Matching Items (164)
Description
Influenza remains a constant concern for public health agencies across the nation and worldwide. Current methods of surveillance suffice but they fall short of their true potential. Incorporation of evolutionary data and analysis through studies such as phylogeography could reveal geographic sources of variation. Identification and targeting of such sources for public health initiatives could yield increased effectiveness of influenza treatments. As it stands there is a lack of evolutionary data available for such use, particularly in the southwest. Our study focused on the sequencing and phylogeography of southwestern Influenza A samples from the Mayo Clinic. We fully sequenced two neuraminidase genes and combined them with archived sequence data from the Influenza Research Database. Using RAxML we identified the clade containing our sequences and performed a phylogeographic analysis using ZooPhy. The resultant data were analyzed using programs such as SPREAD and Tracer. Our results show that the southwest sequences emerged from California and the ancestral root of the clade came from New York. Our Bayesian maximum clade credibility (MCC) tree data and SPREAD analysis implicates California as a source of influenza variation in the United States. This study demonstrates that phylogeography is a viable tool to incorporate evolutionary data into existing forms of influenza surveillance.
ContributorsTurnock, Adam Ryan (Author) / Scotch, Matthew (Thesis director) / Halden, Rolf (Committee member) / Pycke, Benny (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
Trichloroethene (TCE) and hexavalent chromium [Cr(VI)] are toxic and carcinogenic contaminants found in drinking water resources across the United States. A series of Bench-scale treatability studies were conducted to evaluate the effectiveness of a consortium of facultative and strictly anaerobic bacteria, KB-1®, to remove TCE and Cr(VI) from a contaminated aquifer in San Diego. These series of treatability studies were also performed to prepare data and mature packed sediment columns for the deployment of the In Situ Microcosm Array (ISMA), a diagnostic device for determining optimal treatments for a contaminated aquifer, at this particular site. First, a control panel for the ISMA’s Injection Module (IM) was created in order to deliver nutrients to the columns. Then, a column treatability study was performed in order to produce columns with an established KB-1® consortium, so that all TCE in the column influent was converted to ethene by the time it had exited the column. Finally, a batch bottle treatability study was performed to determine KB-1®’s effectiveness at remediating both TCE and Cr(VI) from the San Diego ground-water samples. The results from the column study found that KB-1® was able to reduce TCE in mineral media. However, in the presence of site ground-water for the batch bottle study, KB-1® was only able to reduce Cr(VI) and no TCE dechlorination was observed. This result suggests that the dechlorinating culture cannot survive prolonged exposure to Cr(VI). Therefore, future work may involve repeating the batch bottle study with Cr(VI) removed from the groundwater prior to inoculation to determine if KB-1® is then able to dechlorinate TCE.
ContributorsDuong, Benjamin Taylor (Author) / Halden, Rolf (Thesis director) / Torres, Cesar (Committee member) / Krajmalnik-Brown, Rosa (Committee member) / Barrett, The Honors College (Contributor) / School of Dance (Contributor) / Chemical Engineering Program (Contributor)
Created2013-05
Description
Plastics continue to benefit society in innumerable ways, even though recent public focus on plastics has centered mostly on human health and environmental concerns, including their endocrine-disrupting properties and the long-term pollution they represent. The benefits of plastics are particularly apparent in medicine and public health. Plastics are versatile, cost-effective, require less energy to produce than alternative materials like metal or glass, and can be manufactured to have many different properties. Due to these characteristics, polymers are used in diverse health applications like disposable syringes and intravenous bags, sterile packaging for medical instruments as well as in joint replacements, tissue engineering, etc. However, not all current uses of plastics are prudent and sustainable, as illustrated by the widespread, unwanted human exposure to endocrine-disrupting bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP), problems arising from the large quantities of plastic being disposed of, and depletion of non-renewable petroleum resources as a result of the ever-increasing mass production of plastic consumer articles. Using the health-care sector as example, this review concentrates on the benefits and downsides of plastics and identifies opportunities to change the composition and disposal practices of these invaluable polymers for a more sustainable future consumption. It highlights ongoing efforts to phase out DEHP and BPA in the health-care and food industry and discusses biodegradable options for plastic packaging, opportunities for reducing plastic medical waste, and recycling in medical facilities in the quest to reap a maximum of benefits from polymers without compromising human health or the environment in the process.
ContributorsNorth, Emily Jean (Co-author) / Halden, Rolf (Co-author, Thesis director) / Mikhail, Chester (Committee member) / Hurlbut, Ben (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Chemical Engineering Program (Contributor)
Created2013-05
Description
Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that AMPylation could be a more fundamental and physiologically significant regulatory PTM. For the first time, we characterized the auto-AMPylation capability of the human protein SOS1 through in vitro AMPylation experiments using full-length protein and whole-domain truncation mutants. We found that SOS1 can become AMPylated at a tyrosine residue possibly within the Cdc25 domain of the protein, the Dbl homology domain is vital for efficient auto-AMPylation activity, and the C-terminal proline-rich domain exhibits a complex regulatory function. The proline-rich domain alone also appears to be capable of catalyzing a separate, unidentified covalent self-modification using a fluorescent ATP analogue. Finally, SOS1 was shown to be capable of catalyzing the AMPylation of two endogenous human protein substrates: a ubiquitous, unidentified protein of ~49kDa and another breast-cancer specific, unidentified protein of ~28kDa.
ContributorsOber-Reynolds, Benjamin John (Author) / LaBaer, Joshua (Thesis director) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
In this thesis, glycan nodes, the basic subunits of complex biological sugars, were studied to determine the reproducibility of gas chromatography-mass spectrometry (GC/MS) based methylation analysis of whole blood plasma by normalization using an internal standard of heavy permethylated glycans. Glycans are complex biological sugars that have a variety of applications in the human body and will display aberrant compositions when produced by cancerous cells. Thus an assay to determine their composition can be used as a diagnostic tool. It was shown that the assay may have potential use, but needs further refinement to become an improvement over current methods by analyzing the results of ratio-determination and replicate experiments.
ContributorsMiyasaki, Tyler Takeo (Author) / Borges, Chad (Thesis director) / Van Horn, Wade (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05
Description
Western diets, high in dietary fat and red meat, are associated with hyperglycemia and weight gain, symptoms that promote insulin resistance and diabetes. Previous studies have shown that elevated glucose promotes glycation of circulating proteins such as albumin, which is thought to lead to hyperglycemia complications. It was hypothesized that diets with no meat consumption (pesco-vegetarian and lacto-vegetarian) would reduce protein glycation, in comparison to a diet with meat. Forty six healthy adult omnivorous subjects were randomized into one of three groups and instructed to either consume red meat (i.e. meat) or poultry twice per day (control), eliminate meat and increase fish consumption (pesco-vegetarian), or adopt a vegetarian diet devoid of fish, meat or poultry (lacto-vegetarian) for four weeks. Fasting plasma samples were collected from participants at baseline and after 4 weeks of the dietary intervention. Plasma glucose concentrations were measured using a commercially available kit. Percent glycated albumin was measured on a separate aliquot of plasma by mass spectrometry. Plasma glucose concentrations were significantly increased following 4-weeks of pesco-vegetarian diet (P=0.002, paired t-test). Neither the lacto-vegetarian (P=0.898) or the control diet (P=0.233) affected plasma glucose concentrations. Despite the significant increase in plasma glucose following a pesco-vegetarian diet, no change in percent glycated albumin was observed (P>0.50, ANOVA). These findings may indicate a protective effect of the pesco-vegetarian diet on protein glycation in the presence of elevated plasma glucose and suggest the need for additional studies to examine the link between increased fish consumption and glucose regulation.
ContributorsRaad, Noor (Author) / Sweazea, Karen (Thesis director, Committee member) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The objective of this research was to predict the persistence of potential future contaminants in indirect potable reuse systems. In order to accurately estimate the fates of future contaminants in indirect potable reuse systems, results describing persistence from EPI Suite were modified to include sorption and oxidation. The target future contaminants studied were the approximately 2000 pharmaceuticals currently undergoing testing by United States Food and Drug Administration (US FDA). Specific organic substances such as analgesics, antibiotics, and pesticides were used to verify the predicted half-lives by comparing with reported values in the literature. During sub-surface transport, an important component of indirect potable reuse systems, the effects of sorption and oxidation are important mechanisms. These mechanisms are not considered by the quantitative structure activity relationship (QSAR) model predictions for half-lives from EPI Suite. Modifying the predictions from EPI Suite to include the effects of sorption and oxidation greatly improved the accuracy of predictions in the sub-surface environment. During validation, the error was reduced by over 50% when the predictions were modified to include sorption and oxidation. Molecular weight (MW) is an important criteria for estimating the persistence of chemicals in the sub-surface environment. EPI Suite predicts that high MW compounds are persistent since the QSAR model assumes steric hindrances will prevent transformations. Therefore, results from EPI Suite can be very misleading for high MW compounds. Persistence was affected by the total number of halogen atoms in chemicals more than the sum of N-heterocyclic aromatics in chemicals. Most contaminants (over 90%) were non-persistent in the sub-surface environment suggesting that the target future drugs do not pose a significant risk to potable reuse systems. Another important finding is that the percentage of compounds produced from the biotechnology industry is increasing rapidly and should dominate the future production of pharmaceuticals. In turn, pharmaceuticals should become less persistent in the future. An evaluation of indirect potable reuse systems that use reverse osmosis (RO) for potential rejection of the target contaminants was performed by statistical analysis. Most target compounds (over 95%) can be removed by RO based on size rejection and other removal mechanisms.
ContributorsLim, Seung (Author) / Fox, Peter (Thesis advisor) / Abbaszadegan, Morteza (Committee member) / Halden, Rolf (Committee member) / Arizona State University (Publisher)
Created2011
Description
Dielectrophoresis is a separations strategy that has the potential to separate small amounts of different proteins from each other. The forces at play in the channel used for dielectrophoresis are electroosmotic flow (EOF), electrophoresis (EP), and dielectrophoresis (DEP). EOF is the force exerted on liquid from an applied potential (1). EP is the force exerted on charged particles in a uniform electric field (2). DEP is the force exerted on particles (charged and uncharged) in a non-uniform electric field (3). This experiment was focused on the testing of a new microfluidic device to see if it could improve the focusing of proteins in dielectrophoresis. It was predicted that the addition of a salt bridge would improve focusing by preventing the ions created by the electrolysis of water around the electrodes from interacting with the proteins and causing aggregation, among other problems. Control trials using the old device showed that electrolysis was likely occurring and was the causal agent for poor outcomes. After applying the electric potential for some time a pH front traveled through the channel causing aggregation of proteins and the current in the channel decreased rapidly, even while the voltage was held constant. The resistance in the channels of the control trials also slightly decreased over time, until the pH shift occurred, at which time it increased rapidly. Experimental trials with a new device that included salt bridges eliminated this pH front and had a roughly linear increase of current in the channel with the voltage applied. This device can now be used in future research with protein dielectrophoresis, including in the potential differentiation of different proteins. References: 1) Electroosmosis. Oxford Dictionary of Biochemistry and Molecular Biology. 2. Oxford University Press: Oxford, England. 2006. 2) Electrophoresis. Oxford Dictionary of Biochemistry and Molecular Biology. 2. Oxford University Press: Oxford, England. 2006. 3) Dielectrophoresis. Oxford Dictionary of Biochemistry and Molecular Biology. 2. Oxford University Press: Oxford, England. 2006.
ContributorsHayes, Katelyn Donna (Author) / Hayes, Mark (Thesis director) / Borges, Chad (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
A meta-analysis was conducted to compare the total amount of ionic liquid (IL) literature (n = 39,036) to the body of publications dealing with IL toxicity (n = 213), with the goal of establishing the state of knowledge and existing information gaps. Publications on IL toxicity were collected from the SciFinder database and sorted by cation and model organism studied. Studies focusing on pharmacokinetics and drug development were excluded, as were structure-activity relationship methods of data collection. Total publishing activity was used as a measure to gauge research and industrial usage of ILs as well as the knowledge base of toxicology. Five of the most commonly studied IL cations were identified and used to establish a relationship between toxicity data and potential of commercial use: imidazolium, ammonium, phosphonium, pyridinium, and pyrrolidinium. Toxicology publications for all IL cations represented 1.2% ± 0.62% of the total publishing activity; compared with other industrial chemicals, these numbers indicate that there is still a paucity of studies on the adverse effects of this class of chemicals. In vitro models and marine bacteria were the most frequently studied biological systems, contributing 18% and 15%, respectively, to the total body of IL toxicity studies. Whole animal studies (n = 87) comprised 41% of IL toxicity studies, with a subset of in vivo mammalian models consisting of 8%. Human toxicology data were found to be limited to in vitro analyses, indicating substantial knowledge gaps. Risks from long-term and chronic low-level exposure to ILs have not been established yet for any model organisms, reemphasizing the need for filling crucial knowledge gaps concerning human health effects and the environmental safety of ILs. Adding to the existing knowledge of the molecular toxicity characteristics of ILs can help inform the design of greener, less toxic and more benign IL technologies.
ContributorsHeckenbach, Mary (Co-author) / Halden, Rolf (Co-author, Thesis director) / Jehn, Megan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Viral protein U (Vpu) is a type-III integral membrane protein encoded by Human Immunodeficiency Virus-1 (HIV- 1). It is expressed in infected host cells and plays several roles in viral progeny escape from infected cells, including down-regulation of CD4 receptors. But key structure/function questions remain regarding the mechanisms by which the Vpu protein contributes to HIV-1 pathogenesis. Here we describe expression of Vpu in bacteria, its purification and characterization. We report the successful expression of PelB-Vpu in Escherichia coli using the leader peptide pectate lyase B (PelB) from Erwinia carotovora. The protein was detergent extractable and could be isolated in a very pure form. We demonstrate that the PelB signal peptide successfully targets Vpu to the cell membranes and inserts it as a type I membrane protein. PelB-Vpu was biophysically characterized by circular dichroism and dynamic light scattering experiments and was shown to be an excellent candidate for elucidating structural models.
ContributorsDeb, Arpan (Author) / Johnson, William (Author) / Kline, Alexander (Author) / Scott, Boston (Author) / Meador, Lydia (Author) / Srinivas, Dustin (Author) / Martin Garcia, Jose Manuel (Author) / Dorner, Katerina (Author) / Borges, Chad (Author) / Misra, Rajeev (Author) / Hogue, Brenda (Author) / Fromme, Petra (Author) / Mor, Tsafrir (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / Biodesign Institute (Contributor) / School of Molecular Sciences (Contributor) / Applied Structural Discovery (Contributor) / Personalized Diagnostics (Contributor)
Created2017-02-22