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Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …

Illuminating The Drivers Of Genomic Diversification In Lamprologine Cichlids Of The Lower Congo River, Naoko P. Kurata

Dissertations, Theses, and Capstone Projects

Freshwater fishes are extraordinarily diverse, considering their available habitats represent a tiny proportion of the earth’s surface. Rivers connect heterogeneous habitats in a linear form and provide excellent simplified models to understand how aquatic biodiversity evolves. In particular, the lower Congo River (LCR) in west Central Africa consists of a dynamic hydroscape exhibiting extraordinary aquatic biodiversity, endemicity, and morphological and ecological specialization. This system is thus an excellent natural laboratory for understanding complex speciation and population diversification processes. In my research, I explore various drivers of diversification, and adaptive evolution in rheophilic lamprologine cichlids endemic to the LCR, including Lamprologus …

Extraction Of Challenging Forensic Samples Using The Microgem Dna Extraction Kit, Falyn R. Vega

Student Theses

In forensic science, DNA extraction can be a tedious and resource-intensive process. Extraction with Proteinase K is an industry standard but has its drawbacks, such as requiring multiple ionic detergents and washing steps. MicroGEM has developed a new enzyme called forensicGEM that is temperature-dependent and compatible with mesophilic enzymes, offering complete DNA extraction in about 20 minutes in a single tube, limiting contamination, loss of sample, and working time. ForensicGEM can extract DNA from highly degraded samples, potentially leading to more complete STR profiles. Highly degraded tissue and bone samples were collected and extracted with the forensicGEM …

Examining Transcriptional Regulators During Muscle Development In Drosophila Melanogaster, Chaamy Yapa

Student Theses and Dissertations

In Drosophila melanogaster embryos, a distinct approach to study the transcriptional regulation is to examine the larval somatic muscle development. Transcription factors are essential regulatory proteins that help to control gene expression and respond to signaling pathways and various cues. Today, there are at least twenty transcription factors that have been discovered to contribute to the development of the 30 distinct larval somatic muscles in each abdominal hemisegment of Drosophila melanogaster. Several studies have already been conducted on muscle regulatory transcription factors including midline and apterous. These transcription factors were shown to control the development of muscles through mutant …

The Effects Of Glycolytic Mutations In Drosophila Melanogaster Muscle Development, Coco Lim

Student Theses and Dissertations

Muscle atrophy, or muscle wasting, is caused due to lack of physical activity for an extended period of time, due to muscle diseases (such as muscle dystrophies), cancer chemotherapies, and aging. It is also extensively found on astronauts after spaceflight, particularly missions of long durations. Muscle cells are dependent on different metabolic pathways to optimize Adenosine triphosphate (ATP) production to compensate for muscle exertion. Glycolysis converts glucose into ATP producing pyruvate, which can be sent into the citric acid cycle or converted to lactate (lactic acid). Muscles preferentially use lactate production, despite the fact that fewer molecules of ATP are …

Tgf-B Signaling Mechanisms In Caenorhabditis Elegans Response To Bacterial Pathogens, Emma J. Ciccarelli

Dissertations, Theses, and Capstone Projects

When exposed to infection, the nematode C. elegans mounts an innate immune response through secretion of antimicrobial peptides (AMPs). Different signaling pathways in the worm regulate release of these AMPs. One highly conserved pathway is the C. elegans BMP like pathway – regulated by the ligand DBL-1. The DBL-1 pathway is noted for its significant role in development but has also been shown to regulate many post-developmental processes within the worm, including the immune response. We are interested in determining how DBL-1 signaling can mediate a response specific to immunity, separate from its other functions in the worm. Through survival …

Fine Characterization Of Leafing Phenology In The Brazilian Atlantic Forest By Optical And Microwave Remote Sensing, James B. Bell

Dissertations and Theses

Tropical forests provide important ecosystem functions in the global biosphere, but they remain among the most poorly understood elements of land surface models, especially with regard to their seasonal dynamics. For instance, in seasonally dry forests, the pattern of the annual green-up in their canopies closely follows annual patterns of rainfall. The same, however, does not occur in wet forest canopies which are dominated by evergreen trees. In the latter, water is not scarce enough to limit leaf photosynthetic function. Canopy leafing phenology in these forests is therefore poorly characterized by optical remote sensing methods which are not sensitive to …

Function Of Atm And Msh2 During Dna Repair And Recombination, Emily Sible

Dissertations, Theses, and Capstone Projects

Class switch recombination (CSR) produces secondary immunoglobulin isotypes and requires AID-dependent DNA deamination of intronic switch (S) regions within the immunoglobulin heavy chain (Igh) gene locus. Non-canonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal S regions. ATM-dependent phosphorylation of AID at serine-38 (pS38-AID) promotes its interaction with APE1, a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm^-/- mice …

Role Of The G Protein Beta Gamma Subunits In Serotonin Transporter Dynamics, Nora Awadallah

Dissertations, Theses, and Capstone Projects

Serotonin is a vital neurotransmitter and hormone with significant roles in almost every organ system. In the central nervous system, serotonin mediates physiological functions that in turn guide behavior and mood. Here, serotonin is released from serotonergic neurons and exerts its effects through serotonin receptors. Regulation of serotonin neurotransmission is important for the maintenance of its physiological functions; thus, extracellular serotonin must be sequestered to limit the intensity and duration of serotonin transmission. Disproportionate transmission is strongly linked with neurological and psychiatric ailments.

Extracellular serotonin levels are primarily mediated by the serotonin transporter (SERT), a critically important plasma membrane protein …

Gamma Protocadherin Synaptic Localization And Intracellular Trafficking Is Consistent With Distinct Adhesive And Anti-Adhesive Roles In Development, Nicole Lamassa

Dissertations, Theses, and Capstone Projects

Clustered protocadherins (Pcdhs) constitute a family of cell adhesion molecules with approximately 60 Pcdh genes clustered in a 1 MB locus on chromosome 5q31 in humans. The Pcdh gene cluster is subdivided into α, β, and γ subclusters which encode related proteins. Individual neurons activate different subsets of Pcdh-α, Pcdh-β and Pcdh-γ genes by epigenetic mechanisms to generate distinct Pcdh adhesive units expressed by each neuron. This is thought to serve as a “surface barcode” for single-cell identity and synaptic recognition in the nervous system. The actual role for Pcdhs in neural development is still relatively unknown and different roles …

Clustered Protocadherins Ubiquitination And Phosphorylation Regulates Surface Expression, Albert Ptashnik

Dissertations, Theses, and Capstone Projects

Clustered protocadherins (Pcdhs) are a family of 60 adhesion-like molecules forming a neural barcode. In vertebrate neurons, 60 Pcdhs are coded by a large gene cluster. Numerous axons in the cluster are coding for the different extracellular, transmembrane, variable portion of the cytoplasmic and constant cytoplasmic domains where their expression is controlled epigenetically. These proteins mediate interactions between axons, dendrites, and glial cells during neural development. Yet, Pcdhs are not strictly adhesion molecules. In the amacrine cells of the retina, Pcdhs promote avoidance of the same cell dendrites, where in the cortex Pcdhs promote interactions between dendrites and astrocytes. In …

Nup211 Plays An Important Role In Regulating Mrna Export And Stress Response, Ayana Ikenouchi

Theses and Dissertations

Nup211 is a nuclear pore basket component in Schizosaccharomyces pombe and roles in the gating functions of NPCs. Using RT-qPCR, I found that in nup211-shutoff cells, the transcript levels of genes in mRNA export and stress-response pathways were significantly changed, suggesting nup211 is involved in regulating stress response pathways.

Biological Factors Affecting Dna Shedding Propensity, Ines G. Cedillo-Cruz

Student Theses

Recovery of trace DNA is important in forensic casework because it is the main type of biological evidence found in both violent and non-violent crimes. Researchers have been trying to determine if there are individual differences in shedding propensity, or how much DNA an individual leaves behind. A model for determining this would benefit evidence interpretation if passive transfer scenarios are being considered, as it can affect the probative value of DNA evidence. This study compared the amount of DNA collected with adhesive D-Squame tape disks from the fingers of individual’s washed non-dominant and dominant hands after 30 minutes of …

Robert Rosen And Relational System Theory: An Overview, James Lennox

Dissertations, Theses, and Capstone Projects

Relational system theory is the science of organization and function. It is the study of how systems are organized which is based on their functions and the relations between their functions. The science was originally developed by Nicolas Rashevsky, and further developed by Rashevsky’s student Robert Rosen, and continues to be developed by Rosen’s student A. H. Louie amongst others. Due to its revolutionary character, it is often misunderstood, and to some, controversial. We will mainly be focusing on Rosen’s contributions to this science. The formal and conceptual setting for Rosen’s relational system theory is category theory. Rosen was the …

Understanding Species Interactions And Their Impacts In Restored Communities, Jennifer Zhu

Dissertations, Theses, and Capstone Projects

Species interactions may mediate the ability of organisms to survive in a community and provide valued services but are rarely fully considered in restoration planning. To address this, I considered how service provisioning will change as restored marsh communities mature and the value of incorporating antipredator training into captive-rearing programs.

For chapter 1, I explored how a facultative mutualism between Atlantic ribbed mussels Geukensia demissa and cordgrass Spartina alterniflora may enhance marsh growth and nitrogen cycling in a eutrophic setting. I created experimental plots in Jamaica Bay, NY, that contained live mussels, mussel shells, or no mussels (control) and measured …

Molecular Mechanisms Of Microrna-1205 In Aggressive Prostate Cancer, Michelle K. Naidoo

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men in the United States. High mortality rates of PCa are associated with metastatic castration-resistant prostate cancer (mCRPC) due to the maintenance of androgen receptor (AR) signaling despite androgen deprivation therapies (ADTs). Resistance to second generation ADTs leads to the progression of AR-independent treatment related-neuroendocrine PCa (t-NEPC), which is observed in nearly 1 in 5 men with mCRPC and is associated with very poor outcomes. The 8q24 chromosomal locus is a region of very high PCa susceptibility that carries genetic variants associated with PCa aggressiveness. Located at this …

Novel Strategies For Glutamate Clearance In The Glia-Deprived Synaptic Hub Of C. Elegans, Joyce Chan

Dissertations, Theses, and Capstone Projects

As the major excitatory neurotransmitter in the mammalian brain, Glutamate (Glu) is critical for normal neuronal physiology. Disruption in Glu clearance results in hyper-stimulation of glutamatergic circuits, potentially leading to excitotoxic neurodegeneration. The canonical model of brain connectivity describes glutamatergic synapses as well insulated and enveloped by glia. These glia express Glu Transporters (GluTs) which work to clear Glu following synaptic activity. However, critical areas of the brain such as the mammalian hippocampus display poor synaptic isolation, which may result in Glu spillover between adjacent synapses and subsequent loss of circuit specificity. How accurate signal transmission is achieved in these …

The Role Of Slu7 In Spliceosome Function In Saccharomyces Cerevisiae, Sovira A. Chaudhry

Theses

The removal of introns from pre-messenger RNA via splicing in the nucleus is an essential step in gene expression. In recent decades, significant effort has been made to understand the chemical mechanisms of splicing reactions and the composition of the spliceosome that catalyzes them. Yet very little is known about the exact function of many splicing factors and small proteins within the spliceosome. Slu7, a pre-mRNA splicing factor, is essential during the second catalytic step of splicing because it interacts with several proteins and stabilizes the active site conformation. It has been found that Slu7 is involved in 3' splice …

The Role Of Rna Helicase Rhau In Immunoglobulin Class Switch Recombination, Sabine Jean Guillaume

Dissertations and Theses

B cells alter the expression of immunoglobulin isotypes through a process known as class switch recombination (CSR). In these cells, activation induced cytidine deaminase (AID) binds Gquadruplex (G4) switch transcripts, which serve as guide RNAs to target AID to the immunoglobulin heavy chain switch (S) regions in the DNA for CSR. Sequence alignment revealed homology between the AID G4 binding domain and the RNA helicase associated with AU-rich element (RHAU) specific motif (RSM), which allows RHAU binding to G4 RNAs and subsequent unwinding of G4 RNA into single-stranded transcripts. We hypothesize that RHAU functions in CSR by binding G4 S …

Exosome- And Microrna-Based Therapeutic Approach For Tendinopathy, Angela Wang Ilaltdinov

Dissertations and Theses

Tendinopathy, characterized by degeneration and chronic inflammation, is a significant clinical burden. Current treatments focus on symptom management but do not sufficiently address its underlying pathology; however, stem cell-based approaches aimed at repairing diseased tissues may overcome this limitation. Therapeutic effects of stem cells may be due in part to paracrine actions, including some mediated by exosomes – extracellular vesicles secreted by cells that play a role in cell communication. MicroRNA (miRNA), small non-coding RNA carried by exosomes, are likely responsible for many exosome effects. Exosomes and miRNA therapies show promise in treating diseases such as cancer and arthritis, but …

Evaluating A Test For Shedding Propensity Using Tape Lifts From Different Skin Locations, Xiao M. Chen

Student Theses

The shedding propensity of a person can assist data interpretation in casework when assessing the possibility of passive transfer for DNA analysis. Past studies on shedding propensity evaluated palmar skin (washed and unwashed) deposits. This study compared different skin locations with respect to shedding propensity, and explored the potential of tape-lifts as a skin surface collection method. Eight different skin types and samples were collected with adhesive tape disks from 28 participants over three non-consecutive days; the washed and unwashed fingers from both hands, toe, and arm, neck below ear, and nape. Samples were extracted, quantified, amplified, genotyped, and evaluated …

Understanding The Influence Of Zinc On Grain Cadmium Accumulation And Bioaccessibility In Rice, Michael A. Tavarez

Dissertations, Theses, and Capstone Projects

The effect of cadmium and zinc on mineral concentrations in three cultivars of rice

Interactions between the essential mineral zinc (Zn) and the toxic heavy metal cadmium (Cd) play an important role in regulating transport of both minerals to rice grains. Understanding these interactions is crucial for limiting cadmium and increasing zinc transfer to the food chain. Previous studies on the matter have had conflicting results suggesting synergistic and antagonistic relationships between the minerals. The goal of this work was to identify the effect of external cadmium and zinc on the uptake and translocation of both minerals from roots to …

Estrogen Modulation Of Vta Dopamine Neuron Physiology And Behavioral Responsivity To Variable Social Stressors, Mary R. Shanley

Dissertations, Theses, and Capstone Projects

The behavioral output of different animals, or even the same animal in different contexts, is remarkably variable in response to the same external stimulus. This behavioral diversity is due to the complex integration of external and internal stimuli, through both neuronal and hormonal signals that selects the best behavioral response. By their nature as long-distance signaling molecules, hormones play a critical role in communicating information about internal states across the organism. Many hormones produced in the periphery target the central nervous system to modulate animal behavior, selecting for behaviors that are appropriate over behaviors that are maladaptive in that specific …

Three Lc-Ms Plant Metabolomics Studies Of Hop (Humulus) Species: Wild H. Neomexicanus, Drought Stress, And Agricultural Terroir, Taylan Morcol

Dissertations, Theses, and Capstone Projects

The hop plant (Humulus L., Cannabaceae) is a dioecious, perennial, twining vine with a long history of human use. Nowadays, hop plants are generally grown for their inflorescences (“cones”), which are used in brewing for their phytochemical metabolites. Many of these metabolites are involved in plant stress response and communication. Genetics and environment are two major factors that affect plant metabolism. In three separate metabolomics studies, this project examined the effects of both genetic and environmental factors on hop phytochemistry.

In the first study, 23 hop genotypes were grown in two different locations in the Pacific Northwest region of …

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

Molecular Mechanisms Underlying Cell Fate Choice Within Specific Retinal Lineages, Estie Schick

Dissertations, Theses, and Capstone Projects

During development, retinal progenitor cells (RPCs) divide to form all of the cell types that make up the retina. Multipotent RPCs are competent to generate all retinal cell types, while restricted RPCs form specific lineages of cells. In particular, one genetically-defined RPC type preferentially gives rise to cone photoreceptors and horizontal cells. Many of the mechanisms that are responsible for directing cell fate choice within this lineage are unknown. This thesis largely focuses on examining the development of specific cell types and subtypes from restricted RPCs and on investigating the gene regulatory events that underlie cone photoreceptor and horizontal cell …

Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich

Student Theses and Dissertations

Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary …

Cell Cycle Progression Effects Of Albumin, Sharmeen Uddin

Dissertations, Theses, and Capstone Projects

Progression through G₁ phase of the cell cycle is controlled largely by growth factors in early G₁ and by nutrients in late G₁ indicating sufficient raw material for cell division. We previously mapped a late G₁ cell cycle checkpoint for lipids upstream from a mammalian target of rapamycin complex 1 (mTORC1)-mediated checkpoint and downstream from a mid-G₁ checkpoint known as the Restriction point. We therefore investigated a role for lipids in progression through late G₁ into S-phase. Quiescent BJ-hTERT human fibroblasts primed back into G1 with FBS treatment, were treated with a mixture of …

The C. Neoformans Cell Wall: A Scaffold For Virulence, Christine Chrissian

Dissertations, Theses, and Capstone Projects

Cryptococcus neoformans is a globally distributed opportunistic fungal pathogen and the causative agent of life threatening cryptococcal meningoencephalitis in immunocompromised individuals, resulting in ~180,000 deaths each year worldwide. A primary virulence-associated trait of this organism is the production of melanin. Melanins are a class of diverse pigments produced via the oxidation and polymerization of aromatic ring compounds that have a characteristically complex, heterogenous, and amorphous structure. They are synthesized by representatives of all biological kingdoms and share a multitude of remarkable properties such as the ability to absorb ultraviolet (UV) light and protect against ionizing radiation. Melanin production in fungi …