The Human Neuronal Nitric Oxide Synthase Gene Microform Rna Biology Guiding Expressional Regulation
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| Author | : Derek Colin Newton |
| Publisher | : National Library of Canada = Bibliothèque nationale du Canada |
| Total Pages | : 644 |
| Release | : 2004 |
| Genre | : |
| ISBN | : 9780612917705 |
Protein synthesis is the ultimate goal of gene expression and a key control point for regulation. In particular, it enables the cell to rapidly manipulate protein production without new mRNA synthesis, processing or export. The human neuronal nitric oxide synthase (nNOS) gene is an excellent model to study the regulated translation of a mRNA to protein. Numerous and distinct nNOS mRNAs are generated from a single gene locus as a result of alternate promoter usage and alternate splicing patterns. A comprehensive analysis of the structure of neuronal NOS (nNOS) mRNA species revealed NOS1 to be one of the most structurally diverse human genes described to date in terms of promoter usage. Unique exon 1 variants are utilized for transcript initiation in diverse tissues and this dependence on unique genomic regions to control transcription initiation in a cell-specific fashion burdens the transcripts with complex 5'-mRNA leader sequences. These highly structured nNOS mRNA 5'-untranslated regions (5'-UTRs) were demonstrated to have profound effects on translation in both in vitro assays and cells and to contain cis-RNA elements that modulate translational efficiency in response to changes in cellular phenotype. In addition to promoter diversity, the human nNOS gene contains an alternately spliced (AS) exon present within the 5' -UTR. Alternative splicing events that do not affect the open reading frame are distinctly uncommon in mammals; therefore we assessed its functional relevance. Transient and stable transfection methods revealed that this alternatively spliced exon acts as a potent translational repressor. Hence a unique splicing event within a 5'-UTR is demonstrated to introduce a translational control element. Importantly, this represented a newer model for the translational control in mammalian cells. Mutational analysis identified a putative stem-loop structure within this exon that acts as the functional cis-element. Subsequent RNA-EMSA analyses revealed that a specific cytoplasmic RNA-binding complex interacts with this motif. An affinity purification scheme was developed and the cytoskeletal proteins actin and alpha-actinin were identified as components of the ribonucleoprotein complex associated with this exon. This intriguing finding indicates that this exon acts as a subcellular localization signal for select nNOS mRNAs.
| Author | : Gregory Thomas Hartt |
| Publisher | : |
| Total Pages | : |
| Release | : 2003 |
| Genre | : Gene expression |
| ISBN | : |
Abstract: Nitric oxide is a gaseous, free radical molecule that functions in the nervous system as an atypical neurotransmitter, second messenger, vasodilator, and potent neurotoxin, depending on cell type and level of expression. Physiologically, nitric oxide is thought to mediate long-term potentiation, the cellular correlate of learning and memory formation, as well as synaptic plasticity and remodeling. Under pathologic conditions such as cerebral ischemia, NOS1 overproduces nitric oxide, which is a key mediator of excitotoxic cell death and neurodegeneration. Our laboratory discovered that multiple, individually functioning promoters (5'1 and 5'2) regulate human NOS1 gene expression. The present work describes the discovery and cloning of a novel human NOS1 promoter, 5'3, and the demonstration of its unique, developmentally regulated expression pattern in the central nervous system. Promoter-specific alternative splicing contributes to NOS1 mRNA diversity in both the 5' untranslated and coding regions of the gene. We generated several lines of transgenic mice that express reporter genes under the control of separate human NOS1 promoter complexes (PR(5'1+5'2) and PR(5'3+5'4)), and studied how these alternate promoters contribute to NOS1 expression in various physiologic and pathophysiologic states in vivo. To this end, transgene expression is documented throughout normal development, which demonstrates overlapping but distinct patterns of promoter use that contribute to the overall recapitulation of endogenous NOS1 gene expression. In a murine model of striatal neurotoxicity, systemic methamphetamine administration results in promoter-specific transcriptional activation in the transgenic mice. NOS1 enzymatic activity is stimulated in motor neuron cell bodies after peripheral transection of the facial nerve; however, the transgenic NOS1 promoter complexes are insufficient to recapitulate NOS1 activation in this model. These findings help clarify how multiple promoters and mRN A diversity contribute to the complex regulation of the human NOS1 gene, and further our general understanding of transcriptional regulation of gene expression via alternate promoters.
| Author | : Lorenzo Lamattina |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 291 |
| Release | : 2007-01-30 |
| Genre | : Science |
| ISBN | : 3540451315 |
This book presents recent advances in the study of nitric oxide (NO) biology, biochemistry, molecular biology, and physiology in plants. It provides an overview of current understanding of the NO actions involved in adaptive responses of plant fitness to environmental constraints. Coverage places special emphasis on NO-dependent signaling, molecular adjustments, and targets as key elements in plant growth, development, and stress physiology.
