Dual Action of BPC194: A Membrane Active Peptide Killing Bacterial Cells

Membrane active peptides can perturb the lipid bilayer in several ways, such as poration and fusion of the target cell membrane, and thereby efficiently kill bacterial cells. We probe here the mechanistic basis of membrane poration and fusion caused by membrane-active, antimicrobial peptides. We show that the cyclic antimicrobial peptide, BPC194, inhibits growth of Gram-negative bacteria and ruptures the outer and inner membrane at the onset of killing, suggesting that not just poration is taking place at the cell envelope. To simplify the system and to better understand the mechanism of action, we performed Förster resonance energy transfer and cryogenic transmission electron microscopy studies in model membranes and show that the BPC194 causes fusion of vesicles. The fusogenic action is accompanied by leakage as probed by dual-color fluorescence burst analysis at a single liposome level. Atomistic molecular dynamics simulations reveal how the peptides are able to simultaneously perturb the membrane towards porated and fused states. We show that the cyclic antimicrobial peptides trigger both fusion and pore formation and that such large membrane perturbations have a similar mechanistic basis

Business-science research collaboration under moral hazard

I analyze, in the context of business and science research collaboration, how the characteristics of partnership agreements are the result of an optimal contract between partners. The final outcome depends on the structure governing the partnership, and on the informational problems towards the efforts involved. The positive effect that the effort of each party has on the success of the other party, makes collaboration a preferred solution. Divergence in research goals may, however, create conflicts between partners. This paper shows how two different structures of partnership governance (a centralized, and a decentralized ones) may optimally use the type of project to motivate the supply of non-contractible efforts. Decentralized structure, however, always choose a project closer to its own preferences. Incentives may also come from monetary transfers, either from partners sharing each other benefits, or from public funds. I derive conditions under which public interventio

El naturalismo científico en la obra de John Tyndall: Fragments of science

El análisis de los ensayos de John Tyndall, Fragments of Science, permite identificar la teoría atómica, el principio de conservación de la energía y el evolucionismo darwinista como los elementos constitutivos del andamiaje teórico del naturalismo científico. Así, en su ensayo “On the Study of Physics” se resumen sus brillantes facetas como educador y divulgador científico, desarrolladas fundamentalmente en el seno de la Royal Institution. En la lectura “On Force”, Tyndall da por finalizada la controversia Joule- Mayer sobre la primacía del descubrimiento del principio de conservación de la energía, a la vez que plantea algunas de las claves de la lucha por el liderazgo en el seno de la comunidad científica. El discurso presidencial ante la British Association de 1874 en Belfast ejemplifica el coraje de Tyndall en su empeño por demarcar los territorios de la ciencia y la religión, a la luz de los nuevos desafíos científicos. En el trasfondo subyacen los procesos de secularización de la sociedad y de profesionalización de una comunidad científica heterogénea. El compromiso cívico que Tyndall demuestra en “The Belfast Address” es digno corolario de una vida y obra que permite situarlo como paradigma de lo que, en la terminología de Turner, se ha dado en denominar científico público.