| 1. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 3. |
- Namkoong, H, et al.
(författare)
-
DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
-
Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
|
|
| 4. |
|
|
| 5. |
- Wang, QBS, et al.
(författare)
-
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
-
Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
|
|
| 6. |
|
|
| 7. |
- Kaptoge, S., et al.
(författare)
-
World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
-
Ingår i: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
-
Tidskriftsartikel (refereegranskat)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
|
|
| 8. |
|
|
| 9. |
- Wang, HD, et al.
(författare)
-
Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015
- 2016
-
Ingår i: Lancet (London, England). - : Elsevier. - 1474-547X .- 0140-6736. ; 388:10053, s. 1725-1774
-
Tidskriftsartikel (refereegranskat)
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Boschi, Samuele, et al.
(författare)
-
Late Eocene 3He and Ir anomalies associated with ordinary chondritic spinels
- 2017
-
Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037. ; 204, s. 205-218
-
Tidskriftsartikel (refereegranskat)abstract
- During the late Eocene there was an enigmatic enhancement in the flux of extraterrestrial material to Earth. Evidence comes from sedimentary 3He records indicating an increased flux of interplanetary dust during ca. 2 Myr, as well as two very large impact structures, Popigai (100 km diameter) and Chesapeake Bay (40–85 km), that formed within 10–20 kyr at the peak of the 3He delivery. The Massignano section in Italy has one of the best sedimentary records of these events, including a well-defined 3He record, an Ir-rich ejecta bed related to the Popigai impact event, and two smaller Ir anomalies. Recently we showed that the Popigai ejecta is associated with a significant enrichment of chromite grains (>63 μm) with an H-chondritic elemental composition (17 grains in 100 kg of rock). Most likely these grains are unmelted fragments from the impactor. Slightly higher up (ca. 20 cm) in the section, where a small Ir anomaly possibly related to the Chesapeake Bay impact has been measured, we found a weak enrichment in L-chondritic grains (8 grains in 208 kg of rock). Here we report an extended data set increasing the total amount of sediment dissolved in acid and searched for extraterrestrial chromite grains from 658 to 1168 kg. In altogether 760 kg of background sediment from 17 levels over 14 m of strata outside the interval corresponding to the Popigai and Chesapeake Bay impacts, we only found 2 extraterrestrial chromite grains. Both grains have L-chondritic compositions and were found in a 100 kg sample from the ca. 10.25 m level in the section where the second of the smaller Ir anomalies has been reported. A correlation appears to exist between Ir, 3He and chromite from ordinary chondrites. We also report oxygen three-isotope measurements of the extraterrestrial chromite grains associated with the Popigai ejecta and confirm an H-chondritic composition. The new results strengthen our scenario that the upper Eocene 3He and Ir enrichments originate from the asteroid belt rather than the Oort cloud as originally proposed when the 3He anomaly was discovered. The generally low background concentrations of extraterrestrial chromite through the section speak against any major single asteroid breakup event such as in the mid-Ordovician after the break-up of the L-chondrite parent body. Instead the data reconcile with a small, possibly a factor of 2–3, increase in the flux of extraterrestrial material to Earth, but of both H- and L-chondritic composition. We also report the composition of all the 2310 terrestrial chrome spinel grains recovered, and show that their chemical composition indicates a dominantly regional ophiolitic source. Four anomalous chrome spinel grains with high Ti and V concentrations were found in the Popigai ejecta. These grains originate from Siberian Traps basalts in the Popigai crater at the time of impact.
|
|
| 15. |
|
|
| 16. |
- Heck, Philipp R., et al.
(författare)
-
A single asteroidal source for extraterrestrial Ordovician chromite grains from Sweden and China: High-precision oxygen three-isotope SIMS analysis
- 2010
-
Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037. ; 74:2, s. 497-509
-
Tidskriftsartikel (refereegranskat)abstract
- We examined oxygen three-isotope ratios of 48 extraterrestrial chromite (EC) grains extracted from mid-Ordovician sediments from two different locations in Sweden, and one location in south-central China. The ages of the sediments (similar to 470 Ma) coincide with the breakup event of the L chondrite parent asteroid. Elemental compositions of the chromite grains are generally consistent with their origin from L or LL chondrite parent bodies. The average Delta O-17 (parts per thousand-deviation from the terrestrial mass-fractionation line, measured in situ from 15 mu m spots by secondary ion mass spectrometry; SIMS) of EC grains extracted from fossil meteorites from Thorsberg and Brunflo are 1.17 +/- 0.09 parts per thousand (2 sigma) and 1.25 +/- 0.16 parts per thousand, respectively, and those of fossil micrometeorites from Thorsberg and Puxi River are 1.10 +/- 0.09 parts per thousand, and 1.11 +/- 0.12 parts per thousand, respectively. Within uncertainty these values are all the same and consistent with the L chondrite group average Delta O-17 = 1.07 +/- 0.18 parts per thousand, but also with the LL chondrite group average Delta O-17 = 1.26 +/- 0.24 parts per thousand. (Clayton et al., 1991). We conclude that the studied EC grains from correlated sediments from Sweden and China are related, and most likely originated in the same event, the L chondrite parent body breakup. We also analyzed chromites of modern H, L and LL chondrites and show that their Delta O-17 values coincide with averages of Delta O-17 of bulk analyses of H, L and LL chondrites. This study demonstrates that in situ oxygen isotope data measured by SIMS are accurate and precise if carefully standardized, and can be used to classify individual extraterrestrial chromite grains found in sediments. (c) 2009 Elsevier Ltd. All rights reserved.
|
|
| 17. |
|
|
| 18. |
- Heck, Philipp R., et al.
(författare)
-
Unusual sources of fossil micrometeorites deduced from relict chromite in the small size fraction in ~467 Ma old limestone
-
Ingår i: Meteoritics and Planetary Science. - 1086-9379.
-
Tidskriftsartikel (refereegranskat)abstract
- Extraterrestrial chrome spinel and chromite extracted from the sedimentary rock record are relicts from coarse micrometeorites and rarely meteorites. They are studied to reconstruct the paleoflux of meteorites to the Earth and the collisional history of the asteroid belt. Minor element concentrations of Ti and V, and oxygen isotopic compositions of these relict minerals were used to classify the meteorite type they stem from, and thus to determine the relative meteorite group abundances through time. While coarse sediment-dispersed extraterrestrial chrome-spinel (SEC) grains from ordinary chondrites dominate through the studied time windows in the Phanerozoic, there are exceptions: We have shown that ~467 Ma ago, 1 Ma before the breakup of the L chondrite parent body (LCPB), more than half of the largest (>63 μm diameter) grains were achondritic and originated from differentiated asteroids in contrast to ordinary chondrites which dominated the meteorite flux throughout most of the past 500 Ma. Here, we present a new data set of oxygen isotopic compositions and elemental compositions of 136 grains of a smaller size fraction (32–63 μm) in ~467 Ma old pre-LCPB limestone from the Lynna River section in western Russia, that was previously studied by elemental analysis. Our study constitutes the most comprehensive oxygen isotopic data set of sediment-dispersed extraterrestrial chrome spinel to date. We also introduce a Raman spectroscopy-based method to identify SEC grains and distinguish them from terrestrial chrome spinel with ~97% reliability. We calibrated the Raman method with the established approach using titanium and vanadium concentrations and oxygen isotopic compositions. We find that ordinary chondrites are approximately three times more abundant in the 32–63 μm fraction than achondrites. While abundances of achondrites compared to ordinary chondrites are lower in the 32–63 μm size fraction than in the >63 μm one, achondrites are approximately three times more abundant in the 32–62 μm fraction than they are in the present flux. We find that the sources of SEC grains vary for different grain sizes, mainly as a result of parent body thermal metamorphism. We conclude that the meteorite flux composition ~467 Ma ago ~1 Ma before the breakup of the LCPB was fundamentally different from today and from other time windows studied in the Phanerozoic, but that in contrast to the large size fraction ordinary chondrites dominated the flux in the small size fraction. The high abundance of ordinary chondrites in the studied samples is consistent with the findings based on coarse extraterrestrial chrome-spinel from other time windows.
|
|
| 19. |
- Kita, Noriko T., et al.
(författare)
-
Fall, classification, and exposure history of the Mifflin L5 chondrite
- 2013
-
Ingår i: Meteoritics and Planetary Science. - : Wiley. - 1086-9379. ; 48:4, s. 641-655
-
Tidskriftsartikel (refereegranskat)abstract
- The Mifflin meteorite fell on the night of April 14, 2010, in southwestern Wisconsin. A bright fireball was observed throughout a wide area of the midwestern United States. The petrography, mineral compositions, and oxygen isotope ratios indicate that the meteorite is a L5 chondrite fragmental breccia with light/dark structure. The meteorite shows a low shock stage of S2, although some shock-melted veins are present. The U,Th-He age is 0.7Ga, and the K-Ar age is 1.8Ga, indicating that Mifflin might have been heated at the time of the 470Ma L-chondrite parent body breakup and that U, Th-He, and K-Ar ages were partially reset. The cosmogenic radionuclide data indicate that Mifflin was exposed to cosmic rays while its radius was 3065cm. Assuming this exposure geometry, a cosmic-ray exposure age of 25 +/- 3Ma is calculated from cosmogenic noble gas concentrations. The low 22Ne/21Ne ratio may, however, indicate a two-stage exposure with a longer first-stage exposure at high shielding. Mifflin is unusual in having a low radiogenic gas content combined with a low shock stage and no evidence of late stage annealing; this inconsistency remains unexplained.
|
|
| 20. |
- Montero-Melis, Guillermo, 1982-, et al.
(författare)
-
Satellite- vs. Verb-Framing Underpredicts Nonverbal Motion Categorization : Insights from a Large Language Sample and Simulations
- 2017
-
Ingår i: Cognitive Semantics. - : Brill. - 2352-6408 .- 2352-6416. ; 3:1, s. 36-61
-
Tidskriftsartikel (refereegranskat)abstract
- Is motion cognition influenced by the large-scale typological patterns proposed in Talmy’s (2000) two-way distinction between verb-framed (V) and satellite-framed (S) languages? Previous studies investigating this question have been limited to comparing two or three languages at a time and have come to conflicting results. We present the largest cross-linguistic study on this question to date, drawing on data from nineteen genealogically diverse languages, all investigated in the same behavioral paradigm and using the same stimuli. After controlling for the different dependencies in the data by means of multilevel regression models, we find no evidence that S- vs. V-framing affects nonverbal categorization of motion events. At the same time, statistical simulations suggest that our study and previous work within the same behavioral paradigm suffer from insufficient statistical power. We discuss these findings in the light of the great variability between participants, which suggests flexibility in motion representation. Furthermore, we discuss the importance of accounting for language variability, something which can only be achieved with large cross-linguistic samples.
|
|
| 21. |
- Schmitz, Birger, et al.
(författare)
-
Determining the impactor of the Ordovician Lockne crater: Oxygen and neon isotopes in chromite versus sedimentary PGE signatures
- 2011
-
Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 1385-013X .- 0012-821X. ; 306:3-4, s. 149-155
-
Tidskriftsartikel (refereegranskat)abstract
- Abundant chromite grains with L-chondritic composition in the resurge deposits of the Lockne impact crater (458 Myr old: dia. similar to 10 km) in Sweden have been inferred to represent relict fragments of an impactor from the break-up of the L-chondrite parent body at 470 Ma. This view has been challenged based on It/Cr and platinum group element (PGE) patterns of the same resurge deposits, and a reinterpretation of the origin of the chromite grains. An impactor of the non-magmatic iron meteorite type was proposed instead. Here we show that single-grain oxygen and noble-gas isotope analyses of the chromite grains from the resurge deposits further support an origin from an L-chondritic asteroid. We also present PGE analyses and Ir/Cr ratios for fossil L-chondritic meteorites found in mid-Ordovician marine limestone in Sweden. The L-chondritic origin has been confirmed by several independent methods, including major element and oxygen isotopic analyses of chromite. Although the meteorites show the same order-of-magnitude PGE and Cr concentrations as recent L chondrites, the elements have been redistributed to the extent that it is problematic to establish the original meteorite type from these proxies. Different PGE data processing approaches can lead to highly variable results, as also shown here for the Lockne resurge deposits. We conclude that the Lockne crater was formed by an L-chondritic impactor, and that considerable care must be taken when inferring projectile type from PGEs in sedimentary ejecta deposits. (C) 2011 Elsevier B.V. All rights reserved.
|
|
| 22. |
- Schmitz, Birger, et al.
(författare)
-
Meteorite flux to Earth in the Early Cretaceous as reconstructed from sediment-dispersed extraterrestrial spinels
- 2017
-
Ingår i: Geology. - 0091-7613. ; 45:9, s. 807-810
-
Tidskriftsartikel (refereegranskat)abstract
- We show that Earth’s sedimentary strata can provide a record of the collisional evolution of the asteroid belt. From 1652 kg of pelagic Maiolica limestone of Berriasian–Hauterivian age from Italy, we recovered 108 extraterrestrial spinel grains (32–250 μm) representing relict minerals from coarse micrometeorites. Elemental and three oxygen isotope analyses were used to characterize the grains, providing a first-order estimate of the major types of asteroids delivering material at the time. Comparisons were made with meteorite-flux time “windows” in the Ordovician before and after the L-chondrite parent-body breakup. In the Early Cretaceous, ∼80% of the extraterrestrial spinels originated from ordinary chondrites. The ratios between the three groups of ordinary chondrites, H, L, LL, appear similar to the present, ∼1:1:0.2, but differ significantly from Ordovician ratios. We found no signs of a hypothesized Baptistina LL-chondrite breakup event. About 10% of the grains in the Maiolica originate from achondritic meteorite types that are very rare (<1%) on Earth today, but that were even more common in the Ordovician. Because most meteorite groups have lower spinel content than the ordinary chondrites, our data indicate that the latter did not dominate the flux during the Early Cretaceous to the same extent as today. Based on studies of three windows in deep time, we argue that there may have been a gradual long-term (a few hundred million years) turnover in the meteorite flux from dominance of achondrites in the early Phanerozoic to ordinary chondrites in the late Phanerozoic, interrupted by short-term (a few million years) meteorite cascades from single asteroid breakup events.
|
|
| 23. |
- Valentine, WJ, et al.
(författare)
-
Lipidomic Analyses Reveal Specific Alterations of Phosphatidylcholine in Dystrophic Mdx Muscle
- 2022
-
Ingår i: Frontiers in physiology. - : Frontiers Media SA. - 1664-042X. ; 12, s. 698166-
-
Tidskriftsartikel (refereegranskat)abstract
- In Duchenne muscular dystrophy (DMD), lack of dystrophin increases the permeability of myofiber plasma membranes to ions and larger macromolecules, disrupting calcium signaling and leading to progressive muscle wasting. Although the biological origin and meaning are unclear, alterations of phosphatidylcholine (PC) are reported in affected skeletal muscles of patients with DMD that may include higher levels of fatty acid (FA) 18:1 chains and lower levels of FA 18:2 chains, possibly reflected in relatively high levels of PC 34:1 (with 16:0_18:1 chain sets) and low levels of PC 34:2 (with 16:0_18:2 chain sets). Similar PC alterations have been reported to occur in themdxmouse model of DMD. However, altered ratios of PC 34:1 to PC 34:2 have been variably reported, and we also observed that PC 34:2 levels were nearly equally elevated as PC 34:1 in the affectedmdxmuscles. We hypothesized that experimental factors that often varied between studies; including muscle types sampled, mouse ages, and mouse diets; may strongly impact the PC alterations detected in dystrophic muscle ofmdxmice, especially the PC 34:1 to PC 34:2 ratios. In order to test our hypothesis, we performed comprehensive lipidomic analyses of PC and phosphatidylethanolamine (PE) in several muscles (extensor digitorum longus, gastrocnemius, and soleus) and determined themdx-specific alterations. The alterations in PC 34:1 and PC 34:2 were closely monitored from the neonate period to the adult, and also in mice raised on several diets that varied in their fats. PC 34:1 was naturally high in neonate’s muscle and decreased until age ∼3-weeks (disease onset age), and thereafter remained low in WT muscles but was higher in regeneratedmdxmuscles. Among the muscle types, soleus showed a distinctive phospholipid pattern with early and diminishedmdxalterations. Diet was a major factor to impact PC 34:1/PC 34:2 ratios becausemdx-specific alterations of PC 34:2 but not PC 34:1 were strictly dependent on diet. Our study identifies high PC 34:1 as a consistent biochemical feature of regeneratedmdx-muscle and indicates nutritional approaches are also effective to modify the phospholipid compositions.
|
|
