1. Blice-Baum AC, Mihailescu MR. {{Biophysical characterization of G-quadruplex forming FMR1 mRNA and of its interactions with different fragile X mental retardation protein isoforms}}. {RNA};2013 (Nov 18)
Fragile X syndrome, the most common form of inherited mental impairment in humans, is caused by the absence of the fragile X mental retardation protein (FMRP) due to a CGG trinucleotide repeat expansion in the 5′-untranslated region (UTR) and subsequent translational silencing of the fragile x mental retardation-1 (FMR1) gene. FMRP, which is proposed to be involved in the translational regulation of specific neuronal messenger RNA (mRNA) targets, contains an arginine-glycine-glycine (RGG) box RNA binding domain that has been shown to bind with high affinity to G-quadruplex forming mRNA structures. FMRP undergoes alternative splicing, and the binding of FMRP to a proposed G-quadruplex structure in the coding region of its mRNA (named FBS) has been proposed to affect the mRNA splicing events at exon 15. In this study, we used biophysical methods to directly demonstrate the folding of FMR1 FBS into a secondary structure that contains two specific G-quadruplexes and analyze its interactions with several FMRP isoforms. Our results show that minor splice isoforms, ISO2 and ISO3, created by the usage of the second and third acceptor sites at exon 15, bind with higher affinity to FBS than FMRP ISO1, which is created by the usage of the first acceptor site. FMRP ISO2 and ISO3 cannot undergo phosphorylation, an FMRP post-translational modification shown to modulate the protein translation regulation. Thus, their expression has to be tightly regulated, and this might be accomplished by a feedback mechanism involving the FMRP interactions with the G-quadruplex structures formed within FMR1 mRNA.
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2. Engelhardt CR, Mazurek MO, Sohl K. {{Media Use and Sleep Among Boys With Autism Spectrum Disorder, ADHD, or Typical Development}}. {Pediatrics};2013 (Nov 18)
OBJECTIVE:The current study examined the relationships between media use (television, computer, and video games) and sleep among boys with autism spectrum disorder (ASD) compared with those with attention-deficit/hyperactivity disorder (ADHD) or with typical development (TD).METHODS:Participants included parents of boys with ASD (n = 49), ADHD (n = 38), or TD (n = 41) (ages 8-17 years). Questionnaires assessed daily hours of media use, bedroom access to media, and average sleep hours per night.RESULTS:Bedroom media access was associated with less time spent sleeping per night, irrespective of diagnostic group. Bedroom access to a television or a computer was more strongly associated with reduced sleep among boys with ASD compared with boys with ADHD or TD. Multivariate models showed that, in addition to bedroom access, the amount of time spent playing video games was uniquely associated with less sleep among boys with ASD. In the ASD group only, the relationship between bedroom access to video games and reduced sleep was mediated by hours of video game play.CONCLUSIONS:The current results suggest that media-related variables may be an important consideration in understanding sleep disturbances in children with ASD. Further research is needed to better characterize the processes by which media use may affect sleep among individuals with ASD. Overall, the current findings suggest that screen-based media time and bedroom media access should be routinely assessed and may be important intervention targets when addressing sleep problems in children with ASD.
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3. Sesarini CV, Costa L, Naymark M, Granana N, Cajal AR, Garcia Coto M, Pallia RC, Argibay PF. {{Evidence for Interaction Between Markers in GABA(A) Receptor Subunit Genes in an Argentinean Autism Spectrum Disorder Population}}. {Autism Res};2013 (Nov 18)
Autism spectrum disorders (ASD) can be conceptualized as a genetic dysfunction that disrupts development and function of brain circuits mediating social cognition and language. At least some forms of ASD may be associated with high level of excitation in neural circuits, and gamma-aminobutyric acid (GABA) has been implicated in its etiology. Single-nucleotide polymorphisms (SNP) located within the GABA receptor (GABAR) subunit genes GABRA1, GABRG2, GABRB3, and GABRD were screened. A hundred and thirty-six Argentinean ASD patients and 150 controls were studied, and the contribution of the SNPs in the etiology of ASD was evaluated independently and/or through gene-gene interaction using multifactor dimensionality reduction (MDR) method. From the 18 SNP studied, 11 were not present in our Argentinean population (patients and controls) and 1 SNP had minor allele frequency < 0.1%. For the remaining six SNPs, none provided statistical significant association with ASD when considering allelic or genotypic frequencies. Non-significant association with ASD was found for the haplotype analysis. MDR identified evidence for synergy between markers in GABRB3 (chromosome 15) and GABRD (chromosome 1), suggesting potential gene-gene interaction across chromosomes associated with increased risk for autism (testing balanced accuracy: 0.6081 and cross-validation consistency: 10/10, P < 0.001). Considering our Argentinean ASD sample, it can be inferred that GABRB3 would be involved in the etiology of autism through interaction with GABRD. These results support the hypothesis that GABAR subunit genes are involved in autism, most likely via complex gene-gene interactions. Autism Res 2013, : -. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
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4. Taylor LJ, Maybery MT, Whitehouse AJ. {{Moving beyond behaviour-only assessment: Incorporating biomarkers to improve the early detection and diagnosis of autism spectrum disorders}}. {Int J Speech Lang Pathol};2013 (Nov 18)
This paper presents a response to the Camarata (2014) lead article regarding the accuracy and effectiveness of early identification and early intervention for young children with autism spectrum disorders (ASD). While Caramata focused heavily on the challenges of behavioural screening for ASD, we believe that he has overlooked the potential that the identification of ASD biomarkers may have for the early detection of the disorder. We propose that the discovery of biomarkers, particularly those that may be used in conjunction with behavioural screening, may provide an important next step in reliably detecting and accurately diagnosing ASD in the early years. This would have important clinical implications in terms of providing early intervention, which may alter the developmental path for the child.
