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- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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- Butler-Laporte, G, et al.
(author)
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Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
- 2022
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 18:11, s. e1010367-
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Journal article (peer-reviewed)abstract
- Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
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| 8. |
- Kroes, JA, et al.
(author)
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Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis
- 2023
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In: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:2
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Journal article (peer-reviewed)abstract
- An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking non-standardized, patient-level registry-data. Mepolizumab has shown clinical efficacy in RCTs and prospective real-world studies and could therefore serve as a proof of principle for this novel approach.AimTo harmonize data from 10 national severe asthma registries and characterize patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.MethodsIn this observational cohort study, registry data (5871 patients) were extracted for harmonization. Where harmonization was possible, patients who initiated mepolizumab between 1-1-2016 and 31-12-2021 were examined. Changes of a 12 (range 11–18) months period in frequent (≥2) exacerbations, maintenance OCS use and dose were analyzed in a privacy-preserving manner using meta-analysis of generalized estimating equation parameters. Periods before and during the COVID-19 pandemic were analyzed separately.ResultsIn 912 patients who fulfilled selection criteria mepolizumab significantly reduced frequent exacerbations (OR;95%CI: 0.18;0.13–0.25), maintenance OCS use (OR;95%CI: 0.75;0.61–0.92) and dose (mean; 95%CI: −3.93 mg·day−1; −5.24–2.62) in the Pre-Pandemic group, with similar trends in the Pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.ConclusionsBy harmonizing patient-level registry data and applying federated analysis, SHARP demonstrated the real-wold effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
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| 11. |
- Donis, Daphne, et al.
(author)
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Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
- 2021
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In: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
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Journal article (peer-reviewed)abstract
- To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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| 12. |
- Hon, Marc, et al.
(author)
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A close-in giant planet escapes engulfment by its star
- 2023
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 618:7967, s. 917-920
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Journal article (peer-reviewed)abstract
- When main-sequence stars expand into red giants, they are expected to engulf close-in planets(1-5). Until now, the absence of planets with short orbital periods around post-expansion, core-helium-burning red giants(6-8) has been interpreted as evidence that short-period planets around Sun-like stars do not survive the giant expansion phase of their host stars(9). Here we present the discovery that the giant planet 8 Ursae Minoris b(10) orbits a core-helium-burning red giant. At a distance of only 0.5 au from its host star, the planet would have been engulfed by its host star, which is predicted by standard single-star evolution to have previously expanded to a radius of 0.7 au. Given the brief lifetime of helium-burning giants, the nearly circular orbit of the planet is challenging to reconcile with scenarios in which the planet survives by having a distant orbit initially. Instead, the planet may have avoided engulfment through a stellar merger that either altered the evolution of the host star or produced 8 Ursae Minoris b as a second-generation planet(11). This system shows that core-helium-burning red giants can harbour close planets and provides evidence for the role of non-canonical stellar evolution in the extended survival of late-stage exoplanetary systems.
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| 13. |
- Ozkan, M., et al.
(author)
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Early-Middle Jurassic metamorphic and non-metamorphic supra-subduction zone ophiolite fragments in a Late Cretaceous ophiolitic melange (northern Turkey): implications for long-lived and supra-subduction zone ophiolite formation
- 2022
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In: International Journal of Earth Sciences. - : Springer Science and Business Media LLC. - 1437-3254 .- 1437-3262. ; 111, s. 2391-2408
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Journal article (peer-reviewed)abstract
- The Late Cretaceous accretionary complexes along the Izmir-Ankara-Erzincan (IAE) Neo-Tethyan suture zone in northern Turkey record the subduction-accretion processes of the oceanic lithosphere ranging in age from the Late Triassic to the Late Cretaceous. These accretionary complexes contain fragments of Early and Middle Jurassic metamorphic and non-metamorphic ophiolites. Here, we report new geochemical and geochronological data from the metamorphic and non-metamorphic ophiolitic rocks, which are observed in the Tekelidag melange (northern Sivas) of the IAE suture zone. Geochemical characteristics of these rocks point to formation in a subduction-related tectonic setting. Igneous zircons from meta-plagiogranite injected into the meta-ophiolitic rocks yielded zircon U-Pb age of 188 +/- 4 Ma (2 sigma, Early Jurassic), and those from a non-metamorphic plagiogranite crosscutting the non-metamorphic ophiolitic rocks gave an age value of 168 +/- 2 Ma (2 sigma, Middle Jurassic). The igneous crystallization age of the non-metamorphic plagiogranite is identical with the metamorphic age of meta-ophiolitic rocks, which has been dated as Middle Jurassic (166.7 +/- 2 Ma, 2 sigma) by the Ar-40-Ar-39 method. These age data indicate that (i) the supra-subduction zone ophiolite formation lasted about 20 Ma, (ii) the supra-subduction zone ophiolite and the meta-ophiolitic rocks formed simultaneously in the Middle Jurassic, and (iii) the meta-ophiolitic rocks are remnants of the metamorphosed equivalents of the Early Jurassic supra-subduction zone oceanic crust. The supra-subduction zone ophiolite formation probably occurred over an extended period of time in the Jurassic Neo-Tethys.
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| 14. |
- Peker, Yüksel, 1961, et al.
(author)
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Reliability of the Turkish version of the European Obstructive Sleep Apnea Screening (EUROSAS) questionnaire for drivers
- 2021
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In: Sleep and Breathing. - : Springer Science and Business Media LLC. - 1520-9512 .- 1522-1709. ; 25:2, s. 907-913
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Journal article (peer-reviewed)abstract
- Purpose The European Union Driver License Committee recently developed a questionnaire as a screening tool for obstructive sleep apnea (OSA) named the European Obstructive Sleep Apnea Screening (EUROSAS) questionnaire for drivers. We sought to address the reliability of the Turkish version of this questionnaire. Methods The EUROSAS was translated into Turkish. Using a "test-retest approach", data were collected twice with a 15-day interval among 150 participants (50 professional male drivers [PMD], 50 non-professional male drivers [NPMD], and 50 non-professional female drivers [NPFD]). The EUROSAS score ranges between 2 and 25, with scores >= 10 suggesting the presence of OSA. Results The median EUROSAS scores in the first test were 8.0 (interquartile range [IQR] 6.8-12.0) in PMD, 8.0 (IQR 6.0-11.0) in NPMD, and 5.0 (IQR 4.0-8.0) in NPFD (p< 0.001). Corresponding values in the retest were 9.5 (IQR 7.0-13.0), 8.0 (IQR 6.0-10.0), and 5.0 (IQR 4.0-8.0), respectively (p< 0.001). The EUROSAS score >= 10 was found among 34% in the first test and 50% in the retest in PMD (ns), 34% vs 24% in NPMD (ns), and 8% vs 16% in NPFD (ns). There was a positive correlation between the tests (r= 0.864,p< 0.001), and Cronbach's alpha value for the whole group was 0.477 (0.514 for PMD, 0.512 for NPMD, and 0.543 NPFD, respectively). Conclusions The EUROSAS-Turkish version is easy to understand and is reproducible. However, the test-retest reliability level is poor among the Turkish drivers. Further validation of the questionnaire by objective sleep studies and fitness-to-drive testing is necessary.
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| 15. |
- Wenzel, Michaela, 1986, et al.
(author)
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Control of septum thickness by the curvature of SepF polymers
- 2021
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:2
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Journal article (peer-reviewed)abstract
- Gram-positive bacteria divide by forming a thick cross wall. How the thickness of this septal wall is controlled is unknown. In this type of bacteria, the key cell division protein FtsZ is anchored to the cell membrane by two proteins, FtsA and/or SepF. We have isolated SepF homologs from different bacterial species and found that they all polymerize into large protein rings with diameters varying from 19 to 44 nm. Interestingly, these values correlated well with the thickness of their septa. To test whether ring diameter determines septal thickness, we tried to construct different SepF chimeras with the purpose to manipulate the diameter of the SepF protein ring. This was indeed possible and confirmed that the conserved core domain of SepF regulates ring diameter. Importantly, when SepF chimeras with different diameters were expressed in the bacterial host Bacillus subtilis, the thickness of its septa changed accordingly. These results strongly support a model in which septal thickness is controlled by curved molecular clamps formed by SepF polymers attached to the leading edge of nascent septa. This also implies that the intrinsic shape of a protein polymer can function as a mold to shape the cell wall.
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