Olomoucine II,but Not Purvalanol A,Is Transported by Breast Cancer Resistance Protein (ABCG2) and P-Glycoprotein (ABCB1)

Purine cyclin-dependent kinase inhibitors have been recognized as promising candidates for the treatment of various cancers; nevertheless, data regarding interaction of these substances with drug efflux transporters is still lacking. Recently, we have demonstrated inhibition of breast cancer resistance protein (ABCG2) by olomoucine II and purvalanol A and shown that these compounds are able to synergistically potentiate the antiproliferative effect of mitoxantrone, an ABCG2 substrate. In this follow up study, we investigated whether olomoucine II and purvalanol A are transported by ABCG2 and ABCB1 (P-glycoprotein). Using monolayers of MDCKII cells stably expressing human ABCB1 or ABCG2, we demonstrated that olomoucine II, but not purvalanol A, is a dual substrate of both ABCG2 and ABCB1. We, therefore, assume that pharmacokinetics of olomoucine II will be affected by both ABCB1 and ABCG2 transport proteins, which might potentially result in limited accumulation of the compound in tumor tissues or lead to drug-drug interactions. Pharmacokinetic behavior of purvalanol A, on the other hand, does not seem to be affected by either ABCG2 or ABCB1, theoretically favoring this drug in the potential treatment of efflux transporter-based multidrug resistant tumors. In addition, we observed intensive sulfatation of olomoucine II in MDCKII cell lines with subsequent active efflux of the metabolite out of the cells. Therefore, care should be taken when performing pharmacokinetic studies in MDCKII cells, especially if radiolabeled substrates are used; the generated sulfated conjugate may largely contaminate pharmacokinetic analysis and result in misleading interpretation. With regard to chemical structures of olomoucine II and purvalanol A, our data emphasize that even drugs with remarkable structure similarity may show different pharmacokinetic behavior such as interactions with ABC transporters or biotransformation enzymes.     

Midpoint attractors and species richness: Modelling the interaction between environmental drivers and geometric constraints

We introduce a novel framework for conceptualising, quantifying and unifying discordant patterns of species richness along geographical gradients. While not itself explicitly mechanistic, this approach offers a path towards understanding mechanisms. In this study, we focused on the diverse patterns of species richness on mountainsides. We conjectured that elevational range midpoints of species may be drawn towards a single midpoint attractor – a unimodal gradient of environmental favourability. The midpoint attractor interacts with geometric constraints imposed by sea level and the mountaintop to produce taxon‐specific patterns of species richness. We developed a Bayesian simulation model to estimate the location and strength of the midpoint attractor from species occurrence data sampled along mountainsides. We also constructed midpoint predictor models to test whether environmental variables could directly account for the observed patterns of species range midpoints. We challenged these models with 16 elevational data sets, comprising 4500 species of insects, vertebrates and plants. The midpoint predictor models generally failed to predict the pattern of species midpoints. In contrast, the midpoint attractor model closely reproduced empirical spatial patterns of species richness and range midpoints. Gradients of environmental favourability, subject to geometric constraints, may parsimoniously account for elevational and other patterns of species richness.     

Effect of losartan on the Na+/Ca2+ exchanger in left ventricle of the insulin resistant and hypertensive hHTg rat

As the Na+/Ca2+ exchanger plays an important role in the regulation of myocyte contractility, it has been suggested that alterations in this system might be involved in the development of insulin resistance and/or diabetes-induced myocardial alterations. Moreover, gene expression and function of the Na+/Ca2+ exchanger in states of combined hypertension and insulin resistance is of a special interest. Thus, we used hereditary hypertriglyceridemic (hHTg) rat (a model of genetically induced insulin resistance and hypertension) to study the effect of losartan, the blocker of type 1 angiotensin receptors, on the Na+/Ca2+ exchanger in the rat heart. We found that gene expression, but not activity of the Na+/Ca2+ exchanger was decreased in the left ventricle of hHTg rats when compared to their normotensive mates. No changes were observed in the right ventricle. In addition, losartan decreased mRNA levels of the Na+/Ca2+ exchanger in the left, but not in the right ventricle of normotensive rats. In hHTg rats, losartan had no effect on the gene expression of this transporter. Our results point to different modulatory pathways of Na+/Ca2+ exchanger in normotensive and hHTg rats.     

