Analysis of Drosophila melanogaster early embryos (pre-zygotic genome activation) following the germ line-specific depletion of the dMLL3/4 histone methyltransferase (also known as Trr). These results provide insight into the molecular mechanisms responsible for the assembly of the zygotic genome at fertilization.
The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization.
Specimen part
View SamplesBACKGROUND: Dietary ABA-supplementation modulates immune and inflammatory responses in mouse models of chronic and infectious disease. However, the underlying mechanisms by which ABA elicits its immune modulatory effects are not well understood. This project used a systems approach in combination with functional and in vivo studies to investigate the target gene pathways modulated by ABA in the context of an inflammatory LPS challenge.
Abscisic acid regulates inflammation via ligand-binding domain-independent activation of peroxisome proliferator-activated receptor gamma.
No sample metadata fields
View SamplesRhesus macaques (Macaca mulatta) infected with a lethal dose of lymphocytic choriomeningitis virus-strain WE (LCMV-WE) provide a model for Lassa fever virus infection of man. Like Lassa fever in human beings, disease begins with flu-like symptoms but can progress to morbidity fairly rapidly. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al. J. Virol. 2007: PMID 17522210) showing distinct pre-viremic and viremic stages that discriminated between virulent and benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. We observed gene expression changes that occurred before the viremic stage of the disease, and could potentially serve as biomarkers that discriminate between exposure to a hemorrhagic fever virus and exposure to a benign virus. Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a much broader effect on liver cell function than non-virulent virus. During the first few days of infection, virulent virus impacted gene expression associated with the generation of energy, such as fatty acid metabolism and glucose metabolism, with the complement and coagulation cascades, and with steroid metabolism, MAPK signaling and cell adhesion. For example, the energy profile resembled that of an organism entering starvation: acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis, was shut down and gene products involved in gluconeogenesis were up-regulated. In conclusion, this study identifies several potential gene markers of LCMV-WE-associated liver disease and contributes to the database of gene expression changes correlated with LCMV pathogenesis in primates.
Gene expression in primate liver during viral hemorrhagic fever.
Specimen part, Time
View SamplesFacultative intracellular Brucella infect and survive inside macrophages, and the outcome of macrophage-Brucella interaction is a basis for establishment of a chronic Brucella infection. The majority of Brucella are killed at the early infection stage. A subpopulation of virulent Brucella strains is instead trafficked to an intracellular replicative phagosome, and are resistant to further attack and begin to multiply dramatically. Virulent Brucella also inhibit macrophage apoptosis that in turn favors pathogen survival and replication.
Brucella melitensis triggers time-dependent modulation of apoptosis and down-regulation of mitochondrion-associated gene expression in mouse macrophages.
No sample metadata fields
View SamplesLassa fever virus is a zoonotic pathogen that plagues the endemic areas of West Africa. Rhesus macaques infected with a related arenavirus, LCMV-WE, serve as a model for Lassa-infection of human beings. Using a dose similar to that expected from a needle-stick, monkeys experience an early pre-viremic phase (day 1-3), a viremic phase with febrile onset (day 4-7), and, like human beings who succumb, they die within two weeks. Our goal was to monitor changes in gene expression that parallel disease progression in an effort to 1) identify genes with altered expression after infection, 2) identify genes that could discriminate between a virulent and non-virulent infection, and 3) identify genes encoding products that could serve as treatment targets for FDA-approved pharmaceuticals. Genes related to all three of these categories have been identified and some have been given preliminary validation by quantitative PCR and proteomic studies. These genes will be valuable candidates for future validation as prognostic biomarkers
Early blood profiles of virus infection in a monkey model for Lassa fever.
No sample metadata fields
View Samplesretinal ganglion cells die after optic nerve injury, either crush or transection. The molecular causesunderlying this degeneration are largely unkwon
Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush.
No sample metadata fields
View SamplesStroke is a brain attack cutting off vital blood, and consequently the nutrients and oxygen vital to the brain cells that control everything we do. Stroke is a complex disease with unclear pathogenesis resulting from environmental and genetic factors.
TTC7B emerges as a novel risk factor for ischemic stroke through the convergence of several genome-wide approaches.
Sex
View SamplesWe generated genome-wide RNASeq data from freshly isolated airway epithelial cells of asthmatics and non-asthmatics. This data was paired with genome-wide genetic and methylation data from the same individuals allowing for an integrated analysis of genetic, transcriptional, and epigenetic signatures in asthma. Overall design: examination of genome-wide genome-wide gene expression levels and comparison to phenotypes
DNA methylation in lung cells is associated with asthma endotypes and genetic risk.
Specimen part, Disease, Subject
View SamplesDuring development neuronal progenitors compete for growth factors such as nerve growth factor NGF and require the prolyl hydroxylase EglN3 and the kinesin KIF1Bß for developmental apoptosis. Inherited KIF1Bß loss-of-function mutations in neuroblastomas and pheochromocytomas implicate KIF1Bß as a 1p36.2 tumor suppressor, however the mechanism of tumor suppression is unknown. We found that KIF1Bß interacts with the RNA helicase A (DHX9) resulting in DHX9 nuclear accumulation to regulate apoptosis. KIF1Bß-dependent DHX9 nuclear localization leads to transcription of the apoptotic target XIAP-associated factor 1. DHX9 is induced when NGF is limiting and required for apoptosis in cells deprived of NGF. Overall design: NB1 cells were transduced to incorporate shRNA against DHX9 or a scrambled control, and transfected with a KIF1Bß expression vector or control, then transfected cells were isolated and lysed after 48h.
RNA helicase A is a downstream mediator of KIF1Bβ tumor-suppressor function in neuroblastoma.
Cell line, Subject
View SamplesDNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours, compared to control cells.
Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.
Specimen part, Time
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