Reversible Control of Magnetic Interactions by Electric Field in a Single Phase Material

Intrinsic magnetoelectric coupling describes the interaction between magnetic and electric polarization through an inherent microscopic mechanism in a single phase material. This phenomenon has the potential to control the magnetic state of a material with an electric field, an enticing prospect for device engineering. We demonstrate 'giant' magnetoelectric cross-field control in a single phase rare earth titanate film. In bulk form, EuTiO3 is antiferromagnetic. However, both anti and ferromagnetic interactions coexist between different nearest neighbor europium ions. In thin epitaxial films, strain can be used to alter the relative strength of the magnetic exchange constants. Here, we not only show that moderate biaxial compression precipitates local magnetic competition, but also demonstrate that the application of an electric field at this strain state, switches the magnetic ground state. Using first principles density functional theory, we resolve the underlying microscopic mechanism resulting in the EuTiO3 G-type magnetic structure and illustrate how it is responsible for the 'giant' cross-field magnetoelectric effect

Mdm2 is involved in the ubiquitination and degradation of G-protein-coupled receptor kinase 2

G-protein-coupled receptor kinase 2 (GRK2) is a central regulator of G-protein-coupled receptor signaling. We report that Mdm2, an E3-ubiquitin ligase involved in the control of cell growth and apoptosis, plays a key role in GRK2 degradation. Mdm2 and GRK2 association is enhanced by β(2)-adrenergic receptor stimulation and β-arrestin. Increased Mdm2 expression accelerates GRK2 proteolysis and promotes kinase ubiquitination at defined residues, whereas GRK2 turnover is markedly impaired in Mdm2-deficient cells. Moreover, we find that activation of the PI3K/Akt pathway by insulin-like growth factor-1 alters Mdm2-mediated GRK2 degradation, leading to enhanced GRK2 stability and increased kinase levels. These data put forward a novel mechanism for controlling GRK2 expression in physiological and pathological conditions

β-Arrestin-1 links mitogenic sonic hedgehog signaling to the cell cycle exit machinery in neural precursors

Development of the cerebellum, a brain region regulating posture and coordination, occurs post-natally and is marked by rapid proliferation of granule neuron precursors (CGNPs), stimulated by mitogenic Sonic hedgehog (Shh) signaling. β-Arrestin (βArr) proteins play important roles downstream of Smoothened, the Shh signal transducer. However, whether Shh regulates βArrs and what role it plays in Shh-driven CGNP proliferation remains to be determined. Here, we report that Shh induces βArr1 accumulation and localization to the nucleus, where it participates in enhancing expression of the cyclin dependent kinase (cdk) inhibitor p27, whose accumulation eventually drives CGNP cell cycle exit. βArr1 knockdown enhances CGNP proliferation and reduces p27 expression. Thus, Shh-mediated βArr1 induction represents a novel negative feedback loop within the Shh mitogenic pathway, such that ongoing Shh signaling, while required for CGNPs to proliferate, also sets up a cell-intrinsic clock programming their ultimate exit from the cell cycle