Adenylate Kinase and AMP Signaling Networks: Metabolic Monitoring, Signal Communication and Body Energy Sensing

Adenylate kinase and downstream AMP signaling is an integrated metabolic monitoring system which reads the cellular energy state in order to tune and report signals to metabolic sensors. A network of adenylate kinase isoforms (AK1-AK7) are distributed throughout intracellular compartments, interstitial space and body fluids to regulate energetic and metabolic signaling circuits, securing efficient cell energy economy, signal communication and stress response. The dynamics of adenylate kinase-catalyzed phosphotransfer regulates multiple intracellular and extracellular energy-dependent and nucleotide signaling processes, including excitation-contraction coupling, hormone secretion, cell and ciliary motility, nuclear transport, energetics of cell cycle, DNA synthesis and repair, and developmental programming. Metabolomic analyses indicate that cellular, interstitial and blood AMP levels are potential metabolic signals associated with vital functions including body energy sensing, sleep, hibernation and food intake. Either low or excess AMP signaling has been linked to human disease such as diabetes, obesity and hypertrophic cardiomyopathy. Recent studies indicate that derangements in adenylate kinase-mediated energetic signaling due to mutations in AK1, AK2 or AK7 isoforms are associated with hemolytic anemia, reticular dysgenesis and ciliary dyskinesia. Moreover, hormonal, food and antidiabetic drug actions are frequently coupled to alterations of cellular AMP levels and associated signaling. Thus, by monitoring energy state and generating and distributing AMP metabolic signals adenylate kinase represents a unique hub within the cellular homeostatic network

Toward a Unified Framework of Perceived Negative Leader Behaviors Insights from French and British Educational Sectors

In this paper, we challenge the commonly held assumption that actors in the education sector are largely ethical, and that there is therefore little need to scrutinize leader behaviors in this sector. We also overcome past scholars’ tendencies to either focus selectively on positive leader behaviors, or to stay content with categorizing leader behaviors into effective and ineffective (if at all they do focus on negative leader behaviors). Using data (Critical Incidents) from three case studies previously conducted in eight British and French academic establishments, we show that not only do negative leader behaviors abound in the education sector, but they can also be differentiated into three types: (1) behaviors emanating from leaders’ lack of functional skills i.e., ineffective behaviors, (2) behaviors emanating from leaders’ insouciance toward harming the organization and its members i.e., dysfunctional behaviors, and (3) behaviors emanating from leaders’ lack of honesty, integrity, ethicality, and transparency i.e., unauthentic behaviors. We enrich current understanding on ineffective, dysfunctional, and unauthentic leader behaviors, and offer a unified (yet differentiated) framework of negative leader behaviors in the academic sector. Since each type of negative behavior emanates from different motivational drivers, different measures are required to curb them. These are also discussed. A comparison of our findings with those from leadership studies in other sectors reveals that negative leader behaviors in the education sector are quite similar to those in other sectors

Oncostatin M regulates neural precursor activity in the adult brain

The regulation of neural precursor cell (NPC) activity is the major determinant of the rate of neuronal production in neurogenic regions of the adult brain. Here, we show that Oncostatin M(Osm) and its receptor, OsmR beta, are both expressed in the subventricular zone (SVZ) and that in contradistinction to leukemia inhibitory factor and ciliary neutrophic factor, Osm directly inhibits the proliferation of adult NPCs as measured by a decreased level of neurosphere formation in vitro. Similarly, intraventricular infusion of Osm dramatically decreases the pool of NPCs in both the SVZ and the hippocampus. In keeping with the inhibitory action of Osm, we reveal that mice lacking OsmR beta have substantially more NPCs in the SVZ, the hippocampus and the olfactory bulb, demonstrating that endogenous Osm signaling is important for NPC homeostasis. Finally, we show that Osm can also inhibit clonal growth of glioblastoma-derived neurospheres, further supporting the close link between NPCs and tumor stem cells. (c) 2011 Wiley Periodicals, Inc. Develop Neurobiol 71: 619-633, 201