The Drosophila drop-dead (drd) mutant undergoes massive brain degeneration, resulting in sudden death. drd encodes a multi-pass membrane protein possessing nose resistant to fluoxetine (NRF) and putative acyltransferase domains. However, the etiology of brain degeneration that occurs in drd mutant flies is still poorly understood. Herein, we show that drd neurodegeneration may be because of an oxygen deficit in the brain. We found that DRD protein is selectively expressed in cells secreting cuticular and eggshell layers. These layers exhibit blue fluorescence upon UV excitation, which is reduced in drd flies. The drd tracheal air sacs lacking blue fluorescence collapse, which likely contributes to hypoxia. Consistently, genes induced in hypoxia are up-regulated in drd flies. Feeding of anti-reactive oxygen species agents partially rescue the drd from sudden death. We propose that drd flies can provide a noninvasive animal model for hypoxia-induced cell death.
Inhibitor development is the most significant complication in the therapy of haemophilia A (HA) patients. In spite of many studies, not much is known regarding the mechanism underlying inhibitor development. To understand the mechanism, we analysed profiles of differentially expressed genes (DEGs) between inhibitor and non-inhibitor HA via a microarray technique. Twenty unrelated Korean HAs were studied: 11 were non-inhibitor and nine were HA with inhibitor (≥5 BU mL(-1)). Microarray analysis was conducted using a Human Ref-8 expression Beadchip system (Illumina) and the data were analysed using Beadstudio software. We identified 545 DEGs in inhibitor HA as compared with the non-inhibitor patients; 384 genes were up-regulated and 161 genes were down-regulated. Among them, 75 genes whose expressions were altered by at least two-fold (>+2 or <-2) were selected and classified via the PANTHER classification method. The expressions of signal transduction and immunity-related genes differed significantly in the two groups. For validation of the DEGs, semi-quantitative RT-PCR (semi-qRT-PCR) was conducted with the six selected DEGs. The results corresponded to the microarray data, with the exception of one gene. We also examined the expression of the genes associated with the antigen presentation process via real-time PCR. The average levels of IL10, CTLA4 and TNFα slightly reduced, whereas that of IFNγ increased in the inhibitor HA group. We are currently unable to explain whether this phenomenon is a function of the inhibitor-inducing factor or is an epiphenomenon of antibody production. Nevertheless, our results provide a possible explanation for inhibitor development.
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