The motility regulator flhDC drives intracellular accumulation and tumor colonization of Salmonella View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Vishnu Raman, Nele Van Dessel, Owen M. O’Connor, Neil S. Forbes

ABSTRACT

BACKGROUND: Salmonella have potential as anticancer therapeutic because of their innate tumor specificity. In clinical studies, this specificity has been hampered by heterogeneous responses. Understanding the mechanisms that control tumor colonization would enable the design of more robust therapeutic strains. Two mechanisms that could affect tumor colonization are intracellular accumulation and intratumoral motility. Both of these mechanisms have elements that are controlled by the master motility regulator flhDC. We hypothesized that 1) overexpressing flhDC in Salmonella increases intracellular bacterial accumulation in tumor cell masses, and 2) intracellular accumulation of Salmonella drives tumor colonization in vitro. METHODS: To test these hypotheses, we transformed Salmonella with genetic circuits that induce flhDC and express green fluorescent protein after intracellular invasion. The genetically modified Salmonella was perfused into an in vitro tumor-on-a-chip device. Time-lapse fluorescence microscopy was used to quantify intracellular and colonization dynamics within tumor masses. A mathematical model was used to determine how these mechanisms are related to each other. RESULTS: Overexpression of flhDC increased intracellular accumulation and tumor colonization 2.5 and 5 times more than control Salmonella, respectively (P < 0.05). Non-motile Salmonella accumulated in cancer cells 26 times less than controls (P < 0.001). Minimally invasive, ΔsipB, Salmonella colonized tumor masses 2.5 times less than controls (P < 0.05). When flhDC was selectively induced after penetration into tumor masses, Salmonella both accumulated intracellularly and colonized tumor masses 2 times more than controls (P < 0.05). Mathematical modeling of tumor colonization dynamics demonstrated that intracellular accumulation increased retention of Salmonella in tumors by effectively causing the bacteria to bind to cancer cells and preventing leakage out of the tumors. These results demonstrated that increasing intracellular bacterial density increased overall tumor colonization and that flhDC could be used to control both. CONCLUSIONS: This study demonstrates a mechanistic link between motility, intracellular accumulation and tumor colonization. Based on our results, we envision that therapeutic strains of Salmonella could use inducible flhDC to drive tumor colonization. More intratumoral bacteria would enable delivery of higher therapeutic payloads into tumors and would improve treatment efficacy. More... »

PAGES

44

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40425-018-0490-z

DOI

http://dx.doi.org/10.1186/s40425-018-0490-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112086666

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30755273


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Massachusetts Amherst", 
          "id": "https://www.grid.ac/institutes/grid.266683.f", 
          "name": [
            "Department of Chemical Engineering, University of Massachusetts, 159 Goessmann Laboratory, 686 North Pleasant St, 01003, Amherst, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Raman", 
        "givenName": "Vishnu", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Massachusetts Amherst", 
          "id": "https://www.grid.ac/institutes/grid.266683.f", 
          "name": [
            "Department of Chemical Engineering, University of Massachusetts, 159 Goessmann Laboratory, 686 North Pleasant St, 01003, Amherst, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Van Dessel", 
        "givenName": "Nele", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Massachusetts Amherst", 
          "id": "https://www.grid.ac/institutes/grid.266683.f", 
          "name": [
            "Department of Chemical Engineering, University of Massachusetts, 159 Goessmann Laboratory, 686 North Pleasant St, 01003, Amherst, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "O\u2019Connor", 
        "givenName": "Owen M.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Massachusetts Amherst", 
          "id": "https://www.grid.ac/institutes/grid.266683.f", 
          "name": [
            "Department of Chemical Engineering, University of Massachusetts, 159 Goessmann Laboratory, 686 North Pleasant St, 01003, Amherst, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Forbes", 
        "givenName": "Neil S.", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1371/journal.ppat.1002810", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000342527"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2958.2001.02380.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001911952"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature05272", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002086298", 
          "https://doi.org/10.1038/nature05272"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature05272", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002086298", 
          "https://doi.org/10.1038/nature05272"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature05272", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002086298", 
          "https://doi.org/10.1038/nature05272"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0046828", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002195569"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1205405", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003415329"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1205405", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003415329"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2958.2003.03598.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004313307"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0168-6445(03)00064-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005339942"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/cgt.2011.10", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007023238", 
