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Our results suggest that if hypervirulent but slow replicating and hypovirulent but fast replicating strains (or coinfecting plant viruses with differential replicative and virulence properties) had to evolve in nature, a rapid extinction of the hypervirulent would take place due to differences in accumulation rates.
This may especially be true when targeting genes of viruses which are fast replicating and which can still infect cells that have not been transfected with the antiviral siRNAs.
Our model also shows a wide region in parameter space for which slow replicating and hypovirulent strains can still outcompete fast replicating hypervirulent ones.
In conclusion, in agreement with the experimental results, a fast replicating hypovirulent viral strain can outcompete a hypervirulent one provided it replicates slower.
Consistent with this hypothesis, less virulent T. gondii strains which are characterized by a slower replication rate showed a reduced P-gp expression compared with the virulent and fast replicating RH strain [9].
Moreover, we would see a correlation between fast replicating stem cells and levels of aneuploidy in the corresponding tissue.
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Given the evolution of faster replicating parasites, units of replication that rely on helpers for survival, such as the master sequence, are counterselected and go extinct (as explained above).
This is because there are many copies of the organellar genomes in one cell and, without mechanisms to synchronize their replication, a selfish faster replicating genome may spread in the population.
There is a number of experiments that could be directly infered from our results, e.g. transfer a significantly slower or faster replicating segment to another location in the genome and check whether the replication time is conserved, or mutate the sequence of this segment to investigate the potential changes of the elongation time.
To simulate natural death causes for unicells, a random death cause is introduced which effectively kills these accumulated unicells while having lesser effects on the smaller, faster replicating unicells much (because these smaller cells replicate multiple times before succumbing to random death).
At 72 h post-inoculation, the average number of population doublings was 8.9±1.3 and 10.0±0.1 for wt Alab49 and the ΔfctA mutant, respectively, which more closely approximates the values for the faster replicating Alab49 rofA::aad9 mutant after only 48 h of skin infection (Figures 4 and S2).
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