Bipolar disorder is one of the most common, and disabling, conditions affecting human kind. Each year, millions of individuals struggle with the effects of this illness. Although clinically well recognized for decades, if not centuries, the causes of this condition remain incompletely understood. However, in the past decade, significant technological advances in both neuroimaging and genetic research have revealed clues about the neurophysiological basis of bipolar illness. In this book, leading experts in neuroimaging and genetics discuss recent discoveries in bipolar disorder that identify both the structural, functional and chemical brain changes that seem to underlie this condition, as well as the possible genetic causes of these brain events. Based upon these discussions, the book then integrates these diverse considerations to develop a specific neurophysiological model of bipolar disorder. This model provides a resource to guide clinicians and patients as they struggle to understand this illness, as well as a guide for future investigations into the causes of bipolar disorder. With this guide in hand, this book will lead to a new framework for understanding bipolar disorder in order to, ultimately, develop improved therapies for affected individuals and novel strategies to prevent the onset in children at risk for this condition.

This issue of Rheumatic Disease Clinics focuses on Genetics. Article topics cover: Genetic Influences on Susceptibility and Severity of Rheumatoid Arthritis; HLA-disease associations in rheumatoid arthritis; Autoinflammatory Syndromes as a Model of Monogenic Diseases; Genomic Influences on Hyperuricaemia and Gout; Genetics of Systemic Lupus Erythematosus; Genetics of Ankylosing Spondylitis;Genetics of Scleroderma; Genetics of Osteoarthritis; Genetics of Juvenile Inflammatory Arthritis; Genetic Influences on Treatment Response in Rheumatic Diseases; Integrative approaches/computational biology; Future directions of genetic research in rheumatic diseases; and Population genetics and natural selection in rheumatic disease.

This book is open access under a CC BY 4.0 license. CRISPR-Cas9 is a rapid, efficient, versatile and relatively cheap method for dissecting the molecular pathways that are the basis of life, as well as for investigating and potentially rectifying faults in these pathways that result in disease. This book reviews how CRISPR-Cas9 and other genome editing techniques are advancing our understanding of development and function in the nervous system, uncovering the molecular causes of neurological disorders and providing tools for gene therapy.

This book provides a timely state-of-the-art overview of voltage-gated sodium channels, their structure-function, their pharmacology and related diseases. Among the topics discussed are the structural basis of Na+ channel function, methodological advances in the study of Na+ channels, their pathophysiology and drugs and toxins interactions with these channels and their associated channelopathies.

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.

This issue of Endocrinology and Metabolism Clinics, guest edited by Dr. Constantine A. Stratakis, is devoted to Genetics in Endocrine Disorders. Articles in this issue include: Genetics of Short Stature; Genetics of Diabetes Insipidus; Pituitary Hypoplasia; Pituitary Tumor Genetics and Associated Syndromes; Defects of Thyroid Hormone Synthesis; Molecular Genetics of Thyroid Cancer; Genetics of Hyperparathyroidism Including Parathyroid Cancer; Genetics of Adrenocortical Development and Tumors; Genetics of Congenital Adrenal Hyperplasia; Genetics of Pheochromocytomas and Related Conditions; Genetics of Multiple Endocrine Neoplasia Type 1 and Type 2 Syndromes; Genetics of Hypogonadotrophic Hypogonadism and Kallman Syndrome; Disorders of Sex Development; Genetics of Lipodystrophy; and PTEN-Spectrum Disorders.

This issue of Physical Medicine and Rehabilitation Clinics of North America will cover regenerative medicine. Rapid advances in stem cell science are opening new avenues for drug discovery and may lead to new uses of stem cells for other musculoskeletal disorders. Artcles to be included are: Evidence-Based Regenerative Prolotherapy and Perineural Injection Approaches; Platelet Rich Plasma; Autologous Conditioned Serum; Stem Cell Considerations for the Clinician; Adipose Derived Stromal Vascular Faction and Stem Cell Use, as well as many others.

This book should serve as a resource for professionals in all fields regarding diagnosis, management, and counseling of patients with FXTAS, FXPOI and their families, as well as presenting the molecular basis for disease that may lead to the identification of new markers to predict disease risk and eventually lead to target treatments. The book will present information on all aspects of FXTAS, FXPOI and other premutation disorders including clinical features and current supportive management, radiological, psychological, and pathological findings, genotype-phenotype relationships, animal models and basic molecular mechanisms. Genetic counseling issues are also discussed.

Epigenetics and Systems Biology highlights the need for collaboration between experiments and theoretical modeling that is required for successful application of systems biology in epigenetics studies. This book breaks down the obstacles which exist between systems biology and epigenetics researchers due to information barriers and segmented research, giving real-life examples of successful combinations of systems biology and epigenetics experiments. Each section covers one type of modeling and one set of epigenetic questions on which said models have been successfully applied. In addition, the book highlights how modeling and systems biology relate to studies of RNA, DNA, and genome instability, mechanisms of DNA damage signaling and repair, and the effect of the environment on genome stability.

This book provides an overview of the latest experimental work on sex-based differences in lung function and inflammation. Readers will learn how these differences relate to individual predispositions for the development of lung disease in men and women, and in different stages of their reproductive lives. Further, the book focuses on diseases that predominantly affect women or men, with an emphasis on the physiological mechanisms underlying their pathobiology. In turn, these findings are complemented by chapters on recent studies, which investigate how circulating sex hormone levels impact the lung's innate immune response to environmental agents and air pollution. The pathogeneses of asthma and viral respiratory infection are also major focus areas. As an outlook, the book also discusses current and future research directions aimed at developing sex-specific therapies for lung disease. To examine these anatomical and physiological differences in the male and female respiratory systems, the authors employ a broad range of methods from molecular and clinical biology. Accordingly, the book will be a fascinating read for physiologists and clinicians alike.

This book describes the most important techniques used for studying cfDNA in the different samples; serum, plasma, urine. Chapters detail methods on liquid biopsy for cancer disease, methods in cancer, epigenetic modifications, fetal and pediatric diseases, physical activity, and urinary cell free DNA. 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. Authoritative and cutting-edge, Cell-Free DNA as Diagnostic Markers: Methods and Protocols aims to ensure successful results in the further study of this vital field.

This detailed book presents an up-to-date view on methods and experimental approaches developed to identify and explore the chromothripsis phenomenon. Beginning with a section exploring the genesis and impact of chromothripsis, the collection continues by covering the identification of chromothripsis, the causal mechanisms of chromothripsis, the bioinformatics tools for chromothripsis analysis, and experimental systems recently developed for the in vitro investigation of chromothripsis. 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, Chromothripsis: Methods and Protocols serves as a vital resource for cell biologists, molecular biologists, cytogeneticists, and geneticists investigating chromothripsis, but also for students and researchers new to the field of chromothripsis and genomic instability.

This volume presents a comprehensive collection of quick assays for the detection of nuclear and mitochondrial DNA damage and its effects in live and fixed cells and tissues, and in bacterial genomes. Although, such rapid techniques are in demand in the "research trenches" they are not covered well in the literature. This volume is the first such compendium of the time-saving techniques for detection of DNA damage and its direct physiological outcomes including apoptosis, necrosis and phagocytic clearance. The volume demonstrates all levels of detection, starting from the molecular level up to the level of the entire live organism. 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. Authoritative and cutting-edge, Fast Detection of DNA Damage: Methods and Protocols aims to provide easily reproducible techniques requiring only few steps to perform.

Glutathione ( -glutamyl-cysteinyl-glycine) is a ubiquitously distributed sulfurcontaining antioxidant molecule that plays key roles in the regulation of plant growth, development, and abiotic and biotic stress tolerance. It is one of the most powerful low-molecular-weight thiols, which rapidly accumulates in plant cells under stress. Recent in-depth studies on glutathione homeostasis (biosynthesis, degradation, compartmentalization, transport, and redox turnover) and the roles of glutathione in cell proliferation and environmental stress tolerance have provided new insights for plant biologists to conduct research aimed at deciphering the mechanisms associated with glutathione-mediated plant growth and stress responses, as well as to develop stress-tolerant crop plants. Glutathione has also been suggested to be a potential regulator of epigenetic modifications, playing important roles in the regulation of genes involved in the responses of plants to changing environments. The dynamic relationship between reduced glutathione (GSH) and reactive oxygen species (ROS) has been well documented, and glutathione has been shown to participate in several cell signaling and metabolic processes, involving the synthesis of protein, the transport of amino acids, DNA repair, the control of cell division, and programmed cell death. Two genes, gamma-glutamylcysteine synthetase (GSH1) and glutathione synthetase (GSH2), are involved in GSH synthesis, and genetic manipulation of these genes can modulate cellular glutathione levels. Any fluctuations in cellular GSH and oxidized glutathione (GSSG) levels have profound effects on plant growth and development, as glutathione is associated with the regulation of the cell cycle, redox signaling, enzymatic activities, defense gene expression, systemic acquired resistance, xenobiotic detoxification, and biological nitrogen fixation. Being a major constituent of the glyoxalase system and ascorbate-glutathione cycle, GSH helps to control multiple abiotic and biotic stress signaling pathways through the regulation of ROS and methylglyoxal (MG) levels. In addition, glutathione metabolism has the potential to be genetically or biochemically manipulated to develop stress-tolerant and nutritionally improved crop plants. Although significant progress has been made in investigating the multiple roles of glutathione in abiotic and biotic stress tolerance, many aspects of glutathione-mediated stress responses require additional research. The main objective of this volume is to explore the diverse roles of glutathione in plants by providing basic, comprehensive, and in-depth molecular information for advanced students, scholars, teachers, and scientists interested in or already engaged in research that involves glutathione. Finally, this book will be a valuable resource for future glutathione-related research and can be considered as a textbook for graduate students and as a reference book for frontline researchers working on glutathione metabolism in relation to plant growth, development, stress responses, and stress tolerance.

This comprehensive handbook synthesizes the often-fractured relationship between the study of biology and the study of society. Bringing together a compelling array of interdisciplinary contributions, the authors demonstrate how nuanced attention to both the biological and social sciences opens up novel perspectives upon some of the most significant sociological, anthropological, philosophical and biological questions of our era. The six sections cover topics ranging from genomics and epigenetics, to neuroscience and psychology to social epidemiology and medicine. The authors collaboratively present state-of-the-art research and perspectives in some of the most intriguing areas of what can be called biosocial and biocultural approaches, demonstrating how quickly we are moving beyond the acrimonious debates that characterized the border between biology and society for most of the twentieth century. This landmark volume will be an extremely valuable resource for scholars and practitioners in all areas of the social and biological sciences. The chapter 'Ten Theses on the Subject of Biology and Politics: Conceptual, Methodological, and Biopolitical Considerations' is open access under a CC BY 4.0 license via link.springer.com. Versions of the chapters 'The Transcendence of the Social', 'Scrutinizing the Epigenetics Revolution', 'Species of Biocapital, 2008, and Speciating Biocapital, 2017' and 'Experimental Entanglements: Social Science and Neuroscience Beyond Interdisciplinarity' are available open access via third parties. For further information please see license information in the chapters or on link.springer.com.

This volume brings together recent developments in quasispecies theory extended to variable environments and practical applications in elucidating viral dynamics and treatment designs. In particular, the existence of an error threshold in rugged fitness landscapes has opened the way to a new antiviral strategy termed lethal mutagenesis, which is now under intensive theoretical, experimental and clinical investigation. As such the book explains how an understanding of quasispecies dynamics within infected organisms has increased our knowledge of viral disease events. From a clinical perspective, population dynamics highlights important problems for viral disease control, such as the selection of drug-resistant mutants that often accompanies treatment failures, and suggests means of increasing the effectiveness of antiviral treatments. The book is intended for students and scientists interested in basic and applied aspects of biophysics, chemistry, biology, evolution and medical virology.

This volume explores and explains how digital PCRs (dPCRs) help in the study of numerous topics, such as infectious diseases, evolution of cancer and treatment responses, somatic mosaicism, genome editing and cell therapy, and food testing for GMOs and pathogens. 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. Authoritative and thorough, Digital PCR: Methods and Protocols is a valuable resource for specialists in various fields, including geneticists, neurologists, immunologists, oncologists, and researchers who are interested in environmental sciences."

This book approaches the differential diagnosis and management of rare, hereditary cancer syndromes from a practical angle, addressing the issues pertinent to each tumour type as encountered by health professionals in their day-to-day practice. This book enables readers to correctly identify patients with rare cancer syndromes who would benefit from genetic counselling and testing, and provides the necessary knowledge for appropriate patient management and advising at-risk family members. It begins by describing recent advances in genetic testing for cancer-predisposing genes. Leading experts from Europe and Australia then offer detailed, up-to-date guidance on the diagnosis and management of a wide range of hereditary cancers. The concluding chapter examines the wider issues that are raised by genetic testing for rare cancer syndromes for patients, families and health professionals. This book is an invaluable source of information for all specialists involved in the care of such patients and their families.

This volume provides an overview of zygotic genome activation (ZGA) and the use of recent tools to elucidate the events that occur during ZGA. The chapters in this book cover topics such as: clearance of maternal RNAs, detection of miRNA in mammalian oocytes and embryos, RNA FISH to study ZGA in early mouse embryos, and CRISPR/Cas9-mediated gene targeting during embryogenesis in the mouse and pig. 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. Thorough and cutting-edge, Zygotic Genome Activation: Methods and Protocols is a valuable resource for scientists and researchers who are interested in learning more about practical approaches to monitor the changes seen during ZGA.

This book provides a cutting-edge review of polyglutamine disorders. It primarily focuses on two main aspects: (1) the mechanisms underlying the pathologies' development and progression, and (2) the therapeutic strategies that are currently being explored to stop or delay disease progression. Polyglutamine (polyQ) disorders are a group of inherited neurodegenerative diseases with a fatal outcome that are caused by an abnormal expansion of a coding trinucleotide repeat (CAG), which is then translated in an abnormal protein with an elongated glutamine tract (Q). To date, nine polyQ disorders have been identified and described: dentatorubral-pallidoluysian atrophy (DRPLA); Huntington's disease (HD); spinal-bulbar muscular atrophy (SBMA); and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17). The genetic basis of polyQ disorders is well established and described, and despite important advances that have opened up the possibility of generating genetic models of the disease, the mechanisms that cause neuronal degeneration are still largely unknown and there is currently no treatment available for these disorders. Further, it is believed that the different polyQ may share some mechanisms and pathways contributing to neurodegeneration and disease progression.

This book offers a comprehensive introduction to using Mathematica and the Wolfram Language for Bioinformatics. The chapters build gradually from basic concepts and the introduction of the Wolfram Language and coding paradigms in Mathematica, to detailed worked examples derived from typical research applications using Wolfram Language code. The coding examples range from basic sequence analysis, accessing genomic databases, differential gene expression, and machine learning implementations to time series analysis of longitudinal omics experiments, multi-omics integration and building dynamic interactive bioinformatics tools using the Wolfram Language. The topics address the daily bioinformatics needs of a broad audience: experimental users looking to understand and visualize their data, beginner bioinformaticians acquiring coding expertise in providing biological research solutions, and practicing expert bioinformaticians working on omics who wish to expand their toolset to include the Wolfram Language.

There are several types of damage that can be found in the male gamete. This book covers the genetic damage in spermatozoa that can originate during spermatogenesis, or during transit in both male and female genital tracts. Damage can also be due to ageing, environmental or iatrogenic conditions, as well as to the protocols to cryopreserve and to select spermatozoa in assisted reproduction techniques. The purpose of this book is to provide a comprehensive resource for all possible DNA damages in sperm, the relation to fertility and infertility, and possible transgenerational heritable effects.