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Jessica L. Tischler Basel Abuaita Sierra C. Cuthpert Christopher Fage Kristi Murphy Andrew Saxe 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):549-555
Butyric acid and trichostatin A (TSA) are anti-cancer compounds that cause the upregulation of genes involved in differentiation and cell cycle regulation by inhibiting histone deacetylase (HDAC) activity. In this study we have synthesized and evaluated compounds that combine the bioavailability of short-chain fatty acids, like butyric acid, with the bidentate binding ability of TSA. A series of analogs were made to examine the effects of chain length, simple aromatic cap groups, and substituted hydroxamates on the compounds' ability to inhibit rat-liver HDAC using a fluorometric assay. In keeping with previous structure-activity relationships, the most effective inhibitors consisted of longer chains and hydroxamic acid groups. It was found that 5-phenylvaleric hydroxamic acid and 4-benzoylbutyric hydroxamic acid were the most potent inhibitors with IC50's of 5 μM and 133 μM respectively. 相似文献
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Mike Letnic Aaron Greenville Elizabeth Denny Christopher R. Dickman Max Tischler Christopher Gordon Freya Koch 《Global Ecology and Biogeography》2011,20(2):343-353
Aim We examined evidence for the mesopredator release hypothesis at a subcontinental scale by investigating the relationship between indices of abundance of the dingo Canis lupus dingo (top‐order predator) and the invasive red fox Vulpes vulpes (mesopredator) in three large regions across mainland Australia. The red fox is known to be one of the major threats to the persistence of small and medium‐sized native vertebrates across the continent. Location Australia. Methods Indices of abundance were calculated from three independently collected datasets derived from bounty returns and field surveys. Data were analysed using univariate parametric, semi‐parametric and nonparametric techniques. Results Predator abundance indices did not conform to a normal distribution and the relationships between dingo and fox abundance indices were not well described by linear functions. Semi‐parametric and nonparametric techniques revealed consistently negative associations between indices of dingo and fox abundance. Main conclusions The results provide evidence that mesopredator suppression by a top predator can be exerted at very large geographical scales and suggest that relationships between the abundances of top predators and mesopredators are not linear. Our results have broad implications for the management of canid predators. First, they suggest that dingoes function ecologically to reduce the activity or abundance of red foxes and thus are likely to dampen the predatory impacts of foxes. More generally, they provide support for the notion that the mesopredator‐suppressive effects of top predators could be incorporated into broad‐scale biodiversity conservation programmes in many parts of the world by actively maintaining populations of top predators or restoring them in areas where they are now rare. Determining the population densities at which the interactions of top predators become ecologically effective will be a critical goal for conservation managers who aim to maintain or restore ecosystems using the ecological interactions of top predators. 相似文献
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Parkinson's disease is a neurodegenerative disorder manifesting in debilitating motor symptoms. This disorder is characterized by abnormal activity throughout the cortico-basal ganglia loop at both the single neuron and network levels. Previous neurophysiological studies have suggested that the encoding of movement in the parkinsonian state involves correlated activity and synchronized firing patterns. In this study, we used multi-electrode recordings to directly explore the activity of neurons from the globus pallidus of parkinsonian primates during passive limb movements and to determine the extent to which they interact and synchronize. The vast majority (80/103) of the recorded pallidal neurons responded to periodic flexion-extension movements of the elbow. The response pattern was sinusoidal-like and the timing of the peak response of the neurons was uniformly distributed around the movement cycle. The interaction between the neuronal activities was analyzed for 123 simultaneously recorded pairs of neurons. Movement-based signal correlation values were diverse and their mean was not significantly different from zero, demonstrating that the neurons were not activated synchronously in response to movement. Additionally, the difference in the peak responses phase of pairs of neurons was uniformly distributed, showing their independent firing relative to the movement cycle. Our results indicate that despite the widely distributed activity in the globus pallidus of the parkinsonian primate, movement encoding is dispersed and independent rather than correlated and synchronized, thus contradicting current views that posit synchronous activation during Parkinson's disease. 相似文献
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Grasslands worldwide have been invaded by woody species during the last200 years. Atmospheric CO2 enrichment may indirectly havefacilitatedinvasion by reducing soil water depletion by grasses. We used a two-stepcorrelative approach to test this hypothesis with the invasive and native shrubhoney mesquite (Prosopis glandulosa Torr. var.glandulosa). 1) Water content to 0.15 m depthwas measured in grassland exposed to a CO2 gradient from 200 to 550mol/mol to evaluate the prediction that CO2enrichment lessens soil water depletion by grasses. 2) Soil water content andemergence and survival of mesquite seedlings were measured in adjacentgrasslandplots from which grass roots were excluded to 0.15 m depth toreduce water depletion or that were irrigated to increase soil water levels.With these measurements, we tested the hypothesis that mesquite establishmentislimited by water.Excluding grass roots doubled emergence of mesquite and almost tripledthe fraction of emergent seedlings that survived for 12 weeks following thefirst of two plantings. Seedlings were taller, heavier, and had greater leafarea when grown without grass roots. Root exclusion did not measurably affectsoil water during the 3-week period of seedling emergence, but soilwatercontent over the 12 weeks that seedling survival was studied was higher inplotsfrom which grass roots were excluded and following an April than May planting.Survivorship of mesquite seedlings correlated positively with soil watercontent. Percentage survival of seedlings increased from 1.5% to15% and 28% at the soil water content measured in grasslandexposed to CO2 concentrations of 270 (preindustrial), 360 (current),and 550 mol/mol (future), respectively. We infer thatrecent and projected increases in atmospheric CO2 concentration maybe large enough to increase establishment of invading mesquite seedlings ingrasslands that are severely water-limited. 相似文献