Breeding on the leading edge of a northward range expansion: differences in morphology and the stress response in the arctic Gambel's white-crowned sparrow

Individuals at the forefront of a range shift are likely to exhibit phenotypic traits that distinguish them from the population breeding within the historic range. Recent studies have examined morphological, physiological and behavioral phenotypes of individuals at the edge of their range. Several studies have found differences in the hypothalamic-pituitary-adrenal (HPA) axis activity in response to acute restraint stress in individuals at the range limits. HPA axis activation leads to elevations in glucocorticoids that regulate physiology and behavior. Here we compare the hormonal profiles and morphometrics from Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) breeding at the northern limit of the population's range to those birds breeding within the historic population range. Birds breeding at the northern limit experienced a harsher environment with colder temperatures; however, we found no differences in arthropod prey biomass between the northern limit and more southern (historic) sites. Males at the northern limit had higher body condition scores (mass corrected for body size) compared to individuals within the historic range, but no differences were found in beak and tarsus lengths, wing chord, muscle profile or fat stores. In males during the pre-parental stage, before breeding commenced, HPA axis activity was elevated in birds at the northern limit of the range, but no differences were found during the parental or molt stages. Females showed no differences in HPA axis activity during the parental stage. This study suggests that "pioneering" individuals at the limits of their breeding range exhibit physiology and morphology that are distinct from individuals within the historic range

Ein neues klinisches Syndrom bedingt durch eine Defizienz des muskarinergen M3-Rezeptors: Trias aus bilateraler Mydriasis, Blasenentleerungsstörung und schlankem Habitus

Die autoimmun-vermittelte Myasthenia gravis ist die wahrscheinlich bekannteste Erkrankung aus dem Spektrum der auf eine Defizienz nicotinerger Acetylcholin-Rezeptoren zurückzuführenden Krankheitsbilder. Dem gegenüber wurde bislang keine Erkrankung infolge einer Störung muskarinerger Acetylcholin-Rezeptoren (M1-M5) beschrieben. Wir stellen hier einen männlichen Patienten mittleren Alters vor, dessen führendes Symptom Rückenschmerzen infolge rezidvierender Harnwegsinfekte bei schwerer Blasenentleerungsstörung waren. Neben dieser als Detrusorakontraktilität identifizierten Blasenstörung fielen ein schlanker Habitus (BMI 18,5) und eine extreme bilaterale Mydriasis, subjektiv als langjährige Lichtempfindlichkeit empfunden, auf. Nach ausführlicher Pupillendiagnostik, apparativer Prüfung anderer vegetativer Funktionen und dem Vergleich zum Phänotyp von männlichen M3-knockout Mäusen konnte eine Funktionsstörung des muskarinergen M3-Rezeptors als Ursache des klinischen Bildes geschlussfolgert werden. Auf Proteinebene ließ sich ein ausgeprägter Mangel des M3-Rezeptors mittels Western Blots und einer Radioliganden-Bindungsstudie nachweisen. Während in der genetischen Untersuchung kein Defekt der M3-Protein-kodierenden Sequenz und deren Promotoren festzustellen war, zeigten sich stark erhöhte antinukleäre Antikörper als Ausdruck einer autoimmunen Disposition, so dass wir als Ursache der M3-Defizienz einen Mechanismus analog zur autoimmun-vermittelten Myasthenia gravis vermuten. Über die Beschreibung dieses M3-Defizienz-Syndroms hinaus lassen sich die folgenden Erkenntnisse ableiten: a) die Akkommodation der Augenlinse ist im Gegensatz zur Steuerung der Pupillenweite nicht abhängig vom M3-Rezeptor, was die Suche nach Subtyp-spezifischen antiglaukomatösen Medikamenten ermutigt, b) eines der Konzepte beim Sjögren-Syndrom, eine allein auf der M3-antagonistischen Wirkung von M3-Antikörpern beruhenden Trockenheit von Augen und Mund, muss infrage gestellt werden, c) der M3-Rezeptor scheint auch beim Menschen, ähnlich zur Maus, für die Körpergewichtskontrolle relevant zu sein, d) der M3-Rezeptor ist essentiell für die lebenslang funktionierende Blasenentleerung beim Mann und e) es bestätigt sich eine relevante Rolle des M3-Rezeptors für die Schweisssekretion

A novel clinical syndrome revealing a deficiency of the muscarinic M3 receptor.

Objectives: No clinical disorders have been caused by dysfunction of any of the 5 subtypes (M1– M5) of muscarinic receptors. We present a patient with a novel clinical syndrome that we suggest results from a deficiency of the muscarinic M3 receptor. Methods: We conducted a comprehensive workup of autonomic function. The patient’s disorder was compared to the phenotypic features of male M3 knockout mice. M3 protein quantity was assessed by Western blot and radioligand binding in peripheral blood lymphocytes. Tests for autoantibodies and genetic abnormalities were performed. Results: The disease pattern was characterized by disturbances in micturition, pupil constriction, body weight, and sudomotor function, with normal accommodation, gastrointestinal motility, salivation, and lacrimation, similar to features of maleM3knockout mice.M3protein quantity was reduced. Genetic tests were unrevealing, but unspecific antinuclear antibodies were present. Conclusions: The presented clinical syndrome suggests a deficiency of the muscarinic M3 receptor. These results and future evaluation of patients with autonomic deficits may provide insights into the site and functional role of the muscarinic M3 receptor in humans

Integrated results from the COPERNICUS and GALILEO studies

Amelie Pielen,1,2 W Lloyd Clark,3 David S Boyer,4 Yuichiro Ogura,5 Frank G Holz,6 Jean-Francois Korobelnik,7,8 Brigitte Stemper,9,10 Friedrich Asmus,9 Kay D Rittenhouse,11 Christiane Ahlers,9 Robert Vitti,12 Namrata Saroj,12 Oliver Zeitz,9,13,14 Julia A Haller15 On behalf of the COPERNICUS and GALILEO study group 1Eye Center, University Hospital Freiburg, Eye Hospital, Freiburg, 2Hannover Medical School, University Eye Hospital, Hannover, Germany; 3Palmetto Retina Center, Columbia, SC, USA; 4Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA; 5Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 6Department of Ophthalmology, University of Bonn, Bonn, Germany; 7Service d’ophtalmologie, CHU de Bordeaux, 8Service d’ophtalmologie, University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team LEHA, UMR 1219, Bordeaux, France; 9Bayer AG, Berlin, 10Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany; 11Bayer US LLC, Whippany, NJ, 12Regeneron Pharmaceuticals, Tarrytown, NY, USA; 13AKH Eye Clinic, Braunschweig, 14Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Augenheilkunde, Hamburg, Germany; 15Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA Objectives: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. Patients and methods: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. Results: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in <10% of patients. Conclusion: This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO. Keywords: macular edema, central retinal vein occlusion, anti-vascular endothelial growth factor, aflibercept, COPERNICUS, GALILE