| 1. |
- Palmgren, Michael, et al.
(författare)
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AS3MT-mediated tolerance to arsenic evolved by multiple independent horizontal gene transfers from bacteria to eukaryotes
- 2017
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Organisms have evolved the ability to tolerate toxic substances in their environments, often by producing metabolic enzymes that efficiently detoxify the toxicant. Inorganic arsenic is one of the most toxic and carcinogenic substances in the environment, but many organisms, including humans, metabolise inorganic arsenic to less toxic metabolites. This multistep process produces mono-, di-, and trimethylated arsenic metabolites, which the organism excretes. In humans, arsenite methyltransferase (AS3MT) appears to be the main metabolic enzyme that methylates arsenic. In this study, we examined the evolutionary origin of AS3MT and assessed the ability of different genotypes to produce methylated arsenic metabolites. Phylogenetic analysis suggests that multiple, independent horizontal gene transfers between different bacteria, and from bacteria to eukaryotes, increased tolerance to environmental arsenic during evolution. These findings are supported by the observation that genetic variation in AS3MT correlates with the capacity to methylate arsenic. Adaptation to arsenic thus serves as a model for how organisms evolve to survive under toxic conditions.
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| 2. |
- Abdelhady, Dalia, et al.
(författare)
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The Nile and the Grand Ethiopian Renaissance Dam: Is There a Meeting Point between Nationalism and Hydrosolidarity?
- 2015
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Ingår i: Journal of Contemporary Water Research and Education. - 1936-704X. ; 155:1, s. 73-82
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Tidskriftsartikel (refereegranskat)abstract
- The soon-to-be completed Grand Ethiopian Renaissance Dam (GERD), which will be the largest hydroelectric power plant and among the largest reservoirs in Africa, has highlighted the need for expanding traditional integrated water resources management to better include the cultural, social, and political complexities of large water infrastructure in development projects. The GERD will store a maximum of 74 billion cubic meters of water corresponding to approximately the average annual outflow of the Nile from the Aswan high dam. Undoubtedly, the GERD will be vital for energy production and a key factor for food production, economic development, and poverty reduction in Ethiopia and the Nile Basin. However, the GERD is also a political statement that in one stroke has re-written the hydropolitical map of the Nile Basin. The GERD has become a symbol of Ethiopian nationalism or “renaissance” (hidase in Amharic). A contrasting concept to nationalism is hydrosolidarity. This concept has been put forward to better stress equitable use of water in international water management challenges that would lead to sustainable socioeconomic development. We use the opposing notions of nationalism and hydrosolidarity at three different scales, everyday politics, state policies, and interstate and global politics to analyse some aspects of the new hydropolitical map of the Nile Basin. We argue that nationalism and national interests are not necessarily negative standpoints but that there may instead be a meeting point where regional and national interests join with hydrosolidarity principles. We believe that this meeting point can maximize not only the common good, but also the good from a national interest point of view. For this, it is important not increase collaboration instead of being locked in to the historical narrative of nationalistic culture and historical discourse. This would benefit and improve future sustainability.
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| 3. |
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| 4. |
- Engström, Karin, et al.
(författare)
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Genetic variation in arsenic (+3 oxidation state) methyltransferase (AS3MT), arsenic metabolism and risk of basal cell carcinoma in a European population.
- 2015
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 56:1, s. 60-69
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to inorganic arsenic increases the risk of basal cell carcinoma (BCC). Arsenic metabolism is a susceptibility factor for arsenic toxicity, and specific haplotypes in arsenic (+3 oxidation state) methyltransferase (AS3MT) have been associated with increased urinary fractions of the most toxic arsenic metabolite, methylarsonic acid (MMA). The aim of this study is to elucidate the association of AS3MT haplotypes with arsenic metabolism and the risk of BCC. Four AS3MT polymorphisms were genotyped in BCC cases (N = 529) and controls (N = 533) from Eastern Europe with low to moderate arsenic exposure (lifetime average drinking water concentration: 1.3 µg/L, range 0.01-167 µg/L). Urinary metabolites [inorganic arsenic (iAs), MMA, dimethylarsinic acid (DMA)] were analyzed by HPLC-ICPMS. Five AS3MT haplotypes (based on rs3740400 A/C, rs3740393 G/C, rs11191439 T/C and rs1046778 T/C) had frequencies >5%. Individuals with the CCTC haplotype had lower %iAs (P = 0.032) and %MMA (P = 0.020) in urine, and higher %DMA (P = 0.033); individuals with the CGCT haplotype had higher %MMA (P < 0.001) and lower %DMA (P < 0.001). All haplotypes showed increased risk of BCC with increasing arsenic exposure through drinking water (ORs 1.1-1.4, P values from <0.001 to 0.082), except for the CCTC haplotype (OR 1.0, CI 0.9-1.2, P value 0.85). The results suggest that carriage of AS3MT haplotypes associated with less-efficient arsenic methylation, or lack of AS3MT haplotypes associated with a more-efficient arsenic methylation, results in higher risk of arsenic-related BCC. The fact that AS3MT haplotype status modified arsenic metabolism, and in turn the arsenic-related BCC risk, supports a causal relationship between low-level arsenic exposure and BCC. Environ. Mol. Mutagen., 2014. © 2014 Wiley Periodicals, Inc.
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| 5. |
- Kuehnelt, Doris, et al.
(författare)
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Selenium metabolism to the trimethylselenonium ion (TMSe) varies markedly because of polymorphisms in the indolethylamine N-methyltransferase gene
- 2015
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 102:6, s. 1406-1415
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Tidskriftsartikel (refereegranskat)abstract
- Background: Selenium is an essential element, but its metabolism in humans is not well characterized. A few small studies indicate that the trimethylselenonium ion (TMSe) is a common selenium metabolite in humans. Objective: This study aimed to elucidate the human metabolism of selenium to TMSe. Design: Study individuals constituted subsamples of 2 cohorts: 1) pregnant women (n = 228) and their 5-y-old children (n = 205) in rural Bangladesh with poor selenium status [median urinary selenium (U-Se): 6.4 mu g/L in mothers, 14 mu g/L in children] and 2) women in the Argentinian Andes (n = 83) with adequate selenium status (median U-Se: 24 mu g/L). Total U-Se and blood selenium were measured by inductively coupled plasma mass spectrometry (ICPMS), and urinary concentrations of TMSe were measured by high-performance liquid chromatography/vapor generation/ICPMS. A genomewide association study (GWAS) was performed for 1,629,299 (after filtration) single nucleotide polymorphisms (SNPs) in the Bangladeshi women (n = 72) by using Illumina Omni5M, and results were validated by using real-time polymerase chain reaction. Results: TMSe "producers" were prevalent (approximately one-third) among the Bangladeshi women and their children, in whom TMSe constituted similar to 10-70% of U-Se, whereas "nonproducers" had, on average, 0.59% TMSe. The TMSe-producing women had, on average, 2-mu g U-Se/L higher concentrations than did the nonproducers. In contrast, only 3 of the 83 Andean women were TMSe producers (6-15% TMSe in the urine); the average percentage among the nonproducers was 0.35%. Comparison of the percentage of urinary TMSe in mothers and children indicated a strong genetic influence. The GWAS identified 3 SNPs in the indolethylamine N-methyltransferase gene (INMT) that were strongly associated with percentage of TMSe (P < 0.001, false-discovery rate corrected) in both cohorts. Conclusions: There are remarkable population and individual variations in the formation of TMSe, which could largely be explained by SNPs in INMT. The TMSe-producing women had higher U-Se concentrations than did nonproducers, but further elucidation of the metabolic pathways of selenium is essential for the understanding of its role in human health.
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| 6. |
- Schlebusch, Carina M., et al.
(författare)
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Human Adaptation to Arsenic-Rich Environments
- 2015
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 32:6, s. 1544-1555
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Tidskriftsartikel (refereegranskat)abstract
- Adaptation drives genomic changes; however, evidence of specific adaptations in humans remains limited. We found that inhabitants of the northern Argentinean Andes, an arid region where elevated arsenic concentrations in available drinking water is common, have unique arsenic metabolism, with efficient methylation and excretion of the major metabolite dimethylated arsenic and a less excretion of the highly toxic monomethylated metabolite. We genotyped women from this population for 4,301,332 single nucleotide polymorphisms (SNPs) and found a strong association between the AS3MT (arsenic [+3 oxidation state] methyltransferase) gene and mono- and dimethylated arsenic in urine, suggesting that AS3MT functions as the major gene for arsenic metabolism in humans. We found strong genetic differentiation around AS3MT in the Argentinean Andes population, compared with a highly related Peruvian population (F-ST = 0.014) from a region with much less environmental arsenic. Also, 13 of the 100 SNPs with the highest genome-wide Locus-Specific Branch Length occurred near AS3MT. In addition, our examination of extended haplotype homozygosity indicated a selective sweep of the Argentinean Andes population, in contrast to Peruvian and Colombian populations. Our data show that adaptation to tolerate the environmental stressor arsenic has likely driven an increase in the frequencies of protective variants of AS3MT, providing the first evidence of human adaptation to a toxic chemical.
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| 7. |
- Wahlberg, Karin E, et al.
(författare)
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Common polymorphisms in the solute carrier SLC30A10 are associated with blood manganese and neurological function.
- 2016
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-0929 .- 1096-6080. ; 149:2, s. 473-483
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Tidskriftsartikel (refereegranskat)abstract
- Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes a Mn transporter, influence blood Mn concentrations and neurological function. We measured blood Mn concentrations by ICP-MS or atomic absorption spectroscopy and genotyped two SLC30A10 non-coding SNPs (rs2275707 and rs12064812) by TaqMan PCR in cohorts from Bangladesh (N=406), the Argentinean Andes (N=198), and Italy (N=238). We also measured SLC30A10 expression in whole blood by TaqMan PCR in a sub-group (N=101) from the Andean cohort, and neurological parameters (sway velocity and finger-tapping speed) in the Italian cohort.The rs2275707 variant allele was associated with increased Mn concentrations in the Andes (8%, p=0.027) and Italy (10.6%, p=0.012), but not as clear in Bangladesh (3.4%, p=0.21; linear regression analysis adjusted for age, gender, and plasma ferritin). This allele was also associated with increased sway velocity (15%, p=0.033; adjusted for age and sex) and reduced SLC30A10 expression (-24.6%, p=0.029). By contrast, the rs12064812 variant homozygous genotype was associated with reduced Mn concentrations, particularly in the Italian cohort (-18.4%, p=0.04), and increased finger-tapping speed (8.7%, p=0.025).We show that common SNPs in SLC30A10 are associated with blood Mn concentrations in three unrelated cohorts and that their influence may be mediated by altered SLC30A10 expression. Moreover, the SNPs appeared to influence neurological functions independent of blood Mn concentrations, suggesting that SLC30A10 could regulate brain Mn levels.
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| 8. |
- Fic, A, et al.
(författare)
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Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S.
- 2015
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Ingår i: Toxicology in Vitro. - : Elsevier BV. - 1879-3177 .- 0887-2333. ; 29:5, s. 1060-1069
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Tidskriftsartikel (refereegranskat)abstract
- The bisphenols AF (BPAF) and S (BPS) are structural analogs of the endocrine disruptor bisphenol A (BPA), and are used in common products as a replacement for BPA. To elucidate genome-wide gene expression responses, estrogen-dependent osteosarcoma cells were cultured with 10nM BPA, BPAF, or BPS, for 8h and 3months. Genome-wide gene expression was analyzed using the Illumina Expression BeadChip. Three months exposure had significant effects on gene expression, particularly for BPS, followed by BPAF and BPA, according to the number of differentially expressed genes (1980, 778, 60, respectively), the magnitude of changes in gene expression, and the number of enriched biological processes (800, 415, 33, respectively) and pathways (77, 52, 6, respectively). 'Embryonic skeletal system development' was the most enriched bone-related process, which was affected only by BPAF and BPS. Interestingly, all three bisphenols showed highest down-regulation of genes related to the cardiovascular system (e.g., NPPB, NPR3, TXNIP). BPA only and BPA/BPAF/BPS also affected genes related to the immune system and fetal development, respectively. For BPAF and BPS, the 'isoprenoid biosynthetic process' was enriched (up-regulated genes: HMGCS1, PDSS1, ACAT2, RCE1, DHDDS). Compared to BPA, BPAF and BPS had more effects on gene expression after long-term exposure. These findings stress the need for careful toxicological characterization of BPA analogs in the future.
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| 9. |
- Hossain, Bakhtiar, et al.
(författare)
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Exposure to welding fumes is associated with hypomethylation of the F2RL3 gene: a cardiovascular disease marker.
- 2015
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 72:12, s. 845-851
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Tidskriftsartikel (refereegranskat)abstract
- Welders are at risk for cardiovascular disease. Recent studies linked tobacco smoke exposure to hypomethylation of the F2RL3 (coagulation factor II (thrombin) receptor-like 3) gene, a marker for cardiovascular disease prognosis and mortality. However, whether welding fumes cause hypomethylation of F2RL3 remains unknown.
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| 10. |
- Li, Huiqi, et al.
(författare)
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A Cross-Sectional Study of the Cardiovascular Effects of Welding Fumes.
- 2015
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Occupational exposure to particulate air pollution has been associated with an increased risk of cardiovascular disease. However, the risk to welders working today remains unclear. We aimed to elucidate the cardiovascular effects of exposure to welding fumes. METHODS: In a cross-sectional study, structured interviews and biological sampling were conducted for 101 welders and 127 controls (all non-smoking males) from southern Sweden. Personal breathing zone sampling of respirable dust was performed. Blood pressure (BP) and endothelial function (using peripheral arterial tonometry) were measured. Plasma and serum samples were collected from peripheral blood for measurement of C-reactive protein, low-density lipoprotein, homocysteine, serum amyloid A, and cytokines. RESULTS: Welders were exposed to 10-fold higher levels of particles than controls. Welders had significantly higher BP compared to controls, an average of 5 mm Hg higher systolic and diastolic BP (P≤0.001). IL-8 was 3.4 ng/L higher in welders (P=0.010). Years working as a welder were significantly associated with increased BP (β=0.35, 95%CI 0.13 - 0.58, P=0.0024 for systolic BP; β=0.32, 95%CI 0.16 - 0.48, P<0.001 for diastolic BP, adjusted for BMI) but exposure to respirable dust was not associated with BP. No clear associations occurred between welding and endothelial function, or other effect markers. CONCLUSIONS: A modest increase in BP was found among welders compared to controls suggesting that low-to-moderate exposure to welding fumes remains a risk factor for cardiovascular disease.
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