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

A Study on \u22Poetry (詩刊)\u22 Around the Struggle against the Rightists

Satellite telemetry has become a common technique to investigate avian life-histories, but whether such tagging will affect fitness is a critical unknown. In this study, we evaluate multi-year effects of implanted transmitters on migratory timing and reproductive performance in shorebirds. Shorebirds increasingly are recognized as good models in ecology and evolution. That many of them are of conservation concern adds to the research responsibilities. In May 2009, we captured 56 female Black-tailed Godwits Limosa limosa limosa during late incubation in The Netherlands. Of these, 15 birds were equipped with 26-g satellite transmitters with a percutaneous antenna (7.8 % ± 0.2 SD of body mass), surgically implanted in the coelom. We compared immediate nest survival, timing of migration, subsequent nest site fidelity and reproductive behaviour including egg laying with those of the remaining birds, a comparison group of 41 females. We found no effects on immediate nest survival. Fledging success and subsequent southward and northward migration patterns of the implanted birds conformed to the expectations, and arrival time on the breeding grounds in 2010–2012 did not differ from the comparison group. Compared with the comparison group, in the year after implantation, implanted birds were equally faithful to the nest site and showed equal territorial behaviour, but a paucity of behaviours indicating nests or clutches. In the 3 years after implantation, the yearly apparent survival of implanted birds was 16 % points lower. Despite intense searching, we found only three eggs of two implanted birds; all were deformed. A similarly deformed egg was reported in a similarly implanted Whimbrel Numenius phaeopus returning to breed in central Alaska. The presence in the body cavity of an object slightly smaller than a normal egg may thus lead to egg malformation and, likely, reduced egg viability. That the use of implanted satellite transmitters in these large shorebirds reduced nesting propensity and might also lead to fertility losses argues against the use of implanted transmitters for studies on breeding biology, and for a careful evaluation of the methodology in studies of migration

Testing evolutionary hypotheses about species borders: patterns of genetic variation towards the southern borders of two rainforest Drosophila and a related habitat generalist

Several evolutionary hypotheses help explain why only some species adapt readily to new conditions and expand distributions beyond borders, but there is limited evidence testing these hypotheses. In this study, we consider patterns of neutral (microsatellite) and quantitative genetic variation in traits in three species of Drosophila from the montium species group in eastern Australia. We found little support for restricted or asymmetrical gene flow in any species. In rainforest-restricted Drosophila birchii, there was evidence of selection for increased desiccation and starvation resistance towards the southern border, and a reduction in genetic diversity in desiccation resistance at this border. No such patterns existed for Drosophila bunnanda, which has an even more restricted distribution. In the habitat generalist Drosophila serrata, there was evidence for geographic selection for wing size and development time, although clinal patterns for increased cold and starvation resistance towards the southern border could not be differentiated from neutral expectations. These findings suggest that borders in these species are not limited by low overall genetic variation but instead in two of the species reflect patterns of selection and genetic variability in key traits limiting borders

Forces on a magnet moving past figure-eight coils

For the first time, the lift, drag, and guidance forces acting on a permanent magnet are measured as the magnet passes over different arrays of figure-eight (null-flux) coils. The experimental results are in good agreement with the predictions of dynamic circuit theory, which is used to explain more optimal coil arrays

Contrasting extreme long-distance migration patterns in bar-tailed godwits <i>Limosa lapponica</i>

Migrating birds make the longest non-stop endurance flights in the animal kingdom. Satellite technology is now providingdirect evidence on the lengths and durations of these flights and associated staging episodes for individual birds. Using thistechnology, we compared the migration performance of two subspecies of bar-tailed godwit Limosa lapponica travellingbetween non-breeding grounds in New Zealand (subspecies baueri) and northwest Australia (subspecies menzbieri) andbreeding grounds in Alaska and eastern Russia, respectively. Individuals of both subspecies made long, usually non-stop,flights from non-breeding grounds to coastal staging grounds in the Yellow Sea region of East Asia (average 10 060 ? SD290 km for baueri and 5860 ? 240 km for menzbieri). After an average stay of 41.2 ? 4.8 d, baueri flew over the North PacificOcean before heading northeast to the Alaskan breeding grounds (6770 ? 800 km). Menzbieri staged for 38.4 ? 2.5 d,and flew over land and sea northeast to high arctic Russia (4170 ? 370 km). The post-breeding journey for baueri involvedseveral weeks of staging in southwest Alaska followed by non-stop flights across the Pacific Ocean to New Zealand (11 690 kmin a complete track) or stopovers on islands in the southwestern Pacific en route to New Zealand and eastern Australia. Bycontrast, menzbieri returned to Australia via stopovers in the New Siberian Islands, Russia, and back at the Yellow Sea; birdstravelled on average 4510 ? 360 km from Russia to the Yellow Sea, staged there for 40.8 ? 5.6 d, and then flew another5680–7180 km to Australia (10 820 ? 300 km in total). Overall, the entire migration of the single baueri godwit with afully completed return track totalled 29 280 km and involved 20 d of major migratory flight over a round-trip journey of174 d. The entire migrations of menzbieri averaged 21 940 ? 570 km, including 14 d of major migratory flights out of 154 dtotal. Godwits of both populations exhibit extreme flight performance, and baueri makes the longest (southbound) andsecond-longest (northbound) non-stop migratory flights documented for any bird. Both subspecies essentially make singlestops when moving between non-breeding and breeding sites in opposite hemispheres. This reinforces the critical importanceof the intertidal habitats used by fuelling godwits in Australasia, the Yellow Sea, and Alaska