The Parkinson's disease-associated GPR37 receptor interacts with striatal adenosine A2A receptor controlling its cell surface expression and function in vivo

G protein-coupled receptor 37 (GPR37) is an orphan receptor associated to Parkinson's disease (PD) neuropathology. Here, we identified GPR37 as an inhibitor of adenosine A2A receptor (A2AR) cell surface expression and function in vivo. In addition, we showed that GPR37 and A2AR do oligomerize in the striatum. Thus, a close proximity of GPR37 and A2AR at the postsynaptic level of striatal synapses was observed by double-labelling post-embedding immunogold detection. Indeed, the direct receptor-receptor interaction was further substantiated by proximity ligation in situ assay. Interestingly, GPR37 deletion promoted striatal A2AR cell surface expression that correlated well with an increased A2AR agonist-mediated cAMP accumulation, both in primary striatal neurons and nerve terminals. Furthermore, GPR37−/− mice showed enhanced A2AR agonist-induced catalepsy and an increased response to A2AR antagonist-mediated locomotor activity. Overall, these results revealed a key role for GPR37 controlling A2AR biology in the striatum, which may be relevant for PD management

Interaction of 8He with 208Pb at near-barrier energies: 4He and 6He production

Angular distributions for the inclusive 4He and 6He production cross sections in the 8He+208Pb system at incident energies of 16 and 22 MeV measured at the SPIRAL facility of the GANIL laboratory are presented. Using a combination of kinematical arguments and distorted wave Born approximation (DWBA) calculations, neutron transfer reactions were inferred to be the dominant contributors to both inclusive cross sections. Model-dependent values for the ratios of two- to one-neutron stripping, s2n/s1n, were derived and compared with previous results for 8He and 6He projectiles incident on other heavy targets. Three- and four-neutron stripping were inferred to be the main processes leading to 4He production, although the exact mechanism remains to be elucidated.The authors would like to thank the staff of the GANIL accelerator facility for providing the high-quality 8He beam. This work was supported in part by Grants No. FPA-2010-22131-CO2-01 (FINURA) and No. FPA2013-47327-C2-1-R from the Spanish Ministry of Economy and Competitiveness, UNAM-PAPIIT IA103218 (Mexico); Grant No. N202 033637 from the Ministry of Science and Higher Education of Poland; the National Science Centre of Poland under Contracts No. 2013/08/M/ST2/00257 (LEA-COPIGAL) and No. 2014/14/M/ST2/00738 (COPIN-INFN Collaboration); and Grant No. EUI2009-04163432 (EUROGENESIS) from the European Science Foundation

Sub-barrier fusion of 6He with 206Pb

Cross-sections for the production of 210Po nuclei in 6He + 206Pb collisions over the incident energy range 14–18MeV were measured by means of the activation technique and a radiochemical analysis. The elastic scattering at 18.0MeV was also measured providing a precise value for the 210Po production cross-section at this energy. The results are at variance with the earlier experimental data and rather in accord with the predictions of a density-dependent barrier penetration model for the fusion process. A proper treatment of beam energy distribution for the evaluation of the activation data is discussed

Breakup and neutron-transfer effects on 6He+206Pb elastic scattering below the Coulomb barrier

The elastic scattering and inclusive α-particle yield for the 6He + 206Pb system at an incident energy of 18 MeV, just below the nominal Coulomb barrier, have been measured. The α-particle yield at forward angles is also reported. The data are analyzed by means of continuum-discretized coupled-channels, distorted wave Born approximation, and coupled reaction channels calculations. Couplings to the one-neutron- and two-neutron-transfer reactions are found to be able to account for most of the absorption in the entrance channel.This work was supported in part by Grant No. FPA2010-22131-C02-01 from the Spanish Ministry of Science

Cómo afrontar la elaboración y defensa de mi TFG: propuestas para la Facultad de Ciencias Sociales y de la Comunicación

El Plan Bolonia introdujo como novedad la obligatoriedad de elaborar un Trabajo Fin de Grado. Al ser una asignatura no presencial y dependiente de la relación alumno-tutor, la elaboración y desarrollo de estos trabajos suponen tanto para los alumnos como profesores además de una carga de trabajo importante, una ansiedad y desasosiego superior al resto de las materias (Sánchez et al., 2018). Este proyecto pretende desarrollar un contexto de enseñanza que incorpore un conjunto de metodologías didácticas y actividades que vertebren el aprendizaje cooperativo y autónomo de los estudiantes y mejore la adquisición de las competencias asignadas al desarrollo del TFG según el Reglamento Marco de 2012. Para ello, se han llevado a cabo las I Jornadas para la promoción de la calidad de los TFG en la Facultad de Ciencias Sociales y de la Comunicación y se creó un curso en el Campus Virtual para tutorizar experiencias de aprendizaje y facilitar a los estudiantes información de todos los aspectos relacionados con sus proyectos de investigación. Para medir los resultados se diseñó un cuestionario de satisfacción dirigido a todos los asistentes de las jornadas que nos ha servido para establecer una serie de mejoras de cara a años consecutivos

