{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T13:13:20Z","timestamp":1648905200141},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurosci"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The slow Wallerian Degeneration (<jats:italic>Wld<\/jats:italic>\n              <jats:sup>\n                <jats:italic>S<\/jats:italic>\n              <\/jats:sup>) gene specifically protects axonal and synaptic compartments of neurons from a wide variety of degeneration-inducing stimuli, including; traumatic injury, Parkinson's disease, demyelinating neuropathies, some forms of motor neuron disease and global cerebral ischemia. The <jats:italic>Wld<\/jats:italic>\n              <jats:sup>\n                <jats:italic>S<\/jats:italic>\n              <\/jats:sup>gene encodes a novel Ube4b-Nmnat1 chimeric protein (Wld<jats:sup>S<\/jats:sup> protein) that is responsible for conferring the neuroprotective phenotype. How the chimeric Wld<jats:sup>S<\/jats:sup> protein confers neuroprotection remains controversial, but several studies have shown that expression in neurons <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> modifies key cellular pathways, including; NAD biosynthesis, ubiquitination, the mitochondrial proteome, cell cycle status and cell stress. Whether similar changes are induced in non-neuronal tissue and organs at a basal level <jats:italic>in vivo<\/jats:italic> remains to be determined. This may be of particular importance for the development and application of neuroprotective therapeutic strategies based around <jats:italic>Wld<\/jats:italic>\n              <jats:sup>\n                <jats:italic>S<\/jats:italic>\n              <\/jats:sup>-mediated pathways designed for use in human patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We have undertaken a detailed analysis of non-neuronal <jats:italic>Wld<\/jats:italic>\n              <jats:sup>\n                <jats:italic>S<\/jats:italic>\n              <\/jats:sup>expression in <jats:italic>Wld<\/jats:italic>\n              <jats:sup>\n                <jats:italic>S<\/jats:italic>\n              <\/jats:sup>mice, alongside gravimetric and histological analyses, to examine the influence of <jats:italic>Wld<\/jats:italic>\n              <jats:sup>\n                <jats:italic>S<\/jats:italic>\n              <\/jats:sup>expression in non-neuronal tissues. We show that expression of <jats:italic>Wld<\/jats:italic>\n              <jats:sup>\n                <jats:italic>S<\/jats:italic>\n              <\/jats:sup>RNA and protein are not restricted to neuronal tissue, but that the relative RNA and protein expression levels rarely correlate in these non-neuronal tissues. We show that <jats:italic>Wld<\/jats:italic>\n              <jats:sup>\n                <jats:italic>S<\/jats:italic>\n              <\/jats:sup>mice have normal body weight and growth characteristics as well as gravimetrically and histologically normal organs, regardless of Wld<jats:sup>S<\/jats:sup> protein levels. Finally, we demonstrate that previously reported <jats:italic>Wld<\/jats:italic>\n              <jats:sup>\n                <jats:italic>S<\/jats:italic>\n              <\/jats:sup>-induced changes in cell cycle and cell stress status are neuronal-specific, not recapitulated in non-neuronal tissues at a basal level.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We conclude that expression of Wld<jats:sup>S<\/jats:sup> protein has no adverse effects on non-neuronal tissue at a basal level <jats:italic>in vivo<\/jats:italic>, supporting the possibility of its safe use in future therapeutic strategies targeting axonal and\/or synaptic compartments in patients with neurodegenerative disease. Future experiments determining whether Wld<jats:sup>S<\/jats:sup> protein can modify responses to injury in non-neuronal tissue are now required.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2202-10-148","type":"journal-article","created":{"date-parts":[[2009,12,17]],"date-time":"2009-12-17T07:15:07Z","timestamp":1261034107000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expression of the neuroprotective slow Wallerian degeneration (Wld\n                S\n              ) gene in non-neuronal tissues"],"prefix":"10.1186","volume":"10","author":[{"given":"Thomas M","family":"Wishart","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G","family":"Brownstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anca M","family":"Tabakova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine M","family":"Boothe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack W","family":"Tsao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas H","family":"Gillingwater","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2009,12,16]]},"reference":[{"key":"1152_CR1","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1126\/science.1068613","volume":"296","author":"MC Raff","year":"2002","unstructured":"Raff MC, Whitmore AV, Finn JT: Axonal self-destruction and neurodegeneration. Science. 2002, 296: 868-871. 10.1126\/science.1068613.","journal-title":"Science"},{"key":"1152_CR2","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1097\/01.jnen.0000228202.35163.c4","volume":"65","author":"TM Wishart","year":"2006","unstructured":"Wishart TM, Parson SH, Gillingwater TH: Synaptic vulnerability in neurodegenerative disease. J Neuropathol Exp Neurol. 2006, 65: 733-739. 10.1097\/01.jnen.0000228202.35163.c4.","journal-title":"J Neuropathol Exp Neurol"},{"key":"1152_CR3","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1126\/science.1074069","volume":"298","author":"DJ Selkoe","year":"2002","unstructured":"Selkoe DJ: Alzheimer's disease is a synaptic failure. Science. 2002, 298: 789-791. 10.1126\/science.1074069.","journal-title":"Science"},{"key":"1152_CR4","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1097\/nen.0b013e31815f3899","volume":"67","author":"S Partanen","year":"2008","unstructured":"Partanen S, Haapanen A, Kielar C, Pontikis C, Alexander N, Inkinen T, Saftig P, Gillingwater TH, Cooper JD, Tyynel\u00e4 J: Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: A model of human congenital neuronal ceroid-lipofuscinosis. J Neuropathol Exp Neurol. 2008, 67: 16-29. 10.1097\/nen.0b013e31815f3899.","journal-title":"J Neuropathol Exp Neurol"},{"key":"1152_CR5","doi-asserted-by":"publisher","first-page":"4066","DOI":"10.1093\/hmg\/ddp355","volume":"18","author":"C Kielar","year":"2009","unstructured":"Kielar C, Wishart TM, Palmer A, Dihanich S, Wong AM, Macauley SL, Chun C-H, Sands MS, Pearce D, Cooper JD, Gillingwater TH: Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Hum Mol Genet. 2009, 18: 4066-4080. 10.1093\/hmg\/ddp355.","journal-title":"Hum Mol Genet"},{"key":"1152_CR6","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1056\/NEJM199801293380502","volume":"338","author":"BD Trapp","year":"1998","unstructured":"Trapp BD, Peterson J, Ransohoff RM, Rudick R, M\u00f6rk S, B\u00f6 L: Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998, 338: 278-285. 10.1056\/NEJM199801293380502.","journal-title":"N Engl J Med"},{"key":"1152_CR7","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.expneurol.2003.10.004","volume":"185","author":"LR Fischer","year":"2004","unstructured":"Fischer LR, Culver DG, Tennant P, Davis AA, Wang M, Castellano-Sanchez A, Khan J, Polak MA, Glass JD: Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol. 2004, 185: 232-240. 10.1016\/j.expneurol.2003.10.004.","journal-title":"Exp Neurol"},{"key":"1152_CR8","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1093\/hmg\/ddm367","volume":"17","author":"LM Murray","year":"2008","unstructured":"Murray LM, Comley LH, Thomson D, Parkinson N, Talbot K, Gillingwater TH: Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy. Hum Mol Genet. 2008, 17: 949-962. 10.1093\/hmg\/ddm367.","journal-title":"Hum Mol Genet"},{"key":"1152_CR9","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/j.1460-9568.1989.tb00771.x","volume":"1","author":"ER Lunn","year":"1989","unstructured":"Lunn ER, Perry VH, Brown MC, Rosen H, Gordon S: Absence of Wallerian degeneration does not hinder regeneration in peripheral nerve. Eur J Neurosci. 1989, 1: 27-33. 10.1111\/j.1460-9568.1989.tb00771.x.","journal-title":"Eur J Neurosci"},{"key":"1152_CR10","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1093\/brain\/awl101","volume":"129","author":"TH Gillingwater","year":"2006","unstructured":"Gillingwater TH, Ingham CA, Parry KE, Wright AK, Haley JE, Wishart TM, Arbuthnott GW, Ribchester RR: Delayed synaptic degeneration in the CNS of Wld\n                    S\n                  mice after cortical lesion. Brain. 2006, 129: 1546-1556. 10.1093\/brain\/awl101.","journal-title":"Brain"},{"key":"1152_CR11","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.cub.2004.01.053","volume":"14","author":"A Sajadi","year":"2004","unstructured":"Sajadi A, Schneider BL, Aebischer P: Wlds-mediated protection of dopaminergic fibres in an animal model of Parkinson disease. Curr Biol. 2004, 14: 326-330.","journal-title":"Curr Biol"},{"key":"1152_CR12","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.expneurol.2006.05.017","volume":"202","author":"DM Hasbani","year":"2006","unstructured":"Hasbani DM, O'Malley KL: WldS mice are protected against the Parkinsonian mimetic MPTP. Exp Neurol. 2006, 202: 93-99. 10.1016\/j.expneurol.2006.05.017.","journal-title":"Exp Neurol"},{"key":"1152_CR13","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1523\/JNEUROSCI.23-07-02833.2003","volume":"23","author":"M Samsam","year":"2003","unstructured":"Samsam M, Mi W, Wessig C, Zielasek J, Toyka KV, Coleman MP, Martini R: The Wlds mutation delays robust loss of motor and sensory axons in a genetic model for myelin-related axonopathy. J Neurosci. 2003, 23: 2833-2839.","journal-title":"J Neurosci"},{"key":"1152_CR14","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/S0960-9822(03)00206-9","volume":"13","author":"A Ferri","year":"2003","unstructured":"Ferri A, Sanes JR, Coleman MP, Cunningham JM, Kato AC: Inhibiting axon degeneration and synapse loss attenuates apoptosis and disease progression in a mouse model of motorneurone disease. Curr Biol. 2003, 13: 669-673. 10.1016\/S0960-9822(03)00206-9.","journal-title":"Curr Biol"},{"key":"1152_CR15","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1097\/01.WCB.0000095798.98378.34","volume":"24","author":"TH Gillingwater","year":"2004","unstructured":"Gillingwater TH, Haley JE, Ribchester RR, Horsburgh K: Neuroprotection after transient global cerebral ischaemia in Wld\n                    S\n                  mutant mice. J Cereb Blood Flow Metab. 2004, 24: 62-66. 10.1097\/01.WCB.0000095798.98378.34.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1152_CR16","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1002\/ana.10039","volume":"50","author":"MS Wang","year":"2001","unstructured":"Wang MS, Fang G, Culver DG, Davis AA, Rich MM, Glass JD: The Wld\n                    S\n                  protein protects against axonal degeneration: a model of gene therapy for peripheral neuropathy. Ann Neurol. 2001, 50: 773-779. 10.1002\/ana.10039.","journal-title":"Ann Neurol"},{"key":"1152_CR17","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1126\/science.1098014","volume":"305","author":"T Araki","year":"2004","unstructured":"Araki T, Sasaki Y, Milbrandt J: Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science. 2004, 305: 1010-1013. 10.1126\/science.1098014.","journal-title":"Science"},{"key":"1152_CR18","doi-asserted-by":"publisher","first-page":"9985","DOI":"10.1073\/pnas.95.17.9985","volume":"95","author":"MP Coleman","year":"1998","unstructured":"Coleman MP, Conforti L, Buckmaster EA, Tarlton A, Ewing RM, Brown CM, Lyone MF, Perry VH: An 85-Kb tandem triplication in the slow Wallerian degeneration (WldS) mouse. Proc Natl Acad Sci USA. 1998, 95: 9985-9990. 