Identification of a novel functional deletion variant in the 5'-UTR of the DJ-1 gene

<p>Abstract</p> <p>Background</p> <p>DJ-1 forms part of the neuronal cellular defence mechanism against oxidative insults, due to its ability to undergo self-oxidation. Oxidative stress has been implicated in the pathogenesis of central nervous system damage in different neurodegenerative disorders including Alzheimer's disease and Parkinson's disease (PD). Various mutations in the <it>DJ-1 </it>(<it>PARK7</it>) gene have been shown to cause the autosomal recessive form of PD. In the present study South African PD patients were screened for mutations in <it>DJ-1 </it>and we aimed to investigate the functional significance of a novel 16 bp deletion variant identified in one patient.</p> <p>Methods</p> <p>The possible effect of the deletion on promoter activity was investigated using a Dual-Luciferase Reporter assay. The <it>DJ-1 </it>5'-UTR region containing the sequence flanking the 16 bp deletion was cloned into a pGL4.10-Basic luciferase-reporter vector and transfected into HEK293 and BE(2)-M17 neuroblastoma cells. Promoter activity under hydrogen peroxide-induced oxidative stress conditions was also investigated. Computational (<it>in silico</it>) <it>cis</it>-regulatory analysis of <it>DJ-1 </it>promoter sequence was performed using the transcription factor-binding site database, TRANSFAC via the PATCH™ and rVISTA platforms.</p> <p>Results</p> <p>A novel 16 bp deletion variant (g.-6_+10del) was identified in <it>DJ-1 </it>which spans the transcription start site and is situated 93 bp 3' from a Sp1 site. The deletion caused a reduction in luciferase activity of approximately 47% in HEK293 cells and 60% in BE(2)-M17 cells compared to the wild-type (<it>P </it>< 0.0001), indicating the importance of the 16 bp sequence in transcription regulation. The activity of both constructs was up-regulated during oxidative stress. Bioinformatic analysis revealed putative binding sites for three transcription factors AhR, ARNT, HIF-1 within the 16 bp sequence. The frequency of the g.-6_+10del variant was determined to be 0.7% in South African PD patients (2 heterozygotes in 148 individuals).</p> <p>Conclusion</p> <p>This is the first report of a functional <it>DJ-1 </it>promoter variant, which has the potential to influence transcript stability or translation efficiency. Further work is necessary to determine the extent to which the g.-6_+10del variant affects the normal function of the <it>DJ-1 </it>promoter and whether this variant confers a risk for PD.</p

Pretend play and parents\u27 view of social competence: the construct validity of the Child-Initiated Pretend Play Assessment.

Background and Aims: Play is the primary means through which children develop skills and socially interact with other children. The aim of this study was to investigate the relationship between pretend play and social competence in 4&ndash;5-year-old typically developing children, thereby adding further knowledge to the construct validity of the Child-Initiated Pretend Play Assessment (ChIPPA). Procedure: The pretend play ability of 35 preschool children aged 4&ndash;5 years was assessed using the ChIPPA. Parent/guardians of the children were interviewed regarding their child\u27s social competence using the Vineland Social&ndash;Emotional Early Childhood Scales (Vineland SEEC Scales). Main Findings: No significant correlations were found between the children\u27s play scores and their Vineland SEEC Scales scores. A significant and negative relationship was found between cooperation and sharing and elaborate play scores, suggesting that children who scored poorly on the play assessment were rated as cooperative by parents. Principal Conclusions: Parent report of social competence cannot be inferred from play scores. Reasons for the negative and significant finding are put forward and clinical implications of the findings are discussed. Additional investigations are necessary to further explore the construct validity of inferring social competence using the ChIPPA. <br /

Impact of a Nature-Based Intervention on Incarcerated Women

Purpose: The purpose of this paper is to understand the impact of a short-term nature-based intervention on the social-emotional well-being of women incarcerated on a mental health unit in a state prison. Design/methodology/approach: This research used a mixed method approach with individual interviews, a focus group and a visual analog scale (VAS). Findings: Qualitative results found that women appreciated the planting party and the way the plants improved the physical environment. Women were also emotionally and relationally impacted by their participation and practiced skills related to planting and working with people. Quantitative results indicate that women were happier, calmer, and more peaceful after the intervention than before. Research limitations/implications: Study limitations include sample size, self-report data and use of a scale not yet tested for reliability and validity. Practical implications: Findings suggest that nature-based interventions can serve as an adjunct to traditional mental health therapies in correctional settings. Nature-based interventions can support womenÕs goals to improve their mental health. Social implications: Findings suggest that nature-based interventions can serve to improve relationships among incarcerated women, which may make a positive impact on the prison community. Such interventions may also assist them in developing relational and technical skills that are useful upon release. Originality/value: To date, there is limited knowledge about the impact of nature-based interventions on incarcerated individuals coping with mental health concerns. © 2018, Emerald Publishing Limited

Designing the Correctional Landscape: An Invitation to Landscape Architecture Professionals

The United States currently incarcerates more than two million men and women, the majority of whom struggle with poor mental health, substance abuse, and limited job prospects. Research suggests that access to natural environments improves personal and social well-being. Well-designed and well-built correctional landscapes have the potential to positively influence the lives of incarcerated people by improving their mental health and reentry outcomes and by reducing stress and fatigue among staff. This cannot happen without the active and committed involvement of landscape architects with the expertise to design environments that enhance the well-being of those who live and work in correctional facilities. We invite landscape architecture professionals to use their expertise to enhance and transform the correctional landscape, and we offer seven actions to facilitate such involvement. These actions emerged from lessons learned through three successful design-build projects inside IowaÕs only womenÕs state prison. © 2018, University of Wisconsin Press. All rights reserved

Nasopharyngeal rhinolith associated with chronic otorrhoea : a case report

The original publication is available at http://www.samj.org.zaCITATION: Hoffmann, A. J. & Wagenfeld, D. J. H. 1986. Rinoliet (neussteen) geassosieer met chroniese otorree : 'n gevalbespreking. South African Medical Journal, 69:200-201.A rare case of a 12-year-old girl with a nasopharyngeal rhinolith causing chronic unilateral otorrhoea is presented. The role of posterior rhinoscopy as an integral part of a routine otological examination is highlighted.Publisher’s versio