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Cover Crop Application On Dredged Sediments Increases Corn Yield Through Microorganism-Associated Enzyme-Driven Nutrient Mineralization, Ashley N. Julian, Louise M. Stevenson, Megan A. Rúa May 2023

Cover Crop Application On Dredged Sediments Increases Corn Yield Through Microorganism-Associated Enzyme-Driven Nutrient Mineralization, Ashley N. Julian, Louise M. Stevenson, Megan A. Rúa

Biological Sciences Faculty Publications

Background & Aims

Common strategies to mitigate soil degradation of agricultural soils include cover crop application and soil amendment addition. Applying dredged sediments as a soil amendment is gaining popularity since they often provide benefits other amendments lack; however, their use with cover crops is largely unexplored. To understand how cover crop use changes the restorative properties of dredged sediments, we assessed soil physical and chemical properties, enzymatic activities, and corn yield for plots of dredged sediments with and without a cover crop.

Methods

We assessed soil texture, bulk density, water content, pH, nitrogen, phosphorus, cation exchange capacity, calcium, magnesium, …


A Standard Protocol To Report Discrete Stage-Structured Demographic Information, Samuel J. L. Gascoigne, Simon Rolph, Daisy Sankey, Nagalakshmi Nidadavolu, Adrian S. Stell Pičman, Christina M. Hernández, Matthew E. R. Philpott, Aiyla Salam, Connor Bernard, Erola Fenollosa, Young Jun Lee, Jessica Mclean, Shathuki Hetti Achchige Perera, Oliver G. Spacey, Maja Kajin, Anna C. Vinton, C. Ruth Archer, Jean H. Burns, Danielle L. Buss, Hal Caswell, Judy P. Che-Castaldo, Dylan Z. Childs, Pol Capdevila, Aldo Compagnoni, Elizabeth Crone, Thomas H. G. Ezard, Dave Hodgson, Tiffany M. Knight, Owen R. Jones, Eelke Jongejans, Jenni Mcdonald, Brigitte Tenhumberg, Chelsea C. Thomas, Andrew J. Tyre, Satu Ramula, Iain Stott, Raymond L. Tremblay, Phil Wilson, James James Vaupel, Roberto Salguero-Gómez May 2023

A Standard Protocol To Report Discrete Stage-Structured Demographic Information, Samuel J. L. Gascoigne, Simon Rolph, Daisy Sankey, Nagalakshmi Nidadavolu, Adrian S. Stell Pičman, Christina M. Hernández, Matthew E. R. Philpott, Aiyla Salam, Connor Bernard, Erola Fenollosa, Young Jun Lee, Jessica Mclean, Shathuki Hetti Achchige Perera, Oliver G. Spacey, Maja Kajin, Anna C. Vinton, C. Ruth Archer, Jean H. Burns, Danielle L. Buss, Hal Caswell, Judy P. Che-Castaldo, Dylan Z. Childs, Pol Capdevila, Aldo Compagnoni, Elizabeth Crone, Thomas H. G. Ezard, Dave Hodgson, Tiffany M. Knight, Owen R. Jones, Eelke Jongejans, Jenni Mcdonald, Brigitte Tenhumberg, Chelsea C. Thomas, Andrew J. Tyre, Satu Ramula, Iain Stott, Raymond L. Tremblay, Phil Wilson, James James Vaupel, Roberto Salguero-Gómez

School of Biological Sciences: Faculty Publications

  1. Stage-based demographic methods, such as matrix population models (MPMs), are powerful tools used to address a broad range of fundamental questions in ecology, evolutionary biology and conservation science. Accordingly, MPMs now exist for over 3000 species worldwide. These data are being digitised as an ongoing process and periodically released into two large open-access online repositories: the COMPADRE Plant Matrix Database and the COMADRE Animal Matrix Database. During the last decade, data archiving and curation of COMPADRE and COMADRE, and subsequent comparative research, have revealed pronounced variation in how MPMs are parameterized and reported.

  2. Here, we summarise current issues related to …


The Synergistic Response Of Primary Production In Grasslands To Combined Nitrogen And Phosphorus Addition Is Caused By Increased Nutrient Uptake And Retention, Eduardo Vázquez, Elizabeth T. Borer, Miguel N. Bugalho, Maria C. Caldeira, Rebecca L. Mcculley, Anita C. Risch, Eric W. Seabloom, George R. Wheeler, Marie Spohn May 2023

The Synergistic Response Of Primary Production In Grasslands To Combined Nitrogen And Phosphorus Addition Is Caused By Increased Nutrient Uptake And Retention, Eduardo Vázquez, Elizabeth T. Borer, Miguel N. Bugalho, Maria C. Caldeira, Rebecca L. Mcculley, Anita C. Risch, Eric W. Seabloom, George R. Wheeler, Marie Spohn

School of Biological Sciences: Faculty Publications

Background and aims A synergistic response of aboveground plant biomass production to combined nitrogen (N) and phosphorus (P) addition has been observed in many ecosystems, but the underlying mechanisms and their relative importance are not well known. We aimed at evaluating several mechanisms that could potentially cause the synergistic growth response, such as changes in plant biomass allocation, increased N and P uptake by plants, and enhanced ecosystem nutrient retention.

Methods We studied five grasslands located in Europe and the USA that are subjected to an element addition experiment composed of four treatments: control (no element addition), N addition, …


Ecological Boundaries And Constraints On Viable Eco-Evolutionary Pathways, Kyle E. Coblentz, John P. Delong May 2023

Ecological Boundaries And Constraints On Viable Eco-Evolutionary Pathways, Kyle E. Coblentz, John P. Delong

School of Biological Sciences: Faculty Publications

Evolutionary dynamics are subject to constraints ranging from limitations on what is physically possible to limitations on the pathways that evolution can take. One set of evolutionary constraints, known as ‘demographic constraints’, constrain what can occur evolutionarily due to the demographic or dynamical consequences of evolution leading to conditions that make populations susceptible to extinction. These demographic constraints can limit the strength of selection or the rates of environmental change populations can experience while remaining extant and the trait values a population can express. Here we further hypothesize that the population demographic and dynamic consequences of evolution also can constrain …


Investigating The Role Of Tgf-Beta Signaling In Acoel Regeneration & Fission, Franchesca A. Aziz May 2023

Investigating The Role Of Tgf-Beta Signaling In Acoel Regeneration & Fission, Franchesca A. Aziz

Undergraduate Honors Theses

Whole-body regeneration and asexual reproduction are widespread in the Metazoa, yet little is known about the genetic systems that drive the regeneration process outside of a few model organisms. While many animals utilize fission followed by regeneration to accomplish asexual reproduction, Convolutriloba longifissura is unusual in performing a double fission, requiring significant anterior-posterior and medial-lateral regeneration that alters the orthogonal body axes in adult tissues. To better understand the process of axial re-specification during postembryonic development, we studied the genetic mechanisms used by C. longifissura to modify and respecify axial polarity during asexual reproduction and subsequent regeneration. Because conserved signaling …


Roles Of The Transcription Factors Bcl6, Irf2, And Notch2 In Myeloid Development, Kevin William O'Connor May 2023

Roles Of The Transcription Factors Bcl6, Irf2, And Notch2 In Myeloid Development, Kevin William O'Connor

Arts & Sciences Graduate Student Theses and Dissertations

Development of immune cells is orchestrated by expression of transcription factors which function to control differentiation of progenitor populations and survival of mature cells. Nonclassical monocytes are a population of myeloid cells which patrol the bloodstream and are thought to maintain vascular endothelium. Conventional dendritic cells (cDCs) are antigen-presenting myeloid cells which serve to activate naïve T cells during infections. cDCs are further differentiated into cDC1s capable of cross-presenting exogenous antigens to activate CD8 T cells and cDC2s which are thought to play essential roles in activating Th2 and Th17 responses. These disparate cells originate from a shared bone marrow …


Dynamics Of Epithelial Differentiation Following Intestinal Villus Injury, Takahiro Erick Ohara May 2023

Dynamics Of Epithelial Differentiation Following Intestinal Villus Injury, Takahiro Erick Ohara

