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Comparative genome sequencing of wild type rhesus cytomegalovirus (RhCMV) with a recombinant RhCMV lacking ORF 178

ABSTRACT: Recombinant RhCMV was created to study super-infection of Rhesus macaques. These viruses (RhCMV Î178;RhCMV Î182-189;RhCMV Î178Î182-189) were co-hybridized with a wild-type BAC-derived RhCMV to a RhCMV tiling array to ensure that there were no additional mutations beyond the intended deleted regions. Comparison of wild-type BAC-derived RhCMV Î178, RhCMV Î182-189, and RhCMV Î178Î182-189

ORGANISM(S): Macacine herpesvirus 3

SUBMITTER: Rebecca Richards

PROVIDER: E-GEOD-20308 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Comparative genome sequencing of wild type rhesus cytomegalovirus (RhCMV) with a recombinant RhCMV lacking ORF 178

Project description:Recombinant RhCMV was created to study super-infection of Rhesus macaques. These viruses (RhCMV Δ178;RhCMV Δ182-189;RhCMV Δ178Δ182-189) were co-hybridized with a wild-type BAC-derived RhCMV to a RhCMV tiling array to ensure that there were no additional mutations beyond the intended deleted regions.

2010-02-19 | GSE20308 | GEO

Non-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia VirusNon-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia VirusNon-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia VirusV

Project description:Vaccinia virus is a large enveloped DNA virus, which, like all poxviruses, replicates in the cytoplasm of infected cells. Vaccinia was historically thought to encode all the proteins required for its replication. However, recent findings have shown that nuclear host proteins are redirected to the cytoplasm to facilitate viral replication. Among these, topoisomerase 2α (TOP2A) and 2β (TOP2B), which mediate nuclear transcription, DNA replication, and chromosome segregation are the most abundant host proteins associated with nascent viral genomes. Here, we investigate the mechanisms driving TOP2A and TOP2B cytoplasmic translocation and their role in viral replication. We found that early viral protein synthesis induces the cytosolic relocalization of both isoforms, which are subsequently recruited to viral factories by an interaction of their C-terminal domains with the viral ligase, A50. TOP2A promotes replication by interacting with the vaccinia DNA replication machinery. In contrast, TOP2B suppresses replication by enhancing the formation of double-stranded RNA and antiviral granules, containing components of the tRNA splicing ligase complex. Our analysis provides new insights into host-pathogen interactions during poxvirus infection and the role of topoisomerase 2 outside of the nucleus.

2025-06-30 | PXD060689 | Pride

Activation of γ-globin gene expression by GATA1 and NF-Y in hereditary persistence of fetal hemoglobin

Project description:Naturally occurring mutations in the Î³-globin promoters can result in hereditary persistence of fetal hemoglobin (HPFH), a benign condition that ameliorates the severity of Î²-hemoglobinopathies through increased post-natal fetal hemoglobin (HbF) expression. Mutations in the Î³-globin promoters result in loss or de novo recruitment of transcription factors, yet the cis-regulatory elements involved in Î³-globin transcription in the context of HPFH are not clearly defined. We demonstrate that the -115 cluster of HPFH mutations require GATA1 binding to at -186 in cooperation with NF-Y at the proximal CCAAT box at -85 for Î³-globin expression. We show that multiple HPFH mutations increase HbF in an erythroid cell line and result in GATA1 binding at -186. Mutation of the -186 GATA motif in HPFH erythroid cell lines and erythroid-differentiated CD34+ cells resulted in loss of GATA1 binding and reduction in fetal hemoglobin. NF-Y ChIP-seq in HPFH erythroid cell lines demonstrated binding to the proximal CCAAT box at -85 was also found to be critical for HPFH-mediated Î³-globin expression. Together, the -186 GATA motif and -85 proximal CCAAT box function in an additive and independent manner. Our results reveal detailed evidence for common, positive acting cis-regulatory elements that may provide more general mechanisms for erythroid gene expression.

2021-04-22 | GSE152338 | GEO

Somatic Mutation Patterns in Cloned Dogs: Implications for Aging

Project description:Studies on somatic mutations in cloned animals have revealed slight genetic variances between clones and their originals but have yet to identify the precise effects of these differences within the organism. Somatic mutations contribute to aging and are implicated in tumor development and other age-related diseases. To explore this, we compared whole genome sequencing data of an original dog with cloned dogs, identifying 8,155 candidate somatic mutations. By analyzing mutational signatures and rates within relevant genes, we identified potential associations with aging. Further analysis of 239 homozygous mutations within 189 genes revealed significant enrichment of traits related to chronotype, adult body size, height, spherical equivalent or myopia, and age at first sexual intercourse, suggesting these genes play roles in both growth and aging, as indicated by changes during adolescence.

2024-06-17 | E-MTAB-13924 | biostudies-arrayexpress

Genome-wide comparison of Chicken Embryo Fibroblasts (CEF) and DF-1 in response to recombinant chicken chIFN-Î± and infection with Infectious Bursal Disease Virus (IBDV)

Project description:The spontaneously immortalised chicken DF-1 cell line is rapidly replacing its progenitor primary chicken embryo fibroblasts (CEF) in studies on avian viruses but no comprehensive study has as yet been reported comparing their immune phenotype. We conducted microarray analysis of the DF-1 and CEF, in both normal and stimulated conditions using recombinant chicken chIFN-Î± and the CEF-adapted infectious bursal disease virus vaccine strain PBG98.

2016-01-15 | E-MTAB-4028 | biostudies-arrayexpress

Transcription profiling of human melanoma cell lines treated or not with inflammatory cytokines

Project description:Melanomas are often infiltrated by activated inflammatory cells. Thus, melanoma cells are very likely stimulated by inflammatory cytokines. In order to assess the impact of common inflammatory cytokines, we investigated the gene expression profile of melanoma cell lines before and after cytokine treatment in vitro. Experiment Overall Design: 5 human melanoma cell lines were treated with either IFN-Î± 1,000 U/ml, IFN-Î³ 100 U/ml or TNF-Î± 10 ng/ml for 72 hours, or were left untreated. We analyzed their expression profile with Affymetrix expression arrays.

2009-12-19 | E-GEOD-19428 | biostudies-arrayexpress

X-chromosome inactivation in monkey embryos and pluripotent stem cells

Project description:In this study, we explored x-inactivation in monkey embryos (ICM and TE separately) and pluripotent stem cells (IVF derived ES, SCNT-derived ES and monkey iPS) To elucidate x-inactivation in experimentally reprogrammed pluripotent cells, we derived pluripotent stem cells by both SCNT and iPS approaches from same parental skin fibroblasts. We also compared gene patterns of those cells to IVF-derived counterpart. The transcriptomes of rhesus monkey embryonic stem cell lines derived by both SCNT (CRES) and iPS (RiPS) from same monkey skin fibroblasts were compared each other. Both experimentally reprogrammed cells were also compared with IVF-derived counterpart (ORMES23). Finally, the adult somatic skin fibroblasts were analyzed. Three biological replicates of each cell line (A, B, C) were analyzed.

2012-08-31 | E-GEOD-36252 | biostudies-arrayexpress

A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors.

Project description:This is a clinical study with an orally administered drug, BDTX-189 in participants with advanced solid tumors that have select mutations or alterations in human epidermal growth factor receptor 2 (HER2/ErbB2) genes or epidermal growth factor receptor (EGFR/ErbB1). The main goals of this study are to: * Find the recommended dose of BDTX-189 that can be given safely to participants * Learn more about the side effects of BDTX-189 * Learn what the body does to BDTX-189 after it has been taken (pharmacokinetics or PK) * Determine the antitumor activity of BDTX-189 in participants with select allosteric ErbB gene mutations

| 2325490 | ecrin-mdr-crc

Comparison of proteome alternations during aging in temporal lobe from human and rhesus macaque

Project description:Aging of population is a great challenge of healthcare. In china, the number of the elderly is rapidly growing, and it was estimated that there will be approximately 400 million citizens above 65 years old in 2050.Study on the changes of brain during aging may help elucidate the mechanism of the pathological process, and hence prevent or treat these neurological diseases.Rhesus macaque (Macaca mulatta) and human have a genetic homology of 95%, and their anatomy structures or physiological process are highly similar, which make rhesus macaque one of the most important nonhuman primate models.Thus, the comparison between the change of protein profile during aging in human and rhesus macaque is still necessary, and the characteristics of proteins that are conservative or divergent are of interest.The aim of the(our) study is to identify the conservative changes of pathways during aging, and to reveal the potential difference between human and rhesus macaque so that relevant studies based on primate models can be interpreted more accurately.

2020-06-25 | PXD013597 | Pride

An Inducible TGF-Î²2-TGFÎ²R Pathway Modulates the Sensitivity of HNSCC Cells to Tyrosine Kinase Inhibitors Targeting Dominant Receptor Tyrosine Kinases

Project description:The epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of head and neck squamous cell carcinomas (HNSCC), and molecularly targeted therapy against the EGFR with the monoclonal antibody cetuximab modestly increases overall survival in head and neck cancer patients. We hypothesize that co-signaling through additional pathways limits the efficacy of cetuximab and EGFR-specific tyrosine kinase inhibitors (TKIs) in the clinical treatment of HNSCC. Analysis of gene expression changes in HNSCC cell lines treated 4 days with TKIs targeting EGFR and/or fibroblast growth factor receptors (FGFRs) identified transforming growth factor beta 2 (TGF-Î²2) induction in the three cell lines tested. Measurement of TGF-Î²2 mRNA validated this observation and extended it to additional cell lines. Moreover, TGF-Î²2 mRNA was increased in primary patient HNSCC xenografts treated for 4 weeks with cetuximab, demonstrating in vivo relevance of these findings. Functional genomics analyses with shRNA libraries identified TGF-Î²2 and TGF-Î² receptors (TGFÎ²Rs) as synthetic lethal genes in the context of TKI treatment. Further, direct RNAi-mediated silencing of TGF-Î²2 inhibited cell growth, both alone and in combination with TKIs. Also, a pharmacological TGFÎ²RI inhibitor similarly inhibited basal growth and enhanced TKI efficacy. In summary, the studies support a TGF-Î²2-TGFÎ²R pathway as a TKI-inducible growth pathway in HNSCC that limits efficacy of EGFR-specific inhibitors. HNSCC cell lines treated 4 days with TKIs targeting EGFR and/or fibroblast growth factor receptors (FGFRs) identified transforming growth factor beta 2 (TGF-Î²2) induction in the three cell lines tested

2016-03-22 | E-GEOD-67500 | biostudies-arrayexpress

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