Differences In Brainstem Level Encoding Of Am And Fm Signals In A Rat Model For Dyslexia

Developmental dyslexia is a language learning disorder that affects a significant portion of the population. Many subjects who suffer from dyslexia show auditory processing deficits as children, some of which persist into adulthood, which impair their ability to learn one or more aspects of language. There is evidence that some types of training can correct the auditory processing deficits and bring the subject to a normal reading or speaking proficiency for their age group. One common rodent model for dyslexia is the cortical freeze lesion model. This model induces a lesion in the rat cortex similar to the microgyria present in many dyslexic brains, as well as changes to the thalamus similar to those seen in human dyslexics. The goal of this study was to determine what effect, if any, did the cortical lesions have on brainstem level responses to simple sinusoidal amplitude or frequency modulated stimuli. The study showed reduced response strengths of lesioned rats to AM signals below a 1000 Hz amplitude modulation rate. In comparing recordings done under anesthetic to recordings done under sedation, the recordings under sedation showed no significant differences between sham and dyslexic rats under a 256 Hz modulation frequency, while the rats recorded under anesthetic showed differences down to 64 Hz modulation frequency. This would suggest that the cortex influences the brainstem responses on both a permanent and transient level, as the changes in the responses are evident even when cortical activity is at a minimal level to the effect of anesthetics

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine