{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:07:48Z","timestamp":1791209268767,"version":"4.1.0"},"reference-count":56,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,7,15]]},"abstract":"<jats:p>TGF-\u03b2 (transforming growth factor-\u03b2) plays a critical role in modulating the inflammatory response and other biological processes through its regulation of the production of MMPs (matrix metalloproteinases). In both Mono-Mac-6 and RAW264.7 monocyte\/macrophage cells, TGF-\u03b2 abrogated lipopolysaccharide-induced increases in the enzymic activity and mRNA level of MMP-9. A fragment of the human MMP-9 promoter was used to characterize its regulation by TGF-\u03b2 signalling. In RAW264.7\u00a0cells, TGF-\u03b2 or its downstream signalling protein, Smad3 (Sma- and Mad-related protein 3), inhibited lipopolysaccharide-stimulated promoter activity. The suppressive activity of TGF-\u03b2 on the MMP-9 promoter was abrogated by an inhibitory Smad, Smad7. The MMP-9 promoter contains a putative TIE (TGF-\u03b2 inhibitory element). However, neither mutation nor deletion of the TIE had any effect on the inhibitory activity of TGF-\u03b2 on MMP-9 transcription, indicating that the consensus TIE is not required for this effect of TGF-\u03b2. Analysis using a series of deletion mutants of the MMP-9 promoter revealed that a region containing a consensus NF-\u03baB (nuclear factor-\u03baB) site is required for the basal activity and TGF-\u03b2-mediated suppression of the promoter. Mutation of the putative NF-\u03baB site not only markedly reduced the basal transcriptional activity of the promoter, but also abrogated the responsiveness of the promoter to TGF-\u03b2. In addition, a minimal promoter containing one copy of the NF-\u03baB sequence was responsive to TGF-\u03b2 treatment. Furthermore, an electrophoretic mobility shift assay was performed with the nuclear extracts from RAW264.7\u00a0cells, and it was found that TGF-\u03b2 treatment did not disrupt the binding of NF-\u03baB p50 and p65 proteins to the NF-\u03baB sequence. Taken together, these studies indicate that the NF-\u03baB site is indispensable for the suppressive activity of TGF-\u03b2 in the regulation of MMP-9 transcription.<\/jats:p>","DOI":"10.1042\/bj20040058","type":"journal-article","created":{"date-parts":[[2004,7,9]],"date-time":"2004-07-09T15:05:07Z","timestamp":1089385507000},"page":"413-422","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["Suppression of matrix metalloproteinase-9 transcription by transforming growth factor-\u03b2 is mediated by a nuclear factor-\u03baB site"],"prefix":"10.1042","volume":"381","author":[{"given":"Kenji","family":"OGAWA","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Genetics, Walther Oncology Center, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A."},{"name":"Laboratory of Cellular Biochemistry, RIKEN, Wako, Saitama 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"CHEN","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Walther Oncology Center, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenzhong","family":"KUANG","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Walther Oncology Center, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"CHEN","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Walther Oncology Center, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A."},{"name":"Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2004,7,6]]},"reference":[{"key":"2021112217412176100_B1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/jlb.65.2.137","article-title":"The cell biology of leukocyte-mediated proteolysis","volume":"65","author":"Owen","year":"1999","journal-title":"J. Leukocyte Biol."},{"key":"2021112217412176100_B2","doi-asserted-by":"crossref","first-page":"21491","DOI":"10.1074\/jbc.274.31.21491","article-title":"Matrix metalloproteinases","volume":"274","author":"Nagase","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B3","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/jcb.240530404","article-title":"Cytokine regulation of metalloproteinase gene expression","volume":"53","author":"Mauviel","year":"1993","journal-title":"J. Cell. Biochem."},{"key":"2021112217412176100_B4","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1172\/JCI111949","article-title":"Human alveolar macrophages produce a fibroblast-like collagenase and collagenase inhibitor","volume":"76","author":"Welgus","year":"1985","journal-title":"J. Clin. Invest."},{"key":"2021112217412176100_B5","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1172\/JCI114867","article-title":"Neutral metalloproteinases produced by human mononuclear phagocytes. Enzyme profile, regulation, and expression during cellular development","volume":"86","author":"Welgus","year":"1990","journal-title":"J. Clin. Invest."},{"key":"2021112217412176100_B6","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1172\/JCI113253","article-title":"Expression of a metalloproteinase that degrades native type V collagen and denatured collagens by cultured human alveolar macrophages","volume":"80","author":"Hibbs","year":"1987","journal-title":"J. Clin. Invest."},{"key":"2021112217412176100_B7","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.4049\/jimmunol.161.6.3071","article-title":"Differential regulation of monocyte matrix metalloproteinase and TIMP-1 production by TNF-alpha, granulocyte-macrophage CSF, and IL-1 beta through prostaglandin-dependent and -independent mechanisms","volume":"161","author":"Zhang","year":"1998","journal-title":"J. Immunol."},{"key":"2021112217412176100_B8","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1002\/j.1460-2075.1987.tb02449.x","article-title":"Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor","volume":"6","author":"Edwards","year":"1987","journal-title":"EMBO J."},{"key":"2021112217412176100_B9","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.4049\/jimmunol.152.7.3637","article-title":"Regulatory mechanisms for the expression of type IV collagenases\/gelatinases in murine macrophages","volume":"152","author":"Xie","year":"1994","journal-title":"J. Immunol."},{"key":"2021112217412176100_B10","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1189\/jlb.69.4.613","article-title":"Transforming growth factor-beta suppresses tumor necrosis factor alpha-induced matrix metalloproteinase-9 expression in monocytes","volume":"69","author":"Vaday","year":"2001","journal-title":"J. Leukocyte Biol."},{"key":"2021112217412176100_B11","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1146\/annurev.immunol.16.1.137","article-title":"Regulation of immune responses by TGF-beta","volume":"16","author":"Letterio","year":"1998","journal-title":"Annu. Rev. Immunol"},{"key":"2021112217412176100_B12","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/359693a0","article-title":"Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease","volume":"359","author":"Shull","year":"1992","journal-title":"Nature (London)"},{"key":"2021112217412176100_B13","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1073\/pnas.90.2.770","article-title":"Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death","volume":"90","author":"Kulkarni","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021112217412176100_B14","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1093\/emboj\/18.5.1280","article-title":"Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta","volume":"18","author":"Yang","year":"1999","journal-title":"EMBO J."},{"key":"2021112217412176100_B15","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0092-8674(00)81730-4","article-title":"Smad3 mutant mice develop metastatic colorectal cancer","volume":"94","author":"Zhu","year":"1998","journal-title":"Cell"},{"key":"2021112217412176100_B16","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/370341a0","article-title":"Mechanism of activation of the TGF-beta receptor","volume":"370","author":"Wrana","year":"1994","journal-title":"Nature (London)"},{"key":"2021112217412176100_B17","doi-asserted-by":"crossref","first-page":"28107","DOI":"10.1074\/jbc.272.44.28107","article-title":"Phosphorylation of Ser465 and Ser467 in the C terminus of Smad2 mediates interaction with Smad4 and is required for transforming growth factor-beta signaling","volume":"272","author":"Souchelnytskyi","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B18","doi-asserted-by":"crossref","first-page":"27678","DOI":"10.1074\/jbc.272.44.27678","article-title":"TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling","volume":"272","author":"Abdollah","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B19","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1126\/science.271.5247.350","article-title":"DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1","volume":"271","author":"Hahn","year":"1996","journal-title":"Science"},{"key":"2021112217412176100_B20","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1038\/383832a0","article-title":"Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways","volume":"383","author":"Lagna","year":"1996","journal-title":"Nature (London)"},{"key":"2021112217412176100_B21","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1093\/emboj\/19.8.1745","article-title":"Transcriptional control by the TGF-beta\/Smad signaling system","volume":"19","author":"Massague","year":"2000","journal-title":"EMBO J."},{"key":"2021112217412176100_B22","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0092-8674(00)81600-1","article-title":"Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling","volume":"94","author":"Shi","year":"1998","journal-title":"Cell"},{"key":"2021112217412176100_B23","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S1097-2765(00)80061-1","article-title":"Human Smad3 and Smad4 are sequence-specific transcription activators","volume":"1","author":"Zawel","year":"1998","journal-title":"Mol. Cell"},{"key":"2021112217412176100_B24","doi-asserted-by":"crossref","first-page":"21145","DOI":"10.1074\/jbc.273.33.21145","article-title":"Identification and functional characterization of a smad binding element (SBE) in the JunB promoter that acts as a transforming growth factor-beta, activin, and bone morphogenetic protein-inducible enhancer","volume":"273","author":"Jonk","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B25","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1093\/emboj\/17.11.3091","article-title":"Direct binding of Smad3 and Smad4 to critical TGF beta-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene","volume":"17","author":"Dennler","year":"1998","journal-title":"EMBO J."},{"key":"2021112217412176100_B26","doi-asserted-by":"crossref","first-page":"39237","DOI":"10.1074\/jbc.M003339200","article-title":"Synergistic cooperation between Sp1 and Smad3\/Smad4 mediates transforming growth factor beta1 stimulation of alpha 2(I)-collagen (COL1A2) transcription","volume":"275","author":"Zhang","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B27","doi-asserted-by":"crossref","first-page":"14769","DOI":"10.1073\/pnas.95.25.14769","article-title":"SMAD3\/4-dependent transcriptional activation of the human type VII collagen gene (COL7A1) promoter by transforming growth factor beta","volume":"95","author":"Vindevoghel","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021112217412176100_B28","doi-asserted-by":"crossref","first-page":"6176","DOI":"10.1046\/j.0014-2956.2001.02565.x","article-title":"Identification of an element within the promoter of human selenoprotein P responsive to transforming growth factor-beta","volume":"268","author":"Mostert","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"2021112217412176100_B29","doi-asserted-by":"crossref","first-page":"33412","DOI":"10.1074\/jbc.274.47.33412","article-title":"Regulation of smad7 promoter by direct association with smad3 and smad4","volume":"274","author":"Nagarajan","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B30","doi-asserted-by":"crossref","first-page":"30373","DOI":"10.1074\/jbc.M304856200","article-title":"Transcriptional regulation of tristetraprolin by transforming growth factor-beta in human T cells","volume":"278","author":"Ogawa","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B31","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1101\/gad.12.14.2114","article-title":"TGF-beta-stimulated cooperation of smad proteins with the coactivators CBP\/p300","volume":"12","author":"Janknecht","year":"1998","journal-title":"Genes Dev."},{"key":"2021112217412176100_B32","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1101\/gad.12.14.2153","article-title":"The tumor suppressor Smad4\/DPC4 and transcriptional adaptor CBP\/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation","volume":"12","author":"Feng","year":"1998","journal-title":"Genes Dev."},{"key":"2021112217412176100_B33","doi-asserted-by":"crossref","first-page":"22865","DOI":"10.1074\/jbc.273.36.22865","article-title":"Physical and functional interaction of SMADs and p300\/CBP","volume":"273","author":"Pouponnot","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B34","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0092-8674(90)90807-Q","article-title":"TGF-beta 1 inhibition of transin\/stromelysin gene expression is mediated through a Fos binding sequence","volume":"61","author":"Kerr","year":"1990","journal-title":"Cell"},{"key":"2021112217412176100_B35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0167-4781(00)00002-6","article-title":"Transforming growth factor beta inhibitory element in the rabbit matrix metalloproteinase-1 (collagenase-1) gene functions as a repressor of constitutive transcription","volume":"1490","author":"White","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"2021112217412176100_B36","doi-asserted-by":"crossref","first-page":"10304","DOI":"10.1074\/jbc.M212334200","article-title":"The comparative role of activator protein 1 and Smad factors in the regulation of Timp-1 and MMP-1 gene expression by transforming growth factor-beta 1","volume":"278","author":"Hall","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B37","doi-asserted-by":"crossref","first-page":"38502","DOI":"10.1074\/jbc.M107081200","article-title":"Transforming growth factor-beta repression of matrix metalloproteinase-1 in dermal fibroblasts involves Smad3","volume":"276","author":"Yuan","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B38","doi-asserted-by":"crossref","first-page":"25766","DOI":"10.1074\/jbc.M002664200","article-title":"Transforming growth factor-beta 1 inhibits cytokine-mediated induction of human metalloelastase in macrophages","volume":"275","author":"Feinberg","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B39","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1084\/jem.193.7.793","article-title":"Matrix metalloproteinase 9 protects mice from anti-glomerular basement membrane nephritis through its fibrinolytic activity","volume":"193","author":"Lelongt","year":"2001","journal-title":"J. Exp. Med."},{"key":"2021112217412176100_B40","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S0092-8674(00)00087-8","article-title":"The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B\/MMP-9 in vivo","volume":"102","author":"Liu","year":"2000","journal-title":"Cell"},{"key":"2021112217412176100_B41","doi-asserted-by":"crossref","first-page":"14657","DOI":"10.1074\/jbc.271.25.14657","article-title":"Degradation of interleukin 1beta by matrix metalloproteinases","volume":"271","author":"Ito","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B42","doi-asserted-by":"crossref","first-page":"3340","DOI":"10.4049\/jimmunol.161.7.3340","article-title":"Generation of biologically active IL-1 beta by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1 beta processing","volume":"161","author":"Schonbeck","year":"1998","journal-title":"J. Immunol."},{"key":"2021112217412176100_B43","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1101\/gad.14.2.163","article-title":"Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis","volume":"14","author":"Yu","year":"2000","journal-title":"Genes Dev."},{"key":"2021112217412176100_B44","doi-asserted-by":"crossref","first-page":"16485","DOI":"10.1016\/S0021-9258(18)55326-6","article-title":"Complete structure of the human gene for 92-kDa type IV collagenase. Divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080\u00a0cells","volume":"266","author":"Huhtala","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B45","first-page":"395","article-title":"Regulatory mechanism of 92\u00a0kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells","volume":"8","author":"Sato","year":"1993","journal-title":"Oncogene"},{"key":"2021112217412176100_B46","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S0006-291X(82)80120-4","article-title":"Detergent-activation of latent collagenase and resolution of its component molecules","volume":"107","author":"Birkedal-Hansen","year":"1982","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021112217412176100_B47","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1093\/nar\/19.9.2499","article-title":"A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells","volume":"19","author":"Andrews","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"2021112217412176100_B48","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1002\/j.1460-2075.1995.tb07214.x","article-title":"GS domain mutations that constitutively activate T beta R-I, the downstream signaling component in the TGF-beta receptor complex","volume":"14","author":"Wieser","year":"1995","journal-title":"EMBO J."},{"key":"2021112217412176100_B49","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/S0092-8674(00)80303-7","article-title":"The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling","volume":"89","author":"Hayashi","year":"1997","journal-title":"Cell"},{"key":"2021112217412176100_B50","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/39369","article-title":"Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling","volume":"389","author":"Nakao","year":"1997","journal-title":"Nature (London)"},{"key":"2021112217412176100_B51","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0014-5793(02)02718-7","article-title":"Phosphorylation regulation of the interaction between Smad7 and activin type I receptor","volume":"519","author":"Liu","year":"2002","journal-title":"FEBS Lett."},{"key":"2021112217412176100_B52","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.1074\/jbc.M111023200","article-title":"Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter","volume":"277","author":"Korchynskyi","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B53","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1074\/jbc.M106826200","article-title":"Direct binding of Smad1 and Smad4 to two distinct motifs mediates bone morphogenetic protein-specific transcriptional activation of Id1 gene","volume":"277","author":"Lopez-Rovira","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2021112217412176100_B54","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1146\/annurev.immunol.14.1.649","article-title":"The NF-kappa B and I kappa B proteins: new discoveries and insights","volume":"14","author":"Baldwin","year":"1996","journal-title":"Annu. Rev. Immunol."},{"key":"2021112217412176100_B55","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1042\/bj3480591","article-title":"Repression of transforming-growth-factor-beta-mediated transcription by nuclear factor kappaB","volume":"348","author":"Nagarajan","year":"2000","journal-title":"Biochem. J."},{"key":"2021112217412176100_B56","doi-asserted-by":"crossref","first-page":"28937","DOI":"10.1074\/jbc.M909923199","article-title":"Interaction and functional cooperation of NF-kappa B with Smads. Transcriptional regulation of the junB promoter","volume":"275","author":"Lopez-Rovira","year":"2000","journal-title":"J. Biol. Chem."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/381\/2\/413\/714332\/bj3810413.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/381\/2\/413\/714332\/bj3810413.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T23:44:49Z","timestamp":1682725489000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/381\/2\/413\/91397\/Suppression-of-matrix-metalloproteinase-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7,6]]},"references-count":56,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2004,7,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20040058","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,7,6]]}}}