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Calcium Signaling And Regulation Of Ecdysteroid Molting Hormone Production In Y-Organs Of The Blue Crab (Callinectes Sapidus), Megan Elizabeth Roegner
Calcium Signaling And Regulation Of Ecdysteroid Molting Hormone Production In Y-Organs Of The Blue Crab (Callinectes Sapidus), Megan Elizabeth Roegner
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In the blue crab (Callinectes sapidus), molting, and subsequent incremental growth, is triggered by the release of molting hormones, or ecdysteroids, from paired endocrine glands termed Y-organs. The method that triggers the increase in ecdysteroid release before molting is not fully resolved, but previous evidence suggests a calcium (Ca2+) signal may be involved. The goal of this research is to better understand the role Ca2+ signaling plays in blue crab molt hormone production. The first part of my dissertation focused on the Ca2+ regulatory protein sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), which removes Ca2+ to the ER after a Ca2+ influx. …
Combinatorial Withaferin A And Sulforaphane And Their Potential Roles In Breast Cancer Prevention And Therapy, Kendra Jeanine Royston
Combinatorial Withaferin A And Sulforaphane And Their Potential Roles In Breast Cancer Prevention And Therapy, Kendra Jeanine Royston
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Cancer is a leading cause of death worldwide and is a devastating disease. Breast cancer is of particular interest because it is a major cause of cancer-related fatality in women in the United States. To date, more than 40,000 women are expected to die due to breast cancer and more than 200,000 will be diagnosed every year. Despite numerous advancements in the field, breast cancer remedies can be harsh and while life may be prolonged, the quality of life may decrease. This being said, preventive measures and less harsh treatment options are needed to help eliminate breast cancer as a …
Effects Of Stored Red Blood Cells On The Components Of The Lung-Capillary Membrane, Kaitlyn S. Ryan
Effects Of Stored Red Blood Cells On The Components Of The Lung-Capillary Membrane, Kaitlyn S. Ryan
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Trauma is the leading cause of death for Americans between the ages of 1 and 44. Implementation of massive transfusion protocols has improved early mortality due to traumatic hemorrhage; however, long-term complication rates associated with hemorrhagic shock remain high due to the development of multiple organ failure. In particular, resuscitation with large volumes of stored red blood cells (RBC) introduces high concentrations of free heme, which contributes to the development of acute lung injury (ALI) after trauma. Angiopoietin-2 (Agpt-2) is a mediator of trauma-related lung injury, but the effect of RBC storage-derived free heme on Agpt-2 regulation is unknown. The …
Molecular Characterization Of The Rare Cftr Mutation P67l As A Model For Genotype-Specific Drug Development And Personalized Medicine In Cystic Fibrosis, Carleen Mae Pomperada Sabusap
Molecular Characterization Of The Rare Cftr Mutation P67l As A Model For Genotype-Specific Drug Development And Personalized Medicine In Cystic Fibrosis, Carleen Mae Pomperada Sabusap
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The traditional CFTR functional defect subcategories (i.e. protein misfolding, gating, conductance, etc.) are sometimes inadequate for determining patients most likely to benefit from emerging modulator treatment. We employ the P67L variant as emblematic of ways a thorough biochemical analysis of a rare CF defect can guide new therapeutic approaches, help predict drug response, and facilitate clinical precision. Historically, P67L has been designated a class IV conductance abnormality (i.e., malformed ion pore). In contrast, our studies demonstrate P67L disrupts CFTR protein maturation, prompts misfolding, causes gating defects, and exhibits wild-type like conductance. We show that P67L CFTR is robustly rescued by …
Endothelin-1 And The Diurnal Regulation Of Sodium Excretion, Jermaine Gajrae Johnston
Endothelin-1 And The Diurnal Regulation Of Sodium Excretion, Jermaine Gajrae Johnston
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Healthy individuals typically have a diurnal rhythm in sodium (Na+) excretion, with levels higher during the daytime and lower at nighttime. While the mechanism behind this rhythm is not yet fully understood, molecular clock genes such as Bmal1 may contribute to the diurnal variation in urinary Na+ excretion (UNaV). Endothelin-1 (ET-1) is a peptide that aids in the regulation of Na+ balance through activation of the endothelin B (ETB) receptor. Although the ETB receptor has been shown to play an important role in promoting natriuresis, whether this varies according to time of day is unknown. This dissertation examines the role …
Simulation Of Correlated Variables, Mixture Distributions, And Repeated Measures And Comparison Of Pharmacogenetic Prediction With Machine Learning Methods, Allison Cynthia Fialkowski
Simulation Of Correlated Variables, Mixture Distributions, And Repeated Measures And Comparison Of Pharmacogenetic Prediction With Machine Learning Methods, Allison Cynthia Fialkowski
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Pharmacogenetics aims to improve individualized medicine by combining genetic information with clinical data when assigning drug treatments. Different diseases are often associated with different factors, each with its own distributional characteristics. For rare or complex diseases, these characteristics may not be well understood and standard analysis methods may not be appropriate. In psychiatric disorders, for example, multiple drug treatments need to be compared across small sample sizes with heterogeneous patient populations, making implementation of standard methods difficult. Simulating data that mirrors clinical data is important because it allows investigators to determine which method is best suited for data from their …
African American Caregivers’ Decision To Use Hospice Services For A Loved One: A Grounded Theory Study, Paula M. Gordon
African American Caregivers’ Decision To Use Hospice Services For A Loved One: A Grounded Theory Study, Paula M. Gordon
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This qualitative grounded theory study explored the process of decision making for African American family caregivers in the southeastern United States, as they make hospice decisions for their loved ones, Although hospice use in the United States has grown over the last decade, a disparity continues to exist between African American and Caucasian populations. African Americans represent a small percentage of hospice users in the United States, despite research that has found that patients who use hospice experience improved symptom control, fewer unmet needs, and better end of life care. Research has identified many reasons for this disparity; however, little …
Risk Factors Associated With Multiple Myeloma, Stephen Gragg
Risk Factors Associated With Multiple Myeloma, Stephen Gragg
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Multiple myeloma (MM) is a hematologic malignancy in which clonal plasma cells accumulate in the bone marrow, leading to the formation of lytic bone lesions, hypercalcemia, anemia, renal insufficiency, and immunosuppression. It develops from a pre-malignant condition known as monoclonal gammopathy of undetermined significance (MGUS), which is prevalent in up to 3% of White populations over the age of 50 years, and twice that in Black populations. Although much progress has been made toward understanding the large scale genomic aberrations that facilitate the formation of MGUS clones and the various copy-number variations and mutations that trigger the development of MM, …
Trichomonas Vaginalis Virus (Tvv) And Its Role In Trichomoniasis Infection, Keonte Graves
Trichomonas Vaginalis Virus (Tvv) And Its Role In Trichomoniasis Infection, Keonte Graves
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Background: Trichomonas vaginalis virus (TVV) is a non-segmented, 4.5-5.5 kbp, double-stranded RNA (dsRNA) virus infecting T. vaginalis (TV). The objectives of this study were to examine TVV prevalence in U.S. TV isolates and associations with patient demographics, clinical outcomes, and metronidazole (MTZ) resistance. Methods: Archived TV isolates from the enrollment visit of 355 women participating in a TV treatment trial in Birmingham, AL were thawed and grown in culture. Total RNA was extracted using Trizol reagent. Contaminating single-stranded RNA was precipitated using 4.0M LiCl and centrifugation. Samples were analyzed by gel electrophoresis to visualize a 4.5kbp band representative of TVV. …
Role Of Diminished Pulsatility From Continous Flow Ventricular Assist Devices On Small Vessel Endothelial Dysfunction, Thomas Haglund
Role Of Diminished Pulsatility From Continous Flow Ventricular Assist Devices On Small Vessel Endothelial Dysfunction, Thomas Haglund
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Ventricular assist devices (VADs) are standard therapy for patients with advanced heart failure that is refractory to medical therapy. VADs can be categorized as pulsatile flow VADs (PF-VADs) and continuous flow VADs (CF-VADs). Both PF-VADs and CF-VADs are similarly effective in providing hemodynamic benefit and improving the quality of life and functional capacity of patients. CF-VADs are preferred over the PF-VADs due to advantages such as compact size, reliability, energy efficiency, installation and operation. However, CF-VAD support results in non-physiological diminished arterial pressure and flow pulsatility. Using the endothelial cell culture model (ECCM), we previously established that diminished pulsatility resulted …
Mechanisms Of Leucine-Rich Repeat Kinase 2 And Alphα-Synuclein In Pathogenesis Of Parkinson Disease, Hisham Abdelmotilib
Mechanisms Of Leucine-Rich Repeat Kinase 2 And Alphα-Synuclein In Pathogenesis Of Parkinson Disease, Hisham Abdelmotilib
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Two pathological hallmarks define Parkinson disease (PD) including dopaminergic neurodegeneration in substantia nigra pars compacta (SNpc) and accumulation of α-synuclein insoluble inclusions, called Lewy pathology, in surviving neurons. LRRK2 (encoding Leucine-rich repeat kinase 2) and SNCA (encoding α-synuclein (α-syn)) are two major genes linked to PD. Pathogenic mutations in these two genes cause autosomal dominant (AD) PD. Additionally, genetic variations in LRRK2 and SNCA are associated with increased risk of sporadic PD. Cellular and animal studies using preformed α-syn fibrils (PFF) demonstrate that the fibrils can be internalized by neurons and act as seeds that can recruit and corrupt endogenously …
Prohealing Multifunctional Endothelium Nanomatrix Coated Stents, Grant Alexander
Prohealing Multifunctional Endothelium Nanomatrix Coated Stents, Grant Alexander
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Cardiovascular disease is currently the number one cause of death in the United States, and indeed, worldwide. Stents are the most commonly implanted devices used to treat cardiovascular disease. Bare metal stent use remains limited by relatively high rates of in-stent restenosis, a re-narrowing of the artery after stent deployment. Restenosis within stents is a result of neointimal proliferation of smooth muscle cells and the accom-panying extracellular matrix deposition in response to vessel injury. To address this, drug-eluting stents have been developed to reduce restenosis; however, difficulties with late stent thrombosis, inflammation, and poor re-endothelialization remained. Thus, alt-hough numerous approaches …
Effects Of Novel Inhibitors Against Wnt/Β-Catenin Signaling In Ovarian And Triple-Negative Breast Cancers, Abhishek Gangrade
Effects Of Novel Inhibitors Against Wnt/Β-Catenin Signaling In Ovarian And Triple-Negative Breast Cancers, Abhishek Gangrade
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Ovarian and triple-negative breast cancers (TNBC) are aggressive due to their dependence on Wnt/β-catenin signaling. Niclosamide, a strong inhibitor of Wnt/β-catenin signaling, is an efficacious cytotoxic agent for various cancers in vitro, including ovarian and breast cancers. However, it has cross-reactivity with mTOR, STAT3, and Notch pathways. A limitation of using the agent in animal studies involves its poor water solubility and bioavailability. This study investigates novel compounds based on the structure of niclosamide to improve specificity for the Wnt/β-catenin signaling pathway. The investigation evaluates three questions: 1) whether WNT974 inhibits Wnt/β-catenin signaling in ovarian cancer; 2) whether novel analogs …
Effects Of Proanthocyanidins In Combination With Resveratrol And Sulforaphane Respectively On Human Breast Cancer Cells, Yifeng Gao
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Breast cancer is the second most common cancer and the second leading cause of death from cancer among women in the United States. Cancer prevention and therapy through use of phytochemicals that have epigenetic properties has gained considerable popularity during the past few decades. Such dietary components include but are not limited to grape seed proanthocyanidins (GSPs), resveratrol (Res) and sulforaphane (SFN). Here we report for the first time that GSPs and Res in combination dose- and time-dependently inhibited cell viability and posttreatment colony forming ability synergistically in MDA-MB-231 and MCF-7 human breast cancer cells, while GSPs and SFN in …
Examining The Relationship Between Teacher Beliefs, Prekindergartener’S Self-Regulation And Classroom Quality: Informing Professional Development Programs, Cailin Jane Kerch
Examining The Relationship Between Teacher Beliefs, Prekindergartener’S Self-Regulation And Classroom Quality: Informing Professional Development Programs, Cailin Jane Kerch
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The purpose of this convergent parallel, mixed methods study was to examine and explore the relationship between subjective teacher beliefs, classroom quality, and pre-kindergartener’s self-regulatory abilities within a publicly funded pre-kindergarten program. Teacher subjective beliefs (beliefs of classroom management, classroom practice, and beliefs of children) were studied operantly using Q-Methodology, in addition to, audio-recorded focus groups to explore the lived experience of teachers within the sample (n = 20). Classroom quality was measured using the Classroom Assessment Scoring System (CLASS) and pre-kindergartener’s self-regulatory abilities were studied using pre/post proxy items from the Devereux Early Childhood Assessment for Preschoolers, Second Edition …
