The Antirheumatic Drug Gold, a Coin With Two Faces: AU(I) and AU(III). Desired and Undesired Effects on the Immune System

Three new findings are reviewed that help to understand the mechanisms of action of antirheumatic Au(I) drugs, such as disodium aurothiomalate (Na2Au(I)TM): (i) We found that Na2Au(I)TM selectively inhibits T cell receptor (TCR)-mediated antigen recognition by murine CD4+ T cell hybridomas specific for antigenic peptides containing at least two cysteine residues. Presumably, Au(I) acts as a chelating agent forming linear complexes (Cys-Au(I)-Cys) which prevent correct antigen-processing and/or peptide recognition by the TCR. (ii) We were able to show that Au(I) is oxidized to Au(III) in phagocytic cells, such as macrophages. Because Au(III) is re-reduced to Au(I) this may introduce an Au(I)/Au(III) redox system into phagocytes which scavenges reactive oxygen species, such as OCl- and inactivates lysosomal enzymes. (iii) Pretreatment with Au(III) of a model protein antigen, bovine ribonuclease A (RNase A), induced novel antigenic determinants recognized by CD4+ T lymphocytes. Analysis of the fine specificity of these ‘Au(III)-specific’ T cells revealed that they react to RNase peptides that are not presented to T cells when the native protein, i.e., not treated with Au(III), is used as antigen. The T cell recognition of these cryptic peptides did not require the presence of gold. This finding has important implications for understanding the pathogenesis of allergic and autoimmune responses induced by Au(I) drugs. Taken together, our findings indicate that Au(I) and Au(III) each exert specific effects on several distinct components of macrophages and the subsequent activation of T cells; these effects may explain both the desired anti-inflammatory and the adverse effects of antirheumatic gold drugs

“Trust me, do not trust anyone”: how epistemic mistrust and credulity are associated with conspiracy mentality

Previous research shows that the propensity to endorse conspiracy theories is associated with disrupted forms of epistemic trust, i.e., the appropriate openness towards interpersonally communicated information. There are associations, first, with an increased mistrust in several actors and institutions responsible for the communication of information in society, and second, with a pronounced credulity in unreliable sources and implausible phenomena (e.g., superstition, astrology). This study aims to investigate whether these phenomena are associated with specific personality-related disruptions of epistemic trust. Based on selfreported data of 417 individuals (mean = 33.28; standard deviation = 11.11) from a UK population sampled online, the potential relationships between disruptions in epistemic trust and the endorsement of a conspiracy mentality are explored. The epistemic stances characterized by mistrust and credulity (independent variables) are measured with the epistemic trust, mistrust, and credulity questionnaire (ETMCQ), and conspiracy mentality (dependent variable) is measured with the conspiracy mentality questionnaire. In a multiple linear regression model, mistrust is associated with the endorsement of a conspiracy mentality, even when accounting for other contributing factors (e.g., individual narcissism, attachment avoidance and anxiety, authoritarianism, loneliness). In a bootstrapped mediation model controlling for other relevant predictors, the association between credulity and conspiracy mentality is fully mediated by mistrust. In future research, the impact of disrupted epistemic trust on conspiracy beliefs should be investigated in terms of the specific epistemic stances of mistrust and credulity. In this respect, the ETMCQ represents a highly promising instrument to assess individual differences in factors underpinning aspects of conspiracy endorsement

Enhancement of the helium resonance lines in the solar atmosphere by suprathermal electron excitation II: non-Maxwellian electron distributions

In solar EUV spectra the He I and He II resonance lines show unusual behaviour and have anomalously high intensities compared with other transition region lines. The formation of the helium resonance lines is investigated through extensive non-LTE radiative transfer calculations. The model atmospheres of Vernazza, Avrett & Loeser are found to provide reasonable matches to the helium resonance line intensities but significantly over-estimate the intensities of other transition region lines. New model atmospheres have been developed from emission measure distributions derived by Macpherson & Jordan, which are consistent with SOHO observations of transition region lines other than those of helium. These models fail to reproduce the observed helium resonance line intensities by significant factors. The possibility that non-Maxwellian electron distributions in the transition region might lead to increased collisional excitation rates in the helium lines is studied. Collisional excitation and ionization rates are re-computed for distribution functions with power law suprathermal tails which may form by the transport of fast electrons from high temperature regions. Enhancements of the helium resonance line intensities are found, but many of the predictions of the models regarding line ratios are inconsistent with observations. These results suggest that any such departures from Maxwellian electron distributions are not responsible for the helium resonance line intensities.Comment: 23 pages, 11 figures, accepted to appear in MNRAS, LaTeX uses mn.st

Probing commitment in individuals with borderline personality disorder

Interpersonal problems are a core symptom of borderline personality disorder (BPD). In particular, patients with BPD exhibit a heightened sensitivity to cues of acceptance or rejection in their relationships. The current study investigated the psychological processes underpinning this heightened responsiveness. In a between-subjects design, we implemented a reactivity induction designed to trigger either acceptance or rejection of a partner in two separate groups, and measured the effects which this manipulation had upon 49 patients with BPD, as well as 52 control participants. The experimental paradigm required participants to repeatedly choose whether to coordinate with their partner on a decision-making task. When both players coordinate on the same option, both are rewarded. The experiment probed participants’ commitment to their partners: participants were sometimes presented with tempting opportunities to unilaterally defect from the coordination. The results show that participants in the BPD group were less committed than participants in the control group when exposed to the rejection manipulation

The reinforcement of xenophobia by limited mentalizing capacities

Recent mentalization theory has given greater attention to the social contexts of mentalizing, whereupon it has been hypothesized that limited mentalizing on societal levels (e.g. when psychic equivalence becomes institutional) may lead to the reinforcement of prejudices against individuals perceived as "the other", especially in contexts of threat (Asen et al., 2019). Along with this hypothesis, a representative population survey in Germany has revealed, by using a screening instrument, that limited mentalizing is associated with increased group-focused enmity (e.g., xenophobia, racism) (Krott & Reininger, 2021). Besides, empirical hints to potential links between mentalizing and outgroup-related attitudes can also be derived from other studies: In several fMRI studies, neuronal networks associated with mentalizing (e.g. VMPFC, DMPFC, OFC) are found to influence race-related assumptions (Mattan et al., 2018). In several cross-sectional studies, low levels of perspective-taking abilities are associated with prejudices against racial or ethnic outgroup members (Todd & Galinsky 2014); longitudinal and experimental designs also show reinforcing effects of limited perspective-taking on anti-immigrant attitudes (e.g. Miklikowska et al., 2017; Shih et al., 2009). Within a mentalization-based framework, perspective-taking can be understood as a crucial subdimension of mentalizing (Luyten et al. 2020). Building on these previous findings, the aim of our study is to investigate whether limited mentalizing capacities can contribute to the reinforcement of xenophobia

Interpersonal Problems in Borderline Personality Disorder: Associations with Mentalizing, Emotion Regulation, and Impulsiveness

Interpersonal problems are a core symptom of borderline personality disorder (BPD). This study investigated the relationship between emotion dysregulation, impulsiveness, and impaired mentalizing in the context of predicting interpersonal problems in BPD. A total of 210 patients with BPD completed the Difficulties in Emotion Regulation Scale (DERS), Barratt Impulsiveness Scale (BIS-11), Reflective Functioning Questionnaire (RFQ), and Inventory of Interpersonal Problems (IIP-32). The authors conducted three path models, with either mentalizing, emotion regulation, or impulsiveness as the exogenous variable. Emotion dysregulation and attentional impulsiveness predicted interpersonal problems directly, whereas hypomentalizing predicted interpersonal problems only indirectly throughout emotion dysregulation and attentional impulsiveness. The results suggest that these domains contribute significantly to interpersonal problems in BPD. Moreover, hypomentalizing might affect on interpersonal problems via its effect on impulsiveness and emotion regulation. The authors argue that focusing on emotion regulation and mentalizing in BPD treatments might have interlinked beneficial effects on interpersonal problems