Community and the creation of provincial identities: a re-interpretation of the aisled building at North Warnborough

The aisled hall at North Warnborough has attracted attention as one of a handful of examples frequently included in surveys and analyses of this common architectural type as well as for arguments related to the gendered use of space. This article presents a new architectural analysis of this building and attempts to set it within its immediate and wider archaeological and geological landscape context. A theoretically informed interpretation of the social significance of this site is offered, which has broader implications for the studies of Romano-British architecture, rural settlement, and landscape

Optical Light Curves of Supernovae

Photometry is the most easily acquired information about supernovae. The light curves constructed from regular imaging provide signatures not only for the energy input, the radiation escape, the local environment and the progenitor stars, but also for the intervening dust. They are the main tool for the use of supernovae as distance indicators through the determination of the luminosity. The light curve of SN 1987A still is the richest and longest observed example for a core-collapse supernova. Despite the peculiar nature of this object, as explosion of a blue supergiant, it displayed all the characteristics of Type II supernovae. The light curves of Type Ib/c supernovae are more homogeneous, but still display the signatures of explosions in massive stars, among them early interaction with their circumstellar material. Wrinkles in the near-uniform appearance of thermonuclear (Type Ia) supernovae have emerged during the past decade. Subtle differences have been observed especially at near-infrared wavelengths. Interestingly, the light curve shapes appear to correlate with a variety of other characteristics of these supernovae. The construction of bolometric light curves provides the most direct link to theoretical predictions and can yield sorely needed constraints for the models. First steps in this direction have been already made.Comment: To be published in:"Supernovae and Gamma Ray Bursters", Lecture Notes in Physics (http://link.springer.de/series/lnpp

Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases

Effector functions of immunoglobulin G (IgG) are regulated by the composition of a glycan moiety, thus affecting activity of the immune system. Aberrant glycosylation of IgG has been observed in many diseases, but little is understood about the underlying mechanisms. We performed a genome-wide association study of IgG N-glycosylation (N = 8090) and, using a data-driven network approach, suggested how associated loci form a functional network. We confirmed in vitro that knockdown of IKZF1 decreases the expression of fucosyltransferase FUT8, resulting in increased levels of fucosylated glycans, and suggest that RUNX1 and RUNX3, together with SMARCB1, regulate expression of glycosyltransferase MGAT3. We also show that variants affecting the expression of genes involved in the regulation of glycoenzymes colocalize with variants affecting risk for inflammatory diseases. This study provides new evidence that variation in key transcription factors coupled with regulatory variation in glycogenes modifies IgG glycosylation and has influence on inflammatory diseases.Molecular Epidemiolog

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