Cell and Developmental Biology Commons^™

Gamma Protocadherin Synaptic Localization And Intracellular Trafficking Is Consistent With Distinct Adhesive And Anti-Adhesive Roles In Development, Nicole Lamassa

Dissertations, Theses, and Capstone Projects

Clustered protocadherins (Pcdhs) constitute a family of cell adhesion molecules with approximately 60 Pcdh genes clustered in a 1 MB locus on chromosome 5q31 in humans. The Pcdh gene cluster is subdivided into α, β, and γ subclusters which encode related proteins. Individual neurons activate different subsets of Pcdh-α, Pcdh-β and Pcdh-γ genes by epigenetic mechanisms to generate distinct Pcdh adhesive units expressed by each neuron. This is thought to serve as a “surface barcode” for single-cell identity and synaptic recognition in the nervous system. The actual role for Pcdhs in neural development is still relatively unknown and different roles …

Clustered Protocadherins Ubiquitination And Phosphorylation Regulates Surface Expression, Albert Ptashnik

Dissertations, Theses, and Capstone Projects

Clustered protocadherins (Pcdhs) are a family of 60 adhesion-like molecules forming a neural barcode. In vertebrate neurons, 60 Pcdhs are coded by a large gene cluster. Numerous axons in the cluster are coding for the different extracellular, transmembrane, variable portion of the cytoplasmic and constant cytoplasmic domains where their expression is controlled epigenetically. These proteins mediate interactions between axons, dendrites, and glial cells during neural development. Yet, Pcdhs are not strictly adhesion molecules. In the amacrine cells of the retina, Pcdhs promote avoidance of the same cell dendrites, where in the cortex Pcdhs promote interactions between dendrites and astrocytes. In …

Function Of Atm And Msh2 During Dna Repair And Recombination, Emily Sible

Dissertations, Theses, and Capstone Projects

Class switch recombination (CSR) produces secondary immunoglobulin isotypes and requires AID-dependent DNA deamination of intronic switch (S) regions within the immunoglobulin heavy chain (Igh) gene locus. Non-canonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal S regions. ATM-dependent phosphorylation of AID at serine-38 (pS38-AID) promotes its interaction with APE1, a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm^-/- mice …

Investigating The Role Of The Transcriptional Coregulator Cited2 In Regulating Intermediate Progenitor Proliferation And Modulating Behavior, Nikolaus R. Wagner

Dissertations - ALL

The mammalian neocortex develops from a thin layer of neuroepithelial cells into a robust mosaic of differentiated neurons organized into distinct layers and functional areas. This process requires a complex choreography of transcription factors and epigenetic regulators to be spatially and temporally activated in a precise manner. Disruptions in any aspect of this delicate process may lead to neurodevelopmental disorders like autism spectrum disorder, schizophrenia, or intellectual disability. One such transcriptional coregulator that is a crucial regulator of neocortical development is Cited2. Previous work demonstrated that forebrain-specific Cited2 loss-of-function causes a reduction in neocortical progenitor proliferation which leads to reduced …

Investigating The Effects Of Cell Signaling Mutants And Inhibitors On Chemokinesis In Dictyostelium Discoideum., James Rybczyk

Honors Scholar Theses

Chemokinesis is the augmentation of cellular motility in response to chemical stimuli. While it is known that chemical factors induce changes in the behavior of a cell with regards to motility, the mechanism by which this process occurs is poorly understood. The aim of this project is to identify potential proteins within the signaling pathways that integrate the message brought on by chemical ligands and consequently lead to changes in cellular motility. In order to accomplish this goal, various gene knockout mutants of the amoeboid species Dictyostelium discoideum are compared to an axenic wild-type strain (AX2) based on their relative …

Arabidopsis Shoot Gravitropism Requires The Mediator Coactivator Complex, Gabriella Newton

Honors Theses

Gravitropism is a plant response to gravity in directing the growth of its organs, such as the root and the stem. Gravity is sensed by statocytes, unique cells that contain starch-filled amyloplasts, which trigger gravitropic growth response by modulating the distribution of growth hormone auxin in the elongation zone of the stem and root. Despite the fact that multiple factors have been identified as key regulators of shoot negative gravitropism, how these factors are regulated at the transcriptional level is largely unknown. In this study, we explore the role of transcriptional machinery in regulating shoot gravity sensing and responses by …

Mechanisms And Roles Of Dynamic Actin Assembly Around Dysfunctional Mitochondria, Tak Shun Fung

Dartmouth College Ph.D Dissertations

Possessing the ability to efficiently generate ATP required to sustain cellular functions, mitochondria are often considered the ‘powerhouses of the cell’. However, our understanding of mitochondria in cell biology was further expanded when we recognized that communication between this unique organelle and the rest of the cell regulates cellular bioenergetics, metabolism and signaling processes such as mitophagy and apoptosis. Here, I investigate signaling between mitochondria and the actin cytoskeleton, and how this signaling regulates mitochondrial dynamics and cellular function. Specifically, I find that, upon mitochondrial dysfunction, actin polymerizes rapidly around the dysfunctional organelle, which we term ‘acute damage-induced actin’ (ADA). …

Nup211 Plays An Important Role In Regulating Mrna Export And Stress Response, Ayana Ikenouchi

Theses and Dissertations

Nup211 is a nuclear pore basket component in Schizosaccharomyces pombe and roles in the gating functions of NPCs. Using RT-qPCR, I found that in nup211-shutoff cells, the transcript levels of genes in mRNA export and stress-response pathways were significantly changed, suggesting nup211 is involved in regulating stress response pathways.

Mechanisms Of Carbapenemase-Mediated Resistance Among High-Risk Pseudomonas Aeruginosa Lineages In Peru, Isabella A. Tickler, Juan Carlos Gomez De La Torre, Luis Alvarado, Anne E. Obradovich, Fred C. Tenover

Biology Faculty Publications

Objectives: Pseudomonas aeruginosa is one of the leading causes of healthcare-associated infections globally. High-risk carbapenemase-encoding P. aeruginosa clones are disseminating in many regions. The aim of this study was to learn more about the lineages and mechanisms of resistance of P. aeruginosa circulating in Peru.

Methods: A total of 141 carbapenemase-producing isolates recovered from hospitalized and ambulatory patients in Lima were sequenced and analyzed to infer their lineages through whole-genome sequence typing (wgST) and to identify their antimicrobial resistance genes.

Results: wgST identified nine sequence types (STs); ST111 and ST357 were the most frequently encountered (44.0% and 38.3%, respectively), followed …

Establishing The Freestyle 293 Expression System As A Tool To Generate Recombinant Apolipoprotein E In Mammalian Cells, Michaela Cunningham

Honors Program Theses and Projects

Alzheimer’s disease (AD) is a devastating form of dementia with 5 million people suffering from the disease in the United States alone. Thus, there is a need to understand the cause of AD so that therapeutics can be developed to treat it. The greatest risk factor for AD is the APOE gene, which encodes the apolipoprotein Eprotein. Three predominant APOE alleles exist humans, which give rise to three isoforms, called apoE2, E3, and E4. Individuals with apoE4 are ten times more likely to develop AD. In contrast, the apoE2 isoform has a neuroprotective effect and is associated with a 2-fold …

Characterization Of Exosomes And Their Role In Cellular Migration In Chemosensitive And Chemoresistant Ovarian Cancer Cells, Courtney Mceneaney

Honors Program Theses and Projects

Chemotherapy-resistant cells that remain after primary cancer treatment lead to recurrence and metastasis, resulting in a poor prognosis for patients. Chemoresistant cells were created by our collaborators using the human ovarian cancer cell line, OVCAR8, by selection of cells that survived serial culture with cisplatin, a platinum-based chemotherapeutic. The cisplatin-resistant cells (OVCAR8R) demonstrate a morphology unique from the original cisplatin-sensitive cells (OVCAR8) which could correlate with their difference in aggressiveness. My research goal is to isolate and characterize exosomes from the OVCAR8 and OVCAR8Rlines. Exosomes are small vesicles secreted from cells and contribute to the tumor microenvironment(TME). It has been …

