His452Tyr polymorphism in the human 5-HT2A receptor affects clozapine-induced signaling networks revealed by quantitative phosphoproteomics

Antipsychotic drugs remain the current standard for schizophrenia treatment. Although they directly recognize the orthosteric binding site of numerous monoaminergic G protein-coupled receptors (GPCRs), these drugs, and particularly second-generation antipsychotics such as clozapine, all have in common a very high affinity for the serotonin 5-HT receptor (5-HTR). Using classical pharmacology and targeted signaling pathway assays, previous findings suggest that clozapine and other atypical antipsychotics behave principally as 5-HTR neutral antagonists and/or inverse agonists. However, more recent findings showed that antipsychotics may also behave as pathway-specific agonists. Reversible phosphorylation is a common element in multiple signaling networks. Combining a quantitative phosphoproteomic method with signaling network analysis, we tested the effect of clozapine treatment on the overall level of protein phosphorylation and signal transduction cascades in vitro in mammalian cell lines induced to express either the human 5-HTR or the H452Y variant of the gene encoding the 5-HTR receptor. This naturally occurring variation within the 5-HTR gene was selected because it has been repeatedly associated with schizophrenia patients who do not respond to clozapine treatment. Our data show that short time exposure (5 or 10 min) to clozapine (10 M) led to phosphorylation of numerous signaling components of pathways involved in processes such as endocytosis, ErbB signaling, insulin signaling or estrogen signaling. Cells induced to express the H452Y variant showed a different basal phosphoproteome, with increases in the phosphorylation of mTOR signaling components as a translationally relevant example. However, the effect of clozapine on the functional landscape of the phosphoproteome was significantly reduced in cells expressing the 5-HTR-H452Y construct. Together, these findings suggest that clozapine behaves as an agonist inducing phosphorylation of numerous pathways downstream of the 5-HTR, and that the single nucleotide polymorphism encoding 5-HTR-H452Y affects these clozapine-induced phosphorylation-dependent signaling networks

Co-construcción del conocimiento en GrupoLab

En este proyecto pretende dar respuesta a la necesidad de crear sinergias académicas entre alumnado, personal docente e investigador y usuarios de proyectos, cuyo punto en común es el interés en la investigación social y el trabajo social, en concreto en la intervención con grupos. Asimismo, da respuesta a la necesidad del alumnado de crear espacios de aprendizaje donde desarrollar propuestas que favorezcan el impulso de la carrera universitaria y donde se pueda colaborar de forma horizontal con otras personas de forma que se potencie la creatividad y la iniciativa

El podcast como herramienta docente desde una perspectiva participativa

Depto. de Trabajo Social y Servicios SocialesFac. de Trabajo SocialFALSEsubmitte

Trabajo social digital con grupos: evolución, estado del arte, y agenda de investigación renovada

This chapter systematically reviews the social work scholarly literature to investigate the origins, evolution and state of the art of digital social work with groups. Two academic databases “Social Work Abstracts” and “Social Services Abstracts” were explored to identify the most relevant papers on this topic in the period from the early 1990s to the present. A total of 167 papers were selected and analyzed. The results highlight the main trends and changes in e-social group work in the selected time period. The analysis also classifies the types of papers published, the most relevant authors, the needs or problems focused on, the types of groups developed and the technologies that were employed. The chapter questions if the accelerated and widespread digitization arising from COVID-19 has had any significant impact on e-social group work reports. The chapter ends by proposing a renewed agenda for the specialized field of digital social work with groups among practitioners, researchers and educators. Special emphasis is also placed on how the social work curriculum can best prepare students to meet the anticipated future demand for online social work practice with groups in the years to come.Depto. de Trabajo Social y Servicios SocialesFac. de Trabajo SocialTRUEpu

Essential role of the C148–C227 disulphide bridge in the human 5-HT2A homodimeric receptor

The 5-HT receptor is a homodimeric G protein-coupled receptor implied in multiple diseases, including schizophrenia. Recently, its co-crystallisation with the antipsychotic drugs zotepine and risperidone has revealed the importance of its extracellular domains in its pharmacology. Previous studies have shown that the non-specific disruption of extracellular disulphide bridges in the 5-HT receptor decreases ligand binding and receptor activation. There is enough evidence to hypothesize that this decrease may be due to a reduction of the disulphide bridge that links transmembrane domain 3 (TM-3) and extracellular loop 2 (ECL-2) of the 5-HT receptor via cysteine 148 (C148) and C227. Thus, to study the influence of the C148–C227 disulphide bridge on 5-HT receptor pharmacology, we substituted C148 and C227 in the human 5-HT receptor (WT) with alanines, to obtain two single mutants (C148A and C227A) and a double mutant (C148A/C227A), and the resultant DNA constructs were used to generate four stable cell lines. These substitutions reduced the binding of the 5-HT receptor to [H]lysergic acid diethylamide ([H]LSD) and impeded the 5-HT receptor-mediated activation of phospholipase C (PLC). Furthermore, bioluminescence resonance energy transfer (BRET) and western blotting analysis revealed that these mutations did not alter the homodimeric nature of the 5-HT receptor. However, fluorescence microscopy showed that these mutations hindered receptor trafficking to the cell membrane. These results illustrate the importance of the disulphide bridge between TM-3 and ECL-2 in maintaining the correct 5-HT receptor conformation to allow ligand binding and migration of the homodimeric receptor to the cell membrane.This work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2014-57138-C2-1-R and SAF2017-85225-C3-1-R) and the European Regional Development Fund (ERDF). MC and LGG were supported by a grant from the Consellería de Cultura, Educación y Ordenación Universitaria, partially co-funded by the European Social Fund (ESF) program

Survey results on online teaching during COVID of the degree in Geology (University of Barcelona): Teaching staff.

[cat] Resultats de l'enquesta en línia feta al professorat de la facultat de Ciències de la Terra per percebre la seva opinió sobre la docència del grau de Geologia en línia durant la pandèmia COVID-19.[eng] Results of the online survey of the faculty of Earth Sciences to perceive their opinion about online teaching in the degree of Geology during the COVID-19 pandemic

Anàlisi i repercussions de la docència en línia en el Grau de Geologia (Universitat de Barcelona). Estudiants

[cat] Resultats de l'enquesta en línia feta a l'alumnat de la facultat de Ciències de la Terra per percebre la seva opinió sobre la docència del grau de Geologia en línia durant la pandèmia COVID-19.[eng] Results of the online survey adress to students of the faculty of Earth Sciences to perceive their opinion about online teaching in the degree of Geology during the COVID-19 pandemic

The impact of online teaching on Geology degree programs during COVID-19: A case study from the University of Barcelona (Spain)

The sudden shift during the COVID-19 lockdown from face-to-face to online teaching clearly impacted degree programmes in Geology characterized by a substantial practical teaching methodology. This study analyses the suitability of online teaching in the degree at Geology of the University of Barcelona by: (a) describing the strengths, weaknesses, opportunities, and threats (SWOT) from the point of view of online teaching and learning, (b) addressing two surveys to teachers and students to explore the consequences of online teaching on learning and gained competencies, and (c) analyzing pre-, syn- and post-pandemic academic results. Results show that both teachers and students value the learning resulting from online activities and the acquisition of new skills. However, some perceived that critical competencies cannot be achieved online, such as the field and laboratory work required for professional development. Moreover, students had difficulties maintaining attention and starting discussions, while instructors had difficulties properly monitoring students such as to control exam fraud, due to the lack of the necessary tools. Online teaching during the pandemic influenced instructors' grading of students and likely led to some leniency with grading, as teachers admit, consistent with the higher student grades and decrease in second-chance examinations in 2019-20. We conclude that in a potential new online or blended teaching scenario, the full acquisition of practical and communicative competencies is a key point that should be accurately managed in Earth Science degree programmes

MSIMEP : Predicting microsatellite instability from microarray DNA methylation tumor profiles

Altres ajuts: Xunta de Galicia (ED481A-2017/299); Xunta de Galicia (ED481A 2022/491)Deficiency in DNA MMR activity results in tumors with a hypermutator phenotype, termed microsatellite instability (MSI). Beyond its utility in Lynch syndrome screening algorithms, today MSI has gained importance as predictive biomarker for various anti-PD-1 therapies across many different tumor types. Over the past years, many computational methods have emerged to infer MSI using either DNA- or RNA-based approaches. Considering this together with the fact that MSI-high tumors frequently exhibit a hypermethylated phenotype, herein we developed and validated MSIMEP, a computational tool for predicting MSI status from microarray DNA methylation tumor profiles of colorectal cancer samples. We demonstrated that MSIMEP optimized and reduced models have high performance in predicting MSI in different colorectal cancer cohorts. Moreover, we tested its consistency in other tumor types with high prevalence of MSI such as gastric and endometrial cancers. Finally, we demonstrated better performance of both MSIMEP models vis-à-vis a MLH1 promoter methylation-based one in colorectal cancer