It is also shown that the combination of Orowan's precipitate hardening model and our critical condition for dislocation nucleation at a nanoprecipitate immediately provides a criterion to select precipitate size and spacing in material design. The findings reported here thus may help establish a foundation for strength-ductility optimization through densely dispersed nanoprecipitates in multiple-element alloy systems. Copyright © 2020 the Author(s). Published by PNAS.As people live longer, ages at death are becoming more similar. This dual advance over the last two centuries, a central aim of public health policies, is a major achievement of modern civilization. Some recent exceptions to the joint rise of life expectancy and life span equality, however, make it difficult to determine the underlying causes of this relationship. Here, we develop a unifying framework to study life expectancy and life span equality over time, relying on concepts about the pace and shape of aging. We study the dynamic relationship between life expectancy and life span equality with reliable data from the Human Mortality Database for 49 countries and regions with emphasis on the long time series from Sweden. Our results demonstrate that both changes in life expectancy and life span equality are weighted totals of rates of progress in reducing mortality. This finding holds for three different measures of the variability of life spans. The weights evolve over time and indicate the ages at which reductions in mortality increase life expectancy and life span equality the more progress at the youngest ages, the tighter the relationship. The link between life expectancy and life span equality is especially strong when life expectancy is less than 70 y. In recent decades, life expectancy and life span equality have occasionally moved in opposite directions due to larger improvements in mortality at older ages or a slowdown in declines in midlife mortality. Saving lives at ages below life expectancy is the key to increasing both life expectancy and life span equality. Copyright © 2020 the Author(s). Published by PNAS.The lateral hypothalamus (LH) has long been implicated in maintaining behavioral homeostasis essential for the survival of an individual. However, recent evidence suggests its more widespread roles in behavioral coordination, extending to the social domain. The neuronal and circuit mechanisms behind the LH processing of social information are unknown. Here, we show that the LH represents distinct reward variables for "self" and "other" and is causally involved in shaping socially motivated behavior. During a Pavlovian conditioning procedure incorporating ubiquitous social experiences where rewards to others affect one's motivation, LH cells encoded the subjective value of self-rewards, as well as the likelihood of self- or other-rewards. The other-reward coding was not a general consequence of other's existence, but a specific effect of other's reward availability. Coherent activity with and top-down information flow from the medial prefrontal cortex, a hub of social brain networks, contributed to signal encoding in the LH. Furthermore, deactivation of LH cells eliminated the motivational impact of other-rewards. These results indicate that the LH constitutes a subcortical node in social brain networks and shapes one's motivation by integrating cortically derived, agent-specific reward information. Copyright © 2020 the Author(s). Published by PNAS.Multicellularity is a key evolutionary innovation, leading to coordinated activity and resource sharing among cells, which generally occurs via the physical exchange of chemical compounds. However, filamentous cable bacteria display a unique metabolism in which redox transformations in distant cells are coupled via long-distance electron transport rather than an exchange of chemicals. This challenges our understanding of organismal functioning, as the link among electron transfer, metabolism, energy conservation, and filament growth in cable bacteria remains enigmatic. Here, we show that cells within individual filaments of cable bacteria display a remarkable dichotomy in biosynthesis that coincides with redox zonation. Nanoscale secondary ion mass spectrometry combined with 13C (bicarbonate and propionate) and 15N-ammonia isotope labeling reveals that cells performing sulfide oxidation in deeper anoxic horizons have a high assimilation rate, whereas cells performing oxygen reduction in the oxic zone show very little or no label uptake. Accordingly, oxygen reduction appears to merely function as a mechanism to quickly dispense of electrons with little to no energy conservation, while biosynthesis and growth are restricted to sulfide-respiring cells. Still, cells can immediately switch roles when redox conditions change, and show no differentiation, which suggests that the "community service" performed by the cells in the oxic zone is only temporary. Overall, our data reveal a division of labor and electrical cooperation among cells that has not been seen previously in multicellular organisms. Copyright © 2020 the Author(s). Published by PNAS.Terminal oligopyrimidine (TOP) motifs are sequences at the 5' ends of mRNAs that link their translation to the mTOR Complex 1 (mTORC1) nutrient-sensing signaling pathway.  https://www.selleckchem.com/products/neo2734.html  They are commonly regarded as discrete elements that reside on ∼100 mRNAs that mostly encode translation factors. However, the full spectrum of TOP sequences and their prevalence throughout the transcriptome remain unclear, primarily because of uncertainty over the mechanism that detects them. Here, we globally analyzed translation targets of La-related protein 1 (LARP1), an RNA-binding protein and mTORC1 effector that has been shown to repress TOP mRNA translation in a few specific cases. We establish that LARP1 is the primary translation regulator of mRNAs with classical TOP motifs genome-wide, and also that these motifs are extreme instances of a broader continuum of regulatory sequences. We identify the features of TOP sequences that determine their potency and quantify these as a metric that accurately predicts mTORC1/LARP1 regulation called a TOPscore.