Gastric ezrin was initially identified as a phosphoprotein associated with parietal cell activation. To explore the nature of ezrin phosphorylation, proteins from resting and secreting gastric glands were subjected to two-dimensional SDS-PAGE. Histamine triggers acid secretion and a series of acidic isoforms of ezrin on two-dimensional SDS-PAGE. Mass spectrometric analysis of these acidic ezrin spots induced by stimulation suggests that Ser 66 is phosphorylated. To determine whether Ser 66 is a substrate of protein kinase A (PKA), recombinant proteins of ezrin, both wild type and S66A mutant, were incubated with the catalytic subunit of PKA and [ Ezrin is an actin-binding protein of the ezrin/radixin/moesin (ERM) 1 family of cytoskeleton membrane linker proteins (1). Within the gastric epithelium, ezrin has been localized exclusively to parietal cells and primarily to the apical canalicular membrane of these cells (e.g. Refs. 2 and 3). Because of its cytolocalization and observed stimulation-dependent phosphorylation, an implied role for ezrin was suggested in the apical surface membrane remodeling associated with parietal cell activation via the protein kinase A pathway. Phosphorylation of ezrin has also been shown to be associated with surface membrane remodeling of A431 cells stimulated by epidermal growth factor, although activation in this case was via protein tyrosine kinase (4, 5). Our previous studies showed that gastric ezrin is co-distributed with the ␤-actin isoform in vivo (6) and preferentially bound to the ␤-actin isoform in vitro (7). However, it is still not clear how ezrin is involved in the membrane cytoskeletal dynamics triggered by histamine stimulation.Using fluorescence resonance energy transfer monitored by fluorescence lifetime imaging microscopy and chemotaxis assays (8), it has been shown that protein kinase C-mediated phosphorylation of CD44 and ezrin modulates the interaction between these two proteins in vivo and that this phosphorylation was critical for CD44-directed cell motility, suggesting that phosphorylation of ezrin and its accessory proteins provides means to regulate the membrane cytoskeletal dynamics in response to stimulation. Whereas protein kinase C-mediated phosphorylation of CD44 was mapped to Ser 291 , the nature of ezrin phosphorylation is not characterized.Phosphorylation has been proposed to regulate ERM activation, since phosphorylation of ERM proteins correlates with their cytoskeletal association, whereas dephosphorylation of ezrin is parallel to its liberation from actin-based cytoskeleton (e.g. Refs. 9 and 10). Ezrin is phosphorylated on tyrosine residues upon growth factor stimulation (11-13). In response to epidermal growth factor, ezrin phosphorylation on tyrosines 145 and 353 is concomitant with an increase in dimer formation, suggesting a causal relationship between phosphorylation and oligomerization (14, 15). However, mutations of these tyrosines into phenylalanines does not alter ezrin localization in microvilli, and production of this mutated ezrin d...

CaAl2O4:Eu is a persistent luminescence (PL) material in the blue light region with potentially wide commercial applications. With the doping of Nd, the decay time can be elongated to more than 19 h. These excellent properties are believed to be in close relation with the electronic structures of the dopants, the defects, and the host material. In this work, we attempt to achieve a better understanding of the PL mechanism of CaAl2O4:Eu based on first-principles calculations. The electronic structures of the host CaAl2O4, the luminescent center Eu, the O and Ca vacancies, and the dopant Nd are systematically studied. According to the calculations, the 4f and 5d levels of Eu are located within the band gap and slightly above the conduction band minimum (CBM), respectively. The electrons on the 4f levels can be excited into the 5d levels via ultraviolet radiation. The excited electrons on the 5d levels can move to the conduction bands and become free electron carriers. The electron carriers can be trapped for a short period by the empty defect levels below the CBM if they are very close to the defects and then return back into the conduction band. After the trap–release process, the electrons may re-enter the 5d levels of Eu and then move back to the 4f levels accompanied by light emission. The +2 charged-state O vacancies can serve as electron traps. The Ca vacancies cannot contribute to the PL property directly but can assist in stabilizing the +2 charged-state O vacancies. Nd dopants can serve as both electron donors and electron traps. These new insights into the electronic structures are useful for determining which materials may possess good PL properties, thereby motivating more experimental efforts in synthesizing improved PL materials.

Purpose The early detection of lung cancer in heavy smokers by low-dose CT (LDCT) can reduce the mortality. However, LDCT screening increases the number of indeterminate solitary pulmonary nodules (SPNs) in asymptomatic individuals, leading to overdiagnosis. Making a definitive preoperative diagnosis of malignant SPNs has been a clinical challenge. We have demonstrated that sputum miRNAs could provide potential biomarkers for lung cancer. Here we aimed to develop sputum miRNA biomarkers for diagnosis of malignant SPNs. Experimental Design Using quantitative reverse transcriptase PCR, we evaluated expressions of 13 sputum miRNAs, previously identified sputum miRNA signatures of lung cancer, in a training set of 122 patients with either malignant (n=60) or benign SPNs (n=62) to define a panel of biomarkers. We then validated the biomarker panel in an internal testing set of 136 patients with either malignant (n=67) or benign SPNs (n=69), and an external testing cohort of 155 patients with either malignant (n=76) or benign SPNs (n=79). Results In the training set, a panel of three miRNA biomarkers (miRs-21, 31, and 210) was developed, producing 82.93% sensitivity and 87.84% specificity for identifying malignant SPNs. The sensitivity and specificity of the biomarkers in the two independent testing cohorts were 82.09% and 88.41%, 80.52% and 86.08%, respectively, confirming the diagnostic value. Conclusions Sputum miRNA biomarkers may improve LDCT screening for lung cancer in heavy smokers by preoperatively diagnosing malignant SPNs. Nevertheless, a prospective study in a large population to validate the biomarkers is needed.

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