331 research outputs found

    Flunisolide Decreases Exhaled Nitric Oxide and Nitrotyrosine Levels in Asthmatic Children

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    Background. Exhaled nitric oxide (FeNO) has been reported to be elevated in the oxidative stress involved in asthmatic patients, and the reaction of nitric oxide (NO) with superoxide anions results in the formation of nitrotyrosine. The purpose of this study was to investigate the effect of inhaled steroid treatment on nitrotyrosine levels collected by exhaled breath condensate (EBC) and on FeNO. Methods. This was a single-blind placebo-controlled study. The lung function, FeNO, and nitrotyrosine levels were evaluated in 10 asthmatic children. Results. The nitrotyrosine levels were stable during the placebo period (T0 = 1.16 ng/ml versus T1 = 1.05 ng/ml; NS.), whereas they decreased after the treatment with flunisolide (T2 = 1.14 ng/ml versus T3 = 0.88 ng/ml; P < .001). No significant reduction in FeNO levels was observed after placebo treatment (T0 = 38.4 ppb versus T1 = 34.7 ppb, NS.). In contrast, FeNO values decreased significantly being at T3 = 14.9 ppb (T1 versus T3; P = .024). Conclusions. This study shows that corticosteroid treatment reduces nitrotyrosine levels in EBC of asthmatic subjects

    Behavioral flexibility of vervet monkeys in response to climatic and social variability

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    Responses to environmental variability sheds light on how individuals are able to survive in a particular habitat and provides an indication of the scope and limits of its niche. To understand whether climate has a direct impact on activity, and determine whether vervet monkeys have the behavioral flexibility to respond to environmental change, we examined whether the amount of time spent resting and feeding in the nonmating and mating seasons were predicted by the thermal and energetic constraints of ambient temperature. Our results show that high temperatures during the nonmating season were associated with an increase in time spent resting, at the expense of feeding. Cold temperatures during the nonmating season were associated with an increase in time spent feeding, at the expense of resting. In contrast, both feeding and resting time during the mating season were independent of temperature, suggesting that animals were not adjusting their activity in relation to temperature during this period. Our data indicate that climate has a direct effect on animal activity, and that animals may be thermally and energetically compromised in the mating season. Our study animals appear to have the behavioral flexibility to tolerate current environmental variability. However, future climate change scenarios predict that the time an animal has available for behaviors critical for survival will be constrained by temperature. Further investigations, aimed at determining the degree of behavioral and physiological flexibility displayed by primates, are needed if we are to fully understand the consequences of environmental change on their distribution and survival

    Human papillomavirus 16 L2 inhibits the transcriptional activation function, but not the DNA replication function, of HPV-16 E2

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    In this study we analysed the outcome of the interaction between HPV-16 L2 and E2 on the transactivation and DNA replication functions of E2. When E2 was expressed on its own, it transactivated a number of E2-responsive promoters but co-expression of L2 led to the down-regulation of the transcription transactivation activity of the E2 protein. This repression is not mediated by an increased degradation of the E2 protein. In contrast, the expression of L2 had no effect on the ability of E2 to activate DNA replication in association with the viral replication factor E1. Deletion mutagenesis identified L2 domains responsible for binding to E2 (first 50 N-terminus amino acid residues) and down-regulating its transactivation function (residues 301ā€“400). The results demonstrate that L2 selectively inhibits the transcriptional activation property of E2 and that there is a direct interaction between the two proteins, although this is not sufficient to mediate the transcriptional repression. The consequences of the L2ā€“E2 interaction for the viral life cycle are discussed

    Probabilistic movement model with emigration simulates movements of deer in Nebraska, 1990ā€“2006

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    Movements of deer can affect population dynamics, spatial redistribution, and transmission and spread of diseases. Our goal was to model the movement of deer in Nebraska in an attempt to predict the potential for spread of chronic wasting disease (CWD) into eastern Nebraska. We collared and radio-tracked \u3e600 white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) in Nebraska during 1990ā€“2006.We observed large displacements (\u3e10 km) for both species and sexes of deer, including migrations up to 100 km and dispersals up to 50 km. Average distance traveled between successive daily locations was 166m for male and 173 for female deer in eastern Nebraska, and 427m for male and 459 for female deer in western Nebraska. Average daily displacement from initial capture point was 10m for male and 14m for female deer in eastern Nebraska, and 27m for male and 28m for female deer in western Nebraska.We used these data on naturally occurring movements to create and test 6 individual-based models of movement for white-tailed deer and mule deer in Nebraska, including models that incorporated sampling from empirical distributions of movement lengths and turn angles (DIST), correlated random walks (CRW), home point fidelity (FOCUS), shifting home point (SHIFT), probabilistic movement acceptance (MOVE), and probabilistic movement with emigration (MOVEwEMI). We created models in sequence in an attempt to account for the shortcomings of the previous model(s). We used the Kolmogrovā€“Smirnov goodness-of-fit test to verify improvement of simulated annual displacement distributions to empirical displacement distributions. The best-fit model (D = 0.07 and 0.08 for eastern and western Nebraska, respectively) included a probabilistic-movement chance with emigration (MOVEwEMI) and resulted in an optimal daily movement length of 350m (maximum daily movement length of 2800m for emigrators) for eastern Nebraska and 370m (maximum of 2960m) for western Nebraska. The proportion of deer that moved as emigrators was 0.10 and 0.13 for eastern and western Nebraska, respectively. We propose that the observed spread of CWD may be driven by large movements of a small proportion of deer that help to establish a low prevalence of the disease in areas east of the current endemic area. Our movement models will be used in a larger individual-based simulation of movement, survival, and transmission of CWD to help determine future surveillance and management actions

    A framework for tracing timber following the Ukraine invasion

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    Scientific testing including stable isotope ratio analysis (SIRA) and trace element analysis (TEA) is critical for establishing plant origin, tackling deforestation and enforcing economic sanctions. Yet methods combining SIRA and TEA into robust models for origin verification and determination are lacking. Here we report a (1) large Eastern European timber reference database (Betula, Fagus, Pinus, Quercus) tailored to sanctioned products following the Ukraine invasion; (2) statistical test to verify samples against a claimed origin; (3) probabilistic model of SIRA, TEA and genus distribution data, using Gaussian processes, to determine timber harvest location. Our verification method rejects 40ā€“60% of simulated false claims, depending on the spatial scale of the claim, and maintains a low probability of rejecting correct origin claims. Our determination method predicts harvest location within 180 to 230ā€‰km of true location. Our results showcase the power of combining data types with probabilistic modelling to identify and scrutinize timber harvest location claims

    Variation in Reproductive Success Across Captive Populations: Methodological Differences, Potential Biases and Opportunities

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    Our understanding of fundamental organismal biology has been disproportionately influenced by studies of a relatively small number of model\u27 species extensively studied in captivity. Laboratory populations of model species are commonly subject to a number of forms of past and current selection that may affect experimental outcomes. Here, we examine these processes and their outcomes in one of the most widely used vertebrate species in the laboratory - the zebra finch (Taeniopygia guttata). This important model species is used for research across a broad range of fields, partly due to the ease with which it can be bred in captivity. However despite this perceived amenability, we demonstrate extensive variation in the success with which different laboratories and studies bred their subjects, and overall only 64% of all females that were given the opportunity, bred successfully in the laboratory. We identify and review several environmental, husbandry, life-history and behavioural factors that potentially contribute to this variation. The variation in reproductive success across individuals could lead to biases in experimental outcomes and drive some of the heterogeneity in research outcomes across studies. The zebra finch remains an excellent captive animal system and our aim is to sharpen the insight that future studies of this species can provide, both to our understanding of this species and also with respect to the reproduction of captive animals more widely. We hope to improve systematic reporting methods and that further investigation of the issues we raise will lead both to advances in our fundamental understanding of avian reproduction as well as to improvements in future welfare and experimental efficiency

    Many continuous variables should be analyzed using the relative scale: a case study of Ī²2-agonists for preventing exercise-induced bronchoconstriction

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    BACKGROUND: The relative scale adjusts for baseline variability and therefore may lead to findings that can be generalized more widely. It is routinely used for the analysis of binary outcomes but only rarely for continuous outcomes. Our objective was to compare relative vs absolute scale pooled outcomes using data from a recently published Cochrane systematic review that reported only absolute effects of inhaled Ī²2-agonists on exercise-induced decline in forced-expiratory volumes in 1ā€‰s (FEV1). METHODS: From the Cochrane review, we selected placebo-controlled cross-over studies that reported individual participant data (IPD). Reversal in FEV1 decline after exercise was modeled as a mean uniform percentage point (pp) change (absolute effect) or average percent change (relative effect) using either intercept-only or slope-only, respectively, linear mixed-effect models. We also calculated the pooled relative effect estimates using standard random-effects, inverse-variance-weighting meta-analysis using study-level mean effects. RESULTS: Fourteen studies with 187 participants were identified for the IPD analysis. On the absolute scale, Ī²2-agonists decreased the exercise-induced FEV1 decline by 28ā€‰pp., and on the relative scale, they decreased the FEV1 decline by 90%. The fit of the statistical model was significantly better with the relative 90% estimate compared with the absolute 28ā€‰pp. estimate. Furthermore, the median residuals (5.8 vs. 10.8ā€‰pp) were substantially smaller in the relative effect model than in the absolute effect model. Using standard study-level meta-analysis of the same 14 studies, Ī²2-agonists reduced exercise-induced FEV1 decline on the relative scale by a similar amount: 83% or 90%, depending on the method of calculating the relative effect. CONCLUSIONS: Compared with the absolute scale, the relative scale captures more effectively the variation in the effects of Ī²2-agonists on exercise-induced FEV1-declines. The absolute scale has been used in the analysis of FEV1 changes and may have led to sub-optimal statistical analysis in some cases. The choice between the absolute and relative scale should be determined based on biological reasoning and empirical testing to identify the scale that leads to lower heterogeneity.Peer reviewe

    Expression of TopBP1 in hereditary breast cancer

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    TopBP1 protein displays structural as well as functional similarities to BRCA1 and is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Aberrant expression of TopBP1 may lead to genomic instability and can have pathological consequences. In this study we aimed to investigate expression of TopBP1 gene at mRNA and protein level in hereditary breast cancer. Real-time quantitative PCR was performed in 127 breast cancer samples. Expression of TopBP1 mRNA in lobular carcinoma was significantly lower compared with ductal carcinoma (pĀ <Ā 0.05). The level of TopBP1 mRNA appeared to be lower in poorly differentiated (III grade) hereditary breast cancer in comparison with moderately (II grade) and well-differentiated cancer (I grade) (pĀ <Ā 0.05 and pĀ <Ā 0.001 respectively). We analyzed TopBP1 protein expression using immunohistochemistry and Western blot techniques. Expression of TopBP1 protein was found to be significantly increased in poorly differentiated breast cancer (III grade) (pĀ <Ā 0.05). The percentage of samples with cytoplasmic apart from nuclear staining increased with increasing histological grade. There was no significant association between level and intracellular localization of TopBP1 protein in hereditary breast cancer and other clinicopathological parameters such as estrogen and progesterone receptors status, appearance of metastasis in the axillary lymph nodes and type of cancer. Our data suggest that decreased level of TopBP1 mRNA and increased level of TopBP1 protein might be associated with progression of hereditary breast cancer
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