25 research outputs found

    Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats

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    MDMA causes selective depletion of serotonergic terminals in experimental animals and the consequent decrease in synaptic 5-HT may, inter alia, increase impulsivity. To study the effects of MDMA upon brain function, the behaviour of male Dark Agouti rats exposed to MDMA (15 mg/kg i.p.), two 5-HT1B agonists (CGS-12066A and CP-94,253, both 5 mg/kg i.p.) or saline were investigated in the resident-intruder test. Studies were performed in drug-naive rats and also in rats exposed to MDMA (15 mg/kg i.p.) 21 d earlier. In parallel experiments the functional neuroanatomy of MDMA effects were assessed using 2-deoxyglucose imaging of local cerebral metabolic rate of glucose utilization (LCMRGlu) and neurotoxicity was assessed by measuring [H-3]paroxetine binding. There was no significant difference in aggressive behaviour (biting, boxing, wrestling and their latencies) between drug-naive rats and rats previously exposed to MDMA 21 d earlier, despite reduced social behaviour, decreased LCMRGlu in several brain areas involved in aggression, and reductions in paroxetine binding by 30-60'% in the forebrain. CGS12066A, CP-94,253 and acute MDMA produced marked decreases in aggressive behaviours, especially in biting, boxing and kicking found in drug-naive rats. In animals previously exposed to the drug, acute antiaggressive effects of MDMA were, in general, preserved as were MDMA-induced increases in LCMRGlu. Our studies provide evidence that in the resident-intruder test, where social isolation is a requirement, aggressive behaviour and acute anti-aggressive effects of MDMA and 5-HT,I, receptor agonists remain intact 3 wk after a single dose of the drug despite significant damage to the serotonergic system

    Resonance Damping in Ferromagnets and Ferroelectrics

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    The phenomenological equations of motion for the relaxation of ordered phases of magnetized and polarized crystal phases can be developed in close analogy with one another. For the case of magnetized systems, the driving magnetic field intensity toward relaxation was developed by Gilbert. For the case of polarized systems, the driving electric field intensity toward relaxation was developed by Khalatnikov. The transport times for relaxation into thermal equilibrium can be attributed to viscous sound wave damping via magnetostriction for the magnetic case and electrostriction for the polarization case.Comment: 5 pages no figures ReVTeX

    The impact of intermediate-term alcohol abstinence on memory retrieval and suppression

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    Background: The nature of episodic memory deficit in intermediate-term abstinence from alcohol in alcohol dependence (AD) is not yet clarified. Deficits in inhibitory control are commonly reported in substance use disorders. However, much less is known about cognitive control suppressing interference from memory. The Think/No-think (TNT) paradigm is a well established method to investigate inhibition of associative memory retrieval.Methods: Thirty-six unmedicated alcohol dependent (AD) patients and 36 healthy controls (HC) performed the TNT task. Thirty image-word pairs were trained up to a predefined accuracy level. Cued recall was examined in three conditions: Think (T) for items instructed to-be-remembered, No-think (NT) assessing the ability to suppress retrieval and Baseline (B) for general relational memory. Premorbid IQ, clinical variables and impulsivity measures were quantified. Results: AD patients had a significantly increased demand for training. Baseline memory abilities and effect of practice on retrieval were not markedly different between the groups. We found a significant main effect of group (HC vs AD) x condition (B, T and NT) and a significant difference in mean NT-B scores for the two groups. Discussion: AD and HC groups did not differ essentially in their baseline memory abilities. Also, the instruction to focus on retrieval improved episodic memory performance in both groups. Crucially, control participants were able to suppress relational words in the NT condition supporting the critical effect of cognitive control processes over inhibition of retrieval. In contrast to this, the ability of AD patients to suppress retrieval was found to be impaired

