A receptor fusion protein for the inhibition of murine oncostatin M

<p>Abstract</p> <p>Background</p> <p>Most cytokines signal through heteromeric receptor complexes consisting of two or more different receptor subunits. Fusion proteins of the extracellular parts of receptor subunits turned out to be promising cytokine inhibitors useful in anti-cytokine therapy and cytokine research.</p> <p>Results</p> <p>We constructed receptor fusion proteins (RFP) consisting of the ligand binding domains of the murine oncostatin M (mOSM) receptor subunits mOSMR and mgp130 connected by a flexible linker as potential mOSM inhibitors. mgp130 is a shared cytokine receptor that is also used by other cytokines such as IL-6 and leukemia inhibitory factor (LIF). In this study we compare four types of mOSM-RFPs that contain either domains D1-D3 or domains D2-D3 of mgp130 and are arranged in two ways. Domain D1 of mgp130 turned out to be dispensable for mOSM-binding. However, the arrangement of the two receptor subunits is essential for the inhibitory activity. We found mOSM induced STAT3 phosphorylation to be suppressed only when the mOSMR fragment was fused in front of the mgp130 fragment.</p> <p>Conclusions</p> <p>mOSM-RFP consisting of D1-D4 of mOSMR and D2-D3 of mgp130 is a highly potent and specific inhibitor of mOSM. Since mOSM-RFP is encoded by a single gene it offers numerous possibilities for specific cytokine inhibition in gene delivery approaches based on viral vectors, transgenic animals and finally gene therapy.</p

Fire and resprouting in Mediterranean ecosystems: Insights from an external biogeographical region, the mexical shrubland

7 páginas, 3 tablas.We investigated modes of regeneration of dominant species of the mexical vegetation after fire. The mexical shrubland shows a remarkable structural, morphological, and floristic similarity to Mediterranean-type vegetation and is considered a relict of the Madro-Tertiary Geoflora under a non- mediterranean climate. This vegetation provides an ideal scenario to test the role of fire in Mediterranean ecosystems because historical fire occurrence is absent and the species assembly is constituted mostly by Madro-Tertiary elements and Neotropical species (some of them, endemic species from Mexico). The existence of congeneric species of the California chaparral allows us to determine the regeneration ability of these communities after fire in relation to resprouting and seeding strategies, which are widespread modes reported in the Mediterranean-type vegetation. By the experimental application of fire in the two biogeographical groups of species, we tested the hypothesis that low resprouting ability of California congeneric species (Madro-Tertiary species) after fire would indicate that fire has played an important selective force in the resprouting habit. A low resprouting ability in the Neotropical group of species would suggest that fire has molded the set of species dominating fire-prone environments. Our results indicated that resprouting is a widespread trait in the mexical species characterized by the presence of lignotubers and burls. Resprouting can be considered an ancient trait, probably linked to losses of aboveground biomass, that became a pre-adaptation in Mediterranean fire-prone communities. The Neotropical group of species showed less ability to regenerate after fire, and small plants were more likely to die after disturbance in this group than in the Madro-Tertiary group. The resprouting feature and the seeder strategy of other species after a fire in the mexical shrubland are similar to Mediterranean-type ecosystems, emphasizing their common origin and the relevance of phylogenetic and biogeographical studies to explain current patterns of vegetation.Peer reviewe