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 hospitalization2–4 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

The role of hydrogen and fuel cells in the global energy system

Hydrogen technologies have experienced cycles of excessive expectations followed by disillusion. Nonetheless, a growing body of evidence suggests these technologies form an attractive option for the deep decarb onisation of global energy systems, and that recent improvements in their cost and performance point towards economic viability as well. This paper is a comprehensive review of the potential role that hydrogen could play in the provision of electricity, h eat, industry, transport and energy storage in a low - carbon energy system, and an assessment of the status of hydrogen in being able to fulfil that potential. The picture that emerges is one of qualified promise: hydrogen is well established in certain nic hes such as forklift trucks, while mainstream applications are now forthcoming. Hydrogen vehicles are available commercially in several countries, and 225,000 fuel cell home heating systems have been sold. This represents a step change from the situation of only five years ago. This review shows that challenges around cost and performance remain, and considerable improvements are still required for hydrogen to become truly competitive. But such competitiveness in the medium - term future no longer seems an unrealistic prospect, which fully justifies the growing interest and policy support for these technologies around the world

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

Body Slap: An Innovative Aggressive Display by Breeding Male Gray Seals (Halichoerus grypus).

Aggression in male gray seals has been extensively studied; however it is often simplistically assumed that threat signals are mainly cephalic in nature for this species.We report on an undescribed and apparently new kind of threat signal used by male gray seals we term a Body Slap. The behavior has been observed at breeding sites in eastern England since 1993 but has not been studied ethologically or reported elsewhere.The aims of this study were to describe the behavior, test the influence of topographic variation on its frequency of occurrence, examine if it is used to signal dominance or submission, and to place it in intra- and interspecific contexts. Our results show Body Slaps were performed in 66.3% of interactions and by 57.2% of males; it was not performed by females. The Body Slap was positively associated with the Approach and Open-Mouth Threat behaviors but was not related to dominance; nevertheless, display rates were greater for subsequent winners. These findings suggest that the Body Slap carries information about male resource holding potential and does not signal submission. This study furthers our understanding of geographic variants of male threat behaviors and of pinniped nonvocal communication

Food and feeding ecology of Wilson's storm petrel Oceanites oceanicusat South Georgia

At South Georgia, the diet of Wilson's storm petrel was studied using the regurgitates of adults arriving to feed chicks. Feeding frequency and meal size were estimated by weighing chicks twice daily, or in some cases every 3 h during daytime. Crustaceans contributed 98% of the total number of individual items and 68% of the total weight consumed; fish, 1% of the number of items and 28% of the weight. The most abundant crustacean was the amphipod Themisto gaudichaudii, which accounted for 90% of the total number but only 44% of the total weight of crustaceans eaten. Most (79%) of the Themisto were juveniles. Euphausiids were much less numerous in the diet (5% by number) but were the main group by weight (55%); most (52%) were Antarctic krill, with juveniles and sub‐adults (25–50 mm long) predominating. Mysids, copepods and barnacle larvae were also present. Fish were all myctophids (lanternfish), Protomyctophum normani and P. bolini being identified; specimens were 50–85 mm long and weighed 1–4 g. Meal sizes averaged 6‐5‐7‐5 g (14–22% adult body mass); about 75% of chicks were fed each day (mainly at night), about 10% probably receiving meals from both parents. A review of storm petrel diets emphasizes the importance of fish to Oceanodroma species and of crustaceans to Oceanites, Garrodia and Pelagodroma. Euphausiids and amphipods (chiefly Themisto and Hyperia) are the main crustacean prey and range from 5–50 mm and 0‐005‐0‐7 g. Myctophids are the main fish prey and range from 20–100 mm and 1–5 g. Meal size ranges from 15–25% adult body mass and chicks are fed on 50–85% of days. This low delivery rate is mainly responsible for the disproportionately slow growth and long fledging period of storm petrel chicks

Obesity and mental disorders in the general population: results from the world mental health surveys

Objectives: (1) To investigate whether there is an association between obesity and mental disorders in the general populations of diverse countries, and (2) to establish whether demographic variables (sex, age, education) moderate any associations observed. Design: Thirteen cross-sectional, general population surveys conducted as part of the World Mental Health Surveys initiative. Subjects: Household residing adults, 18 years and over (n = 62 277). Measurements: DSM-IV mental disorders (anxiety disorders, depressive disorders, alcohol use disorders) were assessed with the Composite International Diagnostic Interview (CIDI 3.0), a fully structured diagnostic interview. Obesity was defined as a body mass index (BMI) of 30 kg/m(2) or greater; severe obesity as BMI 35+. Persons with BMI less than 18.5 were excluded from analysis. Height and weight were self-reported. Results: Statistically significant, albeit modest associations (odds ratios generally in the range of 1.2-1.5) were observed between obesity and depressive disorders, and between obesity and anxiety disorders, in pooled data across countries. These associations were concentrated among those with severe obesity, and among females. Age and education had variable effects across depressive and anxiety disorders. Conclusions: The findings are suggestive of a modest relationship between obesity (particularly severe obesity) and emotional disorders among women in the general population. The study is limited by the self-report of BMI and cannot clarify the direction or nature of the relationship observed, but it may indicate a need for a research and clinical focus on the psychological heterogeneity of the obese population