Project description:Transcriptional profiling of cynomolgus macaques liver tissue comparing control young macaques with elder macaques. Goal was to determine the liver genetic change with aging of macaques.
Project description:Infinium 450K is a hybridization array designed for the human genome, but the relative conservation between the macaque and human genomes makes its use in macaques feasible. We used the Infinium450K array to assay twelve Cynomolgus macaque muscle biopsies and compared it to Reduced Representation Bisulphite Sequencing (RRBS) data generated on the same samples. Muscle biopsies were performed on eleven adult male cynomologus macaques
Project description:The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed evaluation of safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a system biology approach to compare hematological, biochemical, transcriptomic, innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination. Immune response progression in cynomolgus macaques followed a similar course as in adult humans, but with slightly earlier onset. Yellow fever virus neutralizing antibody responses occurred earlier in cynomolgus macaques (by Day 7 [D7]), but titers >10 were reached in both species by D14 post-vaccination and were not significantly different by D28 (PRNT50 titers 3.6 Log vs 3.5 Log in cynomolgus macaques and human participants, respectively; p = 0.821). Changes in neutrophils, NK cells, monocytes, T and B cell frequency were higher in cynomolgus macaques and persisted for four weeks versus less than two weeks in humans. Low levels of systemic inflammatory cytokines (IL-1Ra, IL-8, MIP-1α, IP-10, MCP-1 or VEGF) were detected in either or both species, but with no or only slight changes versus baseline. Similar changes in gene expression profiles were elicited in both species. These included enriched and up-regulated type I IFN-associated viral sensing, antiviral innate response, and dendritic cell activation pathways D3–D7 post-vaccination in both species. Hematological and blood biochemical parameters remained relatively unchanged versus baseline in both species. Low level YF-17D viremia (RNAemia) was transiently detected in some cynomolgus macaques (28% [5/18]) but generally absent in humans (except one participant [5%; 1/20]). Importance: Cynomolgus macaques were confirmed as a valid surrogate model for replicating YF-17D vaccine-induced responses in humans, and suggest a key role for type I IFN.
Project description:Background: Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results: Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions: We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration. Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. In a second approach, ERV-K-(HML-2) RNA and protein expression was analysed in extracts from the same cynomolgus macaques.
Project description:We performed gene expression profiling of total RNA from brain samples derived from BSE-infected versus non-infected cynomolgus macaques (Macaca fascicularis).
Project description:Antifreeze protein III (AFP III) has been used in the cryopreservation of germ cells in several kinds of animals, but it is not yet known what the specific cryoprotective mechanism of AFP III is, except for reducing the formation of ice crystals during cryopreservation. In order to study the cryoprotective mechanism of AFP III on sperm cryopreservation, the proteomic profile of Cynomolgus macaques sperm were identified after cryopreservation. Compared to fresh sperm, 141 and 32 proteins were differentially identified in Cynomolgus macaques sperm cryopreserved without and with 0.1µg/ml AFP III, respectively. These proteins were mainly involved in mitochondrial production of reactive oxygen species (ROS), glutathione (GSH) synthesis and cell apoptosis. According to the differential proteins, we supposed that AFP Ⅲ mainly reduce sperm lipid, protein and DNA damage, as well as the release of cytochrome c, and thereby reduce sperm apoptosis by modulating the production of ROS in mitochondria. The molecular mechanism that how AFP III acts with sperm proteins and protects cell from cryoinjuries needs further study.
Project description:We set out to test the hypothesis that formaldehyde inhalation exposure significantly alters miRNA expression profiles within the nasal epithelium of nonhuman primates. Here, cynomolgus macaques were exposed to 0, 2, and 6 ppm formaldehyde for 6 hours/day across two consecutive days. RNA was extracted from the nasal maxilloturbinate region, a direct target of formaldehyde inhalation exposure. Genome-wide miRNA expression levels were assessed using microarrays. Cynomolgus macaques (Macaca fascicularis) were exposed to 0, 2 and 6 ppm formaldehyde for 6 hours/day across two consecutive days using whole body exposure chambers. RNA was extracted from the nasal maxilloturbinate region, a direct target of formaldehyde inhalation exposure. Genome-wide miRNA expression levels were assessed using microarrays.
Project description:Infinium 450K is a hybridization array designed for the human genome, but the relative conservation between the macaque and human genomes makes its use in macaques feasible. We used the Infinium450K array to assay twelve Cynomolgus macaque muscle biopsies and compared it to Reduced Representation Bisulphite Sequencing (RRBS) data generated on the same samples. Muscle biopsies were performed on eleven adult male cynomologus macaques