HMOX1 Gene Promoter Alleles and High HO-1 Levels Are Associated with Severe Malaria in Gambian Children

Heme oxygenase 1 (HO-1) is an essential enzyme induced by heme and multiple stimuli associated with critical illness. In humans, polymorphisms in the HMOX1 gene promoter may influence the magnitude of HO-1 expression. In many diseases including murine malaria, HO-1 induction produces protective anti-inflammatory effects, but observations from patients suggest these may be limited to a narrow range of HO-1 induction, prompting us to investigate the role of HO-1 in malaria infection. In 307 Gambian children with either severe or uncomplicated P. falciparum malaria, we characterized the associations of HMOX1 promoter polymorphisms, HMOX1 mRNA inducibility, HO-1 protein levels in leucocytes (flow cytometry), and plasma (ELISA) with disease severity. The (GT)_n repeat polymorphism in the HMOX1 promoter was associated with HMOX1 mRNA expression in white blood cells in vitro, and with severe disease and death, while high HO-1 levels were associated with severe disease. Neutrophils were the main HO-1-expressing cells in peripheral blood, and HMOX1 mRNA expression was upregulated by heme-moieties of lysed erythrocytes. We provide mechanistic evidence that induction of HMOX1 expression in neutrophils potentiates the respiratory burst, and propose this may be part of the causal pathway explaining the association between short (GT)_n repeats and increased disease severity in malaria and other critical illnesses. Our findings suggest a genetic predisposition to higher levels of HO-1 is associated with severe illness, and enhances the neutrophil burst leading to oxidative damage of endothelial cells. These add important information to the discussion about possible therapeutic manipulation of HO-1 in critically ill patients.     

In human chromosomes telomeric regions are enriched in CpGs relative to R-bands

Human chromosomes were in situ nick-translated using as nicking agents the endonucleases MspI (CCGG), its methyl-sensitive isoschizomer HpaII, HaeIII (GGCC), SacII (CCGCGG), EcoRI (GAATTC) and DNaseI. We show that in metaphase chromosomes R-bands are enriched, as compared with G-bands, in the dinucleotide CpG but no more than what is expected on the basis of their relative G+C content. The telomeric regions, on the contrary, besides having a chromatin conformation that is particularly relaxed and accessible to endonucleases, also show an enrichment in CpGs.     

Biologically relevant effects of mRNA amplification on gene expression profiles

Background  

Gene expression microarray technology permits the analysis of global gene expression profiles. The amount of sample needed limits the use of small excision biopsies and/or needle biopsies from human or animal tissues. Linear amplification techniques have been developed to increase the amount of sample derived cDNA. These amplified samples can be hybridised on microarrays. However, little information is available whether microarrays based on amplified and unamplified material yield comparable results.     

Effect of sex and bright coloration on survival and predator‐induced wing damage in an aposematic lantern fly with startle display

1. Aposematic coloration in prey promotes its survival by conspicuously advertising unpalatability to predators. Although classical examples of aposematic signals involve constant presentation of a signal at a distance, some animals suddenly display warning colours only when they are attacked. 2. Characteristics of body parts suddenly displayed, such as conspicuous coloration or eyespot pattern, may increase the survival of the prey by startling the predator, and/or by signalling unpalatability to the predators at the moment of attack. 3. The adaptive value of such colour patterns suddenly displayed by unpalatable prey has not been studied. We experimentally blackened the red patch in the conspicuous red–white–black hindwing pattern displayed by an unpalatable insect Lycorma delicatula White (Hemiptera: Fulgoridae) in response to predator's attack. 4. There was no evidence that the presence of the red patch increased prey survival over several weeks. We hypothesise that predators generalised from the red–white–black patches on the hindwings of unpalatable L. delicatula to any similar wing display as a signal of unpalatability. Because a higher proportion of males than females stay put at their resting sites, displaying their wings in response to repeated attacks by predators, wing damage was more frequent in males than in females. 5. To our knowledge, this is the first experimental test of an adaptive role of aposematic signals presented by unpalatable prey during sudden displays triggered by direct predatory attack.     

Increase of the production of tumor necrosis factor in endotoxin shock in mice presensitized with sera of tumor-bearing mice or tumor cell factor]

We investigated the phenomenon of increased sensitivity of tumor-bearing mice to endotoxin shock. I/V administration of sera from tumor (EL-4, B16, R815, MOPC-315) bearers or tumoral culture media into intact mice caused the increased sensitivity to lethal action of LPS plus GMDP. Production of TNF in above mice was also significantly increased under the influence of LPS plus GMDP. Sensitivity induced factors in tumor bearing mice sera have mol. weight more than 50 kDa. This action was partially abolished by indomethacin.