Inhibition of Aggregation of Mutant Huntingtin by Nucleic Acid Aptamers In Vitro and in a Yeast Model of Huntington's Disease.

Elongated polyglutamine stretch in mutant huntingtin (mhtt) correlates well with the pathology of Huntington's disease (HD). Inhibition of aggregation of mhtt is a promising strategy to arrest disease progression. In this work, specific, high-affinity RNA aptamers were selected against monomeric mhtt (51Q-htt). Some of them inhibited its aggregation in vitro by stabilizing the monomer. They also recognized 103Q-htt but not 20Q-htt (nonpathogenic length). Inhibition of aggregation corresponded with reduced leakage of a fluorescent probe from liposomes and diminished oxidative stress in RBCs. The presence of aptamers was able to rescue the sequestration of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by aggregated mhtt. Some of the aptamers were able to enhance the partitioning of mhtt in the soluble fraction in a yeast model of HD. They were also able to rescue endocytotic defect due to aggregation of mhtt. The beneficial effect of a combination of aptamers was enhanced with improvement in cell survival. Since HD is a monogenic autosomal dominant disorder, aptamers may be developed as a viable strategy to slow down the progress of the disease. Since they are nonimmunogenic and nontoxic, aptamers may emerge as strong candidates to reduce protein-protein interaction and hence protein aggregation in protein misfolding disorders in general.

Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat model.

BACKGROUND: Polycystic ovarian syndrome (PCOS), characterized by ovulatory infertility and hyperandrogenism, is associated with metabolic complications such as dyslipidemia, insulin resistance and endothelial dysfunction. Almost 70% PCOS women have abnormal serum lipid levels (dyslipidemia) and 50% of these women are obese. Several classes of pharmacological agents have been used to manage dyslipidemia. However, studies have shown adverse effects associated with these drugs. In the light of alternate therapy, many medicinal herbs have been reported to show hypoglycemic, anti-hyperlipidemic potential. Aloe barbadensis Mill. or Aloe vera is reported as one such herb. This study was to evaluate the lipid correcting effect of Aloe vera gel (AVG) in a PCOS rat model. MATERIALS AND METHODS: PCOS was induced in Charles Foster female rats by oral administration of non-steroidal aromatase inhibitor letrozole (0.5 mg/kg body weight, 21 days). All rats were hyperglycemic and 90% rats also showed elevated plasma triglycerides, elevated LDL cholesterol levels, and lowered plasma HDL cholesterol levels indicative of a dyslipidemic profile. PCOS positive rats with an aberrant lipid profile were selected for treatment. An AVG formulation (1 ml (10 mg)/day, 30 days) was administered orally. RESULTS AND CONCLUSION: AVG treated PCOS rats exhibited significant reduction in plasma triglyceride and LDL cholesterol levels, with an increase in HDL cholesterol. The gel treatment also caused reversion of abnormal estrous cyclicity, glucose intolerance, and lipid metabolizing enzyme activities, bringing them to normal. In conclusion, AVG has phyto components with anti-hyperlipidemic effects and it has shown efficacy in management of not only PCOS but also the associated metabolic complication : dyslipidemia.

Evidence for H(2)O(2) as the product of reduction of oxygen by alternative oxidase in mitochondria from potato tubers.

Oxygen consumption by alternative oxidase (AOX), present in mitochondria of many angiosperms, is known to be cyanide-resistant in contrast to cytochrome oxidase. Its activity in potato tuber (Solanum tuberosum L.) was induced following chilling treatment at 4 degrees C. About half of the total O(2) consumption of succinate oxidation in such mitochondria was found to be sensitive to SHAM, a known inhibitor of AOX activity. Addition of catalase to the reaction mixture of AOX during the reaction decreased the rate of SHAM-sensitive oxygen consumption by nearly half, and addition at the end of the reaction released nearly half of the consumed oxygen by AOX, both typical of catalase action on H(2)O(2). These findings with catalase suggest that the product of reduction of AOX is H(2)O(2) and not H(2)O, as previously surmised. In potatoes subjected to chill stress (4 degrees C) for periods of 3, 5 and 8 days the activity of AOX in mitochondria increased progressively with a corresponding increase in the AOX protein detected by immunoblot of the protein.

Image compression using binary space partitioning trees.

For low bit-rate compression applications, segmentation-based coding methods provide, in general, high compression ratios when compared with traditional (e.g., transform and subband) coding approaches. In this paper, we present a new segmentation-based image coding method that divides the desired image using binary space partitioning (BSP). The BSP approach partitions the desired image recursively by arbitrarily oriented lines in a hierarchical manner. This recursive partitioning generates a binary tree, which is referred to as the BSP-tree representation of the desired image. The most critical aspect of the BSP-tree method is the criterion used to select the partitioning lines of the BSP tree representation, In previous works, we developed novel methods for selecting the BSP-tree lines, and showed that the BSP approach provides efficient segmentation of images. In this paper, we describe a hierarchical approach for coding the partitioning lines of the BSP-tree representation. We also show that the image signal within the different regions (resulting from the recursive partitioning) can be represented using low-order polynomials. Furthermore, we employ an optimum pruning algorithm to minimize the bit rate of the BSP tree representation (for a given budget constraint) while minimizing distortion. Simulation results and comparisons with other compression methods are also presented.