Browsing by Author "Cook, S."
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Item Differences in Alcohol Consumption and Drinking Patterns in Ghanaians in Europe and Africa: The RODAM Study(PloS one, 2018-11) Addo, J.; Cook, S.; Galbete, C.; Agyemang, C.; Klipstein-Grobusch, K.; Nicolaou, M.; Danquah, I.; Schulze, M.B.; Brathwaite, R.; Mockenhaupt, F.P.; Beune, E.; Meeks, K.; de-Graft Aikins, A.; Bahendaka, S.; Owusu-Dabo, E.; Smeeth, L.BACKGROUND: Little is known about alcohol consumption among Africans living in rural and urban Africa compared to African migrants in Europe. We compared the patterns of alcohol consumption in a group of Ghanaians living in different locations in Ghana and in Europe and examined the factors associated with drinking alcohol. METHODS: Data were from a cross-sectional study (RODAM) of Ghanaians aged 25-70 years living in rural and urban Ghana and in Amsterdam, Berlin and London. Information on how often participants consumed at least one standard alcoholic drink in the preceding 12 months, the type of alcoholic beverage and the average serving size was obtained using a food propensity questionnaire. The associations between drinking alcohol and socio-demographic variables, and frequency of attending religious services were investigated using logistic regression models stratified by site and sex. For Ghanaians living in Europe, the number of years since migration and acculturation were also included in the model as covariates. RESULTS: 4280 participants (62.2% women) were included in the analyses. In both men and women, the prevalence of drinking and amount of alcohol consumed per day was highest in Berlin (prevalence of drinking 71.0% and 61.7%) and lowest in urban Ghana (41.4% and 26.8%). After adjustment for age and education in both men and women in Europe, those attending religious services less frequently reported higher levels of drinking alcohol than non-attendants (never attend/no religion compared to attending service at least once a week men OR 4.60 95% CI 2.85, 7.44; women OR 1.80 95% CI 1.12, 2.90) p-trend with frequency <0.001 in men; 0.002 in women); this association was seen also in men in rural Ghana (p-trend = 0.001) and women in urban Ghana (p-trend = 0.02). The prevalence of drinking was positively associated with years since migration in both men and women in Europe ((OR per years increase in time lived in Europe 1.25 (95% CI 1.02,1.53) test for trend p = 0.03 in women; OR 1.29 (95% CI 1.03, 1.62 p = 0.03 in men) but no association was found with self-reported measures of acculturation (ethnic identity, cultural orientation or social networks). CONCLUSION: There are marked differences in alcohol consumption between Ghanaians living in Europe and in Ghana suggesting migration has an important influence of drinking patterns and also suggesting the possibility of requiring different strategies in alcohol reduction campaigns among Ghanaians in different locations.Item Setting Our Sights on Infectious Diseases(ACS Infectious Diseases, 2019-12-06) Amewu, R.K.; De Rycker, M.; Horn, D.; Aldridge, B.; Barry, C.E.; Buckner, F.S.; Cook, S.; Ferguson, M.A.J.; Gobeau, N.; Herrmann, J.; Herrling, P.; Hope, W.; Keiser, J.; Lafuente-Monasterio, M.J.; Leeson, P.D.; Leroy, D.; Manjunatha, U.H.; Miles, T.J.; Mizrahi, V.; Moshynets, O.; Niles, J.; Overington, J.P.; Pottage, J.; Rao, S.P.S.; Read, K.D.; Ribeiro, I.; Silver, L.L.; Southern, J.; Spangenberg, T.; Sundar, S.; Taylor, C.; Van Voorhis, W.; White, N.J.; Wyllie, S.; Wyatt, P.G.; Gilbert, I.H.In May 2019, the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee, UK, held an international conference with the aim of discussing some key questions around discovering new medicines for infectious diseases and a particular focus on diseases affecting Low and Middle Income Countries. There is an urgent need for new drugs to treat most infectious diseases. We were keen to see if there were lessons that we could learn across different disease areas and between the preclinical and clinical phases with the aim of exploring how we can improve and speed up the drug discovery, translational, and clinical development processes. We started with an introductory session on the current situation and then worked backward from clinical development to combination therapy, pharmacokinetic/pharmacodynamic (PK/PD) studies, drug discovery pathways, and new starting points and targets. This Viewpoint aims to capture some of the learningsItem Shedding of somatic angiotensin-converting enzyme (ACE) is inefficient compared with testis ACE despite cleavage at identical stalk sites.(Biochemical Journal, 2000) Woodman, Z.L.; Oppong, S.Y.; Cook, S.; Hooper, N.M.; Schwager, S.L.U.; Brandt, W.F.; Sturrock, E.D.The somatic and testis isoforms of angiotensin-converting enzyme (ACE) are both C-terminally anchored ectoproteins that are shed by an unidentified secretase. Although testis and somatic ACE both share the same stalk and membrane domains the latter was reported to be shed inefficiently compared with testis ACE, and this was ascribed to cleavage at an alternative site [Beldent, Michaud, Bonnefoy, Chauvet and Corvol (1995) J. Biol. Chem. 270, 28962-28969]. These differences constitute a useful model system of the regulation and substrate preferences of the ACE secretase, and hence we investigated this further. In transfected Chinese hamster ovary cells, human somatic ACE (hsACE) was indeed shed less efficiently than human testis ACE, and shedding of somatic ACE responded poorly to phorbol ester activation. However, using several analytical techniques, we found no evidence that the somatic ACE cleavage site differed from that characterized in testis ACE. First, anti-peptide antibodies raised to specific sequences on either side of the reported cleavage site (Arg(1137)/Leu(1138)) clearly recognized soluble porcine somatic ACE, indicating that cleavage was C-terminal to Arg(1137). Second, a competitive ELISA gave superimposable curves for porcine plasma ACE, secretase-cleaved porcine somatic ACE (eACE), and trypsin-cleaved ACE, suggesting similar C-terminal sequences. Third, mass-spectral analyses of digests of released soluble hsACE or of eACE enabled precise assignments of the C-termini, in each case to Arg(1203). These data indicated that soluble human and porcine somatic ACE, whether generated in vivo or in vitro, have C-termini consistent with cleavage at a single site, the Arg(1203)/Ser(1204) bond, identical with the Arg(627)/Ser(628) site in testis ACE. In conclusion, the inefficient release of somatic ACE is not due to cleavage at an alternative stalk site, but instead supports the hypothesis that the testis ACE ectodomain contains a motif that activates shedding, which is occluded by the additional domain found in somatic ACE.