Vesicular stomatitis virus glycoprotein is necessary for H-2-restricted lysis of infected cells by cytotoxic T lymphocytes

Vesicular stomatitis virus (VSV) elicited cytotoxic thymus-derived lymphocytes (CTLs) in mice of the BALB/c and three congenic strains (BALB.b, BALB.k, BALB.HTG). CTL lysis of VSV-infected fibroblasts from the four strains was restricted by the target cells' major histocompatibility complex (H-2). Target cells were also infected with two temperature-sensitive mutants of VSV, tsM and tsG in which, respectively, the viral matrix protein and glycoprotein are not expressed at 39 degrees (restrictive temperature) on the infected cell's surface membrane. At the restrictive temperature, cells infected with wild-type VSV or tsM were lysed by CTLs, but cells infected with tsG were not. The requirement for the glycoprotein on the target cell was also evident from the ability of antisera to the glycoprotein to block completely CTL lysis of VSV-infected cells

The Three Uses of the Law: A Protestant Source of the Purposes of Criminal Punishment

In this article, we focus on the interaction of Anglo-American criminal law and Protestant theological doctrine. We argue (1) that the sixteenth-century Protestant theological doctrine of the uses of moral law provided a critical analogue, if not antecedent to the classic Anglo-American doctrine of the purposes of criminal law and punishment; and (2) that this theological doctrine provides important signposts to the development of a more integrated moral theory of criminal law and punishment in late twentieth century America. Part One of this Article sets out the theological doctrine of the civil, theological, and educational uses of the moral law, as formulated by sixteenth century Lutherans and Calvinists, and elaborated by later Protestant writers in England and America. Part Two analyzes the analogous deterrent, retributive, and rehabilitative purposes of criminal law, as articulated by early modem Anglo-American jurists and moralists, and explores the historical cross-fertilization between these theological and legal doctrines. Part Three reflects on contemporary American criminal law developments in light of this three uses doctrine

Antimicrobial Resistance Gene Delivery in Animal Feeds

Avoparcin, a glycopeptide antimicrobial agent related to vancomycin, has been used extensively as a growth promoter in animal feeds for more than 2 decades, and evidence has shown that such use contributed to the development of vancomycin-resistant enterococci. A cluster that includes three genes, vanH, vanA, and vanX, is required for high-level resistance to glycopeptides. In the vancomycin producer Amycolatopsis orientalis C329.2, homologs of these genes are present, suggesting an origin for the cluster. We found substantial bacterial DNA contamination in animal-feed-grade avoparcin. Furthermore, nucleotide sequences related to the cluster vanHAX are present in this DNA, suggesting that the prolonged use of avoparcin in agriculture led to the uptake of glycopeptide resistance genes by animal commensal bacteria, which were subsequently transferred to humans

Sammelrezension aktueller Literatur

Rezension zu: 1) Annen, Silvia: Anerkennung von Kompetenzen - Kriterienorientierte Analyse ausgewählter Verfahren in Europa. Bielefeld: W. Bertelsmann Verlag 2012. Schriftenreihe des Bundesinstituts für Berufsbildung Bonn. ISBN 978-3-7639-1151-6. 2) Elke Gruber, Gisela Wiesner (Hg.): Erwachsenenpädagogische Kompetenzen stärken - Kompetenzbilanzierung für Weiterbildner/innen. Bielefeld: W. Bertelsmann Verlag 2012. ISBN 978-3-7639-4908-3. 3) Rolf Arnold: Systemische Erwachsenenbildung - die transformierende Kraft des begleiteten Selbstlernens. Baltmannsweiler: Schneider Verlag Hohengehren 2013. Schriftenreihe Systhemia - Systemische Pädagogik, Bd. 10. ISBN 978-3-8340-1210-4. 4) Matthias Herrle: Ermöglichung pädagogischer Interaktionen - Disponibilitätsmanagement in Veranstaltungen der Erwachsenen-/Weiterbildung. Wiesbaden: Springer VS 2013. ISBN 978-3-531-18632-0. 5) Katrin Kaufmann: Informelles Lernen im Spiegel des Weiterbildungsmonitorings. Wiesbaden: Springer VS 2012. ISBN 978-3-531-19384-7. 6) Hans-Christoph Koller, Roland Reichenbach, Norbert Ricken (Hg.): Philosophie des Lehrens. Paderborn: Ferdinand Schöningh Verlag 2012. Schriftenreihe der Kommission Bildungs- und Erziehungsphilosophie in der Deutschen Gesellschaft für Erziehungswissenschaft. ISBN 978-3-506-77587-0. 7) Bernhard Leipold: Lebenslanges Lernen und Bildung im Alter. Stuttgart: Kohlhammer Verlag 2012. Grundriss Gerontologie, Bd. 9. ISBN 978-3-17-017583-9. 8) Joachim Ludwig (Hg.): Lernen und Lernberatung - Alphabetisierung als Herausforderung für die Erwachsenendidaktik. Bielefeld: W. Bertelsmann Verlag 2012. Reihe: Theorie und Praxis der Erwachsenenbildung. ISBN 978-3-7639-5067-6. 9) Nadja Miersch: Anspruch und Wirklichkeit wissenschaftlicher Weiterbildung an öffentlichen Hochschulen - Implementierung einer Qualitätspolitik. Hamburg: Verlag Dr. Kovac 2012. Schriftenreihe Lehre & Forschung, Bd. 15. ISBN 978-3-8300-6638-5. 10) Elke Heidrun Schmidt: Altersbilder in der Erwachsenenbildung - Ältere Menschen im Spiegel westdeutscher Volkshochschulprogramme: Längsschnittuntersuchungen 1950-2000. Hamburg: Verlag Dr. Kovac 2013. Schriftenreihe Studien zur Erwachsenenbildung, Bd. 36. ISBN 978-3-8300-6725-2. 11) Hildegard Schröteler-von Brandt, Thomas Coelen, Andreas Zeising, Angela Ziesche (Hg.): Raum für Bildung - Ästhetik und Architektur von Lern- und Lebensorten. Bielefeld: transcript Verlag 2012. ISBN 978-3-8376-2205-8

