ADAM15 modulates outside-in signalling in chondrocyte–matrix interactions

ADAM15 belongs to a family of transmembrane multi-domain proteins implicated in proteolysis, cell–cell and cell–matrix interactions in various disease conditions. In osteoarthritis (OA), ADAM15 is up-regulated in the chondrocytes already at early stages of cartilage degeneration where it seems to exert homeostatic effects likely associated with its ability to enhance integrin-mediated chondrocyte adhesion to the surrounding collagen matrix. The aim of our present study was, therefore, to characterize functional domains of ADAM15 involved in collagen II (CII) interaction and to analyse associated outside-in signalling events. Accordingly, ADAM15 and respective deletion mutants were stably transfected into the chondrocyte cell line T/C28a4. Transfected cells were adhered to CII and phosphoproteins analysed by Western blotting. Co-immunoprecipitation served to identify protein binding to ADAM15. Our results elucidate the prodomain as critical for the capacity of ADAM15 to enhance CII adhesion, thereby identifying for the first time a cell-adhesive role of a metalloproteinase prodomain. Moreover, the cytoplasmic tail of ADAM15 confers a modulatory effect on the autophosphorylation site Y397 of the focal adhesion kinase (FAK) during chondrocyte–collagen interaction. In conclusion, the newly uncovered impact of ADAM15 on signalling events that arise from chondrocyte interactions with its collagen matrix might contribute to the elucidation of the mechanism underlying its proposed chondroprotective role in degenerative cartilage disease

Identification of low-frequency TRAF3IP2 coding variants in psoriatic arthritis patients and functional characterization

Introduction: In recent genome-wide association studies for psoriatic arthritis (PsA) and psoriasis vulgaris, common coding variants in the TRAF3IP2 gene were identified to contribute to susceptibility to both disease entities. The risk allele of p.Asp10Asn (rs33980500) proved to be most significantly associated and to encode a mutant protein with an almost completely disrupted binding property to TRAF6, supporting its impact as a main disease-causing variant and modulator of IL-17 signaling. Methods: To identify further variants, exons 2-4 encoding both known TNF-receptor-associated factor (TRAF) binding domains were sequenced in 871 PsA patients. Seven missense variants and one three-base-pair insertion were identified in 0.06% to 1.02% of alleles. Five of these variants were also present in 931 control individuals at comparable frequency. Constructs containing full-length wild-type or mutant TRAF3IP2 were generated and used to analyze functionally all variants for TRAF6-binding in a mammalian two-hybrid assay. Results: None of the newly found alleles, though, encoded proteins with different binding properties to TRAF6, or to the cytoplasmic tail of the IL-17-receptor α-chain, suggesting that they do not contribute to susceptibility. Conclusions: Thus, the TRAF3IP2-variant p.Asp10Asn is the only susceptibility allele with functional impact on TRAF6 binding, at least in the German population

Bending our ethics code: Avoidable deception and its justification in psychological research

Deception of research participants has long been and remains a hot-button issue in the behavioral sciences. At the same time, the field of psychology is fortunate to have an ethics code to rely on in determining whether and how to use and report on deception of participants. Despite ongoing normative controversies, the smallest common denominator among psychologists is that deception ought to be a last resort – to be used only when there is no other defensible way to study a question or phenomenon. Going beyond previous normative discussions or inquiries into the mere prevalence of deception, we ask the fundamental question whether common practice is compatible with this interpretation of our field’s ethical standards. Findings from an empirical literature review – focusing on the feasibility of nondeceptive alternative procedures and the presence of explicit justifications for the use of deception – demonstrate that there is a notable gap between the last resort interpretation of our ethical standards and common practice in psychological research. The findings are discussed with the aim of identifying viable ways in which researchers, journal editors, and the scientific associations crafting our ethics codes may narrow this gap

Economic games: An introduction and guide for research

Prosocial behaviors constitute vital ingredients for all types of social interactions and relationships as well as for society at large. Corresponding to this significance, the study of prosocial behaviors has received considerable attention across scientific disciplines. A striking feature of this research is that most disciplines rely on economic games to measure actual prosocial behavior in controlled experimental settings. However, empirical research often fails to fully exploit the richness of this class of paradigms. The current work aims to overcome this issue by providing a theory-driven overview of and introduction to the variety of economic games for researchers in psychology and beyond. Specifically, we introduce prominent theories of games (Game Theory and Interdependence Theory) and show how the concepts from these theories can be integrated in a unifying theoretical framework considering games as providing specific situational affordances for behavior. Additionally, we describe several games in detail, including their structural features, the affordances they involve, the social motives that may guide behavior, the flexibility they entail to manipulate specific situational aspects and, thus, affordances, and typical research findings. We conclude that tailored selection and combination of games and game variants allows to obtain a unique understanding of the underlying psychological processes involved in prosocial behavior. As a practical tool for researchers, we also provide standardized game instructions and guidelines for the implementation of games in future research. Ultimately, the review can foster optimal use of economic games in future work and thereby set the stage for high-class, replicable, and innovative research on human prosociality

Supersymmetric Corrections to the Threshold Production of Top Quark Pairs

In this paper we investigate supersymmetric effects to the threshold production cross section of top quark pairs in electron positron annihilation. In particular, we consider the complete one-loop corrections from the strong and weak sector of the Minimal Supersymmetric Standard Model.Comment: 18 pages, 7 figure