Syntenin regulates TGF-ß1-induced Smad activation and the epithelial-to-mesenchymal transition by inhibiting caveolin-mediated TGF-ß type I receptor internalization.

Syntenin, a tandem PDZ domain containing scaffold protein, functions as a positive regulator of cancer cell progression in several human cancers. We report here that syntenin positively regulates transforming growth factor (TGF)-ß1-mediated Smad activation and the epithelial-to-mesenchymal transition (EMT) by preventing caveolin-1-mediated internalization of TGF-ß type I receptor (TßRI). Knockdown of syntenin suppressed TGF-ß1-mediated cell migration, transcriptional responses and Smad2/3 activation in various types of cells; however, overexpression of syntenin facilitated TGF-ß1-mediated responses. In particular, syntenin knockdown abolished both the basal and TGF-ß1-mediated repression of E-cadherin expression, as well as induction of vimentin expression along with Snail and Slug upregulation; thus, blocking the TGF-ß1-induced EMT in A549 cells. In contrast, overexpression of syntenin exhibited the opposite effect. Knockdown of syntenin-induced ubiquitination and degradation of TßRI, but not TGF-ß type II receptor, leading to decreased TßRI expression at the plasma membrane. Syntenin associated with TßRI at its C-terminal domain and a syntenin mutant lacking C-terminal domain failed to increase TGF-ß1-induced responses. Biochemical analyzes revealed that syntenin inhibited the interaction between caveolin-1 and TßRI and knockdown of syntenin induced a massive internalization of TßRI and caveolin-1 from lipid rafts, indicating that syntenin may increase TGF-ß signaling by inhibiting caveolin-1-dependent internalization of TßRI. Moreover, a positive correlation between syntenin expression and phospho-Smad2 levels is observed in human lung tumors. Taken together, these findings demonstrate that syntenin may act as an important positive regulator of TGF-ß signaling by regulating caveolin-1-mediated internalization of TßRI; thus, providing a novel function for syntenin that is linked to cancer progression.

Four-photon absorption in the single-crystal polymer bis(paratoluene) sulfonate.

Strong four-photon absorption corresponding to Im[x((7)) (-?; ?, -?, ?, -?, ?, -?, ?)] has been measured for the first time to the authors' knowledge with 100-fs pulses at 1600 nm in the single-crystal polymer poly[bis (p-toluene sulfonate)] of 2, 4-hexadiyne-1, 6-diol. The transition involved is from the even-symmetry ground state into the vibronic subband of the dominant, even-symmetry, excited two-photon state at an energy of 2.7 eV.

Optical inhomogeneity and microstructure of ZrO(2) thin films prepared by ion-assisted deposition.

The index inhomogeneity and the microstructure of ZrO(2) films prepared by Ar-ion-assisted deposition are investigated. The results show that as the Ar-ion momentum transferred to the growing film increases, the average refractive index increases, the vacuum-to-air spectral shift becomes almost zero, the sign of relative inhomogeneity transits from negative to positive, and the void fraction of the top layer next to air becomes smaller than that of the bottom one. These optical properties result from the improved packing density and denser outer region next to air. The Ar-ion bombardment also induces the changes in microstructure of ZrO(2) films, such as the preferential (111) orientation of cubic phase, increase in compressive stress, and reduction of surface roughness.

Ion assisted deposition of thermally evaporated Ag and Al films.

Optical, electrical, and microstructural effects of Ar-ion bombardment and Ar incorporation on thermally evaporated Ag and Al thin films are investigated. The results show that as the momentum supplied to the growing films by the bombarding ions per arriving metal atom increases, the refractive index at 632.8 nm increases and the extinction coefficient decreases, lattice spacing expands, grain size decreases, electrical resistivity increases, and trapped Ar increases slightly. In Ag films, stress reverses from tensile to compressive and in Al films compressive stress increases. In the Al films the change in optical constants can be explained by the variation in void volume. The reversal of stress from tensile to compressive in Ag films requires a threshold level of momentum. The increase in electrical resistivity is related to the decrease in grain size and increase in trapped Ar in both types of film. Many of these properties correlate well with the momentum transferred, suggesting that the momentum is an important physical parameter in describing the influence of ion beam on growing thin films and determining the characteristics of thin metal films prepared by ion assisted deposition.

Reactive ion assisted deposition of aluminum oxynitride thin films.

Optical properties, stoichiometry, chemical bonding states, and crystal structure of aluminum oxynitride (AlO(x)N(y)) thin films prepared by reactive ion assisted deposition were investigated. The results show that by controlling the amount of reactive gases the refractive index of aluminum oxynitride films at 550 nm is able to be varied from 1.65 to 1.83 with a very small extinction coefficient. Variations of optical constants and chemical bonding states of aluminum oxynitride films are related to the stoichiometry. From an x-ray photoelectron spectroscopy analysis it is observed that our aluminum oxynitride film is not simply a mixture of aluminum oxide and aluminum nitride but a continuously variable compound. The aluminum oxynitride films are amorphous from an x-ray diffraction analysis. A rugate filter using a step index profile of aluminum oxynitride films was fabricated by nitrogen ion beam bombardment of a growing Al film with backfill oxygen pressure as the sole variation. This filter shows a high resistivity to atmospheric moisture adsorption, suggesting that the packing density of aluminum oxynitride films is close to unity and the energetic ion bombardment densifies the film as well as forming the compound.

Rapid radiometric methods to detect and differentiate Mycobacterium tuberculosis/M. bovis from other mycobacterial species.

Rapid methods for the differentiation of Mycobacterium tuberculosis/M. bovis (TB complex) from other mycobacteria (MOTT bacilli) were developed and evaluated in a three-phase study. In the first phase, techniques for identification of Mycobacterium species were developed by using radiometric technology and BACTEC Middlebrook 7H12 liquid medium. Based on 14CO2 evolution, characteristic growth patterns were established for 13 commonly encountered mycobacterial species. Mycobacteria belonging to the TB complex were differentiated from other mycobacteria by cellular morphology and rate of 14CO2 evolution. For further differentiation, radiometric tests for niacin production and inhibition by Q-nitro-alpha-acetyl amino-beta-hydroxy-propiophenone (NAP) were developed. In the second phase, 100 coded specimens on Lowenstein-Jensen medium were identified as members of the TB complex, MOTT bacilli, bacteria other than mycobacteria, or "no viable organisms" within 3 to 12 (average 6.4) days of receipt from the Centers for Disease Control. Isolation and identification of mycobacteria from 20 simulated sputum specimens were carried out in phase III. Out of 20 sputum specimens, 16 contained culturable mycobacteria, and all of the positives were detected by the BACTEC method in an average of 7.3 days. The positive mycobacterial cultures were isolated and identified as TB complex or MOTT bacilli in an average of 12.8 days. The radiometric NAP test was found to be highly sensitive and specific for a rapid identification of TB complex, whereas the radiometric niacin test was found to have some inherent problems. Radiometric BACTEC and conventional methodologies were in complete agreement in Phase II as well as in Phase III.

Rapid radiometric susceptibility testing of Mycobacterium tuberculosis.

A 48-hour radiometric test for determining the drug susceptibility of Mycobacterium tuberculosis has been developed. The test is based on the measurement of 14CO2 produced by the oxidation of formate labeled with carbon-14. The test system uses 5 X 10(7) organisms in 1 ml of Middlebrook 7H9 medium plus albumin-dextrose-catalase enrichment and 1 muCi of [14C]formate. The 14CO2 produced is measured in an ionization chamber at 24-, 48-, and 72-hour intervals, with and without the addition of antituberculous drugs. Isoniazid, streptomycin, rifampin, and ethambutol were each tested at 3 concentrations by the radiometric method and the reference (agar dilution) method. Six standard strains and 21 patient isolates were compared by both methods. Production of 14CO2 was quantitatively decreased in the presence of drugs that inhibit the organism. The radiometric method requires 2 days; the agar dilution, 14 to 21 days.