Life Sciences Commons^™

Phospholipase D-Dependent Mtorc1 Activation By Glutamine, Elyssa Bernfeld

Dissertations, Theses, and Capstone Projects

Glutamine, the conditionally essential amino acid and most abundant amino acid in human sera, is a key nutrient required for sustaining cell proliferation. Glutamine is essential for nucleotide, protein, and lipid synthesis, all of which are essential for cell proliferation. The mammalian target of rapamycin complex 1 (mTORC1) is a highly conserved protein complex that acts as a sensor of nutrients, relaying signals for the shift from catabolic to anabolic metabolism. While glutamine plays an important role in activating mTORC1, the mechanism is not completely clear. Here we describe a Rag-independent mechanism of mTORC1 activation by glutamine that is dependent …

The Inter-Subject Correlation Of Eeg In Response To Naturalistic Stimuli, Samantha S. Cohen

Dissertations, Theses, and Capstone Projects

Inter-subject correlation is a measure of the similarity of the brain activity of a group of people as they respond to the same naturalistic stimulus, typically a story or video, meant to simulate a real world experience. This thesis tests the hypothesis that the correlation of the brain responses of a group of people is indicative of stimulus engagement. The rationale is that the content of the stimulus drives brain activity in a consistent manner, while internal thoughts are divergent and result in uncorrelated activity. The inter-subject correlation (ISC) of neural responses have previously been assessed with fMRI, EEG, and …

Compact Gene Regulatory Cassettes Support Hallmark Features Of T-Cell Receptor (Tcr)-Alpha Gene Locus Control Region (Lcr) Activity, Jordana Lovett

Dissertations, Theses, and Capstone Projects

Despite the promise of emerging stem cell transplant gene therapy strategies, there remains a gap in the ability to predictably generate robust, temporally controlled long-lasting, therapeutic gene expression in specific target cell lineages following stem cell differentiation. There exists a locus control region (LCR) in the mouse T-cell receptor (TCR)-α locus that confers an ab TCR-like spatiotemporal expression pattern upon a linked transgene, regardless of its site of integration in the genome. These properties are well suited to direction of high-level, physiological expression of therapeutic antigen receptor genes to the T cell progeny of vector-transduced stem cells. The endogenous LCR …

Towards An Atomic Level Model Of The Structure And Calmodulin Mediated Activation Of Eef-2k, Nathan E. Will

Dissertations, Theses, and Capstone Projects

Eukaryotic elongation factor 2 kinase (eEF-2K), the only calmodulin (CaM) dependent member of the a-kinase, phosphorylates eukaryotic elongation factor 2 (eEF-2) on a specific residue (Thr-56), decreasing its affinity for the ribosome and reducing the rate of peptide chain elongation during protein translation. In contrast to the “release-of-inhibition’ mechanism operative in most CaM-dependent proteins kinases, the activation of eEF-2K is proposed to occur through a two-step process subsequent to the engagement of CaM and involves (1) auto-phosphorylation on T348 and (2) engagement of an allosteric site by phospho-T348 leading to a state with the highest activity towards the substrate eEF-2. …

Characterizing Venom Gene Expression, Function And Species Diversity In Predatory Marine Snails Of The Terebridae, Juliette Gorson

Dissertations, Theses, and Capstone Projects

The Terebridae is a group of predatory marine snails that use their venom to feed on marine annelids. Similar to other venomous organisms, the Terebridae have evolved over millions of years, diverging from their closest relative in the Paleocene era. This thesis investigates what is driving terebrid evolution and species diversification by applying a multidimensional approach.

The Fragmented Mind: Working Memory Cannot Implement Consciousness, Javier Gomez-Lavin

Dissertations, Theses, and Capstone Projects

In both philosophy and the sciences of the mind there is a shared commitment to the idea that there is a center—the seat of consciousness, the source of deliberation and reflection, and the core of personal identity—in the mind. My dissertation challenges this deeply entrenched view. I review the empirical literature on working memory, psychology’s best candidate for the workspace of the mind, and argue that it is not a natural kind and cannot inform these central cognitive processes. This deflationary view directly imperils many naturalistic theories of consciousness that rely on working memory, which are reviewed in this project. …

Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer, Sumit Mukherjee

Dissertations, Theses, and Capstone Projects

Glioblastoma (GBM) is one of the most deadly forms of cancer with a mean 5-year survival rate of ≤5%. We have used the non-invasive strategy of long-term intranasal (IN) delivery of a glioblastoma-directed adduct of curcumin (CC), CC-CD68Ab, into the brain of murine GBM cell line GL261-implanted mice to study the therapeutic effect of CC on GBM remission. The treatment caused GBM tumor remission in 50% of GL261-implanted GBM mice. A similar rescue rate (60%) was also achieved through long-term intraperitoneal (i.p) infusion of a highly bioavailable phosphotidylcholine (PC)-encapsulated formulation of CC, Curcumin Phytosome Meriva (CCP), into the GL261-implanted GBM …

Dietary Curcumin Promotes Resilience To Chronic Social Defeat Stress In A Highly Susceptible Mouse Strain, Antonio V. Aubry

Dissertations, Theses, and Capstone Projects

Chronic exposure to stress is a risk factor for the development of major depression and post traumatic stress disorder in humans and induces depressive- and anxiety-like phenotypes in rodents. However, there are few pharmacological interventions available that effectively treat maladaptive responses to chronic stress in the clinical setting. One therapeutic agent that has recently shown promise in treating psychiatric disorders is curcumin, a yellow-pigmented polyphenol compound found in the turmeric plant. Curcumin has been shown to prevent the development of stressed-induced depressive-like behavior in rodents and reduce symptoms of depression in clinically diagnosed patients. In this dissertation, I investigated whether …

The Relationship Between Cognitive And Neural Bases Of Metamemory Judgments, Alexandra M. Gaynor

Dissertations, Theses, and Capstone Projects

Metamemory monitoring, the process of making subjective assessments of the status of one’s own memory, is crucial to guiding behavior and effective learning. Past cognitive research has shown that subjective confidence judgments are inferential in nature, and based on cues available at the time of the judgment. When confidence is based on cues that are related to objective memory performance, metamemory accuracy is high. However, past studies have shown that metamemory monitoring tends to be inaccurate because individuals base their confidence on information that is not predictive of memory success, such as the fluency with which items were encoded during …

Renal Risk Variants Of Apolipoprotein L-1 Form Channels At The Plasma Membrane That Lead To A Cytotoxic Influx Of Calcium, Joseph A. Giovinazzo

Dissertations, Theses, and Capstone Projects

Apolipoprotein L-1 (APOL1) is a secreted protein that provides protection against several protozoan parasites due to its channel forming properties. Recently evolved variants, G1 and G2, increase kidney disease risk when present in two copies. In mammalian cells, overexpression of G1 and G2, but not wild-type G0, leads to swelling and eventual lysis. However, the mechanism of cell death remains elusive with multiple pathways being invoked, such as autophagic cell death mediated by a BH3 domain in APOL1, which we evaluated in this study. We hypothesized that the common trigger for these pathways is the APOL1 cation channel, which is …

Underlying Contribution Of Executive Functioning To Cognition And Academic Achievement In Individuals With Dystrophinopathy, Robert Fee

Dissertations, Theses, and Capstone Projects

Dystrophinopathy is a genetic disorder that results in the lack of or abnormal expression of the protein dystrophin. It is a disorder that alters cell structure and function, impacts the developing brain and brain function, presents with multi-domain cognitive deficits, and influences both mood and behavior. Cognitive impairments appear to be more localized to specific areas of functioning rather than a global deficit; however, deficits have been identified across multiple cognitive domains including language and aspects of executive functioning. A careful examination of the cognitive phenotype and its association to mutations affecting CNS isoforms is necessary to clarify the neuropsychological …

Integration Of Bmp And Insulin/Igf-1 Signaling Regulates Multiple Homeostatic Functions In Caenorhabditis Elegans, James F. Clark

Dissertations, Theses, and Capstone Projects

The maintenance of homeostatic functions is key to the survival and well-being of an organism. Regulation of homeostasis relies on varied inputs, both intrinsic and extrinsic, to potentiate a web of interconnected signaling relays. Insulin/IGF-1 signaling (IIS) is a well-known regulator of glucose and lipid metabolism, as well as having far reaching effects in other homeostatic mechanisms. On the other hand, bone morphogenetic protein (BMP), a member of the transforming growth factor beta signaling superfamily, is known for its role in differentiation and development, with only recent studies highlighting potential roles in metabolic homeostasis. Here we elucidate new functions for …

Supercharged Models Of Intrinsically Disordered Proteins And Their Utility In Sensing, Peter J. Schnatz

Dissertations, Theses, and Capstone Projects

In this thesis I show that greatly increasing the magnitude of a protein’s net charge using surface supercharging transforms that protein into a ligand-gated or counterion-gated conformational molecular switch. To demonstrate this I first modified the designed helical bundle hemoprotein H4 using simple molecular modeling, creating a highly charged protein which both unfolds reversibly at low ionic strength and undergoes the ligand-induced folding transition commonly observed in signal transduction by intrinsically disordered proteins in biology. Due to the high surface charge density, ligand binding to this protein is allosterically activated by low concentrations of divalent cations and the polyamine spermine. …

Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy

Dissertations, Theses, and Capstone Projects

Dengue, the most rapidly spreading flavivirus, threatens to affect almost half of the human global population. We previously showed that dengue-2 protects canine kidney cells (MDCK) from cytotoxic chemicals. We showed, independently, that cell protection, as well as viral replication and maturation, are positively regulated by PI3K-dependent autophagy. However, we had not identified the specific pathway that induces autophagy in infected cells. The current study explores the role of a specific branch of the endoplasmic reticulum (ER) stress-mediated Unfolded Protein Response (UPR), the PERK/eIF2α/ATF4 pathway in the induction of autophagy by …

Investigation Of Biogeochemical Mechanisms Of Greenhouse Gas Production In The Urban Hudson River Estuary, Brian Alan Brigham

Dissertations, Theses, and Capstone Projects

Coastal megacities deposit significant amounts of carbon (C), nitrogen (N) and other pollutants into surrounding waters. These inputs, including wastewater and surface water runoff, may affect estuarine and adjacent wetland biogeochemical cycles, microbial production and ultimately greenhouse gas (GHG) efflux. In many megacities pollutant loading is typically greatest after periods of precipitation when the volume of wastewater and storm water runoff exceeds local sanitation capacity, resulting in the discharge of raw sewage into adjacent waters. These combined sewage overflow (CSO) events have received considerable attention primarily due to their potential impact on human health and eutrophication. However, whether these events …

Ulva Spp. Bloom Dynamics In A Hyper-Eutrophic Estuary: Jamaica Bay, New York, Annesia Lamb

Dissertations, Theses, and Capstone Projects

In this dissertation, I present three studies that further our understanding of macroalgae identity, growth, and proliferation. Eutrophication is prevalent in shallow coastal ecosystems world-wide. One of the ecosystem consequences is the development of a bloom forming green marine macroalgae, Ulva spp. Ulva can have negative effects such as Zostera spp. degradation, fish, and shellfish declines. I performed assessments of (1) identity of the bloom-forming Ulva and other macroalgae assemblage, (2) physical, chemical, and biological drivers of Ulva bloom growth and proliferation, and (3) optimal irradiance and temperature requirements for early growth stages in Ulva linza.

The first study …

Curcumin Inhibits The Ikk:Nf-Kappa B Pathway In Neural Fear Circuits, Miguel A. Briones

Dissertations, Theses, and Capstone Projects

The study of how the brain acquires fearful memories has attracted considerable experimental attention, due in part to the promise of discovering novel therapeutic approaches for psychiatric disorders that are characterized by unusually strong and persistent traumatic memories. In recent years, extensive research has focused on studying the neural and molecular mechanisms by which fear memories are acquired, stored, and retrieved in the brain. Once acquired, fear memories may be attenuated using one of 2 procedures: 1) fear extinction, which involves repeated presentation of the fear-arousing stimulus in the absence of an aversive consequence, or 2) interference with the reconsolidation …

A Contribution Toward A Global Monograph Of Gyroporus: Taxonomy, Phylogeny, Biogeography, Naveed Davoodian

Dissertations, Theses, and Capstone Projects

Gyroporus (Sclerodermatineae, Boletales, Agaricomycetes, Basidiomycota, Fungi) is a genus of ectomycorrhizal mushroom-forming fungi distributed throughout the world in suitable habitats. Previous attempts to untangle the diversity of this genus proved difficult due to the presence of semi-cryptic species and equivocal results from phylogenetic analysis of ribosomal RNA markers. To overcome these obstacles, a combined taxonomic and phylogenetic (emphasizing protein-coding genes) approach is used here to delimit species and elucidate geographic and evolutionary patterns of Gyroporus. Careful study of relevant literature and herbarium specimens was augmented by field work in North America, Australia, and East Asia for observation and collection …

Non-Canonical Activation Of Creb/Crh-1 Mediates Neuroprotection In A Caenorhabditis Elegans Model Of Excitotoxic Necrosis, K. Genevieve Feldmann

Dissertations, Theses, and Capstone Projects

Excitotoxicity, which is a major cause of neurodegeneration in brain ischemia, can also activate neuroprotective pathways. A frequently suggested neuroprotective cascade involves the activation of the transcription factor CREB by its phosphorylation, but on its own this mode of CREB activation is promiscuous. We aim to elucidate the specific mechanism of CREB activation in excitotoxicity-induced neuroprotection, focusing on three suggested models: CREB phosphorylation by calcium-activated kinases in the cytoplasm or nucleus, and the activation of CREB by CRTC (an important cofactor). Using a C. elegans model of excitotoxicity, we demonstrate that CREB’s neuroprotective effect is mainly seen in neurons exposed …

The Role Of Oxidative Stress And Signal Transduction In Chemotherapy-Mediated Cognitive Impairment In The Menopause Rat Model, Ciara Bagnall

Dissertations, Theses, and Capstone Projects

Systemic chemotherapy treatment is associated with long-term cognitive impairment in breast cancer survivors. While many studies have established the forms of cognition and corresponding regions in the brain most affected, very little is revealed about the potential molecular mechanisms that mediate these changes. The effects of systemic treatment on the brain is likely attributed to many different mechanisms including oxidative stress and immune dysregulation. Earlier studies from our lab have investigated the effects of the chemotherapy cocktail doxorubicin and cyclophosphamide (AC Chemotherapy) in an ovariectomized menopause animal model of ‘chemo brain’ (Salas-Ramirez et al., 2015). We observed that animals injected …

Event-Related Potential Studies Of Error Monitoring To Affective And Non-Affective Stimuli In Adolescents And Emerging Adults, Rebecca K. Reed

Dissertations, Theses, and Capstone Projects

It is hypothesized that prefrontal cortex (PFC) and anterior cingulate cortex (ACC) function may be still under development in adolescents. As the generator of the error-related negativity (ERN) and the N2, the ACC is expected to be sensitive to the degree of development with age. In adults, these top-down control areas ideally serve to direct attention to goal-relevant information, which can increase the likelihood of making a correct choice, even in fast-response laboratory based tasks. However, adolescents may show increased susceptibility in these top-down control areas when the stimulus is social and emotional. In the first study, event-related potentials were …

Mechanism And Development Of Peptide-Based Inhibitors To Human Islet Amyloid Polypeptide (Hiapp) Self-Assembly, Jayson Vedad

Dissertations, Theses, and Capstone Projects

Amyloid fibrils formed by of hIAPP_1-37 (also known as amylin) has been linked to type-II diabetes mortalities and its formation was found to be related to the three aromatic residues in hIAPP_1-37. In this dissertation, the role of aromatic amino acids, particularly that of Phe-23, and its various interactions to the self-assembly of human islet amyloid polypeptide (hIAPP)_22-29 were investigated. Using a variety of spectroscopic techniques with emphasis to vibrational spectroscopy (FT-IR and Raman spectroscopies) in conjunction with computational methods, different factors leading to aggregation as well as its inhibition were identified. Among the driving forces …

Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek

Dissertations, Theses, and Capstone Projects

Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …

Binding Of Maize Necrotic Streak Virus (Mnesv) 3’ I-Shaped Structure (3’ Iss) To Eukaryotic Translation Factors (Eifs) And Implication In Eif4f Mediated Translation Initiation, Qiao Liu

Dissertations, Theses, and Capstone Projects

5' m⁷GpppN cap and the 3' poly adenosine (A) tail of eukaryotic mRNAs are key elements for recruiting translation initiation machinery in canonical translation initiation. Unlike host mRNAs, many viruses lack these elements and yet they are translated efficiently. Plant viruses, in particular, have complex structures within their untranslated regions (UTR) that allow them to bypass some cellular translation control steps. In Maize necrotic streak virus (MNeSV) 3' UTR, an I-Shaped RNA Structure (ISS) has been reported to mediate the virus translation initiation progress. 3’ ISS binding with eIF4F has been shown to facilitate translation. 5’ -3’ kissing …

Niche Shifts, Species Distributions, And Genetic Diversity In Gymnophthalminae Lizards, With A Focus On Microclimates And Thermophysiology, Maria Strangas

Dissertations, Theses, and Capstone Projects

The environmental niche is a central organizing concept in the study of ecology and evolution, as the environmental conditions in which species can persist (their fundamental niches) and the conditions in which they occur (their realized niches) can shape spatial and temporal patterns of biodiversity at multiple scales. How organisms at different levels of biological organization are affected by environmental heterogeneity has consequences for the distribution of genetic and phenotypic diversity, yet the mechanisms through which this occurs are poorly studied. In this dissertation, I present three research chapters that explore how species’ traits and their microclimatic environments shape biodiversity …

Using Molecular Markers To Trace The Population History Of Volant Organisms At Differing Temporal Scales, Noah A. Burg

Dissertations, Theses, and Capstone Projects

Using molecular markers to test phylogenetic and phylogeographic hypotheses is critical for tracking the population origin of invasive, introduced species (Chapter 2, Chapter 4) and to identify the systematic relationships of disparate lineages at both shallow and deep evolutionary time scales (Chapters 3, Chapter 4). In this thesis, Sanger Sequencing was used to generate datasets based on fresh and preserved tissue from specimens collected in the field, as well as museum tissue vouchers granted from various institutions in the US and Europe. In combining these source materials, data were generated for three focal studies: 1) In the first research section …

Evidence For Organelle-Like Extracellular Vesicles From A Parasite Of Drosophila And Their Function In Suppressing Host Immunity, Mary Heavner

Dissertations, Theses, and Capstone Projects

Parasitic wasps act as keystone species in natural ecosystems. Adept at suppressing immunity of their insect hosts, these natural enemies of insect pests are used for biocontrol in many parts of the world. Female parasitic wasps of the closely-related species Leptopilina heterotoma (Lh), a generalist of many Drosophilia flies, and Leptopilina boulardi (Lb), a specialist on flies of the melanogaster subgroup, produce venom and virus-like particles (VLPs) in their long gland-reservoir complexes, a secretory organ connected to ovipositors. Venom and VLPs are deposited, along with wasp eggs, into the body of the wasp’s larval fly host …

Functional Interactions Of Tau, Pin1, P53 And Mrna 3′ Processing Factors In Non-Neuronal Cells, Jorge E. Baquero

Dissertations, Theses, and Capstone Projects

ABSTRACT

mRNA 3’ end processing, an essential step in eukaryotic RNA metabolism, regulates the steady-state levels of different mRNAs and contributes to the cells rapid response to stress. Studies have described potential contributions of mRNA 3’ end processing to numerous human diseases, including cancer and Alzheimer’s disease (AD). Therefore, the main purpose of this dissertation is to further elucidate some of the roles of disease-related factors Pin1, p53 and tau in the regulation mRNA 3’ end processing in non-neuronal cells under different cellular conditions, including during the DNA damage response (DDR).

The results from Chapter II show that the prolyl …

Insights Into The Cyclooxygenase Pathway In A Progressive Rat Model Of Parkinson’S Disease Induced By Prostaglandin J2: Protection With Ibuprofen, Chuhyon Corwin

Dissertations, Theses, and Capstone Projects

Parkinson’s disease (PD) is a neurodegenerative disease with aging as a major risk factor. Its defining symptoms are motor deficits that are primarily associated with dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc) in the midbrain. Post-mortem PD brains exhibit abnormal intraneuronal inclusions of α-synuclein and ubiquitinated protein aggregates known as Lewy bodies, a hallmark of PD pathology.

Currently, there is no validated biomarker for PD. Especially the early stage of PD is difficult to detect as the pathology develops progressively. While symptom-managing treatments are available, there is no neuroprotective treatment as of yet, mainly due to the …

The Therapeutic Potential Of Natural Products From Vaccinium Berries For Viral And Lung Diseases Through An Improved Lc-Ms-Based Chemometric Approach, Vanya I. Petrova

Dissertations, Theses, and Capstone Projects

Smoking is a global epidemic that creates serious health and economic burden. It is the primary, preventative factor for the majority of causes of death worldwide. Analysis of publicly available data revealed that smoking prevalence rates among the youth in developing countries, especially in Bulgaria, are alarmingly high. The Bulgarian population has one of the highest percentages of smokers and the second highest rate among teenage girls. Consequently, chronic diseases affected by smoking, such as chronic obstructive pulmonary disorder (COPD), have been increasing there in the last five years. Poland, on the other hand, is an exemplary outlier for the …