Life Sciences Commons^™

The Default Network And Autism Spectrum Disorder: Characterizing Sub-Networks And Behavioral Correlates, Alyssa K. Kozlowski

Theses and Dissertations

The default network (DN), and specifically its sub-networks default network A (DN A) and default network B (DN B), has been strongly implicated in social cognition. This study examined its role in predicting social behavior, and also differences that may exist across diagnostic groups that may explain discrepancies in social cognition and behavior. One of the popular methods of study is functional connectivity, or analyzing correlated activity in the brain. Autism Spectrum Disorder (ASD) is a disorder characterized by social impairment and abnormal social behavior. To date, much of the functional connectivity research in ASD has focused on global connectivity, …

The Influence Of Thc, Opioids, And Age On The Plasticity Of Excitatory Inputs To Ventral Tegmental Area Gaba Neurons, Isaac Brent Ostlund

Theses and Dissertations

Adults exhibit significant differences in drug vulnerability, learning ability, and emotive processing than adolescents. Long-lasting synaptic changes, including long-term depression (LTD), can endure many hours and are believed to be key to encoding memories and persistent cognitive changes such as addiction. The ventral tegmental area (VTA) is the primary source of midbrain dopamine (DA) and is regulated by local inhibitory GABA neurons. GABA regulation can decrease, resulting in dis-inhibition of DA neurons and increased feelings of reward, learning, or salience attachment to memories. Endocannabinoids (eCBs) are signaling molecules that often result in synaptic plasticity changes, and the eCB system has …

Negative Regulation Of The Kinase Lin-45 By The E3/E4 Ubiquitin Ligase Ufd-2, Augustin Deniaud

Theses and Dissertations

The serine/threonine kinase BRAF is a key part of the Ras-Raf-MEK-ERK pathway, an inducer of cell growth, differentiation, and survival. In humans, activating mutations, most commonly BRAF(V600E), have been detected in several cancers, including melanoma and thyroid cancer. In the Caenorhabditis elegans ortholog LIN-45, the equivalent mutation LIN-45(V627E) results in elevated Raf-MEK-ERK signaling. We performed an unbiased genetic screen to identify negative regulators of LIN-45(V627E). Here, we report the identification of the E3/E4 ubiquitin ligase UFD-2, and show it is a negative regulator of LIN-45 protein activity and levels. Loss of UFD-2 leads to accumulation of wild-type LIN-45 protein as …

Developmental Regression Analysis And Investigation Of Genotype Correlations In Individuals With Classic Rett Syndrome, Aubrey Lynn Rose

Theses and Dissertations

Rett syndrome (RTT) is a neurodevelopmental disorder impacting 1 in 10,000 females worldwide, making it one of the most common causes of complex disability in girls. RTT is caused by pathogenic variants in the MECP2 gene and is characterized by developmental regression, stereotypical hand movements, and an abnormal gait. Despite consistency in the presence of these core features, a wide range of features and varying severity can be observed in girls with RTT. Similarly, the particular type of MECP2 variant present also differs between patients. Previous studies have assessed correlations between genotype and phenotype in patients with RTT. While past …

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 …

Role Of Transient Receptor Potential Channels In Epithelial Morphogenesis In Chick Embryo, Trinity Q. Waddell

Theses and Dissertations

Transient Receptor Potential channels (TRP) are a superfamily of cationic specific ionchannels that are regulated by various stimuli such as temperature, pH, mechanical stress, ligandsand ion concentration. The role of TRP channels in disease states such as autosomal dominantpolycystic kidney disease, cancer metastasis, and developmental defects lend credence to thebelief that they play an important part in epithelial morphogenesis events. The development ofsomites, neural tube closure and migration of neural crest cells to form things such as the faceand heart is a good developmental model for the aforementioned cellular processes. We haveshown that TRP channels can be found in the …

Characterization Of Pth Type-2 Receptor ( Pth2rb ) And Its Endogenous Ligand Pth2 In Zebrafish Development, Nicholas Seitz

Theses and Dissertations

Members of the parathyroid hormone family of ligands, PTH (parathyroid hormone), PTH2, and PTHLH (parathyroid hormone-like hormone). These hormones interact with the class B GCPRs parathyroid hormone receptors PTH1R, PTH2R, and PTH3R to regulate a variety of biological processes. In mammals, PTH and PTHLH activate PTH1R and PTH3R to mediate serum calcium homeostasis, chondrogenesis, and bone maintenance. PTH2R activation by PTH2 has been studied primarily in regard to its neuroendocrine roles but is also found in the skin where it contributes to wound healing and keratinocyte differentiation. Still, little is known about the impacts of PTH2R signaling relative to PTH1R …

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 …

The Role Of Phototaxis In The Initial Swim Bladder Inflation Of Larval Yellow Perch (Perca Flavescens)., Christopher Ryan Suchocki

Theses and Dissertations

The North Central Regional Aquaculture Center has designated the yellow perch (Perca flavescens) as a high priority species for culture. The demand for this species is high and it is estimated that the market could readily consume 50 to 100 million pounds per year. Tank culturing of yellow perch has several advantages over pond culture and this method has been growing in popularity, but is currently held back by problems in larval development. One of these problems, failed swim bladder inflation (SBI), is frequently reported in the literature as a bottleneck in the culture of many fishes. Unsuccessful SBI increases …

Development Of Mechanosensory Innervation In The Frog, Xenopus Laevis, Peter Andrew Feuk

Theses and Dissertations

ABSTRACT

DEVELOPMENT OF MECHANOSENSORY INNERVATION IN THE FROG, XENOPUS LAEVIS

by

Peter Feuk

The University of Wisconsin-Milwaukee, 2017

Under the Supervision of Dr. R. David Heathcote

This study aims to investigate whether a specific target cell in the epidermis of the African clawed frog, Xenopus laevis, guides the initial outgrowth and pattern of Rohon-Beard (RB) cells and their survival. RB cells are primary mechanosensory neurons present during the early developmental stages of X. laevis. These neurons provide sensory input to the frog throughout embryonic and larval development before initiating apoptosis around the start of metamorphosis. The innervation of embryonic skin …

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

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

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 …

Development Of A Sandwich Hybridization Assay For The Harmful Cyanobacteria Microcystis Spp., Nicole M. Dearth

Theses and Dissertations

Cyanobacteria are responsible for the largest number of harmful blooms (HABs) worldwide. HABs caused by the genus Microcystis pose public health threats because they often occur within close proximity to humans and produce microcystin (hepatotoxin), which can contaminate drinking water and recreational areas. Novel molecular techniques facilitate monitoring, ‘early warnings’ of HAB events, and appropriate management responses. Sandwich hybridization assay (SHA), the technique considered here, directly (no amplification) identifies and quantifies planktonic species using ribosomal RNA (rRNA)-targeted oligonucleotides. This project developed SHA for Microcystis 16S rRNA and validated the assay using laboratory cultures and samples from a multi-specific cyanobacteria bloom …

Applying The Water Governance Framework On Rural Water Development Projects In Guatemala, Muhanad M. Alkharaz

Theses and Dissertations

According to the Organization for Economic Cooperation and Development (OECD), ‘Water crisis is mainly a governance crisis’, (OECD, 2013). Many water experts, as individuals, organizations and even governmental bodies have developed water governance frameworks to overcome water challenges on local, national, and international levels such as Integrated Water Resource Management. In rural areas, especially in developing countries, access to safe drinking water is a daily challenge due to a variety of political, economic, and social constraints. For in-stance, some developing countries have a strong centralized governance system. Due to lack of capacity and resources, central governments are incapable of providing …

Effects Of The Developmental Environment On Oxidative Damage And Antioxidants In Red-Eared Slider Turtle ( Trachemys Scripta Elegans ) Hatchlings, Lisa Allison Treidel

Theses and Dissertations

Developmental environments influence many individual phenotypes. However, currently we have a limited understanding of how the developmental environment influences oxidative stress resistance phenotypes. Oxidative stress is defined as a physiological state during which the production of harmful free radicals exceeds the protective capabilities of antioxidants. Variations among adults in susceptibility to oxidative stress can have important consequences for life history strategies and fitness related traits. Our work was aimed at providing insight in to the role that the developmental environment plays on oxidative stress phenotypes in the model oviparous reptile the red-eared slider turtle (Trachemys scripta elegans). Here, we conducted …

Role Of Non-Muscle Myosin Ii And Calcium In Zebrafish Midbrain-Hindbrain Boundary Morphogenesis, Srishti Upasana Sahu

Theses and Dissertations

Elucidating the molecular mechanisms that play a role in cellular morphogenesis is critical to our understanding of brain development and function. The midbrain-hindbrain boundary (MHB) is one of the first folds in the vertebrate embryonic brain and is highly conserved across species. We used the zebrafish MHB as a model for determining the molecular mechanisms that regulate these cell shape changes. Cellular morphogenesis is tightly regulated by signaling pathways that rearrange the cytoskeleton and produce mechanical forces that enable changes in cell and tissue morphology. The generation of force within a cell often depends on motor proteins, particularly non-muscle myosins …

The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki

Theses and Dissertations

Developing neurons extend processes to specific targets and establish connections that are essential for future function of the nervous system. One of these processes, the axon, has a motile tip called a growth cone that rearranges its membrane-associated actin cytoskeleton to turn toward or away from environmental guidance cues. Growth associated protein 43 (GAP-43) is one of the most abundant proteins associated with axonal growth cone membranes and is known to modulate the formation and stability of the actin cytoskeleton during axon guidance. Protein kinase C (PKC)-mediated phosphorylation of GAP-43 on serine 42 regulates its interactions with actin. Phosphorylated GAP-43 …

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 …

Tissue Specific Porcupine Deletion Reveals A Novel Role For Ectodermal Wnts In Musculotendon Development, Aaron P. Smith

Theses and Dissertations

The Wnt family of secreted proteins consists of 19 family members (in the mouse) and is known to signal through multiple pathways that regulate crucial processes in the development of almost all tissues. Dissecting the roles of individual Wnts has been hampered due to functional redundancy that exists between family members. We made use of a conditional allele of the acyltransferase, Porcupine (Porcn), that is required for the secretion of all Wnt ligands, and the Msx2Cre deleter to eliminate the secretion of all Wnt ligands from the ventral limb ectoderm, ventral abdominal ectoderm, and urogenital ectoderm. Phenotypically the …

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

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 …

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. …

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 …

Expression Of Nicotinic Acetylcholine Receptor Mrna As A Function Of Age In Whole Hippocampus Preparations From Wistar Rats, Kasey C. Welch

Theses and Dissertations

Whole hippocampus preparations, isolated bilaterally, from untreated Wistar rats at various ages (10-90 days old) were analyzed for the mRNA expression of the alpha 2, alpha 3, alpha 4, alpha 5, alpha 7, beta 2, beta 3, and beta 4 neuronal nicotinic acetylcholine receptor subunits. To do so, RNA was isolated from acutely isolated hippocampal samples, converted to cDNA by means of a reverse transcription reaction, then analyzed with quantitative real-time PCR to determine the relative levels of the mRNAs the cells were expressing at the age when the samples were obtained. The relative expression of the levels of RNA …

Characterization Of A Novel Nuclear Variant Of Bmp2 And Coordinate Regulation Of Col11a2 And Col27a1 By The Transcription Factor Lc-Maf, Jaime Lynn Mayo

Theses and Dissertations

ABSTRACT I CHARACTERIZATION OF A NOVEL NUCLEAR VARIANT OF BMP2

Bone morphogenetic protein 2 (Bmp2) is a signaling protein that was first detected by its ability to induce cartilage and bone formation. It has since been implicated in broad variety of developmental, patterning, and disease processes. To date, Bmp2 has only been known to function as an extracellular signaling molecule. However, we have obtained clear evidence for a nuclear form of Bmp2. This nuclear variant, nBmp2, contains a bipartite NLS that overlaps the site of proteolytic cleavage. The NLS remains intact and functional when translation of Bmp2 initiates from a …

Fgf4 And Wnt5a/Pcp Signaling Promote Limb Outgrowth By Polarizing Limb Mesenchyme, Keri Lynn Low

Theses and Dissertations

The focus of this study was to elucidate the molecular and cellular mechanisms whereby fibroblast growth factors (FGFs) mediate outgrowth of the limb. Specifically, we examined the epistatic relationship between FGF and Wnt/Planar cell polarity (PCP) signaling in establishing cell polarity as a mechanism for outgrowth. By implanting beads into embryonic limbs and lateral plate mesoderm, we established that FGF activates Wnt5a in a gradient fashion. Once it was established that Wnt5a was expressed at the right time and place to turn on PCP signaling, we investigated the ability of Wnt5a to influence cell migration and/or cell polarity. Our analysis …

The Role Of Fgfr4 In Trigeminal Placode Cell Development, Stephanie Beth Reynolds

Theses and Dissertations

In vertebrate embryos, the ophthalmic trigeminal (opV) placode contributes sensory neurons to the trigeminal ganglion during development of the peripheral nervous system. FGFR4 is expressed transiently in the trigeminal placode as cells undergo an epithelial-mesenchymal transition and begin to migrate toward the condensing ganglion. Because of the restricted spatiotemporal expression of FGFR4 in the opV placode, it was hypothesized that FGFR4 is necessary for the process of epithelial-mesenchymal transition in the opV placode. Using electroporation, an FGFR4 inhibitory gene construct was introduced into 6—10 somite stage chick embryos. This secreted inhibitory form of the FGFR4 gene blocked endogenous FGFR4 signaling, …