Project description:Hypochlorous acid (HOCl) is a potent oxidant that is produced endogenously in mammalian tissue by phagocytes. Exogenous exposure to HOCl also can occur following inhalation of chlorine gas. HOCl has been implicated as a source of oxidative stress associated atherosclerosis and other diseases. The purpose of this study was to identify dose-dependent transitions in cellular response to hypochlorous acid (HOCl), with a focus on understanding how various cellular defense and stress dose-responses overlap.
Project description:Profiled the effect of oxidative stress on gene expression in the heads of adult Drosophila. The flies were fed sucrose with 15mM paraquat (experimental condition) or regular sucrose (control condition) for 30 hours, before harvesting at adult d3. Keywords = oxidative stress Keywords = paraquat Keywords: dose response
Project description:Duplicate hybridizations with fluorochrome switching were performed following the first two fractions of total body irradiation for accumulated doses of 1.5 Gy and 3.0 Gy. Control samples for all hybridizations were from the same patient before the beginning of treatment. Keywords: dose response
Project description:Transcriptional profiling of M. tuberculosis growing in log phase treated with various concentrations of carbon monoxide versus untreated controls Keywords: Dose response
Project description:Lymphocytes are the standard cell of a majority of biodosimetry approaches because of their availability and radiosensitivity. But progresses remain to be performed to bring down the minimum threshold of dose sensitivity. To find a lymphocyte subtype able to respond to low doses of ionizing radiation, we examined gene expression variations in different lymphocyte subpopulations using the microarray technology. Blood samples were independently exposed to 0, 0.05 and 0.5 Gray of ionizing radiations. Three and 24 hours after exposure, CD56+, CD4+ and CD8+ cells were negatively isolated. RNA from each condition was competitively hybridized on oligonucleotide microarrays. Keywords: Dose response, stress response, cell type comparison
Project description:More than 70 million people worldwide are still infected with the hepatitis C virus 30 years after its discovery, underscoring the need for a vaccine. To develop an effective prophylactic vaccine, detailed knowledge of the correlates of protection and an immunocompetent surrogate model are needed. In this study, we describe the minimum dose required for robust equine hepacivirus (EqHV) infection in equids and examined how this relates to duration of infection, seroconversion, and transcriptomic responses. To investigate mechanisms of hepaciviral persistence, immune response, and immune- mediated pathology, we inoculated eight EqHV naive horses with doses ranging from 1 to 2 to 1.3 106 RNA copies per inoculation. We characterized infection kinetics, pathology, and transcriptomic responses via new generation sequencing. The minimal infec- tious dose of EqHV in horses was estimated at 13 RNA copies, whereas 6 to 7 copies were insufficient to cause infection. Peak viremia did not correlate with infectious dose, while seroconversion and duration of infection appeared to be affected. Notably, sero- conversion was undetectable in the low-dose infections within the surveillance period (40 to 50 days). In addition, transcriptomic analysis revealed a nearly dose dependent effect, with greater immune activation and inflammatory response observed in high-dose infections than in low-dose infections. Interestingly, inoculation with 6 to 7 copies of RNA that did not result in productive infection was associated with a strong immune response, similar to that observed in the high-dose infections. IMPORTANCE We demonstrated that the EqHV dose of infection plays an important role for inducing immune responses, possibly linked to early clearance in high-dose and prolonged viremia in low-dose infections. In particular, pathways associated with innate and adaptive immune responses, as well as inflammatory responses, were more strongly upregulated in high-dose infections than in lower doses. Hence, inoculation with low doses may enable EqHV to evade strong immune responses in the early phase and therefore promote robust, long-lasting infection.
Project description:Transcriptional profiling of M. tuberculosis growing in log phase treated with various concentrations of carbon monoxide versus untreated controls Keywords: Dose response Two condition experiment, CO treated cells at 2000, 200 and 20 ppm versus untreated controls. Biological replicates: 2 replicates per dose, 1 array per replicate
Project description:ErbB receptor ligands, epidermal growth factor (EGF) and heregulin (HRG), induce dose-dependent transient and sustained intracellular signaling, proliferation and differentiation of MCF-7 breast cancer cells, respectively. In an effort to delineate the ligand-specific cell determination mechanism, we investigated time-course gene expressions induced by EGF and HRG that induce distinct cellular phenotypes in MCF-7 cells. To analyze the effects of ligand dosage and time for the gene expression independently, we developed a statistical method for decomposing the expression profiles into the two effects. Our results indicated that signal transduction pathways devotedly convey quantitative properties of the dose-dependent activation of ErbB receptor to early transcription. The results also implied that moderate changes in the expression levels of numbers of genes, not the predominant regulation of a few specific genes, might cooperatively work at the early stage of the transcription for determining the cell fate. However, the EGF- and HRG-induced distinct signal durations resulted in the ligand-oriented biphasic induction of proteins after 20 min. The selected gene list and HRG-induced prolonged signaling suggested that transcriptional feedback to the intracellular signaling results in a graded to biphasic response in the cell determination process, and that each ErbB receptor is inextricably responsible for the control of amplitude and duration of cellular biochemical reactions. Keywords: time course, dose response