The Effects Of Glucose And Amino Acid Restriction On Protein Turnover And Micro-Rna Composition In The Muscle Of Rainbow Trout, Mary Neslund Latimer
The Effects Of Glucose And Amino Acid Restriction On Protein Turnover And Micro-Rna Composition In The Muscle Of Rainbow Trout, Mary Neslund Latimer
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Changes in nutritional status, through glucose and amino acid restriction, have the ability to augment both the protein turnover and micro-RNA (miR) composition in the skeletal muscle of rainbow trout in vitro and in vivo. In vitro, the restriction of glucose in the media for a period of 24h was able to reduce protein synthesis by 41.2% compared to control conditions. In addition, 48h of glucose restriction affected the expression of both mstn2a and igfbp5, genes involved in muscle growth dynamics and synthesis. The restriction of amino acids, specifically the amino acid methionine, in vitro was able to reduce the …
Mechanisms And Treatment Of Halogen Inhalation-Induced Pulmonary And Systemic Injuries In Pregnant Mice, James Lambert
Mechanisms And Treatment Of Halogen Inhalation-Induced Pulmonary And Systemic Injuries In Pregnant Mice, James Lambert
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Toxic chemicals may pose an increased threat to vulnerable populations such as pregnant women and their unborn fetuses. The halogen bromine has numerous industrial utilities that include flame retardant, pharmaceutical, insecticide, and bleaching additive production. At room temperature, bromine is a volatile liquid. When the gas is inhaled, bromine causes exposure-dependent acute and chronic pulmonary and systemic injuries that range from mild eye and airway irritation to severe damage to the cardiopulmonary system and other organs, which can lead to death. If exposure is survived, patients still may develop reactive airway disease syndrome and pulmonary fibrosis as well as restrictive …
Gender-Specific Facilitators And Barriers To Health-Related Quality Of Life In Adults With Cystic Fibrosis: A Mixed Methods Study, Leigh Ann Bray
Gender-Specific Facilitators And Barriers To Health-Related Quality Of Life In Adults With Cystic Fibrosis: A Mixed Methods Study, Leigh Ann Bray
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BACKGROUND: With the life expectancy of individuals with cystic fibrosis (CF) doubling over the last two decades, it is critical that healthcare providers address both quantity and quality of life. Health-related quality of life (HRQoL) encompasses physical, social, psychological, and functional aspects of daily living and how CF impacts each one. Women with CF consistently report having an overall poorer quality of life across international studies, but the cause of the gender difference is unknown. The purpose of this study was to explore gender differences in HRQoL and then build upon those results to better understand gender-specific facilitators and barriers …
The Effects Of Growth Hormone In Human Melanoma Cell Lines, Ashiya Buckels
The Effects Of Growth Hormone In Human Melanoma Cell Lines, Ashiya Buckels
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Melanoma is less common than basal and squamous cell skin cancers, but is the most aggressive form of skin cancer. ~90% of melanomas carry a mutation in the RAS-RAF pathway, which promotes progression by constitutive activation of the extracellular sig-nal-regulated kinase (ERK) signaling cascade. BRAF inhibition is an effective line of therapy for advance melanoma, but patients often progress due to the development of several forms of treatment resistance. Therapeutic resistance often results in increased invasion and migration of the cancer into proximal and distant tissues leading to the formation of metastasis. Examination of various cancer genomics data sets using …
Multimodal Imaging (Fmri Bold Task, Functional Connectivity & Spectroscopy) Longitudinal Analysis Of Antipsychotic Treatment Effects In Unmedicated Patients With Schizophrenia, Elyse Cadena
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Schizophrenia is a mental disorder that affects around 1% of the world’s population. Antipsychotic medication does not effectively treat all symptoms as around 1/3 of those diagnosed will remain unresponsive to treatment. Patients with schizophrenia (SZ) present dysfunction in cognitive control processes compared to healthy controls (HC). Neuroimaging SZ studies report abnormalities in brain function and neurochemistry, although the majority of these studies involve medicated patients. To better determine SZ brain abnormalities, it is vital to characterize brain function without the confounding effect of antipsychotic medication, determine the extent of medication’s effects on brain function, and the relationship with symptom …
Mitochondria-To-Nucleus Retrograde Signaling And Its Role In Cancer, Trevor Carden
Mitochondria-To-Nucleus Retrograde Signaling And Its Role In Cancer, Trevor Carden
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Mitochondrial dysfunction is considered a hallmark of cancer. Mitochondria are essential, cellular organelles that participate in processes including energy production, calcium homeostasis and steroid metabolism. Mitochondria have been more recently appreciated for their role in cellular signaling, bringing about a greater understanding of their role in many diseases including cancer. Retrograde signaling is a mechanism by which the nucleus responds to mitochondrial dysfunction by modulating its own transcriptional programs to maintain metabolic and cellular processes. Many genes have already been identified as participants in or mediators of this signaling mechanism; these include cell signaling, metabolic and structural genes as well …
The Mechanism Of Tgf-Β Function In Development Of The Axial Skeleton, Ga I Ban
The Mechanism Of Tgf-Β Function In Development Of The Axial Skeleton, Ga I Ban
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THE MECHANISM OF TGF-β FUNCTION IN DEVELOPMENT OF THE AXIAL SKELETON GA I BAN CELL, MOLECULAR DEVELOPMENTAL BIOLOGY ABSTRACT Back pain is caused by degeneration of intervertebral discs (IVD). IVD consists of two compartments: the annulus fibrosus (AF) and the nucleus pulposus (NP). One strategy for treatment of IVD degeneration is stem cell therapy, which would require an in-depth knowledge of how the IVD develops. Currently, the molecular mechanism of IVD development are not well defined. AF and vertebral bodies (VB) are derived from the same embryonic progenitor, sclerotome. Specification of sclerotome is determined by complex interactions among various growth …
Psychosocial Job Stress And Oxidative Stress In Emergency Department Nurses, Rupkatha Bardhan
Psychosocial Job Stress And Oxidative Stress In Emergency Department Nurses, Rupkatha Bardhan
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Job stress often causes work-related physical injuries and chronic exposure to such environment may lead to poor health outcomes. Job stress in recent years has grown significantly within the workforce due to performance pressure, long work hours and poor pay structures. Nurses work in the forefront to save patients’ lives. High job demand in this noble profession often leads to progressive decline in physical and mental health. There are existing reports that nurses in the United States (US) suffer from “burnout” syndrome which may also negatively affect patient care. There are very few studies that measured work-related stress in nurses …
Wear, Corrosion, And Micromotion In Retrieval And Autopsy Components Of Tkr, Heath Mitchell Baskin
Wear, Corrosion, And Micromotion In Retrieval And Autopsy Components Of Tkr, Heath Mitchell Baskin
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Total knee replacement (TKR) is used to remedy end-stage joint deterioration. Despite advancements in TKR design, thousands of patients still experience aseptic loosening and the revision surgeries that follow. Wear and corrosion processes can lead to the harmful production of debris, causing osteolysis in the periprosthetic space. This study seeks to quantify the relationships of wear, corrosion, and micromotion as it relates to aseptic loosening in TKR. 17 TKR devices harvested at revision surgeries and 6 necropsy devices available through UAB’s retrieval program were scored for wear and inflammatory cell-induced corrosion (ICIC). All devices were implanted ≤ 10 years. All …
Connecting Cilium Proteins Bbs5 And Mks6 And Their Roles In Retinal Degeneration, Katie Leigh Bales
Connecting Cilium Proteins Bbs5 And Mks6 And Their Roles In Retinal Degeneration, Katie Leigh Bales
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The primary cilium is an evolutionary conserved structure with numerous motility and sensory-related functions, dynamically concentrating signaling molecules to developmental, homeostatic and sensory pathways. Rod and cone photoreceptor cells are highly modified primary cilia, which reside in the back of the eye within the neural retina and are responsible for dim light sensitivity and visual acuity/ color vision, respectfully. These cells require massive protein production and proper protein trafficking on a daily basis. The major protein complexes that govern protein trafficking within photoreceptors form the connecting cilium, are the transition zone which serves as a gatekeeper, regulating protein trafficking into …
Immunophenotype In The Molecular Epidemiology Of Breast Cancer, Michael Behring
Immunophenotype In The Molecular Epidemiology Of Breast Cancer, Michael Behring
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This research analyzes the underlying genomic features of breast tumors during immune response, with the overall goal of discovering markers of how tumor immunity and the known features of disease pathology relate. We aimed to 1) identify and validate somatic copy number variation and RNA expression associated with nodal metastasis; 2) construct an array-based measure of tumor infiltrating immune cells and determine its prominent clinical and transcriptional features; and 3) examine the relationship between somatic mutations within p53 and tumor immune cell infiltration status. In two sets of data, gene-level copy number variation (CNV) and RNA expression from the primary …
Racial Disparities In Oncology Clinical Trial Participation: A Qualitative Exploration, Soumya J. Niranjan
Racial Disparities In Oncology Clinical Trial Participation: A Qualitative Exploration, Soumya J. Niranjan
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Introduction: Current rates of participation for racial and ethnic minorities in cancer clinical trials are significantly lower when compared to non-Hispanic whites. The patients’ perspective on reasons for low participation is abundant. Yet, very little is known from the perspective of clinical and research professionals who are actively involved in patient recruitment. This study seeks to understand their perspective on how the external environment associated with the health care system contributes to limited participation of racial and ethnic minority groups in cancer clinical trials. To that effect, the health services utilization framework was utilized. Data/Methods: EMPaCT data with 91 qualitative …
Aberrant Astrocyte Maturation Contributes To Rett Syndrome Pathogenesis, Natasha Lynn Pacheco
Aberrant Astrocyte Maturation Contributes To Rett Syndrome Pathogenesis, Natasha Lynn Pacheco
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Rett syndrome (RTT) is caused by mutations in the gene encoding the transcriptional modulator, Methyl-CpG-Binding Protein 2 (MeCP2). RTT is characterized by motor, behavioral and physiological deficits. MECP2 mutations are associated with other disorders such as autism, schizophrenia, and intellectual disability, underscoring the important role of MeCP2 for typical brain function. Much of our understanding of MeCP2 function is derived from transcriptomic studies carried out over the last 10 years with the general assumption that alterations in the transcriptome correlate with proteomic changes. Advances in mass spectrometry-based proteomics have facilitated recent interest in the examination of global protein expression. In …
Effect Of Dietary Compounds In Epigenetic Modulation And Microbial Alteration And Their Roles In Breast Tumor Inhibition, Bidisha Paul
Effect Of Dietary Compounds In Epigenetic Modulation And Microbial Alteration And Their Roles In Breast Tumor Inhibition, Bidisha Paul
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Breast cancer is a major cause of cancer death among women in the United States. Current methods of chemoprevention and therapy have cytotoxic effects and have several short-term and long-term side effects. Therefore, the use of natural dietary bioactive compounds has gained prominence as safe and effective agents of chemoprevention and therapy. Genistein (GE), an isoflavone found in soy products, has been shown to exhibit several anticancer properties, particularly as an epigenetic modifier. We have observed that GE has the ability to alter the gut microbiome of germ-free mice humanized with fecal transplants from breast cancer patients undergoing chemotherapy. We …
The Role Of Astrocytes In The Development Of Central Chemosensitivity, Kelsey Patterson
The Role Of Astrocytes In The Development Of Central Chemosensitivity, Kelsey Patterson
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In the two decades since MECP2 was identified as the causative gene in the majority of Rett Syndrome (RTT) cases, transgenic mouse models have played a critical role in our understanding of this X-linked neurodevelopmental disease. However, their exclusive use presents a limitation in translating findings from animal models to the clinic. Here, we characterized growth, anatomical, behavioral, and motor deficits in a novel zinc-finger nuclease murine RTT model from birth through adulthood. Male rats lacking the transcriptional regulatory protein, MeCP2 (Mecp2ZFN/y), are noticeably symptomatic as early as postnatal day (P) 21 and die prematurely, while females lacking one copy …