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

Observation of cycloidal features on Enceladus

We observe geologically young cycloidal segments in different places on the surface of Saturn’s moon Enceladus. These features likely have formed as tension cracks with their form being con-trolled by diurnal variation of tides, as suggested for Europa. For this model to work the ice must be weak and, to allow for sufficient tidal amplitude, there must be a fluid layer below the icy surface. Thus, rather than being confined to just southern latitudes, our observations hint at the presence of fluid layers in also other areas on Enceladus, potentially at a global sub-suface ocean in recent times

Implications of Europa's global cycloid population

International audienceIntroduction: Cycloids are arcuate features observed on the surface of Europa proposed to record the stress changes that occurred during their formation [1,2]. These features are interpreted to be tensile cracks that form due to diurnal stresses from Europa's orbital eccentricity [1,2,3]. The shapes of cycloids can, thus, be used to constrain parameters that contribute to tidal stress, such as the interior structure and rotation history of Europa. Cycloids have been mapped regionally from Voyager and Galileo images [4,5], but the only published global map of cycloids [3] did not include a database or digital map, limiting its usefulness. For this study, we completed a global map of cycloids and generated a database of cusp angle measurements to obtain new constraints on the thickness and rheology of Europa's icy shell and on the formation of different fracture types observed on Europa Background: Physical models have been developed to successfully explain the orientations and locations of many fractures observed on Europa's surface, including the arcuate paths of cycloids [6]. Early models were heavily based on an eccentricity-driven stress field; other parameters have also been considered, including stress from non-synchronous rotation (NSR) of Europa's ice shell and the possibility of Europa having a forced obliquity due to interactions with Jupiter's other large moons [1,7]. A stress field that includes obliquity and spin pole precession provides the best matches to individual cycloids [1], the orientations of lineaments [7], and the global distribution of strike-slip faults [10]. However, cycloids and lineaments have different implications for NSR; cycloids record substantial longitudinal reorientation while lineaments do not. Both cycloids and lineaments are thought to form through tensile failure, at orientations perpendicular to the maximum tensile stress direction [2]. Hence, the reason for this discrepancy is not obvious. It could indicate a change in tidal stress conditions with time, perhaps due to a change in ice shell thickness or rheology. Unfortunately, the challenging nature of cycloid modeling has limited its application to only six features whereas more than 100 lineaments have been mapped and analyzed. To further investigate the formation conditions of cycloids, and their relationship to lineaments, we measure the orientations of all observed cycloids at their cusps, when the physical model of their formation would be most similar to that of a lineament. We then compare the results to the orientations predicted by the tidal stress model most compatible with observed lineaments [7]. Our preliminary results indicate a lack Figure 1. The global distribution of cycloids on Europa, which combines features from a global mapping study (red) and features identified during the measurement phase of this study (blue), reveals two main clusters of cycloids that are offset from the equator. Green circles represent cusps whose orientations we measured; no cusps were found in areas shaded in red

Surface, Subsurface and Atmosphere Exchanges on the Satellites of the Outer Solar System

The surface morphology of icy moons is affected by several processes implicating exchanges between their subsurfaces and atmospheres (if any). The possible exchange of material between the subsurface and the surface is mainly determined by the mechanical properties of the lithosphere, which isolates the deep, warm and ductile ice material from the cold surface conditions. Exchanges through this layer occur only if it is sufficiently thin and/or if it is fractured owing to tectonic stresses, melt intrusion or impact cratering. If such conditions are met, cryomagma can be released, erupting fresh volatile-rich materials onto the surface. For a very few icy moons (Titan, Triton, Enceladus), the emission of gas associated with cryovolcanic activity is sufficiently large to generate an atmosphere, either long-lived or transient. For those moons, atmosphere-driven processes such as cryovolcanic plume deposition, phase transitions of condensable materials and wind interactions continuously re-shape their surfaces, and are able to transport cryovolcanically generated materials on a global scale. In this chapter, we discuss the physics of these different exchangeprocesses and how they affect the evolution of the satellites’ surfaces

Surface, subsurface and atmosphere exchanges on the satellites of the outer Solar System

International audienc

The Neighborhood Characteristics of Malapropisms

lexical density This study examined the phonological neighborhood characteristics (frequency, density, and neighborhood frequency) of 138 malapropisms. Malapropisms are whole word substitutions that are phonologically, but not semantically, related. A statistical analysis of a speech error corpus suggests that neighborhood density and word frequency differentially affected the number of malapropisms. Specifically, a greater number of speech production malapropisms were found among high frequency words with dense neigh-borhoods than with sparse neighborhoods. Exactly the opposite pattcrn was found among low frequency words. That is, more errors nere found among low frequency words with sparse neighborhoods than with dense neighborhoods. More malapropisms resided in low frcquency neighborhoods than in high. The average word frequency, average neighborhood density, and average neighborhood frequency ofthe malapropisms were significantly loner than the same avenges computed from randomly sampled control words. Finally, more target words were replaced by error words that had relatively higher frequency than by error words that had relatively lower frequency. The implica-tions of these findings for models of lexical representation and processing are discussed. malapropism