{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:29:46Z","timestamp":1761708586574},"reference-count":90,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dendritic cells are antigen-presenting cells that play an essential role in linking the innate and adaptive immune systems. Much research has focused on the signaling pathways triggered upon infection of dendritic cells by various pathogens. The high level of activity in the field makes it desirable to have a pathway-based resource to access the information in the literature. Current pathway diagrams lack either comprehensiveness, or an open-access editorial interface. Hence, there is a need for a dependable, expertly curated knowledgebase that integrates this information into a map of signaling networks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Description<\/jats:title><jats:p>We have built a detailed diagram of the dendritic cell signaling network, with the goal of providing researchers with a valuable resource and a facile method for community input. Network construction has relied on comprehensive review of the literature and regular updates. The diagram includes detailed depictions of pathways activated downstream of different pathogen recognition receptors such as Toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors and nucleotide-binding oligomerization domain-like receptors. Initially assembled using CellDesigner software, it provides an annotated graphical representation of interactions stored in Systems Biology Mark-up Language. The network, which comprises 249 nodes and 213 edges, has been web-published through the Biological Pathway Publisher software suite. Nodes are annotated with PubMed references and gene-related information, and linked to a public wiki, providing a discussion forum for updates and corrections. To gain more insight into regulatory patterns of dendritic cell signaling, we analyzed the network using graph-theory methods: bifan, feedforward and multi-input convergence motifs were enriched. This emphasis on activating control mechanisms is consonant with a network that subserves persistent and coordinated responses to pathogen detection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This map represents a navigable aid for presenting a consensus view of the current knowledge on dendritic cell signaling that can be continuously improved through contributions of research community experts. Because the map is available in a machine readable format, it can be edited and may assist researchers in data analysis. Furthermore, the availability of a comprehensive knowledgebase might help further research in this area such as vaccine development. The dendritic cell signaling knowledgebase is accessible at<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/tsb.mssm.edu\/pathwayPublisher\/DC_pathway\/DC_pathway_index.html\" ext-link-type=\"uri\">http:\/\/tsb.mssm.edu\/pathwayPublisher\/DC_pathway\/DC_pathway_index.html<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1752-0509-4-137","type":"journal-article","created":{"date-parts":[[2010,10,7]],"date-time":"2010-10-07T18:15:56Z","timestamp":1286475356000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Signaling network of dendritic cells in response to pathogens: a community-input supported knowledgebase"],"prefix":"10.1186","volume":"4","author":[{"given":"Sonali","family":"Patil","sequence":"first","affiliation":[]},{"given":"Hanna","family":"Pincas","sequence":"additional","affiliation":[]},{"given":"Jeremy","family":"Seto","sequence":"additional","affiliation":[]},{"given":"German","family":"Nudelman","sequence":"additional","affiliation":[]},{"given":"Irina","family":"Nudelman","sequence":"additional","affiliation":[]},{"given":"Stuart C","family":"Sealfon","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,10,7]]},"reference":[{"key":"548_CR1","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1182\/blood.V90.4.1458","volume":"90","author":"C Caux","year":"1997","unstructured":"Caux C, Massacrier C, Vanbervliet B, Dubois B, Durand I, Cella M, Lanzavecchia A, Banchereau J: CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to granulocyte-macrophage colony-stimulating factor plus tumor necrosis factor alpha: II. Functional analysis. Blood. 1997, 90: 1458-1470.","journal-title":"Blood"},{"key":"548_CR2","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/S1074-7613(03)00208-5","volume":"19","author":"G Jego","year":"2003","unstructured":"Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J: Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity. 2003, 19: 225-234. 10.1016\/S1074-7613(03)00208-5","journal-title":"Immunity"},{"key":"548_CR3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.coi.2003.11.007","volume":"16","author":"C Reis e Sousa","year":"2004","unstructured":"Reis e Sousa C: Activation of dendritic cells: translating innate into adaptive immunity. Curr Opin Immunol. 2004, 16: 21-25. 10.1016\/j.coi.2003.11.007","journal-title":"Curr Opin Immunol"},{"key":"548_CR4","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S1286-4579(00)00302-6","volume":"2","author":"GJ Clark","year":"2000","unstructured":"Clark GJ, Angel N, Kato M, Lopez JA, MacDonald K, Vuckovic S, Hart DN: The role of dendritic cells in the innate immune system. Microbes Infect. 2000, 2: 257-272. 10.1016\/S1286-4579(00)00302-6","journal-title":"Microbes Infect"},{"key":"548_CR5","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1084\/jem.20020470","volume":"196","author":"GD Brown","year":"2002","unstructured":"Brown GD, Taylor PR, Reid DM, Willment JA, Williams DL, Martinez-Pomares L, Wong SY, Gordon S: Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med. 2002, 196: 407-412. 10.1084\/jem.20020470","journal-title":"J Exp Med"},{"key":"548_CR6","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/79815","volume":"1","author":"TB Geijtenbeek","year":"2000","unstructured":"Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG, van Kooyk Y: DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol. 2000, 1: 353-357. 10.1038\/79815","journal-title":"Nat Immunol"},{"key":"548_CR7","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1126\/science.1103685","volume":"307","author":"S Maeda","year":"2005","unstructured":"Maeda S, Hsu LC, Liu H, Bankston LA, Iimura M, Kagnoff MF, Eckmann L, Karin M: Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science. 2005, 307: 734-738. 10.1126\/science.1103685","journal-title":"Science"},{"key":"548_CR8","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.it.2007.03.008","volume":"28","author":"A Macagno","year":"2007","unstructured":"Macagno A, Napolitani G, Lanzavecchia A, Sallusto F: Duration, combination and timing: the signal integration model of dendritic cell activation. Trends Immunol. 2007, 28: 227-233. 10.1016\/j.it.2007.03.008","journal-title":"Trends Immunol"},{"key":"548_CR9","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.4049\/jimmunol.178.5.2623","volume":"178","author":"PJ Murray","year":"2007","unstructured":"Murray PJ: The JAK-STAT signaling pathway: input and output integration. J Immunol. 2007, 178: 2623-2629.","journal-title":"J Immunol"},{"key":"548_CR10","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/89863","volume":"7","author":"FO Nestle","year":"2001","unstructured":"Nestle FO, Banchereau J, Hart D: Dendritic cells: On the move from bench to bedside. Nat Med. 2001, 7: 761-765. 10.1038\/89863","journal-title":"Nat Med"},{"key":"548_CR11","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1038\/nbt1111","volume":"23","author":"H Kitano","year":"2005","unstructured":"Kitano H, Funahashi A, Matsuoka Y, Oda K: Using process diagrams for the graphical representation of biological networks. Nat Biotechnol. 2005, 23: 961-966. 10.1038\/nbt1111","journal-title":"Nat Biotechnol"},{"key":"548_CR12","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/nar\/27.1.29","volume":"27","author":"H Ogata","year":"1999","unstructured":"Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M: KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 1999, 27: 29-34. 10.1093\/nar\/27.1.29","journal-title":"Nucleic Acids Res"},{"key":"548_CR13","doi-asserted-by":"publisher","first-page":"R39","DOI":"10.1186\/gb-2007-8-3-r39","volume":"8","author":"I Vastrik","year":"2007","unstructured":"Vastrik I, D'Eustachio P, Schmidt E, Gopinath G, Croft D, de Bono B, Gillespie M, Jassal B, Lewis S, Matthews L, et al.: Reactome: a knowledge base of biologic pathways and processes. Genome Biol. 2007, 8: R39- 10.1186\/gb-2007-8-3-r39","journal-title":"Genome Biol"},{"key":"548_CR14","doi-asserted-by":"publisher","first-page":"2006 0015","DOI":"10.1038\/msb4100057","volume":"2","author":"K Oda","year":"2006","unstructured":"Oda K, Kitano H: A comprehensive map of the toll-like receptor signaling network. Mol Syst Biol. 2006, 2: 2006 0015- 10.1038\/msb4100057","journal-title":"Mol Syst Biol"},{"key":"548_CR15","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S1478-5382(03)02370-9","volume":"1","author":"A Funahashi","year":"2003","unstructured":"Funahashi A, Tanimura N, Morohashi M, Kitano H: CellDesigner: a process diagram editor for gene-regulatory and biochemical networks. BioSilico. 2003, 1: 159-162. 10.1016\/S1478-5382(03)02370-9.","journal-title":"BioSilico"},{"key":"548_CR16","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/1471-2105-8-168","volume":"8","author":"GA Viswanathan","year":"2007","unstructured":"Viswanathan GA, Nudelman G, Patil S, Sealfon SC: BioPP: a tool for web-publication of biological networks. BMC Bioinformatics. 2007, 8: 168- 10.1186\/1471-2105-8-168","journal-title":"BMC Bioinformatics"},{"key":"548_CR17","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1146\/annurev.biochem.76.060605.122847","volume":"76","author":"MS Lee","year":"2007","unstructured":"Lee MS, Kim YJ: Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem. 2007, 76: 447-480. 10.1146\/annurev.biochem.76.060605.122847","journal-title":"Annu Rev Biochem"},{"key":"548_CR18","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","volume":"124","author":"S Akira","year":"2006","unstructured":"Akira S, Uematsu S, Takeuchi O: Pathogen recognition and innate immunity. Cell. 2006, 124: 783-801. 10.1016\/j.cell.2006.02.015","journal-title":"Cell"},{"key":"548_CR19","doi-asserted-by":"publisher","first-page":"41443","DOI":"10.1074\/jbc.M301742200","volume":"278","author":"A Dunne","year":"2003","unstructured":"Dunne A, Ejdeback M, Ludidi PL, O'Neill LA, Gay NJ: Structural complementarity of Toll\/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88. J Biol Chem. 2003, 278: 41443-41451. 10.1074\/jbc.M301742200","journal-title":"J Biol Chem"},{"key":"548_CR20","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1084\/jem.20031023","volume":"198","author":"KA Fitzgerald","year":"2003","unstructured":"Fitzgerald KA, Rowe DC, Barnes BJ, Caffrey DR, Visintin A, Latz E, Monks B, Pitha PM, Golenbock DT: LPS-TLR4 signaling to IRF-3\/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J Exp Med. 2003, 198: 1043-1055. 10.1084\/jem.20031023","journal-title":"J Exp Med"},{"key":"548_CR21","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nature01180","volume":"420","author":"T Horng","year":"2002","unstructured":"Horng T, Barton GM, Flavell RA, Medzhitov R: The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature. 2002, 420: 329-333. 10.1038\/nature01180","journal-title":"Nature"},{"key":"548_CR22","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1038\/ni0901-835","volume":"2","author":"T Horng","year":"2001","unstructured":"Horng T, Barton GM, Medzhitov R: TIRAP: an adapter molecule in the Toll signaling pathway. Nat Immunol. 2001, 2: 835-841. 10.1038\/ni0901-835","journal-title":"Nat Immunol"},{"key":"548_CR23","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/ni886","volume":"4","author":"H Oshiumi","year":"2003","unstructured":"Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T: TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol. 2003, 4: 161-167. 10.1038\/ni886","journal-title":"Nat Immunol"},{"key":"548_CR24","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nature01182","volume":"420","author":"M Yamamoto","year":"2002","unstructured":"Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, Hoshino K, Takeuchi O, Kobayashi M, Fujita T, et al.: Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature. 2002, 420: 324-329. 10.1038\/nature01182","journal-title":"Nature"},{"key":"548_CR25","doi-asserted-by":"publisher","first-page":"6449","DOI":"10.4049\/jimmunol.174.10.6449","volume":"174","author":"P Henneke","year":"2005","unstructured":"Henneke P, Morath S, Uematsu S, Weichert S, Pfitzenmaier M, Takeuchi O, Muller A, Poyart C, Akira S, Berner R, et al.: Role of lipoteichoic acid in the phagocyte response to group B streptococcus. J Immunol. 2005, 174: 6449-6455.","journal-title":"J Immunol"},{"key":"548_CR26","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1111\/j.1574-695X.2007.00353.x","volume":"52","author":"MG Netea","year":"2008","unstructured":"Netea MG, van de Veerdonk F, Verschueren I, van der Meer JW, Kullberg BJ: Role of TLR1 and TLR6 in the host defense against disseminated candidiasis. FEMS Immunol Med Microbiol. 2008, 52: 118-123. 10.1111\/j.1574-695X.2007.00353.x","journal-title":"FEMS Immunol Med Microbiol"},{"key":"548_CR27","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1084\/jem.20040520","volume":"199","author":"H Hemmi","year":"2004","unstructured":"Hemmi H, Takeuchi O, Sato S, Yamamoto M, Kaisho T, Sanjo H, Kawai T, Hoshino K, Takeda K, Akira S: The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J Exp Med. 2004, 199: 1641-1650. 10.1084\/jem.20040520","journal-title":"J Exp Med"},{"key":"548_CR28","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S1097-2765(00)80136-7","volume":"2","author":"R Medzhitov","year":"1998","unstructured":"Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, Janeway CA: MyD88 is an adaptor protein in the hToll\/IL-1 receptor family signaling pathways. Mol Cell. 1998, 2: 253-258. 