Medicine and Health Sciences Commons^™

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 …

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 …

The Anatomical Embodiment Of Morning Routines In The Reduction Of Anxiety: An Intervention, Natalie Wright

Expressive Therapies Capstone Theses

The topic under investigation is whether physically embodying a morning routine that was designed through the lens of Laban Bartenieff Movement Analysis (LBMA) will reduce daily symptoms of individuals diagnosed with Generalized Anxiety Disorder.

Since morning routines play a significant part in one’s preparation for the day, I created an individualized LBMA morning routine for a specific client to embody. In addition to the routine, the client documented the process of their anxiety levels on a weekly basis. This client was a white, female, 19-year-old, lesbian college student who was previously diagnosed with Generalized Anxiety Disorder (GAD). The movement analysis …

Panorama Of Human Embryo-Derived Cells In Biomedicine And Progress In Their Research And Regulation, Jianchao Gao, Yaojin Peng, Wei Wei, Shuang Lu, Chenyan Gao

Bulletin of Chinese Academy of Sciences (Chinese Version)

Since the establishment of the first human diploid cell line derived from aborted fetal tissue in the 1960s, human embryoderived cells have been widely used in biomedical field and significantly contributes to improving human health. In recent years, human pluripotent stem cells, including human embryonic stem cells (hESCs), have shown great therapeutic potential in regenerative medicine, and thus received great attention from governments and the public. However, due to various factors such as history, culture, religious beliefs, ethics and morality, research and application involving human embryo-derived cells have been controversial worldwide. This study explores the history and progress of human …

Can Biology Define A Human Life?, Katelyn De Leon

Regis University Student Publications (comprehensive collection)

I grew up contemplating the concept of life. From my Catholic grandmother to my pediatrician mother, I always received mixed perspectives on the hot topics of abortions, vaccines, and embryo use. I found that the controversy lies in an ambiguous, mixed understanding of what constitutes a human life. From biochemical approaches to extraterrestrial life forms and spirituality there is no clear, coherent all-encompassing definition of life. However, that does not mean we can merely agree to disagree. The concept of a human life has drastic implications on our everyday lives. An insufficient definition has, and will continue to, diminish quality …

The 14-Day Rule For In Vitro Human Embryo Research Requires Adjustment: From A Comprehensive Perspective Of Science, Ethics And Policy Research, Xiao Lu, Ming Zhao, Huihui Liu, Tianqing Li, Tao Tan, Weizhi Ji

Bulletin of Chinese Academy of Sciences (Chinese Version)

Since it was proposed, in vitro human embryo research had been following the 14-day rule, which limited in vitro research on human embryos within 14 days after fertilization. With the advancement in embryo culturing technology, this ethical rule has been greatly challenged. In 2021, the International Society for Stem Cell Research (ISSCR) recommended a conditional extension of the existing time limit in ISSCR Guidelines for Stem Cell Research and Clinical Translation, hence the international scientific community has restarted the debate on the 14-day rule. This study systematically analyzed the historical background and controversies of the 14-day rule ethical regulation of …

Examining Pi3k-Signaling-Dependent Regulation Of Lens Organelle Free Zone Formation Via Immunolocalization And Immunoblotting In Chick Embryos, Rifah Gheyas, A. Sue Menko

Computational Medicine Center Faculty Papers

The elimination of lens organelles during development, required for mature lens function, is an autophagy-dependent mechanism induced through suppression of PI3K signaling. Here, we present a protocol for investigating the signaling pathways responsible for induction of the formation of this lens organelle free zone. We describe steps for preparation of lens organ culture and use of signaling pathway inhibitors. We then detail procedures for analyzing their impact using both confocal microscopy imaging of immunolabeled lens cryosections and immunoblot approaches. For complete details on the use and execution of this protocol, please refer to Gheyas et al. (2022).

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 …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations & Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Understanding The Expression And Role Of Pros-1 In The Male Gonad Of C. Elegans, Jack Bozik

Undergraduate Theses

The gene pros-1 is a transcription factor that is highly expressed within neuronal sheath cells, glial cells, and excretory canal cells. pros-1 plays a role in cell determination of those cell types in the nematode C. elegans, which promotes organismal development. But the degree to which pros-1 presence is important is still not fully understood, because there are many genes involved in development that when mutated or damaged can result in unexpected phenotypes or even total loss of function to a certain developmental mechanism. What makes pros-1 valuable to research is that it is a functional homologue to a …

Intellectual Disability Related To De Novo Germline Loss Of The Distal End Of The P-Arm Of Chromosome 17: A Case Report, Eden Pope, Matthew Huertas, Amar Paul, Braden Cunningham, Matthew Jennings, Ryan Perry, Stephanie Chavez, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient.

Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv).

