Oligomerization of the Rev protein of human immuno-deficiency virus type 1 on its cognate response element is essential for export of the late viral mRNAs from the nucleus. Two regions of the protein, flanking the RNA binding site, have been defined as oligomerization sites after mutants (M4 and M7) had been reported to bind specifically to the response element but not to oligomerize in vivo or in vitro. These mutants are often used as paradigms for studies of Rev multimerization. We have re-examined the in vitro binding of these mutants to model Rev response elements, using improved gel mobility assays. We find that both mutants will form oligomers on the Rev response element, but have somewhat lower affinities for RNA than the wild-type protein. M7 has lower specific affinity, but shows little deficiency in oligomerization once binding starts. In contrast, M4 is multimerization deficient, as previously reported. Therefore, whilethe sites are correctly defined, it is inappropriate to employ the original M7 deletion mutant to study Rev oligomerization.
The aim of this paper is to provide an overview of the current scientific and economic thinking on the use of genetic technologies for cystic fibrosis (CF) screening. The paper takes a public health genetics viewpoint and gives an overview of the genetics behind CF, then describes current practices in screening for the disease. We then discuss the current literature on the economic evaluations of screening for CF. As the "wet" science improves, there are direct implications for health service. Therefore, it is important to keep examining both clinical practice and economics behind the technologies.
Genetics, Health Care and Public Policy is an introduction to the new discipline of public health genetics. It brings together the insights of genetic and molecular science as a means of protecting and improving the health of the population. Its scope is wide and requires an understanding of genetics, epidemiology, public health and the principles of ethics, law and the social sciences. This book sets out the basic principles of public health genetics for a wide audience from those providing health care to those involved in establishing policy. The emphasis throughout the text is on providing an accessible introduction to the field. The content moves from the basic concepts, including definitions and history, through chapters on genetics, genetic technology, epidemiology, genetics in medicine, genetics in health services, ethical, legal and social implications, to the implications for health policy. It provides one-stop, introductory coverage of this rapidly developing and multidisciplinary field.
We were delighted to read the recent review by Khoury et al. 1 describing the Genomic Applications in Practice and Prevention Network. Translation of genomic medicine is an essential goal for the medical and public health communities, and we welcome GAPPNet as a laudable initiative to accelerate the effective transfer of emerging genomic knowledge and applications into improved clinical care. We agree with the authors' assertion that a coordinated system for translation can have a substantial impact on current barriers to progress in the translational process. However, we suggest that their model, although an excellent one, does not adequately address two key elements additionally required for optimal translation: recognition of the limitations of translational research and the need for explicit processes of policy and service development.Recent years have heralded a growing commitment to translational research on both sides of the Atlantic, 2 typically separated into two distinct categories: the translation of scientific understanding into a product or intervention and the translation of these new products into practice for patient benefit. 3 It was perceived that greater attention to these two activities, referred to respectively as "from bench to bedside" and "research into practice," or as "T1" and "T2" research, could overcome delays in the translational process. 4 This became the focus of a new "roadmap" by the National Institutes of Health. 5,6 The Cooksey Report, 7 a strategy for the funding of UK health research, similarly identified first and second gaps in translation, proposing that translational research would serve to plug them. More recently, Khoury further dissected the translational process, suggesting that T2 research could be subdivided into three phases of translation in addition to T1 research: T2, the evaluation and development of evidence-based guidelines; T3, research to move evidence-based guidelines into health practice; and T4, research to evaluate the health outcomes of a genomic application in practice. 8 In practice, interest, activity, and funding are not evenly distributed along the translational pathway; US authors have shown how T1 research typically overshadows T2. 3 Similarly, UK figures also show that the bulk of research funding goes on basic research and Type 1 translation. 7 However, the paucity of funding for translational work is not the only obstacle to progress. Policy makers, academics, and research funders equate this need too tightly with the research paradigm and conflate translation with translational research. For example, the influential UK Genomic Medicine report is explicitly focused solely on the first of the two "gaps in translation" as discussed by Cooksey; it calls for the Office for the Strategic Co-ordination of Health Research to be charged with developing a strategic vision for translation, and the National Institute for Health Research with monitoring developments in genomic medicine and their implications for health services. 8 GAPPNet builds...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.