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An increase in proliferation, inhibition of p21cip and p27kip and a reduction in differentiation following SIRT1 overexpression in rat myoblasts have also been previously reported (Rathbone et al., 2009).
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Analysis of the cross-linked proteome in these mice reveals a reduction in differentiation-associated type I and type II cutaneous keratins (Krt1, Krt2, etc).
Neurite outgrowth was not significantly altered in SH-SY5Y cells, but the neuronal differentiation markers indicated a reduction in neuronal differentiation induction after nanoparticle exposure.
These changes were consistent with a reduction in secretory differentiation of prostatic luminal cells and possible increase in autophagy in the proliferating mPIN regions.
It remains to be determined if the lack of myofibroblasts in capsules from textured implants is due to a more rapid progression of the capsule to a mature state or due to a reduction in myofibroblast differentiation from fibroblasts.
Using a knockout mouse model for IL-11, the cytokine was determined to be required for normal bone turnover, with the knockout mice exhibiting increased bone mass as a result of a reduction in osteoclast differentiation [ 14].
In contrast, transgenic mice expressing a dominant negative β1 integrin subunit under the control of the MMTV (mouse mammary tumor virus) promoter do not exhibit altered mammary gland branching morphogenesis, but instead showed a reduction in alveolar differentiation and an increase in alveolar apoptosis [ 35].
Additional studies by this group demonstrated that high-dose TCDD treatment in rats resulted in a reduction in preadipocyte differentiation to mature adipocytes, which was associated with decreases in transcription factor mRNAs (PPARγ, aP2, C/EBPβ) normally elevated during adipocyte differentiation (Brodie et al. 1997).
The acquisition of low expression levels of RARRES3 in ER− BC primary tumors that metastasize to the lung is directly associated with a reduction in GATA differentiation genes (Chou et al, 2010) and inversely correlated with expression of the EZH2 pluripotency gene marker (Sparmann & van Lohuizen, 2006).
Oil Red O staining revealed a dramatic reduction in differentiation for individual shRNAs and an almost completely abolished differentiation when the shRNA pool was used, an effect that mimicked that of PPARγ KD.
Similarly, overexpression of TET2 or TET3 also leads to a remarkable reduction in differentiation rates (TET2 overexpression: 17.1%; TET3 overexpression: 13.7%) (Fig. 3B).
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