33 research outputs found

    FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression.

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    Sialyl-Lewis x (sLex, CD15s) is a tetra-saccharide on the surface of leukocytes required for E-selectin-mediated rolling, a prerequisite for leukocytes to migrate out of the blood vessels. Here we show using flow cytometry that sLex expression on basophils and mast cell progenitors depends on fucosyltransferase 6 (FUT6). Using genetic association data analysis and qPCR, the cell type-specific defect was associated with single nucleotide polymorphisms (SNPs) in the FUT6 gene region (tagged by rs17855739 and rs778798), affecting coding sequence and/or expression level of the mRNA. Heterozygous individuals with one functional FUT6 gene harbor a mixed population of sLex+ and sLex- basophils, a phenomenon caused by random monoallelic expression (RME). Microfluidic assay demonstrated FUT6-deficient basophils rolling on E-selectin is severely impaired. FUT6 null alleles carriers exhibit elevated blood basophil counts and a reduced itch sensitivity against insect bites. FUT6-deficiency thus dampens the basophil-mediated allergic response in the periphery, evident also in lower IgE titers and reduced eosinophil counts

    Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

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    Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

    Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial

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    The wide-field, multiplexed, spectroscopic facility WEAVE : survey design, overview, and simulated implementation

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    Funding for the WEAVE facility has been provided by UKRI STFC, the University of Oxford, NOVA, NWO, Instituto de AstrofĂ­sica de Canarias (IAC), the Isaac Newton Group partners (STFC, NWO, and Spain, led by the IAC), INAF, CNRS-INSU, the Observatoire de Paris, RĂ©gion Île-de-France, CONCYT through INAOE, Konkoly Observatory (CSFK), Max-Planck-Institut fĂŒr Astronomie (MPIA Heidelberg), Lund University, the Leibniz Institute for Astrophysics Potsdam (AIP), the Swedish Research Council, the European Commission, and the University of Pennsylvania.WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959 nm at R ∌ 5000, or two shorter ranges at R ∌ 20,000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∌ 3 million stars and detailed abundances for ∌ 1.5 million brighter field and open-cluster stars; (ii) survey ∌ 0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey  ∌ 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z 1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.PostprintPeer reviewe

    The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation

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    WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366−-959\,nm at R∌5000R\sim5000, or two shorter ranges at R∌20 000R\sim20\,000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∌\sim3 million stars and detailed abundances for ∌1.5\sim1.5 million brighter field and open-cluster stars; (ii) survey ∌0.4\sim0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey ∌400\sim400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z<0.5z<0.5 cluster galaxies; (vi) survey stellar populations and kinematics in ∌25 000\sim25\,000 field galaxies at 0.3â‰Čzâ‰Č0.70.3\lesssim z \lesssim 0.7; (vii) study the cosmic evolution of accretion and star formation using >1>1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z>2z>2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.Comment: 41 pages, 27 figures, accepted for publication by MNRA

    The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation

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    WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366−959\,nm at R∌5000, or two shorter ranges at R∌20000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∌3 million stars and detailed abundances for ∌1.5 million brighter field and open-cluster stars; (ii) survey ∌0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey ∌400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z>2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator

    Local Vibrio isolates exhibit molecular characteristics distinct from reference V. harveyi and V. campbellii strains

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    Six Vibrio isolates identified biochemically as Vibrio campbellii from Southeast Asian Fisheries Development Center (SEAFDEC) in Tigbauan, Iloilo, were characterized by 16 rDNA sequence, total protein profile, and DNA profile analyses. Genomic DNA from the isolates were subjected to PCR using four sets of primers targeting gene fragments of hemolysin and toxR based on sequences from reference Vibrio harveyi (IFO15634), V. campbellii (IFO1563), and local isolates identified as V. harveyi. Total protein profile could not distinguish the isolates from one another and from the reference V. harveyi (IFO15634) and V. campbellii (IFO15631). Analysis of 16s rDNA sequences revealed high degree of sequence similarity (96% - 99%) of the six local isolates with other Vibrio species including V. campbellii and V. parahaemolyticus, indicating that this analysis will not be useful in resolving their identity. All six isolates exhibited characteristic reference V. harveyi PCR profile when a primer set designed to amplify a 308-bp fragment of hemolysin gene in that species was used. However, no amplicons were generated for these isolates using primers that amplify toxR gene fragments in V. harveyi. This suggests that the six isolates were not bonafide V. harveyi strains. The isolates also did not exhibit V. campbellii characteristics since the primer designed to target the toxR gene in V. campbellii could not amplify DNA from any of the six isolates, suggesting that they were not bonafide V. campbellii strains either. The toxR gene from the six isolates could be amplified using a primer based on toxR gene sequences from a SEAFDEC isolate previously identified as V. harveyi (PN-9801). These data suggest that the six isolates previously identified as V. campbellii as well as PN-9801 may be classified in one group separate from bonafide reference V. harveyi and reference V. campbellii strains, based on the identical results in the molecular analyses performed in this study
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