Associations between autistic traits and fractional anisotropy values in white matter tracts in a nonclinical sample of young adults.

Whereas a number of studies have examined relationships among brain activity, social cognitive skills, and autistic traits, fewer studies have evaluated whether structural connections among brain regions relate to these traits and skills. Uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF) are white matter tracts that may underpin the behavioral expression of these skills because they connect regions within or provide sensory information to brain areas implicated in social cognition, and structural differences in these tracts have been associated with autistic traits. We examined relationships among self-reported autistic traits, mentalizing, and water diffusivity in UF and ILF in a nonclinical sample of 24 young adults (mean age = 21.92 years, SD = 4.72 years; 15 women). We measured autistic traits using the Autism-Spectrum Quotient, and we measured mentalizing using the Dynamic Interactive Shapes Clips task. We used Tract-Based Spatial Statistics and randomize to examine relationships among fractional anisotropy (FA) values in bilateral ILF and UF, age, cognitive abilities, autistic traits, and mentalizing. Autistic traits were positively related to FA values in left ILF. No other relationships between FA values and other variables were significant. Results suggest that left ILF may be involved in the expression of autistic traits in individuals without clinical diagnoses.

Redox-sensitive DNA binding by homodimeric Methanosarcina acetivorans MsvR is modulated by cysteine residues.

BACKGROUND: Methanoarchaea are among the strictest known anaerobes, yet they can survive exposure to oxygen. The mechanisms by which they sense and respond to oxidizing conditions are unknown. MsvR is a transcription regulatory protein unique to the methanoarchaea. Initially identified and characterized in the methanogen Methanothermobacter thermautotrophicus (Mth), MthMsvR displays differential DNA binding under either oxidizing or reducing conditions. Since MthMsvR regulates a potential oxidative stress operon in M. thermautotrophicus, it was hypothesized that the MsvR family of proteins were redox-sensitive transcription regulators. RESULTS: An MsvR homologue from the methanogen Methanosarcina acetivorans, MaMsvR, was overexpressed and purified. The two MsvR proteins bound the same DNA sequence motif found upstream of all known MsvR encoding genes, but unlike MthMsvR, MaMsvR did not bind the promoters of select genes involved in the oxidative stress response. Unlike MthMsvR that bound DNA under both non-reducing and reducing conditions, MaMsvR bound DNA only under reducing conditions. MaMsvR appeared as a dimer in gel filtration chromatography analysis and site-directed mutagenesis suggested that conserved cysteine residues within the V4R domain were involved in conformational rearrangements that impact DNA binding. CONCLUSIONS: Results presented herein suggest that homodimeric MaMsvR acts as a transcriptional repressor by binding Ma PmsvR under non-reducing conditions. Changing redox conditions promote conformational changes that abrogate binding to Ma PmsvR which likely leads to de-repression.