10.1073\/pnas.95.17.9985.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1152_CR19","volume-title":"FENS Forum Session 225-Trauma","author":"W Mi","year":"2002","unstructured":"Mi W, Conforti L, Coleman MP: The slow Wallerian degeneration mutation (WldS): genotyping methods and mutation stability studies. FENS Forum Session 225-Trauma. 2002, Abstract 225.2"},{"key":"1152_CR20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S0027-5107(03)00011-3","volume":"526","author":"W Mi","year":"2003","unstructured":"Mi W, Glass JD, Coleman MP: Stable inheritance of an 85 Kb triplication in C57BL\/Wld\n                    S\n                  mice. Mutation Res. 2003, 526: 33-37.","journal-title":"Mutation Res"},{"key":"1152_CR21","doi-asserted-by":"publisher","first-page":"9717","DOI":"10.1073\/pnas.90.20.9717","volume":"90","author":"MF Lyon","year":"1993","unstructured":"Lyon MF, Ogunkolade BW, Brown MC, Atherton DJ, Perry VH: A gene affecting Wallerian nerve degeneration maps distally on mouse chromosome 4. Proc Natl Acad Sci USA. 1993, 90: 9717-9720. 10.1073\/pnas.90.20.9717.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1152_CR22","doi-asserted-by":"publisher","first-page":"11377","DOI":"10.1073\/pnas.97.21.11377","volume":"97","author":"L Conforti","year":"2000","unstructured":"Conforti L, Tarlton A, Mack TG, Mi W, Buckmaster EA, Wagner D, Perry VH, Coleman MP: A Ufd2\/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration (WldS) mouse. Proc Natl Acad Sci USA. 2000, 97: 11377-11382. 10.1073\/pnas.97.21.11377.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1152_CR23","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1038\/nn770","volume":"4","author":"TGA Mack","year":"2001","unstructured":"Mack TGA, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, Thomson D, Gillingwater T, Court F, Conforti L, Shama Fernando F, Tarlton A, Andressen C, Addicks K, Magni G, Ribchester RR, Perry VH, Coleman MP: Wallerian degeneration of injured axons and synapses is delayed by a Ube4b\/Nmnat chimeric gene. Nat Neurosci. 2001, 4: 1199-1206. 10.1038\/nn770.","journal-title":"Nat Neurosci"},{"key":"1152_CR24","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/j.1460-9568.2004.03833.x","volume":"21","author":"R Adalbert","year":"2005","unstructured":"Adalbert R, Gillingwater TH, Haley JE, Bridge K, Beirowski B, Berek L, Wagner D, Grumme SG, Thomson D, Addicks K, Ribchester RR, Coleman MP: A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses. Eur J Neurosci. 2005, 21: 271-277. 10.1111\/j.1460-9568.2004.03833.x.","journal-title":"Eur J Neurosci"},{"key":"1152_CR25","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/j.neuron.2006.04.028","volume":"50","author":"JM MacDonald","year":"2006","unstructured":"MacDonald JM, Beach MG, Porpiglia E, Sheehan AE, Watts RJ, Freeman MR: The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons. Neuron. 2006, 50: 869-881. 10.1016\/j.neuron.2006.04.028.","journal-title":"Neuron"},{"key":"1152_CR26","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1074\/mcp.M600457-MCP200","volume":"6","author":"TM Wishart","year":"2007","unstructured":"Wishart TM, Paterson JM, Short DM, Meredith S, Robertson KA, Sutherland C, Cousin MA, Dutia MB, Gillingwater TH: Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene. Mol Cell Proteomics. 2007, 6: 1318-1330. 10.1074\/mcp.M600457-MCP200.","journal-title":"Mol Cell Proteomics"},{"issue":"6","key":"1152_CR27","doi-asserted-by":"publisher","first-page":"R101","DOI":"10.1186\/gb-2008-9-6-r101","volume":"9","author":"TM Wishart","year":"2008","unstructured":"Wishart TM, Pemberton HN, James SR, McCabe CJ, Gillingwater TH: Modified cell cycle status in a mouse model of altered neuronal vulnerability (Wallerian Degeneration Slow; Wld\n                    S\n                  ). Genome Biol. 2008, 9 (6): R101-10.1186\/gb-2008-9-6-r101.","journal-title":"Genome Biol"},{"key":"1152_CR28","doi-asserted-by":"publisher","first-page":"6276","DOI":"10.1523\/JNEUROSCI.4304-08.2009","volume":"29","author":"N Yahata","year":"2009","unstructured":"Yahata N, Yuasa S, Araki T: Nicotinamide mononucleotide adenylyltransferase expression in mitochondrial matrix delays Wallerian degeneration. J Neurosci. 2009, 29: 6276-6284. 10.1523\/JNEUROSCI.4304-08.2009.","journal-title":"J Neurosci"},{"key":"1152_CR29","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1093\/hmg\/ddi478","volume":"15","author":"TH Gillingwater","year":"2006","unstructured":"Gillingwater TH, Wishart TM, Chen PE, Haley JE, Robertson K, MacDonald SH-F, Middleton S, Wawrowsky K, Shipston MJ, Melmed S, Wyllie DJA, Skehel PA, Coleman MP, Ribchester RR: The neuroprotective Wld\n                    S\n                  gene regulates expression of PTTG1 and erythroid differention regulator 1-like gene in mice and human cells. Hum Mol Genet. 2006, 15: 625-635. 10.1093\/hmg\/ddi478.","journal-title":"Hum Mol Genet"},{"key":"1152_CR30","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.mcn.2008.03.004","volume":"38","author":"A Wilbrey","year":"2008","unstructured":"Wilbrey A, Haley J, Wishart T, Conforti L, Morreale G, Beirowski B, Babetto E, Adalbert R, Gillingwater TH, Smith T, Wyllie DJA, Ribchester RR, Coleman MP: VCP binding influences intracellular distribution of the slow Wallerian degeneration protein, WldS. Mol Cell Neurosci. 2008, 38: 325-340. 10.1016\/j.mcn.2008.03.004.","journal-title":"Mol Cell Neurosci"},{"key":"1152_CR31","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/j.neuroscience.2005.06.078","volume":"135","author":"C Fang","year":"2005","unstructured":"Fang C, Bernardes-Silva M, Coleman MP, Perry VH: The cellular distribution of the WldS chimeric protein and its constituent proteins in the CNS. Neuroscience. 2005, 135: 1107-1118. 10.1016\/j.neuroscience.2005.06.078.","journal-title":"Neuroscience"},{"key":"1152_CR32","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/nrn2124","volume":"8","author":"K Herrup","year":"2007","unstructured":"Herrup K, Yang Y: Cell cycle regulation in the postmitotic neuron: oxymoron or new biology?. Nat Rev Neurosci. 2007, 8: 368-378. 10.1038\/nrn2124.","journal-title":"Nat Rev Neurosci"},{"key":"1152_CR33","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1111\/j.1460-9568.1990.tb00472.x","volume":"2","author":"VH Perry","year":"1990","unstructured":"Perry VH, Brown MC, Lunn ER, Tree P, Gordon S: Evidence that very slow Wallerian degeneration in C57BL\/Ola mice is an intrinsic property of the peripheral nerve. Eur J Neurosci. 1990, 2: 802-808. 10.1111\/j.1460-9568.1990.tb00472.x.","journal-title":"Eur J Neurosci"},{"key":"1152_CR34","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/1750-1326-2-21","volume":"2","author":"TM Wishart","year":"2007","unstructured":"Wishart TM, MacDonald SHF, Chen PE, Shipston MJ, Coleman MP, Gillingwater TH, Ribchester RR: Design of a novel quantitative PCR (QPCR)-based protocol for genotyping mice carrying the neuroprotective Wallerian degeneration slow (Wld\n                    S\n                  ) gene. Mol Neurodegen. 2007, 2: 21-10.1186\/1750-1326-2-21.","journal-title":"Mol Neurodegen"}],"container-title":["BMC Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2202-10-148.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T07:16:52Z","timestamp":1630480612000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurosci.biomedcentral.com\/articles\/10.1186\/1471-2202-10-148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["1152"],"URL":"https:\/\/doi.org\/10.1186\/1471-2202-10-148","relation":{},"ISSN":["1471-2202"],"issn-type":[{"value":"1471-2202","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12]]},"assertion":[{"value":"15 September 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2009","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2009","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"148"}}