Qatar Islamic Archaeology and Heritage Project: End of Season Report : 2011-2012

International audienc

Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease

Ankylosing spondylitis (AS) is a common inflammatory arthritic condition. Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis. Spondyloarthritis is also common in IBD patients. We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases. Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions. We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS. Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK. Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.6×10−10, odds ratio (OR) = 0.74, 95% CI:0.68–0.82). Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6×10−4. OR = 0.86 (95% CI:0.79–0.93); rs744166, P = 2.6×10−5, OR = 0.84 (95% CI:0.77–0.91)). Association was confirmed for IL23R (rs11465804, P = 1.2×10−5, OR = 0.65 (95% CI:0.54–0.79)), and further associations were detected for IL12B (rs10045431, P = 5.2×10−5, OR = 0.83 (95% CI:0.76–0.91)), CDKAL1 (rs6908425, P = 1.1×10−4, OR = 0.82 (95% CI:0.74–0.91)), LRRK2/MUC19 (rs11175593, P = 9.9×10−5, OR = 1.92 (95% CI: 1.38–2.67)), and chr13q14 (rs3764147, P = 5.9×10−4, OR = 1.19 (95% CI: 1.08–1.31)). Excluding cases with clinical IBD did not significantly affect these findings. This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci. It also further confirms association for IL23R and detects suggestive association with another 4 loci. STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis. Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases

Dynamics of Convectively Driven Banded Jets in the Laboratory

The banded organization of clouds and zonal winds in the atmospheres of the outer planets has long fascinated observers. Several recent studies in the theory and idealized modeling of geostrophic turbulence have suggested possible explanations for the emergence of such organized patterns, typically involving highly anisotropic exchanges of kinetic energy and vorticity within the dissipationless inertial ranges of turbulent flows dominated (at least at large scales) by ensembles of propagating Rossby waves. The results from an attempt to reproduce such conditions in the laboratory are presented here. Achievement of a distinct inertial range turns out to require an experiment on the largest feasible scale. Deep, rotating convection on small horizontal scales was induced by gently and continuously spraying dense, salty water onto the free surface of the 13-m-diameter cylindrical tank on the Coriolis platform in Grenoble, France. A “planetary vorticity gradient” or “β effect” was obtained by use of a conically sloping bottom and the whole tank rotated at angular speeds up to 0.15 rad s−1. Over a period of several hours, a highly barotropic, zonally banded large-scale flow pattern was seen to emerge with up to 5–6 narrow, alternating, zonally aligned jets across the tank, indicating the development of an anisotropic field of geostrophic turbulence. Using particle image velocimetry (PIV) techniques, zonal jets are shown to have arisen from nonlinear interactions between barotropic eddies on a scale comparable to either a Rhines or “frictional” wavelength, which scales roughly as (β/Urms)−1/2. This resulted in an anisotropic kinetic energy spectrum with a significantly steeper slope with wavenumber k for the zonal flow than for the nonzonal eddies, which largely follows the classical Kolmogorov k−5/3 inertial range. Potential vorticity fields show evidence of Rossby wave breaking and the presence of a “hyperstaircase” with radius, indicating instantaneous flows that are supercritical with respect to the Rayleigh–Kuo instability criterion and in a state of “barotropic adjustment.” The implications of these results are discussed in light of zonal jets observed in planetary atmospheres and, most recently, in the terrestrial oceans.Engineering and Applied Science

The dynamics of Baroclinic Zonal jets

Multiple alternating zonal jets are a ubiquitous feature of planetary atmospheres and oceans. However, most studies to date have focused on the special case of barotropic jets. Here, the dynamics of freely evolving baroclinic jets are investigated using a two-layer quasigeostrophic annulus model with sloping topography. In a suite of 15 numerical simulations, the baroclinic Rossby radius and baroclinic Rhines scale are sampled by varying the stratification and root-mean-square eddy velocity, respectively. Small-scale eddies in the initial state evolve through geostrophic turbulence and accelerate zonally as they grow in horizontal scale, first isotropically and then anisotropically. This process leads ultimately to the formation of jets, which take about 2500 rotation periods to equilibrate. The kinetic energy spectrum of the equilibrated baroclinic zonal flow steepens from a −3 power law at small scales to a −5 power law near the jet scale. The conditions most favorable for producing multiple alternating baroclinic jets are large baroclinic Rossby radius (i.e., strong stratification) and small baroclinic Rhines scale (i.e., weak root-mean-square eddy velocity). The baroclinic jet width is diagnosed objectively and found to be 2.2–2.8 times larger than the baroclinic Rhines scale, with a best estimate of 2.5 times larger. This finding suggests that Rossby wave motions must be moving at speeds of approximately 6 times the turbulent eddy velocity in order to be capable of arresting the isotropic inverse energy cascade

The Need for Laboratory Measurements and Ab Initio Studies to Aid Understanding of Exoplanetary Atmospheres

We are now on a clear trajectory for improvements in exoplanet observations that will revolutionize our ability to characterize their atmospheric structure, composition, and circulation, from gas giants to rocky planets. However, exoplanet atmospheric models capable of interpreting the upcoming observations are often limited by insufficiencies in the laboratory and theoretical data that serve as critical inputs to atmospheric physical and chemical tools. Here we provide an up-to-date and condensed description of areas where laboratory and/or ab initio investigations could fill critical gaps in our ability to model exoplanet atmospheric opacities, clouds, and chemistry, building off a larger 2016 white paper, and endorsed by the NAS Exoplanet Science Strategy report. Now is the ideal time for progress in these areas, but this progress requires better access to, understanding of, and training in the production of spectroscopic data as well as a better insight into chemical reaction kinetics both thermal and radiation-induced at a broad range of temperatures. Given that most published efforts have emphasized relatively Earth-like conditions, we can expect significant and enlightening discoveries as emphasis moves to the exotic atmospheres of exoplanets.Comment: Submitted as an Astro2020 Science White Pape

Investigating the genetic association between ERAP1 and ankylosing spondylitis

A strong association between ERAP1 and ankylosing spondylitis (AS) was recently identified by the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium (WTCCC-TASC) study. ERAP1 is highly polymorphic with strong linkage disequilibrium evident across the gene. We therefore conducted a series of experiments to try to identify the primary genetic association(s) with ERAP1. We replicated the original associations in an independent set of 730 patients and 1021 controls, resequenced ERAP1 to define the full extent of coding polymorphisms and tested all variants in additional association studies. The genetic association with ERAP1 was independently confirmed; the strongest association was with rs30187 in the replication set (P = 3.4 × 10−3). When the data were combined with the original WTCCC-TASC study the strongest association was with rs27044 (P = 1.1 × 10−9). We identified 33 sequence polymorphisms in ERAP1, including three novel and eight known non-synonymous polymorphisms. We report several new associations between AS and polymorphisms distributed across ERAP1 from the extended case–control study, the most significant of which was with rs27434 (P = 4.7 × 10−7). Regression analysis failed to identify a primary association clearly; we therefore used data from HapMap to impute genotypes for an additional 205 non-coding SNPs located within and adjacent to ERAP1. A number of highly significant associations (P < 5 × 10−9) were identified in regulatory sequences which are good candidates for causing susceptibility to AS, possibly by regulating ERAP1 expression

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype

Genomewide association study of acute anterior uveitis identifies new susceptibility loci

