71 research outputs found
The development of novel LTA4H modulators to selectively target LTB4 generation
The pro-inflammatory mediator leukotriene B4 (LTB4) is implicated in the pathologies of an array of diseases and thus represents an attractive therapeutic target. The enzyme leukotriene A4 hydrolase (LTA4H) catalyses the distal step in LTB4 synthesis and hence inhibitors of this enzyme have been actively pursued. Despite potent LTA4H inhibitors entering clinical trials all have failed to show efficacy. We recently identified a secondary anti-inflammatory role for LTA4H in degrading the neutrophil chemoattractant Pro-Gly-Pro (PGP) and rationalized that the failure of conventional LTA4H inhibitors may be that they inadvertently prevented PGP degradation. We demonstrate that these inhibitors do indeed fail to discriminate between the dual activities of LTA4H, and enable PGP accumulation in mice. Accordingly, we have developed novel compounds that potently inhibit LTB4 generation whilst leaving PGP degradation unperturbed. These novel compounds could represent a safer and superior class of LTA4H inhibitors for translation into the clinic
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Trapping Dasinuera mali (Diptera: Cecidomyiidae) in apples
The midge Dasineura mali (Kieffer) (Diptera: Cecidomyiidae) is a significant pest of apples (Malus spp.), and the recent identification of the female sex pheromone is enabling new direct control tactics to be considered. Direct control using male suppression will require knowledge of the frequency of multiple mating, dispersal and colonization rates, and the efficiency of male removal. Males were able to mate up to five times, with a mean of 2.7 times when presented in a 10 female-to-1 male group, designed to simulate male suppression. Male catch in response to the pheromone loading was curvilinear over 4 orders of magnitude from 3 microg to 30 mg on rubber septa. Trapping using a high-dose pheromone lure was combined with oil-based traps similar to the inexpensive New Zealand "Lynfield trap" used for tephritid surveillance, to test male suppression in young orchard blocks at 500 traps per ha. Monitoring traps indicated 96% lower catch in the treated plots compared with control plots, over 137 d. However, a lack of shoot tip infestation in both treated and untreated plots indicated limited colonization and prevented an assessment of potential population suppression. Furthermore, a contribution to these results from communication disruption cannot be ruled out. Replicated transects of frequency of infested shoots from a mature orchard across the adjacent young block confirmed that colonization by ovipositing females was essentially limited to the first 30 m
Body size and fitness relation in male and female Diaeretiella rapae
A strong relationship exists between body size and fitness in parasitoids. However, it is unclear whether the relationship is symmetric or asymmetric in males and females. The present study investigated the body size and fitness relationship in Diaeretiella rapae emerged from small and large nymphs of cabbage aphid Brevicoryne brassicae. A positive relationship existed between the size of the aphid host and growth of parasitoid larva developing in it. The fitness gain in males and females was not proportionate to their body size gain. Females mated with larger males produced 10 % more female offspring than females mated with smaller males. However, females that developed in large hosts produced 62 % more offspring (total male and female) than the females emerged from smaller hosts. The findings suggest that the number of offspring and the progeny sex ratio were affected by the body size of both male and female D. rapae
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