The Modulation of Epileptiform Activity in Rat Hippocampal Slices by Adenine Nucleotides

In this study the most consistent method of inducing epileptiform activity in hippocampal slices involved recording from the pyramidal cell layer of the CA3 region whilst bathing the slice in a medium containing no added magnesium and 4-aminopyridine (4AP) (50?M). The bursts produced were interictal in nature and inhibited by kynurenate (ImM) or 2-amino-5-phosphonopentanoic acid (20 and 40muM) suggesting that both NMDA and non-NMDA receptors were involved. The effect of ATP and other adenine nucleotides on the rate of spontaneous epileptiform activity was investigated. ATP and adenosine were equipotent at decreasing discharge rate at concentrations above 10muM. The depression produced by ATP was characterised by being inhibited by the A1 receptor antagonist 8-cyclopentyl, 1,3-dimethylxanthine (CPT) but resistant to adenosine deaminase (at a concentration which annulled the effect of adenosine). P2 receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) and suramin) were also unable to block ATP depression of bursting. AMP depressed epileptiform activity similarly to ATP. Its effect was inhibited by CPT and 5'-adenylic acid deaminase (AMPase). AMPase also blocked the depression in discharge rate elicited by ATP. 5'-nucleotidase is involved in the metabolism of AMP to adenosine. The combination of 5'-nucleotidase and adenosine deaminase with AMP or ATP resulted in no significant change in the frequency of activity. These later results, therefore, suggest that ATP acts through metabolism to AMP. The antagonism by CPT supports the involvement of A1 receptors. The ATP analogues alpha,beta-methyleneATP and 2-methylthioATP were also tested as well as uridine triphosphate. Only alpha,beta-methyleneATP (10muM) altered the discharge rate producing an increase in the frequency of spontaneous activity which was inhibited by suramin and PPADS. These results are indicative of an excitatory P2X receptor in the hippocampal CA3 region. Several have been cloned and found expressed in the hippocampus but none with the characteristics displayed in this study. BzATP, an agonist at the P2Z receptor, decreased the discharge rate during a 10 minute perfusion. This depression was not reversed upon washing but continued to progress. The combination of BzATP and CPT produced an increase in discharge rate which was smaller than that caused by CPT alone. This suggests that A1 receptors may not be involved in producing the effect of BzATP. The alpha, omega-adenine dinucleotides Ap4A and Ap5A produced a concentration-dependent depression in discharge rate. Adenosine deaminase inhibited the effect of 1muM but not the early stages of the depression produced by 10?M Ap4A and Ap5A. CPT but not AMPase antagonised the depression in rate produced by Ap4A. This suggests that in the CA3 region of the hippocampus AP4A and Ap5A act partly by stimulating xanthine sensitive receptors directly and partly through the formation of the metabolite, adenosine. AMPase initially elevated the discharge rate to a small extent but a subsequent fall in rate occurred during the wash period which continued until a plateau was reached at which the rate remained for up to 90 minutes. IMP was ineffective. Dialysis of AMPase neither affected the enzymatic activity of AMPase nor the following depression. Boiling the enzyme rendered it inactive in that it could no longer prevent the effect of AMP. The sustained depression in activity produced by AMPase was also inhibited by denaturisation. It was proposed, therefore, that AMPase induces a form of long term depression (LTD). The induction of this LTD, as measured by an effect on discharge rate, was not altered by antagonists of A1, opioid or GABAA receptors nor inhibitors of cyclo-oxygenase, nitric oxide synthase or protein kinase

Cosmic clocks: A Tight Radius - Velocity Relationship for HI-Selected Galaxies

HI-Selected galaxies obey a linear relationship between their maximum detected radius Rmax and rotational velocity. This result covers measurements in the optical, ultraviolet, and HI emission in galaxies spanning a factor of 30 in size and velocity, from small dwarf irregulars to the largest spirals. Hence, galaxies behave as clocks, rotating once a Gyr at the very outskirts of their discs. Observations of a large optically-selected sample are consistent, implying this relationship is generic to disc galaxies in the low redshift Universe. A linear RV relationship is expected from simple models of galaxy formation and evolution. The total mass within Rmax has collapsed by a factor of 37 compared to the present mean density of the Universe. Adopting standard assumptions we find a mean halo spin parameter lambda in the range 0.020 to 0.035. The dispersion in lambda, 0.16 dex, is smaller than expected from simulations. This may be due to the biases in our selection of disc galaxies rather than all halos. The estimated mass densities of stars and atomic gas at Rmax are similar (~0.5 Msun/pc^2) indicating outer discs are highly evolved. The gas consumption and stellar population build time-scales are hundreds of Gyr, hence star formation is not driving the current evolution of outer discs. The estimated ratio between Rmax and disc scale length is consistent with long-standing predictions from monolithic collapse models. Hence, it remains unclear whether disc extent results from continual accretion, a rapid initial collapse, secular evolution or a combination thereof.Comment: 14 pages, 7 figures, 3 in colour. Published in MNRAS. This v2 corrects wrong journal in the references section (all instances of "Astrophysics and Space Sciences" should have been ApJ). The Posti+2017 has also been updated. An erratum has been submitted to MNRA

Estimating the Magnitude of Illicit Cigarette Trade in Bangladesh:Protocol for a Mixed-Methods Study

The illicit tobacco trade undermines the effectiveness of tobacco tax policies; increases the availability of cheap cigarettes, which, in turn, increases tobacco use and tobacco related deaths; and causes huge revenue losses to governments. There is limited evidence on the extent of illicit tobacco trade particularly cigarettes in Bangladesh. The paper presents the protocol for a mixed-methods study to estimate the extent of illicit cigarette trade in Bangladesh. The study will address three research questions: (a) What proportion of cigarettes sold as retail are illicit? (b) What are the common types of tax avoidance and tax evasion? (c) Can pack examination from the trash recycle market be considered as a new method to assess illicit trade in comparison to that from retailers and streets? Following an observational research method, data will be collected utilizing empty cigarette packs from three sources: (a) retailers; (b) streets; and (c) trash recycle market. In addition, a structured questionnaire will be used to collect information from retailers selling cigarettes. We will select post codes as Primary Sampling Unit (PSU) using a multi-stage random sampling technique. We will randomly select eight districts from eight divisions stratified by those with land border and non-land border; and within each district, we will randomly select ten postcodes, stratified by rural (five) and urban (five) PSU to ensure maximum geographical variation, leading to a total of eighty post codes from eight districts. The analysis will report the proportions of packs that do not comply with the study definition of illicit. Independent estimates of illicit tobacco are rare in low-and middle-income countries such as Bangladesh. Findings will inform efforts by revenue authorities and others to address the effects of illicit trade and counter tobacco industry claims