Digital Commons Network^™

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 …

Unexpected Arousal Suppresses Memory And Metamemory Predictions During Associative Face-Name Recognition Task, Sameer Sabharwal-Siddiqi

Dissertations, Theses, and Capstone Projects

Successful recognition often depends on probabilistic estimation of memory-signal. Arousal has been shown to offset the influence of heuristic evidence on memory prediction. We conducted three experiments that tested whether arousal also suppresses predictions relevant to memory confidence. Experiments employed associative face-name memory tasks that included retrospective (Experiments 1 and 2) or concurrent (Experiment 3) judgements of confidence. During test, subjects were presented with a masked-affective face on a subset of trials. By timing the masked-affective face to precede a recognition judgement (Experiment 1), we replicated the finding that unexpected arousal offsets the influence of heuristic evidence on expectations of …

Novel Therapeutic Strategies For Alzheimer’S Disease: Prostaglandin D2 Signaling And Its Human Polymorphisms As Well As A Polypharmacological Approach, Charles H. Wallace

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is an age related neurodegenerative disease with pathology that includes amyloid plaques, neurofibrillary tangles and non-resolving neuroinflammation. Non-resolving neuroinflammation lasts the entire course of the disease and has deleterious effects and is often thought to accelerate AD pathology. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) have commonly been used as therapeutics to treat pain, inflammation and vascular. NSAIDs work by altering the cyclooxygenase (COX) mediated biosynthesis of prostaglandins which are lipid mediators that have many physiological functions, for example nociception, inflammation and vasodilation. Epidemiological studies support the notion that NSAIDs could be used to treat AD. Yet, clinical trials using …

Development And Characterization Of A Novel, Genetically- Encoded Sensor To Image Sonic Hedgehog Signaling In Functional Circuits, Sonia Bernal

Dissertations, Theses, and Capstone Projects

Dynamic neurotransmitter and neuromodulator signaling in functional circuits is the neural substrate of animal behavior and cognition. The study of said circuits requires tools with sufficient spatiotemporal dynamics that can probe complex signaling patterns and decode their functional relevance by coupling the signal to behavioral output, ideally in awake, behaving animals. Much is known about the role of classical neurotransmitters such as dopamine in behavior, but a wide variety of peptides and small molecules also regulate neuronal transmission. One of these is Shh, whose presence has been observed in a variety of brain regions known to modulate movement, perception, and …

The Effects Of False Heartbeat Feedback On Moral Judgment, Scott Koenig

Dissertations, Theses, and Capstone Projects

Research on human morality is at a crossroads, with one side claiming that moral judgment is the result of rational inference and the other side claiming that it is the result of emotion-laden intuition. This study investigated whether emotion drives moral judgment by manipulating a core component of the experience of emotion: physiological arousal. The sample consisted of 77 undergraduate students at Brooklyn College (57% women, 43% men; mean age = 20.1). One group of participants was led to believe their heart was beating quickly, and another group slowly, while they read and evaluated a series of text vignettes depicting …

Role Of Nuclear Lamins In Oligodendrocyte Lineage Cells, Camila Yattah

Dissertations, Theses, and Capstone Projects

Differentiation of oligodendrocytes from progenitor cells is a highly regulated process characterized by a series of molecular changes, resulting in nuclear and morphological features unique to the mature oligodendrocyte state. Heterochromatin formation starting at the nuclear periphery, as well as increased nuclear rigidity are characteristically observed. The nuclear periphery is characterized by the presence of the nuclear lamina and it has been implicated in higher-order genome organization in cells. Lamins are the protein components of the nuclear lamina, and their expression is dependent upon the cell differentiation stage of the cells. While Lamin B1 (LMNB1) expression is high in progenitors …

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 …

Prenatal Choline Supplementation During Maternal Obesity Alters Offspring Response To Western Diets, Hunter W. Korsmo

Dissertations, Theses, and Capstone Projects

Maternal obesity has led to an increase in adverse offspring developmental outcomes and a greater risk for long-term metabolic diseases. Choline, a semi-essential nutrient, can be incorporated into phosphatidylcholine (PC) as well as sphingomyelin (SM) and donate its labile methyl group for the remethylation of homocysteine after choline is oxidized to betaine. Prenatal choline insufficiency has been related to maternal obesity and metabolic diseases, such as metabolic associated fatty liver disease (MAFLD). Choline may interact with maternal obesity to influence the programming offspring.

Chapter 1 presents an introduction of choline and the various clinical outcomes associated with choline supplementation during …

Mechanism Of Tau Propagation: Putative Therapeutic Approaches, Viktoriya Morozova

Dissertations, Theses, and Capstone Projects

One of the characteristics of Alzheimer’s disease and associated tauopathies is the accumulation and aggregation of hyperphosphorylated tau protein. The biological activity of tau is to bind to tubulin and promote its assembly into microtubules with subsequent stabilization of the latter. When tau gets hyperphosphorylated it cannot bind to tubulin and carry on its function, instead, it binds to normal tau and sequesters it from microtubules leading to disruption of microtubular assembly and ultimately to the death of neurons. Our lab had previously shown that tau phosphorylation sites 199, 212, 231, and 262, combined with the FTDP-17 mutation R406W (Pathological …

Nutrient Dynamics And Ecosystem Development Of Urban Forests, Gisselle A. Mejía

Dissertations, Theses, and Capstone Projects

Urban growth and expansion are a major component of global environmental change, with impacts on climate, air and water quality, biodiversity, and human well-being. Forests embedded in urban landscapes are critical in mitigating these impacts at local, regional, and continental scales. However, assessing urban forests is difficult because cities are heterogenous in physical, chemical, biological, and social dimensions. This heterogeneity has constrained how urban forests are defined, and therefore, how they are studied. The objective of this dissertation is to determine how these biophysical and social factors drive ecological processes in urban forests and will address three outstanding challenges in …

Expulsive Greening: A Cross-Sectional Analysis Of Green Gentrification In The Resilience Paradigm, Brooklyn 2010–2020, Rose Jimenez

Dissertations, Theses, and Capstone Projects

Background: This project analyzes the spatial coincidence between gentrification typologies and urban greening in Brooklyn, New York from 2010 to 2020. Assets formed under the NYC Green Infrastructure Program were chosen as a proxy for urban greening to represent the spatial practice specifically within the 21st-century climate change resilience paradigm of development. Methods: First, five indexes measuring variations of economic and demographic conditions related to gentrification were applied to Brooklyn for comparative analysis: NOAA’s Social Vulnerability Indicators of Gentrification Pressure, The NYC Heat Vulnerability Index, The Small Area Index of Gentrification, Typologies of Gentrification and Displacement, and The Housing Risk …

Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor

Dissertations, Theses, and Capstone Projects

The tumor suppressor p53 (TP53) gene is often mutated in cancer, with missense mutations found in the central DNA binding domain, and less often in the oligomerization domain (OD) and C-terminal domain (CTD). The OD and CTD have been found to be critical for the tumor suppressor functionality of wild-type p53 (wtp53). Specific missense mutations in the DNA binding domain have been found to confer new gain-of-function (GOF) activities. Mutations that destabilize tetramer formation, or deletion of key lysine residues within the CTD, downregulate the ability of wtp53 to transactivate (increase the rate of transcription of) its target …

The Microscopical Evidence Traces Analysis Of Household Dust And Its Statistical Significance As A Definitive Identification Technique, Stephanie Polifroni

Dissertations, Theses, and Capstone Projects

Evidence found at crime scenes is used to assist in creating a link the suspect, the victim, and the scene. As stated by the Locard’s Principle, every contact leaves a trace, that evidence can be used to link together an investigation. Traces are collected in hopes that they can be identified and associated to an individual or individuals to help solve that particular crime. However, the strongest conclusion for evidence traces is an association to a source, and unless a physical match of some kind is found, an individualization cannot be established even when known sample is available. However, having …

Competitive And Facilitative Interactions Between Pavlovian Cues In Human Associative Learning: A Behavioral And Neural Analysis, Fahd Alhazmi

Dissertations, Theses, and Capstone Projects

Learning to anticipate significant events accurately is a crucial element of survival for all species. The process by which animals acquire this knowledge has been a central question of psychological research. A fundamental assumption of many learning theories is that the predictive value assigned to cues is not simply determined by their probability of reinforcement but rather by their ability to compete with other cues present during learning. The assumption of cue competition has significantly contributed to the development of behavioral and neuroscience research for decades, as it has opened the door to new empirical and theoretical advances on the …

Mechanism Of Activation And Regulation Of By-Kinases, A Unique Family Of P-Loop Enzymes, Fatlum Hajredini

Dissertations, Theses, and Capstone Projects

The bacterial tyrosine kinases (BY-kinase) represent a class of membrane-bound enzymes that utilize a cycle of auto-phosphorylation and de-phosphorylation to drive the synthesis and export of exopolysaccharides in both Gram-positive and Gram-negative bacteria. The catalytic domain of BY-kinases utilizes a P-loop nucleoside triphosphatase (NTPase) fold that is commonly used by NTPases and small molecule kinases, being the only protein kinase to do so. In the work presented in this thesis, we aimed to obtain an understanding of the mechanisms of the BY-kinases’ unconventional deployment of P-loop scaffold to phosphorylate on tyrosine. We used the BY-kinase of Escherichia coli (K12) as …

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 …

Conformation Of The U12-U6atac Snrna Complex Of The Minor Spliceosome And Binding By Ntc-Related Protein Rbm22, Joanna Ciavarella

Dissertations, Theses, and Capstone Projects

Splicing of precursor messenger (pre-m)RNA is a critical process in eukaryotes in which the non-coding regions, called introns, are removed and coding regions, or exons, are ligated to form a mature mRNA. This process is catalyzed by the spliceosome, a multi-mega Dalton ribonucleoprotein complex assembled from five small nuclear ribonucleoproteins (snRNP) in the form of small nuclear (sn)RNA-protein complexes (U1, U2, U4, U5 and U6) and >100 proteins. snRNA components catalyze the two transesterification reactions while proteins perform critical roles in assembly and rearrangement. U2 and U6 snRNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA. …

Novel Therapeutic Strategies For Alzheimer’S Disease: Targeting Toll-Like Receptor Signaling And A Multi-Target Approach, Giovanni Oliveros

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is multifactorial, and its hallmarks include the formation of amyloid-beta (Ab) plaques and neurofibrillary tau tangles, accompanied by an increase in glial cell activation, culminating in neurodegeneration, chronic neuroinflammation, and cognitive decline in human patients. AD will cost the United States over $300 million this year alone and is projected to cost over $1 trillion by 2050, AD is a serious concern for the aging population, and efforts need to be redirected towards more effective therapeutic intervention strategies. Drugs aimed at halting AD progression have so far proven unsuccessful due to the development of pharmaceuticals that target …

Antisocial Behavior And Callous Unemotional Traits In Youth: A Biosocial Approach, Yong Lin Huang

Dissertations, Theses, and Capstone Projects

Early life presence of antisocial behavior (e.g., aggression/delinquency) and psychopathic/callous-unemotional (CU) traits (lacking empathy/remorse, shallow affect) are precursors to juvenile crime and criminal offending in adulthood. Etiological research on antisocial/CU tendencies has implicated both neurobiological (e.g., alterations in brain function and structure) and environmental (social adversity, prenatal stress) underpinnings. It has been proposed that reward and punishment processing deficits may induce problematic traits and behavior, such that antisocial/CU tendencies may be linked to hypersensitivity to rewards and hyposensitivity to punishment. Studies in this area have generated inconsistent findings and focused primarily on adult and clinical samples, leaving youth and community …

A Polypharmacological Approach To Relapse Prevention In An Animal Model Of Heroin Addiction, Scott T. Ewing

Dissertations, Theses, and Capstone Projects

Chemical compounds that target dopamine (DA) D1 or D3 receptors have shown promise as potential interventions in animal models of cue-induced relapse. However, undesirable side effects or pharmacodynamic profiles have limited the advancement of new compounds in preclinical studies when administered as independent treatments. In this series of experiments, we explored the effects of co-administration of a D1-recepter partial agonist (SKF 77434) and a D3-receptor antagonist (NGB 2904) in heroin-seeking rats within a ‘conflict’ model of abstinence and cue-induced relapse. Rats were first trained to press a lever to self-administer heroin and drug delivery was paired contingently with cues (e.g., …

Dietary Regulation Of Silent Synapses In The Dorsolateral Striatum, Allison M. Meyers

Dissertations, Theses, and Capstone Projects

Obesity and drugs of abuse share overlapping neural circuits and behaviors. Cravings for drugs of abuse increase during abstinence, a phenomenon known as incubation. In obesity, increased craving is observed in individuals during dieting. Diets often fail, with return to- or increase above- original weight. The extent to which this reflects an incubation phenomenon has not been carefully examined. One mechanism underlying incubation is the reemergence of a developmental mechanism called silent synapses. Silent synapses are 'temporary' synapses that are important for remodeling brain circuits. They are prevalent during early development but largely disappear by adulthood. Drugs of abuse increase …

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 …

The Impact Of Focused Attention And Opening Monitoring Meditation Styles On Attention, Jennifer Wheary

Dissertations, Theses, and Capstone Projects

Mindfulness meditation – often broken down into two distinct types, focused attention (FA) and open monitoring (OM) – has been associated with a range of affective and attentional benefits. Using an attentional blink (AB) paradigm that demonstrated improved attention for novice FA meditators, we explored whether novices who engaged in a single, brief bout of meditation exhibited any differences in alpha or theta power during meditation, and whether these differences were apparent by meditation type. In the AB paradigm, participants are asked to identify two targets, T1 and T2, which are separated by 200-500 ms. Our results showed no significant …

Genetic Impacts Of Deforestation On Mouse Lemurs, Darice Westphal

Dissertations, Theses, and Capstone Projects

The impact of deforestation on the genetic structure of mouse lemurs is poorly understood. In this project, I assess deforestation of Madagascar’s terrestrial protected regions, quantify genomic wide genetic variation in two sympatric mouse lemurs, and evaluate the role of landscape structure in genetic relatedness patterns within two sympatric mouse lemur species. Overall deforestation rates across the 98 terrestrial protected areas in Madagascar are increasing, resulting in an average annual deforestation rate of 0.68% per year, with approximately 10,600 km² lost between 2000 and 2019. In a comparison of relatedness patterns between the sympatric gray mouse lemur (Microcebus …

Approach To Dual Base And Sugar Modification Of Adenosine, Cross-Dehydrogenative Coupling Reactions Of Quinazolinones, And A Novel Entry To Carbazolones And Indolones, Dellamol Sebastian

Dissertations, Theses, and Capstone Projects

Analogues of purine nucleosides are of interest due to their antiviral, antibacterial, and anticancer properties. Although there are large number of reports on C6-modification of 6-chloropurine nucleosides with alkyl amines via the S_NAr reaction pathway, there are fewer reports on comparable reactions with aryl amines. Notably, S_NAr reactions of 6-chloropurine nucleosides with electron-deficient aryl amines is a relatively understudied area. A simple method has been developed for the S_NAr reactions of 6-chloropurine ribonucleosides with electron-deficient-, electron-rich-, and electronically neutral aryl amines. Under the developed conditions, S_NAr reactions of 2’,3’,5’-O-(tert …

Testing An Overtraining Protocol For Fear Learning In Humans, Gordon M. Haskell

Dissertations, Theses, and Capstone Projects

Successful regulation of fear memories is a fundamental tenet to the exposure-based therapies often employed by mental health professionals for individuals with PTSD, phobias, and other anxiety disorders. Consequently, the efficacy of these treatment methodologies is largely dependent on the strength of the fear memory, as stronger memories are often characterized by an increased resistance to extinction and heightened fear recovery. However, there is little consensus within the scientific community regarding how to effectively maximize fear memory strength in human studies, and the literature exploring the impact of variability in acquisition parameters on memory strength is sparse. Here, we tested …

Withdrawal From Voluntary Oral Methamphetamine Reveals Female Specific Susceptibilities To Behavioral Deficits And Neurochemical Perpetuators Of Neurotoxicity And Drug Seeking Behavior, Nicoletta K. Memos

Dissertations, Theses, and Capstone Projects

MA is a potent, highly addictive psychomotor stimulant known to produce neurotoxic effects on the brain leading to neurological impairments^1-6 characterized by neurodegeneration of dopaminergic fibers, cell bodies and pathways, as well as brain regions such as the hippocampus, frontal cortex, and midbrain^1,5.

In MA addiction, women are more vulnerable to the behavioral and cognitive effects of MA compared to men. Adult human literature reveals gender differences in usage patterns and women demonstrate increased vulnerability to the neurotoxic effects and health effects of MA use. Women begin drug use at an earlier age, escalate drug use quicker, …

The Effects Of Near-Threshold Color Manipulation On Perceptual Decision-Making And Confidence Report, Trevor Caruso

Dissertations, Theses, and Capstone Projects

Confidence measures are sometimes used to index awareness below a participant’s criterion for what counts as being subjectively aware of a stimulus or stimulus property. If confidence ratings index awareness below subjective thresholds, then one might be tempted to use confidence ratings in place of subjective reports of whether a stimulus/stimulus property was “seen” or “unseen”. As such, a dissociation of confidence from performance may be construed as a dissociation of subjective awareness from objective task performance. This methodology has been used as supporting evidence for blindsight in typical observers (Balsdon and Azzopardi 2015; Peters and Lau 2015; Peters et …

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 …

Diet And Nutrition Of Lemurs In The Lean Season, Santiago Cassalett

Dissertations, Theses, and Capstone Projects

Animals must navigate complex food and nutrient environments that are constantly in flux to obtain the macro and micronutrients necessary for their growth, reproduction, and survival. The nutritional needs of animals also vary over the life course, further complicating the search for adequate foods and the nutrients within them. The hypervariable and unpredictable environment of Madagascar creates a complex nutrient landscape for lemurs in particular because they are subject to large fluctuations in food availability. These fluctuations are thought to create extreme periods of nutritional stress during the dry season (known as the lean season) for lemurs. In response, lemurs …