• An exploration of the impact of SARS-CoV-2 (COVID-19) restrictions on marginalised groups in the UK

      Eshareturi, Cyril; Wareham, C.; Rattray, Marcus; Haith-Cooper, Melanie; McCarthy, R. (2021-08)
      Background: To contain the spread of COVID-19 within the UK over the past year, there have been a series of local and national lockdowns. These restrictions are likely to have impacted upon the health and well-being of marginalised groups who rely on now closed social and community support services to stay healthy. An understanding of the experiences of marginalised people is important; therefore, this study aimed to explore the impact of the COVID-19 restrictions on the health and well-being of marginalised groups in the UK. Methods: In summer 2020, a rapid telephone survey was conducted by trained, trusted volunteers with 76 participants who were from marginalised groups. As part of this survey, 64 participants consented to describe their experience of lockdown. These case studies were thematically analysed to identify patterns of meaning. Results: Findings indicate that lockdown led to the deterioration of health of participants, impacted adversely on their socio-economic positions and affected access to food and essential supplies. In addition, government public health messaging was considered confusing and inadequate. Conclusions: This study highlights the need for pathways into services which support marginalised groups to remain accessible during periods of restrictions and essential supplies and food to be mapped and protected for marginalised individuals within our local communities.
    • Exploring a role for regulatory miRNAs in wound healing during ageing: involvement of miR-200c in wound repair

      Aunin, Eerik; Broadley, David; Ahmed, Mohammed I.; Mardaryev, Andrei N.; Botchkareva, Natalia V. (2017)
      Multiple factors and conditions can lead to impaired wound healing. Chronic non-healing wounds are a common problem among the elderly. To identify microRNAs negatively impacting the wound repair, global miRNA profiling of wounds collected from young and old mice was performed. A subset of miRNAs that exhibited an age-dependent expression pattern during wound closure was identified, including miR-31 and miR-200c. The expression of miR-200 family members was markedly downregulated upon wounding in both young and aged mice, with an exception of acute upregulation of miR-200c at the early phase of wound healing in aged skin. In unwounded aged skin (versus unwounded younger skin), the level of miR-200c was also found elevated in both human and mice. Overexpression of miR-200c in human ex vivo wounds delayed re-epithelialisation and inhibited cell proliferation in the wound epithelium. Modulation of miR-200c expression in both human and mouse keratinocytes in vitro revealed inhibitory effects of miR-200c on migration, but not proliferation. Accelerated wound closure in vitro induced by anti-miR-200c was associated with upregulation of genes controlling cell migration. Thus, our study identified miR-200c as a critical determinant that inhibits cell migration during skin repair after injury and may contribute to ageassociated alterations in wound repair.
    • Exploring and Exploiting Acceptor Preferences of the Human Polysialyltransferases as a Basis for an Inhibitor Screen

      Ehrit, J.; Keys, T.G.; Sutherland, Mark H.; Wolf, S.; Meier, C.; Falconer, Robert A.; Gerardy-Schahn, R. (2017)
      α2,8-Linked polysialic acid (polySia) is an oncofoetal antigen with high abundance during embryonic development. It reappears in malignant tumours of neuroendocrine origin. Two polysialyltransferases (polySTs) ST8SiaII and IV are responsible for polySia biosynthesis. During development, both enzymes are essential to control polySia expression. However, in tumours ST8SiaII is the prevalent enzyme. Consequently, ST8SiaII is an attractive target for novel cancer therapeutics. A major challenge is the high structural and functional conservation of ST8SiaII and -IV. An assay system that enables differential testing of ST8SiaII and -IV would be of high value to search for specific inhibitors. Here we exploited the different modes of acceptor recognition and elongation for this purpose. With DMB-DP3 and DMB-DP12 (fluorescently labelled sialic acid oligomers with a degree of polymerisation of 3 and 12, respectively) we identified stark differences between the two enzymes. The new acceptors enabled the simple comparative testing of the polyST initial transfer rate for a series of CMP-activated and N-substituted sialic acid derivatives. Of these derivatives, the non-transferable CMP-Neu5Cyclo was found to be a new, competitive ST8SiaII inhibitor.
    • Exploring digital teaching tools, including the use of social media, to support teaching; perspectives of M.Pharm. students

