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This volume provides the reader with an overview of the diverse functions of the RUNX family of genes. As highlighted in the introduction and several of the 29 chapters, humans and other mammals have three RUNX genes that are known to play specific roles in blood, bone and neuronal development. However, their evolutionary history has recently been traced back to unicellular organisms and their involvement in many well-known signaling pathways (Wnt, TGFb, Notch, Hippo) is indicative of a more general function in cell biology. Their documented roles in cell fate decisions include control of proliferation, differentiation, survival, senescence and autophagy. The pleiotropic effects of RUNX in development are mirrored in cancer, where RUNX genes can function as oncogenes that collaborate strongly with Myc family oncogenes or as tumour suppressor genes. In the latter role, they display hallmarks of both ‘gatekeepers’ that modulate p53 responses and ‘caretakers’ that protect the genome from DNA damage. Several chapters focus on the importance of these genes in leukemia research, where RUNX1 and CBFB are frequently affected by chromosomal translocations that generate fusion oncoproteins, while recent studies suggest wider roles for RUNX modulation in solid cancers. Moreover, RUNX genes are intimately involved in the development and regulation of the immune system, while emerging evidence suggests a role in innate immunity to infectious agents, including HIV. At the biochemical level, the RUNX family can serve as activators or repressors of transcription and as stable mediators of epigenetic memory through mitosis. Not surprisingly, RUNX activity is controlled at multiple levels, this includes miRNAs and a plethora of post-translational modifications. Several chapters highlight the interplay between the three mammalian RUNX genes, where cross-talk and partial functional redundancies are evident. Finally, structural analysis of the RUNX/CBFB interaction has led to the development of small molecule inhibitors that provide exciting new tools to decipher the roles of RUNX in development and as targets for therapy. This volume provides a compendium and reference source that will be of broad interest to cancer researchers, developmental biologists and immunologists.
T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.
This volume has a strong focus on homo-oligomerization, which is surprisingly common. However, protein function is so often linked to both homo- and hetero-oligomerization and many heterologous interactions likely evolved from homologous interaction, so this volume also covers many aspects of hetero-oligomerization.
​This volume provides simple and accessible experiment protocols to explore thymus biology. T-Cell Development: Methods and Protocols is divided into three parts presenting short reviews on T cell development, analysis strategies, protocols for cell preparation, flow cytometry analyses, and multiple aspects of thymocyte biology. As a volume in the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, T-Cell Development: Methods and Protocols aims to ensure successful results in the further study of this vital field.
DNA Methylation and Complex Human Disease reviews the possibilities of methyl-group-based epigenetic biomarkers of major diseases, tailored epigenetic therapies, and the future uses of high-throughput methylome technologies. This volume includes many pertinent advances in disease-bearing research, including obesity, type II diabetes, schizophrenia, and autoimmunity. DNA methylation is also discussed as a plasma and serum test for non-invasive screening, diagnostic and prognostic tests, as compared to biopsy-driven gene expression analysis, factors which have led to the use of DNA methylation as a potential tool for determining cancer risk, and diagnosis between benign and malignant disease. Therapies are at the heart of this volume and the possibilities of DNA demethylation. In cancer, unlike genetic mutations, DNA methylation and histone modifications are reversible and thus have shown great potential in the race for effective treatments. In addition, the authors present the importance of high-throughput methylome analysis, not only in cancer, but also in non-neoplastic diseases such as rheumatoid arthritis. - Discusses breaking biomarker research in major disease families of current health concern and research interest, including obesity, type II diabetes, schizophrenia, and autoimmunity - Summarizes advances not only relevant to cancer, but also in non-neoplastic disease, currently an emerging field - Describes wholly new concepts, including the linking of metabolic pathways with epigenetics - Provides translational researchers with the knowledge of both basic research and clinic applications of DNA methylation in human diseases
Cancer was thought to originate from alterations in intercellular signaling that resulted in the transformation of cells, their uncontrolled proliferation and metastasis. There is now an increasing body of evidence demonstrating that the surrounding matrix and cell-matrix interactions are also major players in this process. Cells adhere and receive signals from various extracellular matrices via transmembrane receptors, the best known of which are the heterodimeric glycoproteins, integrins.
At the moment, there is no dedicated book to summarize the roles, the significance, and potential therapeutic targeting of transcriptional factors from the perspective of signaling cascade, and thus, directly impacting the functionality of transcriptional factors in cancer. In addition, this book will offer a comprehensive basic and clinical science behind the functions of representative core transcriptional factors. These chapters will serve as a treasure for all those who have an interest in the basis, progression, and targeting of human cancer. Each chapter will be intended to provide comprehensive, up-to-date information by the leaders about the physiologic and pathologic roles of TFs in specific representative organ systems of prime importance. The book will consist of chapters that will give biomedical students, under and graduate students, basic sciences and clinical cancer fellows, residents and researchers, and oncology educators will get a thorough summary of the overall subject. The readers will be able to understand the important current information and views on specific TFs and its role in cancer in areas outside their own expertise or experience. A special emphasis will be also placed on the "classic" papers as well as perspectives on future directions for the field.
Nuclear Structure and Gene Expression assimilates the contributions of genome organization and of the components of the nuclear matrix to the control of DNA and RNA synthesis. Nuclear domains which accommodate DNA replication and gene expression are considered in relation to short-term developmental and homeostatic requirements as well as to long-term commitments to phenotypic gene expression in differentiated cells. Consideration is given to the involvement of nuclear structure in gene localization as well as to the targeting and concentration of transcription factors. Aberrations in nuclear architecture associated with and potentially functionally related to pathologies are evaluated. Tumor cells are described from the perspective of the striking modifications in both the composition and organization of nuclear components. Nuclear Structure and Gene Expression presents concepts as well as experimental approaches, which define functionality of nuclear morphology.* Mechanisms of interaction between nuclear structure and genes* Gene expression regulation by elements of the nuclear matrix* How nuclear structure exerts a regulatory effect on other aspects of cell function/physiology