Using sound to understand protein sequence data:New sonification algorithms for protein sequences and multiple sequence alignments

Funding: This work was supported by the UKRI Biotechnology and Biological Sciences Research Council (BBSRC) grant number BB/M010996/1.Background The use of sound to represent sequence data – sonification – has great potential as an alternative and complement to visual representation, exploiting features of human psychoacoustic intuitions to convey nuance more effectively. We have created five parameter-mapping sonification algorithms that aim to improve knowledge discovery from protein sequences and small protein multiple sequence alignments. For two of these algorithms, we investigated their effectiveness at conveying information. To do this we focussed on subjective assessments of user experience. This entailed a focus group session and survey research by questionnaire of individuals engaged in bioinformatics research. Results For single protein sequences, the success of our sonifications for conveying features was supported by both the survey and focus group findings. For protein multiple sequence alignments, there was limited evidence that the sonifications successfully conveyed information. Additional work is required to identify effective algorithms to render multiple sequence alignment sonification useful to researchers. Feedback from both our survey and focus groups suggests future directions for sonification of multiple alignments: animated visualisation indicating the column in the multiple alignment as the sonification progresses, user control of sequence navigation, and customisation of the sound parameters. Conclusions Sonification approaches undertaken in this work have shown some success in conveying information from protein sequence data. Feedback points out future directions to build on the sonification approaches outlined in this paper. The effectiveness assessment process implemented in this work proved useful, giving detailed feedback and key approaches for improvement based on end-user input. The uptake of similar user experience focussed effectiveness assessments could also help with other areas of bioinformatics, for example in visualisation.Publisher PDFPeer reviewe

EXPERIMENTAL ECOLOGICAL GENETICS IN PLANTAGO. III. GENETIC VARIATION AND DEMOGRAPHY IN RELATION TO SURVIVAL OF PLANTAGO CORDATA, A RARE SPECIES

ABSTRACT Plantago cordata, the heart-leaved plantain, is a species of woodland streams that was Jbrmerly widespread in the easter

Surface grafting of electrospun fibers using ATRP and RAFT for the control of biointerfacial interactions

BACKGROUND The ability to present signalling molecules within a low fouling 3D environment that mimics the extracellular matrix is an important goal for a range of biomedical applications, both in vitro and in vivo. Cell responses can be triggered by non-specific protein interactions occurring on the surface of a biomaterial, which is an undesirable process when studying specific receptor-ligand interactions. It is therefore useful to present specific ligands of interest to cell surface receptors in a 3D environment that minimizes non-specific interactions with biomolecules, such as proteins. METHOD In this study, surface-initiated atom transfer radical polymerization (SI-ATRP) of poly(ethylene glycol)-based monomers was carried out from the surface of electrospun fibers composed of a styrene/vinylbenzyl chloride copolymer. Surface initiated radical addition-fragmentation chain transfer (SI-RAFT) polymerisation was also carried out to generate bottle brush copolymer coatings consisting of poly(acrylic acid) and poly(acrylamide). These were grown from surface trithiocarbonate groups generated from the chloromethyl styrene moieties existing in the original synthesised polymer. XPS was used to characterise the surface composition of the fibers after grafting and after coupling with fluorine functional XPS labels. RESULTS Bottle brush type coatings were able to be produced by ATRP which consisted of poly(ethylene glycol) methacrylate and a terminal alkyne-functionalised monomer. The ATRP coatings showed reduced non-specific protein adsorption, as a result of effective PEG incorporation and pendant alkynes groups existing as part of the brushes allowed for further conjugation of via azide-alkyne Huisgen 1,3-dipolar cycloaddition. In the case of RAFT, carboxylic acid moieties were effectively coupled to an amine label via amide bond formation. In each case XPS analysis demonstrated that covalent immobilisation had effectively taken place. CONCLUSION Overall, the studies presented an effective platform for the preparation of 3D scaffolds which contain effective conjugation sites for attachment of specific bioactive signals of interest, as well as actively reducing non-specific protein interactions.This research was supported by the Cooperative Research Centre for Polymers (CRCP)

Route of administration affects corticosteroid sensitivity of a combined ovalbumin and lipopolysaccharide model of asthma exacerbation in guinea-pigs

Lipopolysaccharide (LPS) contributes to asthma exacerbations and development of inhaled corticosteroid insensitivity. Complete resistance to systemic corticosteroids is rare and most patients lie on a continuum of steroid responsiveness. The objective of this study was to examine the sensitivity of combined ovalbumin- (Ova) and LPS-induced functional and inflammatory responses to inhaled and systemic corticosteroid in conscious guinea-pigs, to test the hypothesis that the route of administration affects its sensitivity. Guinea-pigs were sensitised to Ova and challenged with inhaled Ova alone or combined with LPS. Airways function was determined by measuring specific airways conductance via whole-body plethysmography. Airways hyperresponsiveness to histamine was determined pre- and 24h post-Ova challenge. Airways inflammation and underlying mechanisms were determined from bronchoalveolar lavage cell counts and lung tissue cytokines. Vehicle or dexamethasone was administered by once-daily intraperitoneal injection (5, 10 or 20 mg/kg) or twice-daily inhalation (4 or 20 mg/ml) for 6 days before Ova challenge or Ova with LPS. LPS exacerbated Ova-induced responses, elongating early asthmatic responses (EAR), prolonging bronchoconstriction by histamine and further elevating airways inflammation. Intraperitoneal dexamethasone (20 mg/kg) significantly reduced the elongated EAR and airways inflammation but not the increased bronchoconstriction to histamine. In contrast, inhaled dexamethasone (20 mg/ml), which inhibited responses to Ova alone, did not significantly reduce functional and inflammatory responses to combined Ova and LPS. Combined Ova and LPS-induced functional and inflammatory responses are insensitive to inhaled but only partially sensitive to systemic dexamethasone. These results suggest that the route of corticosteroid administration may be important in determining the sensitivity of asthmatic responses to these agents

Bringing bioinformatics to schools with the 4273pi project

The work was supported by the Science and Technology Facilities Council (STFC) under Grants STFC ST/R000328/1 (including salary to S.A.B., D.B., H.P., T.R.M. and non-salary costs) and STFC ST/T000872/1 (including salary to S.A.B., D.B., K.C., T.R.M. and non-salary costs), the Darwin Trust of Edinburgh (https://darwintrust.bio.ed.ac.uk; including salary to S.A.B. and H.P. and non-salary costs), the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund under Wellcome Trust Grant number 204804/Z/16/Z (salary to H.P.), a Public Engagement with Genetics Tier 2 Grant from the Genetics Society (https://genetics.org.uk; non-salary costs), the Natural Environment Research Council (NERC) under Grant NE/P000592/1 (including salary to N.C. and M.G.R. and non-salary costs), the Biotechnology and Biological Sciences Research Council (BBSRC) under Grant BB/S018506/1 (including salary to F.A. and non-salary costs), the School of Biological Sciences at the University of Edinburgh (https://www.ed.ac.uk/biology; including salary to S.A.B. and H.P. and non-salary costs) and its Institute of Evolutionary Biology (https://www.ed.ac.uk/biology/evolutionary-biology; non-salary costs), the Access for Rural Communities project (ARC) at University of St Andrews (https://www.st-andrews.ac.uk/study/access/projects/arc; non-salary costs) and the Engineering and Physical Sciences Research Council (EPSRC) under Grant EP/V52038X/1 (including salary to S.A.B. and non-salary costs). E.W.J.W. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society [208779/Z/17/Z] (including salary to E.W.J.W.).Over the last few decades, the nature of life sciences research has changed enormously, generating a need for a workforce with a variety of computational skills such as those required to store, manage, and analyse the large biological datasets produced by next-generation sequencing. Those with such expertise are increasingly in demand for employment in both research and industry. Despite this, bioinformatics education has failed to keep pace with advances in research. At secondary school level, computing is often taught in isolation from other sciences, and its importance in biological research is not fully realised, leaving pupils unprepared for the computational component of Higher Education and, subsequently, research in the life sciences. The 4273pi Bioinformatics at School project (https://4273pi.org) aims to address this issue by designing and delivering curriculum-linked, hands-on bioinformatics workshops for secondary school biology pupils, with an emphasis on equitable access. So far, we have reached over 180 schools across Scotland through visits or teacher events, and our open education resources are used internationally. Here, we describe our project, our aims and motivations, and the practical lessons we have learned from implementing a successful bioinformatics education project over the last 5 years.Publisher PDFPeer reviewe

Plant biodiversity drivers in Brazilian campos rupestres : insights from phylogenetic structure

MMwas funded by the São Paulo Research Foundation (FAPESP 2013/15280–9) at the initial stages of this work.Old, climate-buffered infertile landscapes (Ocbils) have attracted increasing levels of interest in recent years because of their exceptionally diverse plant communities. Brazil’s campos rupestres (rupestrian grasslands) are home to almost 15% of Brazil’s native flora in less than 0.8% of Brazil’s territory: an ideal study system for exploring variation in floristic diversity and phylogenetic structure in sites differing in geology and phytophysiognomy. We found significant differences in floristic diversity and phylogenetic structure across a range of study sites encompassing open vegetation and forest on quartzite and on ironstone substrates, commonly termed canga. Substrate was key in structuring floristic diversity with physiognomy having a secondary effect. In contrast physiognomy was more important than substrate in structuring phylogenetic diversity, with neither substrate nor its interaction with physiognomy accounting for significant variation in phylogenetic structure. Phylogenetic clustering was significant in open vegetation on both canga and quartzite, reflecting the potential role of environmental filtering in these exposed montane communities adapted to multiple environmental stressors. In forest communities, phylogenetic clustering was significant only at relatively deep nodes of the phylogeny in forest on quartzite while no significant phylogenetic clustering was detected across forest on canga, which may be attributable to proximity to the megadiverse Atlantic forest biome and/or comparatively benign environmental conditions in forest on canga with relatively deep, nutrient-rich soils and access to edaphic water reliable in comparison to those for open vegetation on canga and open or forest communities on quartzite. Clades representing relatively old lineages are significantly over-represented in campos rupestres on quartzite, consistent with the Gondwanan Heritage Hypothesis of Ocbil theory. In contrast, forested sites on canga are recognized as Yodfels. To be effective, conservation measures must take account of the distinct communities which are encompassed within the broad term campos rupestres, and the differing vulnerabilities of Ocbils and Yodfels.Publisher PDFPeer reviewe

Best practices for virtual participation in meetings : experiences from synthesis centers

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Green Plants in the Red: A Baseline Global Assessment for the IUCN Sampled Red List Index for Plants

Plants provide fundamental support systems for life on Earth and are the basis for all terrestrial ecosystems; a decline in plant diversity will be detrimental to all other groups of organisms including humans. Decline in plant diversity has been hard to quantify, due to the huge numbers of known and yet to be discovered species and the lack of an adequate baseline assessment of extinction risk against which to track changes. The biodiversity of many remote parts of the world remains poorly known, and the rate of new assessments of extinction risk for individual plant species approximates the rate at which new plant species are described. Thus the question ‘How threatened are plants?’ is still very difficult to answer accurately. While completing assessments for each species of plant remains a distant prospect, by assessing a randomly selected sample of species the Sampled Red List Index for Plants gives, for the first time, an accurate view of how threatened plants are across the world. It represents the first key phase of ongoing efforts to monitor the status of the world’s plants. More than 20% of plant species assessed are threatened with extinction, and the habitat with the most threatened species is overwhelmingly tropical rain forest, where the greatest threat to plants is anthropogenic habitat conversion, for arable and livestock agriculture, and harvesting of natural resources. Gymnosperms (e.g. conifers and cycads) are the most threatened group, while a third of plant species included in this study have yet to receive an assessment or are so poorly known that we cannot yet ascertain whether they are threatened or not. This study provides a baseline assessment from which trends in the status of plant biodiversity can be measured and periodically reassessed

On handling urban informality in southern Africa

In this article I reconsider the handling of urban informality by urban planning and management systems in southern Africa. I argue that authorities have a fetish about formality and that this is fuelled by an obsession with urban modernity. I stress that the desired city, largely inspired by Western notions of modernity, has not been and cannot be realized. Using illustrative cases of top–down interventions, I highlight and interrogate three strategies that authorities have deployed to handle informality in an effort to create or defend the modern city. I suggest that the fetish is built upon a desire for an urban modernity based on a concept of formal order that the authorities believe cannot coexist with the “disorder” and spatial “unruliness” of informality. I question the authorities' conviction that informality is an abomination that needs to be “converted”, dislocated or annihilated. I conclude that the very configuration of urban governance and socio-economic systems in the region, like the rest of sub-Saharan Africa, renders informality inevitable and its eradication impossible

Benefits of a ball and chain: simple environmental enrichments improve welfare and reproductive success in farmed American mink (Neovison vison)

Can simple enrichments enhance caged mink welfare? Pilot data from 756 sub-adults spanning three colour-types (strains) identified potentially practical enrichments, and suggested beneficial effects on temperament and fur-chewing. Our main experiment started with 2032 Black mink on three farms: from each of 508 families, one juvenile male-female pair was enriched (E) with two balls and a hanging plastic chain or length of hose, while a second pair was left as a non-enriched (NE) control. At 8 months, more than half the subjects were killed for pelts, and 302 new females were recruited (half enriched: ‘late E’). Several signs of improved welfare or productivity emerged. Access to enrichment increased play in juveniles. E mink were calmer (less aggressive in temperament tests; quieter when handled; less fearful, if male), and less likely to fur-chew, although other stereotypic behaviours were not reduced. On one farm, E females had lower cortisol (inferred from faecal metabolites). E males tended to copulate for longer. E females also weaned more offspring: about 10% more juveniles per E female, primarily caused by reduced rates of barrenness (‘late E’ females also giving birth to bigger litters on one farm), effects that our data cautiously suggest were partly mediated by reduced inactivity and changes in temperament. Pelt quality seemed unaffected, but E animals had cleaner cages. In a subsidiary side-study using 368 mink of a second colour-type (‘Demis’), similar temperament effects emerged, and while E did not reduce fur-chewing or improve reproductive success in this colour-type, E animals were judged to have better pelts. Overall, simple enrichments were thus beneficial. These findings should encourage welfare improvements on fur farms (which house 60-70 million mink p.a.) and in breeding centres where endangered mustelids (e.g. black-footed ferrets) often reproduce poorly. They should also stimulate future research into more effective practical enrichments