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This book reviews the latest developments in the design, synthesis, and molecular mechanism of action of Histone Deacetylase (HDAC) inhibitors in the context of potential cancer therapy. HDAC inhibitors are emerging as promising anticancer drug molecules that promote growth arrest, differentiation and apoptosis of cancer cells with tumor selective toxicity. The book begins with an overview of various epigenetic modifying enzymes that are involved in cancer transition and progression; before exploring the potential of HDACs in cancer treatment. It provides a classification of HDAC inhibitors based on their structural attributes, and addresses HDAC-induced cytotoxicity.. Lastly, it discusses and assesses the rationale behind therapies that combine HDAC inhibitors with other anticancer agents to treat solid tumors. Given its scope, it offers a valuable resource for all researchers, clinicians, and students working in formulation, drug discovery, oncology, and personalized medicine.

This book presents the latest knowledge and the most recent research results on glycosphingolipid (GSL)-mediated signaling. GSLs are important constituents of the plasma membrane that exert their distinct functions through binding to certain functional proteins. They play a role in various human diseases and also function as human alloantigens. Cellular GSLs are associated with many biological functions such as cellular oncotransformation, phenotype change, neuronal or embryonic development, regulation of cell division, cell–cell interaction, cell attachment, adhesion, and motility, and intracellular signaling via protein–carbohydrate or carbohydrate–carbohydrate interactions. This book opens by providing the key background on GSL glycan–receptor interactions and mammalian GSL synthesis. Up-to-date information is then presented on all aspects of GSL-dependent signaling. Viral protein and bacterial toxin protein interactions with host cell GSLs are examined in depth, and the concluding chapter is devoted to signaling regulation. The book should assist in the further development of new strategies against emerging infectious agents and intractable diseases.

In response to various environmental cues and cellular stress, cells need to modify their protein expression pattern for proper cell functioning. The cell experiences diverse cellular stress as oxidative, genotoxic, and etc. The damage of the genome by certain chemicals or agents affects the cell integrity and leads to genotoxic stress. As such, this compilation discusses how different cellular stresses affect the polyadenylation process and modulate the polyadenylation machinery. Cytoplasmic polyadenylation plays an important role in oocyte maturation, mitotic cell cycle progression, cellular senescence and synaptic plasticity. Poly(A) tails can be elongated post-transcriptionally by noncanonical poly(A) polymerases, which can impact cells with limited transcriptional activity. A recent study is discussed wherein it is shown that that alternative cleavage and polyadenylation isoform expression influences about 10% of targeting by miRNAs between any two cell types analysed and, more importantly, that the accuracy of target prediction can be improved if the cellular alternative cleavage and polyadenylation profile is considered. The authors go on to focus on how altering the polyadenylation process and components of RNA polyadenylation machinery leads to abnormal physiological conditions. The targeting of elements of RNA polyadenylation machinery as therapeutics in clinical research is also discussed. The majority of eukaryotic mRNAs are polyadenylated at their 3´end. This poly(A) tail is not encoded by DNA and is added co-transcriptionally. Cleavage and polyadenylation specific factor (CPSF1) is part of multiple subunit factors required for a site-specific cleavage, which is involved in determining specificity and efficency of the 3´ end processing of pre-mRNAs in the nucleus by recognizing the polyadenylation signal. Following this, mutations in the poly(A) signal (AAUAAA hexamer) present in the globin pre-mRNA were identified in hematological disorders caused by defects in the synthesis of one or more of the globin chains (thalassemia). The point mutation AATAAA to AACAAA of a human β-globin gene detected in 1985 in DNA from a patient with β-thalassemia led to the formation of an elongated β-globin mRNA isoform. This compilation addresses how RNA processing at the pre-mRNA level occurs in the cell nucleus and regulates gene expression. Newly synthesized mRNA contains a poly(A) tail, which is added through canonical polyadenylation coupled to transcription. Canonical mRNA 3´ processing involves endonucleolytic cleavage within the pre-mRNA sequences and the addition of a poly(A) tail to the upstream cleavage fragment. The closing chapter discusses how the poly(A) tail at the 3´end of the majority of eukaryotic messenger RNAs (mRNAs), with the exception of histone transcripts, is not simply a static entity but more likely a dynamic matter. Its length added to an mRNA is regulated by the concerted action of poly(A) polymerases and deadenylases.

