Matching Items (366)
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
Identifying disease biomarkers may aid in the early detection of breast cancer and improve patient outcomes. Recent evidence suggests that tumors are immunogenic and therefore patients may launch an autoantibody response to tumor associated antigens. Single-chain variable fragments of autoantibodies derived from regional lymph node B cells of breast cancer patients were used to discover these tumor associated biomarkers on protein microarrays. Six candidate biomarkers were discovered from 22 heavy chain-only variable region antibody fragments screened. Validation tests are necessary to confirm the tumorgenicity of these antigens. However, the use of single-chain variable autoantibody fragments presents a novel platform for diagnostics and cancer therapeutics.
ContributorsSharman, M. Camila (Author) / Magee, Dewey (Mitch) (Thesis director) / Wallstrom, Garrick (Committee member) / Petritis, Brianne (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor) / Virginia G. Piper Center for Personalized Diagnostics (Contributor) / Biodesign Institute (Contributor)
Created2012-12
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
A series of mitochondria targeting probes was synthesized for the purpose of exploring the feasibility of a mitochondria targeting fluorescent sensor. Of the probes, the probe with a two carbon spacer showed the best co-localization from staining with the established MitoTracker Red® FM, indicating a potential development of the probe into mitochondria targeting sensor. However, cytotoxicity was observed for the probe with a six carbon spacer. Three additional mitochondria targeting fluorescent probes of longer spacer groups were synthesized, but the cytotoxicity was not observed to be as high as that of the probe with a two carbon spacer. The cytotoxicity was characterized to be that of caspase dependent cell death. To screen for a possible effect on apoptosis due to the mitochondrial probe, three fluorescent fusion proteins binding the anti-apoptotic proteins were designed and expressed. Each purified fusion protein was then incubated with the cytotoxic mitochondrial probe, and the mixture was isolated by running an affinity column. The fluorescence analysis of eluted fractions showed preliminary data of possible interaction between the protein and the mitochondrial probe.
ContributorsLee, Fred (Author) / Meldrum, Deirdre R. (Thesis director) / Tian, Yanqing (Committee member) / Zhang, Liqiang (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-12
Description
Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children with ASD, and significantly worsen their behavior and their quality of life. Here we first summarize previously published data supporting that GI dysfunction is common in individuals with ASD and the role of the microbiota in ASD. Second, by comparing with other publically available microbiome datasets, we provide some evidence that the shifted microbiota can be a result of westernization and that this shift could also be framing an altered immune system. Third, we explore the possibility that gut–brain interactions could also be a direct result of microbially produced metabolites.
ContributorsKrajmalnik-Brown, Rosa (Author) / Lozupone, Catherine (Author) / Kang, Dae Wook (Author) / Adams, James (Author) / Biodesign Institute (Contributor)
Created2015-03-12
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