Arts & Sciences Graduate Student Theses and Dissertations

Millions of finger-like structures called villi line the small intestine, providing an enormous surface area for rapid and efficient nutrient absorption. Collapse of the villus architecture, known as villus atrophy, is often observed in response to pathogen invasion, inflammation, medications, and ischemia due to loss of intestinal epithelial cells, resulting in symptoms of diarrhea and malabsorption. Though removal of the inciting agent generally allows for near complete tissue recovery, some individuals take longer to restore their villi, a condition known as persistent villus atrophy, for reasons that are unknown. How intestinal villi cope with tissue damage and re-establish their structure …


Development Of Myelin In Wolfram Syndrome, Olga Reine Neyman May 2023

Development Of Myelin In Wolfram Syndrome, Olga Reine Neyman

Arts & Sciences Graduate Student Theses and Dissertations

Wolfram syndrome is a rare, autosomal recessive disease traditionally characterized by juvenile onset insulin dependent diabetes, optic atrophy, deafness, and neurodegeneration often beginning in childhood and adolescence. The disease is caused by mutations in WFS1, which encodes for the protein wolframin and is associated with endoplasmic (ER) stress-mediated apoptosis. ER stress-related dysfunction may inhibit production of myelin during neurodevelopment in Wolfram syndrome, as active and developing oligodendrocytes are more vulnerable to ER stress than mature ones. It is known that white matter tracts are compromised in the disease, but many questions related to the vulnerability of myelin and its impact …


An Investigation Of Second-Site Non-Complementation Among Motile Cilia Genes In Chlamydomonas Reinhardtii, Gervette M. Penny May 2023

An Investigation Of Second-Site Non-Complementation Among Motile Cilia Genes In Chlamydomonas Reinhardtii, Gervette M. Penny

Arts & Sciences Graduate Student Theses and Dissertations

ABSTRACT OF THE DISSERTATIONAn Investigation of Second-Site Non-Complementation among Motile Cilia Genes in Chlamydomonas reinhardtii by Gervette M. Penny Doctor of Philosophy in Biology and Biomedical Sciences Molecular Genetics and Genomics Washington University in St. Louis, 2023 Professor Susan K. Dutcher, ChairMotile cilia are complex microtubule-based organelles used by eukaryotic cells for locomotion or directing fluid flow. In humans, motile cilia defects cause primary ciliary dyskinesia (PCD), characterized by neonatal respiratory distress, recurrent lung infections, bronchiectasis, and low nitric oxide. Situs inversus and/or male infertility are present in about 50% of cases. PCD inheritance is recessive; both copies (alleles) of …


Evaluating The Function Of Dnmt3a Mutations Associated With Acute Myeloid Leukemia And Dnmt3a Overgrowth Syndrome, Yang Li May 2023

Evaluating The Function Of Dnmt3a Mutations Associated With Acute Myeloid Leukemia And Dnmt3a Overgrowth Syndrome, Yang Li

Arts & Sciences Graduate Student Theses and Dissertations

Heterozygous loss-of-function mutations in the DNMT3A gene are the most common cause of clonal hematopoiesis, and among the most common initiating events for Acute Myeloid Leukemia (AML). Meanwhile, mutant DNMT3A cause an overgrowth syndrome, DNMT3A Overgrowth Syndrome (DOS, also known as Tatten-Brown-Rahmen syndrome, TBRS). Amino acid R882H mutation is the most frequent variance of DNMT3A, while the rest of the mutations spread out on the entire gene of DNMT3A. Over 70% of DNMT3A mutants cause loss of function change. A reduction of DNMT3A activity causes a canonical, focal hypomethylation phenotype in hematopoietic cells, which is associated with immortalization of hematopoietic …


The Influence Of The Gut Microbiota On Asthma In School-Aged Children And Adults, Naomi Grace Wilson May 2023

The Influence Of The Gut Microbiota On Asthma In School-Aged Children And Adults, Naomi Grace Wilson

Arts & Sciences Graduate Student Theses and Dissertations

Asthma is a common respiratory disease with a highly heterogeneous pathophysiology. The human gut microbiota, comprising of all the microorganisms that inhabit the gastrointestinal tract, is linked to the development of asthma and can alter airway inflammation in animal models. The idea that the gut microbiota can have bidirectional cross-talk with the lung, such as gut dysbiosis affecting lung disease, is termed the gut-lung axis. While the gut microbiota of early life has been an area of particular interest for asthma pathogenesis research, the effect of its taxonomic and functional composition after asthma diagnosis is less clear. This dissertation employs …


Mapping Brain Development And Decoding Brain Activity With Diffuse Optical Tomography, Kalyan Tripathy May 2023

Mapping Brain Development And Decoding Brain Activity With Diffuse Optical Tomography, Kalyan Tripathy

Arts & Sciences Graduate Student Theses and Dissertations

Functional neuroimaging has been used to map brain function as well as decode information from brain activity. However, applications like studying early brain development or enabling augmentative communication in patients with severe motor disabilities have been constrained by extant imaging modalities, which can be challenging to use in young children and entail major tradeoffs between logistics and image quality. Diffuse optical tomography (DOT) is an emerging method combining logistical advantages of optical imaging with enhanced image quality. Here, we developed one of the world’s largest DOT systems for high-performance optical brain imaging in children. From visual cortex activity in adults, …


Investigating Disease Progression And Therapeutic Targets In Multiple Myeloma Using Single-Cell Technologies, Lijun Yao May 2023

Investigating Disease Progression And Therapeutic Targets In Multiple Myeloma Using Single-Cell Technologies, Lijun Yao

Arts & Sciences Graduate Student Theses and Dissertations

Multiple Myeloma (MM) is a highly heterogeneous disease characterized by uncontrolled clonal expansion of plasma cells. Single-cell techniques are advantageous in providing a more granular understanding of inter- and intratumoral genomics and surrounding microenvironments. The high relapse rate and intrinsic complexity of MM make the application of single-cell technologies particularly beneficial. Understanding the concordance of the measurements across single cell techniques in MM is of great interest. In this dissertation, we first integrated three single-cell technologies, namely scRNA-seq, CyTOF, and CITE-seq, to characterize MM immune microenvironment and assess their concordances of measurement. Overall, cell type abundances were relatively consistent, while …


Trpm5'S Role In Vascular Development, Megan Goeckel May 2023

Trpm5'S Role In Vascular Development, Megan Goeckel

Arts & Sciences Graduate Student Theses and Dissertations

Blood vessels are composed of two main cell types, endothelial cells (ECs) and mural cells (MCs). Endothelial cells comprise of the inner-most layer of the vessel and sense changes in blood flow to recruit mural cells. The mechanism for how endothelial cells sense these hemodynamic changes is not well understood and deciphering this mechanism is the focus of this thesis. We hypothesize that transient receptor potential melastatin 5 (TRPM5), a transmembrane channel protein, is involved in this process. Here, using cultured human endothelial cells and the zebrafish model, we show that inhibition of TRPM5 decreases vessel formation and increases EC-MC …


Cancer Immunogenomics Approaches To Characterizing And Treating Malignant Brain Tumors, Maximilian Oswald Schaettler May 2023

Cancer Immunogenomics Approaches To Characterizing And Treating Malignant Brain Tumors, Maximilian Oswald Schaettler

Arts & Sciences Graduate Student Theses and Dissertations

Fueled by a deeper understanding of the fundamental mechanisms of anti-tumor immune responses, cancer immunotherapy has experienced a resurgence over the last decade with remarkable success in the treatment of certain malignancies. However, despite a multitude of treatment approaches ranging from immune checkpoint blockade to adoptive cellular therapy to neoantigen vaccines, certain cancer types have shown limited response to immunotherapy. Glioblastoma multiforme (GBM), the most common primary malignancy of the central nervous system, represents a particularly challenging tumor where new treatment approaches are desperately needed. Despite multimodality treatment consisting of surgical resection, chemotherapy, and radiation therapy, patients with GBM face …


Influence Of Environmental Gradients On Genomic Variation In Pediatric Commensals And Pathogens, Sanjam Sawhney May 2023

Influence Of Environmental Gradients On Genomic Variation In Pediatric Commensals And Pathogens, Sanjam Sawhney

Arts & Sciences Graduate Student Theses and Dissertations

Microbes interact with humans in a myriad of ways. They come together in the human gut to form complex communities that collectively transform and individually evolve in response to changing environmental conditions. Individual microbes can also cause human infection and escape antibiotic clearance through acquisition and development of novel resistance mechanisms. In this thesis, I chronicle the relationships between microbes and humans across two axes: from complex communities to single isolates, and from targeted studies of pediatric populations vulnerable to microbiome perturbations and pathogen challenge, to broader human and animal cohorts spanning colonizing and diagnostic environments.In Chapter 2, I extensively …


Assessing Paleoenvironmental Change Of A Boca Raton Inlet Through Midden Shell Artifact Analysis, Maria Gabriella Almeida May 2023

Assessing Paleoenvironmental Change Of A Boca Raton Inlet Through Midden Shell Artifact Analysis, Maria Gabriella Almeida

Graduate Student Dissertations, Theses, Capstones, and Portfolios

In this archeological study of a barrier island shell midden in Boca Raton, FL, we evaluate possible environmental and cultural changes that occurred through time by performing a quantitative analysis of shell artifacts of Giant False Donax (Iphigenia brasiliana) and Common Atlantic Oyster (Crassostrea virginica) collected from the shell midden. Middens are archeological trash sites used by researchers to identify artifacts used by past populations to understand their behaviors. The artifacts collected in shallow portion of the midden are younger (therein representing more recent time periods) and the artifacts collected at the deeper portion are older …


Secondary Channel Backwaters May Be Superior Nurseries For Native Fishes In The San Juan River Of The American Southwest, But Monsoon-Driven Deteriorations May Lessen Their Quality, Blake Hansen May 2023

Secondary Channel Backwaters May Be Superior Nurseries For Native Fishes In The San Juan River Of The American Southwest, But Monsoon-Driven Deteriorations May Lessen Their Quality, Blake Hansen

Electronic Theses & Dissertations

The Razorback Sucker (Xyrauchen texanus) and Colorado Pikeminnow (Ptychocheilus lucius) are federally-endangered species occurring in the San Juan River of NM, CO, and UT, USA. These species have shown little natural recruitment in this system, with a lack of high-quality nursery habitats being one potential explanation for this phenomenon. The young-of-year of both species prefer backwaters, including those that form in secondary channels or in association with islands. However, it is unknown how factors that could limit imperiled fish recruitment, such as hydrologic stability, physicochemical features, resource availability, and nonnative fish densities, differ between secondary channel …


The Effects Of Aluminum Ion Exposure On Planarian Photophobic Response To Different Wavelengths Of Light, Anden J. Velez May 2023

The Effects Of Aluminum Ion Exposure On Planarian Photophobic Response To Different Wavelengths Of Light, Anden J. Velez

Graduate Student Dissertations, Theses, Capstones, and Portfolios

Aluminum exposure has been linked to the development of neurological diseases (Kim et al., 2021). It has increased in quantity in the environment due to industrial activity in producing personal care products and fast food (Tietz et al., 2019). The freshwater invertebrate planarian flatworm Giardia dorotocephala (G. dorotocephala) serves as a model organism. Humans and planarians both express the ion channel transient receptor potential ankyrin 1 (TRPA1), which is responsible for thermotaxis, locomotive response to heat, and pain reception (Arenas et al., 2017). Aluminum exposure can exert ion channel-related toxicity via the TRPA1 protein. It has been found …


Evaluating The Impact Of Temperature And Artificial Light At Night On The Growth, Swimming Performance, And Corticosterone Levels Of Southern Leopard Frog (Lithobates Sphenocephalus) Tadpoles, Skylar Alexander May 2023

Evaluating The Impact Of Temperature And Artificial Light At Night On The Growth, Swimming Performance, And Corticosterone Levels Of Southern Leopard Frog (Lithobates Sphenocephalus) Tadpoles, Skylar Alexander

Honors Theses

Anthropogenic activities caused by urbanization have considerably altered our world’s ecosystems which has led to a global amphibian population decline. Encroaching and unyielding urbanization by humans has contributed to a rise in artificial light at night due to light pollution as well as increased temperature due to climate change. Both rising temperatures and artificial light at night (ALAN) have been shown to individually have negative effects on amphibian physiology such as increased stress and decreased behavior. However, due to the drastic nature of human imposition, amphibians typically encounter these anthropogenic stressors in combination. Therefore, it is important to understand how …


Bioinformatic Tools To Alleviate The Annotation Bottleneck Within Precision Oncology, Erica Kay Barnell May 2023

Bioinformatic Tools To Alleviate The Annotation Bottleneck Within Precision Oncology, Erica Kay Barnell

Arts & Sciences Graduate Student Theses and Dissertations

In the era of advanced ability to perform complex genomic sequencing, precision oncology has been adopted as the ideal paradigm for optimization of outcomes for patients with cancer. However, despite technological advances in all aspects of the massively parallel sequencing pipeline, the application of precision oncology to every clinical workflow has been unattainable. Suboptimal adoption of custom medicine within oncology is attributable to the annotation bottleneck, which currently demands inordinate manual and computational requirements for completion. Alleviation of the annotation bottleneck requires co-development of bioinformatic strategies and analysis knowledgebanks to automate variant identification and variant annotation for clinical utility. The …


Maternal-Fetal Circadian Communication During Pregnancy, Keenan Bates May 2023

Maternal-Fetal Circadian Communication During Pregnancy, Keenan Bates

Arts & Sciences Graduate Student Theses and Dissertations

Circadian rhythms in gene expression and hormones are ubiquitous across species and across cell types. Circadian rhythms depend on a transcription-translation negative feedback loop that drives many daily rhythms in behavior and physiological processes. Circadian rhythms regulate many aspects of reproduction, such as fetal development and birth timing. Mammalian pregnancy presents a unique situation with circadian rhythms in the mom and, eventually, in the fetus. Prior studies showed that circadian rhythms develop in utero and that maternal signals, such as glucocorticoids, may act to entrain or drive daily rhythms in the fetus. However, there remains considerable debate about when and …


Understanding The Spectrum Of Dnmt3a Mutations In Neurodevelopmental Disease, Diana Christian Beard May 2023

Understanding The Spectrum Of Dnmt3a Mutations In Neurodevelopmental Disease, Diana Christian Beard

Arts & Sciences Graduate Student Theses and Dissertations

Epigenetic mechanisms are critical for precisely controlling gene expression programs to allow for the development and function of the brain, and disruptions of these processes are highly associated with neurodevelopmental disease. DNA methylation is one mechanism used to regulate gene expression, and neurons employ a unique form of DNA methylation particularly at CA dinucleotides (mCA), that is not widely observed in other somatic cell types. The DNA methyltransferase DNMT3A is required to establish mCA, and mutations in DNMT3A are associated with autism spectrum disorder (ASD) and an overgrowth and intellectual disability disorder called Tatton-Brown Rahman Syndrome (TBRS). However, it remains …


Mechanisms And Consequences Of Microtubule-Based Symmetry Breaking In Plant Roots, Natasha Anriel Bilkey May 2023

Mechanisms And Consequences Of Microtubule-Based Symmetry Breaking In Plant Roots, Natasha Anriel Bilkey

Arts & Sciences Graduate Student Theses and Dissertations

Directional growth in plants is primarily determined by the axis of cell expansion, which is specified by the net orientation of cortical microtubules. Microtubules guide the deposition of cellulose and other cell wall materials. In rapidly elongating cells, transversely oriented microtubules create material anisotropy in the cell wall that prevents radial cell expansion, channeling cell expansion in the longitudinal direction. Mutations perturbing microtubule organization frequently lead to aberrant cell growth in land plants, with some mutations leading to helical growth patterns (called ‘twisted mutants’), often in roots. This phenotype manifests as right-handed or left-handed twisting of cell files along the …


Dissecting Tau Isoform Control And Modeling Tauopathies In Directly-Reprogrammed Neurons, Lucia Capano May 2023

Dissecting Tau Isoform Control And Modeling Tauopathies In Directly-Reprogrammed Neurons, Lucia Capano

Arts & Sciences Graduate Student Theses and Dissertations

Tauopathies are a family of neurodegenerative disorders whose pathology include intracellular tau aggregates, synaptic dysfunction, and neuronal death. Advanced age is the strongest risk factor for developing a tauopathy, independent of a predisposing mutation, therefore the ability to study tauopathies in adult human neurons is vital to understand the age-associated changes which underly disease onset. Tau, the protein product of the gene Microtubule Associated Protein Tau (MAPT), is expressed highly in neurons. There are six tau isoforms whose splicing control and expression is both developmentally and tightly regulated, with only one isoform expressed in fetal brain and all six expressed …


The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen May 2023

The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen

Arts & Sciences Graduate Student Theses and Dissertations

Recent human genetic studies have associated mutations in a gene called Myelin Transcription Factor 1 Like (MYT1L) with neurodevelopmental disorders (NDDs). Patients with MYT1L loss of function (LoF) mutations (MYT1L Syndrome patients) demonstrate shared symptoms such as microcephaly, attention deficit and hyperactivity disorder (ADHD), and obesity. Despite prior studies showing MYT1L overexpression facilitates neuronal differentiation in vitro, its functions in vivo, especially in the mammalian brain, and how its mutation leads to human disease pathology remains poorly understood. Here, I established the first mouse model of MYT1L Syndrome mimicking a patient specific LoF mutation. I found mice with Myt1l heterozygous …


Multi-Scalar Contributions To Sex Differences In Brain Tumor Incidence And Outcome, Lauren Broestl May 2023

Multi-Scalar Contributions To Sex Differences In Brain Tumor Incidence And Outcome, Lauren Broestl

Arts & Sciences Graduate Student Theses and Dissertations

Nearly all complex human diseases exhibit some degree of sex difference in incidence, age of onset, disease severity, and/or response to treatment. Sex differences are observed in a wide range of nervous system disorders, including neurodevelopmental disorders, psychiatric diseases, neuroimmunological disorders, neurodegenerative diseases, and central nervous system (CNS) tumors. Males have increased incidence rates for most CNS tumor types. Sex differences in brain tumor incidence rates are observed in studies from around the world, across a wide range of cultures, in both pediatric and adult populations, and even extend to other species. Males also have decreased survival from brain tumors, …


Assessment Of Cross-Protective Responses To Emerging Variant Viruses, Rita Elaine Chen May 2023

Assessment Of Cross-Protective Responses To Emerging Variant Viruses, Rita Elaine Chen

Arts & Sciences Graduate Student Theses and Dissertations

Viruses pose a great threat to human health. Outbreaks and pandemics due to different viruses occur in all areas of the world. Two viruses, which emerged globally in the 1980s and in 2020, that are still causing ongoing pandemics in 2021 are dengue virus (DENV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively. These viruses circulate widely and currently infect hundreds of millions of people. Immunity from a previous infection may confer protection against subsequent infection of a related virus. Thus, understanding the degree of cross-protection can help define correlates of protection that are necessary to determine which people …


The Microbes Within: Pathogen In-Host Adaptation And The Gut Microbiome During Persistent Colonization And Recurrent Infection, Joohee Choi May 2023

The Microbes Within: Pathogen In-Host Adaptation And The Gut Microbiome During Persistent Colonization And Recurrent Infection, Joohee Choi

Arts & Sciences Graduate Student Theses and Dissertations

Microbes not just surround us; they are inside of us. The gut microbiome has emerged in recent years as an important modulator of health and is thought to have co-evolved with us throughout evolutionary history. On the other hand, our immune systems are constantly surveilling and battling infection by external pathogens— some of which still manage to evade our immune response and colonize our bodies long-term. In this Thesis, I investigated microbes inhabiting our bodies in various contexts to understand their impact on human health.In Chapter 2, I discuss the effects of fecal microbiome transplant (FMT) study drug RBX2660 on …


Leveraging Protein Dynamics To Drug Filovirus Protein-Nucleic Acid Interactions Using Simulations And Experiments, Matthew Alberto Cruz May 2023

Leveraging Protein Dynamics To Drug Filovirus Protein-Nucleic Acid Interactions Using Simulations And Experiments, Matthew Alberto Cruz

Arts & Sciences Graduate Student Theses and Dissertations

Drug discovery targeting protein nucleic acid (PNI) and protein-protein interactions (PPI) remains a difficult task. How to identify druggable conformations and discover compounds binding to these conformations is an unsolved problem. Here, I describe how we apply computational and experimental approaches to probe the conformational landscape of a key immune antagonist protein from the Zaire ebolavirus. Viral Protein 35 (VP35) binds to the viral pathogen associated molecular pattern, double stranded RNA (dsRNA), and blocks activation of the interferon (IFN) response. Long time scale molecular dynamics simulations reveal that VP35 adopts an alternative conformation which opens a pocket absent in experimental …