Alberto Sols Biomedical Research Institute
Biblos-e Archivo. Repositorio Institucional de la UAMNot a member yet
65432 research outputs found
Sort by
A general and biomedical perspective of viral quasispecies
Get PDFViral quasispecies refers to the complex and dynamic mutant distributions (also termed mutant spectra, clouds, or swarms) that arise as a result of high error rates during RNA genome replication. The mutant spectrum of individual RNA virus populations is modified by continuous generation of variant genomes, competition and interactions among them, environmental influences, bottleneck events, and bloc transmission of viral particles. Quasispecies dynamics provides a new perspective on how viruses adapt, evolve, and cause disease, and sheds light on strategies to combat them. Molecular flexibility, together with ample opportunity of mutant cloud traffic in our global world, are key ingredients of viral disease emergences, as exemplified by the recent COVID-19 pandemic. In the present article, we present a brief overview of the molecular basis of mutant swarm formation and dynamics, and how the latter relates to viral disease and epidemic spread. We outline future challenges derived of the highly diverse cellular world in which viruses are necessarily installe
Expanding the chemical space for antiviral discovery: The potential of twistenediones
Get PDFDespite significant progress in drug discovery, there remains an urgent need to identify new structures capable of targeting drug-resistant diseases, as well as novel pathogens, to address the growing challenges in global health. This work highlights the underexplored potential of twistane-like structures as promising candidates for drug development, particularly as antiviral agents. We provide the first comprehensive study of their antiviral activity, in particular against SARS-CoV-2. We report the synthesis of a family of chiral indolyl-twistenediones, with the separation and characterization of both enantiomers via chiral semipreparative HPLC. The absolute configurations were determined using experimental and theoretical ECD techniques, supported by DFT calculations. A detailed biological study of their antiviral activity against various pathogenic RNA viruses demonstrates selective efficacy against members of the Coronaviridae family, specifically targeting a post-entry step in the viral replication cycle. Further investigation revealed a remarkable chiral distinction in the antiviral activity between the two enantiomers, opening new avenues for research in the 3D space of chiral cage compoundsWe thank MICINN (Grant PID2023-146801NB-C32, PID2023-146801NB-C31, PID2020-113059GB-C22, PID2021-1248553NB100), the Comunidad de Madrid (S2022/BMD-7403 RENIM-CM) co-financed by the European Structural and Investment Fund for financial support. This study was supported by Spanish National Research Council (PIE-RD-COVID-19 ref. E202020E079 and PIE_CNB_SC Ref. 202320E187 to the CNB-CSIC). This research work was also funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global). We acknowledge R. Molenkamp (Erasmus University Medical Center, Rotterdam, The Netherlands; participant of the EU-funded EVA-GLOBAL project, grant agreement 871029) for the SARS-CoV-2 strain NL/ 2020 virus; Dr. Pei-Yong Shi (UTMB; Galveston, TX,USA) for the WNV (NY99) plasmid construct, Dr. Rodriguez (CNB-CSIC, Madrid, SPAIN) for the VSV-GFP virus, Dr. Volker Thiel (U. of Lausanne, CH) for the hCoV-229E-GFP virus and Dr. Enjuanes (CNB-CSIC, Madrid, SPAIN) for the MERS-CoV-EMC12 virus. Paula Bueno is supported by PIPF2022/SAL-GL-25488 fellowship from Comunidad de Madri
Field-induced antiferromagnetic correlations in a nanopatterned van der waals ferromagnet: a potential artificial spin ice
Get PDFNano-patterned magnetic materials have opened new venues for the investigation of strongly correlated phenomena including artificial spin-ice systems, geometric frustration, and magnetic monopoles, for technologically important applications such as reconfigurable ferromagnetism. With the advent of atomically thin 2D van der Waals (vdW) magnets, a pertinent question is whether such compounds could make their way into this realm where interactions can be tailored so that unconventional states of matter can be assessed. Here, it is shown that square islands of CrGeTe3 vdW ferromagnets distributed in a grid manifest antiferromagnetic correlations, essential to enable frustration resulting in an artificial spin-ice. By using a combination of SQUID-on-tip microscopy, focused ion beam lithography, and atomistic spin dynamic simulations, it is shown that a square array of CGT island as small as 150 × 150 × 60 nm3 have tunable dipole–dipole interactions, which can be precisely controlled by their lateral spacing. There is a crossover between non-interacting islands and significant inter-island anticorrelation depending on how they are spatially distributed allowing the creation of complex magnetic patterns not observable at the isolated flakes. These findings suggest that the cross-talk between the nano-patterned magnets can be explored in the generation of even more complex spin configurations where exotic interactions may be manipulated in an unprecedented wayThis work was supported by the European Research Council (ERC) Foundation grant No. 802952 and the Israel Science Foundation (ISF) Grant Nos. 645/23, 586/22, 862/19, 576/21. The international collaboration on this work was fostered by the EU-COST Action CA21144. H. Steinberg acknowledges funding provided by the DFG Priority program grant 443404566 and Israel Science Foundation (ISF) grant 861/19. O. Millo is grateful for support from the Academia Sinica \u2013 Hebrew University Research Program, the ISF grant no. 576/21, and the Harry de Jur Chair in Applied Science. S. Gazit acknowledges support from the ISF grant no. 586/22.\u00A0H. Suderow and E. Herrera acknowledge support from the Spanish State Research Agency (PID2023-150148OB-I00, CEX2023-001316-M, TED2021-130546B-I00) and the Comunidad de Madrid through the NANOMAGCOST-CM program (Program No.S2018/NMT-4321)
Key conservation actions for European steppes in the context of the Post-2020 Global Biodiversity Framework
Get PDFArtículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMThe Kunming–Montreal Global Biodiversity Framework (KM–GBF) envisions a world living in harmony with nature by 2050, with 23 intermediate targets to be achieved by 2030. However, aligning international policy and national and local implementation of effective actions can be challenging. Using steppe birds, one of the most threatened vertebrate groups in Europe, as a model system, we identified 36 conservation actions for the achievement of the KM–GBF targets and we singled out—through an expert-based consensus approach—ten priority actions for immediate implementation. Three of these priority actions address at least five of the first eight KM–GBF targets, those related to the direct causes of biodiversity loss, and collectively cover all the targets when implemented concurrently. These actions include (i) effectively protecting priority areas, (ii) implementing on-the-ground habitat management actions, and (iii) improving the quality and integration of monitoring programmes. Our findings provide a blueprint for implementing effective strategies to halt biodiversity loss in steppe-like ecosystems. Our approach can be adapted to other taxonomic groups and ecosystems and has the potential to serve as a catalyst for policy-makers, prompting a transition from political commitment to tangible actions, thereby facilitating the attainment of the KM–GBF targets by 2030This paper is a contribution by MD and EDC to the PTI AGRIAMBIO, partially financed by the Spanish Ministry of Agriculture. The paper contributes to the ELECTROSTEPPE Project (TED2021-130352B-I00), funded by MCIN/AEI/ https://doi.org/10.13039/501100011033 and the European Union (\u201CNextGenerationEU\u201D/PRTR)
The influence of menstrual cycle phase on neuromuscular performance and subjective perception of effort in elite football players
Get PDFThis study aimed to investigate the potential fluctuations in neuromuscular performance and
subjective perception of effort during three different phases of the menstrual cycle. Fifteen elite female football
players (age: 23.47 ± 6.14) volunteered to participate in the study. Tympanic temperature, saliva hormone
measurement, urine concentration of the luteinizing hormone and a calendar tracker were used to verify the
following phases of the menstrual cycle: early follicular phase (EFP), late follicular phase (LFP), and mid-luteal
phase (MLP). For each phase, mean concentric velocity and the rate of perceived exertion (RPE) with loads that
represented 60% and 80% of their 1RM in the half-squat, deadlift and hip thrust exercises were compared.
