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Skeletal muscle fibers are infected efficiently by adenoviral vectors only in neonatal animals. This lack of tropism for mature skeletal muscle may be partly due to inefficient binding of adenoviral particles to the cell surface. We evaluated in developing mouse muscle the expression levels of two high-affinity receptors for adenovirus, MHC class I and the coxsackie and adenovirus receptor (CAR). The moderate levels of MHC class I transcripts that were detected in quadriceps, gastrocnemius, and heart muscle did not vary between postnatal day 3 and day 60 adult tissue. A low level of CAR expression was detected on postnatal day 3 in quadriceps and gastrocnemius muscles, but CAR expression was barely detectable in adult skeletal muscle even by reverse transcriptase-polymerase chain reaction. In contrast, CAR transcripts were moderately abundant at all stages of heart muscle development. Ectopic expression of CAR in C2C12 mouse myoblast cells increased their transducibility by adenovirus at all multiplicities of infection (MOIs) tested as measured by lacZ reporter gene activity following AVCMVlacZ infection, with an 80-fold difference between CAR-expressing cells and control C2C12 cells at an MOI of 50. Primary myoblasts ectopically expressing CAR were injected into muscles of syngeneic hosts; following incorporation of the exogenous myoblasts into host myofibers, an increased transducibility of adult muscle fibers by AVCMVlacZ was observed in the host. Expression of the lacZ reporter gene in host myofibers coincided with CAR immunoreactivity. Furthermore, sarcolemmal CAR expression was markedly increased in regenerating muscle fibers of the dystrophic mdx mouse, fibers that are susceptible to adenovirus transduction. These analyses show that CAR expression by skeletal muscle correlates with its susceptibility to adenovirus transduction, and that forced CAR expression in mature myofibers dramatically increases their susceptibility to adenovirus transduction.

Many high-prevalence neurological disorders involve dysfunctions of oculomotor control and attention, including attention deficit hyperactivity disorder (ADHD), fetal alcohol spectrum disorder (FASD), and Parkinson's disease (PD). Previous studies have examined these deficits with clinical neurological evaluation, structured behavioral tasks, and neuroimaging. Yet, time and monetary costs prevent deploying these evaluations to large at-risk populations, which is critically important for earlier detection and better treatment. We devised a high-throughput, low-cost method where participants simply watched television while we recorded their eye movements. We combined eye-tracking data from patients and controls with a computational model of visual attention to extract 224 quantitative features. Using machine learning in a workflow inspired by microarray analysis, we identified critical features that differentiate patients from control subjects. With eye movement traces recorded from only 15 min of videos, we classified PD versus age-matched controls with 89.6 % accuracy (chance 63.2 %), and ADHD versus FASD versus control children with 77.3 % accuracy (chance 40.4 %). Our technique provides new quantitative insights into which aspects of attention and gaze control are affected by specific disorders. There is considerable promise in using this approach as a potential screening tool that is easily deployed, low-cost, and high-throughput for clinical disorders, especially in young children and elderly populations who may be less compliant to traditional evaluation tests.

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Objective: To assess performance on two nondeclarative (implicit) memory tasks of Parkinson disease (PD) patients without dementia in the earlier or later stages of the disease (Hoehn and Yahr Scale scores of 1-2.5 or 3-4, respectively).Background: Different subtypes of nondeclarative memory appear to depend on different components of frontostriatal circuitry. Performance on a probabilistic classification learning (PCL) task was impaired by striatal damage (eg, in PD or Huntington disease) but not by circumscribed frontal lobe damage. On the other hand, performance on the Iowa Gambling Task (IGT) was impaired by damage to the prefrontal cortex.Method and Results: On the PCL, the learning of the control (age-and education-matched) group (n = 19) and the early PD group (n = 16) was comparable with each other, and both groups showed better performance than the later PD group (n = 16). On the IGT, the control group learned better than both of the PD groups. The control and early PD groups were similar on measures from the Wisconsin Card Sorting Test, Stroop Test, Mini-Mental State Examination, and Beck Depression Inventory II. Conclusions:The PCL and IGT tasks appear to rely on different parts of the frontostriatal circuitry in patients with early PD. The current finding that IGT performance was impaired in early PD implies ventromedial prefrontal cortical dysfunction early in the disease.