An Experimental Study Comparing Two Different Training Strategies on how to use Statistical Packages in an Introductory Statistics Course

Statistics education reform advocated the use of statistical software packages, such as SPSS, Minitab, and R, in introductory statistics courses. However, little research has focused on finding effective methods of training students how to use these packages. This experimental study evaluated the effectiveness of two different training strategies. A sample of 100 first year psychology students were randomly allocated to either a Guided training (GT) strategy or an error management training (EMT) strategy. GT consisted of step-by-step instructions that aimed to explicitly direct participants through training to use the statistical package SPSS. EMT avoided step-by-step instructions, instead focusing on minimal instruction which aimed to engage participants in actively exploring the statistical package. In EMT, errors were viewed as beneficial to training as they help develop a deeper understanding of SPSS. Participants completed five statistical package training sessions across the semester. Following four of these training sessions, participants completed self-assessment tasks that measured training transfer performance. After controlling for statistical knowledge and self-assessment compliance, the results of the study indicated no statistically significant differences between the two training strategies. However, this conclusion must be interpreted with caution due to a number of study imitations which are discussed in this article

The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein

In mammalian cells, MCTs (monocarboxylate transporters) require association with an ancillary protein to enable plasma membrane expression of the active transporter. Basigin is the preferred binding partner for MCT1, MCT3 and MCT4, and embigin for MCT2. In rat and rabbit erythrocytes, MCT1 is associated with embigin and basigin respectively, but its sensitivity to inhibition by AR-C155858 was found to be identical. Using RT (reverse transcription)–PCR, we have shown that Xenopus laevis oocytes contain endogenous basigin, but not embigin. Co-expression of exogenous embigin was without effect on either the expression of MCT1 or its inhibition by AR-C155858. In contrast, expression of active MCT2 at the plasma membrane of oocytes was significantly enhanced by co-expression of exogenous embigin. This additional transport activity was insensitive to inhibition by AR-C155858 unlike that by MCT2 expressed with endogenous basigin that was potently inhibited by AR-C155858. Chimaeras and C-terminal truncations of MCT1 and MCT2 were also expressed in oocytes in the presence and absence of exogenous embigin. L-Lactate Km values for these constructs were determined and revealed that the TM (transmembrane) domains of an MCT, most probably TM7–TM12, but not the C-terminus, are the major determinants of L-lactate affinity, whereas the associated ancillary protein has little or no effect. Inhibitor titrations of lactate transport by these constructs indicated that embigin modulates MCT2 sensitivity to AR-C155858 through interactions with both the intracellular C-terminus and TMs 3 and 6 of MCT2. The C-terminus of MCT2 was found to be essential for its expression with endogenous basigin

Faculty members engaging in transformative PETE: a feminist perspective

The purpose of this study was to describe sport pedagogy faculty members’ (FMs) efforts at engaging in transformative physical education teacher education (T-PETE). T-PETE stresses the importance of FMs creating social change through their pedagogical approach and begins by asking preservice teachers (PTs) to reflect on their perspectives and practices (Tinning, 2017 Tinning, R. (2017). Transformative pedagogies and physical education. In C. Ennis (Ed.), The Routledge handbook of physical education pedagogies (pp. 295–306). New York: Taylor & Francis. [Google Scholar]. Transformative pedagogies and physical education. In C. Ennis (Ed.), The Routledge handbook of physical education pedagogies (pp. 295–306). New York: Taylor & Francis; Ukpokodu, 2009. The practice of transformative pedagogy. Journal on Excellence in College Teaching, 20(2), 43–67.). Participants were three white, female, able-bodied, lesbian/gay sport pedagogy FMs. The study was conducted in the United States. Feminist theory and feminist pedagogy drove data collection and analysis. Data were collected by employing a series of qualitative methods. An inductive and deductive analysis revealed that FMs had specific T-PETE goals, content, and pedagogies. Furthermore, several factors served to facilitate and limit the FMs’ effectiveness when engaging in T-PETE. The findings suggest that program-wide PETE reform is necessary in the United States for creating social change, and influencing PTs perspectives and practices. In addition, they suggest that American PETE programs might benefit from greater diversity among the FMs who staff them

Blocking AMPK β1 myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis

AMP-activated protein kinase (AMPK) is a master regulator of cellular energy homeostasis and a therapeutic target for metabolic diseases. Co/post-translational N-myristoylation of glycine-2 (Gly2) of the AMPK β subunit has been suggested to regulate the distribution of the kinase between the cytosol and membranes through a “myristoyl switch” mechanism. However, the relevance of AMPK myristoylation for metabolic signaling in cells and in vivo is unclear. Here, we generated knockin mice with a Gly2-to-alanine point mutation of AMPKβ1 (β1-G2A). We demonstrate that non-myristoylated AMPKβ1 has reduced stability but is associated with increased kinase activity and phosphorylation of the Thr172 activation site in the AMPK α subunit. Using proximity ligation assays, we show that loss of β1 myristoylation impedes colocalization of the phosphatase PPM1A/B with AMPK in cells. Mice carrying the β1-G2A mutation have improved metabolic health with reduced adiposity, hepatic lipid accumulation, and insulin resistance under conditions of high-fat diet-induced obesity

AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7–10

In the present study we characterize the properties of the potent MCT1 (monocarboxylate transporter 1) inhibitor AR-C155858. Inhibitor titrations of L-lactate transport by MCT1 in rat erythrocytes were used to determine the Ki value and number of AR-C155858-binding sites (Et) on MCT1 and the turnover number of the transporter (kcat). Derived values were 2.3±1.4 nM, 1.29±0.09 nmol per ml of packed cells and 12.2±1.1 s−1 respectively. When expressed in Xenopus laevis oocytes, MCT1 and MCT2 were potently inhibited by AR-C155858, whereas MCT4 was not. Inhibition of MCT1 was shown to be time-dependent, and the compound was also active when microinjected, suggesting that AR-C155858 probably enters the cell before binding to an intracellular site on MCT1. Measurement of the inhibitor sensitivity of several chimaeric transporters combining different domains of MCT1 and MCT4 revealed that the binding site for AR-C155858 is contained within the C-terminal half of MCT1, and involves TM (transmembrane) domains 7–10. This is consistent with previous data identifying Phe360 (in TM10) and Asp302 plus Arg306 (TM8) as key residues in substrate binding and translocation by MCT1. Measurement of the Km values of the chimaeras for L-lactate and pyruvate demonstrate that both the C- and N-terminal halves of the molecule influence transport kinetics consistent with our proposed molecular model of MCT1 and its translocation mechanism that requires Lys38 in TM1 in addition to Asp302 and Arg306 in TM8 [Wilson, Meredith, Bunnun, Sessions and Halestrap (2009) J. Biol. Chem. 284, 20011–20021]

Synthesis and Electronic Structure Determination of Uranium(VI) Ligand Radical Complexes

   Pentagonal bipyramidal uranyl complexes of salen ligands, N,N’-bis(3-tert-butyl-(5R)-salicylidene)-1,2-phenylenediamine, in which R = tBu (1a), OMe (1b), and NMe2 (1c), were prepared and the electronic structure of the one-electron oxidized species [1a-c]+ were investigated in solution. The solid-state structures of 1a and 1b were solved by X-ray crystallography, and in the case of 1b an asymmetric UO22+ unit was found due to an intermolecular hydrogen bonding interaction. Electrochemical investigation of 1a-c by cyclic voltammetry showed that each complex exhibited at least one quasi-reversible redox process assigned to the oxidation of the phenolate moieties to phenoxyl radicals. The trend in redox potentials matches the electron-donating ability of the para-phenolate substituents. The electron paramagnetic resonance spectra of cations [1a-c]+ exhibited gav values of 1.997, 1.999, and 1.995, respectively, reflecting the ligand radical character of the oxidized forms, and in addition, spin-orbit coupling to the uranium centre. Chemical oxidation as monitored by ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy afforded the one-electron oxidized species. Weak low energy intra-ligand charge transfer (CT) transitions were observed for [1a-c]+ indicating localization of the ligand radical to form a phenolate / phenoxyl radical species. Further analysis using density functional theory (DFT) calculations predicted a localized phenoxyl radical for [1a-c]+ with a small but significant contribution of the phenylenediamine unit to the spin density. Time-dependent DFT (TD-DFT) calculations provided further insight into the nature of the low energy transitions, predicting both phenolate to phenoxyl intervalence charge transfer (IVCT) and phenylenediamine to phenoxyl CT character. Overall, [1a-c]+ are determined to be relatively localized ligand radical complexes, in which localization is enhanced as the electron donating ability of the para-phenolate substituents is increased (NMe2 > OMe > tBu)

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.

Further characterisation of substrate, inhibitor and ancillary protein specificity of MCT1, MCT2, MCT4 and MCT6

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Triplex staples: DNA double-strand cross-linking at internal and terminal sites using psoralen-containing triplex-forming oligonucleotides

A method has been developed to attach 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen to the 5 position of thymine bases during solid-phase oligonucleotide synthesis. UV irradiation of triplex-forming oligonucleotides (TFOs) containing internally attached psoralens produces photoadducts at TpA steps within target duplexes, thus relaxing the constraints on selection of psoralen target sequences. Photoreaction of TFOs containing two psoralens, located at the 5'- and 3'-ends, has been used to create double-strand cross-links (triplex staples) at both termini of the TFO. Such complexes have no free single-stranded ends. TFOs containing 4'-(hydroxymethyl)-4,5',8-trimethyl-psoralen, 3-methyl-2-aminopyridine, and 5-(3-aminoprop-2-ynyl)deoxyuridine formed photoadducts with target duplexes under near-physiological conditions