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Blanc, Mélanie
Publications (10 of 11) Show all publications
Blanc, M., Alfonso, S., Begout, M.-L., Barrachina, C., Hyötyläinen, T., Keiter, S. H. & Cousin, X. (2021). An environmentally relevant mixture of polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) disrupts mitochondrial function, lipid metabolism and neurotransmission in the brain of exposed zebrafish and their unexposed F2 offspring. Science of the Total Environment, 754, Article ID 142097.
Open this publication in new window or tab >>An environmentally relevant mixture of polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) disrupts mitochondrial function, lipid metabolism and neurotransmission in the brain of exposed zebrafish and their unexposed F2 offspring
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2021 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 754, article id 142097Article in journal (Refereed) Published
Abstract [en]

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants still present in aquatic environments despite their total or partial ban. Previously, we observed that an environmentally realistic mixture of these compounds affects energy balance, growth, and reproduction in exposed zebrafish (F0), and behavior in their unexposed offspring (F1-F4). In the present work, we performed lipidomic and transcriptomic analyses on brains of zebrafish (F0-F2) from exposed and control lineages to identify molecular changes that could explain the observed phenotypes. The use of both technologies highlighted that F0 zebrafish displayed impaired mitochondrial function and lipid metabolism regulation (depletion in triacylglycerols and phospholipids) which can explain disruption of energy homeostasis. A subset of the regulated biological pathways related to energetic metabolism and neurotransmission were inherited in 12. In addition, there were increasing effects on epigenetic pathways from the F0 to the F2 generation. Altogether, we show that the effects of an environmental exposure to PCBs and PBDEs on energetic metabolism as well as neurotransmission extend over 2 generations of zebrafish, possibly due to transgenerational epigenetic inheritance.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Danio rerio, Persistent-organic pollutant, Neurotoxicity, Brain metabolism, RNA-Seq
National Category
Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-88292 (URN)10.1016/j.scitotenv.2020.142097 (DOI)000593899600029 ()32911150 (PubMedID)2-s2.0-85090281316 (Scopus ID)
Note

Funding Agencies:

French National Research Agency (ANR)ANR-13-CESA-020 ANR-10-INBS-09

Available from: 2021-01-19 Created: 2021-01-19 Last updated: 2021-01-19Bibliographically approved
Cormier, B., Le Bihanic, F., Cabar, M., Crebassa, J.-C., Blanc, M., Larsson, M., . . . Cousin, X. (2021). Chronic feeding exposure to virgin and spiked microplastics disrupts essential biological functions in teleost fish. Journal of Hazardous Materials, 415, Article ID 125626.
Open this publication in new window or tab >>Chronic feeding exposure to virgin and spiked microplastics disrupts essential biological functions in teleost fish
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2021 (English)In: Journal of Hazardous Materials, ISSN 0304-3894, E-ISSN 1873-3336, Vol. 415, article id 125626Article in journal (Refereed) Published
Abstract [en]

Toxicity of polyethylene (PE) and polyvinyl chloride (PVC) microplastics (MPs), either virgin or spiked with chemicals, was evaluated in two short-lived fish using a freshwater species, zebrafish, and a marine species, marine medaka. Exposures were performed through diet using environmentally relevant concentrations of MPs over 4 months. No modification of classical biomarkers, lipid peroxidation, genotoxicity or F0 behaviour was observed. A significant decrease in growth was reported after at least two months of exposure. This decrease was similar between species, independent from the type of MPs polymer and the presence or not of spiked chemicals, but was much stronger in females. The reproduction was evaluated and it revealed a significant decrease in the reproductive output for both species and in far more serious numbers in medaka. PVC appeared more reprotoxic than PE as were MPs spiked with PFOS and benzophenone-3 compared to MPs spiked with benzo[a]pyrene. Further, PVC-benzophenone-3 produced behavioural disruption in offspring larvae. These results obtained with two species representing different aquatic environments suggest that microplastics exert toxic effects, slightly different according to polymers and the presence or not of sorbed chemicals, which may lead in all cases to serious ecological disruptions.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Adsorbed chemicals, Growth alteration, Polyethylene, Polyvinyl chloride, Reproductive toxicity
National Category
Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-90622 (URN)10.1016/j.jhazmat.2021.125626 (DOI)000657737000003 ()33740727 (PubMedID)2-s2.0-85102562731 (Scopus ID)
Funder
Swedish Research Council Formas, 2015-01865
Note

Funding Agencies:

French National Research Agency (ANR) ANR-15-JOCE-0002-05

University of Bordeaux, France  

JPI Oceans 

Available from: 2021-03-22 Created: 2021-03-22 Last updated: 2021-06-18Bibliographically approved
Blanc, M., Antczak, P., Cousin, X., Grunau, C., Scherbak, N., Rüegg, J. & Keiter, S. (2021). The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio). Science of the Total Environment, 779, Article ID 146404.
Open this publication in new window or tab >>The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio)
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2021 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 779, article id 146404Article in journal (Refereed) Published
Abstract [en]

The pyrethroid insecticide permethrin is widely used for agricultural and domestic purposes. Previous data indicated that it acts as a developmental neurotoxicant and can induce transgenerational effects in non-target organisms. However, associated underlying mechanisms remain unclear. The aim of this study was to investigate permethrin-related transgenerational effects in the zebrafish model, and to identify possible molecular mechanisms underlying inheritance. Zebrafish (F0) were exposed to permethrin during early-life (2 h post-fertilization up to 28 days). The F1 and F2 offspring generations were obtained by pairing exposed F0 males and females, and were bred unexposed. Locomotor and anxiety behavior were investigated, together with transcriptomic and epigenomic (DNA methylation) changes in brains. Permethrin exposed F0 fish were hypoactive at adulthood, while males from the F1 and F2 generations showed a specific decrease in anxiety-like behavior. In F0, transcriptomic data showed enrichment in pathways related to glutamatergic synapse activity, which may partly underlie the behavioral effects. In F1 and F2 males, dysregulation of similar pathways was observed, including a subset of differentially methylated regions that were inherited from the F0 to the F2 generation and indicated stable dysregulation of glutamatergic signaling. Altogether, the present results provide novel evidence on the transgenerational neurotoxic effects of permethrin, as well as mechanistic insight: a transient exposure induces persistent transcriptional and DNA methylation changes that may translate into transgenerational alteration of glutamatergic signaling and, thus, into behavioral alterations.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
DNA methylation, Developmental neurotoxicity, Glutamatergic signaling, Pesticide, Transgenerational epigenetic inheritance
National Category
Developmental Biology
Identifiers
urn:nbn:se:oru:diva-90673 (URN)10.1016/j.scitotenv.2021.146404 (DOI)000655687200016 ()33752003 (PubMedID)2-s2.0-85102882062 (Scopus ID)
Funder
Knowledge FoundationHelge Ax:son Johnsons stiftelse
Note

Funding Agency:

French National Research Agency (ANR) ANR-10-LABX-04-01

Available from: 2021-03-23 Created: 2021-03-23 Last updated: 2021-06-18Bibliographically approved
Blanc, M. (2020). How can an organism´s life experience affect their descendants? Insights from epigenetic and transgenerational effects of chemical exposure in zebrafish. (Doctoral dissertation). Örebro: Örebro University
Open this publication in new window or tab >>How can an organism´s life experience affect their descendants? Insights from epigenetic and transgenerational effects of chemical exposure in zebrafish
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Environmental pollution causes approx. 10% of human diseases, and some develop in the progeny because of parental exposure. Effects passed on to subsequent generations may be a consequence of genetic mutations, or of inherited changes in epigenetic patterns. Epigenetics is the study of mitotically or meiotically heritable changes in gene function that cannot be explained by changes in the DNA sequence. Several chemicals have been suggested to induce epigenetic dysregulation leading to multigenerational and transgenerational effects, i.e. effects that can be observed in completely unexposed generations. However, mechanisms underlying the inheritance of epigenetic changes and their implication in phenotypic adversities are complex and not well-understood. The overall aim of this thesis was to study adverse effects and underlying molecular changes in several generations of zebrafish after parental exposure to selected industrial chemicals. To this end, molecular (lipidomic, transcriptomic, epigenomic) and behavioral analyses were performed. Zebrafish is an acknowledged model for vertebrates in toxicology and biomedicine; as such, the findings can be relevant to many organisms including human. The results from this thesis showed that different types of chemicals, polychlorinated biphenyls, polybromodiphenyl ethers, and permethrin, induced transgenerational effects in concentrations relevant to environmental or human exposures. Impact on anxiety and locomotor activity of zebrafish was observed over several generations. Gene expression and epigenetic (DNA methylation) alterations were partly inherited and suggest stable alteration of specific functions such as glutamatergic/GABAergic neurotransmission and synaptic plasticity. Finally, the findings shed light on experimental limitations and research perspectives, which we expect will contribute to the design of future studies on epigenetically inherited effects of any environmental stress.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 71
Series
Örebro Studies in Environmental Science, ISSN 1650-6278 ; 18
Keywords
Neurotoxicity, behavior, RNA-Seq, RRBS, TEI, permethrin, PCBs, PBDEs, coumarin 47
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-82807 (URN)978-91-7529-347-9 (ISBN)
Public defence
2020-09-14, Örebro universitet, Långhuset, Hörsal L2, Fakultetsgatan 1, Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2020-06-09 Created: 2020-06-09 Last updated: 2020-11-24Bibliographically approved
Blanc, M., Cormier, B., Hyötyläinen, T., Krauss, M., Scherbak, N., Cousin, X. & Keiter, S. (2020). Multi- and transgenerational effects following early-life exposure of zebrafish to permethrin and coumarin 47: Impact on growth, fertility, behavior and lipid metabolism. Ecotoxicology and Environmental Safety, 205, Article ID 111348.
Open this publication in new window or tab >>Multi- and transgenerational effects following early-life exposure of zebrafish to permethrin and coumarin 47: Impact on growth, fertility, behavior and lipid metabolism
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2020 (English)In: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 205, article id 111348Article in journal (Refereed) Published
Abstract [en]

Transgenerational effects induced by environmental stressors are a threat to ecosystems and human health. However, there is still limited observation and understanding of the potential of chemicals to influence life outcomes over several generations. In the present study, we investigated the effects of two environmental contaminants, coumarin 47 and permethrin, on exposed zebrafish (FO) and their progeny (F1-F3). Coumarin 47 is commonly found in personal care products and dyes, whereas permethrin is used as a domestic and agricultural pyrethroid insecticide/insect repellent. Zebrafish (F0) were exposed during early development until 28 days post-fertilization and their progeny (F1-F3) were bred unexposed. On one hand, the effects induced by coumarin 47 suggest no multigenerational toxicity. On the other hand, we found that behavior of zebrafish larvae was significantly affected by exposure to permethrin in F1 to F3 generations with some differences depending on the concentration. This suggests persistent alteration of the neural or neuromuscular function. In addition, lipidomic analyses showed that permethrin treatment was partially correlated with lysophosphatidylcholine levels in zebrafish, an important lipid for neurodevelopment. Overall, these results stress out one of the most widely used pyrethroids can trigger long-term, multi- and possibly transgenerational changes in the nervous system of zebrafish. These neurobehavioral changes echo the effects observed under direct exposure to high concentrations of permethrin and therefore call for more research on mechanisms underlying effect inheritance.

Place, publisher, year, edition, pages
Academic Press, 2020
Keywords
Pyrethroid, Endocrine disrupter, Epigenetic, Transgenerational, Neurotoxic
National Category
Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-87300 (URN)10.1016/j.ecoenv.2020.111348 (DOI)000582219300087 ()32979803 (PubMedID)2-s2.0-85091211836 (Scopus ID)
Funder
Knowledge Foundation, 20160019
Available from: 2020-11-11 Created: 2020-11-11 Last updated: 2020-11-11Bibliographically approved
Blanc, M., Rüegg, J., Scherbak, N. & Keiter, S. (2019). Environmental chemicals differentially affect epigenetic-related mechanisms in the zebrafish liver (ZF-L) cell line and in zebrafish embryos. Aquatic Toxicology, 215, Article ID 105272.
Open this publication in new window or tab >>Environmental chemicals differentially affect epigenetic-related mechanisms in the zebrafish liver (ZF-L) cell line and in zebrafish embryos
2019 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 215, article id 105272Article in journal (Refereed) Published
Abstract [en]

A number of chemicals have been shown to affect epigenetic patterning and functions. Since epigenetic mechanisms regulate transcriptional networks, epigenetic changes induced by chemical exposure can represent early molecular events for long-term adverse physiological effects. Epigenetics has thus appeared as a research field of major interest within (eco)toxicological sciences. The present study aimed at measuring effects on epigenetic-related mechanisms of selected environmental chemicals (bisphenols, perfluorinated chemicals, methoxychlor, permethrin, vinclozolin and coumarin 47) in zebrafish embryos and liver cells (ZFL). Transcription of genes related to DNA methylation and histone modifications was measured and global DNA methylation was assessed in ZFL cells using the LUMA assay. The differences in results gathered from both models suggest that chemicals affect different mechanisms related to epigenetics in embryos and cells. In zebrafish embryos, exposure to bisphenol A, coumarin 47, methoxychlor and permethrin lead to significant transcriptional changes in epigenetic factors suggesting that they can impact early epigenome reprogramming related to embryonic development. In ZFL cells, significant transcriptional changes were observed upon exposure to all chemicals but coumarin 47; however, only perfluorooctane sulfonate induced significant effects on global DNA methylation. Notably, in contrast to the other tested chemicals, perfluorooctane sulfonate affected only the expression of the histone demethylase kdm5ba. In addition, kdm5ba appeared as a sensitive gene in zebrafish embryos as well. Taken together, the present results suggest a role for kdm5ba in regulating epigenetic patterns in response to chemical exposure, even though mechanisms remain unclear. To confirm these findings, further evidence is required regarding changes in site-specific histone marks and DNA methylation together with their long-term effects on physiological outcomes.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Chemical pollutant, DNA methylation, Danio rerio, Histone modification, LUMA, qPCR
National Category
Developmental Biology
Identifiers
urn:nbn:se:oru:diva-77033 (URN)10.1016/j.aquatox.2019.105272 (DOI)000489354800005 ()31442592 (PubMedID)2-s2.0-85070872497 (Scopus ID)
Funder
Swedish Research Council Formas
Note

Funding Agency:

EnForce platform - KK Foundation  201660019

Available from: 2019-10-07 Created: 2019-10-07 Last updated: 2020-08-24Bibliographically approved
Alfonso, S., Blanc, M., Joassard, L., Keiter, S., Munschy, C., Loizeau, V., . . . Cousin, X. (2019). Examining multi- and transgenerational behavioral and molecular alterations resulting from parental exposure to an environmental PCB and PBDE mixture. Aquatic Toxicology, 208, 29-38
Open this publication in new window or tab >>Examining multi- and transgenerational behavioral and molecular alterations resulting from parental exposure to an environmental PCB and PBDE mixture
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2019 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 208, p. 29-38Article in journal (Refereed) Published
Abstract [en]

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants extensively used during the 20th century and still present in aquatic environments despite their ban. Effects of exposure to these compounds over generations are poorly documented. Therefore, our aims were to characterize behavioral responses and underlying molecular mechanisms in zebrafish exposed to an environmentally relevant mixture of PCBs and PBDEs as well as in four unexposed offspring generations. Zebrafish (F0) were chronically exposed from the first meal onward to a diet spiked with a mixture containing 22 PCB and 7 PBDE congeners in proportions and concentrations reflecting environmental situations (ΣPCBs = 1991 and ΣPBDEs = 411 ng/g). Four offspring generations (F1 to F4) were obtained from this F0 and were not further exposed. Behavior was assessed at both larval and adult stages. Mechanisms related to behavioral defects (habenula maturation and c-fos transcription) and methylation (dnmts transcription) were monitored in larvae. Exposed adult F0 as well as F1 and F3 adults displayed no behavioral change while F2 expressed anxiety-like behavior. Larval behavior was also disrupted, i.e. hyperactive after light to dark transition in F1 or hypoactive in F2, F3 and F4. Behavioral disruptions may be related to defect in habenula maturation (observed in F1) and change in c-fos transcription (observed in F1 and F2). Transcription of the gene encoding DNA methyltransferase (dnmt3ba) was also modified in all generations. Our results lead us to hypothesize that chronic dietary exposure to an environmentally relevant mixture of PCB and PBDE triggers multigenerational and transgenerational molecular and behavioral disruptions in a vertebrate model.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Behavior, Epigenetic, Gene transcription, Offspring, Parental exposure, Zebrafish
National Category
Developmental Biology Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-71178 (URN)10.1016/j.aquatox.2018.12.021 (DOI)000459950500004 ()30605867 (PubMedID)2-s2.0-85059240354 (Scopus ID)
Note

Funding Agencies:

French National Research Agency, project Fish'N'POPs  ANR-13-CESA-020 

Ifremer 

Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2020-08-24Bibliographically approved
Blanc, M., Kärrman, A., Kukučka, P., Scherbak, N. & Keiter, S. (2017). Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). Science of the Total Environment, 590-591, 249-257
Open this publication in new window or tab >>Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126)
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2017 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 590-591, p. 249-257Article in journal (Refereed) Published
Abstract [en]

Perfluorooctane sulfonic acid (PFOS) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) are persistent organic pollutants of high concern because of their environmental persistence, bioaccumulation and toxic properties. Besides, the amphiphilic properties of fluorinated compounds such as PFOS and perfluorohexanoic acid (PFHxA) suggest a role in increasing cell membrane permeability and solubilizing chemicals. The present study aimed at investigating whether PFOS and PFHxA are capable of modifying the activation of PCB126 toxicity-related pathways. For this purpose, zebrafish embryos were exposed in semi-static conditions to 7.5 μg/L of PCB126 alone, in the presence of 25 mg/L of PFOS, 15.7 mg/L of PFHxA or in the presence of both PFOS and PFHxA. Quantitative PCR was performed on embryos aged from 24 h post fertilization (hpf) to 96 hpf to investigate expression changes of genes involved in metabolism of xenobiotics (ahr2, cyp1a), oxidative stress (gpx1a, tp53), lipids metabolism (acaa2, osbpl1a), and epigenetic mechanisms (dnmt1, dnmt3ba). Cyp1a and ahr2 expression were significantly induced by the presence of PCB126. However, after 72 and 78 h of exposure, induction of cyp1a expression was significantly lower when embryos were co-exposed to PCB126 + PFOS + PFHxA when compared to PCB126-exposed embryos. Significant upregulation of gpx1a occurred after exposure to PCB126 + PFHxA and to PCB126 + PFOS + PFHxA at 30 and 48 hpf. Besides, embryos appeared more sensitive to PCB126 + PFOS + PFHxA at 78 hpf: acaa2 and osbpl1a were significantly downregulated; dnmt1 was significantly upregulated. While presented as environmentally safe, PFHxA demonstrated that it could affect gene expression patterns in zebrafish embryos when combined to PFOS and PCB126, suggesting that such mixture may increase PCB126 toxicity. This is of particular relevance since PFHxA is persistent and still being ejected into the environment. Moreover, it provides additional information as to the importance to integrate mixture effects of chemicals in risk assessment and biomonitoring frameworks.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Mixture toxicity PFAS Molecular pathway Zebrafish cyp1a Lipids
National Category
Environmental Sciences Biochemistry and Molecular Biology
Research subject
Enviromental Science
Identifiers
urn:nbn:se:oru:diva-57792 (URN)10.1016/j.scitotenv.2017.02.232 (DOI)000399511800026 ()28283292 (PubMedID)2-s2.0-85014558344 (Scopus ID)
Note

Funding agencies:

ERASMUS program 

Available from: 2017-05-22 Created: 2017-05-22 Last updated: 2022-02-03Bibliographically approved
Blanc, M., Alfonso, S., Bégout, M.-L., Barrachina, C., Hyötyläinen, T., Keiter, S. & Cousin, X.An environmentally relevant mixture of polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) disrupts mitochondrial function, lipid metabolism and neurotransmission in exposed zebrafish and their unexposed F2 offspring.
Open this publication in new window or tab >>An environmentally relevant mixture of polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) disrupts mitochondrial function, lipid metabolism and neurotransmission in exposed zebrafish and their unexposed F2 offspring
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(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-85014 (URN)
Available from: 2020-08-24 Created: 2020-08-24 Last updated: 2020-08-24Bibliographically approved
Blanc, M., Cormier, B., Hyötyläinen, T., Krauss, M., Scherbak, N., Cousin, X. & Keiter, S.Multi- and transgenerational effects following early-life exposure of zebrafish to permethrin and coumarin 47: impact on growth, fertility, behavior and lipid metabolism.
Open this publication in new window or tab >>Multi- and transgenerational effects following early-life exposure of zebrafish to permethrin and coumarin 47: impact on growth, fertility, behavior and lipid metabolism
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(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-85015 (URN)
Available from: 2020-08-24 Created: 2020-08-24 Last updated: 2020-08-24Bibliographically approved
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