8 recherche sur le mot-clé 'Stem cells'

CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons / Yin ZHOU in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 42p. Titre : CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons Type de document : texte imprimé Auteurs : Yin ZHOU, Auteur ; Daman KUMARI, Auteur ; Nicholas SCIASCIA, Auteur ; Karen USDIN, Auteur Article en page(s) : 42p. Langues : Anglais (eng) Mots-clés : 5' Untranslated Regions  Alleles  Cell Differentiation  Cell Line  DNA Methylation  Embryonic Stem Cells/metabolism/pathology  Fragile X Mental Retardation Protein/genetics/metabolism  Fragile X Syndrome/genetics/metabolism/pathology  Gene Silencing  Humans  Induced Pluripotent Stem Cells/metabolism/pathology  Male  Neurons/metabolism/pathology  Primary Cell Culture  Time Factors  Trinucleotide Repeat Expansion  Fragile X syndrome  Repeat contractions  Repeat expansion mutation  Repeat-mediated gene silencing  Stem cells Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5' untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. METHODS: We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons. We used a PCR assay optimized for the amplification of large CGG repeats for sizing, and a quantitative methylation-specific PCR for the analysis of FMR1 promoter methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were determined by western blotting and immunofluorescence. Chromatin immunoprecipitation was used to study the association of repressive histone marks with the FMR1 gene in FXS ESCs. RESULTS: We show here that while FMR1 gene silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles contract and when the repeat number drops below ~400, DNA methylation erodes, even when the repeat number remains >200. The resultant active alleles do not show the large step-wise expansions seen in stem cells from other repeat expansion diseases. Furthermore, there may be selection against large active alleles and these alleles do not expand further or become silenced on neuronal differentiation. CONCLUSIONS: Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats. En ligne : http://dx.doi.org/10.1186/s13229-016-0105-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons [texte imprimé] / Yin ZHOU, Auteur ; Daman KUMARI, Auteur ; Nicholas SCIASCIA, Auteur ; Karen USDIN, Auteur . - 42p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 42p. Mots-clés : 5' Untranslated Regions  Alleles  Cell Differentiation  Cell Line  DNA Methylation  Embryonic Stem Cells/metabolism/pathology  Fragile X Mental Retardation Protein/genetics/metabolism  Fragile X Syndrome/genetics/metabolism/pathology  Gene Silencing  Humans  Induced Pluripotent Stem Cells/metabolism/pathology  Male  Neurons/metabolism/pathology  Primary Cell Culture  Time Factors  Trinucleotide Repeat Expansion  Fragile X syndrome  Repeat contractions  Repeat expansion mutation  Repeat-mediated gene silencing  Stem cells Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5' untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. METHODS: We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons. We used a PCR assay optimized for the amplification of large CGG repeats for sizing, and a quantitative methylation-specific PCR for the analysis of FMR1 promoter methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were determined by western blotting and immunofluorescence. Chromatin immunoprecipitation was used to study the association of repressive histone marks with the FMR1 gene in FXS ESCs. RESULTS: We show here that while FMR1 gene silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles contract and when the repeat number drops below ~400, DNA methylation erodes, even when the repeat number remains >200. The resultant active alleles do not show the large step-wise expansions seen in stem cells from other repeat expansion diseases. Furthermore, there may be selection against large active alleles and these alleles do not expand further or become silenced on neuronal differentiation. CONCLUSIONS: Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats. En ligne : http://dx.doi.org/10.1186/s13229-016-0105-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Do the Stem Cells Really Work with Autism Spectrum Disorders Associated with Neuro-Immune Interaction? / Gao SHANE in Autism - Open Access, 5-3 ([01/06/2015])  

Public ISBD [article]  inAutism - Open Access > 5-3 [01/06/2015] . - 7 p. Titre : Do the Stem Cells Really Work with Autism Spectrum Disorders Associated with Neuro-Immune Interaction? Type de document : texte imprimé Auteurs : Gao SHANE, Auteur ; Xu JUN, Auteur ; Wang JUAN, Auteur ; Wu ZEYANG, Auteur ; Yuan PING, Auteur ; Gao FENGJUAN, Auteur ; Cao LIMEI, Auteur ; Chen XU, Auteur ; Zhou FEI, Auteur ; Zhu HONGWEN, Auteur Article en page(s) : 7 p. Langues : Anglais (eng) Mots-clés : Stem cells  Mesenchymal stem cells (Mscs)  Autism spectrum disorders (Asds)  Neuro-immune interaction Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASDs), namely neurodevelopmental disorders encompassing impairments in communication, social interactions and restricted stereotypical behaviors, induces a relatively high morbidity and mortality ratio (1/166) in modern children's life. One of the serious factors accounting for ASDs is the failure of the appropriate neuro-immune interaction. Although a relationship between altered immune responses and ASDs was firstly recognized nearly 40 years ago, only recently has new evidence started to shed light on the complex multifaceted communication between neuro-immune dysfunction and behavior in ASDs. Extensive alterations in immune function have now been described in both children and adults with ASDs, including ongoing inflammation in brain specimens, elevated pro-inflammatory cytokine profiles in the Cerebro-Spinal Fluid (CSF) and blood, increased presence of brain-specific auto-antibodies and altered immune cell function. Accumulated data both from clinical and lab research proposed the essential role of neuro-immune interaction during the pathogenesis of ASDs. Stem cells, which account for normal turnover and injury repair, might do great favors on ASDs due to their ability to give rise to new functional cells as a cell replacement source, paracrine secretion as trophic and cytokine contributor, immune modulator to balance the pro-inflammation and anti-inflammation as well as the inhibitor of chronic inflammation in ASDs brain, etc. Here in this review, we focus on the current development of stem cell administration in ASDs especially on mesenchymal stem cells (MSCs), which proved to be the most plastic and efficient to interfere with ASDs neuro-immune interaction, moreover summarize the propbable mechanism and efficient therapeutic methods to treat ASDs with MSCs. En ligne : https://dx.doi.org/10.4172/2165-7890.1000151 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Do the Stem Cells Really Work with Autism Spectrum Disorders Associated with Neuro-Immune Interaction? [texte imprimé] / Gao SHANE, Auteur ; Xu JUN, Auteur ; Wang JUAN, Auteur ; Wu ZEYANG, Auteur ; Yuan PING, Auteur ; Gao FENGJUAN, Auteur ; Cao LIMEI, Auteur ; Chen XU, Auteur ; Zhou FEI, Auteur ; Zhu HONGWEN, Auteur . - 7 p. Langues : Anglais (eng) in Autism - Open Access > 5-3 [01/06/2015] . - 7 p. Mots-clés : Stem cells  Mesenchymal stem cells (Mscs)  Autism spectrum disorders (Asds)  Neuro-immune interaction Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASDs), namely neurodevelopmental disorders encompassing impairments in communication, social interactions and restricted stereotypical behaviors, induces a relatively high morbidity and mortality ratio (1/166) in modern children's life. One of the serious factors accounting for ASDs is the failure of the appropriate neuro-immune interaction. Although a relationship between altered immune responses and ASDs was firstly recognized nearly 40 years ago, only recently has new evidence started to shed light on the complex multifaceted communication between neuro-immune dysfunction and behavior in ASDs. Extensive alterations in immune function have now been described in both children and adults with ASDs, including ongoing inflammation in brain specimens, elevated pro-inflammatory cytokine profiles in the Cerebro-Spinal Fluid (CSF) and blood, increased presence of brain-specific auto-antibodies and altered immune cell function. Accumulated data both from clinical and lab research proposed the essential role of neuro-immune interaction during the pathogenesis of ASDs. Stem cells, which account for normal turnover and injury repair, might do great favors on ASDs due to their ability to give rise to new functional cells as a cell replacement source, paracrine secretion as trophic and cytokine contributor, immune modulator to balance the pro-inflammation and anti-inflammation as well as the inhibitor of chronic inflammation in ASDs brain, etc. Here in this review, we focus on the current development of stem cell administration in ASDs especially on mesenchymal stem cells (MSCs), which proved to be the most plastic and efficient to interfere with ASDs neuro-immune interaction, moreover summarize the propbable mechanism and efficient therapeutic methods to treat ASDs with MSCs. En ligne : https://dx.doi.org/10.4172/2165-7890.1000151 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

From wings to whiskers to stem cells: why every model matters in fragile X syndrome research / Soraya O. SANDOVAL in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : From wings to whiskers to stem cells: why every model matters in fragile X syndrome research Type de document : texte imprimé Auteurs : Soraya O. SANDOVAL, Auteur ; Natasha M. MÉNDEZ-ALBELO, Auteur ; Zhiyan XU, Auteur ; Xinyu ZHAO, Auteur Langues : Anglais (eng) Mots-clés : Animals  Humans  Disease Models, Animal  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/genetics/physiopathology  Pluripotent Stem Cells  Drosophila  Fmr1  Fmrp  Fragile X syndrome  Human  Mouse  Neuron  Organoid  Stem cells  iPSCs Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is caused by epigenetic silencing of the X-linked fragile X messenger ribonucleoprotein 1 (FMR1) gene located on chromosome Xq27.3, which leads to the loss of its protein product, fragile X messenger ribonucleoprotein (FMRP). It is the most prevalent inherited form of intellectual disability and the highest single genetic cause of autism. Since the discovery of the genetic basis of FXS, extensive studies using animal models and human pluripotent stem cells have unveiled the functions of FMRP and mechanisms underlying FXS. However, clinical trials have not yielded successful treatment. Here we review what we have learned from commonly used models for FXS, potential limitations of these models, and recommendations for future steps. En ligne : https://dx.doi.org/10.1186/s11689-024-09545-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] From wings to whiskers to stem cells: why every model matters in fragile X syndrome research [texte imprimé] / Soraya O. SANDOVAL, Auteur ; Natasha M. MÉNDEZ-ALBELO, Auteur ; Zhiyan XU, Auteur ; Xinyu ZHAO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Animals  Humans  Disease Models, Animal  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/genetics/physiopathology  Pluripotent Stem Cells  Drosophila  Fmr1  Fmrp  Fragile X syndrome  Human  Mouse  Neuron  Organoid  Stem cells  iPSCs Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is caused by epigenetic silencing of the X-linked fragile X messenger ribonucleoprotein 1 (FMR1) gene located on chromosome Xq27.3, which leads to the loss of its protein product, fragile X messenger ribonucleoprotein (FMRP). It is the most prevalent inherited form of intellectual disability and the highest single genetic cause of autism. Since the discovery of the genetic basis of FXS, extensive studies using animal models and human pluripotent stem cells have unveiled the functions of FMRP and mechanisms underlying FXS. However, clinical trials have not yielded successful treatment. Here we review what we have learned from commonly used models for FXS, potential limitations of these models, and recommendations for future steps. En ligne : https://dx.doi.org/10.1186/s11689-024-09545-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Untangling the Molecular Mechanisms Contributing to Autism Spectrum Disorder Using Stem Cells / Zoe MATTINGLY in Autism Research, 18-3 (March 2025)  

Public ISBD [article]  inAutism Research > 18-3 (March 2025) . - p.476-485 Titre : Untangling the Molecular Mechanisms Contributing to Autism Spectrum Disorder Using Stem Cells Type de document : texte imprimé Auteurs : Zoe MATTINGLY, Auteur ; Sundari CHETTY, Auteur Article en page(s) : p.476-485 Langues : Anglais (eng) Mots-clés : autism  disease modeling  molecular and cellular mechanisms  personalized medicine  stem cells Index. décimale : PER Périodiques Résumé : ABSTRACT Autism spectrum disorder (ASD) is a complex neuro developmental condition characterized by significant genetic and phenotypic variability, making diagnosis and treatment challenging. The heterogeneity of ASD-associated genetic variants and the absence of clear causal factors in many cases complicate personalized care. Traditional models, such as postmortem brain tissue and animal studies, have provided valuable insights but are limited in capturing the dynamic processes and human-specific aspects of ASD pathology. Recent advances in human induced pluripotent stem cell (iPSC) technology have transformed ASD research by enabling the generation of patient-derived neural cells in both two-dimensional cultures and three-dimensional brain organoid models. These models retain the donor's genetic background, allowing researchers to investigate disease-specific cellular and molecular mechanisms while identifying potential therapeutic targets tailored to individual patients. This commentary highlights how stem cell-based approaches are advancing our understanding of ASD and paving the way for more personalized diagnostic and therapeutic strategies. En ligne : https://doi.org/10.1002/aur.70005 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=550 [article] Untangling the Molecular Mechanisms Contributing to Autism Spectrum Disorder Using Stem Cells [texte imprimé] / Zoe MATTINGLY, Auteur ; Sundari CHETTY, Auteur . - p.476-485. Langues : Anglais (eng) in Autism Research > 18-3 (March 2025) . - p.476-485 Mots-clés : autism  disease modeling  molecular and cellular mechanisms  personalized medicine  stem cells Index. décimale : PER Périodiques Résumé : ABSTRACT Autism spectrum disorder (ASD) is a complex neuro developmental condition characterized by significant genetic and phenotypic variability, making diagnosis and treatment challenging. The heterogeneity of ASD-associated genetic variants and the absence of clear causal factors in many cases complicate personalized care. Traditional models, such as postmortem brain tissue and animal studies, have provided valuable insights but are limited in capturing the dynamic processes and human-specific aspects of ASD pathology. Recent advances in human induced pluripotent stem cell (iPSC) technology have transformed ASD research by enabling the generation of patient-derived neural cells in both two-dimensional cultures and three-dimensional brain organoid models. These models retain the donor's genetic background, allowing researchers to investigate disease-specific cellular and molecular mechanisms while identifying potential therapeutic targets tailored to individual patients. This commentary highlights how stem cell-based approaches are advancing our understanding of ASD and paving the way for more personalized diagnostic and therapeutic strategies. En ligne : https://doi.org/10.1002/aur.70005 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=550

Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons / Nora URRACA in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 6p. Titre : Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons Type de document : texte imprimé Auteurs : Nora URRACA, Auteur ; Kevin HOPE, Auteur ; A. Kaitlyn VICTOR, Auteur ; T. Grant BELGARD, Auteur ; Rawaha MEMON, Auteur ; Sarita GOORHA, Auteur ; Colleen VALDEZ, Auteur ; Quynh T. TRAN, Auteur ; Silvia SANCHEZ, Auteur ; Judyth RAMIREZ, Auteur ; Martin DONALDSON, Auteur ; Dave BRIDGES, Auteur ; Lawrence T. REITER, Auteur Article en page(s) : 6p. Langues : Anglais (eng) Mots-clés : Autism  Genomic disorders  Neurogenetic syndrome  Stem cells  mRNAseq Index. décimale : PER Périodiques Résumé : Background: The inability to analyze gene expression in living neurons from Angelman (AS) and Duplication 15q (Dup15q) syndrome subjects has limited our understanding of these disorders at the molecular level. Method: Here, we use dental pulp stem cells (DPSC) from AS deletion, 15q Duplication, and neurotypical control subjects for whole transcriptome analysis. We identified 20 genes unique to AS neurons, 120 genes unique to 15q duplication, and 3 shared transcripts that were differentially expressed in DPSC neurons vs controls. Results: Copy number correlated with gene expression for most genes across the 15q11.2-q13.1 critical region. Two thirds of the genes differentially expressed in 15q duplication neurons were downregulated compared to controls including several transcription factors, while in AS differential expression was restricted primarily to the 15q region. Here, we show significant downregulation of the transcription factors FOXO1 and HAND2 in neurons from 15q duplication, but not AS deletion subjects suggesting that disruptions in transcriptional regulation may be a driving factor in the autism phenotype in Dup15q syndrome. Downstream analysis revealed downregulation of the ASD associated genes EHPB2 and RORA, both genes with FOXO1 binding sites. Genes upregulated in either Dup15q cortex or idiopathic ASD cortex both overlapped significantly with the most upregulated genes in Dup15q DPSC-derived neurons. Conclusions: Finding a significant increase in both HERC2 and UBE3A in Dup15q neurons and significant decrease in these two genes in AS deletion neurons may explain differences between AS deletion class and UBE3A specific classes of AS mutation where HERC2 is expressed at normal levels. Also, we identified an enrichment for FOXO1-regulated transcripts in Dup15q neurons including ASD-associated genes EHPB2 and RORA indicating a possible connection between this syndromic form of ASD and idiopathic cases. En ligne : http://dx.doi.org/10.1186/s13229-018-0191-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 [article] Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons [texte imprimé] / Nora URRACA, Auteur ; Kevin HOPE, Auteur ; A. Kaitlyn VICTOR, Auteur ; T. Grant BELGARD, Auteur ; Rawaha MEMON, Auteur ; Sarita GOORHA, Auteur ; Colleen VALDEZ, Auteur ; Quynh T. TRAN, Auteur ; Silvia SANCHEZ, Auteur ; Judyth RAMIREZ, Auteur ; Martin DONALDSON, Auteur ; Dave BRIDGES, Auteur ; Lawrence T. REITER, Auteur . - 6p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 6p. Mots-clés : Autism  Genomic disorders  Neurogenetic syndrome  Stem cells  mRNAseq Index. décimale : PER Périodiques Résumé : Background: The inability to analyze gene expression in living neurons from Angelman (AS) and Duplication 15q (Dup15q) syndrome subjects has limited our understanding of these disorders at the molecular level. Method: Here, we use dental pulp stem cells (DPSC) from AS deletion, 15q Duplication, and neurotypical control subjects for whole transcriptome analysis. We identified 20 genes unique to AS neurons, 120 genes unique to 15q duplication, and 3 shared transcripts that were differentially expressed in DPSC neurons vs controls. Results: Copy number correlated with gene expression for most genes across the 15q11.2-q13.1 critical region. Two thirds of the genes differentially expressed in 15q duplication neurons were downregulated compared to controls including several transcription factors, while in AS differential expression was restricted primarily to the 15q region. Here, we show significant downregulation of the transcription factors FOXO1 and HAND2 in neurons from 15q duplication, but not AS deletion subjects suggesting that disruptions in transcriptional regulation may be a driving factor in the autism phenotype in Dup15q syndrome. Downstream analysis revealed downregulation of the ASD associated genes EHPB2 and RORA, both genes with FOXO1 binding sites. Genes upregulated in either Dup15q cortex or idiopathic ASD cortex both overlapped significantly with the most upregulated genes in Dup15q DPSC-derived neurons. Conclusions: Finding a significant increase in both HERC2 and UBE3A in Dup15q neurons and significant decrease in these two genes in AS deletion neurons may explain differences between AS deletion class and UBE3A specific classes of AS mutation where HERC2 is expressed at normal levels. Also, we identified an enrichment for FOXO1-regulated transcripts in Dup15q neurons including ASD-associated genes EHPB2 and RORA indicating a possible connection between this syndromic form of ASD and idiopathic cases. En ligne : http://dx.doi.org/10.1186/s13229-018-0191-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354

Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism / Michael S. BREEN in Molecular Autism, 11 (2020)  

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Cell therapy approaches to autism: a review of clinical trial data / Jack PRICE in Molecular Autism, 11 (2020)  

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Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development / Shaun HURLEY in Molecular Autism, 12 (2021)  

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