1,463 research outputs found

    An integrated targeted and untargeted approach for the analysis of ergot alkaloids in cereals using UHPLC - hybrid quadrupole time-of-flight mass spectrometry

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    An ultra-high performance liquid chromatography hybrid quadrupole time of flight (Q-TOF) mass spectrometry (MS) method is described for the simultaneous quantitative determination of common ergot alkaloids and the screening, detection and identification of unexpected (less studied or novel) members of this class of toxic fungal secondary metabolites. The employed analytical strategy involves an untargeted data acquisition (consisting of full scan TOF MS survey and information dependent acquisition MS/MS scans) and the processing of data using both targeted and untargeted approaches. Method performance characteristics for the quantitative analysis of 6 common ergot alkaloids i.e. ergometrine, ergosine, ergotamine, ergocornine, ergocristine, ergokryptine and their corresponding epimers in rye were comparable to those previously reported for triple-quadrupole (QqQ) MS/MS. The method limits of quantification (LOQ) were in the range from 3 to 19 mu g/kg, and good linearity was observed for the different ergot alkaloids in the range from LOQ to 1000 mu g/kg. Furthermore, the method demonstrated good precision (relative standard deviations at 50 mu g/kg not higher than 14.6 and 16.2% for the intra-day and inter-day precision, respectively), and the trueness values at different concentration levels were all between 89 and 115%. The method was applied for the analysis of a set of 17 rye samples and demonstrated the presence of these ergot alkaloids in the range from <LOQ to 2,811 mu g/kg. Further mining of the same data based on a 'non-targeted peak finding' algorithm and the use of full MS and MS/MS accurate mass data allowed the detection and identification of 19 ergot alkaloids that are commonly not included in most analytical methods using QqQ instruments. Some of these alkaloids are reported for the first time in naturally contaminated samples

    Efecto del ejercicio sobre las subpoblaciones HDL, la enzima lecitina-colesterol acil-transferasa y la proteína transportadora de ésteres de colesterol en estudiantes de Medicina

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    ResumenObjetivoEvaluar el efecto del ejercicio físico sobre los niveles de las subpoblaciones HDL, enzima lecitina-colesterol acil-transferasa y la proteína transportadora de ésteres de colesterol en estudiantes de Medicina.MétodoLa población se dividió de manera voluntaria en 2 grupos: ejercicio y no ejercicio. Se midieron perímetro abdominal e índice de masa corporal, subfracciones de HDL2 y HDL3 por precipitación iónica, y enzima lecitina-colesterol acil-transferasa y proteína transportadora de ésteres de colesterol mediante Enzyme-Linked Immuno Sorbent Assay (ELISA).ResultadosEl perfil lipídico de riesgo aumentó en ambos grupos: las HDL, HDL3 y HDL2 disminuyeron en ambos grupos, pero solo las HDL2 lo hicieron de forma significativa en el grupo que realizó ejercicio. La lecitina-colesterol acil-transferasa y la proteína transportadora de ésteres de colesterol permanecieron sin cambios significativos. Sin embargo, en el grupo que hizo ejercicio hubo disminución estadísticamente significativa de HDL2 y lecitina-colesterol acil-transferasa, en las mujeres.ConclusionesEl ejercicio logra modificar algunas variables como el perímetro abdominal, el índice de masa corporal y las HDL3. Estas modificaciones son dependientes del género, pero, a pesar de la intervención de 3 meses con un programa de ejercicio, este no logra reducir los factores de riesgo lipídico en esta población de estudiantes de Medicina, debido a que su entorno hace muy compleja la respuesta metabólica al ejercicio.AbstractObjectiveTo evaluate exercise effect on HDL subpopulations, lecithin-cholesterol acyltransferase enzyme and ester transfer protein cholesterol levels in medical students.MethodPopulation was divided voluntarily into 2 groups, exercise and no exercise. Waist circumference and body mass index were measured; subfractions HDL2 and HDL3 by ion precipitation and LCAT and CETP enzymes Enzyme-Linked Immuno-Sorbent Assay (ELISA).ResultsLipidrisk profile increased in both groups; HDL, HDL2 and HDL3 decreased in both groups, but only the HDL2 decreased significantly in students who exercised. LCAT and CETP remained without significant changes, however, in the exercise group, there was statistically significant decrease in HDL2 and LCAT in women.ConclusionsThis study shows that exercise does alter some variables such as waist circumference, body mass index and HDL3. These changes are dependent on gender, but despite the intervention of 3 months with an exercise program, it fails reducing lipid risk factors in this medical student populations, given their environment, which complicates their metabolic response to exercise

    Challenges to Foster Resilience

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    The work aims to provoke critical educational reflections on the current state of the scientific-pedagogical conception of inclusive education in the university context. In this sense, we are aware of the existence of an extremely positive conceptual evolution in recent times. It is necessary to articulate new discourses and teaching practices that project and illuminate the idea that inclusive education as a permanent process of change in education and for which the development of psychological activities outlined in resilience can play an important role. The Ecuadorian higher education system has experienced, for a few years, changes of great pedagogical interest. In this framework, a whole process of generating educational policies and inclusive education is shown, taking as a framework the professors and managers of the Technical University of Manabí (UTM) (Ecuador), to contribute to the greater inclusive development of the said university. The main challenges for university institutions regarding fostering the resilience of the academic process are presented

    Epistemologías culturales del Caribe: modelos conceptuales metafóricos en el ensayo caribeño del siglo XX

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    El Caribe ha sido reconocido por considerarse una pluralidad de espacios que simultáneamente son solo uno. Contrario al contexto de su fragmentada geografía, su segregada historia colonial y su diversidad racial y lingüística, los intelectuales caribeños han establecido puentes de unidad cultural con la intención de configurar una identidad pan-caribeña. Por consiguiente, los ensayistas del siglo XX se enfrentan a la necesidad de examinar críticamente los factores que formulan sus respectivas identidades, en contraste con aquellas tradicionalmente impuestas bajo el discurso colonial y metropolitano. Desde el tercer cuarto del siglo, pensadores como Aimé Césaire (1913-2008), Fernando Ortiz (1881-1969), Fidel Castro (1926-), George Lamming (1927-), Kamau Brathwaite (1930-), Juan I. Jiménes-Grullón (1903-1983), Hubert Devonish (1953-), Edouard Glissant (1928-2011), Antonio Benítez-Rojo (1931-2005), Arcadio Díaz Quiñones y Maryse Condé (1937-), entre otros, cuestionan el sistema colonial, los procesos étnicos y las propuestas lingüísticas, relacionándolos con conceptos tales como la hibridez, el sincretismo, la transculturación y la heterogeneidad. Estas teorías culturales, de alguna manera, reescriben ideas antecedentes en reacción a discursos hegemónicos previos como consecuencia de los cambios políticos que trajeron las guerras de independencia en América Latina durante el siglo XIX. En mi tesis demuestro que estos planteamientos delinean un mapa de modelos epistemológicos de la cultura del Caribe. Para indicar que estas propuestas constituyen metáforas que muestran una consciencia cultural, las proposiciones acerca de la cultura de Jorge Luis Borges (1899-1986) y Hayden White (1928-) sirven como marco teórico apropiado. Así, a través de las representaciones literarias ensayísticas de los modelos metafóricos de la cultura caribeña, este trabajo redefine algunos aspectos importantes de la identidad cultural vis a vis la mirada parcial que usualmente se utiliza para estudiar el archipiélago antillano. Igualmente, incluso aunque estos modelos proponen una representación metafórica de la cultura pan-caribeña, la construcción de un modelo del Caribe puede ser utilizado en otras regiones y espacios culturales en el contexto de la globalización, ya que elucida una gnoseología cultural que sirve para describir distintas realidades globales

    Asociación entre incidencia de Tuberculosis e índice de desarrollo humano en 165 países del mundo

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    Objetivos: Evaluar la relación entre el índice de desarrollo humano (IDH) y la incidencia de tuberculosis (TB) en 165 países del mundo en el período 2005-2011. Materiales y métodos: Se realizó un estudio ecológico para el cual el IDH se obtuvo de la base de datos del Fondo de Naciones Unidas para el Desarrollo (PNUD) y la incidencia de TB del Programa Alto a la TB de la Organización Mundial de la Salud (OMS). Se evaluó la variación anual de las variables y se realizaron modelos de regresión no lineales (exponencial). Resultados. Al analizar los datos con los modelos de regresión no lineal, se observó que los países con mayores tasas de incidencia de TB fueron aquellos con menores valores de IDH, siendo significativa su asociación (p<0,01). De igual forma se observó que en los países, la variación en el tiempo se asoció significativamente con la variación en el IDH. Conclusiones: Se ha encontrado una relación inversa y significativa entre el IDH y la morbilidad por TB en los países estudiados, incluidos tanto los países de mayor carga de enfermedad como los de la región andina en Latinoamérica. Esta información refleja la influencia significativa de indicadores socioeconómicos como el IDH sobre la tasa de incidencia de la TB, especialmente en países endémicos, siendo inversa entre ambos tipos de variables; con el incremento o mejoría del IDH la tasa de incidencia de la enfermedad disminuyó o se encontró siendo significativamente menor.Objectives: Assess relationship between the Human Development Index (HDI) and the incidence of tuberculosis (TB) in 165 countries in the World in the period 2005-2011. Materials and methods. An ecological study was done, using HDI data that were obtained from the United Nations Development Program (UNDP), and the incidence rates from the Stop TB Program of the World Health Organization (WHO). The annual variation of the variables was assessed and non-linear regression models (Exponential), were done. Results. At the non-linear regression models, it was observed that the relationship between epidemiological and HDI was significant, those countries with higher rates presented lower values of HDI (p<0.01). Additionally the variation in time was significantly associated with HDI variation. Conclusions: This information reflect the significant influence of socioeconomical indicators such as the HDI on the TB incidence rates in the World, particularly in endemic countries, being an inverse relationship between both types of variables; with an increase or improvement in the HDI, the disease incidence rate decreased or it is found lower

    Disruption of exocytosis in sympathoadrenal chromaffin cells from mouse models of neurodegenerative diseases

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    Synaptic disruption and altered neurotransmitter release occurs in the brains of patients and in murine models of neurodegenerative diseases (NDDs). During the last few years, evidence has accumulated suggesting that the sympathoadrenal axis is also affected as disease progresses. Here, we review a few studies done in adrenal medullary chromaffin cells (CCs), that are considered as the amplifying arm of the sympathetic nervous system; the sudden fast exocytotic release of their catecholamines—stored in noradrenergic and adrenergic cells—plays a fundamental role in the stress fight-or-flight response. Bulk exocytosis and the fine kinetics of single-vesicle exocytotic events have been studied in mouse models carrying a mutation linked to NDDs. For instance, in R6/1 mouse models of Huntington’s disease (HD), mutated huntingtin is overexpressed in CCs; this causes decreased quantal secretion, smaller quantal size and faster kinetics of the exocytotic fusion pore, pore expansion, and closure. This was accompanied by decreased sodium current, decreased acetylcholine-evoked action potentials, and attenuated [Ca2+]c transients with faster Ca2+ clearance. In the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS), CCs exhibited secretory single-vesicle spikes with a slower release rate but higher exocytosis. Finally, in the APP/PS1 mouse model of Alzheimer’s disease (AD), the stabilization, expansion, and closure of the fusion pore was faster, but the secretion was attenuated. Additionally, α-synuclein that is associated with Parkinson’s disease (PD) decreases exocytosis and promotes fusion pore dilation in adrenal CCs. Furthermore, Huntington-associated protein 1 (HAP1) interacts with the huntingtin that, when mutated, causes Huntington’s disease (HD); HAP1 reduces full fusion exocytosis by affecting vesicle docking and controlling fusion pore stabilization. The alterations described here are consistent with the hypothesis that central alterations undergone in various NDDs are also manifested at the peripheral sympathoadrenal axis to impair the stress fight-or-flight response in patients suffering from those diseases. Such alterations may occur: (i) primarily by the expression of mutated disease proteins in CCs; (ii) secondarily to stress adaptation imposed by disease progression and the limitations of patient autonomy.Spanish Ministry of Science, Technology and Innovation SAF2016-78892R; EU Horizon 2020 Research and Innovation Programme under Marie Slodowska-Curie Grant Agreement N. 766124. We acknowledge the continuous support of Fundación Teófilo Hernando

    Vaccinia-related kinase 1 (VRK1) is an upstream nucleosomal kinase required for the assembly of 53BP1 foci in response to ionizing radiation-induced DNA damage

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    Cellular responses to DNA damage require the formation of protein complexes in a highly organized fashion. The complete molecular components that participate in the sequential signaling response to DNA damage remain unknown. Here we demonstrate that vaccinia-related kinase 1 (VRK1) in resting cells plays an important role in the formation of ionizing radiationinduced foci that assemble on the 53BP1 scaffold protein during the DNA damage response. The kinase VRK1 is activated by DNA double strand breaks induced by ionizing radiation (IR) and specifically phosphorylates 53BP1 in serum-starved cells. VRK1 knockdown resulted in the defective formation of 53BP1 foci in response to IR both in number and size. This observed effect on 53BP1 foci is p53- and ataxia-telangiectasia mutated (ATM)-independent and can be rescued with VRK1 mutants resistant to siRNA. VRK1 knockdown also prevented the activating phosphorylation of ATM, CHK2, and DNA-dependent protein kinase in response to IR. VRK1 activation in response to DNA damage is a novel and early step in the signaling of mammalian DNA damage responses.This work was supported in part by Ministerio de Ciencia e Innovación Grants SAF2010-14935 and CSD2007-0017, Junta de Castilla y León Grants CSI006A11-2 and GR-15, and the Kutxa-Fundación Inbiomed. Supported by Junta para la Ampliación de Estudios-CSIC-Fondo Social Europeo fellowships.Peer Reviewe

    Cognitive function in childhood and lifetime cognitive change in relation to mental wellbeing in four cohorts of older people

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    Background: poorer cognitive ability in youth is a risk factor for later mental health problems but it is largely unknown whether cognitive ability, in youth or in later life, is predictive of mental wellbeing. The purpose of this study was to investigate whether cognitive ability at age 11 years, cognitive ability in later life, or lifetime cognitive change are associated with mental wellbeing in older people.Methods: we used data on 8191 men and women aged 50 to 87 years from four cohorts in the HALCyon collaborative research programme into healthy ageing: the Aberdeen Birth Cohort 1936, the Lothian Birth Cohort 1921, the National Child Development Survey, and the MRC National Survey for Health and Development. We used linear regression to examine associations between cognitive ability at age 11, cognitive ability in later life, and lifetime change in cognitive ability and mean score on the Warwick Edinburgh Mental Wellbeing Scale and meta-analysis to obtain an overall estimate of the effect of each.Results: people whose cognitive ability at age 11 was a standard deviation above the mean scored 0.53 points higher on the mental wellbeing scale (95% confidence interval 0.36, 0.71). The equivalent value for cognitive ability in later life was 0.89 points (0.72, 1.07). A standard deviation improvement in cognitive ability in later life relative to childhood ability was associated with 0.66 points (0.39, 0.93) advantage in wellbeing score. These effect sizes equate to around 0.1 of a standard deviation in mental wellbeing score. Adjustment for potential confounding and mediating variables, primarily the personality trait neuroticism, substantially attenuated these associations.Conclusion: associations between cognitive ability in childhood or lifetime cognitive change and mental wellbeing in older people are slight and may be confounded by personality trait difference
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