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Cell membranes are one of the main targets of oxidative processes mediated by reactive oxygen species (ROS). These chemical species interact with unsaturated fatty acids of membrane lipids, triggering an autocatalytic chain reaction, producing lipid hydroperoxides (LOOHs) as the first relatively stable product of the ROS-mediated lipid peroxidation (LPO) process. Numerous biophysical and computational studies have been carried out to elucidate the LPO impact on the structure and organization of lipid membranes. However, although LOOHs are the major primary product of LPO of polyunsaturated fatty acids (PUFAs), to the best of our knowledge, there is no experimental evidence on the effects of the accumulation of these LPO byproducts on the electrical properties and the underlying dynamics of lipid membranes. In this work, bilayer lipid membranes (BLMs) containing 1-palmitoyl-2–oleoyl-sn-glycero-3-phosphocoline (POPC) with increasing hydroperoxidized POPC (POPC-OOH) molar proportions (BLMPC/PC‑OOH) are used as model membranes to investigate the effect of LOOH-mediated LPO propagation on the electrical behavior of lipid bilayers. Voltage-induced ion current signals are analyzed by applying the fractal method of power spectrum density (PSD) analysis. We experimentally prove that, when certain LOOH concentration and energy threshold are overcome, oxidized membranes evolve toward a critical state characterized by the emergence of non-linear electrical behavior dynamics and the pore-type metastable structures formation. PSD analysis shows that temporal dynamics exhibiting “white” noise (non-time correlations) reflects a linear relationship between the input and output signals, while long-term correlations (β > 0.5) begin to be observed closely to the transition (critical point) from linear (Ohmic) to nonlinear (non-Ohmic) behavior. The generation of lipid pores appears to arise as an optimized energy dissipation mechanism based on the system’s ability to self-organize and generate ordered structures capable of dissipating energy gradients more efficiently under stressful oxidative conditions.

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The RDL receptor is one of the most relevant protein targets for insecticide molecules. It belongs to the pentameric ligand-gated ion channel (pLGIC) family. Given that the experimental structures of pLGICs are difficult to obtain, homology modeling has been extensively used for these proteins, particularly for the RDL receptor. However, no detailed assessments of the usefulness of homology models for virtual screening (VS) have been carried out for pLGICs. The aim of this study was to evaluate which are the determinant factors for a good VS performance using RDL homology models, specially analyzing the impact of the template conformational state. Fifteen RDL homology models were obtained based on different pLGIC templates representing the closed, open, and desensitized states. A retrospective VS process was performed on each model, and their performance in the prioritization of active ligands was assessed. In addition, the three best-performing models among each of the conformations were subjected to molecular dynamics simulations (MDS) in complex with a representative active ligand. The models showed variations in their VS performance parameters that were related to the structural properties of the binding site. VS performance tended to improve in more constricted binding cavities. The best performance was obtained with a model based on a template in the closed conformation. MDS confirmed that the closed model was the one that best represented the interactions with an active ligand. These results imply that different templates should be evaluated and the structural variations between their channel conformational states should be specially examined, providing guidelines for the application of homology modeling for VS in other proteins of the pLGIC family.

Fluralaner is a relatively new insecticide belonging to the isoxazoline group, whose action mechanism involves the blocking of GABA A -receptors in the insect nervous system. Because of its high hydrophobicity, fluralaner could bioaccumulate and reach toxic local concentrations. Since there are no data available about the penetration and persistence of isoxazolines in biological membranes, we intend to evaluate fluralaner permanence as a pollutant by using model membranes. We used experimental and in silico models to characterize the incorporation of fluralaner into the lipid phase at different packing states. We determined its impact in the membrane structure and organization. Our results confirm that fluralaner is capable of penetrating, holding, and accumulating in the lipid membrane and provide details on its precise location and orientation. These properties would allow fluralaner to reach high local concentrations in different membranes and organs, which could be dangerous for vertebrate organisms if its handling is not properly controlled.

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Resumen: Los contenidos de naturaleza de la ciencia (NOS, por sus siglas en inglés) se pueden clasificar en tres ejes: epistemológico, histórico y sociológico. La investigación didáctica ha priorizado el eje epistemológico y persiste un debate sobre qué contenidos de NOS enseñar y cómo hacerlo. El objetivo del trabajo es analizar las concepciones y prácticas de enseñanza declaradas sobre aspectos sociológicos de la NOS en docentes de Metodología de la Investigación en Ciencias Naturales de la ciudad de Córdoba, Argentina. Se utilizó una metodología cualitativa con entrevistas semiestructuradas. Los docentes entrevistados/as enfatizan la enseñanza explícita del eje epistemológico. Reconocen las influencias mutuas entre ciencia y sociedad, aunque persisten algunas concepciones ingenuas, particularmente respecto a la imagen del científico/a. En cuanto a las prácticas de enseñanza, se evidenció que las temáticas sociológicas se trabajan en el aula, a veces de manera planificada y otras de manera espontánea.