The Mitochondria-Targeted Antioxidant MitoQ Modulates Mitochondrial Function and Endoplasmic Reticulum Stress in Pancreatic β Cells Exposed to Hyperglycaemia.

BACKGROUND/AIMS: Mitochondria-targeted antioxidants such as mitoquinone (MitoQ) have demonstrated protective effects against oxidative damage in several diseases. The increase in reactive oxygen species (ROS) production during glucose metabolism in β cells can be exacerbated under hyperglycaemic conditions such as type 2 diabetes (T2D), thus contributing to β cell function impairment. In the present work, we aimed to evaluate the effect of MitoQ on insulin secretion, oxidative stress, endoplasmic reticulum (ER) stress and nuclear factor kappa B (NFκB) signalling in a pancreatic β cell line under normoglycaemic (NG, 11.1 mM glucose), hyperglycaemic (HG, 25 mM glucose) and lipidic (palmitic acid (PA), 0.5mM) conditions. METHODS: We incubated the pancreatic β cell line INS-1E with or without MitoQ (0.5µM) under NG, HG and PA conditions. We then assessed the following parameters: glucose-induced insulin secretion, O₂ consumption (with a Clark-type electrode); mitochondrial function, oxidative stress parameters and calcium levels (by fluorescence microscopy); ER stress markers and NFκB-p65 protein levels (by western blotting). RESULTS: MitoQ increased insulin secretion and prevented the enhancement of ROS production and O₂ consumption and decrease in GSH levels that are characteristic under HG conditions. MitoQ also reduced protein levels of ER stress markers (GRP78 and P-eIF2α) and the proinflammatory nuclear transcription factor NFκB-p65, both of which increased under HG. MitoQ did not significantly alter ER stress markers under lipidic conditions. CONCLUSION: Our findings suggest that treatment with MitoQ modulates mitochondrial function, which in turn ameliorates endoplasmic reticulum stress and NFκB activation, thereby representing potential benefits for pancreatic β cell function

Orbifolds, Penrose Limits and Supersymmetry Enhancement

We consider supersymmetric PP-wave limits for different N=1 orbifold geometries of the five sphere S^5 and the five dimensional Einstein manifold T^{1,1}. As there are several interesting ways to take the Penrose limits, the PP-wave geometry can be either maximal supersymmetric N=4 or half-maximal supersymmetric N=2. We discuss in detail the cases AdS_5 x S^5/Z_3, AdS_5 x S^5/(Z_m x Z_n) and AdS_5 x T^{1,1}/(\Z_m \times \Z_n) and we identify the gauge invariant operators which correspond to stringy excitations for the different limits.Comment: 22 pages, Latex,v2:additional comments in section 2,references update

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Perturbative Instabilities on the Non-Commutative Torus, Morita Duality and Twisted Boundary Conditions

We study one-loop corrections in scalar and gauge field theories on the non-commutative torus. For rational theta, Morita equivalence allows these theories to be reformulated in terms of ordinary theories on a commutative torus with twisted boundary conditions. UV/IR mixing does not lead to singularities, however there can be large corrections. In particular, gauge theories show tachyonic instabilities for some of the modes. We discuss their relevance to spontaneous Z_N x Z_N symmetry breaking in the Morita dual SU(N) theory due to electric flux condensation.Comment: 30 page

New polymorph of InVO4: A high-pressure structure with six-coordinated vanadium

This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Inorganic Chemestry, copyright © American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/ic402043xA new wolframite-type polymorph of InVO4 is identified under compression near 7 GPa by in situ high-pressure (HP) X-ray diffraction (XRD) and Raman spectroscopic investigations on the stable orthorhombic InVO4. The structural transition is accompanied by a large volume collapse (Delta V/V = -14%) and a drastic increase in bulk modulus (from 69 to 168 GPa). Both techniques also show the existence of a third phase coexisting with the low- and high-pressure phases in a limited pressure range close to the transition pressure. XRD studies revealed a highly anisotropic compression in orthorhombic InVO4. In addition, the compressibility becomes nonlinear in the HP polymorph. The volume collapse in the lattice is related to an increase of the polyhedral coordination around the vanadium atoms. The transformation is not fully reversible. The drastic change in the polyhedral arrangement observed at the transition is indicative of a reconstructive phase transformation. The HP phase here found is the only modification of InVO4 reported to date with 6-fold coordinated vanadium atoms. Finally, Raman frequencies and pressure coefficients in the low- and high-pressure phases of InVO4 are reported.This research supported by the Spanish government MINECO under Grant Nos. MAT2010-21270-C04-01/04 and CSD2007-00045. O.G. acknowledges support from Vicerrectorado de Investigacion y Desarrollo of UPV (Grant No. UPV2011-0914 PAID-05-11 and UPV2011-0966 PAID-06-11). S.N.A. acknowledges support provided by Universitat de Valencia during his visit to it. B.G.-D. acknowledges the financial support from MINECO through the FPI program.Errandonea, D.; Gomis Hilario, O.; García-Domene, B.; Pellicer Porres, J.; Katari, V.; Achary, SN.; Tyagi, AK.... (2013). New polymorph of InVO4: A high-pressure structure with six-coordinated vanadium. Inorganic Chemistry. 52(21):12790-12798. https://doi.org/10.1021/ic402043xS1279012798522

Aspects of noncommutative descriptions of planar systems in high magnetic fields

We study some aspects of recent proposals to use the noncommutative Chern-Simons theory as an effective description of some planar condensed matter models in strong magnetic fields, such as the Quantum Hall Effect. We present an alternative justification for such a description, which may be extended to other planar systems where a uniform magnetic field is present

Top-quark physics at the CLIC electron-positron linear collider

ABSTRACT: The Compact Linear Collider (CLIC) is a proposed future high-luminosity linear electron-positron collider operating at three energy stages, with nominal centre-of-mass energies √s = 380 GeV, 1.5 TeV, and 3 TeV. Its aim is to explore the energy frontier, providing sensitivity to physics beyond the Standard Model (BSM) and precision measurements of Standard Model processes with an emphasis on Higgs boson and top-quark physics. The opportunities for top-quark physics at CLIC are discussed in this paper. The initial stage of operation focuses on top-quark pair production measurements, as well as the search for rare flavour-changing neutral current (FCNC) top-quark decays. It also includes a top-quark pair production threshold scan around 350 GeV which provides a precise measurement of the top-quark mass in a well-defined theoretical framework. At the higher-energy stages, studies are made of top-quark pairs produced in association with other particles. A study of t̄tH production including the extraction of the top Yukawa coupling is presented as well as a study of vector boson fusion (VBF) production, which gives direct access to high-energy electroweak interactions. Operation above 1 TeV leads to more highly collimated jet environments where dedicated methods are used to analyse the jet constituents. These techniques enable studies of the top-quark pair production, and hence the sensitivity to BSM physics, to be extended to higher energies. This paper also includes phenomenological interpretations that may be performed using the results from the extensive top-quark physics programme at CLIC.the Spanish Ministry of Economy, Industry and Competitiveness under projects MINEICO/FEDER-UE, FPA2015-65652-C4-3-R, FPA2015-71292-C2-1-Pand FPA2015-71956-REDT; and the MECD grant FPA2016-78645-P, Spai