Resultados de investigación

Neurodegenerative diseases involve progressive neuronal death. Traditional treatments often struggle due to solubility, bioavailability, and crossing the Blood-Brain Barrier (BBB). Nanoparticles (NPs) in biomedical field are garnering growing attention as neurodegenerative disease drugs (NDDs) carrier to the central nervous system. Here, IFPTML technique was used, which combined Information Fusion (IF) + Perturbation Theory (PT) + Machine Learning (ML) to select the most promising NDDS and NP candidates and to address the few data in the literature. IF-process was carried out between 4403 NDDS assays and 260 cytotoxicity NP assays conducting a dataset of 500000 cases. The optimal IFPTML identified was the DT algorithm, demonstrating satisfactory performance with specificity values of 96.4% and 96.2%, and sensitivity values of 79.3% and 75.7% in the training (375k/75%) and validation (125k/25%) set. Moreover, the DT model obtained AUROC scores of 0.97 and 0.96 in the training and validation series, highlighting its effectiveness in classification tasks. On the other hand, two samples of NPs (Fe3O4_A and Fe3O4_B) were synthesized and structurally characterized by different methods. Additionally, in order to make the as-synthesized hydrophobic NPs (Fe3O4_A and Fe3O4_B) soluble in water the amphiphilic CTAB (hexadecyltrimethylammonium bromide) molecule was employed. Therefore, to conduct a study with a wider range of NP system variants, an experimental illustrative simulation experiment was performed using the IFPTML-DT model. For this, a set of 500000 prediction dataset was created involving n(NP cores)=5 vs. n(cell lines) =53 vs. n(NP shapes) =5 vs. n(NP coats) =16 vs. n(drugs) =123. The outcome of this experiment highlighted certain NANO.PTML systems as promising candidates for further investigation. Specifically, the experiment revealed that the cell line Lycopersicon esculentum showed promise for ecotoxicity studies across various coating systems. In contrast, Danio rerio cell lines (embryos, juveniles, and adults) showed lower predictive values, suggesting less favorable candidates. MacGowan volume was notably relevant for CTAB, PS, and PEG as coating agents, excluding PVA. The NANO.PTML approach holds potential to accelerate experimental investigations and offer initial insights into various NP and NDDS compounds, serving as an efficient alternative to time-consuming trial-and-error procedures., Basque Government / Eusko Jaurlaritza (IT1558-22); AIMOFGIF (KK-2022/00032); Ministry of Science and Innovation (PID2022-137365NB-I00); IKERDATA 2022/IKER/000040, Peer reviewed

Cells sense and respond to mechanical forces through mechanotransduction, which regulates processes in health and disease. In single adhesive cells, mechanotransduction involves the transmission of force from the extracellular matrix to the cell nucleus, where it affects nucleocytoplasmic transport (NCT) and the subsequent nuclear localization of transcriptional regulators such as YAP. However, if and how NCT is mechanosensitive in multicellular systems is unclear. Here, we characterize and use a fluorescent sensor of nucleocytoplasmic transport (Sencyt) and demonstrate that nucleocytoplasmic transport responds to mechanics but not cell density in cell monolayers. Using monolayers of both epithelial and mesenchymal phenotype, we show that NCT is altered in response both to osmotic shocks, and to the inhibition of cell contractility. Further, NCT correlates with the degree of nuclear deformation measured through nuclear solidity, a shape parameter related to nuclear envelope tension. In contrast, YAP but NCT is sensitive to cell density, showing that YAP response to cell‐cell contacts is not via a mere mechanical effect of NCT. Our results demonstrate the generality of the mechanical regulation of NCT. (2024-07-24), Peer reviewed

Figure S1. Relative amount of cholesteryl esters in cells treated with micellar fractions isolated from digested lipid and carbohydrate matrix (LCM), protein matrix (JM), and carbohydrate matrix (CM). Significant differences between pairs of data are marked (p < 0.05); Figure S2. Relative amount of triacylglycerides in cells treated with micellar fractions isolated from digested lipid and carbohydrate matrix (LCM), protein matrix (JM), and carbohydrate matrix (CM). Significant differences between pairs of data are marked (p < 0.05); Figure S3. Relative amount of neutral lipids in cells treated with micellar fractions isolated from digested lipid and carbohydrate matrix (LCM), protein matrix (JM), and carbohydrate matrix (CM). Significant differences between pairs of data are marked (p < 0.05). Table S1. Lipid composition of BM-MFGM; Table S2. Triacylglyceride species and cholesterol analyzed in the study, following the methodology described in [22], showing the corresponding numbers in Figure 1, Figure 2, Figure 3, Figure 4 and Figure 5; Table S3. Fatty acids analyzed in the study, following the methodology described in [23], showing the corresponding numbers in Figure 1, Figure 2, Figure 3, Figure 4 and Figure 5; Table S4. Lipid classes analyzed in the study, following the methodology described in [15], showing the corresponding numbers in Figure 1, Figure 2, Figure 3, Figure 4 and Figure 5. Table S5. PLS-DA performance considering lipid profile in BM-MFGM supplemented food matrices, in micelles from digested MFGM-supplemented food matrices or in cell cultures after incubation with those micellar fractions., Peer reviewed

Figure S1. Photographs of different fractions obtained during pectin isolation; Figure S2. Representative GC-FID chromatograms of acid-soluble (CAP, a) and Ca-bound (AOPP, b) pectin-rich fractions monosaccharide composition obtained after complete hydrolysis. Table S1. Results of a two-tailed Student’s t-test of acid-soluble (CAP) and Ca-bound (AOPP) pectin-rich fractions influence on S. epidermidis strains growth compared to control sample without supplementation. Table S2. Results of a two-tailed Student’s t-test of acid-soluble (CAP) and Ca-bound (AOPP) pectin-rich fractions influence on S. aureus strains growth compared to control sample without supplementation., Peer reviewed

Individual penetration vs angle plots for each metal atom in (LMX)2 dimers and L2M–X covalent or incipient bonds, and table with fitting parameters and size of the data sets (PDF)., All of the data used, including CSD refcode, fragment number when there is more than one hit in a particular structure, crystallographic labels for the interacting atoms M and X, bond angle, covalent, and van der Waals radii of the M and X atoms, the calculated penetration index, and a label to indicate whether the M–X atom pair was retrieved as an M–X bond or an M···X contact (XLSX)., Peer reviewed

Peer reviewed

Experimental details, characterization data, DFT calculations, and NMR spectra., Peer reviewed

A—Protein sequence alignment comparing Vfr from A. baumannii AB5075 and its orthologue from P. aeruginosa PAO1. Residues involved in the interaction with cAMP, according to Beatson et al. [76], are framed in red. The strong conservation between these residues in both orthologues suggests that both proteins will interact with cAMP with the same specificity. The DNA binding domain of both proteins, as predicted by an InterPro sequence scan (PF00325), appears framed in green. The conservation in this region suggests a similar target promoter sequence for both orthologues. (*): identical residues; (:): highly similar residues; (.): somewhat similar residues. The sequence alignment was performed using Clustal Omega. B-D–Structural alignment of VfrAB5075 and VfrPAO1 in PyMOL. Overall alignment of the two proteins (VfrAB5075 in magenta and VfrPAO1 in cyan) indicates root mean square deviation (RMSD) of 1.938811 over 208 residues (B). Highlighted are the DNA binding domains (C) and cAMP binding sites (D) in VfrAB5075 (magenta) and VfrPAO1 (blue). E–Two residues (threonine 138 and threonine 139) from the VfrAB5075 cAMP binding site (magenta) were modified to alanine and tryptophan respectively resulting in VfrT138A,T139W variant which was subsequently used to demonstrate the necessity of cAMP binding for proper Vfr function in A. baumannii. Protein structure visualised using PyMOL., Peer reviewed

Images of nests were taken in a saltpan and rice fields in southern Spain, considering whether the nests were on natural or on substrates of anthropogenic origin. The images were analysed using specific software and the camouflage of eggs in relation to both nests and the microhabitats surrounding nests was estimated. The camouflage was considered as the differences in textures among such categories. Nest survival according to substrate type was estimated using a logistic exposure model. Further details on field, laboratory and statistical methods can be obtained from: Liñán-Cembrano, G., Castro, M., Ramo, C., Rendón, M. A., Amat, J. A., and Pérez-Hurtado, A. 2025. Effects of the anthropogenic introduction of substrates on egg camouflage and nest success in a ground-nesting bird. Animal Conservation. https://doi.org/10.1111/acv.70008, This dataset corresponds to information employed for analysis in Liñán-Cembrano, G., Castro, M., Ramo, C., Rendón, M. A., Amat, J, A., Pérez-Hurtado, A. 2025. Effects of the anthropogenic introduction of substrates on egg camouflage and nest success in a ground-nesting bird. Animal Conservation https://doi.org/10.1111/acv.70008, The dataset includes three files. One with information relative to egg characteristics (i). A second file contains data on egg camouflage according to the visual systems of the main predators in the study area (ii). Lastly, the third file presents information on the fate of nests (iii). (i) File : Characteristics of nests according to total area of eggshell covered by spots, fractal dimension of spottieness, and eggshell coloration. (ii) File : Nests according to habitat type, substrate type, and camouflage of eggs relative to both nests and microhabitats. Camouflage according to the visual systems of predators. (iii) File : Fate of nests according to substrate type, habitat type, and egg camouflage according to the visual systems of predators., No

Document S1. Tables S1–S3. Table S4. Peak-to-gene annotations, related to Figure 6., Peer reviewed