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  • 1
    Online Resource
    Online Resource
    Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 46 ( 2016-11-15), p. 13150-13155
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 46 ( 2016-11-15), p. 13150-13155
    Abstract: Prodigiosin, a natural red pigment produced by numerous bacterial species, has exhibited promising anticancer activity; however, the molecular mechanisms of action of prodigiosin on malignant cells remain unclear. Aberrant activation of the Wnt/β-catenin signaling cascade is associated with numerous human cancers. In this study, we identified prodigiosin as a potent inhibitor of the Wnt/β-catenin pathway. Prodigiosin blocked Wnt/β-catenin signaling by targeting multiple sites of this pathway, including the low-density lipoprotein-receptor-related protein (LRP) 6, Dishevelled (DVL), and glycogen synthase kinase-3β (GSK3β). In breast cancer MDA-MB-231 and MDA-MB-468 cells, nanomolar concentrations of prodigiosin decreased phosphorylation of LRP6, DVL2, and GSK3β and suppressed β-catenin–stimulated Wnt target gene expression, including expression of cyclin D1. In MDA-MB-231 breast cancer xenografts and MMTV-Wnt1 transgenic mice, administration of prodigiosin slowed tumor progression and reduced the expression of phosphorylated LRP6, phosphorylated and unphosphorylated DVL2, Ser9 phosphorylated GSK3β, active β-catenin, and cyclin D1. Through its ability to inhibit Wnt/β-catenin signaling and reduce cyclin D1 levels, prodigiosin could have therapeutic activity in advanced breast cancers.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1616336113
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
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    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    A model of synesthetic metaphor interpretation based on cross-modality similarity
    Elsevier BV ; 2019
    In:  Computer Speech & Language Vol. 58 ( 2019-11), p. 1-16
    Details
    In: Computer Speech & Language, Elsevier BV, Vol. 58 ( 2019-11), p. 1-16
    Type of Medium: Online Resource
    ISSN: 0885-2308
    URL: Article
    DOI: 10.1016/j.csl.2019.03.003
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 1462883-1
    detail.hit.zdb_id: 56461-8
    SSG: 7,11
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  • 3
    Online Resource
    Online Resource
    A Mesoproterozoic iron formation
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 17 ( 2018-04-24)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 17 ( 2018-04-24)
    Abstract: We describe a 1,400 million-year old (Ma) iron formation (IF) from the Xiamaling Formation of the North China Craton. We estimate this IF to have contained at least 520 gigatons of authigenic Fe, comparable in size to many IFs of the Paleoproterozoic Era (2,500–1,600 Ma). Therefore, substantial IFs formed in the time window between 1,800 and 800 Ma, where they are generally believed to have been absent. The Xiamaling IF is of exceptionally low thermal maturity, allowing the preservation of organic biomarkers and an unprecedented view of iron-cycle dynamics during IF emplacement. We identify tetramethyl aryl isoprenoid (TMAI) biomarkers linked to anoxygenic photosynthetic bacteria and thus phototrophic Fe oxidation. Although we cannot rule out other pathways of Fe oxidation, iron and organic matter likely deposited to the sediment in a ratio similar to that expected for anoxygenic photosynthesis. Fe reduction was likely a dominant and efficient pathway of organic matter mineralization, as indicated by organic matter maturation by Rock Eval pyrolysis combined with carbon isotope analyses: Indeed, Fe reduction was seemingly as efficient as oxic respiration. Overall, this Mesoproterozoic-aged IF shows many similarities to Archean-aged ( 〉 2,500 Ma) banded IFs (BIFs), but with an exceptional state of preservation, allowing an unprecedented exploration of Fe-cycle dynamics in IF deposition.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1720529115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    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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  • 4
    Online Resource
    Online Resource
    Sufficient oxygen for animal respiration 1,400 million years ago
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 7 ( 2016-02-16), p. 1731-1736
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 7 ( 2016-02-16), p. 1731-1736
    Abstract: The Mesoproterozoic Eon [1,600–1,000 million years ago (Ma)] is emerging as a key interval in Earth history, with a unique geochemi cal history that might have influenced the course of biological evolution on Earth. Indeed, although this time interval is rather poorly understood, recent chromium isotope results suggest that atmospheric oxygen levels were 〈 0.1% of present levels, sufficiently low to have inhibited the evolution of animal life. In contrast, using a different approach, we explore the distribution and enrichments of redox-sensitive trace metals in the 1,400 Ma sediments of Unit 3 of the Xiamaling Formation, North China Block. Patterns of trace metal enrichments reveal oxygenated bottom waters during deposition of the sediments, and biomarker results demonstrate the presence of green sulfur bacteria in the water column. Thus, we document an ancient oxygen minimum zone. We develop a simple, yet comprehensive, model of marine carbon−oxygen cycle dynamics to show that our geochemical results are consistent with atmospheric oxygen levels 〉 4% of present-day levels. Therefore, in contrast to previous suggestions, we show that there was sufficient oxygen to fuel animal respiration long before the evolution of animals themselves.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1523449113
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
    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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  • 5
    Online Resource
    Online Resource
    A functional SNP of interferon-γ gene is important for interferon-α-induced and spontaneous recovery from hepatitis C virus infection
    Proceedings of the National Academy of Sciences ; 2007
    In:  Proceedings of the National Academy of Sciences Vol. 104, No. 3 ( 2007-01-16), p. 985-990
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 3 ( 2007-01-16), p. 985-990
    Abstract: Cytokine polymorphisms are associated with disease outcome and interferon (IFN) treatment response in hepatitis C virus (HCV) infection. We genotyped eight SNPs spanning the entire IFN-γ gene in two cohorts and assessed the association between those polymorphisms and treatment response or spontaneous viral clearance. The first cohort was composed of 284 chronically HCV-infected patients who had received IFN-α-based therapy and the second was 251 i.v. drug users who had either spontaneously cleared HCV or become chronically infected. A SNP variant located in the proximal IFN-γ promoter region next to the binding motif of heat shock transcription factor (HSF), −764G, was significantly associated with sustained virological response [ P = 0.04, odds ratio (OR) = 3.51 (confidence interval 1.0–12.5)]. The association was independently significant in multiple logistic regression ( P = 0.04) along with race, viral titer, and genotype. This variant was also significantly associated with spontaneous recovery [ P = 0.04, OR = 3.51 (1.0–12.5)] in the second cohort. Functional analyses show that the G allele confers a two- to three-fold higher promoter activity and stronger binding affinity to HSF1 than the C allele. Our study suggests that the IFN-γ promoter SNP −764G/C is functionally important in determining viral clearance and treatment response in HCV-infected patients and may be used as a genetic marker to predict sustained virological response in HCV-infected patients.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0609954104
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2007
    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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