GDF-15 is elevated in children with mitochondrial diseases and is induced by mitochondrial dysfunction

Background We previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction. Methods We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA. Results Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM) relative to healthy (350, 21) and myopathic (350, 32) controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4%) and 92.3% (81.5%-97.9%), respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated lev- els of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated. Conclusions Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochon- drial dysfunction and that its levels correlate in vitro with FGF-21 level

Near barrier scattering of 8He on 208Pb

The exotic nucleus 8He is investigated by means of the measurement of the angular distributions of the elastic channel and the 6He and 4He fragment yields produced in the collision with a 208Pb target at two energies around the Coulomb barrier, 16 and 22 MeV. The experiment was performed at the GANIL-SPIRAL facility, with the aim of extracting information about the structure of 8He and the relevant reaction mechanisms. In this contribution, details of the experimental setup and preliminary data on elastic cross sections are reported

Lmo2 expression defines tumor cell identity during T-cell leukemogenesis

The impact of LMO2 expression on cell lineage decisions during T-cell leukemogenesis remains largely elusive. Using genetic lineage tracing, we have explored the potential of LMO2 in dictating a T-cell malignant phenotype. We first initiated LMO2 expression in hematopoietic stem/progenitor cells and maintained its expression in all hematopoietic cells. These mice develop exclusively aggressive human-like T-ALL. In order to uncover a potential exclusive reprogramming effect of LMO2 in murine hematopoietic stem/progenitor cells, we next showed that transient LMO2 expression is sufficient for oncogenic function and induction of T-ALL. The resulting T-ALLs lacked LMO2 and its target-gene expression, and histologically, transcriptionally, and genetically similar to human LMO2-driven T-ALL. We next found that during T-ALL development, secondary genomic alterations take place within the thymus. However, the permissiveness for development of T-ALL seems to be associated with wider windows of differentiation than previously appreciated. Restricted Cre-mediated activation of Lmo2 at different stages of B-cell development induces systematically and unexpectedly T-ALL that closely resembled those of their natural counterparts. Together, these results provide a novel paradigm for the generation of tumor T cells through reprogramming in vivo and could be relevant to improve the response of T-ALL to current therapies.J.H. has been supported by the German Cancer Aid (Project 110997 and Translational Oncology Program 70112951), the German Jose Carreras Leukemia Foundation (DJCLS 02R/2016), Deutsches Konsortium für Translationale Krebsforschung (DKTK), Joint funding (Targeting MYC L*10), the Kinderkrebsstiftung (2016/17), and the “Elterninitiative Kinderkrebsklinik e.V. Düsseldorf”. SG has been supported by a scholarship of the Hochschule Bonn-Rhein-Sieg. AB has been supported by the German Children's Cancer Foundation and the Federal Ministry of Education and Research, Bonn, Germany. Research in ISG group is partially supported by FEDER and by MINECO (SAF2012-32810, SAF2015-64420-R, and Red de Excelencia Consolider OncoBIO SAF2014-57791-REDC), Instituto de Salud Carlos III (PIE14/00066), ISCIII- Plan de Ayudas IBSAL 2015 Proyectos Integrados (IBY15/00003), by Junta de Castilla y León (BIO/SA51/15, CSI001U14, UIC-017, and CSI001U16), Fundacion Inocente Inocente, and by the ARIMMORA project (European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282891). ISG Lab is a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program. AB and ISG have been supported by the German Carreras Foundation (DJCLS R13/26). IGR was supported by BES-Ministerio de Economía y Competitividad (BES-2013-063789). AML and GRH were supported by FSE-Conserjería de Educación de la Junta de Castilla y León (CSI001-13, CSI001-15). Research in CVD group is partially supported by FEDER, “Miguel Servet” Grant (CP14/00082—AES 2013-2016) from the Instituto de Salud Carlos III (Ministerio de Economía y Competitividad), “Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III” (PI17/00167), and by the Lady Tata International Award for Research in Leukaemia 2016–2017