Gremlin1 preferentially binds to Bone Morphogenetic Protein-2 (BMP-2) and BMP-4 over BMP-7

Gremlin (Grem1) is a member of the DAN family of secreted bone morphogenetic protein (BMP) antagonists. Bone morphogenetic protein-7 (BMP-7) mediates protective effects during renal fibrosis-associated with diabetes and other renal diseases. The pathogenic mechanism of Grem1 during DN has been suggested to be binding and inhibition of BMP-7. However, the precise interactions between Grem1, BMP-7 and other BMPs have not been accurately defined. Here we show the affinity of Grem1 for BMP-7 is lower than that of BMP-2 and BMP-4, using a combination of surface plasmon resonance and cell culture techniques. Using kidney proximal tubule cells and HEK-293 cell Smad1/5/8 phosphorylation and BMP-dependent gene expression as readout, Grem1 consistently demonstrated a higher affinity for BMP-2>4>7. Cell-associated Grem1 did not inhibit BMP-2 or BMP-4 mediated signalling, suggesting that Grem1-BMP-2 binding occurred in solution, preventing BMP receptor activation. These data suggest that Grem1 preferentially binds to BMP-2 and this may be the dominant complex in a disease situation where levels of Grem1 and BMPs are elevated.

The Deconstructed Church: Understanding Emerging Christianity

The Emerging Church Movement (ECM) is a reform movement within Western Christianity that reacts against its roots in conservative evangelicalism by “de-constructing” contemporary expressions of Christianity. Emerging Christians see themselves as overturning out-dated interpretations of the bible, transforming hierarchical religious institutions, and re-orientating Christianity to step outside the walls of church buildings toward working among and serving others in the “real world.”

Drawing on ethnographic observations from emerging congregations, pub churches, neo-monastic communities, conferences, online networks, in-depth interviews, and congregational surveys in the US, UK, and Ireland, this book provides a comprehensive social scientific analysis of the development and significance of the ECM. Emerging Christians are shaping a distinct religious orientation that encourages individualism, deep relationships with others, new ideas around the nature of truth, doubt, and God, and innovations in preaching, worship, Eucharist, and leadership.

Northern Ireland, America and the Emerging Church Movement: Exploring the Significance of Peter Rollins andthe Ikon Collective

The Emerging Church Movement (ECM) is a primarily Western religious phenomenon, identifiable by its critical ‘deconstruction’ of ‘modern’ religion. While most prominent in North America, especially the United States, some of the most significant contributors to the ECM ‘conversation’ have been the Belfast-based Ikon Collective and one of its founders, philosopher Peter Rollins. Their rootedness in the unique religious, political and social landscape of Northern Ireland in part explains their position on the ‘margins’ of the ECM, and provides many of the resources for their contributions. Ikon’s development of ‘transformance art’ and its ‘leaderless’ structure raise questions about the institutional viability of the wider ECM. Rollins’ ‘Pyrotheology’ project, grounded in his reading of post-modern philosophy, introduces more radical ideas to the ECM conversation. Northern Ireland’s ‘Troubles’ and ‘marginal’ location provides the ground from which Rollins and Ikon have been able to expose the boundaries of the ECM and raise questions about just how far the ECM may go in its efforts to transform Western Christianity.

'When I Look I am Seen, So I Exist to Change': Supplementing Honneth's Recognition Model for Social Work

The subject of identity continues to attract widespread interest and debate in the social sciences. The nature of who we are, our potential to be different, and our similarity with others, underpins many present-day social issues. This paper contributes to this debate by examining critically the work of Axel Honneth on optimal identity-formation. Although broadly supporting Honneth’s chief construct of inter-personal recognition, a gap in his thinking is highlighted and addressed through proffering a fourth dimension to his tripartite model. This additional dimension requires demonstrations of recognition that instil hope in the face of hardship and empower positive transformations in identity. The implications of this reworked model for social work are then considered in terms of a range of approaches that can be utilised to build flourishing identities characterised by self-esteem, self-confidence, self-respect and self-belief.

