This book will provide an overview of basic epigenetic phenomena; interaction between epigenetic and genetic factors; and the influence of epigenetic factors on inheritance. Epigenetic states may contribute to the penetrance of genetic polymorphisms or mutations and thereby modify inheritance patterns. This may result in non-Mendelian inheritance of genetic traits such as observed in common human disease. The relationship between epigenetics and genetics, however, has not been comprehensively summarized yet. The topic is being more and more appreciated lately due to considerable advances in genomic and epigenomic approaches to study the origins of human disease. The editors will focus not only on describing epigenetic characteristics, mechanisms and results, but also on how considerations of epigenetics can alter interpretation and analysis of risks for complex traits. This book will be a resource for those who have been working in human genetics or analysis of human genetic data and are studying the impact of epigenetics on inheritance. An overview will be given of the impacts of inter-individual variation in epigenetic states from major changes (errors in genomic imprinting) that cause congenital developmental defects to subtle changes and their impact on complex traits. The editors will discuss the relationship between epigenetic changes and genetic changes in human disease. Several chapters will also focus on statistical analysis of epigenetics effects, either in human disease genetic studies, or in population genetics.

The gastrointestinal mucosal defense system serves to minimize mucosal injury by either ingested or endogenously produced noxious substances. The mucosal defense system is stratified into pre-epithelial (alkaline mucus), epithelial (dynamic epithelial lining), and post-epithelial (microcirculation) components. The mucus lining the epithelial surface presents a diffusional barrier to ingested material (e.g., lipids) and also serves as an unstirred layer in which a pH gradient can be established to prevent acid-induced injury. The epithelial lining prevents entrance of any toxic material to the interstitium and, should it be damaged, it is rapidly resealed by migration of adjacent viable epithelial cells to cover the defect. Any acid or other material that has entered the interstitium is washed out by an intense neurogenic hyperemia. In general, the mucosal defense system is quite effective and any adverse gastrointestinal effects associated with the normal course of nutrient assimilation are minimal. However, there are two situations in which the mucosal defense system is known to be ineffective and result in gastric mucosal injury: inadvertent ingestion of H. pylori. or intentional ingestion of NSAIDs. H. pylori can penetrate the mucus layers and cause epithelial injury and inflammation, while at the same time preventing its clearance by the host immune system. NSAIDs weaken the mucus layer and cause epithelial cell injury.

Molecular Biology of Aging, the latest volume in the Progress in Molecular Biology and Translational Science series, focuses on placental development and disease.

Tumor-Induced Immune Suppression - Prospects and Progress in Mechanisms and Therapeutic Reversal presents a comprehensive overview of large number of different mechanisms of immune dysfunction in cancer and therapeutic approaches to their correction. This includes the number of novel mechanisms that has never before been discussed in previous monographs. The last decades were characterized by substantial progress in the understanding of the role of the immune system in tumor progression. Researchers have learned how to manipulate the immune system to generate tumor specific immune response, which raises high expectations for immunotherapy to provide breakthroughs in cancer treatment. It is increasingly clear that tumor-induced abnormalities in the immune system not only hampers natural tumor immune surveillance, but also limits the effect of cancer immunotherapy. Therefore, it is critically important to understand the mechanisms of tumor-induced immune suppression to make any progress in the field and this monograph provides these important insights.

How do we find the life that's right for each of us? More and more of us are feeling overwhelmed by the everyday struggle to lead the lives to which we aspire. Children are placed under unbearable pressure to achieve; adults fight a constant battle to balance family life with work and economic demands; old people suffer from social isolation and a lack of emotional security. People of every age are feeling increasingly at odds with the world, and less able to live a life that corresponds to their individual needs and talents. At the root of this problem, argues internationally renowned child development expert Remo Largo, is a mistaken idea of what makes us human. A distillation of forty years of research and medical experience, The Right Life sets out a new theory of human thriving. Tracing our development as individuals from the beginnings of evolution to the twenty-first century, he sets out his own theory, the 'Fit Principle', which proposes that every human strives to live in harmony with their fellow humans and their environment. Rather than a ceaseless quest for self-improvement and growth, he argues, our collective goals should be individual self-acceptance, as we embrace the unique matrix of skills, needs and limitations that makes each of us who we are. Not only, Largo suggests, can a true understanding of human thriving help people find their way back to their individuality; it can help us to reshape society and economy in order to live as fully as possible.

