103 research outputs found
An analysis of child safeguarding cases managed by National Governing Bodies of sport across England and Wales
This study responded to a recommendation in the independent Duty of Care Report that called for standardised data to be collected and analysed regarding safeguarding cases in sport. A standardised case data tool was developed and piloted before being adopted by National Governing Bodies across England and Wales. An analysis of the first 4 years of data shows that a total of 3129 cases were managed. Overall, 54% of cases concerned behaviour outside of the context of sport. This demonstrates that sport plays an important role in the broader child protection system. In the remaining 46% of cases, the safeguarding concern was related to behaviour in the context of sport. The most commonly reported forms of concern in sport were physical abuse (20%), contact sexual abuse (20%), non‐contact sexual abuse (17%) and emotional abuse (17%). The threshold for cases to be included in the analysis was that the case was judged to be sufficiently serious to involve referral to, or consultation with, the Local Authority Designated Officer (LADO), Children's Services or the Police. There are clearly many cases that did not meet this threshold or were never reported, and hence, these data provide an indication of the safeguarding issues related to sport. The need to expand the tool to collect lower level concerns as well as to include safeguarding concerns regarding adults is advocated
Global Profiling of DNA Replication Timing and Efficiency Reveals that Efficient Replication/Firing Occurs Late during S-Phase in S. pombe
10.1371/journal.pone.0000722PLoS ONE2
Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis through downregulating Wee1 kinase
Cytokinesis involves temporally and spatially coordinated action of the cell cycle, cytoskeletal and membrane systems to achieve separation of daughter cells. The septation initiation network (SIN) and mitotic exit network (MEN) signaling pathways regulate cytokinesis and mitotic exit in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively. Previously, we have shown that in fission yeast the nucleolar protein Dnt1 negatively regulates SIN pathway in a manner independent of Cdc14-family phosphatase Clp1/Flp1, but the detailed mechanism of how Dnt1 modulates this pathway has remained elusive. In contrast, it is clear that its budding yeast relative, Net1/Cfi1, regulates the homologous MEN signaling pathway through sequestering the Cdc14 phosphatase in the nucleolus before mitotic exit. In this study, we have obtained evidence indicating that dnt1+ positively regulates the G2/M transition during cell cycle. By conducting epistasis analyses measuring the cell length at division of double mutants between dnt1Δ and genes involved in G2/M control, we found a link between dnt1+ and wee1+. Furthermore, we showed that elevated protein level of mitotic inhibitor Wee1 kinase and the corresponding attenuation in Cdk1 activity is responsible for the rescuing effect of dnt1Δ on SIN mutants. Finally, our data also suggest that Dnt1 modulates Wee1 activity in parallel with SCF-mediated Wee1 degradation. Therefore, this study reveals an unexpected missing link between the nucleolar protein Dnt1 and the SIN signaling pathway which is mediated by Cdk1 regulator Wee1 kinase. Our findings also define a novel mode of Wee1/Cdk1 regulation which is important for the integration of signals controlling SIN pathway in fission yeast.</jats:p
A Dynamic Stochastic Model for DNA Replication Initiation in Early Embryos
Background: Eukaryotic cells seem unable to monitor replication completion during normal S phase, yet must ensure a reliable replication completion time. This is an acute problem in early Xenopus embryos since DNA replication origins are located and activated stochastically, leading to the random completion problem. DNA combing, kinetic modelling and other studies using Xenopus egg extracts have suggested that potential origins are much more abundant than actual initiation events and that the time-dependent rate of initiation, I(t), markedly increases through S phase to ensure the rapid completion of unreplicated gaps and a narrow distribution of completion times. However, the molecular mechanism that underlies this increase has remained obscure.Methodology/Principal Findings: Using both previous and novel DNA combing data we have confirmed that I(t) increases through S phase but have also established that it progressively decreases before the end of S phase. To explore plausible biochemical scenarios that might explain these features, we have performed comparisons between numerical simulations and DNA combing data. Several simple models were tested: i) recycling of a limiting replication fork component from completed replicons; ii) time-dependent increase in origin efficiency; iii) time-dependent increase in availability of an initially limiting factor, e. g. by nuclear import. None of these potential mechanisms could on its own account for the data. We propose a model that combines time-dependent changes in availability of a replication factor and a fork-density dependent affinity of this factor for potential origins. This novel model quantitatively and robustly accounted for the observed changes in initiation rate and fork density.Conclusions/Significance: This work provides a refined temporal profile of replication initiation rates and a robust, dynamic model that quantitatively explains replication origin usage during early embryonic S phase. These results have significant implications for the organisation of replication origins in higher eukaryotes
Faculty Opinions recommendation of Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase.
Faculty Opinions recommendation of Mechanism of DNA translocation in a replicative hexameric helicase.
Faculty Opinions recommendation of Spliceosomal cleavage generates the 3' end of telomerase RNA.
Faculty Opinions recommendation of A dynamic stochastic model for DNA replication initiation in early embryos.
Faculty Opinions recommendation of Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.
Faculty Opinions recommendation of Formation and branch migration of Holliday junctions mediated by eukaryotic recombinases.
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