Genetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and latent TGFβ binding protein 4 (LTBP4). We now evaluated the functional effect of these modifiers in the context of muscle injury and repair to elucidate their mechanisms of action. We found that excess osteopontin exacerbated sarcolemmal injury, and correspondingly, that loss of osteopontin reduced injury extent both in isolated myofibers and in muscle in vivo. We found that ablation of osteopontin was associated with reduced expression of TGFβ and TGFβ-associated pathways. We identified that increased TGFβ resulted in reduced expression of Anxa1 and Anxa6, genes encoding key components of the muscle sarcolemma resealing process. Genetic manipulation of Ltbp4 in dystrophic muscle also directly modulated sarcolemmal resealing, and Ltbp4 alleles acted in concert with Anxa6, a distinct modifier of muscular dystrophy. These data provide a model in which a feed forward loop of TGFβ and osteopontin directly impacts the capacity of muscle to recover from injury, and identifies an intersection of genetic modifiers on muscular dystrophy.

Organisations have been forced to change their philosophy due to the vast amount of information made available when running software process improvement (SPI) programmes and working in a way leading to maintaining and converting this information into knowledge in order to adapt and integrate changes quickly and thereby ensuring remaining in the competitive market. This article presents some of the most significant antecedents in defining and implementing knowledge management (KM) in SPI programmes which have been adapted for use in small software companies, as such management represents a philosophy of true organisational capital for companies involved in software improvement projects. The advisability of implementing KM in SPI programmes or projects arising from primary knowledge management targets is analysed, as is its adaptation for such projects according to identified needs, especially related to documenting and manipulating tangible and intangible products produced in an SPI programme.