A Qualitative Analysis of a Positive Elite Parasport Performance Culture.

Organizational culture in sports affects well-being, performance, and overall success. Although team culture has been explored within able-bodied teams, little is known about culture development within parasport. Using a descriptive case study approach, our study examined the culture development and experiences of an elite parasport team. Two semistructured individual telephone interviews were conducted with nine participants (athletes and staff), and one athlete-participant completed one interview. An inductive thematic analysis revealed two themes: approach to culture development and team culture components. Culture development was linked with facilitative leadership and important resources. This supported the team to create their shared values and mechanisms, including a behavioral framework, other artifacts (e.g., shared language and team motto), and a relaxed environment. These helped to maintain their agreed culture and benefited their well-being, progress, and team cohesion. Our results offer a starting point regarding research into the culture of elite parasport and have practical implications for managers, coaches, and psychologists.

Early developmental arrest and impaired gastrointestinal homeostasis in U12-dependent splicing-defective Rnpc3-deficient mice.

Splicing is an essential step in eukaryotic gene expression. While the majority of introns is excised by the U2-dependent, or major class, spliceosome, the appropriate expression of a very small subset of genes depends on U12-dependent, or minor class, splicing. The U11/U12 65K protein (hereafter 65K), encoded by RNPC3, is one of seven proteins that are unique to the U12-dependent spliceosome, and previous studies including our own have established that it plays a role in plant and vertebrate development. To pinpoint the impact of 65K loss during mammalian development and in adulthood, we generated germline and conditional Rnpc3-deficient mice. Homozygous Rnpc3-/- embryos died prior to blastocyst implantation, whereas Rnpc3+/- mice were born at the expected frequency, achieved sexual maturity, and exhibited a completely normal lifespan. Systemic recombination of conditional Rnpc3 alleles in adult (Rnpc3lox/lox ) mice caused rapid weight loss, leukopenia, and degeneration of the epithelial lining of the entire gastrointestinal tract, the latter due to increased cell death and a reduction in cell proliferation. Accompanying this, we observed a loss of both 65K and the pro-proliferative phospho-ERK1/2 proteins from the stem/progenitor cells at the base of intestinal crypts. RT-PCR analysis of RNA extracted from purified preparations of intestinal epithelial cells with recombined Rnpc3lox alleles revealed increased frequency of U12-type intron retention in all transcripts tested. Our study, using a novel conditional mouse model of Rnpc3 deficiency, establishes that U12-dependent splicing is not only important during development but is indispensable throughout life.

Paralympic Legacy: Exploring the Impact of the Games on the Perceptions of Young People With Disabilities.

The London 2012 Olympic and Paralympic Games aimed to deliver a legacy to citizens of the United Kingdom, which included inspiring a generation of young people to participate in sport. This study aimed to understand the legacy of the Paralympic Games for children with disabilities. Eight adolescents (11-16 yr) with physical disabilities were interviewed about their perceptions of the Paralympic Games. Thematic analysis found 3 key themes that further our understanding of the Paralympic legacy. These were Paralympians as role models, changing perceptions of disability, and the motivating nature of the Paralympics. Findings demonstrate that the Games were inspirational for children with disabilities, improving their self-perceptions. This is discussed in relation to previous literature, and core recommendations are made.

Practitioner Review: Pathways to care for ADHD - a systematic review of barriers and facilitators.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder starting in childhood that may persist into adulthood. It can be managed through carefully monitored medication and nonpharmacological interventions. Access to care for children at risk of ADHD varies both within and between countries. A systematic literature review was conducted to investigate the research evidence related to factors which influence children accessing services for ADHD. METHOD: Studies investigating access to care for children at risk of ADHD were identified through electronic searches of the international peer-reviewed and grey literature. Databases were searched from inception till 30th April 2012. This identified 23,156 articles which were subjected to three levels of screening (title, abstract and full text) by a minimum of two independent reviewers. Due to the heterogeneity in the study designs, a narrative approach was used to present the findings. RESULTS: Twenty-seven papers met the inclusion criteria; these were grouped into four main themes, with some papers being included in more than one. These were wider determinants (10 papers); identification of need (9 papers); entry and continuity of care (13 papers) and interventions to improve access (4 papers). Barriers and facilitators to access were found to operate at the individual, organisational and societal level. Limited evidence of effective interventions to improve access was identified. CONCLUSION: This review explored the multilayered obstacles in the pathway to care for children at risk of ADHD and the lack of evidence-based interventions designed to address these issues, thereby indicating areas for service development and further evaluative research.

