The RNA Ontology (RNAO): An ontology for integrating RNA sequence and structure data

Biomedical Ontologies are intended to integrate diverse biomedical data to enable intelligent data-mining and facilitate translation of basic research into useful clinical knowledge. We present the first version of RNAO, an ontology for integrating RNA 3D structural, biochemical and sequence data. While each 3D data file depicts the structure of a specific molecule, such data have broader significance as representatives of classes of homologous molecules, which, while differing in sequence, generally share core structural features of functional importance. Thus, 3D structure data gain value by being linked to homologous sequences in genomic data and databases of sequence alignments. Likewise genomic data can increase in value by annotation of shared structural features, especially when these can be linked to specific functions. The RNAO is being developed in line with the developing standards of the Open Biomedical Ontologies (OBO) Consortium

Spectrum of the Fokker-Planck operator representing diffusion in a random velocity field

We study spectral properties of the Fokker-Planck operator that represents particles moving via a combination of diffusion and advection in a time-independent random velocity field, presenting in detail work outlined elsewhere [J. T. Chalker and Z. J. Wang, Phys. Rev. Lett. {\bf 79}, 1797 (1997)]. We calculate analytically the ensemble-averaged one-particle Green function and the eigenvalue density for this Fokker-Planck operator, using a diagrammatic expansion developed for resolvents of non-Hermitian random operators, together with a mean-field approximation (the self-consistent Born approximation) which is well-controlled in the weak-disorder regime for dimension d>2. The eigenvalue density in the complex plane is non-zero within a wedge that encloses the negative real axis. Particle motion is diffusive at long times, but for short times we find a novel time-dependence of the mean-square displacement, $\sim t^{2/d}$ in dimension d>2, associated with the imaginary parts of eigenvalues.Comment: 8 pages, submitted to Phys Rev

Opening the Woods: Towards a Quantification of Neolithic Clearance Around the Somerset Levels and Moors

Environmental reconstructions from pollen records collected within archaeological landscapes have traditionally taken a broadly narrative approach, with few attempts made at hypothesis testing or formal assessment of uncertainty. This disjuncture between the traditional interpretive approach to palynological data and the requirement for detailed, locally specific reconstructions of the landscapes in which people lived has arguably hindered closer integration of palaeoecological and archaeological datasets in recent decades. Here we implement a fundamentally different method for reconstructing past land cover from pollen records to the landscapes of and around the Somerset Levels and Moors — the Multiple Scenario Approach (MSA) — to reconstruct land cover for a series of 200-year timeslices covering the period 4200–2000 cal BC. Modelling of both archaeological and sediment chronologies enables integration of reconstructed changes in land cover with archaeological evidence of contemporary Neolithic human activity. The MSA reconstructions are presented as a series of land cover maps and as graphs of quantitative measures of woodland clearance tracked over time. Our reconstructions provide a more nuanced understanding of the scale and timing of Neolithic clearance than has previously been available from narrative based interpretations of pollen data. While the archaeological record tends to promote a view of long-term continuity in terms of the persistent building of wooden structures in the wetlands, our new interpretation of the palynological data contributes a more dynamic and varying narrative. Our case study demonstrates the potential for further integration of archaeological and palynological datasets, enabling us to get closer to the landscapes in which people lived

Recent advances in the structural molecular biology of Ets transcription factors: interactions, interfaces and inhibition

The Ets family of eukaryotic transcription factors is based around the conserved Ets DNA-binding domain. Although their DNA-binding selectivity is biochemically and structurally well characterized, structures of homodimeric and ternary complexes point to Ets domains functioning as versatile protein-interaction modules. In the present paper, we review the progress made over the last decade to elucidate the structural mechanisms involved in modulation of DNA binding and protein partner selection during dimerization. We see that Ets domains, although conserved around a core architecture, have evolved to utilize a variety of interaction surfaces and binding mechanisms, reflecting Ets domains as dynamic interfaces for both DNA and protein interaction. Furthermore, we discuss recent advances in drug development for inhibition of Ets factors, and the roles structural biology can play in their future

Home interventions and light therapy for treatment of vitiligo (HI-Light Vitiligo Trial): study protocol for a randomized controlled trial

