Digital Commons Network^™

Analyzing Inhibitors Of The Sars-Cov-2 Endoribonuclease Nsp15, Mary Staunton

Honors Scholar Theses

The global pandemic caused by the virus SARS-CoV-2 has devastated the world. A flurry of research into the structures and activities of the virus have identified several viable targets for drug therapy, including the endoribonuclease nsp15, also known as EndoU. EndoU has been shown to play a role in diminishing the host cell’s immune response to the virus by cleaving signaling dsRNA, specifically targeting uridine sequences. The development of the crystal structure nsp15 allowed our lab along with others to perform virtual screenings to identify inhibitors that might be able to dock at the active site and inhibit the activity …

Comparative Analysis Of Longevity And Stress Resiliency Benefits Of Supplementation With High-Antioxidative Capacity Juices In Organisms That Are Representative Of Humans, Meghan Long

Honors Scholar Theses

Neurodegenerative disease presents itself in a complex array of illnesses that is increasingly affecting the geriatric population. There has not been research on a common cause since there are a culmination of reasons that are probable ranging from genetic to environmental factors. Antioxidants have been known to prevent and protect against the damage that is otherwise caused by reactive oxygen species (ROS). Thus, high-capacity antioxidant juices supplemented into the diet of animal models such as Caenorhabditis elegans, Drosophila melanogaster, rats, and humans will allow for the study of the possible benefits.

Although a conclusion and common causation on the usage …

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …

The Effects Of Infliximab On The Fibrosis Response Of Three-Spine Stickleback, Mita Kale

Honors Scholar Theses

This study was conducted to determine if the monoclonal antibody drug infliximab could effectively suppress the fibrosis immune response in three-spine stickleback fish. Successful suppression of this response could allow for further study of cestode infection and growth without the presence of fibrosis. Infliximab’s efficacy was investigated through conducting two intraperitoneal injection experiments and examinations of the fibrosis in the body cavity of the euthanized stickleback. We used immune adjuvant alum to induce a fibrosis response without the presence of the S. solidus tapeworm parasite. Ultimately, the differences in fibrosis levels between the treatment groups that received alum and the …

The Disproportionate Impact Of Covid-19 On Women, Ava Stallone

Honors Scholar Theses

The impact of COVID-19 is placing a large strain on women. This can be seen through reports of mental health and financial concerns. Women are more vulnerable to COVID-19 related economic effects due to existing gender inequalities, which in turn may also have a negative effect on mental health. Through this study gender disproportion is looked at between mental health and COVID-19 financial concerns among women and men. The aim is to asses how COVID-19 financial concerns may be contributing to stress, anxiety, and depression. It is hypothesized that; women will report worse mental health and greater economic concerns than …

The Regulation Of Chemokinesis By The Soil Amoeba, Dictyostelium Discoideum, Julia Horan

Honors Scholar Theses

Many types of cells crawl on solid surfaces by amoeboid locomotion. Membrane protrusions, such as pseudopods, are generated by outward directed forces and the cell body retracts to allow the cell to migrate on the surface. The movement can be random, or can be directional in response to diffusible (chemotaxis) or surface associated signals (haptotaxis). It has been known for some time that chemotactic signals also lead to an increase in overall cell speed (chemokinesis), however the mechanism of this speed increase is unknown. This project investigates the cellular signaling pathways involved in the regulation of cell speed by ligands …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

Honors Scholar Theses

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing …

Impact Of Angiogenic And Osteogenic Factors In The Presence Of Biodegradable Piezoelectric Films, Jayla Millender

Honors Scholar Theses

One of the most common causes of bone graft rejection is lack of a vascular network connecting the graft to the existing native tissue – allowing for nutrient flow. Under current grafting techniques, the existing blood vessel network in the patient slowly invades the implant in order to supply the injured site with its necessary nutrients. The purpose of this research is to determine if a synthetic bone graft with a stable microvascular network can be developed in vitro. I hypothesize that the use of indirect angiogenic factors such as sonic hedgehog homolog and hypoxia-inducible factor-1 in combination with the …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Development And Evaluation Of Novel Da Transport Inhibitors And Their Effects On Effort-Related Motivation: A Review, Mukund Desibhatla

Honors Scholar Theses

Depression is a debilitating disorder that can cause motivational deficits such as psychomotor retardation, anergia, apathy, and fatigue. Recent research indicates that these motivational deficits, and potential pathways of therapeutic intervention, can be studied in animal models involving rats and mice. Treatments with the VMAT-2 inhibitor tetrabenazine (TBZ) and cytokine interleukin-1ß (IL-1ß) can create a low-effort bias and impair effort-related motivation (Nunes et al. 2013, 2014). A number of high-affinity DA transport inhibitors such as d-amphetamine, methylphenidate, and cocaine can restore extracellular DA, albeit with the cost of undesirable effects such as high abuse liability. These observations have led researchers …

The Effects Of Poor Maternal Nutrition During Gestation On Colostrum And Milk Quality And Immunoglobulin G Concentrations In Sheep, Alexandra Bettencourt

Honors Scholar Theses

Maternal over- and under-nutrition have negative effects on the growth and development of offspring. Colostrum and milk are critical to neonatal development, and composition and quality of colostrum and milk may be influenced by maternal factors, including diet. In this study, 46 pregnant ewes received one of three diets, 60% (RES), 100% (CON), or 140% (OVER) of National Research Council (NRC) nutrition requirements for total digestible nutrients from d 30 of gestation until parturition. Colostrum samples were collected within 24 hours of parturition. Milk samples were collected on d 3 and d 21 postpartum. Total solid concentrations of samples were …

Stoichiometry And Parasitism: Changes In Nutrient Concentrations In The Three-Spined Stickleback-Schistocephalus Solidus System, Megan Braat

Honors Scholar Theses

Ecological stoichiometry is a rapidly growing field of study that assesses the elemental composition of organisms in ecosystems and the impact that changes in these elemental compositions have on populations. Parasitism is widely studied for its role in altering the physiology and behavior of hosts within a population. However, the interaction between parasitism and the stoichiometry of the host-parasite system has not been well-established. To determine the impact of parasitism on stoichiometry of host, we measured the elemental composition (%C, %N, and %P) and ratios (C:N, C:P, and N:P) of a population of parasitized and unparasitized Gasterosteus aculeatus (three-spined stickleback) …

Evaluating Urban Parks Accessibility And Equity: A Case Study Of Hartford, Ct And New Haven, Ct, Natalie Roach, Mara Tu

Honors Scholar Theses

Public parks provide cities with environmental benefits, positive health effects, recreational opportunities, community building, educational spaces, and public amenities. However, certain populations have been systematically denied their fair share of these benefits because of unjust practices in the creation and maintenance of urban parks. With a lens of environmental justice, the goal of this research was to assess park quality and accessibility of two Connecticut cities, Hartford and New Haven, by gathering publicly available information as well as using GIS tools.

The Trust for Public Land (TPL) has an existing ParkScore rating system that evaluates the quality of a city’s …

Effects Of Probiotic Supplementation On Growth And Health Of Pre-Weaned Dairy Calves, Lily Bello

Honors Scholar Theses

Dairy calf immune development leaves calves susceptible to illness during the pre-weaned stage of life. Previous studies have shown that the use of probiotics during this time may result in increased growth rates and decreased incidence of illness, particularly diarrhea and scours. We hypothesized that by providing probiotics during the time from birth until weaning, calves on study would experience similar growth and health benefits. Neonatal calves (N=32) were provided milk replacer three times daily, with half of the calves receiving Probios® supplements mixed in with their first morning feeding. Growth and health measurements were collected weekly. Probiotic administration significantly …

Effects Of A Play-Based Intervention On Locomotor Skills And Strength Performance Of Children With Autism Spectrum Disorder, Amber Bardsley

Honors Scholar Theses

Emerging evidence indicates that around 80-100% of children with autism spectrum disorder (ASD) have motor impairments in gross motor skills, strength, and endurance. In the current study, which is a multisite collaboration with the physical therapy programs at the University of Connecticut and the University of Delaware, we are assessing the effects of two types of movement-based interventions compared to a standard-of-care seated play control intervention on motor performance in children with ASD. This thesis will analyze data from one of the movement training groups, i.e., the play group, that involved children engaging in activities based on music, dance, and …

Using Citizen Science To Determine The Age Of Alewife Fish, Rodchill-Paul Jules

Honors Scholar Theses

Aging scales of economically important fish like the Alewife (Alosa pseudoharengus) is a critical task in the fisheries industry, which can benefit from the help that citizen science offers. In order for those benefits to take effect, common people should be comfortable and fairly knowledgeable about what is expected of them in the study. Then, results can be generated in a way that gives all types of citizens a good opportunity to participate and produces reliable data that can be used for scientific purposes. This experiment studied the effects of simple word instructions versus diagramed instructions on the …

A Computational Analysis Of Selective Metabolism Of Bupropion By Cytochrome P450 2b6, Alyssa Santos

Honors Scholar Theses

Bupropion is an antidepressant and smoking cessation aid that is extensively metabolized by cytochrome P450 (CYP) 2B6. It is a highly lipophilic chiral drug that undergoes stereoselective metabolism with preference for the (S)-enantiomer. Despite chemical reasons for why bupropion can be metabolized by other CYP isozymes, clinically, bupropion is preferentially metabolized by CYP2B6, and at certain concentrations, CYP2E1, CYP2C19, and CYP3A4. A computational analysis with simulated molecular docking was performed using two different scoring algorithms to analyze the specific amino acid interactions between bupropion and various CYP isozymes. Trials were run using one stereoisomer of bupropion (R …

Seasonal Plumage Condition Variation And The Thermal Value Of The Feather Coats Of House Sparrows (Passer Domesticus), Jordana Mf Graveley, Margaret Rubega, Kevin R. Burgio

Honors Scholar Theses

Feathers are critical to how birds thermoregulate, and thus their total energy balance. The feather coat insulates birds by trapping air next to the skin and acting as a physical barrier to heat loss. Despite previous work studying thermal balance in birds, relatively few studies have focused on the thermal contribution of the feather coat alone; most studies have focused on physiological and behavioral responses. Moreover, to our knowledge, no studies have directly measured the effect of feather wear through the annual cycle on the thermal performance of the feather coat. To address this, we used a thermal camera to …

Evaluating The Effect Of Glyphosate On Host Survival And Microbiome, Sandro Cloiseau

Honors Scholar Theses

Glyphosate (N-(Phosphonomethyl) glycine) is the active ingredient in Round-Up Inc. Commonly known as a weed killer, glyphosate targets the enzyme 5-enolpyruvylshikimate-3- phosphate synthase (EPSPS) in the shikimate pathway. Ultimately, glyphosate selectively induces toxicity, targeting EPSPS present in plants and selected microorganisms. Therefore, glyphosate is anticipated to be harmless to animals and humans. Our laboratory studies Drosophila melanogaster - also known as the fruit fly, in an interest to understand its gut microbiota and immune system. The comparable immune response of the model organism is similar to honey bees, fungi, and humans. To understand the effect of glyphosate on host physiology, …

Single-Fluorophore Sensors For Mechanical Force In Living Cells, Sarah Kricheff

Honors Scholar Theses

Mechanotransduction is the process by which a mechanical stimulus is converted to a cellular signal. This process is heavily influential of cell morphology, differentiation, and behavior. However, altered levels of mechanical stimuli are also found in many pathological contexts. For example, cancerous cells have stiffer surrounding tissue than healthy cells, and research suggests that this alters cell behavior and promotes metastasis. Despite these findings, the cellular processes behind these signaling alterations remain widely unknown. Understanding these cascades is critical, as involved proteins can give us a deeper understanding of the role of mechanotransduction, and certain proteins can potentially be targeted …

The Genetic Influence On Subjective Well-Being: A Review Of The Current Knowledge On The Role Of Genetics On Our Sense Of Subjective Well-Being And The Implications It Has For Future Research In Improving Well-Being At Both A Population And Individual Level., Abhishek Gupta

Honors Scholar Theses

This thesis project explores the genetic underpinnings of one of the most cherished attributes in the world, well-being.¹ Specifically, it attempts to understand the influence of the genome on subjective, or experienced, well-being. An investigation was conducted into current literature concerning both the structure of measurement devices of well-being as well as association studies to determine the scope of the correlation that exists between the genome and well-being and identify genetic findings of interest. Ultimately, being able to provide evidence of causality between the genome and sense of well-being at this iteration of well-being and genome research is limited, …

Spirituality As A Moderator Between Ptss And Cardiovascular Reactivity, Kriti Sharda

Honors Scholar Theses

Posttraumatic stress symptoms (PTSS) can be distressing and produce robust cardiovascular symptoms, such as increased heart rate and blood pressure, which have been implicated in higher risk of developing cardiovascular disease (CVD). Identifying factors that may reduce symptoms may suggest therapeutic strategies. One such potential factor is spirituality, given that spirituality is associated with both reducing PTSS and with preventing or improving CVD. We sampled 63 young college women who indicated being exposed to unwanted sexual contact. We asked them to write about their experience while we took heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) …

Study Of A Putative Niche Adapting Operon In Microbes Inhabiting The Gut Of Blood Digesting Animals, Marlene Abouaassi

Honors Scholar Theses

The sialic acid utilization (SAU) operon is a horizontally acquired gene set that allows bacteria to utilize sialic acid as an alternate source of carbon and nitrogen in the guts of blood eating animals. Sialic acid often occurs as a terminal sugar in complex glycoproteins. It functions in cell signaling and adhesion. Sialic acid is an important component of the cellular envelope of animals. Some microorganisms have evolved to decorate their own surface with sialic acid to evade the host’s immune response (molecular mimicry). The SAU operon encodes enzymes that hydrolyze sialic acid from glycoproteins, transport sialic acid into the …

Contributions Of Gyra And Parc Mutations And Qnrs2 Acquisition To Ciprofloxacin Resistance In Aeromonas Veronii Hm21, Daniel J. Silverstein

Honors Scholar Theses

In recent years, ciprofloxacin resistant (CpR) Aeromonas veronii and A. hydrophila strains have been isolated from the wounds of patients receiving leech therapy. Genome comparisons of these CpR isolates revealed the presence of chromosomal mutations in gyrA and parC as well as the gain of qnrS2 on either a large, 34 kb, conjugatable, low-copy plasmid, pAv42, or on a small, 6.8 kb, high-copy plasmid, pAh1471. The minimum inhibitory concentration, MIC, for Cp of these clinical isolates ranged from 1 to ≥32 µg/mL and some harbored a qnrS2 containing plasmid. We wanted to assess the contributions of these factors in an …

3,4-Dihydroxyphenylacetate 2,3-Dioxygenase Modulates The Ability Of Enterobacter Hormaechei To Induce Cryptococcus Neoformans Melanization, Amy Nelson

Honors Scholar Theses

In this study, we performed transposon mutagenesis to create a library of Enterobacter hormaechei mutants and developed a melanization assay to identify mutants that could not induce the typical melanization phenotype in Cryptococcus neoformans. Relevant phenotype labels included: “hypomelanizer”, a total lack of melanization; “hypermelanizer”, an increased melanization; or “abnormal”, an increased melanization with complete color change of the assay plate to a reddish-brown. Genomic sequencing of 47 mutants and bioinformatic analysis allowed us to pinpoint the transposon insertion site in each E. hormaechei mutant to identify the genes that were affected. A single mutant that induced the abnormal …

Kcnq2 Localization In The Brainstem, Christina Valera

Honors Scholar Theses

KCNQ2 channels are potassium channels that serve to control neuronal excitability. Loss of function mutations in these channels are known to cause various forms of epilepsy. Recently, KCNQ2 R201C and R201H gain of function mutations have been shown to exhibit an exaggerated startle response and other unique phenotypes uncharacteristic of epilepsy. These phenotypes resemble hyperekplexia, a condition in which glycine neurotransmission in the spinal cord and brainstem is affected. While KCNQ2 has widespread localization throughout the brain, its presence in the brainstem remains unknown. We used immunostaining to determine the localization of KCNQ2 in the vagus nerve and hypoglossal nerve …

Using Machine Learning To Conduct A Detailed Behavioral Analysis In An Appetitive Social Learning Task, Thomas Shao

Honors Scholar Theses

Learning by watching others, or observational learning, is important for social development and survival. However, not much is known about the brain mechanisms underlying this type of learning. Since the 1960s, observational learning has been widely studied in humans, but developing and analyzing experiments for animals has been challenging. Here, I explore observational learning using a novel paradigm while performing an analysis that involves tracking the rats using an active learning paradigm called DeepLabCut. In this novel paradigm, customized operant conditioning chambers are used for the rats to observe and learn from another animal repeatedly on multiple trials each day. …

Tyrr Regulates The Ability Of Enterobacter Hormaechei To Induce Melanin Production In Cryptoccus Neoformans, Ally Watson

Honors Scholar Theses

The yeast Cryptococcus neoformans is present in the microbiota of many plants and animals and produces melanin, a compound that protects cells against UV light and promotes virulence. Melanin production can be induced by exogenous tyrosine, homogentisic acid, catecholamines, or their precursors such as L-DOPA, all of which may be produced by bacteria. The goal of this study was to investigate the interaction between Enterobacter hormaechei (a mosquito gut isolate) and C. neoformans with respect to the production of melanin by C. neoformans in the presence of E. hormaechei, potentially due to the production of L-DOPA or other metabolites …

The Anti-Proliferative Effects Of Methotrexate And Novel Ucp1162 On Acute Myeloid Leukemia Cell Lines, Jacqueline Klepinger, Charles Giardina, Didem Ozcan

Honors Scholar Theses

Cancer cells proliferate at rapid rates due to the aberrant activity of proteins involved in regulating the cell cycle. This characteristic allows mutated cancer cells to spread and metastasize, causing lesions to form throughout the body. Two treatment conditions, one classical antifolate methotrexate (MTX) and non-classical, novel antifolate UCP1162, were tested on a panel of acute myeloid leukemia (AML) cell lines to determine if UCP1162 has higher anti-proliferative activity. High dose MTX is used as a first line chemotherapy in common childhood malignancies such as acute lymphoid leukemia (ALL). Methotrexate is excluded from acute myeloid leukemia (AML) treatments based on …

Remapping Of Place Cells In The Dorsal And Ventral Hippocampus In Response To Environmental Change, Aditi Anam

Honors Scholar Theses

The hippocampus is an important brain structure involved in memory and navigation of both rats and humans. Neurons in the hippocampus can be “spatially” tuned, meaning they fire in specific physical locations. These spatially tuned cells are referred to as place cells. Collectively, they are thought to provide a map-like representation of the environment around us. If the environment is changed, some place cells can adjust by “remapping”, or altering their firing patterns. There are multiple sub-regions within the hippocampus. During experiments, cells were recorded simultaneously from the dorsal and ventral hippocampus of rats running on a track for food …