Recent Submissions

  • Effect of transforming growth factor-β2 on biological regulation of multilayer primary chondrocyte culture

    Khaghani, Seyed A.; Akbarova, G.; Soon, C.F.; Dilbazi, G. (2018)
    Cytokines are extremely potent biomolecules that regulate cellular functions and play multiple roles in initiation and inhibition of disease. These highly specialised macromolecules are actively involved in control of cellular proliferation, apoptosis, cell migration and adhesion. This work, investigates the effect of transforming growth factor-beta2 (TGF-β2) on the biological regulation of chondrocyte and the repair of a created model wound on a multilayer culture system. Also the effect of this cytokine on cell length, proliferation, and cell adhesion has been investigated. Chondrocytes isolated from knee joint of rats and cultured at 4 layers. Each layer consisted of 2 × 105 cells/ml with and without TGF-β2. The expression of mRNA and protein levels of TGF-β receptors and Smad1, 3, 4, and 7 have been analysed by RT-PCR and western blot analysis. The effect of different supplementations in chondrocyte cell proliferation, cell length, adhesion, and wound repair was statistically analysed by One-way ANOVA test. Our results showed that the TGFβ2 regulates mRNA levels of its own receptors, and of Smad3 and Smad7. Also the TGF-β2 caused an increase in chondrocyte cell length, but decreased its proliferation rate and the wound healing process. TGF-β2 also decreased cell adhesion ability to the surface of the culture flask. Since, TGF-β2 increased the cell size, but showed negative effect on cell proliferation and adhesion of CHC, the effect of manipulated TGF-β2 with other growth factors and/or proteins needs to be investigated to finalize the utilization of this growth factor and design of scaffolding in treatment of different types of arthritis.
  • Act now to close chemical-weapons loophole

    Shang, Lijun; Crowley, Michael J.A.; Dando, Malcolm R. (2018-10-18)
    As the Fourth Review Conference of the Chemical Weapons Convention meets next month, state parties need to address mounting concerns about the potential development and use of law-enforcement weapons involving chemical agents that act on the central nervous system (CNS).
  • Predicting visual acuity from visual field sensitivity in age-related macular degeneration

    Denniss, Jonathan; Baggaley, H.C.; Astle, A.T. (2018-09)
    Purpose: To investigate how well visual field sensitivity predicts visual acuity at the same locations in macular disease, and to assess whether such predictions may be useful for selecting an optimum area for fixation training. Methods: Visual field sensitivity and acuity were measured at nine locations in the central 10° in 20 people with AMD and stable foveal fixation. A linear mixed model was constructed to predict acuity from sensitivity, taking into account within-subject effects and eccentricity. Cross validation was used to test the ability to predict acuity from sensitivity in a new patient. Simulations tested whether sensitivity can predict nonfoveal regions with greatest acuity in individual patients. Results: Visual field sensitivity (P < 0.0001), eccentricity (P = 0.007), and random effects of subject on eccentricity (P = 0.043) improved the model. For known subjects, 95% of acuity prediction errors (predicted − measured acuity) fell within −0.21 logMAR to +0.18 logMAR (median +0.00 logMAR). For unknown subjects, cross validation gave 95% of acuity prediction errors within −0.35 logMAR to +0.31 logMAR (median −0.01 logMAR). In simulations, the nonfoveal location with greatest predicted acuity had greatest “true” acuity on median 26% of occasions, and median difference in acuity between the location with greatest predicted acuity and the best possible location was +0.14 logMAR (range +0.04 to +0.17). Conclusions: The relationship between sensitivity and acuity in macular disease is not strongly predictive. The location with greatest sensitivity on microperimetry is unlikely to represent the location with the best visual acuity, even if eccentricity is taken into account.
  • In vivo selectivity and localization of reactive oxygen species (ROS) induction by osmium anticancer complexes that circumvent platinum resistance

    Coverdale, J.P.C.; Bridgewater, H.E.; Song, J-I.; Smith, N.A.; Barry, Nicolas P.E.; Bagley, I.; Sadler, P.J.; Romero-Canelon, I. (2018-10)
    Platinum drugs are widely used for cancer treatment. Other precious metals are promising, but their clinical progress depends on achieving different mechanisms of action to overcome Pt-resistance. Here, we evaluate 13 organo-Os complexes: 16-electron sulfonyl-diamine catalysts [(η6-arene)Os(N,N′)], and 18-electron phenylazopyridine complexes [(η6-arene)Os(N,N’)Cl/I]+ (arene = p-cymene, biphenyl, or terphenyl). Their antiproliferative activity does not depend on p21 or p53 status, unlike cisplatin, and their selective potency toward cancer cells involves the generation of reactive oxygen species. Evidence of such a mechanism of action has been found both in vitro and in vivo. This work appears to provide the first study of osmium complexes in the zebrafish model, which has been shown to closely model toxicity in humans. A fluorescent osmium complex, derived from a lead compound, was employed to confirm internalization of the complex, visualize in vivo distribution, and confirm colocalization with reactive oxygen species generated in zebrafish.
  • Basal fatty acid oxidation increases after recurrent low glucose in human primary astrocytes

    Weightman Potter, P.G.; Vlachaki Walker, J.M.; Robb, J.L.; Chilton, J.K.; Williamson, Ritchie; Randall, A.D.; Ellacott, K.L.J.; Beall, C. (2018)
    Aims/hypothesis Hypoglycaemia is a major barrier to good glucose control in type 1 diabetes. Frequent hypoglycaemic episodes impair awareness of subsequent hypoglycaemic bouts. Neural changes underpinning awareness of hypoglycaemia are poorly defined and molecular mechanisms by which glial cells contribute to hypoglycaemia sensing and glucose counterregulation require further investigation. The aim of the current study was to examine whether, and by what mechanism, human primary astrocyte (HPA) function was altered by acute and recurrent low glucose (RLG). Methods To test whether glia, specifically astrocytes, could detect changes in glucose, we utilised HPA and U373 astrocytoma cells and exposed them to RLG in vitro. This allowed measurement, with high specificity and sensitivity, of RLG-associated changes in cellular metabolism. We examined changes in protein phosphorylation/expression using western blotting. Metabolic function was assessed using a Seahorse extracellular flux analyser. Immunofluorescent imaging was used to examine cell morphology and enzymatic assays were used to measure lactate release, glycogen content, intracellular ATP and nucleotide ratios. Results AMP-activated protein kinase (AMPK) was activated over a pathophysiologically relevant glucose concentration range. RLG produced an increased dependency on fatty acid oxidation for basal mitochondrial metabolism and exhibited hallmarks of mitochondrial stress, including increased proton leak and reduced coupling efficiency. Relative to glucose availability, lactate release increased during low glucose but this was not modified by RLG. Basal glucose uptake was not modified by RLG and glycogen levels were similar in control and RLG-treated cells. Mitochondrial adaptations to RLG were partially recovered by maintaining euglycaemic levels of glucose following RLG exposure. Conclusions/interpretation Taken together, these data indicate that HPA mitochondria are altered following RLG, with a metabolic switch towards increased fatty acid oxidation, suggesting glial adaptations to RLG involve altered mitochondrial metabolism that could contribute to defective glucose counterregulation to hypoglycaemia in diabetes.
  • Does blue light restore human epidermal barrier function via activation of Opsin during cutaneous wound healing?

    Castellano-Pellicena, Irene; Uzunbajakava, N.E.; Mignon, Charles; Raafs, B.; Botchkarev, Vladimir A.; Thornton, M. Julie (2018)
    Background and Objective Visible light has beneficial effects on cutaneous wound healing, but the role of potential photoreceptors in human skin is unknown. In addition, inconsistency in the parameters of blue and red light‐based therapies for skin conditions makes interpretation difficult. Red light can activate cytochrome c oxidase and has been proposed as a wound healing therapy. UV‐blue light can activate Opsin 1‐SW, Opsin 2, Opsin 3, Opsin 4, and Opsin 5 receptors, triggering biological responses, but their role in human skin physiology is unclear. Materials and Methods Localization of Opsins was analyzed in situ in human skin derived from face and abdomen by immunohistochemistry. An ex vivo human skin wound healing model was established and expression of Opsins confirmed by immunohistochemistry. The rate of wound closure was quantitated after irradiation with blue and red light and mRNA was extracted from the regenerating epithelial tongue by laser micro‐dissection to detect changes in Opsin 3 (OPN3) expression. Retention of the expression of Opsins in primary cultures of human epidermal keratinocytes and dermal fibroblasts was confirmed by qRT‐PCR and immunocytochemistry. Modulation of metabolic activity by visible light was studied. Furthermore, migration in a scratch‐wound assay, DNA synthesis and differentiation of epidermal keratinocytes was established following irradiation with blue light. A role for OPN3 in keratinocytes was investigated by gene silencing. Results Opsin receptors (OPN1‐SW, 3 and 5) were similarly localized in the epidermis of human facial and abdominal skin in situ. Corresponding expression was confirmed in the regenerating epithelial tongue of ex vivo wounds after 2 days in culture, and irradiation with blue light stimulated wound closure, with a corresponding increase in OPN3 expression. Expression of Opsins was retained in primary cultures of epidermal keratinocytes and dermal fibroblasts. Both blue and red light stimulated the metabolic activity of cultured keratinocytes. Low levels of blue light reduced DNA synthesis and stimulated differentiation of keratinocytes. While low levels of blue light did not alter keratinocyte migration in a scratch wound assay, higher levels inhibited migration. Gene silencing of OPN3 in keratinocytes was effective (87% reduction). The rate of DNA synthesis in OPN3 knockdown keratinocytes did not change following irradiation with blue light, however, the level of differentiation was decreased. Conclusions Opsins are expressed in the epidermis and dermis of human skin and in the newly regenerating epidermis following wounding. An increase in OPN3 expression in the epithelial tongue may be a potential mechanism for the stimulation of wound closure by blue light. Since keratinocytes and fibroblasts retain their expression of Opsins in culture, they provide a good model to investigate the mechanism of blue light in wound healing responses. Knockdown of OPN3 led to a reduction in early differentiation of keratinocytes following irradiation with blue light, suggesting OPN3 is required for restoration of the barrier function. Understanding the function and relationship of different photoreceptors and their response to specific light parameters will lead to the development of reliable light‐based therapies for cutaneous wound healing.
  • You Are What You Ate: Consuming the Past to Benefit the Present

    McCleery, I.; Shearman, V.; Buckberry, Jo (2017)
    You Are What You Ate was a British public engagement project funded by the Wellcome Trust between 2010 and 2014. It was a collaboration between the University of Leeds, the University of Bradford and Wakefield Council, especially its museums, schools and libraries, which aimed to use medieval food as a way to encourage reflection about modern food and lifestyle. The innovative project ran three exhibitions in Wakefield and Pontefract, a mobile exhibition, numerous schools and youth workshops, and a series of market stalls and osteology workshops for adults and children in the Yorkshire region. This article provides an overview of the project’s aims, activities, outcomes, including an analysis of how to evaluate them, and its legacy.
  • Estimates of edge detection filters in human vision

    McIlhagga, William H. (2018-12)
    Edge detection is widely believed to be an important early stage in human visual processing. However, there have been relatively few attempts to map human edge detection filters. In this study, observers had to locate a randomly placed step edge in brown noise (the integral of white noise) with a 1/𝑓2 power spectrum. Their responses were modelled by assuming the probability the observer chose an edge location depended on the response of their own edge detection filter to that location. The observer’s edge detection filter was then estimated by maximum likelihood methods. The filters obtained were odd-symmetric and similar to a derivative of Gaussian, with a peak-to-trough width of 0.1–0.15 degrees. These filters are compared with previous estimates of edge detectors in humans, and with neurophysiological receptive fields and theoretical edge detectors.
  • Pharmacist joint-working with general practices: evaluating the Sheffield Primary Care Pharmacy Programme. A mixed- methods study

    Marques, Iuri; Gray, N.J.; Tsoneva, J.; Magirr, P.; Blenkinsopp, Alison (2018)
    Background: The NHS in the UK supports pharmacists’ deployment into general practices. This article reports on the implementation and impact of the Primary Care Pharmacy Programme (PCPP). The programme is a care delivery model that was undertaken at scale across a city in which community pharmacists (CPs) were matched with general practices and performed clinical duties for one half-day per week. Aim: To investigate (a) challenges of integration of CPs in general practices, and (b) the perceived impact on care delivery and community pharmacy practice. Design & setting: This mixed-methods study was conducted with CPs, community pharmacy employers (CPEs), scheme commissioners (SCs), and patients in Sheffield. Method: Semi-structured interviews (n = 22) took place with CPs (n = 12), CPEs (n = 2), SCs (n = 3), and patients (n = 5). A cross-sectional survey of PCPP pharmacists (n = 47, 66%) was also used. A descriptive analysis of patient feedback forms was undertaken and a database of pharmacist activities was created. Results: Eighty-six of 88 practices deployed a pharmacist. Although community pharmacy contracting and backfill arrangements were sometimes complicated, timely deployment was achieved. Development of closer relationships appeared to facilitate extension of initially agreed roles, including transition from ‘backroom’ to patient-facing clinical work. CPs gained understanding of GP processes and patients’ primary care pathway, allowing them to follow up work at the community pharmacy in a more timely way, positively impacting on patients’ and healthcare professionals’ perceived delivery of care. Conclusion: The PCPP scheme was the first of its kind to achieve almost universal uptake by GPs throughout a large city. The study findings reveal the potential for CP–GP joint-working in increasing perceived positive care delivery and reducing fragmented care, and can inform future implementation at scale and at practice level.
  • Advances in antitumor effects of NSAIDs

    Zhang, Z.; Chen, F.; Shang, Lijun (2018-10-15)
    In recent years, the reports on using nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer prevention and treatment have been on the rise. In 2017, the US Preventive Services Working Group issued primary prevention guidelines on the use of NSAIDs, especially aspirin, for cardiovascular disease and colorectal cancer, and formally established the role and status of aspirin in cancer prevention. However, the mechanism of NSAIDs on preventing cancer is still not clear. In this paper, the progress of the application of NSAIDs, especially aspirin, in the prevention and treatment of tumors in recent years is summarized, and new ideas and directions for the follow-up study are also discussed.
  • Engrailed-2 (EN2) - a novel biomarker in epithelial ovarian cancer

    McGrath, S.E.; Annels, N.; Madhuri, T.K.; Tailor, A.; Butler-Manuel, S.A.; Morgan, Richard; Pandha, H.; Michael, A. (2018-10)
    Background: Epithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker. Engrailed-2 (EN2) is a homeodomain-containing transcription factor, essential during embryological neural development, which is dysregulated in several cancer types. We evaluated the expression of EN2 in Epithelial ovarian cancer, and reviewed its role as a biomarker. Methods: We evaluated 8 Epithelial ovarian cancer cell lines, along with > 100 surgical specimens from the Royal Surrey County Hospital (2009–2014). In total, 108 tumours and 5 normal tissue specimens were collected. En2 mRNA was evaluated by semi-quantitative RT-PCR. Histological sub-type, and platinum-sensitive/−resistant status were compared. Protein expression was assessed in cell lines (immunofluorescence), and in > 150 tumours (immunohistochemistry). Results: En2 mRNA expression was elevated in serous ovarian tumours compared with normal ovary (p < 0.001), particularly in high-grade serous ovarian cancer (p < 0.0001) and in platinum-resistant tumours (p = 0.0232). Median Overall Survival and Progression-free Survival were reduced with high En2 expression (OS = 28 vs 42 months, p = 0.0329; PFS = 8 vs 27 months; p = 0.0004). Positive cytoplasmic EN2 staining was demonstrated in 78% of Epithelial ovarian cancers, with absence in normal ovary. EN2 positive high-grade serous ovarian cancer patients had a shorter PFS (10 vs 17.5 months; p = 0.0103). Conclusion: The EN2 transcription factor is a novel ovarian cancer biomarker. It demonstrates prognostic value, correlating with worse Overall Survival and Progression-free Survival. It is hoped that further work will validate its use as a biomarker, and provide insight into the role of EN2 in the development, progression and spread of ovarian cancer.
  • Nanoparticles for post-infarct ventricular remodeling

    Dong, C.; Ma, A.; Shang, Lijun (2018)
    In recent years, tremendous progress has been made in the treatment of acute myocardial infarction (AMI), but pathological ventricular remodeling often causes survivors to suffer from fatal heart failure. Currently, there is no effective therapy to attenuate ventricular remodeling. Recently, nanoparticles-based drug delivery system is widely applied in biomedicine especially in cancer and liver fibrosis, owing to its excellent physical, chemical, and biological properties. Therefore, using nanoparticles as delivery vehicles of small molecules, polypeptides, etc to improve post-infarct ventricular remodeling are expected. In this review, we summarized the updated researches in this fast-growing area and suggested further works needed.
  • Using evidence from hair and other soft tissues to infer the need for and receipt of health-related care provision

    Brown, Emma L.; Wilson, Andrew S. (2018)
    The Bioarchaeology of Care approach developed by Tilley is usually applied to skeletalized human remains, given the usual constraints of preservation bias that are seen with archaeological assemblages. However, other tissues, such as hair are sometimes preserved and can provide a wealth of information that can supplement the skeletal data. Archaeological hair has been analysed for drug compounds for almost thirty years. This article integrates data from hair analyses for coca metabolites, stable light isotope analysis and aDNA to expand the potential of the Bioarchaeology of Care approach using the example of a spontaneously mummified adult female from northern Chile.
  • Alterations in intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in human endothelial cells

    Habas, Khaled S.A.; Shang, Lijun (2018-10)
    Alterations of Endothelial cells (ECs) play a critical role in different pathogenesis of many serious human diseases, and dysfunction of the vascular endothelium is an indicator for human disorders. Endothelial dysfunction is considered to be an early indicator for atherosclerosis, which is characterised by overexpression of adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Hydrogen peroxide (H2O2) released via neutrophils is an important mediator of endothelial cell function. Ambient production of superoxide anion (O2−) and subsequently H2O2 at low levels is critical for regulating endothelial cell functions and proliferation. In this study, we investigated the effects of H2O2 on the expression of adhesion molecules VCAM-1 and ICAM-1 in cultured human umbilical vein endothelial cells (HUVECs). Intracellular superoxide anion production was detected by using p-Nitro Blue Tetrazolium (NBT) assay. Our results showed that administration of 100μM of H2O2 on HUVECs for 2, 6, 12 and 24 h induced a time-dependent increase in ICAM-1 and VCAM-1 mRNA and protein expression levels with a significant increase observed from 6 h. HUVECs exposed to H2O2 exhibit increased O2−, suggesting that H2O2 induced oxidative stress may be a reasonable for atherosclerosis. This increase can be reduced by the flavonoid, N-acetyl cysteine (NAC). The modulation of endothelial cell function through this mechanism may underlie the contribution of H2O2 to the development of vascular disease.
  • Evidence for chromatic edge detectors in human vision using classification images

    McIlhagga, William H.; Mullen, K.T. (2018-09)
    Edge detection plays an important role in human vision, and although it is clear that there are luminance edge detectors, it is not known whether there are chromatic edge detectors as well.We showed observers a horizontal edge blurred by a Gaussian filter (with widths of r ¼ 0.1125, 0.225, or 0.458) embedded in blurred Brown noise. Observers had to choose which of two stimuli contained the edge. Brown noise was used in preference to white noise to reveal localized edge detectors. Edges and noise were defined by either luminance or chromatic contrast (isoluminant L/M and S-cone opponent). Classification image analysis was applied to observer responses. In this analysis, the random components of the stimulus are correlated with observer responses to reveal a template that shows how observers weighted different parts of the stimulus to arrive at their decision.We found classification images for both luminance and isoluminant chromatic stimuli that had shapes very similar to derivatives of Gaussian filters. The widths of these classification images tracked the widths of the edges, but the chromatic edge classification images were wider than the luminance ones. These results are consistent with edge detection filters sensitive to luminance contrast and isoluminant chromatic contrast.
  • Optical control of nanoparticle catalysis influenced by photoswitch positioning in hybrid peptide capping ligands

    Lawrence, R.L.; Hughes, Zak E.; Cendan, V.J.; Liu, Y.; Lim, C.K.; Prasad, P.N.; Swihart, M.T.; Walsh, T.R.; Knecht, M.R. (2018-10)
    Here we present an in-depth analysis of structural factors that modulate peptide-capped nanoparticle catalytic activity via optically driven structural reconfiguration of the biointerface present at the particle surface. Six different sets of peptide-capped Au nanoparticles were prepared, in which an azobenzene photoswitch was incorporated into one of two well-studied peptide sequences with known affinity for Au, each at one of three different positions: The N- or C-terminus, or mid-sequence. Changes in the photoswitch isomerization state induce a reversible structural change in the surface-bound peptide, which modulates the catalytic activity of the material. This control of reactivity is attributed to changes in the amount of accessible metallic surface area available to drive the reaction. This research specifically focuses on the effect of the peptide sequence and photoswitch position in the biomolecule, from which potential target systems for on/off reactivity have been identified. Additionally, trends associated with photoswitch position for a peptide sequence (Pd4) have been identified. Integrating the azobenzene at the N-terminus or central region results in nanocatalysts with greater reactivity in the trans and cis conformations, respectively; however, positioning the photoswitch at the C-terminus gives rise to a unique system that is reactive in the trans conformation and partially deactivated in the cis conformation. These results provide a fundamental basis for new directions in nanoparticle catalyst development to control activity in real time, which could have significant implications in the design of catalysts for multistep reactions using a single catalyst. Additionally, such a fine level of interfacial structural control could prove to be important for applications beyond catalysis, including biosensing, photonics, and energy technologies that are highly dependent on particle surface structures.
  • Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness

    Nwogu, N.; Boyne, James R.; Dobson, S.J.; Poterlowicz, Krzysztof; Blair, G.E.; Macdonald, A.; Mankouri, J.; Whitehouse, A.
    Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is recognised as the causative factor in the majority of MCC cases. The MCPyV small tumour antigen (ST) is considered to be the main viral transforming factor, however potential mechanisms linking ST expression to the highly metastatic nature of MCC are yet to be fully elucidated. Metastasis is a complex process, with several discrete steps required for the formation of secondary tumour sites. One essential trait that underpins the ability of cancer cells to metastasise is how they interact with adjoining tumour cells and the surrounding extracellular matrix. Here we demonstrate that MCPyV ST expression disrupts the integrity of cell-cell junctions, thereby enhancing cell dissociation and implicate the cellular sheddases, A disintegrin and metalloproteinase (ADAM) 10 and 17 proteins in this process. Inhibition of ADAM 10 and 17 activity reduced MCPyV ST-induced cell dissociation and motility, attributing their function as critical to the MCPyV-induced metastatic processes. Consistent with these data, we confirm that ADAM 10 and 17 are upregulated in MCPyV-positive primary MCC tumours. These novel findings implicate cellular sheddases as key host cell factors contributing to virus-mediated cellular transformation and metastasis. Notably, ADAM protein expression may be a novel biomarker of MCC prognosis and given the current interest in cellular sheddase inhibitors for cancer therapeutics, it highlights ADAM 10 and 17 activity as a novel opportunity for targeted interventions for disseminated MCC.
  • Crystallographic texture and mineral concentration quantification of developing and mature human incisal enamel

    Al-Mosawi, M.; Davis, G.R.; Bushby, A.; Montgomery, J.; Beaumont, Julia; Al-Jawad, M. (2018-09)
    For dental human enamel, what is the precise mineralization progression spatially and the precise timings of mineralization? This is an important question in the fundamental understanding of matrix-mediated biomineralization events, but in particular because we can use our understanding of this natural tissue growth in humans to develop biomimetic approaches to repair and replace lost enamel tissue. It is important to understand human tissues in particular since different species have quite distinct spatial and temporal progression of mineralization. In this study, five human central incisors at different stages of enamel maturation/mineralization were spatially mapped using synchrotron X-ray diffraction and X-ray microtomography techniques. From the earliest developmental stage, two crystallite-orientation populations coexist with angular separations between the crystallite populations averaging approximately 40o and varying as a function of position with the tooth crown. In general, population one had significantly lower texture magnitude and contributed a higher percentage to the overall crystalline structure, compared to population two which only contributed 20-30% but had significantly higher texture magnitude. This quantitative analysis allows us to understand the complex and co-operative structure-function relationship between two populations of crystallites within human enamel. There was an increase in the mineral concentration from the enamel-dentin junction peripherally and from the incisal tip cervically as a function of maturation time. Quantitative backscattered-electron analyses revealed that mineralization of prism cores precedes that of prism boundaries. These results provide new insights into the precise understanding of the natural growth of human enamel.
  • Riluzole–Triazole Hybrids as Novel Chemical Probes for Neuroprotection in Amyotrophic Lateral Sclerosis

    Sweeney, J.B.; Rattray, Marcus; Pugh, V.; Powell, L.A. (2018-06-14)
    Despite intense attention from biomedical and chemical researchers, there are few approved treatments for amyotrophic lateral sclerosis (ALS), with only riluzole (Rilutek) and edaravone (Radicava) currently available to patients. Moreover, the mechanistic basis of the activity of these drugs is currently not well-defined, limiting the ability to design new medicines for ALS. This Letter describes the synthesis of triazole-containing riluzole analogues, and their testing in a novel neuroprotective assay. Seven compounds were identified as having neuroprotective activity, with two compounds having similar activity to riluzole.
  • What health-related activities could be delivered by pharmacy students in the Digital Health Enterprise Zone (DHEZ) Academic?

    Medlinskiene, Kristina; Tappas, Theodora; Tomlinson, Justine (2018)
    Background: Digital Health Enterprise Zone (DHEZ) Academic building opened in 2017 with the aim of improving outcomes of people living with long-term conditions. This multi-disciplinary facility houses: physiotherapy and optometry public clinics, health promotion areas, and digital diagnostics. Additionally, a medicines review hub with consultation rooms and teaching space was created for the School of Pharmacy and Medical Sciences (SPMS), University of Bradford. Pharmacy students have already successfully performed health-related activities with the public in international literature (Lawrence, 2018). This project explored SPMS academics’ perspectives on the potential use of the facility for the teaching and delivery of health-related activities by pharmacy students.

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