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.

Fitting models for the joint action of two drugs using SAS(R)

Combinations of drugs are increasingly being used for a wide variety of diseases and conditions. A pre-clinical study may allow the investigation of the response at a large number of dose combinations. In determining the response to a drug combination, interest may lie in seeking evidence of synergism, in which the joint action is greater than the actions of the individual drugs, or of antagonism, in which it is less. Two well-known response surface models representing no interaction are Loewe additivity and Bliss independence, and Loewe or Bliss synergism or antagonism is defined relative to these. We illustrate an approach to fitting these models for the case in which the marginal single drug dose-response relationships are represented by four-parameter logistic curves with common upper and lower limits, and where the response variable is normally distributed with a common variance about the dose-response curve. When the dose-response curves are not parallel, the relative potency of the two drugs varies according to the magnitude of the desired effect and the models for Loewe additivity and synergism/antagonism cannot be explicitly expressed. We present an iterative approach to fitting these models without the assumption of parallel dose-response curves. A goodness-of-fit test based on residuals is also described. Implementation using the SAS NLIN procedure is illustrated using data from a pre-clinical study. Copyright © 2007 John Wiley & Sons, Ltd.

The neuroprotective potential of flavonoids: a multiplicity of effects

Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.

The rise of urban tourism in Havana since 1989

This article looks at the development of urban tourism in Havana, Cuba, in the period since the collapse of state socialism in the USSR and Eastern Europe. It provides an interesting case study of the adoption of an outward-oriented state development policy in the context of a socialist state. The dramatic rise of urban-based tourism in Havana since 1989 is described, followed by a review of the socio-economic impacts of such tourism. These include: income generation; job creation; the rise of the informal economy, including crime and prostitution; increased migration to the primary city, along with spatial concentration on the coastal strip, and associated environmental impacts. In conclusion, the article considers the fat that the promotion of tourism has returned Havana to some of the conditions that existed in the city Socialist Revolution in 1959.

Health Benefits of Organic Food: effects of the environment

Public concern over impacts of chemicals in plant and animal production on health and the environment has led to increased demand for organic produce, which is usually promoted and often perceived as containing fewer contaminants, more nutrients, and being positive for the environment. These benefits are difficult to quantify, and potential environmental impacts on such benefits have not been widely studied. This book addresses these key points, examining factors such as the role of certain nutrients in prevention and promotion of chronic disease, potential health benefits of bioactive compounds in plants, the prevalence of food-borne pesticides and pathogens and how both local and global environmental factors may affect any differences between organic and conventionally produced food. This book is an essential resource for researchers and students in human health and nutrition, environmental science, agriculture and organic farming. Main Contents 1. Organic farming and food systems: definitions and key characteristics. 2. The health benefits of n-3 fatty acids and their concentrations in organic and conventional animal-derived foods. 3. Environmental impacts on n-3 content of foods from ruminant animals. 4. Health benefits and selenium content of organic vs conventional foods. 5. Environmental impacts concerning the selenium content of foods. 6. Contaminants in organic and conventional food: the missing link between contaminant levels and health effects. 7. Mycotoxins in organic and conventional foods and effects of the environment. 8. Human pathogens in organic and conventional foods and effects of the environment. 9. What does consumer science tell us about organic foods? 10. The beneficial effects of dietary flavonoids: sources, bioavailability and biological functions. 11. Environmental regulation of flavonoid biosynthesis. 12. Nitrates in the human diet. 13. Impacts of environment and management on nitrate in vegetables and water. 14. Effects of the environment on the nutritional quality and safety of organically produced foods: Round-up and summary.

The social life of ruins: sites of memory and the politics of a Zimbabwean periphery

This article explores conflicts over a series of ruins located within Zimbabwe's flagship National Park. The relics have long been regarded as sacred places by local African communities evicted from their vicinity, and have come to be seen as their ethnic heritage. Local intellectuals' promotion of this heritage was an important aspect of a defensive mobilization of cultural difference on the part of a marginalized minority group. I explore both indigenous and colonial ideas about the ruins, the different social movements with which they have been associated and the changing social life they have given the stone relics. Although African and European ideas sometimes came into violent confrontation - as in the context of colonial era evictions - there were also mutual influences in emergent ideas about tribe, heritage and history. The article engages with Pierre Nora's notion of 'sites of memory', which has usefully drawn attention to the way in which ideas of the past are rooted and reproduced in representations of particular places. But it criticizes Nora's tendency to romanticize pre-modern 'memory', suppress narrative and depoliticize traditional connections with the past. Thus, the article highlights the historicity of traditional means of relating to the past, highlighting the often bitter and divisive politics of traditional ritual, myth, kinship, descent and 'being first'. It also emphasizes the entanglement of modern and traditional ideas, inadequately captured by Nora's implied opposition between history and memory. (c) 2005 Elsevier Ltd. All rights reserved.

Promoting sustainability: Efficacy and adoption of tobacco-based insecticides in Nigeria

The promotion of technologies seen to be aiding in the attainment of agricultural sustainability has been Popular amongst Northern-based development donors for many years. One of these, botanical insecticides (e.g., those based on neem, Pyrethrum and tobacco) have been a particular favorite as they are equated with being 'natural' and hence less damaging to human health and the environment. This paper describes the outcome of interactions between one non-government organisation (NGO), the Diocesan Development Services (DDS), based in Kogi State, Nigeria, and a major development donor based in Europe that led to the establishment of a programme designed to promote the Virtues of a tobacco-based insecticide to small-scale farmers. The Tobacco Insecticide Programme (TIP) began in the late 1980s and ended in 200 1, absorbing significant quantities of resource in the process. TIP began with exploratory investigations of efficacy on the DDS seed multiplication farm followed by stages of researcher-managed and farmer-managed on-farm trials. A survey in 2002 assessed adoption of the technology by farmers. While yield benefits from using the insecticide were nearly always positive and statistically significant relative to an untreated control, they were not as good as commercial insecticides. However, adoption of the tobacco insecticide by local farmers was poor. The paper discusses the reasons for poor adoption, including relative benefits in gross margin, and uses the TIP example to explore the differing power relationships that exist between donors, their field partners and farmers. (C) 2004 by The Haworth Press, Inc. All rights reserved.

Mediating between hearer's and speaker's views in the generation of adaptive explanations

In this article, we examine the case of a system that cooperates with a “direct” user to plan an activity that some “indirect” user, not interacting with the system, should perform. The specific application we consider is the prescription of drugs. In this case, the direct user is the prescriber and the indirect user is the person who is responsible for performing the therapy. Relevant characteristics of the two users are represented in two user models. Explanation strategies are represented in planning operators whose preconditions encode the cognitive state of the indirect user; this allows tailoring the message to the indirect user's characteristics. Expansion of optional subgoals and selection among candidate operators is made by applying decision criteria represented as metarules, that negotiate between direct and indirect users' views also taking into account the context where explanation is provided. After the message has been generated, the direct user may ask to add or remove some items, or change the message style. The system defends the indirect user's needs as far as possible by mentioning the rationale behind the generated message. If needed, the plan is repaired and the direct user model is revised accordingly, so that the system learns progressively to generate messages suited to the preferences of people with whom it interacts.