• E-Cadherin mediates UVR- and calcium-induced melanin transfer in human skin cells

      Singh, Suman K.; Baker, Richard; Sikkink, Stephen K.; Nizard, C.; Schnebert, S.; Kurfurst, R.; Tobin, Desmond J. (2017)
      Skin pigmentation is directed by epidermal-melanin units, characterized by long-lived and dendritic epidermal melanocytes (MC) that interact with viable keratinocytes (KC) to contribute melanin to the epidermis. Previously we reported that MC:KC contact is required for melanosome transfer, that this can be enhanced by filopodial and by UVR/UVA irradiation, which can up-regulate melanosome transfer via Myosin X-mediated control of MC filopodia. Both MC and KC express Ca2+-dependent E-cadherins. These homophilic adhesion contacts induce transient increases in intra-KC Ca2+, while ultraviolet radiation (UVR) raises intra-MC Ca2+ via calcium selective ORAI1 ion channels; both are associated with regulating melanogenesis. However, how Ca2+ triggers melanin transfer remains unclear, and here we evaluated the role of E-Cadherin in UVR-mediated melanin transfer in human skin cells. MC and KC in human epidermis variably express filopodia-associated E-Cadherin, Cdc42, VASP and β-catenin, all of which were upregulated by UVR/UVA in human MC in vitro. Knockdown of E-cadherin revealed that this cadherin is essential for UVR-induced MC filopodia formation and melanin transfer. Moreover, Ca2+ induced a dose-dependent increase in filopodia formation and melanin transfer, as well as increased β-catenin, Cdc42, Myosin X, and E-Cadherin expression in these skin cells. Together these data suggest that filopodial proteins and E-Cadherin, which are upregulated by intracellular (UVR-stimulated) and extracellular Ca2+ availability, are required for filopodia formation and melanin transfer. This may open new avenues to explore how Ca2+ signalling influences human pigmentation.
    • EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy

      Sturm, G.J.; Varga, E.M.; Roberts, G.; Mosbech, H.; Bilo, M.B.; Akdis, C.A.; Antolın-Amerigo, D.; Cichocka-Jarosz, E.; Gawlik, R.; Jakob, T.; et al. (2018-04-16)
      Hymenoptera venom allergy is a potentially life‐threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic‐allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life‐threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1‐antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom‐allergic children and adults to prevent further moderate‐to‐severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence‐based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.
    • EAC Guidelines for the use of Geophysics in Archaeology: Questions to Ask and Points to Consider.

      Schmidt, Armin R.; Linford, P.; Linford, N.; David, A.; Gaffney, Christopher F.; Sarris, A.; Fassbinder, J. (2015)
      These guidelines provide an overview of the issues to be considered when undertaking or commissioning geophysical survey in archaeology. As every project diff ers in its requirements (e.g. from fi nding sites to creating detailed maps of individual structures) and variations in geological and environmental conditions lead to diff erent geophysical responses, there is no single ‘best’ survey technique or methodology. Th is guide, in its European approach, highlights the various questions to be asked before a survey is undertaken. It does not provide recipebook advice on how to do a geophysical survey or a tick list of which technique is suitable under what conditions. Experienced archaeological geophysicists should be consulted to address the questions that are being posed. Using geophysical techniques and methods inappropriately will lead to disappointment and may, ultimately, result in archaeologists not using them at all. “If all you have is a hammer (or magnetometer), driving a screw becomes impossible”. Especially in the American literature the term ‘remote sensing’ is oft en used to describe geophysical as well as air and space based exploration of underground features (e.g. Wiseman and El-Baz 2007). By contrast, and in line with European traditions, a clear distinction is made here between ground-based geophysical techniques and remote sensing techniques. Th is is based on the imaging principles underlying the respective technologies. Ground based systems usually collect one spatially registered data sample from each sensor location (e.g. a single reading for each magnetometer, or a single trace from each GPR antenna). Remote sensing techniques, by contrast, collect spatially resolved data from a whole area of investigation from each sensor location, using either the system’s optical aperture (e.g. photography) or a scanning device (e.g. laser sampling). These guidelines are based on the experience of the authors in archaeological geophysics and infl uenced by various published sources.
    • Earliest evidence for the use of pottery

