Digital Commons Network^™

Adverse Pregnancy Outcomes And Long Term Risk Of Ischemic Heart Disease In Mothers: National Cohort And Co-Sibling Study, Casey Crump, Jan Sundquist, Mary Ann Mclaughlin, Siobhan M Dolan, Usha Govindarajulu, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

OBJECTIVE: To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers.

DESIGN: National cohort study.

SETTING: Sweden.

PARTICIPANTS: All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015.

MAIN OUTCOME MEASURES: The main outcome measure was incidence of ischemic heart disease from delivery to 2018, identified from nationwide inpatient and outpatient diagnoses. Cox regression was used to calculate hazard ratios for ischemic heart disease associated with preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, adjusting for other adverse pregnancy …

Spatiotemporal View Of Malignant Histogenesis And Macroevolution Via Formation Of Polyploid Giant Cancer Cells, Xiaoran Li, Yanping Zhong, Xudong Zhang, Anil K Sood, Jinsong Liu

Faculty, Staff and Student Publications

To understand how malignant tumors develop, we tracked cell membrane, nuclear membrane, spindle, and cell cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single cells underwent traditional mitosis to generate tissue with uniform nuclear size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, nuclear fusion, and karyokinesis without cytokinesis. PGCCs underwent restitution multipolar endomitosis, nuclear fragmentation, and micronuclei formation to increase nuclear contents and heterogeneity. At the cellular level, the development of PGCCs was associated with forming transient intracellular cells, termed fecundity cells. The fecundity cells …

The Ra-Be-Real Multinational, Prospective, Observational Study In Patients With Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, Or Biologic Disease-Modifying Therapies: A 6-Month Interim Analysis, Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Pedro Lopez-Romero, Walid Fakhouri, Inmaculada De La Torre, Liliana Zaremba-Pechmann, Thorsten Holzkämper, Bruno Fautrel

Faculty, Staff and Student Publications

INTRODUCTION: RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment.

METHODS: RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any …

Phase Ii Trial Of Weekly Erlotinib Dosing To Reduce Duodenal Polyp Burden Associated With Familial Adenomatous Polyposis, N Jewel Samadder, Nathan Foster, Ryan P Mcmurray, Carol A Burke, Elena Stoffel, Priyanka Kanth, Rohit Das, Marcia Cruz-Correa, E Vilar, Gautam Mankaney, Navtej Buttar, Selvi Thirumurthi, Danielle K Turgeon, Michael Sossenheimer, Michelle Westover, Ellen Richmond, Asad Umar, Gary Della'zanna, Luz M Rodriguez, Eva Szabo, David Zahrieh, Paul J Limburg

Faculty, Staff and Student Publications

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate.

Objective: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP.

Design, setting and participants: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres.

Exposures: Participants self-administered 350 mg of erlotinib …

Vip152 Is A Selective Cdk9 Inhibitor With Pre-Clinical In Vitro And In Vivo Efficacy In Chronic Lymphocytic Leukemia, Steven Sher, Ethan Whipp, Janek Walker, Pu Zhang, Larry Beaver, Katie Williams, Shelley Orwick, Janani Ravikrishnan, Brandi Walker, Elizabeth Perry, Charles Gregory, Matthew Purcell, Alexander Pan, Pearlly Yan, Lapo Alinari, Amy J Johnson, Melanie M Frigault, Joy M Greer, Ahmed Hamdy, Raquel Izumi, Xiaokui Mo, Deepa Sampath, Jennifer Woyach, James Blachly, John C Byrd, Rosa Lapalombella

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is effectively treated with targeted therapies including Bruton tyrosine kinase inhibitors and BCL2 antagonists. When these become ineffective, treatment options are limited. Positive transcription elongation factor complex (P-TEFb), a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, functions to regulate short half-life transcripts by phosphorylation of RNA Polymerase II (POLII). These transcripts are frequently dysregulated in hematologic malignancies; however, therapies targeting inhibition of P-TEFb have not yet achieved approval for cancer treatment. VIP152 kinome profiling revealed CDK9 as the main enzyme inhibited at 100 nM, with over a 10-fold increase in …

Updated Virophage Taxonomy And Distinction From Polinton-Like Viruses, Simon Roux, Matthias G. Fischer, Thomas Hackl, Laura A. Katz, Frederik Schulz, Natalya Yutin

Biological Sciences: Faculty Publications

Virophages are small dsDNA viruses that hijack the machinery of giant viruses during the co-infection of a protist (i.e., microeukaryotic) host and represent an exceptional case of “hyperparasitism” in the viral world. While only a handful of virophages have been isolated, a vast diversity of virophage-like sequences have been uncovered from diverse metagenomes. Their wide ecological distribution, idiosyncratic infection and replication strategy, ability to integrate into protist and giant virus genomes and potential role in antiviral defense have made virophages a topic of broad interest. However, one limitation for further studies is the lack of clarity regarding the nomenclature and …

Stressors, Coping Strategies, And Achievement During Teaching Practicum In A Nigerian Public University, Mensah Prince Osiesi, Udukhomose Suleiman Omokhabi, Sunday Ade Adeniran, Oluwayemisi Damilola Akomolafe, Oluwatoyin Tolu Obateru, Chigozie Celestina Oke, Adenike Lucia Aruleba

Higher Learning Research Communications

Objectives: This study assessed pre-service teacher stressors, coping strategies, and achievement during teaching practicum in a Nigerian public university.

Method: The study adopted the quantitative case study approach. The population consisted of all 300-level students in the faculty of education in the university who had completed their teaching practicum for the first semester of the 2020–2021 academic session. The quota sampling technique was used in selecting a sample of 130 pre-service teachers. We analysed data using multiple regression.

Results: Findings revealed the stressors and coping strategies, controlling for gender, did not significantly predict achievement in the teaching practicum. Several coping …

Recruitment In Acute Stroke Trials: Challenges And Potential Solutions, Joseph P Broderick, Yasmin N Aziz, Opeolu M Adeoye, James C Grotta, Andrew M Naidech, Andrew D Barreto, Colin P Derdeyn, Heidi J Sucharew, Jordan J Elm, Pooja Khatri

Faculty, Staff and Student Publications

Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke. One of the largest opportunities to increase the speed of enrollment and make trials more generalizable is expansion of inclusion criteria whose impact on expected recruitment can be assessed by epidemiologic and registry databases. Another barrier to recruitment besides the number of …

Cellular Factors That Shape The Activity Or Function Of Nitric Oxide-Stimulated Soluble Guanylyl Cyclase, Iraida Sharina, Emil Martin

Faculty, Staff and Student Publications

NO-stimulated guanylyl cyclase (SGC) is a hemoprotein that plays key roles in various physiological functions. SGC is a typical enzyme-linked receptor that combines the functions of a sensor for NO gas and cGMP generator. SGC possesses exclusive selectivity for NO and exhibits a very fast binding of NO, which allows it to function as a sensitive NO receptor. This review describes the effect of various cellular factors, such as additional NO, cell thiols, cell-derived small molecules and proteins on the function of SGC as cellular NO receptor. Due to its vital physiological function SGC is an important drug target. An …

Origin And Evolution Of Marsupial-Specific Imprinting Clusters Through Lineage-Specific Gene Duplications And Acquisition Of Promoter Differential Methylation, Wenqi Cao, Kory C. Douglas, Paul B. Samollow, John Vandeberg, Xu Wang, Andrew G. Clark

School of Medicine Publications

Genomic imprinting is a parent-of-origin-specific expression phenomenon that plays fundamental roles in many biological processes. In animals, imprinting is only observed in therian mammals, with ∼200 imprinted genes known in humans and mice. The imprinting pattern in marsupials has been minimally investigated by examining orthologs to known eutherian imprinted genes. To identify marsupial-specific imprinting in an unbiased way, we performed RNA-seq studies on samples of fetal brain and placenta from the reciprocal cross progeny of two laboratory opossum stocks. We inferred allele-specific expression for >3,000 expressed genes and discovered/validated 13 imprinted genes, including three previously known imprinted genes, Igf2r, Peg10, …

