#3 - Inhibition of the Mitochondrial Calcium Uniporter Reduces Oxidative Phosphorylation in SGK1-Knockout VSMC Upon DietInduced Obesity

Obesity is linked to vascular diseases such as atherosclerosis and coronary artery disease which is a major underlying cause of heart attacks. While the mechanism is not fully known, altering mitochondrial respiration which occurs through oxidative phosphorylation (OXPHOS) may influence the development of vascular disease during obesity. Our previous data with diet-induced obese (DIO) mice demonstrated that serum and glucocorticoid-inducible kinase 1 (SGK1), which regulates cell metabolism, was up-regulated in vascular smooth muscle cells (VSMC) from the aorta. Knocking out SGK1 in VSMCs (KOSGK1) was associated with higher OXPHOS and lower vascular disease relative to wildtype VSMCs (WTSGK1) during DIO. The mitochondrial calcium uniporter (MCU) permits calcium uptake into the mitochondrial matrix causing stimulation of OXPHOS thereby contributing to the maintenance of cellular energy homeostasis. We hypothesized that OXPHOS stimulation in KOSGK1 VSMC may be due to enhanced activity of the MCU. To test this hypothesis, an extracellular oxygen consumption (EOC) assay which measures OXPHOS was used to examine the role of MCU-mediated mitochondrial Ca2+ uptake on basal and maximal OXPHOS activity in WTSGK1 and KOSGK1 VSMCs. Thus, WTSGK1 and KOSGK1 VSMCs from DIO mice were treated ± Ru360 (10mM), an MCU inhibitor and ± FCCP (2.5mM) to stimulate maximal OXPHOS. Consistent with previous data, KOSGK1 VSMCs had significantly higher basal and maximal EOC compared to WTSGK1 VSMCs. Remarkably, RU360 significantly decreased both basal and maximal EOC in KOSGK1 VCMCs. Conversely, there was no effect of RU360 on EOC in WTSGK1 VSMCs. These results suggest a disparity in MCU activity in KOSGK1 VSMCs. In conclusion, these findings implicate mitochondrial Ca2+ uptake in the stimulation of OXPHOS in KOSGK1 VSMCs

Editorial

Interactional competence (IC) is a concept gaining growing currency in language learning, teaching and assessment. First proposed by Kramsch (1986), IC focuses on developing second language (L2) speakers’ abilities to use language for functional purposes, ranging from “survival as a tourist or a student to negotiating treaties” (p. 366). The conceptualization of language competence as an ability for use differentiates IC from traditional understanding of proficiency, which consists of componential, de-contextualized ability indicators such as lexical range, grammatical soundness, and pronunciation. The ethos of IC emphasizes that language teaching education needs to focus on cultivating L2 speakers’ abilities to use their linguistic resources (e.g., vocabulary and grammar) to achieve meaningful social actions in real-world interactional contexts. This special issue comprises three research articles and three book reviews, each of which exemplifies the ways in which IC can be applied to face-to-face and online learning opportunities for L2 speakers

Editorial

Interactional competence (IC) is a concept gaining growing currency in language learning, teaching and assessment. First proposed by Kramsch (1986), IC focuses on developing second language (L2) speakers’ abilities to use language for functional purposes, ranging from “survival as a tourist or a student to negotiating treaties” (p. 366). The conceptualization of language competence as an ability for use differentiates IC from traditional understanding of proficiency, which consists of componential, de-contextualized ability indicators such as lexical range, grammatical soundness, and pronunciation. The ethos of IC emphasizes that language teaching education needs to focus on cultivating L2 speakers’ abilities to use their linguistic resources (e.g., vocabulary and grammar) to achieve meaningful social actions in real-world interactional contexts. This special issue comprises three research articles and three book reviews, each of which exemplifies the ways in which IC can be applied to face-to-face and online learning opportunities for L2 speakers.&nbsp

Editorial: Collaboration, training and funding for the professional development of teachers of EAL/D students

This issue of TESOL in Context contains four articles that complement each other in their focus and arguments concerning political ideologies, the commodification of English as an additional language/dialect (EAL/D) teaching and the professional training needs of both EAL/D and mainstream teachers in Australian education. The first two submissions are discussion papers, which set the scene for two articles reporting on results from empirical TESOL research. Four book reviews complete the volume with a focus on the work of EAL/D teachers and learners in a variety of contexts. The articles and book reviews in this issue highlight important issues in EAL/D policy, research and practice, with a particular emphasis on the imperative to prioritise teacher preparation and professional learning. Underpinning all submissions is a clear understanding of the need for authenticity, collaboration, specialisation and utilisation of all of the linguistic competencies EAL/D bring with them to classrooms. This has implications for TESOL within and beyond Australian borders and highlights the need for continued dialogue with government and funding bodies to ensure the teaching and learning of EAL/D students is comprehensively supported in a wide range of educational contexts.

Transformation Kinetics and Mechanism of the Sulfonylurea Herbicides Pyrazosulfuron Ethyl and Halosulfuron Methyl in Aqueous Solutions

Little is known about how popular herbicides react and degrade in soil or aquatic environments. Two of these herbicides include Pyrazosulfuron Ethyl (PE) and Halosulfuron Methyl (HM), which are part of the sulfonylurea herbicide category. Both are post-emergence herbicides and are so highly effective that they need to be applied only at rates of grams per hector. Because these herbicides inhibit the key enzyme that participates in protein synthesis in plants, they can have a major effect on sensitive agricultural areas such as legumes or pastures for grazing. Typically these types of herbicides only degrade because of microbial influences or chemical hydrolysis. To understand the pathway and conditions for chemical hydrolysis degradation, ISTC’s Wei Zheng collaborated with researchers at the U.S. Department of Agriculture to conduct several laboratory experiments. Full results reported in Zheng, Wei et al (2008). "Transformation Kinetics and Mechanism of the Sulfonylurea Herbicides Pyrazosulfuron Ethyl and Halosulfuron Methyl in Aqueous Solutions." Journal of Agricultural and Food Chemistry 56(16), 7367-7372. https://doi.org/10.1021/jf800899eOpe

A Bayesian method for finding interactions in genomic studies

An important step in building a multiple regression model is the selection of predictors. In genomic and epidemiologic studies, datasets with a small sample size and a large number of predictors are common. In such settings, most standard methods for identifying a good subset of predictors are unstable. Furthermore, there is an increasing emphasis towards identification of interactions, which has not been studied much in the statistical literature. We propose a method, called BSI (Bayesian Selection of Interactions), for selecting predictors in a regression setting when the number of predictors is considerably larger than the sample size with a focus towards selecting interactions. Latent variables are used to infer subset choices based on the posterior distribution. Inference about interactions is implemented by a constraint on the latent variables. The posterior distribution is computed using the Gibbs Sampling methods. The finite-sample properties of the proposed method are assessed by simulation studies. We illustrate the BSI method by analyzing data from a hypertension study involving Single Nucleotide Polymorphisms (SNPs)

Environmental Scanning on the Internet

This study investigates the important organizational task of environmental scanning in an Internet context. A theoretical model relating potential causal factors to effectiveness of environmental scanning was formulated based on a synthesis of environmental scanning literature that took into consideration the Internet context. A questionnaire was developed for data collection. Responses from 105 organizations were tested for convergent and discriminant validity before the theoretical model was assessed using PLS analysis. Results showed that smaller organizations tend to scan more frequently on the Internet, both use of external consultants and volatility of competitor sector tend to cause organizations to scan more frequently on the Internet, and both use of external consultants and scanning frequency on the Internet tend to result in effectiveness of environ- mental scanning. Additional insights on these results were obtained through telephone interviews with 10 respondents

Generalized Estimating Equations for Hearing Loss Data with Specified Correlation Structures

Due to the nature of pure-tone audiometry test, hearing loss data often has a complicated correlation structure. Generalized estimating equation (GEE) is commonly used to investigate the association between exposures and hearing loss, because it is robust to misspecification of the correlation matrix. However, this robustness typically entails a moderate loss of estimation efficiency in finite samples. This paper proposes to model the correlation coefficients and use second-order generalized estimating equations to estimate the correlation parameters. In simulation studies, we assessed the finite sample performance of our proposed method and compared it with other methods, such as GEE with independent, exchangeable and unstructured correlation structures. Our method achieves an efficiency gain which is larger for the coefficients of the covariates corresponding to the within-cluster variation (e.g., ear-level covariates) than the coefficients of cluster-level covariates. The efficiency gain is also more pronounced when the within-cluster correlations are moderate to strong, or when comparing to GEE with an unstructured correlation structure. As a real-world example, we applied the proposed method to data from the Audiology Assessment Arm of the Conservation of Hearing Study, and studied the association between a dietary adherence score and hearing loss.Comment: 14 pages, 5 tables, 4 supplementary tables; submitted to Biometrical Journa