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Intrarenal Renin Angiotensin System Imbalance During Postnatal Life Is Associated With Increased Microvascular Density In The Mature Kidney, Carolina Dalmasso, Alejandro R. Chade, Mariela Mendez, Jorge F. Giani, Gregory J. Bix, Kuey Chu Chen, Analia S. Loria 2020 University of Kentucky

Intrarenal Renin Angiotensin System Imbalance During Postnatal Life Is Associated With Increased Microvascular Density In The Mature Kidney, Carolina Dalmasso, Alejandro R. Chade, Mariela Mendez, Jorge F. Giani, Gregory J. Bix, Kuey Chu Chen, Analia S. Loria

Pharmacology and Nutritional Sciences Faculty Publications

Environmental stress during early life is an important factor that affects the postnatal renal development. We have previously shown that male rats exposed to maternal separation (MatSep), a model of early life stress, are normotensive but display a sex-specific reduced renal function and exacerbated angiotensin II (AngII)-mediated vascular responses as adults. Since optimal AngII levels during postnatal life are required for normal maturation of the kidney, this study was designed to investigate both short- and long-term effect of MatSep on (1) the renal vascular architecture and function, (2) the intrarenal renin-angiotensin system (RAS) components status, and (3) the genome-wide expression …


Conditional Loss Of Engrailed 1/2 In Rhombic Lip-Derived Neurons Increases Intrinsic Rhythmicity And Decreases Overall Variability Of Eupneic Respiration, Angela P. Taylor 2020 University of Tennessee Health Science Center

Conditional Loss Of Engrailed 1/2 In Rhombic Lip-Derived Neurons Increases Intrinsic Rhythmicity And Decreases Overall Variability Of Eupneic Respiration, Angela P. Taylor

Theses and Dissertations (ETD)

Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but investigation into cerebellar involvement in eupneic breathing has been inconclusive. Given the view of the cerebellum (CRB) as a temporally coordinating structure, any investigation into the CRB during respiration must evaluate rhythm and variability of the respiratory sequence. In this study, we chose an elegant model of cerebellar neuropathology, Atoh1-En1/2 CKO, where mutant animals have conditional loss of the developmental patterning gene Engrailed 1/2 in rhombic lip-lineage neurons and exhibit a proportional scaling-down of neuron number in hypoplastic lobules of the CRB. We utilized whole-body unrestrained plethysmography …


Systematic Survey Of Creatinine-Based Versus Cystatin C-Based Estimated Gfr In People With Diabetes, Sadik Acaralp, Hossein Akhondi 2020 MountainView Hospital-Nevada

Systematic Survey Of Creatinine-Based Versus Cystatin C-Based Estimated Gfr In People With Diabetes, Sadik Acaralp, Hossein Akhondi

HCA Healthcare Journal of Medicine

Background: Diabetes is a common cause of kidney failure, and most anti-diabetic agents are excreted through the kidneys. Therefore, it is critical to adjust medication dosage and anti-diabetic agents based on kidney function. There are different methods to estimate kidney function, but the common practice is to use creatinine to estimate the glomerular filtration rate.

Objective: In this systematic review, we identify and review publications in order to assess differences between creatinine-based and cystatin C-based estimated glomerular filtration rates in diabetic patients.

Method: The articles were identified using 3 databases and were assessed for eligibility. A total of 4 articles …


Therapeutic Trem2 Activation Ameliorates Amyloid-Beta Deposition And Improves Cognition In The 5xfad Model Of Amyloid Deposition, Brittani R. Price, Tiffany L. Sudduth, Erica M. Weekman, Sherika Johnson, Danielle Hawthorne, Abigail E. Woolums, Donna M. Wilcock 2020 University of Kentucky

Therapeutic Trem2 Activation Ameliorates Amyloid-Beta Deposition And Improves Cognition In The 5xfad Model Of Amyloid Deposition, Brittani R. Price, Tiffany L. Sudduth, Erica M. Weekman, Sherika Johnson, Danielle Hawthorne, Abigail E. Woolums, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Triggering receptor expressed on myeloid cell-2 (TREM2) is a lipid and lipoprotein binding receptor expressed by cells of myeloid origin. Homozygous TREM2 mutations cause early onset progressive presenile dementia while heterozygous, point mutations triple the risk of Alzheimer's disease (AD). Although human genetic findings support the notion that loss of TREM2 function exacerbates neurodegeneration, it is not clear whether activation of TREM2 in a disease state would result in therapeutic benefits. To determine the viability of TREM2 activation as a therapeutic strategy, we sought to characterize an agonistic Trem2 antibody (AL002a) and test its efficacy and mechanism of action …


Glut1 Deficiency: Retinal Detrimental Effects Of Gliovascular Modulation, Matt Henry, John Kitchens, Juan M. Pascual, Ramiro S. Maldonado 2020 The University of Texas Southwestern Medical Center

Glut1 Deficiency: Retinal Detrimental Effects Of Gliovascular Modulation, Matt Henry, John Kitchens, Juan M. Pascual, Ramiro S. Maldonado

Ophthalmology and Visual Science Faculty Publications

No abstract provided.


Heart Failure In Humans Reduces Contractile Force In Myocardium From Both Ventricles, Cheavar A. Blair, Elizabeth A Brundage, Katherine L. Thompson, Arnold J. Stromberg, Maya Guglin, Brandon J Biesiadecki, Kenneth S. Campbell 2020 University of Kentucky

Heart Failure In Humans Reduces Contractile Force In Myocardium From Both Ventricles, Cheavar A. Blair, Elizabeth A Brundage, Katherine L. Thompson, Arnold J. Stromberg, Maya Guglin, Brandon J Biesiadecki, Kenneth S. Campbell

Statistics Faculty Publications

This study measured how heart failure affects the contractile properties of the human myocardium from the left and right ventricles. The data showed that maximum force and maximum power were reduced by approximately 30% in multicellular preparations from both ventricles, possibly because of ventricular remodeling (e.g., cellular disarray and/or excess fibrosis). Heart failure increased the calcium (Ca2+) sensitivity of contraction in both ventricles, but the effect was bigger in right ventricular samples. The changes in Ca2+ sensitivity were associated with ventricle-specific changes in the phosphorylation of troponin I, which indicated that adrenergic stimulation might induce different effects …


In Vivo Evidence Of Exosome-Mediated Aβ Neurotoxicity, Ahmed Elsherbini, Haiyan Qin, Zhihui Zhu, Priyanka Tripathi, Simone M. Crivelli, Erhard Bieberich 2020 University of Kentucky

In Vivo Evidence Of Exosome-Mediated Aβ Neurotoxicity, Ahmed Elsherbini, Haiyan Qin, Zhihui Zhu, Priyanka Tripathi, Simone M. Crivelli, Erhard Bieberich

Physiology Faculty Publications

No abstract provided.


Are We Missing The Target? Are We Aiming Too Low? What Are The Aerobic Exercise Prescriptions And Their Effects On Markers Of Cardiovascular Health And Systemic Inflammation In Patients With Knee Osteoarthritis? A Systematic Review And Meta-Analysis, Jenna M. Schulz, Trevor B. Birmingham, Hayden F. Atkinson, Emilie Woehrle, Codie A. Primeau, Michael J. Lukacs, Baraa K. Al-Khazraji, Michaela C.M. Khan, Bryn O. Zomar, Robert J. Petrella, Frank Beier, C. Thomas Appleton, J. Kevin Shoemaker, DIanne M. Bryant 2020 Western University

Are We Missing The Target? Are We Aiming Too Low? What Are The Aerobic Exercise Prescriptions And Their Effects On Markers Of Cardiovascular Health And Systemic Inflammation In Patients With Knee Osteoarthritis? A Systematic Review And Meta-Analysis, Jenna M. Schulz, Trevor B. Birmingham, Hayden F. Atkinson, Emilie Woehrle, Codie A. Primeau, Michael J. Lukacs, Baraa K. Al-Khazraji, Michaela C.M. Khan, Bryn O. Zomar, Robert J. Petrella, Frank Beier, C. Thomas Appleton, J. Kevin Shoemaker, Dianne M. Bryant

Physiology and Pharmacology Publications

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Objectives We systemically reviewed published studies that evaluated aerobic exercise interventions in patients with knee osteoarthritis (OA) to: (1) report the frequency, intensity, type and time (FITT) of exercise prescriptions and (2) quantify the changes in markers of cardiovascular health and systemic inflammation. Data sources PubMed, CINAHL, Scopus; inception to January 2019. Eligibility criteria Randomised clinical trials (RCT), cohort studies, case series. Design We summarised exercise prescriptions for all studies and calculated effect sizes with 95% CIs for between-group (RCTs that compared exercise and …


Inflammation Profiling Of Critically Ill Coronavirus Disease 2019 Patients., Douglas D Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio Martin, Mark Daley, Michael R Miller, David B O'Gorman, Sean E Gill, Eric K Patterson, Claudia C Dos Santos 2020 University of Western Ontairo

Inflammation Profiling Of Critically Ill Coronavirus Disease 2019 Patients., Douglas D Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio Martin, Mark Daley, Michael R Miller, David B O'Gorman, Sean E Gill, Eric K Patterson, Claudia C Dos Santos

Physiology and Pharmacology Publications

Objectives: Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019.

Design: Daily blood inflammation profiling with immunoassays.

Setting: Tertiary care ICU and academic laboratory.

Subjects: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus …


Olive Oil Diet In Mild Pre-Gestational Diabetes Impacts Offspring Β-Cell Development., Bushra Taqui, Farsad Asadi, Evangelina Capobianco, Daniel Barry Hardy, Alicia Jawerbaum, Edith Juliana Arany 2020 Western University

Olive Oil Diet In Mild Pre-Gestational Diabetes Impacts Offspring Β-Cell Development., Bushra Taqui, Farsad Asadi, Evangelina Capobianco, Daniel Barry Hardy, Alicia Jawerbaum, Edith Juliana Arany

Physiology and Pharmacology Publications

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we showed maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study we examined the effects of this diet on neonatal and adult pancreatic development in both male and female offspring. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy these dams were fed a chow diet supplemented or not with 6% olive oil. Dual immunohistochemistry was performed to detect …


Regulation Of Myofilament Contractile Function In Human Donor And Failing Hearts, Kerry S. McDonald, Laurin M. Hanft, Joel C. Robinett, Maya Guglin, Kenneth S. Campbell 2020 University of Missouri

Regulation Of Myofilament Contractile Function In Human Donor And Failing Hearts, Kerry S. Mcdonald, Laurin M. Hanft, Joel C. Robinett, Maya Guglin, Kenneth S. Campbell

Internal Medicine Faculty Publications

Heart failure (HF) often includes changes in myocardial contractile function. This study addressed the myofibrillar basis for contractile dysfunction in failing human myocardium. Regulation of contractile properties was measured in cardiac myocyte preparations isolated from frozen, left ventricular mid-wall biopsies of donor (n = 7) and failing human hearts (n = 8). Permeabilized cardiac myocyte preparations were attached between a force transducer and a position motor, and both the Ca2+ dependence and sarcomere length (SL) dependence of force, rate of force, loaded shortening, and power output were measured at 15 ± 1°C. The myocyte preparation size was …


Microrna-148a Regulates Low-Density Lipoprotein Metabolism By Repressing The (Pro)Renin Receptor, Na Wang, Lishu He, Hui Lin, Lunbo Tan, Yuan Sun, Xiaoying Zhang, A. H. Jan Danser, Hong S. Lu, Yongcheng He, Xifeng Lu 2020 Shenzhen University, China

Microrna-148a Regulates Low-Density Lipoprotein Metabolism By Repressing The (Pro)Renin Receptor, Na Wang, Lishu He, Hui Lin, Lunbo Tan, Yuan Sun, Xiaoying Zhang, A. H. Jan Danser, Hong S. Lu, Yongcheng He, Xifeng Lu

Saha Cardiovascular Research Center Faculty Publications

High plasma LDL cholesterol (LDL-c) concentration is a major risk factor for atherosclerosis. Hepatic LDL receptor (LDLR) regulates LDL metabolism, and thereby plasma LDL-c concentration. Recently, we have identified the (pro)renin receptor [(P)RR] as a novel regulator of LDL metabolism, which regulates LDLR degradation and hence its protein abundance and activity. In silico analysis suggests that the (P)RR is a target of miR-148a. In this study we determined whether miR-148a could regulate LDL metabolism by regulating (P)RR expression in HepG2 and Huh7 cells. We found that miR-148a suppressed (P)RR expression by binding to the 3’-untranslated regions (3’-UTR) of the (P)RR …


Overexpression Of Mig-6 In The Cartilage Induces An Osteoarthritis-Like Phenotype In Mice, Melina Bellini, Michael A. Pest, Manuela Miranda-Rodrigues, Ling Qin, Jae Wook Jeong, Frank Beier 2020 Western University

Overexpression Of Mig-6 In The Cartilage Induces An Osteoarthritis-Like Phenotype In Mice, Melina Bellini, Michael A. Pest, Manuela Miranda-Rodrigues, Ling Qin, Jae Wook Jeong, Frank Beier

Physiology and Pharmacology Publications

© 2020 The Author(s). Background: Osteoarthritis (OA) is the most common form of arthritis and characterized by degeneration of the articular cartilage. Mitogen-inducible gene 6 (Mig-6) has been identified as a negative regulator of the epidermal growth factor receptor (EGFR). Cartilage-specific Mig-6 knockout (KO) mice display increased EGFR signaling, an anabolic buildup of the articular cartilage, and formation of chondro-osseous nodules. Since our understanding of the EGFR/Mig-6 network in the cartilage remains incomplete, we characterized mice with cartilage-specific overexpression of Mig-6 in this study. Methods: Utilizing knee joints from cartilage-specific Mig-6-overexpressing (Mig-6 over/over ) mice (at multiple time points), we …


The Role Of Central Ace2 And Nrf2 In Sympatho-Excitation: Responses To Central Angiotensin Ii, Anyun Ma 2020 University of Nebraska Medical Center

The Role Of Central Ace2 And Nrf2 In Sympatho-Excitation: Responses To Central Angiotensin Ii, Anyun Ma

Theses & Dissertations

Sympatho-excitation is a key characteristic in cardiovascular diseases such as chronic heart failure (CHF) and primary Hypertension (HTN). Evidence suggests that increased sympathetic tone is closely related to activation of the Renin-Angiotensin-Aldosterone system (RAAS) in the central nervous system. An underlying mechanism for sympatho-excitation is thought to be oxidative stress resulting from Angiotensin II (AngII) type 1 receptor (AT1R) activation. Over the past several decades, pharmacological targeting of components of the RAAS have been used as standard therapy in CHF and HTN. However, additional therapeutic strategies are necessary to control these diseases. Oxidative stress is regulated, in part, by the …


Depressed Neuromuscular Transmission Causes Weakness In Mice Lacking Bk Potassium Channels, Xueyong Wang, Steven R.A. Burke, Robert J. Talmadge, Andrew A. Voss, Mark M. Rich 2020 Wright State University - Main Campus

Depressed Neuromuscular Transmission Causes Weakness In Mice Lacking Bk Potassium Channels, Xueyong Wang, Steven R.A. Burke, Robert J. Talmadge, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Mice lacking functional large-conductance voltage- and Ca2+-activated K+ channels (BK channels) are viable but have motor deficits including ataxia and weakness. The cause of weakness is unknown. In this study, we discovered, in vivo, that skeletal muscle in mice lacking BK channels (BK−/−) was weak in response to nerve stimulation but not to direct muscle stimulation, suggesting a failure of neuromuscular transmission. Voltage-clamp studies of the BK−/− neuromuscular junction (NMJ) revealed a reduction in evoked endplate current amplitude and the frequency of spontaneous vesicle release compared with WT littermates. Responses to 50-Hz stimulation indicated a reduced probability of vesicle release …


Alternative Polyadenylation Modulates Expression Of Pro-Fibrotic Proteins And Contributes To Lung Fibrosis, Junsuk Ko 2020 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Alternative Polyadenylation Modulates Expression Of Pro-Fibrotic Proteins And Contributes To Lung Fibrosis, Junsuk Ko

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects about 5 to 8 million individuals in the world. Despite the high prevalence, there is currently no cure for IPF, and the cause of this disease is still unclear. Our laboratory and collaborators have shown that nudix hydrolase 21 (NUDT21, which is also known as cleavage factor 25, CFIm25) is a key regulator of alternative polyadenylation (APA). NUDT21 depletion causes 3’UTR shortening via APA leading to enhanced mRNA stability and protein translation. This NUDT21 reduction promotes tumor growth in glioblastoma by enhancing expression of oncogenes. Cancer and IPF share …


Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters 2020 East Tennessee State University

Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters

Undergraduate Honors Theses

The nicotinamide riboside (NR) form of vitamin B3and the ketone body ß-hydroxybutyrate (BHB) are two of the most promising natural compounds yet identified for the treatment of aging and aging-related diseases. Forms of vitamin B3are precursors for the synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD(H)) and nicotinamide adenine dinucleotide phosphate (NADP(H)). In aged cells levels of NAD+decline, decreasing metabolism and decreasing activity of protective sirtuin protein deacetylases. In aged cells NR, but not more common forms of vitamin B3, boost NAD+levels. BHB is naturally produced by the body when individuals fast …


Rapid Evolution Of Starvation Resistance In Drosophila: Physiological And Molecular Mechanisms, Austin Joseph McKenna 2020 University of Nevada, Las Vegas

Rapid Evolution Of Starvation Resistance In Drosophila: Physiological And Molecular Mechanisms, Austin Joseph Mckenna

UNLV Theses, Dissertations, Professional Papers, and Capstones

The Gibbs lab has maintained starvation-selected Drosophila melanogaster for >130 generations. These starvation-selected flies evolved an obese phenotype with a suite of physiological differences compared to control-fed flies. Previous studies have shown that long-term starvation-selected Drosophila contain more lipids, have lower metabolic rates and develop more slowly than controls. This dissertation encompasses 1) Examining the molecular mechanisms contributing to starvation resistance, 2) Functional validation of the candidate plin1 allele, and 3) Rapid physiological and genomic evolution in starvation-selected Drosophila.

Starvation-selected Drosophila survive starvation conditions much longer than control-fed flies. This study took a simple approach to identify possible differences in …


Utilizing Breathing Techniques To Maximize Training Performance, Peyton Cater 2020 University of Nevada, Las Vegas

Utilizing Breathing Techniques To Maximize Training Performance, Peyton Cater

UNLV Theses, Dissertations, Professional Papers, and Capstones

Anaerobic exercise causes metabolic acidosis to occur in the muscle, which is unfavorable for sustaining high intensity activity, as fatigue starts to set in. In order to compensate for the onset of fatigue produced by an acidic environment, respiratory alkalosis, induced by hyperventilation, can be performed to mitigate these effects. In contrast, research has shown that slowing down the breath rate, such as a two second inhale and three second exhale, has led to an increase in performance outcomes. Purpose: To investigate power output and the physiological responses after implementation of different breathing techniques during the recovery periods of intermittent …


Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito 2020 Sunrise Health GME Consortium

Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito

HCA Healthcare Journal of Medicine

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system. Clinical manifestations include encephalopathy, motor deficits, ataxia, and meningeal signs. In most cases, ADEM is preceded by either vaccination or viral illness. Here, we present a case with neither of the two predisposing elements.

Discussion: A 28-year-old Hispanic female presenting with substance use and suicidal ideation was placed on an involuntary psychiatric hold, started on olanzapine and scheduled for a psychiatric facility transfer. The following day, she was noted to have neurological deficits when ambulating. Computed tomography of the brain showed a right frontal …


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