3,270 research outputs found
Variability and Proper Motion of X-ray Knots in the Jet of Centaurus A
Accepted to ApJ, 14 pages, 8 figures, 2 tablesWe report results from Chandra observations analyzed for evidence of variability and proper motion in the X-ray jet of Centaurus A. Using data spanning 15 yr, collective proper motion of 11.3 ± 3.3 mas yr -1 , or 0.68 ± 0.20c, is detected for the fainter X-ray knots and other substructure present within the jet. The three brightest knots (AX1A, AX1C, and BX2) are found to be stationary to an upper limit of . Brightness variations up to 27% are detected for several X-ray knots in the jet. For the fading knots, BX2 and AX1C, the changes in spectral slope expected to accompany synchrotron cooling are not found, ruling it out and placing upper limits of ≃80 μG for each of their magnetic field strengths. Adiabatic expansion can account for the observed decreases in brightness. Constraints on models for the origin of the knots are established. Jet plasma overrunning an obstacle is favored as the generator of stationary knots, while moving knots are likely produced either by internal differences in jet speed or the late stages of jet interaction with nebular or cloud material.Peer reviewe
Characterization of a novel angular dioxygenase from fluorene-degrading Sphingomonas sp. strain LB126
In this study, the genes involved in the initial attack on fluorene by
Sphingomonas sp. LB126 were investigated. The ? and ? subunits of a dioxygenase
complex (FlnA1A2), showing 63% and 51% sequence identity respectively, with the
subunits of an angular dioxygenase from Gram-positive Terrabacter sp. DBF63,
were identified. When overexpressed in E. coli, FlnA1A2 was responsible for the
angular oxidation of fluorene, fluorenol, fluorenone, dibenzofuran and
dibenzo-p-dioxin. Moreover, FlnA1A2 was able to oxidize polycyclic aromatic
hydrocarbons and heteroaromatics, some of which were not oxidized by the
dioxygenase from Terrabacter sp. DBF63. Quantification of resulting oxidation
products showed that fluorene and phenanthrene were preferred substrates
Adenosine A2A receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder
Autism spectrum disorders (ASDs) are heterogeneous disorders presenting with increased rates of anxiety. The adenosine A2A receptor gene (ADORA2A) is associated with panic disorder and is located on chromosome 22q11.23. Its gene product, the adenosine A2A receptor, is strongly expressed in the caudate nucleus, which also is involved in ASD. As autistic symptoms are increased in individuals with 22q11.2 deletion syndrome, and large 22q11.2 deletions and duplications have been observed in ASD individuals, in this study, 98 individuals with ASD and 234 control individuals were genotyped for eight single-nucleotide polymorphisms in ADORA2A. Nominal association with the disorder was observed for rs2236624-CC, and phenotypic variability in ASD symptoms was influenced by rs3761422, rs5751876 and rs35320474. In addition, association of ADORA2A variants with anxiety was replicated for individuals with ASD. Findings point toward a possible mediating role of ADORA2A variants on phenotypic expression in ASD that need to be replicated in a larger sample
Neutrophil Granulocytes in Ovarian Cancer - Induction of Epithelial-To- Mesenchymal-Transition and Tumor Cell Migration
Background: Ovarian cancer (OvCa) is a highly aggressive malignoma with a
tumor-promoting microenvironment. Infiltration of polymorphonuclear
neutrophils (PMN) is frequently seen, raising the question of their impact on
tumor development. In that context, effects of PMN on human ovarian cancer
cells were assessed. Methods: Human epithelial ovarian cancer cells were
incubated with human PMN, lysate of PMN, or neutrophil elastase. Morphological
alterations were observed by time-lapse video-microscopy, and the underlying
molecular mechanism was analyzed by flow cytometry and Western blotting.
Functional alternations were assessed by an in vitro wound healing assay. In
parallel, a large cohort of n=334 primary OvCa tissue samples of various
histological subtypes was histologically evaluated. Results: Co-cultivation of
cancer cells with either PMN or PMN lysate causes a change of the polygonal
epithelial phenotype of the cells towards a spindle shaped morphology, causing
a cribriform cell growth. The PMN-induced alteration could be attributed to
elastase, a major protease of PMN. Elastase-induced shape change was most
likely due to the degradation of membranous E-cadherin, which results in loss
of cell contacts and polarity. Moreover, in response to elastase, epithelial
cytokeratins were downmodulated, in parallel with a nuclear translocation of
β-catenin. These PMN-elastase induced alterations of cells are compatible with
an epithelial-to-mesenchymal transition (EMT) of the cancer cells. Following
EMT, the cells displayed a more migratory phenotype. In human biopsies,
neutrophil infiltration was seen in 72% of the cases. PMN infiltrates were
detected preferentially in areas with low E-cadherin expression. Conclusion:
PMN in the microenvironment of OvCa can alter tumor cells towards a
mesenchymal and migratory phenotype
Dose-dependent changes in real-life affective well-being in healthy community-based individuals with mild to moderate childhood trauma exposure
Background
Childhood trauma exposures (CTEs) are frequent, well-established risk factor for the development of psychopathology. However, knowledge of the effects of CTEs in healthy individuals in a real life context, which is crucial for early detection and prevention of mental disorders, is incomplete. Here, we use ecological momentary assessment (EMA) to investigate CTE load-dependent changes in daily-life affective well-being and psychosocial risk profile in n = 351 healthy, clinically asymptomatic, adults from the community with mild to moderate CTE.
Findings
EMA revealed significant CTE dose-dependent decreases in real-life affective valence (p = 0.007), energetic arousal (p = 0.032) and calmness (p = 0.044). Psychosocial questionnaires revealed a broad CTE-related psychosocial risk profile with dose-dependent increases in mental health risk-associated features (e.g., trait anxiety, maladaptive coping, loneliness, daily hassles; p values < 0.003) and a corresponding decrease in factors protective for mental health (e.g., life satisfaction, adaptive coping, optimism, social support; p values < 0.021). These results were not influenced by age, sex, socioeconomic status or education.
Conclusions
Healthy community-based adults with mild to moderate CTE exhibit dose-dependent changes in well-being manifesting in decreases in affective valence, calmness and energy in real life settings, as well as a range of established psychosocial risk features associated with mental health risk. This indicates an approach to early detection, early intervention, and prevention of CTE-associated psychiatric disorders in this at-risk population, using ecological momentary interventions (EMI) in real life, which enhance established protective factors for mental health, such as green space exposure, or social support
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Cholinergic modulation of disorder-relevant human defensive behaviour in generalised anxiety disorder
Drugs that are clinically effective against anxiety disorders modulate the innate defensive behaviour of rodents, suggesting these illnesses reflect altered functioning in brain systems that process threat. This hypothesis is supported in humans by the discovery that the intensity of threat-avoidance behaviour is altered by the benzodiazepine anxiolytic lorazepam. However, these studies used healthy human participants, raising questions as to their validity in anxiety disorder patients, as well as their generalisability beyond GABAergic benzodiazepine drugs. BNC210 is a novel negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor and we recently used functional Magnetic Resonance Imaging to show it reduced amygdala responses to fearful faces in generalised anxiety disorder patients. Here we report the effect of BNC210 on the intensity of threat-avoidance behaviour in 21 female GAD patients from the same cohort. We used the Joystick Operated Runway Task as our behavioural measure, which is a computerised human translation of the Mouse Defense Test Battery, and the Spielberger state anxiety inventory as our measure of state affect. Using a repeated-measures, within-subjects design we assessed the effect of BNC210 at two dose levels versus placebo (300 mg and 2000 mg) upon two types of threat-avoidance behaviour (Flight Intensity and Risk Assessment Intensity). We also tested the effects of 1.5 mg of the benzodiazepine lorazepam as an active control. BNC210 significantly reduced Flight Intensity relative to placebo and the low dose of BNC210 also significantly reduced self-reported state anxiety. Risk Assessment Intensity was not significantly affected. Results show both human defensive behaviour and state anxiety are influenced by cholinergic neurotransmission and there provide converging evidence that this system has potential as a novel target for anxiolytic pharmacotherapy
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