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Elucidating The Role Of Hemodynamic Force In Regulating The Attachment Of Vascular Smooth Muscle Cells (Vsmcs) To Maturing Vessels During Mouse Embryonic Development, Israt Jahan

MSU Graduate Theses

Blood vessel maturation is characterized by the recruitment and attachment of vascular smooth muscle cells (vSMCs) around immature blood vessels, which ultimately form the tunica media. Improper maturation can lead to vascular birth defects ranging from minor birthmarks to lethal brain aneurysms. Previously, our lab demonstrated that hemodynamic force plays an important role to regulate vSMCs recruitment from neighboring low-flow to high-flow vessels followed by the attachment of these vSMCs to the high-flow vessels. To understand the reason for the preferred attachment of vSMCs to high-flow vessels, instead of low-flow vessels, I hypothesize that hemodynamic force modulates the expression of …

The Effects Of D2 Receptor Modulation On Locomotor Development In Danio Rerio, Isaiah Thomas Mcroberts

Senior Projects Spring 2022

This study utilized a novel design to investigate the sensitivity of D2 dopamine receptors to modulating compounds through multiple exposures over early development of zebrafish larvae. Zebrafish were dosed for 30 minutes from 5-8 days post fertilization (dpf) with 16µ/mol of either a D2 antagonist, haloperidol, or a D2 agonist, quinpirole hydrochloride. Two other groups were then dosed with these compounds from 9-12dpf. The effects of D2 receptor modulation were measured by analyzing motor activity on measures of movement distance, frequency, and velocity. Results indicated that larvae dosed with haloperidol on 5dpf had increased activity after the first dosage, but …

Mitochondrial Dynamics Regulation Of The Lung Epithelial Response To Complex Allergen, Sierra White

Graduate College Dissertations and Theses

Asthma is a chronic inflammatory disease of the lungs that affects roughly 25 million Americans, costing the United States upwards of $80 billion annually in management and economic loss. The airway epithelium, which serves as the first line of defense against insults in the lung, are now appreciated as key contributors to initiation of this disease. A key regulator of the epithelial response to allergens and other inhaled irritants that can induce an allergic asthmatic response is the mitochondria. During an allergic response, the airway epithelial energy requirement changes, and mitochondrial function is altered, enhancing production of reactive oxygen species, …

Thyroid Hormone Receptor Beta Inhibits Pi3k Signaling And Glycogen Metabolism In Anaplastic Thyroid Cancer, Cole Davidson

Graduate College Dissertations and Theses

Thyroid cancer is the most common endocrine malignancy, and the global incidence has increased rapidly over the past few decades. While differentiated thyroid cancers often respond to standard therapies, there are no durable long-term treatment options for anaplastic thyroid cancer (ATC). The limited treatment options highlight a need for a deeper understanding of the molecular signaling in these aggressive tumors for development of more effective therapies.Non-steroidal nuclear receptors, such as thyroid hormone receptors (TRs), are an emerging class of therapeutic targets and tumor suppressors in thyroid and other cancers.Loss of expression of the tumor suppressor thyroid hormone receptor beta (TRβ) …

Spatial And Temporal Control Of The Kinesin Motors Kif11 And Kif22 In Mitosis, Alex Frances Thompson

Graduate College Dissertations and Theses

Mitosis requires the control of mechanical forces generated by kinesin motors to ensure equal segregation of chromosomes into two daughter cells. Two kinesins contributing to these forces are KIF11 (or Eg5), which crosslinks and slides anti-parallel microtubules, and KIF22 (or Kid), which binds to microtubules and chromosome arms. This work addresses how post-translational modifications and pathogenic mutations alter the structure and function of KIF11 and KIF22.

The homotetrameric kinesin KIF11 is subject to acetylation at lysine 146, a residue in the a2 helix of the motor domain. The effect of this acetylation was assessed at the single molecule and cellular …

Defining Regional Lung Extracellular Matrix Composition: Implications In Disease And Repair Following Injury, Evan T. Hoffman

Graduate College Dissertations and Theses

Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic lung diseases with significant worldwide impact and poor end-stage prognoses. Despite both diseases differing greatly in pathology, both COPD and IPF are hallmarked by drastic alterations to the extracellular matrix (ECM) within distinct anatomical lung regions. These alterations negatively impact cellular regeneration, and subsequently, lung homeostasis, physiology, and repair following injury. Whole decellularized lungs, stripped of cellular material while retaining lung ECM structure and composition, have previously provided complex models for both high-throughput proteomic evaluation of lung ECM as well as ex vivo culture models to study the …

Visualizing The Forces Exerted During 3d Motility By Toxoplasma Gondii, Rachel Stadler

Graduate College Dissertations and Theses

Intracellular parasites of the phylum Apicomplexa cause pervasive human diseases and are responsible for millions of deaths annually. The apicomplexan, Toxoplasma gondii, causes the disease toxoplasmosis and can infect most warm-blooded vertebrates. These parasites can cause blindness in their hosts. In immunocompromised individuals, the infection can lead to brain lesions and death. T. gondii uses a unique form of cellular motility to invade cells of its host, traverse numerous biological barriers, and disseminate throughout the host. These parasites move with an attachment-dependent mechanism called gliding. In the “linear motor model” of parasite motility, the parasite’s myosin motor, TgMyoA, is thought …

Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson

Graduate Theses, Dissertations, and Problem Reports

Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …

Characterization Of Cofilin And Its Potential Role In The Epha4 Pathway, Brian Donald Condron

Master's Theses and Doctoral Dissertations

EphA4 is a receptor tyrosine kinase that is responsible for cellular adhesion and locomotion using repulsion signaling in early development of Xenopus laevis. EphA4 regulates cellular locomotion by controlling proteins within its signal transduction pathway, which may include the protein cofilin. Cofilin actively severs and removes actin monomers, thus altering the actin cytoskeleton, leading to the cessation of cellular crawl. During the gastrulation phase of embryonic development, individual cells are relocating to create the three primary germ layers of the organism. Failure of this process to occur results in attrition of the embryos, frequently by way of embryonic exogastrulation. …

Alternative Splicing Regulates The Innate Immune Response To Viral Infection, Luke A. White

Graduate Student Theses, Dissertations, & Professional Papers

Rift Valley fever virus (RVFV) is a mosquito-borne RNA virus that infects humans and livestock in sub-Saharan Africa and the Arabian peninsula, causing disease ranging from a mild flu-like illness to liver damage, blindness, hemorrhagic fever, death, and, especially in livestock animals, high rates of abortive pregnancies. There is no approved vaccine for RVFV, and as a disease with a high rate of spread that causes severe illness, it is listed as a Category A pathogen by the USA CDC. A better understanding of RVFV’s molecular virology will be instrumental to combating RVFV as climate change causes its mosquito host …

An Antimicrobial Polydopamine Surface Coating To Reduce Biofouling On Telemetry Tags Used In Marine Conservation Practices, Ariana Smies

Dissertations, Master's Theses and Master's Reports

Satellite telemetry tags are used to track the migration patterns of large cetaceans. These tags penetrate the dermis and remain embedded in the underlying blubber tissue. As the dermis of cetaceans is host to a diverse microbiome, and it is impossible to clean the skin before implanting the devices, the potential for infection is increased when the tags penetrate through the skin. H₂O₂ is a potential antimicrobial agent that, in addition to showing broad-spectrum efficacy against gram-negative and gram-positive bacteria, can promote wound healing outcomes by promoting proliferative factors and peptides that protect against oxidative stress. However, …