Cellular effects and delivery propensity of penetratin is influenced by conjugation to parathyroid hormone fragment 1-34 in synergy with pH

The cell-penetrating peptide (CPP) penetratin has demonstrated potential as a carrier for transepithelial delivery of cargo peptides, such as the therapeutically relevant part of parathyroid hormone, i.e., PTH­(1-34). The purpose of the present study was to elucidate the relevance of pH for PTH­(1-34)–penetratin conjugates and coadministered penetratin with PTH­(1-34) regarding transepithelial permeation of PTH­(1-34) and cellular effects. Transepithelial permeation was assessed using monolayers of the Caco-2 cell culture model, and effects on Caco-2 cellular viability kinetics were evaluated by using the Real-Time-GLO assay as well as by microscopy following Tryphan blue staining. Morphological Caco-2 cell changes were studied exploiting the impedance-based xCELLigence system as well as optically using the oCelloscope setup. Finally, the effect of pH on the folding propensity of the PTH­(1-34)–penetratin conjugate and its ability to disrupt lipid membranes were assessed by circular dichroism (CD) spectroscopy and the calcein release assay, respectively. The transepithelial PTH­(1-34) permeation was not pH-dependent when applying the coadministration approach. However, by applying the conjugation approach, the PTH­(1-34) permeation was significantly enhanced by lowering the pH from 7.4 to 5 but also associated with a compromised barrier and a lowering of the cellular viability. The negative effects on the cellular viability following cellular incubation with the PTH­(1-34)–penetratin conjugate were moreover confirmed during real-time monitoring of the Caco-2 cell viability as well as by enhanced Tryphan blue uptake. In addition, morphological changes were primarily observed for cells incubated with the PTH­(1-34)–penetratin conjugate at pH 5, which was moreover demonstrated to have an enhanced membrane permeating effect following lowering of the pH from 7.4 to 5. The latter observation was, however, not a result of better secondary folding propensity at pH 5 when compared to pH 7.4

Social labs as temporary intermediary learning organizations to help implement complex normative policies. The case of Responsible Research and Innovation in European science governance

This study aims to discuss science governance in Europe and the network of associated nonprofit institutions. The authors posit that this network, which comprises both (partial) learning organizations and non-learning organizations, has been observed to postpone taking up “responsibility” as an issue in science governance and funding decisions

The social lab as a method for experimental engagement in participatory research

How does the Social Lab methodology support participatory research? This paper provides an evidence-based analysis of experiences of 19 implemented Social Labs applying experiential learning cycles on the question of how to induce Responsible Research and Innovation in the Horizon2020 research funding scheme of the European Commission and beyond. It looks at the potentials of Social Labs to allow participation in research and innovation addressing societal challenges and contrasts empirical results with the theoretical conceptualisation of a scientific Social Lab methodology. It discusses drivers and barriers of engagement, and provides evidence for the impacts of experimental engagement on participation in the context of the labs, substantiated by concrete examples from some of these labs

New HoRRIzon: D5.5 Actions and Activities to Realize RRI in Diversity of Approaches

This Deliverable tells about the journey of the Social Labs from their very beginning, in which we struggled to first get an understanding of the particular Funding Line of H2020 and tried to “diagnose” its uptake of RRI, continuing with the identification of our stakeholders and our attempt to incentivize them to participate in the Social Labs. In this Deliverable, we explain which methods we used in our Social Lab Workshops to raise and discuss the question of responsibility in research and innovation and to generate ideas for Pilot Actions, which experiences we made with these group methods and, most importantly, which Pilot Actions the Social Lab participants created, developed, changed and implemented in order to realize their ambitions of RRI and a responsible research and innovation system