51 research outputs found

    Accommodative dynamics and attention: the influence of manipulating attentional capacity on accommodative lag and variability

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    Purpose: There is evidence that attention can modulate ocular dynamics, but its effects on accommodative dynamics have yet to be fully determined. We investigated the effects of manipulating the capacity to focus on task-relevant stimuli, using two levels of dual-tasking (arithmetic task) and auditory feedback, on the accommodative dynamics at three different target distances (500, 40 and 20 cm). Methods: The magnitude and variability of the accommodative response were objectively measured in 20 healthy young adults using the Grand Seiko WAM-5500 autorefractor. In randomised order, participants fixated on a Maltese cross while 1) performing an arithmetic task with two levels of complexity (low and high mental load); 2) being provided with two levels of auditory feedback (low and high feedback); and 3) without performing any mental task or receiving feedback (control). Accommodative and pupil dynamics were monitored for 90 seconds during each of the 15 trials (5 experimental conditions x 3 target distances). Results: The lag of accommodation was sensitive to the attentional state (p = 0.001), where a lower lag of accommodation was observed for the high feedback condition compared to the control (corrected p-value = 0.009). The imposition of mental load while fixating on a distant target led to a greater accommodative response (corrected p-value = 0.010), but no effects were found for the near targets. There was a main effect of the experimental manipulation on the accommodative variability (p < 0.001), with the use of auditory feedback improving the accuracy of the accommodative system. Conclusions: Our data show that accommodative dynamics is affected by varying the capacity to focus on task-relevant stimuli, observing an improvement in accommodative stability and response with auditory feedback. These results highlight an association between attention and ocular dynamics and provide new insight into the control of accommodation

    Protein Phosphatase 2A Mediates Dormancy of Glioblastoma Multiforme-Derived Tumor Stem-Like Cells during Hypoxia

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    The hypoxic microenvironment of glioblastoma multiforme (GBM) is thought to increase resistance to cancer therapies. Recent evidence suggests that hypoxia induces protein phosphatase 2A (PP2A), a regulator of cell cycle and cell death. The effects of PP2A on GBM tumor cell proliferation and survival during hypoxic conditions have not been studied.Expression of PP2A subunits and HIF-α proteins was measured in 65 high-grade astrocytoma and 18 non-neoplastic surgical brain specimens by western blotting. PP2A activity was measured by an immunoprecipitation assay. For in vitro experiments, GBM-derived tumor stem cell-like cells (TSCs) were exposed to severe hypoxia produced by either CoCl₂ or 1% O₂. PP2A activity was inhibited either by okadaic acid or by shRNA depletion of the PP2A C subunit. Effects of PP2A activity on cell cycle progression and cell survival during hypoxic conditions were assessed using flow cytometry.In our patient cohort, PP2A activity was positively correlated with HIF-1∝ protein expression (P = 0.002). Patients with PP2A activity levels above 160 pMP had significantly worse survival compared to patients with levels below this threshold (P = 0.002). PP2A activity was an independent predictor of survival on multivariable analysis (P = 0.009). In our in vitro experiments, we confirmed that severe hypoxia induces PP2A activity in TSCs 6 hours after onset of exposure. PP2A activity mediated G1/S phase growth inhibition and reduced cellular ATP consumption in hypoxic TSCs. Conversely, inhibition of PP2A activity led to increased cell proliferation, exhaustion of intracellular ATP, and accelerated P53-independent cell death of hypoxic TSCs.Our results suggest that PP2A activity predicts poor survival in GBM. PP2A appears to reduce the metabolic demand of hypoxic TSCs and enhances tumor cell survival. Modulation of PP2A may be a potential target for cancer therapy

    Designing programmes of physical activity through sport: Learning from a widening participation intervention, 'City of Football'

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    Background: Implementation profoundly influences how well new audiences engage with sport-based physical activity programmes. Recognising that effective implementation relies on concurrently generating supportive contexts, systems and networks for the least engaged ‘target’ groups; this paper aims to address what underpins children’s (non) engagement with football-based physical activity. Methods: An observational research design, using a non-probability sample of N=594 primary and secondary schoolchildren assessed outcomes of a three-year ‘City of Football’ (CoF) programme. Pupils self-reported football participation, personal friendship networks and exposure to six concurrent sources of influence (SoI). A 2-step hierarchical cluster analysis and univariate analyses assessed between-cluster differences. Results: Girls played football least regularly (χ2 [4] = 86.722, p = 0.000). Overall, participation was significantly associated with personal networks engaged in football. Boys’ personal networks were more stable and structurally effective. Football participation was also positively and linearly association with SoI scores. Girls and pupils with no personal networks around football reported the lowest SoI scores. Three clusters emerged, dominated by social network influences. The Traditional Market (n=157, 27.7%) comprised 81.7% boys; they regularly played football, had the most effective network structure and scored highly across all six domains of SoI. The Sporadically Engaging Socialisers (n=190, 33.5%) comprised 52.9% girls who rarely played football, reported low SoI scores and an inferior network structure. In the Disconnected cluster (n=220, 38.8%), 59.3% were non-footballing girls who reported the lowest motivation and ability SoI scores; and no personal networks engaged in football. Conclusions: This study reveals new insights about the primacy of social network effects for engaging children in football-based physical activity programmes. With little or no attention to these social-oriented issues, such interventions will struggle to attract ‘target’ children, but will readily engage already well-connected, experienced football-playing boys. The challenge for drawing non-footballing children into football-based interventions lies with engaging children – especially girls - whose social networks are not football-focused, while they also find football neither personally motivating nor easy to do

    Effects of Combinatorial Treatment with Pituitary Adenylate Cyclase Activating Peptide and Human Mesenchymal Stem Cells on Spinal Cord Tissue Repair

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    The aim of this study is to understand if human mesenchymal stem cells (hMSCs) and neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) have synergistic protective effect that promotes functional recovery in rats with severe spinal cord injury (SCI). To evaluate the effect of delayed combinatorial therapy of PACAP and hMSCs on spinal cord tissue repair, we used the immortalized hMSCs that retain their potential of neuronal differentiation under the stimulation of neurogenic factors and possess the properties for the production of several growth factors beneficial for neural cell survival. The results indicated that delayed treatment with PACAP and hMSCs at day 7 post SCI increased the remaining neuronal fibers in the injured spinal cord, leading to better locomotor functional recovery in SCI rats when compared to treatment only with PACAP or hMSCs. Western blotting also showed that the levels of antioxidant enzymes, Mn-superoxide dismutase (MnSOD) and peroxiredoxin-1/6 (Prx-1 and Prx-6), were increased at the lesion center 1 week after the delayed treatment with the combinatorial therapy when compared to that observed in the vehicle-treated control. Furthermore, in vitro studies showed that co-culture with hMSCs in the presence of PACAP not only increased a subpopulation of microglia expressing galectin-3, but also enhanced the ability of astrocytes to uptake extracellular glutamate. In summary, our in vivo and in vitro studies reveal that delayed transplantation of hMSCs combined with PACAP provides trophic molecules to promote neuronal cell survival, which also foster beneficial microenvironment for endogenous glia to increase their neuroprotective effect on the repair of injured spinal cord tissue
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