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  • 1
    Online Resource
    Online Resource
    Bacteria-derived metabolite, methylglyoxal, modulates the longevity of C. elegans through TORC2/SGK-1/DAF-16 signaling
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 29 ( 2020-07-21), p. 17142-17150
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 29 ( 2020-07-21), p. 17142-17150
    Abstract: Gut microbes play diverse roles in modulating host fitness, including longevity; however, the molecular mechanisms underlying their mediation of longevity remain poorly understood. We performed genome-wide screens using 3,792 Escherichia coli mutants and identified 44 E. coli mutants that modulated Caenorhabditis elegans longevity. Three of these mutants modulated C. elegans longevity via the bacterial metabolite methylglyoxal (MG). Importantly, we found that low MG-producing E. coli mutants, Δhns E. coli , extended the lifespan of C. elegans through activation of the DAF-16/FOXO family transcription factor and the mitochondrial unfolded protein response (UPR mt ). Interestingly, the lifespan modulation by Δhns did not require insulin/insulin-like growth factor 1 signaling (IIS) but did require TORC2/SGK-1 signaling. Transcriptome analysis revealed that Δhns E. coli activated novel class 3 DAF-16 target genes that were distinct from those regulated by IIS. Taken together, our data suggest that bacteria-derived MG modulates host longevity through regulation of the host signaling pathways rather than through nonspecific damage on biomolecules known as advanced glycation end products. Finally, we demonstrate that MG enhances the phosphorylation of hSGK1 and accelerates cellular senescence in human dermal fibroblasts, suggesting the conserved role of MG in controlling longevity across species. Together, our studies demonstrate that bacteria-derived MG is a novel therapeutic target for aging and aging-associated pathophysiology.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1915719117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Native and second language processing of quantifier scope ambiguity
    SAGE Publications ; 2023
    In:  Second Language Research Vol. 39, No. 3 ( 2023-07), p. 785-810
    Details
    In: Second Language Research, SAGE Publications, Vol. 39, No. 3 ( 2023-07), p. 785-810
    Abstract: The present study investigates native (L1) and second language (L2) processing of scope ambiguities in English sentences containing the universal quantifier every in subject NP and negation. Previous studies in L1 and L2 processing of scope ambiguities have found speakers to generally employ a ‘minimal effort’ principle that highly prefers the surface scope reading regardless of contextual support because accessing the inverse scope reading incurs significant processing cost. The present study compared L1 and L2 scope judgments and processing strategies of sentences such as Every horse didn’t jump over the fence and examined whether the two groups differ in their speed and manner of analysis. Thirty native English speakers and 42 Korean learners of English participated in a self-paced reading/interpretation task that has context (ambiguous vs. unambiguous) and scope reading (surface vs. inverse) as variables. The results revealed significant differences in scope endorsement rates with L2 learners arriving at the surface scope as the dominant reading and L1 learners’ judgments being highly dependent on contextual ambiguity. Moreover, L1 vs. L2 differences in processing strategies were found: L2 learners exhibited a strong tendency to arrive at the most economical interpretation while L1 speakers consulted detailed syntactic and semantic rules of computation.
    Type of Medium: Online Resource
    ISSN: 0267-6583 , 1477-0326
    URL: Article
    DOI: 10.1177/02676583221079741
    RVK:
    EQ 1000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2023712-1
    SSG: 7,11
    SSG: 5,3
    SSG: 7,23
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway
    American Association for the Advancement of Science (AAAS) ; 2015
    In:  Science Vol. 347, No. 6227 ( 2015-03-13), p. 1249-1252
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 347, No. 6227 ( 2015-03-13), p. 1249-1252
    Abstract: Rgs2, a regulator of G proteins, lowers blood pressure by decreasing signaling through Gα q . Human patients expressing Met-Leu-Rgs2 (ML-Rgs2) or Met-Arg-Rgs2 (MR-Rgs2) are hypertensive relative to people expressing wild-type Met-Gln-Rgs2 (MQ-Rgs2). We found that wild-type MQ-Rgs2 and its mutant, MR-Rgs2, were destroyed by the Ac/N-end rule pathway, which recognizes N α -terminally acetylated (Nt-acetylated) proteins. The shortest-lived mutant, ML-Rgs2, was targeted by both the Ac/N-end rule and Arg/N-end rule pathways. The latter pathway recognizes unacetylated N-terminal residues. Thus, the Nt-acetylated Ac-MX-Rgs2 (X = Arg, Gln, Leu) proteins are specific substrates of the mammalian Ac/N-end rule pathway. Furthermore, the Ac/N-degron of Ac-MQ-Rgs2 was conditional, and Teb4, an endoplasmic reticulum (ER) membrane-embedded ubiquitin ligase, was able to regulate G protein signaling by targeting Ac-MX-Rgs2 proteins for degradation through their N α -terminal acetyl group.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aaa3844
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2015
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 51 ( 2020-12-22), p. 32433-32442
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 51 ( 2020-12-22), p. 32433-32442
    Abstract: Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2006828117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
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