Identificación y caracterización de fuentes de resistencia a sequía en guisante

Pea (Pisum sativum L.) is the first grain legume in Europe and the second in the world. Major constraints for its cultivation include abiotic complex stresses such as drought. Both, the availability of resistance sources and a comprehensive understanding of the mechanisms through which pea can tolerate stress are necessary for successful breeding programmes. In the present work, by different approaches we aimed to search and characterize new sources of drought tolerance in pea and further understand mechanisms underlying water stress responses. In a preliminary screening we sought drought tolerance pea genotypes using different physiological parameters related with drought stress under controlled conditions and compared their drought responses with a susceptible check. In addition, their adaptation to different Mediterranean environments was assessed in field trials during four seasons. Further, interaction with resistance to Fusarium oxysporum, an important biotic stress causing wilting of peas, was investigated. In order to ease breeding we identified quantitative trait loci related with tolerance over a recombinant inbred line population and based on model plant databases we developed a genetic model for drought tolerance using bioinformatics tools and verified experimentally by gene expression assays.El guisante (Pisum sativum L.) es la primera leguminosa-grano en Europa y la segunda en el mundo. Entre los principales problemas que afectan a su cultivo se encuentran estreses abióticos complejos como la sequía. La disponibilidad de fuentes de resistencia, así como la comprensión de los mecanismos de tolerancia a estrés en guisante son necesarias para desarrollar programas de mejora exitosos. En el presente trabajo nos propusimos buscar y caracterizar fuentes de tolerancia a la sequía en guisante y profundizar en el conocimiento de los mecanismos implicados en la respuesta a estrés hídrico mediante distintas aproximaciones. En un análisis preliminar buscamos genotipos de guisante tolerantes a la sequía y comprobamos su respuesta frente a un control susceptible. Además evaluamos su adaptación a distintos ambientes Mediterráneos durante cuatro campañas agrícolas. Por otra parte, investigamos la interacción con la resistencia a Fusarium oxisporum, un importante estrés biótico causante de la marchitez del guisante. Por otra parte, identificamos loci de caracteres cuantitativos asociados con la tolerancia sobre una población de líneas recombinantes congénitas, destinados a facilitar el proceso de mejora, y . desarrollamos un modelo genético para la tolerancia a la sequía basado en bases de datos de plantas modelo utilizando herramientas informáticas y lo verificamos experimentalmente mediante ensayos de expresión génica

Integrating the users in the design of a robot for making Comprehensive Geriatric Assessments (CGA) to elderly people in care centers

Lisboa, (28-31 de agosto 2017)Comprehensive Geriatric Assessment (CGA) is a multidimensional and multidisciplinary diagnostic instrument that helps provide personalized care to the elderly, by evaluating their physical and mental state. In a social and economic context of growing ageing populations, medical experts can save time and effort if provided with interactive tools to efficiently assist them in doing CGAs, managing standardized tests or data collection. Recent research proposes the use of social robots as the central part of these tools. These robots must be able to unfold all functionalities that questionnaires or motion-based tests require, including natural language, face tracking and monitoring, human motion capture and so on. But another issue is the robot's acceptability and trust by the end-users, both patients (elderly people) and clinicians: the robot needs to be able to engage with the patients during the interaction sessions, and must be perceived as a useful and efficient tool by the clinicians. This paper presents the acquisition of new user requirements for CLARC, through participatory and user-centered design approach, to inform the improvement of both interface and interaction. Thirty eight persons (elderly people, caregivers and health professionals) were involved in the design process of CLARC, based on user-centered methods and techniques of Human-Computer Interaction discipline.This work has been partially funded by the European Union ECHORD++ project (FP7-ICT-601116) and the TIN2015-65686-C5-1-R Spanish Ministerio de EconomÍa y Competitividad project and FEDER funds

