The Role of G Protein In Alcohol Related Behaviours Using Drosophila melanogaster As A Model

Ethanol, classified as a drug, affects the central nervous system, and its consumption has been linked to the development of several behaviours including tolerance and dependence. Alcohol tolerance is defined as the need for higher doses of alcohol to induce the same changes observed in the initial exposure or where repetitive exposures of the same alcohol dose induce a lower response. Ethanol has been shown to interact with numerous targets and ultimately influence both short and long term adaptation at the cellular and molecular level in brain [1]. These adaptation processes are likely to involve signalling molecules: our work has focussed on G proteins gene expression. Using both wild type and several mutant fruit fly (Drosophila melanogaster) as a model for behaviour and molecular studies, we observed significant increases in sedation time (ST50) in response to alcohol (P<0.001) Fig.A. We also observed a consistent and significant decrease of Gq protein mRNA expression in Drosophila dUNC and DopR2 mutants chronically exposed to alcohol (*P<0.05). Fig B. Method: Six male flies were observed in drosophila polystyrene 25 x 95mm transparent vial in between cotton plugs. To the top plug, 500uL of 100% ethanol was added. Time till 50% of the flies were sedated was recorded on each day following the schedule. Fig. C (n=4-6). Using RT-PCR, we also quantified G protein mRNA expression levels one hour post initial 30 minutes of ethanol expression on day 1 and day 3 relative to expression in naïve flies.(n=2) [A] Increase in sedation time indicative of tolerance in different mutant lines and wild type flies. Six male flies were used in each experiment and (n= 4-6. ***P<0.001 unpaired t tests). [B] RT-PCR results showing significant reduction in Gq mRNA in flies chronically exposed to alcohol. (n=2. *P<0.05) [C] Alcohol exposure schedule. (1) Kaun K.R., R. Azanchi, Z. Maung, J. Hirsh, U. Heberlein. (2011). A Drosophila model for alcohol reward. Nature Neuroscience. 14 (5), 612–619.

During pregnancy, recreational drug-using women stop taking ecstasy (3,4-methylenedioxy-N-methylamphetamine) and reduce alcohol consumption but continue to smoke tobacco and cannabis

While recreational drug use in UK women is prevalent, to date there is little prospective data on patterns of drug use in recreational drug-using women immediately before and during pregnancy. A total of 121 participants from a wide range of backgrounds were recruited to take part in the longitudinal Development and Infancy Study (DAISY) study of prenatal drug use and outcomes. Eighty-six of the women were interviewed prospectively while pregnant and/or soon after their infant was born. Participants reported on use immediately before and during pregnancy and on use over their lifetime. Levels of lifetime drug use of the women recruited were high, with women reporting having used at least four different illegal drugs over their lifetime. Most users of cocaine, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and other stimulants stopped using these by the second trimester and levels of use were low. However, in pregnancy, 64% of the sample continued to use alcohol, 46% tobacco and 48% cannabis. While the level of alcohol use reduced substantially, average tobacco and cannabis levels tended to be sustained at pre-pregnancy levels even into the third trimester (50 cigarettes and/or 11 joints per week). In sum, while the use of ‘party drugs’ and alcohol seems to reduce, levels of tobacco and cannabis use are likely to be sustained throughout pregnancy. The data provide polydrug profiles that can form the basis for the development of more realistic animal models.

Seismic retrofitting of RC buildings using CFRP and post-tensioned metal straps: shake table tests

This article examines the effectiveness of two innovative retrofitting solutions at enhancing the seismic behaviour of a substandard reinforced concrete building tested on a shake table as part of the Pan-European funded project BANDIT. To simulate typical substandard construction, the reinforcement of columns and beam-column joints of the full-scale structure had inadequate detailing. An initial series of shake table tests were carried out to assess the seismic behaviour of the bare building and the effectiveness of a first retrofitting intervention using Post-Tensioned Metal Straps. After these tests, columns and joints were repaired and subsequently retrofitted using a retrofitting solution consisting of Carbon Fibre Reinforced Polymers and Post-Tensioned Metal Straps applied on opposite frames of the building. The building was then subjected to unidirectional and three-dimensional incremental seismic excitations to assess the effectiveness of the two retrofitting solutions at improving the global and local building performance. The article provides details of the above shake table testing programme and retrofitting solutions, and discusses the test results in terms of the observed damage, global damage indexes, performance levels and local strains. It is shown that whilst the original bare building was significantly damaged at a peak ground acceleration (PGA) of 0.15g, the retrofitted building resisted severe threedimensional shake table tests up to PGA=0.60g without failure. Moreover, the retrofitting intervention enhanced the interstorey drift ratio capacity of the 1st and 2nd floors by 160% and 110%, respectively. Therefore, the proposed dual retrofitting system is proven to be very effective for improving the seismic performance of substandard buildings.

Full-Scale Shaking Table Tests on a Substandard RC Building Repaired and Strengthened with Post-Tensioned Metal Straps

The effectiveness of a novel Post-Tensioned Metal Strapping (PTMS) technique at enhancing the seismic behaviour of a substandard RC building was investigated through full-scale shake-table tests during the EU-funded project BANDIT. The building had inadequate reinforcement detailing in columns and joints to replicate old construction practices. After the bare building was initially damaged significantly, it was repaired and strengthened with PTMS to perform additional seismic tests. The PTMS technique improved considerably the seismic performance of the tested building. Whilst the bare building experienced critical damage at an earthquake of PGA=0.15g, the PTMS-strengthened building sustained a PGA=0.35g earthquake without compromising stability.

Alcohol gel ingestion amongst homeless Eastern and Central Europeans in London: assessing the effects on cognitive functioning and psychological health

Background: Intentional consumption of alcohol based hand gels has been reported especially amongst non-UK national, alcohol dependent, homeless individuals in London. Whilst alcohol misuse is known to be associated with impaired cognitive functioning and mental health problems, the effects of additional ingestion of alcohol gel are unknown. Objectives: To explore cognitive and psychological functioning in users who intentionally ingest alcohol gel compared with ethyl-alcohol only misusers and controls. Methods: Male, Central and Eastern European alcohol only misusers, (n=14; mean age 39 years), alcohol gel users (n=14; mean age 43 years) and controls (n=12; mean age 31 years) were recruited from a London Homeless Service during 2013/14. Alcohol misusers, alcohol gel users and controls were compared on the Forwards and Backwards Digit Span Test; Block Design test; Retrospective and Prospective Memory Questionnaire (PRMQ) and the Hospital and Anxiety Depression Scale (HADS). Results: Alcohol gel users performed significantly worse on the Block Design task (p<0.01) and PRMQ (p<0.01) relative to both alcohol only and control groups, and significantly worse on the digit span relative to controls (p=0.01). Both alcohol misusing groups scored comparatively on digit span backwards (p<0.01), with both groups performing significantly worse than controls. The alcohol gel group reported significantly higher levels of anxiety relative to controls (p=0.02). Conclusions: Whilst there could be constitutional differences between alcohol misusers who additionally abuse alcohol gel, the findings suggest that alcohol gel ingestion may have a greater impact on psychological functioning than traditional alcohol misuse.