Project description:Fractionated whole-brain irradiation for the treatment of intracranial neoplasia causes progressive neurodegeneration and neuroinflammation. The long-term consequences of high single dose brain irradiation are unknown. In order to assess the late effects of brain irradiation we have compared transcriptomic gene expression profiles from nonhuman primates (rhesus macaques, Macaca mulatta) receiving single dose total body irradiation to those given fractionated whole brain radiotherapy and control comparators. Gene expression profiles from the dorsolateral prefrontal cortex (Brodmann area 46), hippocampus, and deep white matter (centrum semiovale) were compared. The goals of this study were to identify novel potential molecular effects of radiation-induced brain injury, to evaluate regional differences in the cerebral radiation response, and to assess whether animals receiving high dose total body irradiation demonstrated similar transcriptomic patterns as those observed in animals receiving fractionated whole brain irradiation.
2019-03-27 | GSE120901 | GEO
Project description:Spleen Transcriptome of Rhesus exposed to total- and partial-body irradiation
Project description:Methylomic profiling of rhesus macaque blood samples. The Illumina Infinium MethylationEPIC kit was used to obtain DNA methylation profiles for over 850,000 CpGs, of which 339,081 were determined to be conserved in rhesus macaques based on the Mmul_10 genome build. A total of 29 samples were included, of which 26 remained after processing.
Project description:Background: Idiopathic Chronic Diarrhea (ICD) is a common cause of morbidity and mortality among juvenile rhesus macaques. Characterized by chronic inflammation of the colon and repeated bouts of diarrhea, ICD is largely unresponsive to medical interventions including corticosteroid, antiparasitic and antibiotic treatments. Although ICD is accompanied by large disruptions in the composition of the commensal gut microbiome, no single pathogen has been concretely identified as responsible for the onset and continuation of the disease. Results: Fecal samples were collected from twelve ICD-diagnosed macaques and twelve age and sex-matched controls. RNA was extracted for metatranscriptomic analysis of species and activity within the gut microbiome. Using SAMSA2, these samples were contrasted to identify shifts both in overall organism activity and functional activity. Bacterial, fungal, archaeal, protozoan, and macaque (host) transcripts were simultaneously assessed. ICD-afflicted animals were characterized by increased activity of known bacterial pathogens and by decreased activity of archaeal methanogens. Interestingly, known fungal opportunists were not increased in ICD, nor were the usual enteric protozoans, although Trichomonas activity is up-regualted. Known mucin degrading organisms and mucin-degrading enzymes were up-regulated in the fecal microbiomes of ICD-afflicted animals. Assessment of colon sections using immunohistochemistry confirmed differential mucin composition between healthy control and ICD animals. Finally, assessment of host-derived transcripts confirms colonic inflammation and suggests that the lumen is infiltrated by granulocytes. Conclusions: The simultaneous profiling of bacterial, fungal, archaeal, protozoan, and macaque transcripts from stool samples suggests that ICD of rhesus macaques is associated with increased pathogen activity and altered mucin degradation.
Project description:This SuperSeries is composed of the following subset Series: GSE33090: Dramatic effects of social behavior on gene regulation in rhesus macaques [Individual_expression] GSE34127: Dramatic effects of social behavior on gene regulation in rhesus macaques [Cell type_expression] GSE34128: Dramatic effects of social behavior on gene regulation in rhesus macaques [Bisulfite_seq] Refer to individual Series
Project description:Analysis of gene expression differences in relationship to dominance rank in female rhesus macaques. RNA obtained from isolated peripheral blood mononuclear cells from 49 adult female rhesus macaques of dominance ranks 1 (high) to 5 (low) across 10 social groups. Total 100 samples = (47 individuals X 2 replicates) + (2 individuals X 3 replicates)
Project description:Numerous studies have described the efficacy of heat inactivation, gamma irradiation, or treatment with guanidium-based chaotropic salts (e.g. TRIzol®) for pathogen inactivation of biological samples to ensure biosafety and biosecurity. However, the effect of these methods on the greater serum proteome are less studied. Here we sought to comprehensively measure the effects of three routinely used pathogen inactivation methods on the serum proteome of Rhesus macaques by characterizing the serum proteome pre-and-post inactivation treatment. Using data independent aquisition-based shotgun LCMS/MS, we evaluated total peptide/protein detection and individual protein abundances (e.g. ALB, APOA1, and CRP) across inactivation methods and compared to their untreated controls. Specifically, we observed improved quantitative reproducibility in gamma-irradiated samples across biological, technical, and experimental replicates compared to chemical inactivation and different heat combinations. These findings represent the first direct, experimental comparisons of effective pathogen inactivation methods on the serologic profiles of non-human primates and provide useful criteria for evaluating methods for biological specimen inactivation prior to proteomic analysis.
Project description:Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate aging associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 old (age>18 years) and 4 young (age 3-6 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in PBMC by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the old animals exhibited higher inflammatory biomarkers in plasma and lower CD4 T cells with altered distribution of naïve and memory T cell maturation subsets. The gut microbiome in old animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of old animals compared to the young. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile.
Project description:Background: Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation. Results: The overall mRNA response in the first week reflects a strong inflammatory reaction, infection response with neutrophil and platelet activation. At 1 week, cell cycle arrest and re-entry processes were enriched among mRNA changes, oncogene-induced senescence and MAPK signaling among the proteome changes. Influenza life cycle and infection pathways initiate earlier in mRNA and are reflected among the proteomic changes during the first week. Transcription factor proteins SRC, TGF and NFATC2 were immediately induced at 1 day after irradiation with increased transcriptional activity as predicted by mRNA changes persisting up to 1 week. Cell counts revealed a mild / moderate hematopoietic acute radiation syndrome (H-ARS) reaction to irradiation with expected lymphopenia, neutropenia and thrombocytopenia that resolved within 30 days. Measurements of micronuclei per binucleated cell levels in cytokinesis-blocked T-lymphocytes remained high in the range 0.27-0.33 up to 28 days and declined to 0.1 by day 56. Conclusions: Overall, we show that the TBI 4 Gy dose in NHPs induces many cellular changes that persist up to 1 month after exposure, consistent with damage, death, and repopulation of blood cells.