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The Histone Code and Beyond : New Approaches to Cancer Therapy
Methylation of DNA at cytosine residues as well as post-translational modifications of histones, including phosphorylation, acetylation, methylation and ubiquitylation, contribute to the epigenetic information carried by chromatin. These changes play an important role in the regulation of gene expression by modulating the access of regulatory factors to the DNA. The use of a combination of biochemical, genetic and structural approaches has allowed demonstration of the role of chromatin structure in transcriptional control. The structure of nucleosomes has been elucidated and enzymes involved in DNA or histone modifications have been extensively characterized. Since deregulation of epigenetic marks has been reported in many cancers, a better understanding of the underlying molecular mechanisms bears the promise that new drug targets may soon be found. The newest developments in this quickly developing field are presented in this book.
Tau protein : Methods and protocols
Explores the latest advancements and techniques to study Tau protein that include basic and advanced methods and protocols from in vitro assays to in vivo models that address the molecular and functional aspects of tau physiopathology and many of its related technical issues. The chapters in this book are organized into five parts: Part One describes conformational and functional studies of native tau protein using wet and non-wet lab protocols. Part Two looks at in vitro methods to monitor or control the formation of Tau oligomers and fibrils, and the fibrillization process. Part Three provides protocols for the characterization and in vitro introduction of post-translational modifications in Tau protein for further functional studies. Part Four describes analytical tools for the detection of Tau proteins under various forms, factors associated with Tau pathology, and MAPT gene studies. Finally, Part Five explores cellular and in vivo models for the investigations of Tau physiopathology. 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.
Stress-Activated Protein Kinases
To maximize the probability of survival, cells need to coordinate their intracellular activities in response to changes in the extracellular environment. MAP kinase cascades play an important role in the transduction of signals inside eukaryotic cells. In particular, stress stimuli result in the rapid activation of a highly conserved group of MAP kinases, known as SAPKs (Stress-Activated Protein Kinases). These kinases coordinate the generation of adaptive responses that are essential for cell survival, which include the modulation of several aspects of cell physiology from metabolism to gene expression.
Sparking Signals : Kinases as Molecular Signaltransducers and Pharmacological Drug Targets in Inflammation
Protein phosphorylation is an essential post-translational modification that modulates cell–cell communication. Substrate phosphorylation by protein kinases controls intracellular signal transduction pathways that mediate cell proliferation, migration, differentiation, and metabolism. The importance of the protein kinase family is underscored by numerous disease states that arise due to dysregulation of kinase activity. Recent progress in understanding the molecular regulation of kinases has led to the development of new therapeutics based on the inhibition of kinase activity. Inhibitors that target protein kinases have proven efficacious in clinical settings and their continued development is the current focus of many drug discovery groups.
Oxidative Phosphorylation in Health and Disease
Mitochondrial diseases are often hard to diagnose. From the time they were first researched without animal models, patients of mitochondrial diseases were of equal interest to both clinical and basic scientists. With the new research done, this book includes updates on the normal structure, function, and molecular biology of the mitochondrial respiratory chain, information on traditional diagnostical methodologies, and an overview of the diagnostic promise of new technologies. The hypermetabolism of Luft disease, although only seen twice, is also studied. There are critical reviews of symptoms and signs associated with syndromes, as well as updates on the genetic defects of either the mitochondrial or the nuclear genome responsible for many disorders.
CO-ENZYME Q10
Coenzyme Q10 (CoQ10) is a fat-soluble compound that is synthesized by the body and can be obtained from the diet. Co-Q10 plays a central role in mitochondrial oxidative phosphorylation and the production of adenosine triphosphate (ATP). It also functions as an antioxidant in cell membranes and lipoproteins. Endogenous synthesis and dietary intake provide sufficient C0- Q10 to prevent deficiency in healthy people, although coenzyme Q10 concentrations in tissues decline with age. Oral supplementation of coenzyme Q10 increases coenzyme Q10 concentrations in plasma and lipoproteins. Oral high-dose co- Q10 is usually effective to treat mitochondrial disorders that are caused by mutations in coenzyme Q10 biosynthetic genes.
Biophysical Aspects of Transmembrane Signaling
Transmembrane signaling is one of the most significant cell biological events in the life and death of cells in general and lymphocytes in particular. Until recently biochemists and biophysicists were not accustomed to thinking of these processes from the side of a high number of complex biochemical events and an equally high number of physical changes at molecular and cellular levels at the same time. Both types of researchers were convinced that their findings are the most decisive, having higher importance than the findings of the other scientist population. Both casts were wrong. Life, even at cellular level, has a number of interacting physical and biochemical mechanisms, which finally build up the creation of an "excited" cell that will respond to particular signals from the outer or inner world.
