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1.
Mol Cell ; 54(3): 445-59, 2014 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-24746700

RESUMO

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.


Assuntos
Proteína BRCA1/metabolismo , Reparo do DNA , Instabilidade Genômica , RNA Mensageiro/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , Genoma Humano , Células HEK293 , Humanos , Fosforilação , Processamento de Proteína Pós-Traducional , Splicing de RNA , Tolerância a Radiação , Proteínas Repressoras/metabolismo , Proteínas Supressoras de Tumor/metabolismo
2.
Children (Basel) ; 5(10)2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30257491

RESUMO

Despite the known benefits of engaging in daily moderate to vigorous physical activity (MVPA), only 22% of children in England are meeting the recommended guidelines. School break times have been advocated as a key part of children's daily routines in which their MVPA can be increased. The main aim of this study was to evaluate the effect of installing a walking-track on children's MVPA during school break times. A mixed method design was employed which allowed for the quantitative measurement of children's PA at three time points (baseline, mid-intervention (1⁻5 weeks) and follow-up (6⁻9 weeks)), using pedometers (n = 81, 5⁻9 years) and systematic observation (n = 23, 7⁻9 years). A semi-structured interview (n = 1) was also conducted at 10 weeks' follow-up. The installation of the walking-track was grounded in a unique set of theoretical constructs to aid the behaviour change of the teachers. Short term positive increases in girls' and boys' MVPA and longer term increases in boys' vigorous PA (VPA) were found. Qualitative data highlighted that boys dominated the walking-track and the inconsistent behaviour of school staff negatively impacted upon children's MVPA. A set of principles to guide the installment of walking-tracks in school playgrounds are recommended.

3.
Front Psychol ; 8: 1270, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824479

RESUMO

Mental toughness (MT) is a key psychological variable related to perseverance and success in performance domains. MT and its development has been explored across a range of contexts and across different sports, but no research to date has examined MT in relation to Paralympic athletes. We sought to understand the lived-experiences of mentally tough Paralympians, aiming to conceptualize MT in a Paralympic context and investigate its development. Ten Paralympic athletes were interviewed using in-depth, semi-structured interviews. The verbatim transcripts of the interviews served as the data for an interpretative phenomenological analysis. Three broad themes and several subthemes emerged in conceptualizing Paralympian MT: characteristics (determination, defiance, pragmatic, optimistic, resilient, self-belief and independence and autonomy), cognitions (normalization, sense of escape, non-acceptance of constraints, influence perception and connection) and cognitive strategies (rational thinking, goal setting, pain management and control). In understanding MT development, two broad themes and several subthemes emerged: formative experiences (challenge, classification, setbacks, critical incident, trauma and recovery, sustained commitment, development of mind-set and perspective during challenge, failure, and acceptance), and support and coping resources (social support and significant others, external shaping, social support, overcoming problems, social comparison and reflective practice). The findings suggest that Paralympians benefited from exposure to highly demanding situations in a supportive environment and this helped develop mentally tough characteristics and behaviors and individualized cognitive coping strategies. Our findings highlight the association between the adaptive development of personal characteristics by overcoming physical and mental setbacks over a sustained time period. Overall, the findings suggest that to develop mentally tough characteristics and behaviors, athletes in general could benefit from exposure to highly demanding situations in a supportive environment.

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