Determination of Population Structure of Wheat Core Collection for Association Mapping

The microsatellites, as one of the most robust markers for identification of wheat varieties, were used for assessment of genetic diversity and population structure to promote effective use of genetic resources. In this study, the set of 284 wheat varieties were genotyped using 30 microsatellite markers. The chosen SSR markers were located among almost all linkage groups and covered all three genomes. The genotypes used originate from 24 different breeding centers worldwide and are included in an extensive core collection of the Institute of Field and Vegetable Crops in Novi Sad, Serbia. The total number of detected alleles was 349 at all analyzed loci. The average number of detected allelic variant per locus was 11.5. The mean value of polymorphic information content was 0.68. According to the probability of data obtained by program Structure, the results have shown presence of 6 subpopulations within the studied set of genotypes. The population structure positively correlated to some extent with geographic origin. The available pedigree data were included for additional explanation of population structure. The results of this study should provide valuable information for future association studies using the diverse wheat breeding material

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Integrating outcrop and subsurface data to assess the temporal evolution of a submarine channel-levee system

The morphological evolution of submarine channel systems can be documented using high-resolution three-dimensional seismic data sets. However, these studies provide limited information on the distribution of sedimentary facies within channel fills, channelscale stacking patterns, or the detailed stratigraphic relationship with adjacent levee-overbank deposits. Seismic-scale outcrops of unit C2 in the Permian Fort Brown Formation, Karoo Basin, South Africa, on two subparallel fold limbs comprise thin-bedded successions, interpreted as external levee deposits, which are adjacent to channel complexes, with constituent channels filled with thick-bedded structureless sandstones, thinner-bedded channel margin facies, and internal levee deposits. Research boreholes intersect all these deposits, to link sedimentary facies and channel stacking patterns identified in core and on image logs and detailed outcrop correlation panels. Key characteristics, including depth of erosion, stacking patterns, and cross-cutting relationships, have been constrained, allowing paleogeographic reconstruction of six channel complexes in a 36-km2 (14-mi2) area. The system evolved from an early, deeply incised channel complex, through a series of external levee-confined and laterally stepping channel complexes culminating in an aggradational channel complex confined by both internal and external levees. Down-dip divergence of six channel complexes from the same location suggests the presence of a unique example of an exhumed deep-water avulsion node. Down-dip, external levees are supplied by flows that escaped fromchannel complexes of different ages and spatial positions and are partly confined and share affinities with internal levee successions. The absence of frontal lobes suggests that the channels remained in sand bypass mode immediately after avulsion.Applied Geolog

Leucocyte subset-specific type 1 interferon signatures in SLE and other immune-mediated diseases

10.1136/rmdopen-2015-000183RMD Open21e00018

Biological and clinical insights from a randomized phase 2 study of an anti-oncostatin M monoclonal antibody in systemic sclerosis

OBJECTIVES: The cytokine oncostatin M (OSM) is implicated in the pathology of SSc. Inhibiting OSM signalling using GSK2330811 (an anti-OSM monoclonal antibody) in patients with SSc has the potential to slow or stop the disease process. METHODS: This multicentre, randomized, double-blind, placebo-controlled study enrolled participants ≥18 years of age with active dcSSc. Participants were randomized 3:1 (GSK2330811:placebo) in one of two sequential cohorts to receive GSK2330811 (cohort 1: 100 mg; cohort 2: 300 mg) or placebo s.c. every other week for 12 weeks. The primary endpoint was safety; blood and skin biopsy samples were collected to explore mechanistic effects on inflammation and fibrosis. Clinical efficacy was an exploratory endpoint. RESULTS: Thirty-five participants were randomized to placebo (n = 8), GSK2330811 100 mg (n = 3) or GSK2330811 300 mg (n = 24). Proof of mechanism, measured by coordinate effects on biomarkers of inflammation or fibrosis, was not demonstrated following GSK2330811 treatment. There were no meaningful differences between GSK2330811 and placebo for any efficacy endpoints. The safety and tolerability of GSK2330811 were not favourable in the 300 mg group, with on-target, dose-dependent adverse events related to decreases in haemoglobin and platelet count that were not observed in the 100 mg or placebo groups. CONCLUSION: Despite a robust and novel experimental medicine approach and evidence of target engagement, anticipated SSc-related biologic effects of GSK2330811 were not different from placebo and safety was unfavourable, suggesting OSM inhibition may not be a useful therapeutic strategy in SSc. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03041025; EudraCT, 2016-003417-95