This book presents the latest developments in medicine and biology. Chapters include research on environmental risk factors for diabetic nephropathy; pre-endoscopic management of patients with hematemesis; the benefits of early diagnosis, halo fixation and/or ventral stabilization of dens-fractures in correspondence to age of the patient and fracture type; a discussion on how and to which extent heart rate variability (HRV) is acutely changed in diabetic ketoacidosis (DKA) or in hyperglycemic hyperosmolar syndrome (HHS); an evaluation of the anatomical, refractive and functional results of an innovative technique of deep anterior lamellar keratoplasty; the physical, emotional and quality of life aspects of patients with Cervical Dystonia; the current issues in medical literature regarding androgen use during menopause; an overall report on the benefits and limitations of human milk oligosaccharides (HMOs) mass spectrometry (MS) analysis; the classification methods of the X-ray cerebral angiograms; and the diagnosis and management of intraoperatively necrotizing fasciitis of the breast.

This book presents the latest developments in medicine and biology. Chapters include research on trends in the birth prevalence of boys with isolated hypospadias and undescended testis in Hungary during the last 50 years; alleviating premenstrual syndrome (PMS) symptoms using a natural factor; neutralization-enhancing RF antibodies; advances in the diagnosis, assessment, management and outcome of Takayasu's arteritis; macronutrients and premenstrual syndrome; pressurised intraperitoneal aerosol chemotherapy (PIPAC); the control of MAO expression; and what we know about iMAO.

The pharyngeal arches are embryonic structures that develop into the face, neck, a part of the heart, and several endocrine glands in animals. They are thought to have played a key role in vertebrate evolution as their derivatives impact the mode of feeding and breathing. Moreover, perturbation in pharyngeal arch development is associated with several major groups of birth defects in humans. During early embryonic development, cells from all three germ layers come together to assemble the pharyngeal arches. Subsequently, the pharyngeal arches undergo growth, morphogenesis, and cell type differentiation to give rise to musculoskeletal, cardiovascular, neural, and glandular components. These processes are guided by interactions amongst different tissues, via signaling molecules. A large number of genes, with a complex network of regulatory relationships, govern each aspect of pharyngeal arch development. With the advance of molecular genetics tools in model organisms such as mice, we are beginning to understand the molecular and cellular mechanisms underlying development of the pharyngeal arches and related birth defects. This eBook will provide an introduction into development of the pharyngeal arch system, with a detailed discussion on the genetic regulation of this process.

In the intestine, a unique immunological system that is different from the systemic immune system exists to provide adaptive immunity in response to luminal bacteria and dietary antigens. There are many lymphoid cell aggregates called gut-associated lymphoid tissue (GALT) including Peyer's patches (PPs), which function as important induction sites for the mucosal immune response. M-cells are present in the epithelium of PPs, having a specialized structure for uptake of macromolecules such as bacteria. In addition to GALT, there are abundant lymphoid cells in the intestinal lamina propria, where they mainly play a role as immune effector cells. A strong innate immune system that mainly consists of dendritic cells, macrophages, and T lymphocytes also exists in the intestinal mucosa to assist the barrier function of intestinal epithelial cells. The intestinal mucosa thus shows a unique morphological structure with many immune cells being present under physiological conditions. This condition is known as "controlled inflammation." These abundant immune cells also have characteristic functions: they are "negatively regulated" and have been educated not to overreact unnecessarily to the intestinal luminal milieu. Main players that control inflammation of the intestinal mucosa include regulatory cytokines and regulatory T cells which induce oral tolerance to intestinal bacteria and food antigens, and the secretory IgA system. The maintenance of unique immunological activity in the intestine is also related to an organized, orchestrated lymphocyte migratory mechanism called the "common mucosal immune system." These negative regulatory mechanisms of the intestinal immune system are disturbed in certain disease conditions, causing the immunocompetent cells to respond to food components and commensal bacteria by becoming activated and to overproduce inflammatory cytokines and chemokines. These disease conditions include food allergies, such as celiac disease, and the inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, although their exact etiological mechanisms remain to be revealed. Table of Contents: Introduction / GALT: Its Structure and Formation / Intestinal Epithelial Cells and Their Immune Function / Innate Immunity in the Intestinal Mucosa / Intraepithelial Lymphocytes (IELs) / Lymphoid Cell Trafficking in Intestinal Immunology / Site of Induction of Mucosal Immunity and Antigen Presentation by Dendritic Cells / Production of Secretory IgA (SIgA) / Effector Site of Acquired Immunity and T Helper Cell Subpopulation / Immune Regulatory System and Oral Tolerance / Food Allergy and Celiac Disease / Inflammatory Bowel Diseases / Enteric Infection with Pathogenic Microbes and Mucosal Immunity / References

This monograph, for the first time, presents a comprehensive overview of different mechanisms of immune dysfunction in cancer as well as therapeutic approaches to their correction. It discusses a number of new mechanisms that have never been discussed in a monograph before: T-cell inhibitory molecules, regulatory tolerogenic DCs, and signaling pathways in antigen-presenting cells involved in T-cell tolerance. There is now a pressing need to discuss the already described and newly emerging mechanisms to see how they can be put together in a more or less cohesive structure and how they can help to improve immune response to tumors.

