Uncovering stem cell differentiation factors for salivary gland regeneration by quantitative analysis of differential proteomes
Severe xerostomia (dry mouth) compromises the quality of life in patients with Sjögren's syndrome or radiation therapy for head and neck cancer. A clinical management of xerostomia is often unsatisfactory as most interventions are palliative with limited efficacy. Following up our previous stud...
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| creator | Park, Yun-Jong Koh, Jin Kwon, Jin Teak Park, Yong-Seok Yang, Lijun Cha, Seunghee |
| description | Severe xerostomia (dry mouth) compromises the quality of life in patients with Sjögren's syndrome or radiation therapy for head and neck cancer. A clinical management of xerostomia is often unsatisfactory as most interventions are palliative with limited efficacy. Following up our previous study demonstrating that mouse BM-MSCs are capable of differentiating into salivary epithelial cells in a co-culture system, we further explored the molecular basis that governs the MSC reprogramming by utilizing high-throughput iTRAQ-2D-LC-MS/MS-based proteomics. Our data revealed the novel induction of pancreas-specific transcription factor 1a (PTF1α), muscle, intestine and stomach expression-1 (MIST-1), and achaete-scute complex homolog 3 (ASCL3) in 7 day co-cultured MSCs but not in control MSCs. More importantly, a common notion of pancreatic-specific expression of PTF1 α was challenged for the first time by our verification of PTF1 α expression in the mouse salivary glands. Furthermore, a molecular network simulation of our selected putative MSC reprogramming factors demonstrated evidence for their perspective roles in salivary gland development. In conclusion, quantitative proteomics with extensive data analyses narrowed down a set of MSC reprograming factors potentially contributing to salivary gland regeneration. Identification of their differential/synergistic impact on MSC conversion warrants further investigation. |
| doi_str_mv | 10.1371/journal.pone.0169677 |
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A clinical management of xerostomia is often unsatisfactory as most interventions are palliative with limited efficacy. Following up our previous study demonstrating that mouse BM-MSCs are capable of differentiating into salivary epithelial cells in a co-culture system, we further explored the molecular basis that governs the MSC reprogramming by utilizing high-throughput iTRAQ-2D-LC-MS/MS-based proteomics. Our data revealed the novel induction of pancreas-specific transcription factor 1a (PTF1α), muscle, intestine and stomach expression-1 (MIST-1), and achaete-scute complex homolog 3 (ASCL3) in 7 day co-cultured MSCs but not in control MSCs. More importantly, a common notion of pancreatic-specific expression of PTF1 α was challenged for the first time by our verification of PTF1 α expression in the mouse salivary glands. Furthermore, a molecular network simulation of our selected putative MSC reprogramming factors demonstrated evidence for their perspective roles in salivary gland development. In conclusion, quantitative proteomics with extensive data analyses narrowed down a set of MSC reprograming factors potentially contributing to salivary gland regeneration. Identification of their differential/synergistic impact on MSC conversion warrants further investigation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0169677</identifier><identifier>PMID: 28158262</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biology ; Biology and Life Sciences ; Blotting, Western ; Bone marrow ; Cancer ; Cell culture ; Cell cycle ; Cell differentiation ; Cell Differentiation - genetics ; Cell Differentiation - radiation effects ; Cells, Cultured ; Cluster Analysis ; Data processing ; Dentistry ; Epithelial cells ; Genetic aspects ; Glands ; Head & neck cancer ; Head and neck cancer ; Health aspects ; Homology ; Immunohistochemistry ; Immunology ; Intestine ; Kinases ; Laboratories ; Male ; Medicine and Health Sciences ; Mesenchymal stem cells ; Mice ; Mice, Inbred C57BL ; Mist ; Muscles ; Pancreas ; Proteins ; Proteome - metabolism ; Proteomics ; Quality of Life ; Quantitative analysis ; Radiation ; Radiation therapy ; Regeneration ; Research and Analysis Methods ; Salivary gland ; Salivary glands ; Salivary Glands - metabolism ; Salivary Glands - physiology ; Sjogren's syndrome ; Stem cells ; Stomach ; Studies ; Tandem Mass Spectrometry ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Xerostomia</subject><ispartof>PloS one, 2017-02, Vol.12 (2), p.e0169677-e0169677</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Park et al 2017 Park et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-7c7701a41f323f29e48c5c4692c273e1e7badabfed712b250570d44d6d1b382c3</citedby><cites>FETCH-LOGICAL-c725t-7c7701a41f323f29e48c5c4692c273e1e7badabfed712b250570d44d6d1b382c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291466/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291466/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28158262$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cooney, Austin