Fam83d modulates MAP kinase and AKT signaling and is induced during neurogenic skeletal muscle atrophy.

Skeletal muscle atrophy is a serious health condition that can arise due to aging, cancer, corticosteroid exposure, and denervation. Previous work comparing gene expression profiles in control and denervated muscle tissue revealed for the first time that Fam83d is expressed in skeletal muscle and is significantly induced in response to denervation. Quantitative PCR and Western blot analysis found that Fam83d is more highly expressed in proliferating myoblasts compared to differentiated myotubes. Characterization of the transcriptional regulation of Fam83d showed that ectopic expression of myogenic regulatory factors inhibits Fam83d reporter gene activity. To assess where Fam83d is localized in the cell, Fam83d was fused with green fluorescent protein, expressed in C2C12 cells, and found to localize in a punctate manner to the cytoplasm of muscle cells. To assess function, Fam83d was ectopically expressed in cultured muscle cells and markers of muscle cell differentiation, the MAP Kinase signaling pathway, and the AKT signaling pathway were analyzed. Fam83d overexpression resulted in significant repression of myosin heavy chain and myogenin expression, while phosphorylated ERK and AKT were also significantly repressed. Interestingly, inhibition of the 26S proteasome and the MAP kinase signaling pathway both resulted in stabilization of Fam83d during muscle cell differentiation. Finally, Fam83d has a putative phospholipase D-like domain that appears to be necessary for destabilizing casein kinase Iα and inhibiting ERK phosphorylation in cultured myoblasts. The discovery that Fam83d is expressed in skeletal muscle combined with the observation that Fam83d, a potential modulator of MAP kinase and AKT signaling, is induced in response to neurogenic atrophy helps further our understanding of the molecular and cellular events of skeletal muscle wasting.

Interpreting intelligence test results for children with disabilities: is global intelligence relevant?

School psychological and neuropsychological evaluations typically include intellectual and other standardized assessment tools in the identification of children with disabilities. The clinical utility of intellectual assessment in the identification and treatment of these children has been repeatedly challenged, with alternatives such as a response to intervention or global intelligence score interpretation offered to replace the long-held tradition of idiographic interpretation of intellectual factors or subtests for the purpose of differential diagnosis and individualized intervention. Replicating previous work, this study examined the structure of intellectual functioning for children diagnosed with Learning Disability (LD; n=128), Attention-Deficit/Hyperactivity Disorder (ADHD; n=71), and traumatic brain injury (TBI; n=29) using regression commonality analysis. Across groups, results provide substantial evidence for a multifactorial representation of intellectual functioning for children with LD, ADHD, or TBI, with little shared variance among factor predictors of FSIQ in each analysis. As global intellectual functioning, represented by the shared variance among all predictors, was largely absent and instead composed of several discrete elements with the requisite specificity for individual interpretation, idiographic interpretation appears to be warranted for children with disabilities.