The antimicrobial action of pseudin-2

The amphibian antimicrobial peptide pseudin-2 is a peptide derived from the skin of the South-American frog Pseudis paradoxa (Olson et al., 2001). This peptide possesses tremendous potential as a therapeutic lead since it has been shown to possess both antimicrobial as well insulin-releasing properties (Olson et al., 2001; Abdel-Wahab et al., 2008). This study aimed to develop pseudin-2’s potential by understanding and improving its properties as an antimicrobial agent. The structure-function relationships of pseudin-2 were explored using a combination of in-vitro and in-silico techniques, with an aim to predict how the structure of the peptide may be altered in order to improve its efficacy. A library of pseudin-2 mutants was generated by randomizing codons at positions 10, 14 and 18 of a synthetic gene, using NNK saturation mutagenesis. Analysis of these novel peptides broadly confirmed, in line with literature precedent, that anti-microbial activity increases with increased positive charge. Specifically, 2 positively-charged residues at positions 10 and 14 and a hydrophobic at position 18 are preferred. However, substitution at position 14 with some polar, non-charged residues also created peptides with antimicrobial activity. Interestingly, the pseudin-2 analogue [10-E, 14-Q, 18-L] which is identical to pseudin-2, except that the residues at positions 10 and 14 are switched, showed no anti-microbial activity at all. Molecular dynamics simulations of pseudin-2 showed that the peptide possesses two equilibrium structures in a membrane environment: a linear and a kinked a-helix which both embed into the membrane at an angle. Biophysical characterization using circular dichroism spectroscopy confirmed that the peptide is helical within the membrane environment whilst linear dichroism established that the peptide has no defined orientation within the membrane. Collectively, these data indicate that Pseudin-2 exerts its antimicrobial activity via the carpet model.

Strategic supplier performance evaluation:a case-based action research of a UK manufacturing organisation

The main aim of this research is to demonstrate strategic supplier performance evaluation of a UK-based manufacturing organisation using an integrated analytical framework. Developing long term relationship with strategic suppliers is common in today's industry. However, monitoring suppliers' performance all through the contractual period is important in order to ensure overall supply chain performance. Therefore, client organisations need to measure suppliers' performance dynamically and inform them on improvement measures. Although there are many studies introducing innovative supplier performance evaluation frameworks and empirical researches on identifying criteria for supplier evaluation, little has been reported on detailed application of strategic supplier performance evaluation and its implication on overall performance of organisation. Additionally, majority of the prior studies emphasise on lagging factors (quality, delivery schedule and value/cost) for supplier selection and evaluation. This research proposes both leading (organisational practices, risk management, environmental and social practices) and lagging factors for supplier evaluation and demonstrates a systematic method for identifying those factors with the involvement of relevant stakeholders and process mapping. The contribution of this article is a real-life case-based action research utilising an integrated analytical model that combines quality function deployment and the analytic hierarchy process method for suppliers' performance evaluation. The effectiveness of the method has been demonstrated through number of validations (e.g. focus group, business results, and statistical analysis). Additionally, the study reveals that enhanced supplier performance results positive impact on operational and business performance of client organisation.