Dysregulations of the hypothalamic-pituitary-adrenal (HPA) and sympatho-adrenal medullary (SAM) axis are associated with mental and somatic illness. However, there is lack of knowledge regarding the ...molecular mechanisms underlying these effects. Epigenetic states in the serotonin transporter gene (SLC6A4) were shown to be associated with stress in various forms. We hypothesized that levels of DNA methylation (DNAm) of SLC6A4 would be associated with altered SAM- and HPA regulation in daily life. N = 74 healthy persons participated in the study. An ecological momentary assessment (EMA) approach was used to assess indicators of stress in daily life. Each day included six concurrent assessments of saliva, to quantify cortisol (sCort; HPA axis) and alpha-amylase (sAA; SAM axis), and to assess self-reports on subjective stress. To assess SLC6A4 DNAm, peripheral blood was drawn and analyzed via bisulfite pyrosequencing. All data were assessed in two waves three months apart, each including two days of EMA and the assessment of SLC6A4 DNAm. Data were analyzed using multilevel models. On the between-person level, higher average levels of SLC6A4 DNAm were associated with higher average levels of sAA, but not with average levels of sCort. On the within-person level, higher levels of SLC6A4 DNAm were associated with lower levels of sAA and sCort. There were no associations of subjective stress with SLC6A4 DNAm. The results help to clarify the association between environmental stress and stress axes regulation, pointing towards an important role of differential within- and between-person effects of SLC6A4 DNAm, which might shape this association.
•Repeated assessments of serotonin transporter gene methylation (SLC6A4 DNAm) and psychobiological stress in everyday life.•SLC6A4 DNAm is associated with psychobiological stress in everyday life.•Differential within- and between-person associations of SLC6A4 DNAm with psychobiological stress.•Higher SLC6A4 DNAm (within-person) is associated with a reduced output of salivary alpha-amylase and salivary cortisol.•Higher SLC6A4 DNAm (between-persons) is associated with an increased output of salivary alpha-amylase.
While the overall effects of social relationships on stress and health have extensively been described, it remains unclear how the experience of social interactions covaries with the activity of ...psychobiological stress in everyday life. We hypothesized that the valence as well as quantitative characteristics of social interactions in everyday life would attenuate psychobiological stress. Sixty healthy participants provided data for the analyses. Using an ecological momentary assessment design, participants received 6 prompts on their smartphone for 4 days. At each prompt, they reported on social interactions since the last prompt (
any occurrence
,
frequency
,
duration
,
quality
, and
perceived social support
), current subjective stress, and provided one saliva sample for the analyses of cortisol (sCort) and alpha-amylase (sAA). Experiencing any contact within days as well as higher daily levels of contact quality and perceived social support were associated with reduced levels of sCort. Furthermore, on a daily level, experiencing at least one contact in-between prompts more often as well as having more contacts on average attenuated the sAA output. Perceived social support and contact quality as well as higher daily contact durations were associated with lower subjective stress. For sCort, daily levels of stress moderated the effects of experiencing any contact within days while daily perceived social support moderated the effects of subjective stress. For sAA, experiencing at least one contact in-between prompts more often on a daily level moderated the effects of subjective stress. There were no between-person effects throughout all analyses. The results show ecologically valid evidence for direct attenuating effects of social interactions on psychobiological stress as well as for the stress-buffering hypothesis in everyday life. Increasing the quantity and improving the valence of social interactions
on an intrapersonal level
can possibly reduce psychobiological stress and prevent its consequences.
Purpose: To evaluate the prediction of vertebral fractures in plasma cell dyscrasias using dual-layer CT (DLCT) with quantitative assessment of conventional CT image data (CI), calcium suppressed ...image data (CaSupp), and calculation of virtual calcium-only (VCa) image data. Material and Methods: Patients (n = 81) with the diagnosis of a plasma cell dyscrasia and whole-body DLCT at the time of diagnosis and follow-up were retrospectively enrolled. CI, CaSupp25, and CaSupp100 were quantitatively analyzed using regions of interest in the lumbar vertebral bodies and fractured vertebral bodies on baseline or follow-up imaging. VCa were calculated by subtraction (CaSupp100-CaSupp25), delineating bone only. Logistic regression analyses were performed to assess the possibility of imminent spine fractures. Results: In 24 patients, new vertebral fractures were observed in the follow-up imaging. The possibility of new vertebral fractures was significant for baseline assessment of CT numbers in CI, CaSupp25, and VCa (p = 0.01, respectively), with a higher risk for new fractures in the case of lower CT numbers in CI (Odds ratio = 0.969; 0.994) and VCa (Odds ratio = 0.978; 0.995) and in the case of higher CT numbers in CaSupp 25 (Odds ratio 1.015 1.006; 1.026). Direct model comparisons implied that CT numbers in CaSupp 25 and VCa might show better fracture prediction than those in CI (R2 = 0.18 both vs. 0.15; AICc = 91.95, 91.79 vs. 93.62), suggesting cut-off values for CI at 103 HU (sensitivity: 54.2%; specificity: 82.5; AUC: 0.69), for VCa at 129 HU (sensitivity: 41.7%; specificity: 94.7; AUC: 0.72). Conclusions: Quantitative assessment with CaSupp and calculation of VCa is feasible to predict the vertebral fracture risk in MM patients. DLCT may prove useful in detecting imminent fractures.
