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Development And Structure Of Spinal Interneuron Connectivity In Larval Zebrafish, Saul Bello Rojas

Arts & Sciences Electronic Theses and Dissertations

In vertebrates, spinal interneurons are essential for the initiation and propagation of locomotor activity with each class of interneurons serving its own unique role. Ipsilateral interneurons function to control locomotor speed; whereas, commissural interneurons aid in left – right alternation. To date, most studies have been aimed at studying the impact of each individual class of interneurons onto motor neurons. However, not much work has revolved around studying interneuron – interneuron connectivity among the various cardinal classes. Furthermore, it remains unknown how the connectivity of interneurons changes along their entire axonal reach. This thesis aims to address the developmental patterns …

Genetics Of Hippocampal Subregions Across Development, Jacob Pine

Arts & Sciences Electronic Theses and Dissertations

Behavioral genetic analyses have not demonstrated robust, unique, genetic correlates of hippocampal subregion volume. The following study is the first population-based investigation of a) hippocampal longitudinal axis genetic factors b) hippocampal transverse axis genetic factors using both T1 and T2 MRI images and c) differences in the genetic components of hippocampal volume between post-adolescent adults and pre-adolescent children. Twin-based biometric analyses demonstrated that longitudinal axis subregions are associated with significant, unique, genetic variance, and that longitudinal axis subregions that are closer to one another are more genetically related than those further to one another. Although our analyses find that certain …

Impulsivity And Brain Organization In Childhood Suicide: An Adolescent Brain And Cognitive Development (Abcd) Study, Katherine Lopez

Arts & Sciences Electronic Theses and Dissertations

Rates of suicide have steadily increased across all age cohorts, revealing a particularly concerning rise in suicide among much younger age groups (10-15 years old). Recent efforts aimed at understanding suicide in youth have leveraged work from the adult literature to more pointedly examine candidate risk factors associated with childhood suicide. A noteworthy body of work has begun to clarify the role that impulsivity plays in elevating suicide risk among adults and adolescents, a critical link warranting further research in childhood suicide given the vast and well-documented changes occurring in self-control and brain maturity throughout development. Here, we examined a …

Vestibulospinal Circuit In The Larval Zebrafish, Zhikai Liu

Arts & Sciences Electronic Theses and Dissertations

The vestibular system sense gravity and self-motion to help animals maintain body balance. Although vestibular signals inform the brain of the directions and speed of our body movements, it still remains unclear how these sensory information are processed and organized in the central nervous system. My thesis aims to illustrate neural computation underlying central vestibular tuning and the topographic organization of the vestibular circuits. First I established a novel approach to perform whole-cell recording of synaptic inputs in vivo during multi-axis movements in the central vestibular neurons. This technical advance allowed me to simultaneously measure presynaptic and postsynaptic tuning, along …

Functional Optical Imaging Of The Developing Mouse Cortex In Health And Disease, Rachel Marlene Rahn

Arts & Sciences Electronic Theses and Dissertations

Neurodevelopmental disorders (NDDs) are a heterogeneous family of disorders characterized by the presence of abnormal developmental trajectories. Functional connectivity (FC) neuroimaging provides a minimally-invasive method by which to investigate the progression of these disorders and identify potential biomarkers of disease-related dysfunction for use in therapeutics’ development. My thesis work therefore took several approaches to the question of how the functional connectome reflects developmental change as well as system-wide perturbations from environmental or genetic factors. I explored the use of optical fluorescence and intrinsic signal imaging to characterize FC and stimulation-derived responses in a NDD model of perinatal exposure to selective …

The Origins & Functional Effects Of Postzygotic Mutations Throughout The Human Lifespan, Nicole Briana Rockweiler

Arts & Sciences Electronic Theses and Dissertations

Mosaicism is pervasive in humans and yet we understand little of its causes and functional consequences across the lifespan. To help solve these mysteries, we developed a suite of tools, called Lachesis, to analyze postzygotic mutations (PZMs). LachesisDetect is a novel and accurate method to detect PZMs with VAFs as low as 0.04% from bulk RNA-seq samples. LachesisMap is an innovative supervised method to reconstruct postzygotic mutation phylogenies from putative prenatal PZMs. We applied Lachesis to 17,382 samples derived from 948 donors across 54 diverse tissues and cell types from the NIH’s Genotype-Tissue Expression (GTEx) project to produce the most …

The Role Of Cdx4 During Patterning Of Definitive Hemogenic Mesoderm, John Philip Creamer

Arts & Sciences Electronic Theses and Dissertations

The current standard of treatment for a variety of hematopoietic malignancies and genetic disorders is allogenic bone marrow transplantation, where donor hematopoietic stem cells (HSCs) engraft within the host and give rise to all of them hematopoietic lineages necessary for homeostasis. In many cases, finding a compatible human leukocyte antigen (HLA) matching donor is not possible, due to the large amount of genetic variation at those loci, but with the advent of induced pluripotent stem cells (iPSCs), unlimited sources of patient matched cells can be derived. Hematopoietic differentiations of human pluripotent stem cells (hPSCs) have been shown to recapitulate the …

Fgf20 In Olfactory System And Cochlea Development, Lu Morgan Yang

Arts & Sciences Electronic Theses and Dissertations

The olfactory epithelium (OE) is a neurosensory organ required for the sense of smell. Turbinates, bony projections from the nasal cavity wall, increase the surface area within the nasal cavity lined by the OE. We identified a population of OE progenitor cells that expand horizontally during development to populate all lineages of the mature OE and increase OE surface area. We show that these Fgf20-positive, epithelium-spanning progenitor (FEP) cells are responsive to Wnt/β-Catenin signaling. Wnt signaling suppresses FEP cell differentiation into OE basal progenitors and their progeny, and positively regulates Fgf20 expression. We further show that FGF20 signals to the …

The Ontogeny Of Complex Tool Use Among Chimpanzees Of The Goualougo Triangle, Republic Of Congo, Stephanie L. Musgrave

Arts & Sciences Electronic Theses and Dissertations

Various factors are hypothesized to have contributed to the flourishing of technology during human evolution, including high-fidelity social learning, a propensity for prosocial helping, and sex differences in foraging tool use. In this research, we examined the role of these factors on the development of complex tool-using skills among wild chimpanzees (Pan troglodytes troglodytes) in the Goualougo Triangle, Republic of Congo. These apes exhibit among the most complex tool behaviors of any nonhuman animal, including the flexible use of multiple tool types and the manufacture of tools from specific raw materials, according to a particular design. Specifically, we drew upon …

Exploring Infant Leukemia Through Exome Sequencing And An In Vitro Model Of Hematopoietic Development, Mark Cannon Valentine

Arts & Sciences Electronic Theses and Dissertations

Cancer is a heterogeneous disease with myriad causes and outcomes. Many of the cancers that occur in adult populations have become increasingly well characterized with the advent of affordable high-throughput sequencing. These studies have revealed that cancer is largely a disease of somatic mutation in the adult population. In strong contrast to this, childhood cancers have an exceedingly low rate of somatic mutation. At the extreme end of this spectrum is Infant Leukemia (IL). Sequencing of IL has revealed that these tumors frequently have one or fewer somatic SNP. In the absence of a somatic explanation for IL, many other …

Typical And Atypical Development Of The Brain’S Functional Network Architecture, Ashley Nicole Nielsen

Arts & Sciences Electronic Theses and Dissertations

The human brain is a complex organ that gives rise to many behaviors. Specialized neural regions cooperate as functional networks that form an intricate functional architecture. Development provides a unique window into how brain functioning and human thinking are affected if the necessary neural features and connections are not fully formed. Similarly, developmental disorders can shed light on atypical trajectories of neural systems that may lead to or be a consequence of symptomatic behavior. A description of the typical and atypical development of functional networks is essential to identify the features of brain organization critical for mature human thinking and …

Selection Or Socialization? A Propensity Score Matched Study Of Personality And Life Events, Emorie Beck

Arts & Sciences Electronic Theses and Dissertations

Across the lifespan, personality changes in normative ways, but the source of such change remains ambiguous. Life events may be one impetus of such change, but strong selection effects into such events makes it unclear whether such change is driven by already existing differences (selection) between people or socialization following life events. In a preregistered study, we test socialization and selection effects of the Big 5 and life events using a large (N = 19,627) representative sample of Germans and 12 life events (e.g. marriage, retirement) from the GSOEP. Using propensity score matching and Bayesian multilevel growth curve models, we …

Development Of Social Exclusion Detection: Behavioral And Physiological Correlates, Hyesung Grace Hwang

Arts & Sciences Electronic Theses and Dissertations

The present work aimed to directly test the theoretical claims about how we as human detect social exclusion using both physiological and behavioral methods across different life stages. Because feeling excluded from a group is a common human experience that starts in early childhood, this basic human need to belong or connect with others is argued to be universal and thought to have an evolutionary basis. In fact, it has been argued that the ability to detect being excluded may be present from birth and detecting exclusion occurs rapidly with little cognitive processing. Study 1 tested whether this rapid detection …

“There Is No Care Here”: The Conflictual Ethics Of Kin And Bureaucratic Care In Botswana, Arielle Justine Wright

Arts & Sciences Electronic Theses and Dissertations

How do people make sense of “care” when it fails? My dissertation examines the ethical debates that are provoked by the limitations of care in the setting of home-based care and associated safety net programs in Botswana. The organization of care is negotiated across domestic and public domains, often incorporating concerns about kinship ties, dependency, and labor in the welfare state. Based on 16 months of ethnographic research, I demonstrate that the ethical evaluation of care varies between differently-positioned stakeholders engaged in providing chronic care. Economic conditions and socio-political ideologies shape the ethics of care by way of setting the …

Innate Lymphoid Cells: Transcriptional Profiles And Cytokine Developmental Requirements, Michelle Lauren Robinette

Arts & Sciences Electronic Theses and Dissertations

Innate lymphoid cells (ILCs) are a recently discovered lineage of professional cytokine-producing cells that strikingly mirror T cells in transcriptional circuitry and effector functions, but derive from distinct progenitors and do not express recombined antigen-specific receptors. These cells include natural killer (NK) cells, which parallel cytotoxic CD8+ T cells, and three additional classes of ILCs enriched at mucosal surfaces that generate signature cytokines reminiscent of polarized CD4+ helper T cells subsets, called ILC1, ILC2, and ILC3. As ILCs have been implicated in the pathogenesis of colitis, cancer, allergy, and autoimmunity in both human and mouse, understanding the functional capacity of …

Developmental Trajectories Of Executive And Verbal Processes In Children With Phenylketonuria, Zoe Hawks

Arts & Sciences Electronic Theses and Dissertations

Phenylketonuria (PKU) is a recessive disorder characterized by disruption in the metabolism of the amino acid phenylalanine. Using a verbal fluency task, previous studies demonstrated that word production is reduced in individuals with PKU relative to controls. Beyond word production, verbal fluency output can be scored for clustering and switching, which enable characterization of verbal and executive processes, respectively. The present study is the first to evaluate clustering and switching in PKU within a longitudinal design, thereby elucidating the developmental time course of core cognitive processes. To this end, semantic (animals, food/drink) and phonemic (S words, F words) fluency data …

Modeling Complex Patterns Of Differential Dna Methylation That Associate With Expression Change, Christopher E. Schlosberg

Arts & Sciences Electronic Theses and Dissertations

Gene expression is driven by specific combinations of transcription factors binding to regulatory sequences to define cell type expression profiles. Changes in DNA sequence alter transcription factor binding affinities and gene expression, and DNA methylation is an additional source of variation that is maintained throughout cellular division. Numerous genomic studies are underway to determine which genes are abnormally regulated by DNA methylation in disease. However, we have a poor understanding of how disease-specific methylation variation affects expression. Global DNA demethylation agents have been clinically approved for use in cancer, which has spurred interest in identifying genes which would be most …

Evolutionary Developmental Leaf Morphology Of The Plant Family Araceae, Claudia Liliana Henriquez

Arts & Sciences Electronic Theses and Dissertations

Studying the evolutionary developmental morphology of leaves using next-generation phylogenetics, a candidate gene approach and comparative developmental studies in the plant family Araceae is the overarching theme of the dissertation.

The plant family Araceae is an ancient lineage from the Early Cretaceous and belongs to the monocotyledons. Members of Araceae display striking variation in leaf development; such variation contradicts traditional models of monocot leaf development. Additionally, dissected leaves, which are rare in monocots, seem to have evolved independently multiple times in Araceae by various developmental mechanisms.

Despite extensive efforts to elucidate the evolutionary history of Araceae, phylogenetic ambiguity in the …

How Gains And Losses Influence The Brain And Behavior: Relations To Age, Risk For Depression, And Individual Differences, Katherine R. Luking

Arts & Sciences Electronic Theses and Dissertations

Behavioral and neural response to rewards and punishments has been the subject of a growing literature with particular interest within developmental, psychopathology, and individual difference domains. There is now mounting evidence suggesting that adolescents show heightened response to reward relative to adults, and that adolescents with Major Depressive Disorder (MDD), elevated depressive symptoms, or at high-risk for depression show reduced response to reward. However, it is unclear whether similar relations between response to incentives and development/psychopathology are observed during childhood. Here we examine behavioral, neural (functional magnetic resonance imaging - fMRI), and self-reported responsiveness to gain and loss of rewards …