56 research outputs found

    The Effect of Raw Soybeans in Mixtures for Laying Hens on Egg Quality and Egg Shell Quality

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    The study was conducted on hens at the age of 49 - 57 weeks to identify opportunities for replacing, with raw grain, thermally processed soybean Lana variety with a reduced level and Lydia variety with a standard level of trypsin inhibitor. The effect of using different levels of participation of both varieties of raw soybean in mixtures for layers on egg quality and eggshell quality was examined. The research was conducted according to the principle of two-factorial experiment (2 varieties x 4 levels of participation of raw soybeans). The average values of properties of the external and internal egg quality were under statistically significant influence of the level of participation of raw soybean in the mixture. Share of 8 % of raw soybeans of both varieties in diets for layers influenced significantly lower eggshape index, albumen height and Haugh's unit in relation to the mixture with a lower level of participation of raw soybeans. Yolk color and eggshell firmness were not significantly influenced by the studied factors

    Multidimensional severity assessment in bronchiectasis:An analysis of 7 European cohorts.

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    INTRODUCTION: Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. METHODS: We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. RESULTS: The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. CONCLUSION: The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity

    Application of Consensus Scoring and Principal Component Analysis for Virtual Screening against β-Secretase (BACE-1)

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    BACKGROUND: In order to identify novel chemical classes of β-secretase (BACE-1) inhibitors, an alternative scoring protocol, Principal Component Analysis (PCA), was proposed to summarize most of the information from the original scoring functions and re-rank the results from the virtual screening against BACE-1. METHOD: Given a training set (50 BACE-1 inhibitors and 9950 inactive diverse compounds), three rank-based virtual screening methods, individual scoring, conventional consensus scoring and PCA, were judged by the hit number in the top 1% of the ranked list. The docking poses were generated by Surflex, five scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, and PMF_Score) were used for pose extraction. For each pose group, twelve scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, PMF_Score, LigScore1, LigScore2, PLP1, PLP2, jain, Ludi_1, and Ludi_2) were used for the pose rank. For a test set, 113,228 chemical compounds (Sigma-Aldrich® corporate chemical directory) were docked by Surflex, then ranked by the same three ranking methods motioned above to select the potential active compounds for experimental test. RESULTS: For the training set, the PCA approach yielded consistently superior rankings compared to conventional consensus scoring and single scoring. For the test set, the top 20 compounds according to conventional consensus scoring were experimentally tested, no inhibitor was found. Then, we relied on PCA scoring protocol to test another different top 20 compounds and two low micromolar inhibitors (S450588 and 276065) were emerged through the BACE-1 fluorescence resonance energy transfer (FRET) assay. CONCLUSION: The PCA method extends the conventional consensus scoring in a quantitative statistical manner and would appear to have considerable potential for chemical screening applications

    Syndecan-4 Is Essential for Development of Concentric Myocardial Hypertrophy via Stretch-Induced Activation of the Calcineurin-NFAT Pathway

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    Sustained pressure overload leads to compensatory myocardial hypertrophy and subsequent heart failure, a leading cause of morbidity and mortality. Further unraveling of the cellular processes involved is essential for development of new treatment strategies. We have investigated the hypothesis that the transmembrane Z-disc proteoglycan syndecan-4, a co-receptor for integrins, connecting extracellular matrix proteins to the cytoskeleton, is an important signal transducer in cardiomyocytes during development of concentric myocardial hypertrophy following pressure overload. Echocardiographic, histochemical and cardiomyocyte size measurements showed that syndecan-4−/− mice did not develop concentric myocardial hypertrophy as found in wild-type mice, but rather left ventricular dilatation and dysfunction following pressure overload. Protein and gene expression analyses revealed diminished activation of the central, pro-hypertrophic calcineurin-nuclear factor of activated T-cell (NFAT) signaling pathway. Cardiomyocytes from syndecan-4−/−-NFAT-luciferase reporter mice subjected to cyclic mechanical stretch, a hypertrophic stimulus, showed minimal activation of NFAT (1.6-fold) compared to 5.8-fold increase in NFAT-luciferase control cardiomyocytes. Accordingly, overexpression of syndecan-4 or introducing a cell-permeable membrane-targeted syndecan-4 polypeptide (gain of function) activated NFATc4 in vitro. Pull-down experiments demonstrated a direct intracellular syndecan-4-calcineurin interaction. This interaction and activation of NFAT were increased by dephosphorylation of serine 179 (pS179) in syndecan-4. During pressure overload, phosphorylation of syndecan-4 was decreased, and association between syndecan-4, calcineurin and its co-activator calmodulin increased. Moreover, calcineurin dephosphorylated pS179, indicating that calcineurin regulates its own binding and activation. Finally, patients with hypertrophic myocardium due to aortic stenosis had increased syndecan-4 levels with decreased pS179 which was associated with increased NFAT activation. In conclusion, our data show that syndecan-4 is essential for compensatory hypertrophy in the pressure overloaded heart. Specifically, syndecan-4 regulates stretch-induced activation of the calcineurin-NFAT pathway in cardiomyocytes. Thus, our data suggest that manipulation of syndecan-4 may provide an option for therapeutic modulation of calcineurin-NFAT signaling

    Spatial and temporal trends of the Stockholm Convention POPs in mothers’ milk — a global review

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    Toxic and essential elements in soft wheat grain cultivated in Serbia

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    A survey was carried out with the aim of assessing the level of some toxic (Cd, Pb, Hg and As) and essential (Cu, Zn, Fe and Mn) elements in wheat grown in Serbia. A total of 433 samples of soft winter wheat grain from all the Serbian wheat-growing regions were pooled into 52 representative samples for 2002 harvest. After wet digestion, Cd, As, and Pb were determined by graphite furnace atomic absorption spectrometry (GFAAS), whereas Cu, Zn, Fe and Mn were determined by flame atomic absorption spectrometry (FAAS). Vapour generation accessory was used for Hg determination. The mean and median contents of all samples were (on a dry weight basis) 29 and 24 mu g/kg for Cd, 137 and 87 mu g/kg for Pb, 7 and LT 0.1 mu g/kg for Hg, 55 and 59 mu g/kg for As, 4.1 and 4.0 mg/kg for Cu, 24 and 24 mg/kg for Zn, 53 and 53 mg/kg for Fe, 34 and 33 mg/kg for Mn. The calculated mean and median levels of contamination were compared with the recommended or regulated maximum levels according to the European Commission and the national legislation. The average intake of eight selected elements from wheat-based products was estimated for the Serbian population

    Trace metal distribution in surface soils of Novi Sad and bank sediment of the Danube river

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    Concentration of Cu, Cd, Pb, Zn, As, Mn, and Fe in the Novi Sad city urban area surface soil samples and the Danube bank sediment sample were measured in 2001. The results correspond to a network of six representative sampling sites in which the main soil properties, organic matter, water content, pH, and particle size have also been determined. The geometric mean content of Zn, Cu, Cd, and Pb obtained from soil samples throughout the Novi Sad urban area (61.32, 28.39, 0.151, and 2.70 mg/kg, respectively) was compared with the geometric mean concentration in world soils. it was revealed only one site (sampling site No. 3) with Zn and Cu content higher than the allowed ones set by Dutch authorities used for investigation of a site for possible rehabilitation (Dutch A values)
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