    Evolution of insect innate immunity through domestication of bacterial toxins

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    Toxin cargo genes are often horizontally transferred by phages between bacterial species and are known to play an important role in the evolution of bacterial pathogenesis. Here, we show how these same genes have been horizontally transferred from phage or bacteria to animals and have resulted in novel adaptations. We discovered that two widespread bacterial genes encoding toxins of animal cells, cytolethal distending toxin subunit B ( cdtB ) and apoptosis-inducing protein of 56 kDa ( aip56) , were captured by insect genomes through horizontal gene transfer from bacteria or phages. To study the function of these genes in insects, we focused on Drosophila ananassae as a model. In the D. ananassae subgroup species, cdtB and aip56 are present as singular ( cdtB ) or fused copies ( cdtB::aip56 ) on the second chromosome. We found that cdtB and aip56 genes and encoded proteins were expressed by immune cells, some proteins were localized to the wasp embryo’s serosa, and their expression increased following parasitoid wasp infection. Species of the ananassae subgroup are highly resistant to parasitoid wasps, and we observed that D. ananassae lines carrying null mutations in cdtB and aip56 toxin genes were more susceptible to parasitoids than the wild type. We conclude that toxin cargo genes were captured by these insects millions of years ago and integrated as novel modules into their innate immune system. These modules now represent components of a heretofore undescribed defense response and are important for resistance to parasitoid wasps. Phage or bacterially derived eukaryotic toxin genes serve as macromutations that can spur the instantaneous evolution of novelty in animals

    Advancing aircraft engine RUL predictions: an interpretable integrated approach of feature engineering and aggregated feature importance

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    Abstract In this study, we present a comprehensive approach for predicting the remaining useful life (RUL) of aircraft engines, incorporating advanced feature engineering, dimensionality reduction, feature selection techniques, and machine learning models. The process begins with a rolling time series window, followed by the extraction of a multitude of statistical features, and the application of principal component analysis for dimensionality reduction. We utilize a variety of feature selection methods, such as Genetic Algorithm, Recursive Feature Elimination, Least Absolute Shrinkage and Selection Operator Regression, and Feature Importances from a Random Forest model. As a significant contribution, we introduce the novel aggregated feature importances with cross-validation (AFICv) technique, which ranks features based on their mean importance. We establish a selection criterion that retains features with a cumulative mean sum equal to 70%, thereby reducing the complexity of machine learning models and enhancing their generalizability. Four machine learning regression models—Natural and Extreme Gradient Boosting, Random Forest, and Multi-Layer Perceptron—were employed to evaluate the effectiveness of the selected features. The performance of our proposed method is assessed by the evaluation metrics Root Mean Square Error (RMSE) and R2 Score, and also considered within-interval percentages and relative accuracy metrics. Importantly, a novel PCA interpretability was introduced to provide real-world context and enhance the utility of our findings for domain experts. Our results indicate that the proposed AFICv technique efficiently achieves competitive performance across the Commercial Modular Aero-Propulsion System Simulation (C-MAPSS) sub-datasets using a significantly smaller subset of features, thus contributing to a more effective and interpretable RUL prediction methodology for aircraft engines

    Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids

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    Multinucleated giant hemocytes (MGHs) represent a novel type of blood cell in insects that participate in a highly efficient immune response against parasitoid wasps involving isolation and killing of the parasite. Previously, we showed that circulating MGHs have high motility and the interaction with the parasitoid rapidly triggers encapsulation. However, structural and molecular mechanisms behind these processes remained elusive. Here, we used detailed ultrastructural analysis and live cell imaging of MGHs to study encapsulation in Drosophila ananassae after parasitoid wasp infection. We found dynamic structural changes, mainly driven by the formation of diverse vesicular systems and newly developed complex intracytoplasmic membrane structures, and abundant generation of giant cell exosomes in MGHs. In addition, we used RNA sequencing to study the transcriptomic profile of MGHs and activated plasmatocytes 72 h after infection, as well as the uninduced blood cells. This revealed that differentiation of MGHs was accompanied by broad changes in gene expression. Consistent with the observed structural changes, transcripts related to vesicular function, cytoskeletal organization, and adhesion were enriched in MGHs. In addition, several orphan genes encoding for hemolysin-like proteins, pore-forming toxins of prokaryotic origin, were expressed at high level, which may be important for parasitoid elimination. Our results reveal coordinated molecular and structural changes in the course of MGH differentiation and parasitoid encapsulation, providing a mechanistic model for a powerful innate immune response
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