          "https://doi.org/10.1038/cgt.2011.10"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmeth.1437", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007245272", 
          "https://doi.org/10.1038/nmeth.1437"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmeth.1437", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007245272", 
          "https://doi.org/10.1038/nmeth.1437"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.mib.2005.12.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008316409"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.snb.2011.09.051", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008345488"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2958.2000.02027.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009545966"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4049/jimmunol.174.3.1675", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009704606"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0060499", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010798808"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1242/jcs.00949", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011361354"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.ppat.1003987", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012116420"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jb.183.9.2733-2745.2001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013107167"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.cgt.7700501", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014164495", 
          "https://doi.org/10.1038/sj.cgt.7700501"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.cgt.7700501", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014164495", 
          "https://doi.org/10.1038/sj.cgt.7700501"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.mib.2014.09.019", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015963022"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.micinf.2015.01.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019107849"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2958.2002.02803.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020863981"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.73.2.1204-1208.2005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021308558"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/bit.20883", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021516753"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/bit.20883", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021516753"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc2934", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022355560", 
          "https://doi.org/10.1038/nrc2934"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc2934", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022355560", 
          "https://doi.org/10.1038/nrc2934"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0084681", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025709274"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.00052-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026128006"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ismej.2011.27", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028203313", 
          "https://doi.org/10.1038/ismej.2011.27"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1096/fj.201600701r", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028850549"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-09-4005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032261087"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-06-2618", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035634682"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0070147", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036795562"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.molcel.2016.04.015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037160085"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.molcel.2016.04.015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037160085"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pgen.1002983", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037353310"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/mmi.12136", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039215227"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.120163297", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039276805"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1039/c3ib40021b", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039828645"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.9071", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040612693"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.00468-15", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040942729"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev.ge.26.120192.001023", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041849739"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1039/c2ib00091a", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042988684"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2958.2005.04792.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043143090"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1462-5822.2001.00141.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043471858"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jb.00635-10", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044176876"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/emboj/18.14.3924", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045207311"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni.1800", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045666335", 
          "https://doi.org/10.1038/ni.1800"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni.1800", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045666335", 
          "https://doi.org/10.1038/ni.1800"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni.1800", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045666335", 
          "https://doi.org/10.1038/ni.1800"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2958.2003.03840.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047029988"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jconrel.2014.12.014", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047938682"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1039/b810571e", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049125880"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0135351", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049695611"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/bit.25645", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051156896"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1006098107", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051710290"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jb.01438-13", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052519388"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/auto.7.3.14046", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052756029"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/auto.7.3.14046", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052756029"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1099/mic.0.056036-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060395277"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.00734-16", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062711265"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jb.176.23.7345-7351.1994", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062723315"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074564037", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1076569022", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2002.20.1.142", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1083941830"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmicrobiol.2017.66", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085209790", 
          "https://doi.org/10.1038/nmicrobiol.2017.66"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmicrobiol.2017.66", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085209790", 
          "https://doi.org/10.1038/nmicrobiol.2017.66"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.18392", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085922588"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-12", 
    "datePublishedReg": "2019-12-01", 
    "description": "BACKGROUND: Salmonella have potential as anticancer therapeutic because of their innate tumor specificity. In clinical studies, this specificity has been hampered by heterogeneous responses. Understanding the mechanisms that control tumor colonization would enable the design of more robust therapeutic strains. Two mechanisms that could affect tumor colonization are intracellular accumulation and intratumoral motility. Both of these mechanisms have elements that are controlled by the master motility regulator flhDC. We hypothesized that 1) overexpressing flhDC in Salmonella increases intracellular bacterial accumulation in tumor cell masses, and 2) intracellular accumulation of Salmonella drives tumor colonization in vitro.\nMETHODS: To test these hypotheses, we transformed Salmonella with genetic circuits that induce flhDC and express green fluorescent protein after intracellular invasion. The genetically modified Salmonella was perfused into an in vitro tumor-on-a-chip device. Time-lapse fluorescence microscopy was used to quantify intracellular and colonization dynamics within tumor masses. A mathematical model was used to determine how these mechanisms are related to each other.\nRESULTS: Overexpression of flhDC increased intracellular accumulation and tumor colonization 2.5 and 5 times more than control Salmonella, respectively (P < 0.05). Non-motile Salmonella accumulated in cancer cells 26 times less than controls (P < 0.001). Minimally invasive, \u0394sipB, Salmonella colonized tumor masses 2.5 times less than controls (P < 0.05). When flhDC was selectively induced after penetration into tumor masses, Salmonella both accumulated intracellularly and colonized tumor masses 2 times more than controls (P < 0.05). Mathematical modeling of tumor colonization dynamics demonstrated that intracellular accumulation increased retention of Salmonella in tumors by effectively causing the bacteria to bind to cancer cells and preventing leakage out of the tumors. These results demonstrated that increasing intracellular bacterial density increased overall tumor colonization and that flhDC could be used to control both.\nCONCLUSIONS: This study demonstrates a mechanistic link between motility, intracellular accumulation and tumor colonization. Based on our results, we envision that therapeutic strains of Salmonella could use inducible flhDC to drive tumor colonization. More intratumoral bacteria would enable delivery of higher therapeutic payloads into tumors and would improve treatment efficacy.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/s40425-018-0490-z", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.3806852", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1049249", 
        "issn": [
          "2051-1426"
        ], 
        "name": "Journal for ImmunoTherapy of Cancer", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "7"
      }
    ], 
    "name": "The motility regulator flhDC drives intracellular accumulation and tumor colonization of Salmonella", 
    "pagination": "44", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "1c9fcf47d4adefcd40dc9c1a4daf846e33e8108d110f192c2341b6d96d3184a1"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30755273"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101620585"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s40425-018-0490-z"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1112086666"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s40425-018-0490-z", 
