يعرض 1 - 10 نتائج من 1,253 نتيجة بحث عن '"Ramakrishnan"', وقت الاستعلام: 0.99s تنقيح النتائج
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    دورية أكاديمية

    الوصف: We have designed and developed novel and selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay. In vitro , these agonists significantly induced secretion of cytokines IL-6, IL-1β, IL-10, TNFa, IFNa, and IP-10 in human and mouse whole blood. Pharmacokinetic and pharmacodynamic studies in mice showed a significant secretion of IFNα and TNFα cytokines. When combined with aPD1 in a CT-26 tumor model, the lead compound showed strong synergistic antitumor activity with complete tumor regression in 8/10 mice dosed using the intravenous route. Structure–activity relationship studies enabled by structure-based designs of TLR7 agonists are disclosed.

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    دورية أكاديمية

    المصدر: Ramakrishnan, Chandra; Fort, Cécile; Marques, Sara Rute; Ferguson, David J P; Gransagne, Marion; Baum, Jake; Chaouch, Soraya; Mouray, Elisabeth; Kohl, Linda; Wheeler, Richard J; Sinden, Robert E (2023). Radial spoke protein 9 is necessary for axoneme assembly in Plasmodium but not in trypanosomatid parasites. Journal of Cell Science, 136(11):jcs260655.

    الوصف: Flagella are important for eukaryote cell motility, including in sperm, and are vital for life cycle progression of many unicellular eukaryotic pathogens. The ‘9+2’ axoneme in most motile flagella comprises nine outer doublet and two central-pair singlet microtubules. T-shaped radial spokes protrude from the outer doublets towards the central pair and are necessary for effective beating. We asked whether there were radial spoke adaptations associated with parasite lineage-specific properties in apicomplexans and trypanosomatids. Following an orthologue search for experimentally uncharacterised radial spoke proteins (RSPs), we identified and analysed RSP9. Trypanosoma brucei and Leishmania mexicana have an extensive RSP complement, including two divergent RSP9 orthologues, necessary for flagellar beating and swimming. Detailed structural analysis showed that neither orthologue is needed for axoneme assembly in Leishmania. In contrast, Plasmodium has a reduced set of RSPs including a single RSP9 orthologue, deletion of which in Plasmodium berghei leads to failure of axoneme formation, failed male gamete release, greatly reduced fertilisation and inefficient life cycle progression in the mosquito. This indicates contrasting selection pressures on axoneme complexity, likely linked to the different mode of assembly of trypanosomatid versus Plasmodium flagella.

    وصف الملف: application/pdf

    العلاقة: https://www.zora.uzh.ch/id/eprint/255353/1/Radial_spoke_protein_9_is_necessary.pdfTest; info:pmid/37288670; urn:issn:0021-9533

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    دورية أكاديمية
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    دورية أكاديمية
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    دورية أكاديمية
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    دورية أكاديمية
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