The unusual pattern of expression of hemoglobin (Hb) and myoglobin (Mb) among Antarctic notothenioid fishes provides an exceptional model system for assessing the impact of these proteins on oxidative stress. We tested the hypothesis that the lack of oxygen-binding proteins may reduce oxidative stress. Levels and activity of pro-oxidants and small-molecule and enzymatic antioxidants, and levels of oxidized lipids and proteins in the liver, oxidative skeletal muscle and heart ventricle were quantified in five species of notothenioid fishes differing in the expression of Hb and Mb.
View Article and Find Full Text PDFGeneralized linear models (GLM) with a canonical logit link function are the primary modeling technique used to relate a binary outcome to predictor variables. However, noncanonical links can offer more flexibility, producing convenient analytical quantities (e.g.
View Article and Find Full Text PDFBackground. Obesity in youth is highly prevalent. Physical activity and diet are influential in obesity development.
View Article and Find Full Text PDFMultiepitope-based vaccines against hepatitis C virus (HCV) were designed in the form of three minigenes encompassing four domains of the NS3, NS4 and NS5B proteins that contain multiple class I/II restricted epitopes. The polyEp-WT minigene encodes all four domains in fusion, the polyEp-C minigene encodes the same fusion but optimised for mammalian translation and the polyEp-E3 minigene has an additional endoplasmic reticulum targeting sequence. Whereas the minigenes vectorised by DNA were poorly immunogenic, adenovirus vectorisation induced strong and broader IFNgamma-ELISpot and CTL responses in HLA-A2 transgenic mice.
View Article and Find Full Text PDFOptimal DNA vaccine efficacy requires circumventing several obstacles, including low immunogenicity, a need for adjuvant, and the costs of purifying injection grade plasmid DNA. Bacterial delivery of plasmid DNA may provide an efficient and low-cost alternative to plasmid purification and injection. Also, the bacterial vector may exhibit potential as an immune adjuvant in vivo.
View Article and Find Full Text PDFThe bacterium L. monocytogenes is a proposed vaccine carrier based upon the observation that this pathogen replicates within the intracytoplasmic environment facilitating delivery of Ag to the endogenous Ag processing and presentation pathway with subsequent stimulation of peptide specific MHC class I-restricted CD8(+) effector cells. In this report, we evaluate virulence-attenuated strains of Listeria monocytogenes as vaccine vectors and examine whether existing antivector (antilisterial) immunity limits or alters its efficacy as a therapeutic cancer vaccine.
View Article and Find Full Text PDFThe goal of this study was to develop a new surrogate challenge model for use in evaluating protective cell-mediated immune responses against hepatitis C virus (HCV) antigens. The use of recombinant Listeria monocytogenes organisms which express HCV antigens provides novel tools with which to assay such in vivo protection, as expression of immunity against this hepatotropic bacterial pathogen is dependent on antigen-specific CD8(+) T lymphocytes. A plasmid DNA vaccine encoding a ubiquitin-NS3 fusion protein was generated, and its efficacy was confirmed by in vivo induction of NS3-specific, gamma interferon-secreting T cells following vaccination of BALB/c mice.
View Article and Find Full Text PDFIn this study we evaluated the efficacy of DNA vaccination of IFN-gamma knockout (GKO) mice against Listeria monocytogenes, as these immunodeficient mice are highly susceptible to infection with low numbers of this intracellular bacterial pathogen. Following intramuscular immunization of BALB/c GKO mice with plasmid DNA constructs encoding recombinant forms of the L. monocytogenes hemolysin, listeriolysin O (LLO), we detected the in vivo induction of a LLO(91-99) peptide-specific, protective immune CTL response equivalent to that observed following similar DNA vaccination of normal BALB/c mice.
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