INSIG1 influences obesity-related hypertriglyceridemia in humans

In our analysis of a quantitative trait locus (QTL) for plasma triglyceride (TG) levels [logarithm of odds (LOD) = 3.7] on human chromosome 7q36, we examined 29 single nucleotide polymorphisms (SNPs) across INSIG1, a biological candidate gene in the region. Insulin-induced genes (INSIGs) are feedback mediators of cholesterol and fatty acid synthesis in animals, but their role in human lipid regulation is unclear. In our cohort, the INSIG1 promoter SNP rs2721 was associated with TG levels (P = 2 × 10−3 in 1,560 individuals of the original linkage cohort, P = 8 × 10−4 in 920 unrelated individuals of the replication cohort, combined P = 9.9 × 10−6). Individuals homozygous for the T allele had 9% higher TG levels and 2-fold lower expression of INSIG1 in surgical liver biopsy samples when compared with individuals homozygous for the G allele. Also, the T allele showed additional binding of nuclear proteins from HepG2 liver cells in gel shift assays. Finally, the variant rs7566605 in INSIG2, the only homolog of INSIG1, enhances the effect of rs2721 (P = 0.00117). The variant rs2721 alone explains 5.4% of the observed linkage in our cohort, suggesting that additional, yet-undiscovered genes and sequence variants in the QTL interval also contribute to alterations in TG levels in humans

Role of non-coding RNAs in maintaining primary airway smooth muscle cells

BACKGROUND: The airway smooth muscle (ASM) cell maintains its own proliferative rate and contributes to the inflammatory response in the airways, effects that are inhibited by corticosteroids, used in the treatment of airways diseases. OBJECTIVE: We determined the differential expression of mRNAs, microRNAs (miRNAs) and long noncoding RNA species (lncRNAs) in primary ASM cells following treatment with a corticosteroid, dexamethasone, and fetal calf serum (FCS). METHODS: mRNA, miRNA and lncRNA expression was measured by microarray and quantitative real-time PCR. RESULTS: A small number of miRNAs (including miR-150, −371-5p, −718, −940, −1181, −1207-5p, −1915, and −3663-3p) were decreased following exposure to dexamethasone and FCS. The mRNA targets of these miRNAs were increased in expression. The changes in mRNA expression were associated with regulation of ASM actin cytoskeleton. We also observed changes in expression of lncRNAs, including natural antisense, pseudogenes, intronic lncRNAs, and intergenic lncRNAs following dexamethasone and FCS. We confirmed the change in expression of three of these, LINC00882, LINC00883, PVT1, and its transcriptional activator, c-MYC. We propose that four of these lincRNAs (RP11-46A10.4, LINC00883, BCYRN1, and LINC00882) act as miRNA ‘sponges’ for 4 miRNAs (miR-150, −371-5p, −940, −1207-5p). CONCLUSION: This in-vitro model of primary ASM cell phenotype was associated with the regulation of several ncRNAs. Their identification allows for in-vitro functional experimentation to establish causality with the primary ASM phenotype, and in airway diseases such