Protein disulphide isomerase-assisted functionalization of proteinaceous substrates

Protein disulphide isomerase (PDI) is an enzyme that catalyzes thiol-disulphide exchange reactions among a broad spectrum of substrates, including proteins and low-molecular thiols and disulphides. As the first protein-folding catalyst reported, the study of PDI has mainly involved the correct folding of several cysteine-containing proteins. Its application on the functionalization of protein-based materials has not been extensively reported. Herein, we review the applications of PDI on the modification of proteinaceous substrates and discuss its future potential. The mechanism involved in PDI functionalization of fibrous protein substrates is discussed in detail. These approaches allow innovative applications in textile dyeing and finishing, medical textiles, controlled drug delivery systems and hair or skin care products.We thank to FCT 'Fundacao para a Ciencia e Tecnologia' (scholarship SFRH/BD/38363/2007) for providing Margarida Fernandes the grant for PhD studies

Contribution analysis of a Bolivian innovation grant fund: mixing methods to verify relevance, efficiency and effectiveness

We used contribution analysis to verify the key assumption in the intervention logic of an innovation fund in Bolivia directed to economic farmer organisations to develop value-added activities. We focused the research on three sub-components of the intervention logic: relevance of the farmer groups for local economic development, effectiveness of the fund in strengthening these group, and efficiency of the grant allocation mechanism. We used a case-based comparative analysis to assess effectiveness: improved market access for members, strengthened organisational capacities and the capacity to pay organisational costs. We showed that the grants to already well-endowed organisations were particularly unsuccessful

Abstract 349: Eribulin induces cortical localization of E-cadherin, p120-catenin and beta-catenin in breast cancer cells

Abstract Eribulin provides a survival advantage for breast cancer patients, particularly those with triple-negative and HER2-negative subtypes.1,2 Mechanistically, eribulin was shown to reverse epithelial-to-mesenchymal transition (EMT) in breast cancer models.3 E-cadherin is a central regulator responsible for maintenance of the epithelial phenotype and loss of cortical E-cadherin and its downstream signaling is an early and significant event in EMT. Short term treatment of HCC1937 breast cancer cells with eribulin initiated cortical E-cadherin localization in manner different from other microtubule targeting agents. Cortical E-cadherin plays essential roles in cell adhesion and in regulating the Wnt pathway, whose aberrant activity is implicated in EMT. At the adherens junctions p120-catenin and β-catenin bind to E-cadherin, an interaction facilitated by microtubules. Cortical sequestration of p120- and β-catenin at the adherens junctions stabilizes these complexes and inhibits their ability to stimulate signaling pathways that contribute to EMT. We tested whether eribulin, which binds to the plus ends of microtubules, promotes EMT reversal by influencing p120- and β-catenin localization and activity. Our results show that eribulin induces cortical localization of p120-catenin and β-catenin with E-cadherin in HCC1937 cells, consistent with the formation of normal adherens junctions. Eribulin also stimulated the phosphorylation of Ser33/37 and Thr41 on β-catenin which promotes proteasomal degradation, which would be expected to further inhibit oncogenic signaling. Collectively, our results suggest that eribulin contributes to reversal of EMT through modulation of downstream signaling initiated by cortical localization of p120- and β-catenin at the adherens junctions. Funding for this work was provided by Eisai Inc. 1. Cortes J., et al., Lancet 377:914-923, 2011 2. Twelves, C., et al., Breast Cancer Res Treat 148:553-561, 2014 3. Yoshida, T., et al., Br J of Cancer 110: 1497-1505, 2014 Citation Format: Alison D. Clark, Nicholas F. Dybdal-Hargreaves, Susan L. Mooberry. Eribulin induces cortical localization of E-cadherin, p120-catenin and beta-catenin in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 349. doi:10.1158/1538-7445.AM2017-349</jats:p