The Natural History of Leber Congenital Amaurosis and Cone-Rod Dystrophy Associated with Variants in the GUCY2D Gene

OBJECTIVE: To describe the spectrum of Leber congenital amaurosis (LCA) and cone-rod dystrophy (CORD) associated with the GUCY2D gene, and to identify potential clinical endpoints and optimal patient selection for future therapeutic trials. DESIGN: International multicenter retrospective cohort study. SUBJECTS: 82 patients with GUCY2D-associated CORD and LCA from 54 molecularly confirmed families. METHODS: Data were gathered by reviewing medical records for medical history, symptoms, best-corrected visual acuity (BCVA), ophthalmoscopy, visual fields, full-field electroretinography and retinal imaging (fundus photography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence). MAIN OUTCOMES MEASURES: Age of onset, annual decline of visual acuity, estimated visual impairment per age, genotype-phenotype correlations, anatomic characteristics on funduscopy, and multimodal imaging. RESULTS: Fourteen patients with autosomal recessive LCA and 68 with autosomal dominant CORD were included. The median follow-up time was 5.2 years (interquartile range (IQR), 2.6-8.8) for LCA, and 7.2 years (IQR, 2.2-14.2) for CORD. Generally, LCA presented in the first year of life. The BCVA in LCA ranged from no light perception to 1.00 logMAR, and remained relatively stable during follow-up. Imaging for LCA was limited, but showed little to no structural degeneration. In CORD, progressive vision loss started around the second decade of life. The annual decline rate of visual acuity was 0.022 logMAR (P A and the c.2512C>T GUCY2D variant (P = 0.798). At the age of 40 years the probability of being blind or severely visually impaired was 32%. The integrity of the ellipsoid zone (EZ) and external limiting membrane (ELM) on SD-OCT were correlated significantly with BCVA (Spearman's ρ = 0.744, P = 0.001 and ρ = 0.712, P < 0.001, respectively) in CORD. CONCLUSION: LCA due to variants in GUCY2D results in severe congenital visual impairment with relatively intact macular anatomy on funduscopy and available imaging, suggesting a long preservation of photoreceptors. Despite large variability, GUCY2D-associated CORD generally presented during adolescence with a progressive loss of vision and culminated in severe visual impairment during mid to late-adulthood. The integrity of the ELM and EZ may be suitable structural endpoints for therapeutic studies in GUCY2D-associated CORD

Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-beta and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-beta and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-beta were found especially in MFS patients with aortic root dilatation (124 pg/ml), when compared to MFS patients with normal aorta (10 pg/ml; p = 8x10(-6), 95% CI: 70-159 pg/ml). Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR) = 0%), ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC) = 1.8; 1.4; 1.5, FDR = 0%) and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%). Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF) in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02) and increased number of CD8+ T-cells (p = 0.003) in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients

The Nature of Knowledge in Composition and Literary Understanding: The Question of Specificity

↵PETER SMAGORINSKY is Assistant Professor, College of Education, University of Oklahoma, 820 Van Vleet Oval, Norman, OK 73019-0. He specializes in classroom literacy.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline