In vivo effect of aluminium upon the physical properties of the erythrocyte membrane

Aluminium (Al (III)) is a metal with no biological function. Its organic accumulation can lead to toxic effects. To elucidate the in vivo effect of Al (III) upon the rheological properties of the erythrocyte membrane, male adult Wistar rats have been submitted to periodical injections of Al(OH)3 during three months. Significant decreases in haematocrit (34+/-0.37% versus 36+/-0.20%, p<0.0001) and blood haemoglobin concentration (10.7+/-0.15 g/dl versus 12.3+/-0.49 g/dl, p<0.005) have been found. Haemolysis curves shifted towards the left, indicating that erythrocytes became more resistant to hypotonic haemolysis. Significant increments in rigidity index (29.6+/-1.59 versus 9.2+/-0.40, p<0.0001), relative viscosity at native haematocrit (3.6+/-0.03 versus 3.5+/-0.03, p<0.04), and relative viscosity at standard haematocrit (4.5+/-0.06 versus 3.9+/-0.05, p<0.0001) have been observed. The decrease in the erythrocyte aggregate size (1.6+/-0.01 versus 1.7+/-0.01, p<0.002) and the aggregation rate (0.5+/-0.02 versus 0.6+/-0.03, p<0.002) indicated a significantly dropped aggregability process. In conclusion, Al (III) disorganised the erythrocyte membrane by altering its mechanical properties, suggesting a reduction of the middle life of circulating erythrocytes, which could play a major role in the anaemia of these animals.     

<Emphasis Type="Italic">Pichia stipitis</Emphasis> xylose reductase helps detoxifying lignocellulosic hydrolysate by reducing 5-hydroxymethyl-furfural (HMF)

Background  

Pichia stipitis xylose reductase (Ps-XR) has been used to design Saccharomyces cerevisiae strains that are able to ferment xylose. One example is the industrial S. cerevisiae xylose-consuming strain TMB3400, which was constructed by expression of P. stipitis xylose reductase and xylitol dehydrogenase and overexpression of endogenous xylulose kinase in the industrial S. cerevisiae strain USM21.     

Reduced natural selection associated with low recombination in Drosophila melanogaster

Synonymous codons are not used equally in many organisms, and the extent of codon bias varies among loci. Earlier studies have suggested that more highly expressed loci in Drosophila melanogaster are more biased, consistent with findings from several prokaryotes and unicellular eukaryotes that codon bias is partly due to natural selection for translational efficiency. We link this model of varying selection intensity to the population-genetics prediction that the effectiveness of natural selection is decreased under reduced recombination. In analyses of 385 D. melanogaster loci, we find that codon bias is reduced in regions of low recombination (i.e., near centromeres and telomeres and on the fourth chromosome). The effect does not appear to be a linear function of recombination rate; rather, it seems limited to regions with the very lowest levels of recombination. The large majority of the genome apparently experiences recombination at a sufficiently high rate for effective natural selection against suboptimal codons. These findings support models of the Hill-Robertson effect and genetic hitchhiking and are largely consistent with multiple reports of low levels of DNA sequence variation in regions of low recombination.      

Kappa-chain constant-region gene sequences in genus Rattus: coding regions are diverging more rapidly than noncoding regions

We have determined the nucleotide sequence of a 1,200-base pair (bp) genomic fragment that includes the kappa-chain constant-region gene (C kappa) from two species of native Australian rodents, Rattus leucopus cooktownensis and Rattus colletti. Comparison of these sequences with each other and with other rodent C kappa genes shows three surprising features. First, the coding regions are diverging at a rate severalfold higher than that of the nearby noncoding regions. Second, replacement changes within the coding region are accumulating at a rate at least as great as that of silent changes. Third, most of the amino acid replacements are localized in one region of the C kappa domain--namely, the carboxy-terminal "bends" in the alpha-carbon backbone. These three features have previously been described from comparisons of the two allelic forms of C kappa genes in R. norvegicus. These data imply the existence of considerable evolutionary constraints on the noncoding regions (based on as yet undetermined functions) or powerful positive selection to diversify a portion of the constant-region domain (whose physiological significance is not known). These surprising features of C kappa evolution appear to be characteristic only of closely related C kappa genes, since comparison of rodent with human sequences shows the expected greater conservation of coding regions, as well as a predominance of silent nucleotide substitutions within the coding regions.      

Quantification of the virus-host interaction in human T lymphotropic virus I infection

Background

Cellular infection with human immunodeficiency virus (HIV) both in vitro and in vivo requires a member of the chemokine receptor family to act as a co-receptor for viral entry. However, it is presently unclear to what extent the interaction of HIV proteins with chemokine receptors generates intracellular signals that are important for productive infection.

Results

In this study we have used a recently described family of chemokine inhibitors, termed BSCIs, which specifically block chemokine-induced chemotaxis without affecting chemokine ligands binding to their receptors. The BSCI termed Peptide 3 strongly inhibited CCR5 mediated HIV infection of THP-1 cells (83 ± 7% inhibition assayed by immunofluoresence staining), but had no effect on gp120 binding to CCR5. Peptide 3 did not affect CXCR4-dependent infection of Jurkat T cells.

Conclusion

These observations suggest that, in some cases, intracellular signals generated by the chemokine coreceptor may be required for a productive HIV infection.     

Xanthophylls lutein and zeaxanthin modify gene expression and induce synthesis of hyaluronan in keratinocyte model of human skin

BackgroundClinical trials report benefits of the xanthophylls lutein and zeaxanthin for skin health. Here a keratinocyte culture was used to investigate the effects of in vitro xanthophyll treatment on gene expression and biochemical pathways.MethodsWe employed the EpiDerm tissue model, Affymetrix Human Genome Array U113, bioinformatics analyses, qPCR validation and biochemical assays for glycosaminoglycans.ResultsWe discovered 176 genes were significantly (p<0.05) down-regulated (log 2FC>2) and 47 genes were significantly up-regulated. Among the down-regulated genes we validated by qPCR marked reduction in expression of peptidase inhibitors. Bioinformatic analysis of the up-regulated genes implicated biosynthetic pathways for glycosaminoglycans. We assayed but found no increase in production of sulfated glycosaminoglycans, however there was a significant increase in biosynthesis of hyaluronic acid, a non-sulfated glycan.ConclusionsThe pattern of xanthophyll-regulated genes and the resulting biochemical responses can be linked with the responses observed in clinic trials.General significanceSkin health benefits from xanthophyll supplementation and this study reveals molecular mechanisms for some of the effects.