This volume aims to connect current ideas and concepts about GI disorders with the search for novel therapeutics. Towards this goal, authors provide a timely state-of-the-art overview of the GI tract in health and disease, current treatment approaches and ongoing developments in drug discovery, and their potential for the better treatment of patients with GI disorders.

A Two Ribosome Model for Attenuation (G.W. Hatfield). Regulation of Ribosomal Proteins mRNA Translation in Bacteria (C. Portier, M. GrunbergManago). How Elongation Factors Steer the Ribosomal Elongation Cycle (K.H. Nierhaus, F. Triana). Genetics of Translation Initiation Factors in Saccharomyces cerevisiae (L. Feng, T.F. Donahue). Regulation of GCN4 Expression in Yeast (A.G. Hinnebusch et al.). Co and PostTranslational Processes and Mitochondrial Import of Yeast Cytochrome c (F. Sherman et al.). EIF4E Phosphorylation and the Regulation of Protein Synthesis (R.M. Frederickson, N. Sonenberg). InterferonInduced and DoubleStranded RNAActivated Proteins (A.G. Hovanessian). Translational Regulation by Vaccinia Virus (R. Bablanian). Translational Control by AdenovirusAssociated RNA I (B. Thimmapaya et al.). Translational Regulation in Adenovirus Infected Cells (R.J. Schneider, Y. Zhang). 12 additional articles. Index.

This special issue of the Handbook of Experimental Pharmacology on Heart Failure covers the entire spectrum of the field, from the current understanding and definitions of heart failure, to epidemiology and the importance of co-morbidities, clinical trial design and biomarkers, as well as imaging technologies. The main focus of this book is to review current and emerging heart failure therapies and potential targets for treatment.

This second edition focuses on the study of human interphase chromosomes and its relation to health and disease. Orchestrated organization and behavior of the human genome in interphase nuclei at chromosomal level has been repeatedly shown to play a significant role in almost all basic biological processes involved in the processing and inheritance of genetic information within and between species. Accordingly, post-genomic bioscience appeals to basic and applied studies of interphase nuclei genetics and genomics with special attention to interphase chromosome behavior in health and disease. Additionally, elucidating the role of interphase chromosome behavior during development, chromosome/DNA replication, DNA reparation opens new horizons for basic and applied bioscience Studies of interphase nuclei have an appreciable impact on different areas of biomedical sciences such as cell biology, neurobiology, cancer research, developmental biology, epigenetics, cytogenetics, and medical genetics, as a whole. Moreover, development of innovative and emergent technologies to analyze interphase nuclei are closely associated with application of these techniques in diagnostic and research practices to solve reproductive problems (including infertility and spontaneous abortions), to investigate congenital malformations (including those produced by aneuploidy and other chromosome abnormalities); genetic diseases (including cardiac, immune, neurological and psychiatric diseases), and cancer. This second edition serves as a source of updated valuable information and promising ideas for a wide audience of professionals in biomedicine including researchers, scientists, and healthcare professionals in human genetics, cytogenetics, and developmental biology.

Intrauterine insemination (IUI), also known as artificial insemination, is a fertility treatment that uses a catheter to place washed sperm directly into the uterus. Its aim is to increase the number of sperm reaching the fallopian tubes and subsequently increase the chances of fertilisation (American Pregnancy Association). This book is a step-by-step guide to intrauterine insemination (IUI). Divided into 12 sections, the text begins with detail on counselling, diagnostic work up, and indications of IUI. The following chapters cover ultrasound monitoring of an ART cycle, stimulation protocol, triggering ovulation, and when and how to administer IUI. The book concludes with discussion on complications of IUI, factors affecting success, and sperm preparation. Authored by recognised experts in the field, the text is further enhanced by colour photographs, illustrations and flowcharts. Key points Step-by-step guide to intrauterine insemination (IUI) Covers the complete ART cycle, from initial counselling and work up, to monitoring and procedures, to success factors and complications Highly illustrated with photographs, diagrams and flowcharts Recognised, expert author team

The 3rd World Congress on Genetics, Geriatrics, and Neurodegenerative Disease Research (GeNeDis 2018), focuses on recent advances in genetics, geriatrics, and neurodegeneration, ranging from basic science to clinical and pharmaceutical developments. It also provides an international forum for the latest scientific discoveries, medical practices, and care initiatives. Advanced information technologies are discussed, including the basic research, implementation of medico-social policies, and the European and global issues in the funding of long-term care for elderly people.

