{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T10:45:38Z","timestamp":1751971538717,"version":"3.37.3"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T00:00:00Z","timestamp":1661558400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T00:00:00Z","timestamp":1661558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007051","name":"Uppsala University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Parasit."],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Ribosome biogenesis is a key process in all living organisms, energetically expensive and tightly regulated. Currently, little is known about the components of the ribosomal RNA (rRNA) transcription machinery that are present in intestinal parasites, such as <jats:italic>Giardia duodenalis<\/jats:italic>, <jats:italic>Cryptosporidium parvum<\/jats:italic>, and <jats:italic>Entamoeba histolytica.<\/jats:italic> Thus, in the present work, an analysis was carried out looking for the components of the rRNA transcription machinery that are conserved in intestinal parasites and if these could be used to design new treatment strategies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The different components of the rRNA transcription machinery were searched in the studied parasites with the NCBI BLAST tool in the EuPathDB Bioinformatics Resource Center database. The sequences of the RRN3 and POLR1F orthologs were aligned and important regions identified. Subsequently, three-dimensional models were built with different bioinformatic tools and a structural analysis was performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Among the protozoa examined, <jats:italic>C. parvum<\/jats:italic> is the parasite with the fewest identifiable components of the rRNA transcription machinery. TBP, RRN3, POLR1A, POLR1B, POLR1C, POLR1D, POLR1F, POLR1H, POLR2E, POLR2F and POLR2H subunits were identified in all species studied. Furthermore, the interaction regions between RRN3 and POLR1F were found to be conserved and could be used to design drugs that inhibit rRNA transcription in the parasites studied.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The inhibition of the rRNA transcription machinery in parasites might be a new therapeutic strategy against these microorganisms.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11686-022-00612-7","type":"journal-article","created":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T03:21:12Z","timestamp":1661570472000},"page":"1788-1799","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ribosomal RNA Transcription Machineries in Intestinal Protozoan Parasites: A Bioinformatic Analysis"],"prefix":"10.1007","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7730-6452","authenticated-orcid":false,"given":"Francisco Alejandro","family":"Lagunas-Rangel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,8,27]]},"reference":[{"key":"612_CR1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.DMIH2-0013-2015","author":"ES Theel","year":"2016","unstructured":"Theel ES, Pritt BS (2016) Parasites. Microbiol Spectr. https:\/\/doi.org\/10.1128\/microbiolspec.DMIH2-0013-2015","journal-title":"Microbiol Spectr"},{"key":"612_CR2","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1007\/s00436-015-4423-1","volume":"114","author":"HA El-Taweel","year":"2015","unstructured":"El-Taweel HA (2015) Understanding drug resistance in human intestinal protozoa. Parasitol Res 114:1647\u20131659. https:\/\/doi.org\/10.1007\/s00436-015-4423-1","journal-title":"Parasitol Res"},{"key":"612_CR3","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3390\/pathogens8030116","volume":"8","author":"A Hemphill","year":"2019","unstructured":"Hemphill A, M\u00fcller N, M\u00fcller J (2019) Comparative pathobiology of the intestinal protozoan parasites Giardia lamblia, Entamoeba histolytica, and Cryptosporidium parvum. Pathogens 8:116. https:\/\/doi.org\/10.3390\/pathogens8030116","journal-title":"Pathogens"},{"key":"612_CR4","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1080\/20469047.2018.1479055","volume":"39","author":"K Chifunda","year":"2019","unstructured":"Chifunda K, Kelly P (2019) Parasitic infections of the gut in children. Paediatr Int Child Health 39:65\u201372. https:\/\/doi.org\/10.1080\/20469047.2018.1479055","journal-title":"Paediatr Int Child Health"},{"key":"612_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jgar.2019.01.023","volume":"18","author":"PK Pramanik","year":"2019","unstructured":"Pramanik PK, Alam MN, Roy Chowdhury D, Chakraborti T (2019) Drug resistance in protozoan parasites: an incessant wrestle for survival. J Glob Antimicrob Resist 18:1\u201311. https:\/\/doi.org\/10.1016\/j.jgar.2019.01.023","journal-title":"J Glob Antimicrob Resist"},{"key":"612_CR6","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1128\/CMR.14.1.150-164.2001","volume":"14","author":"P Upcroft","year":"2001","unstructured":"Upcroft P, Upcroft JA (2001) Drug targets and mechanisms of resistance in the anaerobic protozoa. Clin Microbiol Rev 14:150\u2013164. https:\/\/doi.org\/10.1128\/CMR.14.1.150-164.2001","journal-title":"Clin Microbiol Rev"},{"key":"612_CR7","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/s00412-013-0430-0","volume":"122","author":"I Grummt","year":"2013","unstructured":"Grummt I (2013) The nucleolus\u2014guardian of cellular homeostasis and genome integrity. Chromosoma 122:487\u2013497. https:\/\/doi.org\/10.1007\/s00412-013-0430-0","journal-title":"Chromosoma"},{"key":"612_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2021.105872","volume":"217","author":"FA Lagunas-Rangel","year":"2021","unstructured":"Lagunas-Rangel FA, Baz\u00e1n-Tejeda ML, Berm\u00fadez-Cruz RM (2021) Ribosomal DNA in the protozoan parasite Giardia duodenalis has a differential chromatin distribution and epigenetic markings across the subunits. Acta Trop 217:105872. https:\/\/doi.org\/10.1016\/j.actatropica.2021.105872","journal-title":"Acta Trop"},{"key":"612_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2021.126807","volume":"250","author":"FA Lagunas-Rangel","year":"2021","unstructured":"Lagunas-Rangel FA, Yee J, Berm\u00fadez-Cruz RM (2021) An update on cell division of Giardia duodenalis trophozoites. Microbiol Res 250:126807. https:\/\/doi.org\/10.1016\/j.micres.2021.126807","journal-title":"Microbiol Res"},{"key":"612_CR10","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1038\/ncomms2539","volume":"4","author":"L Mancio-Silva","year":"2013","unstructured":"Mancio-Silva L, Lopez-Rubio JJ, Claes A, Scherf A (2013) Sir2a regulates rDNA transcription and multiplication rate in the human malaria parasite Plasmodium falciparum. Nat Commun 4:1530. https:\/\/doi.org\/10.1038\/ncomms2539","journal-title":"Nat Commun"},{"key":"612_CR11","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1146\/annurev.cellbio.24.110707.175259","volume":"24","author":"B McStay","year":"2008","unstructured":"McStay B, Grummt I (2008) The epigenetics of rRNA genes: from molecular to chromosome biology. Annu Rev Cell Dev Biol 24:131\u2013157. https:\/\/doi.org\/10.1146\/annurev.cellbio.24.110707.175259","journal-title":"Annu Rev Cell Dev Biol"},{"key":"612_CR12","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1111\/mmi.14710","volume":"115","author":"FA Lagunas-Rangel","year":"2021","unstructured":"Lagunas-Rangel FA, Yee J, Baz\u00e1n-Tejeda ML et al (2021) Sirtuin GdSir2.4 participates in the regulation of rRNA transcription in the Giardia duodenalis parasite. Mol Microbiol 115:1039\u20131053. https:\/\/doi.org\/10.1111\/mmi.14710","journal-title":"Mol Microbiol"},{"key":"612_CR13","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1042\/bss0730203","volume":"73","author":"J Russell","year":"2006","unstructured":"Russell J, Zomerdijk JCBM (2006) The RNA polymerase I transcription machinery. Biochem Soc Symp 73:203\u2013216. https:\/\/doi.org\/10.1042\/bss0730203","journal-title":"Biochem Soc Symp"},{"key":"612_CR14","doi-asserted-by":"publisher","first-page":"18325","DOI":"10.1038\/s41598-021-97020-0","volume":"11","author":"M Bakari-Soale","year":"2021","unstructured":"Bakari-Soale M, Ikenga NJ, Scheibe M et al (2021) The nucleolar DExD\/H protein Hel66 is involved in ribosome biogenesis in Trypanosoma brucei. Sci Rep 11:18325. https:\/\/doi.org\/10.1038\/s41598-021-97020-0","journal-title":"Sci Rep"},{"key":"612_CR15","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00475-19","author":"D Jaremko","year":"2019","unstructured":"Jaremko D, Ciganda M, Christen L, Williams N (2019) Trypanosoma brucei L11 is essential to ribosome biogenesis and interacts with the kinetoplastid-specific proteins P34 and P37. mSphere. https:\/\/doi.org\/10.1128\/mSphere.00475-19","journal-title":"mSphere"},{"key":"612_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2022.106315","volume":"228","author":"T Nepomuceno-Mej\u00eda","year":"2022","unstructured":"Nepomuceno-Mej\u00eda T, Florencio-Mart\u00ednez LE, Pineda-Garc\u00eda I, Mart\u00ednez-Calvillo S (2022) Identification of factors involved in ribosome assembly in the protozoan parasite Leishmania major. Acta Trop 228:106315. https:\/\/doi.org\/10.1016\/j.actatropica.2022.106315","journal-title":"Acta Trop"},{"key":"612_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2019.107822","volume":"209","author":"FA Lagunas-Rangel","year":"2020","unstructured":"Lagunas-Rangel FA, Baz\u00e1n-Tejeda ML, Garc\u00eda-Villa E, Berm\u00fadez-Cruz RM (2020) Nicotinamide induces G2 cell cycle arrest in Giardia duodenalis trophozoites and promotes changes in sirtuins transcriptional expression. Exp Parasitol 209:107822. https:\/\/doi.org\/10.1016\/j.exppara.2019.107822","journal-title":"Exp Parasitol"},{"key":"612_CR18","doi-asserted-by":"publisher","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","volume":"49","author":"A Bateman","year":"2021","unstructured":"Bateman A, Martin M-J, Orchard S et al (2021) UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res 49:D480\u2013D489. https:\/\/doi.org\/10.1093\/nar\/gkaa1100","journal-title":"Nucleic Acids Res"},{"key":"612_CR19","doi-asserted-by":"publisher","first-page":"D581","DOI":"10.1093\/nar\/gkw1105","volume":"45","author":"C Aurrecoechea","year":"2017","unstructured":"Aurrecoechea C, Barreto A, Basenko EY et al (2017) EuPathDB: the eukaryotic pathogen genomics database resource. Nucleic Acids Res 45:D581\u2013D591. https:\/\/doi.org\/10.1093\/nar\/gkw1105","journal-title":"Nucleic Acids Res"},{"key":"612_CR20","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/1471-2105-10-421","volume":"10","author":"C Camacho","year":"2009","unstructured":"Camacho C, Coulouris G, Avagyan V et al (2009) BLAST+: architecture and applications. BMC Bioinform 10:421. https:\/\/doi.org\/10.1186\/1471-2105-10-421","journal-title":"BMC Bioinform"},{"key":"612_CR21","doi-asserted-by":"publisher","first-page":"D344","DOI":"10.1093\/nar\/gkaa977","volume":"49","author":"M Blum","year":"2021","unstructured":"Blum M, Chang H-Y, Chuguransky S et al (2021) The InterPro protein families and domains database: 20 years on. Nucleic Acids Res 49:D344\u2013D354. https:\/\/doi.org\/10.1093\/nar\/gkaa977","journal-title":"Nucleic Acids Res"},{"key":"612_CR22","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","volume":"46","author":"A Waterhouse","year":"2018","unstructured":"Waterhouse A, Bertoni M, Bienert S et al (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46:W296\u2013W303. https:\/\/doi.org\/10.1093\/nar\/gky427","journal-title":"Nucleic Acids Res"},{"key":"612_CR23","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen EF, Goddard TD, Huang CC et al (2004) UCSF Chimera\u2013\u2013a visualization system for exploratory research and analysis. J Comput Chem 25:1605\u20131612. https:\/\/doi.org\/10.1002\/jcc.20084","journal-title":"J Comput Chem"},{"key":"612_CR24","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1128\/MMBR.00005-16","volume":"80","author":"R Srivastava","year":"2016","unstructured":"Srivastava R, Srivastava R, Ahn SH (2016) The epigenetic pathways to ribosomal DNA silencing. Microbiol Mol Biol Rev 