A Gly98Val mutation in the N-Myc downstream regulated gene 1 (NDRG1) in Alaskan Malamutes with polyneuropathy.

The first cases of early-onset progressive polyneuropathy appeared in the Alaskan Malamute population in Norway in the late 1970s. Affected dogs were of both sexes and were ambulatory paraparetic, progressing to non-ambulatory tetraparesis. On neurologic examination, affected dogs displayed predominantly laryngeal paresis, decreased postural reactions, decreased spinal reflexes and muscle atrophy. The disease was considered eradicated through breeding programmes but recently new cases have occurred in the Nordic countries and the USA. The N-myc downstream-regulated gene (NDRG1) is implicated in neuropathies with comparable symptoms or clinical signs both in humans and in Greyhound dogs. This gene was therefore considered a candidate gene for the polyneuropathy in Alaskan Malamutes. The coding sequence of the NDRG1 gene derived from one healthy and one affected Alaskan Malamute revealed a non-synonymous G>T mutation in exon 4 in the affected dog that causes a Gly98Val amino acid substitution. This substitution was categorized to be "probably damaging" to the protein function by PolyPhen2 (score: 1.000). Subsequently, 102 Alaskan Malamutes from the Nordic countries and the USA known to be either affected (n = 22), obligate carriers (n = 7) or healthy (n = 73) were genotyped for the SNP using TaqMan. All affected dogs had the T/T genotype, the obligate carriers had the G/T genotype and the healthy dogs had the G/G genotype except for 13 who had the G/T genotype. A protein alignment showed that residue 98 is conserved in mammals and also that the entire NDRG1 protein is highly conserved (94.7%) in mammals. We conclude that the G>T substitution is most likely the mutation that causes polyneuropathy in Alaskan Malamutes. Our characterization of a novel candidate causative mutation for polyneuropathy offers a new canine model that can provide further insight into pathobiology and therapy of human polyneuropathy. Furthermore, selection against this mutation can now be used to eliminate the disease in Alaskan Malamutes.

Atypical visual processing in posttraumatic stress disorder

BACKGROUND: Many patients with Posttraumatic Stress Disorder (PTSD) feel overwhelmed in situations with high levels of sensory input, as in crowded situations with complex sensory characteristics. These difficulties might be related to subtle sensory processing deficits similar to those that have been found for sounds in electrophysiological studies. METHOD: Visual processing was investigated with functional magnetic resonance imaging in trauma-exposed participants with (N = 18) and without PTSD (N = 21) employing a picture-viewing task. RESULTS: Activity observed in response to visual scenes was lower in PTSD participants 1) in the ventral stream of the visual system, including striate and extrastriate, inferior temporal, and entorhinal cortices, and 2) in dorsal and ventral attention systems (P < 0.05, FWE-corrected). These effects could not be explained by the emotional salience of the pictures. CONCLUSIONS: Visual processing was substantially altered in PTSD in the ventral visual stream, a component of the visual system thought to be responsible for object property processing. Together with previous reports of subtle auditory deficits in PTSD, these findings provide strong support for potentially important sensory processing deficits, whose origins may be related to dysfunctional attention processes.

Characterization of Optically Stimulated Luminescent Detectors in Photon & Proton Beams for Use in Anthropomorphic Phantoms

This study investigated characteristics of optically stimulated luminescent detectors (OSLDs) in protons, allowing comparison to thermoluminescent detectors, and to be implemented into the Radiological Physics Center’s (RPC) remote audit quality assurance program for protons, and for remote anthropomorphic phantom irradiations. The OSLDs used were aluminum oxide (Al2O3:C) nanoDots from Landauer, Inc. (Glenwood, Ill.) measuring 10x10x2 mm3. A square, 20(L)x20(W)x0.5(H) cm3 piece of solid water was fabricated with pockets to allow OSLDs and TLDs to be irradiated simultaneously and perpendicular to the beam. Irradiations were performed at 5cm depth in photons, and in the center of a 10 cm SOBP in a 200MeV proton beam. Additionally, the Radiological Physics Center’s anthropomorphic pelvic phantom was used to test the angular dependence of OSLDs in photons and protons. A cylindrical insert in the phantom allows the dosimeters to be rotated to any angle with a fixed gantry angle. OSLDs were irradiated at 12 angles between 0 and 360 degrees. The OSLDs were read out with a MicroStar reader from Landauer, Inc. Dose response indicates that at angles where the dosimeter is near parallel with the radiation beam response is reduced slightly. Measurements in proton beams do not show significant angular dependence. Post-irradiation fading of OSLDs was studied in proton beams to determine if the fading was different than that of photons. The fading results showed no significant difference from results in photon beams. OSLDs and TLDs are comparable within 3% in photon beams and a correction factor can be posited for proton beams. With angular dependence characteristics defined, OSLDs can be implemented into multiple-field treatment plans in photons and protons and used in the RPC’s quality assurance program.

Neural reprogramming in retinal degeneration.

PURPOSE: Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degeneration. METHODS: Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degeneration and a sample of human RP. RESULTS: After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, whereas amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the number of bipolar cells expressing functional iGluRs was double that of normal retina. CONCLUSIONS: RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some nonglutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late RP photoreceptor transplantation attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function.

No evidence for a local renin-angiotensin system in liver mitochondria

The circulating, endocrine renin-angiotensin system (RAS) is important to circulatory homeostasis, while ubiquitous tissue and cellular RAS play diverse roles, including metabolic regulation. Indeed, inhibition of RAS is associated with improved cellular oxidative capacity. Recently it has been suggested that an intra-mitochondrial RAS directly impacts on metabolism. Here we sought to rigorously explore this hypothesis. Radiolabelled ligand-binding and unbiased proteomic approaches were applied to purified mitochondrial sub-fractions from rat liver, and the impact of AngII on mitochondrial function assessed. Whilst high-affinity AngII binding sites were found in the mitochondria-associated membrane (MAM) fraction, no RAS components could be detected in purified mitochondria. Moreover, AngII had no effect on the function of isolated mitochondria at physiologically relevant concentrations. We thus found no evidence of endogenous mitochondrial AngII production, and conclude that the effects of AngII on cellular energy metabolism are not mediated through its direct binding to mitochondrial targets.

An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs

An inherited polyneuropathy (PN) observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth (CMT) disease in humans. The Leonberger disorder is a severe, juvenile-onset, chronic, progressive, and mixed PN, characterized by exercise intolerance, gait abnormalities and muscle atrophy of the pelvic limbs, as well as inspiratory stridor and dyspnea. We mapped a PN locus in Leonbergers to a 250 kb region on canine chromosome 16 (Praw = 1.16×10-10, Pgenome, corrected = 0.006) utilizing a high-density SNP array. Within this interval is the ARHGEF10 gene, a member of the rho family of GTPases known to be involved in neuronal growth and axonal migration, and implicated in human hypomyelination. ARHGEF10 sequencing identified a 10 bp deletion in affected dogs that removes four nucleotides from the 3'-end of exon 17 and six nucleotides from the 5'-end of intron 17 (c.1955_1958+6delCACGGTGAGC). This eliminates the 3'-splice junction of exon 17, creates an alternate splice site immediately downstream in which the processed mRNA contains a frame shift, and generates a premature stop codon predicted to truncate approximately 50% of the protein. Homozygosity for the deletion was highly associated with the severe juvenile-onset PN phenotype in both Leonberger and Saint Bernard dogs. The overall clinical picture of PN in these breeds, and the effects of sex and heterozygosity of the ARHGEF10 deletion, are less clear due to the likely presence of other forms of PN with variable ages of onset and severity of clinical signs. This is the first documented severe polyneuropathy associated with a mutation in ARHGEF10 in any species.

Na 1 Nachlass Max Horkheimer, 96 - Korrespondenzen u.a. mit Jürgen Habermas (p. III 6, 1-421)

5 Briefe mit Antwort an Inga Haag, 1951-1955; 1 Brief mit Antwort von Jürgen Habermas an Max Horkheimer, 1955; 1 Brief von Ministerialrat i. R. Theodor Häbich an Max Horkheimer, 1957; 2 Briefe mit Antwort von cand. phil. Walter Hähnle an Max Horkheimer, 1955, 1957; 1 Brief mit Antwort von Sekretärin Jutta Hagen an Max Horkheimer, 1956; 1 Dissertationsauszug von Volker Freiherr von Hagen, 1954; 1 Brief mit Antwort von Julia Hagenbucher an Max Horkheimer, 1951/1952; 1 Entwurf zu einem Gratulationsschreiben von Max Horkheimer an Professor Otto Hahn, ohne Jahr; 2 Drucksachen von Obermagistratsrat Julius Hahn, 1953, 1955; 1 Brief mit Antwort von Theodor W. Adorno, von Dr. Hans Hahn an Max Horkheimer, 1952; 1 Brief von Theodor W. Adorno an Dr. Hans Hahn, 1952; 1 Danksagung von Rabbi Hugo Hahn, 1955; 3 Briefe mit Antwort von Paul Hahn an Max Horkheimer, 1951-1958; 1 Brief von Max Horkheimer an die Gebrüder Haldy, 1952; 1 Brief mit Antwort und Beilage von Professor George W. F. Hallgarten an Max Horkheimer, 1950; 1 Rundschreiben von Arzt und Psychotherapeut Hans Hammer, 1957; 1 Brief von Max Horkheimer an Margarete Hampf-Solm, 1955; 1 Brief mit Antwort von Professor Eduardo Hamuy an Max Horkheimer, 1952; 1 Brief von der Stadtärztin Dr. med. Carola Hannappel an Max Horkheimer, 1951; 1 Brief von Hansenmeister an Max Horkheimer, 1951; 1 Brief mit Antwort und Beilage von der Buchhandlung Ludwig Häntzschel an Max Horkheimer, 1958; 1 Brief von Professor Frederick Harris Harbison an Max Horkheimer, 1952; 3 Briefe mit Antwort von Robert Harcourt an Max Horkheimer, 1958; 1 Brief von Karl Hardach an Max Horkheimer, 1957; 1 Brief mit Antwort von Emilie Harlacher an Max Horkheimer, 1952; 1 Drucksache mit Antwort von Oberkirchenrat Otto L. A. von Harling an Max Horkheimer, 1955; 1 Brief mit Antwort von Gertrud Harms an Max Horkheimer, 1955; 2 Brief mit Antwort von Professor Wolfgang Hartke an Max Horkheimer, 1954-1956; 2 Briefe mit antwort von Max Horkheimer an Senator Georg Hartmann, 1951, 1954; 3 briefe mit Antwort und Beilage von Ökonom Heinz Hartmann an Max Horkheimer, 1956-1958; 1 Brief mit Antwort von Professor Wilbert E. Moore an Max Horkheimer, 1957; 3 Briefe mit Antwort und Beilage von Dr. phil. Leo Hartmann an Max Horkheimer, 1957-1858; 1 Brief mit Antowort von Dr. phil. Eckardt Mesch an Max Horkheimer, 1957; 1 Brief mit Antwort von Luzie Hatch an Max Horkheimer, 1954; 1 Brief von Max Horkheimer an den Direktor H. W. Haupt, 1950; 1 Drucksache von Haus Schwalbach, 1951; 4 Briefe mit Antwort von Professor Gottfried und Ellen Hausmann an Max Horkheimer, 1951-1958; 6 Briefe mit Antwort von Eva Haussner an Max Horkheimer, 1957, 1958; 1 Brief mit Antwort von Professor Robert J. Havighurst an Max Horkheimer, 1951; 1 Brief mit Beilage von Herbert Hax an Max Horkheimer, 1955; 2 Briefe mit Antwort und Beilage von Jean Louis Hébarre an Max Horkheimer, 1950-1952; 1 Brief mit Antwort von dem Hebedienst für Elektrizität, Gas und Wasser an Max Horkheimer, 1951; 5 Briefe mit Antwort und Beilage von Professor Otto Heckmann an Max Horkheimer, 1952, 1954; 1 Brief von Melvin J. Lasky an August Heckscher, 1957; 3 Briefe mit Antwort von Marie Heep an Max Horkheimer, 1956-1858; 1 Brief von der Buchhandlung Thekla Heer an Max Horkheimer, 1953; 1 Brief mit Antwort von dem Verleger Jakob Hegner an Max Horkheimer, 1955; 1 Brief von Dr. phil. Rudolf M. Heilbrunn an Max Horkheimer, 1953; 1 Brief mit Antwort von Professor Eduard Heimann an Max Horkheimer, 1952; 1 Brief von Professor Eduard Heimann an Theodor W. Adorno, 1957; 1 Brief mit Antwort von stud. phil. Wolfgang Heinrich an Max Horkheimer, 1958; 1 Brief von Max Horkheimer an den Direktor Helmuth Heintzmann, 1955; 1 Aktennotiz von Professor Bernhard Heller, 1956; 1 Brief mit Antwort von Philipp A. Heller an Max Horkheimer, 1952; 1 Brief von Max Horkheimer an Assistent Winfried Hellmann, 1957; 2 Briefe mit Antwort von Professor Arthur Henkel an Max Horkheimer, 1953/1954; 1 Brief von Max Horkheiemr an Dorothy Henkel, 1952; 2 Briefe mit Antwort von Dr. jur. Werner Hennig an Max Horkheimer, 1951; 1 Brief von Max Horkheimer an Professor Wilhelm Hennis, 1957; 3 Briefe mit Antwort und Beilage von Professor Fritz Hepner an Max Horkheimer, 1953; 1 Brief von Max Horkheimer an den Hessischer Minister für Erziehung und Volksbildung, 1950; 1 Brief mit Antwort von Professor Henrietta Herbolsheimer an Max Horkheimer, 1957/1958; 2 Briefe mit Antwort von P. G. Herbst an Max Horkheimer, 1952; 1 Brief von Max Horkheimer an den Herder Verlag, 1953; 2 Briefe mit Antwort, Beilagen und Aktennotizen von Guenter R. Herz an Max Horkheimer, 1956-1957; 2 Briefe mit Antwort unv Beilagen von Professor Theodor W. Adorno, von Dr. phil. Günther Herzberg an Max Horkheimer, 1951-1953; 1 Brief von Professor Theodor W. Adrono an Dr. phil. Günther Herzberg, 1951; 1 Brief von Dr. phil. G. Herzfeld an Max Horkheimer, 1952; 1 Brief von dem Herzog-Film an Max Horkheimer, 1952; 1 Brief mit Antwort von Professor Theodor W. Adorno, von Professor Erich Herzog an Max Horkheimer, 1952; 1 Brief von Professor Theodor W. Adorno an Professor Erich Herzog, 1952; 1 Brief mit Antwort von dem Verlag Otto H. Hess an Max Horkheimer, 1954; 1 Brief von Professor Gerhard Hess an Max Horkheimer, 1953; 1 Drucksachevon dem Hessischer Arbeitsausschuss gegen Rekrutierung, 1952; 1 Brief mit Beilage von dem Hotel Hessischer Hof an Max Horkheimer, 1956; 1 Brief mit Antwort von dem Hessischer Landesverband für Erwachsenenbildung an Max Horkheimer, 1956; 2 Briefe mit Antwort und Beilage von Marc Heurgon an Max Horkheimer, 1958; 1 Brief mit Beilage von Ruth Heydebrand an Max Horkheimer, [1955]; 1 Brief mit Antwort von Professor Frederick W. J. Heuser an Max Horkheimer, 1954; 2 Briefe mit Antwort von Professor Joh Erich Heyde an Max Horkheimer, 1958; 1 Befürwortung von Wolf von Heydebrand an Max Horkheimer, 1954; 1 Brief mit Antwort von Professor Heinz Joachim Heydorn an Max Horkheimer, 1953; 1 Brief mit Antwort und Beilage von dem Arzt Otto Heymann an Max Horkheimer, 1955; 5 Briefe zwischen dem Devisenberater und Steuerhelfer Joseph Christ und Max Horkheimer, 1955, 1956, 1961; 1 Brief von dem Office of the United States High Commissioner for Germany an Max Horkheimer, 1953; 1 Lebenslauf von Elen B. Hill, ohne Jahr; 1 Brief von Kurt H. Wolff an Max Horkheimer, 1952; 1 Brief von Rolf Himmelreich an Max Horkheimer, 1956; 1 Brief mit Antwort von Dr. Rolf Hinder an Max Horkheimer, 1953; 1 Brief mit Antwort von Anton Hinsinger an Max Horkheimer, 1953; 1 Brief mit Antwort von dem Hippokrates-Verlag an Max Horkheimer, 1952; 1 Brief von Bernice L. Hirsch anMax Horkheimer, 1957; 4 Briefe und Beilagen zwischen dem Historiker und Soziologe Helmut Hirsch an Max Horkheimer, 1951-1954, 25.05.1951; 3 Briefe mit Antwort von Lux Hirsch an Max Horkheimer, 1958; 1 Brief mit Antwort von Trude