Byerspiper8567

Does stunted upward mobility in an educational system impede beneficial psychological processes of learning? We predicted that growth mindsets of intelligence, a well-established psychological stimulant to learning, would be less potent in low-mobility, as compared to high-mobility, learning environments. An analysis of a large cross-national dataset and a longitudinal experiment accumulated converging evidence for this hypothesis. Study 1 examined data from 15-y-old students across 30 countries (n = 235,141 persons). Replicating past findings, growth mindsets positively predicted students' math, science, and reading literacy. More importantly, the country-level indicator of educational mobility (i.e., the percentage of children from low-education households to graduate from tertiary education) moderated the effect of growth mindsets. Depending on the subject, the gain in predicted academic performance from a one-unit increase in growth mindsets was reduced by 42 to 45% from a high-mobility to a low-mobility country. Results were robust with or without important covariates. Study 2 experimentally manipulated people's perception of mobility in a carefully constructed learning environment. The moderating role of educational mobility was replicated and extended to learning behavior, which subsequently predicted performance. Evidence further suggests that in high-mobility environments, both advantaged and disadvantaged learners benefited from growth mindsets, albeit likely through diverging mechanisms; when the effect of growth mindsets was attenuated in low-mobility environments, the potential for the disadvantaged to overcome the performance gap was also limited. Implications for galvanizing the upward mobility of the disadvantaged, evaluating the effectiveness of mindset interventions, and conceptualizing social mobility from a psychological perspective are discussed.Do conversations end when people want them to? Surprisingly, behavioral science provides no answer to this fundamental question about the most ubiquitous of all human social activities. In two studies of 932 conversations, we asked conversants to report when they had wanted a conversation to end and to estimate when their partner (who was an intimate in Study 1 and a stranger in Study 2) had wanted it to end. Results showed that conversations almost never ended when both conversants wanted them to and rarely ended when even one conversant wanted them to and that the average discrepancy between desired and actual durations was roughly half the duration of the conversation. Conversants had little idea when their partners wanted to end and underestimated how discrepant their partners' desires were from their own. These studies suggest that ending conversations is a classic "coordination problem" that humans are unable to solve because doing so requires information that they normally keep from each other. As a result, most conversations appear to end when no one wants them to.Vaccine-based elicitation of broadly neutralizing antibodies holds great promise for preventing HIV-1 transmission. However, the key biophysical markers of improved antibody recognition remain uncertain in the diverse landscape of potential antibody mutation pathways, and a more complete understanding of anti-HIV-1 fusion peptide (FP) antibody development will accelerate rational vaccine designs. Here we survey the mutational landscape of the vaccine-elicited anti-FP antibody, vFP16.02, to determine the genetic, structural, and functional features associated with antibody improvement or fitness. Using site-saturation mutagenesis and yeast display functional screening, we found that 1% of possible single mutations improved HIV-1 envelope trimer (Env) affinity, but generally comprised rare somatic hypermutations that may not arise frequently in vivo. We observed that many single mutations in the vFP16.02 Fab could enhance affinity >1,000-fold against soluble FP, although affinity improvements against the HIV-1 trimer were more measured and rare. The most potent variants enhanced affinity to both soluble FP and Env, had mutations concentrated in antibody framework regions, and achieved up to 37% neutralization breadth compared to 28% neutralization of the template antibody. Altered heavy- and light-chain interface angles and conformational dynamics, as well as reduced Fab thermal stability, were associated with improved HIV-1 neutralization breadth and potency. We also observed parallel sets of mutations that enhanced viral neutralization through similar structural mechanisms. These data provide a quantitative understanding of the mutational landscape for vaccine-elicited FP-directed broadly neutralizing antibody and demonstrate that numerous antigen-distal framework mutations can improve antibody function by enhancing affinity simultaneously toward HIV-1 Env and FP.Tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) also has an immunological function to suppress T cell activation in inflammatory circumstances, including graft-versus-host disease (GVHD), a fatal complication after allogeneic bone marrow transplantation (allo-BMT). Although the mononuclear cell expression of IDO1 has been associated with improved outcomes in GVHD, the underlying mechanisms remain unclear. Herein, we used IDO-deficient (Ido1-/-) BMT to understand why myeloid IDO limits the severity of GVHD. Hosts with Ido1-/- BM exhibited increased lethality, with enhanced proinflammatory and reduced regulatory T cell responses compared with wild type (WT) allo-BMT controls. Despite the comparable expression of the myeloid-derived suppressor cell (MDSC) mediators, arginase-1, inducible nitric oxide synthase, and interleukin 10, Ido1-/- Gr-1+CD11b+ cells from allo-BMT or in vitro BM culture showed compromised immune-suppressive functions and were skewed toward the Ly6ClowLy6Ghi subset, compared with the WT counterparts. Importantly, Ido1-/-Gr-1+CD11b+ cells exhibited elevated levels of reactive oxygen species (ROS) and neutrophil numbers. These characteristics were rescued by human IDO1 with intact