Pharmaceuticals in wastewater: behavior, preferences, and willingness to pay for a disposal program.

The presence of pharmaceutical compounds in treated wastewater and in surface waters is a growing environmental concern. This paper provides information about general awareness of the issue, disposal practices, willingness to pay for a disposal program, and willingness to participate in a disposal program. The results are based on a telephone survey of 1005 residents in southern California.

Regulation of bone morphogenetic protein-4 activity by sequence elements within the prodomain.

Bone morphogenetic protein-4 (BMP-4) is synthesized as a large precursor protein, which undergoes proprotein convertase-mediated proteolytic maturation along the secretory pathway to release the active ligand. Pro-BMP-4 is initially cleaved at a consensus furin motif adjacent to the mature ligand domain (the S1 site), and this allows for subsequent cleavage at an upstream motif (the S2 site). This sequential cleavage liberates a small, evolutionarily conserved, prodomain fragment (the linker peptide) of unknown fate and function.

Mutation of an upstream cleavage site in the BMP4 prodomain leads to tissue-specific loss of activity.

ProBMP4 is initially cleaved at a site adjacent to the mature ligand (the S1 site) allowing for subsequent cleavage at an upstream (S2) site. Mature BMP4 synthesized from a precursor in which the S2 site cannot be cleaved remains in a complex with the prodomain that is targeted for lysosomal degradation, and is thus less active when overexpressed in Xenopus. Here we report that mice carrying a point mutation that prevents S2 processing show severe loss of BMP4 activity in some tissues, such as testes and germ cells, whereas other tissues that are sensitive to Bmp4 dosage, such as the limb, dorsal vertebrae and kidney, develop normally.

Proprotein convertase genes in Xenopus development.

Proprotein convertases (PCs) are a family of serine endoproteases that proteolytically activate many precursor proteins within various secretory pathway compartments. Loss-of-function studies have demonstrated a critical role for these proteases in embryonic patterning and adult homeostasis, yet little is known about how substrate selectivity is achieved. We have identified Xenopus orthologs of three PCs: furin, PC6, and PC4.