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Biology subjects

Kralj, M.

Publications and source records attributed to Kralj, M..

3 recordsLinked to original sources

Characterization of undocumented CO2 hydrothermal vents in the Mediterranean Sea: implications for ocean acidification studies

A previously undocumented shallow water hydrothermal field from Sicily (Southern Tyrrhenian Sea, Italy), is here described based on a multidisciplinary investigation. The field, covering an area of nearly 8000 m2 and ranging in depth from surface to -5 m, was explored in June 2021, to characterise the main physico-chemical features of the water column, describe bottom topography and features, and identify the main megabenthic and nektonic species. Twenty sites were investigated to characterize the carbonate system. Values of pH ranged between 7.84 and 8.04, {Omega}Ca between 3.68 and 5.24 and {Omega}Ar from 2.41 to 3.44. Geochemical analyses of hydrothermal fluids gases revealed a dominance of CO2 (98.1%) along with minor amounts of oxygen and reactive gases. Helium isotope ratios (R/Ra =2.51) and {delta}13CCO2 (3) support an inorganic origin of hydrothermal degassing of CO2 and the ascent of heat and deep-seated magmatic fluids to the surface. Visual census of fishes and megabenthos (mainly sessile organisms) allowed identification of 62 species, of which four are protected by the SPA/BIO Protocol and two by the International Union for Conservation of Nature. The macroalgae Halopteris scoparia and Jania rubens and the sponge Sarcotragus sp. were the dominant taxa in the area, while among fishes Coris julis and Chromis chromis were predominant. The preliminary description of this venting field indicates this site as an area of considerable interest and suitable for future experimental studies on ocean acidification.

ecology↗

Targeting plasma membrane and mitochondrial instability in breast cancer cells and breast epithelial to mesenchymal transition-model cells by adamantyl diaza-crown ether ZG613

The adamantane derived diaza-crown ether ZG613 was assessed as a potential breast cancer cells and breast epithelial to mesenchymal transition (EMT)-model cells targeting agent. We postulated that ZG613 activity relies on its plasma/mitochondria membrane disruption ability based on adamantane hydrophobicity and/or crown ether related ionophoric properties. We performed molecular dynamics (MD) simulations and next generation sequencing, followed by in vitro study of cell death, membrane perturbations and ionophoric ability, as well as in vivo study of effects on the tumour growth. MD simulation and RNA sequencing pointed toward physical disruption of plasma membrane by ZG613, corroborated by measured increase in membrane permeability leading to cell death. Measurements of ion fluxes confirmed ZG613 inability to transport Na+ and K+, as predicted by MD simulation. EMT-model cells exhibit changes in mitochondrial morphology and ATP levels, successfully targeted by ZG613. ZG613 caused mild retardation of tumour growth in vivo. In conclusion, ZG613 kills breast cancer cells and breast EMT-model cells by physical disruption of plasma membrane and impairments of mitochondrial functions. Breast EMT cells represent good potential targets within the breast tumour, due to their plasma membrane and mitochondrial instability.

cancer biology↗

Salinomycin disturbs Golgi apparatus function and specifically affects cells in epithelial-to-mesenchymal transition

Epithelial-to-mesenchymal transition (EMT) gives rise to cells with properties similar to cancer stem cells (CSCs). Targeting the EMT program to selectively eliminate CSCs is a promising way to improve cancer therapy. Salinomycin (Sal), a K+/H+ ionophore, was identified as highly selective towards CSC-like cells, but its mechanism of action and selectivity remains elusive. Here we show that Sal, similarly to monensin and nigericin, disturbs the function of the Golgi apparatus (GA). Sal alters the expression of GA-related genes and leads to marked changes in GA morphology, particularly in cells that underwent EMT. Moreover, GA disturbing agents severely affect protein post-translational modifications including protein processing, glycosylation and secretion. We discover that the alterations induced by GA disturbing agents specifically affect the viability of EMT cells. Collectively, our work identifies a new vulnerability related to the EMT, suggesting that targeting the GA is a novel therapeutic approach against CSCs.

cancer biology↗