Cell and Developmental Biology Commons^™

Evaluation Of Bioactive Properties Of Lipophilic Fractions Of Edible And Non-Edible Parts Of Nasturtium Officinale (Watercress) In A Model Of Human Malignant Melanoma Cells, Sotiris Kyriakou, Venetia Tragkola, Heba Alghol, Ioannis Anestopoulos, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Watercress is an enriched source of phenethyl isothiocyanate (PEITC), among other phytochemicals, with an antioxidant capacity. The aim of this study was to (i) chemically characterize and (ii) biologically evaluate the profile of the main health-promoting compounds contained in edible (i.e., mixture of leaves and lateral buds) and non-edible (i.e., stems) parts of watercress in an in vitro model of malignant melanoma consisting of human malignant melanoma (A375), non-melanoma (A431) and keratinocyte (HaCaT) cells. The extraction of the main constituents of watercress was performed by subjecting the freeze-dried edible and non-edible samples through different extraction protocols, whereas their concentration was …

A Muscle Cell-Macrophage Axis Involving Matrix Metalloproteinase 14 Facilitates Extracellular Matrix Remodeling With Mechanical Loading, Bailey D. Peck, Kevin A. Murach, R. Grace Walton, Alexander J. Simmons, Douglas E. Long, Kate Kosmac, Cory M. Dungan, Philip A. Kern, Marcas M. Bamman, Charlotte A. Peterson

Center for Muscle Biology Faculty Publications

The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. For successful adaptation to mechanical loading, remodeling processes must occur. In a large cohort of older adults, transcriptomics revealed that genes involved in ECM remodeling, including matrix metalloproteinase 14 (MMP14), were the most upregulated following 14 weeks of progressive resistance exercise training (PRT). Using single-cell RNA-seq, we identified macrophages as a source of Mmp14 in muscle following a hypertrophic exercise stimulus in mice. In vitro contractile activity in myotubes revealed that the gene encoding cytokine leukemia inhibitory factor ( …

Prenatal Exposure To Maternal Psychological Distress And Telomere Length In Childhood, Stephanie A. Stout-Oswald, Laura M. Glynn, Marco Bisoffi, Catherine H. Demers, Elysia Poggi Davis

Psychology Faculty Articles and Research

Telomere length (TL) is a biological marker of cellular aging, and shorter TL in adulthood is associated with increased morbidity and mortality risk. It is likely that these differences in TL are established long before adulthood, and there is growing evidence that TL can reflect prenatal experiences. Although maternal prenatal distress predicts newborn TL, it is unknown whether the relation between prenatal exposure to maternal distress and child TL persists through childhood. The purpose of the current longitudinal, prospective study is to examine the relation between prenatal exposure to maternal distress (perceived stress, depressive symptoms, pregnancy-related anxiety) and TL in …

Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara

Articles

Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …

Harnessing Mycobacterium Bovis Bcg Trained Immunity To Control Human And Bovine Babesiosis, Reginaldo G. Bastos, Heba F. Alzan, Vignesh A. Rathinasamy, Brian M. Cooke, Odir A. Dellagostin, Raul G. Barletta, Carlos E. Suarez

School of Veterinary and Biomedical Sciences: Faculty Publications

Babesiosis is a disease caused by tickborne hemoprotozoan apicomplexan parasites of the genus Babesia that negatively impacts public health and food security worldwide. Development of effective and sustainable vaccines against babesiosis is currently hindered in part by the absence of definitive host correlates of protection. Despite that, studies in Babesia microti and Babesia bovis, major causative agents of human and bovine babesiosis, respectively, suggest that early activation of innate immune responses is crucial for vertebrates to survive acute infection. Trained immunity (TI) is defined as the development of memory in vertebrate innate immune cells, allowing more efficient responses to subsequent …

Bovine Respiratory Microbiota Of Feedlot Cattle And Its Association With Disease, Jianmin Chai, Sarah F. Capik, Beth Kegley, John T. Richeson, Jeremy G. Powell, Jiangchao Zhao

Animal Science Faculty Publications and Presentations

Bovine respiratory disease (BRD), as one of the most common and costly diseases in the beef cattle industry, has significant adverse impacts on global food security and the economic stability of the industry. The bovine respiratory microbiome is strongly associated with health and disease and may provide insights for alternative therapy when treating BRD. The niche-specific microbiome communities that colonize the inter-surface of the upper and the lower respiratory tract consist of a dynamic and complex ecological system. The correlation between the disequilibrium in the respiratory ecosystem and BRD has become a hot research topic. Hence, we summarize the pathogenesis …

Plasma Induced Reactive Oxygen Species-Dependent Cytotoxicity In Glioblastoma 3d Tumourspheres, Janith Wanigasekara, Carlos Barcia, Patrick J. Cullen, Brijesh Tiwari, James F. Curtin

Articles

The aim of this study was to determine the effects of a pin‐to‐plate cold atmospheric plasma (CAP) on U‐251 MG three‐dimensional (3D) glioblastoma spheroids under different conditions. 3D tumorspheres showed higher resistance to the CAP treatment compared to 2D monolayer cells. A single CAP treatment was able to induce cytotoxicity, while multiple CAP treatments augmented this effect. CAP was also able to induce cytotoxicity throughout the tumoursphere, and we identified that reactive oxygen species(ROS) plays a major role, while H2O2plays a partial role in CAP‐induced cytotoxicity in tumour-spheres. We conclude that ROS‐dependent cytotoxicity is induced uniformly throughout glioblastoma and epidermoid …

Upregulation Of Cd36, A Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis By Increasing Mmp28 And Decreasing E-Cadherin Expression, James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Yekaterina Y. Zaytseva

Surgery Faculty Publications

Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation …

Clinical Performance Of The Xpert® Ct/Ng Test For Detection Of Chlamydia Trachomatis And Neisseria Gonorrhoeae: A Multicenter Evaluation In Chinese Urban Hospitals, Fred C. Tenover, Yan Han, Mei-Qin Shi, Qing-Ping Jiang, Wen-Jing Le, Xiao-Lin Qin, Han-Zhen Xiong, He-Ping Zheng, Yi-Wei Tang, Yue-Ping Yin

Biology Faculty Publications

Background: We aimed to evaluate the clinical performance of the GeneXpert® (Xpert) CT/NG assay for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using urine and cervical swabs collected from patients in China.

Methods: This study was conducted from September 2016 to September 2018 in three Chinese urban hospitals. The results from the Xpert CT/NG test were compared to those from the Roche cobas® 4800 CT/NG test. Discordant results were confirmed by DNA sequence analysis.

Results: In this study, 619 first void urine (FVU) specimens and 1,042 cervical swab specimens were included in the final dataset. There were …

Repressive Interactions Between Transcription Factors Separate Different Embryonic Ectodermal Domains., Steven L. Klein, Andre L P Tavares, Meredith Peterson, Charles H Sullivan, Sally A. Moody

Anatomy and Regenerative Biology Faculty Publications

The embryonic ectoderm is composed of four domains: neural plate, neural crest, pre-placodal region (PPR) and epidermis. Their formation is initiated during early gastrulation by dorsal-ventral and anterior-posterior gradients of signaling factors that first divide the embryonic ectoderm into neural and non-neural domains. Next, the neural crest and PPR domains arise, either

Evaluation Of Cell-Matrix Interactions In K14+ Leader Cells On Caf-Modulated Matrix, Trey P. Redman, Jessanne Y. Lichtenberg, Priscilla Y. Hwang

Summer REU Program

No abstract provided.

Predicting Gene Function Of Unknown Yeast Orfs Through Phylogenetic Comparative Analysis, Lewis Barr

Graduate Research Showcase

Yeast (Saccharomyces cerevisiae) has been an instrumental model system for an extraordinary diverse array of research applications for over a century now. The S. cerevisiae genome was fully sequenced in 1996, and, as a result, 6,753 potential proteins were identified. These putative proteins were established by investigating likely open reading frames within the genome. Over the past few decades, nearly 5,000 open reading frames (ORFs) and their expressed proteins have been described, and the remaining undefined open reading frames are labeled as open reading frames of unknown function (ORFans). To better understand the remaining gaps within the S. …

The Role Of Ehd2 In Endothelial Cells, Rachael Judson

Electronic Theses and Dissertations

The role of EHD2 in terms of Cav1 interaction had not been previously characterized and was the main goal of this research. Cav1 has been shown to lead to the ubiquitination of Rac1. Because of this, the role of EHD2 in Rac1 regulation was investigated. An increase in long-term migration in endothelial cells was observed and suggested that EHD2 impacts the RhoA pathway instead of the Rac1 pathway. This lead to the hypothesis that EHD2 controls a part of the RhoA pathway. This hypothesis is supported by the loss of filamentous actin and an increase in serrated junctions in cells …

Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph

Electronic Theses and Dissertations

The aberrant fibrous, extracellular, and intracellular proteinaceous deposits in cells, organs and tissues are referred to as amyloids. These deposits are dominated by β-sheet structures that have been implicated in several neurodegenerative diseases and cancer. In this work, the types of amyloidosis studied include Parkinson’s disease (PD) using UA196 and NL5901 strains of Caenorhabditis elegans (C. elegans), Alzheimer’s disease (AD) using GMC101 strain of C. elegans, and cancer-associated mutant p53 aggregation in MIA PaCa-2 mutant cells. Several molecules including SK-129, NS132, NS163, bexarotene, a polyphenol (-)-epi-gallocatechine gallate (EGCG), ADH40, RD148, and RD242 were screened in vitro and in …

Extracellular Vesicles And Lipid Flippase Regulators In C. Elegans, Lauren Pitts

Electronic Theses and Dissertations

Extracellular vesicles (EVs) are membrane derived organelles released by all cell types and carry a vast array of cargos that can influence communication, development, and disease. One type of EV, known as microvesicles, form by budding directly from the plasma membrane in a process known as ectocytosis, however the mechanisms that govern this process are poorly understood. In C. elegans, the P4-ATPase, TAT-5, along with its activator, PAD-1, inhibit EV release from the plasma membrane by inhibiting phosphatidylethanolamine (PE) exposure on the outer leaflet of the plasma membrane. We identified 3 key domains of PAD-1 that are required to inhibit …

The Pathophysiological Mechanisms Of Alzheimer's Disease; Investigating Therapeutic Interventions For Disease Onset, Alexandra A. Sandberg

Electronic Theses and Dissertations

Alzheimer’s Disease is a multifarious disease that progressively affects more people as both the proportion of older adults in the population and life expectancy increase in both the United States and worldwide. This devastating disease is a result of rampant neuronal loss in the memory centers of the brain that robs the independence of those who are diagnosed and places a heavy burden on those who care for them. Traditionally speaking, research has focused on the hallmark pathology of amyloid plaques, targeting them to try and prevent disease onset. However, countless failures in clinical trials aimed at this said pathology …

Mutations Linked To Rare Diseases Can Be Generated And Tested In Zebrafish, Brianna Jansen, Luke Schipper, Valeria Lacroix, Amy Wilstermann, Rachael Baker

Summer Research

• BCS1L is important for cellular respiration and located in the mitochondria.
• Mutations in BCS1L cause a wide variety of symptoms leading to 3 rare diseases.

Preferential Infection Of Ccr6+ Cd4+ T Cells By Hiv Is Increased By Human Intestinal Endothelial Cells, Fisher Pham, Jessica Eddy, Nathan Dapprich, Anding Shen

Summer Research

Th17 cells are found to be heavily depleted in the gut of HIV patients. Even after successful antiretroviral therapy, HIV patients exhibit a smaller Th17 population for years after treatment. Previous research has found human intestinal endothelial cells (IEC) to increase HIV infection of helper T cells. Using CCR6 as a marker for Th17, we investigated the effect of IEC on HIV infection of Th17 cells. IECs were found to increase the preferential infection of resting and activated CCR6+ cells. Th17 cells are known to be more susceptible to HIV infection than other types of CD4+ T cells. IEC stimulation …

Antioxidant Biomarkers And Nutraceutical Therapeutics In Neurodegeneration And Neurotrauma, Lilia A. Koza

Electronic Theses and Dissertations

Mild traumatic brain injury (mTBI), yielding a Glascow Coma Scale of 13-15, is the most commonly occurring severity of TBI. Pathology from mTBI consists of blood brain barrier disruption, neuroinflammation, oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal degeneration, and resulting neuronal death. These processes deplete the body’s endogenous antioxidant system. We report a retrospective analysis of antioxidant blood biomarkers in patients with a history of mTBI from a local sports medicine clinic, Resilience Code. We found persistent sex-specific antioxidant depletions in mTBI patients associated with worsened symptomology.