Results: Karyotype was …

A Brief Overview Of Triple A Syndrome, Jamaal Khan

Mako: NSU Undergraduate Student Journal

Triple A Syndrome, also known as AAA Syndrome, is a rare autosomal recessive disorder caused by any mutation in the AAAS gene on chromosome 12q13, whose main function is to code for the WD-repeat family regulatory protein, ALADIN. It typically occurs as a group of diseases that are characterized by alacrima, Addison's disease, and achalasia. Alacrima can be defined by a decrease in the amount of tears produced while achalasia is nerve damage in the esophagus that can cause difficulty swallowing. Lastly, Addison's disease is the insufficient production of cortisol and aldosterone produced by the adrenal cortex. There is no …

Parental Instincts: The Neurological And Biological Factors Associated With Parenthood, Jared Reeder

Undergraduate Honors Theses

The following project involves a systematic review of the scientific literature on neural and biological changes of mothers and fathers in parenthood. Until very recently, little scientific research was devoted to studying how bearing children affects a man or woman’s long-term biology. Over the last twenty years, studies of neuroplastic changes in new mothers show specific neural mechanisms responsible for altering the behaviors of mothers during and after pregnancy. These changes in neuroplasticity alter behavior in such a way that led to mothers requiring less sleep and being more prone to hearing the cries of their children. In addition to …

Gestational Vulnerability To Ozone Air Pollution - A Placental Story, Vishnupriya Alavala, Sarah Brent, Russell Hunter, Matthew J. Campen, Andrew Ottens

Undergraduate Research Posters

About 99% of the global population resides in areas with air pollution surpassing World Health Organization standards. Air pollution is associated with adverse neonatal health outcomes such as low fetal birth weight and an increased risk for maternal pre-eclampsia. A particularly reactive air pollutant is ozone, which forms reactive oxygen species that induce cellular damage. Research exists on the dispersion of reactive oxygen species through the bloodstream leading to fetal vulnerability during pregnancy, specifically via the placenta. Yet, placental and fetal development is a temporal process with varied susceptibility to negative gestational outcomes.

To addressing this gap, our laboratory utilized …

Knockout Of Endospanin 1 Via Crispr In Zebrafish, Danio Rerio, Jared Kittinger

Williams Honors College, Honors Research Projects

I made endospanin 1 knockout (KO) zebrafish to examine its effects on lipid and bone metabolism. Endospanin 1, or leptin receptor overlapping transcript (leprot), is a cytosolic protein linked to the protein hormone leptin that influences the trafficking of leptin receptors to the plasma membrane of cells. Genes for endospanin and tyrosinase (a pigmentation enzyme) were targeted via a microinjection of guide RNAs and CRISPR Cas9 into zebrafish embryos at 2-4 cell stages. I was able to disrupt the endospanin 1 gene (based upon the disruption of tyrosinase), but very few mutant zebrafish fully developed into adults. Only low KO …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Full Issue, Winthrop Mcnair Research Bulletin

The Winthrop McNair Research Bulletin

Winthrop McNair Research Bulletin Volume 5, Full Issue

Locating Mutagen-Sensitivity Gene Mus109 In The Drosophila Melanogaster Genome Using Deficiency Mapping, Chandani Mitchell

The Winthrop McNair Research Bulletin

The complex processes involved in repairing damaged DNA are still being elucidated. Some genes that are known to have roles in the DNA repair process have been identified, such as the mutagen-sensitivity genes, or mus genes, in Drosophila melanogaster. However, the precise genomic location of some mus genes is still unknown, including mus109. It is known that mutations in mus109 cause chromosomal aberrations resulting in larval death, and previous research has mapped mus109 to a region of the X chromosome consisting of over 520,000 nucleotides and 41 genes. Therefore, this study aimed to locate mus109 using deficiency mapping. The mus109D2 …

The Effects Of Prenatal Cannabis Exposure On The Basolateral Amygdala, Karen Kw Wong

Undergraduate Student Research Internships Conference

Clinical and preclinical studies indicate prenatal cannabis exposure (PCE) pathologically affects fetal brain development and may increase vulnerability to neuropsychiatric disorders, including schizophrenia and mood/anxiety disorders. In review research from our lab suggests that fetal exposure to Δ9-THC sex-selectively impairs mesocorticolimbic (MCL) circuit function. However, there is a distinct lack of focus on PCE models on the BLA. The BLA plays a central role within the MCL where it directly interacts with the VTA, PFC and HIPP. Importantly, our model exhibits significant VTA hyperdopaminergic activity, and sex-specific alterations to PFC/HIPP glutamate firing, alongside region- and sex-specific changes in dopamine (DA), …

Constructing An In Vitro 3d Model Of The Human Placenta, Michael Zheng

Undergraduate Student Research Internships Conference

The placenta is critical for nurturing fetal growth and development, with dysregulated placentation associated with adverse pregnancy outcomes. The main fetal and maternal placental components consist of trophoblasts and modified endometrial stromal cells known as decidual cells, respectively. Since investigating in vivo placentas in humans through non-invasive methods is challenging, comprehensive in vitro placental models are needed for in-depth studies. However, in vitro 3D placental models that adequately represent and combine fetal and maternal components have been lacking. In this study, we achieved valuable progress in developing an in vitro 3D placental model inclusive of fetal and maternal constituents. We …

The Novel Role Of Dnmbp In Kidney Development, Brandy Walker

Dissertations & Theses (Open Access)

Congenital anomalies of the kidney and urinary tract (CAKUT) accounts for nearly one-fourth of all birth defects and more than 40% of pediatric end-stage renal disease, yet only 10-20% of CAKUT cases have a known monogenetic cause. Human kidneys are composed of up to a million epithelial tubules called nephrons. Disruption of nephron development is one of the many congenital anomalies that cause CAKUT, often resulting in chronic or end-stage renal disease which requires transplant. During nephron epithelialization, the formation of stable cadherin-mediated adhesion junctions is essential for maintaining cell-cell contacts. To understand the cell behaviors underlying abnormalities in renal …

The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams

Electronic Thesis and Dissertation Repository

B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with recurrent mutations and high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine was tested for its ability to prolong lifespan of a mouse model of B-ALL and reduce frequency of mutations. Mice treated with 1g/L of N-acetylcysteine in drinking water were found to have delayed onset of B-ALL at 11 weeks of age and changes in gene expression relating to B cell development, calcium-apoptosis signaling, and pathways in cancer, although no differences in lifespan were observed. Tumours from treated …

The Effect Of Fibrodysplasia Ossificans Progressiva On The Tongue, Amy Backal, Amanda Harrop, David J. Goldhamer Dr.

Honors Scholar Theses

FOP is a rare genetic disorder in which skeletal muscle and associated connective tissue progressively turn to bone through a process called heterotopic ossification (HO). The extra skeletal bone growth is cumulative, eventually trapping patients in a second skeleton that eventually leads to death by asphyxiation. The FOP mutation is autosomal dominant that can be inherited or acquired sporadically. Unfortunately, FOP is currently incurable with no therapeutic options to inhibit bone growth or reduce existing bone nodules. My project intends to further our understanding of the cellular mechanisms of the disease within the tongue muscle. A population of cells known …

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 …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

University Scholar Projects

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

Honors Scholar Theses

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …

Characterization Of Gangliosides And Fatty Acids In Extracellular Vesicles From Human Milk, Aliya Amin

Food Science (MS) Theses

Extracellular vesicles (EVs) are bioactive components of human milk that may impact functionality to regulate growth, cognitive development, metabolism, and immunity in newborns. The biogenesis of EVs and the mechanism by which EVs elicit biologic effects in vivo have not been characterized entirely. Gangliosides and fatty acids are integral in the formation, release, stability, and functionalities of EVs. Presumably, EV function is related to EV composition and lipids in EVs influence the bioavailability of EV cargo and downstream functions of EVs. The objective of this research was to characterize the fatty acid and ganglioside composition of EVs in human milk. …

Connexin 43 Contributes To Phenotypic Variability Of The Mouse Skull, Elizabeth Jewlal

Electronic Thesis and Dissertation Repository

The purpose of this study was to determine whether connexin 43 (Cx43) contributes to craniofacial phenotypic variability. Skull shape and variation were compared within and among two heterozygous mutant mouse models (G60S/+ and I130T/+) that exhibit different levels of Cx43 channel function when compared to their wildtype counterparts (~80% and ~50% reduction in function, respectively). Results indicated mutants have significant differences in skull shape compared to wildtype littermates. Similar patterns of shape difference were found in both mutants. Increased skull shape variation and a disruption in the covariation of skull structures were observed in G60S/+ mutants only. These results show …

The Role Of Glis3 In Zebrafish Endocrine Development And Regeneration, Tasha Swenney

Murray State Theses and Dissertations

Maintenance of proper blood glucose homeostasis is governed by the endocrine cells of the pancreas. Dysregulation of blood glucose is characteristic of the disease, diabetes mellitus. Relatively little is known about the molecular mechanisms that underlie diabetes. The genes associated with more common forms of diabetes remain more enigmatic and likely have less direct roles in blood glucose homeostasis such as glucose sensing, insulin secretion, and β cell maintenance. GLIS3, a transcription factor involved in pancreatic development as well as the transcriptional regulation of insulin has been identified as a risk locus for type 1 and type 2 diabetes …