386 research outputs found

    Error-related anterior cingulate cortex activity and the prediction of conscious error awareness

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    Research examining the neural mechanisms associated with error awareness has consistently identified dorsal anterior cingulate cortex (ACC) activity as necessary but not predictive of conscious error detection. Two recent studies (Steinhauser and Yeung, 2010; Wessel et al., 2011) have found a contrary pattern of greater dorsal ACC (dACC) activity [in the form of the error-related negativity (ERN)] during detected errors, but suggested that the greater activity may instead reflect task influences (e.g., response conflict, error probability) and or individual variability (e.g., statistical power). We re-analyzed fMRI BOLD data from 56 healthy participants who had previously been administered the Error Awareness Task (EAT), a motor Go/No-go response inhibition task in which subjects make errors of commission of which they are aware (Aware errors), or unaware (Unaware errors). Consistent with previous data, the activity in a number of cortical regions was predictive of error awareness, including bilateral inferior parietal and insula cortices, however, in contrast to previous studies, including our own smaller sample studies using the same task, error-related dACC activity was significantly greater during aware errors when compared to unaware errors. While the significantly faster RT for aware errors (compared to unaware) was consistent with the hypothesis of higher response conflict increasing ACC activity, we could find no relationship between dACC activity and the error RT difference. The data suggests that error awareness is associated with error-related dACC activity but that the role of this activity is probably best understood in relation to the activity in other regions. Activity in the dACC may be important to conscious error detection, but it remains unclear what task and individual factors influence error awareness

    Characterisation of equine cytochrome P450s

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    Cytochrome P450s (CYPs) are a superfamily of enzymes involved in the phase I metabolism of endogenous and exogenous substances. They are present in almost all forms of life and have been studied extensively, particularly in relation to human medicine, where knowledge of their activities is essential for predicting drug-drug interactions. In the horse, little is currently known about CYP-specific drug metabolism, which holds importance for animal welfare and for doping control within the horseracing industry where drug-specific metabolites are tested for on race days. Recently the first recombinant equine CYPs have been produced, allowing specific data on equine P450 activity to be gathered for the first time. During the current study,46 full-length P450 sequences were identified from the equine genome. RT-PCR analysis was then carried out on equine liver in order to detect hepatic expression of P450s across various families. After this, cold-induction (pCold) E. coli were used for production of recombinant P450 proteins for subsquent functional testing. Four recombinant equine P450s were successfully expressed (CYP1A1, CYP2A13, CYP2C92 and CYP2D50). Due to being the isoforms most likely to be involved in drug metabolism, rCYP2D50 and rCYP2C92 were selected to be screened against ten of the most commonly used horse drugs to identify potential substrates. rCYP2C92 appeared to metabolise all four NSAIDs tested (flunixin, ketoprofen, phenylbutazone and diclofenac), however presence of the known hydroxylated metabolites of diclofenac and phenylbutazone (4-hydroxydiclofenac and oxyphenbutazone, respectively) could not be confirmed despite being present within equine liver microsome and human recombinant CYP2C9 samples. In spite of the apparant acivity displayed by rCYP2C92 towards all four NSAIDs, no conclussions can be made about this enzyme’s role in NSAID metabolism due to a lack of known hydroxylated metabolite production

    Characterisation of equine cytochrome P450s

    Get PDF
    Cytochrome P450s (CYPs) are a superfamily of enzymes involved in the phase I metabolism of endogenous and exogenous substances. They are present in almost all forms of life and have been studied extensively, particularly in relation to human medicine, where knowledge of their activities is essential for predicting drug-drug interactions. In the horse, little is currently known about CYP-specific drug metabolism, which holds importance for animal welfare and for doping control within the horseracing industry where drug-specific metabolites are tested for on race days. Recently the first recombinant equine CYPs have been produced, allowing specific data on equine P450 activity to be gathered for the first time. During the current study,46 full-length P450 sequences were identified from the equine genome. RT-PCR analysis was then carried out on equine liver in order to detect hepatic expression of P450s across various families. After this, cold-induction (pCold) E. coli were used for production of recombinant P450 proteins for subsquent functional testing. Four recombinant equine P450s were successfully expressed (CYP1A1, CYP2A13, CYP2C92 and CYP2D50). Due to being the isoforms most likely to be involved in drug metabolism, rCYP2D50 and rCYP2C92 were selected to be screened against ten of the most commonly used horse drugs to identify potential substrates. rCYP2C92 appeared to metabolise all four NSAIDs tested (flunixin, ketoprofen, phenylbutazone and diclofenac), however presence of the known hydroxylated metabolites of diclofenac and phenylbutazone (4-hydroxydiclofenac and oxyphenbutazone, respectively) could not be confirmed despite being present within equine liver microsome and human recombinant CYP2C9 samples. In spite of the apparant acivity displayed by rCYP2C92 towards all four NSAIDs, no conclussions can be made about this enzyme’s role in NSAID metabolism due to a lack of known hydroxylated metabolite production

