Alberto Sols Biomedical Research Institute
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Ag/Co-bimetallic cooperation in the C-Hf functionalization of aliphatic amides with propiolic acids
No full textWe herein describe the high-valent cobalt-catalyzed C(sp3)-H functionalization of amide derivatives with silver acetylides generated in situ. The reaction proceeds under kinetic control at 60 °C, with a catalyst loading of 5 mol %. These extraordinarily mild conditions for Co-catalysis enable the synthesis of 5-(Z)-ethylidene pyrrolidin-2-one derivatives in good yield and selectivity. Density functional theory calculations have revealed a unique mechanism involving Co-Ag bimetallic species, rationalizing the nature of the catalytically active species and the role of each additiveWe thank FEDER/Ministerio de Ciencia, Innovación y Universidades–Agencia Estatal de Investigación (grants PGC2018-098660-B-I00 and PID2021-124853NB-100) for financial support. C.S.-G. thanks MINECO for a FPU predoctoral fellowship. We also thank MINECO for the financial support for the RED2022-134331-T and the Centro de Computación Científica at the Universidad Autónoma de Madrid for their generous allocation of computer time
An atomistic description of excitonic effects in the optical response of two-dimensional materials
Get PDFTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Departamento de Física de la Materia Condensada. Fecha de Lectura: 22-01-202
Differential role of DGKζ in the control of bone marrow homeostasis and the onset of aplastic anemia
Get PDFTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 29-01-2025T lymphocytes are essential components of the immune response. Recognition of the antigen by the T cell receptor (TCR) triggers a series of early events that culminate with the activation of phospholipase C gamma (PLCγ) and the generation of diacylglycerol (DAG), which together with other molecules, favors the complete activation of the T cell. In this process, additional signals such as costimulatory or cytokines are of essential importance. In the same way as the ignition mechanisms, the shutdown mechanisms are also key. In this context, diacylglycerol kinases (DGKs), a family of lipid enzymes act as negative regulators of T cell activation by catalyzing the conversion of DAG into phosphatidic acid (PA). Of the 10 isoforms described in mammals, two of them, DGKα and DGKζ, are the most abundant in T lymphocytes, where they exert specific and redundant functions in the maintenance of tolerance and the prevention of autoimmune syndromes.
Studies in aplastic anemia (AA) patients correlate the lower expression of DGKζ in bone marrow (BM) derived T lymphocytes with the severity of the disease. Those studies prompted us to carry out an in-depth characterization of the BM of DGKζ deficient mice. Our analysis identifies the BM of DGKζ deficient mice as a niche for infiltration of activated T cells. Furthermore, we describe defects in hematopoietic differentiation that suggest a specific function of DGKζ in the control of the differentiation cascade. The absence of good preclinical AA models makes the DGKζ deficient mouse a good system for the study of molecular factors that predispose to the disease.
Additionally, we studied the role of DGKζ in the control of the response to interleukin (IL-) 15, a cytokine that is very abundant in the BM and of which incorrect signaling can contribute to autoimmune processes. Our results suggest that the absence of DGKζ results in cytotoxic responses after treatment with IL-15 both in vivo and in vitro. Likewise, we identified the proteins involved in IL-15-mediated signaling, making PLCγ one of the essential elements in this process. Finally, we demonstrate how the activation phenotype previously described in the BM is abrogated in mice deficient for DGKζ and IL-15.
With all this, this doctoral thesis focuses on demonstrating the differential role of DGKζ in the maintenance of homeostasis in the BM and how its deficiency can lead to loss of tolerance in the presence of signals capable of mobilizing DA
Análisis de la Interacción Persona-Máquina para la Salud Digital
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Escuela Politécnica Superior, Departamento de Tecnología Electrónica y de las Comunicaciones. Fecha de Lectura: 17-01-2025This project
has received funding from INTER-ACTION (PID2021- 126521OB-I00 MICINN/FEDER), Human-
CAIC (TED2021-131787BI00 MICINN) and Programme of Financial Support for the Beginning of
Doctoral Studies from the Department of Electronic and Communications Technology of the UA
Analítica sanguínea en la infección urinaria febril pediátrica: consideraciones clínicas y relevancia para el diagnóstico
Get PDFTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Pediatría. Fecha de Lectura: 31-01-202
Radioterapia estereotáctica ablativa (SABR) para la oligorrecurrencia ganglionar pélvica en el cáncer de próstata
Get PDFTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de Lectura: 06-02-202
Modelo de estudio epidemiológico y analítico de posibles casos de agresión sexual atendidos en el Hospital Universitario La Paz
Get PDFTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Obstetricia y Ginecología. Fecha de Lectura: 19-02-2025El análisis de la asistencia prestada a mujeres que acuden a un hospital para el reconocimiento clínico y forense de un presunto delito contra la libertad sexual permite valorar la asistencia prestada, los resultados obtenidos e intentar determinar del perfil de la víctima. En el presente trabajo doctoral se aborda el estudio de las mujeres mayores de 12 años que acudieron al Hospital La Paz con motivo de consulta “agresión sexual” entre los años 2018 y 2020.
Se estudia información objetiva sobre los hechos (cronológicos, ubicación, contexto, relación víctima-agresor, número de agresores, acceso, consumo de tóxicos, amnesia, antecedentes de episodios previos), características epidemiológicas y médicas (edad y nacionalidad, antecedentes patológicos y ginecológicos) de la víctima y la atención médica recibida, clínica y legal, y se compara con otras investigaciones en este campo.
Entre los resultados de las variables analizadas se detecta que las agresiones sexuales se producen con mayor frecuencia de madrugada. La asistencia se realiza en su mayor parte en menos de 24 horas, de noche/madrugada, la mayoría son mujeres jóvenes y no presentan lesiones. El agresor suele estar en el entorno de la víctima -conocido de menos de 24 horas- y un factor de vulnerabilidad muy importante es el consumo abusivo de alcohol que provoca amnesia lacunar.
En la evaluación de los casos de sumisión química se obtiene mayor participación de extraños, ubicación de calle o discoteca y mayor frecuencia de múltiples agresores y amnesia lacunar posterior que en el consumo voluntario de sustancias.
Se ha detectado un importante número de trastornos psiquiátricos, principalmente ansiedad y depresión, y escaso seguimiento posterior por parte de salud mental. Por otra parte, en el ámbito de la violencia de género, se detectan víctimas muy jóvenes y con frecuencia refieren antecedentes de violencia sexual.
Considerando todas estas variables analizadas, concluiremos con la necesidad de establecer programas de prevención y detección de la violencia sexual y programas de educación sexual (con especial dedicación para la población joven).
Además de lo anterior, este estudio también se centra en examinar las ITS en esta población, lo que ha puesto de relieve la similitud de su incidencia con la población general. Ello denota una escasa transmisión de estas infecciones durante la agresión sexual y nos releva la necesidad de individualizar el tratamiento profiláctic
Career lessons from economists' life stories: Brian J. Loasby as an Exemplar
Get PDFThis paper derives career lessons for economists by examining the unusual career of Brian J. Loasby in terms of Loasby's own key ideas. Loasby's early career ran into difficulties after he chose to become a postgraduate for lifestyle rather than career reasons, with his insufficiently ambitious reference standards resulting in unduly narrow search for both options and new connections. His eventual success came because of a path-dependent process whereby he developed an organizing framework that was conducive to finding problems and making intellectual connections. It was a process in which making personal connections also had a key role, though some intellectual connections that he earlier failed to make resulted from trusting other people. In the market for contributions to knowledge, his way of branding and positioning his work in relation to management decision-making and the growth of knowledge gave it a wider appeal than would have been the case if he had aligned himself with a particular school of thought or 'heterodox economics' in genera
From unrealistic to functional optimism in illness perception: A psychometric comparison across 10 countries
Get PDFPeople's perceptions of illness and its risks influence health behaviors, including risk management and precautionary measures. Illness perception often involves unrealistic optimism, reducing infection risk perception. However, crises disrupt self-regulation and optimism due to uncontrollable situations. This study examines optimism's link to risk and illness perception during the first COVID-19 wave in 10 countries, with 7254 participants (48.1% women, mean age = 40, SD = 14.8). We used Bayesian structural equation modeling for psychometric stability and one-way ANOVAs for country comparisons. Multiple regression analyses examined the impact of optimism and demographic variables on illness perception. Significant cross-country variations emerged in illness perception and optimism. In terms of the relationship between variables, optimism correlated with increased COVID-19 risk perception, especially for negative outcomes, concern, and consistency. During crises, optimism shifted from unrealistic to functional, promoting treatment adherence, personal control, and coherence. These dimensions represent individuals' beliefs in managing illness, highlighting optimism's adaptive role in crise
Formulations based on milk fat globule membrane as delivery systems for DHA and lutein: Effects on lipid composition and immunomodulatory properties
Get PDFThe incorporation of bioactive lipids, such as docosahexaenoic acid (DHA) and lutein, into food formulations represents a significant challenge due to their chemical instability and low water solubility. This study investigated the potential of milk fat globule membrane (MFGM)-based formulations as carrier systems for DHA and lutein, comparing their lipidic composition and biological activity (cytotoxicity and immunomodulatory properties) with control formulations prepared with bile salts. Lipid characterization revealed the presence of a greater variety of lipid classes, particularly polar lipids, in the MFGM formulations than in the controls. Bioactivity studies using THP1-Lucia™ NF-κB cells demonstrated that the MFGM-lutein formulation exhibited strong immunosuppressive effects at different concentrations (1:600–1:200 dilutions in PBS), inhibiting the NF-κB pathway by 69% at the 1:200 dilution without compromising cell viability. The MFGMDHA formulation also showed significant immunosuppressive effects, but only when combined with lutein, suggesting that lutein may play a protective role in preventing DHA oxidation. In contrast, the control formulations displayed no evidence of immunosuppressive effects and high cytotoxicity. Thus, these preliminary findings suggest the potential of MFGM-based formulations as effective carrier systems of bioactive lipids, such as DHA and lutein, and contribute to advancing our understanding of their immunomodulatory potentialThis research was funded by the Spanish Ministry of Science, Innovation and Universities and Spanish Ministry of Science and Innovation. Projects: PDI2020-114821RB-I00 and PDC2021-21528-I00 MCIN/AEI//FEDER, U