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Thanathom Chailangkarn Nathiphat Tanwattana Thanakorn Jaemthaworn Sira Sriswasdi Nanchaya Wanasen Sithichoke Tangphatsornruang Kantinan Leetanasaksakul Yuparat Jantraphakorn Wanapinun Nawae Penpicha Chankeeree Porntippa Lekcharoensuk Boonlert Lumlertdacha Challika Kaewborisuth 《International journal of molecular sciences》2021,22(21)
Rabies is a deadly viral disease caused by the rabies virus (RABV), transmitted through a bite of an infected host, resulting in irreversible neurological symptoms and a 100% fatality rate in humans. Despite many aspects describing rabies neuropathogenesis, numerous hypotheses remain unanswered and concealed. Observations obtained from infected primary neurons or mouse brain samples are more relevant to human clinical rabies than permissive cell lines; however, limitations regarding the ethical issue and sample accessibility become a hurdle for discovering new insights into virus–host interplays. To better understand RABV pathogenesis in humans, we generated human-induced pluripotent stem cell (hiPSC)-derived neurons to offer the opportunity for an inimitable study of RABV infection at a molecular level in a pathologically relevant cell type. This study describes the characteristics and detailed proteomic changes of hiPSC-derived neurons in response to RABV infection using LC-MS/MS quantitative analysis. Gene ontology (GO) enrichment of differentially expressed proteins (DEPs) reveals temporal changes of proteins related to metabolic process, immune response, neurotransmitter transport/synaptic vesicle cycle, cytoskeleton organization, and cell stress response, demonstrating fundamental underlying mechanisms of neuropathogenesis in a time-course dependence. Lastly, we highlighted plausible functions of heat shock cognate protein 70 (HSC70 or HSPA8) that might play a pivotal role in regulating RABV replication and pathogenesis. Our findings acquired from this hiPSC-derived neuron platform help to define novel cellular mechanisms during RABV infection, which could be applicable to further studies to widen views of RABV-host interaction. 相似文献
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Many organizations have employed the concepts of ‘asset specificity’ and ‘uncertainty’ from transaction cost theory (TCT), and ‘strategic resources’ from the resource-based view (RBV) as drivers of their information systems (ISs) sourcing decisions. They, however, face a dilemma when TCT and the RBV suggest different sourcing alternatives. The study identifies contexts where sourcing decisions made based on these two theories differ, and examines which theory accounts better for an organization's sourcing decisions. Results show that a high-specificity asset is a major driver of sourcing decisions. It overpowers the effects of uncertainty on sourcing decisions; while a non-strategic resource has no impact on sourcing decisions. In particular, where the two theories make conflicting predictions, organizations should not always outsource non-strategic resources. Non-strategic resources that involve high specificity should be retained internally. The paper concludes with implications for academics and practitioners, and a discussion of future research directions. 相似文献
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