Cell and Developmental Biology Commons^™

Dengue Virus Modulates Critical Cell Cycle Regulatory Proteins In Human Megakaryocyte Cells, Swarnendu Basak, Shovan Dutta, Supreet Khanal, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Suppression of human megakaryocytes by dengue virus (DENV) infection significantly reduces the platelet count that eventually leads to thrombocytopenia, severe dengue and death. To understand DENV interactions with megakaryocytes, we investigated the cell cycle in leukemic human megakaryocytic in vitro cell line (MEG-01 cells). Megakaryocytes are known for complex endomitotic cell cycle leading to their polyploidy state. Our study shows that DENV uses these polyploid cells for its replication. Understanding the modulation of DENV-mediated cell cycle regulation in megakaryocytes is therefore highly important. We show that DENV2 (serotype 2) infection significantly modulates cell cycle signaling. Our protein profile microarray data …

Inductions Of Long-Term Potentiation With Biomimetic Electromagnetic Fields In Primary Neurons, Cooper E. Kansala

Theses and Dissertations (Comprehensive)

Endogenous brain rhythms guide neural communication and plasticity, raising the question of whether weak, temporally structured electromagnetic fields (EMFs) that mimic these rhythms can modulate neuronal activity in a targeted, biomimetic manner. This thesis investigates whether patterned EMFs designed to reflect the temporal structure of hippocampal long-term potentiation (LTP) are more effective at inducing neural plasticity than conventional sinusoidal fields or no stimulation at all. Cortical neurons cultured from postnatal rats were exposed to patterned EMFs for 30 minutes and assessed across three distinct experimental domains. In Chapter 2, microelectrode array (MEA) recordings revealed that the LTP-patterned field significantly increased …

Transcriptome-Wide Gene Expression Analysis Of Skeletal Muscles Of Duchenne Muscular Dystrophy Mouse Models And Patients, Olivia N. Ransiear

Electronic Theses & Dissertations (2024 - present)

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive muscle degenerative disease that frequently proves fatal by age 30. It primarily affects adolescent males with symptoms appearing as early as age 6. Patients quickly lose their ability to walk due to muscle weakness and are confined to wheelchairs for the remainder of their lives. DMD is caused by a mutation in the dystrophin gene. Without dystrophin, mechanical stress, injury, or shock takes a drastic toll on muscle tissue and muscle stem cells, rendering them unable to regenerate or be repaired. This results in a rapid loss of muscular strength and muscle …

Unveiling The Cell Composition Of The Olfactory Migratory Mass: Perspectives On Terminal Nerve Formation, Olfactory Development, And Migration Of The Gnrh-1 Neurons, Enrico Amato Jr.

Electronic Theses & Dissertations (2024 - present)

Puberty is a postnatal developmental process required to initiate key sexual maturation events that are necessary for the propagation of species. Signals to initiate these events first begin with the Gonadotropin releasing hormone-1 (GnRH-1) neurons within the hypothalamus. The hormone GnRH-1 released by these neurons is crucial for puberty, fertility and reproductive processes by establishing the hypothalamic-pituitary-gonadal (HPG) axis, regulating release of sex hormones (Progesterone, Estrogen, Testosterone). Conditions related to inability of the GnRH-1 neurons to correctly release GnRH-1 can lead to aberrant or delayed puberty, a condition known as hypogonadotropic hypogonadism (HH). Interestingly, some patients with the hormonal disorder …

Contactin2(Cntn2)Creert2 Mouse Line, A New Genetic Tool For Temporal Control To Trace The Developing Neurons In The Nose, Alexis M. Semon

Electronic Theses & Dissertations (2024 - present)

Neuronal migration is a vital process in embryonic development. In rodents, the very first neurons that originate from the olfactory placode migrate toward the developing brain as part of the migratory mass. This migratory mass includes Gonadotropin-releasing hormone-1 (GnRH-1) neurons, pioneer/terminal nerve (TN) neurons, and olfactory ensheathing cells—a type of glial cell.

Contactin-2 (Cntn2), also referred to as transiently expressed axonal surface glycoprotein-1 (TAG-1), belongs to the contactin family of proteins, which is part of the immunoglobulin superfamily of cell adhesion molecules. Cntn2 has been extensively utilized as a transient/stage-specific molecular marker for various neuronal populations, including commissural neurons of …

Characterization Of The Erv41-Erv46 Complex As A Retrograde Receptor For Misfolded Secretory Proteins, John Andrew Fuesler

Dartmouth College Ph.D Dissertations

The Endoplasmic Reticulum (ER), the site of secretory protein biosynthesis

provides a favorable environment to promote polypeptide folding, protein

oligomerization and export. Although the ER contains many chaperones and other

factors that assist in protein folding, this process is error prone. Eukaryotes have

evolved protein quality control checkpoints to maintain homeostasis in the secretory

pathway, however these processes are imperfect and may result in proteotoxicity

when toxic levels or aggregates of proteins arise. Mutations in proteins involved in

trafficking in the early secretory pathway are closely associated with disease states.

Therefore, it is of great interest to further understand how …

Xanthine Oxidoreductase, Uric Acid, And Iron Homeostasis: Discovering A Therapeutic Vulnerability In Breast Cancer, Matthew G. Chapa

Graduate Theses, Dissertations, and Problem Reports (ETD)

Breast cancer remains the most frequently diagnosed malignancy and the leading cause of cancer related deaths in women. This is primarily due to distant metastases, which highlight the necessity to understand factors that contribute to breast cancer progression. Emerging evidence associates decreased tumor xanthine oxidoreductase (XOR) expression with a poorer prognosis, increased recurrence, and a more aggressive phenotype. While healthy liver, intestines, kidneys, and breast tissue have robust XOR expression and activity, there is a tendency for this to be ablated in carcinogenesis. This dissertation investigates XOR's role in breast cancer and identifies its product, uric acid (UA), as possessing …

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 …

Reversible Degradation Of Peptidoglycan By Lytic Transglycosylases, Aaron Devereaux

Theses and Dissertations (Comprehensive)

Antimicrobial resistance continues to be a burden on the global healthcare system with an estimated cost of billions of dollars and millions of deaths each year. Recently, there has been little to no development on new antibiotics to treat bacterial infection, and any that are developed become resisted to within a few years. Both Gram-positive and Gram-negative bacteria contain a mesh-like layer called peptidoglycan (PG) that surrounds their cells providing strength, cell shape, and protection from their environments. This layer is a polymer of N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) connected via a b-1,4-glycosidic bond, with each strand being cross-linked …

Penta Ef-Hand Protein Alg-2 Regulates Copii Activity At Eres In Response To Calcium Signaling, Jacob Ryan Lapka

Graduate Student Theses, Dissertations, & Professional Papers

Intracellular protein trafficking is critical for maintaining cellular homeostasis, relying on highly regulated vesicular transport pathways originating from the endoplasmic reticulum (ER). Central to this process is the COPII coat complex, which governs cargo export at ER exit sites (ERES) by selectively packaging secretory proteins into transport vesicles. Recent studies highlight the regulatory role of calcium (Ca²⁺) signaling at ERES, where the Ca²⁺-binding Penta EF-hand proteins ALG-2 and peflin modulate COPII coat dynamics and cargo sorting in a context-dependent manner. In Chapter 2, we show that knockdown of the Inositol 1,4,5-trisphosphate receptor-3 (IP3R-3) in normal rat …

Analysis Of Differential Gene Expression In Androgen-Independent Clones Derived From The Mycap Pca Cell Line, Jessie L. Tignor, Melanie Sinanian, Richard Inho Joh, David Gewirtz, Jason Reed

Undergraduate Research Posters

Androgen deprivation therapy (ADT) is a primary treatment strategy for prostate cancer (PCa), yet many tumors eventually develop androgen independence, leading to treatment resistance. To investigate the molecular changes underlying this transition, we analyzed differential gene expression in four androgen-independent (AI) clones derived from the Myc-CaP prostate cancer cell line using RNA sequencing. Gene expression profiles were compared to the parental Myc-CaP line, and differentially expressed genes (DEGs) were identified using DESeq2 and edgeR. The AI clones exhibited significant downregulation of senescence-associated genes, including Ezh2 and lamin B1, suggesting a loss of senescence-related chromatin repression. Additionally, upregulation of Wnt pathway …

Comprehensive Investigation Of Proteoglycan Gene Expression In Breast Cancer: Discovery Of A Unique Proteoglycan Gene Signature Linked To The Malignant Phenotype, Simone Buraschi, Gabriel Pascal, Federico Liberatore, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Solid tumors present a formidable challenge in oncology, necessitating innovative approaches to improve therapeutic outcomes. Proteoglycans, multifaceted molecules within the tumor microenvironment, have garnered attention due to their diverse roles in cancer progression. Their unique ability to interact with specific membrane receptors, growth factors, and cytokines provides a promising avenue for the development of recombinant proteoglycan-based therapies that could enhance the precision and efficacy of cancer treatment. In this study, we performed a comprehensive analysis of the proteoglycan gene landscape in human breast carcinomas. Leveraging the available wealth of genomic and clinical data regarding gene expression in breast carcinoma and …

Development Of An Injectable Chitosan-Based Bioink For Enhanced Bone Fracture Healing Via Msc-Derived Osteogenesis, Zeina H. Adel, Jana A. Hassan, Hala H. Muhammed, Haneen M. Elsaeid, Raghad M. Nasr, Ahmed M. Deghidy

BAU Journal - Science and Technology

Worldwide, bone fractures are a major public health concern and, there is an urgent requirement to create new treatments to accelerate the rate of the bone healing process. This research mainly relies on creating a hydrogel that satisfies the bone marrow mesenchymal stem cells (BM-MSCs) and makes it a suitable medium to differentiate into osteogenic cells. We combine the BM-MSCs with a chitosan polymer-based hydrogel, infused with PVA to enhance bone healing, this unique mixture forms " Bioink ". We induced a closed fracture model in the rat's right humerus, followed by injection of a single dosage of bioink. On …

Regulation And Function Of Mec-2 Alternative Splicing In Single Cells, Canyon Calovich-Benne

Biological Sciences Theses and Dissertations

One mechanism for generating diversity at the single cell level is selective expression of a unique set of transcription factors (TFs) and RNA binding proteins (RBPs). These regulatory factors contribute to functions of cells by controlling cell fate, turning genes on and off, and processing of transcripts either co- or post-transcriptionally. Many genes, especially neuronal genes, have multiple different splicing events, promoters, and/or polyadenylation sites. Post-transcriptional coordination is in the infancy of being studied and the functional consequences of this coupling at the single cell level has yet to be explored. Here we show, mec-2 coordination of alternative transcription start …

Microwell Fabrication For Impedance And Ac Measurements Of Isolated Ventricular Cardiomyocytes, Fallon Wenck

Multidisciplinary Studies Theses and Dissertations

Electrophysiological behavior of human hearts have been extensively studied for hundreds of years. Even with elucidation of not just biological function, but also time and frequency-dependent current flow, the sheer intricacy of in vivo cardiac tissue function remains somewhat enigmatic. All while heart disease has been the leading cause of death in the United States for over a century, with its rates of occurrence still increasing annually [1]. Thus, new research techniques and tools to quantify cardiac function are still being pursued at smaller and smaller scales to decrease research/innovation time, cost, and diagnostic ambiguity. In fact, it remains incredibly …

P85Α Degradation Mediated By Ubiquitin E3 Ligase Fbxo21 Offers Therapeutic Potential In Leukemia, Kasidy K. Weber

Theses & Dissertations

Acute myeloid leukemia (AML) is a complex and heterogeneous disease characterized by the clonal expansion of myeloid blasts in the bone marrow. Despite significant therapeutic advances over the years, the prognosis for AML patients remains dismal, with high relapse rates and poor overall survival. The ubiquitin-proteasome system (UPS) plays a critical role in maintaining cellular homeostasis by regulating the degradation of proteins involved in essential processes such as cell cycle control, DNA repair, apoptosis, and various signaling pathways. Given this vital function, targeting ubiquitin E3 ligases within the UPS presents a promising strategy for developing more effective and targeted therapies …

Investigating The Expression Of C-Myc And Birc5 In Trail And Pbox-15 Treated Metastatic Prostate Cancer Cells, Corinne Kai Leng Chew, Hannah O'Toole, Daniela M. Zisterer, Seema M. Nathwani, Jade K. Pollock

SURE Journal: Science Undergraduate Research Experience Journal

Purpose Metastatic prostate cancer is associated with poor survival rate and limited treatment options. Overexpression of c-Myc and BIRC5 has been reported in prostate cancer cells which contribute to the development of the tumour environment. The specific tumour receptor mechanism of the death ligand TRAIL (tumour necrosis factor related apoptosis inducing ligand) has attracted remarkable therapeutic interest. However, many cancer cells are resistant to TRAIL monotherapy. A novel microtubule-targeting agent, PBOX-15 is known to exhibit anti-tumour activity in cancer cell lines including those with multi-drug resistance. Previous studies demonstrated that PBOX-15 is capable in sensitising cancer cells to TRAIL-mediated cell …

Comparing Multivalent Cross-Linked Sodium Alginate/ Montmorillonite Beads Containing Curcumin Or Cayenne Pepper As Drug Carriers And Their Antimicrobial Resistance, Shionainn Traynor, Shubham Sharma

SURE Journal: Science Undergraduate Research Experience Journal

The aim of the following work was to investigate and compare curcumin and cayenne pepper in microbeads composed of sodium alginate (SA) crosslinked with montmorillonite (MMT) to act as drug carriers and their antimicrobial resistance. The microbeads were prepared through ion-exchange in multivalent solutions of CaCl₂, MgCl₂ and AlCl₃. The microbeads were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray analysis (EDX) and the time required for intercalation of curcumin and cayenne pepper with MMT. Simulated intestinal fluid (pH 7.3) and gastric fluid (pH 1.2) at 37°C were used for comparison in swelling studies. …

Review: Cell Mechanisms In The Control Of Inflammatory Foundations Of Obesity And Secondary Metabolic Disorders, Kristin Goldstone, Keelin Irwin, Ava O' Meara-Cushen, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Review: Obesity is a global threat to human health that is precipitating epidemically, with almost 2 billion adults categorised as overweight or obese in 2016. Ireland has one of the highest reports of obesity in Europe with 60% of Irish adults reported as overweight or obese. Inflammation plays an integral role in disease pathogenesis and is a major hallmark of obesity and obesity-related secondary co-morbidities. Obesity-related inflammation can precipitate several diseases, such breast cancer, insulin resistance, type II diabetes and cardiovascular issues. As obesity puts human health at inherent risk, the regulation of obesity-related inflammation is therefore a necessary component …

Investigation Into The Effect Of Aspartame On The Expression Of P53 And Bax In Mouse Stomach Tissue, Angelique Cheryl, Aoife Mac Cooey

SURE Journal: Science Undergraduate Research Experience Journal

Introduction: The recent reclassification of aspartame as a Group 2B hazard by the International Agency for Research on Cancer, along with studies suggesting links to cancer, has raised concerns and prompted further investigation. Evidence suggests that aspartame exposure may alter p53 and BAX gene expression, affecting apoptosis in cancer cells. This study aims to examine how aspartame exposure affects p53 and BAX gene expression in normal mouse stomach tissue, shedding light on cellular stress and apoptosis mechanisms.

Methods: Mice were sacrificed, and stomach tissue was excised and divided into control and treatment groups. RNA extraction was carried out in the …