Recent studies indicate that NF-E2 related factor 2 (Nrf2) is a substrate for the ubiquitin-proteasome pathway. The present study is aimed to determine whether increased protein stability is a mechanism by which quinone compounds, like tert-butylhydroquinone (tBHQ), may enhance Nrf2-mediated transcriptional activation and subsequent antioxidant protection. H2O2-induced necrotic cell death, evidenced by transmission electronic microscope (TEM) imaging with no caspase 3 activation and PARP cleavage, was significantly attenuated by pretreatment with tBHQ or overexpression of Nrf2 through advenovirus-mediated infection in human neural stem cells (hNSCs). Microarray analysis showed that those identified antioxidant genes, responsible for antiapoptotic action in IMR-32 cells (J. Li et al., 2002, J. Biol. Chem. 277, 388-394), were also coordinately upregulated through Nrf2-dependent antioxidant responsive element (ARE) activation in hNSC. The stabilization of Nrf2 by tBHQ in IMR-32 cells was evidenced by a pulse-chase assay showing no significant increase in Nrf2 protein synthesis after tBHQ treatment, and by ubiquitin immunoprecipitation showing that tBHQ stabilized ubiquitinated Nrf2. An in vitro proteasomal activity assay showed that tBHQ did not act as a 20S/26S proteasome inhibitor. Nrf2 stabilization by tBHQ also was observed in hNSCs. Taken together, this study suggests that identified antioxidant genes, which were upregulated through tBHQ induced Nrf2 stabilization, confer protection on target cells against H2O2-induced apoptotic cell death in neuroblastoma cells as well as the necrotic cell death in the hNSC. Nrf2 stabilization by pharmacological modulation or adenovirus-mediated Nrf2 overexpression, therefore, might be viable strategies to prevent a wide-spectrum of oxidative stress-related neuronal cell injuries.

RNAseq and microarray methods are frequently used to measure gene expression level. While similar in purpose, there are fundamental differences between the two technologies. Here, we present the largest comparative study between microarray and RNAseq methods to date using The Cancer Genome Atlas (TCGA) data. We found high correlations between expression data obtained from the Affymetrix one-channel microarray and RNAseq (Spearman correlations coefficients of ∼0.8). We also observed that the low abundance genes had poorer correlations between microarray and RNAseq data than high abundance genes. As expected, due to measurement and normalization differences, Agilent two-channel microarray and RNAseq data were poorly correlated (Spearman correlations coefficients of only ∼0.2). By examining the differentially expressed genes between tumor and normal samples we observed reasonable concordance in directionality between Agilent two-channel microarray and RNAseq data, although a small group of genes were found to have expression changes reported in opposite directions using these two technologies. Overall, RNAseq produces comparable results to microarray technologies in term of expression profiling. The RNAseq normalization methods RPKM and RSEM produce similar results on the gene level and reasonably concordant results on the exon level. Longer exons tended to have better concordance between the two normalization methods than shorter exons.

Recent anatomical evidence suggests a functionally significant back-projection pathway from the subiculum to CA1. Here we show that the afferent circuitry of CA1-projecting subicular neurons is biased by inputs from CA1 inhibitory neurons as well as visual cortex, but lacks input from entorhinal cortex. Efferents of the CA1-projecting subiculum neurons also target perirhinal cortex, Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

HCC differentiation, size and vascular invasion have strong relationships with AFP, poor differentiation and HCC size ≥ 10 cm are independent predictors of elevated AFP. BCLC shows better relationship with AFP.

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