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  • 1
  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-15
    Description: Certain genes are only expressed at one allele, a phenomenon called imprinting. Although it is well established that one allele of certain imprinted genes is silenced through methylation, this does not appear to be the case for all imprinted genes. In a thoughtful Perspective, Thorvaldsen and Bartolomei discuss new findings showing that insertion of insulator elements (boundary regions) between the promoter of a gene and its enhancer (a sequence that boosts gene expression) may be another way in which genes are silenced during imprinting.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thorvaldsen, J L -- Bartolomei, M S -- New York, N.Y. -- Science. 2000 Jun 23;288(5474):2145-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. thorvald@mail.med.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10896590" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *DNA Methylation ; DNA-Binding Proteins/metabolism ; Dinucleoside Phosphates ; Enhancer Elements, Genetic ; Fathers ; Female ; *Gene Silencing ; *Genomic Imprinting ; Humans ; Insulin-Like Growth Factor II/genetics ; Male ; Models, Genetic ; Mothers ; Muscle Proteins/genetics ; Ovum/metabolism ; Promoter Regions, Genetic ; RNA, Long Noncoding ; *RNA, Untranslated ; Regulatory Sequences, Nucleic Acid ; *Repressor Proteins ; Spermatozoa/metabolism ; Transcription Factors/metabolism ; Zinc Fingers
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2001-06-02
    Description: Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps in insulin action include phosphorylation of scaffolding proteins and activation of phosphatidylinositol 3-kinase. These early events lead to activation of the serine-threonine protein kinase Akt, also known as protein kinase B. We show that mice deficient in Akt2 are impaired in the ability of insulin to lower blood glucose because of defects in the action of the hormone on liver and skeletal muscle. These data establish Akt2 as an essential gene in the maintenance of normal glucose homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cho, H -- Mu, J -- Kim, J K -- Thorvaldsen, J L -- Chu, Q -- Crenshaw, E B 3rd -- Kaestner, K H -- Bartolomei, M S -- Shulman, G I -- Birnbaum, M J -- GM07229/GM/NIGMS NIH HHS/ -- P30 19525/PHS HHS/ -- P30 DK50306/DK/NIDDK NIH HHS/ -- R01 DK040936/DK/NIDDK NIH HHS/ -- R01 DK56886/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 1;292(5522):1728-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387480" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/metabolism ; Deoxyglucose/metabolism ; Diabetes Mellitus, Type 2/*metabolism ; Female ; Gene Targeting ; Glucose/*metabolism ; Glucose Clamp Technique ; Glucose Tolerance Test ; Homeostasis ; Insulin/administration & dosage/blood/*metabolism ; *Insulin Resistance/genetics/physiology ; Islets of Langerhans/cytology/physiology ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Muscle, Skeletal/enzymology/metabolism ; *Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins/*genetics/*metabolism ; Proto-Oncogene Proteins c-akt ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2002-05-11
    Description: X chromosome inactivation is the silencing mechanism eutherian mammals use to equalize the expression of X-linked genes between males and females early in embryonic development. In the mouse, genetic control of inactivation requires elements within the X inactivation center (Xic) on the X chromosome that influence the choice of which X chromosome is to be inactivated in individual cells. It has long been posited that unidentified autosomal factors are essential to the process. We have used chemical mutagenesis in the mouse to identify specific factors involved in X inactivation and report two genetically distinct autosomal mutations with dominant effects on X chromosome choice early in embryogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Percec, Ivona -- Plenge, Robert M -- Nadeau, Joseph H -- Bartolomei, Marisa S -- Willard, Huntington F -- GM45441/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 May 10;296(5570):1136-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12004136" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Crosses, Genetic ; *Dosage Compensation, Genetic ; Female ; *Genes, Dominant ; Heterozygote ; Male ; Mice ; Mice, Inbred BALB C ; Mutagenesis ; *Mutation ; Pedigree ; Phenotype ; X Chromosome/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-01-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Percec, Ivona -- Bartolomei, Marisa S -- New York, N.Y. -- Science. 2002 Jan 11;295(5553):287-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. ipercec@mail.med.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11786631" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Antisense Elements (Genetics) ; Binding Sites ; DNA Methylation ; DNA-Binding Proteins/genetics/*metabolism ; *Dosage Compensation, Genetic ; Enhancer Elements, Genetic ; Female ; Gene Expression Regulation ; *Gene Silencing ; Humans ; Mice ; Models, Genetic ; RNA, Long Noncoding ; RNA, Untranslated/genetics/metabolism ; *Repressor Proteins ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic ; X Chromosome/*genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-08-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Susiarjo, Martha -- Bartolomei, Marisa S -- P30 ES013508/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):733-4. doi: 10.1126/science.1258654.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. bartolom@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124413" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *DNA Methylation ; Female ; Fetal Nutrition Disorders/*metabolism ; Male ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Spermatozoa/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2004-01-13
    Description: The imprinted regulation of H19 and Insulin-like growth factor 2 expression involves binding of the vertebrate insulator protein, CCCTC binding factor (CTCF), to the maternally hypomethylated differentially methylated domain (DMD). How this hypomethylated state is maintained during oogenesis and the role of CTCF, if any, in this process are not understood. With the use of a transgenic RNA interference (RNAi)-based approach to generate oocytes with reduced amounts of CTCF protein, we found increased methylation of the H19 DMD and decreased developmental competence of CTCF-deficient oocytes. Our results suggest that CTCF protects the H19 DMD from de novo methylation during oocyte growth and is required for normal preimplantation development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fedoriw, Andrew M -- Stein, Paula -- Svoboda, Petr -- Schultz, Richard M -- Bartolomei, Marisa S -- HD-42026/HD/NICHD NIH HHS/ -- T32 HD-07516/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2004 Jan 9;303(5655):238-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14716017" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/genetics ; Animals ; DNA Methylation ; DNA-Binding Proteins/genetics/*metabolism ; Embryonic and Fetal Development ; Female ; Fertilization in Vitro ; Gene Targeting ; *Genomic Imprinting ; Litter Size ; Mice ; Mice, Transgenic ; Nuclear Proteins/genetics ; Oocytes/*metabolism ; *RNA Interference ; RNA, Long Noncoding ; RNA, Messenger/genetics/metabolism ; RNA, Untranslated/*genetics ; Repressor Proteins/genetics/*metabolism ; Zygote/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2013-07-19
    Description: The epigenetic regulation of imprinted genes by monoallelic DNA methylation of either maternal or paternal alleles is critical for embryonic growth and development. Imprinted genes were recently shown to be expressed in mammalian adult stem cells to support self-renewal of neural and lung stem cells; however, a role for imprinting per se in adult stem cells remains elusive. Here we show upregulation of growth-restricting imprinted genes, including in the H19-Igf2 locus, in long-term haematopoietic stem cells and their downregulation upon haematopoietic stem cell activation and proliferation. A differentially methylated region upstream of H19 (H19-DMR), serving as the imprinting control region, determines the reciprocal expression of H19 from the maternal allele and Igf2 from the paternal allele. In addition, H19 serves as a source of miR-675, which restricts Igf1r expression. We demonstrate that conditional deletion of the maternal but not the paternal H19-DMR reduces adult haematopoietic stem cell quiescence, a state required for long-term maintenance of haematopoietic stem cells, and compromises haematopoietic stem cell function. Maternal-specific H19-DMR deletion results in activation of the Igf2-Igfr1 pathway, as shown by the translocation of phosphorylated FoxO3 (an inactive form) from nucleus to cytoplasm and the release of FoxO3-mediated cell cycle arrest, thus leading to increased activation, proliferation and eventual exhaustion of haematopoietic stem cells. Mechanistically, maternal-specific H19-DMR deletion leads to Igf2 upregulation and increased translation of Igf1r, which is normally suppressed by H19-derived miR-675. Similarly, genetic inactivation of Igf1r partly rescues the H19-DMR deletion phenotype. Our work establishes a new role for this unique form of epigenetic control at the H19-Igf2 locus in maintaining adult stem cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896866/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896866/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venkatraman, Aparna -- He, Xi C -- Thorvaldsen, Joanne L -- Sugimura, Ryohichi -- Perry, John M -- Tao, Fang -- Zhao, Meng -- Christenson, Matthew K -- Sanchez, Rebeca -- Yu, Jaclyn Y -- Peng, Lai -- Haug, Jeffrey S -- Paulson, Ariel -- Li, Hua -- Zhong, Xiao-bo -- Clemens, Thomas L -- Bartolomei, Marisa S -- Li, Linheng -- GM51279/GM/NIGMS NIH HHS/ -- R01 GM087376/GM/NIGMS NIH HHS/ -- R37 GM051279/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Aug 15;500(7462):345-9. doi: 10.1038/nature12303. Epub 2013 Jul 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23863936" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology/*physiology ; Animals ; Epigenesis, Genetic/genetics ; Gene Expression Regulation, Developmental ; *Genomic Imprinting ; Insulin-Like Growth Factor II/*genetics/*metabolism ; Mice ; RNA, Long Noncoding/*genetics/*metabolism ; Receptor, IGF Type 1/genetics ; Signal Transduction ; Transcriptional Activation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2013-09-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plasschaert, Robert N -- Bartolomei, Marisa S -- England -- Nature. 2013 Sep 5;501(7465):36-7. doi: 10.1038/nature12553. Epub 2013 Aug 28.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23995684" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*genetics ; DNA Topoisomerases, Type I/*metabolism ; Humans ; *Transcription Elongation, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-05-23
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684952/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684952/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Jieqi -- Wegener, Jan Eike -- Huang, Teng-Wei -- Sripathy, Smitha -- De Jesus-Cortes, Hector -- Xu, Pin -- Tran, Stephanie -- Knobbe, Whitney -- Leko, Vid -- Britt, Jeremiah -- Starwalt, Ruth -- McDaniel, Latisha -- Ward, Chris S -- Parra, Diana -- Newcomb, Benjamin -- Lao, Uyen -- Nourigat, Cynthia -- Flowers, David A -- Cullen, Sean -- Jorstad, Nikolas L -- Yang, Yue -- Glaskova, Lena -- Vingeau, Sebastien -- Kozlitina, Julia -- Yetman, Michael J -- Jankowsky, Joanna L -- Reichardt, Sybille D -- Reichardt, Holger M -- Gartner, Jutta -- Bartolomei, Marisa S -- Fang, Min -- Loeb, Keith -- Keene, C Dirk -- Bernstein, Irwin -- Goodell, Margaret -- Brat, Daniel J -- Huppke, Peter -- Neul, Jeffrey L -- Bedalov, Antonio -- Pieper, Andrew A -- P30 AI036211/AI/NIAID NIH HHS/ -- P30 CA138292/CA/NCI NIH HHS/ -- P30 ES005605/ES/NIEHS NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- P30 HD024064/HD/NICHD NIH HHS/ -- R01 AG031892/AG/NIA NIH HHS/ -- R01 HD062553/HD/NICHD NIH HHS/ -- S10 RR024574/RR/NCRR NIH HHS/ -- T32 AG000183/AG/NIA NIH HHS/ -- T32 HL092332/HL/NHLBI NIH HHS/ -- U01 HL100395/HL/NHLBI NIH HHS/ -- U54 HD083092/HD/NICHD NIH HHS/ -- England -- Nature. 2015 May 21;521(7552):E1-4. doi: 10.1038/nature14444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Gottingen, Robert-Koch-Strasse 40, 37075 Gottingen, Germany. ; 1] Jan and Dan Duncan Neurological Research Institute (Texas Children's Hospital), Baylor College of Medicine, Houston, Texas 77030, USA [2] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; 1] Graduate Program of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. ; Graduate Program of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Jan and Dan Duncan Neurological Research Institute (Texas Children's Hospital), Baylor College of Medicine, Houston, Texas 77030, USA. ; Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, USA. ; Department of Cell &Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA. ; Institute for Cellular and Molecular Immunology; University of Gottingen Medical School, Humboldtallee 34, 37073 Gottingen, Germany. ; 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA [2] Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, USA. ; 1] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA [3] Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA [4] Stem Cell and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030, USA [5] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA [6] Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. ; 1] Jan and Dan Duncan Neurological Research Institute (Texas Children's Hospital), Baylor College of Medicine, Houston, Texas 77030, USA [2] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA [4] Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA [5] Stem Cell and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030, USA [6] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA [2] Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98105, USA. ; 1] Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA [2] Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA [3] Veterans Affairs, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA [4] Weill Cornell Autism Research Program, Weill Cornell Medical College, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25993969" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Disease Progression ; Female ; Male ; Methyl-CpG-Binding Protein 2/*metabolism ; Microglia/*cytology/*physiology ; Rett Syndrome/*pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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