No abstract

Plant-derived essential oils with monoterpenoids have been used as antifungal drugs since ancient times, but the mode of action of these natural hydrocarbons at the molecular level is not understood. In order to understand the mechanisms of toxicity of alpha-terpinene (a cyclic monoterpene), a culture of Saccharomyces cerevisiae was exposed to 0.02% alpha-terpinene for 2 h and transcript profiles were obtained using yeast DNA arrays. These profiles, when compared with transcript profiles of untreated cultures, revealed that the expression of 793 genes was affected. For 435 genes, mRNA levels in treated cells compared with control cells differed by more than two-fold, whereas for 358 genes, it was <0.5-fold. Northern blots were performed for selected genes to verify the microarray results. Functional analysis of the up-regulated genes indicates that, similar to commonly used antifungal drugs, alpha-terpinene exposure affected genes involved in ergosterol biosynthesis and sterol uptake. In addition, transcriptional induction of genes related to lipid metabolism, cell wall structure and function, detoxification and cellular transport was observed in response to terpinene toxicity. Notably, the functions of 192 up-regulated genes are still unknown, but their characterization will probably shed light on the mechanisms of drug resistance and sensitivity. Taken together, this study showed that alpha-terpinene has strong antifungal activities and its modes of action resemble those of presently used antifungal drugs.

No abstract

Based on a recent progress in nonequilibrium statistical mechanics of infinitely extended quantum systems, a nonequlibrium steady state (NESS) is constructed for a single-level quantum dot interacting with two free reservoirs under less general but more practically useful conditions than the previous works. As an example, a model of an Ahoronov-Bohm ring with a quantum dot is studied in detail. Then, NESS is shown to be regarded as a MacLennan-Zubarev ensemble. A formal relation between response and correlation at NESS is derived as well.stands for non-systematic energy flow, or heat flow, to the jth subsystem. A convergence factor e ǫs (ǫ > 0) is introduced in the time integral, where the limit ǫ → 0 is taken after all the calculations. As discussed in Ref. 2), this ensemble well describes nonequilibrium phenomena, but it has a fundamental difficulty. Indeed, because J S (s) is the sum of heat flows divided by subsystem tempertures, it is the entropy production rate of the whole system. Hence, if the ensemble (1 . 1) would describe a state consistent with the second law of thermodynamics, the average of J S (s) over ρ + should be a positive constant and, as a cosequence, the integral in (1 .

For a development of deep tumor treatment in photodynamic therapy, a feasibility of novel radiosensitizers induced by x-ray was investigated. The sensitizers are designed to generate reactive oxygen species (ROS) inside or outside the cell, possibly leading to damage exclusively on tumor cells and reservation of normal cells along the x-ray path. Taking note of the similarity in energy transfer mechanism in photocatalysts, scintillators, and particulate semiconductors, we chose TiO 2 , ZnS:Ag, CeF 3 , and quantum dots (CdTe and CdSe) in particulate form, which contain heavy atoms for efficient absorption of x-rays. A parameter study for x-ray operating conditions showed that in a typical scenario, photons with 20 to 170 keV energy are attenuated by 90% through the region of particle dispersed aqueous solution at varying concentration between 0.01 and 100 wt%. The amount of ROS generation under the exposure of polychromatic x-ray was measured using dihydroethidium reagent which detects an integrated amount of several species. Proportional increase in ROS generation to x-ray dose was observed for varying concentrations of TiO 2 , ZnS:Ag, CeF 3 , and CdSe quantum dot dispersions. Then, HeLa cells were mixed with aqueous solutions dispersed with sensitizing materials at a concentration of 3.0 mg/ml and were exposed to x-ray. Their survival fraction obtained by a cell proliferation reagent WST-1 immediately after the irradiation showed insignificant effects of sensitizing materials except at large doses. To enhance the sensitization effect, bio-conjugated CdSe quantum dots were internalized in the cytoplasm up to a concentration of 1.0 ng/ml. The cells were irradiated by x-ray up to 5 Gy, and their survival fraction was measured by the colony forming ability 9 days after irradiation. Survival fraction of the cells treated with quantum dots were less than those without quantum dots for all doses, suggesting that the colony forming ability is impaired by the internalized quantum dots.