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The Macrophage-Inducible C-type Lectin receptor (Mincle) plays a critical role in innate immune recognition and pathology, and therefore represents a promising target for vaccine adjuvants. Innovative trehalose-based Mincle agonists with improved pharmacology and potency may prove useful in the development of Th17-mediated adaptive immune responses. Herein, we report on in vitro and in silico investigations of specific Mincle ligand–receptor interactions required for the effective receptor engagement and activation of Th17-polarizing cytokines. Specifically, we employed a library of trehalose benzoate scaffolds, varying the degree of aryl lipidation and regiochemistry that produce inflammatory cytokines in a Mincle-dependent fashion. In vitro interleukin-6 (IL-6) cytokine production by human peripheral blood mononuclear cells (hPBMCs) indicated that the lipid regiochemistry is key to potency and maximum cytokine output, with the tri-substituted compounds inducing higher levels of IL-6 in hPBMCs than the di-substituted derivatives. Additionally, IL-6 production trended higher after stimulation with compounds that contained lipids ranging from five to eight carbons long, compared to shorter (below five) or longer (above eight) carbon chains, across all the substitution patterns. An analysis of the additional cytokines produced by hPBMCs revealed that compound 4d, tri-substituted and five carbons long, induced significantly greater levels of interleukin-1β (IL-1β), tumor necrosis factor- α (TNF-α), interleukin-23 (IL-23), and interferon- γ (IFN-γ) than the other compounds tested in this study. An in silico assessment of 4d highlighted the capability of this analogue to bind to the human Mincle carbohydrate recognition domain (CRD) efficiently. Together, these data highlight important structure–activity findings regarding Mincle-specific cytokine induction, generating a lead adjuvant candidate for future formulations and immunological evaluations. [ABSTRACT FROM AUTHOR]

Compared Malaysian (collectivist) and British (individualist) students on their self-liking and self-competence. Malaysians were lower in self-competence when self-liking was held constant but were higher in self-liking when self-competence was held constant. Differences between groups were not reliable after statistically equating groups on two dimensions of individualism-collectivism. (SLD)

Past research suggests that choice in deciding the features of a task can enhance performance. Independent of the quality of performance, choice may also increase the actor's confidence by providing a secondary source of subjective control during the task. In two studies designed to examine this augmentation hypothesis, college students were asked to read and understand a short story. Study 1 revealed that those who selected names to be used in the story felt more confident about their performance than did those who were assigned names, although the groups in fact performed equally. Study 2 revealed that the enhancement was not due to anticipatory confidence, arguing against the possibility that choice was operating as a performance cue. The findings are interpreted in relation to perceived control and implications for motivation and competence are discussed.

According to the cultural trade-off hypothesis, individualism and collectivism entail inverse costs and benefits for the two dimensions of global self-esteem. Specifically, individualism is described as promoting the development of self-competence but inhibiting the development of self-liking. Collectivism is described as doing the opposite. To examine the hypothesis, Malaysian (collectivist) and British (individualist) students were compared on their self liking and self-competence. Consistent with predictions, Malaysians were significantly lower in self-competence when self-liking was held constant but were higher in self-liking when self-competence was held constant. The differences, however, were not reliable after statistically equating the cultural groups on two derived dimensions of individualism-collectivism - deference to the direction of relatives and connectedness to parents - suggesting that these dimensions might account for the trade-off in self-esteem.