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  1. Article ; Online: Exacerbating and reversing lysosomal storage diseases

    Tamayanthi Rajakumar / Andrew B. Munkacsi / Stephen L. Sturley

    Microbial Cell, Vol 4, Iss 9, Pp 278-

    from yeast to humans

    2017  Volume 293

    Abstract: Lysosomal storage diseases (LSDs) arise from monogenic deficiencies in lysosomal proteins and pathways and are characterized by a tissue-wide accumulation of a vast variety of macromolecules, normally specific to each genetic lesion. Strategies for ... ...

    Abstract Lysosomal storage diseases (LSDs) arise from monogenic deficiencies in lysosomal proteins and pathways and are characterized by a tissue-wide accumulation of a vast variety of macromolecules, normally specific to each genetic lesion. Strategies for treatment of LSDs commonly depend on reduction of the offending metabolite(s) by substrate depletion or enzyme replacement. However, at least 44 of the ~50 LSDs are currently recalcitrant to intervention. Murine models have provided significant insights into our understanding of many LSD mechanisms; however, these systems do not readily permit phenotypic screening of compound libraries, or the establish-ment of genetic or gene-environment interaction networks. Many of the genes causing LSDs are evolutionarily conserved, thus facilitating the application of models system to provide additional insight into LSDs. Here, we review the utility of yeast models of 3 LSDs: Batten disease, cystinosis, and Niemann-Pick type C disease. We will focus on the translation of research from yeast models into human patients suffering from these LSDs. We will also discuss the use of yeast models to investigate the penetrance of LSDs, such as Niemann-Pick type C disease, into more prevalent syndromes including viral infection and obesity.
    Keywords lysosomal storage disease ; Niemann Pick Type-C disease ; gene modifier ; exacerbate-reverse ; yeast ; HIV ; Ebola ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2017-08-01T00:00:00Z
    Publisher Shared Science Publishers OG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Publisher Correction

    Bede P. Busby / Eliatan Niktab / Christina A. Roberts / Jeffrey P. Sheridan / Namal V. Coorey / Dinindu S. Senanayake / Lisa M. Connor / Andrew B. Munkacsi / Paul H. Atkinson

    npj Systems Biology and Applications, Vol 6, Iss 1, Pp 1-

    Genetic interaction networks mediate individual statin drug response in Saccharomyces cerevisiae

    2020  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Genetic interaction networks mediate individual statin drug response in Saccharomyces cerevisiae

    Bede P. Busby / Eliatan Niktab / Christina A. Roberts / Jeffrey P. Sheridan / Namal V. Coorey / Dinindu S. Senanayake / Lisa M. Connor / Andrew B. Munkacsi / Paul H. Atkinson

    npj Systems Biology and Applications, Vol 5, Iss 1, Pp 1-

    2019  Volume 13

    Abstract: Genetic interaction networks underlie statin efficacy Genes are wired together in functional genetic interaction networks (GINs) specific for different traits. We asked a simple question: do GINs for particular traits vary with individuals? The trait we ... ...

    Abstract Genetic interaction networks underlie statin efficacy Genes are wired together in functional genetic interaction networks (GINs) specific for different traits. We asked a simple question: do GINs for particular traits vary with individuals? The trait we investigated was response to statins, cholesterol-lowering drugs prescribed to 30 million people worldwide. Building comprehensive GINs requires a library of cells with a different gene deleted covering the entire genome that is available only in Saccharomyces cerevisiae (Baker’s yeast), a well-defined model for human genetics. However, the yeast libraries being limited to one genetic background are not informative of individuals. Therefore, we constructed GINs in additional genetic backgrounds and showed statin-specific GINs were not conserved, albeit there was a common fundamental process mediating statin-resistance. Our results identify a mechanism to further investigate in the millions of people that do not respond to statins and the methodology will enhance the discovery and development of drugs to treat other major diseases.
    Keywords Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Bioactivity-Guided Metabolite Profiling of Feijoa (Acca sellowiana) Cultivars Identifies 4-Cyclopentene-1,3-dione as a Potent Antifungal Inhibitor of Chitin Synthesis

    Mokhtari, Mona / Alistair S. Brown / Andrew B. Munkacsi / David F. Ackerley / Michael D. Jackson / Nigel J. Ritson / Robert A. Keyzers

    Journal of agricultural and food chemistry. 2018 Mar. 16, v. 66, no. 22

    2018  

    Abstract: Pathogenic fungi continue to develop resistance against current antifungal drugs. To explore the potential of agricultural waste products as a source of novel antifungal compounds, we obtained an unbiased GC-MS profile of 151 compounds from 16 commercial ...

    Abstract Pathogenic fungi continue to develop resistance against current antifungal drugs. To explore the potential of agricultural waste products as a source of novel antifungal compounds, we obtained an unbiased GC-MS profile of 151 compounds from 16 commercial and experimental cultivars of feijoa peels. Multivariate analysis correlated 93% of the compound profiles with antifungal bioactivities. Of the 18 compounds that significantly correlated with antifungal activity, 5 had not previously been described from feijoa. Two novel cultivars were the most bioactive, and the compound 4-cyclopentene-1,3-dione, detected in these cultivars, was potently antifungal (IC50 = 1–2 μM) against human-pathogenic Candida species. Haploinsufficiency and fluorescence microscopy analyses determined that the synthesis of chitin, a fungal-cell-wall polysaccharide, was the target of 4-cyclopentene-1,3-dione. This fungal-specific mechanism was consistent with a 22–70-fold reduction in antibacterial activity. Overall, we identified the agricultural waste product of specific cultivars of feijoa peels as a source of potential high-value antifungal compounds.
    Keywords Acca sellowiana ; agricultural wastes ; antibacterial properties ; antifungal agents ; antifungal properties ; Candida ; chitin ; cultivars ; fluorescence microscopy ; fungi ; gas chromatography-mass spectrometry ; inhibitory concentration 50 ; metabolites ; multivariate analysis
    Language English
    Dates of publication 2018-0316
    Size p. 5531-5539.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 241619-0
    ISSN 1520-5118 ; 0021-8561
    ISSN (online) 1520-5118
    ISSN 0021-8561
    DOI 10.1021/acs.jafc.7b06154
    Database NAL-Catalogue (AGRICOLA)

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