Evolution of model proteins on a foldability landscape

We model the evolution of simple lattice proteins as a random walk in a fitness landscape, where the fitness represents the ability of the protein to fold. At higher selective pressure, the evolutionary trajectories are confined to neutral networks where the native structure is conserved and the dynamics are non self-averaging and nonexponential. The optimizability of the corresponding native structure has a strong effect on the size of these neutral networks and thus on the nature of the evolutionary process. Proteins 29:461–466, 1997. © 1997 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38527/1/6_ftp.pd

"The car is my extra legs" - Experiences of outdoor mobility amongst immigrants in Sweden with late effects of polio.

BACKGROUND:The aim of the study was to describe the experience of outdoor mobility among immigrants with late effects of polio living in Sweden. There is a need to understand more about this young group of persons since they often have problems with mobility and gait, but they may also face participation restrictions due to issues associated with integration into a new community and culture. METHOD:A total of 14 young immigrants with late effects of polio participated and were interviewed individually. The study used a qualitative method to explore personal experiences and the interviews were analyzed through an inductive approach, using qualitative content analysis. RESULTS:The analysis led to a major theme; self-image and acceptance, that comprised a changeable process and experiences of cultural, social, and gender-specific barriers, but also of environmental and personal factors that impacted their outdoor mobility. By using a car, the participants felt they could come across as normal which also increased their self-esteem. CONCLUSIONS:Independent mobility is a major enabler for ongoing employment and being able to use a car increases the chances for integration into society for young immigrants with late effects of polio. Public transport is not considered to be adequate or efficient enough due to the participants' mobility impairments, but driving can prevent involuntary isolation and facilitate participation. A car can increase quality of life but may also be a facilitator for work and reduce the demand for societal support

How an epidermal growth factor (EGF)-like domain binds calcium. High resolution NMR structure of the calcium form of the NH2-terminal EGF-like domain in coagulation factor X

Domains homologous to the epidermal growth factor (EGF) are important building blocks for extracellular proteins. Proteins containing these domains have been shown to function in such diverse biological processes as blood coagulation, complement activation, and the developmental determination of embryonic cell fates. Many of these proteins require calcium for their biological function. In the case of coagulation factors IX and X and anticoagulants proteins C and S, calcium has been found to bind to the EGF- like domains. We have now determined the three-dimensional structure of the calcium-bound form of the NH2-terminal EGF-like domain in coagulation factor X by two-dimensional NMR and simulated folding. Ligands to the calcium ion are the two backbone carbonyls in Gly-47 and Gly-64, as well as the side chains in Gln-49, erythro-β-hydroxyaspartic acid (Hya) 63, and possibly Asp- 46. The conserved Asp-48 is not a ligand in our present structures. The remaining ligands are assumed to be solvent molecules or, in the intact protein, ligands from neighboring domains. Other proteins interacting in a calcium-dependent manner may also contribute ligands. A comparison with the calcium-free form shows that calcium binding induces strictly local structural changes in the domain. Residues corresponding to the side chain ligands in factor X are conserved in many other proteins, such as the integral membrane protein TAN-1 of human lymphocytes and its developmentally important homolog, Notch, in Drosophila. Calcium binding to EGF-like domains may be crucial for numerous protein-protein interactions involving EGF-like domains in coagulation factors, plasma proteins, and membrane proteins. Therefore, there is reason to believe that this novel calcium site plays an important role in the biochemistry of extracellular proteins