{"title":"Providing Adverse Outcome Pathways from the AOP-Wiki in a Semantic Web Format to Increase Usability and Accessibility of the Content","authors":"Marvin Martens, C. Evelo, Egon Willighagen","doi":"10.1089/aivt.2021.0010","DOIUrl":"https://doi.org/10.1089/aivt.2021.0010","url":null,"abstract":"Introduction: The AOP-Wiki is the main platform for the development and storage of adverse outcome pathways (AOPs). These AOPs describe mechanistic information about toxicodynamic processes and can be used to develop effective risk assessment strategies. However, it is challenging to automatically and systematically parse, filter, and use its contents. We explored solutions to better structure the AOP-Wiki content, and to link it with chemical and biological resources. Together, this allows more detailed exploration, which can be automated. Materials and Methods: We converted the complete AOP-Wiki content into resource description framework (RDF) triples. We used >20 ontologies for the semantic annotation of property–object relations, including the Chemical Information Ontology, Dublin Core, and the AOP Ontology. Results: The resulting RDF contains >122,000 triples describing 158 unique properties of >15,000 unique subjects. Furthermore, >3500 link-outs were added to 12 chemical databases, and >7500 link-outs to 4 gene and protein databases. The AOP-Wiki RDF has been made available at https://aopwiki.rdf.bigcat-bioinformatics.org Discussion: SPARQL queries can be used to answer biological and toxicological questions, such as listing measurement methods for all Key Events leading to an Adverse Outcome of interest. The full power that the use of this new resource provides becomes apparent when combining the content with external databases using federated queries. Conclusion: Overall, the AOP-Wiki RDF allows new ways to explore the rapidly growing AOP knowledge and makes the integration of this database in automated workflows possible, making the AOP-Wiki more FAIR.","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"8 1","pages":"2 - 13"},"PeriodicalIF":0.0,"publicationDate":"2021-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46010907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Exosomal microRNAs Release as a Sensitive Marker for Drug-Induced Liver Injury In Vitro by Messner CJ, et al. Appl In Vitro Toxicol 2020:6;77–89. DOI: 10.1089/aivt.2020.0008","authors":"","doi":"10.1089/aivt.2020.0008.correx","DOIUrl":"https://doi.org/10.1089/aivt.2020.0008.correx","url":null,"abstract":"","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2020.0008.correx","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42254113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James Gow, Yujie Yang, Mohan Govindraj, Changjiang Guo
{"title":"Nitric Oxide Regulates Macrophage Fungicidal Activity <i>via S</i>-nitrosylation of Dectin-1.","authors":"James Gow, Yujie Yang, Mohan Govindraj, Changjiang Guo","doi":"10.1089/aivt.2020.0009","DOIUrl":"https://doi.org/10.1089/aivt.2020.0009","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Recognition of fungal surface β-glucan by pattern recognition receptor Dectin-1 is a critical process for fungal clearance in the lung. In humans, persistent fungal infection is observed in individuals with particular Dectin-1 polymorphism. We have identified that nitric oxide (NO) modifies critical cysteines in pattern recognition molecules to disassemble and alter protein function. There is a hydrophobic <i>S</i>-nitrosylation motif present in surfactant protein-D (SP-D) that is also present in Dectin-1. We hypothesized that Dectin-1 can be modified by nitrosative stress potentially leading to impairment of fungal clearance. <b><i>Materials and Methods:</i></b> Recombinant Dectin-1 was incubated with l-nitrosocysteine (L-SNOC) and <i>S</i>-nitrosylated Dectin-1 was detected by Biotin-switch assay. Cells of a murine macrophage line (Raw 264.7) were incubated with <i>S</i>-nitroso-glutathione (GSNO) and Dectin-1 shedding from the cell surface was determined by Western blot. Dectin-1 quaternary structure was determined by native gel electrophoresis. Dectin-1 function was assayed by NF-κB activity and IL-6 mRNA real-time polymerase chain reaction (PCR). Phagocytic activity was measured by fluorescence labeled zymosan beads. <b><i>Results:</i></b> Dectin-1 was <i>S</i>-nitrosylated by l-nitrosocysteine (L-SNOC) <i>in vitro,</i> as determined by Biotin-switch assay, resulting in structural disruption. We used Western blotting and flow cytometry to demonstrate that incubation of a murine macrophage cell line (Raw 264.7 cells) with GSNO reduced the surface Dectin-1 expression as a result of shedding to the media. The shedding of Dectin-1 is due to formation of <i>S</i>-nitrosothiol (SNO)-Dectin-1 and disruption of the Dectin-1 oligomeric complex. GSNO also induces Dectin-1 shedding from the cell surface. The functional significance of GSNO treatment of macrophages is shown by reduced β-glucan-mediated signaling in terms of NF-κB function and IL-6 expression. Finally, it was demonstrated that GSNO treatment reduces the capability of macrophages to phagocytose zymosan. <b><i>Conclusions</i>:</b> These data provide mechanistic data to support the role of Dectin-1 nitrosylation as a mediator of reduced fungal clearance in the face of increased NO exposure.</p>","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"6 3","pages":"90-98"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2020.0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38401360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Call for Papers: Applied In Vitro Toxicology","authors":"Editor-in-Chief Andrew Gow","doi":"10.1089/AIVT.2020.29024.CFP2","DOIUrl":"https://doi.org/10.1089/AIVT.2020.29024.CFP2","url":null,"abstract":"","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/AIVT.2020.29024.CFP2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47491192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Precision Cut Lung Slices as a Model for 3R Application in Toxicology","authors":"J. Herbert, A. Gow","doi":"10.1089/aivt.2020.29025.com","DOIUrl":"https://doi.org/10.1089/aivt.2020.29025.com","url":null,"abstract":"","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2020.29025.com","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47303844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martha M. Moore, J. Clements, P. Desai, U. Doshi, M. Gaca, Xiaoqing Guo, Tsuneo Hashizume, Kristen G. Jordan, K. Monica Lee, R. Leverette, D. McHugh, J. Miller-Holt, G. Phillips, H. Raabe, L. Recio, Shambhu K. Roy, Daniel J. Smart, Leon F. Stankowski, D. Thorne, Elisabeth Weber, R. Wieczorek, K. Yoshino, R. Curren
{"title":"Workshop Series to Identify, Discuss, and Develop Recommendations for the Optimal Generation and Use of In Vitro Assay Data for Tobacco Product Evaluation: Phase 1 Genotoxicity Assays","authors":"Martha M. Moore, J. Clements, P. Desai, U. Doshi, M. Gaca, Xiaoqing Guo, Tsuneo Hashizume, Kristen G. Jordan, K. Monica Lee, R. Leverette, D. McHugh, J. Miller-Holt, G. Phillips, H. Raabe, L. Recio, Shambhu K. Roy, Daniel J. Smart, Leon F. Stankowski, D. Thorne, Elisabeth Weber, R. Wieczorek, K. Yoshino, R. Curren","doi":"10.1089/aivt.2020.0004","DOIUrl":"https://doi.org/10.1089/aivt.2020.0004","url":null,"abstract":"Introduction: The Institute for In Vitro Sciences is sponsoring a workshop series to identify, discuss, and develop recommendations for optimal scientific and technical approaches for conducting in...","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2020.0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44284236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling the Lack of Inotropic Response of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Isoproterenol by Chronic External Stimulation","authors":"Haoyu Zeng, Jixin Wang, Holly Clouse, A. Lagrutta","doi":"10.1089/aivt.2020.0002","DOIUrl":"https://doi.org/10.1089/aivt.2020.0002","url":null,"abstract":"Introduction: The lack of positive inotropic response to isoproterenol has been a caveat in the utilization of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for cardiac saf...","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2020.0002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42422764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Call for Papers: Applied In Vitro Toxicology","authors":"Editor-in-Chief James M. McKim","doi":"10.1089/aivt.2019.29021.cfp","DOIUrl":"https://doi.org/10.1089/aivt.2019.29021.cfp","url":null,"abstract":"","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2019.29021.cfp","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49421037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Dickinson, J. Godden, Kateryna Lanovyk, S. Ahmed
{"title":"Assessing the Safety of Nanomedicines: A Mini Review","authors":"A. Dickinson, J. Godden, Kateryna Lanovyk, S. Ahmed","doi":"10.1089/aivt.2019.0009","DOIUrl":"https://doi.org/10.1089/aivt.2019.0009","url":null,"abstract":"Abstract Over the past decade, there has been a significant increase in preclinical development and clinical use of approved nanomedicines. The nanomedicinal field represents a wide variety of prod...","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2019.0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45931423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. K. KraelingMargaret, D. ToppingVanessa, R. BelgraveKathleen, SchlickKristian, SimanekEric, ManSonny, DadiboyenaSureshbabu, K. PatriAnil, L. SprandoRobert, J. YourickJeffrey
{"title":"In Vitro Skin Penetration of Dendrimer Nanoparticles","authors":"E. K. KraelingMargaret, D. ToppingVanessa, R. BelgraveKathleen, SchlickKristian, SimanekEric, ManSonny, DadiboyenaSureshbabu, K. PatriAnil, L. SprandoRobert, J. YourickJeffrey","doi":"10.1089/aivt.2019.0004","DOIUrl":"https://doi.org/10.1089/aivt.2019.0004","url":null,"abstract":"Abstract Introduction: Dendrimers are highly branched, stable polymeric nanoparticles with functional groups capable of binding other molecules and may increase delivery of chemicals into skin. Mat...","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/aivt.2019.0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41922594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}