| 1. |
- Pedersen, Marie, et al.
(författare)
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Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother-Child Study (NewGeneris)
- 2013
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:10, s. 1200-1206
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic-hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from -biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy. Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006-2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires. Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of -129 g (95% CI: -233, -25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (-248 g; 95% CI: -405, -92 g) compared with those with high intake (-58 g; 95% CI: -206, 90 g). Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.
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| 2. |
- Li, Zhijian, et al.
(författare)
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Systematic exploration of essential yeast gene function with temperature-sensitive mutants.
- 2011
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 29:4, s. 361-7
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Tidskriftsartikel (refereegranskat)abstract
- Conditional temperature-sensitive (ts) mutations are valuable reagents for studying essential genes in the yeast Saccharomyces cerevisiae. We constructed 787 ts strains, covering 497 (∼45%) of the 1,101 essential yeast genes, with ∼30% of the genes represented by multiple alleles. All of the alleles are integrated into their native genomic locus in the S288C common reference strain and are linked to a kanMX selectable marker, allowing further genetic manipulation by synthetic genetic array (SGA)-based, high-throughput methods. We show two such manipulations: barcoding of 440 strains, which enables chemical-genetic suppression analysis, and the construction of arrays of strains carrying different fluorescent markers of subcellular structure, which enables quantitative analysis of phenotypes using high-content screening. Quantitative analysis of a GFP-tubulin marker identified roles for cohesin and condensin genes in spindle disassembly. This mutant collection should facilitate a wide range of systematic studies aimed at understanding the functions of essential genes.
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| 3. |
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| 4. |
- Merlo, Domenico Franco, et al.
(författare)
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Micronuclei in Cord Blood Lymphocytes and Associations with Biomarkers of Exposure to Carcinogens and Hormonally Active Factors, Gene Polymorphisms, and Gene Expression : The NewGeneris Cohort
- 2014
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 122:2, s. 193-200
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Tidskriftsartikel (refereegranskat)abstract
- Background: Leukemia incidence has increased in recent decades among European children, -suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M(1)dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M(1)dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX (R) (chemically activated luciferase expression for androgens) (8 genes), ER alpha CALUX (R) (for estrogens) (2 genes), and DR CALUX (R) (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/ 2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.
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| 5. |
- Pedersen, Marie, et al.
(författare)
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Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet : The European Prospective Mother-Child Study (NewGeneris)
- 2012
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 120:12, s. 1739-1745
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. OBJECTIVES: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother child study. METHODS: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006-2010. Maternal diet was estimated through food-frequency questionnaires. RESULTS: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was -132 g (95% CI: -207, -56); the corresponding difference for head circumference was -0.33 cm (95% CI: -0.61, -0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for Factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. CONCLUSIONS: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. IF confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.
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| 6. |
- White, Christopher J., et al.
(författare)
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Potential applications of subseasonal-to-seasonal (S2S) predictions
- 2017
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Ingår i: Meteorological Applications. - : John Wiley & Sons. - 1350-4827 .- 1469-8080. ; 24:3, s. 315-325
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Tidskriftsartikel (refereegranskat)abstract
- While seasonal outlooks have been operational for many years, until recently the extended-range timescale referred to as subseasonal-to-seasonal (S2S) has received little attention. S2S prediction fills the gap between short-range weather prediction and long-range seasonal outlooks. Decisions in a range of sectors are made in this extended-range lead time; therefore, there is a strong demand for this new generation of forecasts. International efforts are under way to identify key sources of predictability, improve forecast skill and operationalize aspects of S2S forecasts; however, challenges remain in advancing this new frontier. If S2S predictions are to be used effectively, it is important that, along with science advances, an effort is made to develop, communicate and apply these forecasts appropriately. In this study, the emerging operational S2S forecasts are presented to the wider weather and climate applications community by undertaking the first comprehensive review of sectoral applications of S2S predictions, including public health, disaster preparedness, water management, energy and agriculture. The value of applications-relevant S2S predictions is explored, and the opportunities and challenges facing their uptake are highlighted. It is shown how social sciences can be integrated with S2S development, from communication to decision-making and valuation of forecasts, to enhance the benefits of ‘climate services’ approaches for extended-range forecasting. While S2S forecasting is at a relatively early stage of development, it is concluded that it presents a significant new window of opportunity that can be explored for application-ready capabilities that could allow many sectors the opportunity to systematically plan on a new time horizon.
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