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JAK-STAT pathway: Testicular development, spermatogenesis and fertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
There are two existing cell populations in Drosophila that include germline and somatic cells. How do these cells achieve sexual identity? In Drosophila somatic cells, male and female identity is defined by counting the ratio of X chromosome to an autosome, where an X/A ratio of 1 indicates normal female and X/A ratio of 0.5 indicates normal male (42). There is a double copy of X-linked signal elements (XSEs) in females as compared to males. These X-linked elements include sisterless-a (sis-a), scute (sis-b), runt (run) which encodes transcription factor and unpaired (sisterless-c) which encodes a secretory ligand (16,42). These double copies of XSEs are important for regulating the transcription of Sxl (sex-lethal) from Sxl-pe (promoter for the establishment) in females. The resultant protein from Sxl-pe regulates its own synthesis from Sxl-pm promoter (promoter for maintenance). Thus, Sex-lethal is turned on only in females. Sxl acts through a transformer (tra) and regulates splicing of doublesex RNA (dsx) in females. But in males, because Sxl is not present, default Splicing of dsx results in males (Figure 15.5). Another ligand, Upd, is considered to be a weak XSE because Upd and other downstream components, such as Hop and STAT92E, in mutational studies had little effect on Sxl expression in females (43–46).
Mepolizumab for the treatment of eosinophilic granulomatosis with polyangiitis
Published in Expert Opinion on Biological Therapy, 2019
Daniel Ennis, Jason Kihyuk Lee, Christian Pagnoux
The majority of patients in published studies on epigenetic abnormalities in AAV had MPA or GPA, with only a minority classified as EGPA. Epigenetic abnormalities can result in increased mRNA expression of Proteinase 3 (PRTN3) and MPO genes in AAV [59]. During disease activity, decreased expression of euchromatic histone-lysine N-methyltransferase genes (EHMT) 1 and 2 and increased expression of male sex lethal 1 homolog (MSL1) and insulin growth factor (ING4) genes correlated with MPO and PRTN3 expression [60]. Furthermore, demethylation of the PRTN3 promoter region was predictive of disease relapse irrespective of ANCA serotype (HR 4.55) [61]. These advances in our understanding of the contributions of genetic and epigenetic variables to EGPA have not yet identified clinically distinct subgroups to guide therapy.