Matching Items (145)
Description
Hepatitis C virus (HCV) is a globally prevalent infection which is a main contributor to the global burden of liver disease. Due to its ability to establish a chronic infection, and the lack of usefulness of traditional neutralizing antibody vaccine design in producing a protective immune response, a preventative vaccine has been notoriously difficult to produce. To overcome this, a vaccine using non-structural protein 3 (NS3) as a target to elicit a T cell specific immune response is thought to be a possible strategy for eliciting a protective immune response against hepatitis C infection. In this paper, a recombinant strain of measles virus (MV) that expresses HCV NS3 protein was analyzed. The replication fitness of this recombinant virus also indicates that this construct replicates at a higher rate than parental measles strain. It is also demonstrated through western blot analysis of protein expression and immunofluorescence that this recombinant virus expresses both the inserted HCV NS3 protein, as well as native measles proteins.
ContributorsWoell, Dana Marie (Author) / Reyes del Valle, Jorge (Thesis director) / Nickerson, Cheryl (Committee member) / Julik, Emily (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2015-05
Description
This study was conducted to observe the effects of vitamin C supplementation upon the expression of sICAM-1 in asthmatic subject. Two groups were created, each with a sample size of 4 subjects. One group was the vitamin C group (VC) and the other was the placebo group (PL). The study was analyzed through observing concentrations of biomolecules present within samples of blood plasma and nasal lavages. These included vitamin C, sICAM-1 expression, and histamine. The following P-values calculated from the data collected from this study. The plasma vitamin C screening was p=0.3, and after 18 days of supplementation, p=0.03. For Nasal ICAM p=0.5 at Day 0, p=0.4 at Day 4, and p=0.9 at Day 18. For the Histamine samples p=0.9 at Day 0 and p=0.9 at Day 18. The following P-values calculated from the data collected from both studies. The plasma vitamin C screening was p=0.8, and after 18 days of supplementation, p=0.03. The change of vitamin C at the end of this study and the combined data both had a P-value that was calculated to be lower than 0.05, which meant that this change was significant because it was due to the intervention and not chance. For Nasal ICAM samples p=0.7 at Day 0, p=0.7 at Day 4, and p=1 at Day 18. For the Histamine p=0.7 at Day 0 and p=0.9 at Day 18. This study carries various implications although the study data was unable to show much significance. This was the second study to test this, and as more research is done, and the sample size grows, one will be able to observe whether this really is the mechanism through which vitamin C plays a role in immunological functions.
ContributorsKapadia, Chirag Vinay (Author) / Johnston, Carol (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Clean water for drinking, food preparation, and bathing is essential for astronaut health and safety during long duration habitation of the International Space Station (ISS), including future missions to Mars. Despite stringent water treatment and recycling efforts on the ISS, it is impossible to completely prevent microbial contamination of onboard water supplies. In this work, we used a spaceflight analogue culture system to better understand how the microgravity environment can influence the pathogenesis-related characteristics of Burkholderia cepacia complex (Bcc), an opportunistic pathogen previously recovered from the ISS water system. The results of the present study suggest that there may be important differences in how this pathogen can respond and adapt to spaceflight and other low fluid shear environments encountered during their natural life cycles. Future studies are aimed at understanding the underlying mechanisms responsible for these phenotypes.
ContributorsKang, Bianca Younseon (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Colorectal cancer (CRC) is one of the most highly diagnosed cancers in the United States and accounts for 9.5% of all new cancer cases worldwide. With a 50% five-year prognosis, it is the second highest cancerous cause of death in the U.S. CRC tumors express antigens that are capable of inducing an immune response. The identification of autoantibodies (AAb) against tumor-associated antigens (TAA) may facilitate personalized tumor treatment in the form of targeted immunotherapy. The objective of this study was to observe the AAb expression raised against a 2000 human gene survey in late-stage colorectal cancer using the Nucleic Acid Programmable Protein Arrays (NAPPA). AAbs from serum samples were collected from 80 patients who died within 24 months of their last blood draw and 80 age and gender matched healthy control were profiled using NAPPA. TAA p53, a well-established protein that is one of the most highly mutated across a variety of cancers, was one of the top candidates based on statistical analysis, which, along with its family proteins p63 and p73 (which showed inverse AAb response profiles) warranted further testing via RAPID ELISA. Statistical analysis from these results revealed an inverse differential relationship between p53 and p63, in which p53 seropositivity was higher in patients than in controls, while the opposite was unexpectedly the case for p63. This study involving the AAb immunoprofiling of advanced stage CRC patients is one of the first to shed light on the high-throughput feasibility of immunoproteomic experiments using protein arrays as well as the identification of immunotherapy targets in a more rapid move towards specialized treatment of advanced CRC.
