Modulation of the slow/common gating of CLC channels by intracellular cadmium.

Members of the CLC family of Cl(-) channels and transporters are homodimeric integral membrane proteins. Two gating mechanisms control the opening and closing of Cl(-) channels in this family: fast gating, which regulates opening and closing of the individual pores in each subunit, and slow (or common) gating, which simultaneously controls gating of both subunits. Here, we found that intracellularly applied Cd(2+) reduces the current of CLC-0 because of its inhibition on the slow gating. We identified CLC-0 residues C229 and H231, located at the intracellular end of the transmembrane domain near the dimer interface, as the Cd(2+)-coordinating residues. The inhibition of the current of CLC-0 by Cd(2+) was greatly enhanced by mutation of I225W and V490W at the dimer interface. Biochemical experiments revealed that formation of a disulfide bond within this Cd(2+)-binding site is also affected by mutation of I225W and V490W, indicating that these two mutations alter the structure of the Cd(2+)-binding site. Kinetic studies showed that Cd(2+) inhibition appears to be state dependent, suggesting that structural rearrangements may occur in the CLC dimer interface during Cd(2+) modulation. Mutations of I290 and I556 of CLC-1, which correspond to I225 and V490 of CLC-0, respectively, have been shown previously to cause malfunction of CLC-1 Cl(-) channel by altering the common gating. Our experimental results suggest that mutations of the corresponding residues in CLC-0 change the subunit interaction and alter the slow gating of CLC-0. The effect of these mutations on modulations of slow gating of CLC channels by intracellular Cd(2+) likely depends on their alteration of subunit interactions

Improved HAC Covariance Matrix Estimation Based on Forecast Errors

We propose computing HAC covariance matrix estimators based on one-stepahead forecasting errors. It is shown that this estimator is consistent and has smaller bias than other HAC estimators. Moreover, the tests that rely on this estimator have more accurate sizes without sacrificing its power.forecast error, HAC estimator, kernel estimator, recursive residual, robust test

Role of Laminins in the Development of the Peripheral Nervous System

To investigate the function of laminins in peripheral nerve development, the laminin γ1 gene was specifically disrupted in Schwann cells. Disruption of laminin γ1 gene expression resulted in depletion of all other laminin chains known to be expressed in Schwann cells. Schwann cells lacking laminins fail to differentiate to myelinating and non-myelinating Schwann cells and do not extend processes required for initiating axonal sorting and mediating axon-Schwann cell interactions. These cells also fail to down-regulate Oct-6 and they arrest at the premyelinating stage. Impaired axon-Schwann cell interactions prevent phosphorylation of β-neuregulin-1 receptors, which results in decreased cell proliferation. Postnatally, laminin-null Schwann cells exhibit reduced phosphatidylinositol 3-kinase activity and activation of caspase cascades, leading to apoptosis. Injection of a laminin peptide into mutant sciatic nerves partially restores PI 3-kinase activity and reduces apoptotic signals. In a Schwann cell/dorsal root ganglion co-culture system, disruption of laminins impairs podia formation as well as the elongation of Schwann cells. These results demonstrate that: 1) laminins initiate axonal sorting and mediate axon-Schwann cell interactions required for Schwann cell proliferation and differentiation; 2) laminins provide a PI 3-kinase/Akt-mediated Schwann cell survival signal

Lepton flavor violating processes in unparticle physics

We study the virtual effects of unparticle physics in the lepton flavor violating processes $M^0\to l^+l'^-$ and $e^+e^-\to l^+l'^-$ scattering, where $M^0$ denotes the pseudoscalar mesons: $\pi^0,K_L, D_0,B_0,B_s^0$ and $l,l'$ denote two different lepton flavors. For the decay of $B^0\to l^+l'^-$, there is no constraint from the current experimental upper bounds on the vector unparticle coupling with leptons. The constraint on the coupling constant between scalar unparticle field and leptons is sensitive to the scaling dimension of the unparticle $d_{\cal U}$. For the scattering process $e^-e^+\to l^-l'^+$, there is only constraint from experiments on the vector unparticle couplings with leptons but no constraint on the scalar unparticle. We study the $\sqrt s$ dependence of the cross section $\frac{1}{\sigma} \frac{d\sigma}{d\sqrt s}$ of $e^+e^-\to l^-l'^+$ with different values of $d_{\cal U}$. If $d_{\cal U}=1.5$, the cross section is independent on the center mass energy. For $d_{\cal U}>1.5$, the cross section increases with $\sqrt s$.Comment: 8 pages, revtex4,with 2 figures, to appear in Phys. Rev.

Exact coefficients for higher dimensional operators with sixteen supersymmetries

We consider constraints on higher dimensional operators for supersymmetric effective field theories. In four dimensions with maximal supersymmetry and SU(4) R-symmetry, we demonstrate that the coefficients of abelian operators F^n with MHV helicity configurations must satisfy a recursion relation, and are completely determined by that of F^4. As the F^4 coefficient is known to be one-loop exact, this allows us to derive exact coefficients for all such operators. We also argue that the results are consistent with the SL(2,Z) duality symmetry. Breaking SU(4) to Sp(4), in anticipation for the Coulomb branch effective action, we again find an infinite class of operators whose coefficient that are determined exactly. We also consider three-dimensional N=8 as well as six-dimensional N=(2,0),(1,0) and (1,1) theories. In all cases, we demonstrate that the coefficient of dimension-six operator must be proportional to the square of that of dimension-four.Comment: typos corrected, minor modificatio