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Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie 2023 University of South Dakota

Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie

Dissertations and Theses

Offspring of diabetic and obese mothers (ODOM) have greater risks of heart disease at birth and later in life. However, prevention is hindered because underlying mechanisms are poorly understood. Mounting studies in the Developmental Origins of Health and Disease field suggest that mitochondria play key roles in developmentally programmed heart disease similar to the roles they play in cardiomyopathy in adults with diabetes and obesity. However, whether mitochondria are responsible for the short[1]and long-term cardiac disease seen in ODOM remains unknown. Here, we sought to delineate the roles of mitochondria in the hearts of ODOM, determine whether mitochondria ...


Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor 2022 The Graduate Center, City University of New York

Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor

Dissertations, Theses, and Capstone Projects

The tumor suppressor p53 (TP53) gene is often mutated in cancer, with missense mutations found in the central DNA binding domain, and less often in the oligomerization domain (OD) and C-terminal domain (CTD). The OD and CTD have been found to be critical for the tumor suppressor functionality of wild-type p53 (wtp53). Specific missense mutations in the DNA binding domain have been found to confer new gain-of-function (GOF) activities. Mutations that destabilize tetramer formation, or deletion of key lysine residues within the CTD, downregulate the ability of wtp53 to transactivate (increase the rate of transcription of) its target genes. We ...


Telomerase Reverse Transcriptase Marks A Novel Population Of Adult Stem Cells In The Mouse Brain That Respond To Metabolic Interventions By Modulating Adult Brain Plasticity, Gabriel S. Jensen 2022 University of Maine

Telomerase Reverse Transcriptase Marks A Novel Population Of Adult Stem Cells In The Mouse Brain That Respond To Metabolic Interventions By Modulating Adult Brain Plasticity, Gabriel S. Jensen

Electronic Theses and Dissertations

Telomerase reverse transcriptase (TERT) is expressed by quiescent adult stem cells (qASC) in numerous adult murine and human tissues but has never been explored in the adult brain. Here, these data demonstrate that TERT+ cells in the adult mouse brain represent a novel population of multipotent qASCs. TERT+ cells were localized to numerous classical neuro/gliogenic niches including the ventricular-subventricular zone, hypothalamus and olfactory bulb, as well as newly discovered regions of adult tissue plasticity such as the meninges and choroid plexus. TERT+ cells expressed neural stem cell markers such as Nestin and Sox2, but not markers of activated stem ...


Establishing The Freestyle 293 Expression System As A Tool To Generate Recombinant Apolipoprotein E In Mammalian Cells, Michaela Cunningham 2022 Bridgewater State University

Establishing The Freestyle 293 Expression System As A Tool To Generate Recombinant Apolipoprotein E In Mammalian Cells, Michaela Cunningham

Honors Program Theses and Projects

Alzheimer’s disease (AD) is a devastating form of dementia with 5 million people suffering from the disease in the United States alone. Thus, there is a need to understand the cause of AD so that therapeutics can be developed to treat it. The greatest risk factor for AD is the APOE gene, which encodes the apolipoprotein Eprotein. Three predominant APOE alleles exist humans, which give rise to three isoforms, called apoE2, E3, and E4. Individuals with apoE4 are ten times more likely to develop AD. In contrast, the apoE2 isoform has a neuroprotective effect and is associated with a ...


The Role Of Increased Matrix Metalloproteinase (Mmp14) Expression On Apoptosis Sensitivity In Human Breast Cancer Cells, Roukayah Rifai 2022 Western University

The Role Of Increased Matrix Metalloproteinase (Mmp14) Expression On Apoptosis Sensitivity In Human Breast Cancer Cells, Roukayah Rifai

Undergraduate Student Research Internships Conference

A member of the matrix metalloproteinase family (MMP14) plays a crucial role in extracellular matrix (ECM) remodeling, as it possesses characteristics that aid in cell proliferation and differentiation. MMP14 domains can bind to FIH-1, which is a protein that can prevent apoptosis in cells when attached to BAX in the mitochondria. This study will investigate the varying expressions of MMP14 on FIH-1 and BAX, and their effects on apoptotic sensitivity. Three cell lines with varying levels of MMP14 expression will be used: C3 (~11 fold), ΔCD (~100 fold), and C2 (~500 fold). With the overexpression of MM14 on the cell ...


Producing And Measuring Oscillatory Shear In A Novel Microfluidic Chip, Sanaz Lordfard, Daniel Lorusso, Tamie L. Poepping, Hristo N Nikolov, Kayla Soon, Stephen Sims, Jeffrey Dixon, David Holdsworth 2022 Western University

Producing And Measuring Oscillatory Shear In A Novel Microfluidic Chip, Sanaz Lordfard, Daniel Lorusso, Tamie L. Poepping, Hristo N Nikolov, Kayla Soon, Stephen Sims, Jeffrey Dixon, David Holdsworth

Undergraduate Student Research Internships Conference

Purpose: To demonstrate the effectiveness of a novel microfluidic device mimicking oscillatory blood flow, allowing cell biologists to examine how endothelial cells respond to a range of oscillatory shear stress levels.

Methods: The microfluidic chip consists of a circular-shaped reservoir, leading to a rectangular channel that is examined under a microscope. The plunger is connected to a speaker system and oscilloscope, allowing the plunger to apply a range of frequencies (5-60Hz) and voltages (5-10 V, leading to a variety in oscillation amplitudes) to the reservoir region. 1.1 um fluorescent particles diluted in distilled water were used for tracking. Processing ...


Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang 2022 Chapman University

Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated potassium (KCa2.x) channels are gated exclusively by intracellular Ca2+. The activation of KCa2.3 channels induces hyperpolarization, which augments Ca2+ signaling in endothelial cells. Cilia are specialized Ca2+ signaling compartments. Here, we identified compound 4 that potentiates human KCa2.3 channels selectively. The subtype selectivity of compound 4 for human KCa2.3 over rat KCa2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of KCa2.3 channels by compound 4 increased flow-induced Ca2 ...


The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia 2022 The Texas Medical Center Library

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME ...


Determining The Full-Length Structure Of Collagenase H Using Small-Angle X-Ray Scattering, Josie Carson 2022 University of Arkansas, Fayetteville

Determining The Full-Length Structure Of Collagenase H Using Small-Angle X-Ray Scattering, Josie Carson

Chemistry & Biochemistry Undergraduate Honors Theses

Known to cause gas gangrene, Hathewaya histolytica secretes two sister collagenases, collagenase G (Col G) and collagenase H (Col H), to degrade the triple helical structure of collagen to further infection in a host. Individual domains of Col H have been crystalized in previous studies, but methods in x-ray crystallization of full-length Col H have been unsuccessful. Using Small Angle X-Ray Scattering (SAXS) data, atomistic modeling was used to generate multiple conformations of Col H while accounting for flexibility between domains. Full-length Col H was found to adopt a two-state conformational model exhibiting a majority compact and a minority elongated ...


What I Talk About When I Talk About Integration Of Single-Cell Data, Yang Xu 2022 University of Tennessee, Knoxville

What I Talk About When I Talk About Integration Of Single-Cell Data, Yang Xu

Doctoral Dissertations

Over the past decade, single-cell technologies evolved from profiling hundreds of cells to millions of cells, and emerged from a single modality of data to cover multiple views at single-cell resolution, including genome, epigenome, transcriptome, and so on. With advance of these single-cell technologies, the booming of multimodal single-cell data creates a valuable resource for us to understand cellular heterogeneity and molecular mechanism at a comprehensive level. However, the large-scale multimodal single-cell data also presents a huge computational challenge for insightful integrative analysis. Here, I will lay out problems in data integration that single-cell research community is interested in and ...


Neonatal Islet-1+ Cardiovascular Progenitor Cell-Derived Exosomes And Their Functional Ability To Regulate Proliferation, Lourdes Ceja 2022 California State University, San Bernardino

Neonatal Islet-1+ Cardiovascular Progenitor Cell-Derived Exosomes And Their Functional Ability To Regulate Proliferation, Lourdes Ceja

Electronic Theses, Projects, and Dissertations

Heart failure affects many people around the world and can lead to disease progression and death. Consequently, new stem and exosome-based therapies are needed to address this major health issue and to provide therapeutic options that will improve outcomes for the increasing number of patients with heart disease. Stem cell-derived exosomes have captivated researchers’ attention over the past couple of years based on their functional role in cellular signaling which highlights the vital component of the secretome of stem and progenitor cells. Since neonates have significantly enhanced regenerative ability, we hypothesized that exosomes isolated from Islet-1+ expressing neonatal human cardiovascular ...


Visualizing Muscle Assembly And Function In C. Elegans, Michael B. Russell 2022 University of South Alabama

Visualizing Muscle Assembly And Function In C. Elegans, Michael B. Russell

Theses and Dissertations

Myofibrils produce the forces that shorten muscles during contraction and are composed of proteins arranged in repeating contractile units (sarcomeres). These are composed of various proteins that self-organize into precise, alternating groups. The process of myofibril assembly is robust, flexible, and medically relevant. Various protein isoforms have evolved to modify the assembly process and generate a variety of muscle types with distinct physiologies and dynamics. To study myofibril assembly, I used the nematode Caenorhabditis elegans (C. elegans) which is an ideal model organism for this because it is transparent and has a variety of different muscle types that are responsible ...


Characterization Of The Wee1 Homologues And The Investigation Of Factors Promoting Cellular Enlargement In Cryptococcus Neoformans, Rodney J. Colón Reyes 2022 Clemson University

Characterization Of The Wee1 Homologues And The Investigation Of Factors Promoting Cellular Enlargement In Cryptococcus Neoformans, Rodney J. Colón Reyes

All Dissertations

Cryptococcus neoformans is an opportunistic fungal pathogen, infecting mainly immunocompromised individuals. As the main cause of cryptococcosis, it is responsible for over 180,000 deaths every year. As an environmental yeast, it has unique adaptations that allow it to proliferate in the human host. Among these adaptations its capacity to transition to an extreme phenotype known as Titan cells is of special interest to researchers. With sizes above 10 um and able to reach 70 um or more in cell size. This size is accompanied with a large vacuole, larger polysaccharide capsule, and an increased resistance to fluconazole (FLC). FLC ...


Extrinsic And Intrinsic Factors Influencing Homeostasis And Repair In Oral Tissues, Georgia Nikoloudaki 2022 The University of Western Ontario

Extrinsic And Intrinsic Factors Influencing Homeostasis And Repair In Oral Tissues, Georgia Nikoloudaki

Electronic Thesis and Dissertation Repository

The oral tissues, including gingiva and buccal mucosa, heal rapidly with minimal scar formation. Although in the oral cavity, the palatal mucosa is associated with excessive scarring in response to injury. In this thesis, first, I investigated the complex relationship between cells and their microenvironment using wound healing models in which extracellular matrix composition and mechanical stiffness affect cellular responses during acute wound repair. I also determined how intrinsic differences of cells recruited during healing contribute to wound resolution.

In Chapter 2, I first investigated cell-extrinsic factors, specifically the influence of the pro-fibrotic matricellular protein periostin on palatal healing. Using ...


Novel Functions For Arp2/3 Complex-Mediated Actin Networks Discovered In Chlamydomonas Reinhardtii, Brae M. Bigge 2022 Dartmouth College

Novel Functions For Arp2/3 Complex-Mediated Actin Networks Discovered In Chlamydomonas Reinhardtii, Brae M. Bigge

Dartmouth College Ph.D Dissertations

Chlamydomonas reinhardtii, a unicellular member of the Chlorophyta or Green Algae phylum, has been used for decades as a model for ciliary studies. Using this tool, previous work from our lab found a role for actin in ciliary assembly and maintenance. However, while the microtubule-based, membrane-ensheathed cilia of Chlamydomonas are highly conserved in relation to mammalian cells, the actin cytoskeleton is not as simple. Chlamydomonas contains two actin genes: IDA5, a conventional actin, and NAP1, a divergent actin. Here, we find that despite the divergence of NAP1, it is still able to interact with the actin nucleator, the Arp2/3 ...


Renal Cell Carcinoma Of Pelvic Kidney With Atypical Nodal Metastasis: A Diagnostic Challenge, Roshan-E-Shahid Rana, Muhammad Hammad Ather 2022 Aga Khan University

Renal Cell Carcinoma Of Pelvic Kidney With Atypical Nodal Metastasis: A Diagnostic Challenge, Roshan-E-Shahid Rana, Muhammad Hammad Ather

Section of Urology

Ectopic pelvic kidney is a known congenital anomaly; however, the presence of renal cell carcinoma (RCC) in an ectopic kidney is rare with the evidence available in the form of a few case reports only. In this case report, we present a case of metastatic RCC in the pelvic kidney which became a diagnostic challenge because of atypical contrast-enhanced computed tomographic (CT) characteristics and unusual pattern of lymph node involvement including cervical lymph node in the absence of visceral metastasis. Because of its unusual location and uncertain vascular anatomy, ectopic kidney poses a surgical challenge. Owing to the rarity of ...


Regulation Of The Heat Shock Response Via Lysine Acetyltransferase Cbp-1 And In Neurodegenerative Disease In Caenorhabditis Elegans, Lindsey N. Barrett 2022 University of South Florida

Regulation Of The Heat Shock Response Via Lysine Acetyltransferase Cbp-1 And In Neurodegenerative Disease In Caenorhabditis Elegans, Lindsey N. Barrett

USF Tampa Graduate Theses and Dissertations

The decline of proteostasis is a hallmark of aging that is, in part, affected by the dysregulation of the heat shock response (HSR), a highly conserved cellular response to proteotoxic stress in the cell. The heat shock transcription factor HSF-1 is well-studied as a key regulator of proteostasis, but mechanisms that could be used to modulate HSF-1 function to enhance proteostasis during aging are largely unknown. In this study, we examined lysine acetyltransferase regulation of the HSR and HSF-1 in C. elegans. We performed an RNA interference screen of lysine acetyltransferases and examined mRNA expression of the heat-shock inducible gene ...


Characterization Of Galectin-16 Expression And Function In Placental Cells, Jennifer Kaminker 2022 The University of Western Ontario

Characterization Of Galectin-16 Expression And Function In Placental Cells, Jennifer Kaminker

Electronic Thesis and Dissertation Repository

The processes of cellular differentiation and apoptosis are critical for placental development. The galectin-16 gene (LGALS16) is associated with these processes in the placenta, but the mechanism by which it acts is poorly characterized. My bioinformatics analysis revealed that LGALS16 expression was limited to specific tissues including the placenta and identified multiple regulatory molecules (transcription factors and miRNAs), which could potentially control relevant transcriptional and post-transcriptional mechanisms. Considering the predominant expression of LGALS16 in placenta, I examined the expression, regulation, and function of LGALS16 in BeWo and JEG-3 cell lines representing in vitro models of trophoblast differentiation. In both models ...


Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don 2022 University of Massachusetts Amherst

Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don

Doctoral Dissertations

Circadian rhythms are 24–hour activity cycles that exist for all organisms, from yeast and bacteria to mammals. Epidemiological data has shown that disruptions to circadian rhythms are associated with various diseases, including cancers. Circadian rhythms are regulated at the cellular level by a "molecular clock,” whose oscillations in protein transcription and translation control a range of downstream pathways. However, the connections between altered rhythms and diseases at the molecular level is unclear. Therefore, in this project, I tracked circadian rhythms in a high-resolution manner and thoroughly analyzed them to more completely reflect circadian behaviors and clock functioning at the ...


Bio-Vascular 3d, Wisdom Shadrach 2022 Department of Biological and Pharmaceutical Sciences, Munster Technological University, Kerry, Ireland

Bio-Vascular 3d, Wisdom Shadrach

ORBioM (Open Research BioSciences Meeting)

Cardiovascular disease is a leading cause of mortality and morbidity across the world and according to the world health organization account for 32% of mortality rate globally. There still remain a need to develop better in vitro vascular models that would aid further in-depth understanding of cardiovascular pathogenesis and proposed therapeutic intervention.

This study intends to characterize four novel medically relevant synthetic polymer scaffolds, and one hydrogel, for their biocompatibility and potential application in a tissue engineered blood vessel (TEBV). A primary human endothelial cell line derived from the vein of the umbilical cord (HUVEC), and a human primary smooth ...


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