Impact of Trauma on Brain Morphology & Maladaptive School Behaviors

Wendi Trummert, DrOT, OTR/L, the collaborating clinician for this project, works with students in a self-contained program. Wendi wanted to know how childhood trauma affects brain structure and morphology and how it is linked to behaviors seen in children affected by trauma. A synthesis of all articles looking at the brain reveals differences in both structure and function in the brains of individuals exposed to childhood trauma versus those not exposed (e.g. Daniels, Lamke, Gaebler, Walter, & Scheel, 2013; McGowan et al., 2009; Saleh et al., 2017). A synthesis of articles looking at maladaptive behaviors finds that those often seen in children affected by trauma, including aggression, emotional dysregulation, decreased executive functioning, and hyporeactivity may be linked to these brain changes and may explain why traditional behavioral approaches are often ineffective with this population (e.g. Briggs-Gowan et al., 2010; Lemmey et al., 2001; Shields & Cicchetti, 1998). It is recommended this information be disseminated to educators and others who work with children exposed to trauma to increase understanding and promote appropriate supports. A toolkit including a presentation, pamphlet, and conversational sound bytes were created for the clinician to increase knowledge and combat bias about problem behaviors in children affected by trauma amongst educators and coworkers. Insiders’ perspectives were included to generate empathy, help guide the best type of support for additional student services, and reduce occurrences of inappropriate interventions for maladaptive behaviors. Options and resources to effectively address maladaptive behaviors should be provided to educators after they are presented with this information

Local models for Galois deformation rings and applications

We construct projective varieties in mixed characteristic whose singularities model, in generic cases, those of tamely potentially crystalline Galois deformation rings for unramified extensions of $\mathbb{Q}_p$ with small regular Hodge-Tate weights. We establish several significant facts about their geometry including a unibranch property at special points and a representation theoretic description of the irreducible components of their special fibers. We derive from these geometric results a number of local and global consequences: the Breuil-M\'ezard conjecture in arbitrary dimension for tamely potentially crystalline deformation rings with small Hodge-Tate weights (with appropriate genericity conditions), the weight part of Serre's conjecture for $U(n)$ as formulated by Herzig (for global Galois representations which satisfy the Taylor-Wiles hypotheses and are sufficiently generic at $p$), and an unconditional formulation of the weight part of Serre's conjecture for wildly ramified representations

The role of ivermectin preventive chemotherapy for the control of soil-transmitted helminth infections and scabies

Neglected tropical diseases (NTDs) are a diverse group of chronic infectious diseases that disproportionately affect resource-poor settings. The large-scale administration of safe and efficacious drugs delivered to entire at-risk populations, a public health intervention known as preventive chemotherapy (PC), is an effective strategy to control several NTDs, including soil-transmitted helminth (STH) infections and scabies. For STH control, current World Health Organization (WHO) guidelines endorse the use of albendazole or mebendazole in school-based targeted PC programmes directed to school-aged children. However, these drugs have poor efficacy against Trichuris trichiura and Strongyloides stercoralis, and school-based delivery does not address the adult reservoir of infections. For scabies, no formal guidelines have been established, although there is growing interest in using oral ivermectin in community-wide PC (or mass drug administration (MDA)) programmes. PC with ivermectin, either alone or in combination with other drugs, may play an important role in improving the integrated control of several NTDs. This thesis aims to generate evidence to support the inclusion of ivermectin-based PC in integrated NTD control programmes, with a specific focus on STH infections and scabies in Solomon Islands and Timor-Leste. First, I evaluated the effectiveness of ivermectin PC, both as a standalone intervention and in combination with albendazole, in reducing the prevalence of STH infections in endemic countries through a systematic review and meta-analysis. There was a large reduction in S. stercoralis prevalence and a moderate reduction in T. trichiura prevalence following ivermectin MDA. Additionally, the co-administration of albendazole yielded a further reduction in T. trichiura prevalence. Second, I provided a detailed characterisation of the epidemiology of STH infections in the Western Province of Solomon Islands. This study reported the results of a population survey of STH using qPCR for diagnosis and identified WASH and environmental risk factors associated with infection. The overall STH prevalence was the highest reported in the country, with the predominant species being N. americanus. There was also a high burden of T. trichiura, Strongyloides spp. and Ancylostoma ceylanicum. Annual precipitation, soil acidity, not owning a household latrine, and drinking water sources were factors associated with increased odds of STH infections. Third, I evaluated the long-term effectiveness of ivermectin MDA in reducing the burden of STH infections, in the context of a cluster-randomised trial comparing one dose vs. two doses of ivermectin for scabies control in Western Province, Solomon Islands. There was a significant reduction in the prevalence of Strongyloides spp. and T. trichiura, and the intensity of T. trichiura infections, 21 months following MDA. Finally, I described the epidemiology of STH infections and scabies in Timor-Leste, and examined the long-term impact of MDA with ivermectin, diethylcarbamazine citrate, and albendazole for lymphatic filariasis elimination and STH control, in reducing the burden of scabies, impetigo, and STH in schoolchildren in Timor-Leste. There was a high prevalence of scabies, impetigo, and STHs in schoolchildren from three municipalities in Timor-Leste, particularly in rural regions. Additionally, there were substantial prevalence reductions in scabies, impetigo, and T. trichiura 18 months after MDA. The findings presented in this thesis provide strong evidence supporting the use of ivermectin in PC programmes to improve the integrated control of STH infections and scabies. Specific recommendations for global health policy and research include: ivermectin should be added to STH control programmes; one dose ivermectin MDA for scabies should be further investigated; and qPCR should be considered in STH diagnostics to enable a detailed characterisation of STH burden

Occurrence of Kanamycin-Resistant Bacteria Relative to Anthropogenic Pollution Along Richland Creek in Nashville, TN​

The overuse of antibiotics has caused an increase in antibiotic-resistant (AR) bacteria, which is a serious public health concern. Previous studies showed a significant correlation between anthropogenic pollution and AR bacteria. This project aims to identify AR bacteria in Richland Creek relative to local anthropogenic pollution. Water samples were collected at four locations along Richland Creek in Nashville, Tennessee. Bacteria resistant to the antibiotic kanamycin were isolated from the water samples, identified to genera using DNA barcoding, and compared among the sites. We expect to see a greater abundance and diversity of kanamycin-resistant bacteria closer to the end than near the head of the creek. This research project can help describe the diversity of AR bacteria species present in the stream in different areas of Nashville and has public health consequences if the disparities in the distribution of AR bacteria correlate to human activity and/or socioeconomic differences along the stream

Genetic effects in context: cellular and molecular quantitative trait loci in stimulated human neural progenitor cells

Genome-wide association studies have identified numerous genetic variants, often in non-coding sequences, that tune the expression of complex traits including brain structure, brain function, and clinical responses to psychiatric medications. However, genetic association studies do not directly nominate regulatory elements, genes, or cellular contexts in which genetic variants function to affect the expression of phenotypes. Chromatin accessibility or gene expression associated quantitative trait loci (caQTls or eQTLs, respectively) measured in bulk post-mortem tissue have explained mechanisms for a subset of brain-trait associated loci, yet these studies still do not show detectable gene regulatory function for many brain-trait associated variants. Ostensibly, GWAS variants additively affect gene regulatory mechanisms, and in turn, cellular processes that go on to influence complex traits, but these functions may only occur in particular cellular contexts. Here, I utilized a primary human neural progenitor cell-culture model to characterize the function of genetic variation on molecular and cellular phenotypes following stimulation of the canonical Wnt signaling pathway or exposure to mood stabilizing drugs, identifying novel context-specific mechanisms that may explain GWAS loci and variance in clinical responses to treatment. Genome-wide effects of Wnt, lithium, and valproic acid stimulation on chromatin accessibility, gene expression, and cellular proliferation were measured, and the genetic diversity across hNPC-lines was used to map QTLs describing common genetic effects on these molecular and cellular phenotypes. Stimulus-specific molecular QTLs colocalized with brain-related GWAS signals, including those for neuropsychiatric disorders and brain structures, providing novel mechanistic hypotheses explaining associated loci that were undetected at baseline unstimulated conditions or in other QTL studies, underscoring the context-specific nature of functional genetic variation. Genome-wide association to hNPC proliferation following stimulation by Wnt, lithium, or VPA, identified a genome-wide significant association to lithium-sensitive proliferation that colocalized with risk for bipolar disorder, schizophrenia, and intelligence. Functional experiments at this locus led to the identification of GNL3 as a lithium-responsive proliferation gene whose expression is influenced by genetic variation. Ongoing work seeks to better understand the genetic basis for variation in clinical response to lithium or VPA by integrating context-specific genetic effects with pharmacogenomic data.Doctor of Philosoph

CDAO-Store: Ontology-driven Data Integration for Phylogenetic Analysis

<p>Abstract</p> <p>Background</p> <p>The <it>Comparative Data Analysis Ontology (CDAO) </it>is an ontology developed, as part of the EvoInfo and EvoIO groups supported by the National Evolutionary Synthesis Center, to provide semantic descriptions of data and transformations commonly found in the domain of phylogenetic analysis. The core concepts of the ontology enable the description of phylogenetic trees and associated character data matrices.</p> <p>Results</p> <p>Using CDAO as the semantic back-end, we developed a triple-store, named <it>CDAO</it>-<it>Store</it>. CDAO-Store is a RDF-based store of phylogenetic data, including a complete import of TreeBASE. CDAO-Store provides a programmatic interface, in the form of web services, and a web-based front-end, to perform both user-defined as well as domain-specific queries; domain-specific queries include search for nearest common ancestors, minimum spanning clades, filter multiple trees in the store by size, author, taxa, tree identifier, algorithm or method. In addition, CDAO-Store provides a visualization front-end, called <it>CDAO</it>-<it>Explorer</it>, which can be used to view both character data matrices and trees extracted from the CDAO-Store. CDAO-Store provides import capabilities, enabling the addition of new data to the triple-store; files in PHYLIP, MEGA, <monospace>nexml</monospace>, and NEXUS formats can be imported and their CDAO representations added to the triple-store.</p> <p>Conclusions</p> <p>CDAO-Store is made up of a versatile and integrated set of tools to support phylogenetic analysis. To the best of our knowledge, CDAO-Store is the first semantically-aware repository of phylogenetic data with domain-specific querying capabilities. The portal to CDAO-Store is available at <url>http://www.cs.nmsu.edu/~cdaostore</url>.</p

Prospectus, February 15, 1995

https://spark.parkland.edu/prospectus_1995/1004/thumbnail.jp

The MBD7 complex promotes expression of methylated transgenes without significantly altering their methylation status.

DNA methylation is associated with gene silencing in eukaryotic organisms. Although pathways controlling the establishment, maintenance and removal of DNA methylation are known, relatively little is understood about how DNA methylation influences gene expression. Here we identified a METHYL-CpG-BINDING DOMAIN 7 (MBD7) complex in Arabidopsis thaliana that suppresses the transcriptional silencing of two LUCIFERASE (LUC) reporters via a mechanism that is largely downstream of DNA methylation. Although mutations in components of the MBD7 complex resulted in modest increases in DNA methylation concomitant with decreased LUC expression, we found that these hyper-methylation and gene expression phenotypes can be genetically uncoupled. This finding, along with genome-wide profiling experiments showing minimal changes in DNA methylation upon disruption of the MBD7 complex, places the MBD7 complex amongst a small number of factors acting downstream of DNA methylation. This complex, however, is unique as it functions to suppress, rather than enforce, DNA methylation-mediated gene silencing