An athletic approach to studying perception-action integration: Does sport-specific training, and the impact of injury, influence how individuals visually guide navigation?

The objective of this thesis was to investigate perception-action integration capabilities of individuals during a choice navigation task. This task assessed navigation strategies in open space while individuals avoided colliding with two vertical obstacles that created a body-scaled, horizontal gap, at three varying obstacle distances from the starting location (3m, 5m, 7m). The two studies completed in this thesis employed the same paradigm to assess the hypothesized group differences. Gaze behaviours and kinematics of navigation strategies were compared between: 1) athletes specifically trained in navigating in open space versus non-athletes; and 2) athletes with post-concussion syndrome (PCS) versus non-concussed, specifically trained athletes. Specifically trained athletes have been identified as demonstrating more successful perception-action integration in discrete motor tasks related to their sport (Mann et al., 2007; Vickers, 2007). However, whether these abilities translate to the continuous motor task of obstacle avoidance in open space was unknown. The purpose of Study 1 was to identify the influence of sport-specific training on navigating in open space (i.e. navigational strategies of large field sport athletes) compared to age-matched, non-athletes. It was hypothesized that specifically-trained athletes would demonstrate fewer, longer fixations, suggesting a more successful perception-action integration strategy (as defined by Mann et al., 2007), and would employ more sport-specific navigation strategies than non-athletes by maintaining their straight trajectory toward the goal (Fajen & Warren, 2003). Athletes were found to make fewer, longer fixations than non-athletes. However, no differences were observed between navigation strategies of the two groups, nor were any kinematic measures found to differ between groups. It can be concluded that athletes and non-athletes differentially obtain visual information to perform the same actions, suggesting that athletes and non-athletes differentially perform perception-action integration when navigating in open space. Future studies are required to identify sport-specific nuances of navigation (moving obstacles, running) to better identify athletic-related navigation strategies. Although athletic training can enhance perception-action integration strategies, sport-related injuries can hinder this process. Following a concussion, individuals experience deficits of perception-action integration that persist well beyond 30 days of recovery, post-concussion (Baker and Cinelli, 2014; Slobounov et al., 2006). These perception-action integration deficits may also exist in individual with postconcussion syndrome (PCS). The purpose of the Study 2 was to identify whether perception-action integration deficits persist with the persistent physical symptoms of concussion characteristic of PCS. The current study revealed that athletes with PCS did not differ from non-concussed athletes on any measure of visual fixation strategy, nor were they found to differ on any kinematic measure assessed. These findings suggest that in the context of the current paradigm, athletes with PCS have no perception-action integration deficit. In that, athletes with PCS may have adapted perception-action integration strategies to navigate with equal efficiency as a specifically-trained group of athletes or that the paradigm was not sensitive enough to identify these differences. Such findings suggest that more research is required to assess what, if any, perception-action integration deficits persist with persisting physical symptoms of PCS to better benefit rehabilitative procedures and outcomes for these individuals. Together, these studies add to what was previously known about perception-action integration, as it relates to navigation. Both studies assessed perception-action integration in unique populations that add to understanding of behavioural dynamics in the sport setting. Study 1 builds on a line of research assessing affordance theory and behavioural dynamics in sport (Fajen, Riley, & Turvey, 2008). The findings of this study suggest that although navigation strategies did not differ between specifically trained athletes and non-athletes, visual search strategies employed in task did. Such findings add to the understanding that sport-specific training influences perception-action integration, through our understanding of how athletes obtain visual information to perform actions. This thesis did not identify perception-action integration deficits in athletes with PCS. These findings suggest that the individuals in the present study likely adapted to their injury as they demonstrated equal ability in gaze and navigation strategies to specifically-trained athletes. As such, further research is required to assess the cognitive, motor, and sensory-motor deficits that may persist with the persisting physical symptoms of PCS. As individuals with PCS do not demonstrate similar visuomotor integration deficits as individuals with acute concussions (Baker & Cinelli, 2014), such individuals must be assessed and researched as a separate population

Dual protection in sexually active women.