      Craig, O.E.; Saul, H.; Lucquin, A.J.A.; Nishida, Y.; Tache, K.; Clarke, Leon J.; Thompson, A.; Altoft, D.T.; Uchiyama, J.; Ajimoto, M.; et al. (2013)
      Pottery was a hunter-gatherer innovation that first emerged in East Asia between 20,000 and 12,000 calibrated years before present (cal bp), towards the end of the Late Pleistocene epoch, a period of time when humans were adjusting to changing climates and new environments. Ceramic container technologies were one of a range of late glacial adaptations that were pivotal to structuring subsequent cultural trajectories in different regions of the world, but the reasons for their emergence and widespread uptake are poorly understood. The first ceramic containers must have provided prehistoric hunter-gatherers with attractive new strategies for processing and consuming foodstuffs, but virtually nothing is known of how early pots were used. Here we report the chemical analysis of food residues associated with Late Pleistocene pottery, focusing on one of the best-studied prehistoric ceramic sequences in the world, the Japanese Jomon. We demonstrate that lipids can be recovered reliably from charred surface deposits adhering to pottery dating from about 15,000 to 11,800 cal bp (the Incipient Jomon period), the oldest pottery so far investigated, and that in most cases these organic compounds are unequivocally derived from processing freshwater and marine organisms. Stable isotope data support the lipid evidence and suggest that most of the 101 charred deposits analysed, from across the major islands of Japan, were derived from high-trophic-level aquatic food. Productive aquatic ecotones were heavily exploited by late glacial foragers, perhaps providing an initial impetus for investment in ceramic container technology, and paving the way for further intensification of pottery use by hunter-gatherers in the early Holocene epoch. Now that we have shown that it is possible to analyse organic residues from some of the world's earliest ceramic vessels, the subsequent development of this critical technology can be clarified through further widespread testing of hunter-gatherer pottery from later periods.
    • Easy and Fast Phase Transfer of CTAB Stabilised Gold Nanoparticles from Water to Organic Phase

      Kittler, S.; Hickey, Stephen G.; Wolff, T.; Eychmüller, A. (2015-02-28)
      Spheric and anisotropic gold nanoparticles (GNPs) such as rods, stars or nanoprism prepared using hexadecyltrimethyl ammonium bromide (CTAB) as the stabilising agent have received a great deal of interest in the last years. The literature procedures exploited lead to GNPs in aqueous solution. We herein describe a fast, efficient, and cheap method to transfer particles of different shapes from water into toluene solution via ligand exchange (CTAB to dodecanethiol), which was mediated by acetone as a cosolvent. Absorption spectra and TEM-pictures before and after the transfer revealed that the particles survived the transfer intact and without change in shape.
    • The Economic Development of the Commercial Triangle

      Jones, Rick F.J.; Robinson, Damian (2005)
    • The Economies of Sheep and Goat Husbandry in Norse Greenland.

      Mainland, Ingrid L.; Halstead, P. (2005)
      Insight into the relative importance of sheep and goat herding and of the economic significance of each species (i.e., milk vs. meat vs. wool) in Medieval Greenland is obtained through the application of Halstead et al.¿s (2002) criteria for the identification of adult ovicaprine mandibles to faunal assemblages from three Norse farmsteads: Sandnes, V52a, and Ø71S. The economic strategies identified are broadly comparable between the two species and the Eastern and Western Settlement sites examined, and are suggestive of the subsistence production of meat and milk. Comparison with farmsteads elsewhere in Greenland indicates that socio-economic status and/or farmstead size interacted with geographical location in determining the economic strategies employed by the Norse farmers. A broader use of resources and a more varied diet are evident at larger farmsteads in Greenland and this paper suggests that such sites would have been better able than their smaller counterparts to withstand environmental deterioration during the early Middle Ages. These analyses have also confirmed that goats were relatively more common in Norse sites in Greenland than in Norse sites in Iceland, Orkney, or Shetland.
    • Effect before cause: supramodal recalibration of sensorimotor timing

      Heron, James; Hanson, James Vincent Michael; Whitaker, David J. (2009)
      Our motor actions normally generate sensory events, but how do we know which events were self generated and which have external causes? Here we use temporal adaptation to investigate the processing stage and generality of our sensorimotor timing estimates. Methodology/Principal Findings: Adaptation to artificially-induced delays between action and event can produce a startling percept¿upon removal of the delay it feels as if the sensory event precedes its causative action. This temporal recalibration of action and event occurs in a quantitatively similar manner across the sensory modalities. Critically, it is robust to the replacement of one sense during the adaptation phase with another sense during the test judgment. Conclusions/Significance: Our findings suggest a high-level, supramodal recalibration mechanism. The effects are well described by a simple model which attempts to preserve the expected synchrony between action and event, but only when causality indicates it is reasonable to do so. We further demonstrate that this model successfully characterises related adaptation data from outside the sensorimotor domain.
    • The effect of adherence to spectacle wear on early developing literacy: a longitudinal study based in a large multi-ethnic city, Bradford, UK

      Bruce, A.; Kelly, B.; Chambers, B.; Barrett, Brendan T.; Bloj, Marina; Bradbury, J.; Sheldon, T.A. (2018-06)
      Objectives: To determine the impact of adherence to spectacle wear on visual acuity (VA) and developing literacy following vision screening at age 4–5 years. Design: Longitudinal study nested within the Born in Bradford birth cohort. Setting and participants: Observation of 944 children: 432 had failed vision screening and were referred (treatment group) and 512 randomly selected (comparison group) who had passed (<0.20 logarithm of the minimum angle of resolution (logMAR) in both eyes). Spectacle wear was observed in school for 2 years following screening and classified as adherent (wearing spectacles at each assessment) or non-adherent. Main outcome measures: Annual measures of VA using a crowded logMAR test. Literacy was measured by Woodcock Reading Mastery Tests-Revised subtest: letter identification. Results: The VA of all children improved with increasing age, −0.009 log units per month (95% CI −0.011 to −0.007) (worse eye). The VA of the adherent group improved significantly more than the comparison group, by an additional −0.008 log units per month (95% CI −0.009 to −0.007) (worse eye) and −0.004 log units per month (95% CI −0.005 to −0.003) in the better eye. Literacy was associated with the VA, letter identification (ID) reduced by −0.9 (95% CI −1.15 to −0.64) for every one line (0.10 logMAR) fall in VA (better eye). This association remained after adjustment for socioeconomic and demographic factors (−0.33, 95% CI −0.54 to −0.12). The adherent group consistently demonstrated higher letter-ID scores compared with the non-adherent group, with the greatest effect size (0.11) in year 3. Conclusions: Early literacy is associated with the level of VA; children who adhere to spectacle wear improve their VA and also have the potential to improve literacy. Our results suggest failure to adhere to spectacle wear has implications for the child’s vision and education.
    • Effect of blur adaptation on blur sensitivity and discrimination in emmetropes and myopes