The counter-movement jump (CMJ) test was also performed. Overall, jump height, mean concentric velocity in
half-squat, deadlift, and hip thrust exercises with loads at 60% and 80% RM and RPE were all similar in all
menstrual cycle phases, without significant differences (p > 0.05). The results of this investigation suggest that
vertical jump, mean concentric velocity in three different exercises at different submaximal loads, and RPE for
each exercise are not affected in eumenorrheic elite female football players throughout different phases of the
menstrual cycle. The study indicated that lower limb mechanical performance in elite female football players
remain consistent across menstrual cycle phases. Coaches can confidently monitor and optimize training without
undue adjustments related to menstrual cycle
Salience effects on recall organization and spatialfrequency processing in the medial temporal lobes
Get PDFTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Anatomía, Histología y Neurociencia. Fecha de Lectura: 31-01-2025¿Qué aspectos de la cognición humana nos definen más, si no, nuestra memoria? En nuestra vida diaria hacemos uso constante de nuestro sistema de memoria, pero hay ciertos eventos que recordamos mejor que otros. En concreto, los eventos con alta carga emocional yacen en un lugar único en nuestras memorias y, a menudo, tienden a ser mejor recordados. Aun así, ¿qué ocurre con los eventos neutros que codificamos cerca en el tiempo de eventos emocionales? En el primer capítulo de esta tesis investigamos esta pregunta con un estudio comportamental combinado con modelos computacionales del recuerdo libre. Encontramos que hay una mayor tendencia hacia moverse en adelante en nuestros recuerdos después de recordar ítems con alto contenido emocional. Los siguientes capítulos de esta tesis tratan sobre el procesado que el hipocampo hace de la información visual simple, un resultado novedoso e inesperado. Con el uso de registros electrofisiológicos de pacientes con epilepsia resistentes a la medicación, encontramos que varias regiones del lóbulo medial temporal procesan distintos extremos del espectro de frecuencias espaciales. Además, esta respuesta dicotómica a las frecuencias espaciales se encuentra presente a lo largo del hipocampo, una región segregada funcionalmente según su eje anterior-posterior. También, en esta tesis, usamos distintas medidas de conectividad con el objetivo de investigar potenciales mecanismos en ondas electrofisiológicas de frecuencias bajas que unan los dos extremos de frecuencias espaciales. En el último capítulo de investigación de esta tesis, usamos la resonancia magnética funcional para hacer un estudio de seguimiento sobre nuestros resultados. Aunque los resultados no replican directamente el estudio electrofisiológico, encontramos que varias regiones del lóbulo medial temporal procesan frecuencias espaciales, cuya respuesta no sufre una fuerte modulación por distintos estímulos o demandas externas. Finalmente, presentamos un experimento de memoria para investigar si la sensibilidad a diferentes frecuencias espaciales sirve de andamio para construir y recordar nuestras memorias. En resumen, esta tesis presenta tres estudios distintos y usa distintos métodos de neuroimagen para investigar cómo nuestros recuerdos son modulados por eventos que sobresalen y presenta resultados novedosos que desafían teorías tradicionales del funcionamiento del hipocampoIf not memory, what aspects of cognition are most fundamental to our existence? We constantly make use of our memory systems in our everyday lives; however, we tend to remember some experiences differently than others. In particular, highly emotional events lay a unique place in our memories in that they are often remembered better. However, what happens to neutral information encoded near emotional events? In the first research chapter of this thesis, we explored such question with a behavioral study combined with computational models of free recall. We found that there was a stronger tendency to move forward in recall after free recalling an emotionally salient item. Next, this thesis built up on an incidental finding that the hippocampus is sensitive to low-level visual information. With the use of direct electrophysiological recordings from medication resistant epilepsy patients, we found that various medial temporal lobe regions were sensitive to different ends of the spatial frequency spectrum. Furthermore, this dichotomous response to spatial frequency was also present along the hippocampal long axis, a functionally segregated region along its anterior-posterior axis. We employed various connectivity analyses with the goal of investigating potential mechanisms nested within low frequency oscillations to bind back the two ends of the spatial frequency spectrum. In the last research chapter of this thesis, we used functional magnetic resonance imaging to conduct a follow-up study. While the latter findings did not directly replicate those of the electrophysiological study, we did find that various medial temporal lobe regions were sensitive to spatial frequency manipulations, a finding which did not show strong modulations by stimulus type or external task demands. Lastly, we conducted a memory experiment to investigate whether the sensitivity to spatial frequency manipulations is used as a scaffold for memory building and retrieving. Overall, this thesis presents three different studies and employs multiple neuroimaging approaches to investigate how recall is shaped by salience and brings novel findings that challenge traditional views of hippocampal functionin
