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Meta-analysis and association of two common polymorphisms of the human oxytocin receptor gene in autism spectrum disorder / Thorsten M. KRANZ in Autism Research, 9-10 (October 2016)
[article]
Titre : Meta-analysis and association of two common polymorphisms of the human oxytocin receptor gene in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Thorsten M. KRANZ, Auteur ; Marnie KOPP, Auteur ; Regina WALTES, Auteur ; Michael SACHSE, Auteur ; Eftichia DUKETIS, Auteur ; Tomasz A. JARCZOK, Auteur ; Franziska DEGENHARDT, Auteur ; Katharina GÖRGEN, Auteur ; Jobst MEYER, Auteur ; Christine M. FREITAG, Auteur ; Andreas G. CHIOCCHETTI, Auteur Article en page(s) : p.1036-1045 Langues : Anglais (eng) Mots-clés : meta-analysis autism spectrum disorder oxytocin receptor genotyping social interaction endophenotype genetics oxytocin Index. décimale : PER Périodiques Résumé : Neuropeptides such as oxytocin (OXT) are known facilitators of social behavior across species. Variants of the OXT receptor gene (OXTR) have been tested for association with autism spectrum disorder (ASD) across manifold ethnicities, yielding both positive and negative findings. A recent meta-analysis, comprising 16 single nucleotide polymorphisms (SNPs), has corroborated the implication of OXTR in the etiology of ASD. Here, we genotyped and tested two additional variants (rs237889 and rs237897) for association with ASD in two German predominantly high-functioning ASD samples. We found nominal over-transmission (OR?=?1.48, CI95?=?1.06-2.08, P?=?0.022) for the minor A allele of variant rs237889G>A in sample 1 (N?=?135 complete parent-offspring trios, 29 parent child duos), but not in sample 2 (362 trios, 69 duos). Still, in a meta-analysis comprising four different studies including the two unreported German data sets (N?=?542 families), this finding was confirmed (OR?=?1.12; CI95?=?1.01–1.24, random effects P?=?0.012). In addition, carriers of the minor risk allele rs237889-A showed significantly increased severity scores, as assessed through the autism diagnostic interview – revised (ADI-R), with highly significant increases in social interaction deficits. Our results corroborate the implication of common OXTR variants in the etiology of ASD. There is a need for functional studies to delineate the neurobiological implications of this and other association findings. (172/250). En ligne : http://dx.doi.org/10.1002/aur.1597 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=294
in Autism Research > 9-10 (October 2016) . - p.1036-1045[article] Meta-analysis and association of two common polymorphisms of the human oxytocin receptor gene in autism spectrum disorder [Texte imprimé et/ou numérique] / Thorsten M. KRANZ, Auteur ; Marnie KOPP, Auteur ; Regina WALTES, Auteur ; Michael SACHSE, Auteur ; Eftichia DUKETIS, Auteur ; Tomasz A. JARCZOK, Auteur ; Franziska DEGENHARDT, Auteur ; Katharina GÖRGEN, Auteur ; Jobst MEYER, Auteur ; Christine M. FREITAG, Auteur ; Andreas G. CHIOCCHETTI, Auteur . - p.1036-1045.
Langues : Anglais (eng)
in Autism Research > 9-10 (October 2016) . - p.1036-1045
Mots-clés : meta-analysis autism spectrum disorder oxytocin receptor genotyping social interaction endophenotype genetics oxytocin Index. décimale : PER Périodiques Résumé : Neuropeptides such as oxytocin (OXT) are known facilitators of social behavior across species. Variants of the OXT receptor gene (OXTR) have been tested for association with autism spectrum disorder (ASD) across manifold ethnicities, yielding both positive and negative findings. A recent meta-analysis, comprising 16 single nucleotide polymorphisms (SNPs), has corroborated the implication of OXTR in the etiology of ASD. Here, we genotyped and tested two additional variants (rs237889 and rs237897) for association with ASD in two German predominantly high-functioning ASD samples. We found nominal over-transmission (OR?=?1.48, CI95?=?1.06-2.08, P?=?0.022) for the minor A allele of variant rs237889G>A in sample 1 (N?=?135 complete parent-offspring trios, 29 parent child duos), but not in sample 2 (362 trios, 69 duos). Still, in a meta-analysis comprising four different studies including the two unreported German data sets (N?=?542 families), this finding was confirmed (OR?=?1.12; CI95?=?1.01–1.24, random effects P?=?0.012). In addition, carriers of the minor risk allele rs237889-A showed significantly increased severity scores, as assessed through the autism diagnostic interview – revised (ADI-R), with highly significant increases in social interaction deficits. Our results corroborate the implication of common OXTR variants in the etiology of ASD. There is a need for functional studies to delineate the neurobiological implications of this and other association findings. (172/250). En ligne : http://dx.doi.org/10.1002/aur.1597 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=294 Non-synonymous single-nucleotide variations of the human oxytocin receptor gene and autism spectrum disorders: a case–control study in a Japanese population and functional analysis / Wen-Jie MA in Molecular Autism, (July 2013)
[article]
Titre : Non-synonymous single-nucleotide variations of the human oxytocin receptor gene and autism spectrum disorders: a case–control study in a Japanese population and functional analysis Type de document : Texte imprimé et/ou numérique Auteurs : Wen-Jie MA, Auteur ; Minako HASHII, Auteur ; Toshio MUNESUE, Auteur ; Kenshi HAYASHI, Auteur ; Kunimasa YAGI, Auteur ; Masakazu YAMAGISHI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Shigeru YOKOYAMA, Auteur Année de publication : 2013 Article en page(s) : 14 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders Inositol-1,4,5-trisphosphate Intracellular free calcium Oxytocin Oxytocin receptor Single-nucleotide variation Index. décimale : PER Périodiques Résumé : Background
The human oxytocin receptor (hOXTR) is implicated in the etiology of autism spectrum disorders (ASDs) and is a potential target for therapeutic intervention. Several studies have reported single-nucleotide polymorphisms (SNPs) of the OXTR gene associated with ASDs. These SNPs, however, reside outside the protein-coding region. Not much is known about genetic variations that cause amino acid substitutions that alter receptor functions.
Methods
Variations in the OXTR gene were analyzed in 132 ASD patients at Kanazawa University Hospital in Japan and 248 unrelated healthy Japanese volunteers by re-sequencing and real-time polymerase chain reaction-based genotyping. Functional changes in variant OXTRs were assessed by radioligand binding assay and measurements of intracellular free calcium concentrations ([Ca2+]i) and inositol 1,4,5-trisphosphate (IP3) levels.
Results
Six subjects (4.5%) in the ASD group and two in the control group (0.8%) were identified as heterozygotes carrying the R376G variation (rs35062132; c.1126C>G); one individual from the ASD group (0.8%) and three members of the control group (1.2%) were found to be carrying R376C (c.1126C>T). The C/G genotype significantly correlated with an increased risk of ASDs (odds ratio (OR) = 5.83; 95% confidence interval (CI) = 1.16 to 29.33; P = 0.024, Fisher’s exact test). Consistently, the G allele showed a correlation with an increased likelihood of ASDs (OR = 5.73; 95% CI = 1.15 to 28.61; P = 0.024, Fisher’s exact test). The frequencies of the C/T genotype and the T allele in the ASD and control groups did not differ significantly. We also examined changes in agonist-induced cellular responses mediated by the variant receptors hOXTR-376G and hOXTR-376C. OXT-induced receptor internalization and recycling were faster in hOXTR-376G-expressing HEK-293 cells than in cells expressing hOXTR-376R or hOXTR-376C. In addition, the elevation in [Ca2+]i and IP3 formation decreased in the cells expressing hOXTR-376G and hOXTR-376C tagged with enhanced green fluorescent protein (EGFP), in comparison with the cells expressing the common-type hOXTR-376R tagged with EGFP.
Conclusions
These results suggest that the rare genetic variation rs35062132 might contribute to the pathogenesis of ASDs, and could provide a molecular basis of individual differences in OXTR-mediated modulation of social behavior.En ligne : http://dx.doi.org/10.1186/2040-2392-4-22 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211
in Molecular Autism > (July 2013) . - 14 p.[article] Non-synonymous single-nucleotide variations of the human oxytocin receptor gene and autism spectrum disorders: a case–control study in a Japanese population and functional analysis [Texte imprimé et/ou numérique] / Wen-Jie MA, Auteur ; Minako HASHII, Auteur ; Toshio MUNESUE, Auteur ; Kenshi HAYASHI, Auteur ; Kunimasa YAGI, Auteur ; Masakazu YAMAGISHI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Shigeru YOKOYAMA, Auteur . - 2013 . - 14 p.
Langues : Anglais (eng)
in Molecular Autism > (July 2013) . - 14 p.
Mots-clés : Autism spectrum disorders Inositol-1,4,5-trisphosphate Intracellular free calcium Oxytocin Oxytocin receptor Single-nucleotide variation Index. décimale : PER Périodiques Résumé : Background
The human oxytocin receptor (hOXTR) is implicated in the etiology of autism spectrum disorders (ASDs) and is a potential target for therapeutic intervention. Several studies have reported single-nucleotide polymorphisms (SNPs) of the OXTR gene associated with ASDs. These SNPs, however, reside outside the protein-coding region. Not much is known about genetic variations that cause amino acid substitutions that alter receptor functions.
Methods
Variations in the OXTR gene were analyzed in 132 ASD patients at Kanazawa University Hospital in Japan and 248 unrelated healthy Japanese volunteers by re-sequencing and real-time polymerase chain reaction-based genotyping. Functional changes in variant OXTRs were assessed by radioligand binding assay and measurements of intracellular free calcium concentrations ([Ca2+]i) and inositol 1,4,5-trisphosphate (IP3) levels.
Results
Six subjects (4.5%) in the ASD group and two in the control group (0.8%) were identified as heterozygotes carrying the R376G variation (rs35062132; c.1126C>G); one individual from the ASD group (0.8%) and three members of the control group (1.2%) were found to be carrying R376C (c.1126C>T). The C/G genotype significantly correlated with an increased risk of ASDs (odds ratio (OR) = 5.83; 95% confidence interval (CI) = 1.16 to 29.33; P = 0.024, Fisher’s exact test). Consistently, the G allele showed a correlation with an increased likelihood of ASDs (OR = 5.73; 95% CI = 1.15 to 28.61; P = 0.024, Fisher’s exact test). The frequencies of the C/T genotype and the T allele in the ASD and control groups did not differ significantly. We also examined changes in agonist-induced cellular responses mediated by the variant receptors hOXTR-376G and hOXTR-376C. OXT-induced receptor internalization and recycling were faster in hOXTR-376G-expressing HEK-293 cells than in cells expressing hOXTR-376R or hOXTR-376C. In addition, the elevation in [Ca2+]i and IP3 formation decreased in the cells expressing hOXTR-376G and hOXTR-376C tagged with enhanced green fluorescent protein (EGFP), in comparison with the cells expressing the common-type hOXTR-376R tagged with EGFP.
Conclusions
These results suggest that the rare genetic variation rs35062132 might contribute to the pathogenesis of ASDs, and could provide a molecular basis of individual differences in OXTR-mediated modulation of social behavior.En ligne : http://dx.doi.org/10.1186/2040-2392-4-22 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 The oxytocin receptor gene predicts brain activity during an emotion recognition task in autism / F. UZEFOVSKY in Molecular Autism, 10 (2019)
[article]
Titre : The oxytocin receptor gene predicts brain activity during an emotion recognition task in autism Type de document : Texte imprimé et/ou numérique Auteurs : F. UZEFOVSKY, Auteur ; Richard A. I. BETHLEHEM, Auteur ; S. SHAMAY-TSOORY, Auteur ; A. RUIGROK, Auteur ; R. HOLT, Auteur ; M. SPENCER, Auteur ; L. CHURA, Auteur ; V. WARRIER, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Edward T. BULLMORE, Auteur ; J. SUCKLING, Auteur ; D. FLORIS, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Autism Imaging genetics Oxytocin receptor Supramarginal gyrus fMRI the relevant national and institutional committees on human experimentation and with the Declaration of Helsinki of 1975, as revised in 2008.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism is a highly varied and heritable neurodevelopmental condition, and common variants explain approximately 50% of the genetic variance of autism. One of the genes implicated in autism is the oxytocin receptor (OXTR). The current study combined genetic and brain imaging (fMRI) data to examine the moderating effect of genotype on the association between diagnosis and brain activity in response to a test of cognitive empathy. Methods: Participants were adolescents (mean age = 14.7 +/- 1.7) who were genotyped for single nucleotide polymorphisms (SNPs) within the OXTR and underwent functional brain imaging while completing the adolescent version of the 'Reading the Mind in the Eyes' Test (Eyes Test). Results: Two (rs2254298, rs53576) of the five OXTR SNPs examined were significantly associated with brain activity during the Eyes Test, and three of the SNPs (rs2254298, rs53576, rs2268491) interacted with diagnostic status to predict brain activity. All of the effects localized to the right supramarginal gyrus (rSMG) and an overlap analysis revealed a large overlap of the effects. An exploratory analysis showed that activity within an anatomically defined rSMG and genotype can predict diagnostic status with reasonable accuracy. Conclusions: This is one of the first studies to investigate OXTR and brain function in autism. The findings suggest a neurogenetic mechanism by which OXTR-dependent activity within the rSMG is related to the aetiology of autism. En ligne : https://dx.doi.org/10.1186/s13229-019-0258-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389
in Molecular Autism > 10 (2019) . - 12 p.[article] The oxytocin receptor gene predicts brain activity during an emotion recognition task in autism [Texte imprimé et/ou numérique] / F. UZEFOVSKY, Auteur ; Richard A. I. BETHLEHEM, Auteur ; S. SHAMAY-TSOORY, Auteur ; A. RUIGROK, Auteur ; R. HOLT, Auteur ; M. SPENCER, Auteur ; L. CHURA, Auteur ; V. WARRIER, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Edward T. BULLMORE, Auteur ; J. SUCKLING, Auteur ; D. FLORIS, Auteur ; Simon BARON-COHEN, Auteur . - 12 p.
Langues : Anglais (eng)
in Molecular Autism > 10 (2019) . - 12 p.
Mots-clés : Autism Imaging genetics Oxytocin receptor Supramarginal gyrus fMRI the relevant national and institutional committees on human experimentation and with the Declaration of Helsinki of 1975, as revised in 2008.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Autism is a highly varied and heritable neurodevelopmental condition, and common variants explain approximately 50% of the genetic variance of autism. One of the genes implicated in autism is the oxytocin receptor (OXTR). The current study combined genetic and brain imaging (fMRI) data to examine the moderating effect of genotype on the association between diagnosis and brain activity in response to a test of cognitive empathy. Methods: Participants were adolescents (mean age = 14.7 +/- 1.7) who were genotyped for single nucleotide polymorphisms (SNPs) within the OXTR and underwent functional brain imaging while completing the adolescent version of the 'Reading the Mind in the Eyes' Test (Eyes Test). Results: Two (rs2254298, rs53576) of the five OXTR SNPs examined were significantly associated with brain activity during the Eyes Test, and three of the SNPs (rs2254298, rs53576, rs2268491) interacted with diagnostic status to predict brain activity. All of the effects localized to the right supramarginal gyrus (rSMG) and an overlap analysis revealed a large overlap of the effects. An exploratory analysis showed that activity within an anatomically defined rSMG and genotype can predict diagnostic status with reasonable accuracy. Conclusions: This is one of the first studies to investigate OXTR and brain function in autism. The findings suggest a neurogenetic mechanism by which OXTR-dependent activity within the rSMG is related to the aetiology of autism. En ligne : https://dx.doi.org/10.1186/s13229-019-0258-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 Association with Autism of Two Polymorphisms in Gene Encoding Oxytocin Receptors in Slovakia / Silvia LAKATOSOVA in Autism - Open Access, 3-3 (December 2013)
[article]
Titre : Association with Autism of Two Polymorphisms in Gene Encoding Oxytocin Receptors in Slovakia Type de document : Texte imprimé et/ou numérique Auteurs : Silvia LAKATOSOVA, Auteur ; Lenka DUDOVA, Auteur ; Anna PIVOVARCIOVA, Auteur ; Veronika HUSAROVA, Auteur ; Katarina BABINSKA, Auteur ; Aneta KUBRANSKA, Auteur ; Daniela OSTATNIKOVA, Auteur Année de publication : 2013 Article en page(s) : 5 p. Langues : Anglais (eng) Mots-clés : Autism Oxytocin receptor Single nucleotide polymorphism Index. décimale : PER Périodiques Résumé : Study background: Autism is a complex neurodevelopmental disorder involving genetic components in its etiology. Oxytocin is a neuropeptide affecting social behavior acting in the CNS via binding its only type of receptor (OXTR). A number of studies have shown an association of polymorphisms in the OXTR gene and the diagnosis of autism in different ethnic populations. The aim of this study is to find an association of polymorphisms in the OXTR gene and the diagnosis of autism in Slovakia. Methods: After acquiring informed consent, 108 autism patients were recruited into the study (83 males, 25 females), in addition to 131 healthy children as a control group (106 males, 25 females). DNA was extracted from whole blood and four single nucleotide polymorphisms (rs223785, rs2270465, rs2268498, rs53576) were assessed using the PCR-RFLP method. Results: We found two positive associations of polymorphisms in OXTR with autism in boys, namely markers rs2270465 and rs237851 (p<0.0001 and p=0.0016). Both markers survived multiple comparison testing (p<0.0005, p<0.001, respectively). There were no significant differences in the genotype and allelic distribution among groups in girls. Conclusion: Polymorphisms in oxytocin receptor are associated with autism. The addition of psychological profiling may reveal possible correlations of gentoypes/alleles within OXTR with symptom severities. En ligne : http://dx.doi.org/10.4172/2165-7890.1000121 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=228
in Autism - Open Access > 3-3 (December 2013) . - 5 p.[article] Association with Autism of Two Polymorphisms in Gene Encoding Oxytocin Receptors in Slovakia [Texte imprimé et/ou numérique] / Silvia LAKATOSOVA, Auteur ; Lenka DUDOVA, Auteur ; Anna PIVOVARCIOVA, Auteur ; Veronika HUSAROVA, Auteur ; Katarina BABINSKA, Auteur ; Aneta KUBRANSKA, Auteur ; Daniela OSTATNIKOVA, Auteur . - 2013 . - 5 p.
Langues : Anglais (eng)
in Autism - Open Access > 3-3 (December 2013) . - 5 p.
Mots-clés : Autism Oxytocin receptor Single nucleotide polymorphism Index. décimale : PER Périodiques Résumé : Study background: Autism is a complex neurodevelopmental disorder involving genetic components in its etiology. Oxytocin is a neuropeptide affecting social behavior acting in the CNS via binding its only type of receptor (OXTR). A number of studies have shown an association of polymorphisms in the OXTR gene and the diagnosis of autism in different ethnic populations. The aim of this study is to find an association of polymorphisms in the OXTR gene and the diagnosis of autism in Slovakia. Methods: After acquiring informed consent, 108 autism patients were recruited into the study (83 males, 25 females), in addition to 131 healthy children as a control group (106 males, 25 females). DNA was extracted from whole blood and four single nucleotide polymorphisms (rs223785, rs2270465, rs2268498, rs53576) were assessed using the PCR-RFLP method. Results: We found two positive associations of polymorphisms in OXTR with autism in boys, namely markers rs2270465 and rs237851 (p<0.0001 and p=0.0016). Both markers survived multiple comparison testing (p<0.0005, p<0.001, respectively). There were no significant differences in the genotype and allelic distribution among groups in girls. Conclusion: Polymorphisms in oxytocin receptor are associated with autism. The addition of psychological profiling may reveal possible correlations of gentoypes/alleles within OXTR with symptom severities. En ligne : http://dx.doi.org/10.4172/2165-7890.1000121 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=228 Oxytocin in the Developing Brain: Relevance as Disease-Modifying Treatment in Autism Spectrum Disorders / Bice CHINI
in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA
Titre : Oxytocin in the Developing Brain: Relevance as Disease-Modifying Treatment in Autism Spectrum Disorders Type de document : Texte imprimé et/ou numérique Auteurs : Bice CHINI, Auteur ; Marianna LEONZINO, Auteur ; Valentina GIGLIUCCI, Auteur Année de publication : 2016 Importance : p.253-266 Langues : Anglais (eng) Mots-clés : Autism Monoamines Neurodevelopment Opioid Oxytocin Oxytocin receptor Perinatal treatment Social behavior Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Among the several neurobiological systems implicated in shaping social behavior, oxytocin (OXT) has been firmly established as a master regulator of the social brain. This has led OXT to be proposed as a drug to ameliorate social deficits in a number of neurodevelopmental and neuropsychiatric conditions including autism spectrum disorders (ASDs). OXT administration has indeed been shown to improve social symptoms in adult ASD patients; even more interestingly, OXT has been shown to regulate key neurodevelopmental events, which suggests that the peptide can modify the onset and progression of ASD symptoms in childhood. We will review here the anatomical and neurochemical basis of these actions, with a special emphasis on the interactions of OXT with other key neurotransmitter systems involved in the regulation of social behavior at the early postnatal developmental stages. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00016-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 Oxytocin in the Developing Brain: Relevance as Disease-Modifying Treatment in Autism Spectrum Disorders [Texte imprimé et/ou numérique] / Bice CHINI, Auteur ; Marianna LEONZINO, Auteur ; Valentina GIGLIUCCI, Auteur . - 2016 . - p.253-266.
in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA
Langues : Anglais (eng)
Mots-clés : Autism Monoamines Neurodevelopment Opioid Oxytocin Oxytocin receptor Perinatal treatment Social behavior Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Among the several neurobiological systems implicated in shaping social behavior, oxytocin (OXT) has been firmly established as a master regulator of the social brain. This has led OXT to be proposed as a drug to ameliorate social deficits in a number of neurodevelopmental and neuropsychiatric conditions including autism spectrum disorders (ASDs). OXT administration has indeed been shown to improve social symptoms in adult ASD patients; even more interestingly, OXT has been shown to regulate key neurodevelopmental events, which suggests that the peptide can modify the onset and progression of ASD symptoms in childhood. We will review here the anatomical and neurochemical basis of these actions, with a special emphasis on the interactions of OXT with other key neurotransmitter systems involved in the regulation of social behavior at the early postnatal developmental stages. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00016-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 Exemplaires
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