The C. Elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway

Inhibitors of Wnt signaling promote normal development and prevent cancer by restraining when and where the Wnt pathway is activated. ROR proteins, a class of Wnt-binding receptor tyrosine kinases, inhibit Wnt signaling by an unknown mechanism. To clarify how RORs inhibit the Wnt pathway, we examined the relationship between Wnts and the sole C. elegans ROR homolog, cam-1, during C. elegans vulval development, a Wnt-regulated process. We found that loss and overexpression of cam-1 causes reciprocal defects in Wnt-mediated cell-fate specification. Our molecular and genetic analyses revealed that the CAM-1 extracellular domain (ECD) is sufficient to non-autonomously antagonize multiple Wnts, suggesting that the CAM-1/ROR ECD sequesters Wnts. A sequestration model is supported by our findings that the CAM-1 ECD binds to several Wnts in vitro. These results demonstrate how ROR proteins help to refine the spatial pattern of Wnt activity in a complex multicellular environment

Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes.

c-Jun N-terminal kinase (JNK) contributes to metalloproteinase (MMP) gene expression and joint destruction in inflammatory arthritis. It is phosphorylated by at least two upstream kinases, the mitogen-activated protein kinase kinases (MEK) MKK4 and MKK7, which are, in turn, phosphorylated by MEK kinases (MEKKs). However, the MEKKs that are most relevant to JNK activation in synoviocytes have not been determined. These studies were designed to assess the hierarchy of upstream MEKKs, MEKK1, MEKK2, MEKK3, and transforming growth factor-beta activated kinase (TAK)1, in rheumatoid arthritis (RA). Using either small interfering RNA (siRNA) knockdown or knockout fibroblast-like synoviocytes (FLSs), MEKK1, MEKK2, or MEKK3 deficiency (either alone or in combination) had no effect on IL-1beta-stimulated phospho-JNK (P-JNK) induction or MMP expression. However, TAK1 deficiency significantly decreased P-JNK, P-MKK4 and P-MKK7 induction compared with scrambled control. TAK1 knockdown did not affect p38 activation. Kinase assays showed that TAK1 siRNA significantly suppressed JNK kinase function. In addition, MKK4 and MKK7 kinase activity were significantly decreased in TAK1 deficient FLSs. Electrophoretic mobility shift assays demonstrated a significant decrease in IL-1beta induced AP-1 activation due to TAK1 knockdown. Quantitative PCR showed that TAK1 deficiency significantly decreased IL-1beta-induced MMP3 gene expression and IL-6 protein expression. These results show that TAK1 is a critical pathway for IL-1beta-induced activation of JNK and JNK-regulated gene expression in FLSs. In contrast to other cell lineages, MEKK1, MEKK2, and MEKK3 did not contribute to JNK phosphorylation in FLSs. The data identify TAK1 as a pivotal upstream kinase and potential therapeutic target to modulate synoviocyte activation in RA

Correlation Inequalities for Quantum Spin Systems with Quenched Centered Disorder

It is shown that random quantum spin systems with centered disorder satisfy correlation inequalities previously proved (arXiv:cond-mat/0612371) in the classical case. Consequences include monotone approach of pressure and ground state energy to the thermodynamic limit. Signs and bounds on the surface pressures for different boundary conditions are also derived for finite range potentials.Comment: 4 page

Hall Voltage with the Spin Hall Effect

The spin Hall effect does not generally result in a charge Hall voltage. We predict that in systems with inhomogeneous electron density in the direction perpendicular to main current flow, the spin Hall effect is instead accompanied by a Hall voltage. Unlike the ordinary Hall effect, we find that this Hall voltage is quadratic in the longitudinal electric field for a wide range of parameters accessible experimentally. We also predict spin accumulation in the bulk and sharp peaks of spin-Hall induced charge accumulation near the edges. Our results can be readily tested experimentally, and would allow the electrical measurement of the spin Hall effect in non-magnetic systems and without injection of spin-polarized electrons

Suzaku X-Ray Observations of the Accreting NGC 4839 Group of Galaxies and the Radio Relic in the Coma Cluster