heme-binding and catalytic activities and were recapitulated by the treatment of WT cells with the IDO1 inhibitor L1-methyl tryptophan. ROS scavenging by N-acetylcysteine reverted the Ido1-/-Gr-1+CD11b+ composition and function to an MDSC state, as well as improved the survival of GVHD hosts with Ido1-/- BM. In summary, myeloid-derived IDO1 enhances GVHD survival by regulating ROS levels and limiting the ability of Gr-1+CD11b+ MDSCs to differentiate into proinflammatory neutrophils. Our findings provide a mechanistic insight into the immune-regulatory roles of the metabolic enzyme IDO1.Increases in cytosolic Ca2+ concentration regulate diverse cellular activities and are usually evoked by opening of Ca2+ channels in intracellular Ca2+ stores and the plasma membrane (PM). For the many signals that evoke formation of inositol 1,4,5-trisphosphate (IP3), IP3 receptors coordinate the contributions of these two Ca2+ sources by mediating Ca2+ release from the endoplasmic reticulum (ER). selleck inhibitor Loss of Ca2+ from the ER then activates store-operated Ca2+ entry (SOCE) by causing dimers of STIM1 to cluster and unfurl cytosolic domains that interact with the PM Ca2+ channel, Orai1, causing its pore to open. The relative concentrations of STIM1 and Orai1 are important, but most analyses of their interactions use overexpressed proteins that perturb the stoichiometry. We tagged endogenous STIM1 with EGFP using CRISPR/Cas9. SOCE evoked by loss of ER Ca2+ was unaffected by the tag. Step-photobleaching analysis of cells with empty Ca2+ stores revealed an average of 14.5 STIM1 molecules within each sub-PM punctum. The fluorescence intensity distributions of immunostained Orai1 puncta were minimally affected by store depletion, and similar for Orai1 colocalized with STIM1 puncta or remote from them. We conclude that each native SOCE complex is likely to include only a few STIM1 dimers associated with a single Orai1 channel. Our results, demonstrating that STIM1 does not assemble clusters of interacting Orai channels, suggest mechanisms for digital regulation of SOCE by local depletion of the ER.Quantitative knowledge of xylem physical tolerance limits to dehydration is essential to understanding plant drought tolerance but is lacking in many long-vessel angiosperms. We examine the hypothesis that a fundamental association between sustained xylem water transport and downstream tissue function should select for xylem that avoids embolism in long-vessel trees by quantifying xylem capacity to withstand air entry of western North American oaks (Quercus spp.). Optical visualization showed that 50% of embolism occurs at water potentials below -2.7 MPa in all 19 species, and -6.6 MPa in the most resistant species. By mapping the evolution of xylem vulnerability to embolism onto a fossil-dated phylogeny of the western North American oaks, we found large differences between clades (sections) while closely related species within each clade vary little in their capacity to withstand air entry. Phylogenetic conservatism in xylem physical tolerance, together with a significant correlation between species distributions along rainfall gradients and their dehydration tolerance, suggests that closely related species occupy similar climatic niches and that species' geographic ranges may have shifted along aridity gradients in accordance with their physical tolerance. Such trends, coupled with evolutionary associations between capacity to withstand xylem embolism and other hydraulic-related traits, yield wide margins of safety against embolism in oaks from diverse habitats. Evolved responses of the vascular system to aridity support the embolism avoidance hypothesis and reveal the importance of quantifying plant capacity to withstand xylem embolism for understanding function and biogeography of some of the Northern Hemisphere's most ecologically and economically important plants.Metal-organic frameworks (MOFs) are crystalline nanoporous materials with great potential for a wide range of industrial applications. Understanding the nucleation and early growth stages of these materials from a solution is critical for their design and synthesis. Despite their importance, the pathways through which MOFs nucleate are largely unknown. Using a combination of in situ liquid-phase and cryogenic transmission electron microscopy, we show that zeolitic imidazolate framework-8 MOF nanocrystals nucleate from precursor solution via three distinct steps 1) liquid-liquid phase separation into solute-rich and solute-poor regions, followed by 2) direct condensation of the solute-rich region into an amorphous aggregate and 3) crystallization of the aggregate into a MOF. The three-step pathway for MOF nucleation shown here cannot be accounted for by conventional nucleation models and provides direct evidence for the nonclassical nucleation pathways in open-framework materials, suggesting that a solute-rich phase is a common precursor for crystallization from a solution.In response to increasing frequencies of antibiotic-resistant pathogens, there has been a resurrection of interest in the use of bacteriophage to treat bacterial infections phage therapy. Here we explore the potential of a seemingly ideal phage, PYOSa, for combination phage and antibiotic treatment of Staphylococcus aureus infections. This K-like phage has a broad host range; all 83 tested clinical isolates of S.aureus tested were susceptible to PYOSa Because of the mode of action of PYOSa, S. aureus is unlikely to generate classical receptor-site mutants resistant to PYOSa; none were observed in the 13 clinical isolates tested. PYOSa kills S. aureus at high rates. On the downside, the results of our experiments and tests of the joint action of PYOSa and antibiotics raise issues that must be addressed before PYOSa is employed clinically. Despite the maintenance of the phage, PYOSa does not clear populations of S. aureus Due to the ascent of a phenotyically diverse array of small-colony variants following an initial demise, the bacterial populations return to densities similar to that of phage-free controls.