MMP-28 as a regulator of myelination

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-28 (MMP-28) is a poorly understood member of the matrix metalloproteinase family. Metalloproteinases are important mediators in the development of the nervous system and can contribute to the maturation of the neural micro-environment.</p> <p>Results</p> <p>MMP-28 added to myelinating rat dorsal root ganglion (DRG) co-cultures reduces myelination and two antibodies targeted to MMP-28 (pAb180 and pAb183) are capable of binding MMP-28 and inhibiting its activity in a dose-dependent manner. Addition of 30 nM pAb180 or pAb183 to rat DRG cultures resulted in the 2.6 and 4.8 fold enhancement of myelination respectively while addition of MMP-28 to DRG co-cultures resulted in enhanced MAPK, ErbB2 and ErbB3 phosphorylation. MMP-28 protein expression was increased within demyelinated lesions of mouse experimental autoimmune encephalitis (EAE) and human multiple sclerosis lesions compared to surrounding normal tissue.</p> <p>Conclusion</p> <p>MMP-28 is upregulated in conditions of demyelination in vivo, induces signaling in vitro consistent with myelination inhibition and, neutralization of MMP-28 activity can enhance myelination in vitro. These results suggest inhibition of MMP-28 may be beneficial under conditions of dysmyelination.</p

Precision measurement of the branching fractions of J/psi -> pi+pi-pi0 and psi' -> pi+pi-pi0

We study the decays of the J/psi and psi' mesons to pi+pi-pi0 using data samples at both resonances collected with the BES III detector in 2009. We measure the corresponding branching fractions with unprecedented precision and provide mass spectra and Dalitz plots. The branching fraction for J/psi -> pi+pi-pi0 is determined to be (2.137 +- 0.004 (stat.) +0.058-0.056 (syst.) +0.027-0.026 (norm.))*10-2, and the branching fraction for psi' -> pi+pi-pi0 is measured as (2.14 +- 0.03 (stat.) +0.08-0.07 (syst.) +0.09-0.08 (norm.))*10-4. The J/psi decay is found to be dominated by an intermediate rho(770) state, whereas the psi' decay is dominated by di-pion masses around 2.2 GeV/c2, leading to strikingly different Dalitz distributions.Comment: 15 pages, 2 figure

Observation of χc1\chi_{c1} decays into vector meson pairs ϕϕ\phi\phi, ωω\omega\omega, and ωϕ\omega\phi

Decays of $\chi_{c1}$ to vector meson pairs $\phi\phi$, $\omega\omega$ and $\omega\phi$ are observed for the first time using $(106\pm4)\times 10^6$ \psip events accumulated at the BESIII detector at the BEPCII $e^+e^-$ collider. The branching fractions are measured to be $(4.4\pm 0.3\pm 0.5)\times 10^{-4}$, $(6.0\pm 0.3\pm 0.7)\times 10^{-4}$, and $(2.2\pm 0.6\pm 0.2)\times 10^{-5}$, for $\chi_{c1}\to \phi\phi$, $\omega\omega$, and $\omega\phi$, respectively. The observation of $\chi_{c1}$ decays into a pair of vector mesons $\phi\phi$, $\omega\omega$ and $\omega\phi$ indicates that the hadron helicity selection rule is significantly violated in $\chi_{cJ}$ decays. In addition, the measurement of $\chi_{cJ}\to \omega\phi$ gives the rate of doubly OZI-suppressed decay. Branching fractions for $\chi_{c0}$ and $\chi_{c2}$ decays into other vector meson pairs are also measured with improved precision.Comment: 4 pages, 2 figure

Higher-order multipole amplitude measurement in ψ(2S)→γχc2\psi(2S)\to\gamma\chi_{c2}

Using $106\times10^6$ $\psi(2S)$ events collected with the BESIII detector at the BEPCII storage ring, the higher-order multipole amplitudes in the radiative transition $\psi(2S)\to\gamma\chi_{c2}\to\gamma\pi\pi/\gamma KK$ are measured. A fit to the $\chi_{c2}$ production and decay angular distributions yields $M2=0.046\pm0.010\pm0.013$ and $E3=0.015\pm0.008\pm0.018$, where the first errors are statistical and the second systematic. Here $M2$ denotes the normalized magnetic quadrupole amplitude and $E3$ the normalized electric octupole amplitude. This measurement shows evidence for the existence of the $M2$ signal with $4.4\sigma$ statistical significance and is consistent with the charm quark having no anomalous magnetic moment.Comment: 14 pages, 4 figure

First Observation of the Decays chi_{cJ} -> pi^0 pi^0 pi^0 pi^0

We present a study of the P-wave spin -triplet charmonium chi_{cJ} decays (J=0,1,2) into pi^0 pi^0 pi^0 pi^0. The analysis is based on 106 million \psiprime decays recorded with the BESIII detector at the BEPCII electron positron collider. The decay into the pi^0 pi^0 pi^0 pi^0 hadronic final state is observed for the first time. We measure the branching fractions B(chi_{c0} -> pi^0 pi^0 pi^0 pi^0)=(3.34 +- 0.06 +- 0.44)*10^{-3}, B(chi_{c1} -> pi^0 pi^0 pi^0 pi^0)=(0.57 +- 0.03 +- 0.08)*10^{-3}, and B(chi_{c2} -> pi^0 pi^0 pi^0 pi^0)=(1.21 +- 0.05 +- 0.16)*10^{-3}, where the uncertainties are statistical and systematical, respectively.Comment: 7 pages, 3 figure

Study of χcJ\chi_{cJ} radiative decays into a vector meson

The decays $\chi_{cJ}\to\gamma V$ ($V=\phi, \rho^0, \omega$) are studied with a sample of radiative \psip\to\gamma\chi_{cJ} events in a sample of (1.06\pm0.04)\times 10^{8} \psip events collected with the BESIII detector. The branching fractions are determined to be: ${\cal B}(\chi_{c1}\to \gamma\phi)=(25.8\pm 5.2\pm 2.3)\times 10^{-6}$, ${\cal B}(\chi_{c1}\to \gamma\rho^0)=(228\pm 13\pm 22)\times 10^{-6}$, and ${\cal B}(\chi_{c1}\to \gamma\omega)=(69.7\pm 7.2\pm 6.6)\times 10^{-6}$. The decay $\chi_{c1}\to \gamma\phi$ is observed for the first time. Upper limits at the 90% confidence level on the branching fractions for $\chi_{c0}$ and \chict decays into these final states are determined. In addition, the fractions of the transverse polarization component of the vector meson in $\chi_{c1}\to \gamma V$ decays are measured to be $0.29_{-0.12-0.09}^{+0.13+0.10}$ for $\chi_{c1}\to \gamma\phi$, $0.158\pm 0.034^{+0.015}_{-0.014}$ for $\chi_{c1}\to \gamma\rho^0$, and $0.247_{-0.087-0.026}^{+0.090+0.044}$ for $\chi_{c1}\to \gamma\omega$, respectively. The first errors are statistical and the second ones are systematic.Comment: 8 pages, 3 figure

Graphene Photonics and Optoelectronics

The richness of optical and electronic properties of graphene attracts enormous interest. Graphene has high mobility and optical transparency, in addition to flexibility, robustness and environmental stability. So far, the main focus has been on fundamental physics and electronic devices. However, we believe its true potential to be in photonics and optoelectronics, where the combination of its unique optical and electronic properties can be fully exploited, even in the absence of a bandgap, and the linear dispersion of the Dirac electrons enables ultra-wide-band tunability. The rise of graphene in photonics and optoelectronics is shown by several recent results, ranging from solar cells and light emitting devices, to touch screens, photodetectors and ultrafast lasers. Here we review the state of the art in this emerging field.Comment: Review Nature Photonics, in pres

Role of Matrix Metalloproteinases and Therapeutic Benefits of Their Inhibition in Spinal Cord Injury

This review will focus on matrix metalloproteinases (MMPs) and their inhibitors in the context of spinal cord injury (SCI). MMPs have a specific cellular and temporal pattern of expression in the injured spinal cord. Here we consider their diverse functions in the acutely injured cord and during wound healing. Excessive activity of MMPs, and in particular gelatinase B (MMP-9), in the acutely injured cord contributes to disruption of the blood-spinal cord barrier, and the influx of leukocytes into the injured cord, as well as apoptosis. MMP-9 and MMP-2 regulate inflammation and neuropathic pain after peripheral nerve injury and may contribute to SCI-induced pain. Early pharmacologic inhibition of MMPs or the gelatinases (MMP-2 and MMP-9) results in an improvement in long-term neurological recovery and is associated with reduced glial scarring and neuropathic pain. During wound healing, gelatinase A (MMP-2) plays a critical role in limiting the formation of an inhibitory glial scar, and mice that are genetically deficient in this protease showed impaired recovery. Together, these findings illustrate complex, temporally distinct roles of MMPs in SCIs. As early gelatinase activity is detrimental, there is an emerging interest in developing gelatinase-targeted therapeutics that would be specifically tailored to the acute injured spinal cord. Thus, we focus this review on the development of selective gelatinase inhibitors

UBR2 of the N-End Rule Pathway Is Required for Chromosome Stability via Histone Ubiquitylation in Spermatocytes and Somatic Cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells