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| 2. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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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.
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| 3. |
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| 4. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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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.
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| 7. |
- Abdellaoui, G., et al.
(författare)
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Meteor studies in the framework of the JEM-EUSO program
- 2017
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Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
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Tidskriftsartikel (refereegranskat)abstract
- We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
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| 8. |
- Abdellaoui, G., et al.
(författare)
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First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
- 2018
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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| 10. |
- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 11. |
- Heuer, V. B., et al.
(författare)
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Temperature limits to deep subseafloor life in the Nankai Trough subduction zone
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6521, s. 1230-1234
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Tidskriftsartikel (refereegranskat)abstract
- Microorganisms in marine subsurface sediments substantially contribute to global biomass. Sediments warmer than 40 degrees C account for roughly half the marine sediment volume, but the processes mediated by microbial populations in these hard-to-access environments are poorly understood. We investigated microbial life in up to 1.2-kilometer-deep and up to 120 degrees C hot sediments in the Nankai Trough subduction zone. Above 45 degrees C, concentrations of vegetative cells drop two orders of magnitude and endospores become more than 6000 times more abundant than vegetative cells. Methane is biologically produced and oxidized until sediments reach 80 degrees to 85 degrees C. In 100 degrees to 120 degrees C sediments, isotopic evidence and increased cell concentrations demonstrate the activity of acetate-degrading hyperthermophiles. Above 45 degrees C, populated zones alternate with zones up to 192 meters thick where microbes were undetectable.
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| 12. |
- Amati, L., et al.
(författare)
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The THESEUS space mission concept : science case, design and expected performances
- 2018
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Ingår i: Advances in Space Research. - : ELSEVIER SCI LTD. - 0273-1177 .- 1879-1948. ; 62:1, s. 191-244
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Tidskriftsartikel (refereegranskat)abstract
- THESEUS is a space mission concept aimed at exploiting Gamma-Ray Bursts for investigating the early Universe and at providing a substantial advancement of multi-messenger and time-domain astrophysics. These goals will be achieved through a unique combination of instruments allowing GRB and X-ray transient detection over a broad field of view (more than 1 sr) with 0.5-1 arcmin localization, an energy band extending from several MeV down to 0.3 keV and high sensitivity to transient sources in the soft X-ray domain, as well as on-board prompt (few minutes) follow-up with a 0.7 m class IR telescope with both imaging and spectroscopic capabilities. THESEUS will be perfectly suited for addressing the main open issues in cosmology such as, e.g., star formation rate and metallicity evolution of the inter-stellar and intra-galactic medium up to redshift similar to 10, signatures of Pop III stars, sources and physics of re-ionization, and the faint end of the galaxy luminosity function. In addition, it will provide unprecedented capability to monitor the X-ray variable sky, thus detecting, localizing, and identifying the electromagnetic counterparts to sources of gravitational radiation, which may be routinely detected in the late '20s/early '30s by next generation facilities like aLIGO/ aVirgo, eLISA, KAGRA, and Einstein Telescope. THESEUS will also provide powerful synergies with the next generation of multi-wavelength observatories (e.g., LSST, ELT, SKA, CTA, ATHENA).
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| 16. |
- Mathieu, Roland, et al.
(författare)
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Bandwidth-disorder phase diagram of half-doped layered manganites
- 2006
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 74:2
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Tidskriftsartikel (refereegranskat)abstract
- Phase diagrams in the plane of rA (the average ionic radius, related to the one-electron bandwidth W) and σ2 (the ionic radius variance, measuring the quenched disorder), or bandwidth-disorder phase diagrams, have been established for perovskite manganites, with a three-dimensional (3D) Mn-O network. Here we establish the intrinsic bandwidth-disorder phase diagram of half-doped layered manganites with a two-dimensional (2D) Mn-O network, examining in detail the parent state of the colossal magnetoresistance phenomenon in crystals without ferromagnetic instability. The consequences of the reduced dimensionality, from 3D to 2D, for the order-disorder phenomena in the charge-orbital sectors are also highlighted.
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| 22. |
- Mathieu, Roland, et al.
(författare)
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Coexistence of long-ranged charge and orbital order and spin-glass state in single-layered manganites with weak quenched disorder
- 2007
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Ingår i: Europhysics letters. - : IOP Publishing. - 0295-5075 .- 1286-4854. ; 80:3, s. 37001-
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between orbital and spin degrees of freedom in the single crystals of the hole-doped Pr1-xCa1+xMnO4, 0.3 <= x <= 0.7 has been investigated by means of ac-magnetometry and charge transport. We show that in an intermediate underdoped region, with 0.35 <= x < 0.5, the "orbital-master spin-slave" relationship commonly observed in half-doped manganites does not take place. The long-ranged charge-orbital order is not accompanied by an antiferromagnetic transition at low temperatures, but by a frustrated short-ranged magnetic state bringing forth a spin-glass phase. We discuss in detail the nature and origin of this true spin-glass state, which, as in the half-doped manganites with large quenched disorder, is not related to the macroscopic phase separation observed in crystals with minor defects or impurities.
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| 23. |
- Tanaka, Kunihiko, et al.
(författare)
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Volume Density Structure of the Central Molecular Zone NGC 253 through ALCHEMI Excitation Analysis
- 2024
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 961:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a spatially resolved excitation analysis for the central molecular zone (CMZ) of the starburst galaxy NGC 253 using the data from the Atacama Large Millimeter/submillimeter Array Comprehensive High-resolution Extragalactic Molecular Inventory, whereby we explore parameters distinguishing NGC 253 from the quiescent Milky Way’s Galactic center (GC). Non-LTE analyses employing a hierarchical Bayesian framework are applied to Band 3-7 transitions from nine molecular species to delineate the position-position-velocity distributions of column density ( N H 2 ), volume density ( n H 2 ), and temperature (T kin) at 27 pc resolution. Two distinct components are detected: a low-density component with ( n H 2 , T kin ) ∼ ( 10 3.3 cm − 3 , 85 K ) and a high-density component with ( n H 2 , T kin ) ∼ ( 10 4.4 cm − 3 , 110 K ) , separated at n H 2 ∼ 10 3.8 cm − 3 . NGC 253 has ∼10 times the high-density gas mass and ∼3 times the dense-gas mass fraction of the GC. These properties are consistent with their HCN/CO ratio but cannot alone explain the factor of ∼30 difference in their star formation efficiencies (SFEs), contradicting the dense-gas mass to star formation rate scaling law. The n H 2 histogram toward NGC 253 exhibits a shallow declining slope up to n H 2 ∼ 10 6 cm − 3 , while that of the GC steeply drops in n H 2 ≳ 10 4.5 cm − 3 and vanishes at 105 cm−3. Their dense-gas mass fraction ratio becomes consistent with their SFEs when the threshold n H 2 for the dense gas is taken at ∼104.2−4.6 cm−3. The rich abundance of gas above this density range in the NGC 253 CMZ, or its scarcity in the GC, is likely to be the critical difference characterizing the contrasting star formation in the centers of the two galaxies.
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