Thus, the reduced expression of aquaporins in short fiber mutants may reduce the influx of water into fiber cells and slow down the elongation process.
Future efficacy considerations will involve monitoring the emergence of regional strain variants, since the selective pressure of 4CMenB could potentially drive the emergence of escape mutants and may reduce vaccine efficacy.
For instance, by reducing transcription of the mutant DNA, they may reduce the amount of toxic mutant protein, and delay the onset of disease.
For example, the clearance of mutant transcripts by NMD may reduce disease severity by eliminating transcripts that encode proteins with dominant-negative effects.
Indeed, several independent studies have shown that the mutant valine allele of MTHFR may reduce the risk of colon cancer [ 2, 5, 20] and acute lymphocytic leukemia [ 6].
Studies using cells transfected with mutant ATP1A3 have suggested mutations may reduce affinity for Na+ and that the resultant dysfunction in ion transport may impair cell viability, but the relative importance of these mechanisms to the actual pathophysiology of rapid onset dystonia-parkinsonism remains uncertain (Rodacker et al., 2006; Blanco-Arias et al., 2009).
Looking at our motor neuron models, we observed that GE reduced the paralysis and neuronal degeneration phenotypes caused by the expression of mutant mTDP-43 or mFUS and reduced the fraction of insoluble mutant proteins (Fig. 1D I), suggesting that GE may reduce the cellular load of toxic misfolded proteins.
However, bottlenecks in parasite numbers during transmission in and out of the mosquito may reduce the efficiency of selecting the desired mutants from a large pool of piggyBac-mutants.
Combination therapy with drugs targeting different viral proteins may reduce the emergence of drug-resistant mutants and may show synergistic inhibitory effects.
For example, impairment of RDR2 may reduce substrate competition between RDR2 and RDR6 and increase methylation in rdr2 mutants (Jauvion et al. 2012).