Identification of a Wnt-induced protein complex by affinity proteomics using an antibody that recognizes a sub-population of ß-catenin.

ß-catenin is a signaling protein with diverse functions in cell adhesion and Wnt signaling. Although ß-catenin has been shown to participate in many protein-protein interactions, it is not clear which combinations of ß-catenin-interacting proteins form discrete complexes. We have generated a novel antibody, termed 4B3, which recognizes only a small subset of total cellular ß-catenin. Affinity proteomics using 4B3, in combination with subcellular fractionation, has allowed us to define a discrete trimeric complex of ß-catenin, α-catenin and the tumor suppressor APC, which forms in the cytoplasm in response to Wnt signaling. Depletion of the limiting component of this complex, APC, implicates the complex in mediating Wnt-induced changes in cell-cell adhesion. APC is also essential for N-terminal phosphorylation of ß-catenin within this complex. Each component of ß-catenin/APC/α-catenin complex co-exists in other protein complexes, thus use of a selective antibody for affinity proteomics has allowed us to go beyond the generation of a list of potential ß-catenin-interacting proteins, and define when and where a specific complex forms.

The A2b adenosine receptor antagonist PSB-603 promotes oxidative phosphorylation and ROS production in colorectal cancer cells via adenosine receptor-independent mechanism.

PURPOSE: Adenosine is a multifaceted regulator of tumor progression. It modulates immune cell activity as well as acting directly on tumor cells. The A2b adenosine receptor (A2b-AR) is thought to be an important mediator of these effects. In this study we sought to analyze the contribution of the A2b-AR to the behavior of colorectal cancer cells. PRINCIPAL RESULTS: The A2b-AR antagonist PSB-603 changed cellular redox state without affecting cellular viability. Quantification of cellular bioenergetics demonstrated that PSB-603 increased basal oxygen consumption rates, indicative of enhanced mitochondrial oxidative phosphorylation. Unexpectedly, pharmacological and genetic approaches to antagonize AR-related signalling of PSB-603 did not abolish the response, suggesting that it was AR-independent. PSB-603 also induced acute increases in reactive oxygen species, and PSB-603 synergized with chemotherapy treatment to increase colorectal cancer cell death, consistent with the known link between cellular metabolism and chemotherapy response. MAJOR CONCLUSIONS: PSB-603 alters cellular metabolism in colorectal cancer cells and increases their sensitivity to chemotherapy. Although requiring more mechanistic insight into its A2b-AR-independent activity, our results show that PSB-603 may have clinical value as an anti-colorectal cancer therapeutic.

Parenting Interventions for ADHD: A Systematic Literature Review and Meta-Analysis.

OBJECTIVE: To evaluate the evidence base relating to the effectiveness of parent-administered behavioral interventions for ADHD. METHOD: A systematic review of randomized controlled trials or non-randomized but adequately controlled trials for children with ADHD or high levels of ADHD symptoms was carried out across multiple databases. For meta-analyses, the most proximal ratings of child symptoms were used as the primary outcome measure. RESULTS: Eleven studies met inclusion criteria (603 children, age range = 33-144 months). Parenting interventions were associated with reduction in ADHD symptoms (Standardized Mean Difference [SMD] = 0.68; 95% confidence interval [CI] [0.32, 1.04]). There was no evidence of attenuation of effectiveness after excluding studies where medication was also used. Parenting interventions were also effective for comorbid conduct problems (SMD = 0.59; 95% CI [0.29, 0.90]) and parenting self-esteem (SMD = 0.93; 95% CI [0.48, 1.39]). CONCLUSION: These findings support clinical practice guidelines and suggest that parenting interventions are effective. There is a need to ensure the availability of parenting interventions in community settings.

