1121. Long-term post-event processes and major reactivation of a complex landslide: 2000–2023 evolution of the Ciprnik landslide, Julian Alps, SloveniaAndrej Novak, Marko Vrabec, Andrej Šmuc, 2025, izvirni znanstveni članek Povzetek: The Ciprnik complex landslide in the Planica valley (NW Slovenia) happened on 19. 11. 2000 as a translation slip-debris flow-hyperconcentrated flow event. It was triggered by a combination of the local geological structure (highly fractured beds dipping parallel to the surface), lithology (alternation of thin bedded carbonates and fine-grained clastics), and record-breaking monthly rainfall (613.6 mm in the month of the event). Twenty-three years later, on the night from 24. to 25. 10. 2023, large parts of the landslide reactivated during intense short-duration rainfall, which has a relatively common occurrence (104.2 mm in 24 h). We use 2006–2023 time series of photogrammetrically derived digital elevation models generated from aerial photographs and unmanned aerial vehicle surveys, sedimentological analysis, and meteorological data to (1) analyze decade-scale post-event processes on the Ciprnik landslide following the initial sliding event in November 2000 and (2) to study the October 2023 event and compare it to the November 2000 event. We find that after the initial November 2000 event, the area of the Ciprnik landslide remained unstable with an average annual erosion rate of 1000 to 3500 m3 of sediment. The 2023 event measured 26,000 m3 and, despite a different triggering rainfall, again occurred as a translation slip-debris flow-hyperconcentrated flow event exhibiting a strong fining down of sediment (from muddy-sandy-gravel to sandy-silt). This study demonstrates the complexity of triggering thresholds in the aftermath of the main mass movement event. Even in the later events, which have the same transport mechanisms as the original event, the triggering precipitation can differ considerably in duration and magnitude.
Ključne besede: complex landslide, translational slip, debris flow, hyperconcentrated flow, UAV, granulometry
Objavljeno v DiRROS: 04.09.2025; Ogledov: 133; Prenosov: 91
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1122. Different glycosylation profiles of cystatin F alter the cytotoxic potential of natural killer cellsEmanuela Senjor, Martina Pirro, Urban Švajger, Mateja Prunk, Jerica Sabotič, Anahid Jewett, Paul J. Hensbergen, Milica Perišić, Janko Kos, 2024, izvirni znanstveni članek Povzetek: Cystatin F, a cysteine peptidase inhibitor, is a potent modulator of NK cytotoxicity. By inhibiting granule-mediated cytotoxicity pathway, cystatin F induces formation of non-functional NK cell stage, called split-anergy. We show that N-glycosylation determines the localization and cellular function of cystatin F. Cystatin F mostly exhibited high-mannose glycosylation in U-937 cells, both high-mannose and complex glycosylation in NK-92 and primary NKs, and predominantly complex glycosylation in super-charged NKs. Manipulating N-glycosylation with kifunensine increased high-mannose glycosylation of cystatin F and lysosome localisation, which decreased cathepsin C activity and reduced NK cytotoxicity. Mannose-6-phosphate could significantly reduce the internalization of extracellular cystatin F. By comparing NK cells with different cytotoxic potentials, we found that high-mannose cystatin F was strongly associated with lysosomes and cathepsin C in NK-92 cell line. In contrast, in highly cytotoxic super-charged NKs, cystatin F with complex glycosylation was associated with the secretory pathway and less prone to inhibit cathepsin C. Modulating glycosylation to alter cystatin F localisation could increase the cytotoxicity of NK cells, thereby enhancing their therapeutic potential for treating cancer patients.
Ključne besede: cystatin F, immunosuppression, NK cells, N-Glycosylation
Objavljeno v DiRROS: 04.09.2025; Ogledov: 303; Prenosov: 86
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1123. Cysteine cathepsins as therapeutic targets in immune regulation and immune disordersEmanuela Senjor, Janko Kos, Milica Perišić, 2023, pregledni znanstveni članek Povzetek: Cysteine cathepsins, as the most abundant proteases found in the lysosomes, play a vital role in several processes—such as protein degradation, changes in cell signaling, cell morphology, migration and proliferation, and energy metabolism. In addition to their lysosomal function, they are also secreted and may remain functional in the extracellular space. Upregulation of cathepsin expression is associated with several pathological conditions including cancer, neurodegeneration, and immune-system dysregulation. In this review, we present an overview of cysteine-cathepsin involvement and possible targeting options for mitigation of aberrant function in immune disorders such as inflammation, autoimmune diseases, and immune response in cancer.
Ključne besede: cysteine cathepsins, inflammation, autoimmune diseases, cancer
Objavljeno v DiRROS: 04.09.2025; Ogledov: 366; Prenosov: 174
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1124. New inhibitors of cathepsin V impair tumor cell proliferation and elastin degradation and increase immune cell cytotoxicityAna Mitrović, Emanuela Senjor, Marko Jukič, Lara Bolčina, Mateja Prunk, Matic Proj, Milica Perišić, Stanislav Gobec, Janko Kos, 2022, izvirni znanstveni članek Povzetek: Cathepsin V is a human lysosomal cysteine peptidase with specific functions during pathological processes and is as such a promising therapeutic target. Peptidase inhibitors represent powerful pharmacological tools for regulating excessive proteolytic activity in various diseases. Cathepsin V is highly related to cathepsin L but differs in tissue distribution, binding site morphology, substrate specificity, and function. To validate its therapeutic potential and extend the number of potent and selective cathepsin V inhibitors, we used virtual high-throughput screening of commercially available compound libraries followed by an evaluation of kinetic properties to identify novel potent and selective cathepsin V inhibitors. We identified the ureido methylpiperidine carboxylate derivative, compound 7, as a reversible, selective, and potent inhibitor of cathepsin V. It also exhibited the most preferable characteristics for further evaluation with in vitro functional assays that simulate the processes in which cathepsin V is known to play an important role. Compound 7 exerted significant effects on cell proliferation, elastin degradation, and immune cell cytotoxicity. The latter was increased because compound 7 impaired conversion of immunosuppressive factor cystatin F to its active monomeric form. Taken together, our results present novel potent inhibitors of cathepsin V and provide new hit compounds for detailed development and optimization. Further, we demonstrate that cathepsin V is a potential target for new approaches to cancer therapy.
Objavljeno v DiRROS: 04.09.2025; Ogledov: 264; Prenosov: 173
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1127. Cysteine cathepsins as regulators of the cytotoxicity of NK and T cellsMilica Perišić, Jerica Sabotič, Anahid Jewett, Janko Kos, 2014, pregledni znanstveni članek Povzetek: Cysteine cathepsins are lysosomal peptidases involved at different levels in the processes of the innate and adaptive immune responses. Some, such as cathepsins B, L, and H are expressed constitutively in most immune cells. In cells of innate immunity they play a role in cell adhesion and phagocytosis. Other cysteine cathepsins are expressed more specifically. Cathepsin X promotes dendritic cell maturation, adhesion of macrophages, and migration of T cells. Cathepsin S is implicated in major histocompatibility complex class II antigen presentation, whereas cathepsin C, expressed in cytotoxic T lymphocytes and natural killer (NK) cells, is involved in processing pro-granzymes into proteolytically active forms, which trigger cell death in their target cells. The activity of cysteine cathepsins is controlled by endogenous cystatins, cysteine protease inhibitors. Of these, cystatin F is the only cystatin that is localized in endosomal/lysosomal vesicles. After proteolytic removal of its N-terminal peptide, cystatin F becomes a potent inhibitor of cathepsin C with the potential to regulate pro-granzyme processing and cell cytotoxicity. This review is focused on the role of cysteine cathepsins and their inhibitors in the molecular mechanisms leading to the cytotoxic activity of T lymphocytes and NK cells in order to address new possibilities for regulation of their function in pathological processes.
Objavljeno v DiRROS: 04.09.2025; Ogledov: 278; Prenosov: 197
Celotno besedilo (5,16 MB)
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1130. Zdravljenje raka prostate : kdaj obsevanjeBorut Kragelj, 2019, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: rak prostate, kirurško zdravljenje, radioterapija, obsevanje
Objavljeno v DiRROS: 03.09.2025; Ogledov: 355; Prenosov: 88
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