Laboratory and Basic Science Research Commons^™

Dpc29 Promotes Post-Initiation Mitochondrial Translation In Saccharomyces Cerevisiae, Kyle A. Hubble, Michael F. Henry

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mitochondrial ribosomes synthesize essential components of the oxidative phosphorylation (OXPHOS) system in a tightly regulated process. In the yeast Saccharomyces cerevisiae, mitochondrial mRNAs require specific translational activators, which orchestrate protein synthesis by recognition of their target gene's 5'-untranslated region (UTR). Most of these yeast genes lack orthologues in mammals, and only one such gene-specific translational activator has been proposed in humans-TACO1. The mechanism by which TACO1 acts is unclear because mammalian mitochondrial mRNAs do not have significant 5'-UTRs, and therefore must promote translation by alternative mechanisms. In this study, we examined the role of the TACO1 orthologue in yeast. We …

Development Of A Method For Identifying And Quantifying Epicatechin In Cinnamon Extract Supplement Capsules, Danielle Valls

Annual Research Symposium

No abstract provided.

Biorisk Management, Laboratory Acquired Infections And Clinical Containment, Kashif Ali, Furqan Kabir, Esmeralda Meyer

Department of Paediatrics and Child Health

No abstract provided.

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 …

Examining The Oxidative Stress Effects In Rats Exposed To 2-Aminoanthracene In Utero And High Fat Diet Three Months After, Brianna A. Lanoix

Honors College Theses

Polycyclic aromatic hydrocarbons are organic compounds that are created synthetically or found in partially burned oil, gasoline, and coal. 2-aminoanthracene (2AA) is a common example of a PAH and can affect lipid and carbohydrate metabolism and resulting in inflammatory problems and oxidative stress. The objective of the research project is to investigate oxidative stress in relation to diabetes in rats exposed to 2AA in utero and a high fat diet later in life. Pregnant dams were separated into treatment groups based on their dosages of 2AA; 0 mg/kg (control), 50 mg/kg (low), 100 mg/kg (high). During the gestation -postpartum period, …

Investigation To Examine The Profile Of Auditory Brainstem And Hearing Thresholds Using Tone Burst Audiometry Brainstem Response In A Preclinical Migraine Model, Megan Huelsing

Graduate Theses/Dissertations

Migraine is a disabling neurological disease that is characterized by prominent auditory symptoms, including hyperacusis, which is defined as extreme sensitivity to sounds. The goal of this study was to investigate changes in hearing sensitivity and neural changes in the brainstem by measuring neural activity of the auditory brainstem in an established preclinical model of chronic migraine. To induce a chronic migraine state within the trigeminal system, male and female Sprague Dawley rats were subjected to three known human risk factors including neck muscle tension and REM sleep deprivation that promote latent sensitization, and exposure to a pungent odor, which …

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …

Amphisbaenian Head Movement And Burrowing Forces In Damp Granular Media, Jacob Newell

Williams Honors College, Honors Research Projects

Damp granular media is a difficult environment to study because it is both practically complex and it lacks equations which fully describe its behavior. In this study, an oscillatory lateral head movement and its effects while penetrating damp granular media were tested using a robophysical model. This experimental research was inspired by the burrowing behavior of the clade Amphisbaenia, a group of usually limbless squamates that employ a variety of different burrowing behaviors, but it can apply to a wide range of burrowers. This research could help with both human burrowing technologies and the further investigation of animal behaviors.

