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McMahon Stark posted an update 19 hours, 58 minutes ago
African swine fever virus (ASFV) is the causal agent of a fatal disease of domestic swine for which no effective antiviral drugs are available. Recently, it has been shown that microtubule-targeting agents hamper the infection cycle of different viruses. In this study, we conducted in silico screening against the colchicine binding site (CBS) of tubulin and found three new compounds with anti-ASFV activity. The most promising antiviral compound (6b) reduced ASFV replication in a dose-dependent manner (IC50 = 19.5 μM) with no cellular (CC50 > 500 μM) and animal toxicity (up to 100 mg/kg). Results also revealed that compound 6b interfered with ASFV attachment, internalization and egress, with time-of-addition assays, showing that compound 6b has higher antiviral effects when added within 2-8 h post-infection. This compound significantly inhibited viral DNA replication and disrupted viral protein synthesis. Experiments with ASFV-infected porcine macrophages disclosed that antiviral effects of the compound 6b were similar to its effects in Vero cells. Tubulin polymerization assay and confocal microscopy demonstrated that compound 6b promoted tubulin polymerization, acting as a microtubule-stabilizing, rather than a destabilizing agent in cells. In conclusion, this work emphasizes the idea that microtubules can be targets for drug development against ASFV.The COVID-19 pandemic presents unique stressors (e.g. social isolation) that may increase substance use risk among young adults with a history of emotional disturbance. This study examined whether emotional disorder symptoms and transdiagnostic vulnerabilities during adolescence predicted young adult substance use during COVID-19, and whether using substances to cope with the pandemic’s social conditions mediated these associations. Adolescents (N = 2,120) completed baseline surveys assessing transdiagnostic emotional vulnerabilities (anhedonia, distress intolerance, anxiety sensitivity, negative urgency) and symptoms (major depression[MD], generalized anxiety[GAD], panic disorder[PD], social phobia[SP], obsessive-compulsive disorder[OCD]) in adolescence (September-December 2016; M[SD] age = 17.45[0.38]). At follow-up (May-August 2020; M[SD] age = 21.16[0.39]), past 30-day substance use and using substances to cope with social isolation during the pandemic were reported. Adjusted models showed that baseline distress intolerance, anxiety sensitivity, negative urgency, and MD symptoms each significantly predicted higher number of past-month single-substance using days and number of substances used at follow-up (βs = 0.04-0.06). In each case, associations were mediated by tendency to use substances to cope with the pandemic (βindirect range 0.028-0.061). To mitigate disproportionate escalation of substance use in young adults with a history of certain types of emotional disturbance, interventions promoting healthy coping strategies to deal with the pandemic’s social conditions warrant consideration.Investigating the recall process of autobiographical memories (AMs) and, particularly, the order in which AMs are recalled has the potential to shed light on the organisation of autobiographical memory. However, research on order effects in the recall of AMs is relatively rare. Moreover, to date, no study addressed the question of where emotion fits into the organisation. The present study aimed to close this gap by examining whether emotional valence serves as one organising principle. Data come from 117 older adults (M = 74.11; SD = 7.06) who reported up to 39 AMs. The use of a multivariate multilevel model with autoregressive effects allows us to analyse the order effect within one person, as well as how the order effect differs between persons. The results replicated a temporal first-order effect that has been shown in previous studies and moreover, demonstrated a temporal second-order effect. Furthermore, our results indicated an emotional first-order effect that was even stronger than the temporal first-order effect and an emotional second-order effect. In addition, both first-order effects differed reliably between persons. Thus, the present study emphasises the need for considering emotion in current theoretical formulations of autobiographical memory and also of considering individual differences in the order of AMs recalled.Episodic future thinking (EFT) represents the ability to mentally simulate scenarios that will occur in our personal future. In the current study, we used the item choice paradigm, which puts chidren in a problematic situation and requires them to envision a solution by selecting one of various items. This ability was assessed in a sample of 92 preschoolers (3-6 years old), taking into account individual differences in age, gender, cognitive (verbal abilities, EFT memory) and affective (anxiety) factors, as well as contextual factors (motivational relevance). Findings indicate developmental progress in preschoolers’ foresight and in their retrospective memory for the item choice problems. The motivational valence of the EFT task played a significant role, as children performed better in the motivationally positive condition, as compared to the neutral and negative ones. However, older children had better performance than younger ones on the motivationally aversive tasks, becoming comparable to their performance in the motivationally appetitive condition. HS-173 nmr Finally, higher social anxiety was negatively related to children’s EFT performance in the aversive condition, when they anticipated negative social exposure. In conclusion, EFT was explained by age-related improvements, the motivational valence of the situation and by individual differences in social anxiety, which is highly relevant for educational and therapeutic practices.
Effort-reward imbalance (ERI) is a typical psychosocial stress. Schizotypal traits are attenuated features of schizophrenia in the general population. According to the diathesis-stress model, schizotypal traits and psychosocial stress contribute to the onset of schizophrenia. However, few studies examined the effects of these factors on brain alterations. This study aimed to examine relationships between ERI, schizotypal traits and brain structures and functions.
We recruited 37 (13 male, 24 female) participants with high levels of schizotypal traits and 36 (12 male, 24 female) participants with low levels of schizotypal traits by the Schizotypal Personality Questionnaire (SPQ). The Chinese school version of the effort-reward imbalance questionnaire (C-ERI-S) was used to measure ERI. We conducted the voxel-based morphometry (VBM) and whole brain resting-state functional connectivity (rsFC) analysis using reward or stress-related regions as seeds.
Participants with high levels of schizotypal traits were more likely to perceive ERI.