Digital Commons Network^™

Investigating Propargyl-Linked Antifolates In Inhibiting Bacterial And Fungal Dihydrofolate Reductase, Joshua Andrade

Honors Scholar Theses

Antimicrobial agents have been invaluable in reducing illness and death associated with bacterial infection. However, over time, bacteria have evolved resistance to all major drug classes as a result of selective pressure. The advancement of new drug compounds is therefore vital. The Anderson-Wright Lab has focused on developing potent and selective inhibitors of dihydrofolate reductase (DHFR), an enzyme key in cell proliferation and survival, in several pathogenic species. The lab has found that a set of compounds, known as propargyl-linked antifolates, are DHFR inhibitors that are both biologically effective and have strong pharmacokinetic properties.

The efficacy of novel propargyl-linked antifolates …

Developing Crosslinking Constructs Of Protein Kinase R, Prisma E. Lopez

Honors Scholar Theses

Protein Kinase R (PKR) is a key component of the innate immune antiviral response. PKR is activated upon binding to dsRNA. However, recent studies have shown that PKR can also bind to and become activated by duplex RNAs containing complex secondary structure. The mechanism of PKR binding and activation by these RNAs is currently not known. The approach taken here to determine the mechanism of PKR binding by these RNAs is through the development of PKR constructs that are capable of covalently binding to RNAs. Constructs were created by site-specific incorporation of an unnatural, photoactivatable amino acid within PKR. These …

Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo

Honors Scholar Theses

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model …

Chemical Profiling And Biological Activity Of Two Tunicate-Associated Marine Bacteria, Lyubina Yankova

Honors Scholar Theses

Marine natural products have recently been an increasingly abundant source of novel antibiotics. Given that there is an increasing resistance to current drug therapies, finding new sources such as marine natural products is essential. Tunicate-associated marine bacteria can be a significant source of antibacterial compounds. Two tunicates of the species Eudistoma were collected from Portobelo National Park on the Salmedina Reef of Panama in the Caribbean Sea. Bacteria associated with the tunicate were isolated, cultured, extracted, and fractionated. Fractions were tested against an array of clinically relevant bacterial pathogens in the BioMAP assay. Two fractions MB0086E and MB0088E demonstrated activity …

An Examination Of The Phylogenetic Diversity Of Green Algae (Chlorophyceae) That Symbiose With Spotted Salamanders (Ambystoma Maculatum) In The Egg Stage., Crystal Xue

Honors Scholar Theses

In 1909, the species Oophila amblystomatis Lambert ex Wille was described for green algae that symbiose with salamanders in the egg stage (Wille). There are two hypotheses about the source of algae: 1) that algae enter from the surrounding water once the egg clutch is laid in a pond, and 2) that they are acquired from the maternal reproductive tract. We developed a third hypothesis developed to account for the salamander reproductive cycle. Male salamanders lay spermatophores, which are protein-filled capsules, on plant matter in and around ponds. Spermatophores are exposed to the environment before use by females in internal …

Characterizing And Improving The Oral Sensations And Preference Of Polyphenol-Rich Aronia Berry Juice, Jeeha Park

Honors Scholar Theses

Background: Aronia berries (chokeberries) have very high levels of health-promoting polyphenols yet cause "choking" sensations due to bitterness and astringency. We aimed to describe oral sensations and palatability of aronia juice by variations in harvest time and oral sensory phenotype. Sensory blocking combinations were tested to improve juice acceptability. Methods: Ripe aronia berries were harvested at 7 time points and juiced for oral sampling by 50 adults who underwent bitter taste phenotyping. The adults reported quality intensities of prototypical tastes, foods, and aronia juices. Ethyl butyrate (10ppm) and/or sucrose (0.15 and 0.3M) were added to prototypical oral stimuli and aronia …

Do Visitors Affect Zebra Behavior In Zoos?, Christine Conte

Honors Scholar Theses

I investigated the effects of visitors on the behavior of two zebra species (Equus grevyi and Equus burchelli) at eight zoos on the East Coast of the United States. I used instantaneous time sampling to record zebra behavior and visitor data. I used these data to run Bayesian hierarchical models and determined that visitors do not negatively affect zebra behavior. This is a positive finding for zoos, since it means that zebras, a highly skittish prey animal, are not disturbed in their exhibits. My data suggest there are behavioral differences between the zebra herds at different zoos, which …

Mutagenesis Of 8-Oxoguanine Adjacent To An Abasic Site In Escherichia Coli Cells Proficient Or Deficient In Dna Polymerase Iv, Savas T. Tsikis

Honors Scholar Theses

It is well established that clustered DNA damages or multiply damaged sites (MDS) are the result of ionizing radiation and that they are characterized by an enhanced mutagenic potential. As a model MDS, we have evaluated the mutagenic and cytotoxic properties of the ubiquitous oxidative DNA damage 8-oxoguanine (G^8-oxo) adjacent to the abasic site lesion (Z) using a single stranded M13mp7L2 vector. The recombinant DNA was used to transform wild type E. coli strains and strains deficient in the translesion DNA polymerase of the Y-family, DNA polymerase IV, in the presence or absence of SOS induction. The percent …

The New Normal: Goodness Judgments Of Non-Invariant Speech, Julia R. Drouin

Honors Scholar Theses

Previous research has found that perceptual learning, or normalizing the idiosyncratic phonemes of speech, causes a shift in speech sound category boundaries. The present study examined if perceptual learning was limited to the boundary or if also caused a shift in internal category structure. Seventeen individuals participated in three behavioral tasks to explicate this question. In the Lexical Decision task, participants were trained in either /s/-biasing or /ʃ/- biasing context. In the Goodness Judgment task, participants rated a continuum of sounds on perceived /s/ goodness using a designated scale. Finally, in the Phoneme Identification task, participants listened to the same …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Numerical Assessment Of Sequence Conservation In Flu-Virus Hemagglutinin, Scott S. Norton

Honors Scholar Theses

The flu virus was investigated to find a common recognition domain to which an antibody against human-infected viruses can bind. If such a target site is structurally and electrostaticly conserved or invariant, only a single antibody would be required to attack the virus in all cases. The sequence of one of the viral surface proteins contains 24 amino acids that do not vary through mutation. However, these amino acids are neither contiguous in sequence or in space, and the ones that are associated with each other are not readily accessible to an antibody. They do provide a first impression of …

The Effect Of Repeated Mild Traumatic Brain Injury On Ventricular Volume And Microglial Activation, Lillian Rose Talbot

Honors Scholar Theses

As the leading cause of death and disability in individuals under the age of 45-years-old, Traumatic Brain Injury (TBI) is a public health crisis that demands the attention of the scientific and medical community [28]. The majority of all TBIs that occur in the United States each year are a non-deadly yet detrimental form of closed brain injury known as mild TBI (mTBI) or concussion [6]. Athletes, young people and military personnel all face a high risk of acquiring mTBI as a result of their environments. In our study we have chosen to model repeated mTBI (rmTBI) in the mouse …

Pelargonium (Geraniaceae) And The Long-Tongued Fly Pollination Guild: Coevolution And Polymorphism In A Specialized Pollination System, Emily M. Blank

Honors Scholar Theses

In South Africa, a group of long-tongued flies and the flowering plants they pollinate form a unique and diverse pollination guild system almost entirely endemic to the Greater Cape Floristic Region. This system makes up only a small portion of the biodiversity of the Region, but it is likely a key to understanding the evolutionary processes that have lead to the observed biodiversity. Aside from its unusual pollinators, this guild system is of particular interest due to the extremely labile morphology of both the fly species and the associated flowering plant species, which geographically vary significantly in proboscis lengths and …

Detection Methods For Small Analytes: Improvement Of Novel Spr Technology Detection Of Toxins And Toxicants, William B. Ollayos

Honors Scholar Theses

Humans are exposed to a variety of toxic substances in their day-to-day activities that may have adverse health effects if not properly identified. An integrated dual-mode instrument that combines grating-coupled surface plasmon resonance (GCSPR) and grating-coupled surface plasmon coupled emissions (GCSPCE) should allow for the efficient detection of toxic analytes in a high-content system using gold-coated superparamagnetic nanobeads. The goal of this study is to validate the binding characteristics of the reagents intrinsic to this innovative assay methodology. Competition enzyme-linked immunosorbent assays (ELISA) and surface plasmon resonance (SPR) assays were conducted on NNK toxicants and SEB toxins, which were the …

Characterization Of Udp-Arabinopyranose Mutase Genes In The Arabidopsis Cell Wall Mutant Mur5, Christopher A. Hart

Honors Scholar Theses

The genome of Arabidopsis thaliana contains several coding regions for UDP-arabinopyranose mutases (UAMs) that are also known as reversibly glycosylated polypeptides (RGPs). The mur5 cell wall mutant of Arabidopsis shows a 30% decrease in cell wall arabinose content, and a missense mutation in the Reversibly Glycosylated Polypeptide 2 gene was recently proposed to cause this mutant phenotype. Through a traditional complementation analysis, mur5 and a T-DNA insertion mutant in the RGP2 gene were shown not to complement each other, indicating that the two genes are mutant alleles of the same locus. The mur5 SNP located in RGP2 caused a more …

Methods Of Bovine Reproduction, Kelsey L. O'Donnell

Honors Scholar Theses

The beef and dairy cattle industries are of immense economic value in the United States and have made impressive advancements over the past century. Their success depends strongly upon the reproductive efficiency of their breeding programs. This overview discusses the major advancements in bovine reproduction that have been integrated into the beef and dairy cattle industries and also the emerging technologies that are currently being researched. Current practices like artificial insemination and estrus synchronization resulted from the development of a strong understanding of cattle physiology and the endocrinology of the estrous cycle. With these technologies, selection of superior genetic traits …