Digital Commons Network^™

Investigating The Role Of The Hedgehog Pathway In Connection To Atrazine Endocrine Disruption, Anusha Kv Lakshmi Dharmavathi

The Journal of Purdue Undergraduate Research

No abstract provided.

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Examining The Effects Of Formal Education Level On The Montreal Cognitive Assessment, Renee S. White, Justin M. Barber, Jordan P. Harp, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Background: Brief, global assessments such as the Montreal Cognitive Assessment (MoCA) are widely used in primary care for assessing cognition in older adults. Like other neuropsychological instruments, lower formal education can influence MoCA interpretation.

Methods: Data from 2 large studies of cognitive aging were used—Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Alzheimer’s Coordinating Center (NACC). Both use comprehensive examinations to determine cognitive status and have brain amyloid status for many participants. Mixed models were used to account for random variation due to data source.

Results: Cognitively intact participants with lower education (≤12 years) were more likely than …

Stat6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis And Asthma, A Model Of Unified Airway Disease, Meng Lin, Amy T Ku, Jie Dong, Fei Yue, Weiyu Jiang, Ahmed Atef Ibrahim, Fanglue Peng, Chad J Creighton, Chandandeep Nagi, Carolina Gutierrez, Jeffrey M Rosen, Xiang H-F Zhang, Susan G Hilsenbeck, Xi Chen, Yi-Chieh Nancy Du, Shixia Huang, Aiping Shi, Zhimin Fan, Yi Li

Faculty, Staff and Student Publications

Signal transducer and activator of transcription 5 (STAT5) promotes cell survival and instigates breast tumor formation, and in the normal breast it also drives alveolar differentiation and lactogenesis. However, whether STAT5 drives a differentiated phenotype in breast tumorigenesis and therefore impacts cancer spread and metastasis is unclear. We found in two genetically engineered mouse models of breast cancer that constitutively activated Stat5a (Stat5aca) caused precancerous mammary epithelial cells to become lactogenic and evolve into tumors with diminished potential to metastasize. We also showed that STAT5aca reduced the migratory and invasive ability of human breast cancer cell lines in …

All The Brain's A Stage For Serotonin: The Forgotten Story Of Serotonin Diffusion Across Cell Membranes, Paul W. Andrews, Catherine Bosyj, Luke Brenton, Laura Green, Paul J. Gasser, Christopher A. Lowry, Virginia M. Pickel

Biomedical Sciences Faculty Research and Publications

In the conventional model of serotonin neurotransmission, serotonin released by neurons in the midbrain raphe nuclei exerts its actions on forebrain neurons by interacting with a large family of post-synaptic receptors. The actions of serotonin are terminated by active transport of serotonin back into the releasing neuron, which is mediated by the serotonin reuptake transporter (SERT). Because SERT is expressed pre-synaptically and is widely thought to be the only serotonin transporter in the forebrain, the conventional model does not include serotonin transport into post-synaptic neurons. However, a large body of evidence accumulating since the 1970s has shown that serotonin, despite …

Clinical Significance And Potential Role Of Trimethylamine N-Oxide In Neurological And Neuropsychiatric Disorders, Sowjanya Mudimela, Narahari Koppa Vishwanath, Anilkumar Pillai, Rodrigo Morales, Sean P Marrelli, Tatiana Barichello, Vijayasree V Giridharan

Faculty, Staff and Student Publications

Research in the last three decades has attracted the attention of many scientists and industrialists on the gut microbiome and its metabolites. Among many of these metabolites, trimethylamine oxide. Dietary choline, phosphatidylcholine, carnitine, and betaine produces TMAO that with other gut metabolites such as TMA (trimethylamine), and short-chain fatty acids (SCFA) enter the circulation. Finally they reach the brain through the blood-brain barrier (BBB) where they are involved in several physiological functions such as brain development, neurogenesis, and behavior. Gut-microbiota composition is influenced by diet, lifestyle, antibiotics, and age resulting in dysbiosis. Several studies have confirmed that altered TMAO levels …

Cerebellar Coordination Of Neuronal And Behavioral Rhythms, Brittany Correia Chapman

Theses and Dissertations (ETD)

Long known for its role in motor control, it is increasingly clear that the cerebellum is also involved in numerous cognitive and affective behaviors. Though the neuronal mechanism for the role of the cerebellum in cognition is still unclear, there is a consensus that it involves cerebellar interactions with the cerebral cortex. Recent studies suggest that the cerebellum monitors, and possibly coordinates, the precise phase alignment or coherence of neuronal oscillations in cerebral cortical areas. Here, we asked how loss of cerebellar function affects respiratory rhythms and the interactions of local field potential (LFP) oscillations between the lobulus simplex (LS) …

Olfactory Processing In The Piriform Cortex Of Awake, Freely Moving Mice, Ian F. Chapman

Theses and Dissertations (ETD)

The piriform cortex (PC) has long been established as the primary cortical recipient of olfactory information in the mammalian brain. In rodents, information extracted from recordings of PC neurons can accurately decode the identity of odors, leading to delineation of PC as the primary cortical region involved in the formation of odor perception. Unfortunately, due to technical limitations, many of the prior studies establishing these coding principles were performed without the ability to track the responses of the same cells over time. Additionally, recordings have often relied on head-fixation to minimize diffusion of odor stimuli, limiting movement range and natural …

A Semi-Mechanistic Dose-Finding Design In Oncology Using Pharmacokinetic/Pharmacodynamic Modeling, Xiao Su, Yisheng Li, Peter Müller, Chia-Wei Hsu, Haitao Pan, Kim-Anh Do

Faculty, Staff and Student Publications

While a number of phase I dose-finding designs in oncology exist, the commonly used ones are either algorithmic or empirical model-based. We propose a new framework for modeling the dose-response relationship, by systematically incorporating the pharmacokinetic (PK) data collected in the trial and the hypothesized mechanisms of the drug effects, via dynamic PK/PD modeling, as well as modeling of the relationship between a latent cumulative pharmacologic effect and a binary toxicity outcome. This modeling framework naturally incorporates the information on the impact of dose, schedule and method of administration (e.g., drug formulation and route of administration) on toxicity. The resulting …

Immune Dysfunction Signatures Predict Outcomes And Define Checkpoint Blockade-Unresponsive Microenvironments In Acute Myeloid Leukemia, Sergio Rutella, Jayakumar Vadakekolathu, Francesco Mazziotta, Stephen Reeder, Tung-On Yau, Rupkatha Mukhopadhyay, Benjamin Dickins, Heidi Altmann, Michael Kramer, Hanna A Knaus, Bruce R Blazar, Vedran Radojcic, Joshua F Zeidner, Andrea Arruda, Bofei Wang, Hussein A Abbas, Mark D Minden, Sarah K Tasian, Martin Bornhäuser, Ivana Gojo, Leo Luznik

Faculty, Staff and Student Publications

Background

Immune exhaustion and senescence are dominant dysfunctional states of effector T cells and major hurdles for the success of cancer immunotherapy. In the current study, we characterized how acute myeloid leukemia (AML) promotes the generation of senescent-like CD8⁺ T cells and whether they have prognostic relevance.

METHODS

We analyzed NanoString, bulk RNA-Seq and single-cell RNA-Seq data from independent clinical cohorts comprising 1,896 patients treated with chemotherapy and/or immune checkpoint blockade (ICB).

Results

We show that senescent-like bone marrow CD8⁺ T cells were impaired in killing autologous AML blasts and that their proportion negatively correlated with overall survival …

Bile Acids Regulate The Epithelial Na+ Channel In Native Tissues Through Direct Binding At Multiple Sites, Xue-Ping Wang, Viktor Tomilin, Andrew J Nickerson, Runze Tian, Merve Ertem, Abagail Mckernan, Xiaoguang Lei, Oleh Pochynyuk, Ossama B Kashlan

Faculty, Staff and Student Publications

Bile acids, originally known to emulsify dietary lipids, are now established signalling molecules that regulate physiological processes. Signalling targets several proteins that include the ion channels involved in regulating intestinal motility and bile viscosity. Studies show that bile acids regulate the epithelial sodium channel (ENaC) in cultured cell models and heterologous expression systems. ENaC plays both local and systemic roles in regulating extracellular fluids. Here we investigated whether bile acids regulate ENaC expressed in native tissues. We found that taurocholic acid and taurohyodeoxycholic acid regulated ENaC in both the distal nephron and distal colon. We also tested the hypothesis that …

Advances In Understanding Cancer-Associated Neurogenesis And Its Implications On The Neuroimmune Axis In Cancer, Ismail Yaman, Didem Ağaç Çobanoğlu, Tongxin Xie, Yi Ye, Moran Amit

Faculty, Staff and Student Publications

Nerves and immunologic mediators play pivotal roles in body homeostasis by interacting with each other through diverse mechanisms. The spread of nerves in the tumor microenvironment increases tumor cell proliferation and disease progression, and this correlates with poor patient outcomes. The effects of sympathetic and parasympathetic nerves on cancer regulation are being investigated. Recent findings demonstrate the possibility of developing therapeutic strategies that target the tumor microenvironment and its components such as immune cells, neurotransmitters, and extracellular vesicles. Therefore, examining and understanding the mechanisms and pathways associated with the sympathetic and parasympathetic nervous systems, neurotransmitters, cancer-derived mediators and their interactions …

Rad Regulation Of Cav12 Channels Controls Cardiac Fight-Or-Flight Response, Arianne Papa, Sergey I Zakharov, Alexander N Katchman, Jared S Kushner, Bi-Xing Chen, Lin Yang, Guoxia Liu, Alejandro Sanchez Jimenez, Robyn J Eisert, Gary A Bradshaw, Wen Dun, Shah R Ali, Aaron Rodriques, Karen Zhou, Veli Topkara, Mu Yang, John P Morrow, Emily J Tsai, Arthur Karlin, Elaine Wan, Marian Kalocsay, Geoffrey S Pitt, Henry M Colecraft, Manu Ben-Johny, Steven O Marx

Faculty, Staff and Student Publications

Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. In the present study, we uncover the primary mechanism underlying the heart's innate contractile reserve. We show that four protein kinase A (PKA)-phosphorylated residues in Rad, a calcium channel inhibitor, are crucial for controlling basal calcium current and essential for β-adrenergic augmentation of calcium influx in cardiomyocytes. Even with intact PKA signaling to other proteins modulating calcium handling, preventing adrenergic activation of calcium channels in Rad-phosphosite-mutant mice (4SA-Rad) has profound physiological effects: reduced heart rate with increased pauses, reduced basal contractility, near-complete attenuation of β-adrenergic contractile response and diminished …

Inhibition Of Cyclin Dependent Kinase 4/6 Overcomes Primary Resistance To Programmed Cell Death 1 Blockade In Malignant Mesothelioma, Hee-Jin Jang, Cynthia Y Truong, Eric M Lo, Hudson M Holmes, Daniela Ramos, Maheshwari Ramineni, Ju-Seog Lee, Daniel Y Wang, Massimo Pietropaolo, R Taylor Ripley, Bryan M Burt, Hyun-Sung Lee

Faculty, Staff and Student Publications

BACKGROUND: Despite the profound number of malignant pleural mesothelioma (MPM) patients now treated with programmed cell death 1 (PD-1) blockade, insight into the underpinnings of rational therapeutic strategies to treat resistance to checkpoint immunotherapy remains unrealized. Our objective was to develop a novel therapeutic approach to overcome primary resistance to PD-1 blockade in MPM.

METHODS: We generated a transcriptome signature of resistance to PD-1 blockade in MPM patients treated with nivolumab (4 responders and 4 nonresponders). We used The Cancer Genome Atlas MPM cohort (n = 73) to determine what genomic alterations were associated with the resistance signature. We tested …

An Optimized Bioassay For Screening Combined Anticoronaviral Compounds For Efficacy Against Feline Infectious Peritonitis Virus With Pharmacokinetic Analyses Of Gs-441524, Remdesivir, And Molnupiravir In Cats, Sarah Cook, Luke Wittenburg, Victoria C Yan, Jacob H Theil, Diego Castillo, Krystle L Reagan, Sonyia Williams, Cong-Dat Pham, Chun Li, Florian L Muller, Brian G Murphy

Faculty, Staff and Student Publications

Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a spectrum of clinical presentations including an effusive ("wet") form and non-effusive ("dry") form, both of which may be complicated by neurologic or ocular involvement. The feline coronavirus (FCoV) biotype, termed feline infectious peritonitis virus (FIPV), is the etiologic agent of FIP. The objective of this study was to determine and compare the in vitro antiviral efficacies of the viral protease inhibitors GC376 and nirmatrelvir and the nucleoside analogs remdesivir (RDV), GS-441524, molnupiravir (MPV; EIDD-2801), and β-D-N

“Racing-Stripe” Modification Of Radial Forearm Free Flap: Technique And Experience (704 Consecutive Cases), Emmanuel G Melissinos, Erik S Marques

Faculty, Staff and Student Publications

The radial forearm fasciocutaneous free flap (RFFF) has proven to be a versatile and reliable tool for the reconstructive microsurgeon when addressing soft-tissue defects. A significant drawback of the traditional RFFF is related to donor site morbidity and wound healing complications, especially when coverage of sizable defects is planned. The authors describe the "racing-stripe" modification of the RFFF (RS-RFFF) that involves harvesting a large segment of the deep forearm fascia with a narrow strip of skin overlying the radial vessels, thus allowing primary closure of the donor site.

METHODS: Retrospective chart review was conducted of a single surgeon's (E.G.M.) experience …

A Subpopulation Of Oxytocin Neurons Initiate Expression Of Crf Receptor 1 (Crfr1) In Females Post Parturition, Lierni Ugartemendia, Rose M De Guzman, Jing Cai, Shivakumar Rajamanickam, Zhiying Jiang, Jonathan Tao, Damian G Zuloaga, Nicholas J Justice

Faculty, Staff and Student Publications

Oxytocin (OT) is essential for successful reproduction, particularly during parturition and lactation. During the postpartum period, OT also influences maternal behavior to promote bonding between mothers and their newborns, and increases stress resilience. However, the mechanism by which stress influences OT neuron activity and OT release has remained unclear. Here, we provide evidence that a subpopulation of OT neurons initiate expression of the receptor for the stress neuropeptide Corticotropin Releasing Factor (CRF), CRFR1, in reproductive females. OT neuron expression of CRFR1 begins at the first parturition and increases during the postpartum period until weaning. The percentage of OT neurons that …

Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis And Muscle Wasting Through Metabolic Reprogramming In Pancreatic Cancer, Zhijun Zhou, Yu Ren, Jingxuan Yang, Mingyang Liu, Xiuhui Shi, Wenyi Luo, Kar-Ming Fung, Chao Xu, Michael S Bronze, Yuqing Zhang, Courtney W Houchen, Min Li

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Rapid deconditioning, also called cachexia, and metabolic reprogramming are two hallmarks of pancreatic cancer. Acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is an acetyl-enzyme A synthetase that contributes to lipid synthesis and epigenetic reprogramming. However, the role of ACSS2 on the nonselective macropinocytosis and cancer cachexia in pancreatic cancer remains elusive. In this study, we demonstrate that ACSS2 potentiates macropinocytosis and muscle wasting through metabolic reprogramming in pancreatic cancer.

METHODS: Clinical significance of ACSS2 was analyzed using samples from patients with pancreatic cancer. ACSS2-knockout cells were established using the clustered regularly interspaced short palindromic repeats-associated protein …

Nab-Paclitaxel, Capecitabine, And Radiation Therapy After Induction Chemotherapy In Treating Patients With Locally Advanced And Borderline Resectable Pancreatic Cancer: Phase 1 Trial And Imaging-Based Biomarker Validation, Eugene J Koay, Mohamed Zaid, Maureen Aliru, Polycarpe Bagereka, Arie Van Wieren, Maria Jovie Rodriguez, Galia Jacobson, Robert A Wolff, Michael Overman, Gauri Varadhachary, Shubham Pant, Huamin Wang, Ching-Wei Tzeng, Naruhiko Ikoma, Michael Kim, Jeffrey E Lee, Matthew Hg Katz, Eric Tamm, Priya Bhosale, Cullen M Taniguchi, Emma B Holliday, Grace L Smith, Ethan B Ludmir, Bruce D Minsky, Christopher H Crane, Albert C Koong, Prajnan Das, Xuemei Wang, Milind Javle, Sunil Krishnan

Faculty, Staff and Student Publications

PURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response.

METHODS AND MATERIALS: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m

RESULTS: Twenty-three patients started and finished …

Antibody Therapeutics For Epithelial Ovarian Cancer, Mason Ruiz, Ningyan Zhang, Anil K Sood, Zhiqiang An

Faculty, Staff and Student Publications

INTRODUCTION: High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. A lack of effective and tolerable therapeutic options and nonspecific symptoms at presentation with advanced stage of disease are among the challenges in the management of the disease.

AREAS COVERED: An overview of ovarian cancer, followed by a discussion of the current therapeutic regimes and challenges that arise during and after the treatment of EOC. We discuss different formats of antibody therapeutics and their usage in targeting validated targets implicated in ovarian cancer, as well as three emerging …

Differential Integrated Stress Response And Asparagine Production Drive Symbiosis And Therapy Resistance Of Pancreatic Adenocarcinoma Cells, Christopher J Halbrook, Galloway Thurston, Seth Boyer, Cecily Anaraki, Jennifer A Jiménez, Amy Mccarthy, Nina G Steele, Samuel A Kerk, Hanna S Hong, Lin Lin, Fiona V Law, Catherine Felton, Lorenzo Scipioni, Peter Sajjakulnukit, Anthony Andren, Alica K Beutel, Rima Singh, Barbara S Nelson, Fran Van Den Bergh, Abigail S Krall, Peter J Mullen, Li Zhang, Sandeep Batra, Jennifer P Morton, Ben Z Stanger, Heather R Christofk, Michelle A Digman, Daniel A Beard, Andrea Viale, Ji Zhang, Howard C Crawford, Marina Pasca Di Magliano, Claus Jorgensen, Costas A Lyssiotis

Faculty, Staff and Student Publications

The pancreatic tumor microenvironment drives deregulated nutrient availability. Accordingly, pancreatic cancer cells require metabolic adaptations to survive and proliferate. Pancreatic cancer subtypes have been characterized by transcriptional and functional differences, with subtypes reported to exist within the same tumor. However, it remains unclear if this diversity extends to metabolic programming. Here, using metabolomic profiling and functional interrogation of metabolic dependencies, we identify two distinct metabolic subclasses among neoplastic populations within individual human and mouse tumors. Furthermore, these populations are poised for metabolic cross-talk, and in examining this, we find an unexpected role for asparagine supporting proliferation during limited respiration. Constitutive …

Cholinergic Receptor-Wnt Pathway Controls Immune Activation By Sensing Intestinal Dysfunction, Jie Ren, Yu Sang, Alejandro Aballay

Faculty, Staff and Student Publications

Alterations in the intestinal physiology caused by pathogen colonization result in immune activation. To provide insights into the mechanisms underlying the control of immune activation by changes in intestinal homeostasis, we conducted a forward genetic screen for suppressors of immune activation by intestinal distension in Caenorhabditis elegans. Our results indicate that C. elegans ACC-4, a member of a family of acetylcholine receptors, is required in immune activation by defects in the defecation motor program or by pathogen infection. ACC-4 acts postsynaptically in non-cholinergic RIM neurons to regulate several immune genes and a Wnt-mediated host immune response. These findings uncover a …

T Cells Specific For Α-Myosin Drive Immunotherapy-Related Myocarditis, Margaret L Axelrod, Wouter C Meijers, Elles M Screever, Juan Qin, Mary Grace Carroll, Xiaopeng Sun, Elie Tannous, Yueli Zhang, Ayaka Sugiura, Brandie C Taylor, Ann Hanna, Shaoyi Zhang, Kaushik Amancherla, Warren Tai, Jordan J Wright, Spencer C Wei, Susan R Opalenik, Abigail L Toren, Jeffrey C Rathmell, P Brent Ferrell, Elizabeth J Phillips, Simon Mallal, Douglas B Johnson, James P Allison, Javid J Moslehi, Justin M Balko

Faculty, Staff and Student Publications

Immune-related adverse events, particularly severe toxicities such as myocarditis, are major challenges to the utility of immune checkpoint inhibitors (ICIs) in anticancer therapy1. The pathogenesis of ICI-associated myocarditis (ICI-MC) is poorly understood. Pdcd1-/-Ctla4+/- mice recapitulate clinicopathological features of ICI-MC, including myocardial T cell infiltration2. Here, using single-cell RNA and T cell receptor (TCR) sequencing of cardiac immune infiltrates from Pdcd1-/-Ctla4+/- mice, we identify clonal effector CD8+ T cells as the dominant cell population. Treatment with anti-CD8-depleting, but not anti-CD4-depleting, antibodies improved the survival of Pdcd1-/-Ctla4+/- mice. Adoptive transfer of immune cells from mice with myocarditis induced fatal myocarditis in recipients, …

Is Loss Of P53 A Driver Of Ductal Carcinoma In Situ Progression?, Rhiannon L Morrissey, Alastair M Thompson, Guillermina Lozano

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive carcinoma. Multiple studies have shown that DCIS lesions typically possess a driver mutation associated with cancer development. Mutation in the TP53 tumour suppressor gene is present in 15-30% of pure DCIS lesions and in ~30% of invasive breast cancers. Mutations in TP53 are significantly associated with high-grade DCIS, the most likely form of DCIS to progress to invasive carcinoma. In this review, we summarise published evidence on the prevalence of mutant TP53 in DCIS (including all DCIS subtypes), discuss the availability of mouse models for the study of DCIS …

Handwashing Results In Incomplete Nicotine Removal From Fingers Of Individuals Who Smoke: A Randomized Controlled Experiment, Thomas F Northrup, Angela L Stotts, Robert Suchting, Amir M Khan, Michelle R Klawans, Charles Green, Eunha Hoh, Melbourne F Hovell, Georg E Matt, Penelope J E Quintana

Faculty, Staff and Student Publications

Objective: Tobacco residue, also known as third-hand smoke (THS), contains toxicants and lingers in dust and on surfaces and clothes. THS also remains on hands of individuals who smoke, with potential transfer to infants during visitation while infants are hospitalized in neonatal intensive care units (NICUs), raising concerns (e.g., hindered respiratory development) for vulnerable infants. Previously unexplored, this study tested handwashing (HW) and sanitization efficacy for finger-nicotine removal in a sample of adults who smoked and were visiting infants in an NICU.

Study design: A cross-sectional sample was recruited to complete an interview, carbon monoxide breath samples, and three nicotine …

Development Of A Novel Mouse Model Of Menopause-Associated Asthma, William P Pederson, Laurie M Ellerman, Estevan C Sandoval, Scott Boitano, Jennifer B Frye, Kristian P Doyle, Heddwen L Brooks, Francesca Polverino, Julie G Ledford

Faculty, Staff and Students Publications

No abstract provided.

Looking On The Horizon; Potential And Unique Approaches To Developing Radiation Countermeasures For Deep Space Travel, Rihana S Bokhari, Afshin Beheshti, Sarah E Blutt, Dawn E Bowles, David Brenner, Robert Britton, Lawrence Bronk, Xu Cao, Anushree Chatterjee, Delisa E Clay, Colleen Courtney, Donald T Fox, M Waleed Gaber, Sharon Gerecht, Peter Grabham, David Grosshans, Fada Guan, Erin A Jezuit, David G Kirsch, Zhandong Liu, Mirjana Maletic-Savatic, Kyle M Miller, Ruth A Montague, Prashant Nagpal, Sivan Osenberg, Luke Parkitny, Niles A Pierce, Christopher Porada, Susan M Rosenberg, Paul Sargunas, Sadhana Sharma, Jamie Spangler, Daniel Naveed Tavakol, Dilip Thomas, Gordana Vunjak-Novakovic, Chunbo Wang, Luke Whitcomb, Damian W Young, Dorit Donoviel

Faculty, Staff and Students Publications

Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human health and performance on future missions beyond low Earth orbit. This paper will describe three funded and complementary avenues for reducing the risk to humans from radiation exposure experienced in deep space. The first focus is on identifying new therapeutic targets to reduce the damaging effects of radiation by focusing on high throughput genetic screens in accessible, sometimes called lower, organism models. The second focus …

A Microtubule-Connexin-43 Regulatory Link Suppresses Arrhythmias And Cardiac Fibrosis In Duchenne Muscular Dystrophy Mice, Eric Himelman, Julie Nouet, Mauricio A Lillo, Alexander Chong, Delong Zhou, Xander H T Wehrens, George G Rodney, Lai-Hua Xie, Natalia Shirokova, Jorge E Contreras, Diego Fraidenraich

Faculty, Staff and Students Publications

Dilated cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), an inherited degenerative disease of the cardiac and skeletal muscle caused by absence of the protein dystrophin. We showed one hallmark of DMD cardiomyopathy is the dysregulation of cardiac gap junction channel protein connexin-43 (Cx43). Proper Cx43 localization and function at the cardiac intercalated disc (ID) is regulated by post-translational phosphorylation of Cx43-carboxy-terminus residues S325/S328/S330 (pS-Cx43). Concurrently, Cx43 traffics along microtubules (MTs) for targeted delivery to the ID. In DMD hearts, absence of dystrophin results in a hyperdensified and disorganized MT cytoskeleton, yet the link with pS-Cx43 …

Opportunities And Challenges In Heart Rhythm Research: Rationale And Development Of An Electrophysiology Collaboratory, Duy T Nguyen, Kenneth C Bilchick, Sanjiv M Narayan, Mina K Chung, Kevin L Thomas, Kenneth R Laurita, Marmar Vaseghi, Roopinder Sandhu, Mihail G Chelu, Prince J Kannankeril, Douglas L Packer, David D Mcmanus, Atul Verma, Matthew Singleton, Khaldoun Tarakji, Sana M Al-Khatib, Jonathan R Kaltman, Ravi C Balijepalli, George F Van Hare, Jodie L Hurwitz, Andrea M Russo, Fred M Kusumoto, Christine M Albert

Faculty, Staff and Students Publications

There are many challenges in the current landscape of electrophysiology (EP) clinical and translational research, including increasing costs and complexity, competing demands, regulatory requirements, and challenges with study implementation. This review seeks to broadly discuss the state of EP research, including challenges and opportunities. Included here are results from a Heart Rhythm Society (HRS) Research Committee member survey detailing HRS members' perspectives regarding both barriers to clinical and translational research and opportunities to address these challenges. We also provide stakeholder perspectives on barriers and opportunities for future EP research, including input from representatives of the U.S. Food and Drug Administration, …

Clearance Of Hiv-1 Or Siv Reservoirs By Promotion Of Apoptosis And Inhibition Of Autophagy: Targeting Intracellular Molecules In Cure-Directed Strategies, Min Chen, Min Li, Marietta M Budai, Andrew P Rice, Jason T Kimata, Mahesh Mohan, Jin Wang

Faculty, Staff and Students Publications

The reservoirs of the HIV display cellular properties resembling long-lived immune memory cells that could be exploited for viral clearance. Our interest in developing a cure for HIV stems from the studies of immunologic memory against infections. We and others have found that long-lived immune memory cells employ prosurvival autophagy and antiapoptotic mechanisms to protect their longevity. Here, we describe the rationale for the development of an approach to clear HIV-1 by selective elimination of host cells harboring replication-competent HIV (SECH). While reactivation of HIV-1 in the host cells with latency reversing agents (LRAs) induces viral gene expression leading to …