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Investigating The Role Of Tryptophan In The Native Photo-Crosslinking Of A Cys-Containing Transmembrane Helix To A Membrane Lipid Double Bond, Michael Jay Telehany

Undergraduate Honors Theses

Our research group has previously discovered that a Cys residue within a transmembrane (TM) helix can directly photo-crosslink to a membrane lipid via an oxythiolation addition reaction to the double bond within the lipid, with a reaction yield of 10-20%. The pH-low Insertion Peptide (pHLIP) serves as our model TM helix, while the POPC lipid bilayer is our model membrane. We had long believed that the Trp residues within the sequence of pHLIP served as the key chromophore for this reaction, and thus they were essential for the formation of the TM helix-lipid adduct. To test this hypothesis, I synthesized …

Ethanol-Induced Alterations To Astrocytic Glutamate Transporter Mrna Expression In The Mpfc Of Adult Mice, Zachary Evans

Undergraduate Honors Theses

The medial prefrontal cortex (mPFC) is one of several brain structures that is contained in the mesolimbocortical pathway and controls many processes involved in alcohol use disorder (AUD). There is vast glutamatergic output from the mPFC to other mesolimbocortical regions; neuroplastic changes to this system are believed to be closely tied to the development and maintenance of AUD. Astrocytes are key regulators of glutamatergic transmission through their uptake of excess glutamate from the synapse and recycling back into neurons. Ethanol (EtOH) alters the expression of astrocytic genes that encode for transporters that control glutamate homeostasis; these include the glutamate transporter-1 …

Variation In Sign-Tracking And Goal-Tracking Behaviors In A Genetically Diverse Inbred Panel Of Mice, Emily A. Schoenblum

Undergraduate Honors Theses

No abstract provided.

Effects Of Acute And Repeated Alcohol Exposure On Expression Of Synaptic-Associated Genes In The Male And Female Mouse Mpfc, Dhruba Podder

Undergraduate Honors Theses

Alcohol use disorder (AUD) is a serious chronic brain disease; in 2021 there were ~29.5 million people in the U.S. diagnosed with AUD. Individuals with AUD often show cognitive impairment such as risky decision-making, difficulties with impulse control, and working memory deficits. This impairment is associated with structural and functional changes in the prefrontal cortex (PFC), an extensively interconnected region of the frontal lobe involved in executive control of goal-directed behaviors. Chronic alcohol exposure in rodents has been seen to cause deficits in performance in behavioral tasks which assess mPFC function such as working memory and behavioral flexibility. It is …

The Synthesis Of 3-Formyltyrosine For The Purpose Of In Virto Fluorescent Visualization Of Microtubules, Angelina Bonacasa

Undergraduate Honors Theses

Microtubules and the desire to visualize them has been of utmost importance in understanding the behavior of the cytoskeleton. Even further, scientists are using this knowledge to elucidate cancerous activities as they occur within cells. In order to acquire this knowledge, the following methods have been established: the expression of tubulin after it has been fused with a fluorescent protein, the insertion of tubulin that has been exogenously labeled, and the use of fluorescent-probe conjugated microtubule ligands, such as paclitaxel. These methods, however, tend to distort the protein’s native function, thereby preventing an accurate analysis. This concern drives the need …

Computational Investigation Of Calmodulin Photocontrol With The Help Of An Azobenzene Derivative, Jeremy Wells

Undergraduate Honors Theses

The ability to control the activity and binding capability of enzymes in a reversible manner offers tremendous control over biological processes. Photocontrol, in particular, is promising in that electromagnetic radiation can be fine-tuned in terms of its strength, location, and duration. Photosensitive compounds, such as the azobenzene family, experience an isomerization at certain wavelengths, and attaching these compounds to enzymes has the potential to alter their structure and activity. Calmodulin (CaM) is a Ca2+ -sensitive signaling protein that has the ability to affect several downstream processes in eukaryotes and is an excellent target for photocontrol due to its small size …

Glypro As A Self-Immolative Spacer For The Release Of Payloads From Antibody-Drug Conjugates, Justin Michael Howe

Undergraduate Honors Theses

Antibody-drug conjugates (ADCs) are an increasingly popular modality for targeted drug delivery in many oncological and immunological applications. The paratope of a monoclonal antibody (mAb) directs the delivery of a conjugated therapeutic payload to antigen expressing cells, resulting in a controlled transport of payload to a desired cell type. Internalization of the ADC followed by lysosomal degradation results in the release of a payload to perform its biochemical function. A chemical linker between the drug and the antibody is responsible for the stability of the conjugate in circulation alongside mediating the release of an unmodified payload under lysosomal conditions. Currently, …

D-Glucose-6-Phosphate Stimulates Sags-Dependent Biofilm Formation In Pseudomonas Aeruginosa, Madison Gowett

Undergraduate Honors Theses

The SagS protein is a two-component regulatory system in Pseudomonas aeruginosa that works to independently regulate biofilm formation and antibiotic tolerance. Previous work found that these two pathways are controlled by two distinct sets of amino acids within the sensory domain of SagS that are thought to be potential ligand binding sites. Despite the extensive research done on the structure and function of SagS, the signals that activate this protein have yet to be identified. In this study we aimed to identify ligands that stimulate SagS-dependent biofilm formation. To do this we utilized ΔsagS mutants, one harboring wild-type sagS under …

Electrophysiological Characterization Of The Inhibitory Effects Of 2-Amino-4-Bis (Aryloxy Benzyl) Amino Butanoic Acids On Alanine Serine Cysteine Transporter 2 And Sodium Coupled Neutral Amino Acid Transporter 2, Paul Serguei Zakrepine

Undergraduate Honors Theses

Alanine Serine Cysteine Transporter 2 (ASCT2) is a member of the solute carrier 1A (SLC1A) family of transport proteins. It is a Na+ dependent, obligatory neutral amino acid exchanger with the capability to transport glutamine and it is a primary glutamine transport protein in cancer cells. This glutamine transport capability confers an important physiological role for ASCT2 in the maintenance of intracellular amino acid pools for various metabolic and cell signaling pathways. Because of this, ASCT2 is found to be overexpressed in many cancers, which rely heavily on glutamine as an essential nutrient for cell survival and growth. A wealth …

Immune System Detection Of Pseudomonas Aeruginosa Persister Cells, Grace Elizabeth Himmler

Undergraduate Honors Theses

Persister cells are a subpopulation of bacterial cells known to be tolerant to antimicrobials. Their reduced susceptibility to antimicrobials allows them to be the source of recurrence of many chronic bacterial infections. As a result, it is vital to understand the mechanisms that allow these cells to be able to evade further treatment. Furthermore, it is currently unknown whether the persister cells are detected and killed by the host immune response. In this work I explored the host-pathogen interactions between Pseudomonas aeruginosa cells, both persister and regular, and human macrophages. I hypothesized that persister cells would be engulfed at a …

Optimization Of Adc Linkers: Design And Evaluation Of A Fret-Based Adc Linker-Library, Jared T. Miller

Undergraduate Honors Theses

Success of Antibody-drug conjugates (ADCs) relies on the maintained integrity of a chemical linker fusing a therapeutic payload to a monoclonal antibody. Recent reports have revealed the lead linker ValCitPABC has poor stability in rodent models compared to mammalian counterparts, resulting in many clinical investigations predicting poorer ADC efficacy due to premature payload release in these model systems. Optimization of this chemical linker to be resistant both in mouse and human models would streamline ADC progression into clinical trials. Herein we describe the synthesis and development of a FRET-based assay for evaluating linker stability in vitro. Evaluation of lysosomal release …

Characterization Of Urban Wetland Vegetation And Management Practices, Megan Anne Larson

Graduate Dissertations and Theses

Urban wetlands are important ecosystems that moderate flooding risks and improve water quality. Vegetation is a key component of urban wetlands; plants promote sedimentation, play critical roles in biogeochemical cycling, and provide food and habitats for other organisms. My research focuses on the standing vegetation and seed banks of urban wetland plant communities. Urban wetlands in south-central New York had a higher percent cover of invasive species in the standing vegetation and significantly lower species richness; however, native species were also common in urban flora. These sites had a high percentage of obligate wetland species, and most closely resembled emergent …

The Role Of Criticality Of Gene Regulatory Networks On Emergent Properties Of Biological Systems, Hyobin Kim

Graduate Dissertations and Theses

The relationship between criticality of gene regulatory networks (GRNs) and dynamics of GRNs at a single cell level has been vigorously studied. However, the relationship between the criticality of GRNs and properties of multicellular organisms at a higher level has not been fully explored. Here we aim at revealing potential roles of the criticality of GRNs at a multicellular and hierarchical level, using a random Boolean network as a GRN. We perform three studies. Firstly, we propose a GRN-based morphogenetic model, and delve into the role of the criticality of GRNs in morphogenesis at a multicellular level. Secondly, we include …

Functional Variation In The Mitochondrial Genome Of The Yeast Saccharomyces Cerevisiae, John F. Wolters

Graduate Dissertations and Theses

Mitochondrial haplotypes contribute to functional diversity in natural populations. Uniparental inheritance makes it difficult to characterize the genetic architecture of mitochondrially driven phenotypes. In this work I explored the natural diversity of mitochondrial genomes in the yeast Saccharomyces cerevisiae. Few complete mitochondrial genomes were available for S. cerevisiae owing to challenges in high-throughput sequencing. I developed sequencing strategies using new technologies to generate complete high quality yeast mitochondrial genomes. Comparisons of 100 complete yeast mitochondrial genomes demonstrated extensive variation between populations in coding sequences and variable introns.

I demonstrated that these mitochondrial variants directly caused growth differences in strains with …

Interaction Graphs Derived From Activation Functions And Their Application To Gene Regulation, Simon Joyce

Graduate Dissertations and Theses

Interaction graphs are graphic representations of complex networks of mutually interacting components. Their main application is in the field of gene regulatory networks, where they are used to visualize how the expression levels of genes activate or inhibit the expression levels of other genes.

First we develop a natural transformation of activation functions and their derived interaction graphs, called conjugation, that is related to a natural transformation of signed digraphs called switching isomorphism. This is a useful tool for the analysis of interaction graphs used throughout the rest of the dissertation.

We then discuss the question of what restrictions, if …

Nitrogen Biogeochemistry In Binghamton, Ny, A Medium-Sized Urban Ecosystem, Stephanie Craig

Graduate Dissertations and Theses

Humans have altered nitrogen (N) cycling on a global scale, and elevated nitrogen levels are characteristic of urban ecosystems. The major reasons that N is higher in cities include imports of food, fuel and fertilizer. High N export from both point- and nonpoint-sources is common in large cities. While N cycling has been studied in large urban areas, less is known about its cycling in medium-sized cities, such as Binghamton, N.Y. We found that point-source N exported from the Binghamton-Johnson City Wastewater Treatment Plant (B-JC WWTP) was greater than nonpoint-source N exported from eight urban streams to the Susquehanna River, …