Life Sciences Commons^™

Structural Studies On Calcium/Calmodulin-Dependent Activation Of Eukaryotic Elongation Factor 2 Kinase, Kwangwoon Lee

Dissertations, Theses, and Capstone Projects

Eukaryotic elongation factor 2 kinase (eEF-2K) is a key modulator of the rate of protein synthesis. Activated by calcium-loaded calmodulin (Ca²⁺-CaM), eEF-2K phosphorylates its only known physiological substrate, eEF-2, on a specific threonine residue (Thr-56). Phosphorylated eEF-2 has reduced affinity for the ribosome, and results in a significant decrease in the rate of translation elongation. Modulation of the rate of translation elongation plays a crucial role in proteostasis – adequate regulation of protein synthesis, protein folding, and protein degradation that greatly influences cellular growth and survival. Binding of Ca²⁺-CaM triggers activation of eEF-2K and remains intact …

Solvation Thermodynamic Mapping In Computer Aided Drug Design, Steven Ramsey

Dissertations, Theses, and Capstone Projects

The displacement of water from surfaces upon biomolecular recognition and association makes a significant contribution to the free energy changes of these processes. We therefore posit that accurate characterization of local structural and thermodynamic molecular water properties can improve computational model accuracy and predictivity of recognition and association processes. In this thesis, we discuss Solvation Thermodynamic Mapping (STM) methods that we have developed using inhomogeneous fluid solvation theory (IST) to better characterize active site water structural and thermodynamic properties on protein surfaces and the open source tools that we have developed, GIST-CPPTRAJ and SSTMap, which implement these methods which we …

Distribution And Population Structure Of The Invasive Nitellopsis Obtusa (Desv. In Loisel.) J. Groves And Native Species Of Characeae In The Northeast U.S.A., Robin Sleith

Dissertations, Theses, and Capstone Projects

Freshwater ecosystems are some of the most biologically diverse environments on Earth. Billions of humans rely on functioning freshwater ecosystems for drinking water and many other services. These ecosystems are increasingly threatened by human impacts including nutrient pollution, invasive species, and climate change. Here I contribute four research chapters that investigate freshwater diversity and ecosystem threats using the Characeae, a family of freshwater green macroalgae, as a study system. Characeae are a diverse and ancient group with more than 500 extant species and a fossil history spanning at least 250 million years. These algae are macrophytes in freshwater ecosystems, and …

Identification And Characterization Of Barrier Insulator Activity In The T-Cell Receptor Alpha Locus Control Region, Gayathri Devi Raghupathy

Dissertations, Theses, and Capstone Projects

Genes of different spatiotemporal expression profiles are often juxtaposed in the genome. This organization raises risks of cross-regulatory influences from neighboring genes; for instance heterochromatin can spread over euchromatin or long-range acting enhancers can inappropriately activate genes. Gene regulatory elements such as Locus Control Regions (LCR) and Insulators prevent such cross-communications and allow for normal gene expression patterns. In transgenic systems, LCRs limit influences from surrounding chromatin by providing site-of-integration independent and specific spatiotemporal expression upon a linked transgene. The field’s understanding of the ability of an LCR to overcome chromatin influences and allow site-of-integration independent expression is minimal. Interestingly, …

Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) is a strong psychostimulant and its exposure can lead to serious neurological complications. METH-induced neuronal injury is the result of a complex interplay of different factors including dopamine (DA) overflow, oxidative stress and neuroinflammation. Although the mechanisms of METH-induced neurotoxicity have been extensively studied, there is still no effective therapeutic treatment. Therefore, it is essential to study potential drug candidates that can treat METH-induced neurotoxicity. Green tea extract, epigallocatechin gallate (EGCG), has emerged as a neuroprotective agent that can protect against several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Recently, our lab has shown that EGCG prevents …

A Study Of The Impact Of The Physical Properties Of Blood On The Interpretation Of Bloodstain Patterns In Forensic Investigations, Ira S. Dubey

Dissertations, Theses, and Capstone Projects

There are many situations when the value of the physical characteristics of blood far outweighs the information gained from DNA analysis of the bloodstain (Brodbeck, 2012; Raymond, Smith and Liesegang, 1996). Analysis of bloodstain patterns at crime scenes or on clothing often provides significant information and serves both as investigate aids and as evidence presented in court. There has been limited work done to evaluate the potential impact of variation in the physical properties of blood on the interpretation of blood spatter patterns. This dissertation will expand on previous work and investigate how changes in the physical properties of blood, …

Preclinical Evaluation Of Gold-Based Chemotherapeutic Candidates For The Treatment Of Metastatic Renal Cancer, Benelita Elie

Dissertations, Theses, and Capstone Projects

Renal cell carcinomas (RCCs) remain a significant health concern in the United States because of a lack of effective treatment. To date, RCCs account for 2.4% of all cancer deaths in the United States, and about 14,970 people will die from the disease in 2018, mostly of advanced or metastasized RCCs1,2. Mutations in metabolic pathways are characteristics of RCCs, including changes in redox metabolism, deregulation of proteolytic factor expression, and inflammation. These molecular events promote tumor vascularization, growth, invasion, and metastasis, which often correlate with a poor prognosis. Many pharmaceutical avenues have been explored, including cytotoxic chemotherapeutics, biologics targeting cellular …

Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon

Theses and Dissertations

This study phylogenetically analyzed 30 AMY-related genes from 11 primates. The results show the gradual expansion of the AMY gene family which could have allowed primates to adapt to various ecological landscapes and maximize energy intake from starch-rich foods in periods of food scarcity.

The Determining Factors Of The Self-Assembly Of Collagen Mimetic Peptide, Fangfang Chen

Dissertations, Theses, and Capstone Projects

We recently reported that a designed triple helix Col108 self-associates to form collagen-like mini-fibrils having a d-periodicity of 35 nm. Recombinant protein Col108 consists of 378-residue triple helix domain organized into three repeating sequence units, and a C-terminal foldon domain. The 35 nm d-period of Col108 mini-fibrils is consistent with the one unit staggered arrangement of the associating helices. To further investigate if the sequence periodicity is crucial for collagen mimetic peptide fibril formation, we studied the self-assembly of four other designed triple helical peptides. Peptide 2U108 has two repeating sequence units; peptide Col877 consists of three repeating …

Pretargeted Radioimmunotherapy Utilizing The Inverse Electron Demand Diels-Alder Reaction, Rosemery Membreno

Dissertations, Theses, and Capstone Projects

Radioimmunotherapy capitalizes on the specificity and affinity of antibodies for their antigens to localize radioactivity at the tumor site. One limitation in using antibodies is their long circulation time, which can take days to weeks to fully clear from blood circulation. When a radioisotope is directly conjugated to this immunoglobulin vector, the red marrow and other healthy organs are receiving a constant radiation dose while it is in blood circulation. This not only harms healthy organs, but limits the dose of radioactivity that can be administered thus prolonging treatment. A promising alternative to limit the radiation dose to non-tumor tissue …

Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang

Dissertations, Theses, and Capstone Projects

Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits …

Post-Synaptic Mechanisms Of Early And Late Prepulse Inhibition In The Goldfish, Daniel Bronson

Dissertations, Theses, and Capstone Projects

Sensorimotor gating, or prepulse inhibition (PPI), attenuates the startle response during sensory processing by limiting sensory input to the startle circuit. In the goldfish startle circuit, a single action potential in the Mauthner-cell (M-cell) triggers the startle response. PPI in the M-cell is mediated by multiple post-synaptic mechanisms, including the activation of a tonic, shunting inhibition as well as a voltage-sensitive conductance, both of which briefly reduce M-cell excitability. However, the specific channels and pathways that modulate PPI are not fully known. This work further characterizes the post-synaptic conductances that mediate PPI by blocking voltage-gated and inward-rectifying potassium channels, antagonizing …

The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.

Activity-regulated cytoskeleton-associated (Arc) …

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT₄R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT₄R expression …

Integrating The Effects Of Biotic Interactions Into Models Of Species Distributions, Jamie M. Kass

Dissertations, Theses, and Capstone Projects

The study of species geographic distributions and their environmental drivers has developed at a fast pace in recent years, owing to improvements in technology and data availability, and is increasingly relevant in this era of advancing global change. Currently, the field focuses heavily on a variety of techniques to statistically estimate species’ ranges I refer to collectively as species distribution models (SDMs). These models are now used across a wide range of disciplines, but inadequacies remain in implementation, methodology, and theory that are in need of new insight. In this thesis I will address two key shortcomings that require improvement …

The Integration Of Multiple Sources Of Sonic Hedgehog In The Spinal Cord Contribute To The Production Of First-Born Oligodendrocyte Precursor Cells Which Become Critical For Synapse Remodeling In Response To Adult Motor Neuron Injury, Lev Starikov

Dissertations, Theses, and Capstone Projects

Oligodendrocyte precursor cells (OPCs) arise sequentially first from a ventral and then from a dorsal precursor domain during spinal cord development. Whether the sequential production of OPCs is of physiological significance has not been examined. Here I show that interrupting Sonic hedgehog (Shh) signaling originating from nascent ventricular zone derivatives (VZD), motor neurons and the lateral floor plate, almost completely blocks ventral but not dorsal oligodendrogenesis without noticeably affecting early tissue patterning and embryonic development. In the absence of ventral OPCs, dorsal OPCs increase proliferation and populate the entire spinal cord with increased density. In these mutant mice, dOPCs take …

An In Vitro And In Vivo Evaluation Of The Anticancer Potential Of Resveratrol And Pterostilbene Against Hpv-E6 Positive Cancers, Kaushiki Chatterjee

Dissertations, Theses, and Capstone Projects

Cervical cancer remains as one of the most prevalent cancers effecting women globally. Lack of awareness and affordable prophylactic and therapeutic options in developing countries drive the need for alternative low-cost approaches. Dietary polyphenols have gained increased attention as possible anti-cancer agents. Our study aims to investigate whether two natural structural analogs, resveratrol and pterostilbene, exhibit anti-HPV (Human papillomavirus) activity in cervical cancer. To determine the efficacy of these polyphenols, extensive in vitro and in vivo analyses were carried out. For the in vitro studies we utilized human HeLa cells (HPV18 positive) and murine TC1 cells (HPV 16 oncogene positive). …

Molecular Analysis Of Cone Photoreceptor Genesis From A Specific Retinal Progenitor Population, Diego F. Buenaventura

Dissertations, Theses, and Capstone Projects

There are two types of photosensitive cells of the retina that contribute to image formation: Cone photoreceptors that mediate color discrimination and rods that provide photosensitivity in low-light conditions. Given the importance of cones in high acuity and color vision, deficiencies in this cell type that result from ailments such as retinitis pigmentosa and macular degeneration can lead to a debilitating loss of vision. Currently, one of the most pressing goals in the field of retinal development is the elucidation of the gene regulatory networks (GRN) involved in inducing an undifferentiated cell into becoming a functional cone photoreceptor.

Recently, an …

A Defense Of Pure Connectionism, Alex B. Kiefer

Dissertations, Theses, and Capstone Projects

Connectionism is an approach to neural-networks-based cognitive modeling that encompasses the recent deep learning movement in artificial intelligence. It came of age in the 1980s, with its roots in cybernetics and earlier attempts to model the brain as a system of simple parallel processors. Connectionist models center on statistical inference within neural networks with empirically learnable parameters, which can be represented as graphical models. More recent approaches focus on learning and inference within hierarchical generative models. Contra influential and ongoing critiques, I argue in this dissertation that the connectionist approach to cognitive science possesses in principle (and, as is becoming …

Novel Biobehavioral Methods For Assessing The Anxiety-Related Attention Bias, Samantha Denefrio

Dissertations, Theses, and Capstone Projects

Anxiety disorders will affect an estimated one in three Americans, significantly impacting emotional health and quality of life. High personal and economic costs make research on the etiology, maintenance, and treatment of anxiety a crucial public health goal. Selective and exaggerated attention towards threat, termed attention bias (AB), has been identified as a core behavioral and neurocognitive mechanism in anxiety. A novel treatment, attention bias modification training (ABMT), targets AB and aims to ameliorate anxiety. Rarely acknowledged, however, are the challenges in the conceptualization and measurement of AB. First, associations between anxiety and AB in anxious populations have been increasingly …

Characterization Of Immunomodulatory Microbial Factors In Medicinal Plants, Kriti Kalpana

Dissertations, Theses, and Capstone Projects

Medicinal plants are one of the biggest sources of natural products with therapeutic importance. There are currently over 28,000 plants with putative medicinal values. Plant-derived compounds have been explored extensively for various biological activities ranging from anti-cancer, immune-boosting to anti-inflammatory and anti-oxidant. Some of the most important therapeutic agents are of plant-origin, such as paclitaxel from Pacific yew (Taxus brevifolia) and artemisinin from qinghao su (a Chinese medicinal herb; a.k.a. Artemisia annua) to name a few.

The study presented in this thesis started out as classical pharmacognosy research, which focused on the identification of immunostimulatory factors in …

The Morphology And Evolution Of The Primate Brachial Plexus, Brian M. Shearer

Dissertations, Theses, and Capstone Projects

Primate evolutionary history is inexorably linked to the evolution of a broad array of locomotor adaptations that have facilitated the clade’s invasion of new niches. Researchers studying the evolution of primates and of their individual locomotor adaptations have traditionally relied on bony morphology – a practical choice given the virtual non-existence of any other type of tissue in the fossil record. However, this focus downplays the potential importance of the many other structures involved in locomotion, such as muscle, cartilage, and neural tissue, which may each be influenced by separate selective forces because of their different roles in facilitating movement. …

Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity, Pardeep Singh

Dissertations and Theses

No abstract provided.

Using Fundamental Properties Of Light To Investigate Photonic Effects In Condensed Matter And Biological Tissues, Laura A. Sordillo

Dissertations and Theses

Light possesses characteristics such as polarization, wavelength and coherence. The interaction of light and matter, whether in a semiconductor or in a biological sample, can reveal important information about the internal properties of a system. My thesis focuses on two areas: photocarriers in gallium arsenide and biomedical optics. Varying the excitation wavelength can be used to study both biological tissue and condensed matter. I altered the excitation wavelengths to be in the longer near-infrared (NIR) optical windows, in the shortwave infrared (SWIR) range, a wavelength region previously thought to be unusable for medical imaging. With this method, I acquired high …

Multi-Locus Phylogenetic Inference Of The Howler Monkey (Alouatta) Radiation In South America., Esmeralda Ferreira

Dissertations and Theses

Abstract

Howler monkeys (Alouatta) are the most widely distributed New World primates, ranging from southern Mexico to northern Argentina. They occur in tropical rain forests, flooded and gallery forests, and deciduous and semi-deciduous environments. Despite their importance as seed dispersers, howlers have also been known to be ecological indicators. Available phylogenetic hypotheses for this genus have used chromosomal characters, morphological characteristics, and a limited number of molecular markers and specimens. In spite of these analyses, branching patterns among howler species lineages conflict between studies or remain unresolved. Using 14 unlinked non-coding intergenic nuclear regions under both a concatenated …

Optimizing Crispr/Cas9 Gene Targeting To Investigate Cone Photoreceptor Development In The Chick Retina, Diana Y. Kim

Dissertations and Theses

Many human eye conditions result in the loss of vision, due to the degeneration of cone photoreceptors in the retina. Thus, the development of methods to regenerate these cone photoreceptors is an active area of study. In order to find ways to regenerate cones, the molecular pathways and gene regulatory networks that a retinal progenitor cell takes to develop into a postmitotic cone photoreceptor needs to be well understood. In an attempt to answer this question, this paper studies the effect of CRISPR/Cas9-mediated mutagenesis of two key transcription factors, Otx2 and Nr2e3, on retinal progenitor cells and cone photoreceptors throughout …

Do Saproxylic Curculionids Affect The Fitness Of Co-Occurring Cerambycids?, Sheila R. Heath

Dissertations and Theses

Saproxylic insects sometimes coexist in incredibly high numbers under bark and share common resources. Thus, interactions between species are possible and could even explain their coexistence. This study investigates evidence of negative or positive effects of curculionid beetles (Coleoptera: Curculionidae) on cerambycid beetles (Coleoptera: Cerambycidae) that coexisted in dead tree branches in Costa Rica. Co-occurrence analysis and generalized regressions were used to test associations between cerambycid and curculionid species. Three cerambycid species that each co-occurred with a curculionid species were selected to measure fitness. Fitness measures of the cerambycid were compared with abundance of the co-occurring curculionid to assess the …

Role Of Moa-1, An Anti-Phosphatase, And Apl-1, An App-Related Protein, In Morphogenesis And Mating Behavior In Caenorhabditis Elegans, Valerie C. Moscoso

Dissertations and Theses

Alzheimer's disease is a neurodegenerative disease that affects more than 30 million people globally. The disease is characterized by an accumulation of extracellular beta-amyloid peptide plaques and intracellular neurofibrillary tangles in the brain. The beta-amyloid peptide is derived from a larger precursor protein, the amyloid precursor protein (APP). Mutations in APP have been correlated with Alzheimer's disease. Due to the presence of two paralogues, APLP1 and APLP2, which have overlapping functions, the normal function of APP is difficult to elucidate. Knockout of the entire APP gene family in mice results in lethality and developmental defects, indicating that the APP gene …

Characterizing Chromosomal Aberrations In Cells Deficient For Both Atm And Msh2, Yeliz Inalman

Dissertations and Theses

Ataxia telangiectasia mutated (ATM) and mutS homologue 2 (MSH2) are important DNA repair proteins that participate in DNA repair pathways to maintain genomic integrity. Mice deficient for ATM and MSH2 mice are viable. However, ATM^-/- mice show growth retardation, neurological defects, and spontaneous lymphomagenesis. MSH2^-/- mice suffer from aggressive lymphoid tumors between two to five months of age and have increased microsatellite instability, which predisposes MSH2^-/- mice to carcinomas. However, mice deficient in both ATM and MSH2 are unable to survive beyond postnatal day 21 (P21). The observed lethality in ATM^-/-MSH2^-/- mice may result …