974 research outputs found

    The influence of pre-fermentative maceration and ageing factors on ester profile and marker determination of Pedro Ximenez sparkling wines

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    The influence of pre-fermentative maceration and ageing factors on the ester profiles of Pedro Ximenez sparkling wines was evaluated. The pre-fermentative maceration consisted of the skin-maceration of musts at 10 degrees C for 6 h. The sparkling wines were produced following the Champenoise method. Samples were monitored at 3, 6 and 9 months of ageing on lees. Sparkling wines with pre fermentative maceration displayed higher contents of ethyl esters of branched acids and cinnamates. Meanwhile, those without maceration showed higher levels of ethyl esters of fatty acids and higher alcohol acetates. The study of statistical interactions elucidated different hydrolytic kinetics and developments in higher alcohol acetates and ethyl esters of branched acids during ageing. The application of a dual criterion based on univariate (ANOVA) and multivariate analyses (OPLS-DA) allowed us to identify new potential volatile markers related to pre-fermentative maceration and ageing time, reported for the first time in sparkling wines

    Evolution of occupational asthma: Does cessation of exposure really improve prognosis?

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    SummaryAimTo assess the evolution of occupational asthma (OA) depending on whether the patient avoids or continues with exposure to the offending agent.MethodsStudy in patients diagnosed with OA using a specific inhalation challenge. Patients underwent the following examinations on the same day: clinical interview, physical examination, forced spirometry, methacholine test and determination of total IgE. Clinical improvement, deterioration or no change were defined according to the changes seen on the GINA severity scale at the time of diagnosis.ResultsOf the 73 patients finally included, 55 had totally ended exposure and 18 continued to be exposed at work. Clinical improvement was observed in 47% of those who had terminated exposure and in 22% of those who remained exposed; clinical deterioration was observed in 14% and 17% respectively (p = 0.805). Logistical regression analysis, including the type of agent and the persistence or avoidance of exposure among the variables, did not show any predictive factors of clinical evolution. Similarly, the changes in FEV1 and in bronchial hyperresponsiveness were not associated with the avoidance or continuation of exposure to the causative agent.ConclusionsAvoiding exposure to the causative agent in patients with OA does not seem to improve prognosis in this disease. Despite these findings, there is insufficient evidence to recommend a change in current management guidelines

    Crystallization Kinetics of LaF3 Nanocrystals in an Oxyfluoride Glass

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    Nanocrystallization of LaF3 in a glass of composition 55SiO2– 20Al2O3–15Na2O–10LaF3 (mol%) has been achieved by heat treatment above the glass transition temperature. A maximum crystal size of 14 nm has been attained, with the crystalline fraction and crystal size dependent on the time and temperature of thermal treatment. The effect of lanthanum fluoride crystallization is noticeable from the microstructural and compositional changes in the glass matrix, which have been studied using several techniques, including viscosity, dilatometry, X-ray diffraction, and quantitative Rietveld refinement, transmission electron microscopy, and differential scanning calorimetry. The crystallization mechanism is shown to occur via regions of La- and Si-phase separation in the glass, from which the fluoride crystals develop during heat treatment. The interface between the glass matrix and the crystals in the demixed ranges is enriched in network formers, mainly SiO2, creating a viscous barrier, which inhibits further crystal growth and limits the crystal size to the nanometric range.Peer reviewe

    Glucose Oxidation to Pyruvate Is Not Essential for Brucella suis Biovar 5 Virulence in the Mouse Model

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    Brucella species cause brucellosis, a worldwide extended zoonosis. The brucellae are related to free-living and plant-associated alpha 2-Proteobacteria and, since they multiply within host cells, their metabolism probably reflects this adaptation. To investigate this, we used the rodent-associated Brucella suis biovar 5, which in contrast to the ruminant-associated Brucella abortus and Brucella melitensis and other B. suis biovars, is fast-growing and conserves the ancestral Entner-Doudoroff pathway (EDP) present in the plant-associated relatives. We constructed mutants in Edd (glucose-6-phosphate dehydratase; first EDP step), PpdK (pyruvate phosphate dikinase; phosphoenolpyruvate pyruvate), and Pyk (pyruvate kinase; phosphoenolpyruvate -> pyruvate). In a chemically defined medium with glucose as the only C source, the Edd mutant showed reduced growth rates and the triple Edd-PpdK-Pyk mutant did not grow. Moreover, the triple mutant was also unable to grow on ribose or xylose. Therefore, B. suis biovar 5 sugar catabolism proceeds through both the Pentose Phosphate shunt and EDP, and EDP absence and exclusive use of the shunt could explain at least in part the comparatively reduced growth rates of B. melitensis and B. abortus. The triple Edd-PpdK-Pyk mutant was not attenuated in mice. Thus, although an anabolic use is likely, this suggests that hexose/pentose catabolism to pyruvate is not essential for B. suis biovar 5 multiplication within host cells, a hypothesis consistent with the lack of classical glycolysis in all Brucella species and of EDP in B. melitensis and B. abortus. These results and those of previous works suggest that within cells, the brucellae use mostly 3 and 4 C substrates fed into anaplerotic pathways and only a limited supply of 5 and 6 C sugars, thus favoring the EDP loss observed in some species

    A chemical probe unravels the reactive proteome of health-associated catechols

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    Catechol-containing natural products are common constituents of foods, drinks, and drugs. Natural products carrying this motif are often associated with beneficial biological effects such as anticancer activity and neuroprotection. However, the molecular mode of action behind these properties is poorly understood. Here, we apply a mass spectrometry-based competitive chemical proteomics approach to elucidate the target scope of catechol-containing bioactive molecules from diverse foods and drugs. Inspired by the protein reactivity of catecholamine neurotransmitters, we designed and synthesised a broadly reactive minimalist catechol chemical probe based on dopamine. Initial labelling experiments in live human cells demonstrated broad protein binding by the probe, which was largely outcompeted by its parent compound dopamine. Next, we investigated the competition profile of a selection of biologically relevant catechol-containing substances. With this approach, we characterised the protein reactivity and the target scope of dopamine and ten biologically relevant catechols. Strikingly, proteins associated with the endoplasmic reticulum (ER) were among the main targets. ER stress assays in the presence of reactive catechols revealed an activation of the unfolded protein response (UPR). The UPR is highly relevant in oncology and cellular resilience, which may provide an explanation of the health-promoting effects attributed to many catechol-containing natural products.Molecular Physiolog

    Los niños y las niñas de infantil piensan, actúan y hablan sobre el comportamiento del aire y del agua

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    En este trabajo se plantea la construcción de modelos sobre temas de ciencias por parte del alumnado de educación infantil. Se presentan dos actividades cuya finalidad es ayudarlo a construir modelos sobre el aire y el agua, iniciando así el desarrollo del pensamiento sistémico. Los niños y las niñas, a partir de las observaciones y mediante las preguntas planteadas, tratan de explicar las propiedades y las características del medio que les rodea. A pesar de las expectativas iniciales, trabajando de esta manera se ha conseguido la construcción de modelos parciales de los fenómenos que observan mediante la verificación de algunas de sus hipótesis de partida. En definitiva, se puede afirmar que desde estas primeras etapas educativas es posible trabajar ideas de la ciencia a partir de proyectos que surgen de la observación de su entorno. In this paper we propose the construction of scientific models by Early Childhood Education students. Two activities are presented whose purpose is to help them to build air and water models, thus initiating the development of systemic thinking. The children, based on the observations and through the questions asked, try to explain the properties and characteristics of the environment that surrounds them. In spite of the initial expectations, working in this way it has been achieved the construction of partial models of the phenomena that they observe from the verification of some of their first hypotheses. In short, it can be affirmed that from these first educational stages it is possible to work the ideas of the science throughout the guided inquiry

    GEN1 from a thermophilic fungus is functionally closely similar to non-eukaryotic junction-resolving enzymes

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    AbstractProcessing of Holliday junctions is essential in recombination. We have identified the gene for the junction-resolving enzyme GEN1 from the thermophilic fungus Chaetomium thermophilum and expressed the N-terminal 487-amino-acid section. The protein is a nuclease that is highly selective for four-way DNA junctions, cleaving 1nt 3′ to the point of strand exchange on two strands symmetrically disposed about a diagonal axis. CtGEN1 binds to DNA junctions as a discrete homodimer with nanomolar affinity. Analysis of the kinetics of cruciform cleavage shows that cleavage of the second strand occurs an order of magnitude faster than the first cleavage so as to generate a productive resolution event. All these properties are closely similar to those described for bacterial, phage and mitochondrial junction-resolving enzymes. CtGEN1 is also similar in properties to the human enzyme but lacks the problems with aggregation that currently prevent detailed analysis of the latter protein. CtGEN1 is thus an excellent enzyme with which to engage in biophysical and structural analysis of eukaryotic GEN1

    Learning curves: analysing pace and challenge in four successful puzzle games

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    The pace at which challenges are introduced in a game has long been identified as a key determinant of both the enjoyment and difficulty experienced by game players, and their ability to learn from game play. In order to understand how to best pace challenges in games, there is great value in analysing games already demonstrated as highly engaging. Play-through videos of four puzzle games (Portal, Portal 2 Co-operative mode, Braid and Lemmings), were observed and analysed using metrics derived from a behavioural psychology understanding of how people solve problems. Findings suggest that; 1) the main skills learned in each game are introduced separately, 2) through simple puzzles that require only basic performance of that skill, 3) the player has the opportunity to practice and integrate that skill with previously learned skills, and 4) puzzles increase in complexity until the next new skill is introduced. These data provide practical guidance for designers, support contemporary thinking on the design of learning structures in games, and suggest future directions for empirical research

    Defective protein prenylation in a spectrum of patients with mevalonate kinase deficiency

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    The rare autoinflammatory disease mevalonate kinase deficiency (MKD, which includes HIDS and mevalonic aciduria) is caused by recessive, pathogenic variants in the MVK gene encoding mevalonate kinase. Deficiency of this enzyme decreases the synthesis of isoprenoid lipids and thus prevents the normal post-translational prenylation of small GTPase proteins, which then accumulate in their unprenylated form. We recently optimized a sensitive assay capable of detecting unprenylated Rab GTPase proteins in peripheral blood mononuclear cells (PBMCs) and showed that this assay distinguished MKD from other autoinflammatory diseases. We have now analyzed PBMCs from an additional six patients with genetically-confirmed MKD (with different compound heterozygous MVK genotypes), and compared these with PBMCs from three healthy volunteers and four unaffected control individuals heterozygous for the commonest pathogenic variant, MVK V377I . We detected a clear accumulation of unprenylated Rab proteins, as well as unprenylated Rap1A by western blotting, in all six genetically-confirmed MKD patients compared to heterozygous controls and healthy volunteers. Furthermore, in the three subjects for whom measurements of residual mevalonate kinase activity was available, enzymatic activity inversely correlated with the extent of the defect in protein prenylation. Finally, a heterozygous MVK V377I patient presenting with autoinflammatory symptoms did not have defective prenylation, indicating a different cause of disease. These findings support the notion that the extent of loss of enzyme function caused by biallelic MVK variants determines the severity of defective protein prenylation, and the accumulation of unprenylated proteins in PBMCs may be a sensitive and consistent biomarker that could be used to aid, or help rule out, diagnosis of MKD.Marcia A. Munoz, Julie Jurczyluk, Anna Simon, Pravin Hissaria, Rob J. W. Arts, David Coman, Christina Boros, Sam Mehr, and Michael J. Roger
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