19468 research outputs found
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Introducing Additional Protein Functionality via Incorporation of Non-Canonical Amino Acids
No full textThe incorporation of non-canonical amino acids introduces unique chemical functionality to proteins, enabling the preparation of useful bioconjugates. Bioconjugates have wide applications in disease treatment, imaging, and the improvement of protein stability. We demonstrated the application of non-canonical amino acid-mediated bioconjugation to the immobilization and resulting stabilization of a hyperthermophilic enzyme. Additionally, a bioconjugate capable of detecting prostate cancer was produced. Finally, two methods of preparing multivalent bioconjugates are in progress: one involving the development of a novel non-canonical amino acid and the other involving the adaptation of an organic diyne reaction to a biological setting. This thesis aims to highlight the importance of bioconjugation and expand the applications of bioconjugation for drug development.ChemistryBachelors of Science (BS
Hypertension Severity Impacts Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer
No full textBackground: American College of Cardiology/American Heart Association hypertension guidelines do not clearly address the pharmacological treatment of increases in blood pressure (BP) in women receiving potentially cardiotoxic chemotherapy for the treatment of breast cancer. Methods and Results: Magnetic resonance measures of left ventricular ejection fraction (LVEF) were performed in women with stage I-III breast cancer prior to and three months after initiating potentially cardiotoxic chemotherapy. Measurements of brachial BP were collected according to AHA recommendations. Using multivariable analysis, we assessed the association between change in LVEF and pre-existing ACC/AHA stages of hypertension (HTN) after accounting for pre-treatment LVEF, diabetes status, age, and body mass index (BMI). We also analyzed the effect of the number of anti-HTN medicines on LVEF decline in the same patient population. All analyses were performed blind to all participant identifiers. Participants (n=227, female) were aged 56±0.69 (Mn±SE) years and were 75% White and 20% Black. Cancer therapies included combinations of anthracyclines (43.2%), trastuzumab (22.9%), paclitaxel (48.0%), and cyclophosphamide (50.7%). After accounting for pre-treatment LVEF, diabetes status, age, and BMI, participants with Stage II HTN experienced a significant decline (p=0.0116) in LVEF relative to individuals with normal blood pressure. No association was found between the number of anti-HTN medicines and LVEF decline. Conclusion: Relative to women with normal blood pressure, women with Stage II HTN experienced a larger decline in LVEF three months after initiating potentially cardiotoxic chemotherapy for breast cancer, independent of HTN treatment. This finding raises the possibility that lower blood pressure targets among women receiving adjuvant treatment for breast cancer may associate with improved preservation of LVEF. Clinical Trial Numbers: NCT02791581 (NIH #: R01CA199167) and NCT01719562 (NIH #: R01CA167821)BiologyBachelors of Science (BS
Machine Learning Analysis Reveals Environmental and Demographic Patterns of Skin Lesions and Scars in Bottlenose Dolphins
No full textTamanend’s bottlenose dolphins (Tursiops erebennus) in the Chesapeake Bay are important ecosystem sentinels in a critical but underrecognized habitat, and have been threatened by major disease-related mortality events. Despite this, researchers have yet to conduct a deeper investigation into the correlation among environmental factors (such as temperature and salinity), demographic factors (such as age and sex), and disease susceptibility in these dolphins. Both skin lesions and rake mark scars can be used as potential indicators of disease susceptibility in dolphin populations, as skin lesions often indicate underlying disease, and rake marks are associated with other stressors that may increase a dolphin’s susceptibility to disease. Analysis of these markings requires photographic data, for which manual processing is inefficient, often resulting in long lags between data collection and the complete analysis needed to inform management decisions. This study uses modern machine learning tools to assess indicators such as the prevalence of skin lesions and extent of rake mark coverage across dolphins photographed in the Chesapeake Bay to test hypotheses about the potential patterns between environmental factors, demographic factors, and potential disease susceptibility indicators. I found a significant association between lower temperature and lesion prevalence and between lower salinity and lesion prevalence for one lesion class thought to be most associated with infectious disease. I also discovered that adult male dolphins had higher rake mark coverage compared to adult females or calves, but no significant difference could be found between rake mark coverage for the latter two demographic classes. These findings could suggest a higher susceptibility to disease for adult male dolphins and more generally dolphins in colder, less saline waters. My work provides new understanding into the trends that may drive disease among T. erebennus in the Chesapeake Bay.BiologyBachelors of Science (BS
Sprouting new directions for restoration: unraveling the influence of seed characteristics to optimize Ruppia maritima germination success
No full textSubmersed aquatic vegetation (SAV) beds form some of the most productive marine ecosystems on Earth, responsible for sequestering carbon, acting as nursery grounds for marine organisms, and stabilizing sediment. The Chesapeake Bay is a historic habitat for SAV, where these aquatic plants play an important role in ecosystem functioning and economic prosperity. A shift in the dominant SAV species from Zostera marina, a subpolar species, to Ruppia maritima, a global generalist, over the past thirty years in the region due to rising water temperatures and increased severity of marine heatwaves has sparked interest in the study of this second, more opportunistic species. While seed characteristics and restoration potential are well known and utilized for Z. marina, metrics of R. maritima seed quality have only been briefly investigated in the past. To identify seed properties that can predict successful germination, we investigated fall velocity and seed shape, and found that both faster fall velocities and “S” shaped seeds help predict successful germination. Additionally, we investigated the role of monthly cold storage on germination and found that cold storage increased germination by 20% - 40% over the course of a year. To assess seed survival and time until germination for seeds stored over multiple years, we then quantified germination patterns of two cohorts of seeds from subsequent separate collection years after being removed from cold storage and planted in sediment. We found that fall velocity and seed shape once again helped predict the probability of germination, as well as cohort. Additionally, a higher proportion of seeds germinated and at a faster rate from the younger cohort compared to the older cohort. We interpret our results to indicate that R. maritima seeds have demonstrable development and germination patterns that can be used in advising future restoration efforts. By expanding our knowledge of Ruppia maritima seed characteristics we hope to enhance restoration and buffer against future detrimental effects of climate change on SAV in the Chesapeake Bay and beyond.BiologyBachelors of Science (BS
Crushing a cockroach versus a butterfly: The effects of female defendant physical attractiveness and crime type on guilt attributions and punishment harshness
No full textIn recent decades, the subarea of psychological research that focuses on the intersection between social psychology and the law has seen tremendous growth. Given that women in patriarchal societies may be especially prized for their physical appearance rather than their other qualities, as well as salient gender-role stereotypes and the increasing rate of female arrests and incarceration in the United States, the present study seeks to investigate the influence of both female defendant physical attractiveness and crime type on guilt attributions and punishment harshness. Non-college adults (n = 274) and undergraduates (n = 149) participated in an online study in which they read a vignette describing an alleged crime and viewed a photo of a defendant of either low, average, or high attractiveness. Participants decided the likelihood of guilt, indicated punishment severity, and justified their judgments. They completed the Facial Trustworthiness Scale, the Modern and Old-Fashioned Sexism Scales, and answered questions about their experience with the criminal justice system. Two 2x3 ANOVAs, as well as moderation and mediation analyses via Hayes PROCESS were conducted following data collection. Within both samples, main effects of crime type on guilt attributions and punishment harshness were uncovered, but no significant main effect of attractiveness on these variables was revealed. Within the non-college adult sample, participants’ fear of the crime mediated the main effect of crime type on guilt attributions, but this finding was not replicated in the undergraduate sample. Within the non-college sample, significant physical attractiveness x crime type x participant sexism interactions occurred. There was a positive relationship between participant sexism and punishment harshness in both the property and violent crime scenarios for the average faces. In the attractive condition, however, there was a negative relationship between participant sexism and punishment harshness in the violent crime scenario, and a positive correlation between these variables in the property crime scenario. Implications, limitations, and directions for future research are discussed.PsychologyBachelors of Arts (BA
Radon Risk Mapping Using Uranium Series Geochemistry and Social Vulnerability in the North Carolina Coastal Plain
No full textRadon (222Rn) is a colorless, odorless, inert radioactive gas that emits alpha radiation, making radon inhalation the leading cause of lung cancer among non-smokers. Based on previous low-resolution radon hazard maps, the Mid-Atlantic Coastal Plain is broadly generalized as low risk, yet indoor radon tests in the coastal plain of North Carolina show measurements as high as 54 pCi/L, approximately 18 times the U.S. Environmental Protection Agency’s action level. Here I combine uranium-series radionuclide measurements from sediment cores with social vulnerability data to create higher resolution radon hazard maps. Using ultra low background high resolution gamma spectrometry, I measure 238U, 226Ra, and 210Pb in sediment cores within Nash and Edgecombe Counties in the North Carolina Coastal Plain. Radon disproportionately affects socially vulnerable and historically excluded populations, and thus the effects of radon gas cannot be generalized across a county’s population. I overlay demographic data relating to the themes of socioeconomic status, household composition/disability, and race/ethnicity/language from the Center for Disease Control’s Social Vulnerability Index (SVI) with measured values of 226Ra in core sections. In addition to high indoor radon levels, my study area shows a high vulnerability with regards to these three SVI themes. My results indicate the presence of elevated 226Ra in sediment in Nash and Edgecombe counties, as well as the need for further mapping efforts in the Mid-Atlantic Coastal Plain to direct radon mitigation, testing, and public health efforts.GeologyBachelors of Science (BS
Investigating Protein Interactions Modulating Thyroid Hormone Receptor Localization
No full textThyroid hormone is an important component of the endocrine system that regulates growth and metabolism. The hormone circulates in the bloodstream and is transported into target cells, where it then enters the nucleus and binds to tissue-specific thyroid hormone receptors (TRs) to facilitate transcription of thyroid hormone-responsive genes. However, TR is known to rapidly shuttle between the nucleus and cytoplasm. Prior research in our lab has demonstrated more cytoplasmic localization of an acetylation mimic of TR compared to a non-acetylation mimic and wild-type TR. This implies that post-translational modification of TRs via lysine acetylation may be an additional mechanism of regulating thyroid hormone signaling. To investigate whether lysine deacetylase HDAC2 might play a role in TR deacetylation and localization, we transfected HeLa cells with expression plasmids for GFP-tagged TR subtypes, TRα1, β1, and β2. Cells were incubated with either Santacruzamate A—an HDAC2 inhibitor—or a DMSO control post-transfection. After fluorescence imaging and nucleocytoplasmic scoring, cellular localization of TR, measured by N/C ratio, was only significantly different for inhibitor-treated TRβ1 relative to the control. However, the observed shift was towards the nucleus, suggesting an indirect effect due to increased histone acetylation, which led us to conclude that HDAC2 is likely not the primary regulator of TR deacetylation. Resistance to Thyroid Hormone Syndrome (RTH) is a known genetic dysfunction of the thyroid hormone signaling pathway characterized by tissue-specific hypothyroidism. Patients with severe RTH, characterized by shortened stature, mental defects, and bradycardia, have mutations in TRα1, which is specific to skeletal, heart, and brain tissues. Two identified mutations, C392X and E403X, result in premature truncation of TRα1's ligand-binding domain. We hypothesized that these mutations might increase the affinity of mutant TRα1 for nuclear corepressor NCoR1 and enhance nuclear retention. Using cotransfection of expression plasmids for mCherry-tagged TRα1 variants with GFP-NCoR1 or an NCoR1 variant that does not bind TR as a control, we found that the nucleocytoplasmic localization of the mutants was not significantly different in the presence of overexpressed NCoR1 relative to the control, likely because both mutants already show a primarily nuclear localization and enhanced nuclear retention may not be measurable. Thus, we expressed the mutant receptors in HeLa cell lines with NCoR1 knocked out. C392X, but not E403X or wild-type TRα1, demonstrated a significant cytoplasmic shift in knockout cells compared to controls with normal expression of NCoR1, validating our model of impaired NCoR1 release in that mutant. Broadly, these results contribute to general understanding of TR's binding partners within the nucleus and highlight the need for further characterization of the structure and binding dynamics of the E403X mutant and more broadly of protein-protein interactions within endocrine pathways.BiologyBachelors of Science (BS
Examining Factors Affecting Nuclear Retention of the Thyroid Hormone Receptor
No full textThe thyroid hormone receptors, TRα1, TRβ1, and TRβ2, are nuclear receptors that regulate many genes involved in development, growth, and homeostasis in response to thyroid hormone (T3). TRs undergo nucleocytoplasmic shuttling and mutations in TR can lead to altered intracellular localization and diseases such as Resistance to Thyroid Hormone (RTH). RTH is caused by mutations in TR leading to a decreased response to T3. Previous studies in our lab have established, using acetylation and non-acetylation mimics, that the acetylation of TR at specific sites leads to a more cytosolic localization and non-acetylation leads to a more nuclear localization, indicating that the deacetylation of TR plays an important role in modulating nucleocytoplasmic shuttling. To determine if histone deacetylases (HDAC) 1 and 3 play a role in altering TR localization by the deacetylation of TR, HeLa cells were transfected with GFP-tagged TRα1, TRβ1, or TRβ2 and an HDAC 1/3 inhibitor was added at 1μM and 10μM concentrations. Analysis of average relative nucleocytoplasmic (N/C) ratios revealed no significant change in localization of any TR variant when compared to the solvent control. These data suggest that the deacetylase activity of HDAC 1 and HDAC 3 is not directly responsible for the localization patterns of TR; as a result, other members of the deacetylase family are now under investigation. While in the nucleus, TR binds to nuclear receptor corepressor 1 (NCoR1), silencing gene expression in the absence of T3. In our investigation of RTHα mutations and NCoR1 binding, it was hypothesized that nuclear retention of RTHα mutants would be increased in the presence of overexpressed NCoR1, since some RTHα mutants have been reported to have increased affinity for NCoR1. RTHα mutants with substitution of arginine for either a cysteine or histidine at position 384 (R384C or R384H) were selected for analysis, because it had previously been shown that these TR variants have a more cytosolic population than wild-type TRα1. HeLa cells were transfected with mCherry-tagged wild type TRα1, R384C, or R384H, as well as GFP-tagged wild type NCoR1 or an NCoR1 mutant that does not bind TR, as a control. N/C ratios for wild-type TRα1 and the RTHα mutants were not significantly different in the presence of overexpressed NCoR1 compared with the non-binding NCoR1. To further investigate the role of NCoR1, HeLa cells were designed with NCoR1 knocked out and transfected with mCherry-tagged wild type TRα1, R384C, or R384H. The N/C ratios for wild-type TRα1 and the RTHα mutants were calculated and compared to those calculated from wild-type HeLa cells. It was determined that the N/C ratios were not significantly different. These experiments suggest that interaction with NCoR1 is not a key factor affecting localization patterns of these RTHα mutants. Overall, these findings provide further insight into TR’s interactions with other proteins and the resulting impacts on nuclear retention. The implications of these findings can be applied to learning more about multiple diseases in the endocrine system including Resistance to Thyroid Hormone syndrome and cancer.BiologyBachelors of Science (BS
A Combination of Environmental and Landscape Variables Drives Movement and Habitat use in Two Anaxyrus spp. in the Eastern Coastal Plain
No full textAmphibians are among the most endangered taxa and are largely threatened by habitat loss. Little work has been conducted on the movement and habitat use of amphibians outside of their breeding season. In this study, we examined the movement patterns of two species of toads inhabiting the Eastern Coastal Plain of Virginia: the Eastern American Toad (Anaxyrus americanus americanus) and the Fowler’s Toad (Anaxyrus fowleri). Based on three years of movement data, we estimated the median migration distance of toads from their breeding locations and the propensity for site fidelity, related variation in distance traveled to environmental (e.g., rain, temperature, humidity) and landscape variables (e.g., coniferous forests, distance to trails, terrain ruggedness index), and compared microhabitat selection for daytime refugia between the two species. We found similar median distances from breeding grounds for the two species, 63 m for the Eastern American Toad and 64 m for the Fowler’s Toad, but Eastern American Toads had a greater range of moved distances (3rd quartiles were 122 m for Eastern American and 73 m for Fowler’s Toads). We also found that both species exhibited site fidelity. Distance to trails and minimum temperature related positively with increased movements. Compared to Fowler’s Toads, Eastern American Toads favored woody structures and leaf litter for daytime refugia. Our research provides crucial information for two toad species about the extent of their movements and habitat use during the nonbreeding season. To lessen the decline of amphibians, habitats occupied during the nonbreeding season need to be included in conservation strategies at biologically relevant distances around breeding areas.BiologyBachelors of Science (BS
From TikTok to Trad Goth: An Exploration of Posers, Subcultural Commodification, and the Function of Gatekeeping in the Goth Subculture
No full textAlthough goths are most readily identified through a conspicuously dark sense of style and affinity for moody alternative music genres, goths are linked through a unique worldview that seeks to embrace all aspects of life--both the light and, most infamously, the dark. Freedom to expression without judgment is perhaps the most important value within goth culture, which is what makes the prevalence of elitism, gatekeeping, and rejection within the subculture precisely so perplexing. These seemingly conflicting values inform the empirical basis of my study emerges as I seek to evaluate the motivations and functions of gatekeeping with alternative subcultures, using goth as my case study. While neo-Marxist perspectives assert that subcultures “die” from commodification through diffusion and defusion, in the postmodern subcultural landscape, fragmentation and hybridization allow subcultures like goth to constantly evolve despite waves of commercialization by mainstream culture. As a result, the styles of dress and music are continually shifting and measures of subcultural capital are in constant flux. Understanding the term poser as synonymous with in-group rejection and gatekeeping, goths engage in gatekeeping and elitism differently depending on how placemaking shapes a goth’s position in the subculture. In-person gatekeeping and physical boundary formation are typically more symbolic, while digital gatekeeping is more explicit and literal. Goths engage in gatekeeping as a means of preserving the integrity and purity of the subculture as it becomes commodified with Trad Goth emerging as a fragmented subculture dedicated to recreating the values, styles, and norms associated with the original post-punk goth subculturists, who are constructed as the most authentic forms of goth. There are two overarching eras of goth becoming commodified, signaled by the mall goths of the 1990s and the InstaGoths of the late 2010s. While the mall goth consumption style has fallen out of vogue and these posers have been incorporated into broader alternative culture, InstaGoths define the newest era of commodified alternative consumption styles and should be a group for researchers to keep an eye on going forward. For most subculturists, physical expressions of goth subcultural identity are associated with variable risk for personal harm. Goth’s prominent position in mainstream culture during its cycle of commodification results in two forms of danger: moral panic and fetishization. Many young goths, seeking integration into their digital goth community, engage in gatekeeping to affirm their individual identity and secure their position in the community. Ultimately, these overarching trends and motivations reveal that patterns of gatekeeping within the goth subculture are driven by mainstream cultural shifts and subcultural commodification, revealing these processes' complicated effects on the alternative subcultural landscape.SociologyBachelors of Arts (BA