93 research outputs found

    PHP30 CAN PRICING SCHEMES IMPROVE MARKET ACCESS FOR INNOVATIVE HIGH PRICED DRUGS?

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    Children's autonomic nervous system activity while transgressing: relations to guilt feelings and aggression

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    Despite the well-established protective functions of guilt across childhood, its underlying physiological mechanisms have received little attention. We used latent difference scores (LDS) to model changes in children's (N = 267; 4- and 8-year-olds, 51% girls) skin conductance (SC) and respiratory sinus arrhythmia (RSA) while they imagined themselves committing antisocial acts. We then tested if their later reports of guilt, caregiver-reported aggressive behavior, and age were associated with these physiological changes. For 8-year-olds, changes in RSA leading up to and during transgressions were uniquely associated with the intensity of guilt feelings after transgressions. Eight-year-olds with higher guilt were rated lower in aggression, although children's physiology and aggression were not directly related. We discuss how fluctuations in physiology while transgressing may prepare children to mount adaptive guilt responses afterward and-more broadly-implications for understanding the mechanisms behind guilt and related behavior in early and middle childhood

    High-confidence glycosome proteome for procyclic form <em>Trypanosoma brucei</em> by epitope-tag organelle enrichment and SILAC proteomics

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    The glycosome of the pathogenic African trypanosome Trypanosoma brucei is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed

    Children’s Moral Emotion Attribution in the Happy Victimizer Task: The Role of Response Format

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    Previous research in the happy victimizer tradition indicated that preschool and early elementary-school children attribute positive emotions to the violator of a moral norm, whereas older children attribute negative moral emotions. Cognitive and motivational processes have been suggested as underlying this developmental shift. The current research investigated whether making the happy victimizer task less cognitively demanding, by providing children with alternative response formats, would increase children’s attribution of moral emotions and moral motivation. In Study 1, 93 4- to 7-year-old British children responded to the happy victimizer questions either in a normal condition (where they spontaneously pointed with a finger), a wait condition (where they had to wait before giving their answers), or an arrow condition (where they had to point with a paper arrow). In Study 2, 40 Spanish 4-year-old children responded in the happy victimizer task either in a normal or a wait condition. In both studies, participants’ attribution of moral emotions and moral motivation was significantly higher in the conditions with alternative response formats (wait, arrow) than in the normal condition. The role of cognitive abilities for emotion attribution in the happy victimizer task is discussed

    Is There a Classical Nonsense-Mediated Decay Pathway in Trypanosomes?

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    In many eukaryotes, messenger RNAs with premature termination codons are destroyed by a process called “nonsense-mediated decay”, which requires the RNA helicase Upf1 and also, usually, an interacting factor, Upf2. Recognition of premature termination codons may rely on their distance from either a splice site or the polyadenylation site, and long 3′-untranslated regions can trigger mRNA decay. The protist Trypanosoma brucei relies heavily on mRNA degradation to determine mRNA levels, and 3′-untranslated regions play a major role in control of mRNA decay. We show here that trypanosomes have a homologue of Upf1, TbUPF1, which interacts with TbUPF2 and (in an RNA-dependent fashion) with poly(A) binding protein 1, PABP1. Introduction of a premature termination codon in either an endogenous gene or a reporter gene decreased mRNA abundance, as expected for nonsense-mediated decay, but a dependence of this effect on TbUPF1 could not be demonstrated, and depletion of TbUPF1 by over 95% had no effect on parasite growth or the mRNA transcriptome. Further investigations of the reporter mRNA revealed that increases in open reading frame length tended to increase mRNA abundance. In contrast, inhibition of translation, either using 5′-secondary structures or by lengthening the 5′-untranslated region, usually decreased reporter mRNA abundance. Meanwhile, changing the length of the 3′-untranslated region had no consistent effect on mRNA abundance. We suggest that in trypanosomes, translation per se may inhibit mRNA decay, and interactions with multiple RNA-binding proteins preclude degradation based on 3′-untranslated region length alone

    Daily Deviations in Anger, Guilt, and Sympathy: A Developmental Diary Study of Aggression

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    With a diary study of 4- and 8-year-olds, we tested the association between daily deviations in anger and aggressive behavior, and whether this link was moderated by feelings of guilt and sympathy. Caregivers reported their children’s anger and aggression for 10 consecutive days (470 records; N = 80, 53 % girls). To calculate daily anger deviations from average anger levels, we subtracted each child’s average anger score (i.e., across 10 days) from his/her daily anger scores. Children reported their guilty feelings in response to vignettes depicting intentional harm, as well as their dispositional sympathy levels. Multilevel modeling indicated that within-child spikes in daily anger were associated with more aggression, above and beyond between-child differences in average anger levels. However, this association was weaker for children who reported higher levels of guilt. Sympathy did not moderate the anger-aggression link. We discuss potential implications for affective-developmental models of aggression and interventions that target anger-related aggressio
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