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Full-Text Articles in Life Sciences

Muscle Defects Lead To Skeletal Deformities In A Zebrafish Model Of Distal Arthrogryposis, Emily A. Tomak Aug 2023

Muscle Defects Lead To Skeletal Deformities In A Zebrafish Model Of Distal Arthrogryposis, Emily A. Tomak

Electronic Theses and Dissertations

Distal Arthrogryposis Type 1 (DA1) involves mild muscle weakness and limb skeletal abnormalities thought to be caused by paralysis in utero. Why the limbs are particularly affected in DA1 and the degree of paralysis that leads to these skeletal deformities in utero remains unclear. Several muscle genes are known to cause DA1, including MYLPF (myosin light chain phosphorylatable), which encodes a myosin light chain protein that binds close to the force-generating head of myosin heavy chains. The zebrafish mylpfa-/- mutant displays a phenotype consistent with DA1, including impaired myosin activity, reduced muscle force overall, and complete fin paralysis. I …


Primary Cilia Of The Cardiac Neural Crest & Hedgehog-Mediated Mechanisms Of Congenital Heart Disease, Lindsey A. Fitzsimons May 2022

Primary Cilia Of The Cardiac Neural Crest & Hedgehog-Mediated Mechanisms Of Congenital Heart Disease, Lindsey A. Fitzsimons

Electronic Theses and Dissertations

Elimination of primary cilia in cardiac neural crest cell (CNCC) progenitors is hypothesized to cause a variety of congenital heart defects (CHDs), including atrioventricular septal defects, and malformations of the developing cardiac outflow tract. We present an in vivo model of CHD resulting from the conditional elimination of primary cilia from CNCC using multiple, Wnt1:Cre-loxP, neural crest-specific systems, targeting two distinctive, but critical, primary cilia structural genes: Intraflagellar transport protein 88 (Ift88) or kinesin family member 3A (Kif3a). CNCC loss of primary cilia leads to widespread CHD, where homozygous mutant embryos (MUT) display a variety of outflow tract malformations, septation …


Deciphering The Perpetual Fight Between Virus And Host: Utilizing Bioinformatics To Elucidate The Host's Genetic Mechanisms That Influence Jc Polyomavirus Infection, Michael P. Wilczek Aug 2021

Deciphering The Perpetual Fight Between Virus And Host: Utilizing Bioinformatics To Elucidate The Host's Genetic Mechanisms That Influence Jc Polyomavirus Infection, Michael P. Wilczek

Electronic Theses and Dissertations

JC polyomavirus (JCPyV) is a human-specific pathogen that infects 50-80% of the population, and can cause a deadly, demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). In most of the population, JCPyV persistently infects the kidneys but during immunosuppression, it can reactivate and spread to the central nervous system (CNS), causing PML. In the CNS, JCPyV targets two cell types, astrocytes, and oligodendrocytes. Due to the hallmark pathology of oligodendrocyte lysis observed in disease, oligodendrocytes were thought to be the main cell type involved during JCPyV infection. However, recent evidence suggests that astrocytes are targeted by the virus and act …


Zebrafish As A Model To Understand The Impact Of Inactivity And Neuromuscular Electrical Stimulation On Duchenne Muscular Dystrophy, Elisabeth Kilroy Aug 2020

Zebrafish As A Model To Understand The Impact Of Inactivity And Neuromuscular Electrical Stimulation On Duchenne Muscular Dystrophy, Elisabeth Kilroy

Electronic Theses and Dissertations

Skeletal muscle plasticity is imperative for functional adaptation to changing demands in activity. Although a great deal is known about the structural and functional plasticity of healthy skeletal muscle, far less is known about plasticity in diseased muscle. Here, we combined the power of the zebrafish model with the adaptability of neuromuscular electrical stimulation (NMES) to study the basic mechanisms of plasticity in the zebrafish model of Duchenne Muscular Dystrophy (DMD). Four NMES paradigms, defined by their frequency, delay, and voltage, were designed to emulate the repetition and load schemes of human resistance training programs. Additionally, two inactivity paradigms were …


Does Circularizing Source-Separated Food Waste Present A Risk To Our Food?, Astha Thakali May 2020

Does Circularizing Source-Separated Food Waste Present A Risk To Our Food?, Astha Thakali

Electronic Theses and Dissertations

About a third of the food produced annually is wasted. Food waste recycling can be a way to close the loop and attain a more sustainable food system, however, the system must be carefully monitored and managed to avoid the introduction and build-up of contaminants. To study the potential presence of contaminants in food waste, source-separated food waste was collected and screened for five classes of contaminants (physical contaminants, heavy metals, halogenated organic contaminants, pathogens, and antibiotic resistance genes) from two separate regulatory environments (voluntary vs mandated food separation). The regulatory environment did not affect the level of contamination, except …


Evaluating The Occurrence Of Age-Related Peripheral Neuropathy In Het3 Mice And Development Of A Whole Tissue Imaging Technique For Analyzing Total Innervation In The Subcutaneous Adipose Depot, Jake Willows Dec 2019

Evaluating The Occurrence Of Age-Related Peripheral Neuropathy In Het3 Mice And Development Of A Whole Tissue Imaging Technique For Analyzing Total Innervation In The Subcutaneous Adipose Depot, Jake Willows

Electronic Theses and Dissertations

Adipose tissue can be characterized as either being a white (energy storing) depot or a brown (energy expending) depot and both have been found to contain dense networks of neural innervation. This adipose nerve supply regulates numerous metabolic functions and likely plays an important role in the function of adipose blood vessels. Recently our lab has shown in the C57BL/6 mouse model that peripheral neuropathy, or the dying back and dysfunction of the nerves in the superficial tissues such as the skin, can extend into the subcutaneous adipose tissue in conditions commonly associated with the neuropathic phenotype (i.e. diabetes, obesity, …


Blacklegged Tick (Ixodes Scapularis) Distribution In Maine, Usa, As Related To Climate Change, White-Tailed Deer, And The Landscape, Susan P. Elias May 2019

Blacklegged Tick (Ixodes Scapularis) Distribution In Maine, Usa, As Related To Climate Change, White-Tailed Deer, And The Landscape, Susan P. Elias

Electronic Theses and Dissertations

Lyme disease is caused by the bacterial spirochete Borrelia burgdorferi, which is transmitted through the bite of an infected blacklegged (deer) tick (Ixodes scapularis). Geographic invasion of I. scapularis in North America has been attributed to causes including 20th century reforestation and suburbanization, burgeoning populations of the white-tailed deer (Odocoileus virginianus) which is the primary reproductive host of I. scapularis, tick-associated non-native plant invasions, and climate change. Maine, USA, is a high Lyme disease incidence state, with a history of increasing I. scapularis abundance and northward range expansion. This thesis addresses the question: “To …


Characterization And Functional Rescue Of Congenital Muscular Dystrophy With Megaconial Myopathy In A Mouse Model Of The Disease, Ambreen A. Sayed Dec 2018

Characterization And Functional Rescue Of Congenital Muscular Dystrophy With Megaconial Myopathy In A Mouse Model Of The Disease, Ambreen A. Sayed

Electronic Theses and Dissertations

Congenital muscular dystrophy with megaconial myopathy (MDCMC) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. Megamitochondria in skeletal muscle biopsies and cognitive impairments in MDCMC patients are observations exclusive to this type of muscular dystrophy. The disease is caused by loss of function mutations in the choline kinase beta (CHKB) gene which results in dysfunction of the Kennedy pathway for the synthesis of phosphatidylcholine (PC). A rostro-caudal muscular dystrophy (rmd) mouse with a deletion in the Chkb gene resulting in MDCMC-like symptoms has been reported by our lab. In order to test if the rmd mice …


Modeling Human Cancer Therapy Response In Patient Derived Xenografts, Joan Malcolm Dec 2018

Modeling Human Cancer Therapy Response In Patient Derived Xenografts, Joan Malcolm

Electronic Theses and Dissertations

Patient‐derived xenografts (PDXs) generated by implanting human tumor tissue into a transplant compliant mouse host have been of increasingly importance to preclinical development and have been demonstrated to have advantages compared to cancer cell lines and cell‐line xenografts (CLX) for modeling therapeutic responses in cancer. Nevertheless, many open questions remain regarding the relationship between study design factors and classification of treatment response and the molecular fidelity of tumors passaged in PDXs relative to the original patient tumor(s). The research described in this dissertation addresses both of these significant issues related to the use of PDXs as a tool for modeling …


Host Mediated Mechanisms Of Fungal Cell Spread In A Transparent Zebrafish Infection Model, Allison Scherer Dec 2018

Host Mediated Mechanisms Of Fungal Cell Spread In A Transparent Zebrafish Infection Model, Allison Scherer

Electronic Theses and Dissertations

Innate immunity has developed elegant processes for the detection and clearance of invasive fungal pathogens. Disseminated candidiasis is of significant concern for those with suppressed immune systems or indwelling medical equipment, and mortality in these groups approaches 70%. Poor patient outcomes have spurred the need to understand how this non-motile pathogen spreads in the host. Technical limitations have previously hindered our ability to visualize the role of innate immunity and host tissue barriers in the spread of C. albicans in vivo. Using the zebrafish model to overcome these limitations, we have examined three potential host-mediated mechanisms of dissemination: movement …


The Effect Of Wild Blueberry Bioactives On Endothelial Cell Migration And Angiogenesis: An In Vitro Mechanistic, Genomic And Proteomic Approach, Panagiotis Tsakiroglou Sep 2018

The Effect Of Wild Blueberry Bioactives On Endothelial Cell Migration And Angiogenesis: An In Vitro Mechanistic, Genomic And Proteomic Approach, Panagiotis Tsakiroglou

Electronic Theses and Dissertations

The goal of this study is to investigate the effects of wild blueberry fractions (Anthocyanins and Phenolic acids) on vascular function and physiology. More specifically the potential effects of the above fractions and their combination in physiological concentrations on endothelial cell migration, angiogenesis, gene expression and proteins synthesis of markers related to the above processes. The objectives are to study whether anthocyanins, phenolic acids and their combinations (ACNs:PAs) affect: a) cell proliferation, b) speed of endothelial cell migration, c) angiogenesis, d) gene expression of genes critical for cell migration and angiogenesis such as RAC1, RHOA, AKT1, eNOS and VEGF and …


Expression Profiling Of Non-Coding Rna By Environmental Interactions In Innate Immunity, Jacob R. Longfellow Aug 2017

Expression Profiling Of Non-Coding Rna By Environmental Interactions In Innate Immunity, Jacob R. Longfellow

Electronic Theses and Dissertations

Cystic fibrosis (CF) is a genetic disorder that affects 30,000 people in the United States and currently has no cure. Although CF affects all of the body’s systems, it is largely characterized as a lung disease. CF is caused by a mutation in both copies of the gene for cystic fibrosis transmembrane conductance regulator (CFTR). A mutation in the CFTR gene leads to improper movement of chloride ions and water into the airways, which dysregulates the airway surface liquid volume and composition. Individuals with CF are prone to lung infections due to inefficient bacterial clearance and by the age of …


Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke Aug 2016

Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke

Electronic Theses and Dissertations

Molecular camouflage is used by a diverse set of pathogens to disguise their identity and avoid recognition by protective host receptors. The opportunistic fungal pathogen Candida albicans is a good example, as it masks the inflammatory component β-glucan in its cell wall to evade detection by the immune receptor Dectin-1. Interestingly, it has been seen that β-glucan becomes unmasked during infection in vivo, though the underlying mechanisms remained unclear. Exposure levels of this epitope may be important, as Dectin-1 mediates protection from some strains of C. albicans and alterations in the organization and composition of the Candida cell wall …


Cell-Matrix Adhesion In Muscle Development And Disease, Michelle F. Goody Aug 2012

Cell-Matrix Adhesion In Muscle Development And Disease, Michelle F. Goody

Electronic Theses and Dissertations

A variety of diseases, both inherited and acquired, affect muscle tissues in humans. The anchoring of muscle fibers to their surrounding environment is critical for muscle homeostasis. Muscle fibers attach to their microenvironment through cell-matrix adhesion complexes. These anchoring complexes are placed under repeated stress during muscle contraction. Genetic mutations in these complexes weaken the attachment between muscle fibers and their microenvironment, making fibers more susceptible to damage and death. This increased fiber degeneration eventually leads to progressive muscle wasting diseases, known as congenital muscular dystrophies. Although clinical trials are ongoing, there is presently no way to cure the loss …