10 research outputs found

    Evidence That a RecQ Helicase Slows Senescence by Resolving Recombining Telomeres

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    RecQ helicases, including Saccharomyces cerevisiae Sgs1p and the human Werner syndrome protein, are important for telomere maintenance in cells lacking telomerase activity. How maintenance is accomplished is only partly understood, although there is evidence that RecQ helicases function in telomere replication and recombination. Here we use two-dimensional gel electrophoresis (2DGE) and telomere sequence analysis to explore why cells lacking telomerase and Sgs1p (tlc1 sgs1 mutants) senesce more rapidly than tlc1 mutants with functional Sgs1p. We find that apparent X-shaped structures accumulate at telomeres in senescing tlc1 sgs1 mutants in a RAD52- and RAD53-dependent fashion. The X-structures are neither Holliday junctions nor convergent replication forks, but instead may be recombination intermediates related to hemicatenanes. Direct sequencing of examples of telomere I-L in senescing cells reveals a reduced recombination frequency in tlc1 sgs1 compared with tlc1 mutants, indicating that Sgs1p is needed for tlc1 mutants to complete telomere recombination. The reduction in recombinants is most prominent at longer telomeres, consistent with a requirement for Sgs1p to generate viable progeny following telomere recombination. We therefore suggest that Sgs1p may be required for efficient resolution of telomere recombination intermediates, and that resolution failure contributes to the premature senescence of tlc1 sgs1 mutants

    The Effects of Multivitamin Supplementation on Diurnal Cortisol Secretion and Perceived Stress

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    Recent evidence suggests that dietary intake of vitamins, in particular the B-vitamins including B6, B9 and B12 may have a number of positive effects on mood and stress. Given the effects of stress on a range of biological mechanisms including the endocrine system, it could be reasonably expected that multivitamin supplementation may also affect markers of these mechanisms such as diurnal cortisol secretion. In the current double-blind placebo-controlled study 138 adults (aged 20 to 50 years) were administered a multivitamin containing B-vitamins versus placebo over a 16-week period. Salivary cortisol measurements were taken at waking, 15-min, 30-min and at bedtime, at baseline, 8-weeks and 16-weeks. Perceived Stress (PSS) was measured at baseline, 8-weeks and 16-weeks, while blood serum measures of B6, B12 and homocysteine (HCy) as well as red cell folate (B9) were also collected at these time points. A significant interaction was found between treatment group and study visit for the Cortisol Awakening Response (CAR). Compared to placebo, at 16-weeks multivitamin supplementation was found to be associated with a near-significant trend towards an increased CAR. No significant differences in PSS were found between groups, with PSS increasing in both groups across the course of the study. Red cell folate was found to be significantly correlated with the CAR response at 16-weeks while HCy levels were not found to be associated with the CAR response, although HCy significantly correlated with waking cortisol levels at 8-weeks. A possible interpretation of the elevation in CAR associated with multivitamin supplementation is that this represents an adaptive response to everyday demands in healthy participants

    Executive functioning in older adults with hoarding disorder.

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    BackgroundHoarding disorder (HD) is a chronic and debilitating psychiatric condition. Midlife HD patients have been found to have neurocognitive impairment, particularly in areas of executive functioning, but the extent to which this is due to comorbid psychiatric disorders has not been clear.Aims/methodThe purpose of the present investigation was to examine executive functioning in geriatric HD patients without any comorbid Axis I disorders (n = 42) compared with a healthy older adult comparison group (n = 25). We hypothesized that older adults with HD would perform significantly worse on measures of executive functioning (Wisconsin Card Sort Task [Psychological Assessment Resources, Lutz, Florida, USA] ( Psychological Assessment Resources, 2003) and the Wechsler Adult Intelligence Scale-IV digit span and letter-number sequencing tests [Pearson, San Antonio, TX, USA]).ResultsOlder adults with HD showed significant differences from healthy older controls in multiple aspects of executive functioning. Compared with healthy controls, older adults with HD committed significantly more total, non-perseverative errors and conceptual level responses on the Wisconsin Card Sort Task and had significantly worse performance on the Wechsler Adult Intelligence Scale-IV digit span and letter-number sequencing tests. Hoarding symptom severity was strongly correlated with executive dysfunction in the HD group.ConclusionsCompared with demographically-matched controls, older adults with HD have dysfunction in several domains of executive functioning including mental control, working memory, inhibition, and set shifting. Executive dysfunction is strongly correlated with hoarding severity and is not because of comorbid psychiatric disorders in HD patients. These results have broad clinical implications suggesting that executive functioning should be assessed and taken into consideration when developing intervention strategies for older adults with HD

    The effects of multivitamin supplementation on mood and general well-being in healthy young adults. A laboratory and at-home mobile phone assessment

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    Previous research has suggested that multivitamin (MV) supplementation may be GHQ-28associated with beneficial effects for mood and general well-being, although treatment durations have typically been less than 90 days, samples have often been restricted to males only and acute effects have not been adequately differentiated from chronic effects. In the current study a MV supplement containing high levels of B-vitamins was administered daily to 138 healthy young adult participants between the ages of 20 and 50 years over a 16-week period. Chronic mood measures (GHQ-28, POMS, Chalder fatigue, PILL, Bond-Lader and custom visual analogue scales) were administered pre-dose at baseline, 8- and 16-weeks. Changes in Bond-Lader and VAS in response to a multi-tasking framework (MTF) were also assessed at 8- and 16-weeks. For a subset of participants, at-home mobile-phone assessments of mood were assessed on a weekly basis using Bond-Lader and VAS. No significant treatment effects were found for any chronic laboratory mood measures. In response to the MTF, a significant treatment x time interaction was found for STAI-S, with a trend towards a greater increase in stress ratings for male participants in the MV group at 16 weeks. However, this finding may have been attributable to a larger proportion of students in the male MV group. In contrast, at-home mobile-phone assessments, where assessments were conducted post-dose, revealed significantly reduced stress, physical fatigue and anxiety in the MV group in comparison to placebo across a number of time points. Further research using both acute and chronic dosing regimens are required in order to properly differentiate these effects
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