Hirschberg an Max Horkheimer, 1951; 1 Brief mit Antwort von Ingineur Paul F. Hirschfelder an Max Horkheimer, 1952; 1 Brief von Johannes Hirzel an Max Horkheimer, 1955; 1 Brief mit Antwort von dem Historisches Seminar Köln an Max Horkheimer, 1956; 1 Brief mit Antwort und Beilage von Professor Wolfgang Hochheimer an Professor Theodor W. Adorno, 1952; 2 Briefe von Max Horkheimer an Professor Wolfgang Hochheimer, 1953, 1954; 2 Memoranden von der Deutschen Gesellschaft für Psychologie, 1953; 1 Brief mit Beilage von Stud. phil. Erna Hochleitner an Max Horkheimer, 1956; 1 Brief mit Antwort von Professor Helmut Coing an Max Horkheimer, 1957; 3 Briefe mit Antwort von der Hochschule für Sozialwissenschaften Wilhelmshaven an Max Horkheimer, 1957, 1958; 1 Brief von Max Horkheimer an die Hochschule für Wirtschafts- und Sozialwissenschaften Nürnberg, 1953; 2 Drucksachen von dem Hochschul-Dienst, 1952; 2 Drucksachen von der Hochschule für politische Wissenschaften München, 1952; 1 Brief mit Antwort von Dr. Wolfram Hodermann an Max Horkheimer, 1951; 4 Briefe zwischen Dr. phil. Walter Höllerer und Max Horkheimer, 1956; 1 Brief mit Antwort von Privatdozent Dr. phil. Walter Hoeres anMax Horkheimer, 1956; 2 Briefe mit Antwort von Stud. phil. Charlotte Hoffmann an Max Horkheimer, 1950; 3 Briefe mit Antwort und Beilage von Professor Walter Hoffmann an Max Horkheimer, 1950-1955; 1 Brief mit Antwort von Wolfhart E. V. Hoffmann an Max Horkheimer, 1953; 1 Brief von Max Horkheimer an Dr. Werner Hofmann, 1956; 1 Glückwunschtelegramm mit Antwort von Ernst und Karl Hohner, 1953; 1 Brief von Dozent Uvo Hölscher an Max Horkheimer, 1950; 2 Briefe mit Antwort von Professor Dr. med. K. Holldack an Max Horkheimer, 1957; 2 Briefe mit Antwort von Dipl. Landwirt Bernhard Hollenhorst an Max Horkheimer, 1956; 1 Brief von Hans Heinz Holz an Max Horkheimer, 1951; 2 Briefe mit Antwort und Beilage von Dr. phil. Rudolf Holzinger an Max Horkheimer, 1951, 1952; 1 Brief mit Antwort von Jakob Hommen an Max Horkheimer, 1953; 1 Brief von Adele Hoppe anMax Horkheimer, 1953; 1 Brief mit Antwort von Dr. jur. Anton Horn an Max Horkheimer, 1954; 1 Brief mit Antwort von Dr. phil. Emil Horn an Max Horkheimer, 1953; 1 Brief von der Landesabgeordneten Ruth Horn an H. Maidon, 1953; 1 Brief mit Antwort von Reg.-Direktor Dr. phil. Kurt Horstmann an Max Horkheimer, 1953; 1 Brief von dem Hotel Baur au Lac an H. Maidon, 1958; 2 Briefe mit 1 Antwort von dem Hotel Frankfurter Hof an Max Horkheimer, 1956, 1958; 1 Brief mit Antwort von dem Hotel Stafflenberg an H. Maidon, 1953; 1 Brief von dem Hotel Vier Jahreszeiten, München an Max Horkheimer, 1951; 1 Brief von Max Horkheimer an Jean J. Hubener, 1951; 2 Briefe mit Antwort und Beilage von Susanna Huber-Weisser an Max Horkheimer, 1956; 1 Todesanzeige von dem Sozialgerichtsdirektor Gustav Adolf Hünniger, 1955; 1 Brief von dem Oberstudiendirektor F. Huf an Max Horkheimer, 1952; 1 Brief mit Antwort von Professor H. D. Huggins an Max Horkheimer, 1954; 2 Briefe mit 1 Antwort und 1 Beilage von dem Humboldt-Verlag, Wien-Stuttgart an Max Horkheimer, 1951; 1 Brief von Helge Pross an stud. rer. pol. Kristian Hungar, 1957; 1 Brief von Helmut Hungerland an Max Horkheimer, 1950; 1 Brief mit Antwort von James R. Huntley an Max Horkheimer, 1954; 1 Brief von Professor Robert Maynard Hutchins an Max Horkheimer, 1957;

Soldiering and surveying in British East Africa 1891 - 1894

by J. R. L. Macdonald