Alberto Sols Biomedical Research Institute
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Exploring mitochondrial function in B cells during the humoral immune response
Get PDFTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 10-01-2025La dinámica y la función de las células B durante el desarrollo de la médula ósea y sus funciones efectoras inmunitarias periféricas tras el encuentro con el antígeno sitúan a las células B como un tipo celular altamente dinámico con diferentes requisitos metabólicos a lo largo de su vida. Tras la inmunización, las células B se activan en los órganos linfoides secundarios dando lugar a la reacción del centro germinal (CG). El CG requiere un suministro bioenergético único para hacer frente a las demandas energéticas de la activación, proliferación y diferenciación de las células B en células plasmáticas (PC) y células B de memoria (MBC). Se ha descrito que la señalización desequilibrada que desencadena el remodelado metabólico altera la homeostasis del CG.
Las mitocondrias se conciben como actores centrales de la homeostasis metabólica de las células B. Aunque las mitocondrias se remodelan tras la estimulación de los receptores de las células B mediada por antígenos en consonancia con una remodelación metabólica, la función mitocondrial en las células B, y especialmente durante la dinámica del CG, sigue siendo poco conocida. Las bases actuales de la regulación inmunometabólica de la función de las células B se han establecido en modelos de ratón mediante la alteración genética de reguladores metabólicos clave como RRAS2 o PKCb, que en última instancia afecta a la remodelación mitocondrial y al remodelado metabólico a través del eje PI3K-Akt-mTORC1.
Para comprender mejor el papel de las mitocondrias en la función de las células B, hemos generado ratones con deficiencia específica Tfam en células B, un factor de transcripción (FT) codificado en el núcleo y necesario para la biogénesis mitocondrial. Los ratones knock-out condicional (KO) de Tfam bajo el promotor de MB1, un gen expresado tempranamente en las primeras fases del desarrollo de las células B, da lugar a un defecto en el desarrollo de las células B a través de un bloqueo en la transición de células B Pro a Pre B. Aunque disminuye la producción de células B, las células B maduras pueblan normalmente los órganos linfoides periféricos. Tras la activación de células B in vivo por inmunización con antígeno T dependiente (TD), los ratones KO muestran un bloqueo de la reacción de CG en el estadio Pre-CG con una regulación al alza de Bcl6 comprometida. La generación de efectores de la respuesta humoral se ve afectada, bloqueándose la generación de células plasmáticas de larga vida (LLPC) y MBC dependientes del centro germinal. Asimismo, el colapso del CG resulta en la generación exacerbada de MBC no-CG y una población doble negativa (DN) con características fenotípicas de células B relacionadas con el envejecimiento (ABCs), sellos distintivos de una respuesta inmune envejecida.
Inesperadamente, la reacción de CG bloqueada en ratones Tfam KO no está causada por defectos en el suministro bioenergético, sino que está asociada a un defecto en la remodelación del compartimento lisosomal en las células B. Tras el encuentro con el antígeno, el fallo en la remodelación mitocondrial desencadena una respuesta retrógrada, que afecta a la función lisosomal y a la capacidad de degradación del antígeno por parte de las células B, con la consiguiente disminución de la presentación del antígeno a las células T.
Así pues, nuestros resultados podrían describir una función mitocondrial independiente a la generación de ATP para la regulación de los lisosomas y la posterior presentación de antígenos en los linfocitos B durante la reacción de CG, cuya alteración se manifiesta como una respuesta inmunitaria envejecidaThe research is supported by the grants RTI2018-101586-A-100 and PID2021-1262980B-100, which are financed by the Ministerio de Ciencia, Innovación y Universidade
Grassland strip width of transhumance drove roads as a key factor of ant biodiversity in agrarian landscapes of central Spain
Get PDFOngoing intensification and fragmentation of European agricultural landscapes have accelerated biodiversity loss and disrupted essential ecological functions. In the Mediterranean region, drove roads, traditionally used for livestock movement, serve a critical ecological role by supporting connectivity and acting as reservoirs for local biodiversity. However, their effectiveness as biodiversity reservoirs is closely linked to the width of their grassland habitats, which are increasingly threatened by land-use changes, such as the abandonment of transhumance, habitat degradation, and invasion by neighbouring croplands. This study evaluated the effect of natural habitat availably, measured as grassland strip width and dirt road width, and surrounding landscape composition on the capacity of drove roads to support ant taxonomic and functional diversity in intensively farmed landscapes in central Spain. We characterized ant assemblages across 20 drove road sections based on taxonomic diversity (species richness and diversity, species composition, and nestedness pattern) and functional diversity (FD). Our results reveal that grassland strip width, rather than landscape composition, is the main factor influencing the role of drove roads as local reservoirs of ant taxonomic and functional diversity. Wider grassland strips supported species-rich and diverse communities and a broader range of functional traits compared to narrower corridors, which only contained a subset of species, predominantly generalists. This study underscores the importance of preserving the natural width of drove roads to maintain biodiversity and ecological functions, particularly in intensively managed agricultural landscapesThis work was supported by the European Union Life Program (project LIFE CAÑADAS, LIFE 18 NAT/ES/000930). The authors thank the Dirección General de Agricultura, Ganadería y Alimentación (Consejería de Medio Ambiente, Ordenación del Territorio y Sostenibilidad, Comunidad de Madrid) for providing us permission to work in protected drove roads. Special thanks to Jorge Chicote Carreras for his assistance in the fiel
Integración de las tecnologías de la información y comunicación en los planteles educativos
Get PDFTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Formación del Profesorado y Educación, Departamento de Didácticas Específicas. Fecha de Lectura: 13-02-2025La investigación se enfocó en la determinación de la incorporación de las tecnologías de la información y comunicación en los planteles educativos de la ciudad de Loja. La metodología se basó en un diseño de investigación no experimental, con un enfoque asumido cuantitativo y el método deductivo–inductivo. La población del estudio está conformada por un total de 675 informantes, universo que está integrado por directivos de instituciones, padres y docentes. Se aplicó la técnica de la encuesta, mediante cuestionarios como instrumentos, se someten a un proceso de validación ante expertos en la materia. Culminada esta fase se procede al trabajo de campo para su aplicación. Los hallazgos arrojaron un bajo nivel de acceso a las tecnologías de la información de los planteles educativos fiscales, fiscomisionales y particulares; por lo cual, se concluyó que un bajo nivel es debido a las deficiencias vinculadas con lo que el 60,0% de los encuestados indicaron que la institución no tiene su propia página web pública, ni cuenta con un entorno virtual de aprendizaje desde fuera del centro para los estudiantes, no se puede acceder a ese entorno virtual de aprendizaje desde fuera del centro para los docentes, no se pueden acceder a ese entorno virtual de aprendizaje desde fuera del centro para los padres, el 100% de los encuestados indicaron que la institución no tiene acceso a ese entorno virtual de aprendizaje desde fuera del centro fuera del horario escolarThe investigation focused on determining the incorporation of information and communication technologies in the educational establishments of the city of Loja. The methodology was based on a non-experimental research design, with an assumed quantitative approach, the deductive-inductive method, the study population will be made up of a total of 675 informants, a universe that is made up of directors of institutions, parents and teachers, the survey technique was applied, using questionnaires as instruments, they are submitted to a validation process before experts in the field, after this phase we proceed to the field work for its application. The findings showed a low level of access to information technologies of fiscal, fiscal and private educational establishments, for which it was concluded that a low level due to the deficiencies related to which 60.0% of the respondents indicated which institution does not have its own public web page, the institution does not have a virtual learning environment from outside the student center, this virtual learning environment cannot be accessed from outside the center teachers, cannot be accessed In this virtual learning environment from outside the parent center, 100% of the respondents indicated that the institution does not have access to this virtual learning environment from outside the center outside of school hour
Finiteness of leaps in the sense of Hasse-Schmidt of unibranch curves in positive characteristic
No full textWe prove that the set of leaps of the chain of m-integrable derivations of a curve X over a perfect field with geometrically unibranch singularities is finite. This result is a consequence of an affirmative answer to Seidenberg's question of extending, in positive characteristic, Hasse–Schmidt derivations of finite length of the local rings of X to their integral closure
Memoria de investigación 2023. Facultad de Derecho, UAM
No full textDifusión y análisis de la actividad investigadora realizada anualmente por los investigadores de los departamentos de la Facultad de Derech
Mechanical forces and ligand binding modulate Pseudomonas aeruginosa PilY1 mechanosensitive protein
No full textSurface sensing initiates bacterial colonization of substrates. The protein PilY1 plays key roles during this process—surface de-tection, host adhesion, and motility—while experiencing mechanical perturbations of varying magnitudes. In Pseudomonas aeruginosa, the adhesion and motility functions of PilY1 are associated with integrin and calcium ligand-binding sites; however, how mechanical forces influence PilY1’s dynamics and its interactions with these ligands remain unknown. Here, using single-molecule magnetic tweezers, we reveal that PilY1 is a mechanosensor protein that exhibits different behaviors depending on the force load. At high forces (>20 pN), PilY1 unfolds through a hierarchical sequence of intermediates, whose mechanical stability increases with calcium binding. This enhanced stability may help counteract type IV pilus retraction forces during motility. At low forces (<7 pN), we identify the dynamics of the integrin-binding domain, which is reminiscent of the behavior of mechanosensor proteins. Integrin binding induces a force-dependent conformational change in this domain, shortening its unfolded extension. Our findings suggest that PilY1 roles are force-and ligand-modulated, which could entail a mechanical-based compartmentalization of its functionsThis project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 101028879. This work was supported by and performed at the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC0102), the UK Medical Research Council (CC0102), and the Wellcome Trust (CC0102). F.J.Cao-Garcia was supported by the Spanish Ministry of Economy and Competitiveness and the
European Regional Development Fund (RTI2018-095802-B-I00), the Spanish Ministry of Science, Innovation and Universities (PID2023-148319NB-I00), and the Universidad Complutense de Madrid (UCM) (PR12/24-31558). J.E.Walker and S.Board were supported by the Leverhulme Trust (RL 2016-015). A.Alonso-Caballero and this work were supported by a European Commission
Marie Sklodowska-Curie fellowship (NIOBMT-101028879), the project PID2023-146082NA-I00 funded by MICIU/AEI/10.13039/501100011033 and by ERDF/EU, and the grant RYC2021-031965-I (MICIU/AEI/10.13039/501100011033
and European Union NextGenerationEU/PRTR
Key adsorbents and influencing factors in the adsorption of micro- and nanoplastics: A review
No full textMicroplastics and nanoplastics (MNPs) are emerging contaminants in drinking water sources that pose serious risks to human health and ecosystems. Several removal strategies, such as adsorption, exist but present challenges for their industrial scalability. This review provides a concise overview of MNP adsorption mechanisms and highlights the limited but critical exploration of column adsorption in the literature, emphasizing its importance for large-scale applications. Special attention is given to carbon-based materials due to their cost-effectiveness, environmental friendliness and sustainability. Other adsorbents (e.g., metal-organic frameworks, clays) are also discussed for their promising performance in realistic water matrixes. To predict and optimize the efficiency of adsorbents, leading simulation models are reviewed. Taken together, this work provides a comprehensive overview of the fundamental factors, such as adsorption mechanisms, adsorbent selection and experimental conditions, to optimize MNP adsorption. By highlighting the underexplored area of column-based processes, it provides valuable information to advance adsorption as a viable industrial-scale solution for MNP contamination
Sex-specific molecular hallmarks point to increased atherogenesis susceptibility in male senescence-accelerated mice
No full textAims: The senescence-accelerated mouse (SAM) model has been extensively used to study neurological alterations associated with aging. The SAM model has also proved to be useful in the study of vascular aging, but there is still work to be done to better define its utility as a model of atherosclerosis, since contradictory data have been published and sex seems to play a crucial role in potential divergences. Materials and methods: With this in mind, we aimed to decipher the molecular mechanisms underlying early vascular aging on SAMP8 mice, analyzing the aorta of 10 months-old animals by means of in-depth proteomic analysis, considering sex-specific differences. Validation of the results obtained were performed by western blot in an independent cohort of mice, as well as in human aortic smooth muscle cells (HASMC). Besides, an exhaustive lipoprotein and glycoprotein analysis was performed in blood plasma. Key findings: Distinct proteomic, lipoprotein and glycoprotein profiles have been found in SAMP8 mice, according to sex. Male SAMP8 mice showed signs of increased atherogenesis susceptibility due to several sex-specific alterations: 1) increased number of VLDLs, as well as in their cholesterol and TG content; 2) upregulation of inflammatory glycoproteins in plasma; and 3) increased features of SASP and vascular calcification: upregulation of exocytic vesicular transport and downregulation of the protein Gas6. On the contrary, female mice showed a much better proteomic and lipoprotein profile. Significance: The results obtained suggest that male SAMP8 mice will be more susceptible to develop atherosclerosis under a HFD than female miceThis work was funded by grants from Programa de Atracción de Talento (Modalidad 1), Comunidad Autónoma de Madrid 2023-5AIND-28938 and Ministerio de Ciencia, e Innovación y Universidades y Fondo Europeo de Desarrollo Regional PID2020-115590RB-I00; PID2021-126274OB-I00; CNS2022-135368 and PID2023-147378OB-I00. Dr. Ibone Rubio was supported by Ayudas para la contratación de ayudantes de investigación y técnicos de laboratorio PEJ-2023-AI/SAL-GL-27307. Miriam M. Rodríguez de Lope was supported by Ayudas para la realización del Programa Investigo, Comunidad de Madrid (INV/09-PIN1-00013.4/2022). Licia Shamoon is a recipient of FPI Universidad Autónoma de Madrid (SFPI / 2020-00053
Is immediate arterial cord blood sampling necessary in vigorous term neonates? A retrospective study of the impact of cord clamping timing on cord blood gas analysis
Get PDFObjective: To evaluate whether immediate arterial cord blood sampling is necessary in vigorous term neonates and to assess the clinical impact of cord clamping timing on umbilical cord blood gas values. Study design: This retrospective observational study included 1156 term, singleton, low-risk vaginal births with f irst-minute Apgar scores >8, occurring across three institutional periods with differing cord clamping protocols (2022–2024). Umbilical artery or venous blood gas parameters were analyzed in relation to cord clamping timing: <60 s, 60–180 s, and ≥180 s. Results: Statistically significant differences in umbilical artery pH were observed among the clamping groups (p < 0.001), with greater acidosis noted when arterial sampling was performed after more than three minutes. However, all values remained within physiological limits. Higher 5-minute Apgar scores were associated with delayed clamping, suggesting improved neonatal adaptation. The rate of unsuccessful arterial sampling did not increase significantly with longer delays in cord clamping. Conclusion: Immediate arterial cord blood sampling may not be necessary in vigorous term neonates following uncomplicated vaginal birth. Delayed cord clamping does not diminish the clinical value of cord blood gas analysis and appears to support neonatal transition. These findings support the safety of postponing sampling in favor of preserving a physiological birth proces