907 research outputs found

    The DNA damage checkpoint pathway promotes extensive resection and nucleotide synthesis to facilitate homologous recombination repair and genome stability in fission yeast.

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    DNA double-strand breaks (DSBs) can cause chromosomal rearrangements and extensive loss of heterozygosity (LOH), hallmarks of cancer cells. Yet, how such events are normally suppressed is unclear. Here we identify roles for the DNA damage checkpoint pathway in facilitating homologous recombination (HR) repair and suppressing extensive LOH and chromosomal rearrangements in response to a DSB. Accordingly, deletion of Rad3(ATR), Rad26ATRIP, Crb2(53BP1) or Cdc25 overexpression leads to reduced HR and increased break-induced chromosome loss and rearrangements. We find the DNA damage checkpoint pathway facilitates HR, in part, by promoting break-induced Cdt2-dependent nucleotide synthesis. We also identify additional roles for Rad17, the 9-1-1 complex and Chk1 activation in facilitating break-induced extensive resection and chromosome loss, thereby suppressing extensive LOH. Loss of Rad17 or the 9-1-1 complex results in a striking increase in break-induced isochromosome formation and very low levels of chromosome loss, suggesting the 9-1-1 complex acts as a nuclease processivity factor to facilitate extensive resection. Further, our data suggest redundant roles for Rad3ATR and Exo1 in facilitating extensive resection. We propose that the DNA damage checkpoint pathway coordinates resection and nucleotide synthesis, thereby promoting efficient HR repair and genome stability

    Social support for and through exercise and sport in a sample of men with serious mental illness.

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    Social support is important for people experiencing serious mental illness and is also important during the initiation and maintenance of exercise. In this article we draw on interpretive research into the experiences of 11 men with serious mental illness to explore four dimensions of social support both for and through exercise. Our findings suggest that informational, tangible, esteem, and emotional support were both provided for and given by participants through exercise. We conclude that experiences of both receiving and giving diverse forms of support in this way are significant for some people living with and recovering from serious mental illness

    Spacial and temporal dynamics of the volume fraction of the colloidal particles inside a drying sessile drop

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    Using lubrication theory, drying processes of sessile colloidal droplets on a solid substrate are studied. A simple model is proposed to describe temporal dynamics both the shape of the drop and the volume fraction of the colloidal particles inside the drop. The concentration dependence of the viscosity is taken into account. It is shown that the final shapes of the drops depend on both the initial volume fraction of the colloidal particles and the capillary number. The results of our simulations are in a reasonable agreement with the published experimental data. The computations for the drops of aqueous solution of human serum albumin (HSA) are presented.Comment: Submitted to EPJE, 7 pages, 8 figure

    Development and preliminary validation of a tool measuring concordance and belief about performing pressure-relieving activities for pressure ulcer prevention in spinal cord injury

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    Objective: To develop and examine the reliability, and validity of a questionnaire measuring concordance for performing pressure-relief for pressure ulcer (PrU) prevention in people with Spinal Cord Injury (SCI). Methods: Phase I included item development, content and face validity testing. In phase II, the questionnaire was evaluated for preliminary acceptability, reliability and validity among 48 wheelchair users with SCI. Results: Thirty-seven items were initially explored. Item and factor analysis resulted in a final 26-item questionnaire with four factors reflecting concordance, perceived benefits, perceived negative consequences, and personal practical barriers to performing pressure-relief activities. The internal consistency reliability for four domains were very good (Cronbach's α = .75-.89). Pearson correlation coefficient on a test-retest of the same subjects yielded significant correlations in concordance (r = .91, p = .005), perceived benefit (r = .71, p < .04), perceived negative consequences (r = .98, p < .0001), personal barriers (r = .93, p= .002). Participants with higher levels of concordance reported a greater amount of pressure-relieving performed. Individuals viewing PrU as a threatening illness were associated with higher scores of concordance and tended to report a greater amount of pressure-relieving performance which provides evidence of criterion related validity. Conclusion: The new questionnaire demonstrated good preliminary reliability and validity in people with SCI. Further evaluation is necessary to confirm these findings using larger samples with follow-up data for predictive validity. Such a questionnaire could be used by clinicians to identify high risk of patients and to design individualised education programme for PrU prevention

    The structure of the nuclear stellar cluster of the Milky Way

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    We present high-resolution seeing limited and AO NIR imaging observations of the stellar cluster within about one parsec of Sgr A*, the massive black hole at the centre of the Milky Way. Stellar number counts and the diffuse background light density were extracted from these observations in order to examine the structure of the nuclear stellar cluster.Our findings are as follows: (a) A broken-power law provides an excellent fit to the overall structure of the GC nuclear cluster. The power-law slope of the cusp is Γ=0.19±0.05\Gamma=0.19\pm0.05, the break radius is Rbreak=6.0′′±1.0′′R_{\rm break} = 6.0'' \pm 1.0'' or 0.22±0.040.22\pm0.04 pc, and the cluster density decreases with a power-law index of Γ=0.75±0.1\Gamma=0.75\pm0.1 outside of RbreakR_{\rm break}. (b) Using the best velocity dispersion measurements from the literature, we derive higher mass estimates for the central parsec than assumed until now. The inferred density of the cluster at the break radius is 2.8±1.3×106M⊙pc−32.8\pm1.3\times 10^{6} {\rm M_{\odot} pc^{-3}}. This high density agrees well with the small extent and flat slope of the cusp. Possibly, the mass of the stars makes up only about 50% of the total cluster mass. (c) Possible indications of mass segregation in the cusp are found (d) The cluster appears not entirely homogeneous. Several density clumps are detected that are concentrated at projected distances of R=3′′R=3'' and R=7′′R=7'' from Sgr A*.(e) There appears to exist an under-density of horizontal branch/red clump stars near R=5′′R=5'', or an over-density of stars of similar brightness at R=3′′R=3'' and R=7′′R=7''. (f) The extinction map in combination with cometary-like features in an L'-band image may provide support for the assumption of an outflow from Sgr A*.Comment: accepted for publication by A&A; please contact first author for higher quality figure
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