Novel Venom Proteins Produced by Differential Domain-Expression Strategies in Beaded Lizards and Gila Monsters (genus Heloderma)

The origin and evolution of venom proteins in helodermatid lizards were investigated by multidisciplinary techniques. Our analyses elucidated novel toxin types resultant from three unique domain-expression processes: 1) The first full-length sequences of lethal toxin isoforms (helofensins) revealed this toxin type to be constructed by an ancestral monodomain, monoproduct gene (beta-defensin) that underwent three tandem domain duplications to encode a tetradomain, monoproduct with a possible novel protein fold; 2) an ancestral monodomain gene (encoding a natriuretic peptide) was medially extended to become a pentadomain, pentaproduct through the additional encoding of four tandemly repeated proline-rich peptides (helokinestatins), with the five discrete peptides liberated from each other by posttranslational proteolysis; and 3) an ancestral multidomain, multiproduct gene belonging to the vasoactive intestinal peptide (VIP)/glucagon family being mutated to encode for a monodomain, monoproduct (exendins) followed by duplication and diversification into two variant classes (exendins 1 and 2 and exendins 3 and 4). Bioactivity characterization of exendin and helokinestatin elucidated variable cardioactivity between isoforms within each class. These results highlight the importance of utilizing evolutionary-based search strategies for biodiscovery and the virtually unexplored potential of lizard venoms in drug design and discovery.

Strategic Complexity and Success - Small Firms Strategies in a Mature Market

his paper develops a typology of strategic options for small firms in the furniture industry and examines the extent to which firms are re-engineering their strategies in response to profit performance. Empirical analysis is based on data from 39 firms with between 10 and 100 employees in the Irish furniture industry. Three main results emerge from the analysis. First, firms in the Irish furniture industry predominantly adopt “simple” business development strategies. Secondly, in terms of profit performance, we find no evidence that simple strategies unambiguously outperform more complex approaches. Instead, the success of both simple and complex business strategies is directly related to the strength of firms’ resource base. Finally, systematic differences were found in firms’ ability or willingness to re-engineer their strategies in the light of their profit performance.