Specific mammalian genes functionally and dynamically associate together within the nucleus. Yet, how an array of many genes along the chromosome sequence can be spatially organized and folded together is unknown. We investigated the 3D structure of a well-annotated, highly conserved 4.3-Mb region on mouse chromosome 14 that contains four clusters of genes separated by gene “deserts.” In nuclei, this region forms multiple, nonrandom “higher order” structures. These structures are based on the gene distribution pattern in primary sequence and are marked by preferential associations among multiple gene clusters. Associating gene clusters represent expressed chromatin, but their aggregation is not simply dependent on ongoing transcription. In chromosomes with aggregated gene clusters, gene deserts preferentially align with the nuclear periphery, providing evidence for chromosomal region architecture by specific associations with functional nuclear domains. Together, these data suggest dynamic, probabilistic 3D folding states for a contiguous megabase-scale chromosomal region, supporting the diverse activities of multiple genes and their conserved primary sequence organization.
Background and Purpose-The modified Rankin Scale (mRS) is the recommended functional outcome assessment in stroke trials. Utility of mRS may be limited by interobserver variability. Prestroke function, described using mRS, is often used as trial entry criterion. We assessed the reliability and validity of prestroke mRS in acute stroke. Methods-We present two complementary analyses of the properties of prestroke mRS: (1) Paired interviewers (trained in mRS) performed independently a blinded assessment of mRS and prestroke mRS. Interobserver variability was described using percentage agreement and weighted (kw) κ statistics with 95% confidence interval (95% CI). Validity was assessed by comparing prestroke mRS with other markers of function (comorbidity; medication count; need for carers). (2) We further assessed validity using a larger retrospective dataset. We compared prestroke mRS with Charlson comorbidity index (CCI) and the Rockwood frailty index. Rank correlation coefficient or Fisher exact test were used as appropriate.
Results-Paired
The Natural History Museum, London (NHM), generates and holds some of the largest global data sets relating to the biological and geological diversity of the natural world. A majority of these data were, until 2015, not widely accessible, and, even when published, were typically hard to find, poorly documented and in formats that impede discovery and integration. To better serve the bespoke needs of user communities outside and within the NHM, a dedicated data portal was developed to surface these data sets and provide a sustainable platform to encourage their citation and reuse. This paper describes the technical development of the data portal, from its inception to beta launch in December 2015, its first 2 years of operation, and future plans for the project. It outlines the development principles adopted for this prototypical project, which subsequently informed new digital project management methodologies at the NHM. The process of developing the data portal acted as a driver to implement policies necessary to encourage a culture of data sharing at the NHM.
A study of 100 papers from five journals that make use of bioacoustic recordings shows that only a minority (21%) deposit any of the recordings in a repository, supplementary materials section or a personal website. This lack of deposition hinders re-use of the raw data by other researchers, prevents the reproduction of a project's analyses and confirmation of its findings and impedes progress within the broader bioacoustics community. We make some recommendations for researchers interested in depositing their data.
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