Total eclipse of the heart: the AM CVn Gaia14aae/ASSASN-14cn

We report the discovery and characterization of a deeply eclipsing AM CVn-system, Gaia14aae (=ASSASN-14cn). Gaia14aae was identified independently by the All-Sky Automated Survey for Supernovae (ASAS-SN; Shappee et al.) and by the Gaia Science Alerts project, during two separate outbursts. A third outburst is seen in archival Pan-STARRS-1 (PS1; Schlafly et al.; Tonry et al.; Magnier et al.) and ASAS-SN data. Spectroscopy reveals a hot, hydrogen-deficient spectrum with clear double-peaked emission lines, consistent with an accreting double-degenerate classification. We use follow-up photometry to constrain the orbital parameters of the system. We find an orbital period of 49.71 min, which places Gaia14aae at the long period extremum of the outbursting AM CVn period distribution. Gaia14aae is dominated by the light from its accreting white dwarf (WD). Assuming an orbital inclination of 90° for the binary system, the contact phases of the WD lead to lower limits of 0.78 and 0.015 M⊙ on the masses of the accretor and donor, respectively, and a lower limit on the mass ratio of 0.019. Gaia14aae is only the third eclipsing AM CVn star known, and the first in which the WD is totally eclipsed. Using a helium WD model, we estimate the accretor's effective temperature to be 12 900 ± 200 K. The three outburst events occurred within four months of each other, while no other outburst activity is seen in the previous 8 yr of Catalina Real-time Transient Survey (CRTS; Drake et al.), Pan-STARRS-1 and ASAS-SN data. This suggests that these events might be rebrightenings of the first outburst rather than individual events.

Endothelium-derived intermedin/adrenomedullin-2 protects human ventricular cardiomyocytes from ischaemia-reoxygenation injury predominantly via the AM1 receptor

Application of intermedin/adrenomedullin-2 (IMD/AM-2) protects cultured human cardiac vascular cells and fibroblasts from oxidative stress and simulated ischaemia-reoxygenation injury (I-R), predominantly via adrenomedullin AM1 receptor involvement; similar protection had not been investigated previously in human cardiomyocytes (HCM). Expression of IMD, AM and their receptor components was studied in HCM. Receptor subtype involvement in protection by exogenous IMD against injury by simulated I-R was investigated using receptor component-specific siRNAs. Direct protection by endogenous IMD against HCM injury, both as an autocrine factor produced in HCM themselves and as a paracrine factor released from HCMEC co-cultured with HCM, was investigated using peptide-specific siRNA for IMD. IMD, AM and their receptor components (CLR, RAMPs1-3) were expressed in HCM. IMD 1 nmol L−1, applied either throughout ischaemia (3 h) and re-oxygenation (1 h) or during re-oxygenation (1 h) alone, attenuated HCM injury (P < 0.05); cell viabilities were 59% and 61% respectively vs. 39% in absence of IMD. Cytoskeletal disruption, protein carbonyl formation and caspase activity followed similar patterns. Pre-treatment (4 days) of HCM with CLR and RAMP2 siRNAs attenuated (P < 0.05) protection by exogenous IMD. Pre-treatment of HCMEC with IMD (and AM) siRNA augmented (P < 0.05) I-R injury: cell viabilities were 22% (and 32%) vs. 39% untreated HCMEC. Pre-treatment of HCM with IMD (and AM) siRNA did not augment HCM injury: cell viabilities were 37% (and 39%) vs. 39% untreated HCM. Co-culture with HCMEC conferred protection from injury on HCM; such protection was attenuated when HCMEC were pre-treated with IMD (but not AM) siRNA before co-culture. Although IMD is present in HCM, IMD derived from HCMEC and acting in a paracrine manner, predominantly via AM1 receptors, makes a marked contribution to cardiomyocyte protection by the endogenous peptide against acute I-R injury.

Near Vienna in the German Land

This is an essay including annotated critical editions documenting the history of reception of this song since 1848. Published in the Liederlexikon for the AHRC and DFG funded project 'The History of Reception of the Songs of the 1848 Revolution' (2009-2013).