Ryan R.E.,1910 University Drive |
Martin B.,1910 University Drive |
Martin B.,Scripps Research Institute |
Mellor L.,1910 University Drive |
And 7 more authors.
Cytokine | Year: 2015
Oncostatin M (OSM) is an interleukin-6-like inflammatory cytokine reported to play a role in a number of pathological processes including cancer. Full-length OSM is expressed as a 26. kDa protein that can be proteolytically processed into 24. kDa and 22. kDa forms via removal of C-terminal peptides. In this study, we examined both the ability of OSM to bind to the extracellular matrix (ECM) and the activity of immobilized OSM on human breast carcinoma cells. OSM was observed to bind to ECM proteins collagen types I and XI, laminin, and fibronectin in a pH-dependent fashion, suggesting a role for electrostatic bonds that involves charged amino acids of both the ECM and OSM. The C-terminal extensions of 24. kDa and 26. kDa OSM, which contains six and thirteen basic amino acids, respectively, enhanced electrostatic binding to ECM at pH 6.5-7.5 when compared to 22. kDa OSM. The highest levels of OSM binding to ECM, though, were observed at acidic pH 5.5, where all forms of OSM bound to ECM proteins to a similar extent. This indicates additional electrostatic binding properties independent of the OSM C-terminal extensions. The reducing agent dithiothreitol also inhibited the binding of OSM to ECM suggesting a role for disulfide bonds in OSM immobilization. OSM immobilized to ECM was protected from cleavage by tumor-associated proteases and maintained activity following incubation at acidic pH for extended periods of time. Importantly, immobilized OSM remained biologically active and was able to induce and sustain the phosphorylation of STAT3 in T47D and ZR-75-1 human breast cancer cells over prolonged periods, as well as increase levels of STAT1 and STAT3 protein expression. Immobilized OSM also induced epithelial-mesenchymal transition-associated morphological changes in T47D cells. Taken together, these data indicate that OSM binds to ECM in a bioactive state that may have important implications for the development of chronic inflammation and tumor metastasis. © 2014 Elsevier Ltd.
Black G.,Boise State University |
Holley D.,Boise State University |
Solan D.,1910 University Drive |
Bergloff M.,Boise State University
Renewable and Sustainable Energy Reviews | Year: 2014
Wind energy production in the United States has seen significant growth over recent years due, in large part, to the state and federal policies designed to encourage wind energy development. This research focuses on measures undertaken at the state level in the western region of the United States. Several of these states have implemented legislation in the form of financial incentives and renewable portfolio standards to support wind development. It is shown that state tax incentives and physical drivers have a significant positive impact on wind energy growth. There has been concern, however, about the fiscal impacts of financial incentives on state tax revenues. As a result, some states have removed tax incentives. A recent example is the removal of sales and use tax rebates for wind producers in Idaho. However, the removal of such incentives results in a net loss of tax revenues as well as negative economic impacts by hindering the development of wind energy projects. It is shown that attendant economic benefits from wind development results in significant positive fiscal impacts by increasing tax revenues for state and local governments. The increased tax revenues begin with the pre-construction and construction phases of such projects and continue to accrue throughout the life of project operations until eventual decommissioning. The removal of this incentive in Idaho results in a net reduction in tax revenues as well as the loss of significant economic benefits in terms of employment, incomes, and total output for the State. © 2014 Elsevier Ltd.