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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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …