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Nutrient Acquisition in the Gram-Positive Pathogens Clostridioides Difficile and Staphylococcus Aureus
No full textBacterial infections are a leading cause of death globally, with the Gram-positive bacterial pathogens Staphylococcus aureus and Clostridioides difficile posing serious threats to human health. The discovery and implementation of antibiotics has increased the global life expectancy. However, several unintended consequences of antibiotic usage have arisen including antibiotic resistance and antibiotic-associated infections. S. aureus is capable of developing resistance to all classes of clinically-relevant antibiotics, and C. difficile is the leading cause of antibiotic-associated infections. These facts highlight the necessity of developing improved therapeutic strategies to treat antibiotic-resistant infections, and reduce infections associated with antibiotic usage. We hypothesized that strategies to obtain essential nutrients serve as a promising target to treat infections. Here we investigated a mechanism used by C. difficile to metabolize a poisonous uracil analog, 4-thiouracil (4-TU) to acquire essential pyrimidine nucleotides. A thiouracil desulfurase protects C. difficile RNA from incorporation of 4-TU, and confers a fitness advantage against gut commensal bacteria that are unable to grow in the presence of 4-TU. Due to the antibacterial properties of 4-TU, we hypothesized 4-TU inhibits the growth of drug-resistant S. aureus. Indeed, 4-TU inhibits the growth of drug-resistant S. aureus, and analysis of RNA from 4-TU-treated S. aureus revealed that 4-TU hijacks the pyrimidine salvage pathway for incorporation into RNA. In addition to acquiring essential pyrimidine nucleotides, bacteria must acquire nutrient metals during infection. The host actively restricts metals from pathogens, and microbes maintain mechanisms to circumvent host-imposed metal limitation. Calprotectin is a pro-inflammatory antimicrobial protein that inhibits bacterial growth by sequestering metals. Calprotectin plays a critical role in the host response to C. difficile infection, and investigation of the cell types responsible for delivering calprotectin to the gut during infection revealed myeloid-derived cells are critical contributors of calprotectin. Analysis of C. difficile genes required for fitness in the presence of calprotectin suggest that high-affinity metal and siderophore transporters are important for competing with calprotectin for metals. Collectively, this Thesis proposes that bacterial mechanisms to obtain essential nutrients may serve as a promising target for therapeutic development
Emotional Disembodiment and Depersonalization Experiences
No full textDepersonalization-Derealization Disorder (DPD) is characterized by profound disconnection from one's sense of self and environment, affecting approximately 1% of the population. Despite widespread reports of emotional numbing and detachment, the underlying mechanisms of emotional processing disruptions in DPD remain poorly understood. The present research examined emotional embodiment, alexithymia, and interoceptive sensibility in both general population and clinical samples to elucidate the mechanisms underlying emotional disconnection in DPD.
Study 1 investigated relationships among trait depersonalization, emotional embodiment, and alexithymia in a general population sample (N=121) using the emBODY tool, Cambridge Depersonalization Scale, and Toronto Alexithymia Scale. High depersonalization participants demonstrated significantly increased alexithymia and altered embodiment patterns, particularly heightened bodily sensations for negative, high-arousal emotions. Study 2 extended this investigation to clinical populations, comparing individuals with diagnosed DPD (n=22) to schizophrenia patients (n=14) and healthy controls (n=22). DPD participants reported significantly higher alexithymia and lower interoceptive self-report than both comparison groups, with particular impairments in trusting, self-regulation, and body listening. Qualitative interviews revealed complex emotion experiences including de-affectualisation, cognitive-bodily disconnect, and paradoxically heightened emotions in certain contexts.
These findings highlight emotional disembodiment as a core feature of DPD, characterized by a disconnect between cognitive awareness and embodied emotional experience. Individuals with DPD retained emotional differentiation capacity but showed altered embodiment patterns and significant interoceptive difficulties, contributing to the characteristic "stranger to myself" phenomenon
RELATIVE EFFECTS OF IMMEDIATE CONTINGENT INSTRUCTION VERSUS REINFORCEMENT-ONLY PROCEDURES WHEN TEACHING EXPRESSIVE LABELS IN ITALIAN
No full textThesis under the direction of Dr. Jennifer Ledford
An adapted alternating treatments design (AATD) was used to assess the differing effects of using punishing procedures (error correction) compared with using reinforcement-only procedures (reinforce attempts, reinforce attempts with delayed instruction, and differential reinforcement) for teaching Italian vocabulary words to preschool-aged children. Additionally, participant preference of each teaching approach was evaluated using a concurrent operant paradigm
Essays in International Intellectual Property
No full textThis dissertation studies bilateral patent flows between countries arising from the firm-level decisions to apply for patents in each market. Chapter One presents a model of these patenting decisions that results in a gravity equation that incorporates patent-specific costs and frictions. Bilateral patent flows are constructed from the PATSTAT database using a novel origin assignment method. Estimation techniques are borrowed from the trade gravity literature to estimate the impact of Patent Cooperation Treaty membership and other trade and intellectual property treaties on bilateral patent flows. I find that joint membership in these treaties has a significant positive impact on patent flows, but this is limited in large part to north-to-north and south-to-south country pairs. Chapter Two enriches the patent data with measures of patent value. Modifying the gravity equation to focus on aggregate and average patent value flows shows that reductions in patenting frictions have a negative impact on average patent values. I estimate the effect of trade and intellectual property treaties and demonstrate this negative relationship for the PCT. Chapter Three enriches the underlying model to allow domestic firms to imitate unpatented innovations imperfectly. This makes the marginal expected value of a patent dependent on the ability of domestic firms to replicate a product efficiently. We measure the imitative capacity of a market using the number of patents generated by firms in the market. Since innovation activity can be highly variable across industries, we control for industries using patent IPC codes. We modify our empirical specification to allow for the inclusion of destination innovative activity and find that increased risk of imitation in a destination market has a strong positive impact on patent flows. Collectively, these papers contribute to the literature studying firms' decisions regarding where to apply for patents and what factors affect them
Relations among Measures of Theory of Mind in Depressed Adolescents Receiving Cognitive Behavior Therapy
No full textAdolescent depression is associated with cognitive and social impairments, including deficits in Theory of Mind (ToM) — the ability to infer others' thoughts and emotions. Cognitive Behavior Therapy (CBT) is a generally effective treatment although further improvements can be made. This study examined the associations among measures of ToM in depressed adolescents and tested whether integrating social cognitive training (CBT+SCT) into CBT enhanced treatment outcomes compared to CBT alone. Forty-five depressed adolescents (ages 12-17) were randomly assigned to CBT+SCT or CBT-only. ToM was assessed using four measures: Faux Pas Recognition Test, Strange Stories, Flexibility and Automaticity of Social Cognition (FASC), and Reading the Mind in the Eyes (RME) tests. Results showed that at baseline, the RME task correlated significantly with FASC Mental State Response Time. Results of the regression analyses showed that CBT+SCT produced significantly greater improvements in ToM particularly in recognizing social faux pas. These effects were strongest in adolescents with lower baseline ToM scores, suggesting that social cognitive training may enhance CBT effectiveness for those with significant ToM deficits. Findings highlight the need for individualized treatment approaches that account for individuals’ levels of social cognitive development. Future research should explore the long-term effects of ToM training on depression and interpersonal functioning.Thesis completed in partial fulfillment of the requirements of the Honors Program in Psychological Sciences
Increasing Visibility and Discoverability of Electronic Theses and Dissertations Using Linked Open Data: A Simple Process for Uploading Metadata to Wikidata
No full textMolecular Mechanisms Underlying Plasticity to Photoperiod in the Suprachiasmatic Nucleus
No full text*Portion of abstract previously published in Cox et al., 2024.
Seasonal daylength, or circadian photoperiod, is a pervasive environmental signal that profoundly influences physiology and behavior. In mammals, the central circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus where it receives retinal input and synchronizes, or entrains, organismal physiology and behavior to the prevailing light cycle. The process of entrainment induces sustained plasticity in the SCN, but the molecular mechanisms underlying SCN plasticity are incompletely understood. Entrainment to different photoperiods persistently alters the timing, waveform, period, and light resetting properties of the SCN clock and its driven rhythms. To elucidate novel candidate genes for molecular mechanisms of photoperiod plasticity, we performed RNAseq and preliminary DNA methylation analysis on whole SCN dissected from mice raised in Long (LD 16:8) and Short (LD 8:16) photoperiods. Further, DNA methylation analysis was conducted in SCN slice culture incubated with DNA methyltransferase inhibitors RG108 and SGI-1027. RNAseq detected fewer rhythmic genes in Long photoperiod, and in general the timing of gene expression rhythms was advanced 4-6 hours. However, a few genes showed significant delays, including Gem. There were significant changes in the expression clock-associated gene Timeless and in SCN genes related to light responses, neuropeptides, GABA, ion channels, and serotonin. Particularly striking were differences in the expression of the neuropeptide signaling genes Prokr2 and Cck, as well as convergent regulation of the expression of three SCN light response genes, Dusp4, Rasd1, and Gem. Transcriptional modulation of Dusp4 and Rasd1, and phase regulation of Gem, are compelling candidate molecular mechanisms for plasticity in the SCN light response through their modulation of the critical NMDAR-MAPK/ERK-CREB/CRE light signaling pathway in SCN neurons. Modulation of Prokr2 and Cck may critically support SCN neural network reconfiguration during photoperiodic entrainment. Overall, the RNAseq findings identify the SCN light response and neuropeptide signaling gene sets as rich substrates for elucidating novel mechanisms of photoperiod plasticity. DNA methylation analysis via sodium bisulfite pyrosequencing of Rasd1 found a significant difference in methylation at the 3’ enhancer region of the gene between photoperiods at the projected time of lights off. In SCN slice culture at baseline (no light stimulus) in the presence of DNA methyltransferase inhibitors, no differences in DNA methylation were detected via sodium bisulfite pyrosequencing in regulatory regions in the core clock genes Bmal1, Per1, and Nr1d1 or in the light-signaling gene Rasd1. Overall, the results of the DNA methylation analyses are preliminary but agree with the results from the RNAseq study in that no changes in expression are observed in the core clock genes, whereas Rasd1 is significantly differentially expressed between photoperiods
Falling in "Another Country"
No full textIn his novel, Another Country, James Baldwin abruptly breaks his reader’s expectations when his protagonist, Rufus Scott, commits suicide by jumping from the George Washington Bridge only eighty pages into the novel. This paper seeks to understand Rufus’s jump by analyzing him through the broader context of loneliness and its relation to physics. Drawing on Baldwin’s essays, as well as Simone Weil’s Gravity and Grace, and affect theorists like Sienne Ngai and Eugenie Brinkema, this paper examines loneliness as an explicitly fundamental concept for Baldwin, and the ways in which affect correlates to physics to determine character actions before they happen. Starting with a close reading of Rufus’s jump, I look at how Rufus’s loneliness is affectively constructed before moving to Simone Weil’s Gravity and Grace to look at other instances of metaphysical gravity, and then look to Baldwin’s invocation of physical touch, in particular, the embrace, as the only remedy for loneliness
On Some Basic Problems of Riesz Kernels in Potential Theory
No full textThis dissertation contains discussions of three open problem areas in Potential Theory involving the Riesz kernels. In the first discussion, we consider the k-nearest neighbor logarithmic energies. We will establish first- and second-order asymptotics of the energies as the number of particles goes to infinity on any Jordan measurable set. The second discussion involves continuous energies with external fields. We will investigate a particular case of dimension reduction phenomena where the support of the equilibrium measure becomes a single sphere. For the third discussion, we study polarization problems or Chebyshev problems under the effect of external fields for Riesz-like kernels. In particular, we try to find a connection between discrete and continuous polarizations with external fields by establishing a minimum principle
