NHERF1 acts as a molecular switch to program metastatic behavior and organotropism via its PDZ domains.

Metastatic cells are highly plastic for differential expression of tumor phenotype hallmarks and metastatic organotropism. The signaling proteins orchestrating the shift of one cell phenotype and organ pattern to another are little known. Na(+)/H(+) exchanger regulatory factor (NHERF1) is a molecular pathway organizer, PDZ-domain protein that recruits membrane, cytoplasmic, and cytoskeletal signaling proteins into functional complexes. To gain insight into the role of NHERF1 in metastatic progression, we stably transfected a metastatic breast cell line, MDA-MB-231, with an empty vector, with wild-type NHERF1, or with NHERF1 mutated in either the PDZ1- or PDZ2-binding domains to block their binding activities. We observed that NHERF1 differentially regulates the expression of two phenotypic programs through its PDZ domains, and these programs form the mechanistic basis for metastatic organotropism. The PDZ2 domain promotes visceral metastases via increased invadopodia-dependent invasion and anchorage-independent growth, as well as by inhibition of apoptosis, whereas the PDZ1 domain promotes bone metastases by stimulating podosome nucleation, motility, neoangiogenesis, vasculogenic mimicry, and osteoclastogenesis in the absence of increased growth or invasion. Collectively, these findings identify NHERF1 as an important signaling nexus for coordinating cell structure with metastatic behavior and identifies the "mesenchymal-to-vasculogenic" phenotypic transition as an essential step in metastatic progression

3D characterization of CdSe nanoparticles attached to carbon nanotubes

The crystallographic structure of CdSe nanoparticles attached to carbon nanotubes has been elucidated by means of high resolution transmission electron microscopy and high angle annular dark field scanning transmission electron microscopy tomography. CdSe rod-like nanoparticles, grown in solution together with carbon nanotubes, undergo a morphological transformation and become attached to the carbon surface. Electron tomography reveals that the nanoparticles are hexagonal-based with the (001) planes epitaxially matched to the outer graphene layer.Comment: 7 pages, 8 figure

Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o-Cells

We previously found that human amniotic mesenchymal stem cells (hAMSCs) in coculture with CF immortalised airway epithelial cells (CFBE41o-line, CFBE) on Transwell\uae filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction-(GJ-) mediated intercellular communication (GJIC) in this rescue, cocultures (hAMSC: CFBE, 1: 5 ratio) were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43), a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C), and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells

Measurement of hadronic cross section and preliminary results on the pion form factor using the radiative return at DAPHNE

In the fixed energy environment of the $e^{+}e^{-}$ collider DA$\Phi$NE, KLOE can measure the cross section of the process $e^{+}e^{-} \to$ hadrons as a function of the hadronic system energy using the radiative return. At energies below 1 GeV, $e^{+}e^{-} \to \rho \to \pi^{+}\pi^{-}$ is the dominating hadronic process. We report here on the status of the analysis for the e^{+}e^{-} \to \ppg channel, which allows to obtain a preliminary measurement of the pion form factor using an integrated luminosity of $\sim73 pb^{-1}$.Comment: Invited talk at the Seventh International Workshop on Tau Lepton Physics (TAU02-WE07), Santa Cruz, Ca, USA, Sept 2002, 9 pages, LaTeX, 9 eps figure

Measuring the hadronic cross section via radiative return

Recently it has been demonstrated that particle factories, such as DAPHNE and PEP-II, operating at fixed center-of-mass energies, are able to measure hadronic cross sections as a function of the hadronic system energy using the raditive return. This paper is an experimental overview of the progress in this aera. Preliminary results from KLOE for the process e+e- -> \rho \gamma -> \pi+\pi-\gamma and a fit to the pion form factor are presented. Some first results from the BABAR collaboration are also shown.Comment: Invited talk presented at RADCOR/Loops and Legs 2002, Kloster Banz/Germany, September 8-13 2002, 6 pages, 2 Figures; v1: references added, typos correcte

Measurement of the branching fraction for the decay KS --> pi e nu

We present a measurement of the branching ratio BR(KS --> pi e nu) performed using the KLOE detector. KS mesons are produced in the reaction e+ e- --> phi --> KS KL at the DAFNE collider. In a sample of about 5 million KS-tagged events we find 624 +- 30 semileptonic KS decays. Normalizing to the KS --> pi+ pi- count in the same data sample, we obtain BR(KS --> pi e nu) = (6.91 +- 0.37) 10^-4, in agreement with the Standard Model expectation.Comment: 9 pages, 5 Encapsulated Postscript figures. Submitted to Phys. Lett.

Measurement of Gamma(phi -> eta' gamma)/Gamma(phi -> eta gamma) and the pseudoscalar mixing angle

We have measured the radiative decays phi -> eta gamma, phi ->etaprime gamma selecting pi+ pi- gamma gamma gamma final state in a sample of about 5 times 10^7 phi mesons produced at the Frascati phi factory DAFNE. We obtain Gamma(phi -> etaprime gamma)/Gamma(phi -> eta gamma)=(4.70 +- 0.47 +- 0.31) times 10^-3. From this result we derive new accurate values for the branching ratio BR(phi ->etaprime gamma) = (6.10 +- 0.61 +- 0.43) times 10^-5, and the mixing angle of pseudoscalar mesons in the flavour basis phi_P=(41.8 +1.9 -1.6) degrees.Comment: Submitted to Phys. Lett.

Study of the Decay phi --> eta pi0 gamma with the KLOE detector

In a sample of 5.3x10^7 phi-decays observed with the KLOE detector at the Frascati phi-factory Dafne we find 605 eta pi0 gamma events with eta --> gamma\gamma and 197 eta pi0 gamma events with eta --> pi+ pi- pi0. The decay phi --> eta pi0 gamma is dominated by the process phi --> a0 gamma. From a fit to the eta pi0 mass spectrum we find BR(phi --> ao(980) gamma)= (7.4 +- 0.7)x10^-5.Comment: 12 pages, 6 figures, submitted to Phys.Lett.