10.1016\/S1097-2765(00)80136-7","journal-title":"Mol Cell"},{"key":"548_CR29","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1038\/ni1243","volume":"6","author":"T Kawai","year":"2005","unstructured":"Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S: IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol. 2005, 6: 981-988. 10.1038\/ni1243","journal-title":"Nat Immunol"},{"key":"548_CR30","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.cell.2005.08.012","volume":"122","author":"RB Seth","year":"2005","unstructured":"Seth RB, Sun L, Ea CK, Chen ZJ: Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005, 122: 669-682. 10.1016\/j.cell.2005.08.012","journal-title":"Cell"},{"key":"548_CR31","doi-asserted-by":"publisher","first-page":"6072","DOI":"10.1128\/JVI.02495-05","volume":"80","author":"R Lin","year":"2006","unstructured":"Lin R, Lacoste J, Nakhaei P, Sun Q, Yang L, Paz S, Wilkinson P, Julkunen I, Vitour D, Meurs E, Hiscott J: Dissociation of a MAVS\/IPS-1\/VISA\/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage. J Virol. 2006, 80: 6072-6083. 10.1128\/JVI.02495-05","journal-title":"J Virol"},{"key":"548_CR32","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/icb.2008.55","volume":"86","author":"SJ van Vliet","year":"2008","unstructured":"van Vliet SJ, Garcia-Vallejo JJ, van Kooyk Y: Dendritic cells and C-type lectin receptors: coupling innate to adaptive immune responses. Immunol Cell Biol. 2008, 86: 580-587. 10.1038\/icb.2008.55","journal-title":"Immunol Cell Biol"},{"key":"548_CR33","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nri1745","volume":"6","author":"GD Brown","year":"2006","unstructured":"Brown GD: Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol. 2006, 6: 33-43. 10.1038\/nri1745","journal-title":"Nat Rev Immunol"},{"key":"548_CR34","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1093\/intimm\/dxp017","volume":"21","author":"T Kawai","year":"2009","unstructured":"Kawai T, Akira S: The roles of TLRs, RLRs and NLRs in pathogen recognition. Int Immunol. 2009, 21: 317-337. 10.1093\/intimm\/dxp017","journal-title":"Int Immunol"},{"key":"548_CR35","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1007\/s10156-008-0596-1","volume":"14","author":"Y Kumagai","year":"2008","unstructured":"Kumagai Y, Takeuchi O, Akira S: Pathogen recognition by innate receptors. J Infect Chemother. 2008, 14: 86-92. 10.1007\/s10156-008-0596-1","journal-title":"J Infect Chemother"},{"key":"548_CR36","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.cell.2004.05.004","volume":"117","author":"F Martinon","year":"2004","unstructured":"Martinon F, Tschopp J: Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell. 2004, 117: 561-574. 10.1016\/j.cell.2004.05.004","journal-title":"Cell"},{"key":"548_CR37","doi-asserted-by":"publisher","first-page":"7438","DOI":"10.4049\/jimmunol.176.12.7438","volume":"176","author":"I Bekeredjian-Ding","year":"2006","unstructured":"Bekeredjian-Ding I, Roth SI, Gilles S, Giese T, Ablasser A, Hornung V, Endres S, Hartmann G: T cell-independent, TLR-induced IL-12p70 production in primary human monocytes. J Immunol. 2006, 176: 7438-7446.","journal-title":"J Immunol"},{"key":"548_CR38","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1084\/jem.20041964","volume":"201","author":"G Gautier","year":"2005","unstructured":"Gautier G, Humbert M, Deauvieau F, Scuiller M, Hiscott J, Bates EE, Trinchieri G, Caux C, Garrone P: A type I interferon autocrine-paracrine loop is involved in Toll-like receptor-induced interleukin-12p70 secretion by dendritic cells. J Exp Med. 2005, 201: 1435-1446. 10.1084\/jem.20041964","journal-title":"J Exp Med"},{"key":"548_CR39","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/ni1223","volume":"6","author":"G Napolitani","year":"2005","unstructured":"Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A: Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol. 2005, 6: 769-776. 10.1038\/ni1223","journal-title":"Nat Immunol"},{"key":"548_CR40","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/35099560","volume":"413","author":"L Alexopoulou","year":"2001","unstructured":"Alexopoulou L, Holt AC, Medzhitov R, Flavell RA: Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001, 413: 732-738. 10.1038\/35099560","journal-title":"Nature"},{"key":"548_CR41","doi-asserted-by":"publisher","first-page":"38133","DOI":"10.1074\/jbc.M507163200","volume":"280","author":"O de Bouteiller","year":"2005","unstructured":"de Bouteiller O, Merck E, Hasan UA, Hubac S, Benguigui B, Trinchieri G, Bates EE, Caux C: Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem. 2005, 280: 38133-38145. 10.1074\/jbc.M507163200","journal-title":"J Biol Chem"},{"key":"548_CR42","doi-asserted-by":"publisher","first-page":"3533","DOI":"10.1073\/pnas.0308496101","volume":"101","author":"Z Jiang","year":"2004","unstructured":"Jiang Z, Mak TW, Sen G, Li X: Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta. Proc Natl Acad Sci USA. 2004, 101: 3533-3538. 10.1073\/pnas.0308496101","journal-title":"Proc Natl Acad Sci USA"},{"key":"548_CR43","doi-asserted-by":"publisher","first-page":"17264","DOI":"10.1073\/pnas.0407639101","volume":"101","author":"J Andrejeva","year":"2004","unstructured":"Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE: The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci USA. 2004, 101: 17264-17269. 10.1073\/pnas.0407639101","journal-title":"Proc Natl Acad Sci USA"},{"key":"548_CR44","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1073\/pnas.022637199","volume":"99","author":"DC Kang","year":"2002","unstructured":"Kang DC, Gopalkrishnan RV, Wu Q, Jankowsky E, Pyle AM, Fisher PB: mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci USA. 2002, 99: 637-642. 10.1073\/pnas.022637199","journal-title":"Proc Natl Acad Sci USA"},{"key":"548_CR45","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.4049\/jimmunol.175.5.2851","volume":"175","author":"M Yoneyama","year":"2005","unstructured":"Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M, Akira S, et al.: Shared and unique functions of the DExD\/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol. 2005, 175: 2851-2858.","journal-title":"J Immunol"},{"key":"548_CR46","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/ni1087","volume":"5","author":"M Yoneyama","year":"2004","unstructured":"Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T: The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004, 5: 730-737. 10.1038\/ni1087","journal-title":"Nat Immunol"},{"key":"548_CR47","doi-asserted-by":"publisher","first-page":"16910","DOI":"10.1074\/jbc.M000524200","volume":"275","author":"T Kim","year":"2000","unstructured":"Kim T, Kim TY, Lee WG, Yim J, Kim TK: Signaling pathways to the assembly of an interferon-beta enhanceosome. Chemical genetic studies with a small molecule. J Biol Chem. 2000, 275: 16910-16917. 10.1074\/jbc.M000524200","journal-title":"J Biol Chem"},{"key":"548_CR48","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/ni1303","volume":"7","author":"T Kawai","year":"2006","unstructured":"Kawai T, Akira S: Innate immune recognition of viral infection. Nat Immunol. 2006, 7: 131-137. 10.1038\/ni1303","journal-title":"Nat Immunol"},{"key":"548_CR49","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.4049\/jimmunol.1000532","volume":"185","author":"I Perrot","year":"2010","unstructured":"Perrot I, Deauvieau F, Massacrier C, Hughes N, Garrone P, Durand I, Demaria O, Viaud N, Gauthier L, Blery M, et al.: TLR3 and Rig-like receptor on myeloid dendritic cells and Rig-like receptor on human NK cells are both mandatory for production of IFN-gamma in response to double-stranded RNA. J Immunol. 2010, 185: 2080-2088. 10.4049\/jimmunol.1000532","journal-title":"J Immunol"},{"key":"548_CR50","doi-asserted-by":"publisher","first-page":"39179","DOI":"10.1074\/jbc.M204885200","volume":"277","author":"MA Wolfert","year":"2002","unstructured":"Wolfert MA, Murray TF, Boons GJ, Moore JN: The origin of the synergistic effect of muramyl dipeptide with endotoxin and peptidoglycan. J Biol Chem. 2002, 277: 39179-39186. 10.1074\/jbc.M204885200","journal-title":"J Biol Chem"},{"key":"548_CR51","doi-asserted-by":"publisher","first-page":"7967","DOI":"10.1128\/IAI.73.12.7967-7976.2005","volume":"73","author":"H Tada","year":"2005","unstructured":"Tada H, Aiba S, Shibata K, Ohteki T, Takada H: Synergistic effect of Nod1 and Nod2 agonists with toll-like receptor agonists on human dendritic cells to generate interleukin-12 and T helper type 1 cells. Infect Immun. 2005, 73: 7967-7976. 10.1128\/IAI.73.12.7967-7976.2005","journal-title":"Infect Immun"},{"key":"548_CR52","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1084\/jem.20021787","volume":"197","author":"BN Gantner","year":"2003","unstructured":"Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM: Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med. 2003, 197: 1107-1117. 10.1084\/jem.20021787","journal-title":"J Exp Med"},{"key":"548_CR53","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.immuni.2005.03.004","volume":"22","author":"NC Rogers","year":"2005","unstructured":"Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, Williams DL, Gordon S, Tybulewicz VL, Brown GD, Reis e Sousa C: Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity. 2005, 22: 507-517. 10.1016\/j.immuni.2005.03.004","journal-title":"Immunity"},{"key":"548_CR54","doi-asserted-by":"publisher","first-page":"5260","DOI":"10.4049\/jimmunol.175.8.5260","volume":"175","author":"S Rothenfusser","year":"2005","unstructured":"Rothenfusser S, Goutagny N, DiPerna G, Gong M, Monks BG, Schoenemeyer A, Yamamoto M, Akira S, Fitzgerald KA: The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J Immunol. 2005, 175: 5260-5268.","journal-title":"J Immunol"},{"key":"548_CR55","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1074\/jbc.M510326200","volume":"281","author":"R Lin","year":"2006","unstructured":"Lin R, Yang L, Nakhaei P, Sun Q, Sharif-Askari E, Julkunen I, Hiscott J: Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. J Biol Chem. 2006, 281: 2095-2103. 10.1074\/jbc.M510326200","journal-title":"J Biol Chem"},{"key":"548_CR56","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.febslet.2004.08.071","volume":"576","author":"YY Wang","year":"2004","unstructured":"Wang YY, Li L, Han KJ, Zhai Z, Shu HB: A20 is a potent inhibitor of TLR3- and Sendai virus-induced activation of NF-kappaB and ISRE and IFN-beta promoter. FEBS Lett. 2004, 576: 86-90. 10.1016\/j.febslet.2004.08.071","journal-title":"FEBS Lett"},{"key":"548_CR57","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1038\/ni1110","volume":"5","author":"DL Boone","year":"2004","unstructured":"Boone DL, Turer EE, Lee EG, Ahmad RC, Wheeler MT, Tsui C, Hurley P, Chien M, Chai S, Hitotsumatsu O, et al.: The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat Immunol. 2004, 5: 1052-1060. 10.1038\/ni1110","journal-title":"Nat Immunol"},{"key":"548_CR58","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S0092-8674(00)00126-4","volume":"103","author":"L Deng","year":"2000","unstructured":"Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ: Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000, 103: 351-361. 10.1016\/S0092-8674(00)00126-4","journal-title":"Cell"},{"key":"548_CR59","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1084\/jem.20071108","volume":"205","author":"EE Turer","year":"2008","unstructured":"Turer EE, Tavares RM, Mortier E, Hitotsumatsu O, Advincula R, Lee B, Shifrin N, Malynn BA, Ma A: Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20. J Exp Med. 2008, 205: 451-464. 10.1084\/jem.20071108","journal-title":"J Exp Med"},{"key":"548_CR60","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nature02794","volume":"430","author":"IE Wertz","year":"2004","unstructured":"Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, et al.: De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature. 2004, 430: 694-699. 10.1038\/nature02794","journal-title":"Nature"},{"key":"548_CR61","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.4049\/jimmunol.174.3.1507","volume":"174","author":"T Saitoh","year":"2005","unstructured":"Saitoh T, Yamamoto M, Miyagishi M, Taira K, Nakanishi M, Fujita T, Akira S, Yamamoto N, Yamaoka S: A20 is a negative regulator of IFN regulatory factor 3 signaling. J Immunol. 2005, 174: 1507-1512.","journal-title":"J Immunol"},{"key":"548_CR62","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/ni1061","volume":"5","author":"E Meylan","year":"2004","unstructured":"Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, Tschopp J: RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol. 2004, 5: 503-507. 10.1038\/ni1061","journal-title":"Nat Immunol"},{"key":"548_CR63","doi-asserted-by":"publisher","first-page":"4018","DOI":"10.1038\/sj.emboj.7600863","volume":"24","author":"J Huang","year":"2005","unstructured":"Huang J, Liu T, Xu LG, Chen D, Zhai Z, Shu HB: SIKE is an IKK epsilon\/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways. EMBO J. 2005, 24: 4018-4028. 10.1038\/sj.emboj.7600863","journal-title":"EMBO J"},{"key":"548_CR64","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/ni1347","volume":"7","author":"T Saitoh","year":"2006","unstructured":"Saitoh T, Tun-Kyi A, Ryo A, Yamamoto M, Finn G, Fujita T, Akira S, Yamamoto N, Lu KP, Yamaoka S: Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1. Nat Immunol. 2006, 7: 598-605. 10.1038\/ni1347","journal-title":"Nat Immunol"},{"key":"548_CR65","doi-asserted-by":"publisher","first-page":"7500","DOI":"10.1073\/pnas.0611551104","volume":"104","author":"K Arimoto","year":"2007","unstructured":"Arimoto K, Takahashi H, Hishiki T, Konishi H, Fujita T, Shimotohno K: Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc Natl Acad Sci USA. 2007, 104: 7500-7505. 10.1073\/pnas.0611551104","journal-title":"Proc Natl Acad Sci USA"},{"key":"548_CR66","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1038\/nature06501","volume":"451","author":"CB Moore","year":"2008","unstructured":"Moore CB, Bergstralh DT, Duncan JA, Lei Y, Morrison TE, Zimmermann AG, Accavitti-Loper MA, Madden VJ, Sun L, Ye Z, et al.: NLRX1 is a regulator of mitochondrial antiviral immunity. Nature. 2008, 451: 573-577. 10.1038\/nature06501","journal-title":"Nature"},{"key":"548_CR67","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.imbio.2007.10.008","volume":"213","author":"A Dalpke","year":"2008","unstructured":"Dalpke A, Heeg K, Bartz H, Baetz A: Regulation of innate immunity by suppressor of cytokine signaling (SOCS) proteins. Immunobiology. 2008, 213: 225-235. 10.1016\/j.imbio.2007.10.008","journal-title":"Immunobiology"},{"key":"548_CR68","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/ni1299","volume":"7","author":"A Mansell","year":"2006","unstructured":"Mansell A, Smith R, Doyle SL, Gray P, Fenner JE, Crack PJ, Nicholson SE, Hilton DJ, O'Neill LA, Hertzog PJ: Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nat Immunol. 2006, 7: 148-155. 10.1038\/ni1299","journal-title":"Nat Immunol"},{"key":"548_CR69","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/sj.emboj.7601489","volume":"26","author":"GN Maine","year":"2007","unstructured":"Maine GN, Mao X, Komarck CM, Burstein E: COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase. EMBO J. 2007, 26: 436-447. 10.1038\/sj.emboj.7601489","journal-title":"EMBO J"},{"key":"548_CR70","doi-asserted-by":"publisher","first-page":"35056","DOI":"10.1074\/jbc.273.52.35056","volume":"273","author":"MM Song","year":"1998","unstructured":"Song MM, Shuai K: The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities. J Biol Chem. 1998, 273: 35056-35062. 10.1074\/jbc.273.52.35056","journal-title":"J Biol Chem"},{"key":"548_CR71","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S0092-8674(02)00827-9","volume":"110","author":"K Kobayashi","year":"2002","unstructured":"Kobayashi K, Hernandez LD, Galan JE, Janeway CA, Medzhitov R, Flavell RA: IRAK-M is a negative regulator of Toll-like receptor signaling. Cell. 2002, 110: 191-202. 10.1016\/S0092-8674(02)00827-9","journal-title":"Cell"},{"key":"548_CR72","doi-asserted-by":"publisher","first-page":"5753","DOI":"10.1074\/jbc.M007773200","volume":"276","author":"M Hanada","year":"2001","unstructured":"Hanada M, Ninomiya-Tsuji J, Komaki K, Ohnishi M, Katsura K, Kanamaru R, Matsumoto K, Tamura S: Regulation of the TAK1 signaling pathway by protein phosphatase 2C. J Biol Chem. 2001, 276: 5753-5759. 10.1074\/jbc.M007773200","journal-title":"J Biol Chem"},{"key":"548_CR73","doi-asserted-by":"publisher","first-page":"12013","DOI":"10.1074\/jbc.M211474200","volume":"278","author":"MG Li","year":"2003","unstructured":"Li MG, Katsura K, Nomiyama H, Komaki K, Ninomiya-Tsuji J, Matsumoto K, Kobayashi T, Tamura S: Regulation of the interleukin-1-induced signaling pathways by a novel member of the protein phosphatase 2C family (PP2Cepsilon). J Biol Chem. 2003, 278: 12013-12021. 10.1074\/jbc.M211474200","journal-title":"J Biol Chem"},{"key":"548_CR74","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/41493","volume":"388","author":"JA DiDonato","year":"1997","unstructured":"DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M: A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature. 1997, 388: 548-554. 10.1038\/41493","journal-title":"Nature"},{"key":"548_CR75","doi-asserted-by":"publisher","first-page":"18347","DOI":"10.1074\/jbc.270.31.18347","volume":"270","author":"SC Sun","year":"1995","unstructured":"Sun SC, Maggirwar SB, Harhaj E: Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites. J Biol Chem. 1995, 270: 18347-18351. 10.1074\/jbc.270.31.18347","journal-title":"J Biol Chem"},{"key":"548_CR76","doi-asserted-by":"publisher","first-page":"35974","DOI":"10.1074\/jbc.M506093200","volume":"280","author":"AE Kray","year":"2005","unstructured":"Kray AE, Carter RS, Pennington KN, Gomez RJ, Sanders LE, Llanes JM, Khan WN, Ballard DW, Wadzinski BE: Positive regulation of IkappaB kinase signaling by protein serine\/threonine phosphatase 2A. J Biol Chem. 2005, 280: 35974-35982. 10.1074\/jbc.M506093200","journal-title":"J Biol Chem"},{"key":"548_CR77","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.molcel.2006.10.015","volume":"24","author":"S Li","year":"2006","unstructured":"Li S, Wang L, Berman MA, Zhang Y, Dorf ME: RNAi screen in mouse astrocytes identifies phosphatases that regulate NF-kappaB signaling. Mol Cell. 2006, 24: 497-509. 10.1016\/j.molcel.2006.10.015","journal-title":"Mol Cell"},{"key":"548_CR78","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1093\/bioinformatics\/bth163","volume":"20","author":"N Kashtan","year":"2004","unstructured":"Kashtan N, Itzkovitz S, Milo R, Alon U: Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs. Bioinformatics. 2004, 20: 1746-1758. 10.1093\/bioinformatics\/bth163","journal-title":"Bioinformatics"},{"key":"548_CR79","doi-asserted-by":"publisher","first-page":"3572","DOI":"10.1093\/bioinformatics\/bti556","volume":"21","author":"F Schreiber","year":"2005","unstructured":"Schreiber F, Schwobbermeyer H: MAVisto: a tool for the exploration of network motifs. Bioinformatics. 2005, 21: 3572-3574. 10.1093\/bioinformatics\/bti556","journal-title":"Bioinformatics"},{"key":"548_CR80","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1093\/bioinformatics\/btl038","volume":"22","author":"S Wernicke","year":"2006","unstructured":"Wernicke S, Rasche F: FANMOD: a tool for fast network motif detection. Bioinformatics. 2006, 22: 1152-1153. 10.1093\/bioinformatics\/btl038","journal-title":"Bioinformatics"},{"key":"548_CR81","doi-asserted-by":"publisher","first-page":"11980","DOI":"10.1073\/pnas.2133841100","volume":"100","author":"S Mangan","year":"2003","unstructured":"Mangan S, Alon U: Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci USA. 2003, 100: 11980-11985. 10.1073\/pnas.2133841100","journal-title":"Proc Natl Acad Sci USA"},{"key":"548_CR82","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.jmb.2003.09.049","volume":"334","author":"S Mangan","year":"2003","unstructured":"Mangan S, Zaslaver A, Alon U: The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks. J Mol Biol. 2003, 334: 197-204. 10.1016\/j.jmb.2003.09.049","journal-title":"J Mol Biol"},{"key":"548_CR83","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/nrg2102","volume":"8","author":"U Alon","year":"2007","unstructured":"Alon U: Network motifs: theory and experimental approaches. Nat Rev Genet. 2007, 8: 450-461. 10.1038\/nrg2102","journal-title":"Nat Rev Genet"},{"key":"548_CR84","doi-asserted-by":"crossref","unstructured":"Schreiber BHJaF: Analysis of Biological Networks. 2008, Hoboken: Wiley","DOI":"10.1142\/9781848164345_0003"},{"key":"548_CR85","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/ng881","volume":"31","author":"SS Shen-Orr","year":"2002","unstructured":"Shen-Orr SS, Milo R, Mangan S, Alon U: Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet. 2002, 31: 64-68. 10.1038\/ng881","journal-title":"Nat Genet"},{"key":"548_CR86","doi-asserted-by":"publisher","first-page":"e184","DOI":"10.1371\/journal.pbio.0060184","volume":"6","author":"AR Pico","year":"2008","unstructured":"Pico AR, Kelder T, van Iersel MP, Hanspers K, Conklin BR, Evelo C: WikiPathways: pathway editing for the people. PLoS Biol. 2008, 6: e184- 10.1371\/journal.pbio.0060184","journal-title":"PLoS Biol"},{"key":"548_CR87","volume-title":"AfCS Research Reports","author":"K Oda","year":"2004","unstructured":"Oda K, Kimura T, Matsuoka Y, Funahashi A, Muramatsu M, Kitano H: Molecular Interaction Map of a Macrophage. AfCS Research Reports. 2004, 2:"},{"key":"548_CR88","doi-asserted-by":"crossref","unstructured":"Raza S, McDerment N, Lacaze PA, Robertson K, Watterson S, Chen Y, Chisholm M, Eleftheriadis G, Monk S, O'Sullivan M: Construction of a large scale integrated map of macrophage pathogen recognition and effector systems. BMC Syst Biol. 4: 63-","DOI":"10.1186\/1752-0509-4-63"},{"issue":"10","key":"548_CR89","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1093\/bioinformatics\/btq143","volume":"26","author":"Y Matsuoka","year":"2010","unstructured":"Matsuoka Y, Ghosh S, Kikuchi N, Kitano H: Payao: A Community Platform for SBML Pathway Model Curation. Bioinformatics. 2010, 26 (10): 1381-3. 10.1093\/bioinformatics\/btq143","journal-title":"Bioinformatics"},{"key":"548_CR90","doi-asserted-by":"crossref","unstructured":"Bateman A: Curators of the world unite: the International Society of Biocuration. Bioinformatics. 26: 991.","DOI":"10.1093\/bioinformatics\/btq101"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-4-137.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T13:09:44Z","timestamp":1636636184000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-4-137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,7]]},"references-count":90,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["548"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-4-137","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,7]]},"assertion":[{"value":"4 May 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"137"}}