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

Campylobacter jejuni gene cj0511 encodes a serine peptidase essential for colonisation

According to MEROPS peptidase database, Campylobacter species encode 64 predicted peptidases. However, proteolytic properties of only a few of these proteins have been confirmed experimentally. In this study we identified and characterised a Campylobacter jejuni gene cj0511 encoding a novel peptidase. The proteolytic activity associated with this enzyme was demonstrated in cell lysates. Moreover, enzymatic studies conducted with a purified protein confirmed a prediction of it being a serine peptidase. Furthermore, cj0511 mutant was found to be severely attenuated in chicken colonisation model, suggesting a role of the Cj0511 protein in infection

Adoption of managerial ideologies in Finnish academic management education 1960-2007

The article analyses when and how different management paradigms have been adopted for teaching, in the subject of organization and management, by examining the curricula and study guides of the eight main business schools in Finland.The data was analysed in three ways: (1) the analysis of all the reading lists in curricula and study guides, (2) the analyses of subject descriptions in the study guides and (3) the analysis of individual course descriptions in the study guides.Theoretically, the study draws on the literature on German-style and American-style business schools, and on the literature on management paradigms and their dissemination.Our findings indicate that there are differences in the adoption of different management paradigms in management education in German-style and American-style business schools in Finland. For example, between 1980 and 1995, the most commonly used paradigm in teaching in German-style schools was the human relations paradigm, while in American-style schools the most popular paradigm was structural analysis.The results suggest that different traditions in arranging higher management education may have an impact on the content of teaching.This provides an interesting point of departure for investigating the contents of management education in other countries, too