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| 2. |
- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Journal article (peer-reviewed)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.
(author)
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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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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Journal article (peer-reviewed)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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| 5. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 6. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 7. |
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| 8. |
- Sugita, S., et al.
(author)
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The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes
- 2019
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In: Science. - : AAAS. - 0036-8075 .- 1095-9203. ; 364:6437
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Journal article (peer-reviewed)abstract
- Asteroids fall to Earth in the form of meteorites, but these provide little information about their origins. The Japanese mission Hayabusa2 is designed to collect samples directly from the surface of an asteroid and return them to Earth for laboratory analysis. Three papers in this issue describe the Hayabusa2 team's study of the near-Earth carbonaceous asteroid 162173 Ryugu, at which the spacecraft arrived in June 2018 (see the Perspective by Wurm). Watanabeet al.measured the asteroid's mass, shape, and density, showing that it is a “rubble pile” of loose rocks, formed into a spinning-top shape during a prior period of rapid spin. They also identified suitable landing sites for sample collection. Kitazatoet al.used near-infrared spectroscopy to find ubiquitous hydrated minerals on the surface and compared Ryugu with known types of carbonaceous meteorite. Sugitaet al.describe Ryugu's geological features and surface colors and combined results from all three papers to constrain the asteroid's formation process. Ryugu probably formed by reaccumulation of rubble ejected by impact from a larger asteroid. These results provide necessary context to understand the samples collected by Hayabusa2, which are expected to arrive on Earth in December 2020.Science, this issue p.268, p.272, p.eaaw0422; see also p.230
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| 9. |
- Sakatani, N., et al.
(author)
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Anomalously porous boulders on (162173) Ryugu as primordial materials from its parent body
- 2021
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In: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:8, s. 766-774
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Journal article (peer-reviewed)abstract
- Planetesimals—the initial stage of the planetary formation process—are considered to be initially very porous aggregates of dusts1,2, and subsequent thermal and compaction processes reduce their porosity3. The Hayabusa2 spacecraft found that boulders on the surface of asteroid (162173) Ryugu have an average porosity of 30–50% (refs. 4,5,6), higher than meteorites but lower than cometary nuclei7, which are considered to be remnants of the original planetesimals8. Here, using high-resolution thermal and optical imaging of Ryugu’s surface, we discovered, on the floor of fresh small craters (<20 m in diameter), boulders with reflectance (~0.015) lower than the Ryugu average6 and porosity >70%, which is as high as in cometary bodies. The artificial crater formed by Hayabusa2’s impact experiment9 is similar to these craters in size but does not have such high-porosity boulders. Thus, we argue that the observed high porosity is intrinsic and not created by subsequent impact comminution and/or cracking. We propose that these boulders are the least processed material on Ryugu and represent remnants of porous planetesimals that did not undergo a high degree of heating and compaction3. Our multi-instrumental analysis suggests that fragments of the highly porous boulders are mixed within the surface regolith globally, implying that they might be captured within collected samples by touch-down operations10,11.
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| 10. |
- Asano, H., et al.
(author)
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Spectroscopic study of the Λ(1405) resonance via the d (K-, n) reaction at J-PARC
- 2019
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In: 13th International Conference on Hypernuclear and Strange Particle Physics, HYP 2018. - : AIP Publishing. - 9780735418721 ; 2130
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Conference paper (peer-reviewed)abstract
- The structure of the Λ(1405) hyperon is an important and long-standing issue related to the K̄-nucleus interaction. The J-PARC E31 experiment has been performed to investigate the Λ(1405) spectrum shape. Because it is hard to form the Λ(1405) directly by a K̄N scattering in free space, E31 uses the d(K-, n) reaction with an incident kaon momentum of 1 GeV/c. We will identify three final states - ς-π+, ς+π-, ς0π0-so that the isospin structure of hyperon resonance states produced can be decomposed. The first physics run of the E31 experiment was performed in 2016. To enhance the statistics of the data set, we have performed the second physics run in the beginning of 2018. During the second run of E31, around 3.9×1010 kaons impacted on the deuteron target.
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| 11. |
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| 12. |
- Fomalont, E. B., et al.
(author)
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THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
- 2015
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
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Journal article (peer-reviewed)abstract
- A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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| 13. |
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| 14. |
- Yamaga, Takumi, et al.
(author)
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Study of the elementary (K -, n) reactions to search for the K NN bound state via the 3He (K -, n) reaction at J-PARC
- 2016
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In: XVIth International Conference on Hadron Spectroscopy, Hadron 2015. - : Author(s). - 9780735413894 ; 1735
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Conference paper (peer-reviewed)abstract
- We have searched for the simplest kaonic nuclear state, K̄NN, using the in-flight 3He (K-, n) reaction at the J-PARC hadron experimental facility. In the semi-inclusive neutron missing-mass spectrum at θnlab=0°, an excess of yield was observed just below the K- pp mass-threshold, which cannot be explained by any elementary reactions [PTEP 2015, 061D01]. To understand the missing-mass spectrum of 3He (K-, n) X, we investigated the elementary (K-, n) reactions using hydrogen and deuterium targets. The p (K-, n) X missing-mass spectrum was well described by the charge-exchange reaction. However, in the d (K-, n) X spectrum, we observed an excess of yield just below the K- p mass-threshold, which was similar to that in the 3He (K-, n) X spectrum.
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| 15. |
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| 16. |
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| 17. |
- Sada, Y., et al.
(author)
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Structure near the K- + p + p threshold in the in-flight 3He(K-, Λp)n reaction
- 2016
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In: Progress of Theoretical and Experimental Physics. - : Oxford University Press (OUP). - 2050-3911. ; 2016:5
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Journal article (peer-reviewed)abstract
- To search for an S = -1 di-baryonic state which decays toΛp, the 3He(K-,Λp)nmissing reaction was studied at 1.0 GeV/c. Unobserved neutrons were kinematically identified from the missing mass MX of the 3He (K-,Λp) X reaction in order to have a large acceptance for the Λpn final state. The observed Λpn events, distributed widely over the kinematically allowed region of the Dalitz plot, establish that the major component comes from a three-nucleon absorption process. A concentration of events at a specific neutron kinetic energy was observed in a region of low momentum transfer to the Λp. To account for the observed peak structure, the simplest S-wave polewas assumed to exist in the reaction channel, having a Breit-Wigner formin energy and with a Gaussian form factor. A minimum X2 method was applied to deduce its mass, MX = 2355+6 -8 (stat.) ±12 (syst.)MeV/c2, and decay width, γX = 110+19 -17 (stat.) ±27 (syst.)MeV/c2, respectively. The form factor parameter QX ∼ 400MeV/c implies that the range of the interaction is about 0.5 fm.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Ishiguro, K, et al.
(author)
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Meiosis-specific cohesin mediates homolog recognition in mouse spermatocytes
- 2014
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In: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 28:6, s. 594-607
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Journal article (peer-reviewed)abstract
- During meiosis, homologous chromosome (homolog) pairing is promoted by several layers of regulation that include dynamic chromosome movement and meiotic recombination. However, the way in which homologs recognize each other remains a fundamental issue in chromosome biology. Here, we show that homolog recognition or association initiates upon entry into meiotic prophase before axis assembly and double-strand break (DSB) formation. This homolog association develops into tight pairing only during or after axis formation. Intriguingly, the ability to recognize homologs is retained in Sun1 knockout spermatocytes, in which telomere-directed chromosome movement is abolished, and this is the case even in Spo11 knockout spermatocytes, in which DSB-dependent DNA homology search is absent. Disruption of meiosis-specific cohesin RAD21L precludes the initial association of homologs as well as the subsequent pairing in spermatocytes. These findings suggest the intriguing possibility that homolog recognition is achieved primarily by searching for homology in the chromosome architecture as defined by meiosis-specific cohesin rather than in the DNA sequence itself.
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| 24. |
- Kumar, R, et al.
(author)
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MEI4 – a central player in the regulation of meiotic DNA double-strand break formation in the mouse
- 2015
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In: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 128:9, s. 1800-1811
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Journal article (peer-reviewed)abstract
- The formation of programmed DNA double strand breaks (DSBs) at the beginning of meiotic prophase marks the initiation of meiotic recombination. Meiotic DSBs are catalyzed by SPO11 and their repair takes place on meiotic chromosome axes. The evolutionarily conserved MEI4 protein is required for meiotic DSB formation and is localized on chromosome axes. Here we show that HORMAD1, one of the meiotic chromosome axis components, is required for MEI4 localization. Importantly, the quantitative correlation between the level of axis-associated MEI4 and DSB formation suggests that axis-associated MEI4 could be a limiting factor for DSB formation. We also show that MEI1, REC8 and RAD21L are important for proper MEI4 localization. These findings on MEI4 dynamics during meiotic prophase suggest that the association of MEI4 to chromosome axes is required for DSB formation, and that the loss of this association upon DSB repair could contribute to turning off meiotic DSB formation.
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