109 research outputs found

    Terrestrial vertebrate survey of Motukawanui

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    Acknowledgements The authors thank the kaumātua roopu of Ngāti Kura for permission to visit the island, Rod Hitchmough for information on reptile species, Maud Quinzin for help in rat trapping, Rod Brown for information on restoration planting, and Graeme Taylor for providing a copy of the unpublished DOC report on the Cavalli Islands. Z.T.C. personally thanks Dean Wright (of Dean Wright Photography; https://www.deanwright.co.nz/) and Stephen Western (of Stephen Western Photography; https://stephenwestern.smugmug.com/) for help in providing photo comparisons. TriOceans provided transport to and from the island. Funding The fieldwork of this study was independently funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 747120 awarded to T. W. B. Research was performed under the University of Auckland animal ethics R2095 and wildlife authority 67914-DOA and research and collection authority 67915-RES. Funding was awarded to Z. T. C. by the New Zealand Government through a New Zealand International Doctoral Research Scholarship.Peer reviewedPostprin

    The clock is ticking : temporally prioritizing eradications on islands

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    Funding Funding was awarded to Z.T.C. by the New Zealand Government through a New Zealand International Doctoral Research Scholarship. Funding was awarded to T.W.B. by the European Union's Horizon 2020 research and innovation programme Marie SkƂodowska Curie Fellowship (Grant No. 747120). Funding was awarded to J.C.R. by the Royal Society of New Zealand Rutherford Discovery Fellowship (Grant No. RDF-UOA1404) and the BioHeritage National Science Challenge (Grant No. 1617-44-003). Additional supporting information may be found in the supplementary material of this article. The associated code and dataset are archived and are publicly available at the University of Auckland figshare database (https://doi.org/10.17608/k6.auckland.13542203.v1) and at GitHub (https://github.com/carterz2/temporal‐island‐prioritization).Peer reviewedPostprin

    Phagocytes produce prostaglandin E2 in response to cytosolic Listeria monocytogenes

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    Listeria monocytogenes is an intracellular bacterium that elicits robust CD8+ T-cell responses. Despite the ongoing development of L. monocytogenes-based platforms as cancer vaccines, our understanding of how L. monocytogenes drives robust CD8+ T-cell responses remains incomplete. One overarching hypothesis is that activation of cytosolic innate pathways is critical for immunity, as strains of L. monocytogenes that are unable to access the cytosol fail to elicit robust CD8+ T-cell responses and in fact inhibit optimal T-cell priming. Counterintuitively, however, activation of known cytosolic pathways, such as the inflammasome and type I IFN, lead to impaired immunity. Conversely, production of prostaglandin E2 (PGE2) downstream of cyclooxygenase-2 (COX-2) is essential for optimal L. monocytogenes T-cell priming. Here, we demonstrate that vacuole-constrained L. monocytogenes elicit reduced PGE2 production compared to wild-type strains in macrophages and dendritic cells ex vivo. In vivo, infection with wild-type L. monocytogenes leads to 10-fold increases in PGE2 production early during infection whereas vacuole-constrained strains fail to induce PGE2 over mock-immunized controls. Mice deficient in COX-2 specifically in Lyz2+ or CD11c+ cells produce less PGE2, suggesting these cell subsets contribute to PGE2 levels in vivo, while depletion of phagocytes with clodronate abolishes PGE2 production completely. Taken together, this work demonstrates that optimal PGE2 production by phagocytes depends on L. monocytogenes access to the cytosol, suggesting that one reason cytosolic access is required to prime CD8+ T-cell responses may be to facilitate production of PGE2

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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