Anatomy Commons^™

Increased Mitochondrial Calcium Sensitivity And Abnormal Expression Of Innate Immunity Genes Precede Dopaminergic Defects In Pink1-Deficient Mice, Ravi S. Akundi, Zhenyu Huang, Joshua Eason, Jignesh D. Pandya, Lianteng Zhi, Wayne A. Cass, Patrick G. Sullivan, Hansruedi Büeler

Neuroscience Faculty Publications

BACKGROUND: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²⁺ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice.

METHODS AND FINDINGS: Purified brain mitochondria of ^Pink1⁻/⁻ mice showed impaired Ca²⁺ storage capacity, resulting in increased Ca²⁺ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. …

Air Pollution & The Brain: Subchronic Diesel Exhaust Exposure Causes Neuroinflammation And Elevates Early Markers Of Neurodegenerative Disease, Shannon Levesque, Michael J. Surace, Jacob Mcdonald, Michelle L. Block

Anatomy and Neurobiology Publications

Background

Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood.

Objective

We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology.

Methods

Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months.

Results

DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception …

Chronic Apocynin Treatment Attenuates Beta Amyloid Plaque Size And Microglial Number In Happ(751)Sl Mice, Melinda E. Lull, Shannon Levesque, Michael J. Surace, Michelle L. Block

Anatomy and Neurobiology Publications

Background

NADPH oxidase is implicated in neurotoxic microglial activation and the progressive nature of Alzheimer's Disease (AD). Here, we test the ability of two NADPH oxidase inhibitors, apocynin and dextromethorphan (DM), to reduce learning deficits and neuropathology in transgenic mice overexpressing human amyloid precursor protein with the Swedish and London mutations (hAPP(751)SL).

Methods

Four month old hAPP(751)SL mice were treated daily with saline, 15 mg/kg DM, 7.5 mg/kg DM, or 10 mg/kg apocynin by gavage for four months.

Results

Only hAPP(751)SL mice treated with apocynin showed reduced plaque size and a reduction in the number of cortical microglia, when compared …

Knee Range Of Motion: Reliability And Agreement Of 3 Measurement Methods, Paul G. Peters, Michael A. Herbenick, Philip A. Anloague, Ronald J. Markert, L. Joseph Rubino

Physical Therapy Faculty Publications

We conducted a study to compare 3 methods of measuring knee range of motion: visual estimation by physicians, hand goniometry by physical therapists, and radiographic goniometry. We hypothesized that reliability would be high within and across all techniques. We found intrarater and interrater reliability to be satisfactory for visual estimation, hand goniometry, and radiographic goniometry. Interrater reliability across methods did not agree satisfactorily. Between-methods differences in estimating knee range of motion may result from variations in technique among physicians and physical therapists.

A Comparison Of Two Pelvic Floor Muscle Training Programs In Females With Stress Urinary Incontinence: A Pilot Study, Betsy Donahoe-Fillmore, Wendy Chorny, C. Jayne Brahler, Ashley Ingley, Jennifer Kennedy, Valerie Osterfeld

Physical Therapy Faculty Publications

Background: Stress urinary incontinence (SUI) is a condition affecting millions of Americans. Few studies have assessed the benefits of different exercises involved in pelvic floor muscle training (PFMT). Purposte: The purpose of this study was to compare the effects of a traditional PFMT program to an assisted pelvic floor muscle training (APFMT) program that included contraction of hip musculature.

Investigating The Associations Between Core Strength, Postural Control And Fine Motor Performance In Children, Rachel Burnett, Nicole Cornett, Gina Rekart, Betsy Donahoe-Fillmore, C. Jayne Brahler, Susan Aebker, Megan Kreill

Physical Therapy Faculty Publications

Study design: Quantitative design including statistical analysis.

Objectives: The objective of this study was to determine if there is an association between core strength, postural control, fine motor precision and integration, specifically in typical children in the first and third grades, ages 6-10. The secondary purpose of this study was to determine if there was an association between BMI and fine and gross motor ability in this same population.

