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 N-glycan breakdown by human gut Bacteroides

The major nutrients available to the human colonic microbiota are complex glycans derived from the diet. To degrade this highly variable mix of sugar structures, gut microbes have acquired a huge array of different carbohydrate-active enzymes (CAZymes), predominantly glycoside hydrolases, many of which have specificities that can be exploited for a range of different applications. Plant N-glycans are prevalent on proteins produced by plants and thus components of the diet, but the breakdown of these complex molecules by the gut microbiota has not been explored. Plant N-glycans are also well characterized allergens in pollen and some plant-based foods, and when plants are used in heterologous protein production for medical applications, the N-glycans present can pose a risk to therapeutic function and stability. Here we use a novel genome association approach for enzyme discovery to identify a breakdown pathway for plant complex N-glycans encoded by a gut Bacteroides species and biochemically characterize five CAZymes involved, including structures of the PNGase and GH92 α-mannosidase. These enzymes provide a toolbox for the modification of plant N-glycans for a range of potential applications. Furthermore, the keystone PNGase also has activity against insect-type N-glycans, which we discuss from the perspective of insects as a nutrient source

Surfactant protein D modulates HIV infection of both T-cells and dendritic cells

Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo

Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown

Epithelial cells that line the gut secrete complex glycoproteins that form a mucus layer to protect the gut wall from enteric pathogens. Here, the authors provide a comprehensive characterisation of endo-acting glycoside hydrolases expressed by mucin-degrading members of the microbiome that are able to cleave the O-glycan chains of a range of different animal and human mucins

Research Participants' Perspectives on Genotype-Driven Research Recruitment

Genotype-Driven Recruitment is a potentially powerful approach for studying human genetic variation but presents ethical challenges. We conducted in-depth interviews with research participants in six studies where such recruitment occurred. Nearly all responded favorably to the acceptability of recontact for research recruitment, and genotype-driven recruitment was viewed as a positive sign of scientific advancement. Reactions to questions about the disclosure of individual genetic research results varied. Common themes included explaining the purpose of recontact, informing decisions about further participation, reciprocity, “information is valuable,” and the possibility of benefit, as well as concerns about undue distress and misunderstanding. Our findings suggest contact about additional research may be least concerning if it involves a known element (e.g., trusted researchers). Also, for genotype-driven recruitment, it may be appropriate to set a lower bar for disclosure of individual results than the clinical utility threshold recommended more generally

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Enrichment measurement by passive γ-ray spectrometry of uranium dioxide fuel pellets using a europium-doped, strontium iodide scintillator

The performance of a europium-doped strontium iodide scintillator for uranium enrichment measurement of a variety of sintered uranium dioxide fuel pellets is described and compared to that of caesium iodide and sodium iodide. Enrichment has been determined via passive γ-ray spectrometry of the 186 keV line from uranium-235 using gross count, net count, and peak ratio analyses. The 38 mm Ø x 38 mm strontium iodide crystal demonstrates superior energy resolution (3.43 ± 0.03% at 662 keV) and competitive detection efficiency for its size in the energy range of interest for uranium enrichment analysis (<250 keV). It demonstrates better χ v 2 and coefficient of determination values than caesium iodide and sodium iodide when measuring uranium enrichment using the gross- and net-count from the 186 keV emission. It is shown to have the least measurement variance of the three scintillators studied in determining the uranium enrichment of pellets in a blind test, with a relative error comparative to sodium iodide and smaller than caesium iodide. This research heralds the potential of strontium iodide in passive γ-ray uranium enrichment applications

Contextualising the pervasive impact of macroeconomic austerity on prison health in England: A qualitative study among international policymakers

Background: Prisons offer the state the opportunity to gain access to a population that is at particularly high risk of ill-health. Despite the supportive legal and policy structures surrounding prison rehabilitation, the oppressive nature of the austerity policy in England threatens its advanced improvement.Methods: Using grounded theory methodology, this is the first interdisciplinary qualitative study to explore the impact of macroeconomic austerity on prison health in England from the perspective of 29 international prison policymakers.Results: The far-reaching impact of austerity in England has established a regressive political system that shapes the societal attitude towards social issues, which has exacerbated the existing poor health of the prisoners. Austerity has undermined the notion of social collectivism, imposed a culture of acceptance among prison bureaucrats and the wider community, and normalised the devastating impacts of prison instability. These developments are evidenced by the increasing levels of suicide, violence, radicalisation and prison gangs among prisoners, as well as the imposition of long working hours and the high levels of absenteeism among prison staff.Conclusions: This study underscores an important and yet unarticulated phenomenon that despite being the fifth largest economy in the world, England’s poorest, marginalised and excluded population continues to bear the brunt of austerity. Reducing the prison population, using international obligations as minimum standards to protect prisoners’ right to health and providing greater resources would create a more positive and inclusive system, in line with England’s international and domestic commitments to the humane treatment of all people