The promotion of grassland forb abundance: A chemical or biological solution?

Techniques that increase the biodiversity value of species-poor grassland are required if conservation targets aimed at reversing the decline in species-rich grassland are to be met. This study investigated the diversification of swards dominated by Lolium perenne by testing the efficacies of two treatments applied to reduce competitive exclusion of species introduced as seed. The 'biological' treatment was the addition of the hemiparasitic plant species introduced as seed. The 'biological' treatment was the application of a selective graminicide, fluazifop-P-butyl (Fusilade 250EW). Changes in plant community composition were monitored for a period of 2 years. Values of plant species richness increased significantly between years regardless of treatment, but to a greater extent in plots sown with R. minor. The number of established sown species and their richness and tended to promote unsown species rather than those introduced as seed. Overall, the R. minor treatment was associated with the greatest impact on sward composition, facilitating establishment and development of the introduced species and promoting forb abundance. (c) 2007 Gessellschaft fur Okologie. Published by Elsevier GmbH. All rights reserved.

Mapping antimalarial pharmacophores as a useful tool for the rapid discovery of drugs effective in vivo: design, construction, characterization, and pharmacology of metaquine

Resistant strains of Plasmodium falciparum and the unavailability of useful antimalarial vaccines reinforce the need to develop new efficacious antimalarials. This study details a pharmacophore model that has been used to identify a potent, soluble, orally bioavailable antimalarial bisquinoline, metaquine (N,N'-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride), which is active against Plasmodium berghei in vivo (oral ID50 of 25 mu mol/kg) and multidrug-resistant Plasmodium falciparum K1 in vitro (0.17 mu M). Metaquine shows strong affinity for the putative antimalarial receptor, heme at pH 7.4 in aqueous DMSO. Both crystallographic analyses and quantum mechanical calculations (HF/6-31+G*) reveal important regions of protonation and bonding thought to persist at parasitic vacuolar pH concordant with our receptor model. Formation of drug-heme adduct in solution was confirmed using high-resolution positive ion electrospray mass spectrometry. Metaquine showed strong binding with the receptor in a 1: 1 ratio (log K = 5.7 +/- 0.1) that was predicted by molecular mechanics calculations. This study illustrates a rational multidisciplinary approach for the development of new 4-aminoquinoline antimalarials, with efficacy superior to chloroquine, based on the use of a pharmacophore model.

Heme-induced biomarkers associated with red meat promotion of colon cancer are not modulated by the intake of nitrite

Red and processed meat consumption is associated with the risk of colorectal cancer. Three hypotheses are proposed to explain this association, via heme-induced oxidation of fat, heterocyclic amines, or N-nitroso compounds. Rats have often been used to study these hypotheses, but the lack of enterosalivary cycle of nitrate in rats casts doubt on the relevance of this animal model to predict nitroso- and heme-associated human colon carcinogenesis. The present study was thus designed to clarify whether a nitrite intake that mimics the enterosalivary cycle can modulate hemeinduced nitrosation and fat peroxidation. This study shows that, in contrast with the starting hypothesis, drinking water added with nitrite to mimic the salivary nitrite content did not change the effect of hemoglobin on biochemicalmarkers linked to colon carcinogenesis, notably lipid peroxidation and cytotoxic activity in the colon of rat. However, ingested sodium nitrite increased fecal nitrosocompounds level, but their fecal concentration and their nature (iron-nitrosyl) would probably not be associated with an increased risk of cancer.We thus suggest that the rat model could be relevant for study the effect of red meat on colon carcinogenesis, in spite of the lack of nitrite in the saliva of rats.

Assembly of an injectable noncytotoxic peptide-based hydrogelator for sustained release of drugs

A new synthetic tripeptide-based hydrogel has been discovered at physiological pH and temperature. This hydrogel has been thoroughly characterized using different techniques including field emission scanning electron microscopic (FESEM) and high-resolution transmission electron microscopic (HR-TEM) imaging, small- and wide-angle X-ray diffraction analyses, FT-IR, circular dichroism, and rheometric analyses. Moreover, this gel exhibits thixotropy and injectability. This hydrogel has been used for entrapment and sustained release of an antibiotic vancomycin and vitamin B12 at physiological pH and temperature for about 2 days. Interestingly, MTT assay of these gelator molecules shows almost 100% cell viability of this peptide gelator, indicating its noncytotoxicity.

Effects of drugs that potentiate GABA on extinction of positively-reinforced operant behaviour

Extinction following positively reinforced operant conditioning reduces response frequency, at least in part through the aversive or frustrative effects of non-reinforcement. According to J.A. Gray's theory, non-reinforcement activates the behavioural inhibition system which in turn causes anxiety. As predicted, anxiolytic drugs including benzodiazepines affect the operant extinction process. Recent studies have shown that reducing GABA-mediated neurotransmission retards extinction of aversive conditioning. We have shown in a series of studies that anxiolytic compounds that potentiate GABA facilitate extinction of positively reinforced fixed-ratio operant behaviour in C57B1/6 male mice. This effect does not occur in the early stages of extinction, nor is it dependent on cumulative effects of the compound administered. Potentiation of GABA at later stages has the effect of increasing sensitivity to the extinction contingency and facilitates the inhibition of the behaviour that is no longer required. The GABAergic hypnotic, zolpidem, has the same selective effects on operant extinction in this procedure. The effects of zolpidem are not due to sedative action. There is evidence across our series of experiments that different GABA-A subtype receptors are involved in extinction facilitation and anxiolysis. Consequently, this procedure may not be an appropriate model for anxiolytic drug action, but it may be a useful technique for analysing the neural bases of extinction and designing therapeutic interventions in humans where failure to extinguish inappropriate behaviours can lead to pathological conditions such as post-traumatic stress disorder.

Tripodal molecules for the promotion of phosphoester hydrolysis

A series of low molecular weight tripodal amide/histidine-containing compounds (1–2) have been synthesised and shown to increase the rate of bis-(p-nitrophenyl) phosphate (BNPP) and soman (GD) breakdown in buffered aqueous solution.

Group 11 (Cu, Ag, Au) promotion of 15%Co/Al(2)O(3) Fischer-Tropsch synthesis catalysts

Co/Al(2)O(3) Fischer-Tropsch synthesis catalysts promoted with different quantities of Group 11 metals (Cu, Ag, Au) were characterized and tested. The presence of relatively small quantities of such metals enhanced Co reducibility and, in the cases of Ag and Au, improved the surface Co metal active site densities. EXAFS experiments with the most loaded catalyst samples show that only Co-Co and Me-Me (Me = Cu, Ag and Au) coordination could be observed. This suggests that the greater fraction of the metals form different phases. However, the reduction promoting effect of the Group 11 metal is severely hampered once the catalyst receives a mild passivation treatment following primary reduction. An explanation in terms of promoter segregation during primary reduction is proposed. At lower promoter levels (0.83%Ag and 1.51%Au) and higher Ag levels (2.76%), significant gains in Co active site densities were achieved resulting in improved CO conversion levels relative to the unpromoted catalyst. Moreover, slight decreases in light product (e.g., CH(4)) selectivity and slight increases in C(5)+ selectivity were achieved. At high Au loading (5.05%), however, too much Au was loaded which, although significantly increasing the fraction of Co reduced, blocked Co surface sites and resulted in decreased Co conversion rates. While Cu facilitated Co reduction, the increased fraction of reduced Co did not translate to improved active site densities. It appears that a fraction of Cu tended to cover the rim of Co clusters, resulting in decreases in CO conversion rates and detrimental increases in light product selectivity. (C) 2009 Elsevier B.V. All rights reserved.