Sympatric Drosophila simulans flies with distinct mtDNA show age related differences in mitochondrial metabolism

The primary causes of age-related changes in mitochondrial metabolism are not known. The goal of this study is to document the influence of naturally occurring mtDNA variation on age dependent changes in mitochondrial respiration, hydrogen peroxide (H(2)O(2)) generation and antioxidant defenses in the fly Drosophila simulans. Possible changes include an increase in rates of reactive oxygen species production with age and/or an age dependent decrease in antioxidant response. For this study we have used flies harboring distinct siII and siIII mtDNA types. Previously we have shown that males harboring siII mtDNA had higher rates of mitochondrial H(2)O(2) production from complex III at 11d compared to males with the siIII mtDNA type. Here, we corroborate those results and show that Drosophila harboring the siII and siIII mtDNA types exhibit significantly different patterns of pro-oxidant and antioxidant activities as they age. Flies harboring siII mtDNA had higher rates of mitochondrial H(2)O(2) production and manganese superoxide dismutase activity at 11 and 18d of age than siIII mtDNA harboring flies. Copper-zinc superoxide dismutase activity increased from 11 to 25d in siII flies while the accumulation of oxidized glutathione did not change between 11 and 25d. In contrast, siIII harboring flies showed an age dependent increase in H(2)O(2) production, reaching higher production rates on day 25 than that observed in siII flies. Copper-zinc superoxide dismutase activities did not change between 11 and 25d while the oxidized glutathione accumulation increased with age. The results show antioxidant levels correlate with pro-oxidant levels in siII but not siIII flies. These results demonstrate our ability to correlate mtDNA variation with differences in whole mitochondrial physiology and individual complex biochemistry.     

Mucin 13: structure, function, and potential roles in cancer pathogenesis

Mucin 13 (MUC13) is a high-molecular-weight transmembrane glycoprotein that is frequently and aberrantly expressed in a variety of epithelial carcinomas, including gastric, colorectal, and ovarian cancers. On the basis of the high expression of MUC13 in cancer cells as well as recent laboratory findings suggesting a malignant phenotype of MUC13-transfected cell lines, the oncogenic potential of MUC13 has emerged. The various functional domains of MUC13 may confer oncogenic potential to MUC13. For example, the bulky extracellular domain with extensive modification with glycan chains may prevent cell-cell and cell-extracellular matrix binding whereas the cytoplasmic tail containing serine and tyrosine residues for potential phosphorylation may participate in cell signaling. MUC13 exhibits the characteristics suitable as an early marker for cancer screening and presents a promising target for antibody-guided targeted therapy.     

Dipeptidyl peptidase III: a multifaceted oligopeptide N-end cutter

Dipeptidyl peptidase III (DPP III), the sole member and representative of the M49 family of metallopeptidases, is a zinc-dependent aminopeptidase. It sequentially hydrolyses dipeptides from the N-terminal of oligopeptides ranging from three to 10 amino acid residues. Although implicated in an array of pathophysiological phenomena, the precise function of this peptidase is still unclear. However, a number of studies advocate its contribution in terminal stages of protein turnover. Altered expression of DPP III which suggests its involvement in primary ovarian carcinoma, oxidative stress (Nrf2 nuclear localization), pain, inflammation and cataractogenesis has recently led to resurgence of interest in delineating the role of the peptidase in these pathophysiological processes. This review article intends to bring forth the latest updates in this arena which may serve as a base for future studies on the peptidase.     

<Emphasis Type="Italic">Kuth</Emphasis> (<Emphasis Type="Italic">Saussurea lappa</Emphasis>) cultivation in the cold desert environment of the Lahaul valley,northwestern Himalaya,India: arising threats and need to revive socio-economic values

Surveys were conducted in the cold desert environment of the Lahaul valley in the northwestern Himalaya for assessing the past and present status of Kuth (Saussurea lappa) cultivation. The findings reveal that this age-old practice now is in bottleneck. Main factors responsible for this setback to the species were the lengthy cultivation cycle, small land holdings, and even fluctuating and relatively low market prices. Owing to these constraints farmers have now started replacing cultivation of this threatened herb with pea (Pisum sativum L.), potato (Solanum tuberosum L.) and hop (Humulus lupulus L.). These crops obtained popularity due to comparatively more economic returns as well as their easy adaptability to the short growth season of the cold desert environment. Kuth cultivation in this region is among the interesting examples of domesticating wild medicinal herb by some innovative farmers during the 1920s. However, in the recent past farmers have been less interested to continue this practice due to its larger cultivation cycle, more profits with cash crops like pea and potato, and permit formalities at the time of export from the valley. In addition to being the oldest cash crop in the cold desert environment, Kuth is an endangered medicinal herb that has to be conserved on a priority basis. This study attempts to find out potential measures such as regular revision of market rates, development of existing uncultivable land under medicinal plant cultivation and strengthening the marketing network through establishment of federations of farmers at village level to revive cultivation of this important species.     

Combination Treatment with Resveratrol and Sulforaphane Induces Apoptosis in Human U251 Glioma Cells

Resveratrol is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Sulforaphane belongs to the family of isothiocyanates and is highly enriched in cruciferous vegetables. Our previous study showed that resveratrol, when used at high concentrations, inhibited cell proliferation, caused the cell cycle arrest and induced apoptotic cell death in glioma cells. In the current study, we tested the effect of combination treatment with resveratrol and sulforaphane, when both were used at low concentrations, on cell proliferation, migration and death in human U251 glioma cells. Our study shows that combination treatment with resveratrol and sulforaphane inhibits cell proliferation and migration, reduces cell viability, induces lactate dehydrogenase release, decreases pro-survival Akt phosphorylation and increases caspase-3 activation. The use of combination of bioactive food components, such as resveratrol and sulforaphane, may be a viable approach for the treatment of glioma.     

Microbial oxidation of naphthalene to cis-1,2-naphthalene dihydrodiol using naphthalene dioxygenase in biphasic media

The selective oxidation of aryl substrates to chiral cis-1,2-dihydrodiols is an industrially important reaction for the production of intermediates that can be used to produce fine chemicals, pharmaceuticals, and many other bioactive natural products. More specifically, the oxidation of naphthalene to produce optically pure (+)-cis-(1R,2S)-1,2-napthalene dihydrodiol (NDHD) to be used as a chiral synthon for specialty chemicals has gained much interest. Escherichia coli JM109(DE3) pDTG141 expresses naphthalene dioxygenase which catalyzes this reaction. Poor substrate solubility and substrate toxicity are barriers to using the power of these enzymes in large-scale aqueous whole cell systems. A biphasic reaction system was chosen to overcome these barriers. The optimal biphasic conditions for E. coli JM109(DE3) pDTG141 were determined to be 20% dodecane as the organic solvent containing 40 g/L naphthalene. The productivity of the biotransformation using resting cells was 1.75 g-diol/g-cdw/h for the first 6 h with 20% organic phase, which was increased from 0.59 g-diol/g-cdw/h for growing cells with 40% organic phase. The biocatalytic activity was retained for at least 12 h. The biocatalyst could be recycled for at least four runs in both suspended and immobilized form. The stability of the 12 h recycle was improved by immobilization in calcium alginate beads. The process has been improved both environmentally and economically by reducing the amount of solvent used and by recycling the biocatalyst.