Cell and Developmental Biology Commons^™

Impact Of Epa And Dha Supplementation And 15-Lox-1 Expression On Colitis And Colitis-Associated Colorectal Cancer, Jonathan Jaoude

Dissertations and Theses (Open Access)

Inflammatory bowel disease (IBD) patients not only suffer from colitis but also from increased morbidity and mortality of colitis-associated colorectal cancer (CAC). The enzyme 15-lipoxygenase-1 (15-LOX-1) is crucial to converting omega-3 fatty acid derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to resolvins, potent anti-inflammatory products. 15-LOX-1 effects on the conversion of EPA and DHA to resolvins that subsequently exert anti-inflammatory and anti-tumorigenic effects have received little attention. To address this knowledge gap, we hypothesize that 15-LOX-1 expression in colonic epithelial cells is essential for resolvin biosynthesis from EPA and DHA to modulate immunophenotype, limit inflammation, promote resolution, and help …

Exosomal Communication By Metastatic Osteosarcoma Cells Modulates Alveolar Macrophages To An M2 Tumor-Promoting Phenotype And Inhibits Tumoricidal Functions, Kerri Wolf

Dissertations and Theses (Open Access)

Osteosarcoma metastasizes to the lung, and there is a link between the predominance of tumor promoting immunosuppressive M2 macrophages in the metastases and poor patient survival. By contrast, M1macrophage predominance correlates with longer survival. M2 macrophages can be induced by various stimuli in the tumor microenvironment, including exosomes, which are 40- to 150-nm vesicles that are involved in intercellular communication and contribute to tumor progression and immune evasion. Recognizing that tumor cells can influence the tumor microenvironment to make it more permissive and because of the link between M2 dominance and curtailed patient survival, we evaluated the effect of …

Understanding Intercellular Signaling During Lung Injury-Repair, Margo Patricia Cain

Dissertations and Theses (Open Access)

The mammalian lung is a complex system of specialized cell types with precise spatial organization designed to cooperate to perform gas exchange. These cell types together coordinate organ development, homeostasis, and repair after injury through signals either presented or secreted, known as ligands, to be received by receptors on the surface of another, or in some cases, the same cell. The alveolar region of the lung, the primary region of gas exchange, responds to various types of injuries with different lung repair mechanisms. In order to explore how the various cell types in the lung communicate to drive tissue repair …

Mitochondrial Deletions And Their Disease-Causing Effects, Austin Bell

Biological Sciences Undergraduate Honors Theses

The mitochondria perform a plethora of important functions within the cell, with one of the most paramount being ATP production. Deregulation of its function can have dire consequences on cellular functions. Mutations such as deletions within the mitochondrial DNA (mtDNA) can cause disease within the patients affected. These diseases often affect children, causing symptoms such as gradual loss of eyesight and hearing, diabetes, and other problems that lower the quality of life. The mitochondria are also very dynamic organelles that undergo rounds of fission and fusion to keep up with the metabolic needs of cells, necessitating a homeostatic balance between …

Characterizing Erad And Antioxidant Response In Ixodes Scapularis Ise6 Cells During Borrelia Infection, Latoyia Downs

Master's Theses

Ticks are hematophagous ectoparasites that transmit a multitude of diseases to humans. Borrelia burgdorferi (BB) and Borrelia miyamotoi (BM) are both tick-borne pathogens that cause disease in humans and are transmitted by the black-legged tick (Ixodes scapularis). A byproduct of blood digestion generates reactive oxygen species that are toxic and cause oxidative stress which promotes cellular damage and dysfunction. The endoplasmic reticulum (ER) is especially affected by oxidative stress, resulting in a buildup of improperly folded proteins in the ER lumen called ER stress. To prevent cellular damage, the tick utilizes an antioxidant system to neutralize ROS and mechanisms …