      Tomlinson, Justine; Azad, Imran; Saleem, Mohammed Adil; Medlinskiene, Kristina (2018)
      Background: The School of Pharmacy and Medical Sciences, University of Bradford, is keen to evaluate the potential benefits of digital tools to enhance the teaching and learning of all M.Pharm. students. Students are increasingly using digital technology for both educational and social purposes (Cheston et al., 2013). This project explored the views of pharmacy students about digital technology, including social media, for teaching in the M.Pharm. programme. Method: Convenience sampling was employed to recruit M.Pharm. students for focus groups. Each focus group, facilitated by student researchers with topic guide, was audio-recorded and analysed for themes. Ethics approval was obtained from the University. Results: Year 2 and 3 students from two focus groups (n1=8 (6 male), n2=10 (8 male)) identified three main digital teaching tools used in the current programme: Blackboard, response clickers, and iSTAN. Blackboard, a virtual learning environment, was seen as a hub for holding all required learning materials. However, its use depended on internet access and some felt they would benefit from offline use and improved compatibility with different devices. Audience response systems and a human patient stimulator were well received by students. However, participants strongly felt that they were underutilised. The main benefit of using social media for learning was instant feedback and the encouragement of informal discussions. Participants were not always comfortable posting within the current digital tools used in the programme (e.g. Blackboard) as they felt ‘monitored’. However, participants acknowledged that information obtained through social media might not be as reliable as information from digital tools moderated by academics. Interestingly, participants reported a lack of engagement with programme specific social media pages (e.g. Facebook page). They felt that the information provided was aimed at qualified pharmacists, rather than current students. Conclusion: Participants valued accessibility, flexibility and availability of instant feedback when using digital tools to support their learning. They felt positive about the digital tools used within the programme but emphasised the need of greater integration. References Cheston, C.C., Flickinger, T.E. & Chisom, M.S. (2013). Social media use in medical education: a systematic review. Academic Medicine, 88(6), 893-901
    • Exploring Late Bronze Age systems of bronzework production in Switzerland through Network Science

      Jennings, Benjamin R. (2016-05-27)
      Many hundreds of Bronze Age bronze artefacts are known from excavations in Switzerland, yet the interpretation of production networks from the object find locations remain problematic. It is proposed that the decorative elements used on items, such as ring-jewellery, can be used as elements to assist in the identification of artisanal traditions and ‘schools’, and also regional or community preference and selection of specific designs. Combining the analysis of over 1700 items of ring-jewellery from Switzerland with approaches from network science has facilitated the identification of regional clustering of design elements, comparable with cultural typologies in the area. It is also possible to identify potential instances of cultural differentiation through decoration within the broader regional cultural traditions. The study highlights important facets of bronzework production in the region of Switzerland, while also demonstrating future potential directions which could build upon the European wide dataset of prehistoric bronzework.
    • Exploring Microstructural Changes in Structural Analogues of Ibuprofen-Hosted In Situ Gelling System and Its Influence on Pharmaceutical Performance

      Patil, S.S.; Venugopal, E.; Bhat, S.; Mahadik, K.R.; Paradkar, Anant R. (2015-10)
      The present work explores inner structuration of in situ gelling system consisting of glyceryl monooleate (GMO) and oleic acid (OA). The system under study involves investigation of microstructural changes which are believed to govern the pharmaceutical performance of final formulation. The changes which are often termed mesophasic transformation were analysed by small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), rheology and plane polarised light (PPL) microscopy. The current work revealed transformation of blank system from W/O emulsion to reverse hexagonal structure upon addition of structural analogues of ibuprofen. Such transformations are believed to occur due to increased hydrophobic volume within system as probed by SAXS analysis. The findings of SAXS studies were well supported by DSC, rheology and PPL microscopy. The study established inverse relationship between log P value of structural analogues of ibuprofen and the degree of binding of water molecules to surfactant chains. Such relationship had pronounced effect on sol-gel transformation process. The prepared in situ gelling system showed sustained drug release which followed Higuchi model.
    • Exploring the community waste sector: Are sustainable development and social capital useful concepts for project-level research?

      Luckin, D.; Sharp, Liz (2005)
      The concept of sustainable development implies that social, economic and environmental objectives should be delivered together, and that they can be achieved through enhanced community participation. The concept of social capital indicates how these objectives interrelate, implying that community involvement enhances trust and reciprocity, thus promoting better governance and greater prosperity. This paper draws on a survey of Community Waste Projects to explore how these concepts can inform investigations of community projects. It argues that the concepts provide useful guides to research and debate, but highlights the resource requirements of empirically confirming the claims of the social capital perspective.
    • Exploring the Sequence Space for (tri-) Peptide Self-assembly to Design and Discover New Hydrogels

      Frederix, P.W.J.M.; Scott, G.G.; Abul-Haija, Y.M.; Kalafatovic, D.; Pappas, C.G.; Javid, Nadeem; Hunt, N.T.; Ulijn, R.V.; Tuttle, T. (2015-01-05)
      Peptides that self-assemble into nanostructures are of tremendous interest for biological, medical, photonic and nanotechnological applications. The enormous sequence space that is available from 20 amino acids probably harbours many interesting candidates, but it is currently not possible to predict supramolecular behaviour from sequence alone. Here, we demonstrate computational tools to screen for the aqueous self-assembly propensity in all of the 8,000 possible tripeptides and evaluate these by comparison with known examples. We applied filters to select for candidates that simultaneously optimize the apparently contradicting requirements of aggregation propensity and hydrophilicity, which resulted in a set of design rules for self-assembling sequences. A number of peptides were subsequently synthesized and characterized, including the first reported tripeptides that are able to form a hydrogel at neutral pH. These tools, which enable the peptide sequence space to be searched for supramolecular properties, enable minimalistic peptide nanotechnology to deliver on its promise.
    • Exploring the use of digital technology in the M.Pharm. programme to prepare students for their first day of practice

      Tomlinson, Justine; Yaqoob, Mohammed U.; Shabbir, Subhaan; Medlinskiene, Kristina (2018)
      Background: Technological developments have facilitated the storage of patient records, enabled electronic prescribing, dispensing and the administration of medicines (Goundrey-Smith, 2014). These innovations are increasingly being used, requiring pharmacists to further develop digital capability. The School of Pharmacy and Medical Sciences, University of Bradford, is keen to explore ways to better equip M.Pharm. graduates with the necessary skills to confidently practise in the modern digital environment. This project explored student and staff perspectives of current digital teaching tools in relation to preparedness for the first day of practice.
    • Exploring urbanisation in the southern French Iron Age through integrated geophysical and topographic prospection

      Armit, Ian; Gaffney, Christopher F.; Marty, F.; Thomas, N.; Friel, R.; Hayes, A. (2014)
    • Exploring urbanisation in the Southern French Iron Age through integrated geophysical and topographic prospection,

      Armit, Ian; Horsley, T.; Gaffney, Christopher F.; Marty, F.; Thomas, N.; Friel, R.; Haye, A. (2014)
    • Expression and localization of human endothelin-converting enzyme-1 isoforms in symptomatic atherosclerotic disease and saphenous vein.

      Jackson, C.D.; Barnes, K.; Homer-Vanniasinkam, Shervanthi; Turner, A.J. (2006)
      Endothelln-converting enzyme (ECE-1) is a critical enzyme in the production of the potent vasoconstrictor peptide endothelin (ET-1). It has previously been shown that the levels of both ET-1 and ECE-1 are raised in atherosclerosis, but the possible relevance of the isoforms of ECE-1 in these changes has not yet been investigated. The aim of this study was to examine the expression of the ECE-1a and ECE-1c isoforms in human atherosclerotic pathologies. Immunohistochemical analysis was carried out on sections from atherosclerotic and non-atherosclerotic vascular tissue using a combination of ECE-1 isoform-specific antibodies, anti-¿-actin antibodies to identify smooth muscle cells (SMC) and anti-CD68 antibodies to identify macrophages. ECE-1 isoform expression was also examined in cultured SMC and in macrophages isolated from human blood. Results indicated differences in isoform expression in atherosclerotic lesions, with distinct patterns of staining for ECE-1 a and ECE-1 c. ECE-1 c immunoreactivity was seen in macrophages, and also correlated with actin staining. ECE-1a was also localized to macrophages and SMC. Results of this study suggest that these local changes influence the expression patterns of the ECE-1 isoforms within individual cell types. Correlation of these isoform expression patterns with the stage of atherosclerosis could provide novel indicators of disease progression.
    • Expression of the MtsA lipoprotein of Streptococcus agalactiae A909 is regulated by manganese and iron

      Bray, B.A.; Sutcliffe, I.C.; Harrington, Dean J. (2009-01)
      Metal ion acquisition and homeostasis are essential for bacterial survival, growth and physiology. A family of metal ion, ABC-type import systems have been identified in Gram-positive bacteria, in which the solute-binding proteins are predicted to be membrane-anchored lipoproteins. The prediction that the MtsA protein of Streptococcus agalactiae A909 is a lipoprotein was confirmed. The expression of MtsA was co-ordinately regulated by the presence of both manganese and ferrous ions suggesting that MtsA may be involved in the uptake of both these ions. MtsA was shown to be expressed at levels of ferrous ions known to be present in amniotic fluid, a growth medium for S. agalactiae during neonatal infection.
    • The extent of crowding in peripheral vision does not scale with target size

