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Povzetek: We consider a multiphase spectral problem on a stratified Lie group.We prove the existence of an eigenfunction of $(2, q)$-eigenvalue problem on a bounded domain. Furthermore, we also establish a Pohozaev-like identity corresponding to the problem on the Heisenberg group.
Ključne besede: multiphase spectral problem, stratified Lie group, Heisenberg group, left invariant vector field, (2, q)-eigenvalue problem
Objavljeno v DiRROS: 15.11.2024; Ogledov: 30; Prenosov: 13
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Povzetek: The rapid development of new chemicals and consumer products has raised concerns about their potential genotoxic effects on human health, including DNA damage leading to serious diseases. For such new chemicals and pharmaceutical products, international regulations require genotoxicity data, initially obtained through in vitro tests, followed by in vivo experiments, if needed. Traditionally, laboratory animals have been used for this purpose, however, they are costly, ethically problematic, and often unreliable due to species differences. Therefore, innovative more accurate in vitro testing approaches are rapidly being developed to replace, refine and reduce (3R) the use of animals for experimental purposes and to improve the relevance for humans in toxicology studies. One of such innovative approaches are in vitro three-dimensional (3D) cell models, which are already being highlighted as superior alternatives to the two-dimensional (2D) cell cultures that are traditionally used as in vitro models for the safety testing of chemicals and pharmaceuticals. 3D cell models provide physiologically relevant information and more predictive data for in vivo conditions. In the review article, we provide a comprehensive overview of 3D hepatic cell models, including HepG2, HepG2/C3A, HepaRG, human primary hepatocytes, and iPSC-derived hepatocytes, and their application in the field of genotoxicology. Through a detailed literature analysis, we identified 31 studies conducted between 2007 and April 2024 that used a variety of standard methods, such as the comet assay, the micronucleus assay, and the γH2AX assay, as well as new methodological approaches, including toxicogenomics, to assess the cytotoxic and genotoxic activity of chemicals, nanoparticles and natural toxins. Based on our search, we can conclude that the use of in vitro 3D cell models for genotoxicity testing has been increasing over the years and that 3D cell models have an even greater potential for future implementation and further refinement in genetic toxicology and risk assessment.
Ključne besede: genotoxicity, advanced 3D in vitro models, hepatic cells, spheroids, comet assay, micronucleus assay, genotoxicology, toxicological studies
Objavljeno v DiRROS: 14.11.2024; Ogledov: 33; Prenosov: 18
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Povzetek: Aim: Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal musclefibers. Previous work showed that PV ablation has a limited impact on cytosolicCa2+ ([Ca2+]cyto) transients and contractile response, while it enhances mitochon-drial density and mitochondrial matrix-free calcium concentration ([Ca2+]mito).Here, we aimed to quantitatively test the hypothesis that mitochondria act tocompensate for PV deficiency.Methods: We determined the free Ca 2+ redistribution during a 2 s 60 Hz tetanicstimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a re-action–diffusion Ca 2+ model, we quantitatively evaluated mitochondrial uptakeand storage capacity requirements to compensate for PV lack and analyzed pos-sible extracellular export.Results: [Ca 2+]mito during tetanic stimulation is greater in knock-out (KO)(1362 ± 392 nM) than in wild-type (WT) (855 ± 392 nM), p < 0.05. Under the as-sumption of a non-linear intramitochondrial buffering, the model predicts an ac-cumulation of 725 μmoles/Lfiber (buffering ratio 1:11 000) in KO, much higherthan in WT (137 μmoles/Lfiber, ratio 1:4500). The required transport rate via mi-tochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with availableliterature. TEM images of calcium entry units and Mn2+ quenching showed a greater capacity of store- operated calcium entry in KO compared to WT. However,levels of [Ca 2+]cyto during tetanic stimulation were not modulated to variations ofextracellular calcium.Conclusions: The model-based analysis of experimentally determined calciumdistribution during tetanic stimulation showed that mitochondria can act as abuffer to compensate for the lack of PV. This result contributes to a better under-standing of mitochondria's role in modulating [Ca2+]cyto in skeletal muscle fibers.
Ključne besede: calcium, mitochondria, mouse skeletal muscle fibers, parvalbumin, reaction-diffusion model
Objavljeno v DiRROS: 13.11.2024; Ogledov: 37; Prenosov: 16
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Ključne besede: monitoring, stanje gozdov, osutost dreves, poškodovanost dreves, rast dreves, meteorološke meritve, ozon, pritalna vegetacija, fenološka opazovanja, foliarni popis, zračne usedline
Objavljeno v DiRROS: 12.11.2024; Ogledov: 54; Prenosov: 0
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Objavljeno v DiRROS: 12.11.2024; Ogledov: 77; Prenosov: 33
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