TAPBPR bridges UDP-glucose : glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

Funding Wellcome: Senior Research Fellowship 104647, Andreas Neerincx, Louise H Boyle Royal Society: University Research Fellowship, UF100371, Janet E Deane Cancer Research UK: Programme Grant, C7056A, Andy van Hateren, Tim Elliott Deutsche Forschungsgemeinschaft: SFB 685, Nico Trautwein, Stefan Stevanović Wellcome: PhD studentship, 089563, Clemens Hermann Wellcome: Strategic Award 100140, Robin Antrobus Wellcome: Programme grant, WT094847MA, Huan Cao Acknowledgements We are extremely grateful to Peter Cresswell and Najla Arshad (Yale University School of Medicine, New Haven, CT) for valuable advice, tapasin and TAP-specific antibody reagents, and the recombinant calreticulin proteins. We thank John Trowsdale (University of Cambridge, UK) for his mentorship and critical reading of this manuscript, and Jim Kaufman (University of Cambridge, UK) for useful discussions. We also thank Yi Cao (Cranfield University, UK) for MATLAB programming for densitometry analysis, and Mark Vickers and Sadie Henderson (Scottish National Blood Transfusion Services, UK) for permitting the use of and assistance with the Amersham WB system. The reagent ARP7099 FEC peptide pool was obtained from the Centre for AIDS Reagents, National Institute for Biological Standards and Control (NIBSC), and was donated by the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH.Peer reviewedPublisher PD

Wie das GOAL-Projekt nachhaltige Kollaborationen zwischen Menschen, Maschinen und Strukturen fördert

Das von swissuniversities geförderte Projekt GOAL fungiert als Drehscheibe in einem Netzwerk, das unterschiedliche Akteure (Autor:innen, Bibliotheken, Herausgeber:innen) zusammen- und verschiedene Kollaborationen voranbringt: Die Kooperation zwischen Menschen und zwischen Maschinen wird gefördert und es sollen kollaborative Strukturen entstehen. Ziel des Projekts ist es, Verlage zu kontaktieren und diese bei der Erstellung und Implementierung einer Green Policy zu unterstützen. Der Blick wird auf die Publikationslandschaft von FH’s und PH’s gerichtet. Häufiger als an Universitäten wird hier in Fachmedien und landessprachlichen Zeitschriften publiziert. Die jeweiligen Geschäftsmodelle sind jedoch schlecht mit einer Umstellung auf Gold Open Access vereinbar. Mit dem gezielten Fokus auf den Green-Open-Acess-Weg wird eine nachhaltige Lösung für alle involvierten Akteure gesucht, die helfen soll, das Ziel der nationalen Open Access Strategie der Schweiz zu erreichen; d. h. bis Ende 2024 100% der öffentlich geförderten, wissenschaftlichen Publikationen im Open Access (OA) verfügbar zu machen

TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst.

Our understanding of the antigen presentation pathway has recently been enhanced with the identification that the tapasin-related protein TAPBPR is a second major histocompatibility complex (MHC) class I-specific chaperone. We sought to determine whether, like tapasin, TAPBPR can also influence MHC class I peptide selection by functioning as a peptide exchange catalyst. We show that TAPBPR can catalyse the dissociation of peptides from peptide-MHC I complexes, enhance the loading of peptide-receptive MHC I molecules, and discriminate between peptides based on affinity in vitro. In cells, the depletion of TAPBPR increased the diversity of peptides presented on MHC I molecules, suggesting that TAPBPR is involved in restricting peptide presentation. Our results suggest TAPBPR binds to MHC I in a peptide-receptive state and, like tapasin, works to enhance peptide optimisation. It is now clear there are two MHC class I specific peptide editors, tapasin and TAPBPR, intimately involved in controlling peptide presentation to the immune system.This is the final version of the article. It first appeared from eLife via http://dx.doi.org/10.755

From Romantic Gothic to Victorian Medievalism: 1817 and 1877

"The Cambridge History of the Gothic was conceived in 2015, when Linda Bree, then Editorial Director at Cambridge University Press, first suggested the idea to us

Impacts of land use and human pressures on riverine fish in European river types

Diese Arbeit untersucht anthropogene Veränderungen (z.B. Landnutzung, Flussverbauung, Staudämme) und dessen Auswirkungen auf Süßwasserfischarten an Europäischen Flüssen. Fünf Landnutzungsklassen (Wald, Strauchvegetation, Weideland, Landwirtschaft, Siedlungsgebiet) wurden für Einzugsgebiete berechnetund ausgewählten fischökologischen Parametern (Fisch Metrics) gegenübergestellt. Der aus diesen Metrics entwickelte Europäische Fisch Index (EFI) zeigte einen besonders stark negativen Zusammenhang zur Landnutzungsklasse Landwirtschaft, etwas schächer zu Siedlungsgebieten. Bei starker Präsenz von Landwirtschaft und Siedlung konnte ein kumulativer Effekt identifiziert werden, der vom Flusstyp abhängig war (Oberlauf, Bäche mit geringem Gefälle, mittelgroße Flüsse, Tieflandflüsse). Es wurde dokumentiert, dass 80 % der Probestellen (n=9330) in Europa durch menschliche Eingriffe belastet sind (Morphologie in alpinen Flüssen, Wasserqualität in Tieflandflüssen). Nach einer Gliederung der Fischartenvergesellschaftungen in vier Flusstypen (Oberläufe, Flüsse mittleren Gefälles, Tieflandflüsse, mediterrane Bäche) konnten typspezifisch unterschiedliche Metrics bzw. Reaktionen der Fische auf menschliche Eingriffe gefunden werden. Vor allem Wasserqualitätsprobleme und hydromorphologische Belastungen wirkten sich besonders negativ auf Fische in drei der vier Flusstypen aus. Mehrfachbelastungen wurden in allen Flusstypen durch geeignete fischökologische Kennzahlen (z.B. Anzahl bzw. relative Dichte an toleranten Arten, relative Anzahl der omnivoren Arten) identifiziert. Das gewonnene Verständnis über die Sensibilität von Fischen als Indikatoren für den Zustand von Flüssen erweitert die Möglichkeiten, Verschlechterungen an Flussökosystemen auf bestimme menschliche Eingriffe zurückzuführen. ^Schlussfolgerung:menschliche Eingriffe in das aquatische Ökosystem wirken sich gewässertypspezifisch sowohl einzeln als auch in Summe abhängig von lokalen und regionalen Umweltbedingungen aus.The objective of the present thesis was to gain better knowledge of how human actions and human disturbance along rivers and in river catchments affect riverine fish assemblages. For the analysis of the impacts of land use and human pressures on riverine fish in European rivers, we used a large, pan-European dataset containing fish assemblage data, basic environmental characteristics, various human pressure data, and land use data. We quantified the relationship between land use within the river catchment and the ecological status of fish assemblages. We sought candidate fish metrics that were correlated with the percentage of five land-use types within the catchment area of the sampling reach (forest, shrubs, pasture, agriculture, urban). Results for Austrian rivers demonstrated strong relationships between land use on the catchment scale and fish assemblages. The response of trait-based fish metrics to agriculture was stronger than to the multi-metric European Fish Index. We were able to identify thresholds and cumulative effects of land use within the catchment. These thresholds varied across river types. Local human pressures on hydrology, morphology, water quality, and connectivity were documented to be widespread at the European scale (80 % of 9330 sites disturbed). Predominately hydromorphological pressures in Alpine rivers and headwaters and water quality and multiple pressures in lowland rivers. We found that suites of fish metrics reacted to human pressures exclusively within particular fish assemblage types, providing a good signal of response to human pressure for headwaters, medium gradient rivers, lowland rivers, and Mediterranean streams. Fish metrics responded specifically to water quality pressures and hydromorphological pressures in three river types and to multiple pressures in all river types. Fish-based indicators of river condition are important to accurately and efficiently detect pressure-specific degradation of river ecosystems.composed and submitted by Clemens TrautweinAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. Sprachehttp://www.boku.ac.at/zid-abstracts.htmlWien, Univ. für Bodenkultur, Diss., 2013OeBB(VLID)193142

The Evolution of International Safeguards - A View from Germany

On March 25 in the year 1957, the treaty creating the European Atomic Energy Community, the so-called 'Euratom Treaty' was signed by West Germany, Belgium, France, Italy, Luxembourg and the Netherlands. This treaty constituted the legal framework to establish a multinational safeguards system in these countries to guarantee that nuclear materials are not diverted to purposes otherthan those intended.In 1973, the European Community signed an agreement with the IAEA to accept safeguards pursuant to the NPT on all nuclear material in all their peaceful activities. This 'Verification Agreement' provided the basic for a co-operation of Euratom and IAEA in conducting their respective safeguards activities. Over the years, this co-operation evolved into a real partnership now governed by the rule of 'one job one person'.In the sixties and the following two decades, Germany embarked into numerous nuclear activities covering nearly the whole spectrum of different nuclear facilities. Germany thus could collect experiences with safeguards approaches and safeguards practices for many installations in the nuclear fuel cycle which we will delineate exemplarily in our presentation.The paper will also deal with the new Safeguards approach based on the State Level Concept and Integrated Safeguards. The implication on Safeguards Implementation and evaluation for Germany will be analyzed

Is the desire for fame related to well-being or ill-being?

The construct of fame in self-determination theory is very similar to the construct of social status in Anderson, Hildreth, and Howland’s (2015) status-as-fundamental-motive perspective. Both fame and social status are characterized by admiration and (admiring) respect by other people. Yet, while desiring fame is believed to distract or interfere with the fulfillment of basic needs (e.g., Ryan et al., 1999), desiring social status is believed to be very much equivalent to a basic need (Anderson et al., 2015). Inspired by these two theoretical standpoints, we tested opposing hypotheses in a pre-registered secondary data analysis of prospective longitudinal data spanning 10 years (N = 4,625; Mage at T1 = 19.60). Specifically, we tested whether or not desire for fame among early adults is related to their (a) concurrent subjective well-being, self-esteem, and health, (b) subsequent subjective well-being, self-esteem, and health, and (c) subsequent changes in subjective well-being, self-esteem, and health. Furthermore, we investigated (d) whether changes in desire for fame are related to contemporaneous changes in subjective well-being, self-esteem, and health. In line with self-determination theory, we found several positive correlations between desire for fame and the negative affect subscale of the PANAS, low self-esteem, and self-reported health complaints. In line with the status-as-fundamental-motive perspective, we found almost no substantial negative correlations between desire for fame and life satisfaction, the positive affect subscale of the PANAS, and self-rated health status. Thus, our results did not support either of the two positions unequivocally, indicating the need for further theoretical refinement