Research in Crohn's disease (CD) and ulcerative colitis (UC), together known as the inflammatory bowel diseases (IBD), has truly seen a revolution in the last 5-10 years. This book examines how these genetic discoveries have led to the identification of biological functions not previously associated with IBD pathophysiology (e.g. autophagy), how multiple genetic risk factors for IBD converge on given biological functions and that together the identified variants in these genes have predisposing and protective roles (e.g. the multiple variants in the receptor for the IL23 cytokine and its signaling cascade), and how having such a large number of known genetic risk factors has changed our understanding not only about the genetic and molecular overlap between CD and UC, but also between these diseases and other chronic inflammatory diseases (e.g. psoriasis, multiple sclerosis, type 1 diabetes and many others).

Since the discovery of microRNAs (miRNAs) some twenty years ago by Victor Ambros, David Baulcombe and Gary Ruvkun, these three scientists worked to uncover the mystery of miRNA, the small segments of nucleotides that silence genes. While studying the development of the nematode worm, Ambros and Ruvkun discovered miRNA in animals, while Baulcombe discovered it in plants. Since their discovery, it took more than two decade to fully appreciate the value of miRNA in human health and diseases. Emerging evidence suggest that the activation of oncogenes and/or the inactivation of tumor suppressor genes contribute to the development and progression of tumors. The regulation of genes is by far controlled by many transcription factors which are often deregulated during the development and progression of cancer. In addition, emerging evidence clearly suggests that the deregulation of miRNAs or small non-coding RNAs could also regulate the expression of genes and likewise, miRNA genes are also regulated by transcription factors. The most attractive feature of miRNAs is that one miRNA can regulate many target genes (mRNAs) and thus miRNA targeted therapy is highly promising because multiple genes could be regulated by targeting a single miRNA, which becomes very important for the killing of highly heterogeneous populations of cancer cells within a tumor mass. Therefore, miRNA targeted therapy is an attractive attribute of miRNA research, which is covered through eighteen chapters complied in this book "MicroRNA targeted Cancer therapy" and it is hoped that the field of miRNA research will be appreciated through critical reading of these chapters on the cutting-edge research on miRNAs.

The discovery of microRNAs and its role as gene expression regulators in human carcinogenesis represents one of the most important scientific achievements of the last decade. More recently, other non-coding RNAs have been discovered and its implications in cancer are emerging as well, suggesting a broader than anticipated involvement of the non-coding genome in cancer. Moreover, completely new and unexpected functions for microRNAs are being revealed, leading to the identification of new anticancer molecular targets. This book represents a comprehensive guide on non-coding RNAs and cancer, spanning from its role as cancer biomarkers, to providing the most useful bioinformatic tools, to presenting some of the most relevant discoveries, which indicates how these fascinating molecules act as fine orchestrators of cancer biology.

This book provides a review of the multitude of nucleic acid polymerases, including DNA and RNA polymerases from Archea, Bacteria and Eukaryota, mitochondrial and viral polymerases, and other specialized polymerases such as telomerase, template-independent terminal nucleotidyl transferase and RNA self-replication ribozyme. Although many books cover several different types of polymerases, no book so far has attempted to catalog all nucleic acid polymerases. The goal of this book is to be the top reference work for postgraduate students, postdocs, and principle investigators who study polymerases of all varieties. In other words, this book is for polymerase fans by polymerase fans. Nucleic acid polymerases play a fundamental role in genome replication, maintenance, gene expression and regulation. Throughout evolution these enzymes have been pivotal in transforming life towards RNA self-replicating systems as well as into more stable DNA genomes. These enzymes are generally extremely efficient and accurate in RNA transcription and DNA replication and share common kinetic and structural features. How catalysis can be so amazingly fast without loss of specificity is a question that has intrigued researchers for over 60 years. Certain specialized polymerases that play a critical role in cellular metabolism are used for diverse biotechnological applications and are therefore an essential tool for research.

Genetic toxicology is recognized by geneticists and researchers concerned with the genetic impact of man-made chemicals. In Genotoxicity Assessment: Methods and Protocols, expert researchers in the field provide comprehensive genetic toxicology protocols. These include in vitro and in vivo protocols on mutation assays, cytogenetic techniques, and primary DNA damage, assays in alternate to animal models, and updated ICH guidelines. Written in the highly successful Methods in Molecular Biology series format, the chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, as well as key tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Genotoxicity Assessment: Methods and Protocols seeks to aid research students and scientists working in regulatory toxicology as well as biomedical, biochemical and pharmaceutical sciences.