      "https://app.dimensions.ai/details/publication/pub.1112086666"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T10:01", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000347_0000000347/records_89819_00000004.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1186%2Fs40425-018-0490-z"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s40425-018-0490-z'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s40425-018-0490-z'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s40425-018-0490-z'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s40425-018-0490-z'


 

This table displays all metadata directly associated to this object as RDF triples.

276 TRIPLES      21 PREDICATES      90 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s40425-018-0490-z schema:about anzsrc-for:06
2 anzsrc-for:0601
3 schema:author N0c7ecbf5de0c4ca79016f6cb5683a184
4 schema:citation sg:pub.10.1038/cgt.2011.10
5 sg:pub.10.1038/ismej.2011.27
6 sg:pub.10.1038/nature05272
7 sg:pub.10.1038/ni.1800
8 sg:pub.10.1038/nmeth.1437
9 sg:pub.10.1038/nmicrobiol.2017.66
10 sg:pub.10.1038/nrc2934
11 sg:pub.10.1038/sj.cgt.7700501
12 https://app.dimensions.ai/details/publication/pub.1074564037
13 https://app.dimensions.ai/details/publication/pub.1076569022
14 https://doi.org/10.1002/bit.20883
15 https://doi.org/10.1002/bit.25645
16 https://doi.org/10.1016/j.jconrel.2014.12.014
17 https://doi.org/10.1016/j.mib.2005.12.006
18 https://doi.org/10.1016/j.mib.2014.09.019
19 https://doi.org/10.1016/j.micinf.2015.01.004
20 https://doi.org/10.1016/j.molcel.2016.04.015
21 https://doi.org/10.1016/j.snb.2011.09.051
22 https://doi.org/10.1016/s0168-6445(03)00064-0
23 https://doi.org/10.1039/b810571e
24 https://doi.org/10.1039/c2ib00091a
25 https://doi.org/10.1039/c3ib40021b
26 https://doi.org/10.1046/j.1365-2958.2000.02027.x
27 https://doi.org/10.1046/j.1365-2958.2001.02380.x
28 https://doi.org/10.1046/j.1365-2958.2002.02803.x
29 https://doi.org/10.1046/j.1365-2958.2003.03598.x
30 https://doi.org/10.1046/j.1365-2958.2003.03840.x
31 https://doi.org/10.1046/j.1462-5822.2001.00141.x
32 https://doi.org/10.1073/pnas.1006098107
33 https://doi.org/10.1073/pnas.120163297
34 https://doi.org/10.1093/emboj/18.14.3924
35 https://doi.org/10.1096/fj.201600701r
36 https://doi.org/10.1099/mic.0.056036-0
37 https://doi.org/10.1111/j.1365-2958.2005.04792.x
38 https://doi.org/10.1111/mmi.12136
39 https://doi.org/10.1126/science.1205405
40 https://doi.org/10.1128/iai.00052-07
41 https://doi.org/10.1128/iai.00468-15
42 https://doi.org/10.1128/iai.00734-16
43 https://doi.org/10.1128/iai.73.2.1204-1208.2005
44 https://doi.org/10.1128/jb.00635-10
45 https://doi.org/10.1128/jb.01438-13
46 https://doi.org/10.1128/jb.176.23.7345-7351.1994
47 https://doi.org/10.1128/jb.183.9.2733-2745.2001
48 https://doi.org/10.1146/annurev.ge.26.120192.001023
49 https://doi.org/10.1158/0008-5472.can-06-2618
50 https://doi.org/10.1158/0008-5472.can-09-4005
51 https://doi.org/10.1200/jco.2002.20.1.142
52 https://doi.org/10.1242/jcs.00949
53 https://doi.org/10.1371/journal.pgen.1002983
54 https://doi.org/10.1371/journal.pone.0046828
55 https://doi.org/10.1371/journal.pone.0060499
56 https://doi.org/10.1371/journal.pone.0070147
57 https://doi.org/10.1371/journal.pone.0084681
58 https://doi.org/10.1371/journal.pone.0135351
59 https://doi.org/10.1371/journal.ppat.1002810
60 https://doi.org/10.1371/journal.ppat.1003987
61 https://doi.org/10.18632/oncotarget.18392
62 https://doi.org/10.18632/oncotarget.9071
63 https://doi.org/10.4049/jimmunol.174.3.1675
64 https://doi.org/10.4161/auto.7.3.14046
65 schema:datePublished 2019-12
66 schema:datePublishedReg 2019-12-01
67 schema:description BACKGROUND: Salmonella have potential as anticancer therapeutic because of their innate tumor specificity. In clinical studies, this specificity has been hampered by heterogeneous responses. Understanding the mechanisms that control tumor colonization would enable the design of more robust therapeutic strains. Two mechanisms that could affect tumor colonization are intracellular accumulation and intratumoral motility. Both of these mechanisms have elements that are controlled by the master motility regulator flhDC. We hypothesized that 1) overexpressing flhDC in Salmonella increases intracellular bacterial accumulation in tumor cell masses, and 2) intracellular accumulation of Salmonella drives tumor colonization in vitro. METHODS: To test these hypotheses, we transformed Salmonella with genetic circuits that induce flhDC and express green fluorescent protein after intracellular invasion. The genetically modified Salmonella was perfused into an in vitro tumor-on-a-chip device. Time-lapse fluorescence microscopy was used to quantify intracellular and colonization dynamics within tumor masses. A mathematical model was used to determine how these mechanisms are related to each other. RESULTS: Overexpression of flhDC increased intracellular accumulation and tumor colonization 2.5 and 5 times more than control Salmonella, respectively (P < 0.05). Non-motile Salmonella accumulated in cancer cells 26 times less than controls (P < 0.001). Minimally invasive, ΔsipB, Salmonella colonized tumor masses 2.5 times less than controls (P < 0.05). When flhDC was selectively induced after penetration into tumor masses, Salmonella both accumulated intracellularly and colonized tumor masses 2 times more than controls (P < 0.05). Mathematical modeling of tumor colonization dynamics demonstrated that intracellular accumulation increased retention of Salmonella in tumors by effectively causing the bacteria to bind to cancer cells and preventing leakage out of the tumors. These results demonstrated that increasing intracellular bacterial density increased overall tumor colonization and that flhDC could be used to control both. CONCLUSIONS: This study demonstrates a mechanistic link between motility, intracellular accumulation and tumor colonization. Based on our results, we envision that therapeutic strains of Salmonella could use inducible flhDC to drive tumor colonization. More intratumoral bacteria would enable delivery of higher therapeutic payloads into tumors and would improve treatment efficacy.
68 schema:genre research_article
69 schema:inLanguage en
70 schema:isAccessibleForFree true
71 schema:isPartOf N716a10f5a82a4178a27f215f7401f7e1
72 N9dd91e9de4fe4c588696cb9ffc7acd85
73 sg:journal.1049249
74 schema:name The motility regulator flhDC drives intracellular accumulation and tumor colonization of Salmonella
75 schema:pagination 44
76 schema:productId N077a8a3086be418482b8abdd59819f5b
77 N08ec20d5094b402ab2c4ab9f7c628348
78 N8a3b6ae349764a40843924a2b834bea9
79 Nc72a3feee6ee4621aab6aea00e808334
80 Nfbfb52e416794ca9aa247d19c2800d87
81 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112086666
82 https://doi.org/10.1186/s40425-018-0490-z
83 schema:sdDatePublished 2019-04-11T10:01
84 schema:sdLicense https://scigraph.springernature.com/explorer/license/
85 schema:sdPublisher N50a77fc3eff44c1b960f0c18512c6b38
86 schema:url https://link.springer.com/10.1186%2Fs40425-018-0490-z
87 sgo:license sg:explorer/license/
88 sgo:sdDataset articles
89 rdf:type schema:ScholarlyArticle
90 N077a8a3086be418482b8abdd59819f5b schema:name nlm_unique_id
91 schema:value 101620585
92 rdf:type schema:PropertyValue
93 N08ec20d5094b402ab2c4ab9f7c628348 schema:name doi
94 schema:value 10.1186/s40425-018-0490-z
95 rdf:type schema:PropertyValue
96 N0c7ecbf5de0c4ca79016f6cb5683a184 rdf:first N6dd07de0b12e44038c6ef73d0de65588
97 rdf:rest N1368bd1ea1174afdb949492acda29129
98 N1368bd1ea1174afdb949492acda29129 rdf:first Nf48d84ac7327441ab619eda9a40164c4
99 rdf:rest N96d2b7a49c54410396eeb966b9c0b977
100 N21805df2527746ffbaa92a8e6fb0d684 schema:affiliation https://www.grid.ac/institutes/grid.266683.f
101 schema:familyName O’Connor
102 schema:givenName Owen M.
