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However, while the increase in gem counts demonstrates proper nuclear localization, it is still unclear whether upregulating SMN levels restore normal functionality.
Hence upregulation of the xCT subunit expression is necessary to upregulate xc− transporter activity, with a corresponding increase in GEM resistance.
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Consistent with the phenotype, the GL2 expression has been observed to increase in gem-1 whereas decrease in GEM-overexpressing plants (Caro, et al. 2007).
Negative controls for fibroblast transfection and cellular reaction included plasmids lacking a viable tsRNA promoter sequence and empty pMU2 plasmid demonstrated therapeutically irrelevant increases in gem numbers (Figure 6A).
Interestingly, we found acridine orange staining (characterized by a punctuation, suggesting vacuole formation) slightly increased in GEM or cannabinoid-treated cells and significantly potentiated in cells treated with GE M/cannabinoidcombinations.
In this study, we demonstrated that T-DM1 binding to HER2 increased in GEM-treated MIA PaCa-2 cells, as GEM enhanced their levels of HER2 expression.
Trichome density increased in gem-1 mutant whereas decreased in GEM-overexpressing plants.
It has been observed that H3K9me3 increases and H3K9me2 decreases in the GL2 promoter in the gem-1 background, but H3K9me3 decreases and H3K9me2 increases in GEM-overexpressing plants (Caro, et al. 2007).
According to the results of the SA-β-gal assay, compared to untreated PANC-1 and ASPC-1 cells, SA-β-gal-positive cells were mildly increased in GEM-treated PANC-1 and ASPC-1 cells, and moderately increased in EX527-treated cells.
Nonetheless, overexpressing xCT and 4F2hc in pancreatic cancer cells resulted in an overall increase in the GEM resistant phenotype.
HPLC analysis demonstrated that while GEM LB-MSNP or GEM plus 1× Abraxane leads to significant increases in total GEM, GE M/PTXco-delivery by LB-MSNP showed the highest total GEM (9-fold) and active metabolite (13-fold) concentrations compared to free GEM.
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