Digital Commons Network^™

Investigating Empathy In Rats: Behavioral Responses To Distress, Isabella Sophia Avery, Kolette Stuhmer, Jeffrey Schell

2025 Symposium

INTRODUCTION: Empathy can be defined as the ability to recognize, understand, and match one’s emotional state to that of another. Previous research has suggested that emotional contagion produces empathetic responses among familiar rats when their cage mate is exposed to a stressor. This study seeks to further explore this relationship and compare responses among familiar vs. unfamiliar rats. METHODS: Male and female Sprague-Dawley rats were divided into cohorts including an observer, demonstrator, and stranger rat. The demonstrator was exposed to shock paired with a tone and the demonstrator, its cage mate, was only exposed a tone but no shock. The …

Fear And Oxytocin: Effects Of Intraperitoneal Pretreatment In Rats, Daniel Yeromenko, Kelsie German, Eros Fuentes, Jenna Meade, Ben Bustos

2025 Symposium

INTRODUCTION: Oxytocin is a neuropeptide widely known for its role in social bonding and emotional regulation. Recent studies have suggested its involvement in modulating fear, stress, and anxiety responses, potentially offering therapeutic applications for trauma-related disorders such as PTSD. This study investigated whether pretreatment with oxytocin reduces behavioral and physiological fear responses in male and female Sprague-Dawley rats using a classical fear conditioning model. METHODS : Twenty-four Sprague-Dawley rats (12 males, 12 females) were assigned to one of four groups: control (no shock, no oxytocin), shock only, shock + low-dose oxytocin (0.5 mg/kg), and shock + high-dose oxytocin (1.0 mg/kg). …

Preparation And In-Vitro Evaluation Of Dompridone Oral Thin Film, Fatima Mohammed Hussein Wais

Maaen Journal for Medical Sciences

The aim of the current study was to formulate and evaluatedompridone nanoparticles and loaded in oral fast dissolve film, for enhance the solubility of poor water soluble dompridone by nanoparticles and fasten the action by prepared as oral thin film and also to improve patient compliance. Domperidone is the recommended medication for nausea and vomiting brought on by viral infections, chemotherapy, migraines, and food poisoning.Domperidonenanoparticles were made using two type of polymers (hydroxypropyl methylcellulose HPMC-K15 and methylcellulose MC-A4C) in a range of ratios (1:1, 1:2, and 1:3) drug:polymer ratio by solvent antisolvent technique. In nanoparticle formulation, HPMC-K15 and MC-A4C were …

Intouch Week Of May 19, 2025, New York Medical College

InTouch

• Vikas Grover, Ph.D., CCC-SLP, and Ronnie Myers, D.D.S., Named Healthcare Heroes by Westchester Magazine
• Annual Louis Del Guercio, M.D., Research Day Showcases Outstanding Surgical Research
• NYMC Celebrates Homecoming 2025 with Alumni, Students, and Campus Tours
• Teaching and Learning Symposium Brings Faculty Together to Enrich Their Educational Practice
• Philip Kuehl, Ph.D., Addresses Drug Development Problem Statements at the Neighborhood Science Seminar Series
• 185 TCDM Students Don White Coats as They Head to Touro Dental Health Clinics in New York and New Mexico
• Student Spotlight: David Zuckerman to Address Graduates Before Beginning Neurology Residency at NYU

Ccaat/Enhancer-Binding Proteins Α And Β Regulate Ovulation And Gene Expression Via Dose- And Stage-Dependent Mechanisms, Hanxue Zhang, Rainer B Lanz, Jimmy Dhillon, Paul D Soloway, Bo Shui, Yi Athena Ren

Faculty, Staff and Students Publications

The preovulatory luteinizing hormone (LH) surge orchestrates complex cellular and molecular events leading to ovulation. CCAAT/enhancer-binding proteins α and β (C/EBPα/β) are transcription factors acutely induced by the LH surge and crucial for ovulation and granulosa cell luteinization. However, biological processes (BPs) and their regulatory mechanisms downstream of C/EBPα/β in the preovulatory ovary are not completely understood. To address this knowledge gap, we generated Cebpa/bfl/fl;Pgr-Cre mutants and compared them with Cebpa/bfl/fl;Cyp19a1-Cre mutant female mice: Cebpa/bfl/fl;Cyp19a1-Cre mutants have undetectable levels of C/EBPα/β throughout the preovulatory stages and do not ovulate, aligning with previous reports; and Cebpa/bfl/fl;Pgr-Cre mutants present gradual depletion of …

Approach To The Patient: From Endocrinopathy To The Diagnosis Of A Histiocytic Disorder, Polyzois Makras, Dana Erickson, Caroline J Davidge-Pitts, Eli L Diamond, Carl E Allen, Kenneth L Mcclain, Jithma P Abeykoon, Ronald S Go, Krishmita Siwakoti, Houman Sotoudeh, Aishwarya Ravindran, Lucinda M Gruber, Gaurav Goyal

Faculty, Staff and Students Publications

Endocrinopathies are frequently the initial presentation of histiocytic neoplasms, which are rare hematologic disorders affecting multiple organ systems. Langerhans cell histiocytosis and Erdheim-Chester disease are 2 such disorders known to infiltrate the hypothalamus and/or pituitary gland, leading to arginine vasopressin deficiency (AVP-D) and anterior pituitary dysfunction (APD) in 20% to 30% of cases, often as the first manifestation. Conversely, histiocytic disorders account for a notable proportion (10-15%) of all pituitary stalk lesions. The diagnosis of histiocytoses is often delayed in such cases due to the nonspecific presentation of endocrinopathies and pituitary involvement. Consequently, endocrinologists are at the frontline and uniquely …

Human Endogenous Retroviruses (Hervs) Associated With Glioblastoma Risk And Prognosis, Harun Mazumder, Hui Yi Lin, Melody Baddoo, Wojciech Gałan, Diana Polania-Villanueva, Chindo Hicks, David Otohinoyi, Francesca Peruzzi, Zbigniew Madeja, Victoria P. Belancio, Erik K. Flemington, Krzysztof Reiss, Monika Rak

School of Medicine Faculty Publications

Emerging evidence suggests expression from human endogenous retrovirus (HERV) loci likely contributes to, or is a biomarker of, glioblastoma multiforme (GBM) disease progression. However, the relationship between HERV expression and GBM malignant phenotype is unclear. Applying several in silico analyses based on data from The Cancer Genome Atlas (TCGA), we derived a locus-specific HERV transcriptome for glioma that revealed 211 HERVs significantly dysregulated in the comparisons of GBM vs. normal brain (NB), GBM vs. low-grade glioma (LGG), and LGG vs. NB. Our analysis supported development of a unique HERV scoring algorithm that segregated GBM, LGG, and NB. Interestingly, lower HERV …

Optimizing Genetic Ancestry Adjustment In Dna Methylation Studies: A Comparative Analysis Of Approaches, Kira D Höffler, Seyma Katrinli, Matthew W Halvorsen, Anne-Kristin Stavrum, Kevin S O'Connell, Alexey Shadrin, Srdjan Djurovic, Ole A Andreassen, James J Crowley, Jan Haavik, Kristen Hagen, Gerd Kvale, Kerry Ressler, Bjarne Hansen, Jair C Soares, Gabriel R Fries, Alicia K Smith, Stéphanie Le Hellard

Faculty, Staff and Student Publications

Background: Genetic ancestry is an important factor to account for in DNA methylation studies because genetic variation influences DNA methylation patterns. One approach uses principal components (PCs) calculated from CpG sites that overlap with common SNPs to adjust for ancestry when genotyping data is not available. However, this method does not remove technical and biological variations, such as sex and age, prior to calculating the PCs. The first PC is therefore often associated with factors other than ancestry.

Methods: We developed and adapted the adapted EpiAnceR + approach, which includes 1) residualizing the CpG data overlapping with common SNPs for …

Neoadjuvant With Low-Dose Radiotherapy, Tislelizumab, Albumin-Bound Paclitaxel, And Cisplatin For Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma: Phase Ii Single-Arm Trial, Zhigang Liu, Dong Wang, Guanjun Li, Muhua Yi, Zhaoyuan Zhang, Guihua Zhong, Liangfu Xu, Rong Jiang, Yannan Zheng, Linxuan Huang, Yingpeng Peng, Lizhong Liang, Jianpeng Li, Ye Liu, Jun Lai, Xianjuan Lv, Yongqiang Xu, Qiaodan Liu, Zhiqiang Wang, Zhutian Liu, Qinan Yang, Li Nie, Jiao Lei, Xiaotao Huang, Zhijie Liu, Wen Jiang

Faculty, Staff and Student Publications

Although pathological complete response (pCR) and major pathological response (MPR) rates of neoadjuvant immunotherapy combined with chemotherapy in head and neck squamous cell carcinoma (HNSCC) trials remain suboptimal, emerging evidence highlights the synergistic potential of combining low-dose radiotherapy with immunotherapy to promote the efficacy of immunotherapy. This phase II, open-label, single-arm, multicenter trial (NCT05343325) enrolled 28 patients with untreated stage III-IVB HNSCC (NeoRTPC02). Patients received neoadjuvant low-dose radiotherapy, the programmed death-1 (PD-1) inhibitor tislelizumab, albumin-bound paclitaxel, and cisplatin for two cycles, followed by radical resection ~4 weeks after treatment completion. The primary endpoint, pCR rate, was achieved in 14 of …

Functional Analysis Of Pathogenic Variants In Lamb1-Related Leukoencephalopathy Reveals Genotype-Phenotype Correlations And Suggests Its Role In Glial Cells, Rei Yasuda, Hirokazu Hashimoto, Mikiko Oka, Jung-Wan Mok, Marium Waqar, Brigitte Dauwalder, Oguz Kanca, Toshiki Mizuno, Shinya Yamamoto

Faculty, Staff and Students Publications

Laminin B1 (LAMB1) is one of the extracellular matrix (ECM) proteins that make up the basement membrane. Early frameshift, late frameshift, and missense variants in LAMB1 have been reported to cause rare monogenic neurological disorders that are collectively known as LAMB1-related leukoencephalopathy. Although there is some genotype-phenotype correlation, functional consequences of pathogenic LAMB1 variants are largely unknown. In this study, we aimed to elucidate function of the fly ortholog of this gene (LanB1) in the nervous system and to further study the functional consequences of the LAMB1 variants using Drosophila melanogaster. We found that the LanB1 gene is expressed on …

Navigating The Future Of Polygenic Risk Scores: Insights From Child And Adolescent Psychiatrists, Page M Trotter, Amanda R Merner, Lauren A Ginn, Abigail C Martinez, Ana L Battaglino, Kaitlynn P Craig, Jason Bach, Katherine J Freedberg, Takahiro Soda, Eric A Storch, Gabriel Lázaro-Muñoz, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Polygenic risk scores (PRS) are a method of calculating genetic risk for polygenic, or multi-gene, disorders. These scores have potential impacts in the realm of child and adolescent psychiatry, given the high prevalence of psychiatric disorders among youth. However, there are concerns about PRS implementation among key stakeholders, namely child and adolescent psychiatrists (CAP). We conducted interviews with 29 U.S.-based CAP to investigate clinician attitudes toward the use of PRS. The data herein correspond to a future scenario we provided CAP in which PRS are accurate and portable to patients of different racial and ethnic backgrounds. We found that CAP …

High Kynu Expression Is Associated With Poor Prognosis, Keap1/Stk11 Mutations, And Immunosuppressive Metabolism In Patient-Derived But Not Murine Lung Adenocarcinomas, Ling Cai, Thomas J Rogers, Reza Mousavi Jafarabad, Hieu Vu, Chendong Yang, Nicole Novaresi, Ana Galán-Cobo, Luc Girard, Edwin J Ostrin, Johannes F Fahrmann, Jiyeon Kim, John V Heymach, Kathryn A O'Donnell, Guanghua Xiao, Yang Xie, Ralph J Deberardinis, John D Minna

Faculty, Staff and Student Publications

Background/Objectives: We aimed to discover genes with bimodal expression linked to patient outcomes, to reveal underlying oncogenotypes and identify new therapeutic insights in lung adenocarcinoma (LUAD).

Methods: We performed meta-analysis to screen LUAD datasets for prognostic genes with bimodal expression patterns. Kynureninase (KYNU), a key enzyme in tryptophan catabolism, emerged as a top candidate. We then examined its relationship with LUAD mutations, metabolic alterations, immune microenvironment states, and expression patterns in human and mouse models using bulk and single-cell transcriptomics, metabolomics, and preclinical model datasets. Pan-cancer prognostic associations were also assessed.

Results: Model-based clustering of KYNU expression outperformed median-based dichotomization …

Roles Of Class Iii Phosphatidylinositol 3-Kinase, Vps34, In Phagocytosis, Autophagy, And Endocytosis In Retinal Pigmented Epithelium, Feng He, Ralph M Nichols, Melina A Agosto, Theodore G Wensel

Faculty, Staff and Students Publications

Phosphatidylinositol-3-phosphate (PI(3)P) is important for multiple functions of retinal pigmented epithelial (RPE) cells, but its functions in RPE have not been studied. In RPE from mouse eyes and in cultured human RPE cells, PI(3)P-enriched membranes include endosomes, the trans-Golgi network, phagosomes, and autophagophores. Mouse RPE cells lacking activity of the PI-3 kinase, Vps34, lack detectable PI(3)P and die prematurely. Phagosomes containing rod discs accumulate, as do membrane aggregates positive for autophagosome markers. These autophagy-related membranes recruit LC3/Atg8 without Vps34, but phagosomes do not. Vps34 loss leads to accumulation of lysosomes which do not fuse with phagosomes or membranes with …

Novel Rpl30 Variant In Diamond Blackfan Anemia Demonstrates Early Impact On Erythroid Differentiation With Downregulated Gata1-Hsp70, Alexandra Prosser-Dombrowski, Irina Pushel, Jacqelyn Nemechek, Priyanka Kumar, Jay L. Vivian, Jennifer Gerton, John M. Perry

Research Days

Background: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome caused by ribosomal protein gene mutations leading to apoptosis of erythroid progenitors. We identified a novel heterozygous variant (c.167+769C>T) in the noncoding region of RPL30 in a patient diagnosed with DBA.

Objectives/Goal: We hypothesized that this variant stunts erythroid differentiation at the proerythroblast stage and is pathogenic for DBA.

Methods/Design: We developed an induced pluripotent stem cell (iPSC) model with a wild type (WT) and three CRISPR-Cas9 edited RPL30 mutant clones. iPSCs were differentiated into hematopoietic stem cells, which were assessed by flow cytometry and single cell …

Pcsk-9 Inhibitors Treatment: The Cardiovascular Disparity, Julia Lees, Seana-Pierre Williams, Tahir Razzaq, Michael B. Roberts

The Journal of Integrated Primary Care

Introduction: According to the Center for Disease Control and Prevention (CDC) and American Heart Association (AHA), cardiovascular disease is the leading cause of death in the United States. This phenomenon disproportionally affects the African American population, who have a 31% higher mortality rate than non-Hispanic Caucasian individuals. A retrospective review of PCSK-9 medication use, specifically in a patient population that had minimal representation in the large, landmark clinical trials, can lead to better understanding about the therapeutic potential in cardiovascular disease reduction and patient outcomes attributed to medication use. Education regarding this novel drug class, medication access and patient support, …

Adults' Intention To Take An Arthritis Prescription Drug Based On Drug Advertisements, Amanda Radola

Seton Hall University Dissertations and Theses (ETDs)

Direct-to-Consumer Prescription Advertising (DTCPA) has rapidly expanded, particularly via social media, but research on its influence on individual decisions regarding prescribed medications remains limited. This gap is notable among chronic disease patients, such as those with arthritis, which affected over 58.5 million U.S. adults as of 2015 and is projected to rise to 78.4 million by 2040 (Barbour et al., 2017; Hootman et al., 2016). Social media discussions show significant activity following television ads for arthritis drugs (Curtis et al., 2017). However, few studies explore how DTCPA impacts patient intentions to take advertised arthritis medications. This study employed a novel …

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 …

Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins

Biomedical Sciences ETDs

Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological …

St6galnac-I Regulates Tumor Cell Sialylation Via Nectin2/Muc5ac-Mediated Immunosuppression And Angiogenesis In Non-Small Cell Lung Cancer, Muthamil Iniyan Appadurai, Sanjib Chaudhary, Ashu Shah, Gopalakrishnan Natarajan, Zahraa W. Alsafwani, Parvez Khan, Dhananjay D. Shinde, Subodh M. Lele, Lynette M. Smith, Mohd W. Nasser, Surinder K. Batra, Apar Kishor Ganti, Imayavaramban Lakshmanan

Journal Articles: Biochemistry & Molecular Biology

Glycosylation controls immune evasion, tumor progression, and metastasis. However, how tumor cell sialylation regulates immune evasion remains poorly characterized. ST6GalNAc-I, a sialyltransferase that conjugates sialic acid to the glycans in glycoproteins, was overexpressed in an aggressive-type KPA (KrasG12D/+ Trp53R172H/+ Ad-Cre) lung adenocarcinoma (LUAD) model and patient samples. Proteomic and biochemical analysis indicated that ST6GalNAc-I mediated NECTIN2 sialylation in LUAD cells. ST6GalNAc-I-deficient tumor cells cocultured with T cells were more susceptible to T cell-mediated tumor cell killing, indicating a key role for NECTIN2 in T cell dysfunction. Mice injected with St6galnac-I-knockdown syngeneic cells showed reduced lung tumor incidence and Nectin2/Tigit-associated immunosuppression. …

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 …

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, …

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 …

Patterns In Antibiotic Susceptibility Before And After Covid-19, Jessica Freely

UNLV Theses, Dissertations, Professional Papers, and Capstones

The COVID-19 pandemic led to a surge in antibiotic use, despite the viral nature of the disease. This widespread and often unnecessary use of antibiotics poses a serious threat on global health by accelerating the development of antibiotic resistance. Healthcare professionals utilize strategies, including Antibiotic Stewardship Programs (ASPs) and the use of antibiograms to mitigate the growing threat of antibiotic resistance. Antibiograms are tools used in healthcare settings to summarize and track bacterial susceptibility to various antibiotics. They provide clinicians critical information to guide selection of effective antibiotic treatment and monitor resistance trends overtime. The Centers for Disease Control and …

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 …

Clinical Benefit Analysis Of Modified Motion Management Protocols, Dyanne S. Macalinao

UNLV Theses, Dissertations, Professional Papers, and Capstones

Radiation therapy is crucial for treating cancer, using ionizing radiation to target and destroy cancer cells. This radiation is produced by machines like linear accelerators or through natural radioactive decay. Radiation therapy treatment planning involves prescribing doses and contouring target areas. However, managing tumors that move with breathing, such as in the lungs, remains a major challenge. Tumor motion exceeding 5 mm, as outlined in the AAPM’s Task Group 76, can compromise treatment accuracy, risking underdosing the tumor and overdosing healthy tissue. This issue is especially critical in high dose treatments like stereotactic body radiation therapy (SBRT). TG-76 provides different …

The Identification Of Xpr1 As A Voltage- And Phosphate-Activated Phosphate-Permeable Ion Channel, Hongjiang Wu, Liang Sun, Tong Huo, Theodore G Wensel, Frank T Horrigan, Zhao Wang

Faculty, Staff and Students Publications

Maintaining a balance of inorganic phosphate (Pi) is vital for cellular functionality. Proper phosphate levels are managed through Pi import and export; and the processes governing Pi export remain the least understood. Xenotropic and Polytropic retrovirus Receptor 1 (XPR1) has been identified as the only known Pi export protein in mammals. In this study, we introduce the cryogenic electron microscopy structure of human XPR1 (hXPR1), unveiling a structural arrangement distinct from that of any known ion transporter. Our structural results suggest that hXPR1 may operate as an ion channel, a hypothesis supported by patch clamp recordings revealing hXPR1's voltage- and …

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 …

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 …

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 …

Clinical And Fundamental Research Progressions On Tumor-Infiltrating Lymphocytes Therapy In Cancer, Jiandong Hu, Mengli Jin, Weihong Feng, Barbara Nassif-Rausseo, Alexandre Reuben, Chunhua Ma, Gregory Lizee, Fenge Li

Faculty, Staff and Student Publications

Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy-encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy-has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form of treatment elicits substantial antigen-specific immune responses, enhances or restores anti-tumor immunity, thereby facilitating the control and destruction of tumor cells, and yielding durable responses across a range of cancers, which can lead to the eradication of tumor lesions and the prevention of recurrence. Tumor-infiltrating lymphocytes (TILs), a subset of ACT, are characterized by their heterogeneity and …