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  • 1
    Online Resource
    Online Resource
    Structural basis for strychnine activation of human bitter taste receptor TAS2R46
    American Association for the Advancement of Science (AAAS) ; 2022
    In:  Science Vol. 377, No. 6612 ( 2022-09-16), p. 1298-1304
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 377, No. 6612 ( 2022-09-16), p. 1298-1304
    Abstract: A structure reveals insights into how a human bitter taste receptor recognizes a ligand and transduces the signal.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abo1633
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    CD24 is a genetic modifier for risk and progression of multiple sclerosis
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 25 ( 2003-12-09), p. 15041-15046
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 25 ( 2003-12-09), p. 15041-15046
    Abstract: Multiple sclerosis (MS) is a chronic neurological disease of unknown etiology, but a genetic basis for the disease is undisputed. We have reported that CD24 is required for the pathogenicity of autoreactive T cells in experimental autoimmune encephalomyelitis, the mouse model of MS. Here we investigate the contribution of CD24 to MS by studying single-nucleotide polymorphism in the ORF among 242 MS patients and 207 population controls. This single-nucleotide polymorphism results in replacement of alanine ( CD24 a ) with valine ( CD24 v ) in the mature protein. We found that the CD24 v/v renders a 〉 2-fold increase in the relative risk of MS in the general population ( P = 0.023). Among familial MS, the CD24 v allele is preferentially transmitted into affected individuals ( P = 0.017). Furthermore, 50% of CD24 v/v patients with expanded disability status scale 6.0 reached the milestone in 5 years, whereas the CD24 a/v ( P = 0.00037) and CD24 a/a ( P = 0.0016) patients did so in 16 and 13 years, respectively. Moreover, our data suggest that the CD24 v/v patients expressed higher levels of CD24 on peripheral blood T cells than did the CD24 a/a patients. Transfection with CD24 a and CD24 v cDNA demonstrated that the CD24 v allele can be expressed at higher efficiency than the CD24 a alleles. Thus, CD24 polymorphism is a genetic modifier for susceptibility and progression of MS in the central Ohio cohort that we studied, perhaps by affecting the efficiency of CD24 expression on the cell surface.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2533866100
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Structural insights into the roles of the IcmS–IcmW complex in the type IVb secretion system of Legionella pneumophila
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 51 ( 2017-12-19), p. 13543-13548
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 51 ( 2017-12-19), p. 13543-13548
    Abstract: The type IVb secretion system (T4BSS) of Legionella pneumophila is a multiple-component apparatus that delivers ∼300 virulent effector proteins into host cells. The injected effectors modulate host cellular processes to promote bacterial infection and proliferation. IcmS and IcmW are two conserved small, acidic adaptor proteins that form a binary complex to interact with many effectors and facilitate their translocation. IcmS and IcmW can also interact with DotL, an ATPase of the type IV coupling protein complex (T4CP). However, how IcmS–IcmW recognizes effectors, and what the roles of IcmS–IcmW are in T4BSSs are unclear. In this study, we found that IcmS and IcmW form a 1:1 heterodimeric complex to bind effector substrates. Both IcmS and IcmW adopt new structural folds and have no structural similarities with known effector chaperones. IcmS has a compact global structure with an α/β fold, while IcmW adopts a fully α-folded, relatively loose architecture. IcmS stabilizes IcmW by binding to its two C-terminal α-helices. Photocrosslinking assays revealed that the IcmS–IcmW complex binds its cognate effectors via an extended hydrophobic surface, which can also interact with the C terminus of DotL. A crystal structure of the DotL–IcmS–IcmW complex reveals extensive and highly stable interactions between DotL and IcmS–IcmW. Moreover, IcmS–IcmW recruits LvgA to DotL and assembles a unique T4CP. These data suggest that IcmS–IcmW also functions as an inseparable integral component of the DotL–T4CP complex in the bacterial inner membrane. This study provides molecular insights into the dual roles of the IcmS–IcmW complex in T4BSSs.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1706883115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    The CsHEC1-CsOVATE module contributes to fruit neck length variation via modulating auxin biosynthesis in cucumber
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 39 ( 2022-09-27)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 39 ( 2022-09-27)
    Abstract: Fruit neck is the proximal portion of the fruit with undesirable taste that has detrimental effects on fruit shape and commercial value in cucumber. Despite the dramatic variations in fruit neck length of cucumber germplasms, the genes and regulatory mechanisms underlying fruit neck elongation remain mysterious. In this study, we found that Cucumis sativus HECATE1 ( CsHEC1 ) was highly expressed in fruit neck. Knockout of CsHEC1 resulted in shortened fruit neck and decreased auxin accumulation, whereas overexpression of CsHEC1 displayed the opposite effects, suggesting that CsHEC1 positively regulated fruit neck length by modulating local auxin level. Further analysis showed that CsHEC1 directly bound to the promoter of the auxin biosynthesis gene YUCCA4 ( CsYUC4 ) and activated its expression. Enhanced expression of CsYUC4 resulted in elongated fruit neck and elevated auxin content. Moreover, knockout of CsOVATE resulted in longer fruit neck and higher auxin. Genetic and biochemical data showed that CsOVATE physically interacted with CsHEC1 to antagonize its function by attenuating the CsHEC1-mediated CsYUC4 transcriptional activation. In cucumber germplasms, the expression of CsHEC1 and CsYUC4 positively correlated with fruit neck length, while that of CsOVATE showed a negative correlation. Together, our results revealed a CsHEC1-CsOVATE regulatory module that confers fruit neck length variation via CsYUC4 -mediated auxin biosynthesis in cucumber.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2209717119
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
    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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