Background: The relationship between core strength, postural control and fine motor skills in children is not well understood. The assumption that trunk stability and control are necessary for the maturation of …

The Influence Of Interleukin-4 On Ligament Healing, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sijian Wang, Xipei Yang, Stacey L. Brickson, Ray Vanderby

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Despite a complex cascade of cellular events to reconstruct the damaged extracellular matrix, ligament healing results in a mechanically inferior scarred ligament. During normal healing, granulation tissue expands into any residual normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise and an inefficient repair process. To control creeping substitution and possibly enhance the repair process, the antiinflammatory cytokine, interleukin-4 (IL-4), was administered to rats before and after rupture of their medial collateral ligaments. In vitro experiments showed a time-dependent effect on fibroblast proliferation after IL-4 treatment. In vivo treatments with IL-4 (100 ng/mL IV) …

Ultrasound Echo Is Related To Stress And Strain In Tendon, Sarah Duenwald, Hirohito Kobayashi, Kayt E. Frisch, Roderic Lakes, Ray Vanderby Jr.

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

The mechanical behavior of tendons has been well studied in vitro. A noninvasive method to acquire mechanical data would be highly beneficial. Elastography has been a promising method of gathering in vivo tissue mechanical behavior, but it has inherent limitations. This study presents acoustoelasticity as an alternative ultrasound-based method of measuring tendon stress and strain by reporting a relationship between ultrasonic echo intensity (B-mode ultrasound image brightness) and mechanical behavior of tendon in vitro. Porcine digital flexor tendons were cyclically loaded in a mechanical testing system while an ultrasonic echo response was recorded. We report that echo intensity …

The Influence Of Macrophage Depletion On Ligament Healing, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sijian Wang, Xipei Yang, Nico Van Rooijen, Geoff S. Baer, Stacey L. Brickson, Ray Vanderby

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Despite a complex cascade of cellular events to reconstruct damaged extracellular matrix (ECM), ligament healing results in a mechanically inferior, scar-like tissue. During normal healing, the number of macrophages significantly increases within the wound site. Then, granulation tissue expands into any residual, normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise, and an inefficient repair process. To study the effects of macrophages on the repair process, bilateral, surgical rupture of their medial collateral ligaments (MCLs) was done on rats. Treatment animals received liposome-encapsulated clodronate, 2 days before rupture to ablate phagocytosing macrophages. Ligaments were …

Development Of Melanopsin-Based Irradiance Detecting Circuitry, David S. Mcneill, Catherine J. Sheely, Jennifer L. Ecker, Tudor C. Badea, Duncan Morhardt, William Guido, Samer Hattar

Anatomy and Neurobiology Publications

Background

Most retinal ganglion cells (RGCs) convey contrast and motion information to visual brain centers. Approximately 2% of RGCs are intrinsically photosensitive (ipRGCs), express melanopsin and are necessary for light to modulate specific physiological processes in mice. The ipRGCs directly target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN) to mediate the pupillary light response. How and when this ipRGC circuitry develops is unknown.

Results

Here, we show that some ipRGCs follow a delayed developmental time course relative to other image-forming RGCs. Specifically, ipRGC neurogenesis extends beyond that of other RGCs, and ipRGCs begin …

Efficacy And Safety Of Once-Daily Aclidinium In Chronic Obstructive Pulmonary Disease, Paul W. Jones, Stephen I. Rennard, Alvar Agusti, Pascal Chanez, Helgo Magnussen, Leonardo Fabbri, James F. Donohue, Eric D. Bateman, Nicholas J. Gross, Rosa Lamarca, Cynthia Caracta, Esther Garcia Gil

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

METHODS: In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1< 80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.

RESULTS: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p< 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p< 0.001). More patients had a SGRQ improvement≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p=0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p=0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p=0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p=0.9). Adverse events were minor in both studies.

CONCLUSION: Aclidinium is effective and well tolerated …

Sleep Estimates In Children: Parental Versus Actigraphic Assessments, Ehab A. Dayyat, Karen Spruyt, Dennis L. Molfese, David Gozal

Center for Brain, Biology, and Behavior: Faculty Publications

Background: In the context of increasing awareness about the need for assessment of sleep duration in community and clinical settings, the use of questionnaire-based tools may be fraught with reporter bias. Conversely, actigraphy provides objective assessments of sleep patterns. In this study, we aimed to determine the potential discrepancies between parentally-based sleep logs and concurrent actigraphic recordings in children over a one-week period.

Methods: We studied 327 children aged 3–10 years, and included otherwise healthy, nonsnoring children from the community who were reported by their parents to be nonsnorers and had normal polysomnography, habitually-snoring children from the community …

Minimal Information For Neural Electromagnetic Ontologies (Minemo): A Standards-Compliant Method For Analysis And Integration Of Event-Related Potentials (Erp) Data, Gwen Frishkoff, Jason Sydes, Kurt Mueller, Tim Curran, John F. Connolly, Kerry Kilborn, Dennis L. Molfese, Charles Perfetti, Allen D. Malony

Center for Brain, Biology, and Behavior: Faculty Publications

We present MINEMO (Minimal Information for Neural ElectroMagnetic Ontologies), a checklist for the description of event-related potentials (ERP) studies. MINEMO extends MINI (Minimal Information for Neuroscience Investigations)to the ERP domain. Checklist terms are explicated in NEMO, a formal ontology that is designed to support ERP data sharing and integration. MINEMO is also linked to an ERP database and web application (the NEMO portal). Users upload their data and enter MINEMO information through the portal. The database then stores these entries in RDF (Resource Description Framework), along with summary metrics, i.e., spatial and temporal metadata. Together these spatial, temporal, and functional …

Reduction Of Exacerbations By The Pde4 Inhibitor Roflumilast--The Importance Of Defining Different Subsets Of Patients With Copd, Stephen I. Rennard, Peter M.A. Calverley, Udo M. Goehring, Dirk Bredenbröker, Fernando J. Martinez

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive. This led to the question of whether a responsive subset existed that could be investigated further.

METHODS: The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in …

Differentiation Of Embryonic Stem Cells Into Fibroblast-Like Cells In Three-Dimensional Type I Collagen Gel Cultures, Shinsaku Togo, Tadashi Sato, Hisatoshi Sugiura, Xingqi Wang, Hesham Basma, Amy J. Nelson, Xiangde Liu, Tom W. Bargar, J. Graham Sharp, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Fibroblasts are heterogeneous mesenchymal cells that play important roles in the production and maintenance of extracellular matrix. Although their heterogeneity is recognized, progenitor progeny relationships among fibroblasts and the factors that control fibroblast differentiation are poorly defined. The current study was designed to develop a reliable method that would permit in vitro differentiation of fibroblast-like cells from human and murine embryonic stem cells (ESCs). Undifferentiated ESCs were differentiated into embryoid bodies (EBs) with differentiation media. EBs were then cast into type I collagen gels and cultured for 21 d with basal media. The spindle-shaped cells that subsequently grew from the …

Genetics Of Sputum Gene Expression In Chronic Obstructive Pulmonary Disease, Weiliang Qiu, Michael H. Cho, John H. Riley, Wayne H. Anderson, Dave Singh, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David A. Lomas, James D. Crapo, Terri H. Beaty, Bartolome R. Celli, Stephen I. Rennard, Ruth Tal-Singer, Steven M. Fox, Edwin K. Silverman, Craig P. Hersh, Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested …

The Mechanosensory Role Of Primary Cilia In Vascular Hypertension, Surya M. Nauli, Xingjian Jin, Beerend P. Hierck

Pharmacy Faculty Articles and Research

Local regulation of vascular tone plays an important role in cardiovascular control of blood pressure. Aside from chemical or hormonal regulations, this local homeostasis is highly regulated by fluid-shear stress. It was previously unclear how vascular endothelial cells were able to sense fluid-shear stress. The cellular functions of mechanosensory cilia within vascular system have emerged recently. In particular, hypertension is insidious and remains a continuous problem that evolves during the course of polycystic kidney disease (PKD). The basic and clinical perspectives on primary cilia are discussed with regard to the pathogenesis of hypertension in PKD.

Spinal Cord Stimulator Induced Artifact During A Sleep Study, Robert J. Corba Do

Department of Anesthesiology

No abstract provided.

The Egg, Sperm, And Beyond: Gendered Assumptions In Gynecology Textbooks, Andrea Bertotti, Regina Rust

Sociology & Criminology Faculty Research

No abstract provided.

Cardiac Jelly And Its Roles In Heart Development, Sara Zucker

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction to this article: The complexity of the developing and functioning heart has always intrigued scientists. One of the many ambiguous areas in the understanding of cardiac development is the role of a gelatinous substance commonly referred to as cardiac jelly, (Davis, 1924) and more recently the myocardial basement membrane (Little and Rongish, 1995). Researchers have been studying this material to determine its roles. Their studies led them to believe that this jelly-like substance may be involved in vital embryological roles including the actual morphogenesis of the heart, such as heart valve formation and pumping. When …