Network Analysis Examining Intrahospital Traffic Of Patients With Traumatic Hip Fracture, Elizabeth A. Secor, David Hamilton, Cecile D'Huyvetter, Kristin Salottolo, David Bar-Or

GME Publications

Introduction: Increased intrahospital traffic (IHT) is associated with adverse events and infections in hospitalized patients. Network science has been used to study patient flow in hospitals but not specifically for patients with traumatic injuries.

Methods: This retrospective analysis included 103 patients with traumatic hip fractures admitted to a level I trauma center between April 2021 and September 2021. Associations with IHTs (moves within the hospital) were analyzed using R (4.1.2) as a weighted directed graph.

Results: The median (interquartile range) number of moves was 8 (7–9). The network consisted of 16 distinct units and showed mild disassortativity (−0.35), similar to …

Titan Success: Faculty Behind The Scenes, February, Thorpe Center

Publications from the Associate Deans

No abstract provided.

Overexpression Of Both Human Sodium Iodide Symporter (Nis) And Brg1-Bromodomain Synergistically Enhances Radioiodine Sensitivity By Stabilizing P53 Through Npm1 Expression, J Na, C-H Lee, J-K Chung, H Youn

Peninsula Medical School

Improved therapeutic strategies are required to minimize side effects associated with radioiodine gene therapy to avoid unnecessary damage to normal cells and radiation-induced secondary malignancies. We previously reported that codon-optimized sodium iodide symporter (oNIS) enhances absorption of I-131 and that the brahma-associated gene 1 bromodomain (BRG1-BRD) causes inefficient DNA damage repair after high-energy X-ray therapy. To increase the therapeutic effect without applying excessive radiation, we considered the combination of oNIS and BRG1-BRD as gene therapy for the most effective radioiodine treatment. The antitumor effect of I-131 with oNIS or oNIS+BRD expression was examined by tumor xenograft models along with functional …

Phenomics Enables Measurement Of Complex Responses Of Developing Animals To Global Environmental Drivers, Oliver Tills, Luke A. Holmes, Elliot Quinn, Tony Everett, Manuela Truebano, John I. Spicer

School of Biological and Marine Sciences

Phenomics offers technological advances for high-dimensional phenotyping, facilitating rapid, high-throughput assessment of physiological performance and has proven invaluable in global research challenges including drug discovery and food security. However, this rapidly growing discipline has remained largely inaccessible to the increasingly urgent challenge of assessing organismal functional sensitivity to global change drivers. Here, we investigate the response of an ecologically important marine invertebrate to multiple environmental drivers using Energy Proxy Traits (EPTs), a new approach for measuring complex phenotypes captured on video as a spectrum of energy levels across different temporal frequencies in fluctuating pixel values. We imaged three developmental stages …

Transeuntis Mundi, A Nomadic Artistic Practice, Cândida Luiza Borges Da Silva

School of Law, Humanities and Social Sciences Theses

In this practice-led Ph.D. research, I investigate how an artistic practice can respond to the migration phenomena performed by human beings across the planet over millennia ¬– what I refer to as the millennial global human journey. Based on the idea of mobility, I chose to frame this research in the articulation of concepts deriving from the prefix trans: transculture, transhumance and transmediality. This research contributes to studies in art composition by developing the processes and concept of transmedial composition, mainly contributing to the field of New Media Art. This investigation resulted in the work Transeuntis Mundi (TM) Project – …

Fibroblast-Generated Extracellular Matrix Guides Anastomosis During Wound Healing In An Engineered Lymphatic Skin Flap, Alvis Chiu, Wenkai Jia, Yumeng Sun, Jeremy Goldman, Feng Zhao

