Cell and Developmental Biology Commons^™

Plastics And Their Interactions With Bacterial Biofilms Of Synechococcus Sp. Pcc 7002 And Escherichia Coli Nissle 1917, Jackson Zmich

Open Access Master's Theses

Plastic waste is a leading global pollutant with increasing concerns, as recent studies have shown that these wastes are not only concentrated on a macro scale but on a micro and nano scale. These micro- and nano- sized plastic particles, denoted as MPs and NPs, have been measured in marine and freshwater sources, air, food products, and within biosolids expelled from organisms, including humans. Due to their small size, MNPs are entering organisms through inhalation, ingestion, or dermal absorption. [1] Humans are ingesting MNPs daily, with median rates of approximately 200 ng/capita/day for children and 600 ng/capita/day for adults. [2] …

Effects Of Round-Up On The Environment, Sandra J. Marcu

Journal of Earth and Life Science

Many people around the world have used and still currently use Roundup but are unaware of the effects it has on the environment. Roundup is a spray on application weedkiller that is widely used around the world today both residentially and commercially. It enables its user to grow a garden or a field of crops with a no-tilling approach to eliminate weeds. It is a well-known and popular choice for killing weeds that has been around since the mid 1970’s (Oca, 2017). John Franz, a Monsanto scientist discovered that glyphosate (main ingredient in Roundup) was an herbicide or weedkiller, and …

Environmental Pollution And Early-Life Metabolic Programming, Lisa Koshko

Wayne State University Dissertations

Substantial evidence demonstrates that parental pollutant exposures can induce harmful health effects in the offspring, including the predisposition to Type II Diabetes. As rates of Type II Diabetes continue to rise in younger populations, a crucial gap lies in understanding the role of parental influence in the etiology of later-life metabolic disease. Therefore, the central goal of this work was to determine how early life exposure to smoking level benzene, an endocrine-disrupting air pollutant, affects the metabolic health of offspring, and to identify potential developmental mechanisms involved in disease susceptibility. This goal was achieved using two models of early life …

Examining The Effect Of A High Fat Diet On The Expression Of Adipokines In A Murine Model Of Barrett's Esophagus, Saagar A. Shah

Honors Undergraduate Theses

Chronic acid reflux results in injury to the esophagus and the development of Barrett’s Esophagus (BE). BE elevates the lifetime risk for a patient to develop Esophageal Adenocarcinoma (EAC). Clinically, one of the main risk factors for BE and EAC is obesity, which alters the secretion of inflammatory cytokines by adipocytes, also referred to as adipokines. Conflicting reports have been made to the expression of adipokines and their receptors in the progression to esophageal cancer. Utilizing an inflammation-based mouse model for BE, we hypothesize that alterations in the expression of adipokines and their receptors favor an inflammatory environment associated with …

Dusp8 Gene Expression Is Increased Upon The Stimulation Of Hek293 Cells, Oanh Vo, Lukas Macha

Student Summer Scholars Manuscripts

Dual specificity phosphatase 8 (DUSP8) is one of the phosphatases that oppose the activity of mitogen-activated protein kinases. Previous mouse studies have demonstrated the functional role of DUSP8 in regulating cardiomyocyte growth. However, it is still unclear how the activity of DUSP8 is regulated, and little is known about the regulation of DUSP8 at the gene level. The goal of this study is to determine whether the DUSP8 gene is immediately transcribed upon MAPK activation in the cells. Here, we found that the expression of the DUSP8 gene was significantly increased after stimulation of cells for 30, 60, 90, and …

Impact Of Tgf-Β And Twist1 On Motility And Proliferation In Estradiol-Treated Mcf-7 Tamr Cells In-Vitro, Thomas L. Scott Iii

Honors Undergraduate Theses

Breast cancer is a highly malignant cancer and is known to be grouped into three main types: adenocarcinoma, invasive ductal carcinoma (IDC) and ductal carcinoma. Breast cancer commonly arises as adenocarcinoma, located in the milk ducts, and becomes IDC when it spreads into the surrounding tissue from the influence of cytokines and hormones. This study outlines the rate of proliferation and motility of a type of adenocarcinoma, MCF-7-TamR, to become invasive ductal carcinoma when Twist1 is downregulated and exposed to TGF- and estradiol (E2) in-vitro. We hypothesize that the downregulation of Twist1 will reduce cell adhesion and cytoskeleton proteins …

Molecular Insights Into The Impact Of Bone Marrow Stroma, Cb-6644 Inhibition Of The Ruvbl1/2 Complex, And Cebpβ On Regulating Drug Sensitivity In Multiple Myeloma, Sebastian Adam Dziadowicz

