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The glucocorticoid receptor (GR) is a ligand-regulated transcription factor (TF) that controls the tissue- and gene-specific transactivation and transrepression of thousands of target genes. https://www.selleckchem.com/products/rvx-208.html Distinct GR DNA-binding sequences with activating or repressive activities have been identified, but how they modulate transcription in opposite ways is not known. We show that GR forms phase-separated condensates that specifically concentrate known coregulators via their intrinsically disordered regions (IDRs) in vitro. A combination of dynamic, multivalent (between IDRs) and specific, stable interactions (between LxxLL motifs and the GR ligand-binding domain) control the degree of recruitment. Importantly, GR DNA binding directs the selective partitioning of coregulators within GR condensates such that activating DNAs cause enhanced recruitment of coactivators. Our work shows that condensation controls GR function by modulating coregulator recruitment and provides a mechanism for the up- and down-regulation of GR target genes controlled by distinct DNA recognition elements.Sensitivity to satiety constitutes a basic requirement for neuronal coding of subjective reward value. Satiety from natural ongoing consumption affects reward functions in learning and approach behavior. More specifically, satiety reduces the subjective economic value of individual rewards during choice between options that typically contain multiple reward components. The unconfounded assessment of economic reward value requires tests at choice indifference between two options, which is difficult to achieve with sated rewards. By conceptualizing choices between options with multiple reward components ("bundles"), Revealed Preference Theory may offer a solution. Despite satiety, choices against an unaltered reference bundle may remain indifferent when the reduced value of a sated bundle reward is compensated by larger amounts of an unsated reward of the same bundle, and then the value loss of the sated reward is indicated by the amount of the added unsated reward. Here, we show psychophysically titrated choice indifference in monkeys between bundles of differently sated rewards. Neuronal chosen value signals in the orbitofrontal cortex (OFC) followed closely the subjective value change within recording periods of individual neurons. A neuronal classifier distinguishing the bundles and predicting choice substantiated the subjective value change. The choice between conventional single rewards confirmed the neuronal changes seen with two-reward bundles. Thus, reward-specific satiety reduces subjective reward value signals in OFC. With satiety being an important factor of subjective reward value, these results extend the notion of subjective economic reward value coding in OFC neurons.The unequal spatial distribution of ambient nitrogen dioxide ([Formula see text]), an air pollutant related to traffic, leads to higher exposure for minority and low socioeconomic status communities. We exploit the unprecedented drop in urban activity during the COVID-19 pandemic and use high-resolution, remotely sensed [Formula see text] observations to investigate disparities in [Formula see text] levels across different demographic subgroups in the United States. We show that, prior to the pandemic, satellite-observed [Formula see text] levels in the least White census tracts of the United States were nearly triple the [Formula see text] levels in the most White tracts. During the pandemic, the largest lockdown-related [Formula see text] reductions occurred in urban neighborhoods that have 2.0 times more non-White residents and 2.1 times more Hispanic residents than neighborhoods with the smallest reductions. [Formula see text] reductions were likely driven by the greater density of highways and interstates in these racially and ethnically diverse areas. Although the largest reductions occurred in marginalized areas, the effect of lockdowns on racial, ethnic, and socioeconomic [Formula see text] disparities was mixed and, for many cities, nonsignificant. For example, the least White tracts still experienced ∼1.5 times higher [Formula see text] levels during the lockdowns than the most White tracts experienced prior to the pandemic. Future policies aimed at eliminating pollution disparities will need to look beyond reducing emissions from only passenger traffic and also consider other collocated sources of emissions such as heavy-duty vehicles.Hybrids account for nearly all commercially planted varieties of maize and many other crop plants because crosses between inbred lines of these species produce first-generation [F1] offspring that greatly outperform their parents. The mechanisms underlying this phenomenon, called heterosis or hybrid vigor, are not well understood despite over a century of intensive research. The leading hypotheses-which focus on quantitative genetic mechanisms (dominance, overdominance, and epistasis) and molecular mechanisms (gene dosage and transcriptional regulation)-have been able to explain some but not all of the observed patterns of heterosis. Abiotic stressors are known to impact the expression of heterosis; however, the potential role of microbes in heterosis has largely been ignored. Here, we show that heterosis of root biomass and other traits in maize is strongly dependent on the belowground microbial environment. We found that, in some cases, inbred lines perform as well by these criteria as their F1 offspring under sterile conditions but that heterosis can be restored by inoculation with a simple community of seven bacterial strains. We observed the same pattern for seedlings inoculated with autoclaved versus live soil slurries in a growth chamber and for plants grown in steamed or fumigated versus untreated soil in the field. In a different field site, however, soil steaming increased rather than decreased heterosis, indicating that the direction of the effect depends on community composition, environment, or both. Together, our results demonstrate an ecological phenomenon whereby soil microbes differentially impact the early growth of inbred and hybrid maize.
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