Alberto Sols Biomedical Research Institute

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    Exposure to low-dose CuO nanoparticles improves fear extinction memory and enhance intrinsic excitability in the infralimbic cortex of male mice

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    Aims: Nanomaterials have gained considerable attention for diverse medical applications, particularly in neurology. Copper oxide nanoparticles (CuO-NPs) exhibit unique nanoscale properties that enable close interactions with neuronal cells, highlighting their potential as therapeutic agents for modulating synaptic plasticity and improving cognitive function. We aimed to investigate whether low-dose CuO-NPs can enhance fear extinction memory and increase intrinsic excitability in the infralimbic cortex (IL) of male mice. Materials and methods: Adult male mice were subjected to fear conditioning using auditory cues paired with footshocks. Following the administration of a low dose of CuO-NPs, behavioral performance was assessed by measuring freezing responses during extinction. Whole-cell patch-clamp recordings were then performed on IL pyramidal neurons to evaluate intrinsic excitability and AMPA/NMDA ratio. Transmission electron microscopy (TEM) was applied after 2 and 24 h to assess the ability of CuO-NPs to reach the brain. Key findings: We demonstrated via TEM that CuO-NPs efficiently cross the blood-brain barrier within 24 h’ post- administration. Using cued fear conditioning, we subsequently found that a single intraperitoneal injection of CuO-NPs enhanced fear extinction memory, as evidenced by a significant reduction in freezing behavior compared to control animals. Patch-clamp analysis confirmed that CuO-NPs increased the excitability of IL pyramidal neurons and induced a sustained reduction in fast, medium, and slow post-spike after hyperpolarizations. Additionally, we demonstrated that CuO-NPs increased N-methylD-aspartate receptor-mediated synaptic currents, suggesting an enhanced synaptic plasticity in the infralimbic cortex. Significance: Our findings offer new insights into the potential use of CuO-NPs for modulating fear extinction memoryThis research was supported by grants PID2020-119358GB-I00 and PID2023-148843NB-I00 from the European Union (Ministerio de Ciencia e Innovacion and Ministerio Ciencia, Innovación y Universidades, AEI/FEDER, UE) to David Fernández de Sevilla and the APC was funded by the CRUE-CSIC agreement with Elsevier

    Charge compensation mechanisms in Ni-rich NMC cathodes

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    Understanding charge compensation mechanisms in nickel-rich lithium nickel–manganese–cobalt alloy oxide (NMC) cathodes is crucial for optimizing their electrochemical performance. This study employs complementary spectroscopic techniques with varying probing depths, including X-ray absorption nearedge structure spectroscopy, hard X-ray photoemission spectroscopy, X-ray photoelectron spectroscopy, and ion beam analysis, to investigate the correlation between transition metal oxidation states and Li depth profile in NMC811. This approach reveals different charge compensation mechanisms depending on the local Li content, which exhibits near-surface gradients. The results show that Ni oxidation is the main charge compensation mechanism for moderate delithiations at a Li stoichiometry x > 0.35. When the Li content drops below the threshold x = 0.3, which occurs near the surface for high state of charge (SOC), compensation by Ni/Li mixing prevails. Meanwhile, the Li-depleted surface (with x 0.3) shows evidence of transformation into electrochemically inactive Li-free cubic phases. The voltage window used to cycle the NMC811 prevents the bulk Li content from falling below x = 0.35, so the different charge compensation mechanisms coexist for high SOCs, allowing to compare between their kinetics. This study contributes to a comprehensive understanding of the electrochemical behavior of nickel-rich NMCs, aiding the development of high-energy Li-ion batteries with improved stabilityThis work has been supported by the SOLIMEC project funded by the M-ERA.NET Call 2021 and by the Spanish Agencia Estatal de Investigación (PCI2022-132998, PCI2022-132955, and PID2021– 124667OB-I00 NanoCatCom project). The authors acknowledge support from the Spanish Ministry of Science, Innovation and Universities through the “María de Maeztu” Programme for Units of Excellence in R&D (CEX2023-001316-M). The authors also acknowledge the support from the Center for Micro-Analysis of Materials (CMAM) - Universidad Autónoma de Madrid for the beamtime with code STD011/23 and its technical staff for their contribution to the operation of the accelerator, and from ReMade@ARI suppor

    Memoria de investigación 2024. Facultad de Filosofía y Letras, UAM

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    Difusión y análisis de la actividad investigadora realizada anualmente por los investigadores de los departamentos de la Facultad de Filosofía y Letras. Recoge publicaciones, grupos de investigación, proyectos I+D+I y tesis doctorale

