MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease

Polyglutamine (polyQ) tract expansion leads to proteotoxic misfolding and drives a family of nine diseases. We study spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder of the neuromuscular system caused by the polyQ androgen receptor (AR). Using a knock-in mouse model of SBMA, AR113Q mice, we show that E3 ubiquitin ligases which are a hallmark of the canonical muscle atrophy machinery are not induced in AR113Q muscle. Similarly, we find no evidence to suggest dysfunction of signaling pathways that trigger muscle hypertrophy or impairment of the muscle stem cell niche. Instead, we find that skeletal muscle atrophy is characterized by diminished function of the transcriptional regulator Myocyte Enhancer Factor 2 (MEF2), a regulator of myofiber homeostasis. Decreased expression of MEF2 target genes is age- and glutamine tract length-dependent, occurs due to polyQ AR proteotoxicity, and is associated with sequestration of MEF2 into intranuclear inclusions in muscle. Skeletal muscle from R6/2 mice, a model of Huntington disease which develops progressive atrophy, also sequesters MEF2 into inclusions and displays age-dependent loss of MEF2 target genes. Similarly, SBMA patient muscle shows loss of MEF2 target gene expression, and restoring MEF2 activity in AR113Q muscle rescues fiber size and MEF2-regulated gene expression. This work establishes MEF2 impairment as a novel mechanism of skeletal muscle atrophy downstream of toxic polyglutamine proteins and as a therapeutic target for muscle atrophy in these disorders

R-parity violating resonant stop production at the Large Hadron Collider

We have investigated the resonant production of a stop at the Large Hadron Collider, driven by baryon number violating interactions in supersymmetry. We work in the framework of minimal supergravity models with the lightest neutralino being the lightest supersymmetric particle which decays within the detector. We look at various dilepton and trilepton final states, with or without b-tags. A detailed background simulation is performed, and all possible decay modes of the lighter stop are taken into account. We find that higher stop masses are sometimes easier to probe, through the decay of the stop into the third or fourth neutralino and their subsequent cascades. We also comment on the detectability of such signals during the 7 TeV run, where, as expected, only relatively light stops can be probed. Our conclusion is that the resonant process may be probed, at both 10 and 14 TeV, with the R-parity violating coupling {\lambda}"_{312} as low as 0.05, for a stop mass of about 1 TeV. The possibility of distinguishing between resonant stop production and pair-production is also discussed.Comment: 20 pages, 4 figures, 6 tables; Version accepted by JHE

Discovering the constrained NMSSM with tau leptons at the LHC

The constrained Next-to-Minimal Supersymmetric Standard Model (cNMSSM) with mSugra-like boundary conditions at the GUT scale implies a singlino-like LSP with a mass just a few GeV below a stau NLSP. Hence, most of the squark/gluino decay cascades contain two tau leptons. The gluino mass >~ 1.2 TeV is somewhat larger than the squark masses of >~ 1 TeV. We simulate signal and background events for such a scenario at the LHC, and propose cuts on the transverse momenta of two jets, the missing transverse energy and the transverse momentum of a hadronically decaying tau lepton. This dedicated analysis allows to improve on the results of generic supersymmetry searches for a large part of the parameter space of the cNMSSM. The distribution of the effective mass and the signal rate provide sensitivity to distinguish the cNMSSM from the constrained Minimal Supersymmetric Standard Model in the stau-coannihilation region.Comment: 18 pages, 3 Figure

Deciphering Universal Extra Dimension from the top quark signals at the CERN LHC

Models based on Universal Extra Dimensions predict Kaluza-Klein (KK) excitations of all Standard Model (SM) particles. We examine the pair production of KK excitations of top- and bottom-quarks at the Large Hadron Collider. Once produced, the KK top/bottom quarks can decay to $b$-quarks, leptons and the lightest KK-particle, $\gamma_1$, resulting in 2 $b$-jets, two opposite sign leptons and missing transverse momentum, thereby mimicing top-pair production. We show that, with a proper choice of kinematic cuts, an integrated luminosity of 100 fb$^{-1}$ would allow a discovery for an inverse radius upto $R^{-1} = 750$ GeV.Comment: 18 pages, 14 figures, Accepted for publication in JHE

Higgs production in CP-violating supersymmetric cascade decays: probing the `open hole' at the Large Hadron Collider

A benchmark CP-violating supersymmetric scenario (known as 'CPX-scenario' in the literature) is studied in the context of the Large Hadron Collider (LHC). It is shown that the LHC, with low to moderate accumulated luminosity, will be able to probe the existing `hole' in the $m_{h_1}$-$\tan\beta$ plane, which cannot be ruled out by the LEP data. We explore the parameter space with cascade decay of third generation squarks and gluino with CP-violating decay branching fractions. We propose a multi-channel analysis to probe this parameter space some of which are background free at an integrated luminosity of 5-10 fb$^{-1}$. Specially, multi-lepton final states (3\l,\, 4\l and like sign di-lepton) are almost background free and have $5\sigma$ reach for the corresponding signals with very early data of LHC for both 14 TeV and 7 TeV center of mass energy.Comment: 24 pages, 9 figures, references added as in the journal versio

Many faces of low mass neutralino dark matter in the unconstrained MSSM, LHC data and new signals

If all strongly interacting sparticles (the squarks and the gluinos) in an unconstrained minimal supersymmetric standard model (MSSM) are heavier than the corresponding mass lower limits in the minimal supergravity (mSUGRA) model, obtained by the current LHC experiments, then the existing data allow a variety of electroweak (EW) sectors with light sparticles yielding dark matter (DM) relic density allowed by the WMAP data. Some of the sparticles may lie just above the existing lower bounds from LEP and lead to many novel DM producing mechanisms not common in mSUGRA. This is illustrated by revisiting the above squark-gluino mass limits obtained by the ATLAS Collaboration, with an unconstrained EW sector with masses not correlated with the strong sector. Using their selection criteria and the corresponding cross section limits, we find at the generator level using Pythia, that the changes in the mass limits, if any, are by at most 10-12% in most scenarios. In some cases, however, the relaxation of the gluino mass limits are larger ($\approx 20$). If a subset of the strongly interacting sparticles in an unconstrained MSSM are within the reach of the LHC, then signals sensitive to the EW sector may be obtained. This is illustrated by simulating the $blj$\etslash, $l= e and \mu$, and $b\tau j$\etslash signals in i) the light stop scenario and ii) the light stop-gluino scenario with various light EW sectors allowed by the WMAP data. Some of the more general models may be realized with non-universal scalar and gaugino masses.Comment: 27 pages, 1 figure, references added, minor changes in text, to appear in JHE