Laboratory and Basic Science Research Commons^™

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. …

Environmental Influences On The Growth Of Inland Cisco Populations In Three Minnesota Sentinel Lakes, Edward Carlson

Biology Graduate Theses

Cisco Coregonus artedi are a pelagic cold-water fish that are widely distributed throughout many inland lakes across the northern Midwest and play an important role as forage for large piscivores. Inland Cisco populations have been observed to vary in their overall size and recruitment potential based on the system in which they are found. Cisco are sensitive to oxythermal stress and with climate change, land use, and invasive species effects becoming more prevalent in Minnesota, aspects of lake ecosystems are changing, ultimately making Cisco more susceptible to these stressors. To investigate how different factors were affecting the population dynamics of …

Changes In Streptococcus Pneumoniae Susceptibility In Wisconsin: Implications For Clinical Treatment Decisions For Respiratory Infections, Erik Munson, Stephen C. Lavey, Megan R. Lasure, Barry C. Fox

Clinical Lab Sciences Faculty Research and Publications

Objective: In 2019, the American Thoracic Society and Infectious Diseases Society of America updated clinical practice guidelines for community-acquired pneumonia (CAP). In contrast to guidelines published in 2007, macrolide monotherapy for outpatients was made a conditional recommendation based on resistance levels. Local knowledge of current antimicrobial susceptibility is needed to guide management of CAP and other bacterial respiratory pathogens. The purpose of this study was to investigate antimicrobial susceptibility profiles and trending for Wisconsin Streptococcus pneumoniae isolates.

Design: Multi-center laboratory surveillance, with testing at a central location utilizing standardized susceptibility testing protocols.

Methods: Data published by the Wisconsin Department of …

Understanding And Targeting The Immunosuppressive Tumor Microenvironment, Li Cai, Li Cai

Dissertations and Theses (Open Access)

Immune checkpoint inhibitors (ICIs), such as anti-PD1/PD-L1 and anti-CTLA-4, have shown impressive antitumor efficacy by improving the activity of T cells. While these inhibitors work in many patients with various cancer types, they have minimal or no effect in many more patients. Mounting evidence indicates that, besides current known immune checkpoints, other immunosuppressive components in the tumor microenvironment (TME) need to be targeted to elicit the full immune responses.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immunosuppressive myeloid cells that are involved in cancer progression and therapeutic resistance. In this work, we demonstrated the essential role of MDSCs …

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 …

Molecular Basis For Integrin Adhesion Receptor Binding To P21-Activated Kinase 4 (Pak4), Byung Hak Ha, Sezin Yigit, Nailini Natarajan, Elizabeth M. Luoma, David A. Calderwood, Titus J. Boggon

SHU Faculty Publications

Integrin adhesion receptors provide links between extracellular ligands and cytoplasmic signaling. Multiple kinases have been found to directly engage with integrin β tails, but the molecular basis for these interactions remain unknown. Here, we assess the interaction between the kinase domain of p21-activated kinase 4 (PAK4) and the cytoplasmic tail of integrin β5. We determine three crystal structures of PAK4-β5 integrin complexes and identify the PAK-binding site. This is a region in the membrane-proximal half of the β5 tail and confirmed by site-directed mutagenesis. The β5 tail engages the kinase substrate-binding groove and positions the non-phosphorylatable integrin residue Glu767 at …

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.

Improvement Value Of Forest Resources By Use Of Cottonseed Protein Meal As A Bio-Based Wood Adhesive For Hardwood Plywood Products, Edward David Entsminger

Theses and Dissertations

Literature shows that production of cottonseed adhesives is feasible to develop an environmentally friendly and competitive bio-based wood adhesive. Defatted cottonseed and water-washed cottonseed meals were prepared from glandless cottonseed and were used in adhesive formulations to produce three-ply yellow poplar (Liriodendron tulipifera) plywood panels as the first objective. These two cottonseed meals were compared with the properties of plywood panels made with an adhesive formulated from a commercial soybean meal, as a control. Adhesive resins were prepared from each protein meal with sodium metabisulfite (Na2S2O5) and one of two polyamido-amine-epichlorohydrin (PAE) wet strength agents, and the plywood panels were …

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 …

Reproductive Ecology And Microbial Communities From Wood Duck Nest Boxes In Georgia And Florida, Jake Shurba

All Theses

Wood ducks (Aix sponsa) are an important game species throughout the Atlantic Flyway that was nearly extirpated by the early 20^th century due to overhunting and the loss of habitat. Wood ducks are secondary cavity-nesters that utilize artificial nest boxes and natural cavities. It is reported that the use of nest boxes is likely what led to re-establishment of the species in North America. Where boxes are numerous, overuse of boxes by multiple hens throughout a nesting season can occur and result in a buildup of bacteria, parasites and other potentially detrimental pathogens that can impact egg …

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) …

Increasing The Resilience Of Plant Immunity To A Warming Climate, Jong Hum Kim, Christian Castroverde, Shuai Huang, Chao Li, Richard Hilleary, Adam Seroka, Reza Sohrabi, Diana Medina-Yerena, Bethany Huot, Jie Wang, Sharon Marr, Mary Wildermuth, Tao Chen, John Macmicking, Sheng Yang He

Biology Faculty Publications

Extreme weather conditions associated with climate change affect many aspects of plant and animal life, including the response to infectious diseases. Production of salicylic acid (SA), a central plant defence hormone, is particularly vulnerable to suppression by short periods of hot weather above the normal plant growth temperature range via an unknown mechanism. Here we show that suppression of SA production in Arabidopsis thaliana at 28 °C is independent of PHYTOCHROME B (phyB) and EARLY FLOWERING 3 (ELF3), which regulate thermo-responsive plant growth and development. Instead, we found that formation of GUANYLATE BINDING PROTEIN-LIKE 3 (GBPL3) defence-activated biomolecular condensates (GDACs) …

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 …

Characterizing Endogenous Dicer Products To Unravel Novel Rnai Biogenesis Pathways, Jacob Oche Peter

Dissertations

ABSTRACT

RNA interference (RNAi) is a pervasive gene regulatory mechanism in eukaryotes based on the action of multiple classes of small RNA (sRNA). Exploiting RNAi pathways in non-model systems have great potential for creating potent RNAi technologies. Here, we accessed RNAi-mediated control of gene expression in the two-spotted spider mite, Tetranychus urticae (T. urticae) using engineered dsRNA designed to modulate the host RNAi pathway and increase RNAi efficacy. Analysis of Dicer (Dcr) generated fragments revealed how exogenous RNAs access the host RNAi pathway in this animal, opening avenues for designing RNAi technology for their control. Further, some organisms …

Developing A Miniature Smart Boat For Marine Research, Michael Isaac Eirinberg

Computer Engineering

This project examines the development of a smart boat which could serve as a possible marine research apparatus. The smart boat consists of a miniature vessel containing a low-cost microcontroller to live stream a camera feed, GPS telemetry, and compass data through its own WiFi access point. The smart boat also has the potential for autonomous navigation. My project captivated the interest of several members of California Polytechnic State University, San Luis Obispo’s (Cal Poly SLO) Marine Science Department faculty, who proposed a variety of fascinating and valuable smart boat applications.

Noxious Cellular Injury Triggers An Oxidative Stress Gene Response, Shawyun Khoshneviszadeh

Master of Science in Integrative Biology Theses

Wound and regeneration involves a series of complex processes that can induce oxidative stress by elevating intracellular reactive oxygen species (ROS) levels. In this study, we used RNA-seq and qPCR to examine the molecular signature of Human Embryonic Kidney cells (HEK-293T) stimulated with Crotalus atrox (CA) venom. NGS data was assembled and annotated utilizing the Illumina paired-end RNA-seq approach with software packages HISAT2 and StringTie. Results showed 243 genes were differentially expressed (106 upregulated, 137 downregulated) between CA venom stimulated and non-stimulated cells (p<0.05). HEK-293T stimulated with CA venom for 4 hours showed an increase in the expression of oxidative stress response genes (e.g., TOMM6, EGR (1,2,3), HSP70 (1A, 1B), SPRY4, ETV5, and EMP1) (Fold-Change (fc) >2.0). Significantly downregulated genes were associated with many novel transcripts/proteins such as AC117378, AD000671, and AC023509. …

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 …

Techniques To Analyze The Pathophysiology Of Aging From Induced Senescence And Sod2 Loss, Asia Davis-Castillo

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Cardiovascular disease is the leading cause of death in the United States. Cardiac function declines with age, and promotes a number of age-related disorders, including atrial fibrillation and heart failure. Mitochondrial oxidative stress has long been suspected as a primary driver of aging pathology in multiple tissues, including the heart and brain. We used several phenotypic assays to characterize chemically-induced accelerated cardiac aging, as well as two transgenic knockout models for heart and brain specific loss of superoxide dismutase (SOD2), a mitochondrial antioxidant protein.

We first accelerated aging in mice by treating with doxorubicin (DOXO), a chemotherapeutic drug. One group …

Evaluating Threats To The Water Quality Of Little Buffalo Creek And Sarver Run Through Water Quality Analysis And Backpack Electrofishing Surveys, Riley Williams

Electronic Theses and Dissertations

Currently, 64.8% and 52.2% of Little Buffalo Creek and Sarver Run stream kilometers are impaired, respectively. Impairment sources to Little Buffalo Creek include agriculture, riparian deforestation, on-site wastewater, and urban runoff. Impairment sources to Sarver Run are unknown. Our goal was to understand sources of impairment through water quality analysis and fish surveys. Water samples were collected monthly and analyzed for cation and anion concentrations. Mass ratio analysis comparing Br/SO₄ and Mg/Li, Ca/Mg and Ca/Sr, Mg/Na and SO₄/Cl, and SO_4/Cl and Mg/Li suggests that mine drainage and conventional oil and gas may be impacting water …

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 …