John</contributor><creatorcontrib>Park, Yun-Jong</creatorcontrib><creatorcontrib>Koh, Jin</creatorcontrib><creatorcontrib>Kwon, Jin Teak</creatorcontrib><creatorcontrib>Park, Yong-Seok</creatorcontrib><creatorcontrib>Yang, Lijun</creatorcontrib><creatorcontrib>Cha, Seunghee</creatorcontrib><title>Uncovering stem cell differentiation factors for salivary gland regeneration by quantitative analysis of differential proteomes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Severe xerostomia (dry mouth) compromises the quality of life in patients with Sjögren's syndrome or radiation therapy for head and neck cancer. A clinical management of xerostomia is often unsatisfactory as most interventions are palliative with limited efficacy. Following up our previous study demonstrating that mouse BM-MSCs are capable of differentiating into salivary epithelial cells in a co-culture system, we further explored the molecular basis that governs the MSC reprogramming by utilizing high-throughput iTRAQ-2D-LC-MS/MS-based proteomics. Our data revealed the novel induction of pancreas-specific transcription factor 1a (PTF1α), muscle, intestine and stomach expression-1 (MIST-1), and achaete-scute complex homolog 3 (ASCL3) in 7 day co-cultured MSCs but not in control MSCs. More importantly, a common notion of pancreatic-specific expression of PTF1 α was challenged for the first time by our verification of PTF1 α expression in the mouse salivary glands. Furthermore, a molecular network simulation of our selected putative MSC reprogramming factors demonstrated evidence for their perspective roles in salivary gland development. In conclusion, quantitative proteomics with extensive data analyses narrowed down a set of MSC reprograming factors potentially contributing to salivary gland regeneration. Identification of their differential/synergistic impact on MSC conversion warrants further investigation.</description><subject>Analysis</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Blotting, Western</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - radiation effects</subject><subject>Cells, Cultured</subject><subject>Cluster Analysis</subject><subject>Data processing</subject><subject>Dentistry</subject><subject>Epithelial cells</subject><subject>Genetic aspects</subject><subject>Glands</subject><subject>Head & neck cancer</subject><subject>Head and neck cancer</subject><subject>Health aspects</subject><subject>Homology</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Intestine</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchymal stem cells</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mist</subject><subject>Muscles</subject><subject>Pancreas</subject><subject>Proteins</subject><subject>Proteome - metabolism</subject><subject>Proteomics</subject><subject>Quality of Life</subject><subject>Quantitative analysis</subject><subject>Radiation</subject><subject>Radiation therapy</subject><subject>Regeneration</subject><subject>Research and Analysis Methods</subject><subject>Salivary gland</subject><subject>Salivary glands</subject><subject>Salivary Glands - metabolism</subject><subject>Salivary Glands - physiology</subject><subject>Sjogren's syndrome</subject><subject>Stem cells</subject><subject>Stomach</subject><subject>Studies</subject><subject>Tandem Mass Spectrometry</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Xerostomia</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11r2zAUhs3YWLtu_2BshsHYLpLpw5Lsm0Ep-wgUCtu6WyHJR46CbaWSHZar_fXJTVqS0YviC1vy8746HzpZ9hqjOaYCf1r5MfSqna99D3OEecWFeJKd4oqSGSeIPj34PslexLhCiNGS8-fZCSkxKwknp9nf6974DQTXN3kcoMsNtG1eO2shQD84NTjf51aZwYeYWx_yqFq3UWGbN63q6zxAAz2EHae3-c2okmxI6w3kKgW4jS7m3h56tvk6-AF8B_Fl9syqNsKr_fssu_765dfF99nl1bfFxfnlzAjChpkwQiCsCmwpoZZUUJSGmYJXxBBBAYPQqlbaQi0w0YQhJlBdFDWvsaYlMfQse7vzXbc-yn3tosQlL6pUJoESsdgRtVcruQ6uS0lKr5y83fChkSoMzrQgGQdTaYq1YqpgWmmNEWO6QhxpKux02uf9aaPuoDYp66DaI9PjP71bysZvJCMVLjhPBh_2BsHfjBAH2bk4tUb14MfbuEtKSYnwY1DGWGp2mdB3_6EPF2JPNSrl6nrrU4hmMpXnhaiqqsCYJGr-AJWeGjpn0p20Lu0fCT4eCRIzwJ-hUWOMcvHzx-PZq9_H7PsDdgmqHZbRt-N0IeMxWOxAE3yMAex9PzCS00jdVUNOIyX3I5Vkbw57eS-6myH6Dy3uHow</recordid><startdate>20170203</startdate><enddate>20170203</enddate><creator>Park, Yun-Jong</creator><creator>Koh, Jin</creator><creator>Kwon, Jin Teak</creator><creator>Park, Yong-Seok</creator><creator>Yang, Lijun</creator><creator>Cha, Seunghee</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20170203</creationdate><title>Uncovering stem cell differentiation factors for salivary gland regeneration by quantitative analysis of differential proteomes</title><author>Park, Yun-Jong ; Koh, Jin ; Kwon, Jin Teak ; Park, Yong-Seok ; Yang, Lijun ; Cha, Seunghee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-7c7701a41f323f29e48c5c4692c273e1e7badabfed712b250570d44d6d1b382c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Blotting, Western</topic><topic>Bone