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[Abstract]: The present thesis addresses the population, conservation and evolutionary genetics of Erebia palarica Chapman, 1905, a narrow endemic butterfly restricted to the mountains of northwest Iberia.The dissertation undertakes (1) the phylogeography of the species by integrating genetics, morphometrics and ecological niche modelling. The result is a reconstruction of the evolutionary history of E. palarica in the context of Pleistocene glaciations. Next, the dissertation presents (2) an insight into the conservation status of E.palarica, as obtained from the combination of genetic and capture release-recapture data gathered in 2021 in a relatively isolated locality in Serra do Courel (NW Spain) as well as the application of IUCN criteria at whole distribution scale. Finally, the project addresses (3) a comparative study regarding the speciation of E. palarica and its sister taxa E. meolans (Prunner, 1789). The differentiation and putative reproductive barriers between both species are discussed, as stemmed from the phylogeny, Wolbachia infection, karyotypes, wing size and genitalia morphologies. Altogether, the case of E. palarica exemplifies the genetic dynamics and conservation needs of both endemic and montane taxa, while highlighting the threats faced by wild insect populations and the importance of implementing a multidisciplinary approach in conservation biology., [Resumen]: Esta tesis estudia la genética de poblaciones, de la conservación y evolutiva de la mariposa Erebia palarica Chapman, 1905, endemismo ibérico restringido a las montañas del noroeste peninsular. El proyecto aborda (1) la filogeografía de la especie, integrando análisis genéticos, morfometría y modelado de nicho ecológico. Como resultado, se reconstruye su historia evolutiva, enmarcándola en las glaciaciones del Pleistoceno. Seguidamente, se presenta (2) una visión del estado de conservación de E. palarica, apoyada en datos genéticos y de captura marcaje-recaptura (recogidos en 2021 en una localidad relativamente aislada en Serra do Courel, N.O. España) y en la aplicación de los criterios de la UICN al total de la distribución. Finalmente, se analiza (3) el proceso de especiación de E. palarica y su especie hermana,E. meolans (Prunner, 1789), abordando la diferenciación y posibles barreras reproductoras entre ambas mediante el análisis de su filogenia, infección por Wolbachia, cariotipo, tamaño alar y morfología genital. En su conjunto, el caso de E. palarica ejemplifica la dinámica genética y necesidades de conservación de las especies endémicas y de montaña, destacando las amenazas a las que se enfrentan las poblaciones silvestres de insectos y la importancia de implementar enfoques multidisciplinarios en biología de la conservación., [Resumo]: Esta tese estuda a xenética de poboacións, da conservación e evolutiva da bolboreta Erebia palarica Chapman, 1905, endemismo ibérico restrinxido ás montañas do noroeste peninsular. O proxecto aborda (1) a filoxeografía da especie, integrando análises xenéticas, morfometría e modelado de nicho ecolóxico. Como resultado reconstrúese a súa historia evolutiva, enmarcándoa nas glaciacións do Pleistoceno. Seguidamente, preséntase (2) unha visión do estado de conservación de E. palarica, apoiada en datos xenéticos e de capturamarcaxe-recaptura (recollidos en 2021 nunha localidade relativamente illada na Serra do Courel, N.O. España), e na aplicación dos criterios da UICN ao total da distribución. Finalmente, analízase (3) o proceso de especiación de E. palarica e a súa especie irmá, E. meolans (Prunner, 1789), abordando a diferenciación e posibles barreiras reprodutoras entre ambas mediante a análise da súa filoxenia, infección por Wolbachia, cariotipo, tamaño alar e morfoloxía xenital. No seu conxunto, o caso de E. palarica exemplifica a dinámica xenética e as necesidades de conservación das especies endémicas e de montaña, salientando as ameazas ás que se enfrontan as poboacións silvestres de insectos e a importancia de implementar enfoques multidisciplinarios na bioloxía da conservación.

An estimated 60% of melanoma patients develop melanoma brain metastases(MBMs). However, the molecular factors that govern the growth of MBMs are still unknown. The excitatory neurotransmitter glutamate has been shown to control the proliferation of various types of cancer cells within the brain parenchyma, but the cellular sources and molecular mechanisms involved in this process remain unclear. By their well-known role in inhibiting synaptic glutamate release, cannabinoid CB1 receptors (CB1Rs) located on glutamatergic nerve terminals are conceivably well-positioned to control the growth of MBMs. In silico data mining in cancer-genome atlases and in vitro studies with melanoma cell lines supported that a glutamate-NMDA receptor axis drives melanoma cell proliferation. Strikingly, grafting melanoma cells into the brain of mice lacking CB1Rs selectively in glutamatergic neurons increased tumour size and concomitantly activated NMDA receptors on tumour cells. Altogether, our findings reveal an unprecedented role of neuronal CB1Rs in controlling MBMs., Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Químicas, Instituto Universitario de Investigación en Neuroquímica (IUIN), Universidad Complutense de Madrid, Fac. de Ciencias Biológicas, TRUE, pub

Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future., Ministerio de Economía y Competitividad, Ministerio de Ciencia, Innovación y Universidades, Ministerio de Ciencia e Innovación (MCIN) / AEI /10.13039/501100011033, Comunidad de Madrid, Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Biológicas, Fac. de Ciencias Químicas, TRUE, pub

The new trends in education increase the need for personalized course material. However, the creation of material for different groups of students requires human efforts. Moreover, changes in the contents and in the learner’s knowledge implies modifications in the course material. The current paper presents a general organization of the course contents that facilitates the creation of personalized learning material. The adaptation of the knowledge organization proposed to a first-year university course is also described., Objectius de Desenvolupament Sostenible::4 - Educació de Qualitat, Postprint (published version)