| Author | : Lutz Hein |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 692 |
| Release | : 2003-10-10 |
| Genre | : Medical |
| ISBN | : 9783540001096 |
Up-to-date information on animal models generated by transgenic or gene targeting techniques. Naturally, the focus is on the mouse system. Each chapter has been written by leading experts in the field and gives an overview on existing animal models. This is facilitated by tables, which list the most important genetically engineered animal models and their phenotypes. This book aims at illustrating the impact of transgenic animal models in the field of Experimental Pharmacology and Toxicology, which includes their role in the understanding of basic cellular mechanisms, the evaluation of potential drug targets or the testing for drug effects.
| Author | : Heinrich Klefenz |
| Publisher | : Wiley-VCH |
| Total Pages | : 328 |
| Release | : 2002-04-22 |
| Genre | : Medical |
| ISBN | : |
This volume focuses on pharmaceutical biotechnology as a key area of life sciences. The complete range of concepts, processes and technologies of biotechnology is applied in modern industrial pharmaceutical research, development and production. The results of genome sequencing and studies of biological-genetic function are combined with chemical, micro-electronic and microsystem technology to produce medical devices and diagnostic biochips. A multitude of biologically active molecules is expanded by additional novel structures created with newly arranged gene clusters and bio-catalytic chemical processes. New organisational structures in the co-operation of institutes, companies and networks enable faster knowledge and product development and immediate application of the results of research and process development. This book is the ideal source of information for scientists and engineers in research and development, for decision-makers in biotech, pharma and chemical corporations, as well as for research institutes, but also for founders of biotech companies and people working for venture capital corporations.
| Author | : David J. Lim |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 274 |
| Release | : 2013-11-11 |
| Genre | : Medical |
| ISBN | : 1461542235 |
Dr. Howard House, founder of the House Ear Institute and House Ear Clinic often uses the analogy of planting a seed when referring to establishing the House Ear Institute in 1946. Two grateful patients of Dr. House put forth the idea that his knowledge and innovative skills could be used to expand the understanding of hearing impairment and its treatment. Those two early patients provided the "seed money" to begin the Institute. Since that time, the growth has been phenomenal from a one-man laboratory to a multidisciplinary facility boasting over 175 scien tists, physicians, and support staff, all dedicated to the advancement of otologic research and education. Six years ago after a half-century of remarkable success with prosthetic and device research, the Institute began cultivating a new field of endeavor-cell and molecular biology. Don Nielsen, then the Institute's Executive Vice President for Research and Scientific Director, began exploring the potential for hair cell regen eration and presented his ideas to the Board of Trustees. For a period of six months, we did a lot of fact finding to assess what role the Institute might take in this excit ing new field.
| Author | : Mauro Giacca |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 318 |
| Release | : 2010-11-01 |
| Genre | : Medical |
| ISBN | : 8847016436 |
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.
| Author | : Richard D. Granstein |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 248 |
| Release | : 2009-02-08 |
| Genre | : Medical |
| ISBN | : 3540359893 |
Much anecdotal information has suggested an influence of psychology and the nervous system on immunity within the skin and the expression of inflammatory skin disorders. Recent years have seen an explosion of knowledge providing a scientific basis for important regulatory interactions between the nervous system, the endocrine system and the immune system within the skin. The results of recent investigations have important implications, not only for an understanding of cutaneous immunity, but also for the development of novel treatments for diseases involving abnormal inflammation or immune reactivity within the skin. This book provides a comprehensive and interdisciplinary review of the molecular biology, cell biology, biochemistry and clinical aspects of nervous system–immune system interactions within the skin. It includes contributions from leading world experts in these areas. The contents are relevant to both investigators and clinicians interested in the skin, its functions and its disorders.
| Author | : Gerhard M. Artmann |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 566 |
| Release | : 2010-10-29 |
| Genre | : Technology & Engineering |
| ISBN | : 3642118658 |
The potential of stem cells for healing and disease prevention in all fields of medicine is tremendous and has revolutionized the high-tech biomedical research. In this book, many of the most prominent researchers discuss the challenging topics of stem cell engineering, for example: Ethical issues of stem cell research; technological challenges, stem cell growth and differentiation, therapeutic applications, bioreactors and bioprocesses, high throughput and microfluidic screening platforms, stem cell identification and sorting, intercellular signaling and engineered niches, novel approaches for embryonic and adult stem cell growth and differentiation, stem cells and drug discovery, screening platforms. Stem Cell Engineering offers valuable background and reference for both the public and professionals including industrial staffers, faculty, researchers, engineers, students and scientific journalists.
| Author | : Biological Sciences Curriculum Study |
| Publisher | : |
| Total Pages | : 0 |
| Release | : 1987 |
| Genre | : Biology |
| ISBN | : |
