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Articles 1 - 6 of 6
Full-Text Articles in Medicine and Health Sciences
Cholesterol Regulation Of Pulmonary Endothelial Calcium Entry Following Chronic Hypoxia, Bojun Zhang
Cholesterol Regulation Of Pulmonary Endothelial Calcium Entry Following Chronic Hypoxia, Bojun Zhang
Biomedical Sciences ETDs
Chronic hypoxia (CH)-induced pulmonary hypertension (PH) is associated with diminished ATP-induced endothelial Ca2+ entry as well as membrane cholesterol in pulmonary arteries. Store-operated Ca2+ entry (SOCE) and depolarization-induced Ca2+ entry are major components of the response to ATP and are similarly decreased after CH. Because endothelium-dependent vasodilation is closely associated with pulmonary endothelial [Ca2+]i, the blunted agonist-induced Ca2+ influx in pulmonary artery endothelial cells (PAEC) may contribute to the development of CH-induced PH. Interestingly, impaired agonist-induced Ca2+ influx in PAEC following CH can be restored by membrane cholesterol supplementation. In the current studies, we hypothesized that impaired Ca2+ entry in …
Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta
Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta
Biomedical Sciences ETDs
This dissertation explores the effects of heterogeneity across different biological scales in cancer as well as normal cells. At the tissue scale, we investigated the variability present in the tumor microenvironment and its effect on patient chemotherapeutic outcomes using a mathematical model of drug transport. We found that parameters such as tumor blood perfusion and radius of blood vessel had an impact on the tumor cytotoxicity. This indicated that the physical microenvironment of the tumor is an important regulator of the tumor response to chemotherapy. At the cellular scale, we investigated the heterogeneity present on the membrane landscape of ErbB2 …
A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner
A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner
Biomedical Engineering ETDs
Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …
Cortico-Striatal Coordination Disrupted In Behaviorally Inflexible Moderate Prenatal Alcohol Exposed Mice, Kristin L. Marquardt
Cortico-Striatal Coordination Disrupted In Behaviorally Inflexible Moderate Prenatal Alcohol Exposed Mice, Kristin L. Marquardt
Biomedical Sciences ETDs
Up to 61% of adolescent school aged children with fetal alcohol spectrum disorder (FASD) have been suspended or expelled. Executive function deficits, like dis-inhibition and cognitive inflexibility, have been proposed to be better predictors of behavioral problems then IQ score, which qualifies these individuals for developmental disability and special school programs. Reversal learning, a widely used behavioral paradigm for assessing cognitive flexibility across species, has been shown to be impaired in rodent models of prenatal alcohol exposure (PAE). Here we show that a mouse model with daily maternal drinking, resulting in a BAC of 85 mg/dl throughout gestation, results in …
Cd82 Membrane Scaffolding Regulates Hematopoietic Cell Functions, Christina M. Termini
Cd82 Membrane Scaffolding Regulates Hematopoietic Cell Functions, Christina M. Termini
Biomedical Sciences ETDs
Through their ability to self-renew and differentiate, hematopoietic stem/progenitor cells (HSPCs) maintain the adult blood and immune systems. The microenvironment, or niche, in which HSPCs reside, serves as a critical regulator of HSPC functions. As previous work has identified the tetraspanin CD82 as a mediator of HSPC-niche interactions, we aimed to determine the mechanism by which this occurs. Our data demonstrate that CD82 expression and scaffolding regulate HSPC interactions with niche components by organizing the α4 integrin subunit into tightly packed nanoclusters. The HSPC niche can also protect acute myeloid leukemia (AML) cells from therapeutics. Therefore, we next examined how …
Validation Of The Pre-B Cell Receptor As A Therapeutic Target In B Cell Precursor Acute Lymphoblastic Leukemia, Michael F. Erasmus
Validation Of The Pre-B Cell Receptor As A Therapeutic Target In B Cell Precursor Acute Lymphoblastic Leukemia, Michael F. Erasmus
Biomedical Sciences ETDs
This dissertation is built upon the fundamental idea that the pre-B cell receptor (pre-BCR) is important to leukemia cell survival and a logical therapeutic target in B cell precursor acute lymphoblastic leukemia (BCP-ALL). The pre-BCR is expressed early at a specific stage during B cell development where it plays a central role in survival of healthy B lymphocytes. This receptor is composed of the membrane heavy chain (mIgμ) associated with surrogate light chain components, 5 and VpreB. Through the use of advanced imaging modalities, in particular two-color single particle tracking (SPT), we showed that pre-BCRs formed transient, homotypic interactions. These …