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Intranasal Oxytocin Enhances Connectivity In The Neural Circuitry Supporting Social Motivation And Social Perception In Children With Autism., Ilanit Gordon, Allison Jack, Charlotte M Pretzsch, Brent Vander Wyk, James F Leckman, Ruth Feldman, Kevin A. Pelphrey 2016 George Washington University

Intranasal Oxytocin Enhances Connectivity In The Neural Circuitry Supporting Social Motivation And Social Perception In Children With Autism., Ilanit Gordon, Allison Jack, Charlotte M Pretzsch, Brent Vander Wyk, James F Leckman, Ruth Feldman, Kevin A. Pelphrey

Pharmacology and Physiology Faculty Publications

Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social perception. Using functional magnetic resonance imaging and a randomized, double blind, placebo-controlled crossover design, we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information. Further, OT enhances connectivity between nodes of the brain's reward and socioemotional processing systems, and does so preferentially ...


Mitochondrial Superoxide Signaling Contributes To Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles., Adam J. Case, Colton T. Roessner, Jun Tian, Matthew C. Zimmerman 2016 University of Nebraska Medical Center

Mitochondrial Superoxide Signaling Contributes To Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles., Adam J. Case, Colton T. Roessner, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Norepinephrine (NE) produces multifaceted regulatory patterns in T-lymphocytes. Recently, we have shown that NE utilizes redox signaling as evidenced by increased superoxide (O2●-) causally linked to the observed changes in these cells; however, the source of this reactive oxygen species (ROS) remains elusive. Herein, we hypothesized that the source of increased O2●- in NE-stimulated T-lymphocytes is due to disruption of mitochondrial bioenergetics. To address this hypothesis, we utilized purified mouse splenic CD4+ and CD8+ T-lymphocytes stimulated with NE and assessed O2●- levels, mitochondrial metabolism, cellular proliferation, and cytokine profiles. We demonstrate that the increase in O2●- levels in response to ...


The Beta-1-Receptor Blocker Nebivolol Elicits Dilation Of Cerebral Arteries By Reducing Smooth Muscle [Ca2+]I, Peter Cseplo, Zoltan Vamos, Ivan Ivic, Orsolya Torok, Attila Toth, Akos Koller 2016 New York Medical College

The Beta-1-Receptor Blocker Nebivolol Elicits Dilation Of Cerebral Arteries By Reducing Smooth Muscle [Ca2+]I, Peter Cseplo, Zoltan Vamos, Ivan Ivic, Orsolya Torok, Attila Toth, Akos Koller

NYMC Faculty Publications

RATIONALE: Nebivolol is known to have beta-1 blocker activity, but it was also suggested that it elicits relaxation of the peripheral arteries in part via release of nitric oxide (NO). However, the effect of nebivolol on the vasomotor tone of cerebral arteries is still unclear.

OBJECTIVE: To assess the effects of nebivolol on the diameter of isolated rat basilar arteries (BA) in control, in the presence of inhibitors of vasomotor signaling pathways of know action and hemolysed blood.

METHODS AND RESULTS: Vasomotor responses were measured by videomicroscopy and the intracellular Ca2+ by the Fura-2 AM ratiometric method. Under control conditions ...


An Excitatory Cortical Feedback Loop Gates Retinal Wave Transmission In Rodent Thalamus, Yasunobu Murata, Matthew T. Colonnese 2016 George Washington University

An Excitatory Cortical Feedback Loop Gates Retinal Wave Transmission In Rodent Thalamus, Yasunobu Murata, Matthew T. Colonnese

Pharmacology and Physiology Faculty Publications

Spontaneous retinal waves are critical for the development of receptive fields in visual thalamus (LGN) and cortex (VC). Despite a detailed understanding of the circuit specializations in retina that generate waves, whether central circuit specializations also exist to control their propagation through visual pathways of the brain is unknown. Here we identify a developmentally transient, corticothalamic amplification of retinal drive to thalamus as a mechanism for retinal wave transmission in the infant rat brain. During the period of retinal waves, corticothalamic connections excite LGN, rather than driving feedforward inhibition as observed in the adult. This creates an excitatory feedback loop ...


White Blood Cell Count Versus Temperature As Predictors Of Pediatric Bacteremia, Ashley Ashby, Loren Moscinski 2016 James Madison University

White Blood Cell Count Versus Temperature As Predictors Of Pediatric Bacteremia, Ashley Ashby, Loren Moscinski

Physician Assistant Capstones

Introduction: Although the prevalence of bacteremia has largely declined with the development of the Haemophilus Influenza Type b (Hib) and pneumococcal vaccines, it continues to be a leading cause of morbidity and mortality in children. Thus, it is crucial to differentiate bacteremia from other illnesses via the clinical picture and laboratory test results. Objective: The purpose of this research was to determine whether there is a clinically significant difference between temperature and white blood cell (WBC) count as determinants of bacteremia in the pediatric population. Methods: A PubMed search was conducted utilizing the following terms and filters: temperature, WBC, pediatrics ...


