Excitation-emission matrix (EEM) fluorescence spectroscopy has been widely used to characterize dissolved organic matter (DOM) in water and soil. However, interpreting the > 10,000 wavelength-dependent fluorescence intensity data points represented in EEMs has posed a significant challenge. Fluorescence regional integration, a quantitative technique that integrates the volume beneath an EEM, was developed to analyze EEMs. EEMs were delineated into five excitation-emission regions based on fluorescence of model compounds, DOM fractions, and marine waters or freshwaters. Volumetric integration under the EEM within each region, normalized to the projected excitation-emission area within that region and dissolved organic carbon concentration, resulted in a normalized region-specific EEM volume (phi(i,n)). Solid-state carbon nuclear magnetic resonance (13C NMR), Fourier transform infrared (FTIR) analysis, ultraviolet-visible absorption spectra, and EEMs were obtained for standard Suwannee River fulvic acid and 15 hydrophobic or hydrophilic acid, neutral, and base DOM fractions plus nonfractionated DOM from wastewater effluents and rivers in the southwestern United States. DOM fractions fluoresced in one or more EEM regions. The highest cumulative EEM volume (phi(T,n) = sigma phi(i,n)) was observed for hydrophobic neutral DOM fractions, followed by lower phi(T,n) values for hydrophobic acid, base, and hydrophilic acid DOM fractions, respectively. An extracted wastewater biomass DOM sample contained aromatic protein- and humic-like material and was characteristic of bacterial-soluble microbial products. Aromatic carbon and the presence of specific aromatic compounds (as indicated by solid-state 13C NMR and FTIR data) resulted in EEMs that aided in differentiating wastewater effluent DOM from drinking water DOM.

No abstract

No abstract

No abstract

No abstract

The MUC1 transforming protein is overexpressed by most human carcinomas. The present studies demonstrate that the MUC1 C-terminal subunit (MUC1 C-ter) localizes to mitochondria in HCT116/MUC1 colon carcinoma cells and that heregulin stimulates mitochondrial targeting of MUC1 C-ter. We also show that MUC1 attenuates cisplatin-induced (1) release of mitochondrial apoptogenic factors, (2) activation of caspase-3, and (3) induction of apoptosis. Moreover, knockdown of MUC1 expression in A549 lung and ZR-75-1 breast carcinoma cells by MUC1siRNA was associated with increased sensitivity to genotoxic drugs in vitro and in vivo. These findings indicate that MUC1 attenuates the apoptotic response to DNA damage and that this oncoprotein confers resistance to genotoxic anticancer agents.

No abstract

Pleiotrophin (PTN) is a platelet-derived growth factor-inducible, 18-kDa heparin-binding cytokine that signals diverse phenotypes in normal and deregulated cellular growth and differentiation. To seek the mechanisms of PTN signaling, we studied the interactions of PTN with the receptor protein tyrosine phosphatase (RPTP) ␤͞ in U373-MG cells. Our results suggest that PTN is a natural ligand for RPTP ␤͞. PTN signals through ''ligand-dependent receptor inactivation'' of RPTP ␤͞ and disrupts its normal roles in the regulation of steady-state tyrosine phosphorylation of downstream signaling molecules. We have found that PTN binds to and functionally inactivates the catalytic activity of RPTP ␤͞. We also have found that an active site-containing domain of RPTP ␤͞ both binds ␤-catenin and functionally reduces its levels of tyrosine phosphorylation when added to lysates of pervanidate-treated cells. In contrast, an (inactivating) active-site mutant of RPTP ␤͞ also binds ␤-catenin but fails to reduce tyrosine phosphorylation of ␤-catenin. Finally, in parallel to its ability to inactivate endogenous RPTP ␤͞, PTN sharply increases tyrosine phosphorylation of ␤-catenin in PTN-treated cells. The results suggest that in unstimulated cells, RPTP ␤͞ is intrinsically active and functions as an important regulator in the reciprocal control of the steady-state tyrosine phosphorylation levels of ␤-catenin by tyrosine kinases and phosphatases. The results also suggest that RPTP ␤͞ is a functional receptor for PTN; PTN signals through ligand-dependent receptor inactivation of RPTP ␤͞ to increase levels of tyrosine phosphorylation of ␤-catenin to initiate downstream signaling. PTN is the first natural ligand identified for any of the RPTP family; its identification provides a unique tool to pursue the novel signaling pathway activated by PTN and the relationship of PTN signaling with other pathways regulating ␤-catenin.