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Biochemistry, Biophysics, and Structural Biology

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2022

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Articles 31 - 60 of 65

Full-Text Articles in Medicine and Health Sciences

The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen Apr 2022

The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen

CSB and SJU Distinguished Thesis

An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be the protein of …


Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen Apr 2022

Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen

CSB and SJU Distinguished Thesis

Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has killed an …


Assessment Of Diversity Of Antimicrobial Resistance Phenotypes And Genotypes Of Mannheimia Haemolytica Isolates From Bovine Nasopharyngeal Swabs, Hannah F. Carter, Robert W. Wills, Matthew A. Scott, Alexis C. Thompson, Randall S. Singer, John Dustin Loy, Brandi B. Karisch, William B. Epperson, Amelia R. Woolums Mar 2022

Assessment Of Diversity Of Antimicrobial Resistance Phenotypes And Genotypes Of Mannheimia Haemolytica Isolates From Bovine Nasopharyngeal Swabs, Hannah F. Carter, Robert W. Wills, Matthew A. Scott, Alexis C. Thompson, Randall S. Singer, John Dustin Loy, Brandi B. Karisch, William B. Epperson, Amelia R. Woolums

School of Veterinary and Biomedical Sciences: Faculty Publications

The threat of bovine respiratory disease (BRD) for cattle operations is exacerbated by increasing prevalence of antimicrobial resistance (AMR) in Mannheimia haemolytica, a leading cause of BRD. Characterization of AMR in M. haemolytica by culture and susceptibility testing is complicated by uncertainty regarding the number of colonies that must be selected to accurately characterize AMR phenotypes (antibiograms) and genotypes in a culture. The study objective was to assess phenotypic and genotypic diversity of M. haemolytica isolates on nasopharyngeal swabs (NPS) from 28 cattle at risk for BRD or with BRD. NPS were swabbed onto five consecutive blood agar plates; …


Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker Mar 2022

Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Nanobodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and the ability to be bioengineered into novel multivalent, multi-specific, and high-affinity molecules, making them a class of emerging powerful therapies against SARS-CoV-2. Recent research efforts on the design, protein engineering, and structure-functional characterization of nanobodies and their binding with SARS-CoV-2 S proteins reflected a growing realization that nanobody combinations can exploit distinct binding epitopes and leverage the intrinsic plasticity of the conformational landscape for the SARS-CoV-2 S protein to produce efficient neutralizing and mutation resistant characteristics. Structural …


Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov Mar 2022

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov

Chemistry & Biochemistry Faculty Publications

n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds …


Vaccinia Virus Arrests And Shifts The Cell Cycle, Caroline K. Martin, Jerzy Samolej, Annabel T. Olson, Cosetta Bertoli, Matthew S. Wiebe, Robertus A. M. De Bruin, Jason Mercer Feb 2022

Vaccinia Virus Arrests And Shifts The Cell Cycle, Caroline K. Martin, Jerzy Samolej, Annabel T. Olson, Cosetta Bertoli, Matthew S. Wiebe, Robertus A. M. De Bruin, Jason Mercer

School of Veterinary and Biomedical Sciences: Faculty Publications

Modulation of the host cell cycle is a common strategy used by viruses to create a proreplicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors and viral effectors that mediate these changes remain unknown. Here, we set out to investigate the effect of VACV infection on cell proliferation and host cell cycle progression. Using a subset of VACV mutants, we characterise the stage of infection required for inhibition of cell proliferation and define the viral effectors required to dysregulate …


Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker Feb 2022

Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with single nanobodies Nb6, VHH E, and complex with VHH E/VHH V nanobody combination. We combined coarse-grained and all-atom molecular simulations and collective dynamics analysis with binding free energy scanning, perturbation-response scanning, and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric …


Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba Feb 2022

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …


Prostacyclin Promotes Degenerative Pathology In A Model Of Alzheimer’S Disease, Tasha R. Womack, Craig T. Vollert, Odochi Ohia-Nwoko, Monika Schmitt, Saghi Montazari, Tina L. Beckett, David Mayerich, M. Paul Murphy, Jason L. Eriksen Feb 2022

Prostacyclin Promotes Degenerative Pathology In A Model Of Alzheimer’S Disease, Tasha R. Womack, Craig T. Vollert, Odochi Ohia-Nwoko, Monika Schmitt, Saghi Montazari, Tina L. Beckett, David Mayerich, M. Paul Murphy, Jason L. Eriksen

Molecular and Cellular Biochemistry Faculty Publications

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression …


Conformational Flexibility And Local Frustration In The Functional States Of The Sars-Cov-2 Spike B.1.1.7 And B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism Of Functional Dynamics And Protein Stability, Gennady M. Verkhivker Jan 2022

Conformational Flexibility And Local Frustration In The Functional States Of The Sars-Cov-2 Spike B.1.1.7 And B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism Of Functional Dynamics And Protein Stability, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structural and functional studies of the SARS-CoV-2 spike proteins have recently determined distinct functional states of the B.1.1.7 and B.1.351 spike variants, providing a molecular framework for understanding the mechanisms that link the effect of mutations with the enhanced virus infectivity and transmissibility. A detailed dynamic and energetic analysis of these variants was undertaken in the present work to quantify the effects of different mutations on functional conformational changes and stability of the SARS-CoV-2 spike protein. We employed the efficient and accurate coarse-grained (CG) simulations of multiple functional states of the D614G mutant, B.1.1.7 and B.1.351 spike variants to characterize …


Evaluation Of Bioactive Properties Of Lipophilic Fractions Of Edible And Non-Edible Parts Of Nasturtium Officinale (Watercress) In A Model Of Human Malignant Melanoma Cells, Sotiris Kyriakou, Venetia Tragkola, Heba Alghol, Ioannis Anestopoulos, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis Jan 2022

Evaluation Of Bioactive Properties Of Lipophilic Fractions Of Edible And Non-Edible Parts Of Nasturtium Officinale (Watercress) In A Model Of Human Malignant Melanoma Cells, Sotiris Kyriakou, Venetia Tragkola, Heba Alghol, Ioannis Anestopoulos, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Watercress is an enriched source of phenethyl isothiocyanate (PEITC), among other phytochemicals, with an antioxidant capacity. The aim of this study was to (i) chemically characterize and (ii) biologically evaluate the profile of the main health-promoting compounds contained in edible (i.e., mixture of leaves and lateral buds) and non-edible (i.e., stems) parts of watercress in an in vitro model of malignant melanoma consisting of human malignant melanoma (A375), non-melanoma (A431) and keratinocyte (HaCaT) cells. The extraction of the main constituents of watercress was performed by subjecting the freeze-dried edible and non-edible samples through different extraction protocols, whereas their concentration was …


Self-Conscious Emotions And The Right Fronto-Temporal And Right Temporal Parietal Junction, Adriana Lavarco, Nathira Ahmad, Qiana Archer, Matthew Pardillo, Ray Nunez Castaneda, Anthony Minervini, Julian Keenan Jan 2022

Self-Conscious Emotions And The Right Fronto-Temporal And Right Temporal Parietal Junction, Adriana Lavarco, Nathira Ahmad, Qiana Archer, Matthew Pardillo, Ray Nunez Castaneda, Anthony Minervini, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

For more than two decades, research focusing on both clinical and non-clinical populations has suggested a key role for specific regions in the regulation of self-conscious emotions. It is speculated that both the expression and the interpretation of self-conscious emotions are critical in humans for action planning and response, communication, learning, parenting, and most social encounters. Empathy, Guilt, Jealousy, Shame, and Pride are all categorized as self-conscious emotions, all of which are crucial components to one’s sense of self. There has been an abundance of evidence pointing to the right Fronto-Temporal involvement in the integration of cognitive processes underlying the …


Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara Jan 2022

Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara

Articles

Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …


Characterizing The Amino Acid Activation Center Of The Naturally Editing-Deficient Aminoacyl-Trna Synthetase Phers In Mycoplasma Mobile, Nien-Ching Han, Arundhati Kavoor, Michael Ibba Jan 2022

Characterizing The Amino Acid Activation Center Of The Naturally Editing-Deficient Aminoacyl-Trna Synthetase Phers In Mycoplasma Mobile, Nien-Ching Han, Arundhati Kavoor, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

To ensure correct amino acids are incorporated during protein synthesis, aminoacyl-tRNA synthetases (aaRSs) employ proofreading mechanisms collectively referred to as editing. Although editing is important for viability, editing-deficient aaRSs have been identified in host-dependent organisms. In Mycoplasma mobile, editing-deficient PheRS and LeuRS have been identified. We characterized the amino acid activation site of MmPheRS and identified a previously unknown hyperaccurate mutation, L287F. Additionally, we report that m-Tyr, an oxidation byproduct of Phe which is toxic to editing-deficient cells, is poorly discriminated by MmPheRS activation and is not subjected to editing. Furthermore, expressing MmPheRS and the hyperaccurate variants renders …


Harnessing Mycobacterium Bovis Bcg Trained Immunity To Control Human And Bovine Babesiosis, Reginaldo G. Bastos, Heba F. Alzan, Vignesh A. Rathinasamy, Brian M. Cooke, Odir A. Dellagostin, Raul G. Barletta, Carlos E. Suarez Jan 2022

Harnessing Mycobacterium Bovis Bcg Trained Immunity To Control Human And Bovine Babesiosis, Reginaldo G. Bastos, Heba F. Alzan, Vignesh A. Rathinasamy, Brian M. Cooke, Odir A. Dellagostin, Raul G. Barletta, Carlos E. Suarez

School of Veterinary and Biomedical Sciences: Faculty Publications

Babesiosis is a disease caused by tickborne hemoprotozoan apicomplexan parasites of the genus Babesia that negatively impacts public health and food security worldwide. Development of effective and sustainable vaccines against babesiosis is currently hindered in part by the absence of definitive host correlates of protection. Despite that, studies in Babesia microti and Babesia bovis, major causative agents of human and bovine babesiosis, respectively, suggest that early activation of innate immune responses is crucial for vertebrates to survive acute infection. Trained immunity (TI) is defined as the development of memory in vertebrate innate immune cells, allowing more efficient responses to subsequent …


Glycocalyx Mechanotransduction Mechanisms Are Involved In Renal Cancer Metastasis, Heriberto Moran, Limary M. Cancel, Peigen Huang, Sylvie Roberge, Tuoye Xu, John M. Tarbell, Lance L. Munn Jan 2022

Glycocalyx Mechanotransduction Mechanisms Are Involved In Renal Cancer Metastasis, Heriberto Moran, Limary M. Cancel, Peigen Huang, Sylvie Roberge, Tuoye Xu, John M. Tarbell, Lance L. Munn

Publications and Research

Mammalian cells, including cancer cells, are covered by a surface layer containing cell bound proteoglycans, glycoproteins, associated glycosaminoglycans and bound proteins that is commonly referred to as the glycocalyx. Solid tumors also have a dynamic fluid microenvironment with elevated interstitial flow. In the present work we further investigate the hypothesis that interstitial flow is sensed by the tumor glycocalyx leading to activation of cell motility and metastasis. Using a highly metastatic renal carcinoma cell line (SN12L1) and its low metastatic counterpart (SN12C) we demonstrate in vitro that the small molecule Suberoylanilide Hydroxamic Acid (SAHA) inhibits the heparan sulfate synthesis enzyme …


Plasma Induced Reactive Oxygen Species-Dependent Cytotoxicity In Glioblastoma 3d Tumourspheres, Janith Wanigasekara, Carlos Barcia, Patrick J. Cullen, Brijesh Tiwari, James F. Curtin Jan 2022

Plasma Induced Reactive Oxygen Species-Dependent Cytotoxicity In Glioblastoma 3d Tumourspheres, Janith Wanigasekara, Carlos Barcia, Patrick J. Cullen, Brijesh Tiwari, James F. Curtin

Articles

The aim of this study was to determine the effects of a pin‐to‐plate cold atmospheric plasma (CAP) on U‐251 MG three‐dimensional (3D) glioblastoma spheroids under different conditions. 3D tumorspheres showed higher resistance to the CAP treatment compared to 2D monolayer cells. A single CAP treatment was able to induce cytotoxicity, while multiple CAP treatments augmented this effect. CAP was also able to induce cytotoxicity throughout the tumoursphere, and we identified that reactive oxygen species(ROS) plays a major role, while H2O2plays a partial role in CAP‐induced cytotoxicity in tumour-spheres. We conclude that ROS‐dependent cytotoxicity is induced uniformly throughout glioblastoma and epidermoid …


Buprenorphine And Its Formulations: A Comprehensive Review., Salomon Poliwoda, Nazir Noor, Jack S. Jenkins, Cain W. Stark, Mattie Steib, Jamal Hasoon, Giustino Varrassi, Ivan Urits, Omar Viswanath, Adam M. Kaye, Alan David Kaye Jan 2022

Buprenorphine And Its Formulations: A Comprehensive Review., Salomon Poliwoda, Nazir Noor, Jack S. Jenkins, Cain W. Stark, Mattie Steib, Jamal Hasoon, Giustino Varrassi, Ivan Urits, Omar Viswanath, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Buprenorphine, a novel long-acting analgesic, was developed with the intention of two purposes: analgesia and opioid use disorder. Regarding its pharmacodynamics, it is a partial agonist at mu receptors, an inverse agonist at kappa receptors, and an antagonist at delta receptors. For the purpose of analgesia, three formulations of buprenorphine were developed: IV/IM injectable formulation (Buprenex®), transdermal patch formulation (Butrans®), and buccal film formulation (Belbuca®). Related to opioid dependence, the formulations developed were subcutaneous extended release (Sublocade®), subdermal implant (Probuphine®), and sublingual tablets (Subutex®). Lastly, in order to avoid misuse of buprenorphine for opioid dependence, two combination formulations paired with …


Rimegepant For The Treatment Of Migraine., Amnon A. Berger, Ariel Winnick, Austin H. Carroll, Alexandra Welschmeyer, Nathan Li, Marc Colon, Antonella Paladini, Giovanni F. Ramírez, Jamal Hasoon, Elyse M. Cornett, Jaehong Song, Giustino Varrassi, Adam M. Kaye, Alan David Kaye, Latha Ganti Jan 2022

Rimegepant For The Treatment Of Migraine., Amnon A. Berger, Ariel Winnick, Austin H. Carroll, Alexandra Welschmeyer, Nathan Li, Marc Colon, Antonella Paladini, Giovanni F. Ramírez, Jamal Hasoon, Elyse M. Cornett, Jaehong Song, Giustino Varrassi, Adam M. Kaye, Alan David Kaye, Latha Ganti

School of Pharmacy Faculty Articles

Migraine is a common form of primary headache, affecting up to 1 in every 6 Americans. The pathophysiology is an intricate interplay of genetic factors and environmental influence and is still being elucidated in ongoing studies. The trigeminovascular system is now known to have a significant role in the initiation of migraines, including the release of pain mediators such as CGRP and substance P. Traditional treatment of migraine is usually divided into acute and preventive treatment. Acute therapy includes non-specific therapy, such as NSAIDs and other analgesics, which may provide relief in mild to moderate migraines. 5-HT1 agonists may provide …


Aduhelm, A Novel Anti-Amyloid Monoclonal Antibody, For The Treatment Of Alzheimer's Disease: A Comprehensive Review., Hannah W. Haddad, Garett W. Malone, Nicholas J. Comardelle, Arielle E. Degueure, Salomon Poliwoda, Rachel J. Kaye, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye Jan 2022

Aduhelm, A Novel Anti-Amyloid Monoclonal Antibody, For The Treatment Of Alzheimer's Disease: A Comprehensive Review., Hannah W. Haddad, Garett W. Malone, Nicholas J. Comardelle, Arielle E. Degueure, Salomon Poliwoda, Rachel J. Kaye, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Alzheimer's disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role of caregivers. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated $290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD; however, these drugs are not curative. The present investigation describes the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, Adulhelm, in …


Clinically Relevant Drug Interactions With Monoamine Oxidase Inhibitors., Amber N. Edinoff, Connor R. Swinford, Amira S. Odisho, Caroline R. Burroughs, Cain W. Stark, Walid A. Raslan, Elyse M. Cornett, Adam M. Kaye, Alan David Kaye Jan 2022

Clinically Relevant Drug Interactions With Monoamine Oxidase Inhibitors., Amber N. Edinoff, Connor R. Swinford, Amira S. Odisho, Caroline R. Burroughs, Cain W. Stark, Walid A. Raslan, Elyse M. Cornett, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Monoamine oxidase inhibitors (MAOI) are a class of drugs that were originally developed for the treatment of depression but have since been expanded to be used in management of affective and neurological disorders, as well as stroke and aging-related neurocognitive changes. Ranging from irreversible to reversible and selective to non-selective, these drugs target the monoamine oxidase (MAO) enzyme and prevent the oxidative deamination of various monoamines and catecholamines such as serotonin and dopamine, respectively. Tyramine is a potent releaser of norepinephrine (NE) and is found in high concentrations in foods such as aged cheeses and meats. Under normal conditions, NE …


Methamphetamine Use: A Narrative Review Of Adverse Effects And Related Toxicities., Amber N. Edinoff, Sarah E. Kaufman, Keionne M. Green, Daniel A. Provenzano, Jesse Lawson, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye Jan 2022

Methamphetamine Use: A Narrative Review Of Adverse Effects And Related Toxicities., Amber N. Edinoff, Sarah E. Kaufman, Keionne M. Green, Daniel A. Provenzano, Jesse Lawson, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Methamphetamine has been labeled "America's most dangerous drug" and has received significant public health attention. Stimulant addiction and tolerance are heavily documented in the literature; increasingly larger doses maintain euphoria in short time periods to withstand stimulant tolerance. Stimulant deaths are high in the United States and abroad. Between 2013 and 2019, deaths related to methamphetamine use quadrupled from 3,616 to 16,127. Methamphetamine use increased four-fold from 2015 to 2016. Due to this increase in methamphetamine use and its associated medical complications, the mortality rate associated with methamphetamine use has doubled over the past ten years. Cardiopulmonary symptoms include chest …


Viloxazine, A Non-Stimulant Norepinephrine Reuptake Inhibitor, For The Treatment Of Attention Deficit Hyperactivity Disorder: A 3 Year Update., Hannah W. Haddad, Paul B. Hankey, Jimin Ko, Zahaan Eswani, Pravjit Bhatti, Amber N. Edinoff, Adam M. Kaye, Alan David Kaye Jan 2022

Viloxazine, A Non-Stimulant Norepinephrine Reuptake Inhibitor, For The Treatment Of Attention Deficit Hyperactivity Disorder: A 3 Year Update., Hannah W. Haddad, Paul B. Hankey, Jimin Ko, Zahaan Eswani, Pravjit Bhatti, Amber N. Edinoff, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Current treatment options for ADHD include pharmacological treatment (stimulants, non-stimulants, anti-depressants, anti-psychotics), psychological treatment (behavioral therapy with or without parent training, cognitive training, neurofeedback), and complementary and alternative therapies (vitamin supplementation, exercise). Central nervous system (CNS) stimulants are the primary pharmacological therapy used in treatment; however, these stimulant drugs carry a high potential for abuse and severe psychological/physical dependence. Viloxazine, a non-stimulant medication without evidence of drug dependence, is a selective norepinephrine reuptake inhibitor that has historically been prescribed as an anti-depressant medication. The extended-release (ER) form …


Phenothiazines And Their Evolving Roles In Clinical Practice: A Narrative Review., Amber N. Edinoff, Grace Armistead, Christina A. Rosa, Alexandra Anderson, Ronan Patil, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye Jan 2022

Phenothiazines And Their Evolving Roles In Clinical Practice: A Narrative Review., Amber N. Edinoff, Grace Armistead, Christina A. Rosa, Alexandra Anderson, Ronan Patil, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Phenothiazines, a diverse class of drugs, can be used to treat multiple mental health and physical conditions. Phenothiazines have been used for decades to treat mental illnesses, including schizophrenia, mania in bipolar disorder, and psychosis. Additionally, these drugs offer relief for physical illnesses, including migraines, hiccups, nausea, and vomiting in both adults and children. Further research is needed to prove the efficacy of phenothiazines in treating physical symptoms. Phenothiazines are dopaminergic antagonists that inhibit D2 receptors with varying potency. High potency phenothiazines such as perphenazine are used to treat various psychiatric conditions such as the positive symptoms of schizophrenia, the …


Selective Serotonin Reuptake Inhibitors And Associated Bleeding Risks: A Narrative And Clinical Review., Amber N. Edinoff, Keerthiga Raveendran, Marc A. Colon, Bennett H. Thomas, Katie A. Trettin, Grace W. Hunt, Adam M. Kaye, Elyse M. Cornett, Alan David Kaye Jan 2022

Selective Serotonin Reuptake Inhibitors And Associated Bleeding Risks: A Narrative And Clinical Review., Amber N. Edinoff, Keerthiga Raveendran, Marc A. Colon, Bennett H. Thomas, Katie A. Trettin, Grace W. Hunt, Adam M. Kaye, Elyse M. Cornett, Alan David Kaye

School of Pharmacy Faculty Articles

Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects …


Phip-Seq Reveals Autoantibodies For Ubiquitously Expressed Antigens In Viral Myocarditis, Mahima T. Rasquinha, Ninaad Lasrado, Erika M. Petro-Turnquist, Eric A. Weaver, Thiagarajan Venkataraman, Daniel R. Anderson, H. Benjamin Larman, Jay Reddy Jan 2022

Phip-Seq Reveals Autoantibodies For Ubiquitously Expressed Antigens In Viral Myocarditis, Mahima T. Rasquinha, Ninaad Lasrado, Erika M. Petro-Turnquist, Eric A. Weaver, Thiagarajan Venkataraman, Daniel R. Anderson, H. Benjamin Larman, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Simple Summary: Myocarditis is the inflammation of the heart muscle, and viral infections are a common cause of this disease. Myocarditis in some patients can progress to dilated cardiomyopathy (DCM). The mouse model of coxsackievirus B3 (CVB3) is commonly used to understand this disease progression in DCM patients. In this paper, we have attempted to analyze antibodies for heart antigens that could be produced as a result of heart damage in animals infected with CVB3 using a technique called Phage ImmunoPrecipitation Sequencing (PhIP-Seq). The analyses led us to identify antibodies for several proteins that were not previously reported that may …


Dissecting The Cellular Landscape And Transcriptome Network In Viral Myocarditis By Single-Cell Rna Sequencing, Ninaad Lasrado, Nicholas Borcherding, Rajkumar Arumugam, Timothy K. Starr, Jay Reddy Jan 2022

Dissecting The Cellular Landscape And Transcriptome Network In Viral Myocarditis By Single-Cell Rna Sequencing, Ninaad Lasrado, Nicholas Borcherding, Rajkumar Arumugam, Timothy K. Starr, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Coxsackievirus B3 (CVB3)-induced myocarditis is commonly employed to study viral pathogenesis in mice.Chronically affected micemaydevelop dilated cardiomyopathy, which may involve the mediation of immune and nonimmune cells. To dissect this complexity, we performed single-cell RNA sequencing on heart cells from healthy and myocarditic mice, leading us to note significant proportions of myeloid cells, T cells, and fibroblasts. Although the transcriptomes of myeloid cells were mainly of M2 phenotype, the Th17 cells, CTLs, and Treg cells had signatures critical for cytotoxic functions. Fibroblasts were heterogeneous expressing genes important in fibrosis and regulation of inflammation and immune responses. The intercellular communication networks …


Does Swab Type Matter? Comparing Methods For Mannheimia Haemolytica Recovery And Upper Respiratory Microbiome Characterization In Feedlot Cattle, William B. Crosby, Lee Pinnell, John T. Richeson, Cory Wolfe, Jake Castle, John Dustin Loy, Sheryl P. Gow, Keun Seok Seo, Sarah F. Capik, Amelia R. Woolums, Paul S. Morley Jan 2022

Does Swab Type Matter? Comparing Methods For Mannheimia Haemolytica Recovery And Upper Respiratory Microbiome Characterization In Feedlot Cattle, William B. Crosby, Lee Pinnell, John T. Richeson, Cory Wolfe, Jake Castle, John Dustin Loy, Sheryl P. Gow, Keun Seok Seo, Sarah F. Capik, Amelia R. Woolums, Paul S. Morley

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine respiratory disease (BRD) is caused by interactions among host, environment, and pathogens. One standard method for antemortem pathogen identification in cattle with BRD is deep-guarded nasopharyngeal swabbing, which is challenging, costly, and waste generating. The objective was to compare the ability to recover Mannheimia haemolytica and compare microbial community structure using 29.5 inch (74.9 cm) deep-guarded nasopharyngeal swabs, 16 inch (40.6 cm) unguarded proctology swabs, or 6 inch (15.2 cm) unguarded nasal swabs when characterized using culture, real time-qPCR, and 16S rRNA gene sequencing. Samples for aerobic culture, qPCR, and 16S rRNA gene sequencing were collected from the …


Radiation Exposure Determination In A Secure, Cloudbased Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Joan H.M. Knoll, Peter Rogan Jan 2022

Radiation Exposure Determination In A Secure, Cloudbased Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Joan H.M. Knoll, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …


Evaluation Of Ivermectin Antiviral Activity Against Avian Infectious Bronchitis Virus Using A Chicken Embryo Model, Donald L. Reynolds, E. Barry Simpson Jan 2022

Evaluation Of Ivermectin Antiviral Activity Against Avian Infectious Bronchitis Virus Using A Chicken Embryo Model, Donald L. Reynolds, E. Barry Simpson

School of Veterinary and Biomedical Sciences: Faculty Publications

Ivermectin is widely used in both animals and humans as an FDA-approved parasiticide. Ivermectin has also been reported to have antiviral activity against several viruses including coronaviruses. There are reports that indicate ivermectin may have some role in diminishing the disease caused by SARS-CoV-2, but the evidence is inconclusive. The objective of this study was to determine if ivermectin was efficacious in inhibiting avian infectious bronchitis virus (IBV, a coronavirus) replication in chicken embryos. Briefly, our approach was to use the Massachusetts vaccine strain of IBV in combination with various doses of ivermectin and then inoculate these preparations into chicken …