This SuperSeries is composed of the SubSeries listed below.
Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence.
Specimen part
View SamplesWe are interested in comparing expression patterns of hematopoletic stem cells, mast cell precursors and mature mast cells. Our group recently reported that murine mast cells express CD34, Sca-1 and c-kit. Microarray analysis may uncover other novel surface antigens useful in separating mast cells from stem cells.
Prion protein expression and release by mast cells after activation.
Sex
View SamplesZaire ebolavirus (ZEBOV) is among the deadliest known human pathogens, causing severe hemorrhagic fever with high case fatality rates ranging from 70-90%. The lack of effective vaccines or treatment available for ZEBOV renders this pathogen as a significant global biodefense threat, as evidenced by the current, highly lethal outbreak of a novel ZEBOV variant in western Africa. Existing mouse models of lethal ZEBOV infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever (EHF) including prolonged blood coagulation, acute hepatitis, disseminated intravascular coagulation (DIC), and death from hemorrhagic shock, thus restricting pathogenesis studies to non-human primates (NHP). This has prevented rapid evaluation of countermeasures in outbreak scenarios, and impeded a comprehensive understanding of how host responses to infection contribute to severe EHF disease. Here we demonstrate that mice from the Collaborative Cross (CC), a panel of reproducible, recombinant inbred animals that span the genetic breadth of three murine subspecies, are susceptible to a spectrum of disease phenotypes following ZEBOV infection. In contrast to C57Bl6/J mice, which develop lethal disease without symptoms of EHF, CC recombinant inbred intercrossed (CC-RIX) lines develop either complete resistance to lethal disease or severe EHF characterized by prolonged coagulation times and 100% mortality. Disease resistance and survival is not dependent on viral tropism, as both resistant and EHF-susceptible lines show similar inflammation and cytopathic effect in target organs. Transcriptomics reveal potential mechanisms for both induction of severe hemorrhage in EHF mediated by IL-6 and vascular activation, and resistance to lethal infection by induction of lymphocyte differentiation and cellular adhesion. These data demonstrate that host responses specific to unique genetic backgrounds determine susceptibility to hemorrhagic syndrome independent of virus replication. The CC represents a novel mouse model for studying EHF pathogenesis, and we anticipate that it will be applied immediately to developing and evaluating therapeutic countermeasures.
Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance.
Sex, Specimen part, Treatment, Time
View SamplesIt is well appreciated that reactive oxygen species (ROS) are deleterious to mammals, including humans, especially when generated in abnormally large quantities from cellular metabolism. Whereas the mechanisms leading to the production of ROS are rather well delineated, the mechanisms underlying tissue susceptibility or tolerance to oxidant stress remain elusive. Through an experimental selection over many generations, we have previously generated Drosophila melanogaster flies that tolerate tremendous oxidant stress and have shown that the family of antimicrobial peptides (AMP) is over-represented in these tolerant flies. Furthermore, we have also demonstrated that overexpression of even one AMP at a time (e.g. Diptericin) allows wild type flies to survive much better in hyperoxia. In the current study, we used a number of experimental approaches to investigate the potential mechanisms underlying hyperoxia tolerance in flies with antimicrobial peptide overexpression. We demonstrate that flies with Diptericin overexpression resist oxidative stress by increasing antioxidant enzyme activities and preventing an increase in ROS level after hyperoxia. Depleting the GSH pool using buthionine sulfoximine limits fly survival, thus confirming that enhanced survival observed in these flies is related to improved redox homeostasis. We conclude that a) AMPs play an important role in tolerance to oxidant stress; b) overexpression of Diptericin changes the cellular redox balance between oxidant and antioxidant, and c) this change in redox balance plays an important role in survival in hyperoxia.
Antimicrobial peptides increase tolerance to oxidant stress in Drosophila melanogaster.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults.
Sex, Specimen part
View SamplesWe tested the hypothesis on the mechanisms responsible for the early control of NK cell function by identifying a discrete set of genes in circulating NK cells that were altered by exercise.
Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults.
Sex, Specimen part
View SamplesWe tested the hypothesis on the mechanisms responsible for the early control of monocytes function by identifying a discrete set of genes in circulating monocytes that were altered by exercise.
Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.
Sex, Specimen part, Time
View SamplesOne of the critical substances that mammals highly regulate via the respiratory, cardiovascular and neurologic systems is O2. Both low and high O2 levels can induce major morbidities as well as mortality. Indeed, O2 has been often considered as both an elixir and a poison in humans. In current study, we have used an experimental selection approach to generate Drosophila strains that are tolerant to severe hyperoxic environment. Gene expression profiling is then applied to investigate the mechanisms underlying hyperoxia tolerance in the newly generated strains.
Experimental selection for Drosophila survival in extremely high O2 environments.
Specimen part
View SamplesDespite timely and successful surgery, 32% of patients with bilateral and 10% with unilateral cryptorchidism will develop azoospermia. Cryptorchid boys at risk of azoospermia display a typical testicular histology of impaired mini-puberty at the time of the orchidopexy.
Testicular gene expression in cryptorchid boys at risk of azoospermia.
Specimen part
View Samples