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This variant was intriguing since it is analogous to the R225Q mutation causing increased muscle glycogen content in pigs, as well as having the same amino acid location as the mutations in the human γ2 subunit that are known to alter AMPK protein function and cause Wolf-Parkinson-White syndrome.
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We show that the R225W mutation causes increased basal and AMP-activated AMPK activity, as well as increased muscle glycogen storage and decreased intramuscular triglyceride (IMTG).
Although these findings were consistent with the point mutation rendering the latent myostatin complex resistant to activation by BMP-1/TLD proteases, it was important to rule out the possibility that the point mutation caused increased muscling by decreasing myostatin expression levels.
The mutation causes increased iron and ferritin deposition in the brain but not other organs.
First, we examined the localization of genes whose mutation causes increased Rnr3 abundance.
The Y6/8A mutation caused increased surface expression, as did the ELV/AAA mutation, although to a lesser extent.
This gain-of-function mutation causes increased current flow through the channel and shortens the action potential duration and QT interval.
The essential gene TAF1 encodes the largest subunit of TFIID, and the taf1 -1 mutation causes increased CIN (Stirling et al. 2011).
The mutation causes increased binding affinities within the SNARE complex and disrupted exocytotic vesicle recycling in vivo, limiting neurotransmission under continued stimulation (76).
In summary, the age-1(hx546) mutation appears to affect the animal only during starvation and in ageing adults, so understanding how AGE-1 regulates DAF-16 during these conditions may reveal how this mutation causes increased longevity.
Other mechanisms have been identified in Streptococcus pneumoniae (including mutations in an RNA methyltransferase that methylates G2445 of the 23S rRNA and mutations causing increased expression of ABC transporter genes) and in Staphylococcus epidermidis.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com