An integrated molecular biology and computational approach to CYP1A1 expression in human brain

The cytochromes P450 comprise a superfamily of heme-containing mono-oxygenases. These enzymes metabolize numerous xenobiotics, but also play a role in metabolism of endogenous compounds. The P450 1A1 enzyme generally metabolizes polycyclic aromatic hydrocarbons, and its expression can be induced by aryl hydrocarbon receptor (AhR) activation. CYP1A1 is an exception to the generality that the majority of CYPs demonstrate highest expression in liver; CYP1Al is present in numerous extrahepatic tissues, including brain. This P450 has been observed in two forms, wildtype (WT) and brain variant (BV), arising from alternatively spliced mRNA transcripts. The CYP1A1 BV mRNA presented an exon deletion and was detected in human brain but not liver tissue of the same individuals. ^ Quantitative PCR analyses were performed to determine CYP1A1 WT and BV transcript expression levels in normal, bipolar disorder or schizophrenic groups. In our samples, we show that CYP1A1 BV mRNA, when present, is found alongside the full-length form. Furthermore, we demonstrate a significant decrease in expression of CYP1A1 in patients with bipolar disorder or schizophrenia. The expression level was not influenced by post-mortem interval, tissue pH, age, tobacco use, or lifetime antipsychotic medication load. ^ There is no indication of increased brain CYP1A1 expression in normal smokers versus non-smokers in these samples. We observed slightly increased CYP1A1 expression only in bipolar and schizophrenic smokers versus non-smokers. This may be indicative of complex interactions between neuronal chemical environments and AhR-mediated CYP1A1 induction in brain. ^ Structural homology modeling demonstrated that P450 1A1 BV has several alterations to positions/orientations of substrate recognition site residues compared to the WT isoform. Automated substrate docking was employed to investigate the potential binding of neurological signaling molecules and neurotropic drugs, as well as to differentiate specificities of the two P450 1A1 isoforms. We consistently observed that the BV isoform produced energetically favorable substrate dockings in orientations not observed for the same substrate in the WT isoform. These results demonstrated that structural differences, namely an expanded substrate access channel and active site, confer greater capacity for unique compound docking positions suggesting a metabolic profile distinct from the wildtype form for these test compounds. ^

Integrated pest management in multi-story public housing for the elderly in Houston, Texas

Integrated pest management is a viable alternative to traditional pest control methods. A paired sample design was utilized to measure the effect of IPM education on the number of cockroaches in a 200 unit, seven story public housing building for the elderly in Houston, TX. Glue traps were placed in 71 randomly selected apartments (5traps/unit) and left in place for two nights. Baseline cockroach counts were shared with the property manager, maintenance/janitorial staff, service coordinator, pest control professional and tenant representatives at the end of a one day “Integrated Pest Management in Multi-Family Housing” training course.^ There was a significant decrease in the average number of cockroaches after IPM education and implementation of IPM principles (P < 0.0003). Positive changes in behavior by members of the IPM team and changes in the housing authority operational plan were also found. Paired t-tests comparing the difference between mean cockroach counts at baseline and follow-up by location within the apartment all demonstrated a significant decrease in the number of cockroaches.^ Results supported the premise that IPM education and the implementation of IPM principles are effective measures to change pest control behaviors and control cockroaches. Cockroach infestations in multi-story housing are not solely determined by the actions of individual tenants. The actions of other residents, property managers and pest control professionals are also important factors in pest control.^ Findings support the implementation of IPM education and the adoption of IPM practices by public housing authorities. This study adds to existing evidence that clear communication of policies, a team approach and a commitment to ongoing inspection and monitoring of pests combined with corrective action to eliminate food, water and harborage and the judicial use of low risk pesticides have the potential to improve the living conditions of elderly residents living in public housing.^