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A finely tuned regulation of gene expression is essential for shaping the nervous system and for maintaining its homeostasis throughout life. Disruptions in gene regulation can impact brain development and physiology in ways that contribute to diverse pathologies. The master orchestrators of gene activity in the nucleus are transcription factors, proteins that recognize and bind to specific DNA motifs in regulatory regions and drive changes in gene expression. Transcription factors act with the help of other co-factor proteins, including components of the Mediator complex, histone modifying enzymes, chromatin modelers, and DNA methylases. In addition, transcription factor activity in the nervous system can be modulated by extracellular signals, including growth factors, hormones, neuropeptides and neurotransmitters that activate specific receptors and intracellular transduction pathways. An in-depth understanding of the mechanisms of transcription regulation is needed in order to better describe how each element, from genes to cells, defines and maintains identities and functionalities in the healthy and diseased brain. This Research Topic is oriented to developing an integrative view about transcription regulation within the nervous system, focusing on developmental and homeostatic processes, dysregulation in functionality and expression levels and consequent associated pathologies such as neurodevelopmental disorders, brain tumors, and neurodegenerative diseases. Transcription regulation investigations will specifically focus on transcription factors that belong to the bHLH (e.g. NeuroD), homeobox (e.g. Islet, Pax, Rax, and Lhx) and CREB families, and on their roles over defined nervous system areas: cerebral cortex, thalamic and hypothalamic areas, interacting with the developing brain.
The functional anatomy of organisms is maintained by the coordination of different systems, that often rely on particular interactions between specialized cells and between macromolecules. The immune system works with the circulatory and the lymphatic systems to protect most of the organs. However, some organs are considered immune privileged due to the presence of highly selective and regulated barriers, such as the blood-brain barrier (BBB) within the brain. The BBB controls periphery-brain molecule exchange and prevents immune effector cells from entering the homeostatic brain. BBB-associated elements, such as endothelial cells, pericytes, astrocytes, and microglia, potentially can function as antigen-presenting cells (APC). Pathological scenarios that induce dysfunction of the BBB and its associated cells may lead to the infiltration of lymphocytes crossing over from the blood to brain. Similarly, traumas can also enable B and T lymphocytes to pass bidirectionally between the CNS and the periphery, via the meningeal lymphatic vessels which drain into the cervical lymph nodes. Research in animals and in humans has revealed that B and T cells are involved in the progression of neurological diseases. It has been showed that under particular conditions, T cells establish themselves and become resident in the brain (T RM cells), from where they can either exert beneficial or detrimental effects on brain function. Amazing efforts have been made to further comprehend interactions between brain-specific cells and peripheral immune cells, and especially their roles and impact on the onset, progression, and eventual resolution of diverse brain pathologies.
More than 18 million people in the United States have diabetes mellitus, and about 90% of these have the type 2 form of the disease. This book attempts to dissect the complexity of the molecular mechanisms of insulin action with a special emphasis on those features of the system that are subject to alteration in type 2 diabetes and other insulin resistant states. It explores insulin action at the most basic levels, through complex systems.
This volume brings together authors working on a wide range of topics to provide an up to date account of the underlying mechanisms and functions of neurogenesis and synaptogenesis in the adult brain. With an increasing understanding of the role of neurogenesis and synaptogenesis it is possible to envisage improvements or novel treatments for a number of diseases and the possibility of harnessing these phenomena to reduce the impact of ageing and to provide mechanisms to repair the brain.
This volume connects current ideas and concepts about sleep functions and circadian rhythms with the search for novel target-selective sleep-wake therapeutics. To do so, it provides a timely, state-of-the-art overview of sleep-wake mechanisms in health and disease, ongoing developments in drug discovery, and their prospects for the clinical treatment of sleep-disordered patients. It particularly focuses on the concept that sleep and wakefulness mutually affect each other, and the future therapeutic interventions with either sleep- or wake-promoting agents that are expected to not only improve the quality of sleep but also the waking behavior, cognition, mood and other sleep-associated physiological functions. The chapter 'Sleep Physiology, Circadian Rhythms, Waking Performance and the Development of Sleep-Wake Therapeutics' available open access under a CC BY 4.0 license at link.springer.com
This fourth edition of the best-selling textbook, Human Genetics and Genomics, clearly explains the key principles needed by medical and health sciences students, from the basis of molecular genetics, to clinical applications used in the treatment of both rare and common conditions. A newly expanded Part 1, Basic Principles of Human Genetics, focuses on introducing the reader to key concepts such as Mendelian principles, DNA replication and gene expression. Part 2, Genetics and Genomics in Medical Practice, uses case scenarios to help you engage with current genetic practice. Now featuring full-color diagrams, Human Genetics and Genomics has been rigorously updated to reflect today’s genetics teaching, and includes updated discussion of genetic risk assessment, “single gene” disorders and therapeutics. Key learning features include: Clinical snapshots to help relate science to practice 'Hot topics' boxes that focus on the latest developments in testing, assessment and treatment 'Ethical issues' boxes to prompt further thought and discussion on the implications of genetic developments 'Sources of information' boxes to assist with the practicalities of clinical research and information provision Self-assessment review questions in each chapter Accompanied by the Wiley E-Text digital edition (included in the price of the book), Human Genetics and Genomics is also fully supported by a suite of online resources at www.korfgenetics.com, including: Factsheets on 100 genetic disorders, ideal for study and exam preparation Interactive Multiple Choice Questions (MCQs) with feedback on all answers Links to online resources for further study Figures from the book available as PowerPoint slides, ideal for teaching purposes The perfect companion to the genetics component of both problem-based learning and integrated medical courses, Human Genetics and Genomics presents the ideal balance between the bio-molecular basis of genetics and clinical cases, and provides an invaluable overview for anyone wishing to engage with this fast-moving discipline.
This indispensable volume highlights recent studies identifying epigenetic mechanisms as essential regulators of skin development, stem cell activity and regeneration. Chapters are contributed by leading experts and promote the skin as an accessible model system for studying mechanisms that control organ development and regeneration. The timely discussions contained throughout are of broad relevance to other areas of biology and medicine and can help inform the development of novel therapeutics for skin disorders as well as new approaches to skin regeneration that target the epigenome. Part of the highly successful Stem Cells and Regenerative Medicine series, Epigenetic Regulation of Skin Development and Regeneration uncovers the fundamental significance of epigenetic mechanisms in skin development and regeneration, and emphasizes the development of new therapies for a number of skin disorders, such as pathological conditions of epidermal differentiation, pigmentation and carcinogenesis. At least six categories of researchers will find this book essential, including stem cell, developmental, hair follicle or molecular biologists, and gerontologists or clinical dermatologists.