Characterization of the glyoxalase I gene from the vascular wilt fungus Verticillium dahliae

A glyoxalase I gene homologue (VdGLO1) was identified in the vascular wilt fungus Verticillium dahliae by sequence tag analysis of genes expressed during resting structure development. The results of the current study show that the gene encodes a putative 345 amino acid protein with high similarity to glyoxalase I, which produces S-D-lactoylglutathione from the toxic metabolic by-product methylglyoxal (MG). Disruption of the V. dahliae gene by Agrobacterium tumefaciens-mediated transformation resulted in enhanced sensitivity to MG. Mycelial growth of disruption mutants was severely reduced in the presence of 5 mmol/L MG. In contrast, spore production in liquid medium was abolished at 1 mmol/L MG, although not at physiologically relevant concentrations of 相似文献   

Towards the biocontrol of bindweeds with a mycoherbicide

Within the framework of the European COST Action 816, afive-year collaboration between scientists from five Europeancountries has made an important contribution to biologicalcontrol of field and hedge bindweeds (Convolvulus arvensis andCalystegia sepium, respectively). A fungus Stagonosporaconvolvuli strain LA39, able to infect both field and hedgebindweed, was found in the UK and its biocontrol efficacyimproved by optimising mass production, formulation and storagetechniques. This fungus controlled bindweeds in both a cemeteryand in maize crops. Its use fits best in an integrated pestmanagement system where a green cover controls most of the weedsexcept the bindweeds. DNA marker analyses indicate that thefungus reproduces sexually, which could be used to furtherimprove this mycoherbicide. In addition, the insect Melanagromyzaalbocilia, which itself exhibits biocontrol potential againstbindweeds, may be used in combination with LA39 to improve theability of the fungus to penetrate the stem of bindweeds.Overall, the results suggest that S. convolvuli LA39 haspromising potential as a bioherbicide for control of field andhedge bindweed.     

Dominance–diversity relationships in ant communities differ with invasion

The relationship between levels of dominance and species richness is highly contentious, especially in ant communities. The dominance‐impoverishment rule states that high levels of dominance only occur in species‐poor communities, but there appear to be many cases of high levels of dominance in highly diverse communities. The extent to which dominant species limit local richness through competitive exclusion remains unclear, but such exclusion appears more apparent for non‐native rather than native dominant species. Here we perform the first global analysis of the relationship between behavioral dominance and species richness. We used data from 1,293 local assemblages of ground‐dwelling ants distributed across five continents to document the generality of the dominance‐impoverishment rule, and to identify the biotic and abiotic conditions under which it does and does not apply. We found that the behavioral dominance–diversity relationship varies greatly, and depends on whether dominant species are native or non‐native, whether dominance is considered as occurrence or relative abundance, and on variation in mean annual temperature. There were declines in diversity with increasing dominance in invaded communities, but diversity increased with increasing dominance in native communities. These patterns occur along the global temperature gradient. However, positive and negative relationships are strongest in the hottest sites. We also found that climate regulates the degree of behavioral dominance, but differently from how it shapes species richness. Our findings imply that, despite strong competitive interactions among ants, competitive exclusion is not a major driver of local richness in native ant communities. Although the dominance‐impoverishment rule applies to invaded communities, we propose an alternative dominance‐diversification rule for native communities.     

Disentangling the Diversity of Arboreal Ant Communities in Tropical Forest Trees

Tropical canopies are known for their high abundance and diversity of ants. However, the factors which enable coexistence of so many species in trees, and in particular, the role of foragers in determining local diversity, are not well understood. We censused nesting and foraging arboreal ant communities in two 0.32 ha plots of primary and secondary lowland rainforest in New Guinea and explored their species diversity and composition. Null models were used to test if the records of species foraging (but not nesting) in a tree were dependent on the spatial distribution of nests in surrounding trees. In total, 102 ant species from 389 trees occurred in the primary plot compared with only 50 species from 295 trees in the secondary forest plot. However, there was only a small difference in mean ant richness per tree between primary and secondary forest (3.8 and 3.3 sp. respectively) and considerably lower richness per tree was found only when nests were considered (1.5 sp. in both forests). About half of foraging individuals collected in a tree belonged to species which were not nesting in that tree. Null models showed that the ants foraging but not nesting in a tree are more likely to nest in nearby trees than would be expected at random. The effects of both forest stage and tree size traits were similar regardless of whether only foragers, only nests, or both datasets combined were considered. However, relative abundance distributions of species differed between foraging and nesting communities. The primary forest plot was dominated by native ant species, whereas invasive species were common in secondary forest. This study demonstrates the high contribution of foragers to arboreal ant diversity, indicating an important role of connectivity between trees, and also highlights the importance of primary vegetation for the conservation of native ant communities.