Laboratory and Basic Science Research Commons^™

Transcription Factor Binding And Discovery Of Novel Gene In The Opportunistic Human Pathogen, Pseudomonas Aeruginosa, Alaina Westee

Symposium of Student Scholars

Pseudomonas aeruginosa (PA) is a gram-negative, ubiquitously-found bacterium that primarily causes nosocomial, or hospital-borne, infections within immunocompromised patients. Therefore, it has been deemed a critical priority pathogen by the World Health Organization (WHO) and the Center for Disease Control (CDC), generating a need for research on its fundamental biology. The Van Dyke laboratory focuses on proteins called transcription factors, which promote or repress gene expression to regulate an organism’s functioning. We are specifically studying the cadmium-responsive transcription factor, CadR, due to the importance of metals in virulence and the lack of information on PA’s response to metal fluctuations. We intend …

The Role Of Horizontal Gene Transfer In Antibiotic Resistance Amidst Prevalent Community And Healthcare-Associated Mrsa Rates, Gabrielle Nascimento

Honors College Theses

In recent decades, cases of community-acquired MRSA (CA-MRSA) and healthcare-associated MRSA (HA-MRSA) have been on the rise. The ability of antibiotic resistance to transfer between microorganisms greatly expands its threat to the effective treatment and containment of bacterial infections. The mecA gene is found on a mobile cassette within the Staphylococcal cell and encodes for PBP2a, an alternate version of penicillin-binding protein (PBP) with less binding affinity for β-lactam antibiotics, increasing resistance to the effects of antibiotics. The goal of this research is to investigate the horizontal transfer of the mecA gene between various Staphylococcus species as well as to …

Investigating Arbuscular Mycorrhizal Fungi-Cover Crop Interactions To Improve Sustainable Agricultural Practices, Isabel M. Zanartu, Connor Morozumi, Natalie Christian

The Cardinal Edge

Arbuscular mycorrhizal fungi (AMF) are fungal species that form beneficial relationships with plants. AMFs are known to help crops acquire important nutrients like nitrogen and phosphorus in the soil, and in return the plants provide carbon to the fungi. At least 80% of all plants partner with AMFs including staple crops such as rice, corn, wheat and soybeans. With so many plants likely relying on AMFs, current farming practices such as planting in monocultures and fallow overwintering may limit these relationships. On top of this, climate change challenges the reliability of these practices in the future. One sustainable agricultural practice …

The Physiological Significance Of Nitric Oxide Synthase In Staphylococci, Ryan M. Singh

Theses & Dissertations

Staphylococci, particularly Staphylococcus epidermidis, are common causes of implant-associated infections that may result in notable morbidity and mortality. One of the ways the innate immune system attempts to combat these invading pathogens is via the respiratory burst, in which free radical species such as nitric oxide (NO^•), toxic to bacterial respiration, are released in large quantities. Despite the toxicity of NO^•, some bacteria, including staphylococci, encode an endogenous bacterial nitric oxide synthase (bNOS), whose physiological role has been unclear until now. In this dissertation, we demonstrate that S. epidermidis is able to overcome the toxicity …

Efficacy Of Mcl-1 Inhibitors In Multiple Myeloma Cells Resistant To Bortezomib, Emily Nelson, Omar S. Al-Odat, Sabrina M. Paparo, Daniel A. Guirguis, Gabriella Yao, Manoj Pandey, Subash Jonnalagadda, Tulin Budak-Alpdogan

Rowan-Virtua Research Day

Multiple myeloma (MM) is a type of cancer that affects plasma B cells. Patients with MM often experience frequent relapses and can develop resistance to drugs. As a medical researcher, it is important to understand the role of Mcl-1 in preventing intrinsic apoptosis and drug resistance. Mcl-1 belongs to the anti-apoptotic subgroup of Bcl-2 family proteins and plays a crucial role in these processes. Mcl-1 plays a crucial role in driving disease progression and contributing to drug resistance in MM. It has been observed that there is an increased expression of Mcl-1 in 52% of patients with MM during diagnosis, …

Antimicrobial Activity Of Cat Flea (Ctenocephalides Felis) Gut Proteins On Different Days After Blood Feeding, Dhruva K. Karnik

Honors College Theses

Cat fleas (Ctenocephalides felis) are a blood-feeding ectoparasitic insect and a common domestic pest found throughout the world. Because of their reliance on host blood, fleas are exposed to blood-borne pathogens; however, the flea gut lumen is a hostile environment for microbial colonization. For example, the gut epithelia differentially express immune genes in response to feeding. In the present study, we measured the antimicrobial activity of gut proteins from cat fleas at different days after feeding (2, 5, 7, and 14). Dissected flea guts were homogenized, passed through a syringe filter, and measured in a protein assay kit. …

Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA–guided, sequence-specific binding of target RNAs, such as phage transcripts, activates the type VI effector, Cas13. Once activated, Cas13 causes collateral RNA cleavage, which induces bacterial cell dormancy, thus protecting the host population from the phage spread. We show here that the principal form of collateral RNA degradation elicited by Leptotrichia shahii Cas13a expressed in Escherichia coli cells is the cleavage of anticodons in a subset of transfer RNAs (tRNAs) with uridine-rich anticodons. This tRNA cleavage is accompanied by inhibition of protein synthesis, thus …

Revolutionizing Our Understanding Of Specific Platelet-Pathogen Interactions, Hammodah Rawhi Hammodah Alfar

Theses and Dissertations--Molecular and Cellular Biochemistry

Aside from their classical role in maintaining hemostasis, platelets are considered first-line vascular guardians that influence both the innate and adaptive immune systems. This is mediated by either direct interactions with immune cells or through the release of pre-stored cytokines and chemokines upon interacting with pathogens such as viruses. While this establishes platelets as potential players in the response to pathogens, it remains unclear what platelets can do with pathogens and how important that is to immune responses, especially against viruses. Most systemic viremias, such as HIV-1, present with mild thrombocytopenia, which is mediated through several mechanisms such as a …

Understanding Cellular Dynamics: Investigating A Yeast-Two Hybrid Protein-Protein Interaction, Riok3:Cse1l; Also By Investigating Trogocytosis Of Cd4+ T Cells From Rhog-/- Mice, Brittnee N. Crane

Graduate Student Theses, Dissertations, & Professional Papers

Rift Valley fever virus (RVFV) is a negative-sense virus that was first described in 1930 when it was isolated from sheep during an outbreak. In the last 25 years there has been a spread in the geographical range into the Middle East. The most susceptible animals are cattle, goats, sheep, and camels. The most overt symptom of livestock infection is that infected pregnant animals experience spontaneous abortion. Humans are susceptible as well and symptoms range from mild febrile illness to liver necrosis, blindness, hemorrhagic fever, and death. An important player in the cellular innate response to RVFV infections is the …

The Sewage Microbiome Dynamics Of Different Serving Neighborhoods In Charleston, Illinois, Sandra Chiamaka Okoye

Masters Theses

The complex microbial ecosystem within sewage systems holds significant implications for environmental and public health. Unlike studies on wastewater treatment plant microbiomes, upstream sewage systems have not been studied widely. This research investigated the dynamic sewage microbiome across diverse serving neighborhoods in Charleston, Illinois, encompassing residential, hospital, industrial, and university areas. Drawing upon recent advancements in microbiome research, the study aimed to unravel the spatial and temporal variations in microbial structures. Three times between June to December 2023 sewage samples were collected from manholes in the areas mentioned above. Community DNA was extracted and sequenced for the V4-V5 region of …

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

The Effects Of Vaping Coil Temperature On The Viability Of Veillonella Parvula And Streptococcus Mutans, Marvelous O. Aluko

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

No abstract provided.

Development Of A Novel Serum Formulation For The Treatment Of C. Acnes, Ariana G. Ngue

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Acne impacts 85% of people between 12-24 years of age. Even after puberty, acne continues to impact a large portion of the population. The treatments are diverse and include prescription drugs. Through this research, a novel formulation was created for the skin to treat acne. This formulation incorporates salicylic acid, a non-prescription acne treatment, as well as a polymeric carbohydrate (hyaluronic acid) known to be a component of skin and involved in the healing of skin. Through an internship with Island Lux Essentials, a company devoted to making all natural body care products, a novel serum formulation was created to …

Sero-Epidemiology Of Rotavirus Gastroenteritis In Children In Ilorin, Kwara State, Omosigho Omoruyi Pius, Izevbuwa Osazee Ekundayo, Saheed Ibrahim Damilare

Journal of Bioresource Management

Rotavirus is responsible for the most severe dehydrating diarrhea among young children due to gastroenteritis. In this study, we aimed to ascertain the occurrence of childhood gastroenteritis caused by Rotavirus among infants and young children who are younger than 5 years of age in Ilorin, Kwara State and determined the risk factors posing the challenges to be susceptible to diarrhea associated with rotavirus in Ilorin, Kwara State. Diarrhea stool samples were collected from children who passed watery stools, who met predetermined inclusion criteria and who presented at the study hospitals Viz: General Hospital and Specialist Hospital Alagbado and Children Specialist …

Spatial Structure Formation By The Post-Transcriptional Gene Regulator Rsme In Pseudomonas Fluorescens Pf0-1, Anton Evans

Electronic Theses and Dissertations

Microorganisms are often found in microbial communities we call biofilms. Organisms living in these crowded environments have significant evolutionary pressure to retain access to the resources necessary to sustain life. My research uses the bacterium Pseudomonas fluorescens Pf0-1 to study how organisms evolve strategies to solve this crowding problem as aging colonies repeatedly generate mutant patches. These mutants expand the reach of the colony resulting in decreased local density as they push themselves up to the resource rich surface. These spatial structures result from social interactions between the mutant and the parental cells mediated through extracellular secretions, resulting in the …

Molecular Mechanisms Behind Sars-Cov-2 Induced Host Genome Restructuring, Erin Simpson

Dissertations and Theses (Open Access)

Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has caused unprecedented morbidity and mortality worldwide. There are two pathophysiological hallmarks associated with severe patient outcomes after SARS-CoV-2 acute infection, namely delayed/weakened interferon production and overactive inflammatory responses. Our previous work has shown that these altered immune responses are due, at least in part, to significant alterations in 3D genome organization and epigenetic landscape following SARS-CoV-2 infection that are distinct from and more severe than changes caused by other viral infections or immune stimulants. While these changes at the chromatin level are important for understanding the immune dysregulation seen in some cases …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Diagnosis Of Urinary Tract Infections And Rapid Molecular Characterization Of Antibiotic Resistance, Mohammed Harris

All Dissertations

Urinary tract infections (UTIs) are one of the most common infectious clinical entities in both community and hospital settings. They have a broad range of clinical severity yet inflict large epidemiological burden of morbidity and mortality on patients and the healthcare system with billions of dollars in cost of treatment. Understanding what methods are optimal for diagnosing UTIs are critical to mitigate the marked impact and cost of these infections.

Chapter 1 and 2 in this work surveys the broad array of diagnostic modalities for UTIs and highlights their advantages and limitations in the context of the current standard of …

Functional Domains Of The Hsv-1 Ul37 Protein In Virus Infectivity And Retrograde Transport In Neurons, Carolyn Clark

LSU Doctoral Dissertations

Herpes simplex virus type 1 is large alphaherpesvirus with 20 envelope proteins and 23 tegument proteins. Virus entry is via fusion of the viral envelope with cellular membranes mediated by a complex of viral glycoproteins. Glycoprotein B (gB) is the only fusogenic glycoprotein, while other viral glycoproteins and membrane proteins including gD, gH, gL, gK and UL20 membrane protein modulate gB’s fusogenicity. Previously, Our laboratory developed the HSV-1 (VC2) vaccines strain with partial deletions in the amino termini of gK (ΔgK(31–68)) and the UL20 membrane protein (ΔUL20(4–22)). VC2 enters epithelial cells only via endocytosis followed by release of the capsid …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Investigating The Antibacterial And Immunomodulatory Properties Of Lactobacillus Acidophilus Postbiotics, Rachael M. Wilson

Graduate School of Biomedical Sciences Theses and Dissertations

Probiotics are nonpathogenic microorganisms that have been extensively studied for their ability to prevent various infectious, gastrointestinal, and autoimmune diseases. The mechanisms underlying these probiotic effects have not been elucidated. However, we and other researchers have evidence suggesting that probiotic bacteria secrete metabolites that are antimicrobial and anti-inflammatory. As such, we developed a methodology to collect the secreted metabolites from a probiotic bacterium, Lactobacillus acidophilus, and tested this cell free filtrate (CFF) both in vitro and in vivo. Using this CFF, we have demonstrated that L. acidophilus secretes a molecule(s) that has specific bactericidal activity against the opportunistic pathogen, Pseudomonas …

Rna Virus-Mediated Changes In Organismal Oxygen Consumption Rate In Young And Old Drosophila Melanogaster Males, Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel Smith Jr, Stephanie Dickinson, Andrew Brown, Maria De Luca, Ashley Turner, Stanislava Chtarbanova

Research, Publications & Creative Work

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due …

Thymic Stromal Lymphopoietin Participates In The Host Response To Intra-Amniotic Inflammation Leading To Preterm Labor And Birth, Tomi Kanninen, Li Tao, Roberto Romero, Yi Xu, Marcia Arenas-Hernandez, Jose Galaz, Zhenjie Liu, Derek Miller, Dustyn Levenson, Jonathan M. Greenberg, Jonathan Panzer, Justin Padron, Kevin Theis, Nardhy Gomez-Lopez Phd

Medical Student Research Symposium

Objective: To determine if bacteria (Ureaplasma parvum and Sneathia spp.) associated with intra-amniotic infection can trigger the induction of cytokine Thymic stromal lymphopoietin (TSLP) in human amnion epithelial cells (hAECs) in vitro.

Material or subjects: Amniotic fluid and chorioamniotic membrane (CAM) were collected from women with sPTL who delivered at term (n=30) or preterm without intra-amniotic inflammation (n=34), with sterile intra-amniotic inflammation (SIAI, n=27), or with intra-amniotic infection (IAI, n=17). Amnion epithelial cells (AECs), Ureaplasma parvum, and Sneathia spp. were also utilized.

Methods: The expression of TSLP, TSLPR, and IL-7Rα was evaluated in amniotic fluid or CAM by …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

Graduate Theses/Dissertations

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …