Proctortychsen2677

No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Through the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such as cell polarization, migration, and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. Napabucasin in vivo We report the first reconstitution of a mammalian mRNA transport system revealing that the tumor suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localized β-actin and β2B-tubulin mRNAs, which are linked to a kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2, and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3'UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal a minimal set of proteins sufficient to transport mammalian mRNAs. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Multi-elemental alloy nanoparticles (MEA-NPs) hold great promise for catalyst discovery in a virtually unlimited compositional space. However, rational and controllable synthesize of these intrinsically complex structures remains a challenge. Here, we report the computationally aided, entropy-driven design and synthesis of highly efficient and durable catalyst MEA-NPs. The computational strategy includes prescreening of millions of compositions, prediction of alloy formation by density functional theory calculations, and examination of structural stability by a hybrid Monte Carlo and molecular dynamics method. Selected compositions can be efficiently and rapidly synthesized at high temperature (e.g., 1500 K, 0.5 s) with excellent thermal stability. We applied these MEA-NPs for catalytic NH3 decomposition and observed outstanding performance due to the synergistic effect of multi-elemental mixing, their small size, and the alloy phase. We anticipate that the computationally aided rational design and rapid synthesis of MEA-NPs are broadly applicable for various catalytic reactions and will accelerate material discovery. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).When two dimensional crystals are atomically close, their finite thickness becomes relevant. Using transport measurements, we investigate the electrostatics of two graphene layers, twisted by θ = 22° such that the layers are decoupled by the huge momentum mismatch between the K and K' points of the two layers. We observe a splitting of the zero-density lines of the two layers with increasing interlayer energy difference. This splitting is given by the ratio of single-layer quantum capacitance over interlayer capacitance C m and is therefore suited to extract C m. We explain the large observed value of C m by considering the finite dielectric thickness d g of each graphene layer and determine d g ≈ 2.6 Å. In a second experiment, we map out the entire density range with a Fabry-Pérot resonator. We can precisely measure the Fermi wavelength λ in each layer, showing that the layers are decoupled. Our findings are reproduced using tight-binding calculations. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).The ballgame represents one of the most enduring and iconic features of ancient Mesoamerican civilization, yet its origins and evolution remain poorly understood, primarily associated with the Gulf Coast and southern Pacific coastal lowlands. While one early ballcourt dates to 1650 BCE from the Chiapas lowlands, ballcourts have remained undocumented in the Mesoamerican highlands until a millennium later, suggesting less involvement by highland civilizations in the ballgame's evolution. We provide new data from the southern highlands of Mexico, from the Early Formative period (1500-1000 BCE), that necessitate revising previous paradigms. Along with ballplayer imagery, we recently excavated the earliest highland Mesoamerican ballcourt, dating to 1374 BCE, at the site of Etlatongo, in the Mixtec region of Oaxaca. We conclude that Early Formative highland villagers played an important role in the origins of the formal Mesoamerican ballgame, which later evolved into a crucial component of subsequent states. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).A reliable projection of future South Asian summer monsoon (SASM) benefits a large population in Asia. Using a 100-member ensemble of simulations by the Max Planck Institute Earth System Model (MPI-ESM) and a 50-member ensemble of simulations by the Canadian Earth System Model (CanESM2), we find that internal variability can overshadow the forced SASM rainfall trend, leading to large projection uncertainties for the next 15 to 30 years. We further identify that the Interdecadal Pacific Oscillation (IPO) is, in part, responsible for the uncertainties. Removing the IPO-related rainfall variations reduces the uncertainties in the near-term projection of the SASM rainfall by 13 to 15% and 26 to 30% in the MPI-ESM and CanESM2 ensembles, respectively. Our results demonstrate that the uncertainties in near-term projections of the SASM rainfall can be reduced by improving prediction of near-future IPO and other internal modes of climate variability. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Aging or injury leads to degradation of the cartilage matrix and the development of osteoarthritis (OA). Because of a paucity of single-cell studies of OA cartilage, little is known about the interpatient variability in its cellular composition and, more importantly, about the cell subpopulations that drive the disease. Here, we profiled healthy and OA cartilage samples using mass cytometry to establish a single-cell atlas, revealing distinct chondrocyte progenitor and inflammation-modulating subpopulations. These rare populations include an inflammation-amplifying (Inf-A) population, marked by interleukin-1 receptor 1 and tumor necrosis factor receptor II, whose inhibition decreased inflammation, and an inflammation-dampening (Inf-D) population, marked by CD24, which is resistant to inflammation. We devised a pharmacological strategy targeting Inf-A and Inf-D cells that significantly decreased inflammation in OA chondrocytes. Using our atlas, we stratified patients with OA in three groups that are distinguished by the relative proportions of inflammatory to regenerative cells, making it possible to devise precision therapeutic approaches. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Diamond and coesite are classic indicators of ultrahigh-pressure (UHP; ≥100-kilometer depth) metamorphism, but they readily recrystallize during exhumation. Crystallographically oriented pyroxene and amphibole exsolution lamellae in garnet document decomposed supersilicic UHP majoritic garnet originally stable at diamond-grade conditions, but majoritic precursors have only been quantitatively demonstrated in mafic and ultramafic rocks. Moreover, controversy persists regarding which silicates majoritic garnet breakdown produces. We present a method for reconstructing precursor majoritic garnet chemistry in metasedimentary Appalachian gneisses containing garnets preserving concentric zones of crystallographically oriented lamellae including quartz, amphibole, and sodium phlogopite. We link this to novel quartz-garnet crystallographic orientation data. The results reveal majoritic precursors stable at ≥175-kilometer depth and that quartz and mica may exsolve from garnet. Large UHP terranes in the European Caledonides formed during collision of the paleocontinents Baltica and Laurentia; we demonstrate UHP metamorphism from the microcontinent-continent convergence characterizing the contiguous and coeval Appalachian orogen. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Previously, we reported that chromodomain Y-like (CDYL) acts as a crotonyl-coenzyme A hydratase and negatively regulates histone crotonylation (Kcr). However, the global CDYL-regulated crotonylome remains unclear. Here, we report a large-scale proteomics analysis for protein Kcr. We identify 14,311 Kcr sites across 3734 proteins in HeLa cells, providing by far the largest crotonylome dataset. We show that depletion of CDYL alters crotonylome landscape affecting diverse cellular pathways. Specifically, CDYL negatively regulated Kcr of RPA1, and mutation of the Kcr sites of RPA1 impaired its interaction with single-stranded DNA and/or with components of resection machinery, supporting a key role of RPA1 Kcr in homologous recombination DNA repair. Together, our study indicates that protein crotonylation has important implication in various pathophysiological processes. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Drop impact on solid surfaces is encountered in numerous natural and technological processes. Although the impact of single-phase drops has been widely explored, the impact of compound drops has received little attention. Here, we demonstrate a self-lubrication mechanism for water-in-oil compound drops impacting on a solid surface. Unexpectedly, the core water drop rebounds from the surface below a threshold impact velocity, irrespective of the substrate wettability. This is interpreted as the result of lubrication from the oil shell that prevents contact between the water core and the solid surface. We combine side and bottom view high-speed imaging to demonstrate the correlation between the water core rebound and the oil layer stability. A theoretical model is developed to explain the observed effect of compound drop geometry. This work sets the ground for precise complex drop deposition, with a strong impact on two- and three-dimensional printing technologies and liquid separation. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.