siRNA screen of microglia to identify neuroprotective drug targets in Parkinson´s disease

The uploaded accepted version corresponds to pages E183-E184 of the publication "GLIA Bilbao 2015: Abstracts Oral Presentations, Posters, Indexes" available at https://doi.org/10.1002/glia.22870.Question: Neuroinflammation is a fundamental process contributing to the death of dopaminergic neurons in Parkinson´s Disease (PD). During this process, activated microglia secrete cytotoxic substances which lead to neuronal death. Therefore, we are looking for the molecular mechanism that reverses the inflammatory activation of microglia, since this knowledge would be essential to protect from neurodegeneration. Methods and Results: Very interestingly our previous data (Neubrand et al., 2014) indicate that adipose derived mesenchymal stem cells (ASCs) exert important anti-inflammatory actions on microglia. We observed that microglia exposed to ASCs or their secreted factors (conditioned medium, CM) underwent a dramatic cell shape change into a highly elongated morphology (Fig 1A), similar to the phenotype of microglia observed in a healthy brain. The elongation induced by ASCs was associated with a decrease of the pro-inflammatory cytokine TNFalpha (Fig 1B) as well as with an upregulation of neurotrophic factors. Thus, ASC stimulated microglia represent an ideal tool to study the intracellular events necessary for the transition from inflammatory activated to non-inflammatory neuroprotective microglia. In this way we have already identified the small RhoGTPases Rac1 and Cdc42, which are important regulators of the actin cytoskeleton, as essential molecules in this transition (Fig 1C). Since these molecules represent possible drug targets to induce the reversion of neurotoxic microglia to neuroprotective ones, we are currently performing an siRNA screen to identify the molecular players of this ASC-induced reversion. Because this transition is easily detectable by light microscopy (see Figs 1A and C) and changes in the cell shape are intrinsically related to changes of the cytoskeleton, we are carrying out a microscopy-based screen of the major cytoskeletal regulators. In addition, we are including in the screen the regulators of microglia-specific activation/inflammatory pathways as siRNA targets. Conclusion: Our project is the first siRNA screen performed in primary microglia and we aim to identify a list of molecules that are specifically implicated in the reversion from activated to neuroprotective microglia. Since positive hits would represent potential neuroprotective drug targets, the outcome of this screen opens up a variety of novel investigation lines and therapies in PD or other neurodegenerative diseases

Integrating Mathematics and Science Teaching in the Context of Education for Sustainable Development: Design and Pilot Implementation of a Teaching-Learning Sequence about Air Quality with Pre-Service Primary Teachers

This article presents an interdisciplinary teaching–learning sequence (TLS) about air quality for pre-service primary teachers using an organic learning garden. The design involved a curricular integration of concepts and competences about sustainability, mathematics, and science disciplines following constructivist and active learning strategies, such as problem-based learning and place-based education. In this TLS, both the topic and the learning context act as facilitators of education for sustainable development (ESD). The contents address the overarching STEM and sustainability concepts related to air pollutants, weather, and climate. Our results show that students learned about a STEM topic within a space and context that enables ESD. Several misconceptions related to air quality, weather, and statistics were identified through the evaluation of students’ initial ideas. Furthermore, students’ attitudes towards the topic of study and self-efficacy and perceived relevance of ESD improved after the implementation. These results will guide further improvements of the designed TLS, which connects STEM education and ESD as a transformative educational experience for pre-service teachers. In this sense, we conclude that such initiatives can improve pre-service primary teachers’ self-efficacy as agents of change towards sustainable development goals.This research was funded by the Vice-Rectorate of Innovation, Social Commitment and Cultural Action (UPV/EHU), through the call for Projects of Educational Innovation, grant number PIE13-PIE-HECA-STEM and the call from the Directorate of Sustainability: Campus Bizia Lab 2018/19 edition, grant number 18ZUAZ

Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function

Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS). Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs) in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs) suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS-) induced maturation of dendritic cells (DCs) in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG) E2 in this process. In vivo, early administration of murine and human ASCs (hASCs) ameliorated myelin oligodendrocyte protein- (MOG35-55-) induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+ and CD11c+TNF-α+) DCs in draining lymph nodes (DLNs). In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.This work has been financed by the Instituto de Salud Carlos III, Spain (http://www.isciii.es) and Fondo Europeo de Desarrollo Regional (FEDER, http://ec.europa.eu/regional_policy/es/funding/erdf/) from the European Union, through the Research Grants PI15/00794, CP09/00228, and CPII15/00032 (Per Anderson); PI12/01097, PI15/02015, and ISCIII Red de Terapia Celular (RD12/0019/0006, http://www.red-tercel.com/) (Francisco Martin); and PS09-00928 (Mario Delgado). Mario Delgado was supported by a grant (PSE-010000-2009-3) from the Ministerio de Ciencia e Innovación, Spain (http://www.idi.mineco.gob.es/), and P09-CTS-4723 from the Junta de Andalucia (Proyecto de Excelencia). Francisco Martin is funded by the Fundación Progreso y Salud (Consejería de Salud, Junta de Andalucía, http://www.juntadeandalucia.es/fundacionprogresoysalud/)

Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed α-helix

The macrophage infectivity potentiator protein from Trypanosoma cruzi (TcMIP) is a major virulence factor secreted by the etiological agent of Chagas' disease. It is functionally involved in host cell invasion. We have determined the three-dimensional crystal structure of TcMIP at 1.7 Å resolution. The monomeric protein displays a peptidyl-prolyl cis-trans isomerase (PPlase) core, encompassing the characteristic rotamase hydrophobic active site, thus explaining the strong inhibition of TcMIP by the immunosuppressant FK506 and related drugs. In TcMIP, the twisted β-sheet of the core is extended by an extra β-strand, preceded by a long, exposed N-terminal α-helix, which might be a target recognition element. An invasion assay shows that the MIP protein from Legionella pneumophila (LpMIP), which has an equivalent N-terminal α-helix, can substitute for TcMIP. An additional exposed α-helix, this one unique to TcMIP, is located in the C-terminus of the protein. The high-resolution structure reported here opens the possibility for the design of new inhibitory drugs that might be useful for the clinical treatment of American trypanosomiasis.This work was supported by grants from Ministerio de Educación y Cultura (PB98-1631 and 2FD97-0518), CSIC and Generalitat de Catalunya (CERBA and 1999SGR188) to M.C., grant PB98-0479 to A.G. and by grant BIO2000-1659 to F.X.G.-R. P.J.B.P. and S.M.-R. acknowledge postdoctoral fellowships from FCT (Portugal). Data collection at DESY was supported by EC grants ERBFMGECT980134 and HPRI-CT-1999-00017 to EMBL-HamburgPeer Reviewe

Analysis of formation in communication and the doctor-patient relationship in the degrees of medicine in Spain

En este artículo recogemos las conclusiones obtenidas de una investigación sobre la comunicación en la formación de los licenciados en medicina en torno al manejo de la relación médico-paciente a través del aná- lisis de las guías docentes de las materias de comunicación impartidas en los grados de Medicina en España. Estas observaciones se contrastaron con la valoración de expertos en comunicación y de los decanos o responsables de las titulaciones de Medicina y de Comunicación en España. Los resultados permiten valorar que la formación en comunicación que reciben los estudiantes de medicina es escasaIn this article we gather the conclusions of a study about the communication in the medical graduates training regarding the doctor-pacient relationship through the analysis of the communication study plans given in the medical schools in Spain. These observations were compared with the assessment of communication experts and those responsible of the communication and medical degrees in Spain. The results show that the communication training received by medical students is insufficientS

Análisis de la formación en comunicación y la relación médico-paciente en los grados de Medicina en España

In this article we gather the conclusions of a study about the communication in the medical graduates training regarding the doctor-pacient relationship through the analysis of the communication study plans given in the medical schools in Spain. These observations were compared with the assessment of communication experts and those responsible of the communication and medical degrees in Spain. The results show that the communication training received by medical students is insufficient.En este artículo recogemos las conclusiones obtenidas de una investigación sobre la comunicación en la formación de los licenciados en medicina en torno al manejo de la relación médico-paciente a través del análisis de las guías docentes de las materias de comunicación impartidas en los grados de Medicina en España. Estas observaciones se contrastaron con la valoración de expertos en comunicación y de los decanos o responsables de las titulaciones de Medicina y de Comunicación en España. Los resultados permiten valorar que la formación en comunicación que reciben los estudiantes de medicina es escasa

La importancia de la erosión en el modelado de los volcanes de la región volcánica del Campo de Calatrava

La Región Volcánica del Campo de Calatrava es una unidad natural situada en el Centro de la provincia de Ciudad Real (Meseta Meridional española). El paisaje del Campo de Calatrava se resuelve en una sucesión de amplias cuencas de sedimentación terciaria enmarcadas por sierras paleozoicas, rotas por importantes procesos de fracturación debidas a las diferentes orogenias que afectaron a estas estructuras(Hercínica y Alpina). Fruto de diferentes procesos compresivo-distensivos, asociados al levantamiento de las cordilleras béticas, se produjeron procesos diapíricos que, favorecidos por la intensa red de fracturación de las sierras cuarcíticas, dieron origen a la aparición de más de 300 edifi cios volcánicos, en un área que abarca alrededor de 5.000 Km2 de extensión

Propiedades psicométricas preliminares de un cuestionario multidimensional de adaptación a la enfermedad para pacientes onco-hematológicos (Cmae-Oh) adaptado a pacientes renales en diálisis (Cmae-Rd)

Este trabajo tiene como objetivo la adaptación de un cuestionario empleado para la evaluación de necesidades y recursos en pacientes con enfermedad onco-hematológica, el CMAE-OH de Arranz y Ulla (2008) a pacientes renales en diálisis. Para ello realizamos tres estudios secuenciales. El primero de ellos es un estudio interjueces, para determinar la validez del cuestionario. El segundo es un estudio piloto para poner a prueba su funcionamiento en pacientes renales. El tercer estudio, consistirá en el empleo de la herramienta en una muestra mayor para determinar las propiedades psicométricas del instrumento. Tras la adaptación del cuestionario, concluimos que la herramienta es útil y adecuada para la evaluación de necesidades y recursos en los pacientes renales en diálisis, así como lo era para el caso de los pacientes oncológicos. Partimos de la adaptación de esta herramienta para iniciar una reflexión acerca de la cercanía, más que el distanciamiento, entre la psicooncología y otras subdisciplinas del ámbito de la Psicología de la Salud como la psiconefrologíaThe aim of this research is to adapt a questionnaire designed for the assessment of needs and resources in patients with onco-haematological diseases – the CMAE-OH- to renal patients under dialysis treatment. We have conducted three different studies. The first one is an inter-judges study to determine the face validity of the tool. The second is a pilot study, to know how the designed tool works when used in renal patients under dialysis. The third study consists of the usage of the questionnaire in a biggest sample to determine the psychometric properties of the tool. After the adaptation of the tool we conclude that the questionnaire we have adapt it is useful to assess needs and resources in renal patients under dialysis, as well as CMAE-OH was when used with oncological patients. On the basis of our study, we reflexionate about the closeness between psychooncology and other subdisciplines in the area of health psychology like psychonephrolog

Inflammasomes NLRP3 and AIM2 in peri-implantitis: A cross-sectional study

Background: Inflammasome components NLRP3 and AIM2 contribute to inflammation development by the activation of caspase-1 and IL-1β. They have not been yet evaluated in samples from patients with active peri-implantitis. Thus, the aim of the present study is to analyze the expression of inflammasomes NLRP3 and AIM2 and subsequent caspase 1 and IL-1β assessing the microenvironment of leukocyte subsets in samples from patients with active peri-implantitis. Methods: Biopsies were collected from 33 implants in 21 patients being treated for peri-implantitis. Biopsies from gingival tissues from 15 patients with healthy periodontium were also collected for control. These tissues were evaluated through conventional histological stainings. Then, immunohistochemical detection was performed to analyze NLRP3, AIM2, caspase-1, and IL-1β and markers of different leukocyte subsets. PCR for inflammasomes and related genes was also done. Results: This manuscript reveals a high immunohistochemical and mRNA expression of NLRP3 and AIM2 inflammasomes, caspase-1, and IL-1β in biopsies collected from human peri-implantitis. The expression of the tested markers was significantly correlated with the increase in inflammatory infiltrate, probing depth, presence of biofilm, and bleeding on probing. In these peri-implantitis lesions, the area of biopsy tissue occupied by inflammatory infiltrate was intense while the area occupied by collagen was significantly lower. In comparison with periodontal healthy tissues, the inflammatory infiltrate was statistically significantly higher in the peri-implantitis biopsies and was mainly composed of plasma cells, followed by T and B lymphocytes. Conclusion: In human peri-implantitis, chronic inflammation can be explained in part by the action of IL-1β/ caspase 1 induced through NLRP3 and AIM2 inflammasome activation.Junta de Andalucía, Grant/Award Number: CTS-138CTS-1028; Universidad de Granada, Grant/Award Number: B-CTS- 504- UGR18Universidad de Granada/CBU

Reducir el desperdicio: pensamiento Lean aplicado a las asignaturas de ingeniería térmica y máquinas de fluidos

La participación activa del profesorado en el proceso de enseñanza-aprendizaje constituye uno de los pilares sobre los que se sustentan los nuevos planes de estudio, lo cual exige el análisis del proceso de formación del alumnado. En este sentido, la filosofía Lean, originaria de Toyota, constituye una herramienta que permite a las instituciones determinar si responden de manera adecuada a las necesidades y expectativas de aquellos a los que se dirigen. Así, la enseñanza, entendida como proceso, tendrá un mayor rendimiento cuanto mayor sea el resultado en comparación con los recursos empleados. Bajo este enfoque, mejorar la eficiencia del proceso formativo significará reducir la necesidad de un determinado recurso para conseguir el resultado necesario. Esto es, que los discentes adquieran las competencias que fija la memoria de título para cada una de las materias que compone el grado. El exceso en el consumo de recursos se considera desperdicio. El objetivo, por tanto, del pensamiento Lean aplicado a la formación superior consiste en identificar y eliminar todo aquello que no añada valor al proceso: las fuentes de desperdicio. Las etapas en las que se estructuró el análisis fueron cuatro: identificar lo que los estudiantes esperan del proceso formativo en las asignaturas de Ingeniería Térmica y Máquinas de Fluidos del Grado en Ingeniería Mecánica, calcular el valor de la formación, identificar todos los pasos del proceso y, por último, utilizar técnicas Lean para generar soluciones y mejorar el rendimiento futuro del proceso. Se identificaron cuatro categorías de desperdicio: personas, procesos, información y activos