OBJECTIVE: To determine the prevalence and co-factors associated with the practice of dual protection against sexually transmitted infections (STIs) and unwanted pregnancy in a cross-sectional sample of South African women. DESIGN: Secondary analysis of cross-sectional household survey data. METHODS: Statistical analysis of responses by sexually active women to the question, 'Was a condom used on the last occasion you had sex?' were obtained from the women's questionnaire of the South African Demographic and Health Survey in relation to a number of other variables. RESULTS: (i) 10.5% of all sexually active women aged 15-49 years used a condom at last sex and 6.3% used a condom as well as another contraceptive method; (ii) condom use is more likely among younger, more educated, more affluent, and urban women, and among women who change partners more frequently; (iii) reasons for not using condoms are more likely to be associated with the personal attitudes of women or their partners than with poor knowledge of or lack of access to condoms; (iv) women who have no need or desire to prevent pregnancy are less likely to use condoms; and (v) there is a minority of sexually active women, characterised by social disadvantage, who have difficulty obtaining condoms. CONCLUSIONS: There is an urgent need for targeted programmes that increase dual protection with condoms

Gadolinium decreases inflammation related to myocardial ischemia and reperfusion injury

<p>Abstract</p> <p>Background</p> <p>The lanthanide cation, gadolinium (GdCl₃) protects the myocardium against infarction following ischemia and reperfusion. Neutrophils and macrophages are the main leukocytes responsible for infarct expansion after reperfusion. GdCl₃interferes with macrophage and neutrophil function in the liver by decreasing macrophage secretion of inflammatory cytokines and neutrophil infiltration. We hypothesized that GdCl₃protects against ischemia and reperfusion injury by decreasing inflammation. We determined the impact of GdCl₃treatment for reperfusion injury on 1) circulating monoctye and neutrophil counts, 2) secretion of inflammatory cytokines, and 3) influx of monocytes and neutrophils into the myocardium.</p> <p>Methods</p> <p>Rats (n = 3-6/gp) were treated with saline or GdCl₃(20 μmol/kg) 15 min prior to a 30 min period of regional ischemia and 120 min reperfusion. Sham rats were not subject to ischemia. Blood was collected either after 30 min ischemia or 120 min reperfusion and hearts were harvested at 120 min reperfusion for tissue analysis. Blood was analyzed for leukocytes counts and cytokines. Tissue was analyzed for cytokines and markers of neutrophil and monocyte infiltration by measuring myeloperoxidase (MPO) and α-naphthyl acetate esterase (ANAE).</p> <p>Results</p> <p>GdCl₃did not affect the number of circulating neutrophils prior to ischemia. Two hours reperfusion resulted in a 2- and 3- fold increase in circulating monocytes and neutrophils, respectively. GdCl₃decreased the number of circulating monocytes and neutrophils during reperfusion to levels below those present prior to ischemia. Furthermore, after 120 min of reperfusion, GdCl₃decreased ANAE and MPO activity in the myocardium by 1.9-fold and 6.5-fold respectively. GdCl₃decreased MPO activity to levels below those measured in the Sham group. Serum levels of the major neutrophil chemoattractant cytokine, IL-8 were increased from pre-ischemic levels during ischemia and reperfusion in both control and GdCl₃treated rats. Likewise, IL-8 levels increased throughout the 3 hour time period in the Sham group. There was no difference in IL-8 detected in the myocardium after 120 min reperfusion between groups. In contrast, after 120 min reperfusion GdCl₃decreased the myocardial tissue levels of macrophage secreted cytokines, GM-CSF and IL-1.</p> <p>Conclusion</p> <p>GdCl₃treatment prior to ischemia and reperfusion injury decreased circulating monocytes and neutrophils, macrophage secreted cytokines, and leukocyte infiltration into injured myocardium. These results suggest GdCl₃decreased monoctye and neutrophil migration and activation and may be a novel treatment for inflammation during ischemia and reperfusion.</p

Period-1 Encodes an ATP-Dependent RNA Helicase that Influences Nutritional Compensation of the Neurospora Circadian Clock

Mutants in the period-1 (prd-1) gene, characterized by a recessive allele, display a reduced growth rate and period lengthening of the developmental cycle controlled by the circadian clock. We refined the genetic location of prd-1 and used whole genome sequencing to find the mutation defining it, confirming the identity of prd-1 by rescuing the mutant circadian phenotype via transformation. PRD-1 is an RNA helicase whose orthologs, DDX5 [DEAD (Asp-Glu-Ala-Asp) Box Helicase 5] and DDX17 in humans and DBP2 (Dead Box Protein 2) in yeast, are implicated in various processes, including transcriptional regulation, elongation, and termination, ribosome biogenesis, and mRNA decay. Although prd-1 mutants display a long period (∼25 h) circadian developmental cycle, they interestingly display a WT period when the core circadian oscillator is tracked using a frq-luciferase transcriptional fusion under conditions of limiting nutritional carbon; the core oscillator in the prd-1 mutant strain runs with a long period under glucose-sufficient conditions. Thus, PRD-1 clearly impacts the circadian oscillator and is not only part of a metabolic oscillator ancillary to the core clock. PRD-1 is an essential protein, and its expression is neither light-regulated nor clock-regulated. However, it is transiently induced by glucose; in the presence of sufficient glucose, PRD-1 is in the nucleus until glucose runs out, which elicits its disappearance from the nucleus. Because circadian period length is carbon concentration-dependent, prd-1 may be formally viewed as a clock mutant with defective nutritional compensation of circadian period length

De novo design of bioactive protein switches.

Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'. Encoded on the latch are functional motifs for binding, degradation or nuclear export that function only when the key displaces the latch from the cage. We describe orthogonal cage-key systems that function in vitro, in yeast and in mammalian cells with up to 40-fold activation of function by key. The ability to design switchable protein functions that are controlled by induced conformational change is a milestone for de novo protein design, and opens up new avenues for synthetic biology and cell engineering

Reducing in-stent restenosis therapeutic manipulation of miRNA in vascular remodeling and inflammation

Background: Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro–ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury.&lt;p&gt;&lt;/p&gt; Objectives: This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents.&lt;p&gt;&lt;/p&gt; Methods: Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis.&lt;p&gt;&lt;/p&gt; Results: We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation.&lt;p&gt;&lt;/p&gt; Conclusions: MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting

SUMO-Targeted Ubiquitin Ligases (STUbLs) Reduce the Toxicity and Abnormal Transcriptional Activity Associated With a Mutant, Aggregation-Prone Fragment of Huntingtin

Cell viability and gene expression profiles are altered in cellular models of neurodegenerative disorders such as Huntington\u27s Disease (HD). Using the yeast model system, we show that the SUMO-targeted ubiquitin ligase (STUbL) Slx5 reduces the toxicity and abnormal transcriptional activity associated with a mutant, aggregation-prone fragment of huntingtin (Htt), the causative agent of HD. We demonstrate that expression of an aggregation-prone Htt construct with 103 glutamine residues (103Q), but not the non-expanded form (25Q), results in severe growth defects in slx5Delta and slx8Delta cells. Since Slx5 is a nuclear protein and because Htt expression affects gene transcription, we assessed the effect of STUbLs on the transcriptional properties of aggregation-prone Htt. Expression of Htt 25Q and 55Q fused to the Gal4 activation domain (AD) resulted in reporter gene auto-activation. Remarkably, the auto-activation of Htt constructs was abolished by expression of Slx5 fused to the Gal4 DNA-binding domain (BD-Slx5). In support of these observations, RNF4, the human ortholog of Slx5, curbs the aberrant transcriptional activity of aggregation-prone Htt in yeast and a variety of cultured human cell lines. Functionally, we find that an extra copy of SLX5 specifically reduces Htt aggregates in the cytosol as well as chromatin-associated Htt aggregates in the nucleus. Finally, using RNA sequencing, we identified and confirmed specific targets of Htt\u27s transcriptional activity that are modulated by Slx5. In summary, this study of STUbLs uncovers a conserved pathway that counteracts the accumulation of aggregating, transcriptionally active Htt (and possibly other poly-glutamine expanded proteins) on chromatin in both yeast and in mammalian cells