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Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report (CTQ), but not for prospectively ascertained objective family adversity. Severity of childhood maltreatment was significantly associated with attenuated cortisol levels among carriers of the rs1360780 CC genotype, while no such effect emerged in carriers of the T allele. These findings point towards the functional involvement of FKBP5 in long-term alterations of neuroendocrine stress regulation related to childhood maltreatment, which have been suggested to represent a premorbid risk or resilience factor in the context of stress-related disorders. (C) 2013 Elsevier B.V. and ECNR This is an open access article under the CC BY-NC-ND license.
In the present study, we investigated the beneficial effects of trait self-compassion (SC) on perceived stress, shame, and the use of coping strategies in reaction to a socio-evaluative stressor while controlling for the effects of neuroticism (N) and conscientiousness (C). Participants (N = 105) performed a mental-arithmetic task with immediate in-person feedback. SC predicted less perceived stress and shame immediately after the stressor. Additionally, SC predicted less shame after a short recovery phase. This effect was fully mediated by less use of denial. Furthermore, SC buffered the effect of N on the use of denial, and C on shame after recovery. SC also predicted more use of positive reframing. Thus, SC may make a socio-evaluative stressor less threatening and may thwart a shame-inducing conception of the stressor by promoting clearer processing. Furthermore, SC may be especially beneficial for those vulnerable to dysfunctional coping and negative self-conscious emotions. This study contributes to the understanding of how trait self-compassion beneficially influences the processing of stressful situations.
Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.
SIRT6 is a NAD(+)-dependent deacetylase that modulates chromatin structure and safeguards genomic stability. Until now, SIRT6 has been assigned to the nucleus and only nuclear targets of SIRT6 are known. Here, we demonstrate that in response to stress, C. elegans SIR-2.4 and its mammalian orthologue SIRT6 localize to cytoplasmic stress granules, interact with various stress granule components and induce their assembly. Loss of SIRT6 or inhibition of its catalytic activity in mouse embryonic fibroblasts impairs stress granule formation and delays disassembly during recovery, whereas deficiency of SIR-2.4 diminishes maintenance of P granules and decreases survival of C. elegans under stress conditions. Our findings uncover a novel, evolutionary conserved function of SIRT6 in the maintenance of stress granules in response to stress.
Background: 'Stress' and 'health-related quality of life' (HRQoL) are two important theoretical constructs for modern therapy evaluation with clinical relevance. Eurythmy therapy (EYT) is a mind-body-therapy derived from anthroposophic medicine with promising effects on heart rate variability (HRV), HRQoL and disease scores. The purpose of this study was to investigate the impact of EYT on stress coping strategies (SCS) and HRQoL in a controlled study with moderately stressed participants.
Methods: 68 healthy, moderately stressed adults (mean age: 42.2; SD: 8.2) performed 10 h of EYT in a group setting over a period of six weeks. A non-randomised control group of 22 healthy adults (mean age: 43.6; SD: 13.7) received no intervention and did only complete the questionnaires at the same data points. Outcomes were measured before and after the intervention (AVEM & SF-36).
Results: A significant impact on SCS was found in seven AVEM scales (MANOVA, F (1/74) = 4.59; p = .04). With regard to changes in risk pattern affiliation (AVEM), 24% of the participants receiving EYT (n = 55) changed over time from a risky stress coping pattern to a healthier pattern. Concerning the HRQoL four normally distributed scales of the SF-36 ('vitality', 'social functioning', 'mental health' and 'physical functioning') showed a significant group x time interaction favouring the EYT group (MANOVA, F (1/74) = 17.26; p < .001). Statistically and clinically relevant mean differences over time of at least eight scale points were found for 'role physical', 'bodily pain', 'vitality' and 'mental health', and of at least 15 scale points for 'role emotional' and 'social functioning'.
Conclusions: A six-week period of EYT training can result in a significant reduction of stress and consequently improve QoL. Because a significant proportion of participants had high levels of stress at baseline the results suggest a health-enhancing benefit of EYT that may have clinical potential for prevention of stress and associated disorders in healthy individuals and possibly in patients with chronic diseases, for example.
Transcription factors (TFs) are ubiquitous gene expression regulators and play essential roles in almost all biological processes. This Ph.D. project is primarily focused on the functional characterisation of MYB112 - a member of the R2R3-MYB TF family from the model plant Arabidopsis thaliana. This gene was selected due to its increased expression during senescence based on previous qRT-PCR expression profiling experiments of 1880 TFs in Arabidopsis leaves at three developmental stages (15 mm leaf, 30 mm leaf and 20% yellowing leaf). MYB112 promoter GUS fusion lines were generated to further investigate the expression pattern of MYB112. Employing transgenic approaches in combination with metabolomics and transcriptomics we demonstrate that MYB112 exerts a major role in regulation of plant flavonoid metabolism. We report enhanced and impaired anthocyanin accumulation in MYB112 overexpressors and MYB112-deficient mutants, respectively. Expression profiling reveals that MYB112 acts as a positive regulator of the transcription factor PAP1 leading to increased anthocyanin biosynthesis, and as a negative regulator of MYB12 and MYB111, which both control flavonol biosynthesis. We also identify MYB112 early responsive genes using a combination of several approaches. These include gene expression profiling (Affymetrix ATH1 micro-arrays and qRT-PCR) and transactivation assays in leaf mesophyll cell protoplasts. We show that MYB112 binds to an 8-bp DNA fragment containing the core sequence (A/T/G)(A/C)CC(A/T)(A/G/T)(A/C)(T/C). By electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation coupled to qPCR (ChIP-qPCR) we demonstrate that MYB112 binds in vitro and in vivo to MYB7 and MYB32 promoters revealing them as direct downstream target genes. MYB TFs were previously reported to play an important role in controlling flavonoid biosynthesis in plants. Many factors acting upstream of the anthocyanin biosynthesis pathway show enhanced expression levels during nitrogen limitation, or elevated sucrose content. In addition to the mentioned conditions, other environmental parameters including salinity or high light stress may trigger anthocyanin accumulation. In contrast to several other MYB TFs affecting anthocyanin biosynthesis pathway genes, MYB112 expression is not controlled by nitrogen limitation, or carbon excess, but rather is stimulated by salinity and high light stress. Thus, MYB112 constitutes a previously uncharacterised regulatory factor that modifies anthocyanin accumulation under conditions of abiotic stress.
Between-individual differences in coping with stress encompass neurophysiological, cognitive and behavioural reactions. The coping style model proposes two alternative response patterns to challenges that integrate these types of reactions. The “proactive strategy” combines a general fight-or-flight response and inflexibility in learning with a relatively low HPA (hypothalamic–pituitary–adrenal) response. The “reactive strategy” includes risk aversion, flexibility in learning and an enhanced HPA response. Although numerous studies have investigated the possible covariance of cognitive, behavioural and physiological responses, findings are still mixed. In the present study, we tested the predictions of the coping style model in an unselected population of bank voles (Myodes glareolus) (N = 70). We measured the voles’ boldness, activity, speed and flexibility in learning and faecal corticosterone metabolite levels under three conditions (holding in indoor cages, in outdoor enclosures and during open field test). Individuals were moderately consistent in their HPA response across situations. Proactive voles had significantly lower corticosterone levels than reactive conspecifics in indoor and outdoor conditions. However, we could not find any co-variation between cognitive and behavioural traits and corticosterone levels in the open field test. Our results partially support the original coping style model but suggest a more complex relationship between cognitive, behavioural and endocrine responses than was initially proposed.
Aim The purpose of this study was to examine physical fitness and psycho-cognitive performance and their associations in young and middle-aged workers with primarily physical versus mental work demands. Subjects and methods Healthy young and middle-aged workers (73 men, age = 33 +/- 7 years; 75 women, age = 35 +/- 9 years) were recruited from German small-to-medium-sized enterprises (< 250 employees) and classified into groups with primarily mental (MD) or physical demands (PD) at work. Participants were tested for cardiorespiratory fitness, trunk flexor/extensor muscular endurance, handgrip strength, balance, leg muscle power, perceived stress, cognitive performance, and work ability. Results Ninety-four workers were allocated to the MD (53% females) and 54 to the PD (46% females) groups. The MD group showed significantly better balance, trunk extensor muscular endurance, and cognitive performance (p < 0.035, 0.35 <= d <= 0.55) and less stress compared with the PD group (p < 0.023, d = 0.38). Group-specific Spearman rank correlation analysis (r(S)) revealed significant small-to-medium-sized correlations between physical fitness and cognitive performance (- 0.205 <= r(S) <= 0.434) in the MD and PD groups. Significant small-to-medium-sized correlations were found for physical fitness and stress/work ability (0.211 <= r(S) <= 0.301) in the MD group only. Further, associations of trunk extensor muscular endurance and work ability were significantly higher in the MD group (r(S) = 0.240) compared with the PD group (r(S) = - 0.141; z = 2.16, p = 0.031). Conclusions MD workers showed better physical fitness measures (balance, trunk extensor muscular endurance) and cognitive performance and lower levels of perceived stress compared with PD workers. Small-to-medium-sized associations between physical fitness and psycho-cognitive performance measures indicate that gains in physical fitness may at least partly contribute to psycho-cognitive performance and/or vice versa, particularly in MD workers.
We study the averaged macroscopic strain tensor for a sand pile consisting of soft convex polygonal particles numerically, using the discrete-element method (DEM). First, we construct two types of "sand piles" by two different pouring protocols. Afterwards, we deform the sand piles, relaxing them under a 10% reduction of gravity. Four different types of methods, three best-fit strains and a derivative strain, are adopted for determining the strain distribution under a sand pile. The results of four different versions of strains obtained from DEM simulation are compared with each other. Moreover, we compare the vertical normal strain tensor between two types of sand piles qualitatively and show how the construction history of the piles affects their strain distribution.
Selective attention toward emotional cues and emotion recognition of facial expressions are important aspects of social cognition. Stress modulates social cognition through cortisol, which acts on glucocorticoid (GR) and mineralocorticoid receptors (MR) in the brain. We examined the role of MR activation on attentional bias toward emotional cues and on emotion recognition. We included 40 healthy young women and 40 healthy young men (mean age 23.9 +/- 3.3), who either received 0.4 mg of the MR agonist fludrocortisone or placebo. A dot-probe paradigm was used to test for attentional biases toward emotional cues (happy and sad faces). Moreover, we used a facial emotion recognition task to investigate the ability to recognize emotional valence (anger and sadness) from facial expression in four graded categories of emotional intensity (20, 30, 40, and 80 %). In the emotional dot-probe task, we found a main effect of treatment and a treatment x valence interaction. Post hoc analyses revealed an attentional bias away from sad faces after placebo intake and a shift in selective attention toward sad faces compared to placebo. We found no attentional bias toward happy faces after fludrocortisone or placebo intake. In the facial emotion recognition task, there was no main effect of treatment. MR stimulation seems to be important in modulating quick, automatic emotional processing, i.e., a shift in selective attention toward negative emotional cues. Our results confirm and extend previous findings of MR function. However, we did not find an effect of MR stimulation on emotion recognition.