This book describes how epigenetic context, in a large sense, affects gene expression and the development of an organism, using the asymptotic limit theorems of information theory to construct statistical models useful in data analysis. The approach allows deep understanding of how embedding context affects development. We find that epigenetic information sources act as tunable catalysts, directing ontogeny into characteristic pathways, a perspective having important implications for epigenetic epidemiology. In sum, environmental stressors can induce a broad spectrum of developmental dysfunctions, and the book explores a number of pandemic chronic diseases, using U.S. data at different scales and levels of organization. In particular, we find the legacy of slavery has been grossly compounded by accelerating industrial decline and urban decay. Individual chapters are dedicated to obesity and its sequelae, coronary heart disease, cancer, mental disorders, autoimmune dysfunction, Alzheimer's disease, and other conditions. Developmental disorders are driven by environmental factors channeled by historical trajectory and are unlikely to respond to medical interventions at the population level in the face of persistent individual and community stress. Drugs powerful enough to affect deleterious epigenetic programming will likely have side effects leading to shortened lifespan. Addressing chronic conditions and developmental disorders requires significant large-scale changes in public policy and resource allocation.

This book summarizes microRNA (miRNA) biology in a variety of pathological processes, emphasizing the significant potential applications of miRNA in diagnostics and prognostics, as well as novel drug targets. The conventional techniques used for miRNA detection including standard PCR, Northern blotting, microarray and clone methods are addressed. Recent emerging strategies in miRNA detection and quantification with superior flexibility and adaptability, such as novel molecular biological techniques and locked nucleic acid (LNA) modified probes, as well as nanotechnology-based approaches, are also included. The book also highlights the latest advances in clinical-related miRNA detection methods in living cells, circulating blood and tissue, such as in situ hybridization (ISH) and molecular imaging techniques, which are useful to elucidate the biogenesis and biological function of miRNAs in vivo. Finally, the respective advantages and drawbacks of various detection techniques in this fast-moving field are discussed, along with the challenges and promising new directions.This book offers a valuable resource for analytical chemists, biologists and physicians involved in miRNA research.Dr. Xueji Zhang and Dr. Haifeng Dong are Professors at the School of Chemistry & Biological Engineering, University of Science & Technology Beijing (USTB), China.Dr. Yaping Tian is a Professor at the Department of Clinical Biochemistry, Chinese PLA General Hospital and Military Medical School, China.

This title includes a number of Open Access chapters. This new volume on gene expression and epigenetics discusses environmental effects related to specific gene expression. The book also shows methods for bioinformatic analysis of the epigenome. The book is broken into two sections: the first looks at eukaryotic DNA methylation and the second addresses how to integrate genomic medicine into clinical practice. The book includes chapters on these topics: • Gene expression in colon cancer tissue • Epigenetics in human acute kidney injury • Embryologically relevant candidate genes in MRKH patients • DNA methylation in common skeletal disorders • Causal relationships in genomics • Predicting severe asthma exacerbations in children • Epigenetic understanding of gene-environment interactions in psychiatric disorders

Timing, racing, combating, struggling and targeting are some actions through which cellular fate could be reflected and evaluated. Interaction between cell territory and environment occur during pre-embryonic, fetal development, and post-natal periods. What the researchers observe as the outcome of telomeres behavior is only the peak of an ice mountain within a stormy ocean. Cellular life depends on programmed behavior of telomeres, capable to surprise the cells. Telomeres provide an introduction to the history of our cells which govern the quality of life and status of health. Telomeres as the cooperative territory are capable of stabilizing the chromosomal territory. The status of telomeres reflects the key information, announcing the real age of individuals, and may be a valuable marker for prognosis and predicting cancer. Telomere territory is characterized with a multi-disciplinary manner. Therefore, this book is aimed to offer a wide range of chapters, hoping to be useful for diverse audiences, including hematologists-oncologists, radiotherapists, surgeons, cancer researchers, and all the sectors who affect the macro- and micro- environmental domains. Finally, telomeres are sensitive, cooperative, and trustable targets. It is worth to state that ‘telomeres are messengers of NATURE', let's to know them as they are.

Why should the gene be suggested to be inconstant when the contrary view, that gene structure is invariant except through mutagenic processes induced by potent external factors, has long been a universal doctrine of genetics? Indeed, during the early part of the present century before mutation was recognized as being of general occurrence, the seeming unvarying nature of the gene led to skepticism regarding the validity of the evolutionary theory; only later could the origins of the morphological differences between individuals and species be attributed to a combination of mutation and evolution, involving natural forces selecting between favorable and unfavorable genetic changes. But during the past several decades, as knowledge of the macromolecular constitution of or­ ganisms has increased to the point where even the primary structures of the genes themselves are being revealed on a routine basis, it has become increas­ ingly difficult to ascribe all the resulting observations to ordinary mutagenesis and natural selection. Some more profound mechanism often seems to be present that influences both the constancy and inconstancy of the genes, an ap­ paratus whose existence this study hopes to reveal. In seeking to demonstrate the universality of this mechanism, data are sought through the numerous activities of organisms of many types wherever gene action changes are manifest.