    Make/shift Pedagogies: Suggestions, Provocations, and Challenges for Teaching Introductory Gender and Women’s Studies Courses

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    Drawing on over four decades of diverse teaching experiences as well as our recent work facilitating the NWSA Curriculum Institute, this article discusses some of the politics and praxis of teaching the introductory Gender and Women’s Studies course in the U.S. academic classroom. While mapping different pedagogical strategies, it offers some suggestions, recommendations, and provocations that inform our commitment to design syllabi, plan courses, and teach materials that introduce students to formative works and concepts in Gender and Women’s Studies, chart current trends, and signal new developments in the field.  RĂ©sumĂ©En s’appuyant sur plus de quatre dĂ©cennies d’expĂ©riences d’enseignement diverses ainsi que sur nos travaux rĂ©cents pour organiser l’institut des programmes d’études de la NWSA, cet article discute certains aspects de la politique et de la pratique de l’enseignement du cours d’introduction Études sur le genre et les femmes dans les classes d’universitĂ© aux É.-U. Tout en exposant diffĂ©rentes stratĂ©gies pĂ©dagogiques, il propose des suggestions, des recommandations, et des idĂ©es provocantes qui contribuent Ă  notre engagement Ă  concevoir un programme d’études, Ă  planifier des cours et Ă  enseigner un contenu qui initient les Ă©tudiants aux travaux et aux concepts formateurs des Ă©tudes sur le genre et les femmes, rendent compte des tendances actuelles et signalent les nouveaux dĂ©veloppements dans le domaine

    Lines of School-University Partnership: Perception, Sensation and Meshwork Reshaping Of Pre-Service Teachers’ Experiences

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    School-university partnerships are complex, entangled and layered. As renewal of initial teacher education is at the forefront, understanding how we approach partnerships is imperative. This paper draws on reflective narratives of a school leader and initial teacher education staff involved in setting up a school-university partnership program. We identify the use of ‘meshworks’, that is complex and layered weaving of ideas or lines (Ingold, 2011; 2015; 2017) – specifically the lines of ‘partnership’, ‘partnership understanding’, ‘involvement’, ‘supporting pre-service teachers’, ‘noticing of pre-service teachers’, and ‘impact’. The analysis of the findings illuminate benefits from co-design and vision, while demonstrating how a call to action from Australian Institute for Teaching and School Leadership (AITSL) can illuminate how working closely together can support the development of pre-service teachers. We conclude by suggesting that future teacher quality is dependent upon the strength of the intersections of these school-university partnerships

    Cannabis use in early adolescence: evidence of amygdala hypersensitivity to signals of threat

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    Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n = 70) of 14-year olds with a history of cannabis use to a group (n = 70) of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated that cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood

    Anxious/depressed symptoms are related to microstructural maturation of white matter in typically developing youths

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    AbstractThere are multiple recent reports of an association between anxious/depressed (A/D) symptomatology and the rate of cerebral cortical thickness maturation in typically developing youths. We investigated the degree to which anxious/depressed symptoms are tied to age-related microstructural changes in cerebral fiber pathways. The participants were part of the NIH MRI Study of Normal Brain Development. Child Behavior Checklist A/D scores and diffusion imaging were available for 175 youths (84 males, 91 females; 241 magnetic resonance imagings) at up to three visits. The participants ranged from 5.7 to 18.4 years of age at the time of the scan. Alignment of fractional anisotropy data was implemented using FSL/Tract-Based Spatial Statistics, and linear mixed model regression was carried out using SPSS. Child Behavior Checklist A/D was associated with the rate of microstructural development in several white matter pathways, including the bilateral anterior thalamic radiation, bilateral inferior longitudinal fasciculus, left superior longitudinal fasciculus, and right cingulum. Across these pathways, greater age-related fractional anisotropy increases were observed at lower levels of A/D. The results suggest that subclinical A/D symptoms are associated with the rate of microstructural development within several white matter pathways that have been implicated in affect regulation, as well as mood and anxiety psychopathology.</jats:p
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