The exploding field of epigenetics is challenging the dogma of traditional Mendelian inheritance. Epigenetics plays an important role in shaping who we are and contributes to our prospects of health and disease. While early epigenetic research focused on plant and animal models and in vitro experiments, population-based epidemiologic studies increasingly incorporate epigenetic components. The relevance of epigenetic marks, such as DNA methylation, genomic imprinting, and histone modification for disease causation has yet to be fully explored.This book covers the basic concepts of epigenetic epidemiology, discusses challenges in study design, analysis, and interpretation, epigenetic laboratory techniques, the influence of age and environmental factors on shaping the epigenome, the role of epigenetics in the developmental origins hypothesis, and provides the state of the art on the epigenetic epidemiology of various health conditions including childhood syndromes, cancer, infectious diseases, inflammation and rheumatoid arthritis, asthma, autism and other neurodevelopmental disorders, psychiatric disorders, diabetes, obesity and metabolic disorders, and atherosclerosis. With contributions from: Peter Jones, Jean-Pierre Issa, Gavin Kelsey, Robert Waterland, and many other experts in epigenetics!

The rapid progression of genetics and molecular biology has turned chromosomal engineering from science fiction to reality, with the successful production of transgenic animals with engineered chromosomes and chromosomes developed for pharmaceutical protein production which are now ready for the medical industry. Mammalian Chromosome Engineering: Methods and Protocols provides the reader with up-to date information on this rapidly evolving field and strives to take the reader into the exciting realm of chromosomal engineering from the basic principles to the practical applications of these new technologies. The five overview and ten protocol chapters cover the engineering of chromosomes with extrachromosomal vectors and transposon systems, the manipulation of naturally occurred minichromosomes, the generation and engineering of synthetic artificial chromosomes, and the induced de novo platform artificial chromosome system. Written in the highly successful Methods in Molecular Biology (TM) series format, protocols chapters contain brief 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 cutting-edge, Mammalian Chromosome Engineering: Methods and Protocols serves as a bench-side resource for current protocols and aims to help scientists to explore the many prospects for future research and vital applications.

Classical methods for microbial strain engineering, used to improve the production of bioproducts, have serious drawbacks and have been found to be unsuitable for complex strain development applications. In Strain Engineering: Methods and Protocols, powerful new genetic engineering-based strain engineering methods are presented for rational modification of a variety of model organisms. These methods are particularly powerful when utilized to manipulate microbes for which sequenced and annotated genomes are available. Collectively, these methods systematically introduce genome alterations in a precise manner, allowing the creation of novel strains carrying only desired genome alterations. In the first section, E. coli-based bacterial strain engineering strategies are reviewed, while the second section presents analogous microbial engineering strategies for eukaryotic cells using the yeast Saccharomyces cerevisiae as a model. The third section covers examples of the proliferative adaptations of these base technologies to strain engineer industrially important prokaryotic or eukaryotic microbial systems. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Strain Engineering: Methods and Protocols serves as an ideal guide to scientists in academia, pharmaceutical science, and biotechnology who perform microbial strain engineering.

Cardiovascular disease is the leading cause of morbidity and premature death of modern era medicine. It is estimated that approximately 81 million people in the United States (US) currently have one or more of the many forms of cardiovascular disease, resulting in 1 in every 2.8 deaths, or 900,000 deaths per year. 40% of all deaths in Europe are a result of cardiovascular disease in people under the age of 75. Aneurysms form a significant portion of these cardiovascular related deaths and are defined as a permanent and irreversible localised dilation of a blood vessel greater than 50% of its normal diameter. Although aneurysms can form in any blood vessel, the more lethal aneurysms develop in the cranial arteries, and in the thoracic aorta and abdominal aorta. Frequently aneurysms are undetected and if left untreated may eventually expand until rupture with very high levels of morbidity and mortality. The biomechanics and mechanobiology of aneursymal diseases are not fully understood and this monograph aims to provide new insights into aneurysm aetiology and behavior based on the most recent biomechanics research related to this important topic. The contributors to this volume bring together a unique blend of expertise in experimental, computational and tissue biomechanics relating to aneurysm behavior and enable the reader to gain a fresh understanding of key factors influencing aneurysm behavior and treatment. Biological risk factors such as tobacco smoking, sex, age, hypertension, family history and mechanobiological risk factors such as aneurysm geometry and shape as well as mechanical properties of the diseased tissues are considered in detail as are many of the diagnostic and treatment options.