marrow</topic><topic>Cancer</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - radiation effects</topic><topic>Cells, Cultured</topic><topic>Cluster Analysis</topic><topic>Data processing</topic><topic>Dentistry</topic><topic>Epithelial cells</topic><topic>Genetic aspects</topic><topic>Glands</topic><topic>Head & neck cancer</topic><topic>Head and neck cancer</topic><topic>Health aspects</topic><topic>Homology</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Intestine</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Mesenchymal stem cells</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mist</topic><topic>Muscles</topic><topic>Pancreas</topic><topic>Proteins</topic><topic>Proteome - metabolism</topic><topic>Proteomics</topic><topic>Quality of Life</topic><topic>Quantitative analysis</topic><topic>Radiation</topic><topic>Radiation therapy</topic><topic>Regeneration</topic><topic>Research and Analysis Methods</topic><topic>Salivary gland</topic><topic>Salivary glands</topic><topic>Salivary Glands - metabolism</topic><topic>Salivary Glands - physiology</topic><topic>Sjogren's syndrome</topic><topic>Stem cells</topic><topic>Stomach</topic><topic>Studies</topic><topic>Tandem Mass Spectrometry</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Xerostomia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Yun-Jong</creatorcontrib><creatorcontrib>Koh, Jin</creatorcontrib><creatorcontrib>Kwon, Jin Teak</creatorcontrib><creatorcontrib>Park, Yong-Seok</creatorcontrib><creatorcontrib>Yang, Lijun</creatorcontrib><creatorcontrib>Cha, Seunghee</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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A clinical management of xerostomia is often unsatisfactory as most interventions are palliative with limited efficacy. Following up our previous study demonstrating that mouse BM-MSCs are capable of differentiating into salivary epithelial cells in a co-culture system, we further explored the molecular basis that governs the MSC reprogramming by utilizing high-throughput iTRAQ-2D-LC-MS/MS-based proteomics. Our data revealed the novel induction of pancreas-specific transcription factor 1a (PTF1α), muscle, intestine and stomach expression-1 (MIST-1), and achaete-scute complex homolog 3 (ASCL3) in 7 day co-cultured MSCs but not in control MSCs. More importantly, a common notion of pancreatic-specific expression of PTF1 α was challenged for the first time by our verification of PTF1 α expression in the mouse salivary glands. Furthermore, a molecular network simulation of our selected putative MSC reprogramming factors demonstrated evidence for their perspective roles in salivary gland development. In conclusion, quantitative proteomics with extensive data analyses narrowed down a set of MSC reprograming factors potentially contributing to salivary gland regeneration. Identification of their differential/synergistic impact on MSC conversion warrants further investigation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28158262</pmid><doi>10.1371/journal.pone.0169677</doi><tpages>e0169677</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2017-02, Vol.12 (2), p.e0169677-e0169677 |
| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Animals Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Biology Biology and Life Sciences Blotting, Western Bone marrow Cancer Cell culture Cell cycle Cell differentiation Cell Differentiation - genetics Cell Differentiation - radiation effects Cells, Cultured Cluster Analysis Data processing Dentistry Epithelial cells Genetic aspects Glands Head & neck cancer Head and neck cancer Health aspects Homology Immunohistochemistry Immunology Intestine Kinases Laboratories Male Medicine and Health Sciences Mesenchymal stem cells Mice Mice, Inbred C57BL Mist Muscles Pancreas Proteins Proteome - metabolism Proteomics Quality of Life Quantitative analysis Radiation Radiation therapy Regeneration Research and Analysis Methods Salivary gland Salivary glands Salivary Glands - metabolism Salivary Glands - physiology Sjogren's syndrome Stem cells Stomach Studies Tandem Mass Spectrometry Transcription Factors - genetics Transcription Factors - metabolism Xerostomia |
| title | Uncovering stem cell differentiation factors for salivary gland regeneration by quantitative analysis of differential proteomes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-16T09%3A54%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Uncovering%20stem%20cell%20differentiation%20factors%20for%20salivary%20gland%20regeneration%20by%20quantitative%20analysis%20of%20differential%20proteomes&rft.jtitle=PloS%20one&rft.au=Park,%20Yun-Jong&rft.date=2017-02-03&rft.volume=12&rft.issue=2&rft.spage=e0169677&rft.epage=e0169677&rft.pages=e0169677-e0169677&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0169677&rft_dat=%3Cgale_plos_%3EA479994112%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1864919370&rft_id=info:pmid/28158262&rft_galeid=A479994112&rft_doaj_id=oai_doaj_org_article_56ec9b31ba5a45babb1055b9060b37fc&rfr_iscdi=true |