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  • 1
    Online Resource
    Online Resource
    Cell Type-Dependent RNA Recombination Frequency in the Japanese Encephalitis Virus
    Hindawi Limited ; 2014
    In:  BioMed Research International Vol. 2014 ( 2014), p. 1-9
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2014 ( 2014), p. 1-9
    Abstract: Japanese encephalitis virus (JEV) is one of approximately 70 flaviviruses, frequently causing symptoms involving the central nervous system. Mutations of its genomic RNA frequently occur during viral replication, which is believed to be a force contributing to viral evolution. Nevertheless, accumulating evidences show that some JEV strains may have actually arisen from RNA recombination between genetically different populations of the virus. We have demonstrated that RNA recombination in JEV occurs unequally in different cell types. In the present study, viral RNA fragments transfected into as well as viral RNAs synthesized in mosquito cells were shown not to be stable, especially in the early phase of infection possibly via cleavage by exoribonuclease. Such cleaved small RNA fragments may be further degraded through an RNA interference pathway triggered by viral double-stranded RNA during replication in mosquito cells, resulting in a lower frequency of RNA recombination in mosquito cells compared to that which occurs in mammalian cells. In fact, adjustment of viral RNA to an appropriately lower level in mosquito cells prevents overgrowth of the virus and is beneficial for cells to survive the infection. Our findings may also account for the slower evolution of arboviruses as reported previously.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2014/471323
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2014
    detail.hit.zdb_id: 2698540-8
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  • 2
    Online Resource
    Online Resource
    Cell-to-Cell Spread of Dengue Viral RNA in Mosquito Cells
    Hindawi Limited ; 2020
    In:  BioMed Research International Vol. 2020 ( 2020-06-26), p. 1-9
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2020 ( 2020-06-26), p. 1-9
    Abstract: Dengue virus (DENV) is an important mosquito-borne arbovirus that is particularly prevalent in tropical and subtropical areas of the world. The virus is generally ingested with a blood meal, replicates in host tissues, and disseminates into salivary glands for transmission to the next host. Membrane-bound vacuoles carrying DENV particles have been documented in mosquito cells and play a role in the cell-to-cell transmission of DENV2. C189 is one member of the tetraspanin family and generally increases its expression as one component of the vacuoles (C189-VCs) within C6/36 cells infected with DENV2. In the present study, we have further demonstrated via sucrose gradient centrifugation as well as magnetic immune isolation (MI) that the RNA of DENV2 was eventually carried by C189-VCs. In addition, viral RNA was shown to spread from donor to recipient cells in a coculture assay even when 20 mM NH 4 Cl was added to inhibit virus replication in the culture. In an alternate assay using the transwell system, viral RNA was only detected in recipient cells in the absence of 40 mM NH 4 Cl, suggesting that cell-cell contact is required for the intercellular spread of DENV2. In turn, the formation of viral synapse (VS) derived from aggregates of viral particles was frequently observed at sites of cell contact. Taken together, the formation of C189-VCs in C6/36 cells is induced by DENV2 infection, which may serve as a vehicle for transferring virions and also viral RNA to neighboring cells by cell-to-cell transmission after cell-cell contact. This finding provides insight into the understanding of viral spread between mosquito cells. It may also elucidate the benign persistent infection in mosquito cells and efficient dissemination of DENV infection within a mosquito vector.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2020/2452409
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2698540-8
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  • 3
    Online Resource
    Online Resource
    XBP1-Mediated BiP/GRP78 Upregulation Copes with Oxidative Stress in Mosquito Cells during Dengue 2 Virus Infection
    Hindawi Limited ; 2017
    In:  BioMed Research International Vol. 2017 ( 2017), p. 1-14
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2017 ( 2017), p. 1-14
    Abstract: Dengue viruses (DENVs) cause dengue fever which is an important mosquito-borne disease in tropical areas. Generally, DENV does not cause cellular damage in mosquito cells. However, alterations in cytosolic calcium ions ([Ca 2+ ]cyt) and the mitochondrial membrane potential (MMP), as well as accumulated reactive oxygen species (ROS), including superoxide anions ( O 2 ∙ - ) and hydrogen peroxide (H 2 O 2 ), can be detected in C6/36 cells with DENV2 infection. Evident upregulation of BiP/GRP78 also appeared at 24 h postinfection in DENV2-infected C6/36 cells. As expression of BiP/GRP78 mRNA was reduced when the transcription factor X-box-binding protein-1 (XBP1) was knocked down in C6/36 cells, it demonstrated that BiP/GRP78 is the target gene regulated by the XBP1 signal pathway. We further demonstrated that the expression and splicing activity of XBP1 were upregulated in parallel with DENV2 infection in C6/36 cells. In C6/36 cells with BiP/GRP78 overexpression, oxidative stress indicators including [Ca 2+ ]cyt, MMP, O 2 ∙ - , and H 2 O 2 were all pushed back to normal. Taken together, DENV2 activates XBP1 at earlier stage of infection, followed by upregulating BiP/GRP78 in mosquito cells. This regulatory pathway contributes a cascade in relation to oxidative stress alleviation. The finding provides insights into elucidating how mosquitoes can healthily serve as a vector of arboviruses in nature.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2017/3519158
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2698540-8
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  • 4
    Online Resource
    Online Resource
    Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane
    Hindawi Limited ; 2012
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2012 ( 2012), p. 1-13
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2012 ( 2012), p. 1-13
    Abstract: We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential ( Δ Ψ m ) . Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    URL: Article
    DOI: 10.1155/2012/415231
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2148302-4
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  • 5
    Online Resource
    Online Resource
    Estrogen-Related Receptor Alpha Confers Methotrexate Resistance via Attenuation of Reactive Oxygen Species Production and P53 Mediated Apoptosis in Osteosarcoma Cells
    Hindawi Limited ; 2014
    In:  BioMed Research International Vol. 2014 ( 2014), p. 1-9
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2014 ( 2014), p. 1-9
    Abstract: Osteosarcoma (OS) is a malignant tumor mainly occurring in children and adolescents. Methotrexate (MTX), a chemotherapy agent, is widely used in treating OS. However, treatment failures are common due to acquired chemoresistance, for which the underlying molecular mechanisms are still unclear. In this study, we report that overexpression of estrogen-related receptor alpha (ERR α ), an orphan nuclear receptor, promoted cell survival and blocked MTX-induced cell death in U2OS cells. We showed that MTX induced ROS production in MTX-sensitive U2OS cells while ERR α effectively blocked the ROS production and ROS associated cell apoptosis. Our further studies demonstrated that ERR α suppressed ROS induction of tumor suppressor P53 and its target genes NOXA and XAF1 which are mediators of P53-dependent apoptosis. In conclusion, this study demonstrated that ERR α plays an important role in the development of MTX resistance through blocking MTX-induced ROS production and attenuating the activation of p53 mediated apoptosis signaling pathway, and points to ERR α as a novel target for improving osteosarcoma therapy.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2014/616025
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2014
    detail.hit.zdb_id: 2698540-8
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