The vascular endothelium lining the inner surface of blood vessels serves as the first interface for circulating blood components to interact with cells of the vascular wall and surrounding extravascular tissues. In addition to regulating blood delivery and perfusion, a major function of vascular endothelia, especially those in exchange microvessels (capillaries and postcapillary venules), is to provide a semipermeable barrier that controls blood-tissue exchange of fluids, nutrients, and metabolic wastes while preventing pathogens or harmful materials in the circulation from entering into tissues. During host defense against infection or tissue injury, endothelial barrier dysfunction occurs as a consequence as well as cause of inflammatory responses. Plasma leakage disturbs fluid homeostasis and impairs tissue oxygenation, a pathophysiological process contributing to multiple organ dysfunction associated with trauma, infection, metabolic disorder, and other forms of disease. In this book, we provide an updated overview of microvascular endothelial barrier structure and function in health and disease. The discussion is initiated with the basic physiological principles of fluid and solute transport across microvascular endothelium, followed by detailed information on endothelial cell-cell and cell-matrix interactions and the experimental techniques that are employed to measure endothelial permeability. Further discussion focuses on the signaling and molecular mechanisms of endothelial barrier responses to various stimulations or drugs, as well as their relevance to several common clinical conditions. Taken together, this book provides a comprehensive analysis of microvascular endothelial cell and molecular pathophysiology. Such information will assist scientists and clinicians in advanced basic and clinical research for improved health care. Table of Contents: Acknowledgments / Introduction / Structure and Function of Exchange Microvessels / Methods for Measuring Permeability / The Endothelial Barrier / Signaling Mechanisms in the Regulation of Endothelial Permeability / Endothelial Barrier Protectors / Pathophysiology and Clinical Relevance / Conclusion / References

During evolution the vertebrate head has acquired a number of unique features including specialized paired sense organs and cranial sensory ganglia. These evolutionary novelties arise from discrete thickenings of the head ectoderm known as cranial placodes. They include the adenohypophyseal, olfactory, lens, trigeminal, profundal, otic, epibranchial and lateral line placodes. While distinct in the derivatives and cell types they will form, all cranial placodes originate from a common preplacodal domain surrounding the anterior neural plate. Recent evidence suggests that the induction of this pre-placodal domain and its subsequent subdivision into individual placodes with specific identities is a multi-step process. Here we describe the development of these placodes and their derivatives and summarize recent advances in the characterization of the repertoire of transcription factors underlying their development. We also review recent studies that have started to address the role of several classes of signaling molecules in placode induction and segregation, including Bone Morphogenetic Proteins, Fibroblast Growth Factors and Wnt molecules.Table of Contents: Introduction / Cranial Placodes and Their Derivatives / Molecular Identity of Cranial Placodes / Induction and Segregation of the Cranial Placodes / Conclusion / Acknowledgments / References / Author Biographies

The unique architecture and physiology of the mammalian intestine, together with a tightly coordinated regulatory system, allows for the handling and absorption of as much as 9 L of fluid a day with 98% or greater efficiency. Advances in the past 40 years have made inroads into revealing the intricacies and interplay of numerous ion transporters and their modulators that are responsible for intestinal electrolyte and water transport. Studies of two devastating diseases, the virulent infectious disease cholera and the autosomal recessive disease cystic fibrosis, were largely responsible for this information explosion. These advances have been critical in the development of new therapeutic strategies to combat life-threatening diseases of varying etiologies ranging from enteric infections to cystic fibrosis and inflammatory bowel diseases. Yet, the story is far from complete, and progress needs to continue on translating information gained from reductionistic cell and tissue culture models, in vivo models, and ultimately human studies and on improving therapeutic approaches. This book reviews the current status of our knowledge of fluid transport across the intestine, including the complexities of transcellular and paracellular ion transport down the length of the intestine and how aberrations of normal physiological processes lead to disease. Table of Contents: Overview / Epithelial Cell and Tissue Architecture / Principles of Transepithelial Electrolyte and Water Movement / Intestinal Architecture and Electrolyte Transport / Electrolyte Transporters--Pumps, Carriers, and Channels / Water Transport / Regulation / Intestinal Disorders and Advances Toward Better Treatment of Intestinal Disorders / Conclusion / References

