Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression

Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Recent work studying the molecular mechanisms of several key examples — including Xist, which orchestrates X chromosome inactivation — has provided new insights into how lncRNAs can control cellular functions by acting in the nucleus. Here we discuss emerging mechanistic insights into how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to target loci and shaping three-dimensional (3D) nuclear organization. We explore these principles to highlight biological challenges in gene regulation, in which lncRNAs are well-suited to perform roles that cannot be carried out by DNA elements or protein regulators alone, such as acting as spatial amplifiers of regulatory signals in the nucleus

Reporting of complex interventions in clinical trials : development of a taxonomy to classify and describe fall-prevention interventions

Background: Interventions for preventing falls in older people often involve several components, multidisciplinary teams, and implementation in a variety of settings. We have developed a classification system (taxonomy) to describe interventions used to prevent falls in older people, with the aim of improving the design and reporting of clinical trials of fall-prevention interventions, and synthesis of evidence from these trials. Methods: Thirty three international experts in falls prevention and health services research participated in a series of meetings to develop consensus. Robust techniques were used including literature reviews, expert presentations, and structured consensus workshops moderated by experienced facilitators. The taxonomy was refined using an international test panel of five health care practitioners. We assessed the chance corrected agreement of the final version by comparing taxonomy completion for 10 randomly selected published papers describing a variety of fall prevention interventions. Results: The taxonomy consists of four domains, summarized as the “Approach”, “Base”, “Components” and “Descriptors” of an intervention. Sub-domains include; where participants are identified; the theoretical approach of the intervention; clinical targeting criteria; details on assessments; descriptions of the nature and intensity of interventions. Chance corrected agreement of the final version of the taxonomy was good to excellent for all items. Further independent evaluation of the taxonomy is required. Conclusions: The taxonomy is a useful instrument for characterizing a broad range of interventions used in falls prevention. Investigators are encouraged to use the taxonomy to report their interventions