The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach

The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed.</jats:p

Gravitational GUT Breaking and the GUT-Planck Hierarchy

It is shown that non-renormalizable gravitational interactions in the Higgs sector of supersymmetric grand unified theories (GUT's) can produce the breaking of the unifying gauge group $G$ at the GUT scale $M_{\rm GUT} \sim 10^{16}$~GeV. Such a breaking offers an attractive alternative to the traditional method where the superheavy GUT scale mass parameters are added ad hoc into the theory. The mechanism also offers a natural explanation for the closeness of the GUT breaking scale to the Planck scale. A study of the minimal SU(5) model endowed with this mechanism is presented and shown to be phenomenologically viable. A second model is examined where the Higgs doublets are kept naturally light as Goldstone modes. This latter model also achieves breaking of $G$ at $M_{\rm GUT}$ but cannot easily satisfy the current experimental proton decay bound.Comment: 11 pages, REVTeX, 1 figure included as an uuencoded Z-compressed PostScript file. Our Web page at http://physics.tamu.edu/~urano/research/gutplanck.html contains ready to print PostScript version (with figures) as well as color version of plot

A Chain Oriented Data Collection Protocol for Energy-Aware and Delay-Constrained WSN

Energy awareness plays an important role in developing routing protocol for the battery powered wireless sensor networks. As the replacement of the battery is often unfeasible in practical situations, we present here an optimal solution for the maximum utilization of precious available energy at the same time trying to minimize the latency in data delivery. We propose to form hierarchical chains with deployed sensors to collect information from a target field where data get fused at every node level before transmitted finally. Our protocol utilizes the higher energy nodes for more frequent long distance transmissions so that the energy expenditure become even between all nodes in the network irrespective of their physical locations. It has been found in our simulation that this protocol outperforms other hierarchical protocols like LEACH and PEGASIS in both the cases of energy consumption and time requirements respectively. It has been also found that the overall lifetime of the sensor network also increases in our protocol

Estrogens promote misfolded proinsulin degradation to protect insulin production and delay diabetes

Summary: Conjugated estrogens (CE) delay the onset of type 2 diabetes (T2D) in postmenopausal women, but the mechanism is unclear. In T2D, the endoplasmic reticulum (ER) fails to promote proinsulin folding and, in failing to do so, promotes ER stress and β cell dysfunction. We show that CE prevent insulin-deficient diabetes in male and in female Akita mice using a model of misfolded proinsulin. CE stabilize the ER-associated protein degradation (ERAD) system and promote misfolded proinsulin proteasomal degradation. This involves activation of nuclear and membrane estrogen receptor-α (ERα), promoting transcriptional repression and proteasomal degradation of the ubiquitin-conjugating enzyme and ERAD degrader, UBC6e. The selective ERα modulator bazedoxifene mimics CE protection of β cells in females but not in males. : Estrogens prevent diabetes in women, but the mechanism is poorly understood. Xu et al. report that estrogens activate the endoplasmic-reticulum-associated protein degradation pathway, which promotes misfolded proinsulin degradation, suppresses endoplasmic reticulum stress, and protects insulin secretion in mice and in human pancreatic β cells. Keywords: estrogens, beta cell, islet, endoplasmic reticulum stress, proinsulin misfolding, diabetes, bazedoxifene, sex dimorphism, ERAD, SER

Magnetic and superconducting properties of Cd2Re2O7: Cd NMR and Re NQR

We report Cd NMR and Re NQR studies on Cd2Re2O7, the first superconductor among pyrochlore oxides Tc=1 K. Re NQR spectrum at zero magnetic field below 100 K rules out any magnetic or charge order. The spin-lattice relaxation rate below Tc exhibits a pronounced coherence peak and behaves within the weak-coupling BCS theory with nearly isotropic energy gap. Cd NMR results point to moderate ferromagnetic enhancement at high temperatures followed by rapid decrease of the density of states below the structural transition temperature of 200 K.Comment: 4 pages, 4 figure

Low Temperature Symmetry of Pyrochlore Oxide Cd2Re2O7

We report the X-ray study for the pyrochlore oxide Cd2Re2O7. Two symmetry-lowering structural transitions were observed at Ts1=200K and Ts2=120K. The former is of the second order from the ideal cubic pyrochlore structure with space group Fd-3m to a tetragonally distorted structure with I-4m2, while the latter is of the first order likely to another tetragonal space group I4122. We discuss the feature of the lattice deformation.Comment: 4 pages, 4 figure

Quasi-One-Dimensional Spin Dynamics in dd-Electron Heavy-Fermion Metal Y1−x_{1-x}Scx_xMn2_2

Slow spin fluctuations ($\nu < 10^{12}$ s$^-1$) observed by the muon spin relaxation technique in Y$_{1-x}$Sc$_x$Mn$_2$ exhibits a power law dependence on temperature ($\nu \propto T^\alpha$), where the power converges asymptotically to unity ($\alpha\rightarrow 1$) as the system moves away from spin-glass instability with increasing Sc content $x$. This linear $T$ dependence, which is common to that observed in LiV$_2$O$_4$, is in line with the prediction of the "intersecting Hubbard chains" model for a metallic pyrochlore lattice, suggesting that the geometrical constraints to t2g bands specific to the pyrochlore structure serve as a basis of the $d$-electron heavy-fermion state.Comment: 5 pages, 4 figures, to appear in J. Phys. Soc. Jp

Non-generality of the Kadowaki-Woods ratio in correlated oxides

An explicit expression for the Kadowaki-Woods ratio in correlated metals is derived by invoking saturation of the (high-frequency) Fermi-liquid scattering rate at the Mott-Ioffe-Regel limit. Significant deviations observed in a number of oxides are quantitatively explained due to variations in carrier density, dimensionality, unit cell volume and the number of individual sheets in the Brillouin zone. A generic re-scaling of the original Kadowaki-Woods plot is also presented.Comment: 9 pages of text, 1 table, 2 figure