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  • American Association for the Advancement of Science (AAAS)  (5)
  • 1
    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
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 2
    In: Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 15, No. 716 ( 2022-01-11)
    Abstract: After ligand stimulation, many G protein–coupled receptors (GPCRs) undergo β-arrestin–dependent desensitization, during which they are internalized and either degraded or recycled to the plasma membrane. Some GPCRs are not subject to this type of desensitization because they lack the residues required to interact with β-arrestins. We identified a mechanism of redox-dependent alternative internalization (REDAI) that promotes the internalization and degradation of the purinergic P2Y 6 receptor (P2Y 6 R). Synthetic and natural compounds containing electrophilic isothiocyanate groups covalently modified P2Y 6 R at Cys 220 , which promoted the ubiquitylation of Lys 137 and receptor internalization and degradation in various mouse and human cultured cell lines. Endogenous electrophiles also promoted ligand-dependent P2Y 6 R internalization and degradation. P2Y 6 R is highly abundant in inflammatory cells and promotes the pathogenesis of colitis. Deficiency in P2Y 6 R protected mice against experimentally induced colitis, and mice expressing a form of P2Y 6 R in which Cys 220 was mutated to nonmodifiable serine were more sensitive to the induction of colitis. Several other GPCRs, including A 2B AR, contain cysteine and lysine residues at the appropriate positions to mediate REDAI, and isothiocyanate stimulated the internalization of A 2B AR and of a form of P2Y 2 R with insertions of the appropriate residues. Thus, endogenous and exogenous electrophiles may limit colitis progression through cysteine modification of P2Y 6 R and may also mediate internalization of other GPCRs.
    Type of Medium: Online Resource
    ISSN: 1945-0877 , 1937-9145
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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  • 3
    In: Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 12, No. 587 ( 2019-06-25)
    Abstract: Chronic exposure to methylmercury (MeHg), an environmental electrophilic pollutant, reportedly increases the risk of human cardiac events. We report that exposure to a low, non-neurotoxic dose of MeHg precipitated heart failure induced by pressure overload in mice. Exposure to MeHg at 10 ppm did not induce weight loss typical of higher doses but caused mitochondrial hyperfission in myocardium through the activation of Drp1 by its guanine nucleotide exchange factor filamin-A. Treatment of neonatal rat cardiomyocytes with cilnidipine, an inhibitor of the interaction between Drp1 and filamin-A, suppressed mitochondrial hyperfission caused by low-dose MeHg exposure. Modification of cysteine residues in proteins with polysulfides is important for redox signaling and mitochondrial homeostasis in mammalian cells. We found that MeHg targeted rat Drp1 at Cys 624 , a redox-sensitive residue whose SH side chain forms a bulky and nucleophilic polysulfide (Cys 624 -S (n) H). MeHg exposure induced the depolysulfidation of Cys 624 -S (n) H in Drp1, which led to filamin-dependent activation of Drp1 and mitochondrial hyperfission. Treatment with NaHS, which acts as a donor for reactive polysulfides, reversed MeHg-evoked Drp1 depolysulfidation and vulnerability to mechanical load in rodent and human cardiomyocytes and mouse hearts. These results suggest that depolysulfidation of Drp1 at Cys 624 -S (n) H by low-dose MeHg increases cardiac fragility to mechanical load through filamin-dependent mitochondrial hyperfission.
    Type of Medium: Online Resource
    ISSN: 1945-0877 , 1937-9145
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
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  • 4
    In: Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 11, No. 556 ( 2018-11-13)
    Abstract: Defective mitochondrial dynamics through aberrant interactions between mitochondria and actin cytoskeleton is increasingly recognized as a key determinant of cardiac fragility after myocardial infarction (MI). Dynamin-related protein 1 (Drp1), a mitochondrial fission–accelerating factor, is activated locally at the fission site through interactions with actin. Here, we report that the actin-binding protein filamin A acted as a guanine nucleotide exchange factor for Drp1 and mediated mitochondrial fission–associated myocardial senescence in mice after MI. In peri-infarct regions characterized by mitochondrial hyperfission and associated with myocardial senescence, filamin A colocalized with Drp1 around mitochondria. Hypoxic stress induced the interaction of filamin A with the GTPase domain of Drp1 and increased Drp1 activity in an actin-binding–dependent manner in rat cardiomyocytes. Expression of the A1545T filamin mutant, which potentiates actin aggregation, promoted mitochondrial hyperfission under normoxia. Furthermore, pharmacological perturbation of the Drp1–filamin A interaction by cilnidipine suppressed mitochondrial hyperfission–associated myocardial senescence and heart failure after MI. Together, these data demonstrate that Drp1 association with filamin and the actin cytoskeleton contributes to cardiac fragility after MI and suggests a potential repurposing of cilnidipine, as well as provides a starting point for innovative Drp1 inhibitor development.
    Type of Medium: Online Resource
    ISSN: 1945-0877 , 1937-9145
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
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  • 5
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 9, No. 20 ( 2023-05-19)
    Abstract: Sema4A increases sensitivity to PD-1–blocking therapy by enhancing co-stimulation of CD8+ T cells in the tumor microenvironment.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 2810933-8
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