Impaired Ca2+-handling in HIF-1α+/− mice as a consequence of pressure overload

The hypoxia-inducible factor (HIF)-1 is critically involved in the cellular adaptation to a decrease in oxygen availability. The influence of HIF-1α for the development of cardiac hypertrophy and cardiac function that occurs in response to sustained pressure overload has been mainly attributed to a challenged cardiac angiogenesis and cardiac hypertrophy up to now. Hif-1α+/+ and Hif-1α+/− mice were studied regarding left ventricular hypertrophy and cardiac function after being subjected to transverse aortic constriction (TAC). After TAC, both Hif-1α+/+ and Hif-1α+/− mice developed left ventricular hypertrophy with increased posterior wall thickness, septum thickness and increased left ventricular weight to a similar extent. No significant difference in cardiac vessel density was observed between Hif-1α+/+ and Hif-1α+/− mice. However, only the Hif-1α+/− mice developed severe heart failure as revealed by a significantly reduced fractional shortening mostly due to increased end-systolic left ventricular diameter. On the single cell level this correlated with reduced myocyte shortenings, decreased intracellular Ca2+-transients and SR-Ca2+ content in myocytes of Hif-1a+/− mice. Thus, HIF-1α can be critically involved in the preservation of cardiac function after chronic pressure overload without affecting cardiac hypertrophy. This effect is mediated via HIF-dependent modulation of cardiac calcium handling and contractility

Understanding of work: The basis for competence development

Developing competence in organisations has received increased attention among both practitioners and academics during the last two decades. This chapter aims to investigate what constitutes competence development at work, that is, what makes competence development possible. Different theories of competence are outlined as a precursor to exploring what enables competence development at work. Based on that review, it is argued that understanding of work forms the basis for competence development. This chapter investigates what understanding is and how it operates by drawing on the phenomenological hermeneutic theory of understanding. It suggests that understanding is constituted by an inevitable circularity, in the sense that developing an understanding of work presupposes that it is already understood. Finally, the implications that this circular nature of understanding has for the way we develop competence at work are discussed