Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review

[Objective] We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature.[Methods] A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed.[Results] Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively.[Conclusions] There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype.This work was supported by the Carlos III Health Institute-European Regional Development Fund (ISCIII-FEDER) [PI14/01823, PI16/01575, PI18/01898, PI19/01576], the Andalusian Regional Ministry of Economics, Innovation, Science and Employment [CVI-02526, CTS-7685], the Andalusian Regional Ministry of Health and Welfare [PI-0741-2010, PI-0471-2013, PE-0210-2018, PI-0459-2018, PE-0186-2019], and the Alicia Koplowitz and Mutua Madrileña Foundations. Pilar Gómez-Garre was supported by the "Miguel Servet" program [MSII14/00018] (from ISCIII-FEDER) and “Nicolás Monardes” program [C-0048-2017] (from the Andalusian Regional Ministry of Health). Silvia Jesús was supported by the "Juan Rodés" program [B-0007-2019] and Daniel Macías-García by the “Río Hortega” program [CM18/00142] (both from ISCIII-FEDER). María Teresa Periñán was supported by the Spanish Ministry of Education [FPU16/05061]. Cristina Tejera was supported by VPPI-US from the University of Seville.Peer reviewe

PhDAY 2020 -FOO (Facultad de Óptica y Optometría)

Por cuarto año consecutivo los doctorandos de la Facultad de Óptica y Optometría de la Universidad Complutense de Madrid cuentan con un congreso propio organizado por y para ellos, el 4º PhDAY- FOO. Se trata de un congreso gratuito abierto en la que estos jóvenes científicos podrán presentar sus investigaciones al resto de sus compañeros predoctorales y a toda la comunidad universitaria que quiera disfrutar de este evento. Apunta en tu agenda: el 15 de octubre de 2020. En esta ocasión será un Congreso On-line para evitar que la incertidumbre asociada a la pandemia Covid-19 pudiera condicionar su celebración

Plasmodium vivax spleen-dependent genes encode antigens associated with cytoadhesion and clinical protection

International audiencePlasmodium vivax, the most widely distributed human malaria parasite, causes severe clinical syndromes despite low peripheral blood parasitemia. This conundrum is further complicated as cytoadherence in the microvasculature is still a matter of investigations. Previous reports in Plasmodium knowlesi, another parasite species shown to infect humans, demonstrated that variant genes involved in cytoadherence were dependent on the spleen for their expression. Hence, using a global transcriptional analysis of parasites obtained from spleen-intact and splenectomized monkeys, we identified 67 P. vivax genes whose expression was spleen dependent. To determine their role in cytoadherence, two Plasmodium falciparum transgenic lines expressing two variant proteins pertaining to VIR and Pv-FAM-D multigene families were used. Cytoadherence assays demonstrated specific binding to human spleen but not lung fibroblasts of the transgenic line expressing the VIR14 protein. To gain more insights, we expressed five P. vivax spleen-dependent genes as recombinant proteins, including members of three different multigene families (VIR, Pv-FAM-A, Pv-FAM-D), one membrane transporter (SECY), and one hypothetical protein (HYP1), and determined their immunogenicity and association with clinical protection in a prospective study of 383 children in Papua New Guinea. Results demonstrated that spleen-dependent antigens are immunogenic in natural infections and that antibodies to HYP1 are associated with clinical protection. These results suggest that the spleen plays a major role in expression of parasite proteins involved in cytoadherence and can reveal antigens associated with clinical protection, thus prompting a paradigm shift in P. vivax biology toward deeper studies of the spleen during infections

Plasmodium vivax spleen-dependent genes encode antigens associated with cytoadhesion and clinical protection.

