Digital Commons Network^™

Exploring A Gene Panel For Parkinson’S Disease In An Egyptian Cohort, Asmaa Saeed Gabr

Theses and Dissertations

Parkinson’s disease is a highly heterogeneous disorder characterized by diverse neuropathological features, clinical presentations and progression patterns. In Egypt, Parkinson’s disease incidence rates lie outside the range reported elsewhere. The genetic background to the pathogenesis of Parkinson's disease has been postulated for a long time. However, Parkinson’s disease has never been systematically investigated in Egypt. This study aimed to explore genetic variants and interactions that are associated with the familial and sporadic forms of Parkinson's disease in an Egyptian cohort. This includes examining variants in PD-related genes, exploring the role of specific genes like MAPT and adjacent genomic regions, and …

Understanding The Expression And Role Of Pros-1 In The Male Gonad Of C. Elegans, Jack Bozik

Undergraduate Theses

The gene pros-1 is a transcription factor that is highly expressed within neuronal sheath cells, glial cells, and excretory canal cells. pros-1 plays a role in cell determination of those cell types in the nematode C. elegans, which promotes organismal development. But the degree to which pros-1 presence is important is still not fully understood, because there are many genes involved in development that when mutated or damaged can result in unexpected phenotypes or even total loss of function to a certain developmental mechanism. What makes pros-1 valuable to research is that it is a functional homologue to a …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac

Theses and Dissertations--Physiology

Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.

First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …

Investigation Of Neurotransmitter’S Knockdown Effect On Drosophila Melanogaster Female Aggression, Asil N. El Galad

Undergraduate Student Research Internships Conference

Drosophila melanogaster (D. melanogaster) is a popular model organism in neurobiology. While aggression has been studied heavily in male drosophila, there's minimal research on aggression in female drosophila. Neurotransmitters influencing aggressive behaviour in female D. melanogaster are poorly understood. Various neurotransmitters such as dopamine, octopamine, and serotonin influence aggression in D. melanogaster Further investigation of the role of neurotransmitters on aggression is thus important. The purpose of our experiment is to observe the effect of the knockdown of dopamine, octopamine and glutamate on aggression in female D. melanogaster.

The Effects Of Physical Function And Genetics On Cognition And Blood Biomarkers In Individuals At-Risk For Alzheimer’S Disease And Related Dementias, Joshua Louis Gills

Graduate Theses and Dissertations

Alzheimer’s disease and related dementia (ADRD) rates are expected to triple by the year 2050. Early detection and specific mitigation efforts are warranted to blunt the alarming rate. Physical function (PF) declines with age, but higher physical function is associated with better cognitive functioning in middle-to- older age individuals. Moreover, greater physical activity (PA) is associated with better global cognition; however, Apoliporotein e4 carriers may not gain the same benefits with exercise. Additionally, plasma phosphorylated tau 217 (p-tau217) has been identified as a novel diagnostic ADRD biomarker which needs further research to examine associations with risk factors. Therefore, the aims …

Genetic Circadian Mosaics And The Clock Network’S Contributions To Sleep, Lukasz Widziszewski

Dissertations, Theses, and Capstone Projects

Circadian rhythms are physiological and behavioral changes which follow a 24-hour cycle. Drosophila Melanogaster’s circadian clock neuronal network (CCNN) has been identified and several subpopulations have been characterized based on previous studies; the classifications of subpopulations of neurons within the CCNN are based on a return of anticipatory locomotor activity preceding the two daily light transitions (Lights on = dawn/Lights off = dusk). The neurons responsible for the return of anticipatory morning locomotor activity have been referred to as the M-cells, the group of neurons known to rescue evening anticipatory locomotor activity have been termed the E-cells. In this …

Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly

Electronic Thesis and Dissertation Repository

ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

Honors Scholar Theses

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing …

Examining Human Apoe Genotype And Sex As Modulators Of Respiratory Plasticity In The Presence And Absence Of Spinal Cord Injury, Lydia Ella Strattan

Theses and Dissertations--Neuroscience

There are over 17,000 new spinal cord injuries (SCIs) every year in the Unites States alone. Almost 60% of these injuries occur at the cervical level, potentially leading to loss of function in a variety of sensory and motor systems including upper and lower limbs, respiratory, and autonomics. In addition to the physical and emotional costs, individuals who experience these higher level injuries also face a massive financial burden, incurring over $1 million in expenses during the first year after injury in addition to substantial yearly costs for the rest of their lifetime. A myriad of therapeutic approaches targeting plasticity …

Optimization And Validation Of The Neurolux Wireless Optoelectronics System For Optogenetics, Karis Courey, Su Hyun Lee Ph.D., Adam Smith Ph.D., Nicholas Cilz Ph.D., Sarah K. Williams Avram Ph.D., Adi Cymerblit-Sabba Ph.D., June Song, Nicholas Leipzig Ph.D., W. Scott Young M.D., Ph.D.

Williams Honors College, Honors Research Projects

Utilizing light and genetic engineering, optogenetics permits the manipulation of events within cells via light using the light-sensitive properties of single-component microbial opsins. Microbial opsins are activated by a light source, such as lasers, light-emitting diodes, and incandescent sources that deliver light to the region of interest either directly or indirectly, such as through fiberoptics. In classical in vivo optogenetics, the wiring of optic fibers necessitates tethering of animals by the optic fiber to the light source. The novel NeuroLux wireless optoelectronic system for optogenetics circumvents issues pertaining to classical optogenetics by utilizing near-field power transfer via magnetic coil antennae …

An Autism-Causing Variant Misregulates Selective Autophagy To Alter Axon Targeting And Behavior, Tyler Buddell

Theses and Dissertations

Neurodevelopmental disorders cause debilitating disruptions to the cellular mechanisms that underlie development of the brain. Unfortunately, the complexities of neurodevelopmental disorders make them difficult to study, and the molecular mechanisms perturbed by these disorders remain elusive. Better understanding of neurodevelopmental mechanisms, and the related genes involved, will likely yield new insight into neurodevelopmental disorders. A gene that has been associated with a number of neurodevelopmental disorders is the calcium voltage-gated channel subunit alpha1 C (CACNA1C) gene. Common and rare variants of the CACNA1C gene have been associated with autism and other neurodevelopmental disorders including schizophrenia, bipolar disorder and ADHD. However, …

The Genetics Of Olfactory And Visually Guided Attractive Behaviors In Aedes Aegypti Mosquito, Joshua Ibukun Raji

FIU Electronic Theses and Dissertations

Mosquitoes detect their hosts and seek suitable resources crucial for survival by integrating chemosensory, thermal, and visual cues. The diversity of the cues involved in mosquito attractive behaviors has made the design of behavioral control strategies a challenge. The genetic basis of mosquito attractive behaviors can now be determined using genome editing. The contribution of the IR8a chemosensory pathway was uncovered by disrupting the IR8a co- receptor in Aedes aegypti using CRISPR/Cas9. Ir8a mutant female mosquitoes are not attracted to lactic acid, a behaviorally active component of human sweat, and lack odor-evoked responses to acidic volatiles. The loss of Ir8a …

The Role Of Ash1l During Human Neurodevelopment, Anna Bagnell

Senior Theses

Autism spectrum disorders (ASD) are associated with defects in neuronal connectivity and are highly heritable. A significant proportion of ASD cases are of complex genetic etiology; complexity which might reflect the impact of gene-environment interactions. However, there is a gap in our understanding of the mechanisms that underlie the gene-environment interaction in autism complex etiology. Genome wide association studies in large ASD cohorts identified high risk variants associated with autism in genes that regulate histone modifications and remodel chromatin. These findings highlight the relevance of chromatin regulatory mechanisms in the pathology of ASD. Changes in Histone H3 methylation have been …

Analysis Of The Genetic And Neurological Components Of Opioid Addiction, With Public Health Perspectives Of The Opioid Epidemic In The United States Of America, Janhavi A. Dubhashi

DISCOVERY: Georgia State Honors College Undergraduate Research Journal

Opioid addiction has reached epidemic levels around the world, with over-prescription of opioid pain relievers being an often-cited reason for the epidemic in the USA. This project looks at opioid addiction from three perspectives: a review of literature dealing with the neural pathways involved in opioid use and addiction; the underlying genetic differences that can increase the risk of opioid use disorder; and an overview of the public health aspects of the epidemic. The paper will conclude with a review of current and new treatments based upon a growing neurobiological and molecular understanding of opioid use disorder.

Dna Methylation Of The Clusterin Promoter: Associations With Alzheimer’S Disease Risk And Related Phenotypes, Madeline Peretti

Theses: Doctorates and Masters

Background

In 2017 approximately 50 million people worldwide were living with dementia. With Alzheimer’s disease (AD), accounting for 50-70% of dementia cases making this debilitating disease, with no current effective prevention, treatment or cure, a critical healthcare concern. Genome wide association studies (GWAS) have identified a number of risk genes for late onset AD (LOAD); Apolipoprotein E (APOE), a gene involved in the cholesterol/lipid pathway is considered the gene with the greatest risk. The third most associated AD risk gene is Clusterin (CLU), is also involved in the cholesterol/lipid pathway. CLU has been implicated in both …

Hpa Axis Genetic Variation And Life Stress Influences On Functional Connectivity In Resting State Networks, Tara Ann Miskovich

Theses and Dissertations

Stressful or traumatic experiences are a key risk factor for developing psychopathology, primarily through the impact that chronic stress has on hypothalamic-pituitary-adrenal (HPA) axis functioning. The HPA axis regulates the stress response but can become dysregulated with chronic activation and impact brain functioning. In addition to environmental stressors, genetic variation in genes in the HPA axis appear to influence HPA axis functioning and is also related to disruption in brain functioning, particularly in the context of high life stress. The current study focused on examining potential mechanisms through which trauma and stress interacts with HPA axis genes to impact key …

Structural And Functional Brain Connectivity In Middle-Aged Carriers Of Risk Alleles For Alzheimer's Disease, Laura Korthauer

Theses and Dissertations

Single nucleotide polymorphisms (SNPs) in APOE, COMT, BDNF, and KIBRA have been associated with age-related memory performance and executive functioning as well as risk for Alzheimer’s disease (AD). The purpose of the present investigation was to characterize differences in brain functional and structural integrity associated with these SNPs as potential endophenotypes of age-related cognitive decline. I focused my investigation on healthy, cognitively normal middle-aged adults, as disentangling the early effects of healthy versus pathological aging in this group may aid early detection and prevention of AD. The aims of the study were 1) to characterize SNP-related differences in functional connectivity …

Genetic Testing Practices Of Genetic Counselors, Geneticists, And Pediatric Neurologists With Regard To Childhood-Onset Neurogenetic Conditions, Sara Wofford

Dissertations & Theses (Open Access)

Identifying genetic diagnoses for neurological conditions with a considerable hereditary component, such as autism spectrum disorder (ASD), intellectual disability, and epilepsy, is critical to providing proper medical management for these patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. The study noted significant variance between the testing strategies selected by pediatric neurologists compared to those of geneticists …

Molecular Brain Adaptations To Ethanol: Role Of Glycogen Synthase Kinase-3 Beta In The Transition To Excessive Consumption, Andrew D. Van Der Vaart

Theses and Dissertations

Alcoholism is a complex neuropsychiatric disease that is characterized by compulsive alcohol use and intensifying cravings and withdrawals, often culminating in physiologic dependency. Fundamental alterations in brain chemistry underlie the transition from initial ethanol exposure to repetitive excessive use. Key mediators of this adaptation include changes in gene expression and signal transduction. Here we investigated gene expression pathways in prefrontal cortex and nucleus accumbens following acute or chronic ethanol treatment, to identify genes with potentially conserved involvement in the long-term response of the corticolimbic system to repeated ethanol exposure. We investigated Gsk3b, which encodes glycogen synthase kinase 3-beta, as a …

Glutamylation Regulates Transport, Specializes Function, And Sculpts The Structure Of Cilia, Robert O'Hagan, Malan Silva, Ken Cq Nguyen, Winnie Zhang, Sebastian Bellotti, Yasmin Ramadan, David Hall, Maureen M. Barr

Department of Biology Faculty Scholarship and Creative Works

Ciliary microtubules (MTs) are extensively decorated with post-translational modifications (PTMs), such as glutamylation of tubulin tails. PTMs and tubulin isotype diversity act as a “Tubulin Code” that regulates cytoskeletal stability and the activity of MT-associated proteins such as kinesins. We previously showed that, in C. elegans cilia, the deglutamylase CCPP-1 affects ciliary ultrastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of kinesin-2 OSM-3/KIF17, while a cell-specific α-tubulin isotype regulates ciliary ultrastructure, intraflagellar transport, and ciliary functions of extracellular vesicle (EV)-releasing neurons. Here, we examine the role of PTMs and the Tubulin Code in the cililary …

Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski

Sanders-Brown Center on Aging Faculty Publications

Background

Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies.

Methods

In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of …

Role Of Mitochondrial Beta-Oxidation In Ethanol Response: A Candidate Gene Study Using Caenorhabditis Elegans, Harini Pallikarana Tirumala

Theses and Dissertations

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role …

Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner

Dissertations & Theses (Open Access)

Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our understanding of the basic biology of noxious cold perception is gravely minimal. Numerous clinical conditions disrupt the sensory machinery, such as in patients suffering from tissue damage (from wound or sunburn), or injury to the peripheral nerves, as in patients with diabetes or undergoing chemotherapy. Our goal is to determine the genetic basis for noxious cold perception and injury-induced nociceptive sensitization using the genetically tractable Drosophila model. Using a novel "cold probe" tool and assay we …

The Association Of Cognitive Endophenotypes And Risky Single Nucleotide Polymorphisms Of Alzheimer's Disease Within The Alzheimer's Disease Neuroimaging Initiative (Adni) Database, Kyle Joseph Jennette

USF Tampa Graduate Theses and Dissertations

Objective: The purpose of this study was to assess the influence of three single nucleotide polymorphisms (SNP) previously associated with Alzheimer's disease on specific domains of cognition, when controlling for Apolipoprotein E gene (APOE), in a sample of individuals with Alzheimer's disease. Methods: The data were drawn from the Alzheimer's Disease Neuroimaging Initiative database, a comprehensive, longitudinal database of controls, persons with mild cognitive impairment, and persons with mild Alzheimer's disease. Each subject has a full neuropsychological assessment, neuroimaging, genetic sequencing, and physical evaluation. For the purposes of this study, individuals were selected based on the presence of the three …

Functional And Developmental Identification Of A Molecular Subtype Of Brain Serotonergic Neuron Specialized To Regulate Breathing Dynamics, Rachael D. Brust, Andrea E. Corcoran, George B. Richerson, Eugene Nattie, Susan M. Dymecki

Dartmouth Scholarship

Serotonergic neurons modulate behavioral and physiological responses from aggression and anxiety to breathing and thermoregulation. Disorders involving serotonin (5HT) dysregulation are commensurately heterogeneous and numerous. We hypothesized that this breadth in functionality derives in part from a developmentally determined substructure of distinct subtypes of 5HT neurons each specialized to modulate specific behaviors. By manipulating developmentally defined subgroups one by one chemogenetically, we find that the Egr2-Pet1 subgroup is specialized to drive increased ventilation in response to carbon dioxide elevation and acidosis. Furthermore, this subtype exhibits intrinsic chemosensitivity and modality-specific projections-increasing firing during hypercapnic acidosis and selectively projecting to respiratory chemosensory …

Impact Of Faah Genotype And Marijuana Use On Brain Structure And Neuropsychological Performance In Emerging Adults, Skyler Gabriel Shollenbarger

Theses and Dissertations

Introduction: Chronic MJ use may be associated with higher cognitive ability impairments (see Lisdahl et al., 2013). Regions undergoing later maturation (Gogtay 2004), may be at increased risk for MJ-induced alterations. Endogenous cannabinoid signaling (ECS) is modulated by the function the enzyme Fatty Acid Amide Hydrolase (see Ho & Hilard, 2005), thus the gene encoding for this enzyme (FAAH) impacts ECS (Sipe et al., 2002). Here, we examine the impact of MJ use and FAAH genotype on PFC complexity and underlying frontal white matter (WM) integrity in young adults. Methods: Participants included 37 MJ users and 37 non-using young adults …

Dopamine D1 Receptor-Mediated Nmda Receptor Insertion Depends On Fyn But Not Src Kinase Pathway In Prefrontal Cortical Neurons, Jian-Li Hu, Gang Liu, Yan-Chun Li, Wen-Jun Gao, Yueqiao Huang

PCOM Scholarly Papers

Background. Interactions between dopamine and glutamate in the prefrontal cortex are essential for cognitive functions such as working memory. Modulation of N-methyl-D-aspartic acid (NMDA) receptor functions by dopamine D1 receptor is believed to play a critical role in these functions. The aim of the work reported here is to explore the signaling pathway underlying D1 receptor-mediated trafficking of NMDA receptors in cultured rat prefrontal cortical neurons. Results. Activation of D1 receptor by selective agonist SKF-81297 significantly increased the expression of NR2B subunits. This effect was completely blocked by small interfering RNA knockdown of Fyn, but not Src. Under control conditions, …

Dopamine Controls Locomotion By Modulating The Activity Of The Cholinergic Motor Neurons In C. Elegans, Andrew T. Allen

Masters Theses 1911 - February 2014

Dopamine is an important neurotransmitter in the brain, where it plays a regulatory role in the coordination of movement and cognition by acting through two classes of G protein-coupled receptors to modulate synaptic activity. In addition, it has been shown these two receptor classes can exhibit synergistic or antagonistic effects on neurotransmission. However, while the pharmacology of the mammalian dopamine receptors have been characterized in some detail, less is known about the molecular pathways that act downstream of the receptors. As in mammals, the soil nematode Caenorhabditis elegans uses two classes of dopamine receptors to control neural activity and thus …