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Experiment 1 (initial gain of resistant trait).
We repeated the loss and gain of resistant trait to examine the effects of repeated reintroduction of antibiotics as selective pressure.
The simulation processes (population culling using fitness scores) of these 200 generations were identical to that of Experiment 1 (initial gain of resistant trait) to simulate reintroduction of antimicrobial chemicals.
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Both diseases are associated with recurrent activating mutations in the ALK2 intracellular domain that render the gain of function resistant to endogenous biological inhibitors, including noggin.
We found that both loss- and gain- of-function slo-1 mutants were resistant to 5-HT treatment (Figure 8).
In gain-of-function experiments, overexpression of GSK3-resistant Mad caused denticle belts to be replaced by naked cuticle, mimicking Wg signaling (Figure 5).
Such targeted therapies may include phenylalkylamines or the quinazolinone class of calcilytic compounds that have also recently been shown to normalize the gain-of-function associated with NPS 2143-resistant ADH1 mutations in vitro (21) and have potential for the management of patients harboring such mutations.
We also observed an inhibitory effect of the BR pathway on drought response as a loss-of-function BR mutant is resistant to drought and a gain-of-function mutant of the BR pathway had compromised drought response.
Antimicrobial combination therapy may be used to extend spectrum coverage, prevent the emergence of resistant mutants and gain synergy between antimicrobials [ 11].
Gain-of-function mutations of CFB and C3 form a C3 convertase resistant to decay by endothelial cell regulators.
Mad knockdown caused Wg-like loss-of-function phenotypes in embryonic cuticles, and overexpression of GSK3-resistant Mad caused naked cuticle, mimicking Wg gain-of-function phenotypes.
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