Heat can be induced within a tissue enriched with magnetic nanoparticles by exposing it to an alternating magnetic field. In this paper we examine the evaluation of the heat distribution and ...therefore the temperature development around such a heat source which can be suitable for magnetic heating treatment. We study the heat transfer from tissue enriched with magnetic nanoparticles to regions of no or minor enrichment of nanoparticles, particularly. The evaluation of the temperature distribution took place with the help of a tissue phantom. The phantom is composed of two concentric cylinders. The inner cylinder consists of a defined mixture of polyurethane gel and magnetic fluid. This cylinder represents tissue enriched with nanoparticles. The outer cylinder, which stands for pure tissue consists of polyurethane only. This tissue phantom has been exposed to an alternating magnetic field according to the protocol of the magnetic heating treatment. The temperature measurements were performed by thermocouples which are placed on defined positions. The experimentally obtained temperature data is the basis for a finite element method (FEM) simulation model. The FEM model allows the determination of heat transition from regions enriched with magnetic nanoparticles to regions with no or minor nanoparticle accumulation.
Skin keratinocytes represent a primary entry site for herpes simplex virus 1 (HSV-1) in vivo. The cellular proteins nectin-1 and herpesvirus entry mediator (HVEM) act as efficient receptors for both ...serotypes of HSV and are sufficient for disease development mediated by HSV-2 in mice. How HSV-1 enters skin and whether both nectin-1 and HVEM are involved are not known. We addressed the impact of nectin-1 during entry of HSV-1 into murine epidermis and investigated the putative contribution of HVEM. Using ex vivo infection of murine epidermis, we showed that HSV-1 entered the basal keratinocytes of the epidermis very efficiently. In nectin-1-deficient epidermis, entry was strongly reduced. Almost no entry was observed, however, in nectin-1-deficient keratinocytes grown in culture. This observation correlated with the presence of HVEM on the keratinocyte surface in epidermis and with the lack of HVEM expression in nectin-1-deficient primary keratinocytes. Our results suggest that nectin-1 is the primary receptor in epidermis, while HVEM has a more limited role. For primary murine keratinocytes, on which nectin-1 acts as a single receptor, electron microscopy suggested that HSV-1 can enter both by direct fusion with the plasma membrane and via endocytic vesicles. Thus, we concluded that nectin-1 directs internalization into keratinocytes via alternative pathways. In summary, HSV-1 entry into epidermis was shown to strongly depend on the presence of nectin-1, but the restricted presence of HVEM can potentially replace nectin-1 as a receptor, illustrating the flexibility employed by HSV-1 to efficiently invade tissue in vivo.
Herpes simplex virus (HSV) can cause a range of diseases in humans, from uncomplicated mucocutaneous lesions to life-threatening infections. The skin is one target tissue of HSV, and the question of how the virus overcomes the protective skin barrier and penetrates into the tissue to reach its receptors is still open. Previous studies analyzing entry into cells grown in vitro revealed nectin-1 and HVEM as HSV receptors. To explore the contributions of nectin-1 and HVEM to entry into a natural target tissue, we established an ex vivo infection model. Using nectin-1- or HVEM-deficient mice, we demonstrated the distinct involvement of nectin-1 and HVEM for HSV-1 entry into epidermis and characterized the internalization pathways. Such advances in understanding the involvement of receptors in tissue are essential preconditions for unraveling HSV invasion of skin, which in turn will allow the development of antiviral reagents.
Mate choice is linked to costs such as time and energy effort or a higher risk of predation. Furthermore, reproduction with a partner of lower than average quality will reduce an individual's ...fitness. Copying the mate choice of others is assumed to reduce such costs. Most studies dealing with mate-choice copying focused on females, as they are usually expected to invest more into reproduction. However, in species where males provide brood care both sexes face high costs. Little is known about mate-choice copying in such mating systems. Male three-spined sticklebacks build nests and care for the offspring alone, facing a high-reproductive investment. Thus, one would expect that both males and females copy the mate choice of others. We gave male and female sticklebacks the opportunity to court either a partner that was visibly courted by another individual or a partner that was not visibly courted. Both spent significantly more time courting next to con-specifics after another individual has visibly courted them. Habituation effects, territorial defence or shoaling behaviour as alternative explanations were excluded by control experiments. The adaptive significance of mate-choice copying is not well understood. The results of this study indicate that in sticklebacks both sexes may reduce the costs of mate choice by copying the preferences of others.
2-Chloro-3-oxoalkanoates and related molecules were prepared by regioselective reaction of the dianion of ethyl 2-chloroacetoacetate with alkyl halides and other electrophiles.
Graphical Abstract
The replication of eukaryotic chromosomes takes place throughout S phase, but little is known how this process is organized in space and time. Early and late replicating chromosomal domains appear to ...localize to distinct spatial compartments of the nucleus where DNA synthesis can take place at defined times during S phase. In general, transcriptionally active chromatin replicates early in S phase whereas transcriptionally inactive chromatin replicates later. Here we provide evidence for significant deviation from this dogma in mouse NIH3T3 cells. While the bulk pericentromeric heterochromatin replicates exclusively during mid to late S phase, centromeric DNA domains associated with constitutive kinetochore proteins are replicated throughout all stages of S phase. On an average, 12+/-4% of centromeres replicate in early S phase. Early replication of a subset of centromeres was also detected in living C2C12 murine cells. Thus, in contrast to expectation, late replication is not an obligatory feature of centromeric heterochromatin in murine cells and it does not determine their 'heterochromatic state'.
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