CLARC: A cognitive robot for helping geriatric doctors in real scenarios

Third Iberian Robotics Conference (ROBOT 2017). 22 to 24 November 2017, Seville, SpainAbstract: Comprehensive Geriatric Assessment (CGA) is an integrated clinical process to evaluate the frailty of elderly persons in order to create therapy plans that improve their quality of life. For robotizing these tests, we are designing and developing CLARC, a mobile robot able to help the physician to capture and manage data during the CGA procedures, mainly by autonomously conducting a set of predefined evaluation tests. Built around a shared internal representation of the outer world, the architecture is composed of software modules able to plan and generate a stream of actions, to execute actions emanated from the representation or to update this by including/removing items at different abstraction levels. Percepts, actions and intentions coming from all software modules are grounded within this unique representation. This allows the robot to react to unexpected events and to modify the course of action according to the dynamics of a scenario built around the interaction with the patient. The paper describes the architecture of the system as well as the preliminary user studies and evaluation to gather new user requirements.This work has been partially funded by the EU ECHORD++ project (FP7-ICT-601116) and the TIN2015-65686-C5-1-R (MINECO and FEDER funds). Javier García is partially supported by the Comunidad de Madrid (Spain) funds under the project 2016-T2/TIC-171

Generation and integrated analysis of advanced patient-derived orthoxenograft models (PDOX) for the rational assessment of targeted therapies in endometrial cancer

Clinical management of endometrial cancer (EC) is handicapped by the limited availability of second line treatments and bona fide molecular biomarkers to predict recurrence. These limitations have hampered the treatment of these patients, whose survival rates have not improved over the last four decades. The advent of coordinated studies such as The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA_UCEC) has partially solved this issue, but the lack of proper experimental systems still represents a bottleneck that precludes translational studies from successful clinical testing in EC patients. Within this context, the first study reporting the generation of a collection of endometrioid-EC-patient-derived orthoxenograft (PDOX) mouse models is presented that is believed to overcome these experimental constraints and pave the way toward state-of-the-art precision medicine in EC. The collection of primary tumors and derived PDOXs is characterized through an integrative approach based on transcriptomics, mutational profiles, and morphological analysis; and it is demonstrated that EC tumors engrafted in the mouse uterus retain the main molecular and morphological features from analogous tumor donors. Finally, the molecular properties of these tumors are harnessed to assess the therapeutic potential of trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor with growing interest in EC, using patient-derived organotypic multicellular tumor spheroids and in vivo experiments

Unha enxeñeira ou científica en cada cole

Póster presentado na V XORNADA UNIVERSITARIA GALEGA EN XÉNERO. TRANSFORMANDO DENDE A UNIVERSIDADE. Vigo, 7 Xullo 2017Nesta comunicación, presentamos o proxecto Unha enxeñeira ou científica en cada cole organizado pola Oficina de Igualdade de Xénero da Universidade de Santiago de Compostela (USC) en colaboración co Concello de Santiago de Compostela. Esta iniciativa pretende incentivar a presenza de rapazas en carreiras relacionadas coas disciplinas STEM (ciencia, enxeñería, tecnoloxía e matemáticas), mediante actividades didácticas nos centros educativos que rachen cos estereotipos sexistas da nosa sociedade. A actividade didáctica consistiu na realización de dezanove obradoiros, dirixidos a nenas e nenos de 5º ou 6º de primaria e realizados nos meses de setembro e outubro de 2016. Os obradoiros foron impartidos por profesoras ou investigadoras da USC e do Centro de Supercomputación de Galicia (CESGA) para crear referentes femininos e incentivar a presenza de rapazas no ámbito científico tecnolóxico. Ademais, estes obradoiros amosaron a relación da ciencia e da tecnoloxía coa nosa vida cotiá e serviron para achegar ao alumnado a estas disciplinas dun xeito lúdicoConcello de Santiago de Compostel

Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002CC) and requirement of biological therapies (rs2241002C-rs2229177T haplotype), and with poor UC prognosis (rs2241002T-rs2229177T haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933G) and poor prognosis (rs12360861G), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933G). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD's clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders

Human Hereditary Cardiomyopathy Shares a Genetic Substrate With Bicuspid Aortic Valve.

The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes. We used CRISPR-Cas9 gene editing to generate mice harboring a nonsense or a missense MIB1 mutation that are both found in LVNC families. We also generated mice separately carrying these MIB1 mutations plus 5 additional cosegregating variants in the ASXL3, APCDD1, TMX3, CEP192, and BCL7A genes identified in these LVNC families by whole exome sequencing. Histological, developmental, and functional analyses of these mouse models were carried out by echocardiography and cardiac magnetic resonance imaging, together with gene expression profiling by RNA sequencing of both selected engineered mouse models and human induced pluripotent stem cell-derived cardiomyocytes. Potential biochemical interactions were assayed in vitro by coimmunoprecipitation and Western blot. Mice homozygous for the MIB1 nonsense mutation did not survive, and the mutation caused LVNC only in heteroallelic combination with a conditional allele inactivated in the myocardium. The heterozygous MIB1 missense allele leads to bicuspid aortic valve in a NOTCH-sensitized genetic background. These data suggest that development of LVNC is influenced by genetic modifiers present in affected families, whereas valve defects are highly sensitive to NOTCH haploinsufficiency. Whole exome sequencing of LVNC families revealed single-nucleotide gene variants of ASXL3, APCDD1, TMX3, CEP192, and BCL7A cosegregating with the MIB1 mutations and LVNC. In experiments with mice harboring the orthologous variants on the corresponding Mib1 backgrounds, triple heterozygous Mib1 Apcdd1 Asxl3 mice showed LVNC, whereas quadruple heterozygous Mib1 Cep192 Tmx3;Bcl7a mice developed bicuspid aortic valve and other valve-associated defects. Biochemical analysis suggested interactions between CEP192, BCL7A, and NOTCH. Gene expression profiling of mutant mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes revealed increased cardiomyocyte proliferation and defective morphological and metabolic maturation. These findings reveal a shared genetic substrate underlying LVNC and bicuspid aortic valve in which MIB1-NOTCH variants plays a crucial role in heterozygous combination with cosegregating genetic modifiers.This study was supported by grants PID2019-104776RB-I00 and PID2020-120326RB-I00, CB16/11/00399 (CIBER CV) financed by MCIN/AEI/10.13039/501100011033, a grant from the Fundación BBVA (Ref. BIO14_298), and a grant from Fundació La Marató de TV3 (Ref. 20153431) to J.L.d.l.P. M.S.-A. was supported by a PhD contract from the Severo Ochoa Predoctor-al Program (SVP-2014-068723) of the MCIN/AEI/10.13039/501100011033. J.R.G.-B. was supported by SEC/FEC-INV-BAS 21/021. A.R. was funded by grants from MCIN (PID2021123925OB-I00), TerCel (RD16/0011/0024), AGAUR (2017-SGR-899), and Fundació La Marató de TV3 (201534-30). J.M.P.-P. was supported by RTI2018-095410-B-I00 (MCIN) and PY2000443 (Junta de Andalucía). B.I. was supported by the European Commission (H2020-HEALTH grant No. 945118) and by MCIN (PID2019-107332RB-I00). DO’R was sup-ported by the Medical Research Council (MC-A658-5QEB0) and KAMcG by the British Heart Foundation (RG/19/6/34387, RE/18/4/34215). The cost of this publication was supported in part with funds from the European Regional Devel-opment Fund. The Centro Nacional de Investigaciones Cardiovasculares is sup-ported by the ISCIII, the MCIN, and the Pro Centro Nacional de Investigaciones Cardiovasculares Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020001041-S) financed by MCIN/AEI/10.13039/501100011033. For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising.S

Aprendizaje basado en juegos online para la mejora de la adquisición de competencias en Patología Médica Bucal

Estamos viviendo una situación complicada debido a la pandemia por el COVID-19. Durante el presente curso académico parte de nuestras asignaturas han pasado de una docencia presencial a una docencia online, esto ha sucedido en la asignatura Patología Médica Bucal del grado en Odontología. Este paso de la presencialidad a la docencia online requiere de nuevas medidas de motivación para aumentar la adquisición de conocimientos y mantener el aprendizaje activo. El objetivo de este proyecto ha sido aplicar diferentes juegos online para mejorar el aprendizaje en Patología Médica Bucal y la transferencia de conocimiento entre alumnos y profesores

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio