42 research outputs found
Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies
To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD
The impact of viral mutations on recognition by SARS-CoV-2 specific TÂ cells.
We identify amino acid variants within dominant SARS-CoV-2 TÂ cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific TÂ cells assessed by IFN-Îł and cytotoxic killing assays. Complete loss of TÂ cell responsiveness was seen due to Q213K in the Aâ01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the Bâ27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the Aâ03:01/Aâ11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ TÂ cell lines unable to recognize variant epitopes have diverse TÂ cell receptor repertoires. These data demonstrate the potential for TÂ cell evasion and highlight the need for ongoing surveillance for variants capable of escaping TÂ cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC â IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC
Ability of the Mandarina Bavaria hop variety to release free odorant polyfunctional thiols in lateâhopped beers
An ultradeep submillimetre map: beneath the SCUBA confusion limit with lensing and robust source extraction
Extracting sources with low signal-to-noise from maps with structured
background is a non-trivial task which has become important in studying the
faint end of the submillimetre number counts. In this article we study source
extraction from submillimetre jiggle-maps from the Submillimetre Common-User
Bolometer Array (SCUBA) using the Mexican Hat Wavelet (MHW), an isotropic
wavelet technique. As a case study we use a large (11.8 arcmin^2) jiggle-map of
the galaxy cluster Abell 2218, with a 850um 1sigma r.m.s. sensitivity of
0.6-1mJy. We show via simulations that MHW is a powerful tool for reliable
extraction of low signal-to-noise sources from SCUBA jiggle-maps and nine
sources are detected in the A2218 850um image. Three of these sources are
identified as images of a single background source with an unlensed flux of
0.8mJy. Further, two single-imaged sources also have unlensed fluxes <2mJy,
below the blank-field confusion limit. In this ultradeep map, the individual
sources detected resolve nearly all of the extragalactic background light at
850um, and the deep data allow to put an upper limit of 44 sources per arcmin^2
to 0.2mJy at 850um.Comment: 11 pages, 6 figures. Accepted for publication in MNRAS. Figures 2 and
4 (lower panel) available in higher resolution
http://www.mpia.de/homes/knudsen/papers/mhw_paper.htm