Scholarly Work - Mathematical Sciences
Permanent URI for this collectionhttps://scholarworks.montana.edu/handle/1/8719
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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 On the intrinsic dimensionality of chemical structure space(1988-01) Veith, D.; Greenwood, B.; Hunter, R. S.; Niemi, G. J.; Regal, R. R.An important expectation in chemistry and pharmacology is that similar chemical structures have similar properties and behavior. New industrial chemicals, pesticides, and therapeutics are often sublte modifications of "lead" structures with known chemical behavior. Chemical properties and recreation rates can be can be estimated from suitable homologs 1,2. Moreover, the safety of untested chemicals is often evaluated by comparing the chemical toanalogous structures for which toxicological data are available. Despite the widespread use of terms such as "homolog" and "analogs" in research, chemical similarity has evaded quantitative interpretation from a perspective where all chemicals are considered simultaneously. One reason is that chemical similarity is inherently a multivariate problem or, in other words, chemicals are simultaneously similar and different from many perspectives. We have approached chemical similarity by attempting to define a structure space in which all chemicals can be identified. Because there are so many potentially important variables, multivariate tools are necessary to reduce the dimensionality of this problem. When this is accomplished, we need to comprehend what this space means and what can be predicted from it . This paper is one of the first attempts to define chemical structure space for a large universe of chemicals.Item Percolation on Fitness Landscapes: Effects of Correlation, Phenotype, and Incompatibilities(2007-10) Gravner, Janko; Pitman, Damien J.; Gavrilets, SergeyWe study how correlations in the random fitness assignment may affect the structure of fitness landscapes, in three classes of fitness models. The first is a phenotype space in which individuals are characterized by a large number n of continuously varying traits. In a simple model of random fitness assignment, viable phenotypes are likely to form a giant connected cluster percolating throughout the phenotype space provided the viability probability is larger than 1/2n. The second model explicitly describes genotype-to-phenotype and phenotype-to-fitness maps, allows for neutrality at both phenotype and fitness levels, and results in a fitness landscape with tunable correlation length. Here, phenotypic neutrality and correlation between fitnesses can reduce the percolation threshold, and correlations at the point of phase transition between local and global are most conducive to the formation of the giant cluster. In the third class of models, particular combinations of alleles or values of phenotypic characters are “incompatible” in the sense that the resulting genotypes or phenotypes have zero fitness. This setting can be viewed as a generalization of the canonical Bateson–Dobzhansky–Muller model of speciation and is related to K-SAT problems, prominent in computer science. We analyze the conditions for the existence of viable genotypes, their number, as well as the structure and the number of connected clusters of viable genotypes. We show that analysis based on expected values can easily lead to wrong conclusions, especially when fitness correlations are strong. We focus on pairwise incompatibilities between diallelic loci, but we also address multiple alleles, complex incompatibilities, and continuous phenotype spaces. In the case of diallelic loci, the number of clusters is stochastically bounded and each cluster contains a very large sub-cube. Finally, we demonstrate that the discrete NK model shares some signature properties of models with high correlations.Item Supporting Information for "Significance of trends toward earlier snowmelt runoff, Columbia and Missouri Basin headwaters, western United States"(American Geophysical Union, 2007-08) Moore, Johnnie N.; Harper, Joel T.; Greenwood, Mark C.This is auxiliary material for this article contains one text file, four tables, and three figures from the article "Significance of trends toward earlier snowmelt runoff, Columbia and Missouri Basin headwaters, western United States" from Geophysical Research Letters on the 28 August 2007. http://onlinelibrary.wiley.com/doi/10.1029/2007GL031022/fullItem Significance of trends toward earlier snowmelt runoff, Columbia and Missouri Basin headwaters, western United States(American Geophysical Union, 2007-08) Moore, Johnnie N.; Harper, Joel T.; Greenwood, Mark C.We assess changes in runoff timing over the last 55 years at 21 gages unaffected by human influences, in the headwaters of the Columbia-Missouri Rivers. Linear regression models and tests for significance that control for “false discoveries” of many tests, combined with a conceptual runoff response model, were used to examine the detailed structure of spring runoff timing. We conclude that only about one third of the gages exhibit significant trends with time but over half of the gages tested show significant relationships with discharge. Therefore, runoff timing is more significantly correlated with annual discharge than with time. This result differs from previous studies of runoff in the western USA that equate linear time trends to a response to global warming. Our results imply that predicting future snowmelt runoff in the northern Rockies will require linking climate mechanisms controlling precipitation, rather than projecting response to simple linear increases in temperature.