The cleavage of biglycan by aggrecanases

SummaryObjectiveAggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4] and aggrecanase-2 (ADAMTS-5) have been named for their ability to degrade the proteoglycan aggrecan. While this may be the preferred substrate for these enzymes, they are also able to degrade other proteins. The aim of this work was to determine whether the aggrecanases could degrade biglycan and decorin.MethodsBiglycan, decorin and aggrecan were purified from human and bovine cartilage and subjected to degradation by recombinant aggrecanase-1 or aggrecanase-2. In vitro degradation was assessed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) and immunoblotting, and the cleavage site in biglycan was determined by N-terminal amino acid sequencing. SDS/PAGE and immunoblotting were also used to assess in situ degradation in both normal and arthritic human articular cartilage.ResultsBoth aggrecanase-1 and aggrecanase-2 are able to cleave bovine and human biglycan at a site within their central leucine-rich repeat regions. Cleavage occurs at an asparagine–cysteine bond within the fifth leucine-rich repeat. In contrast, the closely related proteoglycan decorin is not a substrate for the aggrecanases. Analysis of human articular cartilage from osteoarthritic (OA) and rheumatoid arthritic (RA) joints showed that a biglycan degradation product of equivalent size is present in the extracellular matrix. No equivalent degradation product was, however, detectable in normal adult human articular cartilage.ConclusionBiglycan, which is structurally unrelated to aggrecan, can act as a substrate for aggrecanase-1 and aggrecanase-2, and these proteinases may account for at least part of the biglycan degradation that is present in arthritic cartilage

One Dimensional Chain with Long Range Hopping

The one-dimensional (1D) tight binding model with random nearest neighbor hopping is known to have a singularity of the density of states and of the localization length at the band center. We study numerically the effects of random long range (power-law) hopping with an ensemble averaged magnitude \expectation{|t_{ij}|} \propto |i-j|^{-\sigma} in the 1D chain, while maintaining the particle-hole symmetry present in the nearest neighbor model. We find, in agreement with results of position space renormalization group techniques applied to the random XY spin chain with power-law interactions, that there is a change of behavior when the power-law exponent $\sigma$ becomes smaller than 2

Interactions, Distribution of Pinning Energies, and Transport in the Bose Glass Phase of Vortices in Superconductors

We study the ground state and low energy excitations of vortices pinned to columnar defects in superconductors, taking into account the long--range interaction between the fluxons. We consider the ``underfilled'' situation in the Bose glass phase, where each flux line is attached to one of the defects, while some pins remain unoccupied. By exploiting an analogy with disordered semiconductors, we calculate the spatial configurations in the ground state, as well as the distribution of pinning energies, using a zero--temperature Monte Carlo algorithm minimizing the total energy with respect to all possible one--vortex transfers. Intervortex repulsion leads to strong correlations whenever the London penetration depth exceeds the fluxon spacing. A pronounced peak appears in the static structure factor $S(q)$ for low filling fractions $f \leq 0.3$. Interactions lead to a broad Coulomb gap in the distribution of pinning energies $g(\epsilon)$ near the chemical potential $\mu$, separating the occupied and empty pins. The vanishing of $g(\epsilon)$ at $\mu$ leads to a considerable reduction of variable--range hopping vortex transport by correlated flux line pinning.Comment: 16 pages (twocolumn), revtex, 16 figures not appended, please contact [email protected]

Properties of the Bose glass phase in irradiated superconductors near the matching field

Structural and transport properties of interacting localized flux lines in the Bose glass phase of irradiated superconductors are studied by means of Monte Carlo simulations near the matching field B_Phi, where the densities of vortices and columnar defects are equal. For a completely random columnar pin distribution in the xy-plane transverse to the magnetic field, our results show that the repulsive vortex interactions destroy the Mott insulator phase which was predicted to occur at B = B_Phi. On the other hand, for ratios of the penetration depth to average defect distance lambda/d <= 1, characteristic remnants of the Mott insulator singularities remain visible in experimentally accessible quantities as the magnetization, the bulk modulus, and the magnetization relaxation, when B is varied near B_Phi. For spatially more regular disorder, e.g., a nearly triangular defect distribution, we find that the Mott insulator phase can survive up to considerably large interaction range \lambda/d, and may thus be observable in experiments.Comment: RevTex, 17 pages, eps files for 12 figures include

A microscopic 2D lattice model of dimer granular compaction with friction

We study by Monte Carlo simulation the compaction dynamics of hard dimers in 2D under the action of gravity, subjected to vertical and horizontal shaking, considering also the case in which a friction force acts for horizontal displacements of the dimers. These forces are modeled by introducing effective probabilities for all kinds of moves of the particles. We analyze the dynamics for different values of the time $\tau$ during which the shaking is applied to the system and for different intensities of the forces. It turns out that the density evolution in time follows a stretched exponential behavior if $\tau$ is not very large, while a power law tail develops for larger values of $\tau$. Moreover, in the absence of friction, a critical value $\tau^*$ exists which signals the crossover between two different regimes: for $\tau < \tau^*$ the asymptotic density scales with a power law of $\tau$, while for $\tau > \tau^*$ it reaches logarithmically a maximal saturation value. Such behavior smears out when a finite friction force is present. In this situation the dynamics is slower and lower asymptotic densities are attained. In particular, for significant friction forces, the final density decreases linearly with the friction coefficient. We also compare the frictionless single tap dynamics to the sequential tapping dynamics, observing in the latter case an inverse logarithmic behavior of the density evolution, as found in the experiments.Comment: 10 pages, 15 figures, to be published in Phys. Rev.

Asymmetric Fluid Criticality II: Finite-Size Scaling for Simulations

The vapor-liquid critical behavior of intrinsically asymmetric fluids is studied in finite systems of linear dimensions, $L$, focusing on periodic boundary conditions, as appropriate for simulations. The recently propounded ``complete'' thermodynamic $(L\to\infty)$ scaling theory incorporating pressure mixing in the scaling fields as well as corrections to scaling ${[arXiv:cond-mat/0212145]}$, is extended to finite $L$, initially in a grand canonical representation. The theory allows for a Yang-Yang anomaly in which, when $L\to\infty$, the second temperature derivative, $(d^{2}\mu_{\sigma}/dT^{2})$, of the chemical potential along the phase boundary, $\mu_{\sigma}(T)$, diverges when T\to\Tc -. The finite-size behavior of various special {\em critical loci} in the temperature-density or $(T,\rho)$ plane, in particular, the $k$-inflection susceptibility loci and the $Q$-maximal loci -- derived from $Q_{L}(T,_{L}) \equiv ^{2}_{L}/< m^{4}>_{L}$ where $m \equiv \rho - _{L}$ -- is carefully elucidated and shown to be of value in estimating \Tc and \rhoc. Concrete illustrations are presented for the hard-core square-well fluid and for the restricted primitive model electrolyte including an estimate of the correlation exponent $\nu$ that confirms Ising-type character. The treatment is extended to the canonical representation where further complications appear.Comment: 23 pages in the two-column format (including 13 figures) This is Part II of the previous paper [arXiv:cond-mat/0212145

Aging dynamics of heterogeneous spin models

We investigate numerically the dynamics of three different spin models in the aging regime. Each of these models is meant to be representative of a distinct class of aging behavior: coarsening systems, discontinuous spin glasses, and continuous spin glasses. In order to study dynamic heterogeneities induced by quenched disorder, we consider single-spin observables for a given disorder realization. In some simple cases we are able to provide analytical predictions for single-spin response and correlation functions. The results strongly depend upon the model considered. It turns out that, by comparing the slow evolution of a few different degrees of freedom, one can distinguish between different dynamic classes. As a conclusion we present the general properties which can be induced from our results, and discuss their relation with thermometric arguments.Comment: 39 pages, 36 figure

Novel diabetes gene discovery through comprehensive characterization and integrative analysis of longitudinal gene expression changes

Type 2 diabetes is a complex, systemic disease affected by both genetic and environmental factors. Previous research has identified genetic variants associated with type 2 diabetes risk; however, gene regulatory changes underlying progression to metabolic dysfunction are still largely unknown. We investigated RNA expression changes that occur during diabetes progression using a two-stage approach. In our discovery stage, we compared changes in gene expression using two longitudinally collected blood samples from subjects whose fasting blood glucose transitioned to a level consistent with type 2 diabetes diagnosis between the time points against those who did not with a novel analytical network approach. Our network methodology identified 17 networks, one of which was significantly associated with transition status. This 822-gene network harbors many genes novel to the type 2 diabetes literature but is also significantly enriched for genes previously associated with type 2 diabetes. In the validation stage, we queried associations of genetically determined expression with diabetes-related traits in a large biobank with linked electronic health records. We observed a significant enrichment of genes in our identified network whose genetically determined expression is associated with type 2 diabetes and other metabolic traits and validated 31 genes that are not near previously reported type 2 diabetes loci. Finally, we provide additional functional support, which suggests that the genes in this network are regulated by enhancers that operate in human pancreatic islet cells. We present an innovative and systematic approach that identified and validated key gene expression changes associated with type 2 diabetes transition status and demonstrated their translational relevance in a large clinical resource

From Linear to Nonlinear Response in Spin Glasses: Importance of Mean-Field-Theory Predictions

Deviations from spin-glass linear response in a single crystal Cu:Mn 1.5 at % are studied for a wide range of changes in magnetic field, $\Delta H$. Three quantities, the difference $TRM-(MFC-ZFC)$, the effective waiting time, $t_{w}^{eff}$, and the difference $TRM(t_{w})-TRM(t_{w}=0)$ are examined in our analysis. Three regimes of spin-glass behavior are observed as $\Delta H$ increases. Lines in the $(T,\Delta H)$ plane, corresponding to ``weak'' and ``strong'' violations of linear response under a change in magnetic field, are shown to have the same functional form as the de Almeida-Thouless critical line. Our results demonstrate the existence of a fundamental link between static and dynamic properties of spin glasses, predicted by the mean-field theory of aging phenomena.Comment: 9 pages, 10 figure

Fokker-Planck equations and density of states in disordered quantum wires

We propose a general scheme to construct scaling equations for the density of states in disordered quantum wires for all ten pure Cartan symmetry classes. The anomalous behavior of the density of states near the Fermi level for the three chiral and four Bogoliubov-de Gennes universality classes is analysed in detail by means of a mapping to a scaling equation for the reflection from a quantum wire in the presence of an imaginary potential.Comment: 10 pages, 5 figures, revised versio