AbstractmiRNA-mediated repression in animals is dependent on the GW182 protein family. GW182 proteins are recruited to the miRNA repression complex through direct interaction with Argonaute proteins, and they function downstream to repress target mRNA. Here we demonstrate that in human and Drosophila melanogaster cells, the critical repressive features of both the N-terminal and C-terminal effector domains of GW182 proteins are Gly/Ser/Thr-Trp (G/S/TW) or Trp-Gly/ Ser/Thr (WG/S/T) motifs. These motifs, which are dispersed across both domains and act in an additive manner, function by recruiting components of the CCR 4-NOT deadenylation complex. A heterologous yeast polypeptide with engineered WG/S/T motifs acquired the ability to repress tethered mRNA and to interact with the CCR 4-NOT complex. These results identify previously unknown effector motifs functioning as important mediators of miRNA-induced silencing in both species, and they reveal that recruitment of the CCR 4-NOT complex by tryptophan-containing motifs acts downstream of GW182 to repress mRNA s, including inhibiting translation independently of deadenylation.MicroRNAs (miRNAs) are small, ~21-nt-long RNAs that post-transcriptionally regulate gene expression in eukaryotes. In animals, miRNAs bind to partially complementary sites in mRNAs, leading to translational repression and mRNA deadenylation and degradation [1][2][3][4] . miRNAs function as part of ribonucleoprotein complexes, miRNPs, with Argonaute (AGO) and GW182 family proteins being the crucial components. GW182s interact directly with AGO proteins and function downstream as effectors mediating mRNA repression. Hence, understanding the function of GW182 proteins is critical for understanding miRNAmediated repression.GW182 functional regions have been mapped in D. melanogaster and mammalian proteins. In D. melanogaster, three regions were found to repress tethered mRNA to a similar extent 5
Social thermoregulation theory posits that modern human relationships are pleisiomorphically organized around body temperature regulation. In two studies (N = 1755) designed to test the principles from this theory, we used supervised machine learning to identify social and non-social factors that relate to core body temperature. This data-driven analysis found that complex social integration (CSI), defined as the number of high-contact roles one engages in, is a critical predictor of core body temperature. We further used a cross-validation approach to show that colder climates relate to higher levels of CSI, which in turn relates to higher CBT (when climates get colder). These results suggest that despite modern affordances for regulating body temperature, people still rely on social warmth to buffer their bodies against the cold.
Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect ( p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3–9; median total sample = 1,279.5, range = 276–3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Δ r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols ( r = .05) was similar to that of the RP:P protocols ( r = .04) and the original RP:P replications ( r = .11), and smaller than that of the original studies ( r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00–.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19–.50).
Which is more enjoyable: trying to think enjoyable thoughts or doing everyday solitary activities? Wilson et al. (2014) found that American participants much preferred solitary everyday activities, such as reading or watching TV, to thinking for pleasure. To see whether this preference generalized outside of the United States, we replicated the study with 2,557 participants from 12 sites in 11 countries. The results were consistent in every country: Participants randomly assigned to do something reported significantly greater enjoyment than did participants randomly assigned to think for pleasure. Although we found systematic differences by country in how much participants enjoyed thinking for pleasure, we used a series of nested structural equation models to show that these differences were fully accounted for by country-level variation in 5 individual differences, 4 of which were positively correlated with thinking for pleasure (need for cognition, openness to experience, meditation experience, and initial positive affect) and 1 of which was negatively correlated (reported phone usage). (PsycINFO Database Record
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