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Targeting The Beiging Of Muscle-Associated Adipose Tissue To Promote Muscle Regeneration, Jacob C. Parson May 2025

Targeting The Beiging Of Muscle-Associated Adipose Tissue To Promote Muscle Regeneration, Jacob C. Parson

WUSM Theses and Dissertations – All Programs

The expansion of intra-muscular adipose tissue (IMAT) between myofibers and epi-muscular adipose tissue (EMAT) outside of the muscle boundary accompanies numerous pathologies including diabetes, muscular dystrophy, and aging. IMAT and EMAT are anatomically juxtaposed to myofibers. Some evidence supports that IMAT and EMAT impede muscle function. This is potentially due to paracrine factors that are secreted by IMAT/EMAT. Different adipose depots can be classified in numerous ways including where they are located anatomically as well as the factors in which they secrete. Unlike classical white fat, adipose depots classified as brown or beige, noted by the marker uncoupling protein-1 (UCP-1) …


Unmasking Masculinities In Counseling: From Conformity To Connection, Kyle R. Rose May 2025

Unmasking Masculinities In Counseling: From Conformity To Connection, Kyle R. Rose

Dissertations, 2020-current

This dissertation explored the entanglements of professional counseling and masculinities across three manuscripts, to contribute to (1) healthier forms of gender expression within and beyond the spectrum of masculinities for individuals, (2) the counseling profession’s role in transforming hegemonic masculinity within communities, and (3) larger movements to subvert the patriarchy throughout society. The first manuscript is a conceptual article that presented the Relational Cultural Privileged Identity Counseling (RCPIC) model, an integrative framework designed to help counselors address hegemonic masculinity within the therapeutic relationship. Drawing from Relational-Cultural Theory (RCT) and Privileged Identity Exploration (PIE), this model provided a roadmap for compassionate …


Establishing The Feasibility Of Sustained Sinusoidal Cervical Vestibular Evoked Myogenic Potentials In Young Adults, Ashton Fowlkes May 2025

Establishing The Feasibility Of Sustained Sinusoidal Cervical Vestibular Evoked Myogenic Potentials In Young Adults, Ashton Fowlkes

Dissertations, 2020-current

Cervical vestibular evoked myogenic potentials (cVEMPs) are used in clinics and research to assess the function of primarily the saccule. cVEMPs are typically stimulated with transient clicks or tone bursts through air conduction and are recorded from the sternocleidomastoid (SCM) muscle. The SCM is contracted by turning the head either left or right. In this study, we used sustained sinusoidal bone conducted stimuli. Using this new stimulus method allowed us to look at the possibility of a sustained cVEMP response, compared to the typically recorded transient response, as well as analyze the amplitude and signal-to-noise ratio (SNR) of the responses. …


Ubiquitin-Conjugating Enzyme Ube2n Modulates Proteostasis In Immunoproteasome-Positive Acute Myeloid Leukemia, Chiharu Ishikawa, Laura Barreyro, Avery M Sampson, Kathleen M Hueneman, Kwangmin Choi, Sophia Y Philbrook, Issac Choi, Lyndsey C Bolanos, Mark Wunderlich, Andrew G Volk, Stephanie S Watowich, Kenneth D Greis, Daniel T Starczynowski May 2025

Ubiquitin-Conjugating Enzyme Ube2n Modulates Proteostasis In Immunoproteasome-Positive Acute Myeloid Leukemia, Chiharu Ishikawa, Laura Barreyro, Avery M Sampson, Kathleen M Hueneman, Kwangmin Choi, Sophia Y Philbrook, Issac Choi, Lyndsey C Bolanos, Mark Wunderlich, Andrew G Volk, Stephanie S Watowich, Kenneth D Greis, Daniel T Starczynowski

Faculty, Staff and Student Publications

Altered protein homeostasis through proteasomal degradation of ubiquitinated proteins is a hallmark of many cancers. Ubiquitination, coordinated by E1, E2, and E3 enzymes, involves up to 40 E2-conjugating enzymes in humans to specify substrates and ubiquitin linkages. In a screen for E2 dependencies in acute myeloid leukemia (AML), ubiquitin conjugating enzyme E2 N (UBE2N) emerged as the top candidate. To investigate UBE2N's role in AML, we characterized an enzymatically defective mouse model of UBE2N, revealing UBE2N's requirement in AML without an impact on normal hematopoiesis. Unlike other E2s, which mediate lysine-48 (K48) polyubiquitination and degradation of proteins, UBE2N primarily synthesizes …


G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse May 2025

G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse

Faculty, Staff and Student Publications

Background: Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.

Methods: Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the …


Assessing The Effects Of Streptozotocin-Induced Hyperglycemia On Amyloid Beta Accumulation And Cognitive Behavior In A Mouse Model Of Alzheimer’S Disease-Related Pathology, Andrew Adonay Ortiz May 2025

Assessing The Effects Of Streptozotocin-Induced Hyperglycemia On Amyloid Beta Accumulation And Cognitive Behavior In A Mouse Model Of Alzheimer’S Disease-Related Pathology, Andrew Adonay Ortiz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is an irreversible and devastating neurodegenerative disease characterized by progressive synaptic, dendritic, glial, and neuronal loss, collectively leading to impairments in learning, memory, and deterioration of cognitive and behavioral functions. AD is the most common form of dementia accounting for 60-80% of all cases. AD affects approximately 7 million Americans and is the 6th leading cause of death in the US. Furthermore, by 2050, the US is projected to spend over $1.1 trillion on AD-related treatments. Pathological hallmarks of AD include beta-amyloid (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), and chronic neuroinflammation, which can promote and exacerbate both …


The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna May 2025

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna

Faculty, Staff and Student Publications

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …


Impact Of Safety Practices On Laboratory-Acquired Infections In Clinical Laboratories From 2018 To 2023, Lori Bane May 2025

Impact Of Safety Practices On Laboratory-Acquired Infections In Clinical Laboratories From 2018 To 2023, Lori Bane

Walden Dissertations and Doctoral Studies

Laboratorians identifying unknown pandemic pathogens face elevated risks of laboratory-acquired infections yet limited research examines how regulated safety practices influence these risks. This quantitative, correlational study used the Centers for Disease Control and Prevention’s secondary data (2018–2023) to examine two research questions. The first one questioned whether there were differences in safety incidents between registered and exempt clinical laboratories. The second research question investigated whether there was an association of laboratory incidents between BSL-2 and BSL-3 laboratories. The research was limited to incident reports from registered and exempted clinical laboratories working in BSL-2 and BSL-3 conditions. Guided by the Health …


Detection And Quantification Of Total Airborne Fungi And Coccidioides Species In Environmental Samples, Theresa T. Roehr May 2025

Detection And Quantification Of Total Airborne Fungi And Coccidioides Species In Environmental Samples, Theresa T. Roehr

UNLV Theses, Dissertations, Professional Papers, and Capstones

Fungal exposure can cause acute and chronic illnesses or exacerbate existing illnesses. Some fungi are opportunistic pathogens and can lead to serious systemic fungal infections. In 2020, more than 150 million cases of severe fungal infections were reported globally resulting in an estimated 1.7 million deaths. Coccidioidomycosis, or Valley fever, is classified as a serious fungal infection caused by the fungi Coccidioides immitis and C. posadasii. These particular fungi are prevalent in the soil of the Southwestern United States, including Las Vegas, Nevada. In 2024, there were a total of 269 cases of Valley fever reported in Nevada, and …


Sickle Cell Mice Exhibit Elevated Plasma Bilirubin And Altered Intracranial Cerebral Blood Velocities That Are Exacerbated By Hypoxia-Reoxygenation, Francisco J. Nunez, Ashraf M. Mohieldin, Amy Y. Pan, Sean P. Palecek, Rahima Zennadi, Ramani Ramchandran, Kevin R. Rarick, Surya M. Nauli May 2025

Sickle Cell Mice Exhibit Elevated Plasma Bilirubin And Altered Intracranial Cerebral Blood Velocities That Are Exacerbated By Hypoxia-Reoxygenation, Francisco J. Nunez, Ashraf M. Mohieldin, Amy Y. Pan, Sean P. Palecek, Rahima Zennadi, Ramani Ramchandran, Kevin R. Rarick, Surya M. Nauli

Pharmacy Faculty Articles and Research

Sickle cell disease (SCD) is a genetic disorder characterized by sickle red blood cells (RBCs). Sickle RBCs cause cerebral vasculopathies including vaso-occlusive events, leading to ischemia-reperfusion injury and hypoxic tissue environment. To date, the physiological blood flow velocities in cerebral vessels of preclinical SCD models has not been evaluated under hypoxic-reoxygenation. In our study, we used transcranial ultrasound techniques to measure abnormal blood flow velocities in the internal carotid (ICA) and middle cerebral arteries (MCA) of transgenic sickle cell mice (SS) challenged with hypoxia-reoxygenation. Our study showed that SS mice that underwent hypoxic stress exhibited lower relative mean velocities in …


Finite Element Analysis Of Stress Distribution In Unilateral Distal Extension Partial Dentures: A Comparison Of Four Attachment Designs, Maha Nagy Kamal, Haitham Amr, Abdallah Shokry May 2025

Finite Element Analysis Of Stress Distribution In Unilateral Distal Extension Partial Dentures: A Comparison Of Four Attachment Designs, Maha Nagy Kamal, Haitham Amr, Abdallah Shokry

Dentistry

No abstract provided.


Divergent Dna Methylation Dynamics In Marsupial And Eutherian Embryos, Bryony J. Leeke, Wazeer Varsally, Sugako Ogushi, Jasmin Zohren, Sergio Menchero, Aurélien Courtois, Daniel M. Snell, Aurélie Teissandier, Obah Ojarikre, John L. Vandeberg May 2025

Divergent Dna Methylation Dynamics In Marsupial And Eutherian Embryos, Bryony J. Leeke, Wazeer Varsally, Sugako Ogushi, Jasmin Zohren, Sergio Menchero, Aurélien Courtois, Daniel M. Snell, Aurélie Teissandier, Obah Ojarikre, John L. Vandeberg

School of Medicine Publications

Based on seminal work in placental species (eutherians)1,2,3,4,5,6,7,8,9,10, a paradigm of mammalian development has emerged wherein the genome-wide erasure of parental DNA methylation is required for embryogenesis. Whether such DNA methylation reprogramming is, in fact, conserved in other mammals is unknown. Here, to resolve this point, we generated base-resolution DNA methylation maps in gametes, embryos and adult tissues of a marsupial, the opossum Monodelphis domestica, revealing variations from the eutherian-derived model. The difference in DNA methylation level between oocytes …


Q Fever Pericardial And Pleural Effusions In A Pediatric Patient, Jonathan Ermer, Ben Kazdan, Cooper Bassham, Jacqueline Walker May 2025

Q Fever Pericardial And Pleural Effusions In A Pediatric Patient, Jonathan Ermer, Ben Kazdan, Cooper Bassham, Jacqueline Walker

Research Days

Background: Q fever is a bacterial infection caused by Coxiella burnetii. Q fever commonly presents with flu-like symptoms (fever, chills, fatigue, myalgias) in patients about 2-3 weeks after exposure to farm animals. Less commonly, Q fever can cause severe illness such as myocarditis, pericarditis, or meningitis. We present a rare case of a pediatric patient with pericardial and pleural effusions secondary to Q fever.

Case presentation: History of present illness: The patient is a 9-year-old female who presented as a referral from an outside hospital due to chest pain, shortness of breath, and 2 weeks of fever. The patient started …


“Restless And Uneasy…Thin And Stretched”: The Ring, The Ringbearers, And Bodies In Psychological Crisis In Tolkien’S The Lord Of The Rings., Sara Brown May 2025

“Restless And Uneasy…Thin And Stretched”: The Ring, The Ringbearers, And Bodies In Psychological Crisis In Tolkien’S The Lord Of The Rings., Sara Brown

Journal of Tolkien Research

The attachment that Tolkien’s Ring-bearers have for the Ring, a twisted and perverted form of love, is sterile and barren; it leaves those affected unable to settle and form fruitful, loving relationships with others, an effect that Tolkien referred to as a “Ring-restlessness.” Gollum, Bilbo, and Frodo all suffer, to their own degree, from the psychological crisis caused by the Ring that renders them uneasy and agitated. This paper examines this crisis through a psychological lens, exploring how the Ringbearers are living in discord with their true selves, and struggling with the meaninglessness of life that the Ring leaves behind.


Perceiving The Perceiver: “Viewing” Sauron Through The Gestalt Theory Of Perception, Cameron Bourquein May 2025

Perceiving The Perceiver: “Viewing” Sauron Through The Gestalt Theory Of Perception, Cameron Bourquein

Journal of Tolkien Research

This paper uses Gestalt theory, the Gestalt laws of perception, and the reception theory of Wolfgang Iser to elucidate the character “Sauron” as he appears in The Lord of the Rings, The Rings of Power, and Tolkien’s wider legendarium. It argues firstly that Sauron’s high degree of indeterminacy and ambiguity suggests he can be read as a gestalt entity, one the reader creates by mentally constructing a whole from (seemingly) disparate parts. Building on the semiotics work of Nagy (2013), it argues that Sauron in The Lord of the Rings can be read as gestalt across the spatial, …


Staff Education For Nursing Teach-Back Facilitation To Reduce Frequent Readmission, Chikamunario Joy Ekeke May 2025

Staff Education For Nursing Teach-Back Facilitation To Reduce Frequent Readmission, Chikamunario Joy Ekeke

Walden Dissertations and Doctoral Studies

Background: Teach-Back method of education is a simple technique that can be used to check, and correct inaccurate recall of patients’ instructions. It has a great impact on patients’ recall and understanding of discharged information in a healthcare setting and to help minimize hazards such as non-medication adherence, frequent re-hospitalization, and poor self-care/home care (Talevski et al., 2020). Gap in Practice/Problem: “Frequent readmission (30 days Return) of patients in a Rural Psychiatric Center.” The Practice Focus Question: “Does staff education on “teach-back” facilitate the knowledge and confidence level of staff in providing discharged patient education and subsequently minimize frequent rehospitalization?” …


Autophagy Is Required For The Therapeutic Effects Of The Nad+ Precursor Nicotinamide In Obesity-Related Heart Failure With Preserved Ejection Fraction, Mahmoud Abdellatif, Moydul Islam, Abhinav Diwan, Et Al. May 2025

Autophagy Is Required For The Therapeutic Effects Of The Nad+ Precursor Nicotinamide In Obesity-Related Heart Failure With Preserved Ejection Fraction, Mahmoud Abdellatif, Moydul Islam, Abhinav Diwan, Et Al.

2020-Current year OA Pubs

No abstract provided.


A Role For Δ Subunit-Containing Gabaa Receptors On Parvalbumin-Positive Neurons In Maintaining Electrocortical Signatures Of Sleep States, Peter M Lambert, Sofia V Salvatore, Xinguo Lu, Hong-Jin Shu, Ann Benz, Nicholas Rensing, Carla M Yuede, Michael Wong, Charles F Zorumski, Steven Mennerick May 2025

A Role For Δ Subunit-Containing Gabaa Receptors On Parvalbumin-Positive Neurons In Maintaining Electrocortical Signatures Of Sleep States, Peter M Lambert, Sofia V Salvatore, Xinguo Lu, Hong-Jin Shu, Ann Benz, Nicholas Rensing, Carla M Yuede, Michael Wong, Charles F Zorumski, Steven Mennerick

2020-Current year OA Pubs

GABA


Physician Assistant 20-Minute Introduction, Daniel Fidel Ferrer May 2025

Physician Assistant 20-Minute Introduction, Daniel Fidel Ferrer

Other Scholarly Works

No abstract provided.


Chronic Inflammatory Pain And Chronic Thc Vapor Inhalation Alter Midbrain Neuronal Activity, Leslie K. Kelley, Nicholas W. Gilpin, Jason W. Middleton May 2025

Chronic Inflammatory Pain And Chronic Thc Vapor Inhalation Alter Midbrain Neuronal Activity, Leslie K. Kelley, Nicholas W. Gilpin, Jason W. Middleton

School of Medicine Faculty Publications

In an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic delta-9 tetrahydrocannabinol (THC) vapor inhalation effects on intrinsic and synaptic properties of ventrolateral periaqueductal gray (vlPAG) neurons in male and female rats treated with complete Freund's adjuvant (CFA). We report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically …


Multifaceted Roles Of Epac Signaling In Renal Functions, Oleh Pochynyuk, Kyrylo Pyrshev, Xiaodong Cheng May 2025

Multifaceted Roles Of Epac Signaling In Renal Functions, Oleh Pochynyuk, Kyrylo Pyrshev, Xiaodong Cheng

The Brown Foundation: Institute of Molecular Medicine

3',5'-cyclic adenosine monophosphate (cAMP) is a fundamental secondary messenger capable of rapidly amplifying and propagating cellular signals in response to various extracellular stimuli. cAMP plays a significant role in hormone-mediated regulation of renal fluid and electrolyte balance. Impaired signaling of cAMP has been linked to a variety of pathological ramifications in the kidneys. This review explores the physiological functions of exchange proteins directly activated by cAMP (Epac) in renal water balance and the regulation of solute transport in the renal tubule. Additionally, the involvement of Epac signaling in renal pathologies such as acute kidney injury, chronic kidney disease, and polycystic …


Genome-Wide Allele-Specific Expression In Multi-Tissue Samples From Healthy Male Baboons Reveals The Transcriptional Complexity Of Mammals, Ramesh Ramasamy, Muthuswamy Raveendran, R Alan Harris, Hiep D Le, Ludovic S Mure, Giorgia Benegiamo, Ouria Dkhissi-Benyahya, Howard Cooper, Jeffrey Rogers, Satchidananda Panda May 2025

Genome-Wide Allele-Specific Expression In Multi-Tissue Samples From Healthy Male Baboons Reveals The Transcriptional Complexity Of Mammals, Ramesh Ramasamy, Muthuswamy Raveendran, R Alan Harris, Hiep D Le, Ludovic S Mure, Giorgia Benegiamo, Ouria Dkhissi-Benyahya, Howard Cooper, Jeffrey Rogers, Satchidananda Panda

Faculty, Staff and Students Publications

Allele-specific expression (ASE) is pivotal in understanding the genetic underpinnings of phenotypic variation within species, differences in disease susceptibility, and responses to environmental factors. We processed 11 different tissue types collected from 12 age-matched healthy olive baboons (Papio anubis) for genome-wide ASE analysis. By sequencing their genomes at a minimum depth of 30×, we identified over 16 million single-nucleotide variants (SNVs). We also generated long-read sequencing data, enabling the phasing of all variants present within the coding regions of 96.5% of assayable protein-coding genes as a single haplotype block. Given the extensive heterozygosity of baboons relative to humans, we could …


Forward Genetic Screen In Zebrafish Identifies New Fungal Regulators That Limit Host-Protective Candida-Innate Immune Interaction, Bailey A Blair, Emma Bragdon, Gursimran Dhillon, Nnamdi Baker, Lena Stasiak, Mya Muthig, Pedro Miramon, Michael C Lorenz, Robert T Wheeler May 2025

Forward Genetic Screen In Zebrafish Identifies New Fungal Regulators That Limit Host-Protective Candida-Innate Immune Interaction, Bailey A Blair, Emma Bragdon, Gursimran Dhillon, Nnamdi Baker, Lena Stasiak, Mya Muthig, Pedro Miramon, Michael C Lorenz, Robert T Wheeler

Faculty, Staff and Student Publications

Candida is one of the most frequent causes of bloodstream infections, and our first line of defense against these invasive infections is the innate immune system. The early immune response is critical in controlling Candida albicans infection, but C. albicans has several strategies to evade host immune attack. Phagocytosis of C. albicans blocks hyphal growth, limiting host damage and virulence, but how C. albicans limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131 C. albicans mutants for altered …


Immunotherapy With Nebulized Pattern Recognition Receptor Agonists Restores Severe Immune Paralysis And Improves Outcomes In Mice With Influenza-Associated Pulmonary Aspergillosis, Jezreel Pantaleón García, Sebastian Wurster, Nathaniel D Albert, Uddalak Bharadwaj, Keerthi Bhoda, Vikram K Kulkarni, Mbaya Ntita, Paris Rodríguez Carstens, Madeleine Burch-Eapen, Daniela Covarrubias López, Jania Foncerrada Lizaola, Katherine E Larsen, Lauren M Matula, Seyed J Moghaddam, Yongxing Wang, Dimitrios P Kontoyiannis, Scott E Evans May 2025

Immunotherapy With Nebulized Pattern Recognition Receptor Agonists Restores Severe Immune Paralysis And Improves Outcomes In Mice With Influenza-Associated Pulmonary Aspergillosis, Jezreel Pantaleón García, Sebastian Wurster, Nathaniel D Albert, Uddalak Bharadwaj, Keerthi Bhoda, Vikram K Kulkarni, Mbaya Ntita, Paris Rodríguez Carstens, Madeleine Burch-Eapen, Daniela Covarrubias López, Jania Foncerrada Lizaola, Katherine E Larsen, Lauren M Matula, Seyed J Moghaddam, Yongxing Wang, Dimitrios P Kontoyiannis, Scott E Evans

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a potentially deadly superinfection in patients with influenza pneumonia, especially those with severe disease, underlying immunosuppression, corticosteroid therapy, or requiring intensive care support. Given the high mortality of IAPA, adjunct immunomodulatory strategies remain a critical unmet need. Previously, the desensitization of pattern recognition pathways has been described as a hallmark of IAPA pathogenesis and a predictor of mortality in IAPA patients. Therefore, we studied the impact of nebulized Toll-like receptor 2/6/9 agonists Pam2 CSK4 (Pam2) and CpG oligodeoxynucleotides (ODNs) on infection outcomes and pulmonary immunopathology in a corticosteroid-immunosuppressed murine IAPA model. Mice with IAPA receiving …


Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian May 2025

Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional θ-waves. The resemblances between θ-oscillons and the conventional θ-waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled …


Structural And Molecular Basis Of Pcna-Activated Fan1 Nuclease Function In Dna Repair, F. Li, A. S. Phadte, M. Bhatia, S. Barndt, A.R. Monte Carlo, Iii, C.F.D. Hou, R. Yang, S. Strock, A. Pluciennik May 2025

Structural And Molecular Basis Of Pcna-Activated Fan1 Nuclease Function In Dna Repair, F. Li, A. S. Phadte, M. Bhatia, S. Barndt, A.R. Monte Carlo, Iii, C.F.D. Hou, R. Yang, S. Strock, A. Pluciennik

Department of Biochemistry and Molecular Biology Faculty Papers

FAN1 is a DNA dependent nuclease whose proper function is essential for maintaining human health. For example, a genetic variant in FAN1, Arg507 to His hastens onset of Huntington's disease, a repeat expansion disorder for which there is no cure. How the Arg507His mutation affects FAN1 structure and enzymatic function is unknown. Using cryo-EM and biochemistry, we have discovered that FAN1 arginine 507 is critical for its interaction with PCNA, and mutation of Arg507 to His attenuates assembly of the FAN1-PCNA complex on a disease-relevant extrahelical DNA extrusions formed within DNA repeats. This mutation concomitantly abolishes PCNA-FAN1-dependent cleavage of such …


Dnmt3a Regulates Murine Megakaryocyte-Biased Hematopoietic Stem Cell Fate Decisions, Sarah M Waldvogel, Virginia Camacho, Dandan Fan, Anna G Guzman, Alejandra Garcia-Martell, Elmira Khabusheva, Jacey Rodriguez Pridgen, Josephine De La Fuente, Rachel Rau, Ashlyn G Laidman, Maria N Barrachina, Estelle Carminita, Justin A Courson, Michael R Williamson, Joanne I Hsu, Chun-Wei Chen, Jaime Reyes, Subhashree Pradhan, Rolando E Rumbaut, Alan R Burns, Benjamin Deneen, Jianzhong Su, Kellie R Machlus, Margaret A Goodell May 2025

Dnmt3a Regulates Murine Megakaryocyte-Biased Hematopoietic Stem Cell Fate Decisions, Sarah M Waldvogel, Virginia Camacho, Dandan Fan, Anna G Guzman, Alejandra Garcia-Martell, Elmira Khabusheva, Jacey Rodriguez Pridgen, Josephine De La Fuente, Rachel Rau, Ashlyn G Laidman, Maria N Barrachina, Estelle Carminita, Justin A Courson, Michael R Williamson, Joanne I Hsu, Chun-Wei Chen, Jaime Reyes, Subhashree Pradhan, Rolando E Rumbaut, Alan R Burns, Benjamin Deneen, Jianzhong Su, Kellie R Machlus, Margaret A Goodell

Center on Aging Staff Publications

Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but few differential regulatory mechanisms have been identified. In this work, we explored the role of DNA methyltransferase 3A (DNMT3A) in the megakaryocyte-biased HSC population, which is thought to reside at the top of the hematopoietic hierarchy. We demonstrate that heterozygous loss of DNMT3A (Dnmt3a+/-) in these megakaryocyte-biased HSCs has distinct consequences compared with the rest of the HSC pool. These megakaryocyte-biased …


Investigating Undergraduate Conditioned Place Preference Utilizing Virtual Alcohol Stimuli, Nikole A. Rodriguez Torres, Robert Astur, Jeffrey Divino May 2025

Investigating Undergraduate Conditioned Place Preference Utilizing Virtual Alcohol Stimuli, Nikole A. Rodriguez Torres, Robert Astur, Jeffrey Divino

Honors Scholar Theses

Alcohol use remains a major concern among college students, with binge drinking linked to serious physical and mental health problems. But how much does the environment influence these addictive behaviors? The relationship between environmental cues and alcohol related behaviors is a critical area of study, particularly understanding reward and motivation mechanisms. Binge drinking, common among college students, is associated with a range of negative outcomes such as physical harm, legal issues, poorer overall health, sleep problems, depression, anxiety, and severe thoughts of suicide. In our study, college undergraduates were exposed to two VR rooms: one with alcohol-related stimuli and one …


Polychlorinated Biphenyl-126 Activates Axl/Erb/Dnmt3a Axis To Drive Endometriosis Progression, Yuri Park, Nuri Sung, Eunsu Kim, Jaeyeong Jeong, Juhee Sim, Mi Jin Park, John Lydon, Xiaoming Guan, Sang Jun Han May 2025

Polychlorinated Biphenyl-126 Activates Axl/Erb/Dnmt3a Axis To Drive Endometriosis Progression, Yuri Park, Nuri Sung, Eunsu Kim, Jaeyeong Jeong, Juhee Sim, Mi Jin Park, John Lydon, Xiaoming Guan, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is a pathological condition in which endometrial cells proliferate outside the uterine cavity, resulting in pelvic pain and infertility. Exposure to endocrine-disrupting chemicals (EDCs) has been implicated in the progression of endometriosis, though the precise mechanisms remain largely undefined. Among EDCs, elevated levels of polychlorinated biphenyl (PCB)-126 have been strongly associated with endometriosis, particularly in patients with deep infiltrating disease. In a mouse model of endometriosis, PCB-126 exposure significantly promoted the growth of ectopic lesions by activating the Steroid Receptor Coactivator-1 (SRC-1) isoform/Matrix Metalloproteinase-9 (MMP9)/Estrogen Receptor-β (ERβ) axis, a key driver of disease progression. PCB-126 also enhanced ERβ activity …


Temporal Regulation Of Early-Stage Cytokine Expression In Diabetic Wound Healing Under Negative Pressure Wound Therapy, Hua-Sheng Chiu, Ting-Shuo Huang, Chien-Tzung Chen, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Chih-Chin Hsu, Sonal Somvanshi, Pavel Sumazin, Pang-Hung Hsu, Chi-Chin Sun, Yu-Chiau Shyu May 2025

Temporal Regulation Of Early-Stage Cytokine Expression In Diabetic Wound Healing Under Negative Pressure Wound Therapy, Hua-Sheng Chiu, Ting-Shuo Huang, Chien-Tzung Chen, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Chih-Chin Hsu, Sonal Somvanshi, Pavel Sumazin, Pang-Hung Hsu, Chi-Chin Sun, Yu-Chiau Shyu

Faculty, Staff and Students Publications

Negative pressure wound therapy (NPWT) is widely recognized for its efficacy in treating diabetic wounds, but the mechanisms involved in the wound healing process remain unclear. By examining changes in blood cytokine levels as molecular signaling precursors, we aim to provide a comprehensive cytokine profile to support adjunctive therapy research and clinical applications. A diabetic mouse wound model was established to compare cytokine profiles between NPWT-treated and standard dressing groups, identifying key signaling candidates that may facilitate wound healing. By integrating normal mouse data with large-scale cytokine analysis, we developed a time-stratified NPWT approach to track acute-phase cytokine fluctuations in …