1,109 research outputs found

    Visual scanning patterns and executive function in relation to facial emotion recognition in aging

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    OBJECTIVE: The ability to perceive facial emotion varies with age. Relative to younger adults (YA), older adults (OA) are less accurate at identifying fear, anger, and sadness, and more accurate at identifying disgust. Because different emotions are conveyed by different parts of the face, changes in visual scanning patterns may account for age-related variability. We investigated the relation between scanning patterns and recognition of facial emotions. Additionally, as frontal-lobe changes with age may affect scanning patterns and emotion recognition, we examined correlations between scanning parameters and performance on executive function tests. METHODS: We recorded eye movements from 16 OA (mean age 68.9) and 16 YA (mean age 19.2) while they categorized facial expressions and non-face control images (landscapes), and administered standard tests of executive function. RESULTS: OA were less accurate than YA at identifying fear (p < .05, r = .44) and more accurate at identifying disgust (p < .05, r = .39). OA fixated less than YA on the top half of the face for disgust, fearful, happy, neutral, and sad faces (p values < .05, r values ≥ .38), whereas there was no group difference for landscapes. For OA, executive function was correlated with recognition of sad expressions and with scanning patterns for fearful, sad, and surprised expressions. CONCLUSION: We report significant age-related differences in visual scanning that are specific to faces. The observed relation between scanning patterns and executive function supports the hypothesis that frontal-lobe changes with age may underlie some changes in emotion recognition.Accepted manuscrip

    Investigation of a novel intein-based Escherichia coli expression system for human methylmalonyl CoA mutase : a thesis presented to Massey University in partial fulfilment of the requirements for the degree of Master of Science in Biochemistry

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    Human methylmalonyl CoA mutase (hMCM) is a 78 kDa homodimeric mitochondrial matrix enzyme. hMCM catalyses the conversion of 2R-methylmalonyl CoA to succinyl CoA in the metabolism of propionyl groups, and requires the vitamin B12 -derived cofactor adenosylcobalamin (AdoCbl). The mechanism of catalysis involves homolytic cleavage of AdoCbl's unusual C-Co bond, to generate radicals. Dysfunctional hMCM results in the rare, potentially fatal metabolic disorder methylmalonic acidemia. An experimentally determined structure of hMCM would add to the understanding of both the mechanism of catalysis and the molecular basis of some of the mutations underlying methylmalonic acidemia. The structure of the bacterial orthologue from Propionibacterium shermanii has been solved by x-ray crystallography, enabling the development of structural models of hMCM. Critical differences, however, between these two enzymes, mean that some regions of the models could be inaccurate. There is no x-ray crystal structure of hMCM. Purification of native hMCM for crystallization trials is complicated by ethical problems, low yields, and heterogeneity generated by the cofactor. To provide a more convenient source of pure, active human methylmalonyl CoA mutase for x-ray crystallography, an expression system for recombinant hMCM is required. Other researchers have expressed hMCM in Escherichia coli as (i) insoluble inclusion bodies, (ii) soluble fusion protein that cannot be separated efficiently from the fusion tag, or (iii) in low quantities. This research aimed to develop an E. coli expression system for the production of active human methylmalonyl CoA mutase, to enable x-ray crystallography structural studies. Based on the results of previous expression systems, four novel expression vectors were developed utilising the maltose binding protein and thioredoxin as solubility tags. It was hoped that conventional protease cleavage, to remove these solubility tags, could be circumvented by the use of intein-mediated cleavage. Intein-mediated cleavage was successful, and soluble active hMCM was recovered in low yields from a C-terminal thioredoxin solubility tag construct. hMCM was insoluble when expressed with MBP at the C-terminus

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    Tribute to the Late Dr. Charles D. Hufford

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    © 2019 The Authors. Purpose: Δ9-Tetrahydrocannabinol-valine-hemisuccinate, a hydrophilic prodrug of Δ9-tetrahydrocannabinol, synthesized with the aim of improving the ocular bioavailability of the parent molecule, was investigated in a lipid-based nanoparticle dosage form for ocular delivery. Methods: Solid lipid nanoparticles (SLNs) of Δ9-tetrahydrocannabinol-valine-hemisuccinate and Δ9-tetrahydrocannabinol, along with a nanoemulsion of Δ9-tetrahydrocannabinol-valine-hemisuccinate, were tested for glaucoma management in a normotensive rabbit model by using a multiple-dosing protocol. Marketed formulations of timolol maleate and pilocarpine HCl were also tested for their pharmacodynamic profile, post-single dose administration. Results: A peak intraocular pressure (IOP) drop of 30% from baseline was observed in rabbits treated with SLNs loaded with Δ9-tetrahydrocannabinol-valine-hemisuccinate at 90 minutes. Treated eyes of rabbits receiving Δ9-tetrahydrocannabinol-valine-hemisuccinate SLNs had significantly lower IOP than untreated eyes until 360 minutes, whereas the group receiving the emulsion formulation showed a drop in IOP until 90 minutes only. In comparison to marketed pilocarpine and timolol maleate ophthalmic solutions, Δ9-tetrahydrocannabinol-valine-hemisuccinate SLNs produced a greater effect on IOP in terms of both intensity and duration. In terms of tissue concentrations, significantly higher concentrations of Δ9-tetrahydrocannabinol-valine-hemisuccinate were observed in iris-ciliary bodies and retina-choroid with SLNs. Conclusion: Δ9-Tetrahydrocannabinol-valine-hemisuccinate formulated in a lipid-based nanoparticulate carrier shows promise in glaucoma pharmacotherapy. Translational Relevance: Glaucoma therapies usually focus on decreased aqueous humor production and increased outflow. However, such therapy is not curative, and there lies a need in preclinical research to focus efforts on agents that not only affect the aqueous humor dynamics but also provide neuroprotection. Historically, there have been bench-scale studies looking at retinal ganglion cell death post-axonal injury. However, for a smooth translation of this in vitro activity to the clinic, animal models examining IOP reduction, i.e., connecting the neuroprotective activity to a measurable outcome in glaucoma management (IOP), need to be investigated. This study investigated the IOP reduction efficacy of cannabinoids for glaucoma pharmacotherapy in a normotensive rabbit model, bringing forth a new class of agents with the potential of IOP reduction and improved permeation to the back of the eye, possibly providing neuroprotective benefits in glaucoma management

    Research in Higher Education: The Neverending Story

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    Residence for a suburban estate

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    Thesis (B.S.)--University of Illinois, 1905.Typescript.Bound with 3 other theses. IU-
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