Salud, fenotipos metabólicos y calidad de vida asociados al exposoma: análisis para una nutrición de precisión
Get PDFTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Física Aplicada. Fecha de Lectura: 08-01-202
Metabolic flux analysis in hiPSC-CMs reveals insights into cardiac dysfunction in propionic acidemia
Get PDFPropionic acidemia is an inborn error of metabolism caused by mutations in either the PCCA or PCCB genes. Patients with propionic acidemia experience a range of complications, including life-threatening cardiac dysfunctions. However, the pathological mechanisms underlying propionic acidemia-associated cardiac diseases remain largely unknown. To gain insights into the metabolic alterations in propionic acidemia, we studied human induced pluripotent stem cell-derived cardiomyocytes generated from a patient with propionic acidemia with two pathogenic PCCA mutations (p.Cys616_Val633del and p.Gly477Glufs9*) and from a healthy individual. Using stable isotope-based metabolic fux analysis, we confrmed that the PCCA mutations lead to impaired propionyl-CoA carboxylase activity in human induced pluripotent stem cell-derived cardiomyocytes. In addition to being converted to propionylcarnitine, the accumulated propionyl-CoA can also be hydrolyzed to propionate and exported out of the cell, serving as a secondary “pressure valve” to regulate cellular propionyl-CoA levels. Interestingly, the defciency of propionyl-CoA carboxylase was found to shift fuel metabolism from fatty acid oxidation to increased glucose metabolism human in induced pluripotent stem cell-derived cardiomyocytes from patients with propionic acidemia. This metabolic switch is less energy-efcient and may contribute to the development of chronic cardiac dysfunction in patients with propionic acidemiaThis work was supported by Propionic Acidemia Foundation awards: to G.F.Z. and PAF113 to E. R., NIH R01 AA030026 and NIH R21TR005163 to X.C and G.F.Z, the Fundación Ramón Areces (XX National Call 2020) to E.R. and the MICIU/AEI/https://doi.org/10.13039/501100011033/ and ERDF A way of making Europe (PID2022-137238OB-100) to L.R.D. and E.R. Centro de Biología Molecular Severo Ochoa receives an institutional grant from Fundación Ramón Areces and is a Severo Ochoa Center of Excellence (MICIN, Award CEX2021-001154-S
Ensayos sobre tokenización de activos
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias Económicas y Empresariales, Departamento de Financiación e Investigación Comercial. Fecha de Lectura: 11-02-2025Esta tesis explora las aplicaciones e impactos de las tecnologías blockchainy Non Fungible Token(NFT) en la gestión de activos y los mercados digitales. La investi¬gación consta de tres estudios: (1) una propuesta para un sistema de gestión de ac¬tivos descentralizado basado en block chain en el arrendamiento de aeronaves com¬erciales, (2) una investigación del comportamiento descalpingen los mercados de NFT, y (3) una evaluación de las campañas de lanzamiento de tokens nativos como estrategias de adquisición de clientes en lo smercados de NFT.
Además, presentamos una visión general de la configuración de la infraestructura para la investigación en la cadena, incluyendo el uso de un nodo Ethereum de archivo completo, True Blocks, y ETLs personalizados. Discutimos los desafíos téc¬nicos encontrados y las soluciones desarrolladas durante el proceso de investigación.
Este trabajo contribuye a la comprensión de cómo las tecnologías block chainy NFT están remodelando la gestión de activos, los comportamientos del mercado y el com¬promiso de los clientes en los ecosistemas digitales. Los resultados aportan ideas a los profesionales, los responsables políticos y los investigadores en los campos en evolución de la cadena de bloques y los activos digitales, al tiempo que promueven metodologías para llevar a cabo una sólida investigación en la cadenaThis dissertation was made possible through the generous financial support of the Community of Madrid (Doctorado Industrial Nr.IND2020/SOC-17536), the Centro para el Desarrollo Tecnológico Industria l(NEOTECNr.SNEO-20201032), the Fundación Universidad Autónoma de Madrid (FUAM), in collaboration with Santander Asset Management,S.A., and the IE Business School Data Science progra