E,E,E-1-(4-Arylamino-4-oxo-2-butenoyl)-3,5-bis(arylidene)-4-piperidones: a topographical study of some novel potent cytotoxins

A series of E,E,E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC(50) figures were submicromolar and lower than melphalan. Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan. Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50-100 microM. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice.     

Land Use Implications of Increased Biomass Production Identified by GIS-Based Suitability and Yield Mapping for Miscanthus in England

The need for climate change mitigation and to meet increasing energy demands has led to a rise in the land area under bioenergy crops in many countries. There are concerns that such large-scale land conversion will conflict with food production and impact on the environment. Perennial biomass crops could be grown on more marginal agricultural land. However, for sustainable solutions, biomass yields will need to be sufficient and the wider implications of land-use changes considered. Here, focusing on Miscanthus in England as an example, we combined an empirical model with GIS to produce a yield map and estimated regional energy generation potentials after masking out areas covered by environmental and socio-economic factors which could preclude the planting of energy crops. Agricultural land quality and the distributions of currently grown food crops were then taken into account. Results showed that: (i) regional contrasts occur in the importance of different factors affecting biomass planting; (ii) areas with the highest biomass yields co-locate with food producing areas on high grade land, and; (iii) when such high grade land and unsuitable areas are excluded, a policy-related scenario for increased planting on 350,000 ha utilised 4–28% (depending on the region) of lower grade land and would not necessarily greatly impact on UK food security. We conclude that the GIS-based yield and suitability mapping described here can help identify important issues in bioenergy generation potentials and land use implications at regional or finer spatial scales that would be missed in analyses at the national level.     

Ecology of Australia: the effects of nutrient-poor soils and intense fires

Australia, the flattest, driest, and geologically oldest vegetated continent, has a uniquely high proportion of nutrient-poor soils. We develop a "Nutrient-Poverty/Intense-Fire Theory," which postulates that most anomalous features of organisms and ecosystems of Australia are the evolutionary consequences of adaptations to nutrient poverty, compounded by intense fire that tends to occur as a result of nutrient poverty. The fundamental tenet of the theory is that plants growing in environments with plentiful light and periodic adequate moisture, but on soils poor in phosphorus, zinc, and other indispensible nutrients, can synthesize carbohydrates in excess of the amount that can be combined with, or catalyzed by, these nutrients for metabolism and production of nutrient-rich foliage and reproductive tissues. They use this "expendable energy" to produce well-defended foliage, large quantities of lignified tissues, and readily digestible exudates. Rapid accumulation of nutrient-poor biomass, a result of low rates of herbivory, provides fuel for intense fire. Intense fire exacerbates nutrient poverty by volatilizing certain micronutrients critical for animals. Anomalous features of organisms of Australia that can be explained by this theory, rather than by climate or phylogenetic history alone, include the following: most woody plants have long-lived, durable foliage; plants defend their tissues primarily with carbon-rich but nutrient-poor compounds; an unusually high proportion of plants protects seeds from fire and granivores in sturdy, woody capsules or follicles; plants allocate unusually large amounts of expendable energy to production of carbon-based exudates, such as nectar and gums; an unusually high proportion of plant species is pollinated by vertebrates that average larger size than pollinators on other continents; herbivores are small and have slow metabolism; there are no ruminants, mammals that eat mainly subterranean plant matter, or fungus-culturing termites and ants; vegetation dominated by leaf-spinescent plants is more extensive than vegetation dominated by stem-spinescent plants; nitrogen-fixing plants are major components of most vegetation types; there is a higher proportion of myrmecochorous plant species than on any other continent; there are hardly any stem-succulent and few leaf-succulent, perennial, non-halophytic plant species; and an unusually high proportion of bird species breeds cooperatively. Although the Nutrient-Poverty/Intense-Fire Theory can provide plausible explanations for these anomalous features, some puzzles remain, among them the great success of introduced herbivores, the lack of grazers on extensive grasslands on cracking clays, the apparently low productivity of ants, and the prominence of the parasitic plants of Australia. By examining the ratios of available energy to nutrients, particularly scarce nutrients, ecologists may identify processes not previously recognized as important for life forms or biotic adaptation on other continents.     

Carbon and nitrogen cycling in North American boreal forests

A model of boreal forest dynamics was adapted to examine the factors controlling carbon and nitrogen cycling in the boreal forests of interior Alaska. Empirical relationships were used to simulate decomposition and nitrogen availability as a function of either substrate quality, the soil thermal regime, or their interactive effects. Test comparisons included black spruce forests growing on permafrost soils and black spruce, birch, and white spruce forests growing on permafrost-free soils. For each forest, simulated above-ground tree biomass, basal area, density, litterfall, moss biomass, and forest floor mass, turnover, thickness, and nitrogen concentration were compared to observed data. No one decay equation simulated forests entirely consistent with observed data, but over the range of upland forest types in interior Alaska, the equation that combined the effects of litter quality and the soil thermal regime simulated forests that were most consistent with observed data. For black spruce growing on permafrost soils, long-term simulated forest dynamics in the absence of fire resulted in unproductive forests with a thick forest floor and low nitrogen mineralization. Fires were an important means to interrupt this sequence and to restart forest succession.     