Post-Transcriptional Control Of The Epithelial-To-Mesenchymal Transition (Emt) In Ras-Driven Colorectal Cancers, Chaitra Rao

Theses & Dissertations

Colorectal cancer (CRC) originates from epithelial cells lining the colon or rectum of the gastrointestinal tract. Most cancer deaths result from a tumor spreading to distant organs; however epithelial cells do not normally migrate from their tissue of origin. To do so, epithelial cells undergo biochemical changes allowing them to acquire behavior similar to motile mesenchymal cells termed the epithelial-to-mesenchymal transition (EMT), which contributes to tumor invasion and metastasis. Our study demonstrated that CRC cells require a molecular scaffold, Kinase Suppressor of Ras 1 (KSR1), and ERK to promote the EMT-like phenotype through the preferential translation of Epithelial Stromal Interaction …

Dysregulation Of Mir-10a Promotes Cancer Features In Cholangiocarcinoma, Matthieu Spriet

Theses & Dissertations

Cholangiocarcinoma is a primary liver cancer of the bile duct epithelium that exhibits microRNA-mediated control of tumor cell signaling. Strides toward new treatment rest on a better defining of cholangiocarcinoma tumor biology including the RNA-based layer of regulation. Additionally, there is a gap in knowledge on microRNA expression in human tissue. While there is RNA-seq data of microRNA expression in tissue, it does not differentiate between cell types, thus leaving unanswered questions about cell specific microRNA biology and expression.

Here, we identify miR-10a as an oncogenic microRNA acting through MAPK signaling. Using cholangiocarcinoma cell lines, we determined miR-10a is an …

Investigating The Role Of Splenic Macrophages In Pancreatic Cancer, Daisy V. Gonzalez

Theses & Dissertations

Pancreatic cancer is currently the 3rd leading cause of all cancer-related deaths, with a 5-year survival rate remaining at 10%. The current standard treatment of care and a lack of effective diagnostic markers leaves patients with a dismal prognosis at advanced stages of the disease. This thesis research evaluated the effect of ApoE-expressing macrophages in the spleen. First, we aimed to assess the ApoE expression in the spleen of pancreatic tumor-bearing mice. Results showed that ApoE expression in splenic macrophages increased as the disease progressed. In addition, we saw a significant increase in marginal zone metallophilic macrophages and red pulp …

Ewing Sarcoma Transcriptome: Identification Of Foxn3 As A Novel Target Of Ews-Fli1, Natasha Kreiling

Theses & Dissertations

Ewing Sarcoma is an aggressive cancer characterized by a fusion gene formed from a chromosomal translocation between a RNA binding protein and a transcription factor. The most common fusion gene is EWS-FLI1 a potent oncogenic transcription factor responsible for initiating genome instability. EWS-FLI1 promotes tumor growth by dysregulating several genes and pathways. We have identified FOXN3, an important gene in cell cycle control and development, as being suppressed by EWS-FLI1. In the future, a better understanding of FOXN3 and its ability to act as a tumor suppressor in EWS will unravel novel mechanisms of EWS pathogenesis, potential biomarker and drug …

Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated potassium (K_Ca2.x) channels are gated exclusively by intracellular Ca²⁺. The activation of K_Ca2.3 channels induces hyperpolarization, which augments Ca²⁺ signaling in endothelial cells. Cilia are specialized Ca²⁺ signaling compartments. Here, we identified compound 4 that potentiates human K_Ca2.3 channels selectively. The subtype selectivity of compound 4 for human K_Ca2.3 over rat K_Ca2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of K_Ca2.3 channels by compound 4 increased flow-induced Ca²⁺ signaling and cilia length, while negative …

Dual Mechanisms Implemented By Lin-28 For Positive Regulation Of Hbl-1 Are Necessary For Proper Development Of Distinct Tissues In Caenorhabditis Elegans, Madeleine Minutillo

