An improved measurement scheme for the determination of the retained austenite fraction with X-ray diffraction is extended to area detectors. The scheme reduces the error due to crystallographic ...texture in phase analysis of steel by averaging the results of diffraction patterns at different sample positions. The method is based on the standard ASTM E975, but it can be easily extended to other crystal structures, multi-phase materials or X-ray wavelengths.
Phase transformation, induced by mechanical sample preparation, may lead to a significant reduction of the retained austenite fraction. Electropolishing before the measurement is beneficial to remove the layer affected by sample preparation.
•Improved procedure to determine austenite in steels with crystallographic texture•Extension to X-ray area detectors•Electropolishing is essential to get correct results.
Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a ...mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0-T1: +3.37±2.17%), while non-responders further decreased in methylation (-2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02-0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.
ABSTRACT
Non-thermal emission from relativistic cosmic ray (CR) electrons gives insight into the strength and morphology of intra-cluster magnetic fields, as well as providing powerful tracers of ...structure formation shocks. Emission caused by CR protons on the other hand still challenges current observations and is therefore testing models of proton acceleration at intra-cluster shocks. Large-scale simulations including the effects of CRs have been difficult to achieve and have been mainly reduced to simulating an overall energy budget, or tracing CR populations in post-processing of simulation output and has often been done for either protons or electrons. We introduce crescendo: Cosmic Ray Evolution with SpeCtral Electrons aND prOtons, an efficient on-the-fly Fokker–Planck solver to evolve distributions of CR protons and electrons within every resolution element of our simulation. The solver accounts for CR (re-)acceleration at intra-cluster shocks, based on results of recent particle-in-cell simulations, adiabatic changes, and radiative losses of electrons. We show its performance in test cases as well as idealized galaxy cluster (GC) simulations. We apply the model to an idealized GC merger following best-fitting parameters for CIZA J2242.4 + 5301-1 and study CR injection, radio relic morphology, spectral steepening, and synchrotron emission.
Rationale
While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains ...elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation.
Objective
Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene.
Results
Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2
−/−
) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2
−/−
males displayed increased impulsivity and high aggressiveness. Tph2
−/−
females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2
−/−
male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner.
Conclusions
Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.
Abstract Exposure to prenatal stress (PS) can predispose individuals to the development of psychopathology later in life. We examined the effects of unpredictable chronic mild stress (CMS) exposure ...during adolescence on a background of PS in male and female Sprague-Dawley rats. PS induced more anxiety-like behavior in the elevated zero maze in both sexes, an effect that was normalized by subsequent exposure to CMS. Moreover, PS was associated with increased depression-like behavior in the forced swim test in males only. Conversely, sucrose intake was increased in PS males, whilst being decreased in females when consecutively exposed to PS and CMS. Hypothalamo–pituitary–adrenal (HPA) axis reactivity was affected in males only, with higher stress-induced plasma corticosterone levels after PS. Markedly, CMS normalized the effects of PS on elevated zero maze behavior as well as basal and stress-induced plasma corticosterone secretion. At the neurochemical level, both PS and CMS induced various sex-specific alterations in serotonin (5-HT) and tryptophan hydroxylase 2 (TPH2) immunoreactivity in the dorsal raphe nucleus, hippocampus and prefrontal cortex with, in line with the behavioral observations, more profound effects in male offspring. In conclusion, these findings show that prenatal maternal stress in Sprague-Dawley rats induces various anxiety- and depression-related behavioral and neuroendocrine changes, as well as alterations in central 5-HT and TPH2 function, predominantly in male offspring. Moreover, CMS exposure partially normalized the effects of previous PS experience, suggesting that the outcome of developmental stress exposure largely depends on the environmental conditions later in life and vice versa.
Abstract Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with impairments across the lifespan. The persistence of ADHD is associated with considerable ...liability to neuropsychiatric co-morbidity such as depression, anxiety and substance use disorder. The substantial heritability of ADHD is well documented and recent genome-wide analyses for risk genes revealed synaptic adhesion molecules (e.g. latrophilin-3, LPHN3 ; fibronectin leucine-rich repeat transmembrane protein-3, FLRT3 ), glutamate receptors (e.g. metabotropic glutamate receptor-5, GRM5 ) and mediators of intracellular signalling pathways (e.g. nitric oxide synthase-1, NOS1 ). These genes encode principal components of the molecular machinery that connects pre- and postsynaptic neurons, facilitates glutamatergic transmission, controls synaptic plasticity and empowers intersecting neural circuits to process and refine information. Thus, identification of genetic variation affecting molecules essential for the formation, specification and function of excitatory synapses is refocusing research efforts on ADHD pathogenesis to include the long-neglected glutamate system.
Abstract Background Suicide is a major health problem accounting for up to 1.5 percent of all deaths worldwide and represents one of the most common causes of death in adolescents and young adults. A ...number of studies has been performed to establish risk factors for suicide in patients with psychiatric disorders including temperamental features. This study set out to assess the relationship between suicidal ideation and temperament in young adults. Methods A cross-sectional sample of healthy college students (n = 1381) was examined using a self-rating questionnaire. Suicidal ideation, social background, educational status, substance abuse, and affective temperament according to TEMPS-M were assessed. Predictors of lifetime suicidal ideation were examined in multivariate logistic regression analyses. Results Suicidal ideation was reported by 12.5% of all subjects at some point in their life and was higher in nicotine dependents, youth with alcohol related problems and users of illicit substances as well as in youth with lower educational status. Lifetime suicidal ideation was associated with the anxious, depressive and cyclothymic temperament in both sexes and the irritable temperament in males. These results remained significant after adjustment for smoking status, frequency of alcohol consumption, drug experience and educational status in a multivariate logistic regression analysis. Limitations The use of self-rating instruments always reduces objectivity and introduces the possibility of misreporting. Conclusions Considering the fact that many subjects completing suicide have never been diagnosed with mental disorders it might be reasonable to include an investigation of temperament in screenings for risk of suicide. This might be especially useful for health care professionals without mental health care background.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. Core symptoms of ADHD, such as impulsivity, are caused by an interaction of ...genetic and environmental factors. Epigenetic modifications of DNA, such as DNA methylation, are thought to mediate the interplay of these factors. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin synthesis. The TPH2 gene has frequently been investigated in relation to ADHD, e.g., showing that TPH2 G-703T (rs4570625) polymorphism influences response control and prefrontal signaling in ADHD patients. In this (epi)genetic imaging study we examined 144 children and adolescents (74 patients, 14 females) using fMRI at rest and during performing a waiting impulsivity (WI) paradigm. Both, TPH2 G-703T (rs4570625) genotype and DNA methylation in the 5' untranslated region (5'UTR) of TPH2 were associated with wavelet variance in fronto-parietal regions and behavioral performance, taking TPH2 genotype into account. In detail, comparisons between genotypes of patients and controls revealed highest wavelet variance and longest reaction times in patients carrying the T allele indicative for a gene-dosage effect, i.e., the WI phenotype is a direct result of the cumulative effect of ADHD and TPH2 variation. Regressions revealed a significant effect on one specific DNA methylation site in ADHD patients but not controls, in terms of a significant prediction of wavelet variance in fronto-parietal regions as well as premature responses. By the example of the TPH2 G-703T (rs4570625) polymorphism, we provide insight into how interactive genetic and DNA methylation affect the ADHD and/or impulsive endophenotype.
Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological ...mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
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