Resultados de investigación

Background and Objective: Assessment of drug cardiotoxicity is critical in the development of new compounds and modeling of drug-binding dynamics to hERG can improve early cardiotoxicity assessment. We previously developed a methodology to generate Markovian models reproducing preferential state-dependent binding properties, trapping dynamics and the onset of IKr block using simple voltage clamp protocols. Here, we test this methodology with real IKr blockers and investigate the impact of drug dynamics on action potential prolongation. Methods: Experiments were performed on HEK cells stably transfected with hERG and using the Nanion SyncroPatch 384i. Three protocols, P-80, P0 and P40, were applied to obtain the experimental data from the drugs and the Markovian models were generated using our pipeline. The corresponding static models were also generated and a modified version of the O´Hara-Rudy action potential model was used to simulate the action potential duration. Results: The experimental Hill plots and the onset of IKr block of ten compounds were obtained using our voltage clamp protocols and the models generated successfully mimicked these experimental data, unlike the CiPA dynamic models. Marked differences in APD prolongation were observed when drug effects were simulated using the dynamic models and the static models. Conclusions: These new dynamic models of ten well-known IKr blockers constitute a validation of our methodology to model dynamic drug–hERG channel interactions and highlight the importance of state-dependent binding, trapping dynamics and the time-course of IKr block to assess drug effects even at the steady-state.

[EN] The benchmarking of security tools is endeavored to determine which tools are more suitable to detect system vulnerabilities or intrusions. The analysis process is usually oversimplified by employing just a single metric out of the large set of those available. Accordingly, the decision may be biased by not considering relevant information provided by neglected metrics. This work proposes a novel approach to take into account several metrics, different scenarios, and the advice of multiple experts. The proposal relies on experts quantifying the relative importance of each pair of metrics towards the requirements of a given scenario. Their judgments are aggregated using group decision making techniques, and pondered according to the familiarity of experts with the metrics and scenario, to compute a set of weights accounting for the relative importance of each metric. Then, weight-based multi-criteria-decision-making techniques can be used to rank the benchmarked tools. This dataset contains raw data obtained from 21 experts, who declared their familiarity with considered metrics and their preference for each metric in the considered scenarios. Processed data include the consistency ratio of resulting pairwise comparison matrices so inconsistent matrices are rejected - weight = 0.00), the relative contribution of each expert according to their declared familiarity with metrics and computed CRs, and the contribution (weight) of each metric towards each considered scenario.

Alginate hydrogels can be used to develop a three-dimensional environment in which various cell types can be grown. Cross-linking the alginate chains using reversible ionic bonds opens up great possibilities for the encapsulation and subsequent release of cells or drugs. However, al-ginate also has a drawback in that its structure is not very stable in a culture medium with cellu-lar activity. This work explored the stability of alginate microspheres functionalised by grafting specific biomolecules onto their surface to form microgels in which biomimetic microspheres surrounded the cells in the culture, reproducing the natural microenvironment. A study was made of the stability of the microgel in different typical culture media and the formation of polyelectrolyte multilayers containing polylysine and heparin. Multiple myeloma cell prolifer-ation in the culture was tested in a bioreactor under gentle agitation., The Microscopy Service of the UPV (Universitat Politècnica de València) is gratefully acknowl-edged for helping with cryoFESEM characterisation. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program. The Instituto de Salud Carlos III financed CIBER Actions with assistance from the European Regional Develop-ment Fund.

Base de datos de los museos marítimos españoles con datos sobre fondos recibidos, This research was funded by SPANISH ECONOMY AND COMPETITIVENESS MINISTRY, grant number PID2019-105497 GB-I00, European Fisheries Funds, opportunities for the fisheries sector through diversification, and the FLAGs management (DivPesc).

[EN] Dataset asociated to the paper "Above and belowground male population of the Invasive Cit-rus mealybug Delottococcus aberiae De Lotto (Hemiptera: Pseudococcidae) " The invasive Delottococcus aberiae is one of the most harmful mealybugs on citrus in Spain, since it causes deformations and the premature falling of fruits. To improve control strategies, this study evaluates its population above and belowground, distri-bution in the soil and identify natural enemies emerging from belowground of citrus orchards. The distribution in the soil of emerged males varies significantly with the distance to the tree trunks with an annual average number of 0.95 males/trap/day at 0.5 m, and ranging between 0.25-0.32 at 1 m, 1.5 m and 2 m. There is a constant emergence of males throughout the year, both aboveground and belowground, with four distinct peaks, the first two occurring in February and April. This observation is essential to manage fruit damages that follows between March and June. Among the natural en-emies detected belowground the following are highlighted: Bdellidae mites (52%), Hymenoptera parasitoids (16%) and spiders (11%). When implementing IPM strate-gies, emphasis should be placed on adequate soil management (crops, mulching, or the release of natural enemies) and to the appearance of first generation. We propose a belowground population sampling method as a simple and practical tool to quantify this pest’s the winter and spring populations, which remain undetectable using current methodologies., This research was funded by the Next Generation European Union and the Plan de Recuperación, Transformación y Resiliencia of the Spanish Government, with the support of Generalitat Valenciana (project AGROALNEXT/2022/043), and by the project “Ruralfruit-AgroEco” (Transición al modelo agroecológico y adaptación al cambio climático de la citricultura convencional en Cooperativas valencianas” (project AGCOOP_A/2022/015), subsidized by the PDR-CV 2014-2020 (53% UE, 8,86% MAPA, 38,14% GVA)

[EN] This dataset includes supplementary material (raw data) collected to support research on patent-level altmetrics on X (Twitter). Specifically, it contains the linking tweets to patent US4656917A, an invention owned by musician Eddie Van Halen, all conversations in which those tweets appear, as well as information on the Twitter activity of the users publishing those tweets and the users interacting (like or retweet) with those tweets., This research was funded by MCIN/AEI/ 10.13039/501100011033 project PID2022-142569NA-I00 and by “ERDF A way of making Europe”, by the “European Union”.

[EN] Ti-felt electrodes with high surface area have been used as supports of electroactive coatings (Pt and SnO₂–Sb–Pt). The electrodes obtained have been employed for the electrochemical oxidation of polystyrene nanoplastics (NPs) (100 nm) in solution. Voltammetric characterization of the electrodes with Ru(NH₃)₆Cl₃ and K₃Fe(CN)₆ redox mediators showed a substantial increase in the redox peaks' current density compared to the boron‑doped diamond electrode. For example, this increase was >68‑fold for the SnO₂–Sb–Pt electrode when using the Ru(NH₃)₆Cl₃ redox mediator. This can be attributed to the enhanced surface area of Ti‑felt, composed of 20 μm diameter fibers, and the roughness of the electrocatalyst coatings. Voltammetric characterization of Ti‑Pt and Ti‑SnO₂–Sb–Pt in 0.03 M Na₂SO₄ media showed an increase in the anodic current density when adding NPs, which would account for a direct mechanism of electrooxidation of the electrode. •OH, S₂O₈²⁻, H₂O₂, and O₃ generation were also determined for both types of electrodes. The degradation of NPs was monitored by fluorescence spectroscopy, taking advantage of the fluorescence of styrene. In addition, it was observed that the dispersion of the second‑order diffraction light (this phenomenon takes place in the diffraction grating of the monochromator) by NPs could also be used to monitor the evolution of the NPs concentration in solution. The electrochemical degradation of polystyrene NPs was faster with SnO₂–Sb–Pt modified Ti‑felt‑based electrodes than with the Pt‑modified one (reaching 90 % degradation in 100 and 210 minutes at 25 mA·cm⁻², respectively). Electrochemical energy consumption per order was also lower for SnO₂–Sb–Pt‑modified electrodes., This research is part of the Spanish R+D+i contract TED2021-130905B-I00 funded by MCIN/AEI /10.13039/501100011033 and by the European Union NextGenerationEU/PRTR as well as the Red E3Tech Plus: Proyecto Redes de Investigación de la AEI Network E3Tech PLUS (RED2022-134552-T) project. Funding for open access charge: CRUE-Universitat Politècnica de València. The Electron Microscopy Service of the UPV (Universitat Politècnica de València) is gratefully acknowledged for its help with FESEM, EDX, and TEM characterization.

The development of three-dimensional environments to mimic the in vivo cellular response is a problem in the building of disease models. This study aimed to synthesize and validate three-dimensional support for culturing monoclonal plasma cells (mPCs) as a disease model for multiple myeloma. The three-dimensional environment is a biomimetic microgel formed by alginate microspheres and produced on a microfluidic device whose surface has been functionalized by a layer-by-layer process with components of the bone marrow’s extracellular matrix, which will interact with mPC. As a proof of concept, RPMI 8226 cell line cells were cultured in our 3D culture platform. We proved that hyaluronic acid significantly increased cell proliferation and corroborated its role in inducing resistance to dexamethasone. Despite collagen type I having no effect on proliferation, it generated significant resistance to dexamethasone. Additionally, it was evidenced that both biomolecules were unable to induce resistance to bortezomib. These results validate the functionalized microgels as a 3D culture system that emulates the interaction between tumoral cells and the bone marrow extracellular matrix. This 3D environment could be a valuable culture system to test antitumoral drugs efficiency in multiple myeloma.

[EN] This dataset contains the evolution with time of the following measured variables: relative Norfloxacin concentration, relative total organic carbon Concentration and cell potential These variables was obtained for 3 different anodic materials, CuO (ceramic anode with Cupper as sintering aid), BDD and BCE (basic ceramic electrode, based on SnO2 doped with Sb2O3); and two different electrochemical reactors with and without membrane, EMR and OCR, respectively. All the experiments were under an applied current of 400 mA and at room temperature., The authors want to express their gratitude to the Ministerio de Economía y Competitividad (Spain) and the FEDER funds, which financially support the project RTI2018-101341-B-C21.

[EN] The resulting solutions from the cotton fabrics dyeing using the trichromy Procion HEXL, with NaCl as electrolyte, were electrochemically treated. These dyes have two azo groups as chromophores and two monochlorotriazinic groups as reactive groups in their structure. The combined oxidation/reduction at 125 mA cm-2 in a filter-press cell without compartment separation was carried out using an anode of Ti/SnO2eSbePt and a cathode of stainless steel. This procedure has been effective in previous experiments using sulphate as electrolyte. A significant decrease in total organic carbon (TOC), chemical oxygen demand (COD), and total nitrogen (TN) was obtained. Moreover, the process took place efficiently. The average oxidation state (AOS) and the carbon oxidation state (COS) data confirmed the presence of stable oxidized intermediates in the electrolysed solution. The chromatography and the UVeVisible spectrophotometry assays indicated that full decolourisation is obtained at a loaded charge of around 0.81 Ah L-1 which is associated with an electrical energy per order (EEO) of 1.20 kWh m-3., The authors wish to thank the Spanish Agencia Estatal de Investigación (AEI) and European Union (FEDER funds) for the financial support (contract MAT2016-77742-C2-1-P and Red E3Tech CTQ2017-90659-REDT). The authors wish to acknowledge Tim Vickers for help with the English revision and Texcoy S.L. company (Spain) where the dyeing processes were done.