This volume presents the most recent studies on mRNA polyadenylation in plants. Chapters are divided into three sections covering recent development of the use of bioinformatics tools in the field. numerous molecular, biochemical, and methods used to characterize polyadenylation sites on a genome-wide scale. 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 key tips on troubleshooting and avoiding known pitfalls. Some are specific for plant research, but most can be adopted for research in other organisms. Authoritative and practical, Polyadenylation in Plants: Methods and Protocols provides scientists with a wide range of methods to study mRNA 3'-end formation in plants.

Calcium ions represent Mother Nature's 'ion-of-choice' for regulating fundamental physiological functions, as they initiate a new life at the time of fertilization and guide subsequent developmental and physiological functions of the human body. Calcium channels, which act as gated pathways for the movement of calcium ions across the membranes, play a central part in the initiation of calcium signals, and defects in calcium channel function have been found to result in a plethora of human diseases, referred to as the calcium channelopathies. Pathologies of Calcium Channels brings together leading international experts to discuss our current understanding of human diseases associated with the various calcium channels, from their molecular basis to potential future therapeutic targeting of calcium channels.

JAK tyrosine kinases and STAT transcription factors constitute a signaling pathway, which is activated by cytokines. By activating gene transcription it regulates essential biological responses to environmental cues. The Jak-Stat pathway is involved in the regulation of cell development, differentiation, proliferation and apoptosis. Improper function may contribute to hematopoietic malignancies and cancer. This book provides comprehensive insights into the latest basic and clinical developments in the field. The first part reviews recent findings and new technologies pertaining to basics of Jak-Stat function. The second part describes the evolution of Jak-Stat signaling and the role of the pathway in invertebrate organisms. The third part focuses on Jak-Stat signaling in hematopoietic cells under both physiological and pathophysiological conditions. Finally, chapters in the fourth section describe the relationship of Jak-Stat signaling to various states of disease, particularly infection, leukemias and solid cancers. The book is intended for all scientists in molecular biology, biochemistry and cell biology dealing with biomedical issues.

The existence of 'cancer stem cells' (CSCs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has lead to an abundance of evidence supporting their existence. CSCs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately, leading to metastasis and patient demise. To help aid clinicians, pharmaceutical companies and academic labs investigating how to better kill these highly aggressive cells we have summarized the DNA repair mechanism(s) and their role in the maintenance and regulation of both normal and cancer stem cells. Our book represents a comprehensive investigation into the highly effective DNA repair mechanisms of CSCs and what we need to understand in order to develop more advanced therapies to eradicate them from patients. Currently, there are no other published works entirely on DNA repair and Cancer Stem Cells. In addition, our book provides a comprehensive overview of CSC isolation and characterization from a variety of solid tumor types.

Pancreatic ductal adenocarcinoma is the fifth leading cause of cancer death in the USA. Pancreatic cancer develops as a result of the accumulation of genetic and epigenetic alterations in cancer-causing genes such as oncogenes and tumor-suppressor genes. The second edition of Pancreatic Cancer: Methods and Protocols provides a broad range of protocols for molecular, cellular, pathological, and statistical analyses of sporadic and familial pancreatic cancer. It covers topics from in-vitro cell cultures to in-vivo mouse models, DNA to protein manipulation, and genetic and epigenetic analyses to treatment development. 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 key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, written by highly renowned investigators with expertise in pancreatic cancer, Pancreatic Cancer: Methods and Protocols, Second Edition is an invaluable source of proven protocols to those who are interested in joining the fight against pancreatic cancer.

This volume seeks to understand how organisms and gene functions are influenced by environmental cues while accounting for variation that takes place within and among environmental populations and communities. Microbial Environmental Genomics (MEG) guides readers through methods to analyse the diversity of different organism types (archaea, bacteria, fungi, protists and microfauna), interactions between fungi and trees, and methods to identify and characterize functions and functional diversity of both pro- and eukaryotes. Written for the Methods in Molecular Biology series, 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, Microbial Environmental Genomics (MEG) will serve as a primary research reference for researchers and research managers in environmental microbiology working in the expanding field of molecular ecology and environmental genomics.

This book sheds new light on the development and use of quantitative models to describe the process of skin permeation. It critically reviews the development of quantitative predictive models of skin absorption and discusses key recommendations for model development. Topics presented include an introduction to skin physiology; the underlying theories of skin absorption; the physical laboratory-based processes used to generate skin absorption data, which is in turn used to construct mathematical models describing the skin permeation process; algorithms of skin permeability including quantitative structure-activity (or permeability) relationships (QSARs or QSPRs); relationships between permeability and molecular properties; the development of formulation-focused approaches to models of skin permeability prediction; the use of artificial membranes, e.g. polydimethylsiloxane as alternatives to mammalian skin; and lastly, the use of novel Machine Learning methods in developing the next generation of predictive skin permeability models. The book will be of interest to all researchers in academia and industry working in pharmaceutical discovery and development, as well as readers from the field of occupational exposure and risk assessment, especially those whose work involves agrochemicals, bulk chemicals and cosmetics.

There are several types of damage that can be found in the male gamete. Genetic damage in spermatozoa can originate during spermatogenesis, or it can originate during transit in both male and female genital tracts. Damage can also be due to ageing, environmental or iatrogenic conditions, as well as to the protocols to cryopreserve and to select spermatozoa in assisted reproduction techniques. The purpose of this book is to provide a comprehensive resource for all possible DNA damages in sperm, the relation to fertility and infertility, and possible transgenerational heritable effects.

Aromatase Inhibitors (AIs) treat postmenopausal estrogen receptor positive tumours, which constitute the majority of breast cancer patients. This comprehensive volume brings together the current knowledge from different relevant areas, including molecular mechanisms and translational aspects of drug resistance in AIs. Topics covered include research, experimental , and clinical data specifically focused on AI resistance in breast cancer. The volume will include three sections. The first section covers general knowledge about aromatase inhibitors, including regulation of aromatase genes, and structure and function of aromatase protein. The second section provides the detailed mechanisms of resistance to AIs, while the third section explores prediction of resistance and potential strategies to overcome resistance. Breast cancer is the most common female cancer and AIs significantly improve treatments outcomes compatibly to previously used endocrine treatments. However 10-15% of post-operative patients develop a relapse during adjuvant treatment with AIs; about 25-50% of the patients do not respond to AIs in neo-adjuvant or metastatic setting, and the majority of metastatic patients who initially respond develop resistance within 3 years. There is an important need to understand these mechanisms of resistance in order to develop methods of preventing or overcoming the resistance to AIs, which will ensure a more successful outcome in treating breast cancer.

The ability of a single genome to give rise to hundreds of functionally distinct cell type programs is in itself remarkable. Pioneering studies over the past few decades have demonstrated that this plasticity is retained throughout development, a phenomenon of epigenetic programming and reprogramming that remains one of the most fascinating areas of modern biology, with major relevance to human health and disease. This book presents the basic biology involved, including key mechanistic insights into this rapidly growing field.

The book comprehensively reviews and provides detailed insight into the cellular and molecular signalling mechanisms involved in pathophysiology of various respiratory diseases, towards developing effective therapeutic strategies in the management and treatment of lung disease. It also covers promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing the disease features including novel strategies for targeting chronic lung diseases using advanced drug delivery systems. Importantly, the book examines the significance and relevance of the plant extracts and their constituents with therapeutic efficiencies against lung diseases. As such, the book offers a blend of translational, biological, chemical, and drug delivery aspects relevant to respiratory diseases, thus, offering a valuable resource for pulmonologists and translational researchers working in the field of pulmonary biology and respiratory medicine.

Reproductive medicine is a growing field with new technology emerging faster than we can assess consumer's perceptions of -the number of cancer survivors are growing and there is a great need to attend to their quality of life-this book addresses the needs of males and females, identifies effective communication strategies and proactive measures for health care professionals and researchers to use as well as identifying gaps in the literature where more research is needed.