Motifs tested include tandem PEST elements to promote protein degradation, internal ribosome entry site (IRES) mutations to impede translation initiation, and codon-deoptimized dhfr selection marker to reduce translation efficiency.
In Drosophila, LRRK2 kinase has been shown to regulate the EndoA phosphorylation cycle, and pathogenic mutations appear to impede synaptic endocytosis [ 88].
Since the targets of anti-TB agents include proteins and ribosomal components responsible for transcription, translation and cell wall integrity, resistance mutations may be expected to impede growth or increase the likelihood of cell death in the context of an in vivo infection [16].
Furthermore, it has been demonstrated that RPL11 activates p53 cooperatively with RPL5 and mutations, which are predicted to impede RPL11 interaction with the 5S rRNA, inhibit this induction (Horn and Vousden, 2008).
Unless deleterious mutations were very common, they did little to impede the progression of the most aggressive clones, supporting Beckman and Loeb's previous conclusion (Beckman and Loeb 2005).
This hypothesis could be tested by examining 'cancer genomes' for evidence of clonal mutations (high frequency within the tumour) that are predicted to impede cell growth or survival, or genetically engineering them into cells.
As the probability of a cell acquiring a deleterious mutation was comparable to that of the cell acquiring an advantageous mutation, negative clonal selection impeded the growth of only rare cells within the most aggressive clone, and so failed to impede tumour growth.
And what will be done to impede their growth?
American sanctions continue to impede investment in Iran.
Each gene was known to impede programmed cell death.