Vitiligo is a condition resulting in white patches on the skin. People with vitiligo can suffer from low self-esteem, psychological disturbance and diminished quality of life. Vitiligo is often poorly managed, partly due to lack of high quality evidence to inform clinical care. We describe here a large, independent, randomised controlled trial (RCT) assessing the comparative effectiveness of potent topical corticosteroid, home-based hand-held narrowband ultraviolet B-light (NB-UVB) or combination of the two, for the management of vitiligo. Methods and Analysis The HI-Light Vitiligo Trial is a multi-centre, three-arm, parallel group, pragmatic, placebo-controlled RCT. 516 adults and children with actively spreading, but limited, vitiligo are randomised (1:1:1) to one of three groups: mometasone furoate 0.1% ointment plus dummy NB-UVB light, vehicle ointment plus NB-UVB light, or mometasone furoate 0.1% ointment plus NB-UVB light. Treatment of up to three patches of vitiligo is continued for up to 9 months with clinic visits at baseline, 3, 6 and 9 months and four post treatment questionnaires. The HI-Light Vitiligo Trial assesses outcomes included in the vitiligo core outcome set and places emphasis on participants’ views of treatment success. The primary outcome is proportion of participants achieving treatment success (patient-rated Vitiligo Noticeability Scale) for a target patch of vitiligo at 9 months with further independent blinded assessment using digital images of the target lesion before and after treatment. Secondary outcomes include time to onset of treatment response, treatment success by body region, percentage repigmentation, quality of life, time-burden of treatment, maintenance of response, safety, and within-trial cost effectiveness. Ethics and Dissemination Approvals were granted by East Midlands–Derby Research Ethics Committee (14/EM/1173) and the MHRA (EudraCT 2014-003473-42). The trial was registered 8th January 2015 ISRCTN (17160087). Results will be published in full as open access in the NIHR Journal library and elsewhere

Dovetailing biology and chemistry: integrating the Gene Ontology with the ChEBI chemical ontology.

BACKGROUND: The Gene Ontology (GO) facilitates the description of the action of gene products in a biological context. Many GO terms refer to chemical entities that participate in biological processes. To facilitate accurate and consistent systems-wide biological representation, it is necessary to integrate the chemical view of these entities with the biological view of GO functions and processes. We describe a collaborative effort between the GO and the Chemical Entities of Biological Interest (ChEBI) ontology developers to ensure that the representation of chemicals in the GO is both internally consistent and in alignment with the chemical expertise captured in ChEBI. RESULTS: We have examined and integrated the ChEBI structural hierarchy into the GO resource through computationally-assisted manual curation of both GO and ChEBI. Our work has resulted in the creation of computable definitions of GO terms that contain fully defined semantic relationships to corresponding chemical terms in ChEBI. CONCLUSIONS: The set of logical definitions using both the GO and ChEBI has already been used to automate aspects of GO development and has the potential to allow the integration of data across the domains of biology and chemistry. These logical definitions are available as an extended version of the ontology from http://purl.obolibrary.org/obo/go/extensions/go-plus.owl

Silk garments plus standard care compared with standard care for treating eczema in children: a randomised controlled, observer blind, pragmatic trial (CLOTHES Trial)

Background The role of clothing in the management of eczema (syn. atopic dermatitis, atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments (in addition to standard care) for the management of eczema in children with moderate to severe disease. Methods and findings This was a parallel group randomised controlled, observer-blind trial. Children aged 1 to 15 years with moderate to severe eczema were recruited from secondary care and the community in five UK centres. Participants were allocated using on-line randomisation (1:1) to standard care, or standard care plus silk garments; stratified by age and recruiting centre. Silk garments were worn for 6 months. Primary outcome (eczema severity) was assessed at baseline, 2, 4 and 6 months, by nurses blinded to treatment allocation using the Eczema Area and Severity Index (EASI), which was log-transformed for analysis (intention-to-treat analysis). Safety outcome: number of skin infections. Three hundred children were randomised (26th Nov 2013 to 5th May 2015): 42% girls, 79% white, mean age 5 years. Primary analysis included 282/300 (94%) children (n = 141 in each group). The garments were worn more often at night than in the day (median of 81% of nights (25th to 75th centile 57% to 96%) and 34% of days (25th to 75th centile 10% to 76%)). Geometric mean EASI scores at baseline, 2, 4 and 6 months were 9·2, 6·4, 5·8, 5·4 for silk clothing and 8·4, 6·6, 6·0, 5·4 for standard care. There was no evidence of any difference between the groups in EASI score averaged over all follow up visits adjusted for baseline EASI score, age and centre (adjusted ratio of geometric means: 0·95, 95% CI 0·85 to 1·07). This confidence interval is equivalent to a difference of -1·5 to 0·5 in the original EASI scale units which is not clinically important. Skin infections occurred in 36/142 (25%) and 39/141 (28%) for silk clothing and standard care respectively. Even if the small observed treatment effect was genuine, the incremental cost per QALY was £56,881 in the base case analysis from an NHS perspective, suggesting that silk garments are unlikely to be cost-effective within currently accepted thresholds. Main limitations: whilst minimising detection bias, use of an objective primary outcome may have underestimated treatment effects. Conclusions Silk clothing is unlikely to provide additional benefit over standard care in children with moderate to severe eczema