Editorial

[EN] They allow readers to understand how, through the word and the legacy of inhabitants, through educational experiences and outreach activities, architectural technology in rural areas host a wealthy folk heritage that today is valued as a sustainable resource; as much by the use of materials as by the form of being executed.Palmero, LM. (2020). Editorial. VITRUVIO - International Journal of Architectural Technology and Sustainability. 5(1):VII-VIII. https://doi.org/10.4995/vitruvio-ijats.2020.13758OJSVIIVIII5

Notch/neurogenin 3 signalling is involved in the neuritogenic actions of oestradiol in developing hippocampal neurones

10 pages. - PMID: 21251092 [PubMed - in process]The ovarian hormone oestradiol promotes neuritic outgrowth in different neuronal types, by mechanisms that remain elusive. Recent studies have shown that the Notch-regulated transcription factor neurogenin 3 controls neuritogenesis. In the present study, we assessed whether oestradiol regulates neurogenin 3 in primary hippocampal neurones. As expected, neuritogenesis was increased in the cultures treated with oestradiol. However, the neuritogenic action of oestradiol was not prevented by ICI 182,780, an antagonist of classical oestrogen receptors (ERs). Oestradiol decreased the expression of Hairy and Enhancer of Split-1, a Notch-regulated gene that negatively controls the expression on neurogenin 3. Furthermore, oestradiol increased the expression of neurogenin 3 and regulated its distribution between the neuronal cell nucleus and the cytoplasm. The effect of oestradiol on neurogenin 3 expression was not blocked by antagonists of classical nuclear ER-mediated transcription and was not imitated by selective agonists of nuclear ERs. By contrast, G1, a ligand of G protein receptor 30/G protein-coupled ER, fully reproduced the effect of oestradiol on neuritogenesis, neurogenin 3 expression and neurogenin 3 subcellular localisation. Moreover, knockdown of neurogenin 3 in neurones by transfection with small interference RNA for neurogenin 3 completely abrogated the neuritogenic actions of oestradiol and G1. These results suggest that oestradiol regulates neurogenin 3 in primary hippocampal neurones by a nonclassical steroid signalling mechanism, which involves the down-regulation of Notch activity and the activation of G protein receptor 30/G protein-coupled ER or of other unknown G1 targets. In addition, our findings indicate that neurogenin 3 participates in the neuritogenic mechanisms of oestradiol in hippocampal neurones.Peer reviewe

Active methodologies and teaching performance: a necessary relationship in the field of education

[EN] In the present communication, we present the project developed within the Teaching Innovation Group (APAC) of the Faculty of Education at the University of Burgos: “Active Methodologies and Teacher Performance: a road towards inclusion in the classroom”. The principal objective of this project is to contribute empirical evidence on the impact that the use of active methodologies has on teaching performance in the classroom. Its results are the basis for the transformation of initial teacher training, because Universities are responsible for training the teachers who will be at the forefront of schools in the 21st c. They have therefore to be offered access to the resources in their initial and lifelong education that permit change, allowing them to construct the paradigm of inclusive, sustainable, and quality education.[ES] En la presente comunicación, presentamos el proyecto desarrollado dentro del Grupo de Innovación Docente (APAC) de la Facultad de Educación de la Universidad de Burgos: "Metodologías Activas y Desempeño Docente: un camino hacia la inclusión en el aula". El objetivo principal de este proyecto es aportar evidencia empírica sobre el impacto que tiene el uso de metodologías activas en el rendimiento docente en el aula. Sus resultados son la base para la transformación de la formación inicial del profesorado, porque las universidades son responsables de la formación de los profesores que estarán a la vanguardia de las escuelas en el 21 stdo. Por lo tanto, se les debe ofrecer acceso a los recursos en su educación inicial y de por vida que permitan el cambio, permitiéndoles construir el paradigma de la educación inclusiva, sostenible y de calidad.http://ocs.editorial.upv.es/index.php/HEAD/HEAD18Luis, MI.; De La Torre Cruz, T.; Huelmo, J.; Llamazares, MC.; Ruiz, E.; Prieto, C.; Palmero, C.... (2018). Active methodologies and teaching performance: a necessary relationship in the field of education. Editorial Universitat Politècnica de València. 995-1001. https://doi.org/10.4995/HEAD18.2018.8134OCS995100

