Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis.

RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes). Emerging diverse roles of Pol III genes suggest that individual Pol III genes are exquisitely regulated by transcription and epigenetic factors. Here we report global Pol III expression/methylation profiles and molecular mechanisms of Pol III regulation that have not been as extensively studied, using nc886 as a representative Pol III gene. In a human mammary epithelial cell system that recapitulates early breast tumorigenesis, the fraction of actively transcribed Pol III genes increases reaching a plateau during immortalization. Hyper-methylation of Pol III genes inhibits Pol III binding to DNA via inducing repressed chromatin and is a determinant for the Pol III repertoire. When Pol III genes are hypo-methylated, MYC amplifies their transcription, regardless of its recognition DNA motif. Thus, Pol III expression during tumorigenesis is delineated by methylation and magnified by MYC.

Functional neuroanatomical correlates of the executive clock drawing task (CLOX) performance in Alzheimer's disease: a FDG-PET study.

The executive clock drawing task (CLOX) is one of the widely used clock drawing tests (CDTs) and is composed of CLOX1, an unprompted CDT, and CLOX2, a simple copying CDT. Although it is conceptually believed that CLOX1 is sensitive to both executive function and constructional ability while CLOX2 reflects only constructional ability, there are still lack of studies on the functional neuroanatomical substrates of CLOX1 and 2 performances. This study aimed to identify the functional brain correlates of CLOX1 and 2 performances in patients with Alzheimer's disease (AD). CLOX was administered to 139 AD patients and 50 normal controls, and regional cerebral glucose metabolism (rCMglc) was measured by (18)F-fluoro-2-deoxy-glucose positron emission tomography. Correlations between CLOX scores and rCMglc were examined on a voxel-by-voxel basis in AD patients. For the overall AD group, significant positive correlations between CLOX1 and rCMglc were found in the bilateral temporo-parietal and left middle frontal regions, while CLOX2 was correlated with rCMglc of the bilateral temporo-parietal regions. Additional subgroup analysis showed that CLOX1 was associated with the left temporal metabolism in less severe AD, and with the right temporo-parietal metabolism in more severe AD. In contrast, CLOX2 was correlated with rCMglc of the diffuse right fronto-temporo-parietal regions in more severe AD, but not with any rCMglc in less severe AD. This is the first neuroimaging study on the functional neuroanatomical correlates of CLOX performances in AD. Given the relationships between specific cognitive performances and regional brain functions, the findings probably support the notion that CLOX1 demands not merely visuospatial functions but also executive control, while CLOX2 depends mainly on visuospatial ability. Our results also indicate that each CLOX performance depends on very different functional brain regions according to AD clinical stages.

Diagnostic accuracy of mini-mental status examination and revised hasegawa dementia scale for Alzheimer's disease.

To compare the diagnostic accuracies of the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental Status Examination (MMSE) for Alzheimer's diseases (AD), we administered them simultaneously to 82 AD patients and 82 age- and sex-matched nondemented control subjects. The area under the receiver operator curve (AUC) for AD of the HDS-R (AUC(HDS-R)) and MMSE (AUC(MMSE)) were bigger than 0.90 indicating that both tests are useful for detecting AD. However, AUC(HDS-R) (0.952) was significantly larger than that of the AUC(MMSE )(0.902) regardless of the educational level of the subjects, indicating that the HDS-R is more accurate than MMSE in diagnosing AD. Moreover, the superiority of the HDS-R (AUC(HDS-R) = 0.894) to the MMSE (AUC(MMSE) = 0.704) remained significant in mild AD patients alone, who are the focus of screening. In conclusion, the HDS-R is better than the MMSE as a screening instrument for AD.