{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,15]],"date-time":"2026-11-15T07:22:42Z","timestamp":1794727362494,"version":"4.9.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Vet Res"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>\n            <jats:italic>Brucella melitensis<\/jats:italic> Rev 1 is the best vaccine available for the prophylaxis of small ruminant brucellosis and, indirectly, for reducing human brucellosis. However, Rev 1 shows anomalously high rates of spontaneous dissociation from smooth (S) to rough (R) bacteria, the latter being inefficacious as vaccines. This S-R instability results from the loss of the O-polysaccharide. To overcome this problem, we investigated whether some recently described mechanisms promoting mutations in O-polysaccharide genes were involved in Rev 1\u00a0S-R dissociation. We found that a proportion of Rev 1 R mutants result from genome rearrangements affecting the <jats:italic>wbo<\/jats:italic> O-polysaccharide loci of genomic island GI-2 and the <jats:italic>wbkA<\/jats:italic> O-polysaccharide glycosyltransferase gene of the <jats:italic>wbk<\/jats:italic> region. Accordingly, we mutated the GI-2 <jats:italic>int<\/jats:italic> gene and the <jats:italic>wbk<\/jats:italic> IS transposase involved in those arrangements, and found that these Rev 1 mutants maintained the S phenotype and showed lower dissociation levels. Combining these two mutations resulted in a strain (Rev 2) displaying a 95% decrease in dissociation with respect to parental Rev 1 under conditions promoting dissociation. Rev 2 did not differ from Rev 1 in the characteristics used in Rev 1 typing (growth rate, colonial size, reactivity with O-polysaccharide antibodies, phage, dye and antibiotic susceptibility). Moreover, Rev 2 and Rev 1 showed similar attenuation and afforded similar protection in the mouse model of brucellosis vaccines. We conclude that mutations targeting genes and DNA sequences involved in spontaneous O-polysaccharide loss enhance the stability of a critical vaccine phenotype and complement the empirical stabilization precautions taken during S <jats:italic>Brucella<\/jats:italic> vaccine production.<\/jats:p>","DOI":"10.1186\/1297-9716-44-105","type":"journal-article","created":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T01:29:55Z","timestamp":1383269395000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Deletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine"],"prefix":"10.1186","volume":"44","author":[{"given":"Marcos","family":"Mancilla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-Jes\u00fas","family":"Grill\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-Jes\u00fas","family":"de Miguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"L\u00f3pez-Go\u00f1i","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"San-Rom\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Zabalza-Barangu\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Moriy\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,10,31]]},"reference":[{"key":"449_CR1","first-page":"1","volume":"4","author":"D Grace","year":"2012","unstructured":"Grace D, Mutua F, Ocungo P, Kruska R, Jones K, Brierley L, Lapar L, Said M, Herrero M, Duc Phuc P, Elich Tao N, Akuku I, Ogutu F: Mapping of poverty and likely zoonoses hotspots. Zoonoses Project. 2012, 4: 1-119.","journal-title":"Zoonoses Project"},{"key":"449_CR2","volume-title":"The control of Neglected Zoonoses Diseases: A route to poverty alleviation","author":"Anonymous","year":"2006","unstructured":"Anonymous: The control of Neglected Zoonoses Diseases: A route to poverty alleviation. 2006, Geneva: WHO Press"},{"key":"449_CR3","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/S0167-5877(96)01110-5","volume":"31","author":"JM Blasco","year":"1997","unstructured":"Blasco JM: A review of the use of B. melitensis Rev 1 vaccine in adult sheep and goats. Prev Vet Med. 1997, 31: 275-283. 10.1016\/S0167-5877(96)01110-5.","journal-title":"Prev Vet Med"},{"key":"449_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1051\/vetres:2003037","volume":"35","author":"I Moriy\u00f3n","year":"2004","unstructured":"Moriy\u00f3n I, Grill\u00f3 MJ, Monreal D, Gonz\u00e1lez D, Mar\u00edn C, Lopez-Go\u00f1i I, Mainar-Jaime RC, Moreno E, Blasco JM: Rough vaccines in animal brucellosis: structural and genetic basis and present status. Vet Res. 2004, 35: 1-38. 10.1051\/vetres:2003037.","journal-title":"Vet Res"},{"key":"449_CR5","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/j.vaccine.2009.01.025","volume":"27","author":"MB Barrio","year":"2009","unstructured":"Barrio MB, Grill\u00f3 MJ, Mu\u00f1oz PM, Jacques I, Gonz\u00e1lez D, De-Miguel MJ, Mar\u00edn CM, Barberan M, Letesson JJ, Gorvel JP, Moriy\u00f3n I, Blasco JM, Zygmunt MS: Rough mutants defective in core and O-polysaccharide synthesis and export induce antibodies reacting in an indirect ELISA with smooth lipopolysaccharide and are less effective than Rev 1 vaccine against Brucella melitensis infection of sheep. Vaccine. 2009, 27: 1741-1749. 10.1016\/j.vaccine.2009.01.025.","journal-title":"Vaccine"},{"key":"449_CR6","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.prevetmed.2011.04.007","volume":"102","author":"J Godfroid","year":"2011","unstructured":"Godfroid J, Scholz HC, Barbier T, Nicolas C, Wattiau P, Fretin D, Whatmore AM, Cloeckaert A, Blasco JM, Moriy\u00f3n I, Saegerman C, Muma JB, Al-Dahouk S, Neubauer H, Letesson JJ: Brucellosis at the animal\/ecosystem\/human interface at the beginning of the 21st century. Prev Vet Med. 2011, 102: 118-131. 10.1016\/j.prevetmed.2011.04.007.","journal-title":"Prev Vet Med"},{"key":"449_CR7","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.prevetmed.2004.03.007","volume":"64","author":"A Minas","year":"2004","unstructured":"Minas A, Minas M, Stournara A, Tselepidis S: The \u201ceffects\u201d of Rev-1 vaccination of sheep and goats on human brucellosis in Greece. Prev Vet Med. 2004, 64: 41-47. 10.1016\/j.prevetmed.2004.03.007.","journal-title":"Prev Vet Med"},{"key":"449_CR8","volume-title":"Techniques for the brucellosis laboratory","author":"GG Alton","year":"1988","unstructured":"Alton GG, Jones LM, Angus RD, Verger JM: Techniques for the brucellosis laboratory. 1988, Paris, France: INRA"},{"key":"449_CR9","doi-asserted-by":"publisher","first-page":"e2760","DOI":"10.1371\/journal.pone.0002760","volume":"3","author":"D Gonz\u00e1lez","year":"2008","unstructured":"Gonz\u00e1lez D, Grill\u00f3 MJ, De-Miguel MJ, Ali T, Arce-Gorvel V, Delrue RM, Conde-\u00c1lvarez R, Mu\u00f1oz PM, Lopez-Go\u00f1i I, Iriarte M, Mar\u00edn CM, Weintraub A, Widmalm G, Zygmunt M, Letesson JJ, Gorvel JP, Blasco JM, Moriy\u00f3n I: Brucellosis vaccines: assessment of Brucella melitensis lipopolysaccharide rough mutants defective in core and O-polysaccharide synthesis and export. PLoS One. 2008, 3: e2760-10.1371\/journal.pone.0002760.","journal-title":"PLoS One"},{"key":"449_CR10","doi-asserted-by":"publisher","first-page":"6346","DOI":"10.1128\/JB.00838-10","volume":"192","author":"M Mancilla","year":"2010","unstructured":"Mancilla M, Lopez-Go\u00f1i I, Moriy\u00f3n I, Zarraga AM: Genomic Island 2 is an unstable genetic element contributing to Brucella lipopolysaccharide spontaneous smooth-to-rough dissociation. J Bacteriol. 2010, 192: 6346-6351. 10.1128\/JB.00838-10.","journal-title":"J Bacteriol"},{"key":"449_CR11","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.micinf.2004.04.009","volume":"6","author":"N Vizca\u00edno","year":"2004","unstructured":"Vizca\u00edno N, Caro-Hernandez P, Cloeckaert A, Fernandez-Lago L: DNA polymorphism in the omp25\/omp31 family of Brucella spp.: identification of a 1.7-kb inversion in Brucella cetaceae and of a 15.1-kb genomic island, absent from Brucella ovis, related to the synthesis of smooth lipopolysaccharide. Microbes Infect. 2004, 6: 821-834. 10.1016\/j.micinf.2004.04.009.","journal-title":"Microbes Infect"},{"key":"449_CR12","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.femsle.2005.02.026","volume":"245","author":"D Garc\u00eda-Yoldi","year":"2005","unstructured":"Garc\u00eda-Yoldi D, Mar\u00edn CM, Lopez-Go\u00f1i I: Restriction site polymorphisms in the genes encoding new members of group 3 outer membrane protein family of Brucella spp. FEMS Microbiol Lett. 2005, 245: 79-84. 10.1016\/j.femsle.2005.02.026.","journal-title":"FEMS Microbiol Lett"},{"key":"449_CR13","doi-asserted-by":"publisher","first-page":"e1002675","DOI":"10.1371\/journal.ppat.1002675","volume":"8","author":"R Conde-\u00c1lvarez","year":"2012","unstructured":"Conde-\u00c1lvarez R, Arce-Gorvel V, Iriarte M, Mancek-Keber M, Barquero-Calvo E, Palacios-Chaves L, Chac\u00f3n-D\u00edaz C, Chaves-Olarte E, Martirosyan A, Von-Bargen K, Grill\u00f3 MJ, Jerala R, Brandenburg K, Llobet E, Bengoechea JA, Moreno E, Moriy\u00f3n I, Gorvel JP: The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition. PLoS Pathog. 2012, 8: e1002675-10.1371\/journal.ppat.1002675.","journal-title":"PLoS Pathog"},{"key":"449_CR14","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1128\/JB.06561-11","volume":"194","author":"M Mancilla","year":"2012","unstructured":"Mancilla M, Mar\u00edn CM, Blasco JM, Zarraga AM, Lopez-Go\u00f1i I, Moriy\u00f3n I: Spontaneous excision of the O-polysaccharide wbkA glycosyltranferase gene is a cause of dissociation of smooth to rough Brucella colonies. J Bacteriol. 2012, 194: 1860-1867. 10.1128\/JB.06561-11.","journal-title":"J Bacteriol"},{"key":"449_CR15","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fmicb.2011.00054","volume":"2","author":"JE Turse","year":"2011","unstructured":"Turse JE, Pei J, Ficht TA: Lipopolysaccharide-deficient Brucella variants arise spontaneously during infection. Front Microbiol. 2011, 2: 54-","journal-title":"Front Microbiol"},{"key":"449_CR16","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1128\/CDLI.6.5.760-764.1999","volume":"6","author":"R Vemulapalli","year":"1999","unstructured":"Vemulapalli R, McQuiston JR, Schurig GG, Sriranganathan N, Halling SM, Boyle SM: Identification of an IS711 element interrupting the wboA gene of Brucella abortus vaccine strain RB51 and a PCR assay to distinguish strain RB51 from other Brucella species and strains. Clin Diagn Lab Immunol. 1999, 6: 760-764.","journal-title":"Clin Diagn Lab Immunol"},{"key":"449_CR17","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/1471-2180-9-92","volume":"9","author":"MS Zygmunt","year":"2009","unstructured":"Zygmunt MS, Blasco JM, Letesson JJ, Cloeckaert A, Moriy\u00f3n I: DNA polymorphism analysis of Brucella lipopolysaccharide genes reveals marked differences in O-polysaccharide biosynthetic genes between smooth and rough Brucella species and novel species-specific markers. BMC Microbiol. 2009, 9: 92-10.1186\/1471-2180-9-92.","journal-title":"BMC Microbiol"},{"key":"449_CR18","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1073\/pnas.221575398","volume":"99","author":"VG DelVecchio","year":"2002","unstructured":"DelVecchio VG, Kapatral V, Redkar RJ, Patra G, Mujer C, Los T, Ivanova N, Anderson I, Bhattacharyya A, Lykidis A, Reznik G, Jablonski L, Larsen N, D\u2019Souza M, Bernal A, Mazur M, Goltsman E, Selkov E, Elzer PH, Hagius S, O\u2019Callaghan D, Letesson JJ, Haselkorn R, Kyrpides N, Overbeek R: The genome sequence of the facultative intracellular pathogen Brucella melitensis. Proc Natl Acad Sci USA. 2002, 99: 443-448. 10.1073\/pnas.221575398.","journal-title":"Proc Natl Acad Sci USA"},{"key":"449_CR19","unstructured":"National Center for Biotechnology Information\/Basic Local Aligment Search Tool (NCBI\/BLAST). [http:\/\/www.ncbi.nlm.nih.gov\/BLAST]"},{"key":"449_CR20","unstructured":"European Molecular Biology Laboratory-European Bioinformatics Institute (EMBI-EBI). [http:\/\/www.ebi.ac.uk\/Tools\/clustalo]"},{"key":"449_CR21","unstructured":"National Center for Biotechnology Information\/Primer-BLAST (NCBI\/Primer-BLAST). [http:\/\/www.ncbi.nlm.nih.gov\/tools\/primer-blast\/]"},{"key":"449_CR22","first-page":"2.4.1","volume-title":"Curr Protoc Mol Biol","author":"K Wilson","year":"1997","unstructured":"Wilson K: Preparation of genomic DNA from bacteria. Curr Protoc Mol Biol. 1997, 2.4.1-2.4.5."},{"key":"449_CR23","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.vetmic.2005.06.007","volume":"110","author":"AA Ocampo-Sosa","year":"2005","unstructured":"Ocampo-Sosa AA, Aguero-Balbin J, Garcia-Lobo JM: Development of a new PCR assay to identify Brucella abortus biovars 5, 6 and 9 and the new subgroup 3b of biovar 3. Vet Microbiol. 2005, 110: 41-51. 10.1016\/j.vetmic.2005.06.007.","journal-title":"Vet Microbiol"},{"key":"449_CR24","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/S1045-1056(05)80025-9","volume":"19","author":"N Bosseray","year":"1991","unstructured":"Bosseray N: Brucella melitensis Rev.1 living attenuated vaccine: stability of markers, residual virulence and immunogenicity in mice. Biologicals. 1991, 19: 355-363. 10.1016\/S1045-1056(05)80025-9.","journal-title":"Biologicals"},{"key":"449_CR25","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1006\/biol.2000.0249","volume":"28","author":"MJ Grill\u00f3","year":"2000","unstructured":"Grill\u00f3 MJ, Bosseray N, Blasco JM: In vitro markers and biological activity in mice of seed lot strains and commercial Brucella melitensis Rev 1 and Brucella abortus B19 vaccines. Biologicals. 2000, 28: 119-127. 10.1006\/biol.2000.0249.","journal-title":"Biologicals"},{"key":"449_CR26","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1111\/j.1462-5822.2006.00712.x","volume":"8","author":"R Conde-\u00c1lvarez","year":"2006","unstructured":"Conde-\u00c1lvarez R, Grill\u00f3 MJ, Salcedo SP, De-Miguel MJ, Fugier E, Gorvel JP, Moriy\u00f3n I, Iriarte M: Synthesis of phosphatidylcholine, a typical eukaryotic phospholipid, is necessary for full virulence of the intracellular bacterial parasite Brucella abortus. Cell Microbiol. 2006, 8: 1322-1335. 10.1111\/j.1462-5822.2006.00712.x.","journal-title":"Cell Microbiol"},{"key":"449_CR27","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/0378-1119(93)90611-6","volume":"127","author":"J Quandt","year":"1993","unstructured":"Quandt J, Hynes MF: Versatile suicide vectors which allow direct selection for gene replacement in gram-negative bacteria. Gene. 1993, 127: 15-21. 10.1016\/0378-1119(93)90611-6.","journal-title":"Gene"},{"key":"449_CR28","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1038\/nbt1183-784","volume":"1","author":"R Simon","year":"1983","unstructured":"Simon R, Priefer U, Pehle A: A broad host range mobilization system for the in vitro genetic engineering: transposon mutagenesis in gram negative bacteria. Biotechnology. 1983, 1: 784-890. 10.1038\/nbt1183-784.","journal-title":"Biotechnology"},{"key":"449_CR29","doi-asserted-by":"publisher","first-page":"6243","DOI":"10.1128\/JB.00520-08","volume":"190","author":"G Rajashekara","year":"2008","unstructured":"Rajashekara G, Covert J, Petersen E, Eskra L, Splitter G: Genomic island 2 of Brucella melitensis is a major virulence determinant: Functional analyses of genomic islands. J Bacteriol. 2008, 190: 6243-6252. 10.1128\/JB.00520-08.","journal-title":"J Bacteriol"},{"key":"449_CR30","unstructured":"Oy Growth Curves Ab Ltd. [http:\/\/www.bioscreen.fi]"},{"key":"449_CR31","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1128\/jb.178.4.1070-1079.1996","volume":"178","author":"V Arag\u00f3n","year":"1996","unstructured":"Arag\u00f3n V, D\u00edaz R, Moreno E, Moriy\u00f3n I: Characterization of Brucella abortus and Brucella melitensis native haptens as outer membrane O-type polysaccharides independent from the smooth lipopolysaccharide. J Bacteriol. 1996, 178: 1070-1079.","journal-title":"J Bacteriol"},{"key":"449_CR32","doi-asserted-by":"publisher","first-page":"2910","DOI":"10.1016\/j.vaccine.2005.12.038","volume":"24","author":"MJ Grill\u00f3","year":"2006","unstructured":"Grill\u00f3 MJ, Manterola L, De-Miguel MJ, Mu\u00f1oz PM, Blasco JM, Moriy\u00f3n I, Lopez-Go\u00f1i I: Increases of efficacy as vaccine against Brucella abortus infection in mice by simultaneous inoculation with avirulent smooth bvrS\/bvrR and rough wbkA mutants. Vaccine. 2006, 24: 2910-2916. 10.1016\/j.vaccine.2005.12.038.","journal-title":"Vaccine"},{"key":"449_CR33","first-page":"1","volume-title":"Manual of Diagnostic Tests and Vaccines for Terrestrial Animals","author":"OIE","year":"2009","unstructured":"OIE: Bovine Brucellosis. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. 2009, OIE, 1-35. Chapter 2.4.3"},{"key":"449_CR34","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1297-9716-43-29","volume":"43","author":"MJ Grill\u00f3","year":"2012","unstructured":"Grill\u00f3 MJ, Blasco JM, Gorvel JP, Moriy\u00f3n I, Moreno E: What have we learned from brucellosis in the mouse model?. Vet Res. 2012, 43: 29-10.1186\/1297-9716-43-29.","journal-title":"Vet Res"},{"key":"449_CR35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1128\/br.22.2.81-98.1958","volume":"22","author":"P Gerhardt","year":"1958","unstructured":"Gerhardt P: The nutrition of Brucellae. Bacteriol Rev. 1958, 22: 91-98.","journal-title":"Bacteriol Rev"},{"key":"449_CR36","doi-asserted-by":"publisher","first-page":"2546","DOI":"10.1016\/S0264-410X(02)00159-7","volume":"20","author":"A Cloeckaert","year":"2002","unstructured":"Cloeckaert A, Grayon M, Grepinet O: Identification of Brucella melitensis vaccine strain Rev.1 by PCR-RFLP based on a mutation in the rpsL gene. Vaccine. 2002, 20: 2546-2550. 10.1016\/S0264-410X(02)00159-7.","journal-title":"Vaccine"},{"key":"449_CR37","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1046\/j.1365-2958.2002.03173.x","volume":"46","author":"S Maisnier-Patin","year":"2002","unstructured":"Maisnier-Patin S, Berg OG, Liljas L, Andersson DI: Compensatory adaptation to the deleterious effect of antibiotic resistance in Salmonella Typhimurium. Mol Microbiol. 2002, 46: 355-366. 10.1046\/j.1365-2958.2002.03173.x.","journal-title":"Mol Microbiol"},{"key":"449_CR38","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1111\/j.1365-2958.2006.05262.x","volume":"61","author":"JM Manson","year":"2006","unstructured":"Manson JM, Gilmore MS: Pathogenicity island integrase cross-talk: a potential new tool for virulence modulation. Mol Microbiol. 2006, 61: 555-559. 10.1111\/j.1365-2958.2006.05262.x.","journal-title":"Mol Microbiol"}],"container-title":["Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1297-9716-44-105.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T18:55:58Z","timestamp":1630608958000},"score":1,"resource":{"primary":{"URL":"https:\/\/veterinaryresearch.biomedcentral.com\/articles\/10.1186\/1297-9716-44-105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,31]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["449"],"URL":"https:\/\/doi.org\/10.1186\/1297-9716-44-105","relation":{},"ISSN":["1297-9716"],"issn-type":[{"value":"1297-9716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,31]]},"assertion":[{"value":"17 August 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"105"}}