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Abstract: 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.
Published in DiRROS: 19.07.2024; Views: 2; Downloads: 2
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Abstract: 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.
Keywords: hydrobiology, coastal waters, Gulf of Trieste, chlorophyll-a, Sentinel-3, OLCI, machine learning
Published in DiRROS: 19.07.2024; Views: 6; Downloads: 5
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Abstract: The COST Action ‘European Raptor Biomonitoring Facility’ (ERBFacility) aims to develop pan-European raptor biomonitoring in support of better chemicals management in Europe, using raptors as sentinel species. This presents a significant challenge involving a range of constraints that must be identified and addressed. The aims of this study were to: (1) carry out a comprehensive review of the constraints that may limit the gathering in the field of raptor samples and contextual data, and assess their relative importance across Europe; and (2) identify and discuss possible solutions to the key constraints that were identified. We applied a participatory approach to identify constraints and to discuss feasible solutions. Thirty-one constraints were identified, which were divided into four categories: legal, methodological, spatial coverage, and skills constraints. To assess the importance of the constraints and their possible solutions, we collected information through scientific workshops and by distributing a questionnaire to stakeholders in all the countries involved in ERBFacility. We obtained 74 answers to the questionnaire, from 24 of the 39 COST participating countries. The most important constraints identified were related to the collection of complex contextual data about sources of contamination, and the low number of existing raptor population national/regional monitoring schemes and ecological studies that could provide raptor samples. Legal constraints, such as permits to allow the collection of invasive samples, and skills constraints, such as the lack of expertise to practice necropsies, were also highlighted. Here, we present solutions for all the constraints identified, thus suggesting the feasibility of establishing a long-term European Raptor Sampling Programme as a key element of the planned European Raptor Biomonitoring Facility.
Published in DiRROS: 19.07.2024; Views: 5; Downloads: 4
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Abstract: The surface structures and mucus layers that form an interface between the epithelial layer of organisms and their external environment were studied in the bloom-forming moon jellyfish (Aurelia solida, Scyphozoa) from the northern Adriatic. The surface of the polyps revealed epithelial ciliated cells and numerous nematocysts, both non-discharged and discharged. Cilia were also the most prominent features on the surface of adult medusa, protruding from the epidermal cells and with microvilli surrounding the base. Histochemical methods and various microscopy techniques (light/epifluorescence and electron microscopy) confirmed the presence of abundant mucus around polyps and on the surfaces of adult medusa, and that the mucus contained acidic and neutral mucins. The observed mucus secretions on the exumbrella surface of the medusae were in the form of granules, flocs, and sheets. Scanning electron microscopy and transmission electron microscopy analyses confirmed the presence of various microbes in the mucus samples, but not on the epithelial surfaces of the polyps or the exumbrella of the medusae.
Published in DiRROS: 19.07.2024; Views: 14; Downloads: 6
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Abstract: Background Rosaceae species are economically highly relevant crops. Their cultivation systems are constrained by phytopathogens causing severe losses. Plants respond to invading pathogens through signaling mechanisms, a component of which are of them being plant elicitor peptides (Peps). Exogenous application of Peps activates defense mechanisms and reduces the symptoms of pathogen infection in various pathosystems. We have previously identified the Rosaceae Peps and showed, in an ex vivo system, that their topical application efficiently enhanced resistance to the bacterial pathogen Xanthomonas arboricola pv. pruni (Xap). Results Here we demonstrate the effectiveness of Prunus persica peptides PpPep1 and PpPep2 in protecting peach plants in vivo at nanomolar doses, with 40% reduction of the symptoms following Xap massive infection. We used deep sequencing to characterize the transcriptomic response of peach plants to preventive treatment with PpPep1 and PpPep2. The two peptides induced highly similar massive transcriptomic reprogramming in the plant. One hour, 1 day and 2 days after peptide application there were changes in expression in up to 8% of peach genes. We visualized the transcriptomics dynamics in a background knowledge network and detected the minor variations between plant responses to PpPep1 and PpPep2, which might explain their slightly different protective effects. By designing a P. persica Pep background knowledge network, comparison of our data and previously published immune response datasets was possible. Conclusions Topical application of P. persica Peps mimics the PTI natural response and protects plants against massive Xap infection. This makes them good candidates for deployment of natural, targeted and environmental-friendly strategies to enhance resistance in Prunus species and prevent important biotic diseases.
Published in DiRROS: 19.07.2024; Views: 4; Downloads: 4
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