practice to solve reproductive problems (including infertility and spontaneous abortions), to investigate congenital malformations (including those produced by aneuploidy and other chromosome abnormalities); genetic diseases (including cardiac, immune, neurological and psychiatric diseases), and cancer. This title will serve as a source of new valuable information and promising ideas for a wide audience of professionals in biomedicine including researchers, scientists, and healthcare professionals in human genetics, cytogenetics, and developmental biology.

Heart disease is the leading cause of death in developed countries. Recent experimental advances featuring cellular, molecular, and genetic tools and technologies offer the potential for new therapeutic strategies directed toward remediation of inherited and acquired heart diseases. Whether these recent basic science advances will ultimately translate to clinical efficacy for patients with heart disease is unknown and is important to ascertain. Cardiac Cell and Gene Transfer: Principles, Protocols, and Applications is designed to provide the reader with up-to-date coverage of a myriad of specific methodo- gies and protocols for gene and cell transfer to the myocardium. Each chapter features a "Notes" section that provides useful "how to" problem-solving insights that are often left unstated in standard published protocols. Cardiac Cell and Gene Transfer: Principles, Protocols, and Appli- tions addresses principles and applications of cell and gene transfer to the heart, including protocols for vector production and purification. Detailed step-by-step methods and applications for first/second-generation adenoviral vectors, adeno-associated vectors, gutted adenoviral vectors, and lentiviral vectors are included. Additionally, detailed methods for cardiac cell grafting and transplantation are provided, and these chapters highlight the prospects of cell-based therapies for cardiac repair. The book also covers specific in vivo techniques for cardiac gene transfer, and specifies subsequent cellular and organ-level physiological assessment techniques and protocols. Accordingly, this book is designed for basic science and clinical researchers in the academic, pharmaceutical, and biotechnology sectors of the cardiovascular community.

All physicians practicing medicine encounter patients suffering from cardiovascular disease. This book has been outlined in such a way that vascular surgeons, general internists, neurologists and cardiologists should be able to use it. The book covers the complete scope of cardiac diseases in addition to chapters on hypertension and atherosclerosis. In many patients there is a family history of cerebrovascular accidents, myocardial infarction or peripheral arterial disease. Also in patients reporting collaps, palpitations and arrhythmias the family is crucial and can provide clues to a genetic cause of the disease. This book is published to guide physicians in the process of determining whether a genetic component is likely to be present. Furthermore, information is provided what the possibilities and limitations of DNA diagnostic techniques are. Finally, the importance of newly identified categories of potential patients, i. e. gene carriers without symptoms or any inducible sign of disease, is highlighted. For some patients a genetic diagnosis is essential to determine appropriate therapy and for counseling? In some other diseases DNA diagnostic tools are available but the relevant for the patients may be less clear. In other families the search for a disease causing gene is ongoing and the possibilities to find genes and to unravel the pathophysiology of the disease is limited by the lack of patients. To give insight into the current state of genetic diagnostics, the authors have classified the cardiovascular diseases.

The revised fourth edition includes new chapters on medical ethics, embalming techniques and decomposition of body, back and vertebral column, ethical issues in medical genetics, attitude and communication skills, and x-rays. In each chapter, SAQs are arranged by topic. More than 700 new SAQs have been added in this edition. Useful for undergraduate students and students who are preparing for postgraduate entrance examinations. SAQs will also help the students to answer the MCQs on the same topic. In the Gross Anatomy section, in the beginning of each chapter SAQs on osteology are given, which are useful to the students for viva examinations More than 700 new SAQs have been added in this edition.

Structural Genomics and Drug Discovery: Methods and Protocols focuses on high throughput structure determination methods and how they can be applied to lay the groundwork for structure aided drug discovery. The methods and protocols that are described can be applied in any laboratory interested in using detailed structural information to advance the initial stages of drug discovery. 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, Structural Genomics and Drug Discovery: Methods and Protocols seeks to aid scientists in the further study into structural genomics approach as an efficient initial step toward drug discovery and the methods described will be useful to anyone interested in moving in this direction.

International Review of Cytology presents current advances and comprehensive reviews in cell biology--both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.

Over the past decades, the pathogenesis, diagnosis, treatment and prevention of cardiovascular diseases have been benefited significantly from intensive research activities. In order to provide a comprehensive "manual" in a field that has become as broad and deep as cardiovascular medicine, this volume of "Methods in Molecular Medicine" covers a wide spectrum of in vivo and in vitro techniques encompassing biochemical, pharmacological and molecular biology disciplines which are currently used to assess vascular disease progression. Each chapter included in this volume focuses on a specific vascular biology technique and describes various applications as well as caveats of these techniques. The protocols included here are described in detail, allowing beginners with little experience in the field of vascular biology to embark on new research projects.

Sendai virus (SeV) is not just a mouse pathogen but is evolving into a cutting-edge component of biotechnology. SeV reverse genetics originating from a pure academic need to settle long-held questions in the biology and pathogenicity of nonsegmented negative strand RNA viruses (Mononegavirales) is about to bear the impressive fruit of multipurpose cytoplasmic (non-integrating) RNA vectors. This book brings together in one source the SeV biology revealed by conventional approaches and reverse genetics, the methods to construct the first-generation SeV vector and to generate safer versions, and the applications in medical settings that have left or are about to leave the laboratory bench. The applications, which already are diverse and have high medical impact, include use as vaccine vectors against AIDS and respiratory virus infections, creation of BioKnife to resect malignant tumors, induction of "footprint (transgene) free" pluripotent stem cells, and gene therapy for peripheral arterial disease. These achievements-which are just a few of many examples-were attainable only after rigorously incorporating the rich knowledge of SeV biology that has accumulated during the several decades since the discovery of the virus. Application of SeV vector is certain to expand greatly because of its extremely high performance in transgene expression and its remarkable target cell breadth.

Dr. Elisabeth Bock (Photo Keenpress) This book contains review articles that produce a snapshot of recent developments in the field of the neural cell adhesion molecule NCAM. The chapters are grouped into sections reflecting various aspects of NCAM structure and function. The themes cover the structural basis of cell adhesion mediated by NCAM and NCAM interaction partners, NCAM-mediated signaling determinants of NCAM function under physiological conditions and in disease, and the therapeutic potential of NCAM mimetics. Section 1, "Structure and Ligands of NCAM," introduces the reader to the str- tural basis of NCAM-mediated cell adhesion, discussing the current knowledge of extracellular and intracellular NCAM ligands and the structural basis of NCAM int- actions with the fibroblast growth factor (FGF) receptor. Section 2, "NCAM and Polysialic Acid," focuses on NCAM polysialylation, discussing the structural and functional aspects of the most important posttranslational modifications of NCAM by the addition of a long linear homopolymer of sialic acid to the fifth Ig-like NCAM module. Section 3, "NCAM-mediated Signal Transduction," is devoted to signal v BookID 187530_ChapID FM1_Proof# 1 - 01/03/2011 BookID 187530_ChapID FM1_Proof# 1 - 01/03/2011 vi Preface transduction mechanisms associated with NCAM-mediated adhesion, with a focus on signaling pathways involved in NCAM-mediated neurite outgrowth, the role of growth-associated proteins, signaling through lipid microdomains, and signaling crosstalk with the epidermal growth factor (EGF) receptor. Section 4, "NCAM Metabolism," focuses on current knowledge about NCAM biosynthesis and the g- eration and role of soluble NCAM.

Based on an intensive qualitative study of a diverse group of 51 older widowers, this unique book sets widowhood within the context of life experience and identifies characteristics and patterns of behaviour that contribute to widowers' success, or lack of it, in adjusting satisfactorily to their circumstances. The authors shed light on widowers' specific needs and on the services needed to help widowers develop greater self-reliance. Among the topics discussed are models of resilience, marriage and illness of the spouse, caregiving and communication, death of the wife, grief and adjustment, living alone and remarriage, life values carried forward, adult children and other social support, and cohorts and the future. The authors conclude with a consideration of trends that may influence the next generation's experience of widowhood. This excellent volume offers expert guidance on the needs and care of the nearly invisible population of older widowers.

International Review of Cytology presents current advances and comprehensive reviews in cell biology--both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
Key Features
* Authored by some of the foremost scientists in the field
* Provides up-to-date information and directions for future research
* Valuable reference material for advanced undergraduates, graduate students and professional scientists

This book is an an up-to-date survey and summary of present knowledge and future expectations regarding the environmental causes of congenital malformations in human beings, beginning with the earliest discoveries of the 20th century up to the latest ideas and problems at its end, presents views and comments on the progress made over the century in understanding human prenatal maldevelopment.

Genomic imprinting refers to a recently discovered phenomenon in which the expression pattern of an allele depends on whether that allele was inherited from the mother or the father. This difference in expression strategy correlates with differences in the epigenetic state of the two alleles. These epigenetic differences include DNA methylation at CpG dinucleotides, as well as modifications on the histones associated with the locus. In the simplest possible cases, the promoter region of the imprinted gene is methylated during oogenesis, but not spermatogenesis (or vice versa). This methylation (and its accompanying histone modifications) results in inactivation of the modified allele. Of course, most imprinted genes do not fall into this simplest case. The goal of this book is neither to provide a basic introduction to imprinting, nor to provide a comprehensive survey of the current state of the field (which would necessarily span multiple books). Rather, the book covers on some of the more recent advances, with the goal of drawing attention to some of the emerging subtleties and complexities associated with imprinted genes.

