Skeletal muscle derived Musclin protects the heart during pathological overload

Cachexia is associated with poor prognosis in chronic heart failure patients, but the underlying mechanisms of cachexia triggered disease progression remain poorly understood. Here, we investigate whether the dysregulation of myokine expression from wasting skeletal muscle exaggerates heart failure. RNA sequencing from wasting skeletal muscles of mice with heart failure reveals a reduced expression of Ostn, which encodes the secreted myokine Musclin, previously implicated in the enhancement of natriuretic peptide signaling. By generating skeletal muscle specific Ostn knock-out and overexpressing mice, we demonstrate that reduced skeletal muscle Musclin levels exaggerate, while its overexpression in muscle attenuates cardiac dysfunction and myocardial fibrosis during pressure overload. Mechanistically, Musclin enhances the abundance of C-type natriuretic peptide (CNP), thereby promoting cardiomyocyte contractility through protein kinase A and inhibiting fibroblast activation through protein kinase G signaling. Because we also find reduced OSTN expression in skeletal muscle of heart failure patients, augmentation of Musclin might serve as therapeutic strategy

Modernism's Legacy: Dialogue, Objectivity, and Justice in Mark Bevir's Democratic Governance

This is an Accepted Manuscript of an article published by Taylor & Francis in Local Government Studies on 19th December 2011, available online: http://wwww.tandfonline.com/10.1080/03003930.2011.638372This article looks at Mark Bevir's ideas on the changing nature of the modern state, as expressed in his book, ‘Democratic Governance’. In the book, the author argues that recent developments in the theory and practice of politics have their intellectual roots in wider trends in the academic study of society and politics. In particular, he argues, the rise in what he and others have called ‘the new governance’ – that is, the shift in Britain and elsewhere away from centralised policy making and implementation by state institutions toward policy networks in which the state is merely one actor among many – has emerged as a direct consequence of the rise of ahistorical, universalist social science methodologies