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

Effects of within-tree flowering asynchrony on the dynamics of seed and wasp production in an Australian fig species

Within-tree flowering asynchrony in figs, which may allow pollinating wasps to avoid the risks of dispersal in inclement conditions, has been predicted as a trait to be favoured in highly seasonal environments. Comparisons of such asynchronous figs with better-known species that exhibit within-tree synchrony might also be expected to reveal differences in the outcome of the conflict between pollinator wasp and fig seed production, and the dynamics of non-pollinating wasps. This paper presents data on wasp and seed production in Ficus rubiginosa Desf. ex Vent., an asynchronous species that occurs in the highly seasonal environment of south-eastern Australia. In contrast to recent studies of figs showing within-tree flowering synchrony, syconium size was the main determinant of wasp and seed production in F. rubiginosa. Non-pollinating wasps were highly prevalent but occurred in low numbers and appeared to have relatively little impact on pollinator wasp or fig seed production. Data on flower positions revealed that non-pollinating wasps occurred almost exclusively in the outer layer of flowers, while pollinators were more abundant in the inner flower layer, which may represent an area of enemy-free space. The ratio of seeds to female pollinator wasps, an index of fig sex allocation, was more seed-biased than in several New World fig species that exhibit within-tree synchrony. This last result supports the idea that within-tree fruiting asynchrony permits a degree of self-pollination in F. rubiginosa

Approaches to the study of hillslope development due to mass movement

Slope-angle histograms have traditionally provided a data base for the evaluation of changing angles over geological time. Ideas relating to hillslope development due to mass movement have considered a lowering in regolith shear resistance due to weathering, producing slope-angle decline. Decreasing values for angles of internal friction, along with increasing pore water pressures, have been suggested to explain slope-angle decline through time. These ideas have considered simple changes in undifferentiated regolith. This article considers the role of progressive pedogenesis in determining the changing stability of slopes. For this it is necessary to evaluate the changes which occur within individual horizons to produce an increasingly differentiated soil cover. Angles of internal friction alter at different rates and in different ways depending on whether the horizon is losing or gaining weathered material through translocation. Furthermore, the increasing internal differentiation of the soil cover has complex effects on its hydrological response. Instead of the two scenarios previously envisaged, one involving the water table below the slip surface and the other involving the water table at the ground surface, slope stability needs to be evaluated in the light of continually changing negative or positive pore water pressures. Each storm produces a different response, and this response alters with soil development, complicating the assessment of failure timing and depth. The study of evolving soil profiles is of fundamental significance to a range of geomorphological processes, requiring closer evaluation in the future