Cell and Developmental Biology Commons^™

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 …

Modeling The Tripartite Role Of Cyclin C In Cellular Stress Response Coordination, Steven J. Doyle

Graduate School of Biomedical Sciences Theses and Dissertations

For normal cellular function, exogenous signals must be interpreted and careful coordination must take place to ensure desired fates are achieved. Mitochondria are key regulatory nodes of cellular fate, undergoing fission/fusion cycles depending on the needs of the cell, and help mediate cell death fates. The CKM or Cdk8 kinase module, is composed of cyclin C (CC), Cdk8, Med12/12L, and Med13/13L. The CKM controls RNA polymerase II, acting as a regulator of stress-response and growth-control genes. Following stress, CC translocates to the mitochondria and interacts with both fission and iRCD apoptotic mediators. We hypothesize that CC represents a key mediator, …

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 …

Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley

Graduate School of Biomedical Sciences Theses and Dissertations

Cells are exposed to an enormous amount of diverse extracellular cues but have a limited arsenal of weapons for protecting and maintaining homeostasis. To overcome these restrictions, nature has engineered proteins that have multiple functions. The pleiotropy of using one protein to carry out a variety of functions allows cells to rapidly execute tailored responses to a diverse set of signals. The Cdk8 kinase module (CKM) is a conserved detachable unit of the Mediator complex predominantly known for its role in transcriptional regulation. The CKM is composed of four proteins, the scaffolding proteins Med13 and Med12, as well as the …

Developmental Changes In Electrophysiological Properties Of Auditory Cortical Neurons In The Cntnap2 Knockout Rat, Rajkamalpreet S Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2^-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole cell patch-clamp recordings were conducted in wildtype and Cntnap2^-/- littermates at three postnatal age ranges (P8-12, P18-21, and …

Potentiation Of The Immune Checkpoint Blockade Response By Metabolic Modulation Is Predictable Using Molecular Imaging, Renee L. Chin

Dissertations and Theses (Open Access)

Unregulated cell division is a hallmark of cancer. The high metabolic needs of the tumor cells result in nutrient depletion and produce a hostile tumor microenvironment (TME) for antitumor immune cells, protecting the tumor from immune cell-mediated control and immunotherapy. Two of these environmental factors, acidosis and hypoxia, are commonly found in solid cancers. In my thesis, I posited that modulation of tumor acidosis and hypoxia can serve as biomarkers by indicating immunogenicity and tumor sensitivity to immune checkpoint blockade (ICB) as monitored using molecular imaging. Esomeprazole was found to promote tumor immunogenicity and induce tumor control when used to …

Mc-01 Identification Of Genes In Blastocoel Fluid Associated With Successful Ivf Outcomes Of Women Of Advanced Maternal Age, Hannah C. Archer, Thao Nguyen, Carson Collins, Kayla Vaillant, Molly Riehs, Sarayu Bethi, Renee J. Chosed

SC Upstate Research Symposium

Introduction: A patient may seek the use of IVF technology when they are struggling to become pregnant. To improve IVF outcomes, much research is focused on identifying markers to allow embryologists to transfer embryos with the greatest chance of a successful pregnancy. Women of advanced maternal age, which is thirty-five years and older have a lower chance of success on a first attempt with IVF, women at the age of 40 have a 9% chance of a live birth with IVF. Therefore, identification of an additional biomarker during preimplantation embryo development that is associated with successful implantation in AMA patients, …

The Prognostic Value Of Baseline Clinical And Radiologic Imaging Features In Patients With Unresectable Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab, Mikhail Bogdanov

Faculty, Staff and Student Publications

Membrane asymmetry means that the two sides of membrane are structurally, physically and functionally different. Membrane asymmetry is largely related to the lipid sidedness and particularly to compositional (lipid head and acyl group) and physical (lipid packing order, charge, hydration and H-bonding interactions) differences in the inner and outer leaflets of lipid bilayer. Chemically, structurally and conformationally different non-covalent bound lipid molecules are physically fluid and deformable and enable to interact dynamically to form transient arrangements with asymmetry both perpendicular and parallel to the plane of the lipid bilayer. Although biological membranes are almost universally asymmetric however the asymmetry is …

Renovating A Double Fence With Or Without Notifying The Next Door And Across The Street Neighbors: Why The Biogenic Cytoplasmic Membrane Of Gram-Negative Bacteria Display Asymmetry?, Mikhail Bogdanov

Faculty, Staff and Student Publications

The complex two-membrane organization of the envelope of Gram-negative bacteria imposes an unique biosynthetic and topological constraints that can affect translocation of lipids and proteins synthesized on the cytoplasm facing leaflet of the cytoplasmic (inner) membrane (IM), across the IM and between the IM and outer membrane (OM). Balanced growth of two membranes and continuous loss of phospholipids in the periplasmic leaflet of the IM as metabolic precursors for envelope components and for translocation to the OM requires a constant supply of phospholipids in the IM cytosolic leaflet. At present we have no explanation as to why the biogenic E. …

Time And Temperature Stability Of Tritrichomonas Foetus In Phosphate-Buffered Saline As Evaluated By A Reverse Transcription Real-Time Pcr Assay And Field Analysis, Duan S. Loy, Renata Spuri Gomes, Enakshy Dutta, Bruce W. Brodersen, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Tritrichomonas foetus (TF) is a significant reproductive pathogen of cattle, and sample collection, handling, transport, and testing are significant hurdles to surveillance programs. Recent methods have been developed that allow for the direct detection of TF using a reverse transcription real-time PCR (direct RT-qPCR) approach. To evaluate these methods, a comparative analysis was conducted to assess the technical performance of this assay with a commercially available real- time PCR (qPCR) assay. In addition, the evaluation of two types of collection media (PBS and TF transport tube) was conducted that evaluated sample stability from 0 to 3 days when stored at …

Crosstalk Between The Extracellular Matrix And The Cell- Cell Junction - Associated Rnai Machinery Regulates Colon Cancer Cell Behavior, Amanda Daulagala

MUSC Theses and Dissertations

Colon cancer is the third most common and second deadliest type of cancer. Colon cancer is broadly characterized by compromised epithelial integrity and by aberrant extracellular matrix (ECM) remodeling. However, a potential mechanistic connection between epithelial integrity and ECM remodeling that could be contributing to the disease progression, has not been explored yet. The Adherens Junction (AJ) is a cell-cell adhesion complex composed of cadherin and catenin family proteins and essential for establishing and maintaining epithelial tissue integrity. Our previous work revealed that PLEKHA7, an E-cadherin-p120 catenin partner, recruits the microprocessor and the RNA-induced silencing complex (RISC), key components of …

Amphiphilic Cell-Penetrating Peptides Containing Arginine And Hydrophobic Residues As Protein Delivery Agents, Jonathan Moreno, Khalid Zoghebi, David Salehi, Lois Kim, Sorour Khayyatnejad Shoushtari, Rakesh K. Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The entry of proteins through the cell membrane is challenging, thus limiting their use as potential therapeutics. Seven cell-penetrating peptides, designed in our laboratory, were evaluated for the delivery of proteins. Fmoc solid-phase peptide synthesis was utilized for the synthesis of seven cyclic or hybrid cyclic–linear amphiphilic peptides composed of hydrophobic (tryptophan (W) or 3,3-diphenylalanine (Dip) and positively-charged arginine (R) residues, such as [WR]4, [WR]9, [WWRR]4, [WWRR]5, [(RW)5K](RW)5, [R5K]W7, and [DipR]5. Confocal microscopy was used to screen the peptides as a protein delivery system of model cargo proteins, green and red fluorescein proteins (GFP and RFP). Based on the confocal …

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 …

Functional Analysis Provides Insight Into Missing Heritability, Scott L. Baughan, Michael A. Tainsky, Fatima Darwiche

Medical Student Research Symposium

Accurate ascertainment of genetic risk can be potentially lifesaving for patients who inherit cancer promoting mutations. However, even with the most extensive panel testing clinically available, a large number of patients will test negative despite family history of cancer or test positive for a variant of unknown significance (VUS). For these patients, clinical management is complicated; patients want to know their risk, and may fear disease they are not at great risk for (benign VUS) or they may not be given access to potentially lifesaving early screening procedures (pathogenic VUS). ATM has proven a challenge to clinicians due to its …

Biomarker Metabolite Discovery For Pancreatic Cancer Using Machine Learning, Immanuelle Kezia, Linda Erlina, Aryo Tedjo, Fadilah Fadilah

Indonesian Journal of Medical Chemistry and Bioinformatics

Pancreatic cancer is one of the deadliest cancers in the world. This cancer is caused by multiple factors and mostly detected at late stadium. Biomarker is a marker that can identify some diseases very specific. For pancreatic cancer, biomarker has been recognized using blood sample known as liquid biopsy, breath, pancreatic secret, and tumor marker CA19-9. Those biomarkers are invasive, so we want to identify the disease using a very convenient method. Metabolite is product from cell metabolism. Metabolites can become a biomarker especially from difficult diseases. In this paper, we want to find biomarker from metabolite using machine learning …

Fresh Produce As A Potential Vector And Reservoir For Human Bacterial Pathogens: Revealing The Ambiguity Of Interaction And Transmission, Ahmed Esmael, Rashad R. Al-Hindi, Raed S. Albiheyri, Mona G. Alharbi, Amani A. R. Filimban, Mazen S. Alseghayer, Abdulaziz M. Almaneea, Meshari Ahmed Alhadlaq, Jumaa Ayubu, Addisu D. Teklemariam

Nebraska Center for Virology: Faculty Publications

The consumer demand for fresh produce (vegetables and fruits) has considerably increased since the 1980s for more nutritious foods and healthier life practices, particularly in developed countries. Currently, several foodborne outbreaks have been linked to fresh produce. The global rise in fresh produce associated with human infections may be due to the use of wastewater or any contaminated water for the cultivation of fruits and vegetables, the firm attachment of the foodborne pathogens on the plant surface, and the internalization of these agents deep inside the tissue of the plant, poor disinfection practices and human consumption of raw fresh produce. …

Neuronal Sirt3 Deletion Predisposes To Female-Specific Alterations In Cellular Metabolism, Memory, And Network Excitability, Jennifer N Pearson-Smith, Ruth Fulton, Christopher Q Huynh, Anna G Figueroa, Gia B Huynh, Li-Ping Liang, Lindsey B Gano, Cole R Michel, Nichole Reisdorph, Richard Reisdorph, Kristofer S Fritz, Eric Verdin, Manisha Patel

Faculty, Staff and Students Publications

Mitochondrial dysfunction is an early event in the pathogenesis of neurologic disorders and aging. Sirtuin 3 (SIRT3) regulates mitochondrial function in response to the cellular environment through the reversible deacetylation of proteins involved in metabolism and reactive oxygen species detoxification. As the primary mitochondrial deacetylase, germline, or peripheral tissue-specific deletion of SIRT3 produces mitochondrial hyperacetylation and the accelerated development of age-related diseases. Given the unique metabolic demands of neurons, the role of SIRT3 in the brain is only beginning to emerge. Using mass spectrometry-based acetylomics, high-resolution respirometry, video-EEG, and cognition testing, we report targeted deletion of SIRT3 from select neurons …

Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights …

Differences In Startle And Prepulse Inhibition In Contactin-Associated Protein-Like 2 Knock-Out Rats Are Associated With Sex-Specific Alterations In Brainstem Neural Activity, Alice Zheng, Kaela E Scott, Ashley L Schormans, Rajkamalpreet Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 (CNTNAP2) gene encodes for the CASPR2 protein, which plays an essential role in neurodevelopment. Mutations in CNTNAP2 are associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. Rats with a loss of function mutation in the Cntnap2 gene show increased acoustic startle response (ASR) and decreased prepulse inhibition (PPI). The neural basis of this altered auditory processing in Cntnap2 knock-out rats is currently unknown. Auditory brainstem recordings previously revealed no differences between the genotypes. The next step is to investigate brainstem structures outside of the primary auditory pathway that mediate ASR and PPI, which are …

Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz

UK CARES Faculty Publications

The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not …

Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei

Markey Cancer Center Faculty Publications

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …

Abstract 1858: Active And Allosteric Site Evolution Directs Ordered Water Use In Kinesin Catalysis, Micquel Downs, David Worthylake, Jessica Richard, Courtney Parke, Elizabeth Kim, Edward J. Wojcik, Sunyoung Kim

School of Graduate Studies Faculty Publications

2023 American Society for Biochemistry and Molecular Biology (ASBMB) Annual Meeting; March 25 - 28, 2023; Seattle, WA

Association Of IsvSa3 With Multidrug Resistance In Salmonella Enterica Isolates From Cattle (Bos Taurus), Gentry L. Lewis, Robert J. Fenton, Etsuko Moriyama, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Salmonella enterica is, globally, an important cause of human illness with beef being a significant attributable source. In the human patient, systemic Salmonella infection requires antibiotic therapy, and when strains are multidrug resistant (MDR), no effective treatment may be available. MDR in bacteria is often associated with the presence of mobile genetic elements (MGE) that mediate horizontal spread of antimicrobial resistance (AMR) genes. In this study, we sought to determine the potential relationship of MDR in bovine Salmonella isolates with MGE. The present study involved 111 bovine Salmonella isolates obtained collectively from specimens derived from healthy cattle or their environments …

Split And Join: An Efficient Approach For Simulating Stapled Intestinal Anastomosis In Virtual Reality, Di Qi, Suvranu De

Engineering Faculty Articles and Research

Colorectal cancer is a life-threatening disease. It is the second leading cause of cancer-related deaths in the United States. Stapled anastomosis is a rapid treatment for colorectal cancer and other intestinal diseases and has become an integral part of routine surgical practice. However, to the best of our knowledge, there is no existing work simulating intestinal anastomosis that often involves sophisticated soft tissue manipulations such as cutting and stitching. In this paper, for the first time, we propose a novel split and join approach to simulate a side-to-side stapled intestinal anastomosis in virtual reality. We mimic the intestine model using …

Intellectual Disability Related To De Novo Germline Loss Of The Distal End Of The P-Arm Of Chromosome 17: A Case Report, Eden Pope, Matthew Huertas, Amar Paul, Braden Cunningham, Matthew Jennings, Ryan Perry, Stephanie Chavez, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient.

Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv).

Results: Karyotype was …

Investigating Respiratory Simplification Caused By Prenatal Rage Upregulation, Paul Reynolds

Annual Research Symposium

No abstract provided.

Potential Role For Rage In The Development Of Secondhand Smoke-Induced Chronic Sinusitis, Paul Reynolds

Annual Research Symposium

No abstract provided.

Rage Inhibition Reduces Timp And Decreases Cell Invasion In Cigarette Smoke Extract (Cse) Treated Oral Squamous Carcinoma Cells, Paul Reynolds

Annual Research Symposium

No abstract provided.

Inflammatory Cytokine Elaboration Following Secondhand Smoke Exposure Is Mediated In Part By Rage Signaling, Paul Reynolds

Annual Research Symposium

No abstract provided.

Rage Availability Lessens The Degree Of Dysfunctional Mitochondrial Bioenergetics Following Chronic Secondhand Smoke Exposure, Paul Reynolds

Annual Research Symposium

No abstract provided.