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Alvarez-Rodriguez, M., Atikuzzaman, M., Venhoranta, H., Wright, D. & Rodriguez-Martinez, H. (2019). Expression of Immune Regulatory Genes in the Porcine Internal Genital Tract Is Differentially Triggered by Spermatozoa and Seminal Plasma. International Journal of Molecular Sciences, 20(3), Article ID 513.
Open this publication in new window or tab >>Expression of Immune Regulatory Genes in the Porcine Internal Genital Tract Is Differentially Triggered by Spermatozoa and Seminal Plasma
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2019 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 3, article id 513Article in journal (Refereed) Published
Abstract [en]

Mating or cervical deposition of spermatozoa or seminal plasma (SP) modifies the expression of genes affecting local immune defense processes at the oviductal sperm reservoir in animals with internal fertilization, frequently by down-regulation. Such responses may occur alongside sperm transport to or even beyond the reservoir. Here, immune-related gene expression was explored with cDNA microarrays on porcine cervix-to-infundibulum tissues, pre-/peri-ovulation. Samples were collected 24 h post-mating or cervical deposition of sperm-peak spermatozoa or SP (from the sperm-peak fraction or the whole ejaculate). All treatments of this interventional study affected gene expression. The concerted action of spermatozoa and SP down-regulated chemokine and cytokine (P00031), interferon-gamma signaling (P00035), and JAK/STAT (P00038) pathways in segments up to the sperm reservoir (utero-tubal junction (UTJ)/isthmus). Spermatozoa in the vanguard sperm-peak fraction (P1-AI), uniquely displayed an up-regulatory effect on these pathways in the ampulla and infundibulum. Sperm-free SP, on the other hand, did not lead to major effects on gene expression, despite the clinical notion that SP mitigates reactivity by the female immune system after mating or artificial insemination.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
transcriptomics; microarray; bioinformatics; spermatozoa; seminal plasma; immune-regulation; female internal genitalia; pig
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-156214 (URN)10.3390/ijms20030513 (DOI)000462412500057 ()30691059 (PubMedID)2-s2.0-85060587196 (Scopus ID)
Note

Funding Agencies|Research Council FORMAS, Stockholm [2017-00946]; Swedish Research Council (Vetenskapsradet, VR) [2015-05919]

Available from: 2019-04-09 Created: 2019-04-09 Last updated: 2019-10-18Bibliographically approved
Karlsson, A.-C., Fallahsharoudi, A., Johnsen, H., Hagenblad, J., Wright, D., Andersson, L. & Jensen, P. (2016). A domestication related mutation in the thyroid stimulating hormonereceptor gene (TSHR) modulates photoperiodic response andreproduction in chickens. General and Comparative Endocrinology, 228, 69-78
Open this publication in new window or tab >>A domestication related mutation in the thyroid stimulating hormonereceptor gene (TSHR) modulates photoperiodic response andreproduction in chickens
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2016 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 228, p. 69-78Article in journal (Refereed) Published
Abstract [en]

The thyroid stimulating hormone receptor gene (TSHR) has been suggested to be a ‘‘domestication locus”in the chicken. A strong selective sweep over TSHR in domestic breeds together with significant effects ofa mutation in the gene on several domestication related traits, indicate that the gene has been importantfor chicken domestication. TSHR plays a key role in the signal transduction of seasonal reproduction,which is characteristically less strict in domestic animals. We used birds from an advanced intercross linebetween ancestral Red Junglefowl (RJF) and domesticated White Leghorn (WL) to investigate effects ofthe mutation on reproductive traits as well as on TSHB, TSHR, DIO2 and DIO3 gene expression duringaltered day length (photoperiod). We bred chickens homozygous for either the mutation (d/d) or wildtype allele (w/w), allowing assessment of the effect of genotype at this locus while also controlling forbackground variation in the rest of the genome. TSHR gene expression in brain was significantly lowerin both d/d females and males and d/d females showed a faster onset of egg laying at sexual maturity thanw/w. Furthermore, d/d males showed a reduced testicular size response to decreased day length, andlower levels of TSHB and DIO3 expression. Additionally, purebred White Leghorn females kept under naturalshort day length in Sweden during December had active ovaries and lower levels of TSHR and DIO3expression compared to Red Junglefowl females kept under similar conditions. Our study indicates thatthe TSHR mutation affects photoperiodic response in chicken by reducing dependence of seasonal reproduction,a typical domestication feature, and may therefore have been important for chickendomestication.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Domestication, DIO2, DIO3, TSHB Chicken, Gallus gallus
National Category
Zoology
Identifiers
urn:nbn:se:liu:diva-125283 (URN)10.1016/j.ygcen.2016.02.010 (DOI)000372681400010 ()26873630 (PubMedID)
Note

Funding agencies:  Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, FORMAS (Formel Excel); Swedish Research Council, VR; European Research Council (ERC) [322206]

Available from: 2016-02-19 Created: 2016-02-19 Last updated: 2017-11-30
Bélteky, J., Agnvall, B., Johnsson, M., Wright, D. & Jensen, P. (2016). Domestication and tameness: brain geneexpression in red junglefowl selected for less fear of humans suggests effects on reproduction and immunology. Royal Society Open Science (3), Article ID 160033.
Open this publication in new window or tab >>Domestication and tameness: brain geneexpression in red junglefowl selected for less fear of humans suggests effects on reproduction and immunology
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2016 (English)In: Royal Society Open Science, E-ISSN 2054-5703, no 3, article id 160033Article in journal (Refereed) Published
Abstract [en]

The domestication of animals has generated a set of phenotypicmodifications, affecting behaviour, appearance, physiologyand reproduction, which are consistent across a range ofspecies. We hypothesized that some of these phenotypes couldhave evolved because of genetic correlation to tameness,an essential trait for successful domestication. Starting froman outbred population of red junglefowl, ancestor of alldomestic chickens, we selected birds for either high or lowfear of humans for five generations. Birds from the fifthselected generation (S5) showed a divergent pattern of growthand reproduction, where low fear chickens grew larger andproduced larger offspring. To examine underlying geneticmechanisms, we used microarrays to study gene expressionin thalamus/hypothalamus, a brain region involved in fearand stress, in both the parental generation and the S5. Whileparents of the selection lines did not show any differentiallyexpressed genes, there were a total of 33 genes with adjustedp-values below 0.1 in S5. These were mainly related to spermfunction,immunological functions, with only a few known tobe relevant to behaviour. Hence, five generations of divergentselection for fear of humans produced changes in hypothalamicgene expression profiles related to pathways associated withmale reproduction and to immunology. This may be linked to the effects seen on growth and size of offspring. These results support the hypothesis thatdomesticated phenotypes may evolve because of correlated effects related to reduced fear of humans.

Place, publisher, year, edition, pages
Royal Society Publishing, 2016
Keywords
artificial selection, gene expression, microarray, chicken, fearfulness
National Category
Ecology
Identifiers
urn:nbn:se:liu:diva-130501 (URN)10.1098/rsos.160033 (DOI)000384411000002 ()
Note

Funding agencies:  Research council Formas; Vetenskapsradet; ERC [322206]

Available from: 2016-08-11 Created: 2016-08-11 Last updated: 2017-11-28
Johnsson, M., Gering, E., Willis, P., Lopez, S., Van Dorp, L., Hellenthal, G., . . . Wright, D. (2016). Feralisation targets different genomic loci to domestication in the chicken.. Nature Communications, 7, Article ID 12950.
Open this publication in new window or tab >>Feralisation targets different genomic loci to domestication in the chicken.
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2016 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, article id 12950Article in journal (Refereed) Published
Abstract [en]

Feralisation occurs when a domestic population recolonizes the wild, escaping its previous restricted environment, and has been considered as the reverse of domestication. We have previously shown that Kauai Island's feral chickens are a highly variable and admixed population. Here we map selective sweeps in feral Kauai chickens using whole-genome sequencing. The detected sweeps were mostly unique to feralisation and distinct to those selected for during domestication. To ascribe potential phenotypic functions to these genes we utilize a laboratory-controlled equivalent to the Kauai population-an advanced intercross between Red Junglefowl and domestic layer birds that has been used previously for both QTL and expression QTL studies. Certain sweep genes exhibit significant correlations with comb mass, maternal brooding behaviour and fecundity. Our analyses indicate that adaptations to feral and domestic environments involve different genomic regions and feral chickens show some evidence of adaptation at genes associated with sexual selection and reproduction.

Place, publisher, year, edition, pages
London: Nature Publishing Group, 2016
National Category
Genetics
Identifiers
urn:nbn:se:liu:diva-122279 (URN)10.1038/ncomms12950 (DOI)000385444300002 ()27686863 (PubMedID)
Note

The prevous status of this article was Manuscript and the title was The genomic signals of feralisation: Not just domestication in reverse?

Funding agencies: We thank Tony Lydgate and the Steelgrass Institute for invaluable assistance and accommodation on Kauai. The research was carried out within the framework of the Linkoping University Neuro-network. WGS was performed by the Uppsala Genome Center as part of NGI Sweden. Computations were performed at UPPMAX as part of SNIC Sweden. The project was supported by grants from the Swedish Research Council (VR), the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS), the Carl Trygers Stiftelse and by the National Science Foundation under Cooperative Agreement No. DBI-0939454. S.L. is supported by BBSRC (grant number BB/L009382/1). L.V.D. is supported by CoMPLEX via EPSRC (grant number EP/F500351/1). G.H. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 098386/Z/12/Z) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

Available from: 2015-10-27 Created: 2015-10-27 Last updated: 2017-12-01Bibliographically approved
Johnsson, M., Williams, M. J., Jensen, P. & Wright, D. (2016). Genetical Genomics of Behavior: A novel chicken genomic model for anxiety behavior. Genetics, 202(1), 327+
Open this publication in new window or tab >>Genetical Genomics of Behavior: A novel chicken genomic model for anxiety behavior
2016 (English)In: Genetics, ISSN 0016-6731, Vol. 202, no 1, p. 327+-Article in journal (Refereed) Published
Abstract [en]

The identification of genetic variants responsible for behavioral variation is an enduring goal in biology, with wide-scale ramifications, ranging from medical research to evolutionary theory on personality syndromes. Here, we use for the first time a large-scale genetical genomics analysis in the brain of the chicken to identify genes affecting anxiety as measured by an open field test. We combine quantitative trait locus (QTL) analysis in 572 individuals and expression QTL (eQTL) analysis in 129 individuals from an advanced intercross between domestic chickens and Red Junglefowl. We identify ten putative quantitative trait genes affecting anxiety behavior. These genes were tested for an association in the mouse Heterogenous Stock anxiety (open field) dataset and human GWAS datasets for bipolar disorder, major depressive disorder and schizophrenia. Although comparisons between species are complex, associations were observed for four of the candidate genes in mouse, and three of the candidate genes in humans. Using a multi-model approach we have therefore identified a number of putative quantitative trait genes affecting anxiety behavior, principally in the chicken but also with some potentially translational effects as well. This study demonstrates that the chicken is an excellent model organism for the genetic dissection of behavior.

Place, publisher, year, edition, pages
The Genetics Society, 2016
Keywords
Anxiety, behavioral genes, eQTL, QTL, causal genes, personality
National Category
Genetics
Identifiers
urn:nbn:se:liu:diva-122276 (URN)10.1534/genetics.115.179010 (DOI)000367718100026 ()26733665 (PubMedID)
Note

Funding agencies: Swedish Research Council; Swedish Research Council for Environment; Agricultural Sciences and Spatial Planning; European Research Council [GENEWELL 322206]

Available from: 2015-10-27 Created: 2015-10-27 Last updated: 2016-02-01Bibliographically approved
Johnsson, M., Jonsson, K. B., Andersson, L., Jensen, P. & Wright, D. (2016). Quantitative trait locus and genetical genomics analysis identifies putatively causal genes for fecundity and brooding in the chicken. G3: Genes, Genomes, Genetics, 6(2), 311-319
Open this publication in new window or tab >>Quantitative trait locus and genetical genomics analysis identifies putatively causal genes for fecundity and brooding in the chicken
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2016 (English)In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 6, no 2, p. 311-319Article in journal (Refereed) Published
Abstract [en]

Life history traits such as fecundity are important to evolution because they make up components of lifetime fitness. Due to their polygenic architectures, such traits are difficult to investigate with genetic mapping. Therefore, little is known about their molecular basis. One possible way toward finding the underlying genes is to map intermediary molecular phenotypes, such as gene expression traits. We set out to map candidate quantitative trait genes for egg fecundity in the chicken by combining quantitative trait locus mapping in an advanced intercross of wild by domestic chickens with expression quantitative trait locus mapping in the same birds. We measured individual egg fecundity in 232 intercross chickens in two consecutive trials, the second one aimed at measuring brooding. We found 12 loci for different aspects of egg fecundity. We then combined the genomic confidence intervals of these loci with expression quantitative trait loci from bone and hypothalamus in the same intercross. Overlaps between egg loci and expression loci, and trait–gene expression correlations identify 29 candidates from bone and five from hypothalamus. The candidate quantitative trait genes include fibroblast growth factor 1, and mitochondrial ribosomal proteins L42 and L32. In summary, we found putative quantitative trait genes for egg traits in the chicken that may have been affected by regulatory variants under chicken domestication. These represent, to the best of our knowledge, some of the first candidate genes identified by genome-wide mapping for life history traits in an avian species.

Place, publisher, year, edition, pages
Bethesda, MD, United States: Genetics Society of America, 2016
National Category
Genetics
Identifiers
urn:nbn:se:liu:diva-124211 (URN)10.1534/g3.115.024299 (DOI)000369595300008 ()26637433 (PubMedID)
Note

At the time for thesis presentation publication was in status: Manuscript

At the time for thesis presentation manuscript was named: Quantitative trait locus and genetical genomics analysis identifies putatively causal genes for fecundity and brooding behavior in the chicken

Funding agencies: Swedish Research Council (VR); Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS); European Research Council

Available from: 2016-01-22 Created: 2016-01-22 Last updated: 2017-11-30Bibliographically approved
Fallahshahroudi, A., de Kock, N., Johnsson, M., Ubhayasekera, S. K., Bergqvist, J., Wright, D. & Jensen, P. (2015). Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens. Scientific Reports, 5, 1-10, Article ID 15345.
Open this publication in new window or tab >>Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, p. 1-10, article id 15345Article in journal (Refereed) Published
Abstract [en]

Understanding the genetic basis of phenotypic diversity is a challenge in contemporary biology. Domestication provides a model for unravelling aspects of the genetic basis of stress sensitivity. The ancestral Red Junglefowl (RJF) exhibits greater fear-related behaviour and a more pronounced HPA-axis reactivity than its domesticated counterpart, the White Leghorn (WL). By comparing hormones (plasmatic) and adrenal global gene transcription profiles between WL and RJF in response to an acute stress event, we investigated the molecular basis for the altered physiological stress responsiveness in domesticated chickens. Basal levels of pregnenolone and dehydroepiandrosterone as well as corticosterone response were lower in WL. Microarray analysis of gene expression in adrenal glands showed a significant breed effect in a large number of transcripts with over-representation of genes in the channel activity pathway. The expression of the best-known steroidogenesis genes were similar across the breeds used. Transcription levels of acute stress response genes such as StAR, CH25 and POMC were upregulated in response to acute stress. Dampened HPA reactivity in domesticated chickens was associated with changes in the expression of several genes that presents potentially minor regulatory effects rather than by means of change in expression of critical steroidogenic genes in the adrenal.

Place, publisher, year, edition, pages
Nature Publishing Group, 2015
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:liu:diva-122305 (URN)10.1038/srep15345 (DOI)000362885300001 ()26471470 (PubMedID)
Note

Funding agencies: Swedish Research Council (VR) [621-2011-4731]; Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) [221-2011-1088]; SRC [621-2011-5523]; ERC [322206]; Swedish Centre of Excellence in Animal Welfare

Available from: 2015-10-28 Created: 2015-10-28 Last updated: 2017-12-01
Johnsson, M., Jonsson, K. B., Andersson, L., Jensen, P. & Wright, D. (2015). Genetic Regulation of Bone Metabolism in the Chicken: Similarities and Differences to Mammalian Systems. PLOS Genetics, 11(5), Article ID e1005250.
Open this publication in new window or tab >>Genetic Regulation of Bone Metabolism in the Chicken: Similarities and Differences to Mammalian Systems
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2015 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 5, article id e1005250Article in journal (Refereed) Published
Abstract [en]

Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL) and expression QTL (eQTL) mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken) and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone.

National Category
Genetics
Identifiers
urn:nbn:se:liu:diva-118579 (URN)10.1371/journal.pgen.1005250 (DOI)000355305200057 ()26023928 (PubMedID)
Available from: 2015-06-01 Created: 2015-06-01 Last updated: 2017-12-04
Persson, M., Roth, L., Johnsson, M., Wright, D. & Jensen, P. (2015). Human-directed social behaviour in dogs shows significant heritability. Genes, Brain and Behavior, 14(4), 337-344
Open this publication in new window or tab >>Human-directed social behaviour in dogs shows significant heritability
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2015 (English)In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 14, no 4, p. 337-344Article in journal (Refereed) Published
Abstract [en]

Through domestication and co-evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human-directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h2) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human-directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human-directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs’ social skills, which could also play a significant part into research on human social disorders such as autism.

Place, publisher, year, edition, pages
John Wiley & Sons, 2015
Keywords
Beagles, canine behaviour, dogs, domestic dog, eye contact, genetics, heritability, human-directed communication, problem-solving, social behaviour
National Category
Human Computer Interaction
Identifiers
urn:nbn:se:liu:diva-117523 (URN)10.1111/gbb.12194 (DOI)000353405000003 ()25703740 (PubMedID)
Funder
EU, European Research Council, 1242001390
Available from: 2015-04-30 Created: 2015-04-30 Last updated: 2020-01-21
Atikuzzaman, M., Bhai Mehta, R., Fogelholm, J., Wright, D. & Rodriguez-Martinez, H. (2015). Mating induces the expression of immune- and pH-regulatory genes in the utero-vaginal junction containing mucosal sperm-storage tubuli of hens. Reproduction, 150(6), 473-483
Open this publication in new window or tab >>Mating induces the expression of immune- and pH-regulatory genes in the utero-vaginal junction containing mucosal sperm-storage tubuli of hens
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2015 (English)In: Reproduction, Vol. 150, no 6, p. 473-483Article in journal (Refereed) Published
Abstract [en]

The female chicken, as with other species with internal fertilization, can tolerate the presence of spermatozoa within specialized sperm-storage tubuli (SST) located in the mucosa of the utero-vaginal junction (UVJ) for days or weeks, without eliciting an immune response. To determine if the oviduct alters its gene expression in response to sperm entry, segments from the oviduct (UVJ, uterus, isthmus, magnum and infundibulum) of mated and unmated (control) hens, derived from an advanced inter-cross line between Red Junglefowl and White Leghorn, were explored 24 h after mating using cDNA microarray analysis. Mating shifted the expression of fifteen genes in the UVJ (53.33% immune-modulatory and 20.00% pH-regulatory) and seven genes in the uterus, none of the genes in the latter segment overlapping the former (with the differentially expressed genes themselves being less related to immune-modulatory function). The other oviductal segments did not show any significant changes. These findings suggest sperm deposition causes a shift in expression in the UVJ (containing mucosal SST) and the uterus for genes involved in immune-modulatory and pH-regulatory functions, both relevant for sperm survival in the hen's oviduct.

Place, publisher, year, edition, pages
Bioscientifica, 2015
National Category
Genetics
Identifiers
urn:nbn:se:liu:diva-122573 (URN)10.1530/REP-15-0253 (DOI)000365344400004 ()26370241 (PubMedID)
Note

Funding agencies: Research Council FORMAS, Stockholm [221-2011-512]; FORMAS [221-2012-667]; VR [621-2011-4802]

Available from: 2015-11-09 Created: 2015-11-09 Last updated: 2017-02-20
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2329-2635

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