Trop-2 inhibits prostate cancer cell adhesion to fibronectin through the β1 integrin-RACK1 axis.

Trop-2 is a transmembrane glycoprotein upregulated in several human carcinomas, including prostate cancer (PrCa). Trop-2 has been suggested to regulate cell-cell adhesion, given its high homology with the other member of the Trop family, Trop-1/EpCAM, and its ability to bind the tight junction proteins claudin-1 and claudin-7. However, a role for Trop-2 in cell adhesion to the extracellular matrix has never been postulated. Here, we show for the first time that Trop-2 expression in PrCa cells correlates with their aggressiveness. Using either shRNA-mediated silencing of Trop-2 in cells that endogenously express it, or ectopic expression of Trop-2 in cells that do not express it, we show that Trop-2 inhibits PrCa cell adhesion to fibronectin (FN). In contrast, expression of another transmembrane receptor, α(v) β(5) integrin, does not affect cell adhesion to this ligand. We find that Trop-2 does not modulate either protein or activation levels of the prominent FN receptors, β(1) integrins, but acts through increasing β(1) association with the adaptor molecule RACK1 and redistribution of RACK1 to the cell membrane. As a result of Trop-2 expression, we also observe activation of Src and FAK, known to occur upon β(1) -RACK1 interaction. These enhanced Src and FAK activities are not mediated by changes in either the activity of IGF-IR, which is known to bind RACK1, or IGF-IR\u27s ability to associate with β(1) integrins. In summary, our data demonstrate that the transmembrane receptor Trop-2 is a regulator of PrCa cell adhesion to FN through activation of the β(1) integrin-RACK1-FAK-Src signaling axis

Multiple Residues in the Second Extracellular Loop Are Critical for M3 Muscarinic Acetylcholine Receptor Activation

Recent studies suggest that the second extracellular loop (o2 loop) of bovine rhodopsin and other class I G protein-coupled receptors (GPCRs) targeted by biogenic amine ligands folds deeply into the transmembrane receptor core where the binding of cis-retinal and biogenic amine ligands is known to occur. In the past, the potential role of the o2 loop in agonist-dependent activation of biogenic amine GPCRs has not been studied systematically. To address this issue, we used the M3 muscarinic acetylcholine receptor (M3R), a prototypic class I GPCR, as a model system. Specifically, we subjected the o2 loop of the M3R to random mutagenesis and subsequently applied a novel yeast genetic screen to identity single amino acid substitutions that interfered with M3R function. This screen led to the recovery of about 20 mutant M3Rs containing single amino acid changes in the o2 loop that were inactive in yeast. In contrast, application of the same strategy to the extracellular N-terminal domain of the M3R did not yield any single point mutations that disrupted M3R function. Pharmacological characterization of many of the recovered mutant M3Rs in mammalian cells, complemented by site-directed mutagenesis studies, indicated that the presence of several o2 loop residues is important for efficient agonist-induced M3R activation. Besides the highly conserved Cys220 residue, Gln207, Gly211, Arg213, Gly218, Ile222, Phe224, Leu225, and Pro228 were found to be of particular functional importance. In general, mutational modification of these residues had little effect on agonist binding affinities. Our findings are therefore consistent with a model in which multiple o2 loop residues are involved in stabilizing the active state of the M3R. Given the high degree of structural homology found among all biogenic amine GPCRs, our findings should be of considerable general relevance

Control-oriented implementation and model order reduction of a lithium-ion battery electrochemical model

The use of electrochemical models makes it computationally intractable for online implementation as the model is subject to a complicated mathematical structure including partial-differential equations (PDE). This paper is based on the single particle model with electrolyte dynamics. Methods to solve the PDEs in the governing equations are given. Model order reduction techniques are applied to the electrochemical model to reduce the order from 350 to 14. The models solved by numerical solution, residue grouping method and balanced truncation method are compared with experimental data of a coin cell for validation. The results show that the reduced order model can decrease simulation time 75 times compared with the high order model. And the accuracy of the model is kept with 2.3% root mean square error comparing with the experiment results

Orbital Angular Momentum Waves: Generation, Detection and Emerging Applications

Orbital angular momentum (OAM) has aroused a widespread interest in many fields, especially in telecommunications due to its potential for unleashing new capacity in the severely congested spectrum of commercial communication systems. Beams carrying OAM have a helical phase front and a field strength with a singularity along the axial center, which can be used for information transmission, imaging and particle manipulation. The number of orthogonal OAM modes in a single beam is theoretically infinite and each mode is an element of a complete orthogonal basis that can be employed for multiplexing different signals, thus greatly improving the spectrum efficiency. In this paper, we comprehensively summarize and compare the methods for generation and detection of optical OAM, radio OAM and acoustic OAM. Then, we represent the applications and technical challenges of OAM in communications, including free-space optical communications, optical fiber communications, radio communications and acoustic communications. To complete our survey, we also discuss the state of art of particle manipulation and target imaging with OAM beams