      Tripathy, Srimant P.; Cavanagh, P. (2002)
      Identifying a target is more difficult when distracters are present within a zone of interaction around the target. We investigated whether the spatial extent of the zone of interaction scales with the size of the target. Our target was a letter T in one-of-four orientations. Our distracters were four squared-thetas in one-of-two orientations, presented one in each of the four cardinal directions, equidistant from the target. Target-distracter separation was varied and the proportion of correct responses at each separation was determined. From these the extent of interaction was estimated. This procedure was repeated for different target sizes spread over a 5-fold range. In each case, the contrast of the target was adjusted so that its visibility was constant across target sizes. The experiment was performed in the luminance domain (grey targets on grey background) and in the chromatic domain (green target on equiluminant grey background). In the luminance domain, target size had only a small effect on the extent of interaction; these interactions did not scale with target size. The extents of interaction for chromatic stimuli were similar to those for luminance stimuli. For a fixed target visibility, decreasing the duration of the stimulus resulted in an increase in the extent of interaction. The relevance of our findings is discussed with regard to a variety of proposed explanations for crowding. Our results are consistent with an attention-based explanation for crowding.
    • Extra-nuclear telomerase reverse transcriptase (TERT) regulates glucose transport in skeletal muscle cells

      Shaheen, F.; Grammatopoulos, D.K.; Muller, Jurgen; Zammit, V.A.; Lehnert, H. (2014-09)
      Telomerase reverse transcriptase (TERT) is a key component of the telomerase complex. By lengthening telomeres in DNA strands, TERT increases senescent cell lifespan. Mice that lack TERT age much faster and exhibit age-related conditions such as osteoporosis, diabetes and neurodegeneration. Accelerated telomere shortening in both human and animal models has been documented in conditions associated with insulin resistance, including T2DM. We investigated the role of TERT, in regulating cellular glucose utilisation by using the myoblastoma cell line C2C12, as well as primary mouse and human skeletal muscle cells. Inhibition of TERT expression or activity by using siRNA (100nM) or specific inhibitors (100nM) reduced basal 2-deoxyglucose uptake by ~50%, in all cell types, without altering insulin responsiveness. In contrast, TERT over-expression increased glucose uptake by 3.25-fold. In C2C12 cells TERT protein was mostly localised intracellularly and stimulation of cells with insulin induced translocation to the plasma membrane. Furthermore, co-immunoprecipitation experiments in C2C12 cells showed that TERT was constitutively associated with glucose transporters (GLUTs) 1, 4 and 12 via an insulin insensitive interaction that also did not require intact PI3-K and mTOR pathways. Collectively, these findings identified a novel extra-nuclear function of TERT that regulates an insulin-insensitive pathway involved in glucose uptake in human and mouse skeletal muscle cells.
    • Extraordinary Claims Require Extraordinary Evidence: Centrally Mediated Preservation of Binocular Visual Field in Glaucoma is Unlikely

      Denniss, Jonathan; Artes, Paul H. (2015-01)
      We have read with interest the recent article by Sponsel et al.1 There is much evidence that glaucomatous damage occurs at the optic nerve head,2 and therefore we were surprised by the authors' conjecture that there may be a central mechanism that preserves the binocular visual field in advanced glaucoma.
    • Extrusion - back to the future: using an established technique to reform automated chemical synthesis

      Crawford, Deborah E. (2017-01)
      Herein, the benefits which extrusion can provide for the automated continuous synthesis of organic compounds are highlighted. Extrusion is a well-established technique that has a vital role in the manufacturing processes of polymers, pharmaceuticals and food products. Furthermore, this technique has recently been applied to the solvent-free continuous synthesis of co-crystals and coordination compounds including metal-organic frameworks (MOFs). To date, a vast amount of research has already been conducted into reactive extrusion (REX), particularly in the polymer industry, which in many cases has involved organic transformations, however, it has not received significant recognition for this. This review highlights these transformations and discusses how this previous research can be applied to the future of organic compound manufacture.
    • Extrusion-Spheronization of Talc using Microcrystalline Cellulose as a Pellet Aid: Part I

      Jadhav, N.; Gade, M.; Salunkhe, N.; Paradkar, Anant R. (2014-12)
      The aims of the present work were to pelletize talc by extrusion-spheronization technique using microcrystalline cellulose (MCC) as a pelletization aid and to study its performance as a neutral substrate for coating. A 32 factorial design was used to study the effect of independent variables (X1, amount of talc, and X2, MCC) on pellet properties.