Biochemical and Genetic Studies of UBR3, a Ubiquitin Ligase with a Function in Olfactory and Other Sensory Systems

Our previous work identified E3 ubiquitin ligases, termed UBR1-UBR7, that contain the ~70-residue UBR box, a motif important for the targeting of N-end rule substrates. In this pathway, specific N-terminal residues of substrates are recognized as degradation signals by UBR box-containing E3s that include UBR1, UBR2, UBR4, and UBR5. The other E3s of this set, UBR3, UBR6, and UBR7, remained uncharacterized. Here we describe the cloning and analyses of mouse UBR3. The similarities of UBR3 to the UBR1 and UBR2 E3s of the N-end rule pathway include the RING and UBR domains. We show that HR6A and HR6B, the E2 enzymes that bind to UBR1 and UBR2, also interact with UBR3. However, in contrast to UBR1 and UBR2, UBR3 does not recognize N-end rule substrates. We also constructed UBR3-lacking mouse strains. In the 129SvImJ background, UBR3-/- mice died during embryogenesis, whereas the C57BL/6 background UBR3-/- mice exhibited neonatal lethality and suckling impairment that could be partially rescued by litter size reduction. The adult UBR3-/- mice had female-specific behavioral anosmia. Cells of the olfactory pathway were found to express beta-galactosidase (LacZ) that marked the deletion/disruption UBR3- allele. The UBR3-specific LacZ expression was also prominent in cells of the touch, vision, hearing, and taste systems, suggesting a regulatory role of UBR3 in sensory pathways, including olfaction. By analogy with functions of the UBR domain in the N-end rule pathway, we propose that the UBR box of UBR3 may recognize small compounds that modulate the targeting, by this E3, of its currently unknown substrates

Rats overexpressing the dopamine transporter display behavioral and neurobiological abnormalities with relevance to repetitive disorders

The dopamine transporter (DAT) plays a pivotal role in maintaining optimal dopamine signaling. DAT-overactivity has been linked to various neuropsychiatric disorders yet so far the direct pathological consequences of it has not been fully assessed. We here generated a transgenic rat model that via pronuclear microinjection overexpresses the DAT gene. Our results demonstrate that DAT-overexpression induces multiple neurobiological effects that exceeded the expected alterations in the corticostriatal dopamine system. Furthermore, transgenic rats specifically exhibited behavioral and pharmaco-therapeutic profiles phenotypic of repetitive disorders. Together our findings suggest that the DAT rat model will constitute a valuable tool for further investigations into the pathological influence of DAT overexpression on neural systems relevant to neuropsychiatric disorders

Usage of "GMS Medizin - Bibliothek - Information": analysis of usage data from an Open Access journal

In 2006 the journal "MEDIZIN - BIBLIOTHEK - INFORMATION" changed from the internet platform of the "Arbeitsgemeinschaft für Medizinisches Bibliothekswesen" (AGMB) to the Open Access platform German Medical Science (GMS). The printed journal version ceased. Thitherto it was sent to all members of the AGMB. The editorial staff made a few arrangements in order to support acceptance and perceptibility of this journal, now issued electronic only. The published papers were included in the database of the Deutsches Bibliothekswesen (DABI) and in the Directory of Open Access Journals (DOAJ Content). Furthermore current articles were introduced in MEDINFO, a weblog for medical librarians. The paper compares usage data trends from September 2005 to May 2008 for selected articles.2006 erfolgte der Wechsel von MEDIZIN - BIBLIOTHEK - INFORMATION von der Website der Arbeitsgemeinschaft für Medizinisches Bibliothekswesen (AGMB) auf die Open Access-Plattform German Medical Science; die bis Jahresende 2005 dreimal pro Jahr an die Mitglieder der AGMB verteilte Print-Version wurde eingestellt. Zur Förderung der Akzeptanz und der Wahrnehmbarkeit als E-Only-Zeitschrift konnten von der Redaktion einige Maßnahmen gesetzt werden, wie die Aufnahme der einzelnen Beiträge in die Datenbank Deutsches Bibliothekswesen (DABI) bzw. ins Directory of Open Access Journals (DOAJ Content) sowie die Ankündigung der einzelnen Beiträge von GMS MEDIZIN - BIBLIOTHEK - INFORMATION im medizinbibliothekarischen Weblog MEDINFO. Im Beitrag wird die Entwicklung der Zugriffszahlen zwischen September 2005 und Mai 2008 dargestellt