    Acoustic Rayleigh Wave Turbulence in Soft Viscoelastic Matter

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    Evidence of discrete acoustic Rayleigh wave turbulence (DARWT) is reported on the free surface of complex viscoelastic materials under monochromatic excitation. These surface elastic non-linear Rayleigh waves exhibit dispersionless dynamics governed by bulk shear rigidity at coexistence with dispersive capillary waves supported by surface tension. Using Laser Doppler Vibrometry (LDV), the discrete Kolmogorov–Zakharov (KZ) spectrum is measured, characterized by a power-law envelope in an inertial cascade of discrete harmonics. When shear rigidity dominates, KZ-spectrum characterized by an −5/2 acoustic fingerprint is observed as a conservative solid-like scaling, theoretically predicted from the exact three-wave dispersionless resonance. Conversely, when surface tension dominates overbulk stresses, dispersive CW behavior under the usual −17/6 liquid-like scaling is recovered. These findings support a unique theoretical framework for understanding conservative DARWT and advance the field of surface wave turbulence in viscoelastic media with markedly non-Newtonian rheology. Acoustic Rayleigh wave turbulence represents a conservative mechanism for dispersionless energy transport through weakly nonlinear wave interactions across scales, with relevance to various physics fields, from soft matter and biological systems up to geophysical flowsThis research was partially supported by Ministerio de Investigación, Innovación y Universidades, under grants TED2021-132296B-C52, PID2019-108391RB-I00, FIS2015-70339, and by Comunidad de Madrid under grants S2013/MIT-2807, P2018/NMT4389 and Y2018/BIO5207 (to FM). The authors thank Dr. E. Montoya, who provided insight and expertise with the LDV device, and Prof. J. Fernández-Castillo for his generosity in free leasing laboratory spac

    Palladium(II) Complexes with Noncovalent Interactions with DNA: Solution Speciation Controlled by Solvent Identity, pH, and Concentration

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    The coordination capacity of thiosemicarbazone ligands and their synergism with palladium(II) ions modulate their reactivity, allowing custom design. Using thiosemicarbazones with two potential stable tautomeric forms and imidazole as bioisosteres, we studied how the substitution in the N4 group of the thiosemicarbazone by the p-chlorophenyl group modifies their hydrophilic properties, integrity in solution, and interactions toward their potential targets. The coordination to Pd(II) affects the bioactivity of the ligands, resulting in either improved or reduced antiproliferative effects depending on the cell type (cancerous versus bacterial, respectively)This research was funded by National Research, Development, and Innovation Office-NKFIA (Hungary) through project TKP-2021-EGA-32 and COST Action CA18202, NECTAR - Network for Equilibria and Chemical Thermodynamics Advanced Research, supported by COST (European Cooperation in Science and Technology). A.G.Q., A.I.M., D.F., and F.A.R. also acknowledge the Spanish MCI grant PID2019 106220RB100. D.F. also acknowledges a STMS grant form the COST Action CA18202 and its first-year grant from UAMFPI. F.A.R. acknowledges Comunidad de Madrid for his Ph.D. contract: PIPF-2022/SAL-GL-2529

    Unambiguous Spectroscopic Characterization of a Gold Difluorocarbene

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    Gold(I) carbenes, defined as [LAu═CR2]+, are key intermediates in catalysis. Their isolation is challenging due to the high electrophilic character of the carbene that cannot be tempered solely by π-backdonation from gold. Among those, the simple difluorocarbene complex has been invoked in several studies, but attempts to isolate it have failed, while its identification remains questionable. In this study, we report the unambiguous spectroscopic characterization of the gold difluorocarbene complex [P–Au═CF2]+, providing key insights into its structural and electronic features. The kinetic stabilization of the carbene was only possible owing to the shielding offered by a congested and cavity-shaped phosphine that prevents decomposition under strict anhydrous conditions. Besides, the nature of the anion is key to provide further thermal stability for prolonged timesThis work was supported by the Spanish Ministry of Science and Innovation (PID2019-106184GB-I00). M.N. acknowledges the Spanish Ministry of Science and Innovation and Junta de Andalucía for postdoctoral programs (FJC2018035514-I and DOC_00149). L.D. thanks the Erasmus+ program for funding. A.P.-T. acknowledges support from “laCaixa” Foundation (ID 100010434; fellowship code B005930). The use of computational facilities at the Supercomputing Center of Galicia (CESGA) is also acknowledge

    Breaking Bad y la omisión ¿Mató Walter White a Jane?

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    Self-assembly and lateral cobalt coordination of a five-fold symmetric cyanostar macrocycle on a Au(111) surface

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    The functionalization of solid surfaces with responsive macrocyclic compounds is a key strategy for developing advanced functional materials, with applications in molecular sensing, catalysis, and nanoscale electronics. Here,we report the self-assembly and lateral cobalt coordination, on an Au(111) surface and under ultra-high vacuum conditions, of a fivefold symmetric cyanostar macrocycle, a class of anion recognition molecules. This represents the first example of a close-packed regular assembly of a pentagonal macrocycle at the solid-vacuum interfaceThis project has received funding from the Spanish Ministerio de Ciencia e Innovación (grant PID2022-136961NB-I00). T.T. and G.B. acknowledge financial support from the Spanish MCIN/AEI/10.13039/501100011033 and European Union NextGenerationEU/PRTR (TED2021-131255B-C43), MICIU/AEI/10.13039/501100011033/FEDER, UE (PID2023-151167NBI00), the Comunidad de Madrid and the Spanish State through the Recovery, Transformation and Resilience Plan [“Materiales Disruptivos Bidimensionales (2D)” (MAD2D-CM) (UAM1)-MRR Materiales Avanzados], and the European Union through the Next Generation EU funds. We also acknowledge the support from the ‘(MAD2D-CM)-IMDEA-Nanociencia’ and ‘(MAD2D-CM)-UCM’ projects funded by Comunidad de Madrid, by the Recovery, Transformation and Resilience Plan, and by NextGenerationEU from the European Union. We thank funding from PERTE Chip project PDC2023-145871-I00. A.H.F. acknowledges support from the NSF (CHE-2403941). The authors thank Comunidad de Madrid through the “Programa de Actividades de I+D” (TEC-2024/TEC-459, SYNMOLMAT-CM

    ISG15 modulates inflammatory profiles and ability to activate CD8 + T cells in bone marrow-derived dendritic cells

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    The Interferon-Stimulated Gene 15 (ISG15) has a key role during viral infections, since it can modify and regulate the expression of proteins from the host and from viruses. Isg15−/− mice are more susceptible to infectious diseases. ISG15 is induced by type I Interferons (IFN-I) and apart from defense against pathogens, it can also play an important function in cancer or immune-mediated inflammatory diseases. Previous studies reported that ISG15 expression is increased in post-synaptic dendritic cells (DCs) upon interaction with CD4+T cells. However, data regarding the role of ISG15 in DCs are scarce. The present study assesses the function of ISG15 in DCs activation, migration and ability to mediate T cell activation using bone marrow-derived DCs (BMDCs) and stimulation with lipopolysaccharide (LPS). Activation ofDCs was not impaired but tended to be lower in Isg15-deficient mice, as observed by reduced CD40 induction in Isg15−/−BMDCs. Isg15−/− BMDCs induced less proliferation and Granzyme B expression in co-cultured CD8+T cells. Interestingly, Isg15−/− BMDCs secreted reduced levels of the pro-inflammatory cytokines IL-1β and IL-12 upon LPS stimulation. Mechanistically, our data suggest that ISG15 regulates Caspase-1 activity in DCs leading to lower IL-1 β secretion. In conclusion, this study reveals an essential role for ISG15 modulating DCs inflammatory activity and raises new questions regarding the specific mechanisms of how this protein regulates innate immune responsesF.S.-M.’s laboratory is funded by the Spanish Ministry of Science and Innovation, Agencia Estatal de Investigación grants PID-2020-120412RB-I00, PID2023-149541OB-I00, “La Caixa” Foundation project code LCF/PR/HR23/52430018, P2022/BMD7209 (INTEGRAMUNE) funded by Comunidad de Madrid, and a grant from the Asociación Española Contra el Cáncer (AECC; PRYCO223002PEIN). E.M.-G. was supported by the Spanish Agencia Estatal de Investigación RETOS, Generación de conocimiento and consolidation programs (RTI2018-097485-A-I00;PID2021-127899OB-I00; CNS2023-144841), La Caixa Banking Fundation ETI-CureHIV(HR20-00218) and infectious diseases CIBER from ISCIII (CIBERINFEC) and a Gilead grant (GLD24/00117). R.C.-G. is supported by Ayudas para contratos Juan de la Cierva-formación 2021 (FJC2021-047282-I) from MICIN (Spain). P.M.-F. has been funded by a Rio-Hortega grant CM22/00076 from the Ministerio de Ciencia e Innovación (Instituto de Salud Carlos III) and co-funded by the European Regional Development Fund (ERDF) “A way to make Europe”. R.I.-S. was supported by a grant from the Spanish Agencia Estatal de Investigación (Ministerio de Ciencia e Innovación) (PRE2020-091912). E.M.-R. was supported by a grant from Comunidad de Madrid and co-funded by the European Regional Development Fund (ERDF) “A way to make Europe

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