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While this potential hindrance has been partially overcome by using over-expression of the mutant gene, and/or worsening of the mutation by increasing the length of the trinucleotide repeat expansion, interpretation of results from such models and extrapolation to the human condition should be cautious.
It has been suggested that the S18Y mutant has slightly higher hydrolase activity than wild-type UCH-L1 so we modelled this mutation by increasing UCH-L1 activity by 20%.
We modeled PI3K mutation by increasing its catalytic activity threefold.
Combining these bits of evidence the authors suggest that utilization of citrate involved a mutation in gltA that improved growth on acetate and potentiated the citT mutation, by increasing flux through TCA.
However, once such strand slippage occurs, each additional strand-slipped 5′-template base pair could subtantially increase the likelihood of introduction of a single-base deletion mutation by increasing the barrier for reversal of slippage and restacking.
Alternative hypotheses pertaining to promoter action were described in terms of possible mechanisms by which nonelectrophilic promoters might simulate a second mutation by increasing or decreasing the levels of a nonchromosomal replicating particle in target cells.
Similar(51)
Another set of compounds, such as fenofibrate, mimicked the effect of FAD mutations by increasing Aβ42 production [13], [25].
Bergstrom and Pritchart [24] suggested that long-term bottlenecks increase the selection pressure on deleterious mutations by increasing the variance in fitness among hosts.
If so, there would be indirect selection for large introns in regions of low recombination because they can reduce the load caused by deleterious mutations by increasing the recombination rate.
Preclinical data show that these compounds are able to decrease downstream signalling from the receptor that contains primary and secondary imatinib-resistant mutations by increasing KIT degradation (Bauer et al, 2006).
As a result of natural selection, entry into error catastrophe does not imply the "breakdown of evolutionary adaptation" but, on the contrary, the adaptation to higher mutation rates by increasing the mutational robustness of the population.
Related(15)
transformation by increasing
move by increasing
transfer by increasing
deployment by increasing
mutation by applying
mutation by adding
mutation by combining
mutation by introducing
mutation by analyzing
mutation by inhibiting
mutation by using
mutation by examining
mutation by setting
mutation by pyrosequencing
mutation by sequencing
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Justyna Jupowicz-Kozak
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