Immunopurification of adenomatous polyposis coli (APC) proteins.

BACKGROUND: The adenomatous polyposis coli (APC) tumour suppressor gene encodes a 2843 residue (310 kDa) protein. APC is a multifunctional protein involved in the regulation of ß-catenin/Wnt signalling, cytoskeletal dynamics and cell adhesion. APC mutations occur in most colorectal cancers and typically result in truncation of the C-terminal half of the protein. RESULTS: In order to investigate the biophysical properties of APC, we have generated a set of monoclonal antibodies which enable purification of recombinant forms of APC. Here we describe the characterisation of these anti-APC monoclonal antibodies (APC-NT) that specifically recognise endogenous APC both in solution and in fixed cells. Full-length APC(1-2843) and cancer-associated, truncated APC proteins, APC(1-1638) and APC(1-1311) were produced in Sf9 insect cells. CONCLUSIONS: Recombinant APC proteins were purified using a two-step affinity approach using our APC-NT antibodies. The purification of APC proteins provides the basis for detailed structure/function analyses of full-length, cancer-truncated and endogenous forms of the protein.

Empowering children with special educational needs to speak up: experiences of inclusive physical education.

PURPOSE: The inclusion of children with special educational needs (SEN) has risen up the political agenda since the return of the Labour Government in 1997. This has seen increasing numbers of children with SEN being educated within mainstream schools. METHOD: This study examines the perspectives of children with SEN attending both mainstream and special schools in relation to their experiences of physical education (PE). RESULTS: Findings demonstrate that children with SEN in both mainstream and special schools enjoy PE, although issues were raised in mainstream schools regarding bullying and the appropriateness of activities in PE lessons. The findings show how children offered suggestions about how to improve PE and make it more beneficial. The findings identify how children are empowered through consultation, and are aware of their needs and abilities. CONCLUSION: As such it is evident that schools and those supporting inclusive physical activity for children with SEN must use consultation as a tool for empowering pupils as a means of providing them with choices while gaining a rich insight into their lived experiences of PE.

Independent interactions of phosphorylated ß-catenin with E-cadherin at cell-cell contacts and APC at cell protrusions.

BACKGROUND: The APC tumour suppressor functions in several cellular processes including the regulation of ß-catenin in Wnt signalling and in cell adhesion and migration. FINDINGS: In this study, we establish that in epithelial cells N-terminally phosphorylated ß-catenin specifically localises to several subcellular sites including cell-cell contacts and the ends of cell protrusions. N-terminally phosphorylated ß-catenin associates with E-cadherin at adherens junctions and with APC in cell protrusions. We isolated APC-rich protrusions from stimulated cells and detected ß-catenin, GSK3ß and CK1α, but not axin. The APC/phospho-ß-catenin complex in cell protrusions appears to be distinct from the APC/axin/ß-catenin destruction complex. GSK3ß phosphorylates the APC-associated population of ß-catenin, but not the cell junction population. ß-catenin associated with APC is rapidly phosphorylated and dephosphorylated. HGF and wound-induced cell migration promote the localised accumulation of APC and phosphorylated ß-catenin at the leading edge of migrating cells. APC siRNA and analysis of colon cancer cell lines show that functional APC is required for localised phospho-ß-catenin accumulation in cell protrusions. CONCLUSIONS: We conclude that N-terminal phosphorylation of ß-catenin does not necessarily lead to its degradation but instead marks distinct functions, such as cell migration and/or adhesion processes. Localised regulation of APC-phospho-ß-catenin complexes may contribute to the tumour suppressor activity of APC.