ContributorsSzeto, Emily (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Demirkan, Gokhan (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2014-12
Description
The focus of this project was to look at alternative treatments for endocrine resistant breast cancer (ERBC), which are breast cancers that have become resistant to hormone therapies such as Tamoxifen or aromatase inhibitors. The first part of this project involves investigating the relationship between histone de-acetylase inhibitor Vorinostat and Tamoxifen in MCF7 G11 cells, Tamoxifen resistant sub-clones, according to the PSOC Time grant. The second part involves targeting the androgen receptor (AR) in MCF7 sub-clones with AR antagonists, Bicalutamide and MDV3100, and investigating the possible usage of AR as a biomarker, due to over-expression of AR in ERBC, in accordance with the Mayo ASU Seed Grant.
The synergistic effects between Vorinostat and Tamoxifen observed through a phase II study on breast cancer patients resistant to hormone therapy may involve more than the modulation of ER-alpha to reverse Tamoxifen resistance in ERBC cells. RT-qPCR of genes expressed in Tamoxifen resistant cells, trefoil factor 1(TFF1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC), were evaluated along with ESR1 and Diablo as a control. MYC was observed to have increased expression in the treated cells, whereas the other genes had a decrease in their expression levels after the cells were treated for 3 days with Vorinostat IC30 of 1 µM. As for targeting the AR, MCF7 Tamoxifen sensitive and resistant cells were not affected by the AR antagonists to determine an IC50. The cell viability for all MCF7 sub-clones only decreased for high concentrations of 5.56 µM - 50 µM in Bicalutamide and 16.67 µM – 50 µM of MDV1300. Furthermore, hormone depletion of MCF7 G11 Tamoxifen resistant sub-clones did not show a great response to DHT stimulation or the AR antagonists. In the RT-qPCR, the MCF7 G11 cells showed an increase in mRNA expression for ER, AR, and PR after 4 hours of treatment with estradiol. As for the DHT treatment, ER, AR, PR, and PSA had a minimal increase in the fold change, but the fold change in AR was less than in the estradiol treatment. The Mayo Clinic will investigate the possible usage of AR as a biomarker through immunohistochemistry.
The synergistic effects between Vorinostat and Tamoxifen observed through a phase II study on breast cancer patients resistant to hormone therapy may involve more than the modulation of ER-alpha to reverse Tamoxifen resistance in ERBC cells. RT-qPCR of genes expressed in Tamoxifen resistant cells, trefoil factor 1(TFF1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC), were evaluated along with ESR1 and Diablo as a control. MYC was observed to have increased expression in the treated cells, whereas the other genes had a decrease in their expression levels after the cells were treated for 3 days with Vorinostat IC30 of 1 µM. As for targeting the AR, MCF7 Tamoxifen sensitive and resistant cells were not affected by the AR antagonists to determine an IC50. The cell viability for all MCF7 sub-clones only decreased for high concentrations of 5.56 µM - 50 µM in Bicalutamide and 16.67 µM – 50 µM of MDV1300. Furthermore, hormone depletion of MCF7 G11 Tamoxifen resistant sub-clones did not show a great response to DHT stimulation or the AR antagonists. In the RT-qPCR, the MCF7 G11 cells showed an increase in mRNA expression for ER, AR, and PR after 4 hours of treatment with estradiol. As for the DHT treatment, ER, AR, PR, and PSA had a minimal increase in the fold change, but the fold change in AR was less than in the estradiol treatment. The Mayo Clinic will investigate the possible usage of AR as a biomarker through immunohistochemistry.
ContributorsVorachitti, Merica (Author) / LaBaer, Joshua (Thesis director) / Anderson, Karen (Committee member) / Gonzalez, Laura (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
A coincidence reporter construct, consisting of the p21-promoter and two luciferase genes (Firefly and Renilla), was constructed for the screening of drugs that might inhibit Olig2's tumorigenic role in glioblastoma. The reporter construct was tested using an Olig2 inhibitor, HSP990, as well as short hairpin RNA targeting Olig2. Further confirmatory analysis is needed before the reporter cell line is ready for high-throughput screening at the NIH and lead compound selection.
ContributorsCusimano, Joseph Michael (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Mehta, Shwetal (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
Testosterone (T) is a steroid hormone that affects behavior and reproductive traits (e.g. spermatogenesis and ornamentation) in vertebrates. In addition to long-term influences, T can rapidly increase in males following aggressive male-male encounters. Less is known how females directly influence male T and behavior, though research with humans suggests that sexually attractive females elicit a greater increase in male T and reproductive behavior than unattractive females. In birds, the influence of female attractiveness on male T and behavior is currently untested. We hypothesized that T and courtship behavior in male zebra finches would correlate with female attractiveness. We used red leg bands to make females "attractive" and green bands to make them "unattractive" (unbanded females were controls) as previous research suggests that zebra finches prefer red colors over green in mating contexts. We collected blood from males before and after "speed-dating" trials to measure changes in plasma T and analyzed male courtship behaviors from trial video recordings. The likelihood of plasma T increasing after a trial was significantly greater in males who were with red-banded females compared to control females, suggesting males may find them more attractive than green or control females. Additionally, independent of band color, males who exhibited greater T differences initiated courtship sooner and spent more time closest to females. However, courtship initiation and time spent near females were not correlated with band color. Overall, our results suggest that female attractiveness can influence male reproductive physiology, but the presence of a female may trigger male courtship behavior.
ContributorsBero-Buell, Brianna Danielle (Author) / McGraw, Kevin (Thesis director) / Deviche, Pierre (Committee member) / Ligon, Russell (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
The pathogenesis of type 1 diabetes (T1D) is still not fully understood in the scientific community. Evidence has shown that viral infections are one of the important environmental factors associated with the disease development. Seven of the top T1D related viruses were selected to study the prevalence of viral humoral response in T1D patients using our innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA). In this study, each viral gene was individually captured using various PCR based techniques, cloned into a protein expression vector, and assembled as the first version of T1D viral protein array. Humoral responses of IgG, IgA, and IgM were examined. Although each class of immunoglobulin generated a wide-range of reactivity, responses to various viral proteins from different proteins were observed. In summary, we captured most of the T1D related viral genes, established viral protein expression on the protein array, and displayed the serum response on the viral protein array. The successful progress will help to fulfill the long term goal of testing the viral infection hypothesis in T1D development.
ContributorsDavis, Amy Darlene (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Desi, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (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
Historically, the study of cognition has focused on species-specific learning, memory, problem-solving and decision-making capabilities, and emphasis was placed on the few high-performing individuals who successfully completed cognitive tasks. Studies often deemed the success of a small fraction of individuals as suggestive of the cognitive capacity of the entire species. Recently though, interest in individual variation in cognitive ability within species has increased. This interest has emerged concomitantly with studies of variation in animal personalities (i.e. behavioral syndromes). Cognitive ability may be closely tied to personality because the mechanisms by which an individual perceives and uses environmental input (cognition) should influence how that individual consistently responds to various ecological demands (personality). However, empirical support for links between animal cognition and behavioral syndromes is currently lacking. I examined individual variation in cognition and personality in male veiled chameleons, Chamaeleo calyptratus. I considered three axes of personality (aggression, activity, and exploratory behavior) and cognition in a foraging context using visual cues − specifically, the ability to associate a color with a food reward. I found that aggression was positively correlated with the proportion of correct choices and number of consecutive correct choices. Also, one measure of exploration (the number of vines touched in a novel environment) was correlated negatively with the proportion of correct choices and positively with the number of consecutive incorrect decisions. My investigation suggests that more aggressive, less exploratory chameleons were more successful learners, and that there exists a shared pathway between these personality traits and cognitive ability.
ContributorsBruemmer, Sarah Adele (Author) / McGraw, Kevin (Thesis director) / Rutowski, Ronald (Committee member) / Ligon, Russell (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2013-05