Fifteen subjects with MCI and 12 healthy elderly controls were investigated longitudinally (average follow-up period: 3.4 years) using absolute quantification of metabolites within the mid-parietal grey

matter and the parietal white matter [N-acetylaspartate (NAA), myo-inositol, choline, creatine, glutamine)] Our main findings include that a longitudinal decline in cognitive function (particularly in memory function) within the MCI group was predicted by a decline in absolute concentrations of the Daporinad metabolic markers NAA and creatine. This effect was mainly explained by a significant decrease of NAA and creatine in those MCI subjects who converted to Alzheimer’s dementia (AD) during the follow-up period. No differences were found at baseline between MCI converters and stable subjects, indicating that at least in the present study MRS did provide a predictive

discrimination between converters and stable subjects. Our findings support the use of MRS as a tool for objectively monitoring disease progression even during the earliest stages of AD. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“p53 mutation is associated with “”gain-of-function”" capabilities of human cancers. We aim to identify p53 mutations in human glioma cells and to explore the potential mechanism for mutant p53-promoted cellular growth. Whole AZD3965 concentration genomic DNA was isolated

from SWO-38, a human glioma cell line and amplified for the region of exons 5, 6, and 8 in p53 gene using polymerase chain reaction (PCR). By means of direct sequencing of PCR products and alignment analysis using BLAST database, a mutation of G to C transition at codon 280 of p53 exon 8 (AGA -> ACA), i.e. R280T was detected in SWO-38 cells. Knockdown of R280T mutant p53 by RNA interference inhibited the GSK-3 beta/PTEN associated cell proliferation, and PI3K/Akt but not Wnt/beta-catenin signaling pathway Selleck Vorinostat was involved in this process. Furthermore, depletion or overexpression of PTEN alone did not affect cell proliferation and cell cycle, implicating the impairment of PTEN function in SWO-38 cells. However, knockdown of both PTEN and p53 mutation could significantly rescue the p53 depletion-mediated growth inhibition, suggesting that the R280T mutation in glioma may promote the proliferation through an underlying mechanism related to PTEN. Our observations indicate that the R280T mutation of p53 regulates the proliferation of human glioma cells related to the GSK-3 beta/PTEN pathway. These findings provide valuable insights for better understanding the molecular mechanism of uncontrolled growth of glioma cells. (C) 2012 Elsevier Ireland Ltd. All rights reserved.