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Neurodegenerative diseases can have long preclinical phases and insidious progression patterns, but the mechanisms of disease progression are poorly understood. Because quantitative accounts of neuronal circuitry affected by disease have been lacking, it has remained unclear whether disease progression reflects processes of stochastic loss or temporally(More)
Nuclear receptors regulate gene expression by direct activation of target genes and inhibition of AP-1. Here we report that, unexpectedly, activation by nuclear receptors requires the actions of CREB-binding protein (CBP) and that inhibition of AP-1 activity is the apparent result of competition for limiting amounts of CBP/p300 in cells. Utilizing distinct(More)
The transcription factor Smad2 is released from cytoplasmic retention by TGFbeta receptor-mediated phosphorylation, accumulating in the nucleus where it associates with cofactors to regulate transcription. We uncovered direct interactions of Smad2 with the nucleoporins CAN/Nup214 and Nup153. These interactions mediate constitutive nucleocytoplasmic(More)
TGF-β promotes cell migration and invasion, an attribute that is linked to the pro-metastasis function of this cytokine in late stage cancers. The LIM 1863 colon carcinoma organoid undergoes epithelial-mesenchymal transition (EMT) in response to TGF-β. This process is markedly accelerated by TNF-α, and we found that the levels of miR-21 and miR-31 were(More)
BACKGROUND Exposure to diisocyanates, a group of highly reactive, low-molecular-weight compounds, is a major cause of occupational asthma. In contrast to mouse models of atopic asthma, previous mouse models of diisocyanate-induced asthma have failed to show lung inflammation with characteristics of human disease. OBJECTIVE Our goal was to establish a(More)
BACKGROUND In the spring of 2008, an EV71-caused hand, foot, and mouth disease (HFMD) outbreak occurred in Fuyang city, Anhui Province, China. Jiangsu Province that borders Auhui to the east is presumed as a key station for the spread of EV71 to other regions of the Yangtze River Delta. OBJECTIVES To investigate the HFMD prevalence in Zhenjiang city of(More)
  • Lan Xu
  • Biochimica et biophysica acta
  • 2006
TGF-beta (Transforming Growth Factor-beta) cytokines employ Smad proteins as the intracellular mediator of signaling. Upon TGF-beta stimulation, the cytoplasmic Smads become phosphorylated and consequently accumulate in the nucleus to regulate target gene expression. The cytoplasm-to-nucleus redistribution of Smads, as well as the ability of Smads to(More)
Th2 responses are clearly involved in the pathogenesis of atopic disease. Thus, understanding the factors responsible for Th2 sensitization at sites of allergen exposure, such as airway and skin, is crucial for directing therapeutic or preventive strategies. Contrary to other models of Th2 sensitization to proteins, we have reported that Th2 responses(More)
MyD88 is a common Toll-like receptor (TLR) adaptor molecule found to be essential for induction of adaptive Th1 immunity. Conversely, innate control of adaptive Th2 immunity has been shown to occur in a MyD88-independent manner. In this study, we show that MyD88 is an essential innate component in the induction of TLR4-dependent Th2 responses to intranasal(More)
Trafficking of Smad proteins between the cytoplasm and nucleus is a critical component of transforming growth factor beta (TGF-beta) signal transduction. Smad4 translocates into the nucleus either in response to TGF-beta stimulation or when its nuclear export is blocked by leptomycin B (LMB). We demonstrate that both TGF-beta-induced and basal state(More)