The Accuracy Of Recreational Athletes In Self Detecting Ventilation Threshold During A Maximal Exercise Test, Andrew Biegner

Williams Honors College, Honors Research Projects

INTRODUCTION: Ventilatory threshold (VT) is where minute ventilation (VE) increases nonlinearly with increasing exercise intensity. Prior studies have shown that subjects can recognize VT by changes in breathing during exercise. Teaching recreational athletes to use VT as a training method could result in better quality training. PURPOSE: Determine if recreational athletes can accurately perceive changes in ventilation associated with VT during maximal exercise testing. METHODS: Subjects were recruited (n=20, age= 20.5 ± 1.7 yrs.) to participate in the study. Subjects performed a modified maximal treadmill protocol with gas analysis. Subjects indicated when they noticed a considerable change …

The Development And Characterization Of Nanobodies Specific To Protein Tyrosine Phosphatase 4a3 (Ptp4a3/Prl-3) To Dissect And Target Its Role In Cancer., Caroline Smith

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3) is an oncogenic dual-specificity phosphatase that drives tumor metastasis, promotes cancer cell survival, and is correlated with poor patient prognosis in a variety of solid tumors and leukemias. The mechanisms that drive PRL-3’s oncogenic functions are not well understood, in part due to a lack of research tools available to study this protein. The development of such tools has proven difficult, as the PRL family is ~80% homologous and the PRL catalytic binding pocket is shallow and hydrophobic. Currently available small molecules do not exhibit binding specificity for PRL-3 over PRL family members, …

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 …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Dpc29 Promotes Mitochondrial Translation Post-Initation In Saccharomyces Cerevisiae, Kyle Andrew Hubble

Graduate School of Biomedical Sciences Theses and Dissertations

Although the cytosolic and bacterial translation systems are well studied, much less is known about translation in mitochondria. In the yeast Saccharomyces cerevisiae, mitochondrial gene expression is predominately regulated by translational activators. These regulators are thought to promote translation by binding the elongated 5’-UTRs on their target mRNAs. Since mammalian mitochondrial mRNAs generally lack 5’-UTRs, they must regulate translation by other mechanisms. As expected, most yeast translational activators lack orthologues in mammals. Recently, a mitochondrial gene-specific translational activator, TACO1, was reported in mice and humans. To better define its role in mitochondrial translation I examined the yeast TACO1 orthologue, DPC29. …

Effects Of Expiratory Muscle Strength Training On Oropharyngeal Swallow Physiology In Persons With Obstructive Sleep Apnea (Osa): A Pilot Study, Ankita Murlidhar Bhutada

Graduate Theses and Dissertations (2019 - present)

Obstructive sleep apnea (OSA) is characterized by frequent narrowing of the upper airway during sleep. The estimated prevalence of swallowing impairments (dysphagia) in OSA patients ranges up to 80% and comprises approximately 50% of the caseload of practicing speech-language pathologists in the United States. Despite the high prevalence of dysphagia, there is a paucity of evidence supporting behavioral intervention(s) for ameliorating swallowing impairments in OSA. This pilot study assessed oropharyngeal swallowing physiology in persons with OSA and the feasibility and acceptability of a behavioral dysphagia intervention that specifically targets upper airway musculature – Expiratory Muscle Strength Training (EMST). A total …

Covid-19-Impacted Research And Education In Global Healthcare And Stem: Evaluation Of Case Studies, Yumna Indorewala, Santanu De

Trick to the Treat of Internships and Research

The zoonotic novel coronavirus has posed major challenges to the world’s economy, social development, and public health. Effects in the education and research in the field of healthcare and STEM are accentuated in lower-developed countries or communities where the access to technology and a reliable internet connection are luxuries making it difficult to attain education virtually. The Coronavirus Infectious Disease 2019 (COVID-19) has also disrupted research and training in STEM and healthcare. With significant increases in infection rates there is an urge to redirect projects towards virology research and vaccine development. This comprehensive literature review includes case studies highlighting the …

An Epi-Metabolomics Approach For Studying Epigenetic And Metabolic Changes In Alzheimer’S Disease Brain, Nadia Ashrafi, Sangeetha Vishweswaraiah, Ali Yilmaz, Sumeyya Akyol, Juozas Gordevicius, Stewart Graham

Conference Presentation Abstracts

No abstract provided.

Mild And Severe Traumatic Brain Injury Longitudinally Profiled Using High-Resolution Metabolomics, Ali Yilmaz, Sigal Liraz Zaltsman, Esther Shohami, Juozas Gordevicius, Jack E. Sherman, Ray Bahado-Singh, Stewart F. Graham

Conference Presentation Abstracts

No abstract provided.

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 …

A Microfluidics-Based Approach For Isolation Of Antigen-Specific Cd8+ T Cells, Meredith Frank

Dissertations and Theses (Open Access)

Cancer is a global epidemic: there are predicted to be 200 million new cases this year alone. Almost a quarter of all cancer-related deaths are caused by lung cancer, for which 5-year survival rates are just above 20%. 85% of lung cancer diagnoses are classified as non-small cell lung cancer (NSCLC) for which 5-year survival rates in metastatic disease are less than 10%. Early detection and targeted therapies have improved prognoses, yet relapse is still common among patients.

Immunotherapies that leverage tumor-specific CD8⁺ cytotoxic T cells have shown great promise for the treatment of NSCLC. However, although highly promising, …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Interlaboratory Comparison Of Metabolomics Analyses Of Human And Rodent Blood Using Biocrates Mxp Quant 500 Kit, Nadia Ashrafi, Ali Yilmaz, Stewart F. Graham, Thomas O'Connell, Sumeyya Akyol

Conference Presentation Abstracts

No abstract provided.

Norepinephrine Regulation Of Spatial Memory Using The Barnes Maze In Male And Female Rats, Serena Simpson, Ali Gheidi Phd, Nareen Sadik, Cameron J. Davidson Phd, Shane A. Perrine Phd

Medical Student Research Symposium

The role of norepinephrine (NE) in learning and memory has been extensively studied, yet its contribution remains to be clarified. This study aimed to investigate the role of NE on spatial learning and memory in female and male rats using a Barnes maze assay. We used N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a specific noradrenergic neurotoxin that can cross the blood brain barrier, to deplete NE stores. We hypothesized that brain NE ablation would attenuate spatial learning and memory in rats. Loss of NE by DSP-4 was determined by measuring NE (and dopamine and serotonin) levels in several brain regions using HPLC. For the …

Thromboelastography Profiles Of Hemophilia A Patients On Emicizumab, Daniel J. Vanzweden, Meera Chitlur, Charity J. Stadler

Medical Student Research Symposium

Emicizumab is a new monoclonal antibody developed to dtreat people with Hemophilia A, especially those with antibodies. However, breakthrough bleeding can still occur in patients taking Emicizumab. TEG is a global coagulation assay which measures coagulability through viscosity. This study describes the use of tissue factor activated TEG in measuring bleeding profiles in patients taking Emicizumab. The goal of this prospective study is to determine if TEG can be used, which variables of TEG might be useful, and how much more useful it is than the current standard, aPtt. Findings include a 25% increased R time and 24% increased K …

The Competitive Edge: Improving Absite Scores Through A Team-Based Approach, Sean Masters, Kathryn Howard, Darci Foote, Diane Studzinski, Rose E. Callahan, Felicia Ivascu, Begum Akay

Conference Presentation Abstracts

Introduction: A competitive team-based approach to encourage self-studying and didactic participation is a novel method of American Board of Surgery In-Training Examination (ABSITE) preparation. We aimed to determine if this method significantly improves residents’ percentile performances on the ABSITE. Methods: We reviewed ABSITE performance and preparation from general surgery residents for the last ten years. Percentile scores were compared before and after implementation of a purchased online question bank (TrueLearn LLC, Mooresville, NC), a team-based competition, and a virtual format of the team-based competition. Statistical analysis was performed with ANOVA Kruskal-Wallis and Mann Whitney tests where appropriate. Results: 378 ABSITE …

Cdk8 Kinase Module Modifies Expression Of Specific Translation-Related Proteins Before And After Stress, Brittany Friedson, Katrina Cooper

Rowan-Virtua Research Day

Translation is tightly coupled to growth status. Efficient protein synthesis is necessary for cell growth in nutrient rich environments, while global translation inhibition combined with selective translation of stress-responsive mRNAs helps limit growth in times of stress. Environmental stress cues which inhibit the nutrient-sensing complex TORC1 are known to reduce general translation, but how does the cell alter protein synthesis machinery to adapt to these conditions? A few mechanisms to promote cell survival in nitrogen starvation include post-translational modification and selective degradation of specific mRNA-binding translation factors, as well as inhibition of activators of genes whose products are required for …

Impact Forces And Patterns Of Axonal Injury Differ Between Two Models Of Tbi, Edward Lai, David M Devilbiss

Rowan-Virtua Research Day

Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum …

Conservation And Divergence In The Heterochronic Pathway Of C. Elegans And C. Briggsae, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

The heterochronic pathway of Caenorhabditis elegans is exemplary as a mechanism of developmental timing: mutations in genes of this pathway alter the relative timing of diverse developmental events independent of spatial or cell type specific regulation. It is the most thoroughly characterized developmental timing pathway known. Most of the heterochronic genes are conserved across great evolutionary time, and a few homologs seem to have developmental timing roles in certain contexts. The degree to which other organisms have explicit developmental timing mechanisms, and what factors comprise those mechanisms, isn’t generally known.

Developmental pathways evolve even if the resulting morphology remains the …

Cyclin C Is Sufficient For Myoblast Differentiation-Induced Mitochondrial Fragmentation, Alicia N. Campbell, Randy Strich

Rowan-Virtua Research Day

One of the largest and most dynamic tissues in the body, skeletal muscle, requires constant regeneration and upkeep. Dysregulation of this regeneration process has been implicated in many neuromuscular diseases and myotonic dystrophies. Regeneration requires the differentiation of myogenic lineages including exiting the cell cycle, gene expression changes, and fusing of myoblasts into multinucleate myotubes. Part of this reconstruction requires the breakdown and repopulation of mitochondrial networks. At the early onset of myoblast differentiation, there is an upregulation of dynamin-related protein, Drp1, and an increase in mitophagy mediated by sequestosome (SQSTM1) removal of mitochondria.

Previously, our lab has shown that …

Examining Levels Of Catecholamine Neurotransmitter Regulatory Proteins Within The Prefrontal Cortex Of Rodents Following Traumatic Brain Injury, Eleni Papadopoulos, Christopher P. Knapp, Claire M. Corbett, Jessica Loweth, Rachel L. Navarra

Rowan-Virtua Research Day

Traumatic brain injury (TBI) resulting from impact to the head can cause long lasting impairments of cognitive processes that lead to increased risk-taking behavior in clinical populations. Our laboratory has recently shown that female, but not age-matched male, rats increase preference for risky choices after multiple experimentally-induced mild TBI’s. Our overarching goal is to understand the neural mechanisms underlying TBI-induced increases in risk-taking behavior.

The prefrontal cortex (PFC) plays a prominent role in risk-based decision making. Sub[1]regions of the PFC include the medial PFC (mPFC), the orbitofrontal cortex (OFC), and the anterior cingulate cortex (ACC), and these sub[1]regions play specific …

Ung2 And Rpa Activity On Ssdna-Dsdna Junctions, Kathy Chen, Sharon Greenwood, Brian P. Weiser

Rowan-Virtua Research Day

Uracil DNA glycosylase, or UNG2, is an enzyme that is involved in DNA repair. Its primary job is to eliminate harmful uracil bases from DNA strands. To do this, the enzyme is assisted by replication protein A (RPA). RPA helps UNG2 in the identification of uracil bases by targeting UNG2 activity near ssDNA-dsDNA junctions (1-3). The results from assays presented here agree with published findings that showed UNG2 is heavily targeted by RPA to uracil bases that are close to ssDNA-dsDNA junctions (for example, uracil located 9 bps from the junction as opposed to 33 bps) (1,2). However, these previous …