Experimental and computational investigation of the polar ferrimagnet VOSe2O5

We have re-examined the crystal structure and the physical properties of VOSe2O5 by performing single crystal X-ray and powder neutron diffraction, alternating current (AC) and direct current (DC) magnetization measurements, heat capacity, dielectric properties, and second-harmonic generation (SHG) measurements. From these studies, we observed that the compound undergoes three magnetic transitions near 4, 5.5, and 8 K. In addition, we observed ferrimagnetic behavior as the magnetic ground state, confirmed by the isothermal magnetization measured below 8 K that reveals a saturated magnetic moment of 0.5 μB per formula unit, consistent with density functional calculations of the magnetically ordered ground state. We propose a ferrimagnetic spin arrangement that is consistent with neutron diffraction measurements as well. Frequency dependence in the AC magnetic susceptibility, observed at 5.5 K, is considered as short-range magnetic ordering and may be associated with the competition between nearest neighbor and next nearest neighbor interactions of the V4+ cations. A dielectric anomaly near 240 K and non-centrosymmetric functional properties, notably, second harmonic generation and electric polarization, are also discussed. © 2010 American Chemical Society

The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C(-) monocytes

The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C− monocytes. Ly6C− monocytes, which function in a surveillance role in circulation, were absent from Nr4a1−/− mice. Normal numbers of myeloid progenitor cells were present in Nr4a1−/− mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from Nr4a1−/− mice developed fewer patrolling monocytes than did recipients of wild-type bone marrow. The Ly6C− monocytes remaining in the bone marrow of Nr4a1−/− mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C− monocytes

Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis

Mesenchymal responses are an essential aspect of tissue repair. Failure to terminate this repair process correctly, however, results in fibrosis and organ dysfunction. Therapies that block fibrosis and restore tissue homeostasis are not yet available for clinical use. Here we characterize the nuclear receptor NR4A1 as an endogenous inhibitor of transforming growth factor-β (TGF-β) signaling and as a potential target for anti-fibrotic therapies. NR4A1 recruits a repressor complex comprising SP1, SIN3A, CoREST, LSD1, and HDAC1 to TGF-β target genes, thereby limiting pro-fibrotic TGF-β effects. Even though temporary upregulation of TGF-β in physiologic wound healing induces NR4A1 expression and thereby creates a negative feedback loop, the persistent activation of TGF-β signaling in fibrotic diseases uses AKT- and HDAC-dependent mechanisms to inhibit NR4A1 expression and activation. Small-molecule NR4A1 agonists can overcome this lack of active NR4A1 and inhibit experimentally-induced skin, lung, liver, and kidney fibrosis in mice. Our data demonstrate a regulatory role of NR4A1 in TGF-β signaling and fibrosis, providing the first proof of concept for targeting NR4A1 in fibrotic diseases