The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka 2016 University of Louisville

The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka

Electronic Theses and Dissertations

Global augmentation of protein O-GlcNAcylation occurs in response to a myriad of stressors and confers a survival advantage at the cellular level. This protective phenomenon has been demonstrated to mediate cardioprotection through various in vitro and in vivo studies during ischemia-reperfusion, myocardial infarction, and oxidative stress; however, relatively little is known of the regulation of protein O-GlcNAcylation. Protein O-GlcNAcylation is regulated by two antagonistic enzymes, namely, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ablation of cardiomyocyte OGT, the enzyme that catalyzes the addition of O-GlcNAc to proteins, exacerbates cardiac dysfunction during infarct-induced heart failure (HF). However, little is known of the ...


Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva 2016 University of Louisville

Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva

Electronic Theses and Dissertations

Background: Hyperhomocysteinemia (HHcy) has been observed to promote hypertension, but the mechanisms are unclear. Toll-like receptor 4 (TLR-4) is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. TLR-4 activation has been shown to promote inflammation that has been associated with pathogenesis of hypertension. In this study, we hypothesize that HHcy induces hypertension by TLR-4 activation that promotes inflammatory cytokine up-regulation (IL-1β, IL-6, TNF-α) and initiation of mitochondrial dysfunction leading to cell death and chronic vascular inflammation. Methods: To test this hypothesis, we used C57BL/6J mice (WT); Cystathionine-β-synthase deficient mice (CBS+/-) with genetic ...


Malignant Hyperthermia, Aaron Roth 2016 Otterbein University

Malignant Hyperthermia, Aaron Roth

Master of Science in Nursing (MSN) Student Scholarship

Malignant hyperthermia is a rare disease trait and can take place in a variety of settings. If not treated in a timely manner, the consequences will be dire. It is recommended that nurses and other healthcare personnel be properly educated on MH crises. By detecting the signs and symptoms associated with the disease, providers can efficiently remedy the crisis and save patient lives (Seifert, 2014). Since the discovery of dantrolene in 1975 and the advancement of genetics regarding MH, death rates dropped from about 80% to about 5% (Schneiderbanger et al., 2014). Today there is a MH group called the ...


Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue 2016 Loma Linda University

Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of ...


Complex Regional Pain Syndrome, Maria A. Hendrix 2016 Otterbein University

Complex Regional Pain Syndrome, Maria A. Hendrix

Master of Science in Nursing (MSN) Student Scholarship

Complex regional pain syndrome (CRPS) is a chronic and often disabling condition that is seen in many patients seeking pain management. The condition leaves patients in excruciating pain that is disproportionate to the inciting injury. In addition, patients with this pain disorder experience abnormal sensations such as cold and heat allodynia, hyperalgesia, edema, abnormal sudomotor activity and trophic changes (D. Lee et al., 2015). CRPS disproportionally affects four times as many women as men (Alexander, Peterlin, Perreault, Grothusen, & Schwartzman, 2012). There are two types of CRPS: type 1, often referred to as reflex sympathetic dystrophy (RSD), is not evident of ...


There Is Relief For Constipated Patients Taking Opioids., Ahmad Mohammadieh, James Choi, MD, Chelsea Gonzalez, DO, Diyanah Elyaman, MD 2016 Wayne State University School of Medicine

There Is Relief For Constipated Patients Taking Opioids., Ahmad Mohammadieh, James Choi, Md, Chelsea Gonzalez, Do, Diyanah Elyaman, Md

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Tack J, Lappalainen J, Diva U, Tummala R, Sostek M. Efficacy and safety of naloxegol in patients with opioid-induced constipation and laxative-inadequate response. United European Gastroenterol J. 2015 Oct;3(5):471-80. doi: 10.1177/2050640615604543


Synapse Formation In Monosynaptic Sensory–Motor Connections Is Regulated By Presynaptic Rho Gtpase Cdc42, Fumiyasu Imai, David R. Ladle, Jennifer R. Leslie, Xin Duan, Tilat A. Rizvi, Georgianne M. Ciraolo, Yi Zheng, Yutaka Yoshida 2016 Wright State University - Main Campus

Synapse Formation In Monosynaptic Sensory–Motor Connections Is Regulated By Presynaptic Rho Gtpase Cdc42, Fumiyasu Imai, David R. Ladle, Jennifer R. Leslie, Xin Duan, Tilat A. Rizvi, Georgianne M. Ciraolo, Yi Zheng, Yutaka Yoshida

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in ...


Murine Hypometabolism: A Putative Signaling Pathway., Trevor Thomas Hollinger 2016 Dickinson College

Murine Hypometabolism: A Putative Signaling Pathway., Trevor Thomas Hollinger

Honors Theses By Year

Hypometabolism is an important energy saving, highly regulated physiological response for some mammals; however, its mechanisms of control have yet to be fully described. It induces a reduction in metabolic rate, heart rate, blood pressure and body temperature. Although the degree and rate of body temperature decrease is subject to ambient temperatures, mammals still maintain control over the whole process. A major goal of hypometabolism appears to be maintaining energetic stores within the body as external food sources become sparse. Uncovering the mechanisms by which these mammals control this process is of interest as organ and tissue damage following hypometabolism ...


Race/Sex Group Modification Of The Association Between Allostatic Load And Depression: Findings From The National Health And Nutrition Examination Survey, 2005-2010, Ganga Bey, Sharina D. Person 2016 University of Massachusetts Medical School

Race/Sex Group Modification Of The Association Between Allostatic Load And Depression: Findings From The National Health And Nutrition Examination Survey, 2005-2010, Ganga Bey, Sharina D. Person

UMass Center for Clinical and Translational Science Research Retreat

Objective: We assessed whether the relationship between depression and chronic stress as measured in allostatic load (AL) differs by race and sex among US black and white adults.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, we examined race/sex modification of the relationship between AL and depression in black and white women and men aged 18-64 years (n=6431). AL scores, ranging from 0-9, were calculated using 9 cardiovascular, metabolic, and immunologic biomarkers; scores ≥ 4 were considered “high-risk”. Depression was assessed using the PHQ-9; scores ≥ 10 indicate clinical depression. Logistic regression models estimated odds ...


Airway Smooth Muscle Pathology In Pompe Disease, Lang Xiong, Allison M. Keeler, Donghai Lui, Kaitlyn Desrochers, Ronghua Zhuge, Mai K. Elmallah 2016 University of Massachusetts Medical School

Airway Smooth Muscle Pathology In Pompe Disease, Lang Xiong, Allison M. Keeler, Donghai Lui, Kaitlyn Desrochers, Ronghua Zhuge, Mai K. Elmallah

UMass Center for Clinical and Translational Science Research Retreat

Pompe disease is a rare autosomal recessive disease which results from a deficiency of acid α-glucosidase (GAA) - an enzyme that degrades lysosomal glycogen. Patients with Pompe disease develop intra-lysosomal accumulation of glycogen in multiple tissues including skeletal muscle, CNS and smooth muscle.

Pulmonary dysfunction is a hallmark of Pompe disease and has classically been attributed to muscle weakness and CNS neuropathology. However, the potential role of respiratory smooth muscles in the respiratory pathology is unknown. Therefore we postulated that GAA deficiency results in airway smooth muscle glycogen accumulation that leads to airway smooth muscle dysfunction.

Using the Pompe mouse model ...


Burden Of Adverse Metabolic Factors Is Associated With Increased Left Ventricular Concentricity In Adults With Normal-Range Body Mass Index: The Framingham Heart Study, Philimon Gona, Jane Lee, Carol J. Salton, Christopher J. O'Donnell, Warren J. Manning, Michael L. Chuang 2016 University of Massachusetts Boston

Burden Of Adverse Metabolic Factors Is Associated With Increased Left Ventricular Concentricity In Adults With Normal-Range Body Mass Index: The Framingham Heart Study, Philimon Gona, Jane Lee, Carol J. Salton, Christopher J. O'Donnell, Warren J. Manning, Michael L. Chuang

UMass Center for Clinical and Translational Science Research Retreat

Introduction: Persons with normal-range body mass index (BMI) but adverse metabolic characteristics associated with obesity have been described as metabolically-obese normal weight (MONW). We sought to determine whether adverse metabolic profile is associated with alterations in left ventricular (LV) structure or function among adults with normal BMI. Methods: From the 1794 Framingham Heart Study Offspring cohort adults who underwent cardiac magnetic resonance imaging (CMRI) , we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI<25.0 kg/m2 and complete covariates. We calculated a metabolic score (MS) where 1 point was assigned for each of: a) fasting glucose≥100 mg/dL or diabetes; b) SBP≥140 or DBP≥90 mmHg or antihypertensive treatment; c) TG≥150 or HDL_C <40(M)/<50(W) mg/dL or lipid treatment; d) HOMA-IR≥2.5; e) waist circumference ≥102/88cm for M/W. Participants were classified as MS0 (no points), MS1 (exactly 1 point), or MS2+ (≥2 points). LV mass (LVM), end-diastolic volume (EDV), ejection fraction (EF), and concentricity (LVM/EDV) were measured from breathhold cine SSFP CMR scans; we calculated LVM/BSA. Analysis of covariance (ANCOVA) was used to compare MS1 and MS2+ groups to the MS0 group. CMRI variables were adjusted for sex, age, heart rate (HR) and body size (BSA); LVM/BSA was adjusted for sex, age, HR only. We also tested for linear trend across metabolic groups. Results: LV concentricity increased with worsening metabolic status. This was driven by lower LV EDV, not increased LVM. LVM did not differ across (trend) or between MS-groups. LVEDV decreased across groups but only MS2 differed significantly from MS0. LVEF increased slightly but significantly across MS-groups. Conclusions: In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal BMI, worsening metabolic profile was associated with adverse remodeling of the left ventricle, reflected by greater LV concentricity.


