1. Cortelazzo A, De Felice C, Guerranti R, Signorini C, Leoncini S, Pecorelli A, Scalabri F, Madonna M, Filosa S, Giovampaola CD, Capone A, Durand T, Mirasole C, Zolla L, Valacchi G, Ciccoli L, Guy J, D’Esposito M, Hayek J. {{Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome}}. {Neurosci Res};2015 (Oct 14)
Neurological disorders can be associated with protein glycosylation abnormalities. Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. Remarkable glycosylation pattern changes for a peculiar 50kDa protein i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. Glycosylation changes were rescued by selected brain Mecp2 reactivation. Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5.
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2. Gerhardt J. {{Epigenetic modifications in human fragile X pluripotent stem cells; Implications in fragile X syndrome modeling}}. {Brain Res};2015 (Oct 14)
Patients with fragile X syndrome (FXS) exhibit moderate to severe intellectual disabilities. In addition, one third of FXS patients show characteristics of autism spectrum disorder. FXS is caused by a trinucleotide repeat expansion, which leads to silencing of the fragile X mental retardation (FMR1) gene. The absence of the FMR1 gene product, FMRP, is the reason for the disease symptoms. It has been suggested that repeat instability and transcription of the FMR1 gene occur during early embryonic development, while after cell differentiation repeats become stable and the FMR1 gene is silent. Epigenetic marks, such as DNA methylation, are associated with gene silencing and repeat stability at the FMR1 locus. However, the mechanisms leading to gene silencing and repeat expansion are still ambiguous, because studies at the human genomic locus were limited until now. The FXS pluripotent stem cells, recently derived from FXS adult cells and FXS blastocysts, are new useful tools to examine these mechanisms at the human endogenous FMR1 locus. This review summarizes the epigenetic features and experimental studies of FXS human embryonic and FXS induced pluripotent stem cells, generated so far.
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3. Murray AL, McKenzie K, Kuenssberg R, Booth T. {{Do the Autism Spectrum Quotient (AQ) and Autism Spectrum Quotient Short Form (AQ-S) Primarily Reflect General ASD Traits or Specific ASD Traits? A Bi-Factor Analysis}}. {Assessment};2015 (Oct 16)
In the current study, we fit confirmatory bi-factor models to the items of the Autism Spectrum Quotient (AQ) and Autism Spectrum Quotient Short Form (AQ-S) in order to assess the extents to which the items of each reflect general versus specific factors. The models were fit in a combined sample of individuals with and without a clinical diagnosis of autism spectrum disorders. Results indicated that, with the exception of the Attention to Details factor in the AQ and the Numbers/Patterns factors in the AQ-S, items primarily reflected a general factor. This suggests that when attempting to estimate an association between a specific symptom measured by the AQ or AQ-S and some criterion, associations will be confounded by the general factor. To resolve this, we recommend using a bi-factor measurement model or factor scores from a bi-factor measurement whenever hypotheses about specific symptoms are being assessed.
