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Virginia Commonwealth University

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Incorporating A Developmental Perspective Into Gene Identification Models For Alcohol Use Behaviors, Nathaniel S. Thomas Jan 2023

Incorporating A Developmental Perspective Into Gene Identification Models For Alcohol Use Behaviors, Nathaniel S. Thomas

Theses and Dissertations

Frequent alcohol use can lead to alcohol use disorder, which accounts for three million deaths and over 133 million life years lost to disability and death worldwide per year. Alcohol use behaviors unfold across development, beginning with initiation of drinking and progressing through various escalating stages of use. Alcohol use behaviors are also under genetic influence. Genome-wide association represents the state-of-the-science statistical methodology for identifying genes associated with alcohol use outcomes. However, contemporary genome-wide association study (GWAS) methods typically do not account for variability in genetic effects throughout development. In this project, I applied novel multivariate genomic methods to combine …


Effects Of Gestational Ozone Exposure On Privileged Placental And Brain Barrier Integrity, Alexander I. Hamm Jan 2020

Effects Of Gestational Ozone Exposure On Privileged Placental And Brain Barrier Integrity, Alexander I. Hamm

Theses and Dissertations

Ambient outdoor ozone, a common of component of photochemical smog and urban air pollution, is linked to various neurological and vascular pathologies. Its immediate reaction with lung surfactant after inhalation results in complete reactivity of the gas, with no active ozone passing into circulation. This indicates the presence of secondary and tertiary mediators in ozone-related systemic pathologies after pulmonary insult. In vasculature, ozone exposure is associated with an acute hypertensive phenotype apparent at least 24 hours after dose, such as experienced on a hot summer afternoon in a large metropolitan area like Los Angeles or Mexico City. However, the effects …


Characterizing The Cellular Nature Of The Physical Interactions Necessary For Collective Neuron Migration, Rebecca Vareed Jan 2019

Characterizing The Cellular Nature Of The Physical Interactions Necessary For Collective Neuron Migration, Rebecca Vareed

Theses and Dissertations

Neuronal migration is an essential process in the development of the nervous system. Neurons are born in one location and migrate sizable distances to their final location. In many other developmental processes, cells migrate as collectives, where the migration of one cell influences the migration of another cell; this process has yet to be shown in the developing central nervous system. Using the conserved tangential migration of facial branchiomotor neurons (FBMNs), I aim to determine the nature of the collective migration in the developing nervous system. Here, two models of FBMN collective migration are tested: the “Pioneer” model, where following …


Zebrafish (Danio Rerio) As A Model For Orofacial Research, Kevin A. Ghaffari Jan 2017

Zebrafish (Danio Rerio) As A Model For Orofacial Research, Kevin A. Ghaffari

Theses and Dissertations

Across species, the face and more specifically the mouth, serves as an essential facet of everyday life. Amongst humans the mouth serves as a tool for the ingestion of food, a marker for facial recognition and a medium for communication. In order for the mouth to properly form, a series of precise growth and fusion events are needed. In order to insure that these events are orchestrated properly is a wide array of signals, transcription factors and epigenetic regulators. Due to the needed precision of these events, congenital birth defects of the face such as cleft lip and cleft palate …


Novel Role Of The Nociceptin System As A Regulator Of Glutamate Transporter Expression In Developing Astrocytes, Logan Meyer Jan 2017

Novel Role Of The Nociceptin System As A Regulator Of Glutamate Transporter Expression In Developing Astrocytes, Logan Meyer

Theses and Dissertations

Our previous results showed that oligodendrocyte development is regulated by both nociceptin and its G-protein coupled receptor, the nociceptin/orphanin FQ receptor (NOPR). The present in vitro and in vivo findings show that nociceptin plays a crucial conserved role in both human and rodent brain astrocytes, regulating the levels of the glutamate/aspartate transporter GLAST/EAAT1. This nociceptin-mediated response takes place during a critical developmental window that coincides with astrocyte maturation and synapse formation. GLAST/EAAT1 upregulation by nociceptin is mediated by NOPR and the downstream participation of a complex signaling cascade that involves the interaction of several kinase systems, including PI-3K/AKT, mTOR and …


Persistence Of The Larval Environment On Post-Metamorphic Performance And Population Dynamics In Amphibians, Julie Charbonnier Jan 2017

Persistence Of The Larval Environment On Post-Metamorphic Performance And Population Dynamics In Amphibians, Julie Charbonnier

Theses and Dissertations

Organisms with complex life cycles may experience diverse stressors during their development. Stressors experienced in early life stages may influence the quantity and quality of individuals in later life stages. However, it is unclear if these effects persist later in life and how they may influence population dynamics. This dissertation uses two amphibian species, the Western spadefoot toad (Pelobates cultripes) and the spotted salamander (Ambystoma maculatum) to explore how biotic and abiotic factors experienced in aquatic and terrestrial environments influence phenotype and survival. We use a combination of field mesoscosm studies, laboratory studies and modeling to …


Confocal Microscopy Study Of The Embryonic Development Of The Viviparous Nemertean Prosorhochmus Americanus Reveals Larval Features Supporting Indirect Development In Hoplonemerteans, S Tyler Spindle Aug 2013

Confocal Microscopy Study Of The Embryonic Development Of The Viviparous Nemertean Prosorhochmus Americanus Reveals Larval Features Supporting Indirect Development In Hoplonemerteans, S Tyler Spindle

Theses and Dissertations

Recent studies of hoplonenemertean planuliform larvae have clarified their development and provided insight into larval evolution within the phylum. However, an assessment of viviparous development using modern techniques is lacking. To help facilitate a comprehensive comparative evaluation of developmental diversity within hoplonemerteans, we have conducted a confocal laser scanning microscopy investigation of the development in Prosorhochmus americanus, one of the few viviparous hoplonemertean species. Phalloidin staining provides evidence of a modified transitory larval epidermis, and reveals that the foregut, midgut, proboscis, central nervous system, and body wall musculature form early in development, consistent with observations for planktonic and encapsulated hoplonemertean …


The Role Of A And B Vitamins During Orofacial Development Of Xenopus Laevis, Allyson Kennedy Jun 2012

The Role Of A And B Vitamins During Orofacial Development Of Xenopus Laevis, Allyson Kennedy

Theses and Dissertations

Orofacial anomalies make up about a third of the 120,000 birth defects each year in the United States. Children born with these abnormalities must undergo immense physical and emotional strain in order to correct the defects. In fact, about $697 million is spent every year surgically treating children with cleft lip and/or cleft palate (2011). In countries where surgery is not an option, this abnormality causes immense difficulties in eating, hearing, speech, and psychosocial development. The causes of cleft lip/palate are extremely complex. Genetics play a role in the anomaly; however, 95% of cleft palate cases are non-syndromic and likely …


Opioid Addiction Treatments During Pregnancy And Their Effects On Axonal Growth And Myelination In The Developing Central Nervous System, Manisha Magar Jul 2011

Opioid Addiction Treatments During Pregnancy And Their Effects On Axonal Growth And Myelination In The Developing Central Nervous System, Manisha Magar

Theses and Dissertations

Treatment with buprenorphine represents a promising alternative for pregnant opioid addicts but there is a need to understand potential effects on nervous system development. We previously showed effects of perinatal exposure to buprenorphine on axonal caliber and myelination in 26-day-old rat corpus callosum. These changes, detected at the end of rapid brain myelination and accompanied by earlier oligodendrocyte maturation, suggested interference with mechanisms coordinating axonal growth and myelination. To better understand buprenorphine actions and to establish whether these effects extend to the spinal cord, we analyzed the corpus callosum and corticospinal tract at 16 days of age, just before the …


A Study On The Biochemical And Cellular Effects Of Enviormental Tobacco Smoke On Adult And Developing Rat Brain Biochemistry, Brian Fuller Jan 2011

A Study On The Biochemical And Cellular Effects Of Enviormental Tobacco Smoke On Adult And Developing Rat Brain Biochemistry, Brian Fuller

Theses and Dissertations

Exposure to environmental tobacco smoke (ETS) has been recognized as a significant health risk for adults and children. In adults, ETS exposure has been linked to increased incidences of cardiovascular disease and dementia. In children, exposure has been linked to behavioral and cognitive deficits. Studies on the effects of ETS in the brain have been largely epidemiological, and have lacked a defined explanation of the molecular/biochemical effects of ETS. The present dissertation aims to test whether ETS exposure leads to altered biochemistry in the adult and developing mammalian brain. A rat ETS exposure model was employed to investigate changes at …


Novel Role Of Mecp2 In Developing Oligodendrocytes And Myelination, Daniel Moore Jan 2011

Novel Role Of Mecp2 In Developing Oligodendrocytes And Myelination, Daniel Moore

Theses and Dissertations

Methyl-CpG-binding protein 2 (MeCP2 is) is an epigenetic regulator that binds to methylated DNA. Initially identified as transcriptional repressor, MeCP2 also binds to different proteins functioning as gene activator. Importantly, MecCP2 gene mutations and changes in MeCP2 levels are associated to several forms of mental retardation and autism-related disorders; including Rett, a neurodevelopmental disorder affecting primarily girls. While brain MeCP2 was considered to be exclusively neuronal, this regulator is also present in glia. We found that oligodendrocytes, the myelinating cells of the central nervous system (CNS), express particularly high MeCP2 levels at a developmental stage that precedes their final maturation. …