A unified health algorithm that teaches itself to improve health outcomes for every individual: How far into the future is it?

The single biggest factor driving health outcomes is patient behavior. The CHR Model (County Health Rankings Model) weights socioeconomic factors, lifestyle behaviors, and physical environment factors collectively at 80% in driving impact on health outcomes, to the 20% weight for access to and quality of clinical care. Commercial determinants of health affect everyone today and unhealthy choices worsen pre-existing economic, social, and racial inequities.

Alternate exon insertion controls selective ubiquitination and degradation of different AUF1 protein isoforms.

The A+U-rich element (ARE) in the 3' non-coding region (3' NCR) of short-lived cytokine mRNAs binds several regulatory proteins, including hnRNP D/AUF1, which comprises four isoforms of 37, 40, 42 and 45 kDa. ARE-mRNA degradation involves ubiquitin-proteasome activity, and one or more AUF1 proteins are thought to be ubiquitinated. Here we have characterized the mechanism for differential ubiquitination and degradation of the different AUF1 protein isoforms.

Ubiquitin-dependent mechanism regulates rapid turnover of AU-rich cytokine mRNAs.

An AU rich element (ARE) in the 3' noncoding region promotes the rapid degradation of mammalian cytokine and proto-oncogene mRNAs, such as tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF) and c-fos. Destabilization of ARE-mRNAs involves the association of ARE-binding proteins tristetraprolin or AUF1 and proteasome activity, of which the latter has not been characterized. Here, we show that the stability of a model short-lived mRNA containing the GM-CSF ARE was regulated by the level of ubiquitin-conjugating activity in the cell, which links ARE-mRNA decay to proteasome activity.