Magnetic properties of spinel-type oxides NiMn2-xMexO4

New materials, based on the well-known spinel compound NiMn2O4, have been synthesized and characterized from the magnetic point of view. The manganese cation was partially substituted in the general formula NiMn2-xMexO4 , by nonmagnetic and magnetic elements, such as Me = Ga, Zn, Ni and Cr (0 x 1). Prior to the determination of their magnetic properties, the non-substituted spinel NiMn2O4 was carefully characterized and studied as a function of the oxygen stoichiometry, based on the influence of the annealing atmosphere and quenching rate. The ferrimagnetic character was observed in all samples, with a paramagnetic-to-ferromagnetic transition temperature Tc stabilized at 110 K, and well defined long-range antiferromagnetic interactions at lower temperatures, which depend on the applied field and the substitute concentrationAuthors from Chile and O.P. thank projects Fondecyt-Chile 1020066, 7020066 and 1050178. Authors from France and Brazil thank project CAPES/COFECUB 416/03. Authors from France thank Région Bretagne for financial supportPeer reviewe

An extraordinary chiral exchange-bias phenomenon: Engineering the sign of the bias field in orthogonal bilayers by a magnetically switchable response mechanism

[EN] Isothermal tuning of both the magnitude and the sign of the bias field has been achieved by exploiting a new phenomenon in a system consisting of two orthogonally coupled films: SmCo (out-of-plane anisotropy)-CoFeB (in-plane anisotropy). This has been achieved by using the large dipolar magnetic field of the SmCo layer resulting in the pinning of one of the branches of the hysteresis loop (either the ascending or the descending branch) at a fixed field value while the second one is modulated along the field axis by varying the orientation of an externally applied magnetic field. This means the possibility of controlling the sign of the bias field in a manner not reported to date. Moreover, modulation of the bias field strength is possible by varying the thickness of a spacer between the SmCo and CoFeB layers. This study shows that the observed phenomena find their origin in the competition between the artificially induced anisotropies in both layers, resulting in a reversible chiral bias effect that allows the selection of the initial sign of the bias field by switching (upwards/downwards) the magnetization in the SmCo film.This research was supported by the Joint German-Spanish Actions Programme (DAAD and Fundación Universidad.es via Ref. 57050243), the Spanish Ministerio de Economía y Competitividad (MINECO) through “SIESPER” (MAT2011-25598) Project, and the Regional Government of Madrid through NANOMAGCOST (P2018/NMT-4321) project. D. S. acknowledges financial support from Xunta de Galicia under the postdoctoral program I2C Plan (Modalidade B) and the Strategic Grouping in Materials (AeMAT; grant No.ED431E2018/08). IMDEA Nanoscience is supported by the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D, MINECO [grant number SEV-2016-0686]Electronic supplementary information (ESI) available. See DOI: 10.1039/c9nr08852

Competencias transversales en la formación inicial del profesorado: el caso del ocio

Our research focuses on determining the preeminence of education for leisure within the competencial configuration of teachers in their initial training through the analysis of international, European, and national documents related to profesional teaching skills.The interest lies in the detected need to include within teaching performance aspects related to transversal skills, that may satisfy the educational objective of promoting and developing each student.Nuestra investigación se centra en determinar la preeminencia de la educación para el ocio dentro de la configuración competencial del profesorado en su formación inicial, a través del análisis de documentación de ámbito internacional, europeo y nacional relacionados con las competencias profesionales del profesorado. El interés radica en la necesidad detectada por insertar dentro del desempeño docente aspectos competenciales transversales que satisfagan el objetivo educativo de promover y desarrollar en el individuo las competencias necesarias para desenvolverse con éxito en el mundo global, multicultural y cambiante. El ocio humanista se sitúa como competencia transversal que permite de forma individual y colectiva el desarrollo positivo y sostenible, formando parte de la configuración social contemporánea, lo que plantea la necesidad de ser tenido en cuenta en los planteamientos formativos iniciales de los docentes como agentes de cambio y promotores del cambio educativo

Supersonic Kinks in Coulomb lattices

There exist in nature examples of lattices of elements for which the interaction is repulsive, the elements are kept in place because different reasons, as border conditions, geometry (e.g., circular) and, certainly, the interaction with other elements in the system, which provides an external potential. A primer example are layered silicates as mica muscovite, where the potassium ions form a two dimensional lattice between silicate layers. We propose an extremely simplified model of this layer in order to isolate the properties of a repulsive lattice and study them. We find that they are extremely well suited for the propagation of supersonic kinks and multikinks. Theoretically, they may have as much energy and travel as fast as desired. This striking results suggest that the properties of repulsive lattices may be related with some yet not fully explained direct and indirect observations of lattice excitations in muscovite

Multiplex RNA-based detection of clinically relevant MET alterations in advanced non-small cell lung cancer

We studied MET alterations in 474 advanced non-small-cell lung cancer (NSCLC) patients by nCounter, an RNA-based technique. We identified 3% with MET Δex14 mRNA and 3.5% with very-high MET mRNA expression, a surrogate of MET amplification. MET alterations identified by nCounter correlated with clinical benefit from MET inhibitors. Quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies. MET inhibitors have shown activity in non-small-cell lung cancer patients (NSCLC) with MET amplification and exon 14 skipping (METΔex14). However, patient stratification is imperfect, and thus, response rates have varied widely. Here, we studied MET alterations in 474 advanced NSCLC patients by nCounter, an RNA-based technique, together with next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR), exploring correlation with clinical benefit. Of the 474 samples analyzed, 422 (89%) yielded valid results by nCounter, which identified 13 patients (3%) with MET Δex14 and 15 patients (3.5%) with very-high MET mRNA expression. These two subgroups were mutually exclusive, displayed distinct phenotypes and did not generally coexist with other drivers. For MET Δex14, 3/8 (37.5%) samples positive by nCounter tested negative by NGS. Regarding patients with very-high MET mRNA, 92% had MET amplification by FISH and/or NGS. However, FISH failed to identify three patients (30%) with very-high MET RNA expression, among which one received MET tyrosine kinase inhibitor treatment deriving clinical benefit. Our results indicate that quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies

XAF1 as a modifier of p53 function and cancer susceptibility

Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers.Fil: Pinto, Emilia M.. St. Jude Children's Research Hospital; Estados UnidosFil: Figueiredo, Bonald C.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Chen, Wenan. St. Jude Children's Research Hospital; Estados UnidosFil: Galvao, Henrique C.R.. Hospital de Câncer de Barretos; BrasilFil: Formiga, Maria Nirvana. A.c.camargo Cancer Center; BrasilFil: Fragoso, Maria Candida B.V.. Universidade de Sao Paulo; BrasilFil: Ashton Prolla, Patricia. Universidade Federal do Rio Grande do Sul; BrasilFil: Ribeiro, Enilze M.S.F.. Universidade Federal do Paraná; BrasilFil: Felix, Gabriela. Universidade Federal da Bahia; BrasilFil: Costa, Tatiana E.B.. Hospital Infantil Joana de Gusmao; BrasilFil: Savage, Sharon A.. National Cancer Institute; Estados UnidosFil: Yeager, Meredith. National Cancer Institute; Estados UnidosFil: Palmero, Edenir I.. Hospital de Câncer de Barretos; BrasilFil: Volc, Sahlua. Hospital de Câncer de Barretos; BrasilFil: Salvador, Hector. Hospital Sant Joan de Deu Barcelona; EspañaFil: Fuster Soler, Jose Luis. Hospital Clínico Universitario Virgen de la Arrixaca; EspañaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. St. Jude Children's Research Hospital; Estados UnidosFil: Vaur, Dominique. Comprehensive Cancer Center François Baclesse; FranciaFil: Odone Filho, Vicente. Universidade de Sao Paulo; BrasilFil: Brugières, Laurence. Institut de Cancerologie Gustave Roussy; FranciaFil: Else, Tobias. University of Michigan; Estados UnidosFil: Stoffel, Elena M.. University of Michigan; Estados UnidosFil: Maxwell, Kara N.. University of Pennsylvania; Estados UnidosFil: Achatz, Maria Isabel. Hospital Sirio-libanês; BrasilFil: Kowalski, Luis. A.c.camargo Cancer Center; BrasilFil: De Andrade, Kelvin C.. National Cancer Institute; Estados UnidosFil: Pappo, Alberto. St. Jude Children's Research Hospital; Estados UnidosFil: Letouze, Eric. Centre de Recherche Des Cordeliers; FranciaFil: Latronico, Ana Claudia. Universidade de Sao Paulo; BrasilFil: Mendonca, Berenice B.. Universidade de Sao Paulo; BrasilFil: Almeida, Madson Q.. Universidade de Sao Paulo; BrasilFil: Brondani, Vania B.. Universidade de Sao Paulo; BrasilFil: Bittar, Camila M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Emerson W.S.. Hospital Do Câncer de Cascavel; BrasilFil: Mathias, Carolina. Universidade Federal do Paraná; BrasilFil: Ramos, Cintia R.N.. Hospital de Câncer de Barretos; BrasilFil: Machado, Moara. National Cancer Institute; Estados UnidosFil: Zhou, Weiyin. National Cancer Institute; Estados UnidosFil: Jones, Kristine. National Cancer Institute; Estados UnidosFil: Vogt, Aurelie. National Cancer Institute; Estados UnidosFil: Klincha, Payal P.. National Cancer Institute; Estados UnidosFil: Santiago, Karina M.. A.c.camargo Cancer Center; BrasilFil: Komechen, Heloisa. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Paraizo, Mariana M.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Parise, Ivy Z.S.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Hamilton, Kayla V.. St. Jude Children's Research Hospital; Estados UnidosFil: Wang, Jinling. St. Jude Children's Research Hospital; Estados UnidosFil: Rampersaud, Evadnie. St. Jude Children's Research Hospital; Estados UnidosFil: Clay, Michael R.. St. Jude Children's Research Hospital; Estados UnidosFil: Murphy, Andrew J.. St. Jude Children's Research Hospital; Estados UnidosFil: Lalli, Enzo. Institut de Pharmacologie Moléculaire et Cellulaire; FranciaFil: Nichols, Kim E.. St. Jude Children's Research Hospital; Estados UnidosFil: Ribeiro, Raul C.. St. Jude Children's Research Hospital; Estados UnidosFil: Rodriguez-Galindo, Carlos. St. Jude Children's Research Hospital; Estados UnidosFil: Korbonits, Marta. Queen Mary University of London; Reino UnidoFil: Zhang, Jinghui. St. Jude Children's Research Hospital; Estados UnidosFil: Thomas, Mark G.. Colegio Universitario de Londres; Reino UnidoFil: Connelly, Jon P.. St. Jude Children's Research Hospital; Estados UnidosFil: Pruett-Miller, Shondra. St. Jude Children's Research Hospital; Estados UnidosFil: Diekmann, Yoan. Colegio Universitario de Londres; Reino UnidoFil: Neale, Geoffrey. St. Jude Children's Research Hospital; Estados UnidosFil: Wu, Gang. St. Jude Children's Research Hospital; Estados UnidosFil: Zambetti, Gerard P.. St. Jude Children's Research Hospital; Estados Unido

ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization

BackgroundWhole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.MethodsWe developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA).ResultsClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes.ConclusionsClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses