miRNAome analysis of the mammalian neuronal nicotinic acetylcholine receptor gene family.

Nicotine binds to and activates a family of ligand-gated ion channels, neuronal nicotinic acetylcholine receptors (nAChRs). Chronic nicotine exposure alters the expression of various nAChR subtypes, which likely contributes to nicotine dependence; however, the underlying mechanisms regulating these changes remain unclear. A growing body of evidence indicates that microRNAs (miRNAs) may be involved in nAChR regulation. Using bioinformatics, miRNA library screening, site-directed mutagenesis, and gene expression analysis, we have identified a limited number of miRNAs that functionally interact with the 3'-untranslated regions (3' UTRs) of mammalian neuronal nAChR subunit genes. In silico analyses revealed specific, evolutionarily conserved sites within the 3' UTRs through which the miRNAs regulate gene expression. Mutating these sites disrupted miRNA regulation confirming the in silico predictions. In addition, the miRNAs that target nAChR 3' UTRs are expressed in mouse brain and are regulated by chronic nicotine exposure. Furthermore, we show that expression of one of these miRNAs, miR-542-3p, is modulated by nicotine within the mesocorticolimbic reward pathway. Importantly, overexpression of miR-542-3p led to a decrease in the protein levels of its target, the nAChR ß2 subunit. Bioinformatic analysis suggests that a number of the miRNAs play a general role in regulating cholinergic signaling. Our results provide evidence for a novel mode of nicotine-mediated regulation of the mammalian nAChR gene family.

Anti-social networking: crowdsourcing and the cyber defence of national critical infrastructures.

We identify four roles that social networking plays in the 'attribution problem', which obscures whether or not cyber-attacks were state-sponsored. First, social networks motivate individuals to participate in Distributed Denial of Service attacks by providing malware and identifying potential targets. Second, attackers use an individual's social network to focus attacks, through spear phishing. Recipients are more likely to open infected attachments when they come from a trusted source. Third, social networking infrastructures create disposable architectures to coordinate attacks through command and control servers. The ubiquitous nature of these architectures makes it difficult to determine who owns and operates the servers. Finally, governments recruit anti-social criminal networks to launch attacks on third-party infrastructures using botnets. The closing sections identify a roadmap to increase resilience against the 'dark side' of social networking.