Identification of the Eph receptor pathway as a novel target for eicosapentaenoic acid (EPA) modification of gene expression in human colon adenocarcinoma cells (HT-29)

Abstract Background The health benefits of polyunsaturated fatty acids (PUFAs), particularly those of the n-3 series are well documented. The mechanisms by which these effects are mediated are not fully clarified. Methods We used microarrays to assess the effects on gene expression in HT29 colon adenocarcinoma cells of exposure to the n-3 fatty acid eicosapentaenoic acid (EPA). HT29 cells were cultured with EPA (150 μM) for up to 24 hr prior to harvesting and isolation of RNA. Microarray results were analyzed within the statistical package 'R', and GeneGo MetaCore was used to identify key pathways of altered gene expression. Results EphB4, Vav2 and EphA1 gene expression were identified as significantly altered by EPA treatment. Statistically significant changes in gene expression after HT29 exposure to EPA were confirmed in a second experiment by real-time RT-PCR (TaqMan), This experiment also compared the effects of exposure to EPA to arachadonic acid (AA, n-6). Corresponding changes in protein expression were also assessed by Western blotting. Conclusions Eph receptor mediated signaling is an entirely novel signaling pathway through which EPA may promote a wide range of health benefits, in particular in relation to reduction of colorectal cancer progression.</p

Serum prohepcidin concentration:no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women

Hepcidin plays a major role in iron homeostasis, but understanding its role has been hampered by the absence of analytical methods for quantification in blood. A commercial ELISA has been developed for serum prohepcidin, a hepcidin precursor, and there is interest in its potential use in the clinical and research arena. We investigated the association between serum prohepcidin concentration and iron absorption in healthy men, and its relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients, and pregnant women. Iron absorption was determined in thirty healthy men (fifteen wild-type, fifteen C282Y heterozygote) using the stable isotope red cell incorporation technique. Iron status was measured in 138 healthy men (ninety-one wild-type, forty-seven C282Y heterozygote), six hereditary haemochromatosis patients, and thirteen pregnant women. Mean serum prohepcidin concentrations were 214 (SD 118) ng/ml [208 (SD 122) ng/ml in wild-type and 225 (SD 109) ng/ml in C282Y heterozygotes] in healthy men, 177 (SD 36) ng/ml in haemochromatosis patients, and 159 (SD 59) ng/ml in pregnant women. There was no relationship between serum prohepcidin concentration and serum ferritin in any subject groups, nor was it associated with efficiency of iron absorption. Serum prohepcidin is not a useful biomarker for clinical or research purposes

Iron absorption in male C282Y heterozygotes

Background: The suggestion that carriers of the HFE C282Y mutation absorb nonheme iron more efficiently than do carriers of the wild type has public health implications for countries where the C282Y mutation is common and foods are fortified with iron. Objective: We investigated the effect of C282Y heterozygosity on nonheme-iron absorption from a diet high in bioavailable iron and from iron-fortified cereals. Design: The subjects were recruited from a parallel study investigating the relation between HFE mutations, habitual diet, and iron status. Iron absorption was measured in 15 wild-type carriers and 15 C282Y heterozygotes aged ≥40 y. Each subject consumed 3 meals of high iron bioavailability (labeled with Fe-57) for 2 d and 2 meals with fortified cereal products (labeled with Fe-54) for the next 3 d. Iron absorption was measured from isotope incorporation into red blood cells 14 d after the last labeled meal and was corrected for utilization of absorbed iron by means of an intravenous infusion of Fe-58. Results: Absorption of Fe-57 with the high-iron-bioavailability diet was 6.8 ± 6.8% (0.6 ± 0.6 mg/d) in the wild-type carriers and 7.6 ± 3.2% (0.7 ± 0.3 mg/d) in the C282Y heterozygotes. Absorption of Fe-54 with cereal products was 4.9 ± 2.0% (0.7 ± 0.3 mg/d) in the wild-type carriers and 5.3 ± 1.3% (0.8 ± 0.2 mg/d) in the C282Y heterozygotes. Conclusions: There was no overall significant difference between C282Y heterozygotes and wild-type men in iron absorption from either dietary nonheme iron or fortified cereal products

A rigorous inter-comparison of ground-level ozone predictions

Novel statistical approaches to prediction have recently been shown to perform well in several scientific fields but have not, until now, been comprehensively evaluated for predicting air pollution. In this paper we report on a model inter-comparison exercise in which 15 different statistical techniques for ozone forecasting were applied to ten data sets representing different meteorological and emission conditions throughout Europe. We also attempt to compare the performance of the statistical techniques with a deterministic chemical trajectory model. Likewise, our exercise includes comparisons of sites, performance indices, forecasting horizons, etc. The comparative evaluation of forecasting performance (benchmarking) produced 1340 yearly time series of daily predictions and the results are described in terms of predefined performance indices. Through analysing associations between the performance indices, we found that the success index is of outstanding significance. For models that are excellent in predicting threshold exceedances and have a high success index, we also observe high performance in the overall goodness of fit. The 8-h average ozone concentration forecast accuracy was found to be superior to the 1-h mean ozone concentration forecast, which makes the former very significant for operational forecasting. The best forecasts were achieved for sites located in rural and suburban areas in Central Europe unaffected by extreme emissions (e.g. from industries). Our results demonstrate that a particular technique is often excellent in some respects but poor in others. For most situations, we recommend neural network and generalised additive models as the best compromise, as these can handle nonlinear associations and can be easily adapted to site specific conditions. In contrast, nonlinear modelling of the dynamical development of univariate ozone time-series was not profitable