We found epigenome-wide significant associations (FDR p < 0.05) between [PM.sub.10] exposure and DNA methylation for six CpGs, with higher [PM.sub.10] exposure being associated with an increase in methylation for four CpGs mapping to GNB2L1; SNORD96A, FAM13A, SRPRB, and P4HA2, and a decrease for two CpGs within USP4
, and NOTCH4 (Table 2).
USP4 is found to regulate osteoblast differentiation through the Wnt/[beta]-catenin signaling pathway .
USP15, which is highly similar with USP4 , also is involved in Wnt signaling and bone formation .
The DUBs, A20, CYLD, USP2, USP4
, USP7, USP10, USP18, USP21, and USP25 terminate NF-[kappa]B signaling by removing K63-linked ubiquitin chains from signaling molecules [101-123].
TRAF6 is targeted by a number of inhibitory molecules such as Tumour Necrosis Factor Inducible Protein A20 (A20), Ubiquitin Specific Peptidase 4 (USP4
), Ubiquitin-SpecificProcessing Protease CYLD (CYLD), TRAF Family Member Associated NF-[kappa]B Activator (TANK), Tripartite Motif Containing Protein 38 (TRIM38), and Small Heterodimer Partner (SHP) [96-98].
For EySite encapsulates containing an ophthalmic steroid can be injected at a concentration of 400-500 mg matrix/mL, with 90% drug encapsulation achieved per gram of matrix, allowing release of 1-6 microgram steroid per day, for 180 days in-vitro (USP4
in-vitro release model).
However, ubiquitin specific peptidase 4 (USP4
, proto-oncogene) that is 1 kb away from the C22H3orf62 plays an essential role in the negative regulation of the toll-like receptor/interleukin 1 receptor signaling-mediated innate immune response (Zhou et al., 2012).