BURA Collection: http://bura.brunel.ac.uk/handle/2438/8614 2019-05-26T00:25:12Z A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response http://bura.brunel.ac.uk/handle/2438/18217 Title: A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response Authors: Macare, C; Ducci, F; Zhang, Y; Ruggeri, B; Jia, T; Kaakinen, M; Kalsi, G; Charoen, P; Casoni, F; Peters, J; Bromberg, U; Hill, M; Buxton, J; Blakemore, A; Veijola, J; Büchel, C; Banaschewski, T; Bokde, ALW; Conrod, P; Flor, H; Frouin, V; Gallinat, J; Garavan, H; Gowland, PA; Heinz, A; Ittermann, B; Lathrop, M; Martinot, JL; Paus, T; Desrivières, S; Munafò, M; Järvelin, MR; Schumann, G Abstract: The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10−4) and higher plasma cotinine levels (p = 7.0 × 10−5). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking. 2018-08-11T00:00:00Z Quantification by SIFT-MS of volatile compounds produced by the action of sodium hypochlorite on a model system of infected root canal content http://bura.brunel.ac.uk/handle/2438/18199 Title: Quantification by SIFT-MS of volatile compounds produced by the action of sodium hypochlorite on a model system of infected root canal content Authors: Ioannidis, K; Niazi, S; Deb, S; Mannocci, F; Smith, D; Turner, C Abstract: Root canal irrigation with sodium hypochlorite (NaOCl) is an indispensable part of the chemomechanical preparation of infected root canals in Endodontology. However, there is limited information on the emergence of toxic or hazardous volatile compounds (VOCs) from the interaction of NaOCl with the infected content of tooth biomaterials. The aim of this study was to assess the formation of VOCs and disinfection by-products (DBPs) following the interaction of NaOCl 2.5% v/v with a model system of different sources of natural organic matter (NOM) present in infected root canals, including dentine powder, planktonic multimicrobial suspensions (Propionibacterium acnes, Staphylococcus epidermidis, Actinomyces radicidentis, Streptococcus mitis and Enterococcus faecalis strain OMGS3202), bovine serum albumin 4%w/v and their combination. NaOCl was obtained from a stock solution with iodometric titration. Ultrapure water served as negative control. Samples were stirred at 37˚C in aerobic and anaerobic conditions for 30min to approximate a clinically realistic time. Centrifugation was performed and the supernatants were collected and stored at -800 C until analysis. The reaction products were analysed in real time by selected ion flow tube mass spectrometry (SIFT-MS) in triplicates. SIFT-MS analysis showed that the released VOCs included chlorinated hydrocarbons, particularly chloroform, together with unexpected higher levels of some nitrogenous compounds, especially acetonitrile. No difference was observed between aerobic and anaerobic conditions. The chemical interaction of NaOCl with NOM resulted in the formation of toxic chlorinated VOCs and DBPs. SIFT-MS analysis proved to be an effective analytical method. The risks from the rise of toxic compounds require further consideration in dentistry. 2018-09-10T00:00:00Z TOP2B: The first thirty years http://bura.brunel.ac.uk/handle/2438/18197 Title: TOP2B: The first thirty years Authors: Austin, CA; Lee, KC; Swan, RL; Khazeem, MM; Manville, CM; Cridland, P; Treumann, A; Porter, A; Morris, NJ; Cowell, IG Abstract: Type II DNA topoisomerases (EC are enzymes that catalyse topological changes in DNA in an ATP dependent manner. Strand passage reactions involve passing one double stranded DNA duplex (transported helix) through a transient enzyme-bridged break in another (gated helix). This activity is required for a range of cellular processes including transcription. Vertebrates have two isoforms: topoisomerase IIα and β. Topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the 30 years since its discovery. 2018-09-14T00:00:00Z Temperature-related mortality impacts under and beyond Paris Agreement climate change scenarios http://bura.brunel.ac.uk/handle/2438/18190 Title: Temperature-related mortality impacts under and beyond Paris Agreement climate change scenarios Authors: Vicedo-Cabrera, AM; Guo, Y; Sera, F; Huber, V; Schleussner, CF; Mitchell, D; Tong, S; Coelho, MDSZS; Saldiva, PHN; Lavigne, E; Correa, PM; Ortega, NV; Kan, H; Osorio, S; Kyselý, J; Urban, A; Jaakkola, JJK; Ryti, NRI; Pascal, M; Goodman, PG; Zeka, A; Michelozzi, P; Scortichini, M; Hashizume, M; Honda, Y; Hurtado-Diaz, M; Cruz, J; Seposo, X; Kim, H; Tobias, A; Íñiguez, C; Forsberg, B; Åström, DO; Ragettli, MS; Röösli, M; Guo, YL; Wu, CF; Zanobetti, A; Schwartz, J; Bell, ML; Dang, TN; Do Van, D; Heaviside, C; Vardoulakis, S; Hajat, S; Haines, A; Armstrong, B; Ebi, KL; Gasparrini, A Abstract: The Paris Agreement binds all nations to undertake ambitious efforts to combat climate change, with the commitment to “hold warming well below 2 °C in global mean temperature (GMT), relative to pre-industrial levels, and to pursue efforts to limit warming to 1.5 °C”. The 1.5 °C limit constitutes an ambitious goal for which greater evidence on its benefits for health would help guide policy and potentially increase the motivation for action. Here we contribute to this gap with an assessment on the potential health benefits, in terms of reductions in temperature-related mortality, derived from the compliance to the agreed temperature targets, compared to more extreme warming scenarios. We performed a multi-region analysis in 451 locations in 23 countries with different climate zones, and evaluated changes in heat and cold-related mortality under scenarios consistent with the Paris Agreement targets (1.5 and 2 °C) and more extreme GMT increases (3 and 4 °C), and under the assumption of no changes in demographic distribution and vulnerability. Our results suggest that limiting warming below 2 °C could prevent large increases in temperature-related mortality in most regions worldwide. The comparison between 1.5 and 2 °C is more complex and characterized by higher uncertainty, with geographical differences that indicate potential benefits limited to areas located in warmer climates, where direct climate change impacts will be more discernible. 2018-09-13T00:00:00Z