Anatomy Commons^™

Transforming Growth Factor-Β1 Decreases Β2-Agonist–Induced Relaxation In Human Airway Smooth Muscle, Christie A. Ojiaku, Elena Chung, Vishal Parikh, Jazmean K. Williams, Anthony Schwab, Ana Lucia Fuentes, Maia L. Corpuz, Victoria Lui, Sam Paek, Natalia M. Bexiga, Shreya Narayan, Francisco J. Nunez, Kwangmi An, Rennolds S. Ostrom, Steven S. An, Reynold A. Pannettieri Jr.

Pharmacy Faculty Articles and Research

Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor (TGF)-β1, induces HASM cell shortening and airway hyperresponsiveness. Here, we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β₂-agonists, a mainstay treatment for airway hyperresponsiveness in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated, isolated HASM cells. This single-cell mechanical hyporesponsiveness to ISO was corroborated by sustained increases in myosin light chain phosphorylation. In TGF-β1–treated HASM cells, ISO evoked markedly lower …

Differential Localizations Of Protein Phosphatase 1 Isoforms Determine Their Physiological Function In The Heart, Ruijie Liu, Christian Miller, Christiana D'Annibale, Kimberly Vo, Ashley Jacobs

Peer Reviewed Articles

Protein phosphatase 1 isoforms α, β, and γ (PP1α, PP1β, and PP1γ) are highly homologous in the catalytic domains but have distinct subcellular localizations. In this study, we utilized both primary cell culture and knockout mice to investigate the isoform-specific roles of PP1s in the heart. In both neonatal and adult cardiac myocytes, PP1β was mainly localized in the nucleus, compared to the predominant presence of PP1α and PP1γ in the cytoplasm. Adenovirus-mediated overexpression of PP1α led to decreased phosphorylation of phospholamban, which was not influenced by overexpression of either PP1β or PP1γ. Interestingly, only cardiac-specific knockout of PP1β resulted …

The Effects Of Ocular Dominance On Visual Processing In College Students, William Alexander Holland

James Madison Undergraduate Research Journal (JMURJ)

The role of ocular dominance in processing visual memory and analytic tasks is unknown. Research has variably showed both significant effects and no effect of ocular dominance on visual perception, motor control, and sports performance. The goal of this study was to determine if there is a relationship between ocular dominance and visual processing under a variety of computer gaming tasks. This was accomplished by first determining subjects’ ocular dominance through the Miles test, and then examining the subjects’ visual performance on four different Lumosity games under three conditions: left eye, right eye, and both eyes. Results suggest a relationship …

Fluctuation Of Primary Motor Cortex Excitability During Cataplexy In Narcolepsy, Bei Huang, Zhenying Qian, Zongwen Wang, Jihui Zhang, Kun Chen, Tao Xu, Jijun Wang, David F. Cechetto, Zhongxin Zhao, Huijuan Wu

Anatomy and Cell Biology Publications

Objective Cataplexy is a complicated and dynamic process in narcolepsy type 1 (NT1) patients. This study aimed to clarify the distinct stages during a cataplectic attack and identify the changes of the primary motor cortex (PMC) excitability during these stages. Methods Thirty-five patients with NT1 and 29 healthy controls were recruited to this study. Cataplectic stages were distinguished from a cataplectic attack by video-polysomnogram monitoring. Transcranial magnetic stimulation motor-evoked potential (TMS-MEP) was performed to measure the excitability of PMC during quiet wakefulness, laughter without cataplexy, and each cataplectic stage. Results Based on the video and electromyogram observations, a typical cataplectic …

The Morphology And Evolution Of The Primate Brachial Plexus, Brian M. Shearer

Dissertations, Theses, and Capstone Projects

Primate evolutionary history is inexorably linked to the evolution of a broad array of locomotor adaptations that have facilitated the clade’s invasion of new niches. Researchers studying the evolution of primates and of their individual locomotor adaptations have traditionally relied on bony morphology – a practical choice given the virtual non-existence of any other type of tissue in the fossil record. However, this focus downplays the potential importance of the many other structures involved in locomotion, such as muscle, cartilage, and neural tissue, which may each be influenced by separate selective forces because of their different roles in facilitating movement. …

Human Skeletal Muscle Macrophages Increase Following Cycle Training And Are Associated With Adaptations That May Facilitate Growth, R. Grace Walton, Kate Kosmac, Jyothi Mula, Christopher S. Fry, Bailey D. Peck, Jason S. Groshong, Brian S. Finlin, Beibei Zhu, Philip A. Kern, Charlotte A. Peterson

Center for Muscle Biology Faculty Publications

Skeletal muscle macrophages participate in repair and regeneration following injury. However, their role in physiological adaptations to exercise is unexplored. We determined whether endurance exercise training (EET) alters macrophage content and characteristics in response to resistance exercise (RE), and whether macrophages are associated with other exercise adaptations. Subjects provided vastus lateralis biopsies before and after one bout of RE, after 12 weeks of EET (cycling), and after a final bout of RE. M2 macrophages (CD11b+/CD206+) did not increase with RE, but increased in response to EET (P < 0.01). Increases in M2 macrophages were positively correlated with fiber hypertrophy (r = 0.49) and satellite cells (r = 0.47). M2c macrophages (CD206+/CD163+) also increased following EET (P < 0.001), and were associated with fiber hypertrophy (r = 0.64). Gene expression was quantified using NanoString. Following EET, the change in M2 macrophages was positively associated with changes in HGF, IGF1, and extracellular matrix genes. EET decreased expression of IL6 (P < 0.05), C/EBPβ (P < 0.01), and MuRF (P < 0.05), and increased expression of IL-4 (P < 0.01), TNFα (P < 0.01) and the TWEAK receptor FN14 (P < 0.05). The change in FN14 gene expression was inversely associated with changes in C/EBPβ (r = −0.58) and MuRF (r = −0.46) following EET. In cultured human myotubes, siRNA inhibition of FN14 increased expression of C/EBPβ (P < 0.05) and MuRF (P < 0.05). Our data suggest that macrophages contribute to the muscle response to EET, potentially including modulation of TWEAK-FN14 signaling.

Candidemia Following Ureteric Stent Placement In A Patient With Type 2 Diabetes Treated With Canagliflozin, Rishi Raj, Jon Hendrie, Aasems Jacob, Derick Adams

Internal Medicine Faculty Publications

A 38-year-old female patient with well-controlled type 2 diabetes mellitus treated with canagliflozin underwent ureteral stent placement for obstructive renal calculi. Ten days following ureteroscopy and ureteral stenting, she developed fevers and blood cultures grew Candida glabrata (C. glabrata). The patient was successfully treated with an extended course of broad-spectrum antibiotics and antifungal agents. The clinical presentation of candidemia is indistinguishable from bacteremia resulting in delay in diagnosis and treatment. Candiduria is commonly seen in patients with type 2 diabetes, however it rarely leads to candidemia in an otherwise healthy person following a relatively simple urologic procedure. Sodium-glucose …

Detection Of Active Caspase-3 In Mouse Models Of Stroke And Alzheimer's Disease With A Novel Dual Positron Emission Tomography/Fluorescent Tracer [68ga]Ga-Tc3-Ogdota., Valeriy G Ostapchenko, Jonatan Snir, Mojmir Suchy, Jue Fan, M.Rebecca Cobb, Blaine Chronik, Michael Kovacs, Vania F. Prado, Robert H.E. Hudson, Stephen H. Pasternak, Marco A.M. Prado, Robert Bartha

Anatomy and Cell Biology Publications

Apoptosis is a feature of stroke and Alzheimer's disease (AD), yet there is no accepted method to detect or follow apoptosis in the brain in vivo. We developed a bifunctional tracer [Ga-68]Ga-TC3-OGDOTA containing a cell-penetrating peptide separated from fluorescent Oregon Green and Ga-68-bound labels by the caspase-3 recognition peptide DEVD. We hypothesized that this design would allow [Ga-68]Ga-TC3-OGDOTA to accumulate in apoptotic cells. In vitro, Ga-TC3-OGDOTA labeled apoptotic neurons following exposure to camptothecin, oxygen-glucose deprivation, and -amyloid oligomers. In vivo, PET showed accumulation of [Ga-68]Ga-TC3-OGDOTA in the brain of mouse models of stroke or AD. Optical clearing revealed colocalization of …

Dissociable Cognitive Impairments In Two Strains Of Transgenic Alzheimer's Disease Mice Revealed By A Battery Of Object-Based Tests, Samantha D. Creighton, Ari L. Mendell, Daniel Palmer, Bettina E. Kalisch, Neil J. Maclusky, Vania F Prado, Marco A.M Prado, Boyer D. Winters

Anatomy and Cell Biology Publications

Object recognition tasks detect cognitive deficits in transgenic Alzheimer's disease (AD) mouse models. Object recognition, however, is not a unitary process, and there are many uncharacterized facets of object processing with relevance to AD. We therefore systematically evaluated object processing in 5xFAD and 3xTG AD mice to clarify the nature of object recognition-related deficits. Twelve-month-old male and female 5xFAD and 3xTG mice were assessed on tasks for object identity recognition, spatial recognition, and multisensory object perception. Memory and multisensory perceptual impairments were observed, with interesting dissociations between transgenic AD strains and sex that paralleled neuropathological changes. Overreliance on the widespread …

Effects Of Prenatal Exercise On Fetal Heart Rate, Umbilical And Uterine Blood Flow: A Systematic Review And Meta-Analysis, Rachel J. Skow, Margie H. Davenport, Michelle Mottola, Gregory A. Davies, Veronica J. Poitras, Casey E. Gray, Alejandra Jaramillo Garcia, Nick Barrowman, Victoria L. Meah, Linda G. Slater, Kristi B. Adamo, Ruben Barakat, Stephanie-May Ruchat

Anatomy and Cell Biology Publications

Objective To perform a systematic review and meta-analysis examining the influence of acute and chronic prenatal exercise on fetal heart rate (FHR) and umbilical and uterine blood flow metrics.

Design Systematic review with random-effects meta-analysis and meta-regression.

Data sources Online databases were searched up to 6 January 2017.

Study eligibility criteria Studies of all designs were included (except case studies) if published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other …

Identified Flying Objects: A Multidisciplinary Scientific Approach To The Ufo Phenomenon, Dr. Michael P. Masters

Interdisciplinary Arts and Sciences Books

Identified Flying Objects cautiously examines the premise that ‘UFOs’ & ‘Aliens’ are simply our distant human descendants, returning from the future to study their own hominin evolutionary past. This text challenges readers to consider new possibilities while cultivating conversations about our ever-evolving understanding of time & time travel.

The Effect Of Serratus Anterior Fatigue On Scapular Kinematics, Nathan Curtis Harrison

Theses, Dissertations and Capstones

Background: Shoulder pain is a common occurrence in the general population. Pain has been associated with shoulder impairments and pathology. Associations between shoulder limitations, impairments, and mechanisms of injury and altered scapular motion appear in the literature. Fatigue of the scapular stabilizing muscles resulting from repeated arm motion has been reported to alter scapular kinematics, which could result in shoulder pathology, especially impingement.

Purpose: The purpose of this study was to examine the effects of fatigue of the serratus anterior muscle on scapular kinematics. The hypotheses were that there would be decreased posterior tilt and decreased upward rotation during arm …

Perceived Exertion And The Increase In Risk Of Injury In Rotc Cadets, Courtney D. Chiaramonte

Theses, Dissertations and Capstones

Context: Musculoskeletal injury in military personnel creates problems due to economic losses, and decreased training. The repetitive motions associated with military training and the daily physical training sessions can lead to the development of fatigue. Fatigue has been shown to contribute to 18% - 26% of musculoskeletal injuries. [7] Several studies have explored fatigue as a risk of injury during occupation. Fatigue has been shown to increase the perceived effort during physical exercise. The purpose of this study was to characterize the perception of effort during physical training sessions and injury rates in ROTC cadets throughout an academic year.

Methods …

Cecal Perforation In The Setting Of Campylobacter Jejuni Infection, Seema Jain, Weston Betrner, Dane Olevian, Dhiraj Yadav

Faculty & Staff Scholarship

Campylobacter infection is the leading cause of bacterial gastroenteritis worldwide, yet life-threatening complications are extremely rare. We present a 32-year-old previously healthy man who presented with dysentery from Campylobacter jejuni, which was complicated by cecal perforation and secondary bacterial peritonitis.

Sarcoid-Like Reaction Associated With Renal Cell Carcinoma - A Case Report., Asma Iftikhar, Muhammad A I Cheema, Preethi Ramachandran, Sonu Sahni

Touro College of Osteopathic Medicine (New York) Publications and Research

Renal cell carcinoma (RCC) is a highly vascular tumor, which may spread to the lungs and other organs. It often presents with localized or systemic manifestation, including paraneoplastic syndromes. Sarcoidosis is a systemic granulomatous inflammatory disease characterized by non-caseating granulomas that typically afflicts the respiratory system. In the absence of any evidence of systemic sarcoidosis they are referred to as sarcoid-like reactions. Non-caseating epithelioid granulomas, also regarded to sarcoid-like granulomas have been described in association with certain malignancies such as carcinomas of the breast, colon, seminoma, and Hodgkin's lymphoma. However, sarcoid like reaction associated with renal cell carcinoma is uncommon. …

Toxic Environmental Risk Factors For Alzheimer's Disease: A Systematic Review, Oluwaseyi Olayinka, Olaniyi O. Olayinka, Brook T. Alemu, Muge Akpinar-Elci, George T. Grossberg

Community & Environmental Health Faculty Publications

There is growing evidence of a possible association between toxic environmental factors and Alzheimer’s disease (AD), a disabling neurodegenerative condition with no known cause. Previous reviews of toxic environmental factors for AD either focused on occupational exposures or used a non-systematic methodology. The objective of this systematic review is to assess the evidence on the link between AD and exposure to a variety of toxic environmental risk factors beyond the work environment. Structured database search was used to identify relevant studies. Twenty-nine eligible studies examining the effect of various toxic environmental agents including electromagnetic fields, solvents, pesticides, toxic metals, and …

Dynamic Effects Of Habituation And Novelty Detection On Newborn Event Related Potentials, Cathryn S. Cortesa, Caitlin M Hudac, Dennis Molfese

Center for Brain, Biology, and Behavior: Faculty Publications

Newborns habituate to repeated auditory stimuli, and discriminate syllables, generating opportunities for early language learning. This study investigated trial-by-trial changes in newborn electrophysiological responses to auditory speech syllables as an index of habituation and novelty detection. Auditory event-related potentials (ERPs) were recorded from 16 term newborn infants, aged 1–3 days, in response to monosyllabic speech syllables presented during habituation and novelty detection tasks. Multilevel models demonstrated that newborns habituated to repeated auditory syllables, as ERP amplitude attenuated for a late-latency component over successive trials. Subsequently, during the novelty detection task, earlyand late-latency component amplitudes decreased over successive trials for novel …

Concussion Competencies: A Training Model For School-Based Concussion Management, Arthur C. Maerlender, Jonathan D. Lichtenstein, Jennifer Parent-Nichols, Kate Higgins, Peggy Reisher

Center for Brain, Biology, and Behavior: Faculty Publications

This study reports on the use of ten knowledge competencies related to the behavioral management of concussion in schools. Trainings using these competencies as learning objectives were delivered to school personnel. This aims of the use of competencies in this way are to streamline the education of key stakeholders, to establish clear roles and responsibilities for constituents and equip individuals working with students following a concussion with the relevant knowledge to optimize outcomes. The majority of participants, primarily speech language pathologists working as related service providers in the schoolswhere the trainings occurred, judged the use of the competencies to be …

Confirmatory Factor Analysis Of Two Computerized Neuropsychological Test Batteries: Immediate Post-Concussion Assessment And Cognitive Test (Impact) And C3 Logix, Caitlin Masterson, Julie Tuttle, Arthur C. Maerlender

Center for Brain, Biology, and Behavior: Faculty Publications

Introduction: Tests of memory and speed of cognitive and motor responses have been the primary foci in sports-related concussion assessment. This study sought to assess the construct validity of neuropsychological tests within C3 Logix.

Method: Results of both baseline C3 Logix and the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) computerized tests from 86 Division I collegiate athletes were submitted to a two-factor confirmatory analysis using structural equation modeling. The two factors of Speed and Memory have been confirmed in previous studies of ImPACT.

Results: Results confirmed the two-factor model of ImPACT, whereas C3 Logix did not …

Functional Source Separation For Eeg-Fmri Fusion: Application To Steady-State Visual Evoked Potentials, Hong Ji, Badong Chen, Nathan M. Petro, Zejian Yuan, Nanning Zheng, Andreas Keil

Center for Brain, Biology, and Behavior: Faculty Publications

Neurorobotics is one of the most ambitious fields in robotics, driving integration of interdisciplinary data and knowledge. One of the most productive areas of interdisciplinary research in this area has been the implementation of biologically-inspired mechanisms in the development of autonomous systems. Specifically, enabling such systems to display adaptive behavior such as learning from good and bad outcomes, has been achieved by quantifying and understanding the neural mechanisms of the brain networks mediating adaptive behaviors in humans and animals. For example, associative learning from aversive or dangerous outcomes is crucial for an autonomous system, to avoid dangerous situations in the …

Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A.C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.

METHODS: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, …

Tgf-Β Induces A Heart Failure Phenotype Via Fibroblasts Exosome Signaling, Hesham Basma, Adelaide N. Johanson, Kajari Dhar, Daniel R. Anderson, Fang Qiu, Stephen I. Rennard, Brian D. Lowes

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: The mechanisms for persistent and progressive loss of myocardial function in advanced heart failure (HF) remain incompletely characterized. In the current study, we sought to determine the impact of TGF-β on fibroblasts transcriptional profiles and assess if exosomes from TGF-β treated fibroblasts could induce a heart failure phenotype in co-cultured cardiomyocytes.

METHOD: Normal heart fibroblasts were treated with TGF-β with a final conc. of 2.5 ng/ml in serum free media. HF fibroblasts were also obtained from patients undergoing implantation of left ventricular assist devices. Exosomes were collected using three-step ultracentrifugation. Cardiomyocytes were co-cultured with exosomes from TGF-β-treated, HF and …

Bronchoalveolar Lavage Fluid From Copd Patients Reveals More Compounds Associated With Disease Than Matched Plasma, Eitan Halper-Stromberg, Lucas Gillenwater, Charmion Cruickshank-Quinn, Wanda Kay O'Neal, Nichole Reisdorph, Irina Petrache, Yonghua Zhuang, Wassim W. Labaki, Jeffrey L. Curtis, James Wells, Stephen I. Rennard, Katherine A. Pratte, Prescott Woodruff, Kathleen A. Stringer, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography-mass spectrometry (LC-MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected …

It's More Than Low Bmi: Prevalence Of Cachexia And Associated Mortality In Copd, Merry-Lynn N. Mcdonald, Emiel F.M. Wouters, Erica Rutten, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Marcas Bamman, Bartolome Celli, Alvar Agusti, Ruth Tal-Singer, Craig P. Hersh, Mark Dransfield, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients. However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index. For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.

METHODS: In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation. The …

Diffuse Intrinsic Pontine Glioma Cells Are Vulnerable To Low Intensity Electric Fields Delivered By Intratumoral Modulation Therapy, Andrew Deweyert, Erin Iredale, Hu Xu, Eugene Wong, Susanne Schmid, Matthew O. Hebb

Anatomy and Cell Biology Publications

Introduction

Diffuse intrinsic pontine glioma (DIPG) is a high fatality pediatric brain cancer without effective treatment. The field of electrotherapeutics offers new potential for other forms of glioma but the efficacy of this strategy has not been reported for DIPG. This pilot study evaluated the susceptibility of patient-derived DIPG cells to low intensity electric fields delivered using a developing technology called intratumoral modulation therapy (IMT).

Methods

DIPG cells from autopsy specimens were treated with a custom-designed, in vitro IMT system. Computer-generated electric field simulation was performed to quantify IMT amplitude and distribution using continuous, low intensity, intermediate frequency stimulation parameters. …

Double Deletion Of Panx1 And Panx3 Affects Skin And Bone But Not Hearing, J M. Abitbol, B L. O'Donnell, C B. Wakefield, E Jewlal, J J. Kelly, K Barr, K E. Willmore, B. L. Allman, S Penuela

Anatomy and Cell Biology Publications

Pannexins (Panxs), large-pore channel forming glycoproteins, are expressed in a wide variety of tissues including the skin, bone, and cochlea. To date, the use of single knock-out mouse models of both Panx1 and Panx3 have demonstrated their roles in skin development, bone formation, and auditory phenotypes. Due to sequence homology between Panx1 and Panx3, when one Panx is ablated from germline, the other may be upregulated in a compensatory mechanism to maintain tissue homeostasis and function. To evaluate the roles of Panx1 and Panx3 in the skin, bone, and cochlea, we created the first Panx1/Panx3 double knock-out mouse model (dKO). …

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, Ashbeel Roy, Vania F. Prado, Marco A.M Prado, Robert Gros, Kurt R. Lehner, Harold A. Silvernman, Meghan E. Addorissio, Mohammed A. Al-Onaizi, Yaakov Levine, Peder S. Olofsson, Sangeeta S. Chavan, Neil M. Nathanson, Yousef Al-Abed, Christine N. Metz, Kevin J. Tracey, Valentin A. Pavlov

Anatomy and Cell Biology Publications

The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid …

First M87 Event Horizon Telescope Results. I. The Shadow Of The Supermassive Black Hole, Aaron Faber, Kazunori Akiyama, Antxon Alberdi, Walter Alef, Keiichi Asada, Rebecca Azulay, Anne-Kathrin Baczko, David Ball, Mislav Baloković, John Barrett, Dan Bintley

Anatomy and Cell Biology Publications

When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 +/- 3 mu as, …

The Connexin 30 A88v Mutant Reduces Cochlear Gap Junction Expression And Confers Long-Term Protection Against Hearing Loss, John J. Kelly, Julia Abitbol, Stephanie Hulme, Eric R. Press, Dale Laird, Brian L. Allman

Anatomy and Cell Biology Publications

Mutations in the genes that encode the gap junction proteins connexin 26 (Cx26, encoded by GJB2) and Cx30 (GJB6) are the leading cause of hereditary hearing loss. That said, the Cx30 p.Ala88Val (A88V) mutant causes Clouston syndrome, but not hearing loss. Here, we report that the Cx30-A88V mutant, despite being toxic to inner ear-derived HEI-OC1 cells, conferred remarkable long-term protection against age-related high frequency hearing loss in Cx30(A88V/A88V) mice. During early development, there were no overt structural differences in the cochlea between genotypes, including a normal complement of hair cells; however, the supporting cell Cx30 gap junction plaques in mutant …

Inhibition Of Pannexin 1 Reduces The Tumorigenic Properties Of Human Melanoma Cells, Taylor J. Freeman, Samar Sayedyahossein, Rafael E. Sanchez-Pupo, Brooke O'Donnell, Kenneth Huang, Zameena Lakhani, Daniel Nouri-Nejad, Kevin J. Barr, Luke Harland, Steven Latosinsky, Aaron Grant, Lina Dagnino, Silvia Penuela

Anatomy and Cell Biology Publications

Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of disease progression, as well as in patient-derived cells and established melanoma cell lines. Reducing PANX1 protein levels using shRNA or inhibiting channel function with the channel blockers, carbenoxolone (CBX) and probenecid (PBN), significantly decreased cell growth and migration, and increased melanin production in A375-P and A375-MA2 cell lines. Further, treatment …