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    Diurnal transcriptome atlas of a primate across major neural and peripheral tissues - Diurnal gene expression patterns underlie time-of-the-day–specific functional specialization of tissues. However, available circadian gene expression atlases of a few organs are largely from nocturnal vertebrates. We report the diurnal transcriptome of 64 tissues, including 22 brain regions, sampled every 2 hours over 24 hours, from the primate Papio anubis (baboon). Genomic transcription was highly rhythmic, with up to 81.7% of protein-co...
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    Phenotype risk scores identify patients with unrecognized Mendelian disease patterns - Genetic association studies often examine features independently, potentially missing subpopulations with multiple phenotypes that share a single cause. We describe an approach that aggregates phenotypes on the basis of patterns described by Mendelian diseases. We mapped the clinical features of 1204 Mendelian diseases into phenotypes captured from the electronic health record (EHR) and summarized this evidence as phenotype risk scores (PheRSs)....
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    Random heteropolymers preserve protein function in foreign environments - The successful incorporation of active proteins into synthetic polymers could lead to a new class of materials with functions found only in living systems. However, proteins rarely function under the conditions suitable for polymer processing. On the basis of an analysis of trends in protein sequences and characteristic chemical patterns on protein surfaces, we designed four-monomer random heteropolymers to mimic intrinsically disordered protein...
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    Real-time imaging of adatom-promoted graphene growth on nickel - Single adatoms are expected to participate in many processes occurring at solid surfaces, such as the growth of graphene on metals. We demonstrate, both experimentally and theoretically, the catalytic role played by single metal adatoms during the technologically relevant process of graphene growth on nickel (Ni). The catalytic action of individual Ni atoms at the edges of a growing graphene flake was directly captured by scanning tunneling micr...
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    Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis - Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C–S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe–C) bond between ACP and the enzyme’s [4Fe-4S] cluster. In the presence of the substrate protein, elongation ...
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    Oklahoma's induced seismicity strongly linked to wastewater injection depth - The sharp rise in Oklahoma seismicity since 2009 is due to wastewater injection. The role of injection depth is an open, complex issue, yet critical for hazard assessment and regulation. We developed an advanced Bayesian network to model joint conditional dependencies between spatial, operational, and seismicity parameters. We found that injection depth relative to crystalline basement most strongly correlates with seismic moment release. The jo...
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    Protecting marine mammals, turtles, and birds by rebuilding global fisheries - Reductions in global fishing pressure are needed to end overfishing of target species and maximize the value of fisheries. We ask whether such reductions would also be sufficient to protect non–target species threatened as bycatch. We compare changes in fishing pressure needed to maximize profits from 4713 target fish stocks—accounting for >75% of global catch—to changes in fishing pressure needed to reverse ongoing declines...
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    GDV1 induces sexual commitment of malaria parasites by antagonizing HP1-dependent gene silencing - Malaria is caused by Plasmodium parasites that proliferate in the bloodstream. During each replication cycle, some parasites differentiate into gametocytes, the only forms able to infect the mosquito vector and transmit malaria. Sexual commitment is triggered by activation of AP2-G, the master transcriptional regulator of gametocytogenesis. Heterochromatin protein 1 (HP1)–dependent silencing of ap2-g prevents sexual conversion in prolifera...
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    Precursors of logical reasoning in preverbal human infants - Infants are able to entertain hypotheses about complex events and to modify them rationally when faced with inconsistent evidence. These capacities suggest that infants can use elementary logical representations to frame and prune hypotheses. By presenting scenes containing ambiguities about the identity of an object, here we show that 12- and 19-month-old infants look longer at outcomes that are inconsistent with a logical inference necessary t...
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    Factoring stream turbulence into global assessments of nitrogen pollution - The discharge of excess nitrogen to streams and rivers poses an existential threat to both humans and ecosystems. A seminal study of headwater streams across the United States concluded that in-stream removal of nitrate is controlled primarily by stream chemistry and biology. Reanalysis of these data reveals that stream turbulence (in particular, turbulent mass transfer across the concentration boundary layer) imposes a previously unrecognized u...
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    Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development - Neuronal synapse formation and remodeling are essential to central nervous system (CNS) development and are dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this affects CNS synapses is largely unknown. Here, we show that the interleukin-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers an...
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    Rev-erb{alpha} dynamically modulates chromatin looping to control circadian gene transcription - Mammalian physiology exhibits 24-hour cyclicity due to circadian rhythms of gene expression controlled by transcription factors that constitute molecular clocks. Core clock transcription factors bind to the genome at enhancer sequences to regulate circadian gene expression, but not all binding sites are equally functional. We found that in mice, circadian gene expression in the liver is controlled by rhythmic chromatin interactions between enhan...
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    Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging - In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large l...
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    Mutation dynamics and fitness effects followed in single cells - Mutations have been investigated for more than a century but remain difficult to observe directly in single cells, which limits the characterization of their dynamics and fitness effects. By combining microfluidics, time-lapse imaging, and a fluorescent tag of the mismatch repair system in Escherichia coli, we visualized the emergence of mutations in single cells, revealing Poissonian dynamics. Concomitantly, we tracked the growth and life span ...
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    Comment on "Synthesis and characterization of the pentazolate anion cyclo-N5- in (N5)6(H3O)3(NH4)4Cl" - Zhang et al. (Reports, 27 January 2017, p. 374) reported synthesis of a cyclo-N5– ion putatively stabilized in a solid-state salt by hydrogen bonding from surrounding counterions. We performed theoretical calculations suggesting that HN5 would be favored over the anion in the reported pentazolate salt via proton transfer. ...
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    Topological insulator laser: Theory - Topological insulators are phases of matter characterized by topological edge states that propagate in a unidirectional manner that is robust to imperfections and disorder. These attributes make topological insulator systems ideal candidates for enabling applications in quantum computation and spintronics. We propose a concept that exploits topological effects in a unique way: the topological insulator laser. These are lasers whose lasing mode e...
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    Topological insulator laser: Experiments - Physical systems exhibiting topological invariants are naturally endowed with robustness against perturbations, as manifested in topological insulators—materials exhibiting robust electron transport, immune from scattering by defects and disorder. Recent years have witnessed intense efforts toward exploiting these phenomena in photonics. Here we demonstrate a nonmagnetic topological insulator laser system exhibiting topologically protected...
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    Response to Comment on "Synthesis and characterization of the pentazolate anion cyclo-N5- in (N5)6(H3O)3(NH4)4Cl" - Huang and Xu argue that the cyclo-N5– ion in (N5)6(H3O)3(NH4)4Cl we described in our report is theoretically unfavorable and is instead protonated. Their conclusion is invalid, as they use an improper method to assess the proton transfer in a solid crystal structure. We present an in-depth experimental and theoretical analysis of (N5)6(H3O)3(NH4)4Cl that supports the results in the original paper. ...
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