Eggs of all animals contain mRNAs and proteins that are supplied to or deposited in the egg as it develops during oogenesis. These maternal gene products regulate all aspects of oocyte development, and an embryo fully relies on these maternal gene products for all aspects of its early development, including fertilization, transitions between meiotic and mitotic cell cycles, and activation of its own genome. Given the diverse processes required to produce a developmentally competent egg and embryo, it is not surprising that maternal gene products are not only essential for normal embryonic development but also for fertility. This review provides an overview of fundamental aspects of oocyte and early embryonic development and the interference and genetic approaches that have provided access to maternally regulated aspects of vertebrate development. Some of the pathways and molecules highlighted in this review, in particular, Bmps, Wnts, small GTPases, cytoskeletal components, and cell cycle regulators, are well known and are essential regulators of multiple aspects of animal development, including oogenesis, early embryogenesis, organogenesis, and reproductive fitness of the adult animal. Specific examples of developmental processes under maternal control and the essential proteins will be explored in each chapter, and where known conserved aspects or divergent roles for these maternal regulators of early vertebrate development will be discussed throughout this review. Table of Contents: Introduction / Oogenesis: From Germline Stem Cells to Germline Cysts / Oocyte Polarity and the Embryonic Axes: The Balbiani Body, an Ancient Oocyte Asymmetry / Preparing Developmentally Competent Eggs / Egg Activation / Blocking Polyspermy / Cleavage/ Mitosis: Going Multicellular / Maternal-Zygotic Transition / Reprogramming: Epigenetic Modifications and Zygotic Genome Activation / Dorsal-Ventral Axis Formation before Zygotic Genome Activation in Zebrafish and Frogs / Maternal TGF- and the Dorsal-Ventral Embryonic Axis / Maternal Control After Zygotic Genome Activation / Compensation by Stable Maternal Proteins / Maternal Contributions to Germline Establishment or Maintenance / Perspective / Acknowledgments / References

The neural crest is a remarkable embryonic population of cells found only in vertebrates and has the potential to give rise to many different cell types contributing throughout the body. These derivatives range from the mesenchymal bone and cartilage comprising the facial skeleton, to neuronal derivatives of the peripheral sensory and autonomic nervous systems, to melanocytes throughout the body, and to smooth muscle of the great arteries of the heart. For these cells to correctly progress from an unspecifi ed, nonmigratory population to a wide array of dynamic, differentiated cell types-some of which retain stem cell characteristics presumably to replenish these derivatives-requires a complex network of molecular switches to control the gene programs giving these cells their defi ning structural, enzymatic, migratory, and signaling capacities. This review will bring together current knowledge of neural crest-specifi c transcription factors governing these progressions throughout the course of development. A more thorough understanding of the mechanisms of transcriptional control in differentiation will aid in strategies designed to push undifferentiated cells toward a particular lineage, and unraveling these processes will help toward reprogramming cells from a differentiated to a more naive state. Table of Contents: Introduction / AP Genes / bHLH Genes / ETS Genes / Fox Genes / Homeobox Genes / Hox Genes / Lim Genes / Pax Genes / POU Domain Genes / RAR/RXR Genes / Smad Genes / Sox Genes / Zinc Finger Genes / Other Miscellaneous Genes / References / Author Biographies

Scientists elucidate the astounding collective sensory capacity of Earth and its evolution through time. Chimeras and Consciousness begins the inquiry into the evolution of the collective sensitivities of life. Scientist-scholars from a range of fields-including biochemistry, cell biology, history of science, family therapy, genetics, microbial ecology, and primatology-trace the emergence and evolution of consciousness. Complex behaviors and the social imperatives of bacteria and other life forms during 3,000 million years of Earth history gave rise to mammalian cognition. Awareness and sensation led to astounding activities; millions of species incessantly interacted to form our planet's complex conscious system. Our planetmates, all of them conscious to some degree, were joined only recently by us, the aggressive modern humans. From social bacteria to urban citizens, all living beings participate in community life. Nested inside families within communities inside ecosystems, each metabolizes, takes in matter, expends energy, and excretes. Each of the members of our own and other species, in groups with incessantly shifting alliances, receives and processes information. Mergers of radically different life forms with myriad purposes-the "chimeras" of the title-underlie dramatic metamorphosis and other positive evolutionary change. Since early bacteria avoided, produced, and eventually used oxygen, Earth's sensory systems have expanded and complexified. The provocative essays in this book, going far beyond science but undergirded by the finest science, serve to put sensitive, sensible life in its cosmic context.