Sequence Defined Disulfide-Linked Shuttle for Strongly Enhanced Intracellular Protein Delivery

Intracellular protein transduction technology is opening the door for a promising alternative to gene therapy. Techniques have to address all critical steps, like efficient cell uptake, endolysosomal escape, low toxicity, while maintaining full functional activity of the delivered protein. Here, we present the use of a chemically precise, structure defined three-arm cationic oligomer carrier molecule for protein delivery. This carrier of exact and low molecular weight combines good cellular uptake with efficient endosomal escape and low toxicity. The protein cargo is covalently attached by a bioreversible disulfide linkage. Murine 3T3 fibroblasts could be transduced very efficiently with cargo nlsEGFP, which was tagged with a nuclear localization signal. We could show subcellular delivery of the nlsEGFP to the nucleus, confirming cytosolic delivery and expected subsequent subcellular trafficking. Transfection efficiency was concentration-dependent in a directly linear mode and 20-fold higher in comparison with HIV-TAT-nlsEGFP containing a functional TAT transduction domain. Furthermore, β-galactosidase as a model enzyme cargo, modified with the carrier oligomer, was transduced into neuroblastoma cells in enzymatically active form

A Survey of Economic Theories and Field Evidence on Pro-Social Behavior

In recent years, a large number of economic theories have evolved to explain people's pro-social behavior and the variation in their respective behavior. This paper surveys economic theories on pro-social behavior and presents evidence-mainly from the field-testing these theories. In addition, the survey emphasizes that institutional environment might significantly interact with pro?social preferences and explain some of the variation in observed pro-social behavior

Browser selectivity alters post-fire competition between Erica arborea and E. trimera in the sub-alpine heathlands of Ethiopia

Mammalian herbivores have the potential to alter the competitive relations of woody species, if consumption is unevenly distributed between species. At elevations above 3500 m in the southern Ethiopian highlands, vegetation is dominated by Erica arborea and Erica trimera. Both species can potentially grow into short trees, but are burnt on a rotation of 6 to 10 years, and regenerate by re-sprouting from belowground lignotubers. The regenerating scrub is heavily browsed by cattle. We set up browsing exclosures at three burnt sites to quantify the impact of browsing over a three-year period. When protected from browsing, E. trimera had similar or better height growth than Erica arborea, but in browsed vegetation, Erica arborea instead grew taller. Browsing was more intense on E. trimera in the first years after fire, indicating a difference in palatability between the species. We checked if browse quality differed, by analysing shoot contents of acid detergent fibre, protein, phenolics and tannins. Contrary to expectations the preferred E. trimera contained more acid detergent fibre, less protein and had a higher tannin activity than E. arborea. Although the vegetative growth of E. arborea is favoured relative to E. trimera under high browsing pressure, rapid change in abundance would not be expected, since short-interval fire will repeatedly eradicate any gains in vegetative growth. However, within the typical fire return interval of less than 10 years, E. trimera barely reach a reproductive state, whereas E. arborea flower profusely. Under the current regime of fire and browsing this may in the long run be more important than differences in height growth, leading to a gradual increase in the proportion of E. arborea

Defining Insurance Models within Climate Change European Policies

The paper outlines the role of insurance as a political economic tool that can be used to face the issue of climate change. The magnitude of potential loss, the adverse social and economic consequences for millions of people and considerable fiscal strain imposed on the government budget by weather disasters indicate that governments can benefit significantly from the use of insurance instrument that would seamlessly not only cover damage but also incentivate risk reduction behaviours. Looking at the diversity of existing insurance systems in European countries, natural hazards insurance is examined in terms of private and public involvement, taking into account the EU climate change policies framework. The paper analyses the economic efficiency of different insurance models in relation to the informational imperfections, i.e. adverse selection, moral hazard, and market imperfection, i.e. charity hazard and transaction costs. Moreover, the different models are considered for the way they likely affect incentives to address climate change seeking mechanism to facilitate the mitigation of greenhouse gas emissions, the adaptation to the inevitable impacts of climate change, and the development of climate risk financial management. Conclusive remarks are presented about the possible future development of an European insurance system to find an economic efficient response to natural hazards caused by climate change