Feijoa sellowiana derived natural Flavone exerts anti-cancer action displaying HDAC inhibitory activities

Curative properties of some medicinal plants such as the Feijoa sellowiana Bert. (Myrtaceae), have been often claimed, although the corresponding molecular mechanism(s) remain elusive. We report here that the Feijoa acetonic extract exerts anti-cancer activities on solid and hematological cancer cells. Feijoa extract did not show toxic effects on normal myeloid progenitors thus displaying a tumor-selective activity. In the Feijoa acetonic extract, fractionation and subsequent purification and analyses identified Flavone as the active component. Flavone induces apoptosis which is accompanied by caspase activation and p16, p21 and TRAIL over-expression in human myeloid leukemia cells. Use of ex vivo myeloid leukemia patients blasts confirms that both the full acetonic Feijoa extract and its derived Flavone are able to induce apoptosis. In both cell lines and myeloid leukemia patients blasts the apoptotic activity of Feijoa extract and Flavone is accompanied by increase of histone and non-histone acetylation levels and by HDAC inhibition. Our findings show for the first time that the Feijoa apoptotic active principle is the Flavone and that this activity correlates with the induction of HDAC inhibition, supporting the hypothesis of its epigenetic pro-apoptotic regulation in cancer systems.     

Genetic use restriction technologies (GURTs): strategies to impede transgene movement

No clear consensus has emerged in the debate about the risks posed by transgenic crops and how to assess these risks accurately. In the meantime, interest is growing in strategies to impede transgene movement. This attention is being driven, in part, by expanding interest in using transgenic crops to produce pharmaceutical and industrial products. Potential strategies to impede transgene movement have been published in the scientific literature, and numerous patents have been submitted; however, the efficacy of such strategies has still to be evaluated in a field situation. In this review, we discuss some of the genetic strategies that could be used to restrict the spread of transgenes, although at present many of these technologies are still largely at a theoretical stage of development.     

A comparison of background correction methods for two-colour microarrays

MOTIVATION: Microarray data must be background corrected to remove the effects of non-specific binding or spatial heterogeneity across the array, but this practice typically causes other problems such as negative corrected intensities and high variability of low intensity log-ratios. Different estimators of background, and various model-based processing methods, are compared in this study in search of the best option for differential expression analyses of small microarray experiments. RESULTS: Using data where some independent truth in gene expression is known, eight different background correction alternatives are compared, in terms of precision and bias of the resulting gene expression measures, and in terms of their ability to detect differentially expressed genes as judged by two popular algorithms, SAM and limma eBayes. A new background processing method (normexp) is introduced which is based on a convolution model. The model-based correction methods are shown to be markedly superior to the usual practice of subtracting local background estimates. Methods which stabilize the variances of the log-ratios along the intensity range perform the best. The normexp+offset method is found to give the lowest false discovery rate overall, followed by morph and vsn. Like vsn, normexp is applicable to most types of two-colour microarray data. AVAILABILITY: The background correction methods compared in this article are available in the R package limma (Smyth, 2005) from http://www.bioconductor.org. SUPPLEMENTARY INFORMATION: Supplementary data are available from http://bioinf.wehi.edu.au/resources/webReferences.html.     

An analysis of the DOCA-salt model of hypertension in HO-1-/- mice and the Gunn rat

Heme oxygenase-1 (HO-1) is induced in the vasculature in the DOCA-salt model of hypertension in rats. Whereas the HO system and its products may exert vasodilator effects, recent studies have suggested that the HO system may predispose to hypertension. The present study examined the effects of selected components of the HO system, specifically, the HO-1 isozyme and the product bilirubin in the DOCA-salt model of systemic hypertension; the experimental approach employed mutant rodent models, namely, the HO-1(-/-) mouse and the hyperbilirubinemic Gunn rat. DOCA-salt induced HO-1 protein in the aorta in HO-1(+/+) mice and provoked a significant rise in systolic arterial pressure in HO-1(-/-) mice but not in HO-1(+/+) mice; this effect could not be ascribed to impaired urinary sodium excretion or impaired glomerular filtration rate in the DOCA-salt-treated HO-1(-/-) mice. The administration of DOCA salt to uninephrectomized rats significantly increased systolic arterial pressure in wild-type rats, an effect that was attenuated in the mutant Gunn rat; this reduction in systemic hypertension in the DOCA-salt-treated Gunn rat was not due to a greater induction of HO-1 in the vasculature or to a more avid urinary sodium excretion. DOCA-salt impaired endothelium-dependent and endothelium-independent vasorelaxation in wild-type rats but not in Gunn rats; prior exposure to bilirubin repaired the defect in endothelium-dependent vasorelaxation in aortic rings in DOCA-salt-treated rats. DOCA salt stimulated vascular production of superoxide anion in wild-type but not in Gunn rats. We suggest that HO-1 and the product bilirubin may exert a countervailing effect in the DOCA-salt model of systemic hypertension.     

Behavioral and physiologic responses to environmental enrichment in the maned wolf (Chrysocyon brachyurus)

The ex situ population of maned wolves is not self‐sustaining due to poor reproduction, caused primarily by parental incompetence. Studies have shown that environmental enrichment can promote natural parental behaviors in zoo animals. The objective of this study was to determine the effects of environmental enrichment on behavioral and physiological responses of maned wolves. During an 8‐week experimental period, daily behavior observations and fecal sample collection were conducted on four adult wolves (2.2) individually housed in environments without enrichment. After 2 weeks, the wolves were chronologically provided with 2‐week intervals of hiding dead mice around the exhibit, no enrichment, and introduction of boomer balls. Responses of the wolves to enrichment were assessed based on activity levels and exploratory rates, as well as the level of corticoid metabolites in fecal samples collected daily throughout the study period. Providing wolves with environmental enrichment significantly increased exploratory behaviors (P<0.05), especially when mice were hidden in the enclosure. Fecal corticoid concentrations were increased during periods of enrichment in males (P<0.05), but not in females. Overall, there were no correlations between behavioral responses to enrichment and fecal corticoid levels. Behavioral results suggest that environmental enrichment elicits positive effects on the behavior of captive maned wolves. There is evidence suggesting that providing animals with ability to forage for food is a more effective enrichment strategy than introducing objects. There is need for a longer term study to determine the impact of environmental enrichment in this species. Zoo Biol 26:331–343, 2007. © 2007 Wiley‐Liss, Inc.     

Maximum likelihood estimation of ancestral codon usage bias parameters in Drosophila

We present a likelihood method for estimating codon usage bias parameters along the lineages of a phylogeny. The method is an extension of the classical codon-based models used for estimating dN/dS ratios along the lineages of a phylogeny. However, we add one extra parameter for each lineage: the selection coefficient for optimal codon usage (S), allowing joint maximum likelihood estimation of S and the dN/dS ratio. We apply the method to previously published data from Drosophila melanogaster, Drosophila simulans, and Drosophila yakuba and show, in accordance with previous results, that the D. melanogaster lineage has experienced a reduction in the selection for optimal codon usage. However, the D. melanogaster lineage has also experienced a change in the biological mutation rates relative to D. simulans, in particular, a relative reduction in the mutation rate from A to G and an increase in the mutation rate from C to T. However, neither a reduction in the strength of selection nor a change in the mutational pattern can alone explain all of the data observed in the D. melanogaster lineage. For example, we also confirm previous results showing that the Notch locus has experienced positive selection for previously classified unpreferred mutations.     

Biofilm formation, epiphytic fitness, and canker development in Xanthomonas axonopodis pv. citri

The phytopathogenic bacterium Xanthomonas axonopodis pv. citri is responsible for the canker disease affecting citrus plants throughout the world. Here, we have evaluated the role of bacterial attachment and biofilm formation in leaf colonization during canker development on lemon leaves. Crystal violet staining and confocal laser scanning microscopy analysis of X. axonopodis pv. citri strains expressing the green fluorescent protein were used to evaluate attachment and biofilm formation on abiotic and biotic (leaf) surfaces. Wild-type X. axonopodis pv. citri attached to and formed a complex, structured biofilm on glass in minimal medium containing glucose. Similar attachment and structured biofilm formation also were seen on lemon leaves. An X. axonopodis pv. citri gumB mutant strain, defective in production of the extracellular polysaccharide xanthan, did not form a structured biofilm on either abiotic or biotic surfaces. In addition, the X. axonopodis pv. citri gumB showed reduced growth and survival on leaf surfaces and reduced disease symptoms. These findings suggest an important role for formation of biofilms in the epiphytic survival of X. axonopodis pv. citri prior to development of canker disease.     

Effects of the fish-oil supplementation on the immune and inflammatory responses in elite swimmers

The effect of fish-oil supplementation (FO-S) on the immune responses of elite swimmers was investigated. In a randomized placebo-controlled trial, swimmers received either fish-oil capsules (n=10) containing long chain polyunsaturated fatty acids (FA) of n-3 (LCPUFA n-3) or placebo capsules (n=10), both for 6 weeks. Plasma FA, immunological markers, insulin and cortisol were evaluated. The FO-S resulted in an increase in LCPUFA n-3 and a decrease in arachidonic n-6 FA in plasma and a reduction in the production of interferon-gamma by cultured cells. A reduction in the production of tumor necrosis factor-alpha was observed in both groups. An increase in interleukin-2 production and no significant difference in interleukin-4 were also observed. FO-S was able to attenuate the exercise-induced increases in prostaglandin E2. Circulating concentrations of insulin did not change, while cortisol and glucose showed increase after the study period. These results suggest that FO-S influence exercise-associated immune responses in competitive swimmers.