GW776 modulated both the catabolic and the anabolic pathways of 5-FU, the most striking effect being on the degradative pathway.
Two of the most striking observations of the pyruvate pathway were: 1) Universal downregulation of all enzymes that convert pyruvate to Acetyl-CoA, including a 5-fold decrease for pyruvate dehydrogenase (Pdhb), a 6.8-fold decrease for dihydrolipoamide dehydrogenase (Dld), and a 2.7-fold decrease for dihydrolipoamide S-acetyltransferase (Dlat).
This is most striking for the ent-kaurene biosynthetic pathway that has significantly elevated pathway transcript variance in Accession I but significantly diminished transcript variance in Accession II (Figure 5).
At this time point, 5-Aza-CdR upregulates a set of genes involved in oncogenic pathways, however, the most striking finding is the immediate effect of 5-Aza-CR on RNA metabolism, which was also recently shown by others [30].
One of the most striking observations of the β2m assembly pathways is that the fibrils formed commencing from a highly denatured state or a native-like precursor are apparently indistinguishable, suggesting that their assembly pathways must converge to a similar fibrillar product.
The AP-1 pathway showed the most striking pattern of activation (Figs. 6 and 7).
The link between Cd44 and the Wnt signalling pathway highlights perhaps the most striking finding of this analysis; the altered expression of 34 genes implicated in the Wnt signalling pathway.
All depicted pathways are indicated by numbers according to the table shown in additional file 4. The most striking differences were detected for the glycolytic pathway, ergosterol and sphingolipid biosynthesis, and the oxidative branch of the pentose phosphate pathway.
Among the up-regulated pathways the ECM-associated integrin pathway, the cadherin pathway, as well as WNT signaling, were most striking from a biological perspective.
The most striking finding of this study is the pathway-specific alterations in LTP in DISC1tr mice, providing potential cellular mechanisms by which transgenic expression of DISC1tr could disrupt normal hippocampal function.
