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The mammalian Rel/NF-[kappa]B family of transcription factors plays a central role in the immune system by regulating various processes involving in both innate and adaptive immunity, inflammation, lymphocyte differentiation, and lymphoid malignancies. A wide variety of signals activate NF-[kappa]B driven gene expression through different NF-[kappa]B signaling pathways in a stimulus- and cell type-dependent manner. Due to the diverse regulatory mechanism acting on NF-[kappa]B signaling, the signal dependent activation of NF-[kappa]B remains a challenging area of research. This thesis describes the mechanism of gene regulation by the NF-[kappa]B p52 homodimer with its specific transcriptional co-regulator Bcl3. Chapter I introduces the NF- & kappa;B family transcription factors together with its regulation through the I[kappa]B family, NF-[kappa]B signaling pathways, and its DNA recognition in gene transcription initiation. Chapter II describes the promoter specificity by NF-[kappa]B p52 homodimers. Our results show that a single nucleotide change in the central base pair of [kappa]B DNA discriminates between classical RelA containing NF-[kappa]B dimers versus the p52:Bcl3 complex. Chapter III studies the degradation, re-synthesis, and processing of NF-[kappa]B2/p100 and the generation of p52 in non-canonical NF-[kappa]B signaling pathway as well as inhibitory function of NF-[kappa]2/p100 referred as I[kappa]B[delta]. Our results showed that LT[beta]-mediated non-canonical signaling is a NIK-dependent biphasic event, which induces both the activation and suppression of NF-[kappa]B activity. Chapter IV studies the phosphorylation state of Bcl3 and its function in terms of p52:Bcl3 gene activation. Two new Bcl3 phosphorylation sites were identified and biochemical analysis showed that these two phosphorylations enhance the protein-protein interaction between p52 and Bcl3, which in turn enhance their specific gene activation. Chapter V employed a combination of X-ray crystallography and biochemical technique to investigate the molecular basis of p52:Bcl3 complex formation. Stable p52:Bcl3 core complex was identified and crystallized.
Divided into two volumes the work offers a so far unmatched broad and at the same time deep knowledge on molecular and cellular mechanisms of carcinogenesis and offers comprehensive insight into clinical, therapeutic and technological aspects. This 1st Volume presents tumor entities of the ocular system, the thyroid organ, the oesophagus, gliomas, non-glial brain tumors, head and neck as well as lung cancer. In addition it also discusses in-depth potential novel molecular players and the role of stem cells as well as the endocannabinoid system in carcinogenesis, it furthermore explains tumor metabolism components and signaling pathways. Each of the chapters discusses potential therapeutic strategies and novel drug targets. The book addresses basic scientists and medical researchers interested in translational cancer research.
This book presents the forefront in the science and clinical management of myeloma bone disease. Coverage begins with sections on clinical presentation, imaging, and biochemical markers and goes on to discuss radiation, surgical, and medical therapies.
Epstein Barr virus (EBV) was discovered as the first human tumor virus around 50 years ago. Since its discovery in Burkitt’s lymphoma it has been associated with various other malignancies, infectious mononucleosis and even autoimmune diseases. The two book volumes on EBV summarize the first 50 years of research on this tumor virus, starting with historical perspectives on discovery, oncogenicity and immune control, reviewing the role that the virus plays in the various associated diseases and concluding with a discussion on how the immune system keeps persistent EBV infection under control in healthy EBV carriers and can be used to treat EBV associated diseases. The respective 32 chapters are written by international experts from three continents for health care providers, biomedical researchers and patients that are affected by EBV. The assembled knowledge should help to understand EBV associated diseases better and to develop EBV specific vaccination in the near future.
X-PLOR is a highly sophisticated computer program that provides an interface between theoretical foundations and experimental data in structural biology, with specific emphasis on X-ray crystallography and nuclear magnetic resonance spectroscopy in solution of large biological macro-molecules. This manual to X-PLOR Version 3.1 presents the theoretical background, syntax, and function of the program and also provides a comprehensive list of references and sample input files with comments. It is intended primarily for researchers and students in the fields of computational chemistry, structural biology, and computational molecular biology.
This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.
This book describes recent advances in translational research in breast cancer and presents emerging applications of this research that promise to have meaningful impacts on diagnosis and treatment. It introduces ideas and materials derived from the clinic that have been brought to "the bench" for basic research, as well as findings that have been applied back to "the bedside". Detailed attention is devoted to breast cancer biology and cell signaling pathways and to cancer stem cell and tumor heterogeneity in breast cancer. Various patient-derived research models are discussed, and a further focus is the role of biomarkers in precision medicine for breast cancer patients. Next-generation clinical research receives detailed attention, addressing the increasingly important role of big data in breast cancer research and a wide range of other emerging developments. An entire section is also devoted to the management of women with high-risk breast cancer. Translational Research in Breast Cancer will help clinicians and scientists to optimize their collaboration in order to achieve the common goal of conquering breast cancer.
Immunity and Inflammation in Health and Disease: Emerging Roles of Nutraceuticals and Functional Foods in Immune Support provides a comprehensive description of the various pathways by which the vertebrate immune system works, the signals that trigger immune response and how fnew and novel nutraceuticals and functional foods, can be used to contain inflammation and also to boost immunity and immune health. Inflammation is a tool to fight pathogens and the vertebrate immune system has a very complex network of cells to achieve this. However inflammation that goes awry is also the leding cause of several diseases ranging from cardiovascular diseases to diabetes. This book covers the entire gamut from the various cellular players in the inflammation-immune response to its ramifications in terms of protection against pathogens as well as in onset of metabolic, aging and auto-immune related diseases. Finally, the balancing role of dietary nutrients between host defence and immune support is also showcased. The first three scetions explain the various components of the immune system and their modes of activation. The fourth section deals with the ramifications of a robust and execessive inflammatory response. The fifth section is focused on the association between nutrition and immunity and how deficiencies in certain nutrients may affect immunocompetence. The sixth section chapters represent a vision of paradigm shifts within the field and discusses possible future directions. This bool will be a valuable reference for researchers studying immune health either in academia, or in the nutraceutical or functional food industries. Product developers in nutraceutical, supplement, functional food, and health food companies will also appreciate the information presented here. - Conceptualizes the key features in natural products which can boost immune function and immune health - Explains the intricate mechanistic aspects and balance behind immune health - Presents the pathophysiology of several diseases associated with immune system disruption
This book is a printed edition of the Special Issue "Roles of NF-κB in Cancer and Their Therapeutic Approaches" that was published in Biomedicines
This textbook aims to describe the fascinating area of eukaryotic gene regulation for graduate students in all areas of the biomedical sciences. Gene expression is essential in shaping the various phenotypes of cells and tissues and as such, regulation of gene expression is a fundamental aspect of nearly all processes in physiology, both in healthy and in diseased states. Th is pivotal role for the regulation of gene expression makes this textbook essential reading for students of all the biomedical sciences, in order to be better prepared for their specialized disciplines. A complete understanding of transcription factors and the processes that alter their activity is a major goal of modern life science research. The availability of the whole human genome sequence (and that of other eukaryotic genomes) and the consequent development of next-generation sequencing technologies have significantly changed nearly all areas of the biological sciences. For example, the genome-wide location of histone modifications and transcription factor binding sites, such as provided by the ENCODE consortium, has greatly improved our understanding of gene regulation. Therefore, the focus of this book is the description of the post-genome understanding of gene regulation.