Michigan Tech Publications, Part 1

A healthy lymphatic system is required to return excess interstitial fluid back to the venous circulation. However, up to 49% of breast cancer survivors eventually develop breast cancer-related lymphedema due to lymphatic injuries from lymph node dissections or biopsies performed to treat cancer. While early-stage lymphedema can be ameliorated by manual lymph drainage, no cure exists for late-stage lymphedema when lymph vessels become completely dysfunctional. A viable late-stage treatment is the autotransplantation of functional lymphatic vessels. Here we report on a novel engineered lymphatic flap that may eventually replace the skin flaps used in vascularized lymph vessel transfers. The engineered …

Editorial: Green Chemistry Biocatalysis, Barry J. Ryan, Gary T. Henehan, Bekir E. Eser, Ning Li, Zheng Guo, Gemma K. Kinsella

Articles

Editorial on the Research Topic: Green chemistry biocatalysis

Lightweight And Non-Invasive User Authentication On Earables, Changshuo Hu, Xiao Ma, Dong Ma, Ting Dang

Research Collection School Of Computing and Information Systems

The widespread adoption of wireless earbuds has advanced the developments in earable-based sensing in various domains like entertainment, human-computer interaction, and health monitoring. Recently, researchers have shown an increased interest in user authentication using earables. Despite the successes witnessed in acoustic probing and speech based authentication systems, this paper proposed a lightweight and non-invasive ambient sound based user authentication scheme. It employs the difference between the in-ear and out-ear sounds to estimate the individual-specific occluded ear canal transfer function (OECTF). Specifically, the {out-ear, in-ear} scaling factors at different frequency bands are captured via linear regression and treated as the OECTF …

Clinical Epigenomic Explanation Of The Epidemiology Of Cannabinoid Genotoxicity Manifesting As Transgenerational Teratogenesis, Cancerogenesis And Aging Acceleration, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

As global interest in the therapeutic potential of cannabis and its’ derivatives for the management of selected diseases increases, it is increasingly imperative that the toxic profile of cannabinoids be thoroughly understood in order to correctly assess the balance between the therapeutic risks and benefits. Modern studies across a number of jurisdictions, including Canada, Australia, the US and Europe have confirmed that some of the most worrying and severe historical reports of both congenital anomalies and cancer induction following cannabis exposure actually underestimate the multisystem thousand megabase-scale transgenerational genetic damage. These findings from teratogenic and carcinogenic literature are supported by …

Biostimulation Of Petroleum-Contaminated Soil Using Organic And Inorganic Amendments, Ogochukwu A. Udume, Gideon O. Abu, Herbert O. Stanley, Ijeoma F. Vincent-Akpu, Yusuf Momoh, Michael O. Eze

Chemistry Faculty Research & Creative Works

The most common approaches for the in-situ bioremediation of contaminated sites worldwide are bioaugmentation and bio stimulation. Bio stimulation has often proved more effective for chronically contaminated sites. This study examined the effectiveness of optimized water hyacinth compost in comparison with other organic and inorganic amendments for the remediation of crude oil-polluted soils. Water hyacinth was found to be rich in nutrients necessary to stimulate microbial growth and activity. an organic geochemical analysis revealed that all amendments in this study increased total petroleum hydrocarbon (TPH) biodegradation by ≥75% within 56 days, with the greatest biodegradation (93%) occurring in sterilized soil …

Curcumin Release From Biomaterials For Enhanced Tissue Regeneration Following Injury Or Disease, Adelle E. Hamilton, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Curcumin, a bioactive phenol derived from turmeric, is an antioxidant, anti-inflammatory, and antibacterial molecule. Although curcumin exhibits beneficial effects in its innate form, it is highly hydrophobic, which leads to poor water solubility and, consequently, low bioavailability. The lack of bioavailability limits curcumin's effectiveness as a treatment and restricts its use in clinical applications. Furthermore, to achieve beneficial, clinically relevant results, high doses of curcumin are required for systemic administration. Many researchers have utilized biomaterial carriers, including electrospun fibers, nanoparticles, hydrogels, and composite scaffolds, to overcome curcumin's principle therapeutic limitation of low bioavailability. By using biomaterials to deliver curcumin directly …

Mathematical Modeling Of Microscale Biology: Ion Pairing, Spatially Varying Permittivity, And Born Energy In Glycosaminoglycan Brushes, William J. Ceely, Marina Chugunova, Ali Nadim, James D. Sterling

Business and Information Technology Faculty Research & Creative Works

Biological macromolecules including nucleic acids, proteins, and glycosaminoglycans are typically anionic and can span domains of up to hundreds of nanometers and even micron length scales. The structures exist in crowded environments that are dominated by multivalent electrostatic interactions that can be modeled using mean-field continuum approaches that represent underlying molecular nanoscale biophysics. We develop such models for glycosaminoglycan brushes using steady state modified Poisson-Boltzmann models that incorporate important ion-specific (Hofmeister) effects. The results quantify how electroneutrality is attained through ion electrophoresis, spatially varying permittivity hydration forces, and ion-specific pairing. Brush-salt interfacial profiles of the electrostatic potential as well as …

Salt Doping Of Hyaluronic Acid Glycopolymer Biocondensates, James D. Sterling, Lu Fu, Kenisha Pudun, Shenda Baker, Megan Lord, Henry E. Riggs

Business and Information Technology Faculty Research & Creative Works

Biocondensates are largely studied with regard to intracellular components, while recognition of the formation of extracellular biocondensates are emerging, such as for cell surface heparan sulfate binding with basic fibroblast growth factor. This study analyzed the formation of biocondensates in vitro between the ubiquitous extracellular component, hyaluronan an anionic glycosaminoglycan, and cationic derivitized polyglucosamines known to bind to mucosal interfaces. The effect of molecular weight and net charge ratio was studied using a combination of microscopy, turbidity, laser diffraction particle sizing and zeta potential measurements. These analyses revealed that molecular weight affected the ability to form biocondensates while the surface …

Improving Automatic Melanoma Diagnosis Using Deep Learning-Based Segmentation Of Irregular Networks, Anand K. Nambisan, Akanksha Maurya, Norsang Lama, Thanh Phan, Gehana Patel, Keith Miller, Binita Lama, Jason Hagerty, Ronald Stanley, William V. Stoecker

Chemistry Faculty Research & Creative Works

Deep Learning Has Achieved Significant Success in Malignant Melanoma Diagnosis. These Diagnostic Models Are Undergoing a Transition into Clinical Use. However, with Melanoma Diagnostic Accuracy in the Range of Ninety Percent, a Significant Minority of Melanomas Are Missed by Deep Learning. Many of the Melanomas Missed Have Irregular Pigment Networks Visible using Dermoscopy. This Research Presents an Annotated Irregular Network Database and Develops a Classification Pipeline that Fuses Deep Learning Image-Level Results with Conventional Hand-Crafted Features from Irregular Pigment Networks. We Identified and Annotated 487 Unique Dermoscopic Melanoma Lesions from Images in the ISIC 2019 Dermoscopic Dataset to Create a …

Dissecting Cell Identity Via Network Inference And In Silico Gene Perturbation, Kenji Kamimoto, Blerta Stringa, Christy M Hoffmann, Kunal Jindal, Lilianna Solnica-Krezel, Samantha A Morris

2020-Current year OA Pubs

Cell identity is governed by the complex regulation of gene expression, represented as gene-regulatory networks

Missed Opportunities In The Diagnosis Of Tuberculosis Meningitis, Niamh Simmons, Margaret A Olsen, Joanna Buss, Thomas C Bailey, Carlos Mejia-Chew

2020-Current year OA Pubs

BACKGROUND: Tuberculosis meningitis (TBM) has high mortality and morbidity. Diagnostic delays can impact TBM outcomes. We aimed to estimate the number of potentially missed opportunities (MOs) to diagnose TBM and determine its impact on 90-day mortality.

METHODS: This is a retrospective cohort of adult patients with a central nervous system (CNS) TB

RESULTS: Of 893 patients with TBM, median age at diagnosis was 50 years (interquartile range, 37-64), 61.3% were male, and 35.2% had Medicaid as primary payer. Overall, 407 (45.6%) had a prior hospital or ED visit with an MO code. In-hospital 90-day mortality was not different between those …

The Tetraspanin Transmembrane Protein Cd53 Mediates Dyslipidemia And Integrates Inflammatory And Metabolic Signaling In Hepatocytes, Cassandra B Higgins, Joshua A Adams, Matthew H Ward, Zev J Greenberg, Małgorzata Milewska, Jiameng Sun, Yiming Zhang, Luana Chiquetto Paracatu, Qian Dong, Samuel Ballentine, Weikai Li, Ilona Wandzik, Laura G Schuettpelz, Brian J Debosch

2020-Current year OA Pubs

Tetraspanins are transmembrane signaling and proinflammatory proteins. Prior work demonstrates that the tetraspanin, CD53/TSPAN25/MOX44, mediates B-cell development and lymphocyte migration to lymph nodes and is implicated in various inflammatory diseases. However, CD53 is also expressed in highly metabolic tissues, including adipose and liver; yet its function outside the lymphoid compartment is not defined. Here, we show that CD53 demarcates the nutritional and inflammatory status of hepatocytes. High-fat exposure and inflammatory stimuli induced CD53 in vivo in liver and isolated primary hepatocytes. In contrast, restricting hepatocyte glucose flux through hepatocyte glucose transporter 8 deletion or through trehalose treatment blocked CD53 induction …

Review Of Feature Selection Methods Using Optimization Algorithm (Review Paper For Optimization Algorithm), Zana O. Hamad

Polytechnic Journal

Many works have been done to reduce complexity in terms of time and memory space. The feature selection process is one of the strategies to reduce system complexity and can be defined as a process of selecting the most important feature among feature space.Therefore,themostuseful features will be kept,and the less useful features will be eliminated.In the fault classification and diagnosis field, feature selection plays an important role in reducing dimensionality and sometimes might lead to having a high classification rate. In this paper, a comprehensive review is presented about feature selection processing and how it can be done.The primary goal …

Learning To Count Isomorphisms With Graph Neural Networks, Xingtong Yu, Zemin Liu, Yuan Fang, Xinming Zhang

Research Collection School Of Computing and Information Systems

Subgraph isomorphism counting is an important problem on graphs, as many graph-based tasks exploit recurring subgraph patterns. Classical methods usually boil down to a backtracking framework that needs to navigate a huge search space with prohibitive computational costs. Some recent studies resort to graph neural networks (GNNs) to learn a low-dimensional representation for both the query and input graphs, in order to predict the number of subgraph isomorphisms on the input graph. However, typical GNNs employ a node-centric message passing scheme that receives and aggregates messages on nodes, which is inadequate in complex structure matching for isomorphism counting. Moreover, on …

Modulation Of Trpv4 Protects Against Degeneration Induced By Sustained Loading And Promotes Matrix Synthesis In The Intervertebral Disc, Garrett W D Easson, Alireza Savadipour, Akila Anandarajah, Leanne E Iannucci, Spencer P Lake, Farshid Guilak, Simon Y Tang

2020-Current year OA Pubs

While it is well known that mechanical signals can either promote or disrupt intervertebral disc (IVD) homeostasis, the molecular mechanisms for transducing mechanical stimuli are not fully understood. The transient receptor potential vanilloid 4 (TRPV4) ion channel activated in isolated IVD cells initiates extracellular matrix (ECM) gene expression, while TRPV4 ablation reduces cytokine production in response to circumferential stretching. However, the role of TRPV4 on ECM maintenance during tissue-level mechanical loading remains unknown. Using an organ culture model, we modulated TRPV4 function over both short- (hours) and long-term (days) and evaluated the IVDs' response. Activating TRPV4 with the agonist GSK101 …