60 research outputs found

    Structural basis of tRNA modification with CO2 fixation and methylation by wybutosine synthesizing enzyme TYW4†

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    Wybutosine (yW), one of the most complicated modified nucleosides, is found in the anticodon loop of eukaryotic phenylalanine tRNA. This hypermodified nucleoside ensures correct codon recognition by stabilizing codon-anticodon pairings during the decoding process in the ribosome. TYW4 is an S-adenosylmethionine (SAM)-dependent enzyme that catalyzes the final step of yW biosynthesis, methylation and methoxycarbonylation. However, the structural basis for the catalytic mechanism by TYW4, and especially that for the methoxycarbonylation, have remained elusive. Here we report the apo and cofactor-bound crystal structures of yeast TYW4. The structures revealed that the C-terminal domain folds into a β-propeller structure, forming part of the binding pocket for the target nucleoside. A comparison of the apo, SAM-bound, and S-adenosylhomocysteine-bound structures of TYW4 revealed a drastic structural change upon cofactor binding, which may sequester solvent from the catalytic site during the reaction and facilitate product release after the reaction. In conjunction with the functional analysis, our results suggest that TYW4 catalyzes both methylation and methoxycarbonylation at a single catalytic site, and in the latter reaction, the methoxycarbonyl group is formed through the fixation of carbon dioxide

    Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

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    Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

    Shearwater Foraging in the Southern Ocean: The Roles of Prey Availability and Winds

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    Background Sooty (Puffinus griseus) and short-tailed (P. tenuirostris) shearwaters are abundant seabirds that range widely across global oceans. Understanding the foraging ecology of these species in the Southern Ocean is important for monitoring and ecosystem conservation and management. Methodology/Principal Findings Tracking data from sooty and short-tailed shearwaters from three regions of New Zealand and Australia were combined with at-sea observations of shearwaters in the Southern Ocean, physical oceanography, near-surface copepod distributions, pelagic trawl data, and synoptic near-surface winds. Shearwaters from all three regions foraged in the Polar Front zone, and showed particular overlap in the region around 140°E. Short-tailed shearwaters from South Australia also foraged in Antarctic waters south of the Polar Front. The spatial distribution of shearwater foraging effort in the Polar Front zone was matched by patterns in large-scale upwelling, primary production, and abundances of copepods and myctophid fish. Oceanic winds were found to be broad determinants of foraging distribution, and of the flight paths taken by the birds on long foraging trips to Antarctic waters. Conclusions/Significance The shearwaters displayed foraging site fidelity and overlap of foraging habitat between species and populations that may enhance their utility as indicators of Southern Ocean ecosystems. The results highlight the importance of upwellings due to interactions of the Antarctic Circumpolar Current with large-scale bottom topography, and the corresponding localised increases in the productivity of the Polar Front ecosystem

    A Brief History of Marine Litter Research

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    Göteborgs Stads avfallshantering – en riktig sopa? - En explorativ fallstudie kring hinder och möjligheter till innovativa systemutvecklingar i Göteborgs Stad

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    Bakgrund och problemdiskussion: Att lyckas åstadkomma en hälsosam och levande stadsmiljö i symbios med den exponentiellt ökande urbaniseringen är en global utmaning. Denna utmaning kräver smarta systemlösningar idag för att vi inte skall äventyra kommande generationers möjligheter att tillgodose sina behov i framtiden. Då kommunerna är den främsta aktören inom utvecklingen och planeringen av samhället är dess inställning och kompetens inom systemutveckling viktig. Det krävs ett samarbete mellan kommuner, landsting, stat och privata aktörer för att kunna sammanlänka alla olika aspekter och skapa en långsiktighet. Uppsatsens syfte: Syftet med uppsatsen är att ur ett företagsekonomiskt perspektiv undersöka vilka hinder och möjligheter det finns för innovativa företag med hållbara lösningar att ta sig in på en redan etablerad kommunalstyrd marknad. Vi vill veta vilka samverkansprocesser det finns inom Göteborgs Stads avfallshantering och hur dessa aktörer ser på framtida utmaningar. Metod: Uppsatsen är en explorativ studie med en kvalitativ metod. Intervjuer har genomförts med representanter från fem organisationer/företag vilka är involverade inom stadsplanering och avfallshantering inom Göteborgs Stad. Det empiriska resultat vi fått fram har sedan analyserats mot det valda teoretiska ramverket. Resultat och slutsats: Resultatet av studien visar att det finns en osäkerhet bland marknadens aktörer, vilket leder till en motståndskraft att lämna existerande systemlösningar, då dessa historiskt sett varit fungerande. En av de främsta utmaningarna för en hållbar utveckling är att det krävs nya innovationer och nya kunskaper. En samverkan mellan kommunala och privata aktörer är nödvändig för att en helhetslösning skall kunna implementeras
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