77,342 research outputs found

    Study on the concordance between different SNP‚Äźgenotyping platforms in sheep

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    .Different SNP genotyping technologies are commonly used in multiple studies to perform QTL detection, genotype imputation, and genomic predictions. Therefore, genotyping errors cannot be ignored, as they can reduce the accuracy of different procedures applied in genomic selection, such as genomic imputation, genomic predictions, and false-positive results in genome-wide association studies. Currently, whole-genome resequencing (WGR) also offers the potential for variant calling analysis and high-throughput genotyping. WGR might overshadow array-based genotyping technologies due to the larger amount and precision of the genomic information provided; however, its comparatively higher price per individual still limits its use in larger populations. Thus, the objective of this work was to evaluate the accuracy of the two most popular SNP-chip technologies, namely, Affymetrix and Illumina, for high-throughput genotyping in sheep considering high-coverage WGR datasets as references. Analyses were performed using two reference sheep genome assemblies, the popular Oar_v3.1 reference genome and the latest available version Oar_rambouillet_v1.0. Our results demonstrate that the genotypes from both platforms are suggested to have high concordance rates with the genotypes determined from reference WGR datasets (96.59% and 99.51% for Affymetrix and Illumina technologies, respectively). The concordance results provided in the current study can pinpoint low reproducible markers across multiple platforms used for sheep genotyping data. Comparing results using two reference genome assemblies also informs how genome assembly quality can influence genotype concordance rates among different genotyping platforms. Moreover, we describe an efficient pipeline to test the reliability of markers included in sheep SNP-chip panels against WGR datasets available on public databases. This pipeline may be helpful for discarding low-reliability markers before exploiting genomic information for gene mapping analyses or genomic predictionS

    How Does Reciprocity Affect Undergraduate Student Orientation towards Stakeholders?

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    5987Nowadays, students are more aware of the impact of companies on their stakeholders and the need for properly handling their expectations to operationalize corporate social responsibility. Nevertheless, little is known about how certain individual traits may relate to their stance on the issue. This exploratory research contributes to stakeholder theory by analysing the e ect of the individual’s decision-making process, including the consideration of their social preferences, on their orientation toward stakeholder management. Here, we draw upon a theoretical model for resource-allocation decision-making consisting of reciprocal and non-reciprocal components. Our data, from undergraduate students enrolled in di erent degrees, were collected through a questionnaire and two social within-subject experiments (ultimatum and dictator games). Thus, our results show that the presence of a reciprocal component when decisions are made is positively linked to an instrumental orientation toward stakeholders. In addition, a greater non-reciprocal component in the decision-making process corresponds to a more normative orientation.S

    Identification of Hindbrain Neural Substrates for Motor Initiation in the hatchling Xenopus laevis Tadpole

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    Animal survival profoundly depends on the ability to detect stimuli in the environment, process them and respond accordingly. In this respect, motor responses to a sensory stimulation evolved into a variety of coordinated movements, which involve the control of brain centres over spinal locomotor circuits. The hatchling Xenopus tadpole, even in its embryonic stage, is able to detect external sensory information and to swim away if the stimulus is considered noxious. To do so, the tadpole relies on well-known ascending sensory pathway, which carries the sensory information to the brain. When the stimulus is strong enough, descending interneurons are activated, leading to the excitation of spinal CPG neurons, which causes the undulatory movement of swimming. However, the activation of descending interneurons that marks the initiation of motor response appears after a long delay from the sensory stimulation. Furthermore, the long-latency response is variable in time, as observed in the slow-summating excitation measured in descending interneurons. These two features, i.e. long-latency and variability, cannot be explained by the firing time and pattern of the ascending sensory pathway of the Xenopus tadpole. Therefore, a novel neuronal population has been proposed to lie in the hindbrain of the tadpole, and being able to 'hold' the sensory information, thus accounting for the long and variable delay of swim initiation. In this work, the role of the hindbrain in the maintenance of the long and variable response to trunk skin stimulation is investigated in the Xenopustadpole at developmental stage 37/38. A multifaceted approach has been used to unravel the neuronal mechanisms underlying the delayed motor response, including behavioural experiments, electrophysiology analysis of fictive swimming, hindbrain extracellular recordings and imaging experiments. Two novel neuronal populations have been identified in the tadpole's hindbrain, which exhibit activation patterns compatible with the role of delaying the excitation of the spinal locomotor circuit. Future work on cellular properties and synaptic connections of these newly discovered populations might shed light on the mechanism of descending control active at embryonic stage. Identifying supraspinal neuronal populations in an embryonic organism could aid in understanding mechanisms of descending motor control in more complex vertebrates

    Interactive Sonic Environments: Sonic artwork via gameplay experience

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    The purpose of this study is to investigate the use of video-game technology in the design and implementation of interactive sonic centric artworks, the purpose of which is to create and contribute to the discourse and understanding of its effectiveness in electro-acoustic composition highlighting the creative process. Key research questions include: How can the language of electro-acoustic music be placed in a new framework derived from videogame aesthetics and technology? What new creative processes need to be considered when using this medium? Moreover, what aspects of 'play' should be considered when designing the systems? The findings of this study assert that composers and sonic art practitioners need little or no coding knowledge to create exciting applications and the myriad of options available to the composer when using video-game technology is limited only by imagination. Through a cyclic process of planning, building, testing and playing these applications the project revealed advantages and unique sonic opportunities in comparison to other sonic art installations. A portfolio of selected original compositions, both fixed and open are presented by the author to complement this study. The commentary serves to place the work in context with other practitioners in the field and to provide compositional approaches that have been taken

    Balancing the urban stomach: public health, food selling and consumption in London, c. 1558-1640

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    Until recently, public health histories have been predominantly shaped by medical and scientific perspectives, to the neglect of their wider social, economic and political contexts. These medically-minded studies have tended to present broad, sweeping narratives of health policy's explicit successes or failures, often focusing on extraordinary periods of epidemic disease viewed from a national context. This approach is problematic, particularly in studies of public health practice prior to 1800. Before the rise of modern scientific medicine, public health policies were more often influenced by shared social, cultural, economic and religious values which favoured maintaining hierarchy, stability and concern for 'the common good'. These values have frequently been overlooked by modern researchers. This has yielded pessimistic assessments of contemporary sanitation, implying that local authorities did not care about or prioritise the health of populations. Overly medicalised perspectives have further restricted historians' investigation and use of source material, their interpretation of multifaceted and sometimes contested cultural practices such as fasting, and their examination of habitual - and not just extraordinary - health actions. These perspectives have encouraged a focus on reactive - rather than preventative - measures. This thesis contributes to a growing body of research that expands our restrictive understandings of pre-modern public health. It focuses on how public health practices were regulated, monitored and expanded in later Tudor and early Stuart London, with a particular focus on consumption and food-selling. Acknowledging the fundamental public health value of maintaining urban foodways, it investigates how contemporaries sought to manage consumption, food production waste, and vending practices in the early modern City's wards and parishes. It delineates the practical and political distinctions between food and medicine, broadly investigates the activities, reputations of and correlations between London's guild and itinerant food vendors and licensed and irregular medical practitioners, traces the directions in which different kinds of public health policy filtered up or down, and explores how policies were enacted at a national and local level. Finally, it compares and contrasts habitual and extraordinary public health regulations, with a particular focus on how perceptions of and actual food shortages, paired with the omnipresent threat of disease, impacted broader aspects of civic life

    South Yorkshire low carbon energy supply chains: insulation sector summary

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    South Yorkshire low carbon energy supply chains: hydrogen sector summary

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    Medicina personalizada en lactantes con cáncer: Estudio farmacogenético de polimorfismos relacionados con toxicidad y respuesta a la quimioterapia

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    Introducci√≥n La farmacogen√©tica es una herramienta de la ‚ÄúMedicina personalizada‚ÄĚ que contribuye a optimizar los tratamientos antineopl√°sicos, adapt√°ndolos a las caracter√≠sticas gen√©ticas particulares de cada individuo, maximizando su eficacia y minimizando su toxicidad. El lactante con c√°ncer es un paciente de particular vulnerabilidad y sus comorbilidades tiene una especial repercusi√≥n vital. El estudio farmacogen√©tico en esta poblaci√≥n resulta pionero y novedoso en nuestro medio. La identificaci√≥n de marcadores predictivos espec√≠ficos permitir√° individualizar m√°s la terap√©utica en esta poblaci√≥n tan fr√°gil y mejorar en consecuencia su calidad de vida y su pron√≥stico vital. Material y m√©todos Estudio de cohortes ambispectivo de pacientes oncol√≥gicos entre 1 y 18 meses de edad, receptores de quimioterapia en el Hospital La Fe de Valencia, en el periodo comprendido entre enero 2007 y agosto 2019. La parte retrospectiva comprende hasta diciembre 2015, el estudio prospectivo desde enero 2016 hasta agosto 2019. En primer lugar, se realiza un an√°lisis descriptivo de variables epidemiol√≥gicas, cl√≠nico/biol√≥gicas, terap√©uticas y pron√≥sticas de 72 pacientes con dichas caracter√≠sticas. Se describe la toxicidad derivada de sus 578 ciclos de quimioterapia (37 variables cl√≠nicas), el tiempo de seguimiento y su supervivencia (meses). En segundo lugar, se realiza un estudio anal√≠tico cuyo objetivo es correlacionar los polimorfismos gen√©ticos relacionados con la quimioterapia de 64 de los pacientes, la toxicidad grave secundaria al tratamiento (‚Č• grado 3 seg√ļn CTAE 4.0) y su supervivencia. El genotipado se realiza en el Centro Nacional de Genotipado (CEGEN) mediante la tecnolog√≠a MassArray (AgenaBioscience), previa configuraci√≥n de un panel farmacogen√©tico pedi√°trico en base a las evidencias recogidas en la base de datos PharmGKB, fichas t√©cnicas de los medicamentos y consorcios internacionales expertos. El an√°lisis estad√≠stico descriptivo se realiza con los programas Excel 2016 y R: las variables cualitativas con el recuento num√©rico (porcentaje) y las variables cuantitativas como mediana +/- rango intercuart√≠lico ante ausencia de normalidad en la distribuci√≥n de los datos (p <0,05, prueba de Kolmogorov-Smirnov). En el an√°lisis de supervivencia se utiliza el estimador Kaplan-Meier. El an√°lisis estad√≠stico anal√≠tico de correlaci√≥n entre polimorfismos y toxicidad se realiza mediante regresi√≥n log√≠stica penalizada por Elastic Net empleando R. El an√°lisis estad√≠stico anal√≠tico de correlaci√≥n entre polimorfismos y reca√≠da/muerte se realiza mediante regresi√≥n de Cox penalizada por Elastic Net. Resultados Las variables epidemiol√≥gicas, cl√≠nico/biol√≥gicas y terap√©uticas de los pacientes de la muestra son consecuentes con las descritas en la literatura del lactante con c√°ncer. Las neoplasias con mayor impacto negativo en la supervivencia son la leucemia mielobl√°stica aguda y los tumores del sistema nervioso central. La toxicidad m√°s prevalente es hematol√≥gica, digestiva e infecciosa. Existe correlaci√≥n entre la toxicidad grave secundaria a los quimioter√°picos en forma de anemia, neutropenia y/o trombopenia y 46 polimorfismos gen√©ticos diferentes. As√≠ mismo se encuentra asociaci√≥n estad√≠sticamente significativa entre la supervivencia global y la supervivencia libre de enfermedad y ciertos polimorfismos gen√©ticos (26 y 13 respectivamente). Los polimorfismos obtenidos pertenecen a genes encargados del transporte (6 genes) y metabolismo (17 genes) de los f√°rmacos, de la reparaci√≥n del material gen√©tico y la supresi√≥n tumoral (5 genes) y de otras funciones biol√≥gicas (4 genes). Conclusi√≥n Los resultados del presente estudio muestran correlaci√≥n estad√≠stica entre 46 polimorfismos de genes implicados en la cin√©tica farmacol√≥gica y la reparaci√≥n del material gen√©tico y la variabilidad en la toxicidad quimioter√°pica y supervivencia de pacientes lactantes con c√°ncer. En definitiva, aportaciones de la farmacogen√©tica que pueden contribuir a la optimizaci√≥n del tratamiento antineopl√°sico en esta poblaci√≥n particular y a la predicci√≥n de sus riesgos, de especial impacto en los supervivientes del c√°ncer infantil

    Uso de las histonas circulantes y sus modificaciones post-traduccionales como biomarcadores en sepsis y shock séptico

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    La sepsis es una afecci√≥n potencialmente mortal causada por una respuesta anormal del hu√©sped a una infecci√≥n, produciendo respuestas fisiol√≥gicas alteradas que da√Īan los propios tejidos del paciente y pueden provocar disfunci√≥n org√°nica e incluso la muerte. Asimismo, algunos pacientes s√©pticos progresan a shock s√©ptico, caracterizado por alteraciones circulatorias, celulares y metab√≥licas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunol√≥gico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresi√≥n, la alta complejidad de la fisiopatolog√≠a de la sepsis requiere una mayor investigaci√≥n para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citot√≥xicos en la sepsis, ya que act√ļan como patrones moleculares asociados a da√Īo, que inducen estr√©s oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activaci√≥n de la piroptosis, un mecanismo de muerte celular programada que produce inflamaci√≥n mediante la expresi√≥n de IL-18, IL-1ő≤ and IL-1őĪ. Sin embargo, a pesar de la evidencia de activaci√≥n del inflamasoma en las c√©lulas inmunes durante la sepsis, se desconoce si las histonas extracelulares son capaces de activar los inflamasomas endoteliales y sus consecuencias. En este trabajo destacamos el papel previamente desconocido de las histonas extracelulares, mediando la activaci√≥n del inflamasoma NLRP3 y la piroptosis en las c√©lulas endoteliales, contribuyendo a la disfunci√≥n endotelial y la desregulaci√≥n de la respuesta inmune mediada por el endotelio. Asimismo, tambi√©n demostramos c√≥mo la acetilaci√≥n de histonas disminuye la activaci√≥n de la piroptosis. Adem√°s, demostramos que la piroptosis se produce en pacientes con shock s√©ptico y los niveles de histonas circulantes se correlacionan con la expresi√≥n de citoquinas proinflamatorias y citoquinas piropt√≥ticas, la liberaci√≥n de factores de adhesi√≥n endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones cl√≠nicas. De manera similar, hemos analizado las respuestas inmunorelacionadas que ocurren durante las primeras etapas de la sepsis con el objetivo de proporcionar nuevos datos comparando las cantidades de citoquinas, inmunomoduladores y otros mediadores endoteliales en pacientes cr√≠ticamente enfermos no s√©pticos, s√©pticos y de shock s√©ptico. Nuestro enfoque ayudar√° a caracterizar r√°pidamente las respuestas inmunes alteradas en pacientes s√©pticos y de shock s√©ptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilaci√≥n del ADN en el control del sistema inmune s√©ptico. Nuestros resultados demostraron el papel central de la metilaci√≥n del ADN modulando la respuesta molecular en los pacientes de shock s√©ptico y contribuyendo a la inmunosupresi√≥n, a trav√©s de la alteraci√≥n de los patrones de metilaci√≥n de los promotores de IL-10 y TREM-2.Sepsis is a life-threatening condition caused by an abnormal host response to an infection that produce altered physiological responses which damages own tissues of the patient and can result in organ dysfunction and in some cases death. Likewise, a subset of septic patients progresses to septic shock, characterized by substantial circulatory, cellular and metabolic abnormalities, which substantially increase the risk of mortality. Sepsis is characterized by a malfunction of the immune system and it can lead to an altered immune response and immunosuppression. Moreover, the high complexity of the pathophysiology of sepsis requires of further investigation to characterize the immune responses in sepsis and septic shock. Likewise, circulating extracellular histones have gained relevance as cytotoxic mediators in sepsis pathophysiology, since they act as damage-associated molecular patterns, which induce oxidative stress and activate NLRP3 inflammasome. Subsequently, inflammasome mediates pyroptosis activation, a programmed cell death mechanism that produces inflammation through the release of IL-18, IL-1ő≤ and IL-1őĪ. However, despite inflammasome activation may occur in immune cells during sepsis, it is unknown if this process also takes place in endothelial cells and particularly whether extracellular histones are capable of activating endothelial inflammasomes and their consequences. In this work we highlight a previously unknown role for extracellular histones, that mediates the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how histone acetylation decreases pyroptosis activation. Furthermore, we show how pyroptosis occurs in septic shock patients and how circulating histone levels correlate with the expression of pro-inflammatory and pyroptotic cytokines, the release of endothelial adhesion factors and septic shock severity. We propose histone-mediated pyroptosis as a new target to develop clinical interventions. Similarly, we have analyzed the immune-related responses occurring during the early stages of sepsis with the aim of providing new data by comparing the amounts of cytokines, immune modulators and other endothelial mediators in critically-ill non-septic patients, septic and septic shock patients. Our approach will help to rapidly characterize the altered immune responses in septic and septic shock patients admitted in the Intensive Care Unit. Finally, we also analyzed the role of DNA methylation in the control of septic immune system. Our results demonstrated the central role of DNA methylation modulating the molecular response in septic shock patients and contributing to immunosuppression, through the alteration of DNA methylation patterns of IL-10 and TREM2 promoters

    Metodología de intervención para trabajar ODS. Educación a través de las artes

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    La Agenda 2030 presenta 17 Objetivos de Desarrollo Sostenible (ODS), con sus metas e indicadores universales que los pa√≠ses miembros de la ONU emplean para enmarcar sus pol√≠ticas. Entre las metas del ODS 4 ‚Äúeducaci√≥n de calidad‚ÄĚ encontramos: ‚Äúasegurar que todos los alumnos adquieran los conocimientos te√≥ricos y pr√°cticos necesarios para promover el desarrollo sostenible, entre otras cosas mediante la educaci√≥n para el desarrollo sostenible y los estilos de vida sostenibles, los derechos humanos, la igualdad de g√©nero, la promoci√≥n de una cultura de paz y no violencia, la ciudadan√≠a mundial y la valoraci√≥n de la diversidad cultural y la contribuci√≥n de la cultura al desarrollo sostenible‚ÄĚ. La educaci√≥n, se considera el motor de la Agenda 2030 porque, adem√°s de representar el centro del ODS 4, desempe√Īa tambi√©n un papel notable en la implementaci√≥n de los dem√°s, mejorando su alcance y efectividad. As√≠ pues, entre las disciplinas que sustentan este trabajo se escogi√≥ la Educaci√≥n para el Desarrollo Sostenible y la Ciudadan√≠a Global como marco de acci√≥n y punto de partida en la formaci√≥n de los ciudadanos de un futuro viable, equitativo y habitable. Se continu√≥ investigando las oportunidades del desarrollo de la Competencia Intercultural en las relaciones humanas, aquello que diferencia a unas personas de otras puede aportar al conjunto de la sociedad y c√≥mo la educaci√≥n permitir√≠a su aprovechamiento. Con todo ello, se plante√≥ el marco did√°ctico de interacci√≥n en el cual se implement√≥ la interculturalidad en el ejercicio educativo. Se estudi√≥ as√≠ el poder de las artes como medio de motivaci√≥n e inspiraci√≥n a la hora de transmitir de la manera m√°s eficaz posible los valores considerados m√°s arriba. El objetivo del presente estudio se centra en demostrar el potencial de las artes para fomentar las competencias comunicativas, sociales, interculturales, emocionales, de ciudadan√≠a y sostenibilidad. Para ello, se ha realizado una investigaci√≥n aplicada que deriva en una propuesta concreta de intervenci√≥n con un programa educativo destinado a la ense√Īanza de lenguas, tanto primera como extranjera, en distintos niveles de la educaci√≥n formal en Mali y en Espa√Īa, aplicando un m√©todo hol√≠stico basado en el paradigma interpretativo. A trav√©s de la pintura, la literatura y el cine, se plantean una serie de actividades ideadas para crear un entorno educativo integrador, favorecer el empoderamiento del alumnado y promover el pensamiento cr√≠tico, la empat√≠a, la resiliencia, la comunicaci√≥n, la cooperaci√≥n y la educaci√≥n intercultural, como competencias esenciales para la consecuci√≥n de los 17 ODS, la construcci√≥n de un mundo transcultural sostenible y el desarrollo de una ciudadan√≠a global preparada para los retos del siglo XXI. En la metodolog√≠a de este proceso educativo innovador, multidisciplinar, flexible y adaptable, se ha empleado un an√°lisis del proceso de investigaci√≥n para monitorizarlo adecuadamente (DAFO). Cada una de las propuestas presenta una recogida de datos cualitativos (observaci√≥n, r√ļbricas) y cuantitativos (encuestas, entrevistas) y se ofrece un an√°lisis de contraste de los resultados finales. Con todo, se espera facilitar la exigente tarea que supone hacer consciente a la sociedad de base (desde la misma infancia; desde los niveles m√°s bajos de la misma y en todos los niveles de la educaci√≥n formal) de en qu√© consisten los ODS y su relevancia para hacer de todas las personas corresponsables directas en su consecuci√≥n para garantizar un futuro sostenible para toda la ciudadan√≠a global.The 2030 Agenda presents 17 Sustainable Development Goals (SDGs), with their universal targets and indicators that UN member countries use to frame their policies. Among the targets of SDG 4 ‚Äúquality education,‚ÄĚ we find the one that seeks: ‚Äúto ensure that all students acquire the theoretical and practical knowledge necessary to promote sustainable development, among other things through education for sustainable development and sustainable lifestyles, human rights, gender equality, the promotion of a culture of peace and non-violence, world citizenship and the appreciation of cultural diversity and the contribution of culture to sustainable development‚ÄĚ. Education is considered the engine of the 2030 Agenda because, in addition to representing the centre of SDG 4, it also plays a notable role in the implementation of the others, improving their scope and effectiveness. Among the disciplines that support this research, Education for Sustainable Development and Global Citizenship sets the framework for action and represents a starting point in the formation of citizens for a viable, equitable and habitable future. Global citizenship implies human relations and those and intrinsically shaped by culture. Intercultural Education and, more specifically, the development of Intercultural Competence needed to be considered. What differentiates some people from others can contribute to society as a whole and education is the means to explore and understand. For the design of a didactic framework of interaction, the power of the arts was studied as a means of motivation and inspiration when transmitting the values considered above in the most effective way possible. The objective of this study focuses on proving the potential of the arts to promote communicative, social, intercultural, emotional, citizenship and sustainability skills. For this, the theoretical research derived in a concrete intervention proposal with an educational program in language teaching, both first and foreign languages, at different levels of formal education in Mali and Spain, applying a holistic method based on the interpretive paradigm. Through painting, literature and cinema, a series of activities were designed to create an inclusive educational environment, favour the empowerment of students and promote critical thinking, empathy, resilience, communication, cooperation and intercultural education, as essential skills for the achievement of the 17 SDGs, the construction of a sustainable transcultural world and the development of global citizenship prepared for the challenges of the 21st century. In the methodology of this innovative, multidisciplinary, flexible and adaptable educational process, an analysis of the research process has been used to adequately monitor it (SWOT). Each of the proposals presents a collection of qualitative data (observation, rubrics) and quantitative data (surveys, interviews) and contrast analysis of the final results is offered. All in all, it is expected to facilitate the demanding task of making basic society aware (from childhood itself, from its lowest levels and at all levels of formal education) of what the SDGs consist of and their relevance to make all people directly co-responsible in its achievement to guarantee a sustainable future for all global citizens
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