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Chamberlain, S. J., Germain, N. D., Chen, P. - F., Hsiao, J. S., & Glatt-Deeley, H. (2016). Modeling Genomic Imprinting Disorders Using Induced Pluripotent Stem Cells. Methods Mol Biol, 1353, 45–64.
Abstract: Induced pluripotent stem cell (iPSC) technology has allowed for the invaluable modeling of many genetic disorders including disorders associated with genomic imprinting. Genomic imprinting involves differential DNA and histone methylation and results in allele-specific gene expression. Most of the epigenetic marks in somatic cells are erased and reestablished during the process of reprogramming into iPSCs. Therefore, in generating models of disorders associated with genomic imprinting, it is important to verify that the imprinting status and allele-specific gene expression patterns of the parental somatic cells are maintained in their derivative iPSCs. Here, we describe three techniques: DNA methylation analysis, allele-specific PCR, and RNA FISH, which we use to analyze genomic imprinting in iPSC models of neurogenetic disorders involving copy number variations of the chromosome 15q11-q13 region.
Keywords: Alleles; Animals; Cell Differentiation; Cells, Cultured; DNA Copy Number Variations; DNA Methylation; DNA Primers/chemical synthesis/metabolism; *Epigenesis, Genetic; Feeder Cells/cytology; Fibroblasts/cytology; *Genomic Imprinting; Humans; In Situ Hybridization, Fluorescence/methods; Induced Pluripotent Stem Cells/*metabolism/pathology; Mice; *Models, Genetic; Polymerase Chain Reaction/methods; Prader-Willi Syndrome/diagnosis/*genetics/pathology; RNA/genetics/metabolism; RNA, Small Nucleolar/genetics/metabolism; Ubiquitin-Protein Ligases/genetics/metabolism; Allele-specific PCR; DNA methylation; Genomic imprinting; Induced pluripotent stem cells; Rna Fish
Notes: PMID:25520291
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Wenzel, H. J., Hunsaker, M. R., Greco, C. M., Willemsen, R., & Berman, R. F. (2010). Ubiquitin-positive intranuclear inclusions in neuronal and glial cells in a mouse model of the fragile X premutation. Brain Res, 1318, 155–166.
Abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder caused by CGG trinucleotide repeat expansions in the fragile X mental retardation 1 (FMR1) gene. The neuropathological hallmark of the disease is the presence of ubiquitin-positive intranuclear inclusions in neurons and in astrocytes. Ubiquitin-positive intranuclear inclusions have also been found in the neurons of transgenic mice model carrying an expanded CGG((98)) trinucleotide repeat of human origin but have not previously been described in glial cells. Therefore, we used immunocytochemical methods to determine the pathological features of nuclear and/or cytoplasmic inclusions in astrocytes, Bergmann glia, and neurons, as well as relationships between inclusion patterns, age, and repeat length in CGG knock-in (KI) mice in comparison with wild-type mice. In CGG KI mice, ubiquitin-positive intranuclear inclusions were found in neurons (e.g., pyramidal cells, GABAergic neurons) throughout the brain in cortical and subcortical brain regions; these inclusions increased in number and size with advanced age. Ubiquitin-positive intranuclear inclusions were also present in protoplasmic astrocytes, including Bergmann glia in the cerebellum. The morphology of intranuclear inclusions in CGG KI mice was compared to that of typical inclusions in human neurons and astrocytes in postmortem FXTAS brain tissue. This new finding of previously unreported pathology in astrocytes of CGG KI mice now provides an important mouse model to study astrocyte pathology in human FXTAS.
Keywords: Age Factors; Aged; Animals; Brain/metabolism/*pathology; Cell Nucleus/metabolism/*pathology; Cytoplasm/metabolism/pathology; Disease Models, Animal; Female; Fragile X Mental Retardation Protein/genetics; Fragile X Syndrome/metabolism/*pathology; Gene Knock-In Techniques; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroglia/metabolism/*pathology; Neurons/metabolism/*pathology; Sex Factors; Trinucleotide Repeat Expansion; Ubiquitin/*metabolism
Notes: PMID:20051238; PMCID:PMC3086812
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Busoni, G., De Simone, A., & Huang, W. - C. (2013). On the Minimum Dark Matter Mass Testable by Neutrinos from the Sun. Jcap, 1307, 010.
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Cerasa, A., Gioia, M. C., Fera, F., Passamonti, L., Liguori, M., Lanza, P., et al. (2008). Ventro-lateral prefrontal activity during working memory is modulated by MAO A genetic variation. Brain Research, 1201(27), 114–121.
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Kray, J. (2006). Task-set switching under cue-based versus memory-based switching conditions in younger and older adults. Brain Research, 1105(1), 83–92.
Abstract: Adult age differences in task switching and advance preparation were examined by comparing cue-based and memory-based switching conditions. Task switching was assessed by determining two types of costs that occur at the general (mixing costs) and specific (switching costs) level of switching. Advance preparation was investigated by varying the time interval until the next task (short, middle, very long). Results indicated that the implementation of task sets was different for cue-based switching with random task sequences and memory-based switching with predictable task sequences. Switching costs were strongly reduced under cue-based switching conditions, indicating that task-set cues facilitate the retrieval of the next task. Age differences were found for mixing costs and for switching costs only under cue-based conditions in which older adults showed smaller switching costs than younger adults. It is suggested that older adults adopt a less extreme bias between two tasks than younger adults in situations associated with uncertainty. For cue-based switching with random task sequences, older adults are less engaged in a complete reconfiguration of task sets because of the probability of a further task change. Furthermore, the reduction of switching costs was more pronounced for cue- than memory-based switching for short preparation intervals, whereas the reduction of switch costs was more pronounced for memory- than cue-based switching for longer preparation intervals at least for older adults. Together these findings suggest that the implementation of task sets is functionally different for the two types of task-switching conditions. (PsycINFO Database Record (c) 2007 APA, all rights reserved) (from the journal abstract)
Keywords: task set switching; cue based switching; memory based switching; age differences; time interval; Cues; Interresponse Time; Memory; Task Complexity; Probability; Uncertainty
Notes: 0006-8993Accession Number: 2006-10729-008. First Author & Affiliation: Kray, Jutta; Department of Psychology, Saarland University, SaarbrÃRcken, Germany. Other Journal Title: Brain Research. Release Date: 20070312. Publication Type: Journal (0100) Peer Reviewed Journal (0110). Media Covered: Electronic. Media Available: Electronic; Print. Document Type: Journal Article. Language: English. Major Descriptor: Age Differences; Cues; Interresponse Time; Memory; Task Complexity. Minor Descriptor: Probability; Uncertainty. Classification: Cognitive Processes (2340) . Population: Human (10) Male (30) Female (40) . Location: Germany. Age Group: Adulthood (18 yrs & older) (300) . Grant Information: The present research was funded by the Deutsche Forschungsgemeinschaft (grant KR 1884/3-1). Tests & Measures: Digit Symbol Substitution Test; . Methodology: Empirical Study; Quantitative Study. References Available: Y.
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