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Point Substitutions In G Protein-Coupled Receptors, Jessica Brown 2021 Western University

Point Substitutions In G Protein-Coupled Receptors, Jessica Brown

Undergraduate Student Research Internships Conference

G protein-coupled receptors (GPCRs) are proteins that are important in physiological regulatory processes within the body, and for this reason are important drug targets. When bound to an agonist, such as neurotransmitters or hormones, the receptor adopts an active state to allow these biochemical pathways to occur. However, mutations can arise within the receptor that affect its ability to bind its agonist. This natural variation found within the genome can make it difficult to design pharmaceuticals to target the receptors.

To see the effects of these point substitutions on agonist-induced receptor activation, mutations were made within a negative allosteric site …


Chronic Binge Alcohol And Ovariectomy Dysregulate Omental Adipose Tissue Metaboproteome In Simian Immunodeficiency Virus-Infected Female Macaques, Jonquil M. Poret, Jessie J. Guidry, Liz Simon, Patricia E. Molina 2021 LSU Health Sciences Center- New Orleans

Chronic Binge Alcohol And Ovariectomy Dysregulate Omental Adipose Tissue Metaboproteome In Simian Immunodeficiency Virus-Infected Female Macaques, Jonquil M. Poret, Jessie J. Guidry, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

Effective antiretroviral therapy (ART) has significantly reduced mortality of people living with HIV (PLWH), and the prevalence of at-risk alcohol use is higher among PLWH. Increased survival and aging of PLWH is associated with increased prevalence of metabolic comorbidities especially among menopausal women, and adipose tissue metabolic dysregulation may be a significant contributing factor. We examined the differential effects of chronic binge alcohol (CBA) administration and ovariectomy (OVX) on the omental adipose tissue (OmAT) proteome in a subset of simian immunodeficiency virus (SIV)-infected macaques of a longitudinal parent study. Quantitative discovery-based proteomics identified 1,429 differentially expressed proteins. Ingenuity Pathway Analysis …


A Distinct Difference Between Air And Mucosal Temperatures In Human Respiratory Tract, Mehdi Khosravi, Ruei-Lung Lin, Ashish P. Maskey, Subodh Pandey, An-Hsuan Lin, Lu-Yuan Lee 2021 University of Kentucky

A Distinct Difference Between Air And Mucosal Temperatures In Human Respiratory Tract, Mehdi Khosravi, Ruei-Lung Lin, Ashish P. Maskey, Subodh Pandey, An-Hsuan Lin, Lu-Yuan Lee

Internal Medicine Faculty Publications

xtensive evidence indicates that several types of temperature-sensitive ion channels are abundantly expressed in the sensory nerves innervating airway mucosa. Indeed, airway temperature is known to play an important role in regulating respiratory functions. However, the actual airway mucosal temperature and its dynamic changes during the respiratory cycle have not been directly measured. In previous studies, airway tissue temperature was often estimated by indirect measurement of the peak exhaled breath temperature (PEBT). In view of the poor thermal conductivity of air, we believe that the airway tissue temperature cannot be accurately determined by the exhaled air temperature, and this study …


Maternal Lifelong Western Diet Consumption Impacts Placental And Brain Development In The Term Guinea Pig Fetus, Carlene H. Cihosky 2021 The University of Western Ontario

Maternal Lifelong Western Diet Consumption Impacts Placental And Brain Development In The Term Guinea Pig Fetus, Carlene H. Cihosky

Electronic Thesis and Dissertation Repository

Both metabolic and cognitive dysfunction can originate from fetal reprogramming precipitating from adverse conditions experienced in utero. Of note is the western diet (WD), which is associated with maternal energy imbalances that may hinder fetal development through altered placental function. Brain-derived neurotrophic factor (BDNF), a growth factor that supports the placenta and developing brain, is responsive to such energy imbalances. This study sought to investigate the impact of lifelong maternal WD consumption on fetoplacental development, focusing on relations between placental changes, and fetal growth and neurodevelopment in a guinea pig model. Maternal WD consumption resulting in a lean metabolically …


Myonuclear Transcriptional Dynamics In Response To Exercise Following Satellite Cell Depletion, Yuan Wen, Davis A. Englund, Bailey D. Peck, Kevin A. Murach, John J. McCarthy, Charlotte A. Peterson 2021 University of Kentucky

Myonuclear Transcriptional Dynamics In Response To Exercise Following Satellite Cell Depletion, Yuan Wen, Davis A. Englund, Bailey D. Peck, Kevin A. Murach, John J. Mccarthy, Charlotte A. Peterson

Physical Therapy Faculty Publications

Skeletal muscle is composed of post-mitotic myofibers that form a syncytium containing hundreds of myonuclei. Using a progressive exercise training model in the mouse and single nucleus RNA-sequencing (snRNA-seq) for high-resolution characterization of myonuclear transcription, we show myonuclear functional specialization in muscle. After 4 weeks of exercise training, snRNA-seq reveals that resident muscle stem cells, or satellite cells, are activated with acute exercise but demonstrate limited lineage progression while contributing to muscle adaptation. In the absence of satellite cells, a portion of nuclei demonstrates divergent transcriptional dynamics associated with mixed-fate identities compared with satellite cell replete muscles. These data provide …


Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown 2021 Wright State University - Main Campus

Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and …


Effect Of Metformin On The High-Density Lipoprotein Proteome In Youth With Type 1 Diabetes, Evgenia Gourgari, Kristen J. Nadeau, Laura Pyle, Martin P. Playford, Junfeng Ma, Nehal N. Mehta, Alan T. Remaley, Scott M. Gordon 2021 Georgetown University

Effect Of Metformin On The High-Density Lipoprotein Proteome In Youth With Type 1 Diabetes, Evgenia Gourgari, Kristen J. Nadeau, Laura Pyle, Martin P. Playford, Junfeng Ma, Nehal N. Mehta, Alan T. Remaley, Scott M. Gordon

Saha Cardiovascular Research Center Faculty Publications

Background: Youth with type 1 diabetes (T1D) have normal or elevated High-Density Lipoprotein Cholesterol (HDL-C), however, the function of HDL, partly mediated by the HDL proteome, may be impaired. Metformin can be used as an adjunct therapy in youth with T1D, but its effects on the HDL proteome are unknown.

Objective: To determine the effect of metformin on the HDL proteome.

Subjects: Youth (12-20 years old) with T1D who had a BMI > 90th percentile, HbA1c > 8.0% and Tanner stage 5.

Methods: Double-blinded, placebo-controlled randomized sub-study. We examined the effects of metformin (n = 25) or placebo (n = …


Analysis Of Genetic Variants Associated With Levels Of Immune Modulating Proteins For Impact On Alzheimer’S Disease Risk Reveal A Potential Role For Siglec14, Benjamin C. Shaw, Yuriko Katsumata, James F. Simpson, David W. Fardo, Steven Estus 2021 University of Kentucky

Analysis Of Genetic Variants Associated With Levels Of Immune Modulating Proteins For Impact On Alzheimer’S Disease Risk Reveal A Potential Role For Siglec14, Benjamin C. Shaw, Yuriko Katsumata, James F. Simpson, David W. Fardo, Steven Estus

Biostatistics Faculty Publications

Genome-wide association studies (GWAS) have identified immune-related genes as risk factors for Alzheimer’s disease (AD), including TREM2 and CD33, frequently passing a stringent false-discovery rate. These genes either encode or signal through immunomodulatory tyrosine-phosphorylated inhibitory motifs (ITIMs) or activation motifs (ITAMs) and govern processes critical to AD pathology, such as inflammation and amyloid phagocytosis. To investigate whether additional ITIM and ITAM-containing family members may contribute to AD risk and be overlooked due to the stringent multiple testing in GWAS, we combined protein quantitative trait loci (pQTL) data from a recent plasma proteomics study with AD associations in a recent …


The Role Of Action Potential Waveform In Failure Of Excitation Contraction Coupling, Xueyong Wang, Murad Nawaz, Steve R.A. Burke, Roger Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich 2021 Wright State University - Main Campus

The Role Of Action Potential Waveform In Failure Of Excitation Contraction Coupling, Xueyong Wang, Murad Nawaz, Steve R.A. Burke, Roger Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Excitation contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, ICU acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a range of several mV of resting potential. While some studies have hypothesized the sudden failure of ECC is due to all-or-none failure of excitation, other studies suggest failure of excitation is graded. Intracellular recordings of action potentials …


Weak Evidence, Supplemented With Common Sense For Reduction In Postoperative Pulmonary Complications, Natalie M. Wiseman 2021 Wayne State University

Weak Evidence, Supplemented With Common Sense For Reduction In Postoperative Pulmonary Complications, Natalie M. Wiseman

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Kaminski PN, Forgiarini LA, Jr., Andrade CF. Early respiratory therapy reduces postoperative atelectasis in children undergoing lung resection. Respir Care. 2013;58(5):805-809. https://doi.org/10.4187/respcare.01870

for prevention of postoperative pulmonary complications following thoracic surgery for a patient who is not able to participate in incentive spirometry.


Isolation, Proliferation And Differentiation Of Rhesus Macaque Adipose-Derived Stem Cells, Jonquil M. Poret, Patricia E. Molina, Liz Simon 2021 LSU Health Sciences Center- New Orleans

Isolation, Proliferation And Differentiation Of Rhesus Macaque Adipose-Derived Stem Cells, Jonquil M. Poret, Patricia E. Molina, Liz Simon

School of Medicine Faculty Publications

Adipose tissue provides a rich and accessible source of multipotent stem cells, which are able to self-renew. These adipose-derived stem cells (ADSCs) provide a consistent ex vivo cellular system that are functionally like that of in vivo adipocytes. Use of ADSCs in biomedical research allows for cellular investigation of adipose tissue metabolic regulation and function. ADSC differentiation is necessary for adequate adipocyte expansion, and suboptimal differentiation is a major mechanism of adipose dysfunction. Understanding changes in ADSC differentiation is crucial to understanding the development of metabolic dysfunction and disease. The protocols described in this manuscript, when followed, will yield mature …


Reiki For Recovery: Incorporating Japanese Health Practices To Increase Contemporary Resiliency In American Health, Leif Peterson 2021 The University of San Francisco

Reiki For Recovery: Incorporating Japanese Health Practices To Increase Contemporary Resiliency In American Health, Leif Peterson

Master's Projects and Capstones

The Japanese health practice of Reiki attempts to maximize the latent ability of the human system to heal itself. The Reiki system, established over a century ago, combines multiple Asian health traditions, experimenting with practices that maximize the natural processes of the body to perform its own repairs. Reiki encourages healthy behaviors that balance the mind and body, return the human system to a lowered stress level, and allow for an optimal recovery state for the patient. This paper illustrates how this Japanese health-affirming method can be integrated and utilized within existing health and medical practices. An area that is …


Critically Ill Covid-19 Patients Exhibit Anti-Sars-Cov-2 Serological Responses, Mark Daley, Douglas D. Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio M. Martin, Maitray A. Patel, Michael Miller, Eric K. Patterson, David B. O’gorman, Sean E. Gill, Ian Higgins, Julius P. John, Christopher Melo, Lylia Nini, Xiaoqin Wang, Johannes Zeidler, Jorge A. Cruz-Aguado 2021 University of Western Ontairo

Critically Ill Covid-19 Patients Exhibit Anti-Sars-Cov-2 Serological Responses, Mark Daley, Douglas D. Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio M. Martin, Maitray A. Patel, Michael Miller, Eric K. Patterson, David B. O’Gorman, Sean E. Gill, Ian Higgins, Julius P. John, Christopher Melo, Lylia Nini, Xiaoqin Wang, Johannes Zeidler, Jorge A. Cruz-Aguado

Physiology and Pharmacology Publications

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global health care emergency. Anti-SARS-CoV-2 serological profiling of critically ill COVID-19 patients was performed to determine their humoral response. Blood was collected from critically ill ICU patients, either COVID-19 positive (+) or COVID-19 negative (−), to measure anti-SARS-CoV-2 immunoglobulins: IgM; IgA; IgG; and Total Ig (combined IgM/IgA/IgG). Cohorts were similar, with the exception that COVID-19+ patients had a greater body mass indexes, developed bilateral pneumonias more frequently and suffered increased hypoxia when compared to COVID-19-patients (p < 0.05). The mortality rate for COVID-19+ patients was 50%. COVID-19 status could be determined by anti-SARS-CoV-2 serological responses with excellent classification accuracies on ICU day 1 (89%); ICU day 3 (96%); and ICU days 7 and 10 (100%). The importance of each Ig isotype for determining COVID-19 status on combined ICU days 1 and 3 was: Total Ig, 43%; IgM, 27%; IgA, 24% and IgG, 6%. Peak serological responses for each Ig isotype occurred on different ICU days (IgM day 13 > IgA day 17 > IgG persistently increased), with the Total Ig peaking at approximately ICU day …


Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee 2021 University of Kentucky

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, …


Water Exchange Rate Across The Blood-Brain Barrier Is Associated With Csf Amyloid-Β 42 In Healthy Older Adults, Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J. J. Wang 2021 University of Kentucky

Water Exchange Rate Across The Blood-Brain Barrier Is Associated With Csf Amyloid-Β 42 In Healthy Older Adults, Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J. J. Wang

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function.

METHODS: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion‐prepared, arterial spin labeling (DP‐ASL), which estimates water exchange rate across the BBB (kw). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores.

RESULTS: In multiple brain regions, BBB kw was positively associated with CSF amyloid …


The Role Of Nutrition And Hormone Signaling In Extended Larval Development And Obesity In Starvation-Selected Drosophila Melanogaster, Jennifer M. Clark 2021 University of Nevada, Las Vegas

The Role Of Nutrition And Hormone Signaling In Extended Larval Development And Obesity In Starvation-Selected Drosophila Melanogaster, Jennifer M. Clark

UNLV Theses, Dissertations, Professional Papers, and Capstones

Brief periods of starvation are a common stressor that most animals encounter in the wild and must be able to survive in order to maximize their fitness. Starvation resistance of the adult fruit fly, Drosophila melanogaster, is thought to be primarily conferred by adult fat stores, body size, metabolic rate, behavior, and activity levels. Additionally, flies selected for starvation resistance also often show delayed pupariation, which is usually indicative of altered hormone signaling. How starvation selection extends development and if it contributes to adult starvation resistance remains incompletely studied. Identifying the targets of starvation selection that cause extended development and …


The Mechanism Underlying Transient Weakness In Myotonia Congenita, Jessica H. Myers, Kirsten Denman, Chris DuPont, Ahmed A. Hawash, Kevin R. Novak, Andrew Koesters, Manfred Grabner, Anamika Dayal, Andrew A. Voss, Mark M. Rich 2021 Wright State University

The Mechanism Underlying Transient Weakness In Myotonia Congenita, Jessica H. Myers, Kirsten Denman, Chris Dupont, Ahmed A. Hawash, Kevin R. Novak, Andrew Koesters, Manfred Grabner, Anamika Dayal, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

In addition to the hallmark muscle stiffness, patients with recessive myotonia congenita (Becker disease) experience debilitating bouts of transient weakness that remain poorly understood despite years of study. We performed intracellular recordings from muscle of both genetic and pharmacologic mouse models of Becker disease to identify the mechanism underlying transient weakness. Our recordings reveal transient depolarizations (plateau potentials) of the membrane potential to -25 to -35 mV in the genetic and pharmacologic models of Becker disease. Both Na + and Ca 2+ currents contribute to plateau potentials. Na + persistent inward current (NaPIC) through Na V 1.4 channels is the …


Vitamin D Promotes Skeletal Muscle Regeneration And Mitochondrial Health, Christine M. Latham, Camille R. Brightwell, Alexander R. Keeble, Brooke D. Munson, Nicholas T. Thomas, Alyaa M. Zagzoog, Christopher S. Fry, Jean L. Fry 2021 University of Kentucky

Vitamin D Promotes Skeletal Muscle Regeneration And Mitochondrial Health, Christine M. Latham, Camille R. Brightwell, Alexander R. Keeble, Brooke D. Munson, Nicholas T. Thomas, Alyaa M. Zagzoog, Christopher S. Fry, Jean L. Fry

Athletic Training and Clinical Nutrition Faculty Publications

Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated …


The Crosstalk Between Insulin Resistance, Systemic Inflammation, Redox Imbalance And The Thyroid In Subjects With Obesity, Nicoleta Răcătăianu, Nicoleta Valentina Leach, Sorana D. Bolboacă, Maria Loredana Soran, Mirela Flonta, Ana Valea, Andrada-Luciana Lazăr, Cristina Ghervan 2021 IULIU HAŢIEGANU UNIVERSITY OF MEDICINE AND PHARMACY, DEPARTMENT OF ENDOCRINOLOGY, CLUJ-NAPOCA, ROMANIA

The Crosstalk Between Insulin Resistance, Systemic Inflammation, Redox Imbalance And The Thyroid In Subjects With Obesity, Nicoleta Răcătăianu, Nicoleta Valentina Leach, Sorana D. Bolboacă, Maria Loredana Soran, Mirela Flonta, Ana Valea, Andrada-Luciana Lazăr, Cristina Ghervan

Journal of Mind and Medical Sciences

We aimed at assessing the interaction between visceral adipose tissue (VAT), insulin resistance (IR), circulating levels of monocyte chemoattractant protein-1 (MCP-1) and malondialdehyde (MDA) and the thyroid parameters in obese subjects. Methods. Obese subjects without thyroid pathologies or diseases associated with systemic inflammation and OS were recruited. Insulinemia, visceral fat thickness, metabolic and thyroid parameters were assayed. Circulating levels of MCP-1 and MDA were used to quantify inflammation and OS. Results. A number of 160 obese subjects were included. The MCP-1 level increased with the degree of obesity and HOMA-IR. MCP 1 was positively associated with antithyroperoxidase antibody (TPOab) levels …


A Mouse Model Of Huntington’S Disease Shows Altered Ultrastructure Of Transverse Tubules In Skeletal Muscle Fibers, Shannon H. Romer, Sabrina Metzger, Kristiana Peraza, Matthew C. Wright, D. Scott Jobe, Long-Sheng Song, Mark M. Rich, Brent D. Foy, Robert J. Talmadge, Andrew A. Voss 2021 Wright State University

A Mouse Model Of Huntington’S Disease Shows Altered Ultrastructure Of Transverse Tubules In Skeletal Muscle Fibers, Shannon H. Romer, Sabrina Metzger, Kristiana Peraza, Matthew C. Wright, D. Scott Jobe, Long-Sheng Song, Mark M. Rich, Brent D. Foy, Robert J. Talmadge, Andrew A. Voss

Neuroscience, Cell Biology & Physiology Faculty Publications

Huntington’s disease (HD) is a fatal and progressive condition with severe debilitating motor defects and muscle weakness. Although classically recognized as a neurodegenerative disorder, there is increasing evidence of cell autonomous toxicity in skeletal muscle. We recently demonstrated that skeletal muscle fibers from the R6/2 model mouse of HD have a decrease in specific membrane capacitance, suggesting a loss of transverse tubule (t-tubule) membrane in R6/2 muscle. A previous report also indicated that Cav1.1 current was reduced in R6/2 skeletal muscle, suggesting defects in excitation–contraction (EC) coupling. Thus, we hypothesized that a loss and/or disruption of the skeletal muscle t-tubule …


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