Scholarly Work - Chemistry & Biochemistry
Permanent URI for this collectionhttps://scholarworks.montana.edu/handle/1/8714
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Item Inducible bronchus-associated lymphoid tissue elicited by a protein cage nanoparticle enhances protection in mice against diverse respiratory viruses(2009-09) Wiley, James A.; Richert, Laura E.; Swain, Steve D.; Harmsen, Ann L.; Barnard, Dale L.; Randall, Troy D.; Jutila, Mark A.; Douglas, Trevor; Broomell, Chris; Young, Mark J.; Harmsen, Allen G.Background Destruction of the architectural and subsequently the functional integrity of the lung following pulmonary viral infections is attributable to both the extent of pathogen replication and to the host-generated inflammation associated with the recruitment of immune responses. The presence of antigenically disparate pulmonary viruses and the emergence of novel viruses assures the recurrence of lung damage with infection and resolution of each primary viral infection. Thus, there is a need to develop safe broad spectrum immunoprophylactic strategies capable of enhancing protective immune responses in the lung but which limits immune-mediated lung damage. The immunoprophylactic strategy described here utilizes a protein cage nanoparticle (PCN) to significantly accelerate clearance of diverse respiratory viruses after primary infection and also results in a host immune response that causes less lung damage. Methodology/Principal Findings Mice pre-treated with PCN, independent of any specific viral antigens, were protected against both sub-lethal and lethal doses of two different influenza viruses, a mouse-adapted SARS-coronavirus, or mouse pneumovirus. Treatment with PCN significantly increased survival and was marked by enhanced viral clearance, accelerated induction of viral-specific antibody production, and significant decreases in morbidity and lung damage. The enhanced protection appears to be dependent upon the prior development of inducible bronchus-associated lymphoid tissue (iBALT) in the lung in response to the PCN treatment and to be mediated through CD4+ T cell and B cell dependent mechanisms. Conclusions/Significance The immunoprophylactic strategy described utilizes an infection-independent induction of naturally occurring iBALT prior to infection by a pulmonary viral pathogen. This strategy non-specifically enhances primary immunity to respiratory viruses and is not restricted by the antigen specificities inherent in typical vaccination strategies. PCN treatment is asymptomatic in its application and importantly, ameliorates the damaging inflammation normally associated with the recruitment of immune responses into the lung.Item Something old, something new, something borrowed; how the thermoacidophilic archaeon Sulfolobus solfataricus responds to oxidative stress(2009-09) Maaty, Walid S.; Wiedenheft, Blake A.; Tarlykov, Pavel V.; Schaff, Nathan; Heinemann, Joshua V.; Robison-Cox, James; Dougherty, Amanda; Blum, Paul; Lawrence, C. Martin; Douglas, Trevor; Young, Mark J.; Bothner, BrianTo avoid molecular damage of biomolecules due to oxidation, all cells have evolved constitutive and responsive systems to mitigate and repair chemical modifications. Archaea have adapted to some of the most extreme environments known to support life, including highly oxidizing conditions. However, in comparison to bacteria and eukaryotes, relatively little is known about the biology and biochemistry of archaea in response to changing conditions and repair of oxidative damage. In this study transcriptome, proteome, and chemical reactivity analyses of hydrogen peroxide (H2O2) induced oxidative stress in Sulfolobus solfataricus (P2) were conducted. Microarray analysis of mRNA expression showed that 102 transcripts were regulated by at least 1.5 fold, 30 minutes after exposure to 30 µM H2O2. Parallel proteomic analyses using two-dimensional differential gel electrophoresis (2D-DIGE), monitored more than 800 proteins 30 and 105 minutes after exposure and found that 18 had significant changes in abundance. A recently characterized ferritin-like antioxidant protein, DPSL, was the most highly regulated species of mRNA and protein, in addition to being post-translationally modified. As expected, a number of antioxidant related mRNAs and proteins were differentially regulated. Three of these, DPSL, superoxide dismutase, and peroxiredoxin were shown to interact and likely form a novel supramolecular complex for mitigating oxidative damage. A scheme for the ability of this complex to perform multi-step reactions is presented. Despite the central role played by DPSL, cells maintained a lower level of protection after disruption of the dpsl gene, indicating a level of redundancy in the oxidative stress pathways of S. solfataricus. This work provides the first “omics” scale assessment of the oxidative stress response for an archeal organism and together with a network analysis using data from previous studies on bacteria and eukaryotes reveals evolutionarily conserved pathways where complex and overlapping defense mechanisms protect against oxygen toxicity.Item Surface CO2 leakage during two shallow subsurface CO2 releases(2007-12) Lewicki, Jennifer L.; Oldenburg, Curtis M.; Dobeck, Laura M.; Spangler, Lee H.A new field facility was used to study CO2 migration processes and test techniques to detect and quantify potential CO2 leakage from geologic storage sites. For 10 days starting 9 July 2007, and for seven days starting 3 August 2007, 0.1 and 0.3 t CO2 d−1, respectively, were released from a ∼100‐m long, sub‐water table (∼2.5‐m depth) horizontal well. The spatio‐temporal evolution of leakage was mapped through repeated grid measurements of soil CO2 flux (FCO2). The surface leakage onset, approach to steady state, and post‐release decline matched model predictions closely. Modeling suggested that minimal CO2 was taken up by groundwater through dissolution, and CO2 spread out on top of the water table. FCO2 spatial patterns were related to well design and soil physical properties. Estimates of total CO2 discharge along with soil respiration and leakage discharge highlight the influence of background CO2 flux variations on detection of CO2 leakage signals.Item Eddy covariance observations of surface leakage during shallow subsurface CO2 releases(2009-06) Lewicki, Jennifer L.; Hilley, George E.; Fischer, Marc L.; Pan, Lehua; Oldenburg, Curtis M.; Dobeck, Laura M.; Spangler, Lee H.We tested the ability of eddy covariance (EC) to detect, locate, and quantify surface CO2 flux leakage signals within a background ecosystem. For 10 days starting on 9 July 2007, and for 7 days starting on 3 August 2007, 0.1 (Release 1) and 0.3 (Release 2) t CO2 d−1, respectively, were released from a horizontal well ∼100 m in length and ∼2.5 m in depth located in an agricultural field in Bozeman, Montana. An EC station measured net CO2 flux (Fc) from 8 June 2006 to 4 September 2006 (mean and standard deviation = −12.4 and 28.1 g m−2 d−1, respectively) and from 28 May 2007 to 4 September 2007 (mean and standard deviation = −12.0 and 28.1 g m−2 d−1, respectively). The Release 2 leakage signal was visible in the Fc time series, whereas the Release 1 signal was difficult to detect within variability of ecosystem fluxes. To improve detection ability, we calculated residual fluxes (Fcr) by subtracting fluxes corresponding to a model for net ecosystem exchange from Fc. Fcr had reduced variability and lacked the negative bias seen in corresponding Fc distributions. Plotting the upper 90th percentile Fcr versus time enhanced the Release 2 leakage signal. However, values measured during Release 1 fell within the variability assumed to be related to unmodeled natural processes. Fcr measurements and corresponding footprint functions were inverted using a least squares approach to infer the spatial distribution of surface CO2 fluxes during Release 2. When combined with flux source area evaluation, inversion results roughly located the CO2 leak, while resolution was insufficient to quantify leakage rate.