Based on Suzaku X-ray observations, we study the hot gas around the NGC4839 group of galaxies and the radio relic in the outskirts of the Coma cluster. We find a gradual decline in the gas temperature from 5 keV around NGC4839 to 3.6 keV at the radio relic, across which there is a further, steeper drop down to 1.5 keV. This drop as well as the observed surface brightness profile are consistent with a shock with Mach number M = 2.2 pm 0.5 and velocity vs = (1410 pm 110) km s^-1. A lower limit of B > 0.33 mu G is derived on the magnetic field strength around the relic from upper limits to inverse Compton X-ray emission. Although this suggests that the non-thermal electrons responsible for the relic are generated by diffusive shock acceleration (DSA), the relation between the measured Mach number and the electron spectrum inferred from radio observations are inconsistent with that expected from the simplest, test-particle theory of DSA. Nevertheless, DSA is still viable if it is initiated by the injection of a pre-existing population of non-thermal electrons. Combined with previous measurements, the temperature profile of Coma in the southwest direction is shallower outside NGC4839 and also slightly shallower in the outermost region. The metal abundance around NGC4839 is confirmed to be higher than in its vicinity, implying a significant peak in the abundance profile that decreases to 0.2 solar toward the outskirts. We interpret these facts as due to ram pressure stripping of metal-enriched gas from NGC4839 as it falls into Coma. The relic shock may result from the combined interaction of pre-existing intracluster gas, gas associated with NGC 4839, and cooler gas flowing in from the large-scale structure filament in the southwest.Comment: 13 page, accepted for publication in Publications of the Astronomical Society of Japa

Detecting the Cold Spot as a Void with the Non-Diagonal Two-Point Function

The anomaly in the Cosmic Microwave Background known as the "Cold Spot" could be due to the existence of an anomalously large spherical (few hundreds Mpc/h radius) underdense region, called a "Void" for short. Such a structure would have an impact on the CMB also at high multipoles l through Lensing. This would then represent a unique signature of a Void. Modeling such an underdensity with an LTB metric, we show that the Lensing effect leads to a large signal in the non-diagonal two-point function, centered in the direction of the Cold Spot, such that the Planck satellite will be able to confirm or rule out the Void explanation for the Cold Spot, for any Void radius with a Signal-to-Noise ratio of at least O(10).Comment: v1: 6 pages, 2 figures; v2: 6 pages, 2 figures, text improved, to appear on JCA

Possible Magnetic Chirality in Optically Chiral Magnet [Cr(CN)6_6][Mn(SS)-pnH(H2_2O)](H2_2O) Probed by Muon Spin Rotation and Relaxation

Local magnetic fields in a molecule-based optically chiral magnet [Cr(CN)$_6$][Mn($S$)-pnH(H$_2$O)](H$_2$O) (GN-S) and its enantiomer (GN-R) are studied by means of muon spin rotation and relaxation (muSR). Detailed analysis of muon precession signals under zero field observed below T_c supports the average magnetic structure suggested by neutron powder diffraction. Moreover, comparison of muSR spectra between GN-S and GN-R suggests that they are a pair of complete optical isomers in terms of both crystallographic and magnetic structure. Possibility of magnetic chirality in such a pair is discussed.Comment: 5 pages, 5 figures, submitted to J. Phys. Soc. Jp

Fermi Surface of 3d^1 Perovskite CaVO3 Near the Mott Transition

We present a detailed de Haas van Alphen effect study of the perovskite CaVO3, offering an unprecedented test of electronic structure calculations in a 3d transition metal oxide. Our experimental and calculated Fermi surfaces are in good agreement -- but only if we ignore large orthorhombic distortions of the cubic perovskite structure. Subtle discrepancies may shed light on an apparent conflict between the low energy properties of CaVO3, which are those of a simple metal, and high energy probes which reveal strong correlations that place CaVO3 on the verge of a metal-insulator transition.Comment: 4 pages, 4 figures (REVTeX

Genomic and epigenomic mapping of leptin-responsive neuronal populations involved in body weight regulation.

Genome wide association studies (GWAS) in obesity have identified a large number of noncoding loci located near genes expressed in the central nervous system. However, due to the difficulties in isolating and characterizing specific neuronal subpopulations, few obesity-associated SNPs have been functionally characterized. Leptin responsive neurons in the hypothalamus are essential in controlling energy homeostasis and body weight. Here, we combine FACS-sorting of leptin-responsive hypothalamic neuron nuclei with genomic and epigenomic approaches (RNA-seq, ChIP-seq, ATAC-seq) to generate a comprehensive map of leptin-response specific regulatory elements, several of which overlap obesity-associated GWAS variants. We demonstrate the usefulness of our leptin-response neuron regulome, by functionally characterizing a novel enhancer near Socs3, a leptin response-associated transcription factor. We envision our data to serve as a useful resource and a blueprint for functionally characterizing obesity-associated SNPs in the hypothalamus