{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:31:26Z","timestamp":1778682686656,"version":"3.51.4"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genomics"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The muscle Ras (<jats:italic>MRAS<\/jats:italic>) gene resides on chromosome 3q22.3 and encodes a member of the membrane-associated Ras small GTPase proteins, which function as signal transducers in multiple processes including cell growth and differentiation. Its role in cardiovascular disease is not fully understood yet. In a preliminary study in heterozygous familial hypercholesterolaemia, we identified a locus linking the early onset of coronary artery disease (CAD) to chromosome 3q.22 and elected to sequence the<jats:italic>MRAS<\/jats:italic>gene using the MegaBACE DNA analysis system. In the present study, we investigated the association of seven single-nucleotide polymorphisms (SNPs) at this locus with CAD and its dyslipidaemia-related risk traits in 4,650 Saudi angiographed individuals using TaqMan assays by the Applied Biosystems real-time Prism 7900HT Sequence Detection System.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the studied SNPs, rs6782181 (<jats:italic>p<\/jats:italic>= 0.017) and rs9818870T (<jats:italic>p<\/jats:italic>= 0.009) were associated with CAD following adjustment for sex, age and other confounding risk factors. The rs6782181_GG also conferred risk for obesity (1,764 cases vs. 2,586 controls) [1.16(1.03\u20131.30);<jats:italic>p<\/jats:italic>= 0.017], hypercholesterolaemia (1,686 vs. 2,744) [1.23(1.02\u20131.47);<jats:italic>p<\/jats:italic>= 0.019], hypertriglyceridaemia (1,155 vs. 3,496) [1.29(1.01\u20131.45);<jats:italic>p<\/jats:italic>= 0.043] and low high-density lipoprotein-cholesterol (lHDL-chol) levels (1,935 vs. 2,401) [1.15(1.02\u20131.30);<jats:italic>p<\/jats:italic>= 0.023] after adjustment. Additionally, rs253662_(CT+TT) [1.16(1.01\u20131.32);<jats:italic>p<\/jats:italic>= 0.030] was associated with lHDL-chol levels. Interestingly, rs253662 (<jats:italic>p<\/jats:italic>= 0.014) and rs6782181 (<jats:italic>p<\/jats:italic>= 0.019) were protective against acquiring high low-density lipoprotein-cholesterol (hLDL-chol) levels (<jats:italic>p<\/jats:italic>= 0.014), while rs1720819 showed similar effects against CAD (<jats:italic>p<\/jats:italic>&lt; 0.0001). More importantly, a 7-mer haplotype, ACCTGAC (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>= 7.66;<jats:italic>p<\/jats:italic>= 0.0056), constructed from the studied SNPs, its 6-mer derivative CCTGAC (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>= 6.90;<jats:italic>p<\/jats:italic>= 0.0086) and several other shorter derivatives conferred risk for obesity. hLDL-chol was weakly linked to CTAA (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>= 3.79;<jats:italic>p<\/jats:italic>= 0.052) and CCT (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>= 4.32;<jats:italic>p<\/jats:italic>= 0.038), while several other haplotypes were protective against both obesity and hLDL-chol level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that the genomic locus for the<jats:italic>MRAS<\/jats:italic>gene confers risk for CAD, obesity and dyslipidaemia and point to the possible involvement of other genes or regulatory elements at this locus, rather than changes in the M-Ras protein function, in these events.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1479-7364-7-15","type":"journal-article","created":{"date-parts":[[2013,6,5]],"date-time":"2013-06-05T08:50:09Z","timestamp":1370422209000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["New susceptibility locus for obesity and dyslipidaemia on chromosome 3q22.3"],"prefix":"10.1186","volume":"7","author":[{"given":"Maie","family":"Alshahid","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salma M","family":"Wakil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Al-Najai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nzioka P","family":"Muiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samar","family":"Elhawari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisy","family":"Gueco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Editha","family":"Andres","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samia","family":"Hagos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nejat","family":"Mazhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian F","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nduna","family":"Dzimiri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,6,5]]},"reference":[{"issue":"22","key":"43_CR1","doi-asserted-by":"publisher","first-page":"2675","DOI":"10.1038\/sj.onc.1201674","volume":"15","author":"A Kimmelman","year":"1997","unstructured":"Kimmelman A, Tolkacheva T, Lorenzi MV, Osada M, Chan AM: Identification and characterization of R-ras3: a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution. Oncogene. 1997, 15 (22): 2675-2685. 10.1038\/sj.onc.1201674.","journal-title":"Oncogene"},{"issue":"34","key":"43_CR2","doi-asserted-by":"publisher","first-page":"23850","DOI":"10.1074\/jbc.274.34.23850","volume":"274","author":"LA Quilliam","year":"1999","unstructured":"Quilliam LA, Castro AF, Rogers-Graham KS, Martin CB, Der CJ, Bi C: M-Ras\/R-Ras3, a transforming ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6. J Biol Chem. 1999, 274 (34): 23850-23857. 10.1074\/jbc.274.34.23850.","journal-title":"J Biol Chem"},{"issue":"3","key":"43_CR3","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.yexcr.2009.09.028","volume":"316","author":"H Watanabe-Takano","year":"2010","unstructured":"Watanabe-Takano H, Takano K, Keduka E, Endo T: M-Ras is activated by bone morphogenetic protein-2 and participates in osteoblastic determination, differentiation, and transdifferentiation. Exp Cell Res. 2010, 316 (3): 477-490. 10.1016\/j.yexcr.2009.09.028.","journal-title":"Exp Cell Res"},{"issue":"10","key":"43_CR4","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.4161\/cc.3.10.1182","volume":"3","author":"MC Harrisingh","year":"2004","unstructured":"Harrisingh MC, Lloyd AC: Ras\/Raf\/ERK signalling and NF1. Cell Cycle. 2004, 3 (10): 1255-1258. 10.4161\/cc.3.10.1182.","journal-title":"Cell Cycle"},{"issue":"11","key":"43_CR5","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/S0898-6568(01)00192-9","volume":"13","author":"C Liebmann","year":"2001","unstructured":"Liebmann C: Regulation of MAP kinase activity by peptide receptor signalling pathway: paradigms of multiplicity. Cell Signal. 2001, 13 (11): 777-785. 10.1016\/S0898-6568(01)00192-9.","journal-title":"Cell Signal"},{"issue":"11 Reviews","key":"43_CR6","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1038\/sj.onc.1202185","volume":"17","author":"E Kerkhoff","year":"1998","unstructured":"Kerkhoff E, Rapp UR: Cell cycle targets of Ras\/Raf signalling. Oncogene. 1998, 17 (11 Reviews): 1457-1462.","journal-title":"Oncogene"},{"issue":"10","key":"43_CR7","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/S0898-6568(98)00014-X","volume":"10","author":"S Chakraborti","year":"1998","unstructured":"Chakraborti S, Chakraborti T: Oxidant-mediated activation of mitogen-activated protein kinases and nuclear transcription factors in the cardiovascular system: a brief overview. Cell Signal. 1998, 10 (10): 675-683. 10.1016\/S0898-6568(98)00014-X.","journal-title":"Cell Signal"},{"issue":"5","key":"43_CR8","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/S0898-6568(02)00139-0","volume":"15","author":"H Chong","year":"2003","unstructured":"Chong H, Vikis HG, Guan KL: Mechanisms of regulating the Raf kinase family. Cell Signal. 2003, 15 (5): 463-469. 10.1016\/S0898-6568(02)00139-0.","journal-title":"Cell Signal"},{"issue":"7","key":"43_CR9","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1182\/blood.V94.7.2433.419k31_2433_2444","volume":"94","author":"GR Ehrhardt","year":"1999","unstructured":"Ehrhardt GR, Leslie KB, Lee F, Wieler JS, Schrader JW: M-Ras, a widely expressed 29-kD homologue of p21 Ras: expression of a constitutively active mutant results in factor-independent growth of an interleukin-3-dependent cell line. Blood. 1999, 94 (7): 2433-2444.","journal-title":"Blood"},{"issue":"8","key":"43_CR10","doi-asserted-by":"publisher","first-page":"2949","DOI":"10.1091\/mbc.E07-03-0250","volume":"18","author":"Y Yoshikawa","year":"2007","unstructured":"Yoshikawa Y, Satoh T, Tamura T, Wei P, Bilasy SE, Edamatsu H, Aiba A, Katagiri K, Kinashi T, Nakao K, Kataoka T: The M-Ras-RA-GEF-2-Rap1 pathway mediates tumor necrosis factor-alpha dependent regulation of integrin activation in splenocytes. Mol Biol Cell. 2007, 18 (8): 2949-2959. 10.1091\/mbc.E07-03-0250.","journal-title":"Mol Biol Cell"},{"issue":"16","key":"43_CR11","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1038\/sj.onc.1203530","volume":"19","author":"AC Kimmelman","year":"2000","unstructured":"Kimmelman AC, Osada M, Chan AM: R-Ras3, a brain-specific Ras-related protein, activates Akt and promotes cell survival in PC12 cells. Oncogene. 2000, 19 (16): 2014-2022. 10.1038\/sj.onc.1203530.","journal-title":"Oncogene"},{"issue":"5","key":"43_CR12","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1182\/blood.V94.5.1701","volume":"94","author":"J Louahed","year":"1999","unstructured":"Louahed J, Grasso L, De Smet C, Van Roost E, Wildmann C, Nicolaides NC, Levitt RC, Renauld JC: Interleukin-9-induced expression of M-Ras\/R-Ras3 oncogene in T-helper clones. Blood. 1999, 94 (5): 1701-1710.","journal-title":"Blood"},{"issue":"9","key":"43_CR13","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1111\/j.1349-7006.2006.00256.x","volume":"97","author":"S Muto","year":"2006","unstructured":"Muto S, Katsuki M, Horie S: Rapid induction of skin tumors in human but not mouse c-Ha-ras proto-oncogene transgenic mice by chemical carcinogenesis. Cancer Sci. 2006, 97 (9): 842-847. 10.1111\/j.1349-7006.2006.00256.x.","journal-title":"Cancer Sci"},{"issue":"6","key":"43_CR14","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/bjc.2011.296","volume":"105","author":"A Abuli","year":"2011","unstructured":"Abuli A, Fernandez-Rozadilla C, Giraldez MD, Munoz J, Gonzalo V, Bessa X, Bujanda L, Rene JM, Lanas A, Garcia AM, Salo J, Arguello L, Vilella A, Carreno R, Jover R, Xicola RM, Llor X, Carvajal-Carmona L, Tomlinson IP, Kerr DJ, Houlston RS, Pique JM, Carracedo A, Castells A, Andreu M, Ruiz-Ponte C, Castellvi-Bel S: A two-phase case\u2013control study for colorectal cancer genetic susceptibility: candidate genes from chromosomal regions 9q22 and 3q22. Br J Cancer. 2011, 105 (6): 870-875. 10.1038\/bjc.2011.296.","journal-title":"Br J Cancer"},{"issue":"14","key":"43_CR15","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1038\/sj.onc.1208441","volume":"24","author":"X Guo","year":"2005","unstructured":"Guo X, Schrader KA, Xu Y, Schrader JW: Expression of a constitutively active mutant of M-Ras in normal bone marrow is sufficient for induction of a malignant mastocytosis\/mast cell leukemia, distinct from the histiocytosis\/monocytic leukemia induced by expression of activated H-Ras. Oncogene. 2005, 24 (14): 2330-2342. 10.1038\/sj.onc.1208441.","journal-title":"Oncogene"},{"issue":"4","key":"43_CR16","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1158\/1541-7786.242.2.4","volume":"2","author":"KX Zhang","year":"2004","unstructured":"Zhang KX, Ward KR, Schrader JW: Multiple aspects of the phenotype of mammary epithelial cells transformed by expression of activated M-Ras depend on an autocrine mechanism mediated by hepatocyte growth factor\/scatter factor. Mol Cancer Res. 2004, 2 (4): 242-255.","journal-title":"Mol Cancer Res"},{"issue":"40","key":"43_CR17","doi-asserted-by":"publisher","first-page":"4647","DOI":"10.1038\/sj.onc.1203820","volume":"19","author":"D Wang","year":"2000","unstructured":"Wang D, Yang W, Du J, Devalaraja MN, Liang P, Matsumoto K, Tsubakimoto K, Endo T, Richmond A: MGSA\/GRO-mediated melanocyte transformation involves induction of Ras expression. Oncogene. 2000, 19 (40): 4647-4659. 10.1038\/sj.onc.1203820.","journal-title":"Oncogene"},{"key":"43_CR18","unstructured":"MRAS (muscle RAS oncogene homolog). http:\/\/biogps.org\/#goto=genereport&id=22808,"},{"issue":"3","key":"43_CR19","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/ng.307","volume":"41","author":"J Erdmann","year":"2009","unstructured":"Erdmann J, Grosshennig A, Braund PS, Konig IR, Hengstenberg C, Hall AS, Linsel-Nitschke P, Kathiresan S, Wright B, Tregouet DA, Cambien F, Bruse P, Aherrahrou Z, Wagner AK, Stark K, Schwartz SM, Salomaa V, Elosua R, Melander O, Voight BF, O'Donnell CJ, Peltonen L, Siscovick DS, Altshuler D, Merlini PA, Peyvandi F, Bernardinelli L, Ardissino D, Schillert A, Blankenberg S, et al: New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nat Genet. 2009, 41 (3): 280-282. 10.1038\/ng.307.","journal-title":"Nat Genet"},{"issue":"6","key":"43_CR20","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1161\/CIRCGENETICS.111.960336","volume":"4","author":"KL Ellis","year":"2001","unstructured":"Ellis KL, Frampton CM, Pilbrow AP, Troughton RW, Doughty RN, Whalley GA, Ellis CJ, Skelton L, Thomson J, Yandle TG, Richards AM, Cameron VA: Genomic risk variants at 1p13.3, 1q41, and 3q22.3 are associated with subsequent cardiovascular outcomes in healthy controls and in established coronary artery disease. Circ Cardiovasc Genet. 2001, 4 (6): 636-646.","journal-title":"Circ Cardiovasc Genet"},{"issue":"11","key":"43_CR21","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1161\/ATVBAHA.107.149179","volume":"27","author":"E Galkina","year":"2007","unstructured":"Galkina E, Ley K: Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol. 2007, 27 (11): 2292-2301. 10.1161\/ATVBAHA.107.149179.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"43_CR22","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1534\/genetics.107.078782","volume":"178","author":"HS M\u00e4kinen","year":"2008","unstructured":"M\u00e4kinen HS, Shikano T, Cano JM, Meril\u00e4 J: Hitchhiking mapping reveals a candidate genomic region for natural selection in three-spined stickleback chromosome VIII. Genetics. 2008, 178 (1): 453-465. 10.1534\/genetics.107.078782.","journal-title":"Genetics"},{"issue":"1403","key":"43_CR23","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1098\/rstb.2000.0716","volume":"355","author":"NH Barton","year":"2000","unstructured":"Barton NH: Genetic hitchhiking. Philos Trans R Soc Lond B Biol Sci. 2000, 355 (1403): 1553-1562. 10.1098\/rstb.2000.0716.","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"19","key":"43_CR24","doi-asserted-by":"publisher","first-page":"E1743","DOI":"10.1073\/pnas.1219381110","volume":"110","author":"S Yeaman","year":"2013","unstructured":"Yeaman S: Genomic rearrangements and the evolution of clusters of locally adaptive loci. Proc Natl Acad Sci USA. 2013, 110 (19): E1743-E1751. 10.1073\/pnas.1219381110.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"43_CR25","doi-asserted-by":"publisher","first-page":"e61742","DOI":"10.1371\/journal.pone.0061742","volume":"8","author":"KA Schneider","year":"2013","unstructured":"Schneider KA, Kim Y: Genetic hitchhiking under heterogeneous spatial selection pressures. PLoS One. 2013, 8 (4): e61742-10.1371\/journal.pone.0061742.","journal-title":"PLoS One"},{"key":"43_CR26","unstructured":"Barton NH, Etheridge AM, Kelleher J, Veber A: Genetic hitchhiking in spatially extended populations. Theor Popul Biol. in press"},{"issue":"2","key":"43_CR27","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1534\/genetics.112.147157","volume":"193","author":"MM Desai","year":"2013","unstructured":"Desai MM, Walczak AM, Fisher DS: Genetic diversity and the structure of genealogies in rapidly adapting populations. Genetics. 2013, 193 (2): 565-585. 10.1534\/genetics.112.147157.","journal-title":"Genetics"},{"issue":"12","key":"43_CR28","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.1111\/jeb.12013","volume":"25","author":"SM Flaxman","year":"2012","unstructured":"Flaxman SM, Feder JL, Nosil P: Spatially explicit models of divergence and genome hitchhiking. J Evol Biol. 2012, 25 (12): 2633-2650. 10.1111\/jeb.12013.","journal-title":"J Evol Biol"},{"key":"43_CR29","volume-title":"Genet Res","author":"Y Kim","year":"2013","unstructured":"Kim Y: Stochastic patterns of polymorphism after a selective sweep over a subdivided population. Genet Res. 2013, 10.1017\/S0016672313000062."},{"issue":"5_MeetingAbstra","key":"43_CR30","first-page":"A524","volume":"32","author":"N Dzimiri","year":"2012","unstructured":"Dzimiri N, Al-Najai M, Elhawari S, Gueco D, Vigilla MG, Andres E, Muiya P, Mazher N, Alshahid M, Meyer BF: The interaction of Agt gene polymorphism with cardiovascular risk traits in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012, 32 (5_MeetingAbstracts): A524-","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"6","key":"43_CR31","first-page":"e35","volume":"27","author":"American Heart Association","year":"2007","unstructured":"American Heart Association: Arteriosclerosis, Thrombosis, and Vascular Biology Annual Conference 2007. Arterioscler Thromb Vasc Biol. 2007, 27 (6): e35-e137.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"43_CR32","unstructured":"WMA Declaration of Helsinki - ethical principles for medical research involving human subjects. http:\/\/www.wma.net\/en\/30publications\/10policies\/b3\/index.html,"},{"key":"43_CR33","unstructured":"Schaid DJ: Statistical genetics and genetic epidemiology. http:\/\/mayoresearch.mayo.edu\/mayo\/research\/schaid_lab\/software.cfm,"},{"key":"43_CR34","unstructured":"The R Project for Statistical Computing. http:\/\/www.r-project.org\/,"},{"issue":"2","key":"43_CR35","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1086\/338688","volume":"70","author":"DJ Schaid","year":"2002","unstructured":"Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA: Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet. 2002, 70 (2): 425-434. 10.1086\/338688.","journal-title":"Am J Hum Genet"},{"issue":"1","key":"43_CR36","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1159\/000071811","volume":"55","author":"SL Lake","year":"2003","unstructured":"Lake SL, Lyon H, Tantisira K, Silverman EK, Weiss ST, Laird NM, Schaid DJ: Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Hum Hered. 2003, 55 (1): 56-65. 10.1159\/000071811.","journal-title":"Hum Hered"}],"container-title":["Human Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1479-7364-7-15.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,2]],"date-time":"2023-07-02T06:28:30Z","timestamp":1688279310000},"score":1,"resource":{"primary":{"URL":"https:\/\/humgenomics.biomedcentral.com\/articles\/10.1186\/1479-7364-7-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,5]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["43"],"URL":"https:\/\/doi.org\/10.1186\/1479-7364-7-15","relation":{},"ISSN":["1479-7364"],"issn-type":[{"value":"1479-7364","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,5]]},"assertion":[{"value":"9 April 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"15"}}