Mutations which increase the replication of dengue viruses in cell culture would greatly facilitate the manufacture of both a live attenuated or inactivated dengue virus vaccine.
Women who have tested positive for inherited BRCA gene mutations, which increase their risk for developing a new breast cancer in their other breast, are sometimes advised to consider contralateral mastectomy.
Certain mutations, which increase affinity, are selectively favoured, while those that decrease affinity are eliminated.
As the antigenic overlap of the two B lineages is clearly disadvantageous to their transmission, mutations which increase the genetic difference between the two lineages and, thus, reduce the degree of cross protection should be selected for.
Still, some factor encouraged the increase of complexity, which occurred even when deletions were more common than mutations which increase the number of genes (deletion bias), although mute genes which do nothing were removed from the genome under this bias, as expected.
Although the mechanism for this association remains elusive, some hypotheses have been proposed to explain it, including gain of function caused by GBA mutations, which increases α-synuclein (α-syn) aggregation, loss of function due to lysosomal enzyme deficiency, which affects α-syn clearance, and even a bidirectional feedback loop, but each of these hypotheses has its limitations.
Within the N-terminal region, the largest effects on γ-secretase cleavage activity were found with loss of the polar N8 residue, which increased Aβ40 to nearly 300% and Aβ42 to 180% of that of wt, and the L14A mutation, which increased Aβ40 to ∼160% and Aβ42 to >200% of that of wt.
Conversely, the A352D mutantmutant (a mutation which increases cGMP selectivity in eukaryotic channels) increased both the affinity and the sensitivity for cGMP relative to the WT channel, again leaving those for cAMP unchanged.
We specifically asked whether human ZnT3 harboring the Y372F mutation, which reduces the ZnT3 80 kDa species, was dominant over the Y357F mutation, which increases ZnT3 80 kDa species.
Our model explains well the effect of CDK9 S175A mutation, which increases the association of the mutant CDK9 with HEXIM1 suggesting more efficient 7SK snRNP formation.
