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Interindividual variability in the regulation of the human stress system accounts for a part of the individual's liability to stress-related diseases. These differences are influenced by environmental and genetic factors. Early childhood adversity is a well-studied environmental factor affecting an individual's stress response which has been shown to be modulated by gene environment interaction (GxE). Neuropeptide Y (NPY) plays a role in stress regulation and genetic variation in NPY may influence stress responses. In this study, we analyzed the association of a common variant in the NPY gene promoter, rs16147, with cortisol and ACTH responses to acute psychosocial stress in young adults from the Mannheim Study of Children at Risk (MARS), an ongoing epidemiological cohort study following the outcome of early adversity from birth into adulthood. We found evidence of a GxE interaction between rs16147 and early adversity significantly affecting HPA axis responses to acute psychosocial stress. These findings suggest that the neurobiological mechanisms linking early adverse experience and later neuroendocrine stress regulation are modulated by a gene variant whose functional relevance is documented by increasing convergent evidence from in vitro, animal and human studies.
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.
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.
Background: The use of psychoactive substances to neuroenhance cognitive performance is prevalent. Neuroenhancement (NE) in everyday life and doping in sport might rest on similar attitudinal representations, and both behaviors can be theoretically modeled by comparable means-to-end relations (substance-performance). A behavioral (not substance-based) definition of NE is proposed, with assumed functionality as its core component. It is empirically tested whether different NE variants (lifestyle drug, prescription drug, and illicit substance) can be regressed to school stressors.
Findings: Participants were 519 students (25.8 +/- 8.4 years old, 73.1% female). Logistic regressions indicate that a modified doping attitude scale can predict all three NE variants. Multiple NE substance abuse was frequent. Overwhelming demands in school were associated with lifestyle and prescription drug NE.
Conclusions: Researchers should be sensitive for probable structural similarities between enhancement in everyday life and sport and systematically explore where findings from one domain can be adapted for the other. Policy makers should be aware that students might misperceive NE as an acceptable means of coping with stress in school, and help to form societal sensitivity for the topic of NE among our younger ones in general.
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.
Tea aroma is one of the most important factors affecting the character and quality of tea. Recent advances in methods and instruments for separating and identifying volatile compounds have led to intensive investigations of volatile compounds in tea. These studies have resulted in a number of insightful and useful discoveries. Here we summarize the recent investigations into tea volatile compounds: the volatile compounds in tea products; the metabolic pathways of volatile formation in tea plants and the glycosidically-bound volatile compounds in tea; and the techniques used for studying such compounds. Finally, we discuss practical applications for the improvement of aroma and flavor quality in teas. (C) 2013 Elsevier Ltd. All rights reserved.
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.
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.
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.
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.