Sensing Ribonuclease H Activity With Dna Nanoswitches, Ruju Trivedi

Biological Sciences

Ribonuclease H (RNase H) is a damage-repair protein and ribonuclease that specifically catalyzes the hydrolysis of RNA in an RNA/DNA duplex and breaks down RNA/DNA junctions. It plays an important role in a variety of biological processes including DNA replication, DNA repair, and transcription. It is also pivotal in anti-HIV drug development and the analysis of cellular processes and has been shown to be a potential therapeutic target for various neoplastic diseases. This thesis discusses a unique assay based on DNA nanoswitches to detect RNase H levels and activity. The assay is based on conformational changes of DNA nanoswitches in …

Glutamine Antagonist 6-Diazo-5-Oxo-L-Norleucine, A Hyaluronan Synthesis Inhibitor, Slows Triple Negative Breast Cancer Growth, Le Gia Cat Pham

Biological Sciences

Triple-negative breast cancers (TNBC) are the most aggressive subtype of breast cancer with few treatment options and poor outcomes. TNBCs are characterized by elevations in hexosamine biosynthetic pathway (HBP) enzyme expression, hyaluronan synthase 2 (HAS2) expression and hyaluronan (HA) production. Glutamine is an important substrate for HA production via the HBP. 6-diazo-5-oxo-L-norleucine (DON) is a well-known glutamine antagonist with validated antitumoral efficacy. This project examined the effects of DON on HA production and energy metabolism in TNBC cells. We examined the effect of DON treatment on Hs578T cells, which represent the mesenchymal stem-like subtype of TNBC. We specifically analyzed the …

Photoactivatable Cre Recombinase 3.0 For In Vivo Mouse Applications, Kumi Morikawa, Kazuhiro Furuhashi, Carmen De Sena-Tomas, Alvaro L. Garcia-Garcia, Ramsey Bekdash, Alison D. Klein, Nicholas Gallerani, Hannah E. Yamamoto, Seon Hye E. Park, Grant S. Collins, Fuun Kawano, Moritoshi Sato, Chyuan Sheng Lin, Kimara L. Targoff, Edmund Au, Michael C. Salling, Masayuki Yazawa

School of Medicine Faculty Publications

Optogenetic genome engineering tools enable spatiotemporal control of gene expression and provide new insight into biological function. Here, we report the new version of genetically encoded photoactivatable (PA) Cre recombinase, PA-Cre 3.0. To improve PA-Cre technology, we compare light-dimerization tools and optimize for mammalian expression using a CAG promoter, Magnets, and 2A self-cleaving peptide. To prevent background recombination caused by the high sequence similarity in the dimerization domains, we modify the codons for mouse gene targeting and viral production. Overall, these modifications significantly reduce dark leak activity and improve blue-light induction developing our new version, PA-Cre 3.0. As a resource, …

Preliminary Study: Leucine Supplementation Exacerbates Muscle Wasting Independent Of The Ubiquitin-Proteasome System, Katarina Bejarano

Graduate Theses and Dissertations

Cancer cachexia is the rapid, drastic loss of muscle mass associated with cancer and is not reversible by conventional nutritional means (Brown et al., 2018; Brown et al., 2017). It occurs in ~80% of cancer patients and is responsible for 20-40% of cancer-related deaths (Brown et al., 2018; Brown et al., 2017). This condition leaves patients with fatigue, functional impairment, reduced quality of life, and a decrease in survival rates. Cachexia occurs through an imbalance between protein degradation and protein synthesis (Brown et al., 2018), which is associated with inflammation and altered metabolic processes.

Several studies have investigated the effects …

Nutritional Supplementation And Skeletal Muscle Health In Chronic Diseases, Hexirui Wu

Graduate Theses and Dissertations

Prevalence of chronic diseases in the United States keeps increasing in recent years. There are approximately four in ten adults having chronic diseases in America. Chronic diseases include obesity, aging, heart diseases, cancer and many others. This thesis mainly focuses on obesity and aging. Skeletal muscle performance is impaired in obesity and aging conditions. One common reason causing this could be higher fat mass and lower muscle mass. However, there is no study showing what pathways are involved in the imbalance of body composition. Therefore, the first objective of the thesis is to determine gene expression of selected pathways in …

Inhibition Of The Spectraplakin Protein Microtubule Actin Crosslinking Factor 1 Sensitizes Glioblastomas To Radiation, Kala Bonner, Danielle Borlay, Orica Kutten, Quincy A. Quick

Biology Faculty Research

Background

Microtubule actin crosslinking factor 1 (MACF1) is a spectraplakin cytoskeletal crosslinking protein whose function and role in cancer biology has lacked investigation. Recent studies have identified MACF1 as a novel target in glioblastomas expressed in tissue from tumor patient explants but not normal brain tissue and when silenced has an antitumorigenic impact on these tumors. Radiation as a single agent therapy to treat glioblastomas has been used for decades and has done little to improve survival of individuals diagnosed with this disease. However, contemporary clinical radiotherapy protocols have provided evidence that combinatorial radiotherapy approaches confer a therapeutic benefit in …

An Analysis Of Crispr-Cas Gene Editing In Agriculture, Ashley Laliberte

Honors Scholar Theses

The CRISPR-Cas system is a promising form of gene editing, especially for the agriculture industry. The ability to make single-nucleotide edits within a gene of interest, without the need to introduce foreign DNA, is a powerful tool for designing healthier and more efficient crops and food animals. This system provides opportunity for increased nutritional value, decreased food waste, and more economically and environmentally sustainable food production. Though this biotechnology is facing mechanistic limitations due to off-target effects and inefficient homology-directed repair, vast improvements have already been made to improve its efficacy. The CRISPR-Cas system is already the most advanced form …

Otx2 Represses Sister Cell Fate Choices In The Developing Retina To Promote Photoreceptor Specification, Miruna Georgiana Ghinia Tegla, Diego F. Buenaventura, Diana Y. Kim, Cassandra Thakurdin, Kevin C. Gonzalez, Mark M. Emerson

Publications and Research

During vertebrate retinal development, subsets of progenitor cells generate progeny in a non-stochastic manner, suggesting that these decisions are tightly regulated. However, the gene-regulatory network components that are functionally important in these progenitor cells are largely unknown. Here we identify a functional role for the OTX2 transcription factor in this process. CRISPR/Cas9 gene editing was used to produce somatic mutations of OTX2 in the chick retina and identified similar phenotypes to those observed in human patients. Single cell RNA sequencing was used to determine the functional consequences OTX2 gene editing on the population of cells derived from OTX2-expressing retinal progenitor …

Cd11b+ Depletion Of Bone Marrow Derived Macrophages Negatively Affects Bone Fracture Healing, Sarah Hozain

Seton Hall University Dissertations and Theses (ETDs)

Hematoma formation and inflammation occurs during the beginning stages of fracture repair, which require the presence of innate cells such as macrophages. Macrophages are subdivided into proinflammatory, M1, or anti-inflammatory, M2, phenotypes with different functions, cytokine profiles, and surface markers. In this study, in vitro and in vivo models were used to deplete M1 macrophages, using Mac-1 Sap conjugated antibody (Mac1SAP), to determine the effects on fracture healing. In vitro study, primary macrophages isolated from mice femoral bone marrow were harvested and differentiated into M1 macrophages (+LPS), M2 macrophages (+IL-4), or undifferentiated then treated with either vehicle or 10pM Mac1SAP. …

Exploring Occupational Disruption In Newly Diagnosed Individuals With Cancer With Minor (Dependent) Children, Riley S. Harrold

Student Capstone Papers

Background: According to the American Cancer Society (2019), there were more than 1.7 million new cases of cancer in 2019 alone. Individuals are being diagnosed at a young age with 22.4% of cases occurring in individuals 22-55 years old and whom are childrearing age (Shah et al., 2017). There are an estimated 2.85 million children under the age of 18 who are living with a parent who has cancer (Shah et al., 2017). Newly diagnosed individuals face changes in daily life, the threat of possible death, and fear of dying (Compas et al., 1994). Changes in shared family roles …

Comparative Study Of The Effects Of Light On Photophore Ultrastructure From Two Families Of Deep-Sea Decapod Crustaceans: Oplophoridae And Sergestidae, Jamie E. Sickles

HCNSO Student Theses and Dissertations

Counterillumination, the mechanism by which pelagic species produce bioluminescence to replace the light blocked by their bodies to hide their silhouettes, has been known for over 100 years. However, little is known about how these animals are able to so precisely replicate the intensity of downwelling light. The recent discovery of opsins in photophores (Bracken-Grissom et al. 2020) suggests that these autogenic organs (i.e. non-bacterial) may be sensitive to light, in addition to their function of emitting visible light. The study presented here is 1) the first ultrastructural assessment of photophores in species Systellaspis debilis, Janicella spinicauda, Parasergestes armatus, …

Profiling Of Small Non-Coding Rna In Bovine Somatic Cell Nuclear Transfer Embryos During Early Development Through The Maternal-To-Embryonic Transition, Abby D. Benninghoff, Jocelyn Cuthbert

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Supplementary File 1. Read lengths and annotation summaries of sncRNA: Microsoft Excel document with information from small RNA sequencing on the aligned, annotated reads.

Supplementary File 2. Normalized and variance-stabilized values for annotated sncRNAs: Microsoft Excel document with normalized and variance-stabilized reads generated by RNA sequencing of small non-coding RNA from cattle embryos.

Supplementary File 3. Results of DESeq2 analyses for miRNAs, tRNA fragments and piRNAs: Microsoft Excel document with results of DESeq2 differential expression analysis comparing scNT vs IVF embryos at each developmental stage and sequential comparisons of developmental stage for both IVF and scNT embryos.

Supplementary File 4. …

Mapping Transcriptional Changes Associated With The Maternal-To-Embryonic Transition In Bovine Embryos To Small Non-Coding Rna Profiles In Both In Vitro-Fertilized And Scnt Cattle Embryos, Abby D. Benninghoff, Jocelyn Cuthbert

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Supplementary File 1. Normalized reads for annotated mRNA transcripts. Microsoft Excel document providing normalized sequencing reads per sample.

Supplementary File 2. Results of DESeq2 analyses for annotated mRNAs. Microsoft Excel document with results of DESeq2 differential expression analysis comparing scNT vs IVF embryos at each developmental stage and sequential comparisons of developmental stage for both IVF and scNT embryos.

Supplementary File 3. Results of Metascape ontology analyses for differentially expressed mRNAs. Microsoft Excel document with results of Metascape ontology analyses for biological processes associated with predicted mRNA targets of differentially expressed miRNAs.

Supplementary File 4. Cytoscape networks for differentially expressed …

365— Clobetasol-Induced Quiescence In The Vulvar Carcinoma Cell Line Umscv-4 Can Be Overcome By Repeated Removal And Re-Exposure To This Ultrapotent Corticosteroid, Nolberto Jaramillo Jr., Nina Mustico

GREAT Day Posters

Vulvar cancer is rare, mostly afflicting women aged 60 and older. The cancer is often preceded by a common vulvar rash, Lichen sclerosis, that is usually treated with the ultra-potent corticosteroid, clobetasol propionate. This treatment may, in turn, be associated with vulvar carcinogenesis. Quiescence, a common characteristic of stem cells, is a reversible state of growth arrest. Our results suggest that clobetasol is causing UMSCV-4 vulvar carcinoma cells to enter quiescence, and may allow them to evade the standard treatments that target rapidly proliferating populations. Furthermore, when these cells are removed from clobetasol and re-exposed, they proliferate at higher levels. …

147— The Effect Of A Histone Deacetylase Inhibitor On Pd-L1, Hla-Abc, Hla-E, And Hla-G On Human Breast Cancer Cell Lines, Nikhil Reddy, Alec Toufexis

GREAT Day Posters

Increased expression of human leukocyte antigen (HLA) allows tumor cells to be more easily detected by the immune system. In previous research, epigenetic modifiers including the histone deacetylase inhibitor 3 (HDAC3), RGFP966, has been shown to decrease PD-L1 expression. PD-L1 expression inhibits T cell cytotoxicity, and decreasing it can enhance the immune response. We hope to elucidate whether or not HLA-ABC expression similarly decreases upon exposure to the HDAC3 inhibitor which would be detrimental to immune detection. Two breast cancer cell lines that express HLA-ABC are MCF-7 and MDA-MB-231. Our initial results show that HLA-ABC is expressed on the MDA-MB-231 …