The most widely distributed human malaria parasite, causes severe clinical syndromes despite low peripheral blood parasitemia. This conundrum is further complicated as cytoadherence in the microvasculature is still a matter of investigations. Previous reports in " - ", another parasite species shown to infect humans, demonstrated that variant genes involved in cytoadherence were dependent on the spleen for their expression. Hence, using a global transcriptional analysis of parasites obtained from spleen-intact and splenectomized monkeys, we identified 67 " - " genes whose expression was spleen dependent. To determine their role in cytoadherence, two " - " transgenic lines expressing two variant proteins pertaining to VIR and Pv-FAM-D multigene families were used. Cytoadherence assays demonstrated specific binding to human spleen but not lung fibroblasts of the transgenic line expressing the VIR14 protein. To gain more insights, we expressed five " - " spleen-dependent genes as recombinant proteins, including members of three different multigene families (VIR, Pv-FAM-A, Pv-FAM-D), one membrane transporter (SECY), and one hypothetical protein (HYP1), and determined their immunogenicity and association with clinical protection in a prospective study of 383 children in Papua New Guinea. Results demonstrated that spleen-dependent antigens are immunogenic in natural infections and that antibodies to HYP1 are associated with clinical protection. These results suggest that the spleen plays a major role in expression of parasite proteins involved in cytoadherence and can reveal antigens associated with clinical protection, thus prompting a paradigm shift in " - " biology toward deeper studies of the spleen during infection

. 11-12 Año 6 (2017) enero-agosto. CR. Conservación y restauración

- Editorial por Manuel Alejandro González Gutiérrez y Magdalena Rojas Vences. -Proyecto de atención del acervo documental de Ixcamilpa de Guerrero por Patricia de la Garza Cabrera, Marie Vander Meeren, Laura Olivia Ibarra Carmona, Nora A. Pérez Castellanos, Carlos Orejel Delgadillo, Silvia Yocelin Pérez Ramírez, Débora Y. Ontiveros Ramírez, Denisse Ochoa Gutiérrez, Hugo Arriaga González y Gerardo Gutiérrez. - Haciendo frente a los embates medioambientales: conservación integral del sitio rupestre Cuevas Pintas,Baja California Sur por Sandra Cruz Flores, Alejandra Bourillón Moreno, Anacaren Morales Ortiz, Rodrigo Ruiz Herrera y María Fernanda López-Armenta. - Estrategia para la accesibilidad e inclusión de las personas con discapacidad a zonas arqueológicas “El pasado es de todos” por Daniela Tovar Ortiz y Luis Antonio Huitrón Santoyo. - Atención a grupos sociales. Sistematización de actividades por Manuel González Gutiérrez y Denisse Ochoa Gutiérrez. - Tañendo campanas: trabajando en equipo. Intervención de las campanas robadas en la capilla de Nuestra Señora de la Concepción, Escobedo, Nuevo León por Gabriela Peñuelas Guerrero, Carlos I. Cañete Ibáñez, Claudia Sánchez Gándara, Jannen Contreras Vargas e Ingrid K. Jiménez Cosme. - La apropiación del patrimonio cultural de El Ocote. Una aportación etnográfica para la sostenibilidad por Hugo Arriaga González. - Churubusco. 50 años en la memoria. Una muestra conmemorativa de la conservación en el INAH por Mónica Badillo Leal, Gabriela Gómez Llorente y Mariana Pascual Cáceres. - Los órganos y su conservación en la CNCPC por Norma Cristina Peña Peláez, Sandra María Álvarez Jacinto, José Luis Acevedo Guzmán y Fanny Magaña Nieto. - Conservación de cestería en espiral proveniente de la Cueva de la Candelaria, Torreón, Coahuila: criterios, tratamientos y líneas de investigación por Gloria Martha Sánchez Valenzuela, Miriam Elizabeth Castro Rodríguez y Adriana Reyes García. - Evaluación de recubrimientos de protección para metales. Caso de estudio: Imagen de México, relieve escultórico del Museo Nacional de Antropología. Primera etapa por Aline Moreno Núñez, Arturo A. Egea Salas, Gilda E. Salgado Manzanares, Mauricio B. Jiménez Ramírez, Armando Arciniega Corona y Nora A. Pérez Castellanos. - Patrimonio arqueológico digital. Uso de las tecnologías de la información y la comunicación para la divulgación del patrimonio arqueológico por Eduardo Andrés Escalante Carrillo y Luis Antonio Huitrón Santoyo. - El laboratorio de documentación y análisis tridimensional de la CNCPC. Resultados a un año de operación María Fernanda López-Armenta, Gilberto García Quintana y Celedonio Rodríguez Vidal. - La conservación-restauración de los bienes culturales en el Museo Regional de Querétaro: retos y perspectivas por María del Rosario Bravo Aguilar Conocer y reconocer a los actores sociales en la conservación de los bienes patrimoniales por Mitzi Vania García Toribio y Fanny Magaña Nieto. - Foro Anual de Trabajo. Una historia sin historia en el archivo de la CNCPC por Débora Y. Ontiveros Ramírez. - Expediente de incidentes en el tiempo. El Ehécatl-Quetzalcóatl de Coyoacán y cómo su caso puede ser usado para difundir la conservación en museos por Roberto Velasco Alonso. - Conservación en la vida cotidiana por María Bertha Peña Tenorio. - La Mediateca del INAH por Thalía E. Velasco Castelán. - Finaliza CNCPC la recuperación de sillares simulados originales en la bóveda del templo franciscano de Huaquechula, Puebla por Oscar Adrián Gutiérrez Vargas. - San Francisco de Asís en Huejotzingo, Puebla María Eugenia Rivera Pérez. - Investiga INAH factores de deterioro en la pirámide de la Serpiente Emplumada por Oscar Adrián Gutiérrez Vargas. - Lo que querías saber y no te atrevías a preguntar sobre el INAH en El Ocote por Oscar Adrián Gutiérrez Vargas. - Para saber más de El Caballito por Oscar Adrián Gutiérrez Vargas