Acknowledgments The authors thank all participating subjects with AS and healthy individuals who provided the DNA and clinical information necessary for this study. We would like to acknowledge the contributions of Anna Deminger, Sahlgrenska Academy at University of Gothenburg, and Urban Hellman, Umeå University, for their assistance in case recruitment and assessment and handling biological samples Funding Information: The survey was conducted by NatCen and the genomewide scan data were analyzed and deposited by the Wellcome Trust Sanger Institute. Information on how to access the data can be found on the Understanding Society website https: www. understandingsociety.ac.uk/ . We acknowledge and thank the TCRA AS Group for their support in recruiting patients for the study. M.A.B. is funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship, and support for this study was received from a National Health and Medical Research Council (Australia) program Grant (566938) and project Grant (569829), and from the Australian Cancer Research Foundation and Rebecca Cooper Medical Research Foundation. We are also very grateful for the invaluable support received from the National Ankylosing Spondylitis Society (UK) and Spondyloarthritis Association of America in case recruitment. Additional financial and technical support for patient recruitment was provided by the National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit and NIHR Thames Valley Comprehensive Local Research and an unrestricted educational grant from Abbott Laboratories. The authors acknowledge the sharing of data and samples by the BSRBR-AS Register in Aberdeen. Chief Investigator, Prof Gary Macfarlane and Dr Gareth Jones, Deputy Chief Investigator, created the BSRBR-AS study, which was commissioned by the British Society for Rheumatology, funded in part by Abbvie, Pfizer, and UCB. We are grateful to every patient, past and present staff of the BSRBR-AS register team, and to all clinical staff who recruited patients, followed them up and entered data – details here: https://www.abdn.ac.uk/iahs/research/ epidemiology/spondyloarthritis.php#panel1011. Funding was also received from the Swedish Research Council and The Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement. The Irish data was derived from participants in ASRI – The Ankylosing Spondylitis Registry of Ireland, which is funded by unrestricted grants from Abbvie and Pfizer. Funding bodies involved played no role in the study design, performance, or preparation of this manuscript. Funding Information: X.F.H. was funded by the National Natural Science Foundation of China (31771390). The TASC study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants P01-052915, R01-AR046208. Funding was also received from the University of Texas Health Science Center at Houston CTSA grant UL1RR02418, Cedars-Sinai GCRC grant MO1-RR00425, Intramural Research Program, NIAMS/NIH, and Rebecca Cooper Foundation (Australia). This study was funded, in part, by Arthritis Research UK (Grants 19536 and 18797), by the Wellcome Trust (Grant number 076113), and by the Oxford Comprehensive Biomedical Research Centre ankylosing spondylitis chronic disease cohort (Theme Code: A91202). The New Zealand data was derived from participants in the Spondyloarthritis Genetics and the Environment Study (SAGE) and was funded by The Health Research Council, New Zealand. H.X. was funded by the National Natural Science Foundation of China Grant 81020108029 and 30872339. French sample collection was performed by the Groupe Française d’Etude Génétique des Spondylarthrites, coordinated by Professor Maxime Breban, and funded by the Agence Nationale de Recherche GEMISA grant reference ANR-10-MIDI-0002. We acknowledge the Understanding Society: The UK Household Longitudinal Study. This is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council. Publisher Copyright: © 2020 Association for Research in Vision and Ophthalmology Inc.. All rights reserved.Peer reviewedPublisher PD

Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap

&lt;p&gt;Objectives: Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA.&lt;/p&gt; &lt;p&gt;Methods: Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings.&lt;/p&gt; &lt;p&gt;Results: Thirteen SNP showed significant association (p&#60;0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort.&lt;/p&gt; &lt;p&gt;Conclusions: A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.&lt;/p&gt

Dynamics of convectively driven banded jets in the laboratory

The banded organization of clouds and zonal winds in the atmospheres of the outer planets has long fascinated observers. Several recent studies in the theory and idealized modeling of geostrophic turbulence have suggested possible explanations for the emergence of such organized patterns, typically involving highly anisotropic exchanges of kinetic energy and vorticity within the dissipationless inertial ranges of turbulent flows dominated (at least at large scales) by ensembles of propagating Rossby waves. The results from an attempt to reproduce such conditions in the laboratory are presented here. Achievement of a distinct inertial range turns out to require an experiment on the largest feasible scale. Deep, rotating convection on small horizontal scales was induced by gently and continuously spraying dense, salty water onto the free surface of the 13-m-diameter cylindrical tank on the Coriolis platform in Grenoble, France. A “planetary vorticity gradient” or “β effect” was obtained by use of a conically sloping bottom and the whole tank rotated at angular speeds up to 0.15 rad s−1. Over a period of several hours, a highly barotropic, zonally banded large-scale flow pattern was seen to emerge with up to 5–6 narrow, alternating, zonally aligned jets across the tank, indicating the development of an anisotropic field of geostrophic turbulence. Using particle image velocimetry (PIV) techniques, zonal jets are shown to have arisen from nonlinear interactions between barotropic eddies on a scale comparable to either a Rhines or “frictional” wavelength, which scales roughly as (β/Urms)−1/2. This resulted in an anisotropic kinetic energy spectrum with a significantly steeper slope with wavenumber k for the zonal flow than for the nonzonal eddies, which largely follows the classical Kolmogorov k−5/3 inertial range. Potential vorticity fields show evidence of Rossby wave breaking and the presence of a “hyperstaircase” with radius, indicating instantaneous flows that are supercritical with respect to the Rayleigh–Kuo instability criterion and in a state of “barotropic adjustment.” The implications of these results are discussed in light of zonal jets observed in planetary atmospheres and, most recently, in the terrestrial oceans