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- Creators: College of Integrative Sciences and Arts
Description
This project examined the relationship of science teachers' knowledge about the laws relating to the teaching of creationism/evolution in public schools using multiple demographic factors. Overall, teachers correctly identified only 7 out of 10 "yes" or "no" answers about the laws, this score is only slightly better than the expected 5 out of 10 that would be obtained from guessing. Statistically significant results in differences in the overall score on the survey were found for three major variables. Teachers who say creationism should be taught in the classroom have a lower score than those who say it should not be taught in the classroom, with a large effect size. Teachers who teach biology or a life science had significantly higher scores than those who do not, with a small/medium effect size. Older teachers had significantly higher scores than younger teachers, with a small effect size. Identifying the demographic variables that effect teacher knowledge about the laws is the first step to determining how to educate teachers on the legality teaching of creationism/evolution in public school classrooms to avoid violations of the First Amendment.
ContributorsSorge, Aidan Bennet (Author) / Parker, John (Thesis director) / Lynch, John (Committee member) / School for the Future of Innovation in Society (Contributor) / Department of English (Contributor) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
White-nose syndrome (WNS) is a fungal infection devastating bat populations throughout eastern North America. WNS is caused by a fungus, Pseudogymnoascus destructans (Pd), that invades the skin of hibernating bats. While there are a number of treatments being researched, there is currently no effective treatment for WNS that is deployed in the field, except a few being tested on a limited scale. Bats have lowered immune function and response during hibernation, which may increase susceptibility to infection during the winter months. Antimicrobial peptides (AMPs) are a crucial component of the innate immune system and serve as barriers against infection. AMPs are constitutively expressed on skin and facilitate wound healing, stimulate other immune responses, and may also stay active on bat skin during hibernation. AMPs are expressed by all tissues, have direct killing abilities against microbes, and are a potential treatment for bats infected with Pd. In this investigation, the fungicidal activity of several readily available commercial AMPs were compared, and killing assay protocols previously investigated by Frasier and Lake were replicated to establish a control trial for use in future killing assays. Another aim of this investigation was to synthesize a bat-derived AMP for use in the killing assay. Sequences of bat-derived AMPs have been identified in bat skin samples obtained from a large geographic sampling of susceptible and resistant species. Contact was made with GenScript Inc., the company from which commercially available AMPs were purchased, to determine the characteristics of peptide sequences needed to synthesize an AMP for lab use. Based on recommendations from GenScript Inc., peptide sequences need to have a hydrophobicity of less than 50% and a sequence length of less than 50 amino acids. These criteria serve as a potential barrier because none of the known bat-derived sequences analyzed satisfy both of these requirements. The final aim of this study was to generate a conceptual model of the immune response molecules activated when bats are exposed to a fungal pathogen such as Pd. Overall, this work investigated sources of variability between trials of the killing assay, analyzed known bat-derived peptide sequences, and generated a conceptual model that will serve as a guideline for identification of immune response molecules on the skin of bats in future proteomics work.
ContributorsBarton, Madisen L (Author) / Moore, Marianne (Thesis director) / Penton, Christopher (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
White-nose syndrome (WNS) is a fungal disease that infects hibernating bats of multiple species across large portions of eastern North America. To date, WNS has been responsible for the deaths of over seven million bats. It is not yet known why certain species are able to resist infection. Since the fungus invades the skin and some resistant species show no signs of the characteristic cutaneous lesions, it seems likely that resistant species contain specific defense mechanisms within their skin, such as antimicrobial peptides (AMPs) and other immunologically relevant proteins expressed by specific cell types or as secreted soluble components. Proteomics could be a useful tool for understanding differences in susceptibility, and could help identify AMPs that could be synthesized and used as control agents against the spread of the causative fungus. This study is the first to optimize proteomics methods for bat wing tissues in order to compare the skin proteomes of species variably impacted by WNS, including those of two endangered species. Further tests are planned to investigate methods of increasing protein yield without altering the size of the tissue sample collected, as well as the analysis of mass spectrometry data from processed skin tissues of five bat species differentially affected by WNS.
ContributorsPatrose, Reena Paulene (Author) / Moore, Marianne (Thesis director) / Steele, Kelly (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Across large areas of eastern and midwestern North America, a severe reduction in multiple populations of bat species has been observed as the result of the emerging fungal disease, white-nose syndrome (WNS). WNS is caused by a psychrophilic (i.e. cold loving) fungus, Pseudogymnoascus destructans (Pd), that invades the skin of bats during hibernation. Recent studies have shown that during hibernation, bats have decreased immune system activity which would suggest increased susceptibility to infection. Antimicrobial peptides (AMPs) are an important component of the innate immune system and are expressed constitutively within all tissues that serve as barriers against infection. Killing pathogens at the level of the skin could prevent the need for more complex immune responses likely inhibited during hibernation, and therefore AMPs could be critical in combating infection by Pd and reducing population loss of susceptible bat species. In this investigation, the fungicidal activity of commercially available AMPs derived from the skin of multiple taxa, including amphibians, catfish, and humans were compared in order to study immunity at the level of the skin. Additionally, our aim was to create optimal methods for a low-cost antimicrobial-assay protocol that would provide quantitative results. We found that killing abilities at various concentrations of dermaseptin S-1 against Ca ATCC 10231 were consistent with literature values, while our values for magainin 2 and parasin 1 were far from the values previously recorded by other studies. It is possible that some differences can be accounted for by the difference in antimicrobial assay procedures, but our findings suggest potential differences to the well-known killing abilities of certain peptides nonetheless. Overall, the protocol established for the antimicrobial assays using serial dilutions and Sabouraud Dextrose plates was successful.
ContributorsFrazier, Eric (Co-author) / Lake, Alexis M. (Co-author) / Moore, Marianne (Thesis director) / Penton, Christopher (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Across large areas of eastern and midwestern North America, a severe reduction in multiple populations of bat species has been observed as the result of the emerging fungal disease, white-nose syndrome (WNS). WNS is caused by a psychrophilic (i.e. cold loving) fungus, Pseudogymnoascus destructans (Pd), that invades the skin of bats during hibernation. Recent studies have shown that during hibernation, bats have decreased immune system activity which would suggest increased susceptibility to infection. Antimicrobial peptides (AMPs) are an important component of the innate immune system and are expressed constitutively within all tissues that serve as barriers against infection. Killing pathogens at the level of the skin could prevent the need for more complex immune responses likely inhibited during hibernation, and therefore AMPs could be critical in combating infection by Pd and reducing population loss of susceptible bat species. In this investigation, the fungicidal activity of commercially available AMPs derived from the skin of multiple taxa, including amphibians, catfish, and humans were compared in order to study immunity at the level of the skin. Additionally, our aim was to create optimal methods for a low-cost antimicrobial-assay protocol that would provide quantitative results. We found that killing abilities at various concentrations of dermaseptin S-1 against Ca ATCC 10231 were consistent with literature values, while our values for magainin 2 and parasin 1 were far from the values previously recorded by other studies. It is possible that some differences can be accounted for by the difference in antimicrobial assay procedures, but our findings suggest potential differences to the well-known killing abilities of certain peptides nonetheless. Overall, the protocol established for the antimicrobial assays using serial dilutions and Sabouraud Dextrose plates was successful.
ContributorsLake, Alexis (Co-author) / Frazier, Eric (Co-author) / Moore, Marianne (Thesis director) / Penton, Christopher (Committee member) / W.P. Carey School of Business (Contributor) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Lactase persistence is the ability of adults to digest lactose in milk (Segurel & Bon, 2017). Mammals are generally distinguished by their mammary glands which gives females the ability to produce milk and feed their newborn children. The new born therefore requires the ability to breakdown the lactose in the milk to ensure its proper digestion (Segurel & Bon, 2017). Generally, humans lose the expression of lactase after weaning, which prevents them being able to breakdown lactose from dairy (Flatz, 1987).
My research is focused on the people of Turkana, a human pastoral population inhabiting Northwest Kenya. The people of Turkana are Nilotic people that are native to the Turkana district. There are currently no conclusive studies done on evidence for genetic lactase persistence in Turkana. Therefore, my research will be on the evolution of lactase persistence in the people of Turkana. The goal of this project is to investigate the evolutionary history of two genes with known involvement in lactase persistence, LCT and MCM6, in the Turkana. Variants in these genes have previously been identified to result in the ability to digest lactose post-weaning age. Furthermore, an additional study found that a closely related population to the Turkana, the Massai, showed stronger signals of recent selection for lactase persistence than Europeans in these genes. My goal is to characterize known variants associated with lactase persistence by calculating their allele frequencies in the Turkana and conduct selection scans to determine if LCT/MCM6 show signatures of positive selection. In doing this, we conducted a pilot study consisting of 10 female Turkana individuals and 10 females from four different populations from the 1000 genomes project namely: the Yoruba in Ibadan, Nigeria (YRI); Luhya in Webuye, Kenya; Utah Residents with Northern and Western European Ancestry (CEU); and the Southern Han Chinese. The allele frequency calculation suggested that the CEU (Utah Residents with Northern and Western European Ancestry) population had a higher lactase persistence associated allele frequency than all the other populations analyzed here, including the Turkana population. Our Tajima’s D calculations and analysis suggested that both the Turkana population and the four haplotype map populations shows signatures of positive selection in the same region. The iHS selection scans we conducted to detect signatures of positive selection on all five populations showed that the Southern Han Chinese (CHS), the LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations had stronger signatures of positive selection than the Turkana population. The LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations showed the strongest signatures of positive selection in this region. This project serves as a first step in the investigation of lactase persistence in the Turkana population and its evolution over time.
My research is focused on the people of Turkana, a human pastoral population inhabiting Northwest Kenya. The people of Turkana are Nilotic people that are native to the Turkana district. There are currently no conclusive studies done on evidence for genetic lactase persistence in Turkana. Therefore, my research will be on the evolution of lactase persistence in the people of Turkana. The goal of this project is to investigate the evolutionary history of two genes with known involvement in lactase persistence, LCT and MCM6, in the Turkana. Variants in these genes have previously been identified to result in the ability to digest lactose post-weaning age. Furthermore, an additional study found that a closely related population to the Turkana, the Massai, showed stronger signals of recent selection for lactase persistence than Europeans in these genes. My goal is to characterize known variants associated with lactase persistence by calculating their allele frequencies in the Turkana and conduct selection scans to determine if LCT/MCM6 show signatures of positive selection. In doing this, we conducted a pilot study consisting of 10 female Turkana individuals and 10 females from four different populations from the 1000 genomes project namely: the Yoruba in Ibadan, Nigeria (YRI); Luhya in Webuye, Kenya; Utah Residents with Northern and Western European Ancestry (CEU); and the Southern Han Chinese. The allele frequency calculation suggested that the CEU (Utah Residents with Northern and Western European Ancestry) population had a higher lactase persistence associated allele frequency than all the other populations analyzed here, including the Turkana population. Our Tajima’s D calculations and analysis suggested that both the Turkana population and the four haplotype map populations shows signatures of positive selection in the same region. The iHS selection scans we conducted to detect signatures of positive selection on all five populations showed that the Southern Han Chinese (CHS), the LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations had stronger signatures of positive selection than the Turkana population. The LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations showed the strongest signatures of positive selection in this region. This project serves as a first step in the investigation of lactase persistence in the Turkana population and its evolution over time.
ContributorsJobe, Ndey Bassin (Author) / Wilson Sayres, Melissa (Thesis director) / Paaijmans, Krijn (Committee member) / Taravella, Angela (Committee member) / School of Earth and Space Exploration (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
White-nose syndrome (WNS) is a cutaneous fungal infection caused by Pseudogymnoascus destructans (Pd) which was first observed in the United States in 2006. Pd infects bats during hibernation and leads to the development of cutaneous lesions and behavioral changes that can result in the animal's death. This study generated the first complete bat skin proteome for the WNS resistant gray bat (Myotis grisescens) to optimize sample preparation methods and identify immune proteins that may signal resistance. Wing tissue was collected from a female gray bat and processed in a Barocycler using 4M or 8M urea followed by an in-gel trypsin digestion of pooled samples and processing of separate samples without digestion specifically to capture and identify small antimicrobial peptides. Both undigested and digested samples were analyzed using a Thermo Fisher LTQ Orbitrap Velos mass spectrometer and interpreted using PEAKS software. A total of 29 immune proteins were identified including the antimicrobial peptide dermcidin. This method will be applied to a larger range of samples from five species variably impacted by WNS to compare skin proteomes with the aim of identifying immune proteins that are responsible for resistance at the barrier where Pd invades.
ContributorsBoone, Brianna Marie (Author) / Moore, Marianne (Thesis director) / Steele, Kelly (Committee member) / College of Integrative Sciences and Arts (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
While specific resistance mechanisms to targeted inhibitors in BRAF-mutant cutaneous melanoma have been identified, surprisingly little is known about the rate at which resistance develops under different treatment options. There is increasing evidence that resistance arises from pre-existing clones rather than from de novo mutations, but there remains the need for a better understanding of how different drugs affect the fitness of clones within a tumor population and promote or delay the emergence of resistance. To this end, we have developed an assay that defines the in vitro rate of adaptation by analyzing the progressive change in sensitivity of a melanoma cell line to different treatments. We performed a proof-of-theory experiment based on the hypothesis that drugs that cause cell death (cytotoxic) impose a higher selection pressure for drug-resistant clones than drugs that cause cell-cycle arrest (cytostatic drugs), thereby resulting in a faster rate of adaptation. We tested this hypothesis by continuously treating the BRAFV600E melanoma cell line A375 with the cytotoxic MEK inhibitor E6201 and the cytostatic MEK inhibitor trametinib, both of which are known to be effective in the setting of constitutive oncogenic signaling driven by the BRAF mutation. While the identification of confounding factors prevented the direct comparison between E6201-treated and trametinib-treated cells, we observed that E6201-treated cells demonstrate decreased drug sensitivity compared to vehicle-treated cells as early as 18 days after treatment begins. We were able to quantify this rate of divergence at 2.6% per passage by measuring the increase over time in average viability difference between drug-treated and vehicle-treated cells within a DDR analysis. We argue that this value correlates to the rate of adaptation. Furthermore, this study includes efforts to establish a barcoded cell line to allow for individual clonal tracking and efforts to identify synergistic and antagonist drug combinations for use in future experiments. Ultimately, we describe here a novel system capable of quantifying adaptation rate in cancer cells undergoing treatment, and we anticipate that this assay will prove helpful in identifying treatment options that circumvent or delay resistance through future hypothesis-driven experiments.
ContributorsDe Luca, Valerie Jean (Author) / Wilson Sayres, Melissa (Thesis director) / Trent, Jeff (Committee member) / Hendricks, William (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Unlike the autosomes, recombination on the sex chromosomes is limited to the pseudoautosomal regions (PARs) at each end of the chromosome. PAR1 spans approximately 2.7 Mb from the tip of the proximal arm of each sex chromosome, and a pseudoautosomal boundary between the PAR1 and non-PAR region is thought to have evolved from a Y-specific inversion that suppressed recombination across the boundary. In addition to the two PARs, there is also a human-specific X-transposed region (XTR) that was duplicated from the X to the Y chromosome. Genetic diversity is expected to be higher in recombining than nonrecombining regions, particularly because recombination reduces the effects of linked selection, allowing neutral variation to accumulate. We previously showed that diversity decreases linearly across the previously defined pseudoautosomal boundary (rather than drop suddenly at the boundary), suggesting that the pseudoautosomal boundary may not be as strict as previously thought. In this study, we analyzed data from 1271 genetic females to explore the extent to which the pseudoautosomal boundary varies among human populations (broadly, African, European, South Asian, East Asian, and the Americas). We found that, in all populations, genetic diversity was significantly higher in the PAR1 and XTR than in the non-PAR regions, and that diversity decreased linearly from the PAR1 to finally reach a non-PAR value well past the pseudoautosomal boundary in all populations. However, we also found that the location at which diversity changes from reflecting the higher PAR1 diversity to the lower nonPAR diversity varied by as much as 500 kb among populations. The lack of genetic evidence for a strict pseudoautosomal boundary and the variability in patterns of diversity across the pseudoautosomal boundary are consistent with two potential explanations: (1) the boundary itself may vary across populations, or (2) that population-specific demographic histories have shaped diversity across the pseudoautosomal boundary.
ContributorsCotter, Daniel Juetten (Author) / Wilson Sayres, Melissa (Thesis director) / Stone, Anne (Committee member) / Webster, Timothy (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Tremendous phenotypic variation exists across people with Turner syndrome (45,X). This variation likely stems from differential dosage of genes on the X chromosome. X-inactivation is the process whereby all X chromosomes in excess of one are silenced. However, about 15% of the genes on the silenced X chromosome escape this inactivation and are candidates for affecting phenotype in people with Turner syndrome. In this study we take an evolutionary approach to rank candidate genes that may contribute to phenotypic variation among people with Turner Syndrome. We incorporate analysis of patterns of DNA methylation from 46,XX and 45,X individuals, and estimates of variable X-inactivation status across 46,XX individuals, with patterns of gene expression conservation on the X chromosomes across five tissues and ten species. We find that genes that escape XCI are possible candidate genes for Turner syndrome phenotype, indicated by the constant levels of expression in escape genes and inactivated genes. Variation in these genes is expected to affect phenotype when dosage is altered from typical levels.
ContributorsSchaffer, Kara Nina (Author) / Wilson Sayres, Melissa (Thesis director) / Crook, Sharon (Committee member) / Narang, Pooja (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12