Ultimately, the quality of the tools available for genetic analysis and experimental disease models will be assessed on the basis of whether they provide new information that generates novel treatments for human disease. In addition, the time frame in which genetic discoveries impact clinical practice is also an important dimension of how society assesses the results of the significant public financial investment in genetic research. Because of the investment and the increased expectation that new tre- ments will be found for common diseases, allowing decades to pass before basic discoveries are made and translated into new therapies is no longer acceptable. Computational Genetics and Genomics: Tools for Understanding Disease provides an overview and assessment of currently available and developing tools for genetic analysis. It is hoped that these new tools can be used to identify the genetic basis for susceptibility to disease. Although this very broad topic is addressed in many other books and journal articles, Computational Genetics and Genomics: Tools for Understanding Disease focuses on methods used for analyzing mouse genetic models of biomedically - portant traits. This volume aims to demonstrate that commonly used inbred mouse strains can be used to model virtually all human disea- related traits. Importantly, recently developed computational tools will enable the genetic basis for differences in disease-related traits to be rapidly identified using these inbred mouse strains. On average, a decade is required to carry out the development process required to demonstrate that a new disease treatment is beneficial.

This book provides a conceptual and computational framework to study how the nervous system exploits the anatomical properties of limbs to produce mechanical function. The study of the neural control of limbs has historically emphasized the use of optimization to find solutions to the muscle redundancy problem. That is, how does the nervous system select a specific muscle coordination pattern when the many muscles of a limb allow for multiple solutions? I revisit this problem from the emerging perspective of neuromechanics that emphasizes finding and implementing families of feasible solutions, instead of a single and unique optimal solution. Those families of feasible solutions emerge naturally from the interactions among the feasible neural commands, anatomy of the limb, and constraints of the task. Such alternative perspective to the neural control of limb function is not only biologically plausible, but sheds light on the most central tenets and debates in the fields of neural control, robotics, rehabilitation, and brain-body co-evolutionary adaptations. This perspective developed from courses I taught to engineers and life scientists at Cornell University and the University of Southern California, and is made possible by combining fundamental concepts from mechanics, anatomy, mathematics, robotics and neuroscience with advances in the field of computational geometry. Fundamentals of Neuromechanics is intended for neuroscientists, roboticists, engineers, physicians, evolutionary biologists, athletes, and physical and occupational therapists seeking to advance their understanding of neuromechanics. Therefore, the tone is decidedly pedagogical, engaging, integrative, and practical to make it accessible to people coming from a broad spectrum of disciplines. I attempt to tread the line between making the mathematical exposition accessible to life scientists, and convey the wonder and complexity of neuroscience to engineers and computational scientists. While no one approach can hope to definitively resolve the important questions in these related fields, I hope to provide you with the fundamental background and tools to allow you to contribute to the emerging field of neuromechanics.

Topics covered in this volume include pheromone reception in mammals, elucidation of mammalian bitter taste, synaptic modulation in pain pathways, the vertebrate phototransduction cascade, and amplification and termination mechanisms.

The lipids of cellular membranes not only serve roles in controlling the structure and fluidity of the membrane, but are increasingly recognized for their roles as signalling molecules and modifiers of membrane protein function. Recent studies described in this volume reveal striking changes in membrane lipids during aging and in age-related diseases such as cancer, cardiovascular disease and neurodegenerative disorders. Lipids including inositol phospholipids, cholesterol, sphingolipids and ceramides play important roles in signalling cellular responses to stress and specific stimuli such as growth factors, cytokines and neurotransmitters. One or more of these lipid mediators has been linked to the pathogenesis of age-related diseases.

This book provides a comprehensive review of specific membrane lipid mediators and their roles in aging and age-related disease.

Precis This book is a treatise about the origin of cancers. I would like to convince readers that the basic tenets of the theory of a stem-cell origin of cancers also constitute a unified theory of cancer. Stem-cell origin of normal (and cancer) cells: Vitruvian version Every truth passes through three stages before it is recognized. In the first it is ridiculed, in the second, it is opposed, in the third, it is regarded as self-evident. - Arthur Schopenhauer v vi Preface Every person has a unique story to tell. My story is about cancer. Cancer touches the lives of countless people. Often enough, it leaves indelible tracks. Many lives have been lost; others are forever changed. For those who confront this deadly scourge, there is a sense of urgency, if not of desperation. For those who face im- nent death, life becomes even more precious and carries a special meaning. As an oncologist, I am touched daily by cancer. I feel its inception, evolution, and aft- math. It seems as though we are fighting an incessant war against cancer at the front line in the trenches. This is my story about cancer. Some people are terrific storytellers. Others have incredible tales to tell.