Identifizierung eines Cathepsin B-vermittelten Todessignalwegs in Thymozyten mit Bedeutung für die negative Selektion

Apoptose, programmierter Zelltod, tritt im Verlauf der normalen Entwicklung und als Reaktion auf verschiedene physiologische oder pathophysiologische Stimuli auf. Im Immunsystem nimmt Apoptose bei der Erhaltung der Zellhomöostase eine zentrale Stellung ein. Im Verlauf der T Zellentwicklung ist Apoptose ein wichtiger Mechanismus zur Beseitigung von selbstreaktiven T Zellen im Thymus. Dieser Prozess wird negative Selektion genannt und stellt die Selbsttoleranz der T Zellpopulation sicher. Fehler bei der Apotoseregulation verursachen eine abnormale Zellentwicklung und fördern die Entstehung von Krebs, Immundefizienzen und Autoimmunerkrankungen. Molekular ist Apoptose unter anderem durch die Aktivierung von spezifischen Proteasen, den Caspasen, gekennzeichnet. Allerdings zeigte sich in den letzten Jahren, dass der programmierte Zelltod auch ohne die Beteiligung von Caspasen auftritt und andere Proteasen die Exekution des Zelltodes übernehmen können. Da bislang unklar ist, inwieweit die negative Selektion im Thymus unter Beteiligung von Caspasen abläuft, wurde in dieser Arbeit der aktivierungsinduzierte Zelltod in Thymozyten auf dessen Caspaseabhängigkeit hin untersucht. Dazu wurde die thymischen Lymphomzelllinie D als Modell etabliert. Mit Hilfe dieser Zelllinie konnte gezeigt werden, dass Zelltod nach Stimulation des T-Zellrezeptor (TZR)-Signalweges in Abwesenheit von Caspaseaktivität durch die lysosomale Protease Cathepsin B vermittelt wird. Dieser aktivierungsinduzierte Caspase-unabhängige Zelltod wies charakteristische Kennzeichen der Apoptose auf. Im Verlauf des aktivierungsinduzierten Zelltodes wurden die frühe Permeabilisierung der Lysosomen und die Freisetzung von Cathepsin B ins Zytosol beobachtet. Eine physiologische Relevanz dieses Caspase-unabhängigen Zelltodes wurde in primären murinen Thymozyten gezeigt. Im Vergleich der verschiedenen thymischen T Zellpopulationen wurde eine deutliche Hochregulation der Cathepsin B-mRNA in doppelt-positiven CD4+CD8+-Thymoyzten nachgewiesen. Darüber hinaus war Cathepsin B am TZR induzierten Zelltod in DP-Thymozyten beteiligt. Die in dieser Arbeit gewonnenen Erkenntnisse zeigen einen alternativen, bis dahin unbekannten Todessignalweg in Thymozyten, der möglicherweise eine Bedeutung bei der negativen Selektion im Thymus hat. Diese Arbeit trägt zum molekularen Verständnis der negativen Selektion bei und kann helfen zu verstehen, wie Thymozyten zwischen „Selbst“ und „Nicht-Selbst“ unterscheiden

Gewerke übergreifende Qualifizierung für energetische Bau- und Sanierungsmaßnahmen 3. Wärmedämmung von Außenwänden oder die Kontroverse um den Dämmwahn – Politik- und Lernfeldunterricht in der Bautechnik

Im dritten Band steht das aktuelle Thema ‚Wärmedämmung‘ im Mittelpunkt. Die Sanierung des Gebäudebestands ist ein wesentlicher Beitrag, um das gesteckte Klimaziel in Deutschland erreichen zu können. Nach einem theoretischen Überblick über die Integration der Sozialwissenschaften im Lernfeldunterricht der Berufsschule entwickelt die Autorin ein curriculares Unterrichtskonzept im Rahmen der Lernfelddidaktik. Dafür werden zunächst die Rahmenbedingungen und Begründungen für einen integrativen Unterricht in der Berufsschule erläutert. Daran anknüpfend wird für das Lernfeld 8 „Sanieren einer Außenwand“ für den Ausbildungsberuf Trockenbaumonteur/-in eine integrative berufsbezogene und als vollständige Handlung geplante Lernsituation gestaltet, die politische und gesellschaftliche Inhalte sowie politikdidaktische Ziele mit einbezieht. Dafür wird eine problemorientierte Analyse der gesellschaftlichen und politischen Aspekte des beruflichen Handelns im Themenbereich der Außenwanddämmung durchgeführt. Die gesellschaftliche Kontroverse um den „Dämmwahn“ wird dabei mithilfe der Dimensionen der Nachhaltigkeit strukturiert und aus verschiedenen Interessenlagen betrachtet. Es gelingt der Autorin auf überzeugende Weise, die Möglichkeiten des übergreifenden Unterrichts anhand eines aktuellen Themas aufzuzeigen. (DIPF/Orig.

Das Oracle UIX Framework als frühe Implementierung der JavaServer Faces Spezifikation

Im Mai 2001 wurde JavaServer Faces (JSF) von Sun als Java Specification Request (JSR) 127 vorgestellt. Außer Sun sind an der Entwicklung der JSF Spezifikation unter anderem die Apache Software Foundation, BEA Systems, Borland Software Corporation, IBM, Oracle und Macromedia beteiligt. Seit Dezember 2003 steht die Referenzimplementierung (RI) von Sun als Version 1.0 Beta zur Verfügung. Obwohl die Spezifikation noch nicht ganz abgeschlossen ist und die RI bis zum Final Release noch große Änderungen erfahren wird, zeichnet sich bereits ab, dass hier ein "großer Wurf" gelungen ist. Tool-Hersteller wie auch Anwendungsentwickler bringen JSF großes Interesse entgegen; eine OpenSource-Implementierung der JavaServer Faces ist mit MyFaces1 von SourceForge auch schon zu haben. Dabei gab es JavaServer Faces eigentlich schon, bevor die Entwicklung der Spezifikation begann. Das inzwischen in der Version 2.1.7 vorliegende Framework UIX (User Interface XML) von Oracle versucht schon seit einigen Jahren, eine große Lücke zu füllen. Es ist, genau wie JSF, ein UserInterface-Framework fürs Web. Im Gegensatz zu JSF ist es jedoch schon so ausgereift, dass es in realen Projekten eingesetzt werden kann

Extraskeletal osteosarcoma of the thorax in a goat: case report

BACKGROUND: This report describes the results of clinical, ultrasonographic and computed tomographic examination of a 16-year-old goat with extraskeletal osteosarcoma of the thorax. CASE PRESENTATION: The lead clinical signs were abnormal condition and demeanour, fever, tachycardia, tachypnoea, dyspnoea and dilated jugular veins. Ultrasonographic examination of the thorax revealed a precardial mass, measuring 16.4 by 11.4 by 14.2 cm. Computed tomographic examination showed dorsocaudal displacement of the trachea, heart and lungs to the right. A tentative diagnosis of mediastinal or pleural neoplasia was made, and the goat was euthanased and necropsied. A definitive diagnosis was based on histological examination of the mass. CONCLUSIONS: To our knowledge, this case report is the first description of extraskeletal osteosarcoma of the thorax in goats and serves to broaden the diagnostic spectrum of thoracic diseases in this species. Extraskeletal osteosarcoma should be part of the differential diagnosis in goats with thoracic tumours

Cytokine patterns in nasal secretion of non-atopic patients distinguish between chronic rhinosinusitis with or without nasal polys

Background: Being one of the most common nasal diseases, chronic rhinosinusitis (CRS) is subdivided into CRS with nasal polyps (NP) and CRS without nasal polyps (CRSsNP). CRSsNP presents itself with a T(H)1 milieu and neutrophil infiltration, while NP is characterised by a mixed T(H)1/T(H)2 profile and an influx of predominantly eosinophils, plasma cells and mast cells. For the purpose of discovering disease-specific cytokine profiles, the present study compares levels of mediators and cytokines in nasal secretions between CRSsNP, NP, and healthy controls. Methods: The study included 45 participants suffering from NP, 48 suffering from CRSsNP and 48 healthy controls. Allergic rhinitis constituted an exclusion criterion. Nasal secretions, sampled using the cotton wool method, were analysed for IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, IL-8, GM-CSF, G-CSF, IFN-gamma, MCP-1, MIP-1 alpha, MIP-1 beta, eotaxin, and RANTES, and for ECP and tryptase, using Bio-Plex Cytokine assay or ELISA, respectively. Results: Elevated levels of IL-5, IL-17, G-CSF, MCP-1, MIP-1 alpha, MIP-1 beta, ECP, and tryptase, as well as decreased levels of IL-10, IL-12, IL-13, and IFN-gamma were detected in NP. CRSsNP presented increased levels of RANTES and MIP-1 beta while IL-13 was decreased. No differences between the three groups were found for IL-4, IL-8, GM-CSF, and eotaxin. Conclusions: The present work suggests a disequilibrium of T(H)1 and T(H)2, together with a down-regulation of regulatory T lymphocytes and up-regulated T(H)17 in NP. Moreover, elevated levels of diverse mediators represent the activation of various inflammatory cells in this disease entity. The inflammation in CRSsNP, however, is only weakly depicted in nasal secretions. Therefore, cytokines in nasal secretions may provide helpful information for differential diagnosis

Real-Life Study for the Diagnosis of House Dust Mite Allergy - The Value of Recombinant Allergen-Based IgE Serology

Background: Dermatophagoides pteronyssinus is one of the most important perennial allergen sources worldwide. Molecular diagnostics using the commercially available major allergens (Der p 1 and Der p 2) in combination with Der p 10 do not detect house dust mite (HDM) sensitization in a number of cases when used alone. The objective was to evaluate the IgE reactivity profiles of these patients using an experimental immunoassay biochip. Methods: Sera of HDM-allergic patients (positive skin prick test, CAP class 1 for allergen extract, and positive intranasal provocation) were tested for IgE antibodies against Der p 1, Der p 2, and Der p 10 by ImmunoCAP fluorescence enzyme immunoassay. Negatively tested sera were examined by an experimental chip containing 13 microarrayed HDM allergens. Results: Of 97 patients tested, 16 showed negative results to Der p 1, Der p 2, and Der p 10. MeDALL chip evaluation revealed 5 patients mono-sensitized to Der p 23, and 11 patients were negative for all HDM MeDALL chip components. Seven sera were available for further testing, and 3 of them showed IgE reactivity to dot-blotted nDer p 1, and 2 reacted with high-molecular weight components (>100 kDa) in nitrocellulose-blotted HDM extract when tested with 1251-labeled anti-IgE in a RAST-based assay. The HDM extract-specific IgE levels of the 11 patients were <3.9 kU/I. Conclusions: Recombinant allergen-based IgE serology is of great value when conventional IgE diagnostics fails. Der p 23 is an important HDM allergen, especially when major allergens are negative. Therefore, it would be desirable to have Der p 23 commercially available. Further research concerning the prevalence and clinical significance of different HDM allergens is needed. (C) 2016 S. Karger AG, Base

Role of Eddies in the Carbon Pump of Eastern Boundary Upwelling Systems, REEBUS, Cruise No. M156, 03.07. – 01.08.2019 Mindelo (Cap Verde) – Mindelo

