The comparative toxicity to soil invertebrates of natural chemicals and their synthetic analogues

The introduction of Registration, Evaluation and Authorisation of Chemicals (REACH), requires companies to register and risk assess all substances produced or imported in volumes of >1 tonne per year. Extrapolation methods which use existing data for estimating the effects of chemicals are attractive to industry, and comparative data are therefore increasingly in demand. Data on natural toxic chemicals could be used for extrapolation methods Such as read-across. To test this hypothesis, the toxicity of natural chemicals and their synthetic analogues were compared using standardised toxicity tests. Two chemical pairs: the napthoquinones, juglone (natural) and 1,4-naphthoquinone (synthetic); and anthraquinones, emodin (natural) and quinizarin (synthetic) were chosen, and their comparative effects on the survival and reproduction of collembolans, earthworms, enchytraeids and predatory mites were assessed. Differences in sensitivity between the species were observed with the predatory mite (Hypoaspis aculeifer) showing the least sensitivity. Within the chemical pairs, toxicity to lethal and sub-lethal endpoints was very similar for the four invertebrate species. The exception was earthworm reproduction, which showed differential sensitivity to the chemicals in both naphthoquinone and anthraquinone pairs. Differences in toxicity identified in the present study may be related to degree of exposure and/or subtle differences in the mode of toxic action for the chemicals and species tested. It may be possible to predict differences by identifying functional groups which infer increased or decreased toxicity in one or other chemical. The development of such techniques would enable the use of read-across from natural to synthetic chemicals for a wider group of compounds. (C) 2009 Elsevier Ltd. All rights reserved.

Can the study of natural vegetation succession assist in the control of soil erosion on abandoned croplands on the Loess Plateau, China?

In the Loess Plateau, China, arable cultivation of slope lands is common and associated with serious soil erosion. Planting trees or grass may control erosion, but planted species may consume more soil water and can threaten long-term ecosystem sustainability. Natural vegetation succession is an alternative ecological solution to restore degraded land, but there is a time cost, given that the establishment of natural vegetation, adequate to prevent soil erosion, is a longer process than planting. The aims of this study were to identify the environmental factors controlling the type of vegetation established on abandoned cropland and to identify candidate species that might be sown soon after abandonment to accelerate vegetation succession and establishment of natural vegetation to prevent soil erosion. A field survey of thirty-three 2 × 2–m plots was carried out in July 2003, recording age since abandonment, vegetation cover, and frequency of species together with major environmental and soil variables. Data were analyzed using correspondence analysis, classification tree analysis, and species response curves. Four vegetation types were identified and the data analysis confirmed the importance of time since abandonment, total P, and soil water in controlling the type of vegetation established. Among the dominant species in the three late-successional vegetation types, the most appropriate candidates for accelerating and directing vegetation succession were King Ranch bluestem (Bothriochloa ischaemum) and Lespedeza davurica (Leguminosae). These species possess combinations of the following characteristics: tolerance of low water and nutrient availability, fibrous root system and strong lateral vegetative spread, and a persistent seed bank.

13C-2H correlation NMR spectroscopy studies of the in vivo transformations of natural products from Artemisia annua

13C-2H correlation NMR spectroscopy (13C-2H COSY) permits the identification of 13C and 2H nuclei which are connected to one another by a single chemical bond via the sizeable 1JCD coupling constant. The practical development of this technique is described using a 13C-2H COSY pulse sequence which is derived from the classical 13C-1H correlation experiment. An example is given of the application of 13C-2H COSY to the study of the biogenesis of natural products from the anti-malarial plant Artemisia annua, using a doubly-labelled precursor molecule. Although the biogenesis of artemisinin, the anti-malarial principle from this species, has been extensively studied over the past twenty years there is still no consensus as to the true biosynthetic route to this important natural product – indeed, some published experimental results are directly contradictory. One possible reason for this confusion may be the ease with which some of the metabolites from A. annua undergo spontaneous autoxidation, as exemplified by our recent in vitro studies of the spontaneous autoxidation of dihydroartemisinic acid, and the application of 13C-2H COSY to this biosynthetic problem has been important in helping to mitigate against such processes. In this in vivo application of 13C-2H COSY, [15-13C2H3]-dihydroartemisinic acid (the doubly-labelled analogue of the natural product from this species which was obtained through synthesis) was fed to A. annua plants and was shown to be converted into several natural products which have been described previously, including artemisinin. It is proposed that all of these transformations occurred via a tertiary hydroperoxide intermediate, which is derived from dihyroartemisinic acid. This intermediate was observed directly in this feeding experiment by the 13C-2H COSY technique; its observation by more traditional procedures (e.g., chromatographic separation, followed by spectroscopic analysis of the purified product) would have been difficult owing to the instability of the hydroperoxide group (as had been established previously by our in vitro studies of the spontaneous autoxidation of dihydroartemisinic acid). This same hydroperoxide has been reported as the initial product of the spontaneous autoxidation of dihydroartemisinic acid in our previous in vitro studies. Its observation in this feeding experiment by the 13C-2H COSY technique, a procedure which requires the minimum of sample manipulation in order to achieve a reliable identification of metabolites (based on both 13C and 2H chemical shifts at the 15-position), provides the best possible evidence for its status as a genuine biosynthetic intermediate, rather than merely as an artifact of the experimental procedure.

Total synthesis of (+/-) maculalactone A, maculalactone B and maculalactone C and the determination of the absolute configuration of natural (+) maculalactone A by asymmetric synthesis

Maculalactones A, B and C from the marine cyanobacterium Kyrtuthrix maculans are amongst the only compounds based on the tribenzylbutyrolactone skeleton known in nature and (+) maculalactone A from the natural source possesses significant biological activity against various marine herbivores and marine settlers. We now report a concise synthesis of racemic maculalactone A in five steps from inexpensive starting materials. Maculalactones B and C were synthesized by a minor modification to this procedure, and the synthetic design also permitted an asymmetric synthesis of maculalactone A to be achieved in around 85% ee. The (+) and (-) enantiomers of maculalactone A were assigned, respectively, to the S and R configurations on the basis of the chiral selectivity expected for catecholborane reduction of an unsymmetrical ketone in the presence of Corey's oxazoborolidine catalyst. Surprisingly, it appeared that natural (+) maculalactone A was biosynthesized in K. maculans in a partially racemic form, comprising ca. 90-95% of the (S) enantiomer and 5-10% of its (R) enantiomer. Coincidentally therefore, the percentage enantiomeric excess of the product obtained from asymmetric synthesis almost exactly matched that found in nature. (C) 2004 Elsevier Ltd. All rights reserved.

Cigarette smokers differ in their handling of natural (RRR) and synthetic (all rac) alpha-tocopherol: a biokinetic study in apoE4 male subjects

We have compared the biokinetics of deuterated natural (RPR) and synthetic (all rac) alpha-tocopherol in male apoE4-carrying smokers and nonsmokers. In a randomized, crossover study subjects underwent two 4-week treatments (400 mg/day) with undeuterated RRR- and all rac-alpha-tocopheryl acetate around a 12-week washout. Before and after each supplementation period subjects underwent a biokinetic protocol (48 h) with 150 mg deuterated RRR- or all rac-alpha-tocopheryl acetate. During the biokinetic protocols, the elimination of endogenous plasma alpha-tocopherol was significantly faster in smokers (P < 0.05). However, smokers had a lower uptake of deuterated RRR than nonsmokers, but there was no difference in uptake of deuterated all rac. The supplementation regimes significantly raised plasma alpha-tocopherol (P < 0.001) with no differences in response between smokers and nonsmokers or between alpha-tocopherol forms. Smokers had significantly lower excretion of alpha-carboxyethyl-hydroxychroman than nonsmokers following supplementation (P < 0.05). Nonsmokers excreted more alpha-carboxyethyl-hydroxychroman following RRR than all rac; however, smokers did not differ in excretion between forms. At baseline, smokers had significantly lower ascorbate (P < 0.01) and higher F(2-)isoprostarres (P < 0.05). F-2-isoprostanes in smokers remained unchanged during the study, but increased in nonsmokers following alpha-tocopherol supplementation. These data suggest that apoE4-carrying smokers and nonsmokers differ in their handling of natural and synthetic alpha-tocopherol. (c) 2006 Elsevier Inc. All rights reserved.

Swarms of computational resources and swarms of tasks for building reliable systems

Space applications demand the need for building reliable systems. Autonomic computing defines such reliable systems as self-managing systems. The work reported in this paper combines agent based and swarm robotic approaches leading to swarm-array computing, a novel technique to achieve autonomy for distributed parallel computing systems. Two swarm-array computing approaches based on swarms of computational resources and swarms of tasks are explored. FPGA is considered as the computing system. The feasibility of the two proposed approaches that binds the computing system and the task together is simulated on the SeSAm multi-agent simulator.

The inhibitory effect of natural microflora of food on growth of Listeria monocytogenes in enrichment broths

The aims of this study were to (i) compare the inhibitory effects of the natural microflora of different foods on the growth of Listeria monocytogenes during enrichment in selective and non-selective broths; (ii) to isolate and identify components of the microflora of the most inhibitory food; and (iii) to determine which of these components was most inhibitory to growth of L. monocytogenes in co-culture studies. Growth of an antibioticresistant marker strain of L. monocytogenes was examined during enrichment of a range of different foods in Tryptone Soya Broth (TSB), Half Fraser Broth (HFB) and Oxoid Novel Enrichment (ONE) Broth. Inhibition of L. monocytogenes was greatest in the presence of minced beef, salami and soft cheese and least with prepared fresh salad and chicken pâté. For any particular food the numbers of L. monocytogenes present after 24 h enrichment in different broths increased in the order: TSB, HFB and ONE Broth. Numbers of L. monocytogenes recovered after enrichment in TSB were inversely related to the initial aerobic plate count (APC) in the food but with only a moderate coefficient of determination (R2) of 0.51 implying that microbial numbers and the composition of the microflora both influenced the degree of inhibition of L. monocytogenes. In HFB and ONE Broth the relationship between APC and final L. monocytogenes counts was weaker. The microflora of TSB after 24 h enrichment of minced beef consisted of lactic acid bacteria, Brochothrix thermosphacta, Pseudomonas spp., Enterobacteriaceae, and enterococci. In co-culture studies of L. monocytogenes with different components of the microflora in TSB, the lactic acid bacteria were the most inhibitory followed by the Enterobacteriaceae. The least inhibitory organisms were Pseudomonas sp., enterococci and B. thermosphacta. In HFB and ONE Broth the growth of Gram-negative organisms was inhibited but lactic acid bacteria still reached high numbers after 24 h. A more detailed study of the growth of low numbers of L. monocytogenes during enrichment of minced beef in TSB revealed that growth of L. monocytogenes ceased at a cell concentration of about 102 cfu/ml when lactic acid bacteria entered stationary phase. However in ONE Broth growth of lactic acid bacteria was slower than in TSB with a longer lag time allowing L. monocytogenes to achieve much higher numbers before lactic acid bacteria reached stationary phase. This work has identified the relative inhibitory effects of different components of a natural food microflora and shown that the ability of low numbers of L. monocytogenes to achieve high cell concentrations is highly dependent on the extent to which enrichment media are able to inhibit or delay growth of the more effective competitors.