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  • 1
    In: Nature, Springer Science and Business Media LLC, Vol. 609, No. 7928 ( 2022-09-22), p. 754-760
    Abstract: Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1–5 . 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.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 2
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6634 ( 2023-02-24)
    Abstract: The Hayabusa2 spacecraft made two landings on the asteroid (162173) Ryugu in 2019, during which it collected samples of the surface material. Those samples were delivered to Earth in December 2020. The colors, shapes, and morphologies of the returned samples are consistent with those observed on Ryugu by Hayabusa2, indicating that they are representative of the asteroid. Laboratory analysis of the samples can determine the chemical composition of Ryugu and provide information on its formation and history. RATIONALE We used laboratory analysis to inform the following questions: (i) What are the elemental abundances of Ryugu? (ii) What are the isotopic compositions of Ryugu? (iii) Does Ryugu consist of primary materials produced in the disk from which the Solar System formed or of secondary materials produced in the asteroid or on a parent asteroid? (iv) When were Ryugu’s constituent materials formed? (v) What, if any, relationship does Ryugu have with meteorites? RESULTS We quantified the abundances of 66 elements in the Ryugu samples: H, Li, Be, C, O, Na, Mg, Al, Si, P, S, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Y, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Cd, In, Sn, Te, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Hf, Ta, W, Tl, Pb, Bi, Th, and U. There is a slight variation in chemical compositions between samples from the first and second touchdown sites, but the variations could be due to heterogeneity among the samples that were analyzed. The Cr-Ti isotopes and abundance of volatile elements are similar to those of carbonaceous meteorites in the CI (Ivuna-like) chondrite group. The Ryugu samples consist of the minerals magnetite, breunnerite, dolomite, and pyrrhotite as grains embedded in a matrix composed of serpentine and saponite. This mineral assemblage and the texture are also similar to those of CI meteorites. Anhydrous silicates are almost absent, which indicates extensive liquid water–rock reactions (aqueous alteration) in the material. We conclude that the samples mainly consist of secondary materials that were formed by aqueous alteration in a parent body, from which Ryugu later formed. The oxygen isotopes in the bulk Ryugu samples are also similar to those in CI chondrites. We used oxygen isotope thermometry to determine the temperature at which the dolomite and magnetite precipitated from an aqueous solution, which we found to be 37° ± 10°C. The 53 Mn- 53 Cr isotopes date the aqueous alteration at 5.2 − 0.7 + 0.8 million (statistical) or 5.2 − 2.1 + 1.6 million (systematic) years after the birth of the Solar System. Phyllosilicate minerals are the main host of water in the Ryugu samples. The amount of structural water in Ryugu is similar to that in CI chondrites, but interlayer water is largely absent in Ryugu, which suggests a loss of interlayer water to space. The abundance of structural water and results from dehydration experiments indicate that the Ryugu samples remained below ~100°C from the time of aqueous alteration until the present. We ascribe the removal of interlayer water to a combination of impact heating, solar heating, solar wind irradiation, and long-term exposure to the ultrahigh vacuum of space. The loss of interlayer water from phyllosilicates could be responsible for the comet-like activity of some carbonaceous asteroids and the ejection of solid material from the surface of asteroid Bennu. CONCLUSION The Ryugu samples are most similar to CI chondrite meteorites but are more chemically pristine. The chemical composition of the Ryugu samples is a closer match to the Sun’s photosphere than to the composition of any other natural samples studied in laboratories. CI chondrites appear to have been modified on Earth or during atmospheric entry. Such modification of CI chondrites could have included the alteration of the structures of organics and phyllosilicates, the adsorption of terrestrial water, and the formation of sulfates and ferrihydrites. Those issues do not affect the Ryugu samples. Those modifications might have changed the albedo, porosity, and density of the CI chondrites, causing the observed differences between CI meteorites, Hayabusa2 measurements of Ryugu’s surface, and the Ryugu samples returned to Earth. Representative petrography of a Ryugu sample, designated C0002-C1001. Colors indicate elemental abundances determined from x-ray spectroscopy. Lines of iron, sulfur, and calcium are shown as red, green, and blue (RGB) color channels in that order. Combinations of these elements are assigned to specific minerals, as indicated in the legend. All visible minerals were formed by aqueous alteration on Ryugu’s parent body.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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  • 3
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6634 ( 2023-02-24)
    Abstract: Organic compounds in asteroids and comets contain information about the early history of the Solar System. They could also have delivered organic material to early Earth. The Hayabusa2 spacecraft visited the carbonaceous asteroid Ryugu and collected samples of its surface materials, which were brought to Earth in December 2020. RATIONALE We investigated the macromolecular organic matter in the Ryugu samples, measuring its elemental, isotopic, and functional group compositions along with its small-scale structures and morphologies. Analytical methods used included spectro-microscopies, electron microscopy, and isotopic microscopy. We examined intact Ryugu grains and insoluble carbonaceous residues isolated by acid treatment of the Ryugu samples. RESULTS Organic matter is abundant in the Ryugu grains, distributed as submicrometer-sized organic grains and as organic matter dispersed in matrix. The Ryugu organic matter consists of aromatic carbons, aliphatic carbons, ketones, and carboxyls. The functional group compositions are consistent with those of insoluble organic matter (IOM) from primitive carbonaceous CI (Ivuna-type) and CM (Mighei-type) chondritic meteorites. Those meteorites experienced aqueous alteration (reactions with liquid water) on their parent bodies, which implies that the Ryugu organic material was also modified by aqueous alteration on the asteroid parent body. The functional group distributions of the Ryugu organic matter vary on submicrometer scales in ways that relate to the morphologies: nanoparticulate and/or nanoglobular regions are aromatic-rich, whereas organic matter associated with Mg-rich phyllosilicate matrix and carbonates is IOM-like or occurs as diffuse carbon. The observed macromolecular diversity provides further evidence that the organics were modified by aqueous alteration on Ryugu’s parent body. The diffuse carbon is similar to clay-bound organic matter that occurs in CI chondrites and the ungrouped C2-type meteorite Tagish Lake. No graphite-like material was found, which indicates that the Ryugu organic matter was not subjected to heating events on the parent body. The bulk hydrogen and nitrogen isotopic ratios of the Ryugu grains are between the bulk values of CI chondrites and the IOM in CI chondrites. Some carbonaceous grains showed extreme deuterium (D) and/or nitrogen-15 ( 15 N) enrichments or depletions. These indicate an origin in the interstellar medium or presolar nebula. The bulk hydrogen isotopic ratios of insoluble carbonaceous residues from the Ryugu samples are lower than those in CI and CM chondrites. The range of D enrichments are consistent with the ranges of CI, CM, and Tagish Lake chondrites. The nitrogen isotopic ratios of the IOM from Ryugu samples were close to those in CI chondrites. CONCLUSION The organic matter in Ryugu probably consists of primordial materials that formed during (or before) the early stages of the Solar System’s formation, which were later modified by heterogeneous aqueous alteration on Ryugu’s parent body asteroid. Although the surface of Ryugu is exposed to solar wind, impacts, and heating by sunlight, the macromolecular organics in the surface grains of Ryugu are similar in their chemical, isotopic, and morphological compositions to those seen in primitive carbonaceous chondrites. The properties of Ryugu’s organic matter could explain the low albedo of the asteroid’s surface. Chemical evolution of macromolecular organic matter in samples of asteroid Ryugu. Organic matter formed in the interstellar medium or in the outer region of the protoplanetary disk that formed the Solar System. It was then incorporated into a planetesimal—Ryugu’s parent body—where it experienced varying degrees of reactions with liquid water. An impact ejected material from the parent body, which reassembled to form Ryugu. Samples were brought to Earth by Hayabusa2. CREDIT: HIROSHIMA UNIVERSITY, JAXA, UNIVERSITY OF TOKYO, KOCHI UNIVERSITY, RIKKYO UNIVERSITY, NAGOYA UNIVERSITY, CHIBA INSTITUTE OF TECHNOLOGY, MEIJI UNIVERSITY, UNIVERSITY OF AIZU, AIST
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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  • 4
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 17 ( 2011-04-26), p. 7040-7045
    Abstract: Nuclear reprogramming of differentiated cells can be induced by oocyte factors. Despite numerous attempts, these factors and mechanisms responsible for successful reprogramming remain elusive. Here, we identify one such factor, necessary for the development of nuclear transfer embryos, using porcine oocyte extracts in which some reprogramming events are recapitulated. After incubating somatic nuclei in oocyte extracts from the metaphase II stage, the oocyte proteins that were specifically and abundantly incorporated into the nuclei were identified by mass spectrometry. Among 25 identified proteins, we especially focused on a multifunctional protein, DJ-1. DJ-1 is present at a high concentration in oocytes from the germinal vesicle stage until embryos at the four-cell stage. Inhibition of DJ-1 function compromises the development of nuclear transfer embryos but not that of fertilized embryos. Microarray analysis of nuclear transfer embryos in which DJ-1 function is inhibited shows perturbed expression of P53 pathway components. In addition, embryonic arrest of nuclear transfer embryos injected with anti– DJ-1 antibody is rescued by P53 inhibition. We conclude that DJ-1 is an oocyte factor that is required for development of nuclear transfer embryos. This study presents a means for identifying natural reprogramming factors in mammalian oocytes and a unique insight into the mechanisms underlying reprogramming by nuclear transfer.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
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  • 5
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 312, No. 5778 ( 2006-06-02), p. 1347-1349
    Abstract: The locations of the pole and rotation axis of asteroid 25143 Itokawa were derived from Asteroid Multiband Imaging Camera data on the Hayabusa spacecraft. The retrograde pole orientation had a right ascension of 90.53° and a declination of â66.30° (52000 equinox) or equivalently 128.5° and â89.66° in ecliptic coordinates with a 3.9° margin of error. The surface area is 0.393 square kilometers, the volume is 0.018378 cubic kilometers with a 5% margin of error, and the three axis lengths are 535 meters by 294 meters by 209 meters. The global Itokawa revealed a boomerang-shaped appearance composed of two distinct parts with partly faceted regions and a constricted ring structure.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2006
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  • 6
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 117, No. 3 ( 2021-02-22), p. 805-819
    Abstract: Exercise intolerance in patients with heart failure (HF) is partly attributed to skeletal muscle abnormalities. We have shown that reactive oxygen species (ROS) play a crucial role in skeletal muscle abnormalities, but the pathogenic mechanism remains unclear. Xanthine oxidase (XO) is reported to be an important mediator of ROS overproduction in ischaemic tissue. Here, we tested the hypothesis that skeletal muscle abnormalities in HF are initially caused by XO-derived ROS and are prevented by the inhibition of their production. Methods and results Myocardial infarction (MI) was induced in male C57BL/6J mice, which eventually led to HF, and a sham operation was performed in control mice. The time course of XO-derived ROS production in mouse skeletal muscle post-MI was first analysed. XO-derived ROS production was significantly increased in MI mice from Days 1 to 3 post-surgery (acute phase), whereas it did not differ between the MI and sham groups from 7 to 28 days (chronic phase). Second, mice were divided into three groups: sham + vehicle (Sham + Veh), MI + vehicle (MI + Veh), and MI + febuxostat (an XO inhibitor, 5 mg/kg body weight/day; MI + Feb). Febuxostat or vehicle was administered at 1 and 24 h before surgery, and once-daily on Days 1–7 post-surgery. On Day 28 post-surgery, exercise capacity and mitochondrial respiration in skeletal muscle fibres were significantly decreased in MI + Veh compared with Sham + Veh mice. An increase in damaged mitochondria in MI + Veh compared with Sham + Veh mice was also observed. The wet weight and cross-sectional area of slow muscle fibres (higher XO-derived ROS) was reduced via the down-regulation of protein synthesis-associated mTOR-p70S6K signalling in MI + Veh compared with Sham + Veh mice. These impairments were ameliorated in MI + Feb mice, in association with a reduction of XO-derived ROS production, without affecting cardiac function. Conclusion XO inhibition during the acute phase post-MI can prevent skeletal muscle abnormalities and exercise intolerance in mice with HF.
