Service provision for children and young people with acquired brain injury: Practice recommendations.

BACKGROUND: Providing appropriate rehabilitation services for Acquired Brain Injury (ABI) in childhood presents a number of challenges for caregivers, health and education professionals and the young person as they develop. PRIMARY OBJECTIVE: To record the challenges and possible creative solutions generated by an international group of professionals to address the needs of children with ABI. Review of information: Recommendations were generated from children's special interest group meetings of the International Brain Injury Association (Turin, Italy, 2001; Stockholm, Sweden, 2003; Melbourne, Australia, 2005; Lisbon, Portugal, 2008) and through meetings of the International Paediatric Brain Injury Society (IPBIS), formed in 2009. Delegates participating in the workshops were representative of nations from around the world and included The Netherlands, New Zealand, Australia, the UK, Finland, Germany, South Africa, the US, Canada, Sweden, Brazil and Italy. OUTCOMES: The information presented is based on a retrospective review of those meetings and the summaries of the topics considered.

Mobility of TOAC spin-labelled peptides binding to the Src SH3 domain studied by paramagnetic NMR.

Paramagnetic relaxation enhancement provides a tool for studying the dynamics as well as the structure of macromolecular complexes. The application of side-chain coupled spin-labels is limited by the mobility of the free radical. The cyclic, rigid amino acid spin-label TOAC (2,2,6,6-Tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), which can be incorporated straightforwardly by peptide synthesis, provides an attractive alternative. In this study, TOAC was incorporated into a peptide derived from focal adhesion kinase (FAK), and the interaction of the peptide with the Src homology 3 (SH3) domain of Src kinase was studied, using paramagnetic NMR. Placing TOAC within the binding motif of the peptide has a considerable effect on the peptide-protein binding, lowering the affinity substantially. When the TOAC is positioned just outside the binding motif, the binding constant remains nearly unaffected. Although the SH3 domain binds weakly and transiently to proline-rich peptides from FAK, the interaction is not very dynamic and the relative position of the spin-label to the protein is well-defined. It is concluded that TOAC can be used to generate reliable paramagnetic NMR restraints.