1. Bahrami F, Movahedi A, Marandi SM, Sorensen C. {{The Effect of Karate Techniques Training on Communication Deficit of Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2015 (Nov 17)
This investigation examined the long term effect of Karate techniques training on communication of children with autism spectrum disorders (ASD). Thirty school aged children with ASD were randomly assigned to an exercise (n = 15) or a control group (n = 15). Participants in the exercise group were engaged in 14 weeks of Karate techniques training. Communication deficit at baseline, post-intervention (week 14), and at 1 month follow up were evaluated. Exercise group showed significant reduction in communication deficit compared to control group. Moreover, reduction in communication deficit in the exercise group at one month follow up remained unchanged compared to post-intervention time. We concluded that teaching Karate techniques to children with ASD leads to significant reduction in their communication deficit.
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2. He X, Thacker S, Romigh T, Yu Q, Frazier TW, Jr., Eng C. {{Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits}}. {Mol Autism};2015;6:63.
BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impairment in social communication/interaction and inflexible/repetitive behavior. Several lines of evidence support genetic factors as a predominant cause of ASD. Among those autism susceptibility genes that have been identified, the PTEN tumor suppressor gene, initially identified as predisposing to Cowden heritable cancer syndrome, was found to be mutated in a subset of ASD patients with extreme macrocephaly. However, the ASD-relevant molecular mechanism mediating the effect of PTEN mutations remains elusive. METHODS: We developed a Pten knock-in murine model to study the effects of Pten germline mutations, specifically altering subcellular localization, in ASD. Proteins were isolated from the hemispheres of the male littermates, and Western blots were performed to determine protein expression levels of tyrosine hydroxylase (TH). Immunohistochemical stains were carried out to validate the localization of TH and dopamine D2 receptors (D2R). PC12 cells ectopically expressing either wild-type or missense mutant PTEN were then compared for the differences in TH expression. RESULTS: Mice carrying Pten mutations have high TH and D2R in the striatum and prefrontal cortex. They also have increased phosphorylation of cAMP response element-binding protein (CREB) and TH. Mechanistically, PTEN downregulates TH production in PC12 cells via inhibiting the phosphoinositide 3-kinase (PI3K)/CREB signaling pathway, while PTEN reduces TH phosphorylation via suppressing MAPK pathway. Unlike wild-type PTEN but similar to the mouse knock-in mutant Pten, three naturally occurring missense mutations of PTEN that we previously identified in ASD patients, H93R, F241S, and D252G, were not able to suppress TH when overexpressed in PC12 cells. In addition, two other PTEN missense mutations, C124S (pan phosphatase dead) and G129E (lipid phosphatase dead), failed to suppress TH when ectopically expressed in PC12 cells. CONCLUSIONS: Our data reveal a non-canonical PTEN-TH pathway in the brain that may work as a core regulator of dopamine signaling, which when dysfunctional is pathogenic in ASD.
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3. Jaworski JL, Eigsti IM. {{Low-level visual attention and its relation to joint attention in autism spectrum disorder}}. {Child Neuropsychol};2015 (Nov 15):1-16.
Visual attention is integral to social interaction and is a critical building block for development in other domains (e.g., language). Furthermore, atypical attention (especially joint attention) is one of the earliest markers of autism spectrum disorder (ASD). The current study assesses low-level visual attention and its relation to social attentional processing in youth with ASD and typically developing (TD) youth, aged 7 to 18 years. The findings indicate difficulty overriding incorrect attentional cues in ASD, particularly with non-social (arrow) cues relative to social (face) cues. The findings also show reduced competition in ASD from cues that remain on-screen. Furthermore, social attention, autism severity, and age were all predictors of competing cue processing. The results suggest that individuals with ASD may be biased towards speeded rather than accurate responding, and further, that reduced engagement with visual information may impede responses to visual attentional cues. Once attention is engaged, individuals with ASD appear to interpret directional cues as meaningful. These findings from a controlled, experimental paradigm were mirrored in results from an ecologically valid measure of social attention. Attentional difficulties may be exacerbated during the complex and dynamic experience of actual social interaction. Implications for intervention are discussed.
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4. Khanlou N, Mustafa N, Vazquez LM, Haque N, Yoshida K. {{Stressors and Barriers to Services for Immigrant Fathers Raising Children with Developmental Disabilities}}. {Int J Ment Health Addict};2015;13(6):659-674.
This narrative review examines research on the experiences of immigrant fathers raising children with developmental disabilities, and considers the findings within the Canadian context. Applying Green, Johnson & Adams’ (Journal of Chiropractic Medicine, 5(3), 101-117, 2006) methodology, a step-by-step process was followed to conduct the review. Four databases (PsychINFO, PubMed, CINAHL and Sociological Abstracts) were used for the search. A total of 39 articles were found to be relevant after applying the inclusion/exclusion criteria. Also 20 articles from published reference lists and peer-reviewed journal articles, located through Google Scholar, complimented the initial search. Along with House’s (1981) four dimensions of social support, an intersectional approach underpinned the analysis of findings. Four themes were identified which included: economic challenges, social influences, cultural influences, and the changing gender roles of fathers. Stressors and barriers to accessing health services in the post-migration setting were examined. Based on the review’s findings, the paper recommends 1) addressing income inequality, 2) improving access to health care, social and developmental services, 3) improving cultural-sensitivity of health care, social and developmental services, and 4) increasing participation of fathers. Overall, a more systemic understanding of immigrant fathers’ experiences is called for, taking into account their multiple social locations.
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5. Novak SM, Joardar A, Gregorio CC, Zarnescu DC. {{Regulation of Heart Rate in Drosophila via Fragile X Mental Retardation Protein}}. {PLoS One};2015;10(11):e0142836.
RNA binding proteins play a pivotal role in post-transcriptional gene expression regulation, however little is understood about their role in cardiac function. The Fragile X (FraX) family of RNA binding proteins is most commonly studied in the context of neurological disorders, as mutations in Fragile X Mental Retardation 1 (FMR1) are the leading cause of inherited mental retardation. More recently, alterations in the levels of Fragile X Related 1 protein, FXR1, the predominant FraX member expressed in vertebrate striated muscle, have been linked to structural and functional defects in mice and zebrafish models. FraX proteins are established regulators of translation and are known to regulate specific targets in different tissues. To decipher the direct role of FraX proteins in the heart in vivo, we turned to Drosophila, which harbors a sole, functionally conserved and ubiquitously expressed FraX protein, dFmr1. Using classical loss of function alleles as well as muscle specific RNAi knockdown, we show that Drosophila FMRP, dFmr1, is required for proper heart rate during development. Functional analyses in the context of cardiac-specific dFmr1 knockdown by RNAi demonstrate that dFmr1 is required cell autonomously in cardiac cells for regulating heart rate. Interestingly, these functional defects are not accompanied by any obvious structural abnormalities, suggesting that dFmr1 may regulate a different repertoire of targets in Drosophila than in vertebrates. Taken together, our findings support the hypothesis that dFmr1 protein is essential for proper cardiac function and establish the fly as a new model for studying the role(s) of FraX proteins in the heart.
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6. Shang L, Henderson LB, Cho MT, Petrey DS, Fong CT, Haude KM, Shur N, Lundberg J, Hauser N, Carmichael J, Innis J, Schuette J, Wu YW, Asaikar S, Pearson M, Folk L, Retterer K, Monaghan KG, Chung WK. {{De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism}}. {Neurogenetics};2015 (Nov 17)
Protein phosphatase 2A (PP2A) is a heterotrimeric protein serine/threonine phosphatase and is involved in a broad range of cellular processes. PPP2R5D is a regulatory B subunit of PP2A and plays an important role in regulating key neuronal and developmental regulation processes such as PI3K/AKT and glycogen synthase kinase 3 beta (GSK3beta)-mediated cell growth, chromatin remodeling, and gene transcriptional regulation. Using whole-exome sequencing (WES), we identified four de novo variants in PPP2R5D in a total of seven unrelated individuals with intellectual disability (ID) and other shared clinical characteristics, including autism spectrum disorder, macrocephaly, hypotonia, seizures, and dysmorphic features. Among the four variants, two have been previously reported and two are novel. All four amino acids are highly conserved among the PP2A subunit family, and all change a negatively charged acidic glutamic acid (E) to a positively charged basic lysine (K) and are predicted to disrupt the PP2A subunit binding and impair the dephosphorylation capacity. Our data provides further support for PPP2R5D as a genetic cause of ID.
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7. Tavassoli T, Bellesheim K, Tommerdahl M, Holden JM, Kolevzon A, Buxbaum JD. {{Altered tactile processing in children with autism spectrum disorder}}. {Autism Res};2015 (Nov 16)
Although tactile reactivity issues are commonly reported in children with autism spectrum disorder (ASD), the underlying mechanisms are poorly understood. Less feed-forward inhibition has been proposed as a potential mechanism for some symptoms of ASD. We tested static and dynamic tactile thresholds as a behavioral proxy of feed-forward inhibition in 42 children (21 children with ASD and 21 typically developing [TD] children). Subthreshold conditioning typically raises the dynamic detection threshold, thus comparison of the dynamic to the static threshold generates a metric that predicts gamma-aminobutyric acid (GABA) mediated feed-forward inhibition. Children with ASD had marginally higher static thresholds and a significantly lower ratio between thresholds as compared with TD children. The lower ratio, only seen in children with ASD, might be indicative of less inhibition. Static thresholds were correlated with autism spectrum quotient scores, indicating the higher the tactile threshold, the more ASD traits. The amount of feed-forward inhibition (ratio between dynamic/static) was negatively correlated with autism diagnostic observation schedule repetitive behavior scores, meaning the less inhibition the more ASD symptoms. In summary, children with ASD showed altered tactile processing compared with TD children; thus measuring static and dynamic thresholds could be a potential biomarker for ASD and might be useful for prediction of treatment response with therapeutics, including those that target the GABAergic system. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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8. Tong XJ, Hu Z, Liu Y, Anderson D, Kaplan JM. {{A network of autism linked genes stabilizes two pools of synaptic GABAA receptors}}. {Elife};2015;4
Changing receptor abundance at synapses is an important mechanism for regulating synaptic strength. Synapses contain two pools of receptors, immobilized and diffusing receptors, both of which are confined to post-synaptic elements. Here we show that immobile and diffusing GABAA receptors are stabilized by distinct synaptic scaffolds at C. elegans neuromuscular junctions. Immobilized GABAA receptors are stabilized by binding to FRM-3/EPB4.1 and LIN-2A/CASK. Diffusing GABAA receptors are stabilized by the synaptic adhesion molecules Neurexin and Neuroligin. Inhibitory post-synaptic currents are eliminated in double mutants lacking both scaffolds. Neurexin, Neuroligin, and CASK mutations are all linked to Autism Spectrum Disorders (ASD). Our results suggest that these mutations may directly alter inhibitory transmission, which could contribute to the developmental and cognitive deficits observed in ASD.
