Parallel Rap1>RalGEF>Ral and Ras signals sculpt the C. elegans nervous system.

Ras is the most commonly mutated oncogene in humans and uses three oncogenic effectors: Raf, PI3K, and RalGEF activation of Ral. Understanding the importance of RalGEF>Ral signaling in cancer is hampered by the paucity of knowledge about their function in animal development, particularly in cell movements. We found that mutations that disrupt function of RalGEF or Ral enhance migration phenotypes of mutants for genes with established roles in cell migration. We used as a model the migration of the canal associated neurons (CANs), and validated our results in HSN cell migration, neurite guidance, and general animal locomotion. These functions of RalGEF and Ral are specific to their control of Ral signaling output rather than other published functions of these proteins. In this capacity Ral functions cell autonomously as a permissive developmental signal. In contrast, we observed Ras, the canonical activator of RalGEF>Ral signaling in cancer, to function as an instructive signal. Furthermore, we unexpectedly identified a function for the close Ras relative, Rap1, consistent with activation of RalGEF>Ral. These studies define functions of RalGEF>Ral, Rap1 and Ras signaling in morphogenetic processes that fashion the nervous system. We have also defined a model for studying how small GTPases partner with downstream effectors. Taken together, this analysis defines novel molecules and relationships in signaling networks that control cell movements during development of the nervous system.

The Utility of EEG in Attention Deficit Hyperactivity Disorder: A Replication Study.

The routine use of stimulants in pediatrics has increased dramatically over the past 3 decades and the long-term consequences have yet to be fully studied. Since 1978 there have been 7 articles identifying electroencephalogram (EEG) abnormalities, particularly epileptiform discharges in children with attention deficit hyperactivity disorder (ADHD). Many have studied the prevalence of these discharges in this population with varying results. An article published in 2011 suggests that EEG technology should be considered prior to prescribing stimulants to children diagnosed with ADHD due to a high prevalence of epileptiform discharges. The 2011 study found a higher prevalence (26%) of epileptiform discharges when using 23-hour and sleep-deprived EEGs in comparison with other methods of activation (hyperventilation or photostimulation) and conventional EEG. We sought to replicate the 2011 results using conventional EEG with the added qEEG technologies of automatic spike detection and low-resolution electromagnetic tomography analysis (LORETA) brain mapping. Our results showed 32% prevalence of epileptiform discharges, which suggests that an EEG should be considered prior to prescribing stimulant medications.