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Herráez Aguilar, Diego

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Diego

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Herráez Aguilar

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Ciencias Experimentales

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Now showing 1 - 7 of 7
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    Experimental and theoretical studies of the Xe-OH(A/X) quenching system.
    (The Journal of Chemical Physics, 2018) Klos, J.; McCrudden, G.; Brouard, M.; Perkins, T.; Seamons, S.A.; Herráez Aguilar, Diego; Aoiz, F. J.
    New multi-reference, global ab initio potential energy surfaces (PESs) are reported for the interaction of Xe atoms with OH radicals in their ground X2Π and excited A2Σ+ states, together with the non-adiabatic couplings between them. The 2A′ excited potential features a very deep well at the collinear Xe–OH configuration whose minimum corresponds to the avoided crossing with the 1A′ PES. It is therefore expected that, as with collisions of Kr + OH(A), electronic quenching will play a major role in the dynamics, competing favorably with rotational energy transfer within the 2A′ state. The surfaces and couplings are used in full three-state surface-hopping trajectory calculations, including roto-electronic couplings, to calculate integral cross sections for electronic quenching and collisional removal. Experimental cross sections, measured using Zeeman quantum beat spectroscopy, are also presented here for comparison with these calculations. Unlike similar previous work on the collisions of OH(A) with Kr, the surface-hopping calculations are only able to account qualitatively for the experimentally observed electronic quenching cross sections, with those calculated being around a factor of two smaller than the experimental ones. However, the predicted total depopulation of the initial rovibrational state of OH(A) (quenching plus rotational energy transfer) agrees well with the experimental results. Possible reasons for the discrepancies are discussed in detail.
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    Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation.
    (iScience, 2023) Bouthelier, Antonio; Fernández-Arroyo, Lucía; Mesa-Ciller, Claudia; Cibrian, Danay; Martín-Cófreces, Noa Beatriz; Castillo-González, Raquel; Calero, Macarena; Herráez Aguilar, Diego; Guajardo-Grence, Andrea; Pacheco, Ana María; Marcos-Jiménez, Ana; Quiroga, Borja; Morado, Marta; Monroy, Francisco; Muñoz-Calleja, Cecilia; Sánchez-Madrid, Francisco; Urrutia, Andrés A.; Aragonés, Julián
    Inhibition of the heterodimeric amino acid carrier SLC7A5/SLC3A2 (LAT1/CD98) has been widely studied in tumor biology but its role in physiological conditions remains largely unknown. Here we show that the SLC7A5/SLC3A2 heterodimer is constitutively present at different stages of erythroid differentiation but absent in mature erythrocytes. Administration of erythropoietin (EPO) further induces SLC7A5/SLC3A2 expression in circulating reticulocytes, as it also occurs in anemic conditions. Although Slc7a5 gene inactivation in the erythrocyte lineage does not compromise the total number of circulating red blood cells (RBCs), their size and hemoglobin content are significantly reduced accompanied by a diminished erythroblast mTORC1 activity. Furthermore circulating Slc7a5-deficient reticulocytes are characterized by lower transferrin receptor (CD71) expression as well as mitochondrial activity, suggesting a premature transition to mature RBCs. These data reveal that SLC7A5/SLC3A2 ensures adequate maturation of reticulocytes as well as the proper size and hemoglobin content of circulating RBCs.
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    Lipid nanoparticles for antisense oligonucleotide gene interference into brain border-associated macrophages.
    (Frontiers in Molecular Biosciences, 2022) Calero, Macarena; Moleiro, Lara H.; Sayd, Aline; Dorca, Yeray; Miquel-Rio, Lluis; Paz, Verónica; Robledo-Montaña, Javier; Enciso, Eduardo; Acción, Fernando; Herráez Aguilar, Diego; Hellweg, Thomas; Sánchez, Luis; Bortolozzi, Analía; Leza, Juan C.; García-Bueno, Borja; Monroy, Francisco
    A colloidal synthesis’ proof-of-concept based on the Bligh–Dyer emulsion inversion method was designed for integrating into lipid nanoparticles (LNPs) cell-permeating DNA antisense oligonucleotides (ASOs), also known as GapmeRs (GRs), for mRNA interference. The GR@LNPs were formulated to target brain border-associated macrophages (BAMs) as a central nervous system (CNS) therapy platform for silencing neuroinflammation-related genes. We specifically aim at inhibiting the expression of the gene encoding for lipocalin-type prostaglandin D synthase (L-PGDS), an anti-inflammatory enzyme expressed in BAMs, whose level of expression is altered in neuropsychopathologies such as depression and schizophrenia. The GR@LNPs are expected to demonstrate a bio-orthogonal genetic activity reacting with L-PGDS gene transcripts inside the living system without interfering with other genetic or biochemical circuitries. To facilitate selective BAM phagocytosis and avoid subsidiary absorption by other cells, they were functionalized with a mannosylated lipid as a specific MAN ligand for the mannose receptor presented by the macrophage surface. The GR@LNPs showed a high GR-packing density in a compact multilamellar configuration as structurally characterized by light scattering, zeta potential, and transmission electronic microscopy. As a preliminary biological evaluation of the mannosylated GR@LNP nanovectors into specifically targeted BAMs, we detected in vivo gene interference after brain delivery by intracerebroventricular injection (ICV) in Wistar rats subjected to gene therapy protocol. The results pave the way towards novel gene therapy platforms for advanced treatment of neuroinflammation-related pathologies with ASO@LNP nanovectors.
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    Time Series Analysis Applied to EEG Shows Increased Global Connectivity during Motor Activation Detected in PD Patients Compared to Controls.
    (Applied Sciences, 2020) Maitín, Ana María; Perezzan, Ramiro; Herráez Aguilar, Diego; Serrano, José Ignacio; Del Castillo, María Dolores; Arroyo, Aída; Andreo, Jorge; Romero Muñoz, Juan Pablo
    Background: Brain connectivity has shown to be a key characteristic in the study of both Parkinson’s Disease (PD) and the response of the patients to the dopaminergic medication. Time series analysis has been used here for the first time to study brain connectivity changes during motor activation in PD. Methods: A 64-channel EEG signal was registered during unilateral motor activation and resting-state in 6 non-demented PD patients before and after the administration of levodopa and in 6 matched healthy controls. Spectral entropy correlation, coherence, and interhemispheric divergence differences among PD patients and controls were analyzed under the assumption of stationarity of the time series. Results: During the motor activation test, PD patients showed an increased correlation coefficient (both hands p < 0.001) and a remarkable increase in coherence in all frequency range compared to the generalized reduction observed in controls (both hands p < 0.001). The Kullback–Leibler Divergence (KLD) of the Spectral Entropy between brain hemispheres was observed to increase in controls (right hand p = 0.01; left hand p = 0.015) and to decrease in PD patients (right hand p = 0.02; left hand p = 0.002) with motor activation. Conclusions: Our results suggest that the oscillatory activity of the different cortex areas within healthy brains is relatively independent of the rest. PD brains exhibit a stronger connectivity which grows during motor activation. The levodopa mitigates this anomalous performance.
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    Moulding hydrodynamic 2D-crystals upon parametric Faraday waves in shear-functionalized water surfaces.
    (Nature Communications, 2021) Kharbedia, Mikheil; Caselli, Niccolò; Herráez Aguilar, Diego; López Menéndez, Horacio; Enciso, Eduardo; Santiago, José A.; Monroy, Francisco
    Faraday waves, or surface waves oscillating at half of the natural frequency when a liquid is vertically vibrated, are archetypes of ordering transitions on liquid surfaces. Although unbounded Faraday waves patterns sustained upon bulk frictional stresses have been reported in highly viscous fluids, the role of surface rigidity has not been investigated so far. Here, we demonstrate that dynamically frozen Faraday waves—that we call 2D-hydrodynamic crystals—do appear as ordered patterns of nonlinear gravity-capillary modes in water surfaces functionalized with soluble (bio)surfactants endowing in-plane shear stiffness. The phase coherence in conjunction with the increased surface rigidity bears the Faraday waves ordering transition, upon which the hydrodynamic crystals were reversibly molded under parametric control of their degree of order, unit cell size and symmetry. The hydrodynamic crystals here discovered could be exploited in touchless strategies of soft matter and biological scaffolding ameliorated under external control of Faraday waves coherence.
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    Multiple particle tracking analysis in isolated nuclei reveals the mechanical phenotype of leukemia cells.
    (Scientifics Reports, 2020) Herráez Aguilar, Diego; Madrazo, Elena; López Menéndez, Horacio; Ramírez, Manuel; Monroy, Francisco; Redondo Muñoz, Javier
    The nucleus is fundamentally composed by lamina and nuclear membranes that enclose the chromatin, nucleoskeletal components and suspending nucleoplasm. The functional connections of this network integrate external stimuli into cell signals, including physical forces to mechanical responses of the nucleus. Canonically, the morphological characteristics of the nucleus, as shape and size, have served for pathologists to stratify and diagnose cancer patients; however, novel biophysical techniques must exploit physical parameters to improve cancer diagnosis. By using multiple particle tracking (MPT) technique on chromatin granules, we designed a SURF (Speeded Up Robust Features)-based algorithm to study the mechanical properties of isolated nuclei and in living cells. We have determined the apparent shear stiffness, viscosity and optical density of the nucleus, and how the chromatin structure influences on these biophysical values. Moreover, we used our MPT-SURF analysis to study the apparent mechanical properties of isolated nuclei from patients of acute lymphoblastic leukemia. We found that leukemia cells exhibited mechanical differences compared to normal lymphocytes. Interestingly, isolated nuclei from high-risk leukemia cells showed increased viscosity than their counterparts from normal lymphocytes, whilst nuclei from relapsed-patient's cells presented higher density than those from normal lymphocytes or standard- and high-risk leukemia cells. Taken together, here we presented how MPT-SURF analysis of nuclear chromatin granules defines nuclear mechanical phenotypic features, which might be clinically relevant.