Accretion among preplanetary bodies: the many faces of runaway growth

(abridged) When preplanetary bodies reach proportions of ~1 km or larger in size, their accretion rate is enhanced due to gravitational focusing (GF). We have developed a new numerical model to calculate the collisional evolution of the gravitationally-enhanced growth stage. We validate our approach against existing N-body and statistical codes. Using the numerical model, we explore the characteristics of the runaway growth and the oligarchic growth accretion phases starting from an initial population of single planetesimal radius R_0. In models where the initial random velocity dispersion (as derived from their eccentricity) starts out below the escape speed of the planetesimal bodies, the system experiences runaway growth. We find that during the runaway growth phase the size distribution remains continuous but evolves into a power-law at the high mass end, consistent with previous studies. Furthermore, we find that the largest body accretes from all mass bins; a simple two component approximation is inapplicable during this stage. However, with growth the runaway body stirs up the random motions of the planetesimal population from which it is accreting. Ultimately, this feedback stops the fast growth and the system passes into oligarchy, where competitor bodies from neighboring zones catch up in terms of mass. Compared to previous estimates, we find that the system leaves the runaway growth phase at a somewhat larger radius. Furthermore, we assess the relevance of small, single-size fragments on the growth process. In classical models, where the initial velocity dispersion of bodies is small, these do not play a critical role during the runaway growth; however, in models that are characterized by large initial relative velocities due to external stirring of their random motions, a situation can emerge where fragments dominate the accretion.Comment: Accepted for publication in Icaru

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

RNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency

RNA editing by the adenosine deaminase ADAR1 prevents innate immune responses to endogenous RNAs. In ADAR1-deficient cells, unedited self RNAs form base-paired structures that resemble viral RNAs and inadvertently activate the cytosolic RIG-I-like receptor (RLR) MDA5, leading to an antiviral type I interferon (IFN) response. Mutations in ADAR1 cause Aicardi-Goutieres Syndrome (AGS), an autoinflammatory syndrome characterized by chronic type I IFN production. Conversely, ADAR1 loss and the consequent type I IFN production restricts tumor growth and potentiates the activity of some chemotherapeutics. Here, we show that another RIG-I-like receptor, LGP2, also has an essential role in the induction of a type I IFN response in ADAR1-deficient human cells. This requires the canonical function of LGP2 as an RNA sensor and facilitator of MDA5-dependent signaling. Furthermore, we show that the sensitivity of tumor cells to ADAR1 loss requires LGP2 expression. Finally, type I IFN induction in tumor cells depleted of ADAR1 and treated with some chemotherapeutics fully depends on LGP2 expression. These findings highlight a central role for LGP2 in self RNA sensing with important clinical implications