Inhibition of Cholinesterases by the Oximes P2AM and Toxogonin

The reversible inhibition of electric eel acetylcholinesterase (EC 3.1.1.7) by P2AM (2-(hydroxyimino)methyl-1-methyl-pyridinium chloride) and Toxogonin (1,1\u27-[oxybis(methylene)] bis(4-(hydroxyimino) methyl-pyridinium) dichloride) was studied using ac.etylthiocholine as substrate. Two techniques were applied for measuring acetylthiocholine hydrolysis, the conventional spectrophotometric and the stopped-flow (at 25 °c in 100 mM phosphate buffer pH = 7.4). The correlation between the degree of inhibition, and acetylthiocholine and oxime concentrations fits a theoretical model which postulates that the substrate and the inhibitor bind to two sites on the enzyme: the catalytic site and an allosteric, substrate-inhibition, site. The calculated dissociation constants for the two sites are: 0.13 and 0.76 mM for P2AM, and 0.16 and 2.0 mM for Toxogonin. The suggested model is an alternative to the hypothesis that two types of binding occur within the catalytic site. Horse serum cholinesterase and bovine erythrocyte acetylcholinesterase are also inhibited by P2AM and Toxogonin to about the same degree as the electric eel enzyme. Acetylthiocholine reacts with P2AM and Toxogonin; assuming that the reaction is bimolecular the corresponding rate constants are 13.4 and 22.4 M-1 min-

Inhibition of Cholinesterases by the Oximes P2AM and Toxogonin

The reversible inhibition of electric eel acetylcholinesterase (EC 3.1.1.7) by P2AM (2-(hydroxyimino)methyl-1-methyl-pyridinium chloride) and Toxogonin (1,1\u27-[oxybis(methylene)] bis(4-(hydroxyimino) methyl-pyridinium) dichloride) was studied using ac.etylthiocholine as substrate. Two techniques were applied for measuring acetylthiocholine hydrolysis, the conventional spectrophotometric and the stopped-flow (at 25 °c in 100 mM phosphate buffer pH = 7.4). The correlation between the degree of inhibition, and acetylthiocholine and oxime concentrations fits a theoretical model which postulates that the substrate and the inhibitor bind to two sites on the enzyme: the catalytic site and an allosteric, substrate-inhibition, site. The calculated dissociation constants for the two sites are: 0.13 and 0.76 mM for P2AM, and 0.16 and 2.0 mM for Toxogonin. The suggested model is an alternative to the hypothesis that two types of binding occur within the catalytic site. Horse serum cholinesterase and bovine erythrocyte acetylcholinesterase are also inhibited by P2AM and Toxogonin to about the same degree as the electric eel enzyme. Acetylthiocholine reacts with P2AM and Toxogonin; assuming that the reaction is bimolecular the corresponding rate constants are 13.4 and 22.4 M-1 min-

China's road to a global scientific powerhouse

Drawing on the wider 'catching up' literature, we examine the rapid growth in Chinese spending on science and technology, which, in spite of its growing infrastructure, remains heavily reliant on foreign inputs. We examine both the economic and political drivers behind China's scientific development, making a distinction between domestic investments and international technology trade. Firms provide over two-thirds of total R&D funding, most of which has been spent on 'high-tech' sectors for export production. The fastest growing research area is in environmental sciences and energy technology. China's technology imports are shifting away from 'technologies for production', towards 'technologies for innovation', encouraged by the national development strategy on enhancing scientific research capacities. In particular, we present evidence from China's imported technology contracts. Energy is the second largest sector after manufacturing in terms of imported technology contracts

A comparison of public preferences for different low-carbon energy technologies: Support for CCS, nuclear and wind energy in the United Kingdom

Using a representative national survey in the United Kingdom, we investigated public attitudes towards different low-carbon technologies (carbon capture and storage (CCS), wind and nuclear power) and the factors influencing public support. Overall, we found that respondents were far more likely to support wind energy as their preferred means of mitigating climate change. Older people and those of a higher social grade are more supportive of nuclear power, while age and social grade do not significantly affect support for wind energy. Supporters of the Conservative Party were more likely to oppose wind power. Neither attitudes towards climate change nor environmental attitudes were found to influence public support for wind power or nuclear. Trust in information from environmental groups was associated with greater support for wind energy but lower support for nuclear power. Perceived cost and objective knowledge significantly influenced public support for all three technology types, that is, higher perceived costs and the poorer objective knowledge lead to lower public support. However, self-assessed knowledge did not influence public support. Many factors, including most of the tested demographic factors, did not affect support for any of the three technologies

Refinement of primary Si in hypereutectic Al-Si alloys by intensive melt shearing

Hypereutectic Al-Si based alloys are gaining popularity for applications where a combination of light weight and high wear resistance is required. The high wear resistance arising from the hard primary Si particles comes at the price of extremely poor machine tool life. To minimize machining problems while exploiting outstanding wear resistance, the primary Si particles must be controlled to a uniform small size and uniform spatial distribution. The current industrial means of refining primary Si chemically by the addition of phosphorous suffers from a number of problems. In the present paper an alternative, physical means of refining primary Si by intensive shearing of the melt prior to casting is investigated. Al-15wt%Si alloy has been solidified under varying casting conditions (cooling rate) and the resulting microstructures have been studied using microscopy and quantitative image analysis. Primary Si particles were finer, more compact in shape and more numerous with increasing cooling rate. Intensive melt shearing led to greater refinement and more enhanced nucleation of primary Si than was achieved by adding phosphorous. The mechanism of enhanced nucleation is discussed.EPSRC (grant EP/H026177/1)

Mehanizam toksičnosti i detoksikacije organofosfornih spojeva s naglaskom na istraživanja u Hrvatskoj

This review comprises studies on the mechanisms of toxicity and detoxication of organophosphorus (OP) compounds done in Croatia in different research areas. One area is the synthesis of antidotes against OP poisoning and their in vivo testing in experimental animals. In vitro studies included in this review focus on the mechanisms of reversible inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), protection of cholinesterases from inhibition by OPs, and reactivation of phosphylated cholinesterases. The third area comprises distribution profiles of BChE and paraoxonase (PON) phenotypes in selected population groups and the detection of OPs and metabolites in humans. Finally, methods are described for the detection of OP compounds in human blood and other media by means of cholinesterase inhibitionPrikazana su istraživanja vođena u Hrvatskoj na različitim područjima mehanizma toksičnosti i detoksikacije organofosfornih (OP) spojeva. Jedno je područje sinteza antidota protiv otrovanja OP spojevima i testiranje in vivo antidota na eksperimentalnim životinjama. Istraživanja in vitro odnose se na mehanizam reverzibilne inhibicije acetilkolinesteraze (AChE) i buturilkolinesteraze (BChE), zaštitu kolinesteraza od inhibicije OP spojevima te reaktivaciju fosfiliranih kolinesteraza. Treće je područje distribucija fenotipova BChE i paraoksonaze (PON) u odabranim populacijama te detekcija OP spojeva i njihovih metabolita u ljudima. Na kraju su opisane metode detekcije OP spojeva u ljudskoj krvi i drugim medijima koje se osnivaju na inhibiciji kolinesteraza

Effect of green cardamom on lipoproteins, glycemic control and anthropometric parameters: A meta-analysis of randomized clinical trials

Introduction: The aim of this systematic review and meta-analysis was to summarize all the existing randomized controlled trials (RCTs) evidence and to evaluate the effects of green cardamom on lipoproteins, glycemic control and anthropometric parameters in healthy and/or with disease types compared with the control. Method: Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until 30th July 2019. RCTs complying with the following criteria were included in this meta-analysis: human trials with either cross-over design or parallel design, trials with data on the effects of green cardamom on serum lipoproteins and glycemic control and anthropometric parameters with standard deviation and related 95 confidence interval for the both intervention and placebo groups. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. Result: Seven trials were included in this meta-analysis. Triglycerides were significantly reduced after cardamom supplementation when compared with the control group. Cardamom intake from 3 small studies resulted in a significant increase in BMI when compared with the control group. However, cardamom supplementation did not have any significant effect on total cholesterol, LDL-cholesterol, HDL-cholesterol, fasting plasma glucose and body weight when compared with the control group. Conclusion: This meta-analysis demonstrated that green cardamom intake significantly reduced triglycerides levels which may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders. © 2020 European Society for Clinical Nutrition and Metabolis