La investigación universitaria y sus contribuciones en Mesoamérica

La Universidad Autónoma de Chiapas a través de su Proyecto Académico 2014-2018, reafirma su compromiso con el desarrollo de nuestra región, al establecer líneas de desarrollo de nuestra región, al establecer líneas de desarrollo institucional, donde la vinculación de la investigación ocupa un lugar preponderante; en este sentido, a partir de 2015, junto con la comunidad académica internacional, se unió a la Agenda 2030 para el Desarrollo sostenible de la ONU y priorizó los 17 Objetivos de Desarrollo Sostenible (ODS) y sus 169 metas, con la finalidad de dar soluciona los grandes desafíos sociales, económicos y medioambientales que enfrenta la sociedad. Este libro es la recopilación de trabajos realizados por académicos de diversas Instituciones de Educación Superior y Centros de Investigación, de manera multidisciplinaria, interinstitucional e internacional, los cuales han permitido compartir intereses en diversas líneas de generación y aplicación del conocimiento

La investigación universitaria y sus contribuciones en Mesoamérica

La Universidad Autónoma de Chiapas a través de su Proyecto Académico 2014-2018, reafirma su compromiso con el desarrollo de nuestra región, al establecer líneas de desarrollo de nuestra región, al establecer líneas de desarrollo institucional, donde la vinculación de la investigación ocupa un lugar preponderante; en este sentido, a partir de 2015, junto con la comunidad académica internacional, se unió a la Agenda 2030 para el Desarrollo sostenible de la ONU y priorizó los 17 Objetivos de Desarrollo Sostenible (ODS) y sus 169 metas, con la finalidad de dar soluciona los grandes desafíos sociales, económicos y medioambientales que enfrenta la sociedad. Este libro es la recopilación de trabajos realizados por académicos de diversas Instituciones de Educación Superior y Centros de Investigación, de manera multidisciplinaria, interinstitucional e internacional, los cuales han permitido compartir intereses en diversas líneas de generación y aplicación del conocimiento

Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial

International audienceBackground and Purpose— Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods— FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results— FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions— In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset