Volunteers were assessed at study entry, the day of the third vaccination and 24, 72 hours, two weeks after vaccination, and 5 days after challenge. 13/39 vaccinees were protected and 26/39 were not protected. Eleven vaccinees exhibited delayed onset of parasitemia. All infectivity controls developed parasitemia. Prediction Analysis of Microarrays (PAM-R) identified genes corresponding with protection. Gene Set Enrichment Analysis (GSEA) identified sets of genes associated with protection after the third immunization, before challenge.
Expression of genes associated with immunoproteasome processing of major histocompatibility complex peptides is indicative of protection with adjuvanted RTS,S malaria vaccine.
Specimen part
View SamplesUsing genome-wide expression profiles from persons either experimentally challenged with malaria-infected mosquitoes or naturally-infected with Plasmodium falciparum malaria, we present details of the transcriptional changes that occur with infection and that are either commonly shared between subjects with pre-symptomatic and clinically apparent malaria or that distinguish these two groups. Our findings confirm and extend aspects of the earliest responses to malaria infection at the molecular level and which may be informative in elucidating how innate and adaptive immune responses may be modulated in different stages of infection.
No associated publication
No sample metadata fields
View SamplesOrganophosphorus compounds induce cardiotoxicity through currently unknown mechanisms, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis.
No associated publication
Specimen part
View SamplesOrganophosphorus compounds may induce neurotoxicity through mechanisms other than the cholinergic pathway, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis.
Toxicogenomic studies of human neural cells following exposure to organophosphorus chemical warfare nerve agent VX.
Specimen part
View SamplesViral infection results in an overall downregulation of gene expression that is greatest by the viral set point. Of the 3647 genes downregulated at the viral set point, 1033 are upregulated as the result of successful ARV treatment
No associated publication
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Inflammation-driven carcinogenesis is mediated through STING.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Intrinsic self-DNA triggers inflammatory disease dependent on STING.
Specimen part
View SamplesOrganophosphorus compounds induce hepatotoxicity through currently unknown mechanisms, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis.
No associated publication
Specimen part, Time
View SamplesChronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease
Inflammation-driven carcinogenesis is mediated through STING.
Specimen part
View SamplesInflammatory diseases such as Aicardi-Goutieres Syndrome (AGS) and severe systemic lupus erythematosus (SLE) are generally lethal disorders that have been traced to defects in the exonuclease Trex1 (DNAseIII). Mice lacking Trex1 similarly die at an early age through comparable symptoms, including inflammatory myocarditis, through chronic activation of the STING (stimulator of interferon genes) pathway. Here we demonstrate that phagocytes rather than myocytes are predominantly responsible for causing inflammation, an outcome that could be alleviated following adoptive transfer of normal bone marrow into Trex1-/- mice. Trex1-/- macrophages did not exhibit significant augmented ability to produce pro-inflammatory cytokines compared to normal macrophages following exposure to STING-dependent activators, but rather appeared chronically stimulated by genomic DNA. These results shed molecular insight into inflammation and provide concepts for the design of new therapies.
Intrinsic self-DNA triggers inflammatory disease dependent on STING.
Specimen part
View Samples