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

Reagent Degradation in the Synergistic Solvent Extraction System LIX®63/Versatic™10/Nonyl-4PC

Direct solvent extraction of nickel and cobalt from nitrate-based leach liquors has become of interest due to the successful piloting of nitric acid processes for treating nickel laterite ores. The current study investigated the stability of both hydroxyoxime and nonyl-4PC (nonyl-4-pyridine carboxylate) in LIX 63/Versatic 10/nonyl-4PC under conditions relevant to the recovery of nickel and cobalt from a nitrate-based leach liquor with stripping into sulfuric acid. Nonyl-4PC increased both the rate of hydroxyoxime degradation under the pH 1.5 extract conditions required for a potential nickel–cobalt separation process and the rate of cobalt poisoning of LIX 63. Under strip conditions and the pH 4 extract conditions required for co-extraction of nickel and cobalt, nonyl-4PC did not otherwise affect the rate of hydroxyoxime loss. Additionally, the presence of nitrate anions did not increase the loss of either hydroxyoxime or nonyl-4PC. The combination LIX 63/Versatic 10/nonyl-4PC therefore appears prospective for the co-extraction of nickel and cobalt at pH 4 from nitrate-based leach liquors

Carbon dioxide exchange in leaves of Spartina anglica Hubbard

The gas-exchange method has been used to measure net carbon dioxide assimilation at different temperatures and irradiances in leaves of salt-treated and untreated plants of Spartina anglica. The results together with those of the CO2 compensation point and leaf anatomical data clearly indicate that Spartina anglica is a high photosynthetic capacity plant. At high temperatures and irradiances leaves of the salt-treated plants were able to maintain net photosynthesis, in contrast to the behaviour of leaves of untreated plants. The ecological significance of these results is discussed