NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice.

The interleukin-1 family members, IL-1ß and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1ß processing in myeloid cells have been defined, those involved in IL-18 processing, particularly in non-myeloid cells, are still not well understood. Here we report that the host defence molecule NOD1 regulates IL-18 processing in mouse epithelial cells in response to the mucosal pathogen, Helicobacter pylori. Specifically, NOD1 in epithelial cells mediates IL-18 processing and maturation via interactions with caspase-1, instead of the canonical inflammasome pathway involving RIPK2, NF-κB, NLRP3 and ASC. NOD1 activation and IL-18 then help maintain epithelial homoeostasis to mediate protection against pre-neoplastic changes induced by gastric H. pylori infection in vivo. Our findings thus demonstrate a function for NOD1 in epithelial cell production of bioactive IL-18 and protection against H. pylori-induced pathology.

Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation.

The repeated use of psychostimulants in humans has been associated with progressive enhancement of anxiety, panic attacks, and eventually paranoid psychosis. The appearance of such behaviors has been termed behavioral sensitization, which forms part of the basic pathological mechanisms involved in drug addiction. Psychostimulants act via a circuit involving the ventral tegmental area (VTA), prefrontal cortex (PFC), and nucleus accumbens. The PFC sends glutamatergic projections that activate dopaminergic neurons in the VTA. These projections provide an extremely important excitatory drive necessary for the development of sensitization. The effects of cocaine administration on the response of dopaminergic VTA cells to activation of the PFC have not been reported. Here the effects of acute cocaine administration on VTA cell response to PFC stimulation are examined. Statistical analysis of the changes in spontaneous activity and evoked response revealed a significant decrease in spontaneous activity at 1.0 mg/kg i.v. after cocaine treatment compared to baseline levels. The net effect was an increase in signal-to-noise ratio. Treatment with MK-801 at a dose of 2 mg/kg showed that the excitatory response was, at least partially, NMDA-mediated. Prazosin pretreatment (0.5 mg/kg i.p.) did not prevent a significant decrease in spontaneous activity brought about by cocaine (15 mg/kg, i.p.). Nonetheless, prazosin alone induced a significant decrease in the response to PFC stimulation when compared to baseline. In addition, iontophoretic application of norepinephrine (NE) onto VTA cells revealed that NE potentiated (19.2%), enhanced (26.9%), or suppressed (46.2%) the glutamate-evoked response in VTA cells. The results suggest that a possible role of cocaine in the process of sensitization might be to amplify the PFC-induced excitation at the VTA. Since the iontophoretic release of NE in almost half of the sampled cells produced similar effects to those of cocaine it may suggest a possible NE-mediated mechanism for cocaine actions.

Enhancement of the CDC ovitrap with hay infusions for daily monitoring of Aedes aegypti populations.

An ovitrap containing hay infusion and a second ovitrap adjacent to it containing a 10% dilution of the infusion in tap water together yielded 8 times more Aedes aegypti eggs than single CDC ovitraps containing tap water. These "enhanced pairs" were significantly more attractive than pairs with other combinations of infusion, water or methyl propionate, and have proven useful for daily monitoring of Ae. aegypti populations. Our results shed light on the oviposition behavior of Ae. aegypti in the field.