Determination of the environmental factors involved in neurodegenerative diseases has been elusive. Methylmercury and β-N-methylamino-L-alanine (BMAA) have both been implicated in this role. Exposure of primary cortical cultures to these compounds independently induced concentration-dependent neurotoxicity. Importantly, concentrations of BMAA (10-100 μM) that caused no toxicity alone potentiated methylmercury (3 μM) toxicity. In addition, concentrations of BMAA and methylmercury that had no effect by themselves on the main cellular antioxidant glutathione together decreased glutathione levels. Furthermore, the combined toxicity of methylmercury and BMAA was attenuated by the cell permeant form of glutathione, glutathione monoethyl ester. The results indicate a synergistic toxic effect of the environmental neurotoxins BMAA and methylmercury, and that the interaction is at the level of glutathione depletion.
Methylmercury (MeHg) exposure at high concentrations poses significant neurotoxic threat to humans worldwide. The present study investigated the mechanisms of glutathione-mediated attenuation of MeHg neurotoxicity in primary cortical culture. MeHg (5 μM) caused depletion of mono- and disulfide glutathione in neuronal, glial and mixed cultures. Supplementation with exogenous glutathione, specifically glutathione monoethyl ester (GSHME) protected against the MeHg induced neuronal death. MeHg caused increased reactive oxygen species (ROS) formation measured by dichlorodihydrofluorescein (DCF) fluorescence with an early increase at 30 min and a late increase at 6h. This oxidative stress was prevented by the presence of either GSHME or the free radical scavenger, trolox. While trolox was capable of quenching the ROS, it showed no neuroprotection. Exposure to MeHg at subtoxic concentrations (3 μM) caused an increase in system x(c)(-) mediated (14)C-cystine uptake that was blocked by the protein synthesis inhibitor, cycloheximide (CHX). Interestingly, blockade of the early ROS burst prevented the functional upregulation of system x(c)(-). Inhibition of multidrug resistance protein-1 (MRP1) potentiated MeHg neurotoxicity and increased cellular MeHg. Taken together, these data suggest glutathione offers neuroprotection against MeHg toxicity in a manner dependent on MRP1-mediated efflux.
Classroom assessment tasks and environment are central to supporting student learning, yet are under-studied at the tertiary level, especially in China's test-driven culture. This study explores the relationship between students' perceptions of assessment tasks and classroom assessment environment, within the university context of teaching English as a foreign language (EFL) in China. A questionnaire was designed and administered, based on Dorman & Knightley's (2006) Perceptions of Assessment Tasks Inventory (PATI) and Alkharusi's (2011) scale, in order to measure students' perceptions of the classroom assessment environment. PATI includes five subscales: congruence with planned learning, authenticity, student consultation, transparency, and diversity. Alkharusi's scale comprises two subscales: learning-oriented classroom assessment environment and performance-oriented classroom assessment environment. Participants were 620 university students from three universities in China. The factor analysis findings identified the original five-factor PATI, and Alkharusi's two-factor scales within this Chinese research context. Multiple regression analyses exploring the interrelationship showed that congruence with planned learning, authenticity, student consultation, and transparency significantly predicted the learning-oriented classroom assessment environment, explaining 48 % of the variance. Congruence with planned learning and student consultation negatively, and diversity positively, predicted the performance-oriented classroom assessment environment, explaining 12 % of the variance. The findings highlight the two core values in classroom assessment tasks: congruence with planned learning and student consultation in mediating the classroom environment. This study addresses the research gap in our limited understanding of the relationship between classroom assessment tasks and assessment environment, and aids teachers in structuring their day-to-day classroom assessment practices in support of their students' learning.
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