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  1. Article ; Online: Maternally inherited piRNAs direct transient heterochromatin formation at active transposons during early

    Fabry, Martin H / Falconio, Federica A / Joud, Fadwa / Lythgoe, Emily K / Czech, Benjamin / Hannon, Gregory J

    eLife

    2021  Volume 10

    Abstract: The PIWI-interacting RNA (piRNA) pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. ... ...

    Abstract The PIWI-interacting RNA (piRNA) pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. In
    MeSH term(s) Animals ; Chromatin ; DNA Transposable Elements ; Developmental Biology ; Drosophila/embryology ; Drosophila/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/physiology ; Embryonic Development/genetics ; Embryonic Development/physiology ; Epigenomics ; Female ; Gene Expression ; Germ Cells/metabolism ; Heterochromatin/metabolism ; Histones/metabolism ; Male ; Maternal Inheritance/genetics ; Maternal Inheritance/physiology ; RNA, Small Interfering/metabolism
    Chemical Substances Chromatin ; DNA Transposable Elements ; Drosophila Proteins ; Heterochromatin ; Histones ; RNA, Small Interfering
    Language English
    Publishing date 2021-07-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.68573
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Upconversion nanoparticles as intracellular pH messengers

    Tsai, Evaline S / Joud, Fadwa / Wiesholler, Lisa M / Hirsch, Thomas / Hall, Elizabeth A. H

    Analytical and bioanalytical chemistry. 2020 Sept., v. 412, no. 24

    2020  

    Abstract: Upconversion nanoparticles (UCNPs) should be particularly well suited for measurement inside cells because they can be imaged down to submicrometer dimensions in near real time using fluorescence microscopy, and they overcome problems, such as ... ...

    Abstract Upconversion nanoparticles (UCNPs) should be particularly well suited for measurement inside cells because they can be imaged down to submicrometer dimensions in near real time using fluorescence microscopy, and they overcome problems, such as photobleaching, autofluorescence, and deep tissue penetration, that are commonly encountered in cellular imaging applications. In this study, the performance of an UCNP modified with a pH-sensitive dye (pHAb) is studied. The dye (emission wavelength 580 nm) was attached in a polyethylene imine (PEI) coating on the UCNP and excited via the 540-nm UCNP emission under 980-nm excitation. The UC resonance energy transfer efficiencies at different pHs ranged from 25 to 30% and a Förster distance of 2.56 nm was predicted from these results. Human neuroblastoma SH-SY5Y cells, equilibrated with nigericin H⁺/K⁺ ionophore to equalize the intra- and extracellular pH‚ showed uptake of the UCNP-pHAb conjugate particles and, taking the ratio of the intensity collected from the pHAb emission channel (565–630 nm) to that from the UCNP red emission channel (640–680 nm), produced a sigmoidal pH response curve with an apparent pKₐ for the UCNP-pHAb of ~ 5.1. The UCNP-pHAb were shown to colocalize with LysoBrite dye, a lysosome marker. Drug inhibitors such as chlorpromazine (CPZ) and nystatin (NYS) that interfere with clathrin-mediated endocytosis and caveolae-mediated endocytosis, respectively, were investigated to elucidate the mechanism of nanoparticle uptake into the cell. This preliminary study suggests that pH indicator–modified UCNPs such as UCNP-pHAb can report pH in SH-SY5Y cells and that the incorporation of the nanoparticles into the cell occurs via clathrin-mediated endocytosis. Graphical abstract
    Keywords analytical chemistry ; chlorpromazine ; dyes ; endocytosis ; energy transfer ; fluorescence microscopy ; humans ; imines ; lysosomes ; nigericin ; nystatin ; pH ; photobleaching ; polyethylene ; wavelengths
    Language English
    Dates of publication 2020-09
    Size p. 6567-6581.
    Publishing place Springer Berlin Heidelberg
    Document type Article
    Note NAL-AP-2-clean
    ISSN 1618-2642
    DOI 10.1007/s00216-020-02768-5
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Upconversion nanoparticles as intracellular pH messengers.

    Tsai, Evaline S / Joud, Fadwa / Wiesholler, Lisa M / Hirsch, Thomas / Hall, Elizabeth A H

    Analytical and bioanalytical chemistry

    2020  Volume 412, Issue 24, Page(s) 6567–6581

    Abstract: Upconversion nanoparticles (UCNPs) should be particularly well suited for measurement inside cells because they can be imaged down to submicrometer dimensions in near real time using fluorescence microscopy, and they overcome problems, such as ... ...

    Abstract Upconversion nanoparticles (UCNPs) should be particularly well suited for measurement inside cells because they can be imaged down to submicrometer dimensions in near real time using fluorescence microscopy, and they overcome problems, such as photobleaching, autofluorescence, and deep tissue penetration, that are commonly encountered in cellular imaging applications. In this study, the performance of an UCNP modified with a pH-sensitive dye (pHAb) is studied. The dye (emission wavelength 580 nm) was attached in a polyethylene imine (PEI) coating on the UCNP and excited via the 540-nm UCNP emission under 980-nm excitation. The UC resonance energy transfer efficiencies at different pHs ranged from 25 to 30% and a Förster distance of 2.56 nm was predicted from these results. Human neuroblastoma SH-SY5Y cells, equilibrated with nigericin H
    MeSH term(s) Biosensing Techniques/methods ; Cell Line ; Fluorescent Dyes/chemistry ; Humans ; Hydrogen-Ion Concentration ; Microscopy, Fluorescence/methods ; Nanoparticles/chemistry ; Nanoparticles/ultrastructure
    Chemical Substances Fluorescent Dyes
    Language English
    Publishing date 2020-07-02
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 201093-8
    ISSN 1618-2650 ; 0016-1152 ; 0372-7920
    ISSN (online) 1618-2650
    ISSN 0016-1152 ; 0372-7920
    DOI 10.1007/s00216-020-02768-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: FOXC2 promotes vasculogenic mimicry and resistance to anti-angiogenic therapy.

    Cannell, Ian G / Sawicka, Kirsty / Pearsall, Isabella / Wild, Sophia A / Deighton, Lauren / Pearsall, Sarah M / Lerda, Giulia / Joud, Fadwa / Khan, Showkhin / Bruna, Alejandra / Simpson, Kathryn L / Mulvey, Claire M / Nugent, Fiona / Qosaj, Fatime / Bressan, Dario / Dive, Caroline / Caldas, Carlos / Hannon, Gregory J

    Cell reports

    2023  Volume 42, Issue 8, Page(s) 112791

    Abstract: Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood ... ...

    Abstract Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood vessels, and their presence is generally associated with poor patient prognosis. Here we show that the transcription factor, Foxc2, promotes VM in diverse solid tumor types by driving ectopic expression of endothelial genes in tumor cells, a process that is stimulated by hypoxia. VM-proficient tumors are resistant to anti-angiogenic therapy, and suppression of Foxc2 augments response. This work establishes co-option of an embryonic endothelial transcription factor by tumor cells as a key mechanism driving VM proclivity and motivates the search for VM-inhibitory agents that could form the basis of combination therapies with anti-angiogenics.
    MeSH term(s) Humans ; Neovascularization, Pathologic/metabolism ; Cell Line, Tumor ; Immunotherapy
    Language English
    Publishing date 2023-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112791
    Database MEDical Literature Analysis and Retrieval System OnLINE

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