85 research outputs found
RVB Contribution to Superconductivity in
We view as electronically equivalent to (non-staggered) graphite
( layer) that has undergone a zero gap semiconductor to a superconductor
phase transition by a large c-axis (chemical) pressure due to layers.
Further, like the \ppi bonded planar organic molecules, graphite is an old
resonating valence bond (RVB) system. The RVB's are the `preexisting cooper
pairs' in the `parental' zero gap semiconducting (graphite) sheets that
manifests themselves as a superconducting ground state of the transformed
metal. Some consequences are pointed out.Comment: 4 pages, 2 figure, RevTex. Based on a talk given at the Institute
Seminar Week, IMSc, Madras (12-16, Feb. 2001
Muon-spin-relaxation study of the magnetic penetration depth in MgB2
The magnetic vortex lattice (VL) of polycrystalline MgB2 has been
investigated by transverse-field muon-spin-relaxation (TF-MuSR). The evolution
of TF-MuSR depolarization rate, sigma, that is proportional to the second
moment of the field distribution of the VL has been studied as a function of
temperature and applied magnetic field. The low temperature value s exhibits a
pronounced peak near Hext = 75 mT. This behavior is characteristic of strong
pinning induced distortions of the VL which put into question the
interpretation of the low-field TF-MuSR data in terms of the magnetic
penetration depth lambda(T). An approximately constant value of sigma, such as
expected for an ideal VL in the London-limit, is observed at higher fields of
Hext > 0.4 T. The TF-MuSR data at Hext = 0.6 T are analyzed in terms of a
two-gap model. We obtain values for the gap size of D1 = 6.0 meV (2D1/kBTc =
3.6), D2 = 2.6 meV (2D2/kBTc = 1.6), a comparable spectral weight of the two
bands and a zero temperature value for the magnetic penetration depth of lambda
= 100 nm. In addition, we performed MuSR-measurements in zero external field
(ZF-MuSR). We obtain evidence that the muon site (at low temperature) is
located on a ring surrounding the center of the boron hexagon. Muon diffusion
sets in already at rather low temperature of T > 10 K. The nuclear magnetic
moments can account for the observed relaxation rate and no evidence for
electronic magnetic moments has been obtained.Comment: 15 pages, 4 figure
Thermal conductivity of MgB in the superconducting state
We present thermal conductivity measurements on very pure and dense bulk
samples, as indicated by residual resistivity values as low as 0.5 mW cm and
thermal conductivity values higher than 200 W/mK. In the normal state we found
that the Wiedemann Franz law, in its generalized form, works well suggesting
that phonons do not contribute to the heat transport. The thermal conductivity
in the superconducting state has been analysed by using a two-gap model. Thank
to the large gap anisotropy we were able to evaluate quantitatively intraband
scattering relaxation times of and bands, which depend on the
disorder in different way; namely, as the disorder increases, it reduces more
effectively the relaxation times of than of bands, as
suggested by a recent calculation [1].Comment: 12 pages, 5 figure
Specific heat of classical disordered elastic systems
We study the thermodynamics of disordered elastic systems, applied to vortex
lattices in the Bragg glass phase. Using the replica variational method we
compute the specific heat of pinned vortons in the classical limit. We find
that the contribution of disorder is positive, linear at low temperature, and
exhibits a maximum. It is found to be important compared to other
contributions, e.g. core electrons, mean field and non linear elasticity that
we evaluate. The contribution of droplets is subdominant at weak disorder in
.Comment: 4 pages, RevTe
Caenorhabditis elegans N-glycan Core β-galactoside Confers Sensitivity towards Nematotoxic Fungal Galectin CGL2
The physiological role of fungal galectins has remained elusive. Here, we show that feeding of a mushroom galectin, Coprinopsis cinerea CGL2, to Caenorhabditis elegans inhibited development and reproduction and ultimately resulted in killing of this nematode. The lack of toxicity of a carbohydrate-binding defective CGL2 variant and the resistance of a C. elegans mutant defective in GDP-fucose biosynthesis suggested that CGL2-mediated nematotoxicity depends on the interaction between the galectin and a fucose-containing glycoconjugate. A screen for CGL2-resistant worm mutants identified this glycoconjugate as a Galβ1,4Fucα1,6 modification of C. elegans N-glycan cores. Analysis of N-glycan structures in wild type and CGL2-resistant nematodes confirmed this finding and allowed the identification of a novel putative glycosyltransferase required for the biosynthesis of this glycoepitope. The X-ray crystal structure of a complex between CGL2 and the Galβ1,4Fucα1,6GlcNAc trisaccharide at 1.5 Å resolution revealed the biophysical basis for this interaction. Our results suggest that fungal galectins play a role in the defense of fungi against predators by binding to specific glycoconjugates of these organisms
The Carbohydrate-Binding Site in Galectin-3 Is Preorganized To Recognize a Sugarlike Framework of Oxygens: Ultra-High-Resolution Structures and Water Dynamics
The recognition of carbohydrates by proteins is a fundamental aspect of communication within and between living cells. Understanding the molecular basis of carbohydrate-protein interactions is a prerequisite for the rational design of synthetic ligands. Here we report the high- to ultrahigh-resolution crystal structures of the carbohydrate recognition domain of galectin-3 (Gal3C) in the ligand-free state (1.08 angstrom at 100 K, 1.25 angstrom at 298 K) and in complex with lactose (0.86 angstrom) or glycerol (0.9 angstrom). These structures reveal striking similarities in the positions of water and carbohydrate oxygen atoms in all three states, indicating that the binding site of Gal3C is preorganized to coordinate oxygen atoms in an arrangement that is nearly optimal for the recognition of beta-galactosides. Deuterium nuclear magnetic resonance (NMR) relaxation dispersion experiments and molecular dynamics simulations demonstrate that all water molecules in the lactose-binding site exchange with bulk water on a time scale of nanoseconds or shorter. Nevertheless, molecular dynamics simulations identify transient water binding at sites that agree well with those observed by crystallography, indicating that the energy landscape of the binding site is maintained in solution. All heavy atoms of glycerol are positioned like the corresponding atoms of lactose in the Gal3C complexes. However, binding of glycerol to Gal3C is insignificant in solution at room temperature, as monitored by NMR spectroscopy or isothermal titration calorimetry under conditions where lactose binding is readily detected. These observations make a case for protein cryo-crystallography as a valuable screening method in fragment-based drug discovery and further suggest that identification of water sites might inform inhibitor design
Association of ultra-rare coding variants with genetic generalized epilepsy: A case\u2013control whole exome sequencing study
Objective: We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with individuals with a positive family history. Secondarily, we set out to compare the association of genes independently with familial and sporadic GGE. Methods: We performed a case\u2013control whole exome sequencing study in unrelated individuals of European descent diagnosed with GGE (previously recruited and sequenced through multiple international collaborations) and ancestry-matched controls. The association of ultra-rare variants (URVs; in 18 834 protein-coding genes) with epilepsy was examined in 1928 individuals with GGE (vs. 8578 controls), then separately in 945 individuals with familial GGE (vs. 8626 controls), and finally in 1005 individuals with sporadic GGE (vs. 8621 controls). We additionally examined the association of URVs with familial and sporadic GGE in two gene sets important for inhibitory signaling (19 genes encoding \u3b3-aminobutyric acid type A [GABAA] receptors, 113 genes representing the GABAergic pathway). Results: GABRG2 was associated with GGE (p = 1.8
7 10 125), approaching study-wide significance in familial GGE (p = 3.0
7 10 126), whereas no gene approached a significant association with sporadic GGE. Deleterious URVs in the most intolerant subgenic regions in genes encoding GABAA receptors were associated with familial GGE (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 1.9\u20137.8, false discovery rate [FDR]-adjusted p =.0024), whereas their association with sporadic GGE had marginally lower odds (OR = 3.1, 95% CI = 1.3\u20136.7, FDR-adjusted p =.022). URVs in GABAergic pathway genes were associated with familial GGE (OR = 1.8, 95% CI = 1.3\u20132.5, FDR-adjusted p =.0024) but not with sporadic GGE (OR = 1.3, 95% CI =.9\u20131.9, FDR-adjusted p =.19). Significance: URVs in GABRG2 are likely an important risk factor for familial GGE. The association of gene sets of GABAergic signaling with familial GGE is more prominent than with sporadic GGE
Rare coding variants in genes encoding GABA_A receptors in genetic generalised epilepsies: an exome-based case-control study
BACKGROUND: Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy. METHODS: For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABAA receptors and was compared to the respective GABAA receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes. FINDINGS: Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABAA receptors in cases (odds ratio [OR] 2·40 [95% CI 1·41-4·10]; pNonsyn=0·0014, adjusted pNonsyn=0·019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1·46 [95% CI 1·05-2·03]; pNonsyn=0·0081, adjusted pNonsyn=0·016). Comparison of genes encoding GABAA receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare missense variants for 15 GABAA receptor genes in cases compared with controls (OR 1·46 [95% CI 1·02-2·08]; pNonsyn=0·013, adjusted pNonsyn=0·027). Functional studies for two selected genes (GABRB2 and GABRA5) showed significant loss-of-function effects with reduced current amplitudes in four of seven tested variants compared with wild-type receptors. INTERPRETATION: Functionally relevant variants in genes encoding GABAA receptor subunits constitute a significant risk factor for genetic generalised epilepsy. Examination of the role of specific gene groups and pathways can disentangle the complex genetic architecture of genetic generalised epilepsy. FUNDING: EuroEPINOMICS (European Science Foundation through national funding organisations), Epicure and EpiPGX (Sixth Framework Programme and Seventh Framework Programme of the European Commission), Research Unit FOR2715 (German Research Foundation and Luxembourg National Research Fund)
Rare coding variants in genes encoding GABA(A) receptors in genetic generalised epilepsies : an exome-based case-control study
Background Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy. Methods For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABA(A) receptors and was compared to the respective GABA(A) receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes. Findings Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABA(A) receptors in cases (odds ratio [OR] 2.40 [95% CI 1.41-4.10]; p(Nonsyn)=0.0014, adjusted p(Nonsyn)=0.019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1.46 [95% CI 1.05-2.03]; p(Nonsyn)=0.0081, adjusted p(Nonsyn)=0.016). Comparison of genes encoding GABA(A) receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare missense variants for 15 GABA(A) receptor genes in cases compared with controls (OR 1.46 [95% CI 1.02-2.08]; p(Nonsyn)=0.013, adjusted p(Nonsyn)=0.027). Functional studies for two selected genes (GABRB2 and GABRA5) showed significant loss-of-function effects with reduced current amplitudes in four of seven tested variants compared with wild-type receptors. Interpretation Functionally relevant variants in genes encoding GABA(A) receptor subunits constitute a significant risk factor for genetic generalised epilepsy. Examination of the role of specific gene groups and pathways can disentangle the complex genetic architecture of genetic generalised epilepsy. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe
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