This book, which results from the dramatic increase in interest in the control mechanism employed in gene expression and the importance of the regulated proteins, presents new information not covered in Translational Regulation of Gene Expression, which was published in 1987. It is not a revision of the earlier book but, rather, an extension of that volume witl, special emphasis on mecha­ nIsm. As the reader will discover, there is enormous diversity in the systems employing genes for translational regulation in order to regulate the appearance of the final product-the protein. Thus, we find that important proteins such as protooncogenes, growth factors, stress proteins, cytokines, lymphokines, iron­ storage and iron-uptake proteins, and a panorama of prokaryotic proteins, as well as eukaryotic viral proteins, are translationally regulated. Since for some gene products the degree of control is greater by a few orders of magnitude than their transcription, we can state that for these genes, at least, the expression is translationall y controlled. Translational regulation of gene expression in eukaryotes has emerged in the last few years as a major research field. The present book describes mechanisms of translational regulation in bacteria, yeast, and eukaryotic viruses, as well as in eukaryotic genes. In this book we try to provide in-depth coverage by including important examples from each group rather than systematically including all additional systems not described in the previous volume.

In Gene Regulatory Sequences and Human Disease, the Editor will introduce the different technological advances that led to this breakthrough. In addition, several examples will be provided of nucleotide variants in noncoding sequences that have been shown to be associated with various human diseases.

Genetic analysis of microbial systems provided us with the foundation for un­ derstanding gene structure, expression, and regulation. It was long felt that the ability to generate mutants and conduct genetic studies in mammalian systems would prove to be equally useful. However, genetic analysis based on sexual systems is difficult in mammals because of the long generation times and the inability to perform controlled matings. As a result, genetic analysis of mam­ malian systems had to await the development of parasexual systems. This book is an attempt to bring together descriptions of a number of these parasexual systems. A common theme of all the parasexual systems is the transfer of genetic information from a defined source into a specific cell type. This volume deals with a number of methods of gene transfer into mammalian cells. The early methods of gene transfer involved transfer of relatively large amounts of genetic information. These include somatic cell hybridization, microcell fusion, and chromosome transfer, which constitute the first part of this book. Each of these methods has already proven to be of enormous value in arriving at a genetic understanding of the mammalian genome. Development of recombinant DNA methods, and the ability to introduce purified DNA into mammalian cells, has had a significant impact on our ability to dissect important aspects of mammalian gene expression and regulation. The second part of this book deals with gene transfer systems involving defined nucleic acid sequences.

In situ hybridization has developed as a means of localizing specific DNA and RNA sequences within tissues. The great strength of this approach is the ability to relate the distribution of specific nucleic acids with cell structures and the protein products of the target gene by means of immunohistochemistry. Complementary DNA, RNA or oligonucleotide probes, suitably labelled, are hybridized to specific DNA or RNA targets within tissues. The spatial information thus obtained has contributed greatly to our understanding of such diverse areas of research as gene mapping, viral infection, cytogenetics, protein synthesis, prenatal diagnosis and tissue grafting. This book is not intended as another recipe book, although it does describe theoretical and practical aspects of the technology. Rather, the authors critically describe the contribution made by in situ hybridization to specific areas of medical research.

The literature on recoding is scattered, so this superb book?lls a need by prov- ing up-to-date, comprehensive, authoritative reviews of the many kinds of recoding phenomena. Between 1961 and 1966 my colleagues and I deciphered the genetic code in Escherichia coli and showed that the genetic code is the same in E. coli, Xenopus laevis, and guinea pig tissues. These results showed that the code has been c- served during evolution and strongly suggested that the code appeared very early during biological evolution, that all forms of life on earth descended from a c- mon ancestor, and thus that all forms of life on this planet are related to one another. The problem of biological time was solved by encoding information in DNA and retrieving the information for each new generation, for it is easier to make a new organism than it is to repair an aging, malfunctioning one. Subsequently, small modi?cations of the standard genetic code were found in certain organisms and in mitochondria. Mitochondrial DNA only encodes about 10–13 proteins, so some modi?cations of the genetic code are tolerated that pr- ably would be lethal if applied to the thousands of kinds of proteins encoded by genomic DNA.

MicroRNAs (miRNAs), endogenous noncoding regulatory mRNAs of - nucleotides, have rapidly emerged as the central players in gene expression regulation. Owing to their ever-increasing implications in the control of various biological and pathological processes, miRNAs have now been considered novel biomarkers of various human diseases including, cancer, viral disease, cardiov- cular disorders, metabolic disturbances, etc. Particular expression pro?les have been associated with particular pathological states. Expression pro?ling of miR- NAs have therefore become extremely important not only for fundamentalists but also for clinicians. However, the methodologies used for detecting protein-coding mRNAs cannot be directly applied to miRNAs because of their small size. Over the past years, researchers have made great efforts to developing techniques suitable for miRNA detection and quanti?cation; a wide spectrum of creative and inno- tive techniques (more than 30 different methods) have been invented and validated. It has come to the time now to summarize these methods and present them in an orderly manner for better understanding and utilization of these methods to miRNA research and applications. In particular, the development of methods for quantifying circulating miRNAs opens up a fascinating opportunity for realizing miRNA as diagnostic and prognostic biomarkers of human disease. A book on this subject may help boosting up the passion of researchers to further improve the existing techniques and develop more new methods to?t to new application needs. These considerations prompted us and urged us to undertake the work: writing a book focusing on miRNA expression detection methods.

The study of Hox genes is crucial not only in exploring the enigma of homeosis but also in understanding normal development at the fundamental molecular level.'Hox Gene Expression'starts with the amazing discovery of the homeobox twenty-three years ago and follows the exciting path thereafter of a series of breakthroughs in Genetics, Development and Evolution. It deals with homeotic genes- their evolution, structure, normal and abnormal function. Researchers and graduate students in Biology and Medicine will benefit from this integrated overview of Hox gene activities.

As studies using microarray technology have evolved, so have the data analysis methods used to analyze these experiments. The CAMDA (Critical Assessment of Microarray Data Analysis) conference was the first to establish a forum for a cross section of researchers to look at a common data set and apply innovative analytical techniques to microarray data. Methods of Microarray Analysis V includes selected papers from CAMDA'04, and focuses on data sets relating to a significant global health issue, malaria. Previous books focused on classification (V. I), pattern recognition (V. II), quality control issues (V. III), and associating array data with a survival endpoint, lung cancer, (V. IV). The contributions come from research fields including statistics, biology, computer science and mathematics. Part of the book is devoted to review papers, which provide a more general look at various analytical approaches. It also presents some background readings for the advanced topics discussed in the CAMDA papers.

Gene regulation is an essential process in the development and maintenance of a healthy body, and as such, is a central focus in both basic science and medical research. Gene Regulation, Fifth Edition provides the student and researcher with a clear, up-to-date description of gene regulation in eukaryotes, distilling the vast and complex primary literature into a concise overview.

For the first time, international scientists describe the advances in genetics and nutrition by combining methods of molecular biology with those of functional genetics, also known as systems biology. This book provides the latest data on genetic variation and dietary response, nutrients and gene expression, and the contribution molecular biology has given to systems biology. It also includes a comprehensive critique of genetic association studies in defining the risk of chronic diseases and concludes that molecular diagnostic tests will eventually affect every area of health care from individual risk prediction, early diagnosis of disease, and determination of optimal treatment regimens, to monitoring treatment effectiveness. The appendix contains an extensive glossary of the newly emerging terminology, as well as recommendations for genetic screening. This publication is an essential tool for the future work of all physicians, nutritionists, dietitians, geneticists, physiologists, molecular biologists, anthropologists, food technologists, policy makers, ethicists and educators.

After genomic sequencing, microarray technology has emerged as a widely used platform for genomic studies in the life sciences. Microarray technology provides a systematic way to survey DNA and RNA variation. With the abundance of data produced from microarray studies, however, the ultimate impact of the studies on biology will depend heavily on data mining and statistical analysis. The contribution of this book is to provide readers with an integrated presentation of various topics on analyzing microarray data.

Proteomics is an introduction to the exciting new field of proteomics, an interdisciplinary science that includes biology, bioinformatics, and protein chemistry. The purpose of this book is to provide the active researcher with an overview of the types of questions being addressed in proteomics studies and the technologies used to address those questions. Key subjects covered in this book include: an assessment of the limitations of this approach and outlines new developments in mass spectrometry that will advance future research high-throughput recombinant DNA cloning methods used to systematically clone all of the open reading frames of an organism into plasmid vectors for large scale protein expression and functional studies such as protein-protein interactions with the two-hybrid system protein structure an overview of large-scale experimental attempts to determine the three-dimensional structures of representative sets of proteins computational approaches to determining the three-dimensional structure of proteins. Proteomics provides a starting point for researchers who would like a theoretical understanding of the new technologies in the field, and obtain a solid grasp of the fundamentals before integrating new tools into their experiments. Written with attention to detail, but without being overwhelmingly technical, Proteomics is a user-friendly guide needed by most biologists today.