      Mallen, Edward A.H.; Cufflin, Matthew P.; Mankowska, Aleksandra M. (2007)
      The purpose of this article is to determine whether blur adaptation influences blur sensitivity and blur discrimination thresholds in young adult myopes and emmetropes. In addition, to determine whether there is a differential effect of blur adaptation on blur sensitivity and discrimination between refractive error groups. Proximal and distal blur sensitivity thresholds and blur discrimination thresholds were measured under cycloplegia with a Badal optometer in 24 young adult subjects (8 emmetropes [EMM], 8 early-onset myopes [EOM], and 8 late-onset myopes [LOM]). Adaptation to 1 D of myopic refractive blur was then undertaken for 30 minutes. Blur sensitivity and discrimination thresholds were then remeasured. After blur adaptation, blur sensitivity, and blur discrimination thresholds were found to be elevated. Blur adaptation had a significant effect on distal blur sensitivity threshold, with the largest effect being observed in the EOMs. Mean changes in distal blur sensitivity thresholds were EMMs +0.03 ± 0.14 D, EOMs +0.30 ± 0.21 D, and LOMs +0.08 ± 0.13 D. Adaptation to a degraded stimulus modifies the blur detection mechanisms of the visual system in young adults. Depth of focus is expanded by prolonged exposure to defocus. EOMs are more susceptible to this phenomenon than are LOMs and EMMs.
    • Effect of calcium ions on peptide adsorption at the aqueous rutile titania (110) interface

      Sultan, A.M.; Hughes, Zak E.; Walsh, T.R. (2018)
      We investigate how the presence of Ca2+ ions at the aqueous TiO2 interface influences the binding modes two experimentally-identified titania-binding peptides, Ti-1 and Ti-2, using replica exchange with solute tempering molecular dynamics simulations. We compare our findings with available experimental data and contrast our results with those obtained under NaCl solution conditions. We find that for Ti-1, Ca2+ ions enhances the adsorption of the negatively-charged Asp8 residue in this sequence to the negatively-charged surface, via Asp{Ca2+{TiO2 bridging. This appears to generate a non-local impact on the adsorption of Lys12 in Ti-1, which then pins the peptide to the surface via direct surface contact. For Ti-2, fewer residues were predicted to adsorb directly to the surface in CaCl2, compared with predictions made for NaCl solution, possibly due to competition between the other peptide residues and Ca2+ ions to adsorb to the surface. This reduction in direct surface contact gives rise to a more extensive solvent-mediated contact Ti-2. In general, the presence of Ca2+ ions resulted in a loss of conformational diversity of the surface-adsorbed conformational ensembles of these peptides, compared to counterpart data predicted for NaCl solution. Our findings provide initial insights into how peptide{TiO2 interactions might be tuned at the molecular level via modification of the salt composition of the liquid medium.
    • Effect of cataract surgery incision location and intraocular lens type on ocular aberrations.

      Pesudovs, Konrad; Dietze, Holger H.; Stewart, O.; Noble, B.A.; Cox, Michael J. (2005)
      To determine whether Hartmann-Shack wavefront sensing detects differences in optical performance in vivo between poly(methyl methacrylate) (PMMA) and foldable acrylic intraocular lenses (IOLs) and between clear corneal and scleral tunnel incisions and whether optical differences are manifested as differences in visual performance. SETTING: Department of Optometry, University of Bradford, West Yorkshire, United Kingdom. METHODS: This study comprised 74 subjects; 17 were phakic with no ocular pathology, 20 had implantation of a Pharmacia 722C PMMA IOL through a scleral tunnel, 21 had implantation of an Alcon AcrySof IOL through a scleral tunnel, and 16 had implantation of an AcrySof IOL through a corneal incision. Visual acuity and contrast sensitivity testing, ocular optical quality measurement using Hartmann-Shack wavefront sensing, and corneal surface measurement with a videokeratoscope were performed in all cases. RESULTS: There were significant differences between groups in the total root-mean-square (RMS) wavefront aberration over a 6.0 mm pupil (F=3.91; degrees of freedom=3,70; P<.05) mediated at the 4th-order RMS, specifically spherical and tetrafoil aberrations. The PMMA-scleral group had the least aberrations and the AcrySof-corneal group the most. For a 3.5 mm diameter pupil, the total higher-order RMS wavefront aberration was not significantly different between the groups (P>.05). There were no differences between groups in corneal shape, visual acuity, or contrast sensitivity. CONCLUSIONS: Implantation of the spherical PMMA IOL led to a slight reduction in total wavefront aberration compared to phakic eyes. AcrySof IOLs induced more aberrations, especially spherical aberration. Corneal-based incisions for IOL implantation compounded this increase. Studies of the optical performance of IOLs in vivo should use wavefront sensing as the main outcome measure rather than visual measures, which are readily confounded by multiple factors.
    • The effect of chirality and steric hindrance on intrinsic backbone conformational propensities: tools for protein design

      Childers, M.C.; Towse, Clare-Louise; Daggett, V. (2016-06-09)
      The conformational propensities of amino acids are an amalgamation of sequence effects, environmental effects and underlying intrinsic behavior. Many have attempted to investigate neighboring residue effects to aid in our understanding of protein folding and improve structure prediction efforts, especially with respect to difficult to characterize states, such as disordered or unfolded states. Host-guest peptide series are a useful tool in examining the propensities of the amino acids free from the surrounding protein structure. Here, we compare the distributions of the backbone dihedral angles (φ/ψ) of the 20 proteogenic amino acids in two different sequence contexts using the AAXAA and GGXGG host-guest pentapeptide series. We further examine their intrinsic behaviors across three environmental contexts: water at 298 K, water at 498 K, and 8 M urea at 298 K. The GGXGG systems provide the intrinsic amino acid propensities devoid of any conformational context. The alanine residues in the AAXAA series enforce backbone chirality, thereby providing a model of the intrinsic behavior of amino acids in a protein chain. Our results show modest differences in φ/ψ distributions due to the steric constraints of the Ala side chains, the magnitudes of which are dependent on the denaturing conditions. One of the strongest factors modulating φ/ψ distributions was the protonation of titratable side chains, and the largest differences observed were in the amino acid propensities for the rarely sampled αL region.
    • Effect of cocrystallization techniques on compressional properties of caffeine/oxalic acid 2:1 cocrystal

      Aher, Suyog; Dhumal, Ravindra S.; Mahadik, K.R.; Ketolainen, J.; Paradkar, Anant R. (2013)
      Caffeine/oxalic acid 2:1 cocrystal exhibited superior stability to humidity over caffeine, but compressional behavior is not studied yet. To compare compressional properties of caffeine/oxalic acid 2:1 cocrystal obtained by different cocrystallization techniques. Cocrystal was obtained by solvent precipitation and ultrasound assisted solution cocrystallization (USSC) and characterized by X-ray powder diffraction and scanning electron microscopy. Compaction study was carried out at different compaction forces. Compact crushing strength, thickness and elastic recovery were determined. Compaction was in order, caffeine > solvent precipitation cocrystal > USSC cocrystal. Caffeine exhibited sticking and lamination, where solvent precipitation compacts showed advantage. Caffeine and solvent precipitation compacts showed sudden drop in compactability, higher elastic recovery with severe lamination at 20,000 N. This was due to overcompaction. Crystal habit of two cocrystal products was same, but USSC cocrystals were difficult to compact. Uniform needle shaped USSC cocrystals must be difficult to orient in different direction and fracture during compression. Elastic recovery of USSC cocrystals was also more compared to other powders indicating less fracture and poor bonding between particles resulting in poor compaction. Cocrystal formation did not improve compressional property of caffeine. Cocrystals exposed to different crystallization environments in two techniques may have resulted in generation of different surface properties presenting different compressional properties.
    • The effect of coloured overlays and lenses on reading: a systematic review of the literature

      Griffiths, P.G.; Taylor, R.H.; Henderson, L.M.; Barrett, Brendan T. (2016-09)
      Purpose: There are many anecdotal claims that coloured lenses and overlays improve reading performance and there is a substantial literature on the topic of whether reading performance is enhanced through the use of colour. Here we present the results of a systematic review of this literature and examine the quality of the evidence concerning the assertion that reading can benefit from use of coloured overlays or lenses. Methods: We systematically reviewed the literature concerning the effect of coloured lenses or overlays on reading performance by searching the PsychInfo, Medline and Embase databases. Our searches revealed 51 published items (containing 54 data sets). Different systems are in use for issuing coloured overlays or lenses and we reviewed the evidence under four separate system headings (Intuitive, Irlen, Harris/Chromagen and Other). We classified each published item using the Cochrane Risk of Bias tool. Results: Although the different colour systems have been subjected to different amounts of scientific scrutiny, the results do not differ according to the system type, or whether the sample under investigation have been classified as having visual stress (or a similarly defined condition), reading difficulty, or both. The majority of studies are subject to ‘high’ or ‘uncertain’ risk of bias in one or more key aspects of study design or outcome. Studies at lower risk from bias offered less support for the benefit of colour on reading ability. Whilst many studies report improvements with colour, the effect size is generally small and/or similar to the improvement found with a placebo condition. We discuss the strengths and shortcomings of the published literature and, whilst acknowledging the difficulties associated with conducting trials of this type, offer some suggestions about how future trials might be conducted. Conclusions: Consistent with previous reviews and advice from several professional bodies, we conclude that the use of coloured lenses or overlays to ameliorate reading difficulties cannot be endorsed and that any benefits reported by individuals in clinical settings are likely to be the result of placebo, practice or Hawthorne effects.
    • The effect of conjugated linoleic acid on arachidonic acid metabolism and eicosanoid production in human saphenous vein endothelial cells.

      Urquhart, Paula; Parkin, Susan M.; Rogers, J.S.; Bosley, J.A.; Nicolaou, Anna (2002)
      The effects of a conjugated linoleic acid (CLA) mixture of single isomers (50:50, w/w, cis9,trans11:trans10,cis12) and the individual isomers on (a) the production of resting and calcium ionophore stimulated 14C-eicosanoids and (b) the incorporation of 14C-arachidonic acid (AA) into membrane phospholipids of human saphenous vein endothelial cells were investigated. The CLA mixture and the individual isomers were found to inhibit resting production of 14C-prostaglandin F2a by 50, 43 and 40%, respectively. A dose dependent inhibition of stimulated 14C-prostaglandins was observed with the CLA mixture (IC50 100 ¿M). The cis9,trans11 and trans10,cis12 (50 ¿M) isomers individually inhibited the overall production of stimulated 14C-prostaglandins (between 35 and 55% and 23 and 42%, respectively). When tested at a high concentration (100 ¿M), cis9,trans11 was found to inhibit eicosanoid production in contrast to trans10,cis12 that caused stimulation. The overall degree of 14C-AA incorporation into membrane phospholipids of the CLA (mixture and individual isomers) treated cells was found to be lower than that of control cells and the cis9,trans11 isomer was found to increase the incorporation of 14C-AA into phosphatidylcholine. Docosahexaenoic acid, eicosapentaenoic acid and linoleic acid did not alter the overall degree of incorporation of 14C-AA. The results of this study suggest that both isomers inhibit eicosanoid production, and although trans10,cis12 exhibits pro-inflammatory activity at high concentrations, the CLA mixture maintains its beneficial anti-inflammatory action that contributes to its anti-carcinogenic and anti-atherogenic properties.
    • Effect of drinking water disinfection by-products in human peripheral blood lymphocytes and sperm

      Ali, Aftab H.M.; Kurzawa-Zegota, Malgorzata; Najafzadeh, Mojgan; Gopalan, Rajendran C.; Plewa, M.J.; Anderson, Diana (2014-12)
      Drinking water disinfection by-products (DBPs) are generated by the chemical disinfection of water and may pose hazards to public health. Two major classes of DBPs are found in finished drinking water: haloacetic acids (HAAs) and trihalomethanes (THMs). HAAs are formed following disinfection with chlorine, which reacts with iodide and bromide in the water. Previously the HAAs were shown to be cytotoxic, genotoxic, mutagenic, teratogenic and carcinogenic. OBJECTIVES: To determine the effect of HAAs in human somatic and germ cells and whether oxidative stress is involved in genotoxic action. In the present study both somatic and germ cells have been examined as peripheral blood lymphocytes and sperm. The effects of three HAA compounds: iodoacetic acid (IAA), bromoacetic acid (BAA) and chloroacetic acid (CAA) were investigated. After determining appropriate concentration responses, oxygen radical involvement with the antioxidants, butylated hydroxanisole (BHA) and the enzyme catalase, were investigated in the single cell gel electrophoresis (Comet) assay under alkaline conditions, >pH 13 and the micronucleus assay. In the Comet assay, BHA and catalase were able to reduce DNA damage in each cell type compared to HAA alone. In the micronucleus assay, micronuclei (MNi) were found in peripheral lymphocytes exposed to all three HAAs and catalase and BHA were in general, able to reduce MNi induction, suggesting oxygen radicals play a role in both assays. These observations are of concern to public health since both human somatic and germ cells show similar genotoxic responses.
    • Effect of Education on Myopia: Evidence from the United Kingdom ROSLA 1972 Reform

      Plotnikov, D.; Williams, C.; Atan, D.; Davies, N.M.; Ghorbani Mojarrad, Neema; Guggenheim, J.A. (2020-09-04)
      Cross-sectional and longitudinal studies have consistently reported an association between education and myopia. However, conventional observational studies are at risk of bias due to confounding by factors such as socioeconomic position and parental educational attainment. The current study aimed to estimate the causal effect of education on refractive error using regression discontinuity analysis. Methods: Regression discontinuity analysis was applied to assess the influence on refractive error of the raising of the school leaving age (ROSLA) from 15 to 16 years introduced in England and Wales in 1972. For comparison, a conventional ordinary least squares (OLS) analysis was performed. The analysis sample comprised 21,548 UK Biobank participants born in a nine-year interval centered on September 1957, the date of birth of those first affected by ROSLA. Results: In OLS analysis, the ROSLA 1972 reform was associated with a −0.29 D (95% confidence interval [CI]: −0.36 to −0.21, P < 0.001) more negative refractive error. In other words, the refractive error of the study sample became more negative by −0.29 D during the transition from a minimum school leaving age of 15 to 16 years of age. Regression discontinuity analysis estimated the causal effect of the ROSLA 1972 reform on refractive error as −0.77 D (95% CI: −1.53 to −0.02, P = 0.04). Conclusions: Additional compulsory schooling due to the ROSLA 1972 reform was associated with a more negative refractive error, providing additional support for a causal relationship between education and myopia.
    • Effect of eicosapentaenoic acid on E-type prostaglandin synthesis and EP4 receptor signalling in human colorectal cancer cells

      Hawcroft, G.; Loadman, Paul M.; Belluzzi, A.; Hull, M.A. (2010)
      The ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), in the free fatty acid (FFA) form, has been demonstrated,to reduce adenoma number and size in patients with familial adenomatous polyposis. However, the mechanistic basis of the antineoplastic activity of EPA in the colorectum remains unclear. We tested the hypothesis that EPAFFA negatively modulates synthesis of and signaling by prostaglandin (PG) E2 in human colorectal cancer (CRC) cells.,EPA-FFA induced apoptosis of cyclooxygenase (COX)-2-positive human HCA-7 CRC cells in vitro. EPA-FFA in cell,culture medium was incorporated rapidly into phospholipid membranes of HCA-7 human CRC cells and acted as,a substrate for COX-2, leading to reduced synthesis of PGE2 and generation of PGE3. Alone, PGE3 bound and activated,the PGE2 EP4 receptor but with reduced affinity and efficacy compared with its "natural" ligand PGE2. However,,in the presence of PGE2, PGE3 acted as an antagonist of EP4 receptor-dependent 3',5' cyclic adenosine,monophosphate induction in naturally EP4 receptor-positive LoVo human CRC cells and of resistance to apoptosis,in HT-29-EP4 human CRC cells overexpressing the EP4 receptor. We conclude that EPA-FFA drives a COX-2dependent "PGE2-to-PGE3 switch" in human CRC cells and that PGE3 acts as a partial agonist at the PGE2 EP4 receptor.