Elafin, an Elastase-specific Inhibitor, Is Cleaved by Its Cognate Enzyme Neutrophil Elastase in Sputum from Individuals with Cystic Fibrosis

Elafin is a neutrophil serine protease inhibitor expressed in lung and displaying anti-inflammatory and anti-bacterial properties. Previous studies demonstrated that some innate host defense molecules of the cystic fibrosis (CF) and chronic obstructive pulmonary disease airways are impaired due to increased proteolytic degradation observed during lung inflammation. In light of these findings, we thus focused on the status of elafin in CF lung. We showed in the present study that elafin is cleaved in sputum from individuals with CF. Pseudomonas aeruginosa-positive CF sputum, which was found to contain lower elafin levels and higher neutrophil elastase (NE) activity compared with P. aeruginosa-negative samples, was particularly effective in cleaving recombinant elafin. NE plays a pivotal role in the process as only NE inhibitors are able to inhibit elafin degradation. Further in vitro studies demonstrated that incubation of recombinant elafin with excess of NE leads to the rapid cleavage of the inhibitor. Two cleavage sites were identified at the N-terminal extremity of elafin (Val-5—Lys-6 and Val-9—Ser-10). Interestingly, purified fragments of the inhibitor (Lys-6—Gln-57 and Ser-10—Gln-57) were shown to still be active for inhibiting NE. However, NE in excess was shown to strongly diminish the ability of elafin to bind lipopolysaccharide (LPS) and its capacity to be immobilized by transglutamination. In conclusion, this study provides evidence that elafin is cleaved by its cognate enzyme NE present at excessive concentration in CF sputum and that P. aeruginosa infection promotes this effect. Such cleavage may have repercussions on the innate immune function of elafin.

The silent treatment: Parents’ narratives on sexuality education with their adolescent children

This paper is based on research undertaken in Ireland that sought to understand how parents communicate with their children about sexuality. Forty-three parents were interviewed and data were analysed using analytical induction. Data indicated that while parents tended to pride themselves on the culture of openness to sexuality that prevailed in their home, they often described situations where very little dialogue on the subject actually transpired. However, unlike previous research on the topic that identified parent-related factors (such as ignorance or embarrassment) as the main impediments to parent-young person communication about sex, participants in our study identified the central obstacle to be a reticence on the part of the young person to engage in such dialogue. Participants described various blocking techniques apparently used by the young people, including claims to have full prior knowledge on the issue, physically absenting themselves from the situation, becoming irritated or annoyed, or ridiculing parents' educational efforts. In our analysis, we consider our findings in light of the shifting power of children historically and the new cultural aspiration of maintaining harmonious and democratic relations with one's offspring.

A short synthesis of (+) and (−)-falcarinol

A short, practical synthesis of the bis-acetylenic natural product falcarinol 1 is reported. This method relies on the alternate functionalisation of bis-trimethylsilylbutadiyne 10. This may be achieved in one-pot, however, better yields were obtained more conventionally. Lipase mediated enzymatic kinetic resolution of the racemic adduct in an organic solvent afforded (+)-1 in 97% enantiomeric excess. The analogous process performed with racemic 3-acetoxy falcarinol 11 under aqueous conditions gave (-)-1. Oxidation of 1 with Dess–Martin periodinane gave falcarinone 2.

Using location-aware technology for learning Geography in a real digital space outside the classroom

The use of new mobile technologies is still in its infancy in many secondary schools and there is limited evidence of the educational and pedagogical benefits on pupils’ learning in the formal school context. This qualitative study focuses on the use of handheld devices to teach a topic in geography to an examination class. Action research combined with pupil observations and focus group interviews are used to capture the pupils’ experiences of using mediascapes. Activity Theory is used as a lens to structure the analysis of the data and to report on the cognitive and affective impact of m-learning on pupils’ academic performance in the topic. Increased attainment and the development of wider skills for lifelong learning were identified in the study. The adaptability of the majority of pupils to the technology resulted in increased levels of willingness to learn in this novel context.