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

Atom guiding along high order Laguerre-Gaussian light beams formed by spatial light modulation

A spatial light modulator (SLM) has been used to create high quality Laguerre-Gaussian (LG) light beams, which have been used to study the guiding of cold rubidium atoms. The SLM allows real-time variation of the hollow guiding beam and permits direct comparison of the guided atom fluxes for different LG modes with minimal adjustment of the other optical components. It is demonstrated that, by increasing the azimuthal index l of the Laguerre-Gaussian beam, the radiation pressure pushing the trapped atoms may be reduced while maintaining the same guided flux. This is the first comparative study of hollow beam atom guiding, and further demonstrates the versatility of the SLM for studies in atom optics.</p

Comparison of Ultrasound and MRI with Intraoperative Findings in the Diagnosis of Peroneal Tendinopathy, Tears, and Subluxation

Suspected peroneal tendinopathy, tears, and subluxation are often confirmed preoperatively using magnetic resonance imaging (MRI) or diagnostic ultrasound (US). No study has directly compared the accuracy of these tests for the diagnosis of peroneal tendon pathology. The purpose of this study is to directly compare MRI and US to intraoperative findings in patients who underwent surgery for suspected peroneal pathology to determine the imaging diagnostic accuracy. Operative records and diagnostic images for 21 consecutive patients who had both MRI and US prior to surgery for suspected peroneal tendinopathy, tears, or subluxation were retrospectively reviewed. The results of this review are compared with the intraoperative findings to yield the sensitivity and specificity for each imaging modality. For the diagnosis of peroneal tendon tears, US was found to have a sensitivity of 88% and specificity of 100%, compared to 100% sensitivity and specificity for MRI. In the diagnosis of peroneal tendinopathy, both US and MRI had a sensitivity and specificity of 100%. In diagnosing peroneal subluxation, US was 100% sensitive compared to 66% for MRI, and both were 100% specific. In conclusion, US was found to be more effective in diagnosing peroneal subluxation and MRI was slightly more accurate in the diagnosis of peroneal tendon tears. © 2024 by the authors.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

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

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