Natural SIV infection of sooty mangabeys (SMs) does not progress to disease despite chronic virus replication. In contrast to pathogenic SIV infection of rhesus macaques (RMs), chronic SIV infection of SMs is characterized by low immune activation. To elucidate the mechanisms underlying this phenotype, we longitudinally assessed host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs is consistently associated with a robust innate immune response, including widespread up-regulation of interferon-stimulated genes (ISGs). Our findings indicate that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low immuneactivation of chronically SIV-infected SMs.
Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys.
Sex, Specimen part
View SamplesTranscriptional Profiling Reveals Distinguishing Features of Immune Activation in the Lymphatic Tissues of Sooty Mangabeys and Rhesus Macaques in Early SIV Infection
Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys.
Specimen part
View SamplesThe goal of this study is to measure Arabidopsis mRNA transcription and mRNA decay rates genome wide at two temperatures, and thus to calculate the temperature coefficient of both processes. Sensing and response to ambient temperature is important for controlling growth and development of many organisms, in part by regulating mRNA levels. mRNA abundance can change with temperature, but it is unclear whether this results from changes to transcription or decay rates and whether passive or active temperature regulation is involved. Results Using a base analogue labelling method we directly measured the temperature coefficient (Q10) of mRNA synthesis and degradation rates of the Arabidopsis transcriptome. We show that for most genes transcript levels are buffered against passive increases in transcription rates by balancing passive increases in the rate of decay. Strikingly, for temperature-responsive transcripts, increasing temperature raises transcript abundance primarily by promoting faster transcription relative to decay and not vice versa, suggesting a global transcriptional mechanism process exists for the activethat controls of mRNA abundance by temperature/
Direct measurement of transcription rates reveals multiple mechanisms for configuration of the Arabidopsis ambient temperature response.
Specimen part, Treatment, Time
View SamplesThe objective of the study was identify hepatic genes with expression by deprivation of gut flora. Two models were used: model 1 (study 1443KR) examined germ-free Sprague Dawley and model 2 (1512KR) examined antibiotic treated Han Wistar rats.
Systemic gut microbial modulation of bile acid metabolism in host tissue compartments.
Specimen part, Treatment
View SamplesWe recently identified ISRIB as a potent inhibitor of the integrated stress response (ISR). ISRIB renders cells resistant to the effects of eIF2a phosphorylation and enhances long-term memory in rodents (10.7554/eLife.00498). Here we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2a and induced no major changes in translation or mRNA levels in unstressed cells. eIF2a phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2a phosphorylation, SG formation and cognitive loss. Overall design: Ribosome profiling with paired RNA-seq
The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly.
No sample metadata fields
View SamplesPlant compensatory responses depends on transcriptional reprogramming. We used microarray analysis to understand the differential gene expression pattern between clipped (herbivore browsed)
Overcompensation in response to herbivory in Arabidopsis thaliana: the role of glucose-6-phosphate dehydrogenase and the oxidative pentose-phosphate pathway.
Specimen part
View SamplesTo investigate the epigenetic landscape at the interface between mother and fetus, we provide a comprehensive analysis of parent of origin bias in the placenta. Using F1 interspecies hybrids, we sequenced RNA from 23 individual midgestation placentas, five late stage placentas, and two yolk sac samples and then used SNPs to determine whether transcripts were preferentially generated from the maternal or paternal allele. In the placenta, we find 103 genes that show significant and reproducible parent-of-origin bias, of which 78 are novel candidates. Most (96%) show a strong maternal bias which, using multiple models, we demonstrate is not due to maternal decidual contamination. Analysis of the X chromosome also reveals paternal expression of Xist and several genes that escape inactivation, most significantly Rps4x, Fhl1, and Slc38a5. Finally, sequencing individual placentas allowed us to reveal notable expression similarity between littermates. In all, we observe a striking preference for maternal transcription in the midgestation mouse placenta and a dynamic imprinting landscape in extraembryonic tissues, reflecting the complex nature of epigenetic pathways in the placenta. Overall design: 3''-end Sequencing for Expression Quantification (3SEQ) and SNP Analysis to observe parent-of-origin bias in 28 placental samples at two time points and 2 yolk sac samples
Maternal bias and escape from X chromosome imprinting in the midgestation mouse placenta.
Specimen part, Subject
View SamplesIn this study, using a Patient Derived Xenograft (PDX) system established by transplanting primary tumors from pre-metastatic breast cancer patients we demonstrate that development of distant organ metastases correlates with the presence of Bone Marrow Disseminated Tumor Cells (BM DTCs) in the PDX mice. Comparative gene expression analysis of bone marrow (BM) from tumor bearing PDX mice which developed metastatic disease was carried out with BM from non-tumor bearing controls.
Identifying biomarkers of breast cancer micrometastatic disease in bone marrow using a patient-derived xenograft mouse model.
Specimen part
View SamplesmRNA expression in the spinal cords of the G93A-SOD1 familial ALS transgenic mouse model was compared to that in nontransgenic (Normal mouse) and transgenic mice expressing wild-type (WT)SOD1. Gene Ontology (GO)analysis was used to characterize differences in expression between G93A-SOD1 mouse and nontransgenic mouse spinal cord. Changes in multiple GO categories were found. Many of these were associated with subsystems involving cell-cell communication and intracellular signal transduction. Expression profiles of mice expressing WT-SOD1 did not differ from nontransgenic mice. In contrast, protein profiling using proteomics technology indicated changes in mitochondrial protein expression in the G93A-SOD1 mouse spinal cord that were not found in the mRNA expression analysis.
Informatics-assisted protein profiling in a transgenic mouse model of amyotrophic lateral sclerosis.
Age
View SamplesIntroduction: Mechanisms that contribute to the pathogenesis of liver damage caused by hepatitis C virus (HCV) are not fully understood. Our previous work on liver biopsies from chronic HCV patients has shown modulation of the expression of certain cell cycle proteins indicating HCV-induced modifications of cell cycle events. We therefore hypothesize that HCV infection disrupts normal regulation of cell cycle that contributes to disease progression. Objective: To identify molecular disruptions during the course of HCV-associated disease progression, using liver biopsy specimens of chronic hepatitis C patients. Methods: Liver biopsy samples classified on histological basis as early (fibrosis stage 0-1) or advanced (fibrosis stage 3-4) disease stage were studied using oligonucleotide array ( HG U133 Plus 2.0, Affymetrix GeneChip System). For comparison, liver specimens from patients with non-viral hepatitis were also analyzed by microarray. Expression data was analyzed using Genespring (GX 7.2) and Ingenuity Pathway analysis (3.0). The differential expression of selected cell cycle genes (cyclin D2, KPNA2, HERC5 and Bcl-2) identified after microarray analysis was confirmed by quantitative real-time RT-PCR. Results: Microarray analysis revealed two-fold or greater transcriptional change in 792 genes of the total 38,500 known human genes in HCV-advance disease stage (HCV-A) as compared to HCV-early disease stage (HCV-E). Most of the genes have a defined role in immune response, extracellular matrix and cell cycle and apoptosis.
Gene profiling of early and advanced liver disease in chronic hepatitis C patients.
Specimen part, Disease, Disease stage
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