{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:47:08Z","timestamp":1792061228424,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Understanding intracellular signalling pathways is crucial since they regulate essential functional activities. Bivariate relationships have been useful in delineating these pathways in clinical samples. In our previous studies, we have found many linear associations between pathway components, and we have interpreted these correlations as rheostatic regulators. Increases in an upstream component are correlated with a commensurate downstream increase. Here, we report a quantitative analysis of molecules in the STING pathway by assessing the variance in human peripheral blood mononuclear cell\u2010type\u2010specific molecular expression from patients with atherosclerotic coronary artery disease. The induction of the type I interferon track by this pathway is dependent on the expression levels of STING in T cells and monocytes and the expression levels of phospho\u2010STING in B cells. This relationship in T cells and monocytes demonstrates definitive linearity, indicating that it is regulated as a rheostat. In B cells the relationships are logarithmic, indicating an on\u2010off mechanism of regulation. The STING pathway\u2010dependent stimulation of the NF\u03baB track is also controlled by on\u2010off mechanisms that are modelled by nonlinear bivariate relationships. These on\u2010off switches occur at the bifurcation of the two branches involving phospho\u2010STING, phospho\u2010TBK1 and phospho\u2010RelA. Whereas linear bivariate associations are readily captured by an evaluation of the correlation matrix, significant nonlinear relationships are not. Nonlinear correlations modelled logarithmically or exponentially are easily discerned by the assessment of a natural log\u2010transformed versus non\u2010transformed correlation matrix.<\/jats:p>","DOI":"10.1111\/jcmm.71093","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:38:36Z","timestamp":1773722316000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nonlinear Bivariate Associations and Mononuclear Cell\u2010Type\u2010Specific Expression Level Differences in the\n                    <scp>STING<\/scp>\n                    Signalling Pathway"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-9254","authenticated-orcid":false,"given":"David","family":"Kaplan","sequence":"first","affiliation":[{"name":"CellPrint Biotechnology LLC  Cleveland Ohio USA"},{"name":"Case Western Reserve University  Cleveland Ohio 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