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  1. Article ; Online: 7-Ketocholesterol Promotes Retinal Pigment Epithelium Senescence and Fibrosis of Choroidal Neovascularization via IQGAP1 Phosphorylation-Dependent Signaling

    Haibo Wang / Aniket Ramshekar / Thaonhi Cung / Chris Wallace-Carrete / Chandler Zaugg / Jasmine Nguyen / Gregory J. Stoddard / M. Elizabeth Hartnett

    International Journal of Molecular Sciences, Vol 24, Iss 10276, p

    2023  Volume 10276

    Abstract: Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the ... ...

    Abstract Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, β-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells also developed senescence-associated secretory phenotype (SASP) determined by increased IL-1β, IL-6, and VEGF through mTOR-mediated NF-κB signaling, and reduced barrier integrity that was restored by the mTOR inhibitor, rapamycin. 7KC-induced p21, VEGF, and IL-1β were inhibited by an inhibitor of protein kinase C. The kinase regulates IQGAP1 serine phosphorylation. Furthermore, after 7KC injection and laser-induced injury, mice with an IQGAP1 serine 1441-point mutation had significantly reduced fibrosis compared to littermate control mice. Our results provide evidence that age-related accumulation of 7KC in drusen mediates senescence and SASP in RPE, and IQGAP1 serine phosphorylation is important in causing fibrosis in AMD.
    Keywords retinal pigment epithelium ; cellular senescence ; mammalian target of rapamycin (mTOR) ; macular degeneration ; IQ motif containing GTPase activating protein (IQGAP1) ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 571
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article: Detection and Identification of Fungal Infections in Intact Wheat and Sorghum Grain Using a Hand-Held Raman Spectrometer

    Egging, Veronica / Dmitry Kurouski / Jasmine Nguyen

    Analytical chemistry. 2018 June 13, v. 90, no. 14

    2018  

    Abstract: Global population growth drives increasing food demand, which is anticipated to increase by at least 20% over the next 15 years. Rapid detection and identification of plant pathogens allows for up to a 50% increase in the total agricultural yield ... ...

    Abstract Global population growth drives increasing food demand, which is anticipated to increase by at least 20% over the next 15 years. Rapid detection and identification of plant pathogens allows for up to a 50% increase in the total agricultural yield worldwide. Current molecular methods for pathogen diagnostics, such as polymerase chain reaction (PCR), are costly, time-consuming, and destructive. These limitations recently catalyzed a push toward developing minimally invasive and substrate general techniques that can be used in the field for confirmatory detection and identification of plant pathogens. Raman spectroscopy (RS) is a noninvasive, nondestructive, and label-free technique that can be used to determine chemical structure of analyzed specimens. In this study, we demonstrate that by using a hand-held Raman spectrometer, we can identify whether wheat or sorghum grains are healthy or not and identify present plant pathogens. We show that RS enables diagnosis of simple diseases, such as ergot, that are caused by one pathogen, as well as complex diseases, such as black tip or mold, which are induced by several different pathogens. The combination of chemometric analysis and RS allows for distinguishing between healthy and infected grains with high accuracy. We also show that RS can be used to determine states of disease development on grain. These results demonstrate that Raman-based approach for disease detection on plants is sample agnostic.
    Keywords chemical structure ; chemometrics ; diagnostic techniques ; disease detection ; ergot ; fungi ; plant pathogens ; polymerase chain reaction ; Raman spectroscopy ; rapid methods ; Sorghum bicolor ; spectrometers ; Triticum aestivum ; wheat
    Language English
    Dates of publication 2018-0613
    Size p. 8616-8621.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.8b01863
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Mouse myofibers lacking the SMYD1 methyltransferase are susceptible to atrophy, internalization of nuclei and myofibrillar disarray

    M. David Stewart / Suhujey Lopez / Harika Nagandla / Benjamin Soibam / Ashley Benham / Jasmine Nguyen / Nicolas Valenzuela / Harry J. Wu / Alan R. Burns / Tara L. Rasmussen / Haley O. Tucker / Robert J. Schwartz

    Disease Models & Mechanisms, Vol 9, Iss 3, Pp 347-

    2016  Volume 359

    Abstract: The Smyd1 gene encodes a lysine methyltransferase specifically expressed in striated muscle. Because Smyd1-null mouse embryos die from heart malformation prior to formation of skeletal muscle, we developed a Smyd1 conditional-knockout allele to determine ...

    Abstract The Smyd1 gene encodes a lysine methyltransferase specifically expressed in striated muscle. Because Smyd1-null mouse embryos die from heart malformation prior to formation of skeletal muscle, we developed a Smyd1 conditional-knockout allele to determine the consequence of SMYD1 loss in mammalian skeletal muscle. Ablation of SMYD1 specifically in skeletal myocytes after myofiber differentiation using Myf6cre produced a non-degenerative myopathy. Mutant mice exhibited weakness, myofiber hypotrophy, prevalence of oxidative myofibers, reduction in triad numbers, regional myofibrillar disorganization/breakdown and a high percentage of myofibers with centralized nuclei. Notably, we found broad upregulation of muscle development genes in the absence of regenerating or degenerating myofibers. These data suggest that the afflicted fibers are in a continual state of repair in an attempt to restore damaged myofibrils. Disease severity was greater for males than females. Despite equivalent expression in all fiber types, loss of SMYD1 primarily affected fast-twitch muscle, illustrating fiber-type-specific functions for SMYD1. This work illustrates a crucial role for SMYD1 in skeletal muscle physiology and myofibril integrity.
    Keywords Genetics ; Development ; Muscle ; Myocyte ; SMYD1 ; Methylation ; Myopathy ; Medicine ; R ; Pathology ; RB1-214
    Language English
    Publishing date 2016-03-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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