Life Sciences Commons^™

Association Of Structural Variation (Sv) With Cardiometabolic Traits In Finns, Lei Chen

Arts & Sciences Electronic Theses and Dissertations

Cardiovascular diseases (CVDs) are known to be associated with a variety of quantitative risk factors such as cholesterol, metabolites, and insulin. Understanding the genetic basis of these quantitative traits can shed light on the etiology, prevention, diagnosis, and treatment of disease. However most prior trait-mapping studies have focused on single nucleotide variants (SNVs) and Indels, with the contribution of structural variation (SV) remaining unknown. In this thesis, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. In the first chapter, we used sensitive methods to identify and genotype 129,166 high-confidence …

Examining Early Interactions Between Innate Airway Resident Immune Cells And Mtb-Specific Factors During Pulmonary Infection With Mycobacterium Tuberculosis, Micah D. Dunlap

Arts & Sciences Electronic Theses and Dissertations

Mycobacterium tuberculosis (Mtb) is the leading cause of death by an infectious agent in the world today, infecting roughly one quarter of humans. Despite this, the mechanisms of early pathogenesis and host protective innate immune responses remain poorly understood and uncharacterized.

Lung resident Alveolar Macrophages (AMs) are the first host contact with Mtb bacilli after inhalation and are thus key mediators of the early pulmonary immune response. AMs are generally believed to reside entirely in the airway, but it was recently demonstrated that they have the capacity to egress and enter into granulomas during pulmonary infection with hypervirulent Mtb. Furthermore, …

Understand And Predict Microbiome And Resistome Dynamics In Response To Perturbations Across Diverse Populations And Environments, Manish Boolchandani

Arts & Sciences Electronic Theses and Dissertations

Complex microbial communities are at the interface of human, animal and environment interconnected ecosystem, where they can move within and between these entities. These microbial communities are mostly beneficial, maintaining the host health and homeostatic state. However, these communities can also serve as reservoirs of antibiotic resistance (AR) genes that may disseminate to pathogen bacteria, compromising the treatment options. Like other microbial communities, human gut microbiome is highly dynamic and can get acutely perturbed with the changes in the habitat, diet, lifestyle and disease. A perturbed gut community structure has profound impact on the host health and physiology. Use of …

Modularity Of Feedback For State-Dependent Guidance Of Navigation In Mouse Visual Cortex, Andrew M. Meier

Arts & Sciences Electronic Theses and Dissertations

Navigating through unpredictable environments requires an efficiently organized sensory system capable of adapting to behavioral demands. In the mammalian visual system, two adaptations which have arisen to meet these demands are parallel processing and top-down feedback of internally generated expectations and contextual information for adjusting responses to match the needs of the current behavioral task. Mouse visual cortex exhibits the latter of these organizing principles, like other mammals, in the form of a molecular layer (Layer 1) which receives feedback to contextually adapt sensory responses from the outside world. The first of these organizing principles, parallel processing streams, generally takes …

The Roles Of Plasmepsins Ix And X In Malaria Parasite Biology, Armiyaw Sebastian Nasamu

Arts & Sciences Electronic Theses and Dissertations

Proteases of the malaria parasite Plasmodium falciparum have been targeted for drug discovery for decades. The P. falciparum genome encodes ten aspartic proteases called plasmepsins, which are involved in diverse cellular processes. In this work we address the roles of two of these plasmepsins, plasmepsins IX and X (PM IX and X), the two least studied aspartic proteases in blood stage malaria parasites till date. We explore the essentiality of these proteases in parasite development, attempt to identify their substrates and the ability to drug them. We show that PM IX is essential for erythrocyte invasion, acting on rhoptry secretory …