56 research outputs found
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
Recommended from our members
An Intensity Mapping Constraint on the CO-galaxy Cross-power Spectrum at Redshift ∼3
The abundance of cold molecular gas plays a crucial role in models of galaxy evolution. While deep spectroscopic surveys of CO emission lines have been a primary tool for measuring this abundance, the difficulty of these observations has motivated alternative approaches to studying molecular gas content. One technique, line intensity mapping, seeks to constrain the average molecular gas properties of large samples of individually undetectable galaxies through the CO brightness power spectrum. Here we present constraints on the cross-power spectrum between CO intensity maps and optical galaxy catalogs. This cross-measurement allows us to check for systematic problems in CO intensity mapping data, and validate the data analysis used for the auto-power spectrum measurement of the CO Power Spectrum Survey. We place a 2σ upper limit on the band-averaged CO-galaxy cross-power of P × < 540 μK h-3 Mpc3. Our measurement favors a nonzero TCO at around 90% confidence and gives an upper limit on the mean molecular gas density at z ∼2.6 of 7.7 × 108 M ⊙ Mpc-3. We forecast the expected cross-power spectrum by applying a number of literature prescriptions for the CO luminosity-halo mass relation to a suite of mock light cones. Under the most optimistic forecasts, the cross-spectrum could be detected with only moderate extensions of the data used here, while more conservative models could be detected with a factor of 10 increase in sensitivity. Ongoing CO intensity mapping experiments will target fields allowing for extensive cross-correlation analysis and should reach the sensitivity required to detect the cross-spectrum signal. © 2022. The Author(s). Published by the American Astronomical Society.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]
Acetaldehyde Determination in Fermented Food Products by Direct 2,4-Dinitrophenylhydrazine Derivatization, Extraction and High Performance Liquid Chromatography
Recommended from our members
Design and testing of kinetic inductance detector package for the terahertz intensity mapper
The Terahertz Intensity Mapper (TIM) is designed to probe the star formation history in dust-obscured star-forming galaxies around the peak of cosmic star formation. This will be done via measurements of the redshifted 157.7 μm line of singly ionized carbon ([CII]). TIM employs two R∼250 long-slit grating spectrometers covering 240 to 420 μm. Each is equipped with a focal plane unit containing four wafer-sized subarrays of horn-coupled aluminum kinetic inductance detectors (KIDs). We present the design and performance of a prototype focal plane assembly for one of TIM's KID-based subarrays. The overall detector package must satisfy thermal and mechanical requirements, while maintaining high optical efficiency and a suitable electromagnetic environment for the KIDs. In particular, our design manages to strictly maintain a 50 μm air gap between the array and the horn block. The prototype detector housing in combination with the first flight-like quadrant were tested at 250 mK. A frequency scan using a vector network analyzer shows 823 resonance features, which represents 90% yield, indicating a good performance of our TIM detector wafer and the whole focal plane unit. Initial measurements also showed that many resonances were affected by collisions and/or very shallow transmission dips as a result of a degraded internal quality factor. This is attributed to the presence of an external magnetic field during cooldown. We report on a study of magnetic field dependence of the quality factor of our quadrant array. We implemented a Helmholtz coil to vary the magnetic field at the detectors by (partially) nulling earth's. Our investigation shows that the earth magnetic field can significantly affect our KIDs' performance by degrading the quality factor by a factor of two to five, well below those expected from the operational temperature or optical loading. We find that we can sufficiently recover our detectors' quality factor by tuning the current in the coils to generate a field that matches earth's magnetic field in magnitude to within a few μT. We emphasize that it is impractical to fly a Helmholtz coil on TIM and dynamically "null"earth's. Therefore, it is necessary to employ a properly designed magnetic shield enclosing the TIM focal plane unit. Based on the results presented in this paper, we set a shielding requirement of |B| 3 μT. © 2022 SPIE.Immediate accessThis 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]
Graduates' Work Experiences as Predictors of rganisational Commitment, Intention to Leave, and Turnover: Which Experiences Really Matter?
- …