EBV-Encoded LMP1 Upregulates Igκ 3′Enhancer Activity and Igκ Expression in Nasopharyngeal Cancer Cells by Activating the Ets-1 through ERKs Signaling

Accumulating evidence indicates that epithelial cancer cells, including nasopharyngeal carcinoma (NPC) cells, express immunoglobulins (Igs). We previously found that the expression of the kappa light chain protein in NPC cells can be upregulated by the EBV-encoded latent membrane protein 1 (LMP1). In the present study, we used NPC cell lines as models and found that LMP1-augmented kappa production corresponds with elevations in ERKs phosphorylation. PD98059 attenuates LMP1-induced ERKs phosphorylation resulting in decreased expression of the kappa light chain. ERK-specific small interfering RNA blunts LMP1-induced kappa light chain gene expression. Luciferase reporter assays demonstrate that immunoglobulin κ 3′ enhancer (3′Eκ) is active in Igκ-expressing NPC cells and LMP1 upregulates the activity of 3′Eκ in NPC cells. Moreover, mutation analysis of the PU binding site in 3′Eκ and inhibition of the MEK/ERKs pathway by PD98059 indicate that the PU site is functional and LMP1-enhanced 3′Eκ activity is partly regulated by this site. PD98059 treatment also leads to a concentration-dependent inhibition of LMP1-induced Ets-1 expression and phosphorylation, which corresponds with a dose-dependent attenuation of LMP1-induced ERK phosphorylation and kappa light chain expression. Suppression of endogenous Ets-1 by small interfering RNA is accompanied by a decrease of Ig kappa light chain expression. Gel shift assays using nuclear extracts of NPC cells indicate that the transcription factor Ets-1 is recruited by LMP1 to the PU motif within 3′Eκ in vitro. ChIP assays further demonstrate Ets-1 binding to the PU motif of 3′Eκ in cells. These results suggest that LMP1 upregulates 3′Eκ activity and kappa gene expression by activating the Ets-1 transcription factor through the ERKs signaling pathway. Our studies provide evidence for a novel regulatory mechanism of kappa expression, by which virus-encoded proteins activate the kappa 3′ enhancer through activating transcription factors in non-B epithelial cancer cells

Mild Depression Detection of College Students: an EEG-Based Solution with Free Viewing Tasks

Depression is a common mental disorder with growing prevalence; however current diagnoses of depression face the problem of patient denial, clinical experience and subjective biases from self-report. By using a combination of linear and nonlinear EEG features in our research, we aim to develop a more accurate and objective approach to depression detection that supports the process of diagnosis and assists the monitoring of risk factors. By classifying EEG features during free viewing task, an accuracy of 99.1%, which is the highest to our knowledge by far, was achieved using kNN classifier to discriminate depressed and non-depressed subjects. Furthermore, through correlation analysis, comparisons of performance on each electrode were discussed on the availability of single channel EEG recording depression detection system. Combined with wearable EEG collecting devices, our method offers the possibility of cost effective wearable ubiquitous system for doctors to monitor their patients with depression, and for normal people to understand their mental states in time. © 2015, Springer Science+Business Media New York

Contextual socioeconomic determinants of tooth loss in adults and elderly: a systematic review

OBJECTIVE: To perform a systematic review regarding studies that investigated the association between contextual socioeconomic factors and tooth loss.METHODS: MEDLINE, Embase, and LILACS databases were searched and no language or date restrictions were applied for this research. The search was also carried out at the Brazilian Library of Theses and Dissertations (BDTD), with the objective of seeking unpublished studies. We evaluated the bibliographical and methodological characteristics of the studies, as well as the findings.RESULTS: We found 348 articles, out of which only 6 were included in this study after revision by 2 independent researchers. We also identified an unpublished thesis. In general, these results show that the socioeconomic context interferes in tooth loss. We found an association between the highest number of missing teeth with less favorable contextual variables, despite the weak evidence, due to the fact that all selected studies had a cross-sectional design.CONCLUSION: We suggest the standardization of outcome formats and exposures in order to favor the comparison between studies and their quantitative analysis.</sec