Experimental in vivo models of multiple sclerosis: state of the art

Multiple sclerosis is a multifactorial and heterogeneous neurological disease; hence, several experimental animal models had to be developed to mimic the different features of human pathology. Three main classes of animal models have been developed:experimental autoimmune encephalomyelitis (EAE), cupri- zone intoxication, and Theiler’s murine encephalomyelitis virus (TMEV) infection. The EAE model is the most versatile as it allows the reproduction of different patterns of multiple sclerosis; it is mostly relevant for relapsing-remitting multiple sclerosis and has allowed the development of several first-line, disease-modifying drugs for the treatment of multiple sclerosis. The other two models are less flexi- ble than the EAE model and, to date, have not led to the discovery of any clinically relevant therapies. The cuprizone model mostly mimics the acute and chronic courses of multiple sclerosis, and it may represent a useful tool to develop novel therapies to protect oligodendrocytes and stimulate remyelination. Finally, the TMEV infection is the reference model to specifically study viral-mediated mecha- nisms of acute and primary progressive multiple sclerosis

Narrating Cases: a Storytelling Approach to Case Study Analysis in the Field of Lifelong Learning Policies

The paper aims to discuss the narrative approach to case study analysis, drawing on the research carried out within the H2020 European Project YOUNG_ ADULLLT. It aimed to analyse Lifelong Learning (LLL) policies targeted to young adults in Europe, particularly those in situations of social exclusion, focusing on the different ways in which the policies are socially embedded in specific local contexts across Europe. By a multimethod and multilevel perspective, the research sought to explore the interplay between structural, institutional and individual levels to understand the relationship and complementarity between the LLL policies and the young people\u2019s social conditions, needs and expectations. The paper focuses on the narrative approach, namely the \u201cstorytelling strategy\u201d, adopted to examine the Lifelong Learning policies chosen as case studies in their social, political and economic realities. Different examples of storytelling and their contribution to analyse LLL policies are explored. Lastly, we critically discuss whether the narrative approach allowed to build a dense portrait able to yield the complexity and the specificity of the cases, reconstructing the story of the meaning of Lifelong Learning in different constellations. Epistemological and methodological considerations on the use of narrative approach in social science are provided, highlighting its opportunities and limits

Genes and Aggressive Behavior: Epigenetic Mechanisms Underlying Individual Susceptibility to Aversive Environments

Over the last two decades, the study of the relationship between nature and nurture in shaping human behavior has encountered a renewed interest. Behavioral genetics showed that distinct polymorphisms of genes that code for proteins that control neurotransmitter metabolic and synaptic function are associated with individual vulnerability to aversive experiences, such as stressful and traumatic life events, and may result in an increased risk of developing psychopathologies associated with violence. On the other hand, recent studies indicate that experiencing aversive events modulates gene expression by introducing stable changes to DNA without modifying its sequence, a mechanism known as “epigenetics”. For example, experiencing adversities during periods of maximal sensitivity to the environment, such as prenatal life, infancy and early adolescence, may introduce lasting epigenetic marks in genes that affect maturational processes in brain, thus favoring the emergence of dysfunctional behaviors, including exaggerate aggression in adulthood. The present review discusses data from recent research, both in humans and animals, concerning the epigenetic regulation of four genes belonging to the neuroendocrine, serotonergic and oxytocinergic pathways—Nuclear receptor subfamily 3-group C-member 1 (NR3C1), oxytocin receptor (OXTR), solute carrier-family 6 member 4 (SLC6A4) and monoamine oxidase A (MAOA)—and their role in modulating vulnerability to proactive and reactive aggressive behavior. Behavioral genetics and epigenetics are shedding a new light on the fine interaction between genes and environment, by providing a novel tool to understand the molecular events that underlie aggression. Overall, the findings from these studies carry important implications not only for neuroscience, but also for social sciences, including ethics, philosophy and law

Arquitectura de servicios web basada en modelos: especificación gráfica y derivación automática del código

MDA provee un conjunto de herramientas para especificar un sistema independientemente de la plataforma de implementación, elegir una plataforma para el sistema, y transformar las especificaciones de los sistemas a la misma. Todo esto se complementa con los objetivos de portabilidad, interoperabilidad y reusabilidad. Dentro de la aproximación MDA, tiene especial relevancia la existencia de transformaciones entre modelos. MDA permite reducir los costos de desarrollo de software, adaptarlo rápidamente a los cambios tecnológicos y a cambios en los requisitos, siempre manteniendo la consistencia entre los modelos y el código del software y así dando el protagonismo de la conducción del diseño y desarrollo a los modelos. Spring es un framework basado en J2EE que implementa el modelo MVC. Su gran ventaja es la modularidad definiendo funcionalidad e integrando diferentes tecnologías. Y los Web Services nos permiten comunicar diferentes aplicaciones de forma distribuida entre sí. Decidimos que MDA nos planteó una ágil y eficiente manera de definir nuestros modelos con la utilización del lenguaje UML, agregando información específica para poder generar la estructura de servicios y así mediante una serie de transformaciones derivar al esqueleto de servicios, interfaces y daos en el código correspondiente. De esta manera se logra reducir tiempos, errores y prestar una disposición para el buen uso que ofrece el framework.Facultad de Informátic

Arquitectura de servicios web basada en modelos: especificación gráfica y derivación automática del código

MDA provee un conjunto de herramientas para especificar un sistema independientemente de la plataforma de implementación, elegir una plataforma para el sistema, y transformar las especificaciones de los sistemas a la misma. Todo esto se complementa con los objetivos de portabilidad, interoperabilidad y reusabilidad. Dentro de la aproximación MDA, tiene especial relevancia la existencia de transformaciones entre modelos. MDA permite reducir los costos de desarrollo de software, adaptarlo rápidamente a los cambios tecnológicos y a cambios en los requisitos, siempre manteniendo la consistencia entre los modelos y el código del software y así dando el protagonismo de la conducción del diseño y desarrollo a los modelos. Spring es un framework basado en J2EE que implementa el modelo MVC. Su gran ventaja es la modularidad definiendo funcionalidad e integrando diferentes tecnologías. Y los Web Services nos permiten comunicar diferentes aplicaciones de forma distribuida entre sí. Decidimos que MDA nos planteó una ágil y eficiente manera de definir nuestros modelos con la utilización del lenguaje UML, agregando información específica para poder generar la estructura de servicios y así mediante una serie de transformaciones derivar al esqueleto de servicios, interfaces y daos en el código correspondiente. De esta manera se logra reducir tiempos, errores y prestar una disposición para el buen uso que ofrece el framework.Facultad de Informátic

Gene Expression Analysis of an EGFR Indirectly Related Pathway Identified PTEN and MMP9 as Reliable Diagnostic Markers for Human Glial Tumor Specimens

In this study the mRNA levels of five EGFR indirectly related genes, EGFR, HB-EGF, ADAM17, PTEN, and MMP9, have been assessed by Real-time PCR in a panel of 37 glioblastoma multiforme specimens and in 5 normal brain samples; as a result, in glioblastoma, ADAM17 and PTEN expression was significantly lower than in normal brain samples, and, in particular, a statistically significant inverse correlation was found between PTEN and MMP9 mRNA levels. To verify if this correlation was conserved in gliomas, PTEN and MMP9 expression was further investigated in an additional panel of 16 anaplastic astrocytoma specimens and, in parallel, in different human normal and astrocytic tumor cell lines. In anaplastic astrocytomas PTEN expression was significantly higher than in glioblastoma multiforme, but no significant correlation was found between PTEN and MMP9 expression. PTEN and MMP9 mRNA levels were also employed to identify subgroups of specimens within the different glioma malignancy grades and to define a gene expression-based diagnostic classification scheme. In conclusion, this gene expression survey highlighted that the combined measurement of PTEN and MMP9 transcripts might represent a novel reliable tool for the differential diagnosis of high-grade gliomas, and it also suggested a functional link involving these genes in glial tumors

Presentación: La hospitalidad en el cruce del diálogo entre filosofía y literatura

As part of a series of interdisciplinary studies developed within the framework of the Research Project on hospitality as encounter and challenge, carried out between the Faculty of Philosophy and Literature and the Faculty of Theology of our university, which have been published throughout 2019 (Letras No. 80 and Sapientia No. 246), 2020 (Teología No. 131) and 2021 (Teología No. 134 and 135), this dossier presents the work of six authors in whose articles philosophical reflection and literature intersect.Como parte de una serie de estudios interdisciplinarios desarrollados en el marco del Proyecto de Investigación sobre la hospitalidad como encuentro y desafío, llevado a cabo entre la Facultad de Filosofía y Letras y la Facultad de Teología de nuestra universidad, los cuales se han ido publicando a lo largo de 2019 (Letras Nro. 80 y Sapientia Nro. 246), de 2020 (Teología Nro. 131) y de 2021 (Teología Nro. 134 y 135), en este dossier se presentan recorridos de seis autores en cuyos artículos se entrecruzan la reflexión filosófica y la literatura

MIK2 is a candidate gene of the S-locus for sporophytic self-incompatibility (SSI) in chicory (Cichorium intybus, Asteraceae)

The Cichorium genus offers a unique opportunity to study the sporophytic self incompatibility (SSI) system, being composed of species characterized by highly efficient SI (C. intybus) and complete self compatibility (C. endivia). The chicory genome was used to map 7 previously identified SSI locus-associated markers. The region containing the S locus was restricted to an 4 M bp window on chromosome 5. Among the genes predicted in this region, MDIS1 INTERACTING RECEPTOR LIKE KINASE 2 (MIK2) was promising as a candidate for SSI. Its ortholog in Arabidopsis is involved in pollen stigma recognition reactions, and its protein structure is similar to that of S-receptor kinase (SRK), a key component of the SSI in the Brassica genus. The sequencing of MIK2 in chicory and endive accessions revealed two contrasting scenarios. In C. endivia, MIK2 was fully conserved even comparing different botanical varieties (smooth and curly). In C. intybus, 387 SNPs and 3 INDELs were identified when comparing accessions of different biotypes from the same botanical variety (radicchio). The SNP distribution throughout the gene was uneven, with hypervariable domains preferentially localized in the LRR-rich extracellular region, putatively identified as the receptor domain. The gene was hypothesized to be under positive selection, as the nonsynonymous mutations were more than double the synonymous ones (dN / dS = 2.17). An analogous situation was observed analyzing the first 500 bp of the MIK2 promoter: no SNPs were observed among the endive samples, whereas 44 SNPs and 6 INDELs were detected among the chicory samples. Further analyses are needed to confirm the role of MIK2 in SSI and to demonstrate whether the 23 species-specific nonsynonymous SNPs in the CDS and/or the species-specific 10 bp INDEL found in a CCAAT box region of the promoter are responsible for the contrasting sexual behaviors of the two species