An X-ray microprobe facility using synchrotron radiation

Biological Trace Element Research - An X-ray microprobe for trace elemental analysis at micrometer spatial resolutions, using synchrotron radiation (SR), is under development. The facility consists...     

AMINO ACID METABOLISM AND AMMONIA FORMATION IN BRAIN SLICES

The formation of ammonia and changes in the contents of free amino acids have been investigated in slices of guinea pig cerebral cortex incubated under the following conditions: (1) aerobically in glucose-free saline; (2) aerobically in glucose-free saline containing 10 mM-bromofuroic acid, an inhibitor of glutamate dehydrogenase (EC 1.4.1.2); (3) aerobically in saline containing 11-1 mM-glucose and (4) anaerobically in glucose-free saline. Ammonia was formed at a steady rate aerobically in glucose-free medium. The formation of ammonia was largely suppressed in the absence of oxygen or in the presence of glucose whereas the inhibitor of glutamate dehydrogenase produced about 50 per cent inhibition. Other inhibitors of glutamate dehydrogenase exerted a similar effect. Ammonia formation was also inhibited by some inhibitors of aminotransferases but not by others. Inhibition was generally more pronounced during the second and third hour of incubation. With the exception of glutamine which decreased slightly, the contents of all amino acids increased markedly during the anaerobic incubation. During aerobic incubation in a glucose-free medium, there was an almost complete disappearance of glutamic acid and GABA. Glutamine also decreased, but to a relatively smaller extent. The content of all other amino acids increased during aerobic incubation in glucose-free medium, although to a lesser extent than under anaerobic conditions. The greater increase of amino acids appearing anaerobically in comparison to the increase or decrease occurring under aerobic conditions corresponded closely to the greater amount of ammonia formed aerobically over that formed anaerobically. This finding is interpreted as indicating a similar degree of proteolysis under anaerobic and aerobic conditions; aerobically, the amino acids are partly metabolized with the concomitant liberation of ammonia. In glucose-supplemented medium, the content of glutamine was markedly increased. The content of glutamate and aspartate remained unchanged, whereas that of some other amino acids increased but to a lesser extent than in the absence of glucose. Proteolysis in the presence of glucose was estimated at about 65 per cent of that in its absence. In the presence of bromofuroate the rate of disappearance of glutamate was unchanged, but there was a larger increase in the content of aspartate and a smaller decrease of GABA and glutamine. Other changes did not differ significantly from those observed in the absence of bromofuroate. We conclude that the metabolism of amino acids in general and of glutamic acid in particular differs according to whether they are already present within the brain slice or are added to the incubation medium. Only the endogenous amino acids appear to be able to serve as precursors of ammonia and as substrates for energy production.     

Effect of dung burial by the dung beetle Bubas bison on numbers and viability of Cryptosporidium oocysts in cattle dung

Cryptosporidium oocysts were inoculated into fresh dung (∼1.2 × 10⁴ oocysts per gram wet weight) and fed to dung beetles to assess the effect of dung burial by the dung beetle Bubas bison on the distribution of the oocysts in small cores of soil in the laboratory. The experiment consisted of five replicates of each of two treatments; controls (dung but no dung beetles) and the experimental treatment (inoculated dung and seven pairs of dung beetles). After 5 days, when approximately 90% of the dung was buried, the surface and buried dung was recovered and subsampled. The oocysts in the subsamples were recovered and enumerated using qPCR. Oocyst viability was evaluated using an assay based on the exclusion or inclusion of two fluorogenic vital dyes, 4′,6-diamidino-2-phenylindole (DAPI) and propidium iodide (PI). Results revealed that overall 13.7% of oocysts remained on the surface and 86.3% of oocysts were buried. The viability of oocysts in buried dung was only 10% compared to oocysts the surface dung (58%). Therefore, widespread dung burial by B. bison during the winter months could substantially reduce the numbers of Cryptosporidium oocysts available to be washed into waterways following winter rains.     

SPATIOTEMPORAL VARIATION IN LINEAR NATURAL SELECTION ON BODY COLOR IN WILD GUPPIES (POECILIA RETICULATA)

We conducted 10 mark–recapture experiments in natural populations of Trinidadian guppies to test hypotheses concerning the role of viability selection in geographic patterns of male color variation. Previous work has reported that male guppies are more colorful in low‐predation sites than in high‐predation sites. This pattern of phenotypic variation has been theorized to reflect differences in the balance between natural (viability) selection that disfavors bright male color (owing to predation) and sexual selection that favors bright color (owing to female choice). Our results support the prediction that male color is disfavored by viability selection in both predation regimes. However, it does not support the prediction that viability selection against male color is weaker in low‐predation experiments. Instead, some of the most intense bouts of selection against color occurred in low‐predation experiments. Our results illustrate considerable spatiotemporal variation in selection among experiments, but such variation was not generally correlated with local patterns of color diversity. More complex selective interactions, possibly including the indirect effects of predators on variation in mating behavior, as well as other environmental factors, might be required to more fully explain patterns of secondary sexual trait variation in this system.