Browsing by Author "Piasecka, Agnieszka"
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Item Cyclic mismatch binding ligands interact with disease-associated CGG trinucleotide repeats in RNA and suppress their translation(Oxford University Press, 2021) Konieczny, Patryk; Mukherjee, Sanjukta; Stepniak-Konieczna, Ewa; Taylor, Katarzyna; Niewiadomska, Daria; Piasecka, Agnieszka; Walczak, Agnieszka; Baud, Anna; Dohno, Chikara; Nakatani, Kazuhiko; Sobczak, KrzysztofFragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a limited expansion of CGG repeats in the FMR1 gene. Degeneration of neurons in FXTAS cell models can be triggered by accumulation of polyglycine protein (FMRpolyG), a by-product of translation initiated upstream to the repeats. Specific aims of our work included testing if naphthyridine-based molecules could (1) block FMRpolyG synthesis by binding to CGG repeats in RNA, (2) reverse pathological alterations in affected cells and (3) preserve the content of FMRP, translated from the same FMR1 mRNA. We demonstrate that cyclic mismatch binding ligand CMBL4c binds to RNA structure formed by CGG repeats and attenuates translation of FMRpolyG and formation of nuclear inclusions in cells transfected with vectors expressing RNA with expanded CGG repeats. Moreover, our results indicate that CMBL4c delivery can reduce FMRpolyG-mediated cytotoxicity and apoptosis. Importantly, its therapeutic potential is also observed once the inclusions are already formed. We also show that CMBL4c-driven FMRpolyG loss is accompanied by partial FMRP reduction. As complete loss of FMRP induces FXS in children, future experiments should aim at evaluation of CMBL4c therapeutic intervention in differentiated tissues, in which FMRpolyG translation inhibition might outweigh adverse effects related to FMRP depletion.Item Empirical testing of cryoconite granulation: Role of cyanobacteria in the formation of key biogenic structure darkening glaciers in polar regions(Wiley, 2023-08-13) Wejnerowski, Łukasz; Poniecka, Ewa; Buda, Jakub; Klimaszyk, Piotr; Piasecka, Agnieszka; Dziuba, Marcin Krzysztof; Mugnai, Gianmarco; Takeuchi, Nozomu; Zawierucha, KrzysztofCryoconite, the dark sediment on the surface of glaciers, often aggregates into oval or irregular granules serving as biogeochemical factories. They reduce a glacier’s albedo, act as biodiversity hotspots by supporting aerobic and anaerobic microbial communities, constitute one of the organic matter (OM) sources on glaciers and are a feeder for micrometazoans. Although cryoconite granules have multiple roles on glaciers, their formation is poorly understood. Cyanobacteria are ubiquitous and abundant engineers of cryoconite hole ecosystems. This study tested whether cyanobacteria may be responsible for cryoconite granulation as a sole biotic element. Incubation of Greenlandic, Svalbard and Scandinavian cyanobacteria in different nutrient availability and substratum for the growth (distilled water alone, and water with either quartz powder, furnaced cryoconite without OM or powdered rocks from glacial catchment) revealed that cyanobacteria bind mineral particles into granules. The structures formed in the experiment resembled those commonly observed in natural cryoconite holes: they contained numerous cyanobacterial filaments protruding from aggregated mineral particles. Moreover, all examined strains were confirmed to produce extracellular polymeric substances (EPS), which suggest that cryoconite granulation is most likely due to EPS secretion by gliding cyanobacteria. In the presence of water as the only substrate for growth, cyanobacteria formed mostly carpet-like mats. Our data empirically prove that EPS-producing oscillatorialean cyanobacteria isolated from the diverse community of cryoconite microorganisms can form granules from mineral substrate and that the presence of the mineral substrate increases the probability of the formation of these important and complex biogeochemical microstructures on glaciers.