It would also suggest that attention and visual stimuli elicit ACh release in V1, which modifies synaptic functioning by eliciting LTP-like mechanisms at an early level of cortical processing. However, a subsequent RT-PCR verification of these genes did not reach a statistical level even though there was a trend towards that PGM2L1 was lower, and KCNJ2 and higher, respectively in mucosal biopsies from CD smokers compared to CD neversmokers. A range of genes well known to be associated with CD did not show up in this study as these genes are not predominant in the group of CD patients, and because this genome-wide gene association study focused on the smoking phenotype. As immune cells are absent in culture and oxygen supply is constant, it is obvious that the differentiation states of G-2 cells are regulated by intrinsic factors. PAD expression in mammary tissue has not been documented. However, previous reports have shown that PAD2 is expressed in other reproductive tissues in a hormone dependent Enzalutamide manner. For example, both PAD2 and citrullination levels were found to be higher in the female rodent pituitary gland than in males and PAD2 was also found to be expressed in the luminal and glandular epithelia of the uterine endometrium with expression levels changing in an estrous cycle-dependent manner. Further, ovariectomized mice treated with estrogen displayed both increased PAD2 mRNA levels and increased citrullination in uterine samples compared to vehicle treated controls suggesting E2-mediated regulation. Potential PAD2 targets in reproductive tissues have not been previously identified. However, two in vivo substrates for PAD2 have been described in other tissues: myelin basic protein in neurons and vimentin in skeletal muscle and macrophages. In macrophages, the presence of high calcium levels cause PAD2 to citrullinate vimentin resulting in the breakdown of the vimentin intermediate filament network potentially to play a role in apoptotic events. The brain expresses PAD2 where it citrullinates MBP a major component of the myelin sheath that covers the axons of nerves. MBP normally contains noncitrullinated arginine residues allowing compact myelin sheaths to form; citrullinated MBP is not capable of forming tight sheaths which is hypothesized to lead to neurodegeneration and possibly multiple sclerosis. There is also in vitro evidence that PAD2 can citrullinate arginine residues on histone H4. When incubated with histones, purified skeletal muscle PAD2 converts methyl arginine 3 histone H4 to citrulline, although no evidence yet exists to link PAD2 to histone citrullination in vivo. In G-2 culture around 80% of the cells are colony-forming, but not each colony will form a CCS. Assuming that a newly formed colony is composed of nearly identical cells which with respect to their differentiation state recapitulate the phenotype of the mother cell.