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Old Dominion University

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Articles 1 - 15 of 15

Full-Text Articles in Cellular and Molecular Physiology

Circulating Biomarker Results From A Phase 2 Study Of Seralutinib In Pulmonary Arterial Hypertension, Robin Osterhout, Athénaïs Boucly, Raymond L. Benza, Richard N. Channick, Kelly M. Chin, Robert P. Frantz, Anna R. Hemnes, Luke S. Howard, Vallerie V. Mclaughlin, Olivier Sitbon, Jean-Luc Vachiéry, Rotham T. Zamanian, Richard Aranda, Matt Cravets, Zhaoqing Ding, Thao Duong-Verlé, David Mattola, Robert F. Roscigno, Ravikumar Sitapara, Lawrence S. Zisman, Jean-Marie Bruey, Hossein-Ardeschir Ghofrani Jan 2026

Circulating Biomarker Results From A Phase 2 Study Of Seralutinib In Pulmonary Arterial Hypertension, Robin Osterhout, Athénaïs Boucly, Raymond L. Benza, Richard N. Channick, Kelly M. Chin, Robert P. Frantz, Anna R. Hemnes, Luke S. Howard, Vallerie V. Mclaughlin, Olivier Sitbon, Jean-Luc Vachiéry, Rotham T. Zamanian, Richard Aranda, Matt Cravets, Zhaoqing Ding, Thao Duong-Verlé, David Mattola, Robert F. Roscigno, Ravikumar Sitapara, Lawrence S. Zisman, Jean-Marie Bruey, Hossein-Ardeschir Ghofrani

Department of Medicine Faculty Publications

[Introduction] To the Editor: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by obstructive pulmonary arterial remodeling (1). Seralutinib, an investigational inhaled tyrosine kinase inhibitor, potently and selectively targets kinases relevant to PAH pathobiology including platelet-derived growth factor receptors (PDGFR) α and β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) (2). In preclinical models, seralutinib improved cardiopulmonary hemodynamics, reversed pulmonary vascular pathology and decreased right ventricular hypertrophy (3). In TORREY, a phase 2, multicenter, double-blind, randomized, placebo-controlled trial in PAH, seralutinib significantly reduced pulmonary vascular resistance (PVR) after 24 weeks with good …

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Calculation Of Proton Transmembrane-Electrostatic Interaction Force And Elucidation Of The Water Droplet Experiment With A Transient Protonic Front, James Weifu Lee Jan 2025

Calculation Of Proton Transmembrane-Electrostatic Interaction Force And Elucidation Of The Water Droplet Experiment With A Transient Protonic Front, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The “transmembrane-electrostatically localized proton(s)/cation(s) charge(s) (TELC(s), also known as TELP(s)) model” may serve as a theoretical framework to explain protonic cell energetics including both delocalized and localized protonic couplings. TELCs are held by their corresponding transmembrane-electrostatically localized hydroxides anions (TELAs) across the membrane through mutual transmembrane-electrostatic attractive force, which is now calculated to be in the range from 1.96 × 10⁻¹¹ to 2.28 × 10⁻¹¹ newtons (N) across a 2.5 nm thick membrane in a range of transmembrane potential from 10 to 200 mV. At a moderate transmembrane potential (100 mV), the protonic transmembrane attractive force is now calculated to …

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Fiber Photometry Analysis Of Spontaneous Dopamine Signals: The Z-Scored Data Are Not The Data, Conner W. Wallace, Clare Y. Slinkard, Rachael Shaughnessy, Katherine M. Holleran, Samuel W. Centanni, Christopher C. Lapish, Sara R. Jones Jan 2025

Fiber Photometry Analysis Of Spontaneous Dopamine Signals: The Z-Scored Data Are Not The Data, Conner W. Wallace, Clare Y. Slinkard, Rachael Shaughnessy, Katherine M. Holleran, Samuel W. Centanni, Christopher C. Lapish, Sara R. Jones

Department of Medicine Faculty Publications

Fluorescent sensors have revolutionized the measurement of molecules in the brain, and the dLight dopamine sensor has been used extensively to examine reward- and cue-evoked dopamine release, but only recently has the field turned its attention to spontaneous release events. Analysis of spontaneous events typically requires evaluation of hundreds of events over minutes to hours, and the most common method of analysis, z-scoring, was not designed for this purpose. Here, we compare the accuracy and reliability of three different analysis methods to identify pharmacologically induced changes in dopamine release and uptake in freely moving C57BL/6J mice. The D1-like receptor antagonist …

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The Role Of Tgf-Beta Superfamily Members In Immune Homeostasis And Disease, Natalie Eva Nieuwenhuizen, Ioannis Eleftherianos, Piotr Jan Kraj, Maria Semitekolou Jan 2025

The Role Of Tgf-Beta Superfamily Members In Immune Homeostasis And Disease, Natalie Eva Nieuwenhuizen, Ioannis Eleftherianos, Piotr Jan Kraj, Maria Semitekolou

Biological Sciences Faculty Publications

[Introduction] The Transforming Growth Factor beta (TGF-beta) superfamily, encompassing molecules such as TGFs, activins, Bone Morphogenetic Proteins (BMPs), Growth/Differentiation Factor (GDFs) and Nodals, represents the largest family of growth and differentiation factors, playing crucial roles in developmental and physiological processes across animal species (1). These molecules are integral to tissue homeostasis and cell fate determination. Among them, TGF-beta is particularly noted for its regulatory influence on immune responses and tissue fibrosis (2, 3). Recent research has expanded our understanding of the immune functions of other superfamily members, including activin A and BMPs (4). These molecules signal through receptor complexes composed …

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Sound The (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide Pgpp, Areej Malik, Megan A. Hept, Erin B. Purcell Jan 2023

Sound The (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide Pgpp, Areej Malik, Megan A. Hept, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

It has recently become evident that the bacterial stringent response is regulated by a triphosphate alarmone (pGpp) as well as the canonical tetra- and pentaphosphate alarmones ppGpp and pppGpp [together, (p)ppGpp]. Often dismissed in the past as an artifact or degradation product, pGpp has been confirmed as a deliberate endpoint of multiple synthetic pathways utilizing GMP, (p)ppGpp, or GDP/GTP as precursors. Some early studies concluded that pGpp functionally mimics (p)ppGpp and that its biological role is to make alarmone metabolism less dependent on the guanine energy charge of the cell by allowing GMP-dependent synthesis to continue when GDP/GTP has been …

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Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi Aug 2022

Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi

Biomedical Engineering Theses & Dissertations

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is …

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Isothermal Environmental Heat Energy Utilization By Transmembrane Electrostatically Localized Protons At The Liquid-Membrane Interface, James Weifu Lee Jan 2020

Isothermal Environmental Heat Energy Utilization By Transmembrane Electrostatically Localized Protons At The Liquid-Membrane Interface, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

This study employing the latest theory on transmembrane electrostatic proton localization has now, for the first time, consistently elucidated a decades-longstanding bioenergetic conundrum in alkalophilic bacteria and more importantly discovered an entirely new feature: isothermal environmental heat utilization by electrostatically localized protons at the liquid-membrane interface. It was surprisingly revealed that the protonic motive force (equivalent to Gibbs free energy) from the isothermal environmental heat energy utilization through the electrostatically localized protons is not constrained by the overall energetics of the redox-driven proton pump system because of the following: (a) the transmembrane electrostatically localized protons are not free to move …

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Transient Alt Activation Protects Human Primary Cells From Chromosome Instability Induced By Low Chronic Oxidative Stress, Elisa Coluzzi, Rossella Buonsante, Stefano Leone, Anthony J. Asmar, Kelley L. Miller, Daniela Cimini, Antonella Sgura Jan 2017

Transient Alt Activation Protects Human Primary Cells From Chromosome Instability Induced By Low Chronic Oxidative Stress, Elisa Coluzzi, Rossella Buonsante, Stefano Leone, Anthony J. Asmar, Kelley L. Miller, Daniela Cimini, Antonella Sgura

Bioelectrics Publications

Cells are often subjected to the effect of reactive oxygen species (ROS) as a result of both intracellular metabolism and exposure to exogenous factors. ROS-dependent oxidative stress can induce 8-oxodG within the GGG triplet found in the G-rich human telomeric sequence (TTAGGG), making telomeres highly susceptible to ROS-induced oxidative damage. Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes and their dysfunction is believed to affect a wide range of cellular and/or organismal processes. Acute oxidative stress was shown to affect telomere integrity, but how prolonged low level oxidative stress, which may be more physiologically relevant, affects telomeres …

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P53: "The Wall Watcher", Nektarios Barabutis, John D. Catravas Oct 2015

P53: "The Wall Watcher", Nektarios Barabutis, John D. Catravas

Bioelectrics Publications

No abstract provided.

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Leptin Regulates Cd16 Expression On Human Monocytes In A Sex-Specific Manner, Joseph G. Cannon, Gyanendra Sharma, Gloria Sloan, Christiana Dimitropoulou, R. Randall Baker, Andrew Mazzoli, Barbara Kraj, Anthony Mulloy, Miriam Cortez-Cooper Jan 2014

Leptin Regulates Cd16 Expression On Human Monocytes In A Sex-Specific Manner, Joseph G. Cannon, Gyanendra Sharma, Gloria Sloan, Christiana Dimitropoulou, R. Randall Baker, Andrew Mazzoli, Barbara Kraj, Anthony Mulloy, Miriam Cortez-Cooper

School of Medical Diagnostics & Translational Sciences Publications

Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic-sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16-positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16-positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14++16++ monocytes, which are primary …

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An Extracellular Domain Of The Accessory Beta1 Subunit Is Required For Modulating Bk Channel Voltage Sensor And Gate, Aleksandra Gruslova, Iurii Semenov, Bin Wang Jan 2012

An Extracellular Domain Of The Accessory Beta1 Subunit Is Required For Modulating Bk Channel Voltage Sensor And Gate, Aleksandra Gruslova, Iurii Semenov, Bin Wang

Bioelectrics Publications

A family of tissue-specific auxiliary beta subunits modulates large conductance voltage- and calcium-activated potassium (BK) channel gating properties to suit their diverse functions. Paradoxically, beta subunits both promote BK channel activation through a stabilization of voltage sensor activation and reduce BK channel openings through an increased energetic barrier of the closed-to-open transition. The molecular determinants underlying beta subunit function, including the dual gating effects, remain unknown. In this study, we report the first identification of a beta1 functional domain consisting of Y74, S104, Y105, and I106 residues located in the extracellular loop of beta1. These amino acids reside within two …

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Dose-Dependent Thresholds Of 10-Ns Electric Pulse Induced Plasma Membrane Disruption And Cytotoxicity In Multiple Cell Lines, Bennett L. Ibey, Caleb C. Roth, Andrei G. Pakhomov, Joshua A. Bernhard, Gerald J. Wilmink, Olga N. Pakhomova Jan 2011

Dose-Dependent Thresholds Of 10-Ns Electric Pulse Induced Plasma Membrane Disruption And Cytotoxicity In Multiple Cell Lines, Bennett L. Ibey, Caleb C. Roth, Andrei G. Pakhomov, Joshua A. Bernhard, Gerald J. Wilmink, Olga N. Pakhomova

Bioelectrics Publications

In this study, we determined the LD50 (50% lethal dose) for cell death, and the ED50 (50% of cell population staining positive) for propidium (Pr) iodide uptake, and phosphatidylserine (PS) externalization for several commonly studied cell lines (HeLa, Jurkat, U937, CHO-K1, and GH3) exposed to 10-ns electric pulses (EP). We found that the LD50 varied substantially across the cell lines studied, increasing from 51 J/g for Jurkat to 1861 J/g for HeLa. PS externalized at doses equal or lower than that required for death in all cell lines ranging from 51 J/g in Jurkat, to 199 J/g in CHO-K1. Pr …

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3,4-Methylenedioxymethamphetamine Activates Nuclear Factor- Κb, Increases Intracellular Calcium, And Modulates Gene Transcription In Rat Heart Cells, David A. Tiangco, Frank A. Lattanzio Jr., Christopher J. Osgood, Stephen J. Beebe, Julie A. Kerry, Barbara Y. Hargrave Jan 2005

3,4-Methylenedioxymethamphetamine Activates Nuclear Factor- Κb, Increases Intracellular Calcium, And Modulates Gene Transcription In Rat Heart Cells, David A. Tiangco, Frank A. Lattanzio Jr., Christopher J. Osgood, Stephen J. Beebe, Julie A. Kerry, Barbara Y. Hargrave

Biological Sciences Faculty Publications

3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug that has gained immense popularity among teenagers and young adults. The cardiovascular toxicological consequences of abusing this compound have not been fully characterized. The present study utilized a transient transfection/dual luciferase genetic reporter assay, fluorescence confocal microscopy, and gene expression macroarray technology to determine nuclear factor-κB (NF-κB) activity, intracellular calcium balance, mitochondrial depolarization, and gene transcription profiles, respectively, in cultured rat striated cardiac myocytes (H9c2) exposed to MDMA. At concentrations of 1×10−3 M and 1×10−2 M, MDMA significantly enhanced NF-κB reporter activity compared with 0 M (medium only) control. This …

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Laminin Potentiates Differentiation Of Pcc4uva Embryonal Carcinoma Into Neurons, T. M. Sweeney, Roy C. Ogle, C. D. Little Sep 1990

Laminin Potentiates Differentiation Of Pcc4uva Embryonal Carcinoma Into Neurons, T. M. Sweeney, Roy C. Ogle, C. D. Little

School of Medical Diagnostics & Translational Sciences Publications

The embryonal carcinoma PCC4uva differentiates into neurons in response to treatment with retinoic acid and dbcAMP. We used this in vitro model system to study the effects of laminin on early neural differentiation. Laminin substrata markedly potentiate neural differentiation of retinoic acid and dbcAMP-treated cultures. Only laminin induced more rapid neural cell body clustering, neurite growth and neurite fasciculation as compared to type IV collagen, type I collagen, and fibronectin substrata. Exogenous laminin substrata promoted greater cell attachment, cellular spreading and growth to confluence than type IV collagen, type I collagen, fibronectin and glass substrata. Laminin-induced effects were inhibited by …

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Embryonic Chicken Fibroblast Collagen Binding Proteins: Distribution, Role In Substratum Adhesion, And Relationship To Integrins, Roy C. Ogle, A. Jeannette Potts, Marchall Yacoe, Charles D. Little Oct 1989

Embryonic Chicken Fibroblast Collagen Binding Proteins: Distribution, Role In Substratum Adhesion, And Relationship To Integrins, Roy C. Ogle, A. Jeannette Potts, Marchall Yacoe, Charles D. Little

School of Medical Diagnostics & Translational Sciences Publications

Collagen binding proteins (CBP) are hydrophobic, cell surface polypeptides, isolated by collagen affinity chromatography. Antibodies to CBPs inhibit the attachment of embryonic chicken heart fibroblasts to native type I collagen fibrils in a dose-dependent manner. The CBP antibodies also induce rounding and detachment of cells adherent to a planar substratum. This process of antibody-mediated substratum detachment resulted in a clustering of CBP and cell-associated extracellular matrix at the cell surface, and the rearrangement of filamentous actin. Other functional studies showed that cells grown within a three-dimensional gel of type I collagen cannot be immunostained at the cell surface with CBP …

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