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Background: Life events (LEs) are associated with future physical and mental health. They are crucial for understanding the pathways to mental disorders as well as the interactions with biological parameters. However, deeper insight is needed into the complex interplay between the type of LE, its subjective evaluation and accompanying factors such as social support. The "Stralsund Life Event List" (SEL) was developed to facilitate this research.
Methods: The SEL is a standardized interview that assesses the time of occurrence and frequency of 81 LEs, their subjective emotional valence, the perceived social support during the LE experience and the impact of past LEs on present life. Data from 2265 subjects from the general population-based cohort study "Study of Health in Pomerania" (SHIP) were analysed. Based on the mean emotional valence ratings of the whole sample, LEs were categorized as "positive" or "negative". For verification, the SEL was related to lifetime major depressive disorder (MDD; Munich Composite International Diagnostic Interview), childhood trauma (Childhood Trauma Questionnaire), resilience (Resilience Scale) and subjective health (SF-12 Health Survey).
Results: The report of lifetime MDD was associated with more negative emotional valence ratings of negative LEs (OR = 2.96, p < 0.0001). Negative LEs (b = 0.071, p < 0.0001, beta = 0.25) and more negative emotional valence ratings of positive LEs (b = 3.74, p < 0.0001, beta = 0.11) were positively associated with childhood trauma. In contrast, more positive emotional valence ratings of positive LEs were associated with higher resilience (b = -7.05, p < 0.0001, beta = 0.13), and a lower present impact of past negative LEs was associated with better subjective health (b = 2.79, p = 0.001, beta = 0.05). The internal consistency of the generated scores varied considerably, but the mean value was acceptable (averaged Cronbach's alpha > 0.75).
Conclusions: The SEL is a valid instrument that enables the analysis of the number and frequency of LEs, their emotional valence, perceived social support and current impact on life on a global score and on an individual item level. Thus, we can recommend its use in research settings that require the assessment and analysis of the relationship between the occurrence and subjective evaluation of LEs as well as the complex balance between distressing and stabilizing life experiences.
Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days.
A hotspot at a position compatible with the BL. Lac object 1ES 2322-409 was serendipitously detected with H.E.S.S. during observations performed in 2004 and 2006 on the blazar PKS 2316-423. Additional data on 1ES 2322-409 were taken in 2011 and 2012, leading to a total live-time of 22.3 h. Point-like very-high-energy (VHE; E > 100 GeV) gamma-ray emission is detected from a source centred on the IFS 2322-409 position, with an excess of 116.7 events at a significance of 6.0 sigma. The average VHE gamma-ray spectrum is well described with a power law with a photon index Gamma = 3.40 +/- 0.66(stat) +/- 0.20(sys) and an integral flux Phi(E > 200 GeV) = (3.11 +/- 0.71(stat) 0.62(sys)) x 10(-2)cm(-2)s(-1), which corresponds to 1.1 per cent of the Crab nebula flux above 200 GeV. Multiwavelength data obtained with Fermi LAT, Swift XRT and UVOT, RXTE PCA, ATOM, and additional data from WISE, GROND, and Catalina are also used to characterize the broad-band non-thermal emission of lES 2322-409. The multiwavelength behaviour indicates day-scale variability. Swift UVOT and XRT data show strong variability at longer scales. A spectral energy distribution (SED) is built from contemporaneous observations obtained around a high state identified in Swift data. A modelling of the SED is performed with a stationary homogeneous one-zone synchrotronself-Compton leptonic model. The redshift of the source being unknown, two plausible values were tested for the modelling. A systematic scan of the model parameters space is performed, resulting in a well-constrained combination of values providing a good description of the broad-band behaviour of 1ES 2322-409.
PKS 0625-354 (z = 0.055) was observed with the four High Energy Stereoscopic System (H.E.S.S.) telescopes in 2012 during 5.5 h. The source was detected above an energy threshold of 200 GeV at a significance level of 6.1 sigma. No significant variability is found in these observations. The source is well described with a power-law spectrum with photon index Gamma = 2.84 +/- 0.50(stat) +/- 0.10(syst) and normalization (at E-0 = 1.0 TeV) N-0(E-0)=(0.58 +/- 0.22(stat) +/- 0.12(syst)) x 10(-12) TeV-1 cm(-2) s(-1). Multiwavelength data collected with Fermi-LAT, Swift-XRT, Swift-UVOT, ATOM and WISE are also analysed. Significant variability is observed only in the Fermi-LAT gamma-ray and Swift-XRT X-ray energy bands. Having a good multiwavelength coverage from radio to very high energy, we performed a broad-band modelling from two types of emission scenarios. The results from a one zone lepto-hadronic and a multizone leptonic models are compared and discussed. On the grounds of energetics, our analysis favours a leptonic multizone model. Models associated to the X-ray variability constraint support previous results, suggesting a BL Lac nature of PKS 0625-354 with, however, a large-scale jet structure typical of a radio galaxy.
Dwarf spheroidal galaxies are among the most promising targets for detecting signals of Dark Matter (DM) annihilations. The H.E.S.S. experiment has observed five of these systems for a total of about 130 hours. The data are re-analyzed here, and, in the absence of any detected signals, are interpreted in terms of limits on the DM annihilation cross section. Two scenarios are considered: i) DM annihilation into mono-energetic gamma-rays and ii) DM in the form of pure WIMP multiplets that, annihilating into all electroweak bosons, produce a distinctive gamma-ray spectral shape with a high-energy peak at the DM mass and a lower-energy continuum. For case i), upper limits at 95% confidence level of about <sigma upsilon > less than or similar to 3 x 10(-25) cm(3) s(-1) are obtained in the mass range of 400 GeV to 1TeV. For case ii), the full spectral shape of the models is used and several excluded regions are identified, but the thermal masses of the candidates are not robustly ruled out.