Summary The major goal of the RV METEOR cruise M156 to Cape Verdian waters and the Mauritanian upwelling area off West Africa was to contribute to a better quantitative understanding of the effects of mesoscale eddies on CO2 source/sink mechanisms and the biological carbon pump in eastern boundary upwelling areas as well as their effects to the oligotrophic periphery including the deep-sea floor. The cruise M156 (MOSES Eddy Study I) was conducted within the framework of the BMBF funded REEBUS project (Role of Eddies in the Carbon Pump of Eastern Boundary Upwelling Systems) by a consortium of physical, biological (benthic microbiology, bacterial plankton, protists) and biogeochemical oceanographers. Specific aims were i. the quantification of solute and particle fluxes within and at the periphery of eddies; ii. to determine the turnover of carbon species, air-sea gas exchange of CO2, iii. the determination of the protistan and bacterial plankton community structures in the surface layers of an eddy, and iv. to quantify the magnitude and variability of material fluxes to the seabed and turnover in the sediment underneath the eddy passage. To achieve these aims, the cruise had two major observing strategies: i. an intense benthic/pelagic program along the zonal eddy passage at 18°N. Along this corridor ranging from 24°20’ to 16°30’W, five benthic/pelagic stations (E1 to E5) in different water depths and distances from the Mauritanian coast were performed. The motivation for this survey has been to resolve zonal gradients in pelagic element cycling as well as of organic matter degradation and burial in the seabed, which in turn could potentially be linked with changes in eddy induced primary- and export production. ii. the detailed investigation of an individual eddy to investigate physical, biogeochemical and biological processes on meso- to submeso-scales (100km to 10m). Satellite data analysis was performed before and during the cruise to identify a suitable eddy from a combination of sea-level anomaly, ocean color as Chl-a proxy, and sea-surface temperature supplemented with shipboard current velocity measurements. A total of 171 stations were sampled. The water column program consists of 59 CTD casts, 29 MSS and 20 Marine Snow Catcher deployments. For biogeochemical measurements at the sea surface two deployments of a Lagrangian Surface Drifter and one Waveglider deployment were conducted. At the seafloor, we conducted 10 BIGO deployments. Ten seafloor imaging surveys were performed using the towed camera system OFOS, supplemented with 7 Multibeam and 1 Sidescan surveys. In deviation from the cruise proposal, the planned long-term deployment of a Lander, which was planned to record a time series of oxygen fluxes during the passage of an eddy, was not deployed due to a major delay in its design and manufacturing. The planned AUV (Girona 500) deployments at the shallow E5 station close to the Mauritanian coast station did also not take place. Despite moderate weather conditions, all deployments were successful, hence all the data and sample material aimed for has been achieved. It is to expect that as planned all scientific questions can be addressed. Especially in the synthesis of all REEBUS cruises and the consideration of data from earlier cruises (MSM17/4, M107) into this region a high scientific potential can be expected

Who talks to whom about what? How interdisciplinary communication and knowledge of expertise distribution improves in integrated R&D labs

Although several studies have examined the impact of open workspaces, there is still an on-going debate about its advantages and disadvantages. Our paper contributes to this debate by shedding light on three issues: the effect of open workspaces on (1) the flow of communication along and across hierarchical lines; (2) the content of communication; and (3) the specificities of open integrated laboratories. Our findings derive from a longitudinal case in a large pharmaceutical company that has relocated some R&D teams from enclosed to multi-space offices and labs. The relocation has resulted in (a) increased interdisciplinary communication, particularly at lower hierarchical levels, (b) a shift of the location of discussions and the content of conversations and (c) an improved knowledge about expertise distribution. Practitioner Summary Communication is essential in knowledge-driven organisations. This article examines the impact of a relocation of R&D employees from enclosed to multi-space offices and labs on communication patterns. We explain how the new environment fosters interdisciplinary communication, shifts the location of discussions and increases the knowledge of expertise distribution

Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study

AIMS: To systematically assess late outcomes of acute pulmonary embolism (PE) and to investigate the clinical implications of post-PE impairment (PPEI) fulfilling prospectively defined criteria. METHODS AND RESULTS: A prospective multicentre observational cohort study was conducted in 17 large-volume centres across Germany. Adult consecutive patients with confirmed acute symptomatic PE were followed with a standardized assessment plan and pre-defined visits at 3, 12, and 24 months. The co-primary outcomes were (i) diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), and (ii) PPEI, a combination of persistent or worsening clinical, functional, biochemical, and imaging parameters during follow-up. A total of 1017 patients (45% women, median age 64 years) were included in the primary analysis. They were followed for a median duration of 732 days after PE diagnosis. The CTEPH was diagnosed in 16 (1.6%) patients, after a median of 129 days; the estimated 2-year cumulative incidence was 2.3% (1.2-4.4%). Overall, 880 patients were evaluable for PPEI; the 2-year cumulative incidence was 16.0% (95% confidence interval 12.8-20.8%). The PPEI helped to identify 15 of the 16 patients diagnosed with CTEPH during follow-up (hazard ratio for CTEPH vs. no CTEPH 393; 95% confidence interval 73-2119). Patients with PPEI had a higher risk of re-hospitalization and death as well as worse quality of life compared with those without PPEI. CONCLUSION: In this prospective study, the cumulative 2-year incidence of CTEPH was 2.3%, but PPEI diagnosed by standardized criteria was frequent. Our findings support systematic follow-up of patients after acute PE and may help to optimize guideline recommendations and algorithms for post-PE care