Identification of an N-terminal glycogen synthase kinase 3 phosphorylation site which regulates the functional localisation of polycystin-2 in vivo and in vitro

PKD2 is mutated in 15% of patients with autosomal dominant polycystic kidney disease (ADPKD). Polycystin-2 (PC2), the PKD2 protein, is a nonselective Ca2 + -permeable cation channel which may function at the cell surface and ER. Nevertheless, the factors that regulate the dynamic translocation of PC2 between the ER and other compartments are not well understood. Constitutive phosphorylation of PC2 at a single C-terminal site (Ser812) has been previously reported. Since we were unable to abolish phospholabelling of PC2 in HEK293 cells by site-directed mutagenesis of Ser812 or all 5 predicted phosphorylation sites in the C-terminus, we hypothesised that PC2 could also be phosphorylated at the N-terminus. In this paper, we report the identification of a new phosphorylation site for PC2 within its N-terminal domain (Ser76) and demonstrate that this residue is phosphorylated by glycogen synthase kinase 3 (GSK-3). The consensus recognition sequence for GSK-3 (Ser76/Ser80) is evolutionarily conserved down to lower vertebrates. In the presence of specific GSK-3 inhibitors, the lateral plasma membrane pool of endogenous PC2 redistributes into an intracellular compartment in MDCK cells without a change in primary cilia localization. Finally, co-injection of wild-type but not a S76A/S80A mutant PKD2 capped mRNA could rescue the cystic phenotype induced by an antisense morpholino oligonucleotide to pkd2 in zebrafish pronephric kidney. We conclude that surface localization of PC2 is regulated by phosphorylation at a unique GSK-3 site in its N-terminal domain in vivo and in vitro. This site is functionally significant for the maintenance of normal glomerular and tubular morphology

A Visual Basic program to generate sediment grain-size statistics and to extrapolate particle distributions

This paper is not subject to U.S. copyright. The definitive version was published in Computers & Geosciences 30 (2004): 791-795, doi:10.1016/j.cageo.2004.05.005.Measures that describe and summarize sediment grain-size distributions are important to geologists because of the large amount of information contained in textural data sets. Statistical methods are usually employed to simplify the necessary comparisons among samples and quantify the observed differences. The two statistical methods most commonly used by sedimentologists to describe particle distributions are mathematical moments (Krumbein and Pettijohn, 1938) and inclusive graphics (Folk, 1974). The choice of which of these statistical measures to use is typically governed by the amount of data available (Royse, 1970). If the entire distribution is known, the method of moments may be used; if the next to last accumulated percent is greater than 95, inclusive graphics statistics can be generated. Unfortunately, earlier programs designed to describe sediment grain-size distributions statistically do not run in a Windows environment, do not allow extrapolation of the distribution's tails, or do not generate both moment and graphic statistics (Kane and Hubert, 1963; Collias et al., 1963; Schlee and Webster, 1967; Poppe et al., 2000). Owing to analytical limitations, electro-resistance multichannel particle-size analyzers, such as Coulter Counters, commonly truncate the tails of the fine-fraction part of grain-size distributions. These devices do not detect fine clay in the 0.6–0.1 μm range (part of the 11-phi and all of the 12-phi and 13-phi fractions). Although size analyses performed down to 0.6 μm microns are adequate for most freshwater and near shore marine sediments, samples from many deeper water marine environments (e.g. rise and abyssal plain) may contain significant material in the fine clay fraction, and these analyses benefit from extrapolation. The program (GSSTAT) described herein generates statistics to characterize sediment grain-size distributions and can extrapolate the fine-grained end of the particle distribution. It is written in Microsoft Visual Basic 6.0 and provides a window to facilitate program execution. The input for the sediment fractions is weight percentages in whole-phi notation (Krumbein, 1934; Inman, 1952), and the program permits the user to select output in either method of moments or inclusive graphics statistics (Fig. 1). Users select options primarily with mouse-click events, or through interactive dialogue boxes.Coastal and Marine Geology Program of the US Geological Survey for its financial support

Coulomb gap in one-dimensional disordered electronic systems

We study a one-dimensional system of spinless electrons in the presence of a long-range Coulomb interaction (LRCI) and a random chemical potential at each site. We first present a Tomonaga-Luttinger liquid (TLL) description of the system. We use the bosonization technique followed by the replica trick to average over the quenched randomness. An expression for the localization length of the system is then obtained using the renormalization group method and also a physical argument. We then find the density of states for different values of the energy; we get different expressions depending on whether the energy is larger than or smaller than the inverse of the localization length. We work in the limit of weak disorder where the localization length is very large; at that length scale, the LRCI has the effect of reducing the interaction parameter K of the TLL to a value much smaller than the noninteracting value of unity.Comment: Revtex, 6 pages, no figures; discussions have been expanded in several place

Quantum Interference between Impurities: Creating Novel Many-Body States in s-wave Superconductors

We demonstrate that quantum interference of electronic waves that are scattered by multiple magnetic impurities in an s-wave superconductor gives rise to novel bound states. We predict that by varying the inter-impurity distance or the relative angle between the impurity spins, the states' quantum numbers, as well as their distinct frequency and spatial dependencies, can be altered. Finally, we show that the superconductor can be driven through multiple local crossovers in which its spin polarization, $$, changes between $=0, 1/2$ and 1.Comment: 4 pages, 4 figure

Coulomb Gaps in One-Dimensional Spin-Polarized Electron Systems

We investigate the density of states (DOS) near the Fermi energy of one-dimensional spin-polarized electron systems in the quantum regime where the localization length is comparable to or larger than the inter-particle distance. The Wigner lattice gap of such a system, in the presence of weak disorder, can occur precisely at the Fermi energy, coinciding with the Coulomb gap in position. The interplay between the two is investigated by treating the long-range Coulomb interaction and the random disorder potential in a self-consistent Hartree-Fock approximation. The DOS near the Fermi energy is found to be well described by a power law whose exponent decreases with increasing disorder strength.Comment: 4 pages, revtex, 4 figures, to be published in Phys. Rev. B as a Rapid Communicatio

Variable-range hopping in quasi-one-dimensional electron crystals

We study the effect of impurities on the ground state and the low-temperature dc transport in a 1D chain and quasi-1D systems of many parallel chains. We assume that strong interactions impose a short-range periodicicity of the electron positions. The long-range order of such an electron crystal (or equivalently, a $4 k_F$ charge-density wave) is destroyed by impurities. The 3D array of chains behaves differently at large and at small impurity concentrations $N$. At large $N$, impurities divide the chains into metallic rods. The low-temperature conductivity is due to the variable-range hopping of electrons between the rods. It obeys the Efros-Shklovskii (ES) law and increases exponentially as $N$ decreases. When $N$ is small, the metallic-rod picture of the ground state survives only in the form of rare clusters of atypically short rods. They are the source of low-energy charge excitations. In the bulk the charge excitations are gapped and the electron crystal is pinned collectively. A strongly anisotropic screening of the Coulomb potential produces an unconventional linear in energy Coulomb gap and a new law of the variable-range hopping $-\ln\sigma \sim (T_1 / T)^{2/5}$. $T_1$ remains constant over a finite range of impurity concentrations. At smaller $N$ the 2/5-law is replaced by the Mott law, where the conductivity gets suppressed as $N$ goes down. Thus, the overall dependence of $\sigma$ on $N$ is nonmonotonic. In 1D, the granular-rod picture and the ES apply at all $N$. The conductivity decreases exponentially with $N$. Our theory provides a qualitative explanation for the transport in organic charge-density wave compounds.Comment: 20 pages, 7 figures. (v1) The abstract is abridged to 24 lines. For the full abstract, see the manuscript (v2) several changes in presentation per referee's comments. No change in result

Holes in the t-J_z model: a thorough study

The t-J_z model is the strongly anisotropic limit of the t-J model which captures some general properties of the doped antiferromagnets (AF). The absence of spin fluctuations simplifies the analytical treatment of hole motion in an AF background and allows us to calculate the single- and two-hole spectra with high accuracy using regular diagram technique combined with real-space approach. At the same time, numerical studies of this model via exact diagonalization (ED) on small clusters show negligible finite size effects for a number of quantities, thus allowing a direct comparison between analytical and numerical results. Both approaches demonstrate that the holes have tendency to pair in the p- and d-wave channels at realistic values of t/J. The interactions leading to pairing and effects selecting p and d waves are thoroughly investigated. The role of transverse spin fluctuations is considered using perturbation theory. Based on the results of the present study, we discuss the pairing problem in the realistic t-J-like model. Possible implications for preformed pairs formation and phase separation are drawn.Comment: 21 pages, 15 figure

Squark-, Slepton- and Neutralino-Chargino coannihilation effects in the low-energy effective MSSM

Within the low-energy effective Minimal Supersymmetric extension of the Standard Model (effMSSM) we calculate the neutralino relic density taking into account slepton-neutralino, squark-neutralino and neutralino/chargino- neutralino coannihilation channels. By including squark (stop and sbottom) coannihilation channels we extend our comparative study to all allowed coannihilations and obtain the general result that all of them give sizable contributions to the reduction of the neutralino relic density. Due to these coannihilation processes some models (mostly with large neutralino masses) enter into the cosmologically interesting region for relic density, but other models leave this region. Nevertheless, in general, the predictions for direct and indirect dark matter detection rates are not strongly affected by these coannihilation channels in the effMSSM.Comment: 14 pages, 10 figures, corrected and to be published in Phys. Rev.

Slepton and Neutralino/Chargino Coannihilations in MSSM

Within the low-energy effective Minimal Supersymmetric extension of Standard Model (effMSSM) we calculated the neutralino relic density taking into account slepton-neutralino and neutralino-chargino/neutralino coannihilation channels. We performed comparative study of these channels and obtained that both of them give sizable contributions to the reduction of the relic density. Due to these coannihilation processes some models (mostly with large neutralino masses) enter into the cosmologically interesting region for relic density, but other models leave this region. Nevertheless, in general, the predictions for direct and indirect dark matter detection rates are not strongly affected by these coannihilation channels in the effMSSM.Comment: 12 pages, 9 figures, revte

Higgs boson mass limits in perturbative unification theories

Motivated in part by recent demonstrations that electroweak unification into a simple group may occur at a low scale, we detail the requirements on the Higgs mass if the unification is to be perturbative. We do this for the Standard Model effective theory, minimal supersymmetry, and next-to-minimal supersymmetry with an additional singlet field. Within the Standard Model framework, we find that perturbative unification with sin2(thetaW)=1/4 occurs at Lambda=3.8 TeV and requires mh<460 GeV, whereas perturbative unification with sin2(thetaW)=3/8 requires mh<200 GeV. In supersymmetry, the presentation of the Higgs mass predictions can be significantly simplified, yet remain meaningful, by using a single supersymmetry breaking parameter Delta_S. We present Higgs mass limits in terms of Delta_S for the minimal supersymmetric model and the next-to-minimal supersymmetric model. We show that in next-to-minimal supersymmetry, the Higgs mass upper limit can be as large as 500 GeV even for moderate supersymmetry masses if the perturbative unification scale is low (e.g., Lambda=10 TeV).Comment: 20 pages, latex, 6 figures, references adde