Graduate Theses, Dissertations, and Problem Reports (ETD)

Multiple myeloma (MM), is a hematological cancer originating in plasma cells. Currently multiple myeloma represents a significant clinical challenge due its incurable nature mainly due to inevitable drug resistance. MM is characterized by abnormal plasma cell proliferation within the bone marrow and production of abnormal immunoglobulin resulting in a plethora of physiological abnormalities. Although a rare malignancy, MM accounts for 1% of all cancers and currently has five-year survival rate of around 50%. Utilizing a combination of laboratory experiments and bioinformatics techniques, this dissertation examines multiple layers of MM physiology in the context of regulating drug resistance or sensitivity. First, …

Biomechanics Of The Atherosclerotic Lipidome: (Un)Expected Statin Interactions And Membrane Remodelling, Ethan M. Fong

Pomona Senior Theses

Statins interact with lipid membranes in ways that shape their pharmacokinetics, off-target effects, and pleiotropic actions, yet these interactions' mechanical and biophysical consequences remain poorly understood. This thesis employs a combination of surface plasmon resonance (SPR), quartz crystal microbalance with dissipation monitoring (QCM-D), and rheological modelling to characterize how representative statins intercalate within biomimetic supported lipid bilayers (SLBs) of healthy and diseased composition. SPR reveals that lipophilic statins exhibit higher apparent affinities and slower dissociation kinetics, especially in cholesterol- and anionic lipid-rich membranes. QCM-D analyses demonstrate that statins alter membrane mass, dissipation, and interfacial stiffness in a statin- and membrane-dependent …

Temporal Dynamics Of Programmed Genome Rearrangement In Sea Lamprey Embryogenesis: A Deep Learning & Lightsheet Imaging Approach To Studying Early Developmental Transitions, Kasturi Rajandran

Theses and Dissertations--Biology

Programmed genome rearrangement (PGR) in the sea lamprey (Petromyzon marinus) leads to the elimination of ~0.5Gb (20%) of the germline genome during early embryogenesis, yet its timing relative to the maternal-to-zygotic transition (MZT) remains unclear. In this study, we imaged embryos cleared at 3-hour intervals (up to 72 hours post fertilization (hpf)) using high-resolution lightsheet fluorescence microscopy and a custom deep-learning image-analysis pipeline (~80% accuracy) to quantify nuclei and micronuclei counts. Micronuclei, which are the hallmarks of PGR first appear between 24 to 27hpf (vs ~36hpf previously reported) indicating PGR starts earlier than previously reported in the sea …

The Role Of Metabolic Gate Keepers In Cell Fate Decision Making, Brian Kelly

Theses and Dissertations--Biology

Maintaining cellular energy balance and redox stability is crucial to cell survival, with glutamine metabolism playing a central role. While extensively studied in cancer, where it supports biosynthesis and reduces oxidative stress to promote tumor growth, its function in non-cancerous contexts like tissue development and muscle regeneration remains less understood. A key aspect of stem cell biology is quiescence, a metabolically dormant state that preserves the stem cell pool, yet the mechanisms regulating this state are not fully clear. Here, we identify glutamine metabolism as a critical factor governing myoblast proliferation and quiescence through a metabolic program distinct from that …

Pharmacological Or Genetic Inhibition Of Ltcc Promotes Cardiomyocyte Proliferation Through Inhibition Of Calcineurin Activity, Lynn A. C. Devilée, Abou Bakr M. Salama, Jessica M. Miller, Janice D. Reid, Qinghui Ou, Nourhan M. Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K. Rosengart, Douglas A. Andres, Jonathan Satin, Tamer M. A. Mohamed, James E. Hudson, Riham R. E. Abouleisa

Markey Cancer Center Faculty Publications

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at …

Functional Analysis Of Ligand Binding Domain 2 Of Outer Surface Protein C Of Borreliella Burgdorferi, Gavin Z. Chambers

Theses and Dissertations

Lyme disease, caused by the spirochete Borreliella burgdorferi, is the most common vector-borne infection in North America. A critical determinant of early mammalian infection is outer surface protein C (OspC), a highly variable lipoprotein that is indispensable for spirochete survival but whose precise function remains unresolved. OspC has been proposed to mediate diverse roles, including complement evasion, adhesion, tissue dissemination, and antiphagocytic activity, supporting the view that it is a multifunctional virulence factor. Structural studies have identified two putative ligand-binding domains (LBD1 and LBD2), with LBD2 forming a solvent-exposed crown at the membrane-distal end of the OspC dimer.

To …

Targeting The Achilles’ Heel Of Lung Cancer Induced By Oncogenic P53, Brandon G. Velasco

Theses and Dissertations

Mutations of the tumor suppressor gene, TP53, are the most prevalent oncogenic mutations in lung cancer, occurring in up to 70% of human non-small cell lung cancer (NSCLC). The majority of mutations in p53 are missense mutations that cause not only a loss of tumor suppressor function, but also gain of oncogenic functions, like tumorigenicity, immune suppression, and chemoresistance. Previous studies have shown that the depletion of gain-of-function (GOF) p53 or disruption of its ability to transactivate the expression of genes related to oncogenesis eliminates its tumorigenic properties indicating a dependency of human lung cancer cells expressing GOF p53 …

Unleashing Serine Palmitoyltransferase In Test Tubes And Mice, Matthew W. Peart

Theses and Dissertations

Canonically known both for structural contributions to lipid bilayers and roles in cell signaling, the sphingolipids comprise a dynamic, multifaceted class of molecules which are studied to understand homeostatic cell biology as well as pathophysiology. Sphingolipids contribute to tissue-specific structures such as myelin, a multilayer membrane that allows for rapid conduction of action potentials along neuronal axons. All sphingolipids are downstream products of the rate-limiting and initiating enzyme in the de novo sphingolipid synthesis pathway, Serine palmitoyltransferase (SPT). Demonstrative of its status as the enzyme that catalyzes a crucial step in a biochemical pathway, SPT activity is strictly regulated. This …

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Redirection Of Cancer Cell Fate, Julie Sofie Bjerring, Yara Khodour, Emilee Anne Peterson, Patrick Christian Sachs, Robert David Bruno

School of Medical Diagnostics & Translational Sciences Publications

The mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) by which this alteration occurs has yet to be defined. Here, we test the hypothesis that mitochondrial transfer from normal mammary epithelial cells to breast cancer cells plays a role in this redirection process. We evaluate mitochondrial transfer in 2D and 3D organoids using our unique 3D bioprinting system to produce chimeric organoids containing normal and cancer cells. We demonstrate that breast cancer tumoroid growth is hindered following interaction with mammary epithelial cells …

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

UROP 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 …

Determination Of Structural Factors Contributing To Protection Of Zinc Fingers In Estrogen Receptor Α Through Molecular Dynamic Simulations, Patricia B. Lutz, Wesley R. Coombs, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

The ERα transcription factor that induces tumor growth is a potential target for breast cancer treatment. Each monomer of the ERα DNA-binding domain (ERαDBD) homodimer has two conserved (Cys)₄-type zinc fingers, ZF1 (N-terminal) and ZF2 (C-terminal). Electrophilic agents release Zn²⁺ by oxidizing the coordinating Cys of the more labile ZF2 to inhibit dimerization and DNA binding. Microsecond-length molecular dynamics (MD) simulations show that greater flexibility of ZF2 in the ERαDBD monomer leaves its Cys more solvent accessible and less shielded from electrophilic attack by sulfur-centered hydrogen bonds than ZF1 which is buried in the protein. In the …

Repositioning Antimalarial Drugs As Anticancer Agents: Focus On Tafenoquine, Chris Barton

Funded Scholarship

Due to the expensive and lengthy process of drug design and approval, drug repurposing (or repositioning) has become another option for identifying preexisting molecules that may be used for alternative purposes. Recently, some antimalarial compounds have been shown to display efficacy against cancer cell proliferation. In this study, we provide evidence to suggest that multiple preexisting antimalarial drugs can reduce the viability of human cancer cells in culture. Furthermore, we provide the first evidence that one antimalarial, Tafenoquine (LD50 = 9.6 μM in HCT116 cells), is capable of decreasing viability with an efficacy comparable to Etoposide (LD50 = 15.2 μM …

Comparative Olfactory Anatomy Of Wild And Hatchery-Raised Rainbow Trout (Oncorhynchus Mykiss), Nicole Rahman-Garnier

Cal Poly Humboldt theses and projects

Rainbow trout (Oncorhynchus mykiss) are an ecologically and culturally important salmonid species that exhibits diverse life history strategies, including anadromous and resident freshwater life cycles. Though many studies have examined their olfactory morphology, none have directly compared possible olfactory microstructural differences between wild and hatchery-raised populations. Histology and scanning electron microscopy (SEM) were employed to compare the gross anatomy and ultrastructure of olfactory rosettes in three O. mykiss populations: wild residents from Jacoby Creek (JC), a resident lineage of hatchery fish from Mad River Hatchery (MRH), and an anadromous lineage from the Cal Poly Humboldt (CPH) Hatchery. The …