Re-localization of Cellular Protein SRp20 during Poliovirus Infection: Bridging a Viral IRES to the Host Cell Translation Apparatus

Poliovirus IRES-mediated translation requires the functions of certain canonical as well as non-canonical factors for the recruitment of ribosomes to the viral RNA. The interaction of cellular proteins PCBP2 and SRp20 in extracts from poliovirus-infected cells has been previously described, and these two proteins were shown to function synergistically in viral translation. To further define the mechanism of ribosome recruitment for the initiation of poliovirus IRES-dependent translation, we focused on the role of the interaction between cellular proteins PCBP2 and SRp20. Work described here demonstrates that SRp20 dramatically re-localizes from the nucleus to the cytoplasm of poliovirus-infected neuroblastoma cells during the course of infection. Importantly, SRp20 partially co-localizes with PCBP2 in the cytoplasm of infected cells, corroborating our previous in vitro interaction data. In addition, the data presented implicate the presence of these two proteins in viral translation initiation complexes. We show that in extracts from poliovirus-infected cells, SRp20 is associated with PCBP2 bound to poliovirus RNA, indicating that this interaction occurs on the viral RNA. Finally, we generated a mutated version of SRp20 lacking the RNA recognition motif (SRp20ΔRRM) and found that this protein is localized similar to the full length SRp20, and also partially co-localizes with PCBP2 during poliovirus infection. Expression of this mutated version of SRp20 results in a ∼100 fold decrease in virus yield for poliovirus when compared to expression of wild type SRp20, possibly via a dominant negative effect. Taken together, these results are consistent with a model in which SRp20 interacts with PCBP2 bound to the viral RNA, and this interaction functions to recruit ribosomes to the viral RNA in a direct or indirect manner, with the participation of additional protein-protein or protein-RNA interactions

Risky Decisions and Their Consequences: Neural Processing by Boys with Antisocial Substance Disorder

Adolescents with conduct and substance problems ("Antisocial Substance Disorder" (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys.We compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere.Adolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders

Cephalometric deviations present in children and adolescents with temporomandibular joint disorders

INTRODUCTION: Temporomandibular disorders (TMD) have proved to be a risk factor for developing hyperdivergent facial growth patterns. OBJECTIVE: The aims of this study were: (1) Assess differences between the cephalometric measurements in children with articular TMD and a control group, before and after mandibular growth peak according to cervical vertebral maturation; and (2) Identify a predictive model capable of differentiating patients with TMD and control group patients based on early cephalometric characteristics. METHOD: The study included children and adolescents with maximum age of 17 years, divided into experimental group (n=30) diagnosed with articular TMD-according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) for children and adolescents-subdivided according to growth stage, called pre-peak (n=17) and post-peak (n=13) and control group (n = 30), matched by gender, skeletal maturity stage of the cervical vertebrae and classification of malocclusion. Lateral cephalometric and craniofacial structures were traced and their relations divided into: Cranial base, maxilla, mandible, intermaxillary relations, vertical skeletal relations and dental relations. Differences between the means for each variable were evaluated by applying the statistical Student t test for independent samples. RESULTS: The means of the variables analyzed in the pre-peak showed no statistically significant differences. However, analysis of post-peak showed that the experimental group displayed decreased SNA and SNB and increased SN.Gn and 1.NB (p<0.05). CONCLUSION: It was possible to identify a predictive model able to differentiate patients with TMD and asymptomatic controls from early cephalometric characteristics