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Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays. Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets.

This article investigates a theoretical tension in cultural models theory between their sharedness and their origin in social and culturally mediated experiences. To address this tension empirically, this article presents a mixed-methods analysis of the shared understanding of a typology of emotion in Chuuk Lagoon. Based on a review of contemporary theory, one would expect that while people in Chuuk would have distinct cultural models for specific culturally meaningful paradigmatic emotions, the shared model for the entire typology of emotion would be structured by two universal dimensions of core affect (arousal and hedonic quality). But this theoretical literature ignores the importance of an intersubjective dimension of prereflective experience. This dimension may be culturally muted in industrial, educated, and rich contexts where most prior research has been conducted but culturally emphasized in places like Chuuk. The mixed-methods analysis finds that an intersubjective dimension along with a hedonic quality dimension structures the shared model of a typology for affect and emotion in Chuuk, while the arousal dimension found elsewhere is muted. Thus, shared models of affect and emotion are cultural models both in terms of specific, culturally elaborated emotions and in terms of the cultural emphasis given to underlying affective and intersubjective dimensions.

Oligomeric complexes of Trax and Translin proteins, known as C3POs, participate in several eukaryotic nucleic acid metabolism pathways, including RNA interference and tRNA processing. In RNA interference in humans and Drosophila, C3PO activates the RNA-induced silencing complex (RISC) by removing the passenger strand of the small interfering RNA precursor duplex, using nuclease activity present in Trax. How C3POs engage with nucleic acid substrates is unknown. Here we identify a single protein from Archaeoglobus fulgidus that assembles into an octamer highly similar to human C3PO. The structure in complex with duplex RNA reveals that the octamer entirely encapsulates a single 13-base-pair RNA duplex inside a large inner cavity. Trax-like-subunit catalytic sites target opposite strands of the duplex for cleavage separated by 7 base pairs. The structure provides insight into the mechanism of RNA recognition and cleavage by an archaeal C3PO-like complex.