Certain populations, such as athletes, are at high risk for repetitive mTBI …

Organellar Zn2+ Homeostasis And The Role Of Trpml Channels In Neuronal Lysosome Physiology And Axonal Transport, Taylor Franklin Minckley

Electronic Theses and Dissertations

Zinc (Zn²⁺) is crucial for proper cellular function, and as such it is important to measure and track Zn²⁺ dynamics in living cells. Fluorescent sensors have been used to estimate Zn²⁺ content of subcellular compartments, but little is known about endolysosomal Zn2+ homeostasis. Similarly, although numerous sensors have been reported, it is unclear whether and how Zn²⁺ can be released from intracellular compartments into the cytosol due to a lack of probes that can detect physiological dynamics of cytosolic Zn²⁺. My dissertation started with comparing and characterizing different Zn²⁺ sensors including the …

The Effects Of Neuronal Growth Factors On Lps-Activated Schwann Cells, Caitlyn E. Henry, Peyton Kimmel, Angela Asirvatham Ph.D.

Student Research Poster Presentations 2022

Schwann cells (SCs) are the principal support cells of neurons in the peripheral nervous system, that both myelinate axons for the rapid conduction of electrical impulses as well as assist in axonal repair during nerve injury. During nerve injury, SCs secrete tumor necrosis factor alpha (TNF-α)^1,5,6 and other proinflammatory mediators^1,6, attracting macrophages to the site of injury to induce inflammation and clear myelin debris.^1,6 Once the debris is cleared, the neuron stimulates SC proliferation by secreting neuronal mitogens, such as heregulin^3,4, and an unknown factor that activates the cAMP pathway³, an important …

Simulation Of An Inflammatory Model Using Schwann Cells, Caitlyn Henry, Peyton Kimmel, Angela Asirvatham

Student Research Poster Presentations 2022

During peripheral nerve injury, the myelin surrounding the neuronal axons is damaged, initiating an inflammatory response to remove myelin debris. Once myelin debris is cleared, Schwann cells acquire a proliferating phenotype which allows them to grow and divide so that remyelination can occur. The neuron stimulates Schwann cell division by secreting growth factors, like heregulin, and an unknown growth factor that activates the cAMP pathway. Although the role of cAMP in axonal regeneration is well-known, not much has been explored about its function in Schwann cells during nerve injury and inflammation. To simulate an inflammatory environment, the S16 Schwann cell …

Generalizing Frameworks For Sentience Beyond Natural Species, Michael Levin

Animal Sentience

Crump et al. (2022) offer a well-argued example of an essential development: a rigorous framework for assessing sentience from the perspective of moral concern over an agent’s welfare. Current and forthcoming developments in bioengineering, synthetic morphology, artificial intelligence, biorobotics, and exobiology necessitate an expansion and generalization of this effort. Verbal reports (the Turing Test) and homology to human brains are utterly inadequate criteria for assessing the status of novel, unconventional agents that offer no familiar touchstone of phylogeny or anatomy. We must develop principled approaches to evaluating the sentience of (and thus, our responsibility to) beings of unfamiliar provenance and …

A Novel Chelator For Pb-212/Bi-212-Based Alpha-Particle Radiotherapy For Cancers, Eric Doorn, Mengshi Li, Brianna Cagle, Nicholas Baumhover, Zhiming Dai, Dijie Liu, Ivy Vance, Frances Johnson, Michael K. Schultz

Summer Research

Lead-212 ( 212Pb) has been identified as a promising candidate for alpha(α)- particle radiotherapies for cancers in preclinical and clinical studies. Using a low molecular weight peptide, the radiotherapy will target with high affinity selective markers highly expressed in cancer cells but found in low concentration in healthy tissue. A radiometal is coupled to a chelator moiety linked to the peptide to deliver the α-particle radiation destroying cancer cells.

To develop a novel Pb specific chelator (PSC) that will provide high affinity to Pb212 and improve the in vitro and in vivo binding pharmacokinetics and stability of progeny of the …

Exploring The Role Of Ahr Activation In Bladder Cancer Models, Hyeon Jin Kim, Peter Jones, Josh Jang, Justin Kulchycki

Summer Research

Immune checkpoint inhibitor therapy was designed to reinvigorate immune cells to bind and kill cancer cells. However, the treatment that was intended to help patients resulted in hyper progressive disease (when the tumor shows accelerated growth, leading to an explosion of tumor growth in a short period of time). We searched for a particular gene that could function as a biomarker for hyperprogression. Upon inspecting tumor samples, we discovered a biomarker called CYP1A1. We thought to test if a tumor that expressed high levels of endogenous CYP1A1, treated with immunotherapy, ultimately led to hyper progression. Every step of the project …

Targeting Histone Reader Enl With Protac Degrader, Josiah Harsh, Zhaoyu Xue, Fan Xuan, Xiaobing Shi, Hong Wen

Summer Research

ENL is a histone reader that is part of the super elongation complex and is primarily involved in chromatin and gene expression regulation. ENL has also been found to play an essential role in the progression of a spectrum of acute myeloid leukemia (AML). Some hotspot mutations of its reader module, the YEATS domain, have been found to be oncogenic. For this reason, we explored the efficacy of a newly developed ENL PROTAC degrader in its ability to degrade wild-type and mutant ENL protein and suppress oncogene expression in cancer cells.

The Role Of Integrins In Hiv-1 Infection Of Intestinal Endothelial Cell Stimulated Resting Cd4+ T Cells, Jessica Eddy, Fisher Pham, Nathan Dapprich, Anding Shen

Summer Research

A major barrier to eradicating HIV is latent reservoirs in resting CD4+ T cells. Antiretroviral therapy is effective in bringing the viral load down to undetectable levels but is unable to eradicate the latent reservoir. Previous data from our lab revealed that when stimulated by intestinal endothelial cells (IEC), resting CD4+ T cells can be directly infected while remaining in a resting state, allowing formation of latent reservoirs. An additional study found that integrins, which are cell surface molecules, play a role in the interactions between endothelial cells (EC) and T cells. Our research further examines the role of integrins …

A Tale Of Two Toxicants: How Trichloroethylene (Tce) And Perchloroethylene (Pce) Metabolites Affect Immune Cell Viability Upon Co-Exposure With Lipopolysaccharide (Lps), Eleanor Scheeres, Sean Harris, Erica Boldenow

Summer Research

• TCE and PCE are volatile organic solvents used in industrial processes, such as metal degreasing and dry cleaning, and known human carcinogens.
• GBS is a common bacteria in the vaginal flora but can lead to complications such as preterm birth during pregnancy.
• Lipopolysaccharide (LPS) is a gram-negative bacterial cell wall component that induces inflammatory immune responses and is used as an infection model.
• Co-treatment (GBS+DCVC) in placental membranes lead to inhibition of pathogen stimulated cytokine secretion (Fig. 1).
• We hypothesized that DCVC and TCVC (PCE’s metabolite) would produce decreased cell viability, and DCVC+LPS would produce further immune inhibitory effects, which …

Er-Golgi In Membrane Repair In Cardiomyocytes, Visakuo Tsurho, Hsin-Yu Chen, Daniel Michele

Summer Research

Impaired membrane repair leads to muscular dystrophies like Miyoshi Myopathy and LGMD2B1. The mechanism behind membrane repair is not well understood, and there are few studies on membrane repair in cardiomyocytes. Research in nonmuscle cells suggest that lysosomes are a source of membranes for repairing injuries2. Few lysosomes were found in cardiomyocytes compared to non cardiomyocytes. Therefore, we investigated the ER and Golgi as potential organelles involved in membrane repair in cardiomyocytes. We used Sec22b to investigate ER to Golgi in membrane repair in cardiomyocytes because it is an ER-Golgi protein involved in membrane fusion and Golgi vesicle trafficking in …

Characterization Of Cofilin And Its Potential Role In The Epha4 Pathway, Brian Donald Condron

Master's Theses and Doctoral Dissertations

EphA4 is a receptor tyrosine kinase that is responsible for cellular adhesion and locomotion using repulsion signaling in early development of Xenopus laevis. EphA4 regulates cellular locomotion by controlling proteins within its signal transduction pathway, which may include the protein cofilin. Cofilin actively severs and removes actin monomers, thus altering the actin cytoskeleton, leading to the cessation of cellular crawl. During the gastrulation phase of embryonic development, individual cells are relocating to create the three primary germ layers of the organism. Failure of this process to occur results in attrition of the embryos, frequently by way of embryonic exogastrulation. …