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Povzetek: Glioblastoma (GB), is the most common and aggressive malignant primary brain tumour in adults. Intra- and inter-tumour heterogeneity, infiltrative GB cell invasion and presence of therapy-resistant GB stem cells (GSCs) represent major obstacles to favourable prognosis and poor therapy response. Identifying the biomarkers of the most aggressive tumour cells and their more efficient targeting strategies are; therefore, crucial. Recently, transcription factor TRIM28 has been identified as a GB biomarker and, in this study, we have shown high expression of TRIM28 in GB and in low grade gliomas as well as higher expression in GSCs vs. differentiated GB cells, although in both cases not significant. We demonstrated significant in vitro inhibition of GB cells and GSCs invasiveness and spread in zebrafish brains in vivo by anti-TRIM28 selective nanobody NB237. TRIM28 was also enriched in GB (tumour) core and associated with the expression of stem cell genes, but was not prognostic for overall survival. However, based on the above results, we conclude that TRIM28 nanobody NB237 offers a new opportunity as a GB therapeutic tool.
Objavljeno v DiRROS: 19.07.2024; Ogledov: 317; Prenosov: 224
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Povzetek: Chitosan (Chi) and 77KS, a lysine-derived surfactant, form polyelectrolyte complexes that reverse their charge from positive to negative at higher 77KS concentrations, forming aggregates that have been embedded with amoxicillin (AMOX). Dispersion of this complex was used to coat polydimethylsiloxane (PDMS) films, with an additional layer of anionic and hydrophilic hyaluronic acid (HA) as an outer adsorbate layer to enhance protein repulsion in addition to antimicrobial activity by forming a highly hydrated layer in combination with steric hindrance. The formed polysaccharide-based bilayer on PDMS was analyzed by water contact angle measurements, X-ray photoelectron spectroscopy (XPS), and surface zeta (ζ)-potential. All measurements show the existence and adhesion of the two layers on the PDMS surface. Part of this study was devoted to understanding the underlying protein adsorption phenomena and identifying the mechanisms associated with biofouling. Thus, the adsorption of a mixed-protein solution (bovine serum albumin, fibrinogen, γ-globulin) on PDMS surfaces was studied to test the antifouling properties. The adsorption experiments were performed using a quartz crystal microbalance with dissipation monitoring (QCM-D) and showed improved antifouling properties by these polysaccharide-based bilayer coatings compared to a reference or for only one layer, i.e., the complex. This proves the benefit of a second hyaluronic acid layer. Microbiological and biocompatibility tests were also performed on real samples, i.e., silicone discs, showing the perspective of the prepared bilayer coating for medical devices such as prostheses, catheters (balloon angioplasty, intravascular), delivery systems (sheaths, implants), and stents.
Ključne besede: polysaccharides, chitosan, hyaluronic acid, anti-biofilm, silicone
Objavljeno v DiRROS: 19.07.2024; Ogledov: 500; Prenosov: 230
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Povzetek: Abstract In this study, we conducted and documented workshops and interviews in Norway and Slovenia to identify stakeholder and future generation opinions and mitigation strategies for solving one of the most prominent environmental issues: plastic pollution. As part of the EU H2020 project GoJelly, stakeholders were brought together to explore their perceptions on considering jellyfish mucus as a new resource to contribute to reducing plastic pollution from entering the marine environment. The study was conducted in the spring of 2019, in a context directly after the European Union (EU) announced its Directive to ban the most commonly used single-use plastic (SUP) items. The study applied the snowball method as a methodological choice to identify relevant stakeholders. Systems thinking was utilized as a participatory modelling approach, which allowed for the creation of conceptual mind maps from the various workshops and interviews, to understand consumers’ consciousness, and to map out ideas on plastic pollution reduction. Plastic pollution takes place on a global scale and stakeholders discussed their individual perceptions of national and international solutions that could be put in place to solve it, including the opportunities around utilizing jellyfish mucus to filter and capture micro- and nanoplastic. We found that industry stakeholders in both case areas were generally more accepting of policy and increased innovation moving forward, but placed weight on the scientific community to conduct more research on the pollution issue and propose solutions. Future generation stakeholders (youth aged 14–18), however, put emphasis on consumer behavior and buying patterns of single-use products fueling the plastic crisis.
Ključne besede: ecology, plastics, single-use plastic, stakeholder integration, plastic pollution, systems thinking
Objavljeno v DiRROS: 19.07.2024; Ogledov: 418; Prenosov: 217
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Povzetek: Activating RAS missense mutations are among the most prevalent genomic alterations observed in human cancers and drive oncogenesis in the three most lethal tumor types. Emerging evidence suggests mutant KRAS (mKRAS) may be targeted immunologically, but mKRAS epitopes remain poorly defined. Here we employ a multi-omics approach to characterize HLA class I-restricted mKRAS epitopes. We provide proteomic evidence of mKRAS epitope processing and presentation by high prevalence HLA class I alleles. Select epitopes are immunogenic enabling mKRAS-specific TCRαβ isolation. TCR transfer to primary CD8+ T cells confers cytotoxicity against mKRAS tumor cell lines independent of histologic origin, and the kinetics of lytic activity correlates with mKRAS peptide-HLA class I complex abundance. Adoptive transfer of mKRAS-TCR engineered CD8+ T cells leads to tumor eradication in a xenograft model of metastatic lung cancer. This study validates mKRAS peptides as bona fide epitopes facilitating the development of immune therapies targeting this oncoprotein.
Objavljeno v DiRROS: 19.07.2024; Ogledov: 319; Prenosov: 213
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Povzetek: While satellite remote sensing of ocean color is a viable tool for estimating large-scale patterns of chlorophyll-a (Chl-a) and global ocean primary production, its application in coastal waters is limited by the complex optical properties. An exploratory study was conducted in the Gulf of Trieste (Adriatic Sea) to assess the usefulness of Sentinel-3 satellite data in the Slovenian national waters. OLCI (Ocean and Land Colour Instrument) Chl-a level 2 products (OC4Me and NN) were compared to monthly Chl-a in-situ measurements at fixed sites from 2017 to 2019. In addition, eight other methods for estimating Chl-a concentration based on reflectance in different spectral bands were tested (OC3M, OC4E, MedOC4, ADOC4, AD4, 3B-OLCI, 2B-OLCI and G2B). For some of these methods, calibration was performed on in-situ data to achieve a better agreement. Finally, L1-regularized regression and random forest were trained on the available dataset to test the capabilities of the machine learning approach. The results show rather poor performance of the two originally available products. The same is true for the other eight methods and the fits to the measured values also show only marginal improvement. The best results are obtained with the blue-green methods (OC3, OC4 and AD4), especially the AD4SI (a designated fit of AD4) with R = 0.56 and RMSE = 0.4 mg/m³, while the near infrared (NIR) methods show underwhelming performance. The machine learning approach can only explain 30% of the variability and the RMSE is of the same order as for the blue-green methods. We conclude that due to the low Chl-a concentration and the moderate turbidity of the seawater, the reflectance provided by the Sentinel-3 OLCI spectrometer carries little information about Chl-a in the Slovenian national waters within the Gulf of Trieste and is therefore of limited use for our purposes. This requires that we continue to improve satellite products for use in those marine waters that have not yet proven suitable. In this way, satellite data could be effectively integrated into a comprehensive network that would allow a reliable assessment of ecological status, taking into account environmental regulations.
Ključne besede: hydrobiology, coastal waters, Gulf of Trieste, chlorophyll-a, Sentinel-3, OLCI, machine learning
Objavljeno v DiRROS: 19.07.2024; Ogledov: 384; Prenosov: 697
Celotno besedilo (5,77 MB)
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