Graduate School of Biomedical Sciences Theses and Dissertations

In Caenorhabditis elegans, the heterochronic pathway is comprised of a hierarchy of genes that control the proper timing of developmental events. hbl-1 (Hunchback Like-1) encodes an Ikaros family zinc-finger transcription factor that promotes the L2 stage cell fate events of the hypodermis. The downregulation ofhbl-1 is a crucial step for the transition from the L2 to the L3 stage. There are two known processes through which negative regulation of hbl-1 occurs: suppression of hbl-1 expression by 3 let-7 miRNAs through the hbl-1 3’UTR and inhibition of HBL-1 activity by LIN-46. The mechanisms by which hbl-1 is positively regulated have not …

The Effects Of Stress On The Mammalian Nucleolus And Ribosome Synthesis, Russell T. Sapio

Graduate School of Biomedical Sciences Theses and Dissertations

Ribosomes are responsible for translating every protein in the cell and are essential in all domains of life. Ribosome biosynthesis (RB) takes place in the nucleolus and is an intricate hierarchical process involving over 200 factors, including ribosomal proteins, ribosomal RNA (rRNA), and trans-acting ribosome biogenesis factors (RBFs). Inhibiting RB can disrupt nucleolar integrity, causing ribosomal- and nucleolar-factors to delocalize. This can stabilize the transcription factor p53, which is normally degraded rapidly, ultimately causing cell cycle arrest or apoptosis, through a mechanism termed the nucleolar stress response (NSR). This thesis explores the effects of inhibiting RB post rRNA transcription and …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Determining The Full-Length Structure Of Collagenase H Using Small-Angle X-Ray Scattering, Josie Carson

Chemistry & Biochemistry Undergraduate Honors Theses

Known to cause gas gangrene, Hathewaya histolytica secretes two sister collagenases, collagenase G (Col G) and collagenase H (Col H), to degrade the triple helical structure of collagen to further infection in a host. Individual domains of Col H have been crystalized in previous studies, but methods in x-ray crystallization of full-length Col H have been unsuccessful. Using Small Angle X-Ray Scattering (SAXS) data, atomistic modeling was used to generate multiple conformations of Col H while accounting for flexibility between domains. Full-length Col H was found to adopt a two-state conformational model exhibiting a majority compact and a minority elongated …

Investigations Into Avian Skeletal Adaptations And Spine Fusion Events, Tori Huey

All Theses

Avian dinosaurs evolved skeletal adaptations resulting in numerous fused spinal structures, like the synsacrum, present in extant birds. The synsacrum is a highly fused region necessary for stiffening the spine, and it fuses the spine to the pelvic ilium. Conventional wisdom suggests that fusion occurred in ovo during embryonic development via the cartilage matrix that patterns the future vertebrae. We show that post hatch birds have intervertebral discs separating all vertebrae of the spine, leading us to re-examine this notion in chickens up to 10 weeks of age. Intervertebral discs undergo constant remodeling, then degenerate and undergo tissue clearance, followed …

Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi

Biomedical Engineering Theses & Dissertations

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is …

N6-Methyladenosine Rna Modifications In Myogenesis / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Marina Danielle Infantado

Legacy Theses & Dissertations (2009 - 2024)

Myogenesis involves skeletal muscle stem cells (MuSCs) that produce and regenerate skeletal muscle during regular growth and repair. However, when this system fails to function normally, it can lead to musculoskeletal diseases like Duchenne Muscular Dystrophy (DMD). Therefore, it is important to study the molecular mechanisms behind this developmental process in order to seek therapies and solutions for these types of diseases. Our interest lies in the field of epitranscriptomics, which focuses on post-transcriptional ribonucleic acid (RNA) modifications, particularly N6-methyladenosine (m6A), which involves the addition of a methyl group to the adenosine nucleotide, a process that is mediated by the …

Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham

Legacy Theses & Dissertations (2009 - 2024)

The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …

Gaps In Patient Education On Safe Handling And Disposal Of Oral Chemotherapy Drugs: A Pilot Prospective Cohort Survey Study, Sun Yang, Priya Patel, Alexandra Corcoran, Eric Dobberpuhl, Samantha Isidro, Dustin Le, Analise Klassen, Jay Rho, David Tran, Richard Beuttler, Neda Noori Nassr, Katherine Gruenberg, Siu-Fun Wong

Pharmacy Faculty Articles and Research

Background

Oral anticancer chemotherapy (OC) has been misperceived as being safer than intravenous chemotherapy, leading to its increased risk of improper handling and disposal. This survey study assessed the knowledge, practices and attitudes of pharmacists and patients regarding OC handling and disposal, gaps in knowledge and barriers to patient education. Methods

Surveys were developed based on literature review and pilot study validation results. Patients completed a 33-item paper or electronic survey whereas pharmacists completed a 38-item electronic survey. Descriptive statistics and Fisher’s exact test computed using the R Project were used for analyses. Results

Pharmacist group (16/25, 62.5%) and patient …

College Of Natural Sciences Newsletter, July & August 2022, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 3, Issue 5

Page 1 Dean's Message
Page 2 Awards & Recognition
Page 3 Resources for Student Success
Page 4 Welcome to New Faculty & Staff
Page 5 Summer Activities in CNS
Page 9 Celebrating the lives of those who touched the College
Page 10 Media Coverage of CNS
Page 12 Open PRAIRIE Data
Page 13 Snaps from he start of the semester
Page 14 Science as Art Competition

A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin

Electronic Theses and Dissertations

Computational modeling of metabolic reactions and cellular systems is evolving as a tool for quantitative prediction of metabolic parameters and reaction pathway analysis. In this work, the basics of computational cell biology are presented as well as a summary of physical processes within the cell, and the algorithmic methods used to find time dependent solutions. Protein-protein and enzyme-substrate interactions are mathematically represented via mass action kinetics to construct sets of linear differential equations that describe reaction rates and formation of protein complexes. Using mass action methods, examples of reaction networks and their solutions are presented within the Virtual Cell simulation …

Integrin-Mediated Mechanotransduction Controls Activation Of Yap And Invasive Growth Of Breast Cancer, Xiaobo Wang

Dissertations and Theses (Open Access)

Tumor extracellular matrix (ECM) stiffness is correlated with the aggressiveness of breast cancer. Integrin-mediated adhesion and signaling are crucial for mammary tumorigenesis and tumor progression, in which focal adhesion kinase (FAK) - Src family kinases (SFKs) serves as a hub to relay the mechanical cues from the ECM. We have investigated the mechanisms through which integrin signaling controls mammary tumorigenesis and found that integrin-mediated mechanotransduction controls invasive growth of breast cancer cells in stiff matrices through activation of FAK and YAP. Mechanistic studies revealed that integrin signaling induces - via activation SFKs - tyrosine phosphorylation and inactivation of LATS1 and …

Examining The Expression Patterns Of Desulfotalea Psychrophila Dsrab Operon And Pit At Subfreezing Temperatures And Different Concentrations Of Sulfate Salts As A Model For Mars And Icy Worlds Survival And Colonization, Sergio Luis Mosquera Mora

Graduate Theses and Dissertations

Since ancient times, Humanity has been fascinated with the idea of what lies beyond the borders of our planet. Fortunately, the combined efforts of many nations have made it possible to send unmanned spacecraft to orbit planets located close to Earth. These missions have the principal goal to collect data that could help us understand the basic environmental conditions that persist on those planets, or for evidence of past or present life. Equally important, landers and rovers have been successfully deployed to start the in-situ exploration of many planets of the Solar System. Among them, Mars has been extensively studied …

Characterization Of The Wee1 Homologues And The Investigation Of Factors Promoting Cellular Enlargement In Cryptococcus Neoformans, Rodney J. Colón Reyes

All Dissertations

Cryptococcus neoformans is an opportunistic fungal pathogen, infecting mainly immunocompromised individuals. As the main cause of cryptococcosis, it is responsible for over 180,000 deaths every year. As an environmental yeast, it has unique adaptations that allow it to proliferate in the human host. Among these adaptations its capacity to transition to an extreme phenotype known as Titan cells is of special interest to researchers. With sizes above 10 um and able to reach 70 um or more in cell size. This size is accompanied with a large vacuole, larger polysaccharide capsule, and an increased resistance to fluconazole (FLC). FLC is …