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Jönsson, Maria
Alternative names
Publications (10 of 42) Show all publications
Mentor, A., Bornehag, C.-G., Jönsson, M. & Mattsson, A. (2020). A suggested bisphenol A metabolite (MBP) interfered with reproductive organdevelopment in the chicken embryo while a human-relevant mixture ofphthalate monoesters had no such effects. Journal of Toxicology and Environmental Health, 83(2), 66-81
Open this publication in new window or tab >>A suggested bisphenol A metabolite (MBP) interfered with reproductive organdevelopment in the chicken embryo while a human-relevant mixture ofphthalate monoesters had no such effects
2020 (English)In: Journal of Toxicology and Environmental Health, ISSN 1528-7394, E-ISSN 1087-2620, Vol. 83, no 2, p. 66-81Article in journal (Refereed) Published
Abstract [en]

Bisphenol A (BPA) and phthalate diesters are ubiquitous environmental contaminants. While thesecompounds have been reported as reproductive toxicants, their effects may partially be attributedto metabolites. The aim of this study was to examine reproductive organ development in chickenembryos exposed to the BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP;100 μg/g egg) or a human-relevant mixture of 4 phthalate monoesters (85 μg/g egg). The mixturewas designed within the EU project EDC-MixRisk based upon a negative association with anogenitaldistance in boys at 21 months of age in a Swedish pregnancy cohort. Chicken embryoswere exposed in ovo from an initial stage of gonad differentiation (embryonic day 4) anddissected two days prior to anticipated hatching (embryonic day 19). No discernible effectswere noted on reproductive organs in embryos exposed to the mixture. MBP-treated malesexhibited retention of Müllerian ducts and feminization of the left testicle, while MBPadministeredfemales displayed a diminished the left ovary. In the left testicle of MBP-treatedmales, mRNA expression of female-associated genes was upregulated while the testicular markergene SOX9 was downregulated, corroborating a feminizing effect by MBP. Our results demonstratethat MBP, but not the phthalate monoester mixture, disrupts both male and femalereproductive organ development in an avian embryo model.

Place, publisher, year, edition, pages
Taylor & Francis, 2020
Keywords
Chicken embryo, feminization, mixture, phthalates, 4-methyl-2, 4-bis(4-hydroxyphenyl)pent-1-ene (MBP)
National Category
Environmental Sciences Developmental Biology
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-406961 (URN)10.1080/15287394.2020.1728598 (DOI)000514984300001 ()32077375 (PubMedID)
Funder
EU, Horizon 2020, 634880
Available from: 2020-03-17 Created: 2020-03-17 Last updated: 2020-04-17Bibliographically approved
Mentor, A., Brunström, B., Mattsson, A. & Jönsson, M. (2020). Developmental exposure to a human relevant mixture of endocrine disruptors alters metabolism and adipogenesis in zebrafish (Danio rerio). Chemosphere, 238, Article ID 124584.
Open this publication in new window or tab >>Developmental exposure to a human relevant mixture of endocrine disruptors alters metabolism and adipogenesis in zebrafish (Danio rerio)
2020 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 238, article id 124584Article in journal (Refereed) Published
Abstract [en]

Exposure to endocrine disrupting chemicals has been suggested to contribute to the ongoing globally increasing obesity trend. The complex chemical mixtures that humans and wildlife are exposed to include a number of compounds that may have obesogenic properties. In this study we examined a mixture consisting of phthalate-monoesters, triclosan, and perfiuorinated compounds. The mixture was designed within the EDC-MixRisk project based on serum levels of the compounds in pregnant women of a Swedish mother-child cohort. The compounds were negatively associated with birth weight of the children. We assessed whether developmental exposure to this mixture in combination with a calorie-rich diet affected metabolic rate, blood lipids, adipogenesis and lipid storage, and the whole-body level of neutral lipids in zebrafish (Danio rerio). Wildtype zebrafish were exposed to the mixture from 3 h post fertilization to 5, 14 or 17 days post fertilization (dpf) at water concentrations corresponding to 1, 10, 20, or 100 times the geometrical mean of the serum concentration (hsc) in the women. Exposure to the mixture at 20 times hsc lowered metabolic rate at 2-5 dpf, and increased the number of adipocytes and the amount of visceral adipose tissue at 14 and 17 dpf respectively. Also, mRNA expression of fatty acid binding protein a was increased at 17 dpf by 10 and 20 times hsc of the mixture. This study shows that a human-relevant mixture of environmental pollutants affects metabolic rate, adipogenesis and lipid storage in young zebrafish fed a calorie-rich diet, thus demonstrating its potential to disrupt metabolism.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2020
Keywords
Mixtures, Metabolism, Adipogenesis, Zebrafish, Endocrine disrupting chemicals
National Category
Environmental Sciences
Identifiers
urn:nbn:se:uu:diva-398425 (URN)10.1016/j.chemosphere.2019.124584 (DOI)000497885800054 ()31470313 (PubMedID)
Funder
EU, Horizon 2020, 634880
Available from: 2019-12-06 Created: 2019-12-06 Last updated: 2020-04-17Bibliographically approved
Beijer, K., Jönsson, M., Shaik, S., Behrens, D., Brunström, B. & Brandt, I. (2018). Azoles additively inhibit cytochrome P450 1 (EROD) and 19 (aromatase) in rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology, 198, 73-81
Open this publication in new window or tab >>Azoles additively inhibit cytochrome P450 1 (EROD) and 19 (aromatase) in rainbow trout (Oncorhynchus mykiss)
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2018 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 198, p. 73-81Article in journal (Refereed) Published
Abstract [en]

Antifungal azoles are widely used in medicine, agriculture, and material protection and several antifungal azoles have been found in environmental samples. Although these compounds were designed to inhibit fungal enzymes such as lanosterol-14-demethylase (cytochrome P450 (CYP) 51), it is well established that the inhibitory actions of azoles are not specific for fungal CYP isozymes.

We refined a gill filament assay to determine the inhibition of CYP1, measured as reduced 7-ethoxyresorufin-O-deethylase (EROD) activity, in rainbow trout (Oncorhynchus mykiss) gill tissue ex vivo. The advantage of this method is that both induction and inhibition of EROD are performed ex vivo. Among thirteen azoles studied, the five that caused the strongest inhibition of gill EROD activity at a concentration of 5 μM were selected for concentration–response assessment. These compounds (bifonazole, clotrimazole, imazalil, miconazole, and prochloraz) showed IC50 values ranging from 0.1 to 1.5 μM. CYP19 (aromatase) inhibition was measured using microsomes from rainbow trout brains. Concentration-response curves for CYP19 inhibition were determined for letrozole, bifonazole, clotrimazole, imazalil, miconazole and prochloraz, which gave IC50 values ranging from 0.02 to 3.3 μM. It was further found that mixtures of the five most potent azoles reduced both CYP1 and 19 catalytic activity in an additive fashion (IC50 = 0.7 μM and 0.6 μM, in the respective assay). Bifonazole (IC50 = 0.1 μM) is not previously known to inhibit CYP1 activity.

The additive inhibition of CYP1 and CYP19 catalytic activity is an important finding of the present study. We conclude that this additive action of azoles could mediate adverse impacts on CYP regulated physiological functions in environmentally exposed fish.

Keywords
Azole fungicide, EROD activity, cytochrome P450 (CYP), CYP1A, CYP19, aromatase, pharmaceutical, contaminant, chemical, fish, rainbow trout, gill, EROD aktivitet, cytokrom P450 (CYP), CYP1A, CYP19, aromatase, läkemedel, azol, fungicid, kemikalier, förorening, fisk, regnbågslax, gäle
National Category
Other Biological Topics
Research subject
Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-249010 (URN)10.1016/j.aquatox.2018.02.016 (DOI)000430630100008 ()
Funder
Mistra - The Swedish Foundation for Strategic Environmental Research
Available from: 2015-04-15 Created: 2015-04-10 Last updated: 2018-08-07Bibliographically approved
Wincent, E., Kubota, A., Timme-Laragy, A., Jönsson, M. E., Hahn, M. E. & Stegeman, J. J. (2016). Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner. Biochemical Pharmacology, 110, 117-129
Open this publication in new window or tab >>Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner
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2016 (English)In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 110, p. 117-129Article in journal (Refereed) Published
Abstract [en]

6-Formylindolo[3,2-b]carbazole (FICZ) is a potent aryl hydrocarbon receptor (AHR) agonist that is efficiently metabolized by AHR-regulated cytochrome P4501 enzymes. FICZ is a proposed physiological AHR ligand that induces its own degradation as part of a regulatory negative feedback loop. In vitro studies in cells show that CYP1 inhibition in the presence of FICZ results in enhanced AHR activation, suggesting that FICZ accumulates in the cell when its metabolism is blocked. We used zebrafish (Danio rerio) embryos to investigate the in vivo effects of FICZ when CYP1A is knocked down or inhibited. Embryos were injected with morpholino antisense oligonucleotides targeting CYP1A (CYP1A-MO), Ahr2, or a combination of both. FICZ exposure of non-injected embryos or embryos injected with control morpholino had little effect. In CYP1A-MO-injected embryos, however, FICZ dramatically increased mortality, incidence and severity of pericardial edema and circulation failure, reduced hatching frequency, blocked swim bladder inflation, and strongly potentiated expression of Ahr2-regulated genes. These effects were substantially reduced in embryos with a combined knockdown of Ahr2 and CYP1A, indicating that the toxicity was mediated at least partly by Ahr2. Co-exposure to the CYP1 inhibitor alpha-naphthoflavone (αNF) and FICZ had similar effects as the combination of CYP1A-MO and FICZ. HPLC analysis of FICZ-exposed embryos showed increased levels of FICZ after concomitant CYP1A-MO injection or αNF co-exposure. Together, these results show that a functioning CYP1/AHR feedback loop is crucial for regulation of AHR signaling by a potential physiological ligand in vivo and further highlights the role of CYP1 enzymes in regulating biological effects of FICZ.

Keywords
Aryl hydrocarbon receptor; Cytochrome P4501; 6-Formylindolo[3, 2-b]carbazole; Enzyme inhibition; Zebrafish embryo toxicity; Synergistic receptor activation
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-296689 (URN)10.1016/j.bcp.2016.04.012 (DOI)000377738400011 ()27112072 (PubMedID)
Funder
Swedish Research Council Formas, 2011-963 2008-1249EU, European Research Council, 634880
Available from: 2016-06-19 Created: 2016-06-19 Last updated: 2017-11-28Bibliographically approved
Jönsson, M. E., Mattsson, A., Shaik, S. & Brunström, B. (2016). Toxicity and cytochrome P450 1A mRNA induction by 6-formylindolo[3,2-b]carbazole (FICZ) in chicken and Japanese quail embryos. Comparative Biochemistry and Physiology - Part C: Toxicology & Pharmacology, 179, 125-136
Open this publication in new window or tab >>Toxicity and cytochrome P450 1A mRNA induction by 6-formylindolo[3,2-b]carbazole (FICZ) in chicken and Japanese quail embryos
2016 (English)In: Comparative Biochemistry and Physiology - Part C: Toxicology & Pharmacology, ISSN 1532-0456, E-ISSN 1878-1659, Vol. 179, p. 125-136Article in journal (Refereed) Published
Abstract [en]

The tryptophan derivative formylindolo[3,2-b]carbazole (FICZ) binds with high ligand affinity to the aryl hydrocarbon receptor (AHR) and is readily degraded by AHR-regulated cytochrome P450 family 1 (CYP1) enzymes. Whether in vivo exposure to FICZ can result in toxic effects has not been examined and the main objective of this study was to determine if FICZ is embryotoxic in birds. We examined toxicity and CYP1 mRNA induction of FICZ in embryos from chicken (Gallus domesticus) and Japanese quail (Coturnix japonica) exposed to FICZ (2200 jag kg(-1)) by yolk and air sac injections. FICZ caused liver toxicity, embryo mortality, and CYP1A4 and CYP1A5 induction in both species with similar potency. This is in stark contrast to the very large difference in sensitivity of these species to halogenated AHR agonists. We also exposed chicken embryos to a low dose of FICZ (4 mu g kg(-1)) in combination with a CYP inhibitor, ketoconazole (KCZ). The mixture of FICZ and KCZ was lethal while FICZ alone had no effect at 4 mu g kg(-1). Furthermore, mixed exposure to FICZ and KCZ caused stronger and more long-lasting hepatic CYP1A4 induction than exposure to each compound alone. These findings indicate reduced biotransformation of FICZ by co-treatment with KCZ as a cause for the enhanced effects although additive AHR activation is also possible. To conclude, FICZ is toxic to bird embryos and it seems reasonable that the toxicity by FICZ involves AHR activation. However, the molecular targets and biological events leading to hepatic damage and mortality are unknown.

Keywords
Formylindolo[3, 2-b]carbazole (FICZ), Cytochrome P450 1 (CYP1), Chicken, Japanese quail, Embryo toxicity, Liver necrosis
National Category
Ecology Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-274425 (URN)10.1016/j.cbpc.2015.09.014 (DOI)000366873300016 ()26456929 (PubMedID)
Funder
Swedish Research Council Formas, 216-2008-1249Carl Tryggers foundation , CTS 12:227
Available from: 2016-01-21 Created: 2016-01-21 Last updated: 2018-01-10Bibliographically approved
Gao, K., Yan, P., Tan, C.-l., Luo, Y.-h., Sun, J., Jonsson, M. E., . . . Tang, Y.-p. (2015). Application of Rainbow Trout CYP1 Gene Expression Patterns in Gill and Liver for Haihe River Bio-monitoring. Huanjing Kexue, 36(10), 3878-3883
Open this publication in new window or tab >>Application of Rainbow Trout CYP1 Gene Expression Patterns in Gill and Liver for Haihe River Bio-monitoring
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2015 (English)In: Huanjing Kexue, ISSN 0250-3301, Vol. 36, no 10, p. 3878-3883Article in journal (Refereed) Published
Abstract [en]

CYP1 subfamily genes in gills and liver of rainbow trout as biomarkers were studied to establish methods for quantitative mRNA expression analysis of these genes and to determine their expression pattern. Fish caged in various waters in the Haihe River (Tianjin) were analyzed. The mRNA expression patterns observed in Machangjian River and estuary site of Haihe River were markedly similar but at different levels, reflecting that those sites shared the similar pollution components but with different local pollution load. CYP1C1 and 1C3 were only induced at Gegu site and estuary site of Haihe River, indicating different types of CYP1 agonists in Machangjian River. Response patterns of multiple CYP1 genes in gills and liver could be applied in the monitoring strategy. The response patterns of CYP1 genes could be used for better understanding the relationship between complex mixtures of pollutants and biological response of organisms in aquatic environments.

National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-288997 (URN)
Available from: 2016-04-28 Created: 2016-04-28 Last updated: 2016-06-21Bibliographically approved
Wincent, E., Stegeman, J. J. & Jönsson, M. E. (2015). Combination effects of AHR agonists and Wnt/beta-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions. Toxicology and Applied Pharmacology, 284(2), 163-179
Open this publication in new window or tab >>Combination effects of AHR agonists and Wnt/beta-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions
2015 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 284, no 2, p. 163-179Article in journal (Refereed) Published
Abstract [en]

Wnt/beta-catenin signaling regulates essential biological functions and acts in developmental toxicity of some chemicals. The aryl hydrocarbon receptor (AHR) is well-known to mediate developmental toxicity of persistent dioxin-like compounds (DLCs). Recent studies indicate a crosstalk between beta-catenin and the AHR in some tissues. However the nature of this crosstalk in embryos is poorly known. We observed that zebrafish embryos exposed to the beta-catenin inhibitor XAV939 display effects phenocopying those of the dioxin-like 3,3',4,4',5-pentachlorobiphenyl (PCB126). This led us to investigate the AHR interaction with beta-catenin during development and ask whether developmental toxicity of DLCs involves antagonism of p-catenin signaling. We examined phenotypes and transcriptional responses in zebrafish embryos exposed to XAV939 or to a beta-catenin activator, 1-azakenpaullone, alone or with AHR agonists, either PCB126 or 6-formylindolo[3,2-b]carbazole (FICZ). Alone 1-azakenpaullone and XAV939 both were embryo-toxic, and we found that in the presence of FICZ, the toxicity of 1-azakenpaullone decreased while the toxicity of XAV939 increased. This rescue of 1-azakenpaullone effects occurred in the time window of Ahr2-mediated toxicity and was reversed by morpholino-oligonudeotide knockdown of Ahr2. Regarding PCB126, addition of either 1-azakenpaullone or XAV939 led to lower mortality than with PCB126 alone but surviving embryos showed severe edemas. 1-Azakenpaullone induced transcription of beta-catenin-associated genes, while PCB126 and FICZ blocked this induction. The data indicate a stage-dependent antagonism of p-catenin by Ahr2 in zebrafish embryos. We propose that the AHR has a physiological role in regulating beta-catenin during development, and that this is one point of intersection linking toxicological and physiological AHR-governed processes.

Keywords
Aryl hydrocarbon receptor, Zebrafish embryo, Beta-catenin, 6-Formylindolo[3, 2-b]carbazole 3, 3 ', 4, 4 ', 5-Pentachlorobiphenyl
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-253256 (URN)10.1016/j.taap.2015.02.014 (DOI)000353864000007 ()25711857 (PubMedID)
Funder
Swedish Research Council FormasCarl Tryggers foundation
Note

Correction in: Toxicology and Applied Pharmacology, 2015, Volume: 288, Issue: 2, Pages: 280-280, DOI: 10.1016/j.taap.2015.07.021

Available from: 2015-06-12 Created: 2015-05-25 Last updated: 2018-01-11Bibliographically approved
Jönsson, M., Shaik, S., Rannug, A. & Brunström, B. (2013). Developmental effects of 6-formyl-indolo[3,2-b]carbazole in birds. In: Toxicology Letters: . Paper presented at Society of Toxicology, 52nd Annual Meeting and ToxExpo, March 10–14, 2013, San Antonio, Texas, USA (pp. 68). UK: Oxford University Press
Open this publication in new window or tab >>Developmental effects of 6-formyl-indolo[3,2-b]carbazole in birds
2013 (English)In: Toxicology Letters, UK: Oxford University Press, 2013, p. 68-Conference paper, Poster (with or without abstract) (Refereed)
Place, publisher, year, edition, pages
UK: Oxford University Press, 2013
National Category
Developmental Biology
Identifiers
urn:nbn:se:uu:diva-215099 (URN)
Conference
Society of Toxicology, 52nd Annual Meeting and ToxExpo, March 10–14, 2013, San Antonio, Texas, USA
Available from: 2014-01-10 Created: 2014-01-10 Last updated: 2014-01-10Bibliographically approved
Beijer, K., Gao, K., Jönsson, M. E., Larsson, D. G., Brunström, B. & Brandt, I. (2013). Effluent from drug manufacturing affects cytochrome P450 1 regulation and function in fish. Chemosphere, 90(3), 1149-1157
Open this publication in new window or tab >>Effluent from drug manufacturing affects cytochrome P450 1 regulation and function in fish
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2013 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 90, no 3, p. 1149-1157Article in journal (Refereed) Published
Abstract [en]

We have previously reported very high concentrations of pharmaceuticals in the effluent from a treatment plant receiving wastewater from about 90 bulk drug manufacturers near Hyderabad, India. The main objective of the present study was to examine how high dilutions of this effluent affect mRNA expression of cytochrome P450 (CYP) 1 family genes and ethoxyresorufin O-deethylase (EROD) activity in exposed wildlife, using the three-spined stickleback (Gasterosteus aculeatus) as a model. In gill filaments exposed to diluted effluent ex vivo, EROD activity was strongly inhibited in a concentration-dependent manner. In a subsequent in vivo study, groups of fish were exposed (24. h) to three concentrations of effluent, 0.8%, 1.6% or 3.2%. In this experiment, EROD in gills was induced 27-, 52- or 60-fold, respectively. Accordingly, CYP1A mRNA was markedly up-regulated in gill, liver and brain of fish exposed to all three effluent concentrations. Expression of mRNA for CYP1B1 and CYP1C1 was induced in gills at all concentrations while effects on these genes in liver and brain were weak or absent. The results of a time course study suggested that most CYP1-inducing substances in the effluent were readily metabolised or excreted, because the induced EROD activity and mRNA expression decreased when the fish were transferred to clean water. Considering that CYP1 enzymes play important roles in biotransformation of endogenous and foreign compounds, the observed dual effect of the effluent on CYP1 catalytic activity and mRNA expression suggests that multiple physiological functions could be affected in exposed wildlife.

Keywords
CYP1, EROD, Gills, Pharmaceuticals, Three-spined stickleback, Treated wastewater, Drug products, Effluent treatment, Fish, Gene expression, Wastewater treatment, Effluents, cytochrome P450, cytochrome P450 1, cytochrome P450 1A, cytochrome P450 1B1, cytochrome P450 1C1, cytochrome P450 1C2, ethoxyresorufin deethylase, industrial effluent, messenger RNA, tap water, unclassified drug, biotransformation, concentration (composition), drug, ecological modeling, effluent, enzyme activity, manufacturing, metabolism, pollution exposure, teleost, wastewater, water treatment, animal experiment, animal tissue, article, brain, controlled study, enzyme induction, enzyme inhibition, female, Gasterosteus aculeatus, gene, genetic transcription, gill, liver, mortality, nonhuman, spiggin gene, upregulation, vitellogenin gene, waste water treatment plant, Andhra Pradesh, Hyderabad [Andhra Pradesh], India
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-192012 (URN)10.1016/j.chemosphere.2012.09.023 (DOI)000312978700035 ()
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2013-01-24 Created: 2013-01-15 Last updated: 2017-12-06Bibliographically approved
Jonsson, M. E., Kubota, A., Timme-Laragy, A. R., Woodin, B. & Stegeman, J. J. (2012). Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish. Toxicology and Applied Pharmacology, 265(2), 166-174
Open this publication in new window or tab >>Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish
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2012 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 265, no 2, p. 166-174Article in journal (Refereed) Published
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-289000 (URN)
Note

Times Cited: 14

Available from: 2016-04-28 Created: 2016-04-28 Last updated: 2017-11-30
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