The Influence Of Mir-99a On Mtor Signaling Regulation In Colorectal Cancer Cell Lines., Jonathan Rice 2016 University of Louisville

The Influence Of Mir-99a On Mtor Signaling Regulation In Colorectal Cancer Cell Lines., Jonathan Rice

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. These are staggering statistics for a disease that can essentially be cured if caught early and the pathology is favorable to therapeutic intervention. There is currently a drastic decrease in five year survival as the cancer stage increases from locally confined disease to metastatic disease. These statistics suggest that although some strides have been made with colon cancer screening and early intervention, there is still much room for improvement in both screening and treatment of CRC. One of the pathways that have ...


Role Of Chemokine Rantes In The Regulation Of Perivascular Inflammation, T-Cell Accumulation, And Vascular Dysfunction In Hypertension., Tomasz P Mikolajczyk, Ryszard Nosalski, Piotr Szczepaniak, Klaudia Budzyn, Grzegorz Osmenda, Paul J. Marvar, +10 additional authors 2016 George Washington University

Role Of Chemokine Rantes In The Regulation Of Perivascular Inflammation, T-Cell Accumulation, And Vascular Dysfunction In Hypertension., Tomasz P Mikolajczyk, Ryszard Nosalski, Piotr Szczepaniak, Klaudia Budzyn, Grzegorz Osmenda, Paul J. Marvar, +10 Additional Authors

Pharmacology and Physiology Faculty Publications

Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 ± 1.5% vs. 31 ± 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 ± 0.2 vs. 3.5 ± 1.1; P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES(-/-) knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 ± 5% in wild type Ang II vs. 15 ± 4% in RANTES(-/-)), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-γ-producing CD8(+) and double-negative CD3(+)CD4(-)CD8(-) T cells in perivascular space and reduced vascular oxidative stress while FoxP3(+) T-regulatory cells were unaltered. IFN-γ ex vivo caused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R = -0.3, P < 0.01) or endothelial injury marker von Willebrand factor (R = +0.3; P < 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation.-Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P., Budzyn, K., Osmenda, G., Skiba, D., Sagan, A., Wu, J., Vinh, A., Marvar, P. J., Guzik, B., Podolec, J., Drummond, G., Lob, H. E., Harrison, D. G., Guzik, T. J. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension.


Na/K-Atpase Amplification Of Oxidant Stress; A Universal But Unrecognized Clinical Target?, Zijian Xie, PhD, Joseph I. Shapiro, MD 2016 Marshall University

Na/K-Atpase Amplification Of Oxidant Stress; A Universal But Unrecognized Clinical Target?, Zijian Xie, Phd, Joseph I. Shapiro, Md

Joseph I Shapiro MD

The Na/K-ATPase has a signaling function which appears to be separate from its ion pumping function. This signaling function refers to the transduction of conformational changes in the Na/K-ATPase alpha1 subunit into activating Src’s tyrosine kinase activity, triggering a cascade which generates reactive oxygen species (ROS), modulates other signaling pathways, and causes many physiological and pathophysiological effects. We have recently observed that ROS themselves as well as cardiotonic steroids can actually initiate the signal by directly inducing conformational changes in alpha1. It therefore appears that the Na/K-ATPase signal cascade can serve as a feed forward amplification ...


Na/K-Atpase Amplification Of Oxidant Stress; A Universal But Unrecognized Clinical Target?, Zijian Xie, PhD, Joseph I. Shapiro, MD 2016 Marshall University

Na/K-Atpase Amplification Of Oxidant Stress; A Universal But Unrecognized Clinical Target?, Zijian Xie, Phd, Joseph I. Shapiro, Md

Marshall Journal of Medicine

The Na/K-ATPase has a signaling function which appears to be separate from its ion pumping function. This signaling function refers to the transduction of conformational changes in the Na/K-ATPase alpha1 subunit into activating Src’s tyrosine kinase activity, triggering a cascade which generates reactive oxygen species (ROS), modulates other signaling pathways, and causes many physiological and pathophysiological effects. We have recently observed that ROS themselves as well as cardiotonic steroids can actually initiate the signal by directly inducing conformational changes in alpha1. It therefore appears that the Na/K-ATPase signal cascade can serve as a feed forward amplification ...


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