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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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

“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 …

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 …

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 …

Voting For Corruption: How Poverty And Inequality Undermine Democratic Accountability In Latin America, Peter Colum Casey

All Theses and Dissertations (ETDs)

Why do citizens fail to hold their elected officials democratically accountable for corruption? In this dissertation, I argue that poverty and inequality undermine democratic accountability for corruption by creating opportunities for elected officials to mobilize political support through targeted, personal exchange. I focus on two such types of exchange, clientelism and crony capitalism, and explain how corruption reinforces these two strategies of political mobilization.

I argue that the costs of corruption are very high for the poor, who often lose access to government resources they rely on to meet their basic needs. Because the cost of failing to meet their …

Mechanics And Modeling Of Postnatal Arterial Development In Mouse Models Of Varying Elastin, Jeffrey Karl Cheng

All Theses and Dissertations (ETDs)

Proper arterial function requires a specific composition of extracellular matrix: ECM) proteins to produce a vessel with the right mechanical properties. Closed circulatory systems driven by a beating heart have pulsatile flow, requiring the large elastic arteries to have the ability to distend and recoil to dampen the pulsatile output. This unique ability is made possible by elastin in the ECM that imparts elastic behavior to the artery. Genetic mutations that affect the amount and organization of elastin result in congenital cardiovascular defects that lead to lifelong cardiovascular complications. In order to devise proper treatments we must understand how development …

Humanitarianism And The Anthropology Of Hunger, Kate Klein

Undergraduate Theses—Unrestricted

While the early view of hunger as the product of a world population too large to sustain has largely been eliminated, and the mainstream international community has come to accept that food insecurity results from issues of distribution rather than an insufficient global food supply, the emphasis on biotechnology in agriculture, humanitarianism in international aid, and social justice in international human rights law in the contemporary era has contributed to other barriers that prevent hunger alleviation.

In this thesis, I argue that these previous contemporary developments have had the capacity to hide hunger. My analysis of technology and humanitarian aid …

Growing Up Tamarin: Morphology, Reproduction, And Population Demography Of Sympatric Free-Ranging Saguinus Fuscicollis And S. Imperator, Mrinalini Watsa

All Theses and Dissertations (ETDs)

The Callitrichidae are family of small New World primates with a suite of distinctive morphological and behavioral adaptations that set them apart from other primates. Of primary interest is their reproductive system that includes compulsive twinning: ≥80% of births) and cooperative care of offspring by individuals other than biological parents: termed alloparenting). Further, hematopoietic tissues in callitrichids display signals of both self and sibling DNA, due to an exchange of stem cells early in gestation that renders twin callitrichids as cellular mosaics of each other. This phenomenon is known as genetic chimerism, which increases genetic relatedness between individuals and is …

Characterization Of Normal Development And Injury In The Premature Baboon Brain, Jennifer Griffith

All Theses and Dissertations (ETDs)

Nearly 13% of infants born in the United States each year are preterm - that is, born before 37 weeks gestation. Although improvements in clinical care have contributed to survival rates that now exceed 85%, premature infants are at high risk for motor, sensory, cognitive and behavioral disabilities. In order to develop therapeutic interventions to prevent these adverse neurodevelopmental outcomes, we must first understand the nature of cerebral injury associated with premature birth and the mechanisms by which it leads to altered brain development. A baboon: Papio papio) model of preterm birth was used to evaluate cerebral development from 90 …

The Importance Of Glucose Transport In Reproductive Events, Katie Adastra

All Theses and Dissertations (ETDs)

ABSTRACT OF THE DISSERTATION The Importance of Glucose Transport in Reproductive Events by Katie Lynn Adastra Doctor of Philosophy in Biology and Biomedical Sciences Developmental, Regenerative and Stem Cell Biology Washington University in St. Louis, 2012 Professor Kelle H. Moley, Chairperson Successful pregnancy outcome is contingent on a number of factors, the earliest of which include the events occurring during early pregnancy. This time period from fertilization to implantation requires drastic changes in both the embryo and the uterus, including cell proliferation and differentiation. Alterations in environment may lead to adverse effects during any of these stages. This emphasizes the …

A Marginal Returns Theory Of Politics, Carlos Costa

All Theses and Dissertations (ETDs)

A great deal of contemporary social science rests on a basic, ``primitive'', principle that rational agents are motivated by a quest for marginal returns to investment of time, money, and other resources. In this manuscript we argue that an analogue fundamental principle guides much of modern political science, but has remained largely This manuscript sets out to unearth, reshape and polish this principle into what we term a marginal return theory of politics. We then apply this theory to the study of electioneering in Latin America, focusing on two main elements of vote seeking: the returns of specific votes and …

Development Of Thymic Natural Killer Cells From Double Negative 1 Thymocyte Precursors, Claudia Vargas

All Theses and Dissertations (ETDs)

While there has been much progress in defining the specificity and function of natural killer: NK) cells, their differentiation has not been fully elucidated. Previous studies of thymocyte development in vitro indicate that double negative: CD4&minusCD8&minus, DN) thymocytes can develop into cells with NK cell markers, but these cells have not been well characterized. Moreover, a subpopulation of NK cells which requires an intact thymus, i.e, thymic NK cells, has been described with selective expression of CD127 although their origin and differentiation are also poorly understood. Herein, we generated and characterized NK cells differentiating from thymic DN precursors. We enriched …

Suprachiasmatic Nuclei Development: A Characterization Of Transcription Factors And The Influence Of Retinal Innervation And Vip Signaling, Cassandra Vandunk

All Theses and Dissertations (ETDs)

The suprachiasmatic nuclei: SCN) are highly specialized neural structures with an essential behavioral function; creating the rhythm of the mammalian central clock and entraining that internal clock to the external world. The nuclei each consist of approximately 10,000 neurons, each capable of creating near 24 h rhythms, organized into a highly structured network. While the molecular clockwork underlying the rhythm within neurons and network properties have been well studied, how the nuclei are initially specified and how the network develops is poorly understood. Herein, we seek to elucidate the genes and mechanisms involved in the specification and development of SCN …

Mechanics Of Heart Tube Formation In The Early Chick Embryo, Victor Varner

All Theses and Dissertations (ETDs)

The heart is the first functioning organ to form in the embryo. For decades, biologists have worked to identify many of the genetic and molecular factors involved in heart development, and over the years, these efforts have helped elucidate the vast biochemical signaling networks, which drive cardiac specification and differentiation in the embryo. Still, the biophysical mechanisms which link these molecular factors to actual, physical changes in cardiac morphology remain unclear. The aim of this thesis is to identify some of the mechanical forces which drive heart tube assembly in the early chick embryo. A unique feature of this work …

The Brains Of Babies: A Surface Based Approach To Study Cortical Development In Term And Preterm Human Infants, Jason Hill

All Theses and Dissertations (ETDs)

Half a million infants are born before term gestation each year in the United States. Although advances in newborn medicine have increased survival rates of very preterm infants to almost 90%, surviving preterm infants are at increased risk for developing lasting neurologic impairments. In order to develop a plausible neuroprotective strategy it is imperative that we improve our understanding of normal cortical development and develop tools to evaluate injury. Using a surface based approach we have characterized normal cortical development in healthy term infants and analyzed abnormalities associated with preterm birth. Accurate cortical surface reconstructions for each hemisphere of 12 …

'If We Govern Ourselves, Whose Son Is To Govern Us?': Youth, Independence And The 1960s In Lesotho, John Aerni-Flessner

All Theses and Dissertations (ETDs)

Young people in Lesotho worked actively to bring about their own conceptions of the nation in late colonial and early independence Lesotho. These youth drew on a wide range of local, national and international ideas to push for institutional change that would benefit themselves as individuals, and the nation as a whole. Tapping into larger global debates about development, the Cold War and the role of youth in societies, young Basotho actively participated in and wanted a say in the changes coming with independence. This work rethinks African nationalism, seeing a wider range of people willing and able to identify …