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Disease Modeling Commons™

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2024

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Articles 31 - 38 of 38

Full-Text Articles in Disease Modeling

Role Of Myocardin Effector Genes On The Progression Of Cytoskeletal Remodeling And Phenotype Switching Of Hpmcs, Kasumi Sato Jan 2024

Role Of Myocardin Effector Genes On The Progression Of Cytoskeletal Remodeling And Phenotype Switching Of Hpmcs, Kasumi Sato

Biotechnology Theses

Pleural fibrosis (PF) is characterized by thickening of the pleura around the lungs due to mesothelial cells transitioning into myofibroblasts. Our research delved into the role of Myocardin (MYOCD) in this transition, revealing Twinfilin 1 (TWF1) and Leiomodin 1 (LMOD1) as significant genes influenced by MYOCD. In our investigation, we explored how TWF1 and LMOD1 impact cytoskeletal changes in human pleural mesothelial cells (HPMCs) induced by Transforming growth factor beta (TGF-β). Knocking down TWF1 resulted in reduced expression of Calponin 1 and alpha-Smooth Muscle Actin (α-SMA), while LMOD1 knock-down suppressed α-SMA expression. Inhibition of TWF1 hindered stress fiber formation but …

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When Brain Meets Artificial Intelligence, Lu Zhang Jan 2024

When Brain Meets Artificial Intelligence, Lu Zhang

Computer Science and Engineering Dissertations - Archive

When we review the history of development of artificial intelligence (AI), we will find that brain science plays a pivotal role in fostering breakthroughs in AI, such as artificial neural networks (ANNs). Today, AI has made remarkable strides, particularly with the emergence of large language models (LLMs), surpassing expectations and achieving human-level performance in certain tasks. Nonetheless, an insurmountable gap remains between AI and human intelligence. It is urgent to establish a bridge between brain science and AI, promoting their mutual enhancement and collaborations. This involve establishing connections from brain science to AI (brain-inspired AI), and reversely, from AI to …

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Impacts Of Climate Change On Vector-Borne Disease Burden In The United States: Exploring The Epidemiological Evidence, Leah V. Loetman Jan 2024

Impacts Of Climate Change On Vector-Borne Disease Burden In The United States: Exploring The Epidemiological Evidence, Leah V. Loetman

Honors Theses

Climate change models predict shifts in vector-borne diseases (VBDs) around the world, including in the United States. However, to my knowledge there has yet to be a comprehensive descriptive epidemiological study examining prevalence, geographic distribution, and trends for all tick- and mosquito-borne diseases in the United States. I compiled data from the U.S. Centers for Disease Control (CDC), which publishes yearly case numbers for 17 vector-borne diseases. However, these publications depend on a scattered framework of state regulations regarding disease reporting. I compiled data from the CDC to determine the current geographic distribution, prevalence, and trends of tick- and mosquito-borne …

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Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers Jan 2024

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

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Human Cell Modeling Of Cdkl5-Deficiency Disorder With Patient-Derived Organoids And Hd-Mea, Alyssa Paynton Jan 2024

Human Cell Modeling Of Cdkl5-Deficiency Disorder With Patient-Derived Organoids And Hd-Mea, Alyssa Paynton

Cal Poly Humboldt theses and projects

CDKL5 deficiency disorder (CDD) is an X-linked disorder that leads to severe cognitive impairments as well as infantile epilepsy. The only FDA approved therapy helps to reduce seizure frequency, however there are currently no cures approved. While murine models have proven useful in characterizing CDD, there are limitations due to differences in brain structure and development across species that may lead to the reported lack of spontaneous seizures in the mouse, a hallmark in humans affected by this disorder. By the utilization of patient-specific iPSCs generated into cerebral organoids, a more comprehensive and in-depth analysis into rare neurological disorders, such …

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Employing A Machine Learning Approach In Precision Oncology To Predict Pik3ca Functional Status And Identify Phenocopying Variants Of Deleterious Pik3ca Mutations, Javier Castillo Jan 2024

Employing A Machine Learning Approach In Precision Oncology To Predict Pik3ca Functional Status And Identify Phenocopying Variants Of Deleterious Pik3ca Mutations, Javier Castillo

CMC Senior Theses

The following proposal describes a modular machine learning approach that detects malfunctioning genes and pathways in cancer using the transcriptome of cancer patients. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders. Applied to the PI3K/AKT/mTOR pathway, this method can be used to predict PIK3CA functional status and identify phenocopying variants of deleterious PIK3CA mutations. The classifier will do this by integrating RNA-seq, copy number, and mutation data from tumors to determine the functional status of PIK3CA using a set of learned gene-specific weights. The classifier will then be …

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Advancing Small Molecule Therapies For Myotonic Dystrophy Type 1, Sawyer M. Hicks Jan 2024

Advancing Small Molecule Therapies For Myotonic Dystrophy Type 1, Sawyer M. Hicks

Electronic Theses & Dissertations (2024 - present)

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by the expression of expanded CUG (CUGexp) repeat RNA from the myotonic dystrophy protein kinase (DMPK) gene. This CUGexp repeat RNA’s gain-of-function mechanism leads to the sequestration of muscleblind-like (MBNL) proteins, resulting in widespread alternative splicing dysregulation across tissues. Despite significant research, there are currently no approved therapeutics targeting the underlying causes of DM1. This dissertation explores the development and optimization of a novel class of small molecules, Modified Polycyclic Compounds (MPCs), designed to address splicing dysregulation in DM1. MPCs were designed from previously published …

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Autonomic Modulation Of Cardiac Function In Hypertrophic Cardiomyopathy, Jenna Rose Disser Jan 2024

Autonomic Modulation Of Cardiac Function In Hypertrophic Cardiomyopathy, Jenna Rose Disser

Dissertations, Master's Theses and Master's Reports

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder. HCM is characterized by cardiac hypertrophy, fibrosis, and an increased risk of fatal arrhythmias and sudden cardiac death. Previous studies in humans with HCM have demonstrated increased cardiac norepinephrine spillover and reduced beta-1 receptor (β1R) expression in the left ventricle (LV). We have previously demonstrated that cardiac sympathetic tone is elevated in an alpha-tropomyosin mutant mouse model of HCM. We hypothesized that HCM mice would demonstrate reduced β1R expression in the LV and attenuated heart rate (HR) and dP/dt max responses to ramped infusion of the β1R agonist, dobutamine. …

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