80:545\u2013563. https:\/\/doi.org\/10.1128\/MMBR.00005-16","journal-title":"Microbiol Mol Biol Rev"},{"key":"612_CR25","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1146\/annurev-biochem-062917-012612","volume":"87","author":"S Sharifi","year":"2018","unstructured":"Sharifi S, Bierhoff H (2018) Regulation of RNA polymerase I transcription in development, disease, and aging. Annu Rev Biochem 87:51\u201373. https:\/\/doi.org\/10.1146\/annurev-biochem-062917-012612","journal-title":"Annu Rev Biochem"},{"key":"612_CR26","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1042\/BST20180623","volume":"47","author":"K Kramm","year":"2019","unstructured":"Kramm K, Engel C, Grohmann D (2019) Transcription initiation factor TBP: old friend new questions. Biochem Soc Trans 47:411\u2013423. https:\/\/doi.org\/10.1042\/BST20180623","journal-title":"Biochem Soc Trans"},{"key":"612_CR27","doi-asserted-by":"publisher","first-page":"374","DOI":"10.4161\/epi.4.6.9449","volume":"4","author":"E Sanij","year":"2009","unstructured":"Sanij E, Hannan RD (2009) The role of UBF in regulating the structure and dynamics of transcriptionally active rDNA chromatin. Epigenetics 4:374\u2013382. https:\/\/doi.org\/10.4161\/epi.4.6.9449","journal-title":"Epigenetics"},{"key":"612_CR28","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1016\/j.cell.2007.10.051","volume":"131","author":"C-D Kuhn","year":"2007","unstructured":"Kuhn C-D, Geiger SR, Baumli S et al (2007) Functional architecture of RNA polymerase I. Cell 131:1260\u20131272. https:\/\/doi.org\/10.1016\/j.cell.2007.10.051","journal-title":"Cell"},{"key":"612_CR29","doi-asserted-by":"publisher","first-page":"14670","DOI":"10.1073\/pnas.232580799","volume":"99","author":"G Peyroche","year":"2002","unstructured":"Peyroche G, Levillain E, Siaut M et al (2002) The A14\u2013A43 heterodimer subunit in yeast RNA pol I and their relationship to Rpb4-Rpb7 pol II subunits. Proc Natl Acad Sci 99:14670\u201314675. https:\/\/doi.org\/10.1073\/pnas.232580799","journal-title":"Proc Natl Acad Sci"},{"key":"612_CR30","doi-asserted-by":"publisher","first-page":"11467","DOI":"10.1074\/jbc.M411150200","volume":"280","author":"Y Imazawa","year":"2005","unstructured":"Imazawa Y, Hisatake K, Mitsuzawa H et al (2005) The fission yeast protein Ker1p is an ortholog of RNA polymerase I subunit A14 in Saccharomyces cerevisiae and is required for stable association of Rrn3p and RPA21 in RNA polymerase I. J Biol Chem 280:11467\u201311474. https:\/\/doi.org\/10.1074\/jbc.M411150200","journal-title":"J Biol Chem"},{"key":"612_CR31","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s12038-016-9587-z","volume":"41","author":"A Srivastava","year":"2016","unstructured":"Srivastava A, Bhattacharya A, Bhattacharya S, Jhingan GD (2016) Identification of EhTIF-IA: the putative E. histolytica orthologue of the human ribosomal RNA transcription initiation factor-IA. J Biosci 41:51\u201362. https:\/\/doi.org\/10.1007\/s12038-016-9587-z","journal-title":"J Biosci"},{"key":"612_CR32","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41597-020-0377-y","volume":"7","author":"F Xu","year":"2020","unstructured":"Xu F, Jex A, Sv\u00e4rd SG (2020) A chromosome-scale reference genome for Giardia intestinalis WB. Sci Data 7:38. https:\/\/doi.org\/10.1038\/s41597-020-0377-y","journal-title":"Sci Data"},{"key":"612_CR33","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/S0166-6851(97)00181-3","volume":"90","author":"SM Le Blancq","year":"1997","unstructured":"Le Blancq SM, Khramtsov NV, Zamani F et al (1997) Ribosomal RNA gene organization in Cryptosporidium parvum. Mol Biochem Parasitol 90:463\u2013478. https:\/\/doi.org\/10.1016\/S0166-6851(97)00181-3","journal-title":"Mol Biochem Parasitol"},{"key":"612_CR34","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/S0169-4758(98)01222-8","volume":"14","author":"S Bhattacharya","year":"1998","unstructured":"Bhattacharya S, Som I, Bhattacharya A (1998) The ribosomal DNA plasmids of entamoeba. Parasitol Today 14:181\u2013185. https:\/\/doi.org\/10.1016\/S0169-4758(98)01222-8","journal-title":"Parasitol Today"},{"key":"612_CR35","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1574-6976.2009.00196.x","volume":"34","author":"AL Torres-Machorro","year":"2010","unstructured":"Torres-Machorro AL, Hern\u00e1ndez R, Cevallos AM, L\u00f3pez-Villase\u00f1or I (2010) Ribosomal RNA genes in eukaryotic microorganisms: witnesses of phylogeny? FEMS Microbiol Rev 34:59\u201386. https:\/\/doi.org\/10.1111\/j.1574-6976.2009.00196.x","journal-title":"FEMS Microbiol Rev"},{"key":"612_CR36","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1128\/EC.00254-08","volume":"8","author":"SK Panigrahi","year":"2009","unstructured":"Panigrahi SK, Jhingan GD, Som I et al (2009) Promoter analysis of palindromic transcription units in the ribosomal DNA circle of Entamoeba histolytica. Eukaryot Cell 8:69\u201376. https:\/\/doi.org\/10.1128\/EC.00254-08","journal-title":"Eukaryot Cell"},{"key":"612_CR37","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1158\/1541-7786.MCR-14-0229","volume":"12","author":"K Rothblum","year":"2014","unstructured":"Rothblum K, Hu Q, Penrod Y, Rothblum LI (2014) Selective inhibition of rDNA transcription by a small-molecule peptide that targets the interface between RNA polymerase I and Rrn3. Mol Cancer Res 12:1586\u20131596. https:\/\/doi.org\/10.1158\/1541-7786.MCR-14-0229","journal-title":"Mol Cancer Res"},{"key":"612_CR38","doi-asserted-by":"publisher","first-page":"5473","DOI":"10.1093\/emboj\/19.20.5473","volume":"19","author":"G Peyroche","year":"2000","unstructured":"Peyroche G (2000) The recruitment of RNA polymerase I on rDNA is mediated by the interaction of the A43 subunit with Rrn3. EMBO J 19:5473\u20135482. https:\/\/doi.org\/10.1093\/emboj\/19.20.5473","journal-title":"EMBO J"},{"key":"612_CR39","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1101\/gad.17363311","volume":"25","author":"C Blattner","year":"2011","unstructured":"Blattner C, Jennebach S, Herzog F et al (2011) Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth. Genes Dev 25:2093\u20132105. https:\/\/doi.org\/10.1101\/gad.17363311","journal-title":"Genes Dev"},{"key":"612_CR40","doi-asserted-by":"publisher","first-page":"27423","DOI":"10.1074\/jbc.M201232200","volume":"277","author":"AH Cavanaugh","year":"2002","unstructured":"Cavanaugh AH, Hirschler-Laszkiewicz I, Hu Q et al (2002) Rrn3 phosphorylation is a regulatory checkpoint for ribosome biogenesis. J Biol Chem 277:27423\u201327432. https:\/\/doi.org\/10.1074\/jbc.M201232200","journal-title":"J Biol Chem"},{"key":"612_CR41","doi-asserted-by":"publisher","first-page":"266","DOI":"10.3390\/cells9020266","volume":"9","author":"R Ferreira","year":"2020","unstructured":"Ferreira R, Schneekloth JS, Panov KI et al (2020) Targeting the RNA polymerase I transcription for cancer therapy comes of age. Cells 9:266. https:\/\/doi.org\/10.3390\/cells9020266","journal-title":"Cells"}],"container-title":["Acta Parasitologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11686-022-00612-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11686-022-00612-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11686-022-00612-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T02:35:51Z","timestamp":1669689351000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11686-022-00612-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,27]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["612"],"URL":"https:\/\/doi.org\/10.1007\/s11686-022-00612-7","relation":{},"ISSN":["1230-2821","1896-1851"],"issn-type":[{"type":"print","value":"1230-2821"},{"type":"electronic","value":"1896-1851"}],"subject":[],"published":{"date-parts":[[2022,8,27]]},"assertion":[{"value":"1 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This material is the original work of the author and has not been previously published elsewhere. Bioinformatic work does not require an ethical permit and the goal is to reduce work with animals.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}}]}}