Epidermal growth factor receptor regulates β-catenin location, stability, and transcriptional activity in oral cancer

<p>Abstract</p> <p>Background</p> <p>Many cancerous cells accumulate β-catenin in the nucleus. We examined the role of epidermal growth factor receptor (EGFR) signaling in the accumulation of β-catenin in the nuclei of oral cancer cells.</p> <p>Results</p> <p>We used two strains of cultured oral cancer cells, one with reduced EGFR expression (OECM1 cells) and one with elevated EGFR expression (SAS cells), and measured downstream effects, such as phosphorylation of β-catenin and GSK-3β, association of β-catenin with E-cadherin, and target gene regulation. We also studied the expression of EGFR, β-catenin, and cyclin D1 in 112 samples of oral cancer by immunostaining. Activation of EGFR signaling increased the amount of β-catenin in the nucleus and decreased the amount in the membranes. EGF treatment increased phosphorylation of β-catenin (tyrosine) and GSK-3β(Ser-(9), resulting in a loss of β-catenin association with E-cadherin. TOP-FLASH and FOP-FLASH reporter assays demonstrated that the EGFR signal regulates β-catenin transcriptional activity and mediates cyclin D1 expression. Chromatin immunoprecipitation experiments indicated that the EGFR signal affects chromatin architecture at the regulatory element of cyclin D1, and that the CBP, HDAC1, and Suv39h1 histone/chromatin remodeling complex is involved in this process. Immunostaining showed a significant association between EGFR expression and aberrant accumulation of β-catenin in oral cancer.</p> <p>Conclusions</p> <p>EGFR signaling regulates β-catenin localization and stability, target gene expression, and tumor progression in oral cancer. Moreover, our data suggest that aberrant accumulation of β-catenin under EGFR activation is a malignancy marker of oral cancer.</p

Novel polythiophene derivatives functionalized withconjugated side-chain pendants comprisingtriphenylamine/carbazole moieties for photovoltaic cellapplications†

We synthesized a series of polythiophenes (PTs) featuring 2-ethylhexyl-substituted terthiophene (T) orquaterthiophene (BT) as the conjugated unit in the polymer backbone with pendant conjugated tertbutyl-substituted triphenylamine (tTPA)- or carbazole (tCz)-containing moieties as side chains, namelyPTtTPA, PBTtTPA, PTtCz and PBTtCz. Incorporating T and BT moieties into the polymer backbone andattaching tTPA or tCz units promoted efficient conjugation within the extended conjugated frameworksof the polymers, resulting in lower band-gap energies and red-shifting of the maximal UV-Visabsorption wavelength. The higher electron-donating ability of tTPA resulted in broader absorptionbands and lower band-gap energies of PTtTPA and PBTtTPA as compared with PTtCz and PBTtCz.Incorporation of the T and BT moieties into the polymer backbone enhanced the compatibility of PTand the fullerene derivative by reducing the side-chain density of PT, thus providing sufficient freevolume for efficient incorporation of [6,6]phenyl-C61-butyric acid methyl ester (PC61BM) into thepolymer chains. Polymer solar cells (PSCs) were fabricated by spin-coating a blend of each PT with thefullerene derivative (PC61BM) as a composite film-type photoactive layer; PBTtTPA/PC61BM-based PSCsshowed superior photovoltaic (PV) performance to PTtTPA/PC61BM-based PSCs in terms of conjugationand absorption band broadness. However, PBTtCz/PC61BM-based PSCs showed inferior PV performanceto PTtCz/PC61BM-based PSCs. The lower HOMO level led to a higher open-circuit voltage (Voc; 0.74 V)and larger photo-energy conversion efficiency (h; 2.77%) of PTtCz/PC61BM-based PSCs

The role of TonEBP in regulation of AAD expression and dopamine production in renal proximal tubule cells upon hypertonic challenge

a b s t r a c t Renal proximal tubule cells overexpress aromatic L-amino acid decarboxylase (AAD) to produce dopamine, which inhibits salt absorption in the hypertonic environment. We examined the effect of TonEBP on AAD expression in human proximal tubule epithelial cells, HK-2 cell line. Confocal microscopy showed that after 2 h of exposure to the hypertonic medium, TonEBP accumulation in nuclei increased as compared to the isotonic control. The activated TonEBP enhanced the mRNA expression of the representative downstream genes (i.e., SMIT and TauT). Meanwhile, AAD protein abundance also increased with TonEBP activation. EMSA and luciferase reporter assay showed that TonEBP was involved in transcriptional regulation of AAD upon hypertonic stress. Inactivation of TonEBP by the p38 inhibitor SB203580, or TonEBP shRNA significantly reduced AAD expression, which was rescued by re-expressing Myc-tagged TonEBP. Up-regulation of AAD increased dopamine synthesis, and dopamine inhibited NKA activity in hypertonic condition. These results suggested that TonEBP played an important role in the epithelial cells of renal proximal tubule upon hypertonic stress by enhancing AAD expression, which could promote dopamine secretion to negative regulate NKA activity. The elucidation of a new mechanism described in this study combined with previous findings provides more insights into this issue

Decentralized Base-Graph Routing for the Quantum Internet

Quantum repeater networks are a fundamental of any future quantum Internet and long-distance quantum communications. The entangled quantum nodes can communicate through several different levels of entanglement, leading to a heterogeneous, multi-level network structure. The level of entanglement between the quantum nodes determines the hop distance and the probability of the existence of an entangled link in the network. Here, we define a decentralized routing for entangled quantum networks. The proposed method allows an efficient routing to find the shortest paths in entangled quantum networks by using only local knowledge of the quantum nodes. We give bounds on the maximum value of the total number of entangled links of a path. The proposed scheme can be directly applied in practical quantum communications and quantum networking scenarios.Comment: 13 pages, Journal-ref: Phys. Rev.

Functional roles of arginine residues in mung bean vacuolar H+-pyrophosphatase

AbstractPlant vacuolar H+-translocating inorganic pyrophosphatase (V-PPase EC 3.6.1.1) utilizes inorganic pyrophosphate (PPi) as an energy source to generate a H+ gradient potential for the secondary transport of ions and metabolites across the vacuole membrane. In this study, functional roles of arginine residues in mung bean V-PPase were determined by site-directed mutagenesis. Alignment of amino-acid sequence of K+-dependent V-PPases from several organisms showed that 11 of all 15 arginine residues were highly conserved. Arginine residues were individually substituted by alanine residues to produce R→A-substituted V-PPases, which were then heterologously expressed in yeast. The characteristics of mutant variants were subsequently scrutinized. As a result, most R→A-substituted V-PPases exhibited similar enzymatic activities to the wild-type with exception that R242A, R523A, and R609A mutants markedly lost their abilities of PPi hydrolysis and associated H+-translocation. Moreover, mutation on these three arginines altered the optimal pH and significantly reduced K+-stimulation for enzymatic activities, implying a conformational change or a modification in enzymatic reaction upon substitution. In particular, R242A performed striking resistance to specific arginine-modifiers, 2,3-butanedione and phenylglyoxal, revealing that Arg242 is most likely the primary target residue for these two reagents. The mutation at Arg242 also removed F− inhibition that is presumably derived from the interfering in the formation of substrate complex Mg2+–PPi. Our results suggest accordingly that active pocket of V-PPase probably contains the essential Arg242 which is embedded in a more hydrophobic environment

An Asynchronous Multi-Sensor Micro Control Unit for Wireless Body Sensor Networks (WBSNs)

In this work, an asynchronous multi-sensor micro control unit (MCU) core is proposed for wireless body sensor networks (WBSNs). It consists of asynchronous interfaces, a power management unit, a multi-sensor controller, a data encoder (DE), and an error correct coder (ECC). To improve the system performance and expansion abilities, the asynchronous interface is created for handshaking different clock domains between ADC and RF with MCU. To increase the use time of the WBSN system, a power management technique is developed for reducing power consumption. In addition, the multi-sensor controller is designed for detecting various biomedical signals. To prevent loss error from wireless transmission, use of an error correct coding technique is important in biomedical applications. The data encoder is added for lossless compression of various biomedical signals with a compression ratio of almost three. This design is successfully tested on a FPGA board. The VLSI architecture of this work contains 2.68-K gate counts and consumes power 496-μW at 133-MHz processing rate by using TSMC 0.13-μm CMOS process. Compared with the previous techniques, this work offers higher performance, more functions, and lower hardware cost than other micro controller designs