103 rdf:type schema:Person
104 N50a77fc3eff44c1b960f0c18512c6b38 schema:name Springer Nature - SN SciGraph project
105 rdf:type schema:Organization
106 N5a196cf10cad4932852debb9c186f114 rdf:first Nd9fa36e95c3845beb2487cebb531445e
107 rdf:rest rdf:nil
108 N6dd07de0b12e44038c6ef73d0de65588 schema:affiliation https://www.grid.ac/institutes/grid.266683.f
109 schema:familyName Raman
110 schema:givenName Vishnu
111 rdf:type schema:Person
112 N716a10f5a82a4178a27f215f7401f7e1 schema:issueNumber 1
113 rdf:type schema:PublicationIssue
114 N8a3b6ae349764a40843924a2b834bea9 schema:name readcube_id
115 schema:value 1c9fcf47d4adefcd40dc9c1a4daf846e33e8108d110f192c2341b6d96d3184a1
116 rdf:type schema:PropertyValue
117 N96d2b7a49c54410396eeb966b9c0b977 rdf:first N21805df2527746ffbaa92a8e6fb0d684
118 rdf:rest N5a196cf10cad4932852debb9c186f114
119 N9dd91e9de4fe4c588696cb9ffc7acd85 schema:volumeNumber 7
120 rdf:type schema:PublicationVolume
121 Nc72a3feee6ee4621aab6aea00e808334 schema:name pubmed_id
122 schema:value 30755273
123 rdf:type schema:PropertyValue
124 Nd9fa36e95c3845beb2487cebb531445e schema:affiliation https://www.grid.ac/institutes/grid.266683.f
125 schema:familyName Forbes
126 schema:givenName Neil S.
127 rdf:type schema:Person
128 Nf48d84ac7327441ab619eda9a40164c4 schema:affiliation https://www.grid.ac/institutes/grid.266683.f
129 schema:familyName Van Dessel
130 schema:givenName Nele
131 rdf:type schema:Person
132 Nfbfb52e416794ca9aa247d19c2800d87 schema:name dimensions_id
133 schema:value pub.1112086666
134 rdf:type schema:PropertyValue
135 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
136 schema:name Biological Sciences
137 rdf:type schema:DefinedTerm
138 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
139 schema:name Biochemistry and Cell Biology
140 rdf:type schema:DefinedTerm
141 sg:grant.3806852 http://pending.schema.org/fundedItem sg:pub.10.1186/s40425-018-0490-z
142 rdf:type schema:MonetaryGrant
143 sg:journal.1049249 schema:issn 2051-1426
144 schema:name Journal for ImmunoTherapy of Cancer
145 rdf:type schema:Periodical
146 sg:pub.10.1038/cgt.2011.10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007023238
147 https://doi.org/10.1038/cgt.2011.10
148 rdf:type schema:CreativeWork
149 sg:pub.10.1038/ismej.2011.27 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028203313
150 https://doi.org/10.1038/ismej.2011.27
151 rdf:type schema:CreativeWork
152 sg:pub.10.1038/nature05272 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002086298
153 https://doi.org/10.1038/nature05272
154 rdf:type schema:CreativeWork
155 sg:pub.10.1038/ni.1800 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045666335
156 https://doi.org/10.1038/ni.1800
157 rdf:type schema:CreativeWork
158 sg:pub.10.1038/nmeth.1437 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007245272
159 https://doi.org/10.1038/nmeth.1437
160 rdf:type schema:CreativeWork
161 sg:pub.10.1038/nmicrobiol.2017.66 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085209790
162 https://doi.org/10.1038/nmicrobiol.2017.66
163 rdf:type schema:CreativeWork
164 sg:pub.10.1038/nrc2934 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022355560
165 https://doi.org/10.1038/nrc2934
166 rdf:type schema:CreativeWork
167 sg:pub.10.1038/sj.cgt.7700501 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014164495
168 https://doi.org/10.1038/sj.cgt.7700501
169 rdf:type schema:CreativeWork
170 https://app.dimensions.ai/details/publication/pub.1074564037 schema:CreativeWork
171 https://app.dimensions.ai/details/publication/pub.1076569022 schema:CreativeWork
172 https://doi.org/10.1002/bit.20883 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021516753
173 rdf:type schema:CreativeWork
174 https://doi.org/10.1002/bit.25645 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051156896
175 rdf:type schema:CreativeWork
176 https://doi.org/10.1016/j.jconrel.2014.12.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047938682
177 rdf:type schema:CreativeWork
178 https://doi.org/10.1016/j.mib.2005.12.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008316409
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1016/j.mib.2014.09.019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015963022
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1016/j.micinf.2015.01.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019107849
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1016/j.molcel.2016.04.015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037160085
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1016/j.snb.2011.09.051 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008345488
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1016/s0168-6445(03)00064-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005339942
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1039/b810571e schema:sameAs https://app.dimensions.ai/details/publication/pub.1049125880
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1039/c2ib00091a schema:sameAs https://app.dimensions.ai/details/publication/pub.1042988684
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1039/c3ib40021b schema:sameAs https://app.dimensions.ai/details/publication/pub.1039828645
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1046/j.1365-2958.2000.02027.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1009545966
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1046/j.1365-2958.2001.02380.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1001911952
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1046/j.1365-2958.2002.02803.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1020863981
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1046/j.1365-2958.2003.03598.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1004313307
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1046/j.1365-2958.2003.03840.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1047029988
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1046/j.1462-5822.2001.00141.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1043471858
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1073/pnas.1006098107 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051710290
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1073/pnas.120163297 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039276805
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1093/emboj/18.14.3924 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045207311
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1096/fj.201600701r schema:sameAs https://app.dimensions.ai/details/publication/pub.1028850549
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1099/mic.0.056036-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1060395277
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1111/j.1365-2958.2005.04792.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1043143090
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1111/mmi.12136 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039215227
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1126/science.1205405 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003415329
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1128/iai.00052-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026128006
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1128/iai.00468-15 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040942729
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1128/iai.00734-16 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062711265
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1128/iai.73.2.1204-1208.2005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021308558
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1128/jb.00635-10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044176876
233 rdf:type schema:CreativeWork
234 https://doi.org/10.1128/jb.01438-13 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052519388
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1128/jb.176.23.7345-7351.1994 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062723315
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1128/jb.183.9.2733-2745.2001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013107167
239 rdf:type schema:CreativeWork
240 https://doi.org/10.1146/annurev.ge.26.120192.001023 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041849739
241 rdf:type schema:CreativeWork
242 https://doi.org/10.1158/0008-5472.can-06-2618 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035634682
243 rdf:type schema:CreativeWork
244 https://doi.org/10.1158/0008-5472.can-09-4005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032261087
245 rdf:type schema:CreativeWork
246 https://doi.org/10.1200/jco.2002.20.1.142 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083941830
247 rdf:type schema:CreativeWork
248 https://doi.org/10.1242/jcs.00949 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011361354
249 rdf:type schema:CreativeWork
250 https://doi.org/10.1371/journal.pgen.1002983 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037353310
251 rdf:type schema:CreativeWork
252 https://doi.org/10.1371/journal.pone.0046828 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002195569
253 rdf:type schema:CreativeWork
254 https://doi.org/10.1371/journal.pone.0060499 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010798808
255 rdf:type schema:CreativeWork
256 https://doi.org/10.1371/journal.pone.0070147 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036795562
257 rdf:type schema:CreativeWork
258 https://doi.org/10.1371/journal.pone.0084681 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025709274
259 rdf:type schema:CreativeWork
260 https://doi.org/10.1371/journal.pone.0135351 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049695611
261 rdf:type schema:CreativeWork
262 https://doi.org/10.1371/journal.ppat.1002810 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000342527
263 rdf:type schema:CreativeWork
264 https://doi.org/10.1371/journal.ppat.1003987 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012116420
265 rdf:type schema:CreativeWork
266 https://doi.org/10.18632/oncotarget.18392 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085922588
267 rdf:type schema:CreativeWork
268 https://doi.org/10.18632/oncotarget.9071 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040612693
269 rdf:type schema:CreativeWork
270 https://doi.org/10.4049/jimmunol.174.3.1675 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009704606
271 rdf:type schema:CreativeWork
272 https://doi.org/10.4161/auto.7.3.14046 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052756029
273 rdf:type schema:CreativeWork
274 https://www.grid.ac/institutes/grid.266683.f schema:alternateName University of Massachusetts Amherst
275 schema:name Department of Chemical Engineering, University of Massachusetts, 159 Goessmann Laboratory, 686 North Pleasant St, 01003, Amherst, MA, USA
276 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...