    Type of Medium: Online Resource
    ISSN: 0008-6363 , 1755-3245
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 7
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6634 ( 2023-02-24)
    Abstract: Surface material from the near-Earth carbonaceous (C-type) asteroid (162173) Ryugu was collected and brought to Earth by the Hayabusa2 spacecraft. Ryugu is a dark, primitive asteroid containing hydrous minerals that are similar to the most hydrated carbonaceous meteorites. C-type asteroids are common in the asteroid belt and have been proposed as the parent bodies of carbonaceous meteorites. The samples of Ryugu provide an opportunity to investigate organic compounds for comparison with those from carbonaceous meteorites. Unlike meteorites, the Ryugu samples were collected and delivered for study under controlled conditions, reducing terrestrial contamination and the effects of atmospheric entry. RATIONALE Primitive carbonaceous chondrite meteorites are known to contain a variety of soluble organic molecules (SOMs), including prebiotic molecules such as amino acids. Meteorites might have delivered amino acids and other prebiotic organic molecules to the early Earth and other rocky planets. Organic matter in the Ryugu samples is the product of physical and chemical processes that occurred in the interstellar medium, the protosolar nebula, and/or on the planetesimal that became Ryugu’s parent body. We investigated SOMs in Ryugu samples principally using mass spectrometry coupled with liquid or gas chromatography. RESULTS We identified numerous organic molecules in the Ryugu samples. Mass spectroscopy detected hundreds of thousands of ion signals, which we assigned to ~20,000 elementary compositions consisting of carbon, hydrogen, nitrogen, oxygen, and/or sulfur. Fifteen amino acids, including glycine, alanine, and α-aminobutyric acid, were identified. These were present as racemic mixtures (equal right- and left-handed abundances), consistent with an abiotic origin. Aliphatic amines (such as methylamine) and carboxylic acids (such as acetic acid) were also detected, likely retained on Ryugu as organic salts. The presence of aromatic hydrocarbons, including alkylbenzenes, fluoranthene, and pyrene, implies hydrothermal processing on Ryugu’s parent body and/or presolar synthesis in the interstellar medium. Nitrogen-containing heterocyclic compounds were identified as their alkylated homologs, which could have been synthesized from simple aldehydes and ammonia. In situ analysis of a grain surface showed heterogeneous spatial distribution of alkylated homologs of nitrogen- and/or oxygen-containing compounds. CONCLUSION The wide variety of molecules identified indicates that prolonged chemical processes contributed to the synthesis of soluble organics on Ryugu or its parent body. The highly diverse mixture of SOMs in the samples resembles that seen in some carbonaceous chondrites. However, the SOM concentration in Ryugu is less than that in moderately aqueously altered CM (Mighei-type) chondrites, being more similar to that seen in warm aqueously altered CI (Ivuna-type) chondrites. The chemical diversity with low SOM concentration in Ryugu is consistent with aqueous organic chemistry at modest temperatures on Ryugu’s parent asteroid. The samples collected from the surface of Ryugu were exposed to the hard vacuum of space, energetic particle irradiation, heating by sunlight, and micrometeoroid impacts, but the SOM is still preserved, likely by being associated with minerals. The presence of prebiotic molecules on the asteroid surface suggests that these molecules can be transported throughout the Solar System. SOMs detected in surface samples of asteroid Ryugu. Chemical structural models are shown for example molecules from several classes identified in the Ryugu samples. Gray balls are carbon, white are hydrogen, red are oxygen, and blue are nitrogen. Clockwise from top: amines (represented by ethylamine), nitrogen-containing heterocycles (pyridine), a photograph of the sample vials for analysis, polycyclic aromatic hydrocarbons (PAHs) (pyrene), carboxylic acids (acetic acid), and amino acids (β-alanine). The central hexagon shows a photograph of the Ryugu sample in the sample collector of the Hayabusa2 spacecraft. The background image shows Ryugu in a photograph taken by Hayabusa2. CREDIT: JAXA, University of Tokyo, Kochi University, Rikkyo University, Nagoya University, Chiba Institute of Technology, Meiji University, University of Aizu, AIST, NASA, Dan Gallagher.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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  • 8
    Online Resource
    Online Resource
    American Society for Microbiology ; 2002
    In:  Applied and Environmental Microbiology Vol. 68, No. 1 ( 2002-01), p. 405-407
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 68, No. 1 ( 2002-01), p. 405-407
    Abstract: Here we describe artificial help for the respiratory electron flow supporting anaerobic growth of Thiobacillus ferrooxidans through exogenous electrolysis. Flux between H 2 and a anode through cells was accomplished with electrochemical regeneration of iron. The electrochemical help resulted in a 12-fold increase in yield compared with the yield observed in its absence.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
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    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2002
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  • 9
    Online Resource
    Online Resource
    American Society for Microbiology ; 1999
    In:  Applied and Environmental Microbiology Vol. 65, No. 2 ( 1999-02), p. 837-840
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 65, No. 2 ( 1999-02), p. 837-840
    Abstract: A phylogenetic analysis of the sequences of 60 clones of archaeal small-subunit rRNA genes amplified from the termite Reticulitermes speratus revealed that most of them (56 clones) clustered in the genus Methanobrevibacter . Three clones were classified in the order Thermoplasmales. The Methanobrevibacter -related symbionts were detected by in situ hybridization analysis.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
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    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1999
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  • 10
    In: Acta Histochemica, Elsevier BV, Vol. 120, No. 6 ( 2018-08), p. 566-571
    Type of Medium: Online Resource
    ISSN: 0065-1281
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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    SSG: 12
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