1,511 research outputs found

    GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation

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    COPI is a key mediator of protein trafficking within the secretory pathway. COPI is recruited to the membrane primarily through binding to Arf GTPases, upon which it undergoes assembly to form coated transport intermediates responsible for trafficking numerous proteins, including Golgi-resident enzymes. Here, we identify GORAB, the protein mutated in the skin and bone disorder gerodermia osteodysplastica, as a component of the COPI machinery. GORAB forms stable domains at the trans-Golgi that, via interactions with the COPI-binding protein Scyl1, promote COPI recruitment to these domains. Pathogenic GORAB mutations perturb Scyl1 binding or GORAB assembly into domains, indicating the importance of these interactions. Loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor, and support the view that defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica.Peer reviewe

    Scientific access into Mercer Subglacial Lake: scientific objectives, drilling operations and initial observations

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    © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Priscu, J. C., Kalin, J., Winans, J., Campbell, T., Siegfried, M. R., Skidmore, M., Dore, J. E., Leventer, A., Harwood, D. M., Duling, D., Zook, R., Burnett, J., Gibson, D., Krula, E., Mironov, A., McManis, J., Roberts, G., Rosenheim, B. E., Christner, B. C., Kasic, K., Fricker, H. A., Lyons, W. B., Barker, J., Bowling, M., Collins, B., Davis, C., Gagnon, A., Gardner, C., Gustafson, C., Kim, O-S., Li, W., Michaud, A., Patterson, M. O., Tranter, M., Ryan Venturelli, R., Trista Vick-Majors, T., & Elsworth, C. Scientific access into Mercer Subglacial Lake: scientific objectives, drilling operations and initial observations. Annals of Glaciology, 62(85–86), (2021): 340–352, https://doi.org/10.1017/aog.2021.10.The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.This material is based upon work supported by the US National Science Foundation, Section for Antarctic Sciences, Antarctic Integrated System Science program as part of the interdisciplinary (Subglacial Antarctic Lakes Scientific Access (SALSA): Integrated study of carbon cycling in hydrologically-active subglacial environments) project (NSF-OPP 1543537, 1543396, 1543405, 1543453 and 1543441). Ok-Sun Kim was funded by the Korean Polar Research Institute. We are particularly thankful to the SALSA traverse personnel for crucial technical and logistical support. The United States Antarctic Program enabled our fieldwork; the New York Air National Guard and Kenn Borek Air provided air support; UNAVCO provided geodetic instrument support. Hot water drilling activities, including repair and upgrade modifications of the WISSARD hot water drill system, for the SALSA project were supported by a subaward from the Ice Drilling Program of Dartmouth College (NSF-PLR 1327315) to the University of Nebraska-Lincoln. J. Lawrence assisted with manuscript preparation. Finally, we are grateful to C. Dean, the SALSA Project Manager, and R. Ricards, SALSA Project Coordinator at McMurdo Station, for their organizational skills, and B. Huber of Lamont-Doherty Earth Observatory for providing the SBE39 PT sensors and the Nortek Aquadopp current meter and assisting with interpretation of the data. B. Huber also provided helpful input on programing and calibrating the SBE19PlusV2 6112 CTD

    Search for new physics with dijet angular distributions in proton-proton collisions at root S = 13 TeV

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    Search for light bosons in decays of the 125 GeV Higgs boson in proton-proton collisions at root s=8 TeV

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    Cross section measurement of t-channel single top quark production in pp collisions at root s=13 TeV

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    Search for Evidence of the Type-III Seesaw Mechanism in Multilepton Final States in Proton-Proton Collisions at root s=13 TeV

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    Search for Higgsino pair production in pp collisions at root s=13 TeV in final states with large missing transverse momentum and two Higgs bosons decaying via H -> b(b)over bar

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    Results are reported from a search for new physics in 13 TeV proton-proton collisions in the final state with large missing transverse momentum and two Higgs bosons decaying via H -> b(b)over bar. The search uses a data sample accumulated by the CMS experiment at the LHC in 2016, corresponding to an integrated luminosity of 35.9 fb(-1). The search is motivated by models based on gauge-mediated supersymmetry breaking, which predict the electroweak production of a pair of Higgsinos, each of which can decay via a cascade process to a Higgs boson and an undetected lightest supersymmetric particle. The observed event yields in the signal regions are consistent with the standard model background expectation obtained from control regions in data. Higgsinos in the mass range 230-770 GeV are excluded at 95% confidence level in the context of a simplified model for the production and decay of approximately degenerate Higgsinos.Peer reviewe

    Search for a light pseudoscalar Higgs boson produced in association with bottom quarks in pp collisions at root s=8 TeV

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    Measurement of vector boson scattering and constraints on anomalous quartic couplings from events with four leptons and two jets in proton-proton collisions at root s=13 TeV

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    Measurement of the top quark mass using single top quark events in proton-proton collisions at root s=8 TeV

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