Understanding gene expression and how it changes under normal and pathological conditions is essential to our understanding of the fundamentals of cell biology through to the targeted treatment of disease. In Gene Expression Profiling: Methods and Protocols, Second Edition, experts in their particular fields compile detailed protocols for a broad range of techniques, currently available and being further developed, for the analysis of gene expression at the DNA, RNA, and protein levels. Written in the highly successful Methods in Molecular Biology (TM) 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. Practical and easy-to-use, Gene Expression Profiling: Methods and Protocols, Second Edition presents a collection of clearly described and illustrated chapters, certain to be helpful to researchers in academia, in hospitals, and in industry who are interested in applying techniques, whether basic or advanced, for the analysis of gene expression.

The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution, and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress, and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution then. The mutation mechanism also includes temporary suspension of post-synthesis mismatch repair, resembling mutagenesis characteristic of some cancers. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, pathogenicity of microbes, and many other important evolutionary processes. This book covers pathways of stress-induced mutagenesis in all systems. The principle focus is mammalian systems, but much of what is known of these pathways comes from non-mammalian systems.

Chorea: Causes and Management provides a comprehensive and timely update for the wide variety of neurological conditions, both inherited and acquired, which result in this common hyperkinetic movement disorder. This book describes in detail the latest clinical and etiological information regarding chorea. Management strategies, pathophysiology, and associated medical and psychiatric problems associated with chorea are also addressed. The nineteen chapters are contributed by internationally-recognized authors working at the forefront of research in the specific disorders linked to chorea. Chorea: Causes and Management is aimed at an audience of neurologists, psychiatrists, neuropsychologists, specialists in medical genetics, clinical and basic researchers in neurosciences, and generalist clinical physicians with an interest in movement disorders.

Primary immunodeficiency diseases (PIDs) are a heterogeneous group of inherited disorders characterized by different defects in the development and function of the immune system. This book aims to increase the clinical awareness and knowledge of practicing clinicians regarding the diagnosis and management of PIDs. In order to achieve this goal, about 90 cases drawn from real life are presented, along with approximately 300 related questions. The selected case reports are the result of the invaluable cooperation of more than 40 scientists in the field of immunodeficiency. They focus both on the presenting features of patients with PIDs and on the required further investigation and management. Each of the numbered cases is followed by the questions, their answers, and additional discussion. Each question focuses on a particular aspect of the PID under consideration, and the topics covered include clinical diagnosis, laboratory findings, molecular mechanisms, and therapy.

This volume provides protocols and procedures for determining and modeling RNA structure. Chapters guide the reader through protocols for RNA secondary structure prediction, single sequence modeling, Crumple, RNAstructure to model conserved secondary structures with multiple homologs, the prediction of bimolecular secondary structures with RNAstructure, STarMir, protocols for structure mapping, mapping data to constrain or restrain RNA secondary structure prediction with RNAstructure, unassigned NMR resonances, modeling protocols for Rosetta FARFAR, RNAComposer , ModeRNA, and MC-Fold. 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. Authoritative and Practical, RNA Structure Determination: Methods and Protocols aims to ensure successful results in the further study of this vital field.

GW bodies are novel cytoplasmic foci that were discovered and named by Dr. Chan's group in 2002. These bodies are now known to be active cytoplasmic foci involved with the new gene regulation process mediated by microRNA that leads to translational repression and mRNA degradation. The detailed biological functions of these cytoplasmic structures are still being uncovered and the idea for this book is to provide the history of the discovery and the major work from different laboratories that has led to the characterization and elucidation of the structure and function of these new multiple subcellular structures.

This book is a comprehensive, empirically-grounded exploration of the relationship between bioethics, culture, and the perspective of being affected. It provides a new outlook on how complex "bioethical" issues become questions of everyday life. The authors focus on two contexts, genetic testing and end-of-life care, to locate and demonstrate emerging themes of responsibility, such as self-responsibility, responsibility for kin, and the responsibility of society. Within these themes, the duty to know versus the right not to know one's genetic fate (in the context of genetic testing), or the sanctity of life versus self-determination (in the context of end of life care) are identified as culturally embedded dilemmas that are very much relevant for lay persons. Furthermore, cultural factors such as religion, history, utopian and dystopian views of biomedical technologies, outlooks on the body and on health/illness, and citizenship are examined. Health issues are increasingly becoming a question of assessing risk and responsibility: How can we better prepare ourselves for the future? We all make such assessments in a way that combines personal inclinations, professional recommendations, and cultural framings. There is still much to be learned about the interplay between these three dimensions.

The volume provides a forum for original peer-reviewed short communications, full-length research and review articles on new research findings and developments on the topic of genetic targets on cancer therapies. As the field is highly important it requires co-operation between research communities from all over the world to share their knowledge and experience in order to move the field forward. Each chapter includes a discussion of the impact of the tumor microenvironment and cancer stem cells and cover current knowledge in this area as it pertains to the disease, including emerging therapy targeting the microenvironment and/or cancer stem cells.

The central question of this book is whether or not particular cell entities of human origin ought to be considered human beings. The answer is crucial for making moral decisions for or against research and experimentation. Experts in the field discuss the production of embryonic-like pluripotent stem cells by altered nuclear transfer, parthenogenesis and reprogramming of adult somatic cells. They thoroughly analyse the biological and moral status of different cell entities, such as human stem cells, embryos and human-animal hybrid embryos, and make a decisive step towards establishing final criteria for what constitutes a human being. The topic is challenging in nature and of broad interest to all those concerned with current bioethical thought on embryonic human life and its implications for society.

Circadian rhythms are such an innate part of our lives that we rarely pause to speculate why they even exist. Some studies have suggested that the disruption of the circadian system may be causal for obesity and manifestations of Metabolic Syndrome (MetS). Shift-work, sleep-deprivation and bright-light-exposure at night are related to increased adiposity (obesity) and prevalence of MetS. It has been provided evidence of clock genes expression in human adipose tissue and demonstrated its association with different components of the MetS. Moreover, current studies are illustrating the particular role of different clock genes variants and their predicted haplotypes in MetS. The purpose of "Chronobiology and Obesity" is to describe the mechanisms implicated in the interaction between chonodisruption and metabolic-related illnesses, such as obesity and MetS, with different approaches.

I entered the gene therapy field in the mid-1990s, being fascinated by the immense potential of genes as drugs for the treatment of human disease. Since then, I have experienced the ups and downs of this discipline, and tried to contribute with my work and that of my laboratory to the development of innovative approaches to the treatment of cardiovascular disorders. During these years, I have had several opp- tunities to speak on gene therapy at lectures and academic lessons, and have often noticed that the field is very attractive to scientists of all disciplines. However, as yet no comprehensive book on the subject has been published. Indeed, most books in the field are either a collection of gene transfer laboratory protocols or deal with the subject in a rather superficial manner. Hence the idea to write a gene therapy textbook that is broad and comprehensive, but at the same time provides sufficient molecular and clinical detail to be of interest to students, professors, and specialists in the various disciplines that contribute to gene therapy. I have tried to keep the language plain and, whenever possible, non-technical. Since the book is intended to be a textbook in the field of gene therapy in both the basic science and clinical areas, whenever technical descriptions are required, they are provided.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

Recent studies have indicated that epigenetic processes may play a major role in both cellular and organismal aging. These epigenetic processes include not only DNA methylation and histone modifications, but also extend to many other epigenetic mediators such as the polycomb group proteins, chromosomal position effects, and noncoding RNA. The topics of this book range from fundamental changes in DNA methylation in aging to the most recent research on intervention into epigenetic modifications to modulate the aging process. The major topics of epigenetics and aging covered in this book are: 1) DNA methylation and histone modifications in aging; 2) Other epigenetic processes and aging; 3) Impact of epigenetics on aging; 4) Epigenetics of age-related diseases; 5) Epigenetic interventions and aging: and 6) Future directions in epigenetic aging research. The most studied of epigenetic processes, DNA methylation, has been associated with cellular aging and aging of organisms for many years. It is now apparent that both global and gene-specific alterations occur not only in DNA methylation during aging, but also in several histone alterations. Many epigenetic alterations can have an impact on aging processes such as stem cell aging, control of telomerase, modifications of telomeres, and epigenetic drift can impact the aging process as evident in the recent studies of aging monozygotic twins. Numerous age-related diseases are affected by epigenetic mechanisms. For example, recent studies have shown that DNA methylation is altered in Alzheimer's disease and autoimmunity. Other prevalent diseases that have been associated with age-related epigenetic changes include cancer and diabetes. Paternal age and epigenetic changes appear to have an effect on schizophrenia and epigenetic silencing has been associated with several of the progeroid syndromes of premature aging. Moreover, the impact of dietary or drug intervention into epigenetic processes as they affect normal aging or age-related diseases is becoming increasingly feasible.

With very few exceptions, eukaryotic cells possess two interdependent genomes, chromosomal and extra-chromosomal. Over the past several decades, cancer - search has focused primarily on deciphering the intricate alterations in the chro- somal genome, with until recently, very little attention to its cytoplasmic counterpart. In spite of the enormous complexity of the nuclear genome, which we now fully appreciate after completion of the human genome project, the efforts of cancer researchers are commendable in terms of the tremendous gains made in unraveling the numerous genetic changes in cancer. These changes include d- coveries of tumor suppressor genes, oncogenes, and caretaker genes that are often mutated in cancer. Recent studies of genomic pro?les are uncovering even more altered and mutated genes in cancer. Besides these ?ndings, several therapeutic targets for chemotherapy are currently made from studies of altered nuclear genetic pathways. Inspite of all these positive efforts, the war on cancer, declared in 1971 by Richard Nixon, is far from being worn. Indeed, the failure of chemotherapy is obvious to clinicians, oncologists, and their patients alike. Moreover, the global incidence and prevalence of cancer continue to rise. What are we missing? Which direction should we be taking? Of course, modern integrated nuclear genomics, proteomics, and metabolomics should provide important clues to carcinogenesis, but the contribution of cytoplasmic genetic alterations to carcinogenesis cannot be neglected.

This is the most comprehensive, up-to-date reference on this post-translational modification of proteins, which is intimately linked with DNA repair, maintenance of genomic stability, transcriptional regulation, cell death and a variety of other cellular phenomena as well as with a variety of pathophysiological conditions, including ischemia-reperfusion damage, Parkinson's disease, Type I diabetes mellitus, hemorrhagic and septic shock and other inflammatory conditions. Richly illustrated, it offers 19 chapters written by international experts.

As cells mature they naturally stop dividing and enter a period called senescence. But cellular senescence can also be induced prematurely by certain oncogenes involved in cancer development. Cellular senescence, a growth-arrest program that limits the lifespan of mammalian cells and prevents unlimited cell proliferation, is attracting considerable interest because of its links to tumor suppression.

Gene Expression and its Discontents examines a class of probability models describing how epigenetic context affects gene expression and organismal development, using the asymptotic limit theorems of information theory in a highly formal manner. Taking classic results on spontaneous symmetry breaking abducted from statistical physics in groupoid, rather than group, circumstances, the work suggests that epigenetic information sources act as analogs to a tunable catalyst, directing development into different characteristic pathways according to the structure of external signals. The results have significant implications for epigenetic epidemiology, in particular for understanding how environmental stressors, in a large sense, can induce a broad spectrum of developmental disorders in humans. The authors then apply the perspective to a number of chronic diseases broadly associated with obesity, using data at different scales of observation.

This book presents the diverse clinical, cellular and molecular manifestations of NF-KB-related genetic diseases. It shows that studying patient-related pathologies affecting the components of the NF-KB signaling pathway offers the opportunity to understand the various functions of NF-KB in humans, complementing studies performed with mouse models. In addition, people treating those patients acquire a deeper understanding of the molecular basis of the pathophysiological processes.

In the last ten years there has been a considerable increase of interest on the notion of the minimal cell. With this term we usually mean a cell-like structure containing the minimal and sufficient number of components to be defined as alive, or at least capable of displaying some of the fundamental functions of a living cell. In fact, when we look at extant living cells we realize that thousands of molecules are organized spatially and functionally in order to realize what we call cellular life. This fact elicits the question whether such huge complexity is a necessary condition for life, or a simpler molecular system can also be defined as alive. Obviously, the concept of minimal cell encompasses entire families of cells, from totally synthetic cells, to semi-synthetic ones, to primitive cell models, to simple biomimetic cellular systems. Typically, in the experimental approach to the construction of minimal the main ingredient is the compartment. Lipid vesicles (liposomes) are used to host simple and complex molecular transformations, from single or multiple enzymic reactions, to polymerase chain reactions, to gene expression. Today this research is seen as part of the broader scenario of synthetic biology but it is rooted in origins of life studies, because the construction of a minimal cell might provide biophysical insights into the origins of primitive cells, and the emergence of life on earth. The volume provides an overview of physical, biochemical and functional studies on minimal cells, with emphasis to experimental approaches. 15 International experts report on their innovative contributions to the construction of minimal cells.