134 research outputs found
Biomarkers of Human Exposure to Acrylamide and Relation to Polymorphisms in Metabolizing Genes
Acrylamide (AA) is formed in heat treated carbohydrate rich foods in the so-called Maillard reaction. AA is readily absorbed in the body and converted to glycidamide (GA) by epoxidation by the CYP2E1 (cytochrome P450 2E) enzyme. Both AA and GA may be detoxified through direct conjunction to glutathione by glutathione-S-transferases and GA by hydrolysis to glyceramide. Recently, we reported that biomarkers of AA exposure reflect intake of major food sources of AA; there were large interindividual variations in the blood ratio of GA-Hb/AA-Hb (GA- and AA-hemoglobin adducts). In this study we investigated whether the ratio of GA-Hb/AA-Hb in subjects could be related to polymorphic differences in genes coding for metabolizing enzymes CYP2E1, EPHX1 (microsomal epoxide hydrolase), GSTM1, GSTT1, and GSTP1, all being expected to be involved in the activation and detoxification of AA-associated adducts. We found significant associations between GSTM1 and GSTT1 genotypes and the ratio of GA-Hb/AA-Hb (p = 0.039 and p = 0.006, respectively). The ratio of GA-Hb/AA-Hb in individuals with the combined GSTM1- and GSTT1-null variants was significantly (p = 0.029) higher than those with the wild-type genotypes. Although the number of subjects was small, there were also significant associations with other combinations; CYP2E1 (Val179Val) plus GSTM1-null (p = 0.022); CYP2E1 (Val/Val), GSTM1-null plus GSTT1-null (p = 0.047); and CYP2E1 (Val/Val), GSTT1 null, EPHX1 (Tyr113Tyr) plus EPHX1 (His139Arg) (p = 0.018). Individuals with these combined genotypes had significantly higher blood ratio of GA-Hb/AA-Hb than other combinations. The observed associations correspond with what would be expected from the relative roles of these enzymes in activation and detoxification of AA, except for individuals with the EPHX1 (His139Arg) variant. The internal dose of genotoxic metabolite and also the concentration of AA in blood seem to be affected by these polymorphic genes. The genotypes and their combination may constitute useful biomarkers for the assessment of individual susceptibility to AA intake, and could add to the precision of epidemiological studies of dietary cancer
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Subsampling impact on the climate change signal over poland based on simulations from statistical and dynamical downscaling
Most impact studies using downscaled climate data as input assume that the selection of few global climate models (GCMs) representing the largest spread covers the likely range of future changes. This study shows that including more GCMs can result in a very different behavior. We tested the influence of selecting various subsets of GCMs on the climate change signal over Poland from simulations based on dynamical and empirical-statistical downscaling methods. When the climate variable is well simulated by the GCM, such as temperature, results showed that both downscaling methods agree on a warming over Poland by up to 2° or 5°C assuming intermediate or high emission scenarios, respectively, by 2071-2100. As a less robust simulated signal through GCMs, precipitation is expected to increase by up to 10% by 2071-2100 assuming the intermediate emission scenario. However, these changes are uncertain when the high emission scenario and the end of the twenty-first century are of interest. Further, an additional bootstrap test revealed an underestimation in the warming rate varying from 0.5° to more than 4°C over Poland that was found to be largely influenced by the selection of few driving GCMs instead of considering the full range of possible climate model outlooks. Furthermore, we found that differences between various combinations of small subsets from the GCM ensemble of opportunities can be as large as the climate change signal. © 2019 American Meteorological Society
Biomarkers of Human Exposure to Acrylamide and Relation to Polymorphisms in Metabolizing Genes
Acrylamide (AA) is formed in heat treated carbohydrate rich foods in the so-called Maillard reaction. AA is readily absorbed in the body and converted to glycidamide (GA) by epoxidation by the CYP2E1 (cytochrome P450 2E) enzyme. Both AA and GA may be detoxified through direct conjunction to glutathione by glutathione-S-transferases and GA by hydrolysis to glyceramide. Recently, we reported that biomarkers of AA exposure reflect intake of major food sources of AA; there were large interindividual variations in the blood ratio of GA-Hb/AA-Hb (GA- and AA-hemoglobin adducts). In this study we investigated whether the ratio of GA-Hb/AA-Hb in subjects could be related to polymorphic differences in genes coding for metabolizing enzymes CYP2E1, EPHX1 (microsomal epoxide hydrolase), GSTM1, GSTT1, and GSTP1, all being expected to be involved in the activation and detoxification of AA-associated adducts. We found significant associations between GSTM1 and GSTT1 genotypes and the ratio of GA-Hb/AA-Hb (p = 0.039 and p = 0.006, respectively). The ratio of GA-Hb/AA-Hb in individuals with the combined GSTM1- and GSTT1-null variants was significantly (p = 0.029) higher than those with the wild-type genotypes. Although the number of subjects was small, there were also significant associations with other combinations; CYP2E1 (Val179Val) plus GSTM1-null (p = 0.022); CYP2E1 (Val/Val), GSTM1-null plus GSTT1-null (p = 0.047); and CYP2E1 (Val/Val), GSTT1 null, EPHX1 (Tyr113Tyr) plus EPHX1 (His139Arg) (p = 0.018). Individuals with these combined genotypes had significantly higher blood ratio of GA-Hb/AA-Hb than other combinations. The observed associations correspond with what would be expected from the relative roles of these enzymes in activation and detoxification of AA, except for individuals with the EPHX1 (His139Arg) variant. The internal dose of genotoxic metabolite and also the concentration of AA in blood seem to be affected by these polymorphic genes. The genotypes and their combination may constitute useful biomarkers for the assessment of individual susceptibility to AA intake, and could add to the precision of epidemiological studies of dietary cancer
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CHASE-PL Climate Projection dataset over Poland - Bias adjustment of EURO-CORDEX simulations
The CHASE-PL (Climate change impact assessment for selected sectors in Poland) Climate Projections – Gridded Daily Precipitation and Temperature dataset 5 km (CPLCP-GDPT5) consists of projected daily minimum and maximum air temperatures and precipitation totals of nine EURO-CORDEX regional climate model outputs bias corrected and downscaled to a 5 km × 5 km grid. Simulations of one historical period (1971–2000) and two future horizons (2021–2050 and 2071–2100) assuming two representative concentration pathways (RCP4.5 and RCP8.5) were produced. We used the quantile mapping method and corrected any systematic seasonal bias in these simulations before assessing the changes in annual and seasonal means of precipitation and temperature over Poland. Projected changes estimated from the multi-model ensemble mean showed that annual means of temperature are expected to increase steadily by 1 °C until 2021–2050 and by 2 °C until 2071–2100 assuming the RCP4.5 emission scenario. Assuming the RCP8.5 emission scenario, this can reach up to almost 4 °C by 2071–2100. Similarly to temperature, projected changes in regional annual means of precipitation are expected to increase by 6 to 10 % and by 8 to 16 % for the two future horizons and RCPs, respectively. Similarly, individual model simulations also exhibited warmer and wetter conditions on an annual scale, showing an intensification of the magnitude of the change at the end of the 21st century. The same applied for projected changes in seasonal means of temperature showing a higher winter warming rate by up to 0.5 °C compared to the other seasons. However, projected changes in seasonal means of precipitation by the individual models largely differ and are sometimes inconsistent, exhibiting spatial variations which depend on the selected season, location, future horizon, and RCP. The overall range of the 90 % confidence interval predicted by the ensemble of multi-model simulations was found to likely vary between −7 % (projected for summer assuming the RCP4.5 emission scenario) and +40 % (projected for winter assuming the RCP8.5 emission scenario) by the end of the 21st century. Finally, this high-resolution bias-corrected product can serve as a basis for climate change impact and adaptation studies for many sectors over Poland. The CPLCP-GDPT5 dataset is publicly available at https://doi.org/10.4121/uuid:e940ec1a-71a0-449e-bbe3-29217f2ba31d
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