Cell and Developmental Biology Commons^™

Neurobiological Variables Mediating The Relationship Between Breast Cancer And Sleep Disruption, Brittany Domenique Elliott

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neurobiological Variables Mediating the Relationship between

Breast Cancer and Sleep Disruption

Brittany D. Elliott, MS

Breast cancer is the most commonly diagnosed malignancy in women, with more than two million new cases diagnosed world-wide each year. Improvements in screening technology and diagnostics have increased survival rates, but cancer-associated sleep disruptions persist for the majority of breast cancer survivors well beyond the treatment period. In addition to reducing quality of life, reduced sleep quality is associated with greater incidences of affective dysfunction, reduced treatment efficiency, aggressive cancer progression, increased symptom severity, and increased mortality by all causes. Thus, identifying the variables …

Glutamate Receptors At The Zebrafish Neuromuscular Junction, Trenton Randall

Honors College Theses

Glutamate is the main excitatory neurotransmitter in the CNS, but at the neuromuscular junction, that role is taken by acetylcholine. However, during embryonic development, non-cholinergic receptors, including those for glutamate, are also present at the NMJ, which are not maintained unless used. These receptors can still form functional circuits, as evidenced by a process called neurotransmitter respecification, in which a neuron changes which neurotransmitter it releases, and is accompanied by the upregulation of the corresponding receptor by the muscle. This process has been observed in frogs and in rats. We predict that zebrafish also exhibit this neurotransmitter plasticity. To assess …

The Role Of Eor-1/Plzf In Promoting Soma Compartment Specific Death In A Non-Canonical Cell Death Program In C. Elegans, Nathan Rather

2024 Fall Honors Capstone Projects - Archive

Programmed cell death (PCD) is an essential evolutionarily- conserved and genetically encoded program for normal development and homeostasis. A previous study identified a CED-3 dependent but mechanistically non-apoptotic and highly stereotyped elimination program called Compartmentalized Cell Elimination (CCE) in the C. elegans tail-spike epithelial cell (TSC). Here the transcription factor EOR-1/PLZF is found to promote CCE. The loss of which results in a persisting non-engulfed soma with enlarged nuclei in the first larval stage. This study finds that EOR-1 and its established partners function downstream of CED-3 Caspase protease activity, a role distinct from other PCD contexts where EOR-1 has …

Investigation Of Chondrogenesis, Myogenesis, And Osteogenesis After 2,4-Dtbp, 2-Bp, 4-Bp, 3,5-Dtbc Exposure In Zebrafish, Haley Brashears

All Theses

Synthetic phenolic antioxidants (SPAs) are used in personal care products, food packaging, and water pipes, common SPAs include 2,4-di-tert-butylphenol (2,4-DTBP), 2-tert-butyl phenol (2-BP), and 4-tert-butyl phenol (4-BP). These compounds are detected in the environment and in human biological samples. 2,4-DTBP has been detected in cord plasma, placenta, and breast milk samples. This drives the concern regarding developmental toxicity. In human iPS cells 2,4-DTBP impairs differentiation into somites and osteoblasts. Other SPAs, like 2,6-di-tert-butyl-hydroxytoluene caused increased rates of malformations including yolk and pericardial edema, and spinal curvature in 5-day post fertilization (dpf) zebrafish. …

Lack Of Inflammatory Response In Mouse Embryonic Cells To Listeria Infection, Damilola Oyebode

Master's Theses

Approximately 1 in 5 pregnancies in the United States results in miscarriage, with a significant percentage of these losses attributed to failed implantation due to immunological challenges encountered by the early embryo. Recent research has shown that key cell types within mouse blastocysts, including embryonic stem cells (ESCs) and trophoblast stem cells (TSCs), exhibit remarkable resilience against the cytotoxic effects associated with viral infections and embryotoxic cytokines, such as TNFα and IFNγ, both of which are known to hinder blastocyst development. However, the immune properties of the preimplantation stage embryo, specifically the blastocyst, remain poorly understood. Using mouse cell model, …

The Role Of Wt1 In Müllerian Duct Development, Jace Aloway

Dissertations and Theses (Open Access)

WT1 is a zinc finger transcription factor widely expressed in the urogenital system. Human mutations of WT1 lead to pediatric nephroblastoma as well as frequent differences of sex development (DSDs). Previous studies have suggested that WT1 acts as an activator for Amhr2, a necessary component of typical male differentiation. We used the mouse as a model to investigate the role of WT1 in sex development, where we deleted Wt1 in the Müllerian duct (MD) mesenchyme using a novel conditional null reporter allele, Wt1 flox-RFP. This allele utilizes the Cre-lox system to delete exons 8 and 9 of Wt1 …

Functional Analysis Of The Zebrafish Orthologs Of Host Cell Factor 1 Gene, David Paz

Open Access Theses & Dissertations

Host Cell Factor C1 (HCFC1) is a transcriptional co-activator factor that regulates the expression of over 5000 different downstream target genes in human cells. Missense mutations in the HCFC1 gene cause methylmalonic acidemia homocysteinemia cblX type (cblX). cblX, a multiple congenital anomaly syndrome (MCA) characterized by abnormal brain development, craniofacial abnormalities, metabolic deficits, and intractable epilepsy. Published studies suggest that HCFC1 regulates neural precursor proliferation, number, and differentiation. However, these results were derived from studies that were performed with nonsense alleles or transient knockdown approaches. Although these results demonstrate the importance of HCFC1 in brain development, they do not replicate …

Size Matters: The Characterization Of Telomere Function In Germ Cell Development In Danio Rerio, Jessica Macneil

Graduate Doctoral Dissertations

Infertility is a growing problem worldwide. According to the WHO, 48 million couples across the globe suffer from infertility and many couples turn to Assisted Reproductive Technology (ART) to become pregnant. One readout of gamete quality and successful ART is telomere integrity because telomeres are necessary for chromosome movements during meiosis so that the segregation of chromosomes happens correctly. Telomeres are well known for their role in aging; however, they play an important and understudied role during meiosis. In meiosis, telomeres attach to the nuclear envelope (NE) via a protein chain spanning the NE that interacts with cytoplasmic motor proteins, …

Investigation Of Reproductive Inhibition During Chronic Heat Stress In C. Elegans, Macy Makenna Nielander

Theses and Dissertations

Nearly all organisms experience heterogeneity in environmental conditions that can negatively impact fitness. A common adaptive strategy to reduce the impact of this stress is called facultative diapause, where development and reproduction are temporarily arrested to promote survival. Facultative diapause is characterized by three major criteria, the arrest must be (i) induced by an unfavorable environmental condition, (ii) reversible, and (iii) driven by genetically regulated mechanisms. The aim of this thesis was to determine whether chronic heat-induced inhibition of egg laying in Caenorhabditis elegans represents a novel form of facultative diapause. It was found that the inhibition of egg-laying is …

Old Vs. New: An Experiment On The Efficacy Of Complexity-Focused Reproductive Biology Lectures For Undergraduate Biology Students, Ive N. Muse, Shraddha Patel, Linda Fuselier

The Cardinal Edge

Old vs. New: An Experiment on the Efficacy of Complexity-focused Reproductive Biology Lectures for Undergraduate Biology Students

Muse, Ive N.; Patel, Shraddha; Fuselier, Linda

Abstract

Undergraduate reproductive biology courses are traditionally taught in a reductive manner, prioritizing a binary understanding of sex which oversimplifies reproductive behaviors and reproductive system development across diverse taxa. Although this binary approach to lessons on reproduction is intended to benefit students in learning foundational human reproductive concepts, it does not teach the most recent research in reproductive biology, which identifies reproductive variation as the norm. The current study designed and implemented a lesson on reproductive …

Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman

Biological Sciences: Faculty Scholarship

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in Caenorhabditis elegans embryos, we show that the LC3 ortholog LGG-2 is enriched inside the polar body phagolysosome independent of autophagosome formation. We demonstrate that ATG-16.1 and ATG-16.2, which promote membrane association of lipidated Atg8/LC3 proteins, redundantly promote polar body membrane breakdown in phagolysosomes independent of their role …

Autophagy And Meiotic Fidelity In C. Elegans, Kaitlin E. Kosinski

Dissertations, Theses, and Capstone Projects

Autophagy is an evolutionarily conserved multi-step recycling process in which cellular material is enclosed in the double membrane-bound autophagosome, which fuses with the lysosome to degrade its contents. Autophagy is essential for development and cellular adaptation to environmental or intracellular stress and is an important regulator of germline stem cell homeostasis in the model nematode C. elegans. We sought to determine if autophagy is important for genome stability during meiosis and found that the core adult C. elegans autophagy genes bec-1, atg-7, unc-51, and atg-18 were all required for proper meiotic development of oocytes. Loss of these …

Role Of Sds-22/Pp1 Phosphatase In Polarizing The Germplasm Of Caenorhabditis Elegans Embryo, Aparna Nurni Ravi

Dartmouth College Ph.D Dissertations

During asymmetric cell division, cell polarity and cell cycle are tightly coupled to ensure robust segregation of cell fate determinants and generation of cellular diversity. In the one-cell C. elegans embryo, multiple cell cycle kinases regulate cell polarization and posterior segregation of germline fate determinants (germplasm). For example, PLK-1 kinase inhibits the retention of its germplasm substrate POS-1 in the anterior, driving POS-1 segregation to the posterior (Han et al., 2018). Additionally, MBK-2 kinase disassembles P granules in the anterior through phosphorylation of the P granule scaffold MEG-3, helping to drive P granule segregation to the posterior (Wang et al., …

Soxb1 Transcription Factors Are Essential For Initiating And Maintaining Neural Plate Border Gene Expression, Elizabeth Schock, Joshua R. York, Austin P. Li, Ashlyn Y. Tu, Carole Labonne

Markey Cancer Center Faculty Publications

SoxB1 transcription factors (Sox2/3) are well known for their role in early neural fate specification in the embryo, but little is known about functional roles for SoxB1 factors in non-neural ectodermal cell types, such as the neural plate border (NPB). Using Xenopus laevis, we set out to determine whether SoxB1 transcription factors have a regulatory function in NPB formation. Here, we show that SoxB1 factors are necessary for NPB formation, and that prolonged SoxB1 factor activity blocks the transition from a NPB to a neural crest state. Using ChIP-seq, we demonstrate that Sox3 is enriched upstream of NPB genes in …

Causes And Consequences Of Mitotic Chromosome Missegregation In Human Pluripotent Stem Cells, Chenhui Deng

Dartmouth College Ph.D Dissertations

Mitosis is a fundamental process that ensures the equal distribution of replicated chromosomes, which carry an organism's genetic material, into two daughter cells. The fidelity of mitosis is paramount, as errors in chromosome segregation result in aberrant chromosome numbers, including gains or losses, a state termed aneuploidy. Aneuploidy impacts a broad range of human conditions, including being one of the major hurdles in early human development where it is the primary cause of miscarriages and birth defects. Strikingly, more than 70% of human preimplantation embryos are aneuploid with mitotic chromosome segregation errors being the most common source of aneuploidy. However, …

Adipose-Derived Mesenchymal Stem Cells And Their Derived Epidermal Progenitor Cells Conditioned Media Ameliorate Skin Aging In Rats, Mohamed M. Kamal, Omar Ibrahim Badr, Tasnim Mahmoud

Pharmacy

BACKGROUND: Skin alterations are among the most prominent signs of aging, and they arise from both intrinsic and extrinsic factors that interact and mutually influence one another. The use of D-galactose as an aging model in animals has been widely employed in anti-aging research. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) are particularly promising for skin anti-aging therapy due to their capacity for effective re-epithelization and secretion of various growth factors essential for skin regeneration. Accordingly, we aimed to examine the potential utility of Ad-MSCs as a therapy for skin anti-aging. METHODS: In this study, we isolated and characterized adipose-derived mesenchymal …

The Role Of Edc3 In Drosophila Melanogaster Neuronal Development, Keelan Zius

Electronic Theses and Dissertations

Enhancer of mRNA-decay 3 (Edc3) is a component of multiple decapping complexes that regulates the transcriptome by targeting a subset of transcripts for decapping for 5’-to-3’ messenger RNA (mRNA) decay. A missense mutation in the conserved Lsm domain of Edc3 has been reported in two siblings presenting with mild, non-syndromic intellectual disability (ID), however, the role of Edc3 is neuronal development has never been evaluated. Here, we use the Drosophila melanogaster model system to investigate the effects of Edc3 disruption on neuronal development. We found Edc3 reduction leads to significant hyperplasia at the larval neuromuscular junction (NMJ), providing the first …

Investigating The Regulation Of The Hypothalamic-Pituitary-Interrenal Axis In Atlantic Sturgeon (Acipenser Oxyrinchus) Following An Acute Stressor, Liam Doherty

Undergraduate Theses, Capstones, and Recitals

This study investigated the response to acute stress in Atlantic sturgeon (Acipenser oxyrinchus) and HPI axis regulation of glucocorticoid production during stress by examining the expression of key genes― corticotropin-releasing hormone (crh), corticotropin-releasing hormone receptor (crhr), proopiomelanocortin (pomca/pomcb), melanocortin 2 receptor (mc2r), and steroidogenic acute regulatory protein (star)―that are associated with hypothalamus/pituitary/interrenal (HPI) axis of bony fishes. Additionally, tyrosine hydrogenase (th1 and th2) and phosphoenolpyruvate carboxykinase (pepck), found in catecholamine-producing cells in the head kidney of the sturgeon, were investigated …

Morphological Remodeling Of The Endoplasmic Reticulum During Mitosis And Its Influence On The Integrity Of The Spindle Apparatus, Katie R. Rollins

Electronic Theses and Dissertations

The Endoplasmic Reticulum (ER) is the largest organelle in the cell by surface area and forms contacts with other organelles throughout the cell. In recent work, the ER has been implicated in numerous processes within the cell beyond its canonical roles of protein synthesis and calcium storage. The ER also undergoes a remarkable transition in morphology during cell division, with mitotic divisions requiring a massive remodeling of various membranous organelles such as the nuclear envelope and Golgi. However, whether changes in ER behaviors modulate mitotic events is less clear. The rapid cleavage divisions in the early Drosophila embryo are a …

High Mdmx (Mdm4) In Mutant P53 Expressing Breast Cancer Cells Activates The Cxcl12-Cxcr4 Metastasis Signaling Axis, Rusia H. Lee

Dissertations, Theses, and Capstone Projects

The metastasis-promoting G-protein coupled receptor (GPCR) CXCR4 is activated by the cytokine CXCL12 (also known as SDF-1) to promote metastasis through CXCR4 upregulation. High CXCR4-expressing cancer cells utilize CXCL12, the exclusive endogenous ligand of CXCR4, to intravasate into the blood as circulating tumor cells (CTCs) which then extravasate to distant metastatic sites. We previously determined the oncogenes, Mouse Double Minute 2 and 4 (MDM2 and MDM4, also known as MDMX), drive TNBC metastasis and positively correlate with high expression of CXCR4. Interestingly, this upregulation of CXCR4 was only observed in primary tumor cells grown in the tumor microenvironment …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Identifying Novel Upstream Regulators Of The Hippo Pathway: Forward Genetic Screen In Drosophila Melanogaster, Akshara Iyer

Honors Scholar Theses

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range of human disorders, including cancer. The physiological function of the Hippo pathway is best understood in Drosophila, where inactivation of the Hippo pathway tumor suppressors, or overexpression of the Yorkie (Yki) oncoprotein, results in tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis, and increased transcription of Hippo pathway target genes such as diap1 and expanded (ex). Despite the well-established Hippo pathway core signaling cascade, the upstream regulation of …

Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier

Honors Scholar Theses

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles. In post-infectious hydrocephalus (PIH) cases, the condition presents challenges in understanding the immune response. PIH is a complex condition, often persisting after the initial infection is treated and thus requiring a deeper understanding of the immune mechanisms involved in its development. This thesis will explore the immunopathogenesis of PIH, elucidating the relationship between the immune response and neurological complications that would succeed infection. The immune response of PIH includes a series of events, beginning with the activation of immune cells and finishing with the release …

Regulation Of Intracellular Sorting Of The Bruno Protein In Drosophila Flight Muscles, Travis Main

Master's Theses

Understanding mechanisms of intracellular sorting is a fundamental inquiry of cell biology. We used the B-body and protein Bruno (Bru) as a model to study the formation of nuclear domains that are membraneless organelles inside the cell nucleus. Specifically, we sought to identify protein sequences that regulate Bru's affinity to B-bodies and protein aggregation. We generated various Bru mutants and subsequently tested them in vivo using fluorescence microscopy. We found that the protein solubility of Bru is determined through an interplay of RNA recognition motifs (RRMs) and intrinsically disordered regions (IDRs). Using truncation analysis, we identified a 31-amino acid region …

The Effect Of Diabetes Mellitus On Differentiation Of Mesenchymal Stem Cells Into Insulin-Producing Cells, Mohamed M. Kamal, Omar I. Badr, Shohda A. El-Maraghy, Heba R. Ghaiad

Pharmacy

Background

Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro.

Methods

We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and …

Characterization Of Mitochondrial Morphology In Drosophila: Early Embryogenesis Description Via Confocal Microscopy, Kendall Miller

Biological Sciences Undergraduate Honors Theses

Mitochondria are not static organelles, but instead are dynamic networks that undergo rapid changes in subcellular distribution, organization, and activity in response to external stimuli. Notably, mitochondria can undergo fission and fusion, collectively known as mitochondrial dynamics. Mitochondrial fusion creates assembled networks of mitochondria that are maximally efficient at generating ATP through oxidative phosphorylation. Conversely, mitochondrial fission leads to network fragmentation and a shift towards glycolysis, which is the dominant mode of ATP generation in oxygen-limiting and stressed conditions. While mitochondrial dynamics have been intensively studied in isolated cells under stressful conditions, much less is known about how mitochondria behave …

Role Of M6a Rna Methylation In Skeletal Muscle Regeneration, Isreal Ayobami Onifade

Legacy Theses & Dissertations (2009 - 2024)

Skeletal muscle is essential in orchestrating voluntary movement and contributes to approximately half of the body's overall mass. Dysregulation in proper skeletal muscle development can lead to muscle degenerative disorders, such as severe Duchenne Muscular Dystrophy (DMD). Understanding the process of muscle development has been the central focus of numerous biological studies, focusing on myogenic transcription factors and signaling molecules like Pax3, Pax7, Myf5, MyoD, WNT, TGF-β, and BMP, IGF1, AKT/mTOR pathway. Also, studies have suggested that m6A (N6-methyladenosine) plays a crucial role in various biological processes, including skeletal muscle regeneration and development. m6A modification is the prevalent form of …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …