Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration.

Mast cell chemotaxis is essential for cell recruitment to target tissues, where these cells play an important role in adaptive and innate immunity. Stem cell factor (SCF) is a major chemoattractant for mast cells. SCF binds to the KIT receptor, thereby triggering tyrosine phosphorylation in the cytoplasmic domain and resulting in docking sites for SH2 domain-containing molecules, such as Lyn and Fyn, and the subsequent activation of the small GTPases Rac that are responsible for cytoskeletal reorganization and mast cell migration. In previous works we have reported the role of 3BP2, an adaptor molecule, in mast cells. 3BP2 silencing reduces FcεRI-dependent degranulation, by targeting Lyn and Syk phosphorylation, as well as SCF-dependent cell survival. This study examines its role in SCF-dependent migration and reveals that 3BP2 silencing in human mast cell line (LAD2) impairs cell migration due to SCF and IgE. In that context we found that 3BP2 silencing decreases Rac-2 and Cdc42 GTPase activity. Furthermore, we identified Myo1f, an unconventional type-I myosin, as a new partner for 3BP2. This protein, whose functions have been described as critical for neutrophil migration, remained elusive in mast cells. Myo1f is expressed in mast cells and colocalizes with cortical actin ring. Interestingly, Myo1f-3BP2 interaction is modulated by KIT signaling. Moreover, SCF dependent adhesion and migration through fibronectin is decreased after Myo1f silencing. Furthermore, Myo1f silencing leads to downregulation of β1 and β7 integrins on the mast cell membrane. Overall, Myo1f is a new 3BP2 ligand that connects the adaptor to actin cytoskeleton and both molecules are involved in SCF dependent mast cell migration

The Receptor CMRF35-Like Molecule-1 (CLM-1) Enhances the Production of LPS-Induced Pro-Inflammatory Mediators during Microglial Activation.

CMRF35-like molecule-1 (CLM-1) belongs to a receptor family mainly expressed in myeloid cells that include activating and inhibitory receptors. CLM-1 contains two ITIMs and a single immunoreceptor tyrosine-based switch motif (ITSM), although also displays a binding site for p85α regulatory subunit of PI3K. By using murine primary microglial cultures, we show the presence of all CLM members in microglial cells and characterize the expression of CLM-1 both in basal conditions and during microglial activation. The TLR4 agonist lipopolysaccharide (LPS) and the TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) induce an increase in microglial CLM-1 mRNA levels in vitro, whereas the TLR2/6 heterodimer agonist peptidoglycan (PGN) produces a marked decrease. In this study we also describe a new soluble isoform of CLM-1 that is detected at mRNA and protein levels in basal conditions in primary microglial cultures. Interestingly, CLM-1 engagement enhances the transcription of the pro-inflammatory mediators TNFα, COX-2 and NOS-2 in microglial cells challenged with LPS. These results reveal that CLM-1 can acts as a co-activating receptor and suggest that this receptor could play a key role in the regulation of microglial activation

Case report : characterizing the role of the STXBP2-R190C monoallelic mutation found in a patient with hemophagocytic syndrome and Langerhans cell histiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory disorder. HLH can be considered as a threshold disease depending on the trigger and the residual NK-cell cytotoxicity. In this study, we analyzed the molecular and functional impact of a novel monoallelic mutation found in a patient with two episodes of HLH. A 9-month-old child was diagnosed at 2 months of age with cutaneous Langerhans cell histiocytosis (LCH). After successful treatment, the patient developed an HLH episode. At 16 month of age, the patient went through an HSCT losing the engraftment 5 months later concomitant with an HLH relapse. The genetic study revealed a monoallelic mutation in the STXBP2 gene (.pArg190Cys). We transfected COS7 cells to analyze the STXBP2-R190C expression and to test the interaction with STX11. We used the RBL-2H3 cell line expressing STXBP2-WT-EGFP or R190C-EGFP for degranulation assays. Mutation STXBP2-R190C did not affect protein expression or interaction with syntaxin-11. However, we have demonstrated that STXBP2-R190C mutation diminishes degranulation in the RBL-2H3 cell line compared with the RBL-2H3 cell line transfected with STXBP2-WT or nontransfected. These results suggest that STXBP2-R190C mutation acts as a modifier of the degranulation process producing a decrease in degranulation. Therefore, under homeostatic conditions, the presence of one copy of STXBP2-R190 could generate sufficient degranulation capacity. However, it is likely that early in life when adaptive immune system functions are not sufficiently developed, an infection may not be resolved with this genetic background, leading to a hyperinflammation syndrome and eventually develop HLH. This analysis highlights the need for functional testing of new mutations to validate their role in genetic susceptibility and to establish the best possible treatment for these patients

Competències transversals a les titulacions de grau de la Universitat de Barcelona. Orientacions per al seu desenvolupament

Podeu consultar la versió castellana a recurs relacionat.El text que presentem és fruit de la tasca realitzada per un equip de professors i professores que, en el marc de diferents grups d’innovació docent, fa temps que treballen per incorporar l’aprenentatge de les competències genèriques o transversals a les assignatures de les titulacions on imparteixen docència. L’objectiu principal d’aquest treball és oferir una breu descripció de les sis competències transversals que la Universitat de Barcelona va seleccionar com a fonamentals per incorporar en tots els seus títols de grau adaptats al EEES. La identificació de les dimensions que cal considerar en cada competència i dels elements que les caracteritzen ha de ser útil per orientar el professorat a l’hora d’interpretar-les. Per altra banda, la proposta de diferents nivells en el seu desenvolupament, amb indicació dels resultats d’aprenentatge que s’espera obtenir a cada nivell, ha de facilitar als centres la seva incorporació al pla docent de les assignatures i l’elaboració d’un itinerari que permeti als estudiants anar-les adquirint de forma progressiva al llarg els estudis. La descripció de cada competència es completa amb algunes idees per treballar-la a l’aula i per abordar la seva avaluació

Las competencias transversales en las titulaciones de grado de la Universidad de Barcelona. Orientaciones para su desarrollo

[spa] El texto que presentamos es fruto de la labor realizada por un equipo de profesores que, en el marco de diferentes grupos de innovación docente, que trabajan hace tiempo para incorporar el aprendizaje de las competencias genéricas o transversales en las asignaturas de las titulaciones donde imparten docencia. El objetivo principal de este trabajo es ofrecer una breve descripción de las seis competencias transversales que la Universidad de Barcelona seleccionó como fundamentales para incorporar en todos sus títulos de grado adaptados al EEES. La identificación de las dimensiones que cabe considerar en cada competencia y de los elementos que las caracterizan debe ser útil para orientar al profesorado sobre cómo interpretarlas. Por otra parte, la propuesta de diferentes niveles en su desarrollo, con indicación de los resultados de aprendizaje que se espera obtener en cada nivel, debe facilitar a los centros la incorporación de las asignaturas al plan docente y la elaboración de un itinerario que permita a los estudiantes adquirirlas progresivamente a lo largo de los estudios. La descripción de cada competencia se completa con algunas ideas para trabajarla en el aula y para abordar su evaluación.[eng] The present book is the result of the work carried out by a group of university teachers who have incorporated the learning of transversal competences into their undergraduate courses within the framework of several teaching innovation projects. The aim of this work is to provide a characterization of the six transversal competences that the University of Barcelona considered essential to include in all of their undergraduate degrees adapted to EHEA. On the one hand, the identification of both the dimensions that need to be taken into account in each competence and their distinctive features will assist teachers in their successful interpretation of the six transversal key competences. On the other hand, the proposal made about the different stages of competence development –together with the expected learning outcomes– will help the Faculties to integrate these competences into course syllabi. In addition, this proposal will contribute to planning a schedule that will allow students to acquire them during their undergraduate studies. Last, the characterization of each of the six transversal key competences includes some ideas to work on them in class and some suggestions for their assessment

Mitigation of coupled wind-wave-earthquake responses of a 10 MW fixed-bottom offshore wind turbine

© 2020 Elsevier Ltd In this paper we present a study on the mitigation of dynamic responses of a 10 MW monopile offshore wind turbine under coupled wind-wave-earthquake excitations. We have developed and validated the generic seismic coupled analysis and structural control architecture tool to overcome the limitation of numerical tools when examining the wind-wave-earthquake coupling effects. We investigated the dynamic responses of a 10 MW monopile offshore wind turbine under different loading combinations and found that the earthquake loading increases the tower-top displacement and pile-cap moment by 47.6% and 95.1%, respectively, compared to the wind-wave-only condition. It is found that the earthquake-induced vibration in the fore-aft direction is mitigated by the wind and wave loadings due to the energy dissipated by the aerodynamic and hydrodynamic damping. In addition, the tower responses are dominated by the earthquake excitation. In order to alleviate the tower vibration induced by the earthquake, we implemented the structural control capability within the tool using tuned mass dampers. The tuned mass dampers with appropriately selected design parameters achieve a larger mitigation on the tower-top displacement for the earthquake-only condition compared to the coupled-loading scenario. The reason is that the tuned mass damper is only effective in mitigating tower vibration, and it is not capable of reducing the tower elastic deformation which is the major contribution of the tower displacement for the coupled-loading condition. In addition, we have found that a heavier tuned mass damper requires a lower tuned frequency to achieve a larger mitigation. A configuration for the mitigation control of the 10 MW offshore wind turbine is suggested by using a 5% mass ratio of the tuned mass damper

Effect of Specific Mutations in Cd300 Complexes Formation; Potential Implication of Cd300f in Multiple Sclerosis.

Herein, we have used bioinformatics tools to predict five clusters defining ligand-binding sites on the extracellular domain of human CD300b receptor, presumably involved in the formation of both homodimers and heterodimers with other CD300 family members. Site-directed mutagenesis revealed residues glutamic acid 28 and glutamine 29 in cluster 5 to be necessary for the formation of CD300b complexes. Surprisingly, the disruption of cluster 2 and 4 reconstituted the binding capability lost by the mutation of residues glutamic acid 28 to alanine, glutamine 29 to alanine (E28A-Q29G). We identified a missense mutation arginine 33 to glutamine (R33Q) in CD300f by direct sequencing of exon 2 in peripheral blood samples from 50 patients with multiple sclerosis (MS). Levels of expression of CD300f were almost undetectable on monocytes from the patient bearing the R33Q mutation compared with healthy individuals. Whereas R33Q mutation had no effect in the formation of CD300f complexes, the inhibition of protein synthesis with cycloheximide indicated that CD300f R33Q is less stable than native CD300f. Finally, we report that the levels of expression of CD300f on the surface of classical and intermediate monocytes from MS patients are significantly lower when compared to the same cell populations in healthy individuals

Aprenentatge mòbil en el desenvolupament de la competència plurilingüe en comunitats d’aprenentatge

Projecte: 2018PID-UB/027L’objectiu general d’aquest projecte d'innovació és dissenyar i implementar diverses pràctiques en què es fa ús de la tecnologia mòbil per al desenvolupament de les competències comunicatives en els estudiants dels Graus de Mestre i de Comunicació Audiovisual. Aquestes pràctiques estan pensades per promoure la interacció entre els estudiants i afavorir la creació de comunitats d’aprenentatge més enllà del grup classe. En conseqüència, aquest projecte d’innovació ha pretès, a partir de l’aprenentatge mòbil, que els estudiants participin en accions didàctiques amb companys d’altres grups i disciplines amb la intenció de desenvolupar la seva competència plurilingüe. Les actuacions didàctiques s’han portat a terme en les assignatures de llengua de la Facultat d’Educació -català, castellà i anglès- i en altres assignatures relacionades amb el desenvolupament de les habilitats comunicatives dels estudiants i ha implicat un ús de les llengües amb objectius compartits entre els diferents participants.Projecte d'innovació docent RIMDA - 2018PID-UB/02

De l'autoavaluació a l'avaluació entre iguals: experiències amb el portafolis electrònic a l'educació superior

El present estudi analitza la implementació d’activitats d’avaluació entre iguals dins d’un projecte d’innovació docent de la Facultat de Formació del Professorat de la Universitat de Barcelona. Hi participen professors de llengua catalana, castellana i anglesa dels Graus d’Educació Primària, Educació Infantil i Comunicació Audiovisual. El projecte ha evolucionat des de la incorporació del portafolis com a eina d’avaluació i la implementació de la seva versió electrònica amb Mahara, passant per l’ús de la rúbrica per ajudar a l’autoavaluació, fins a la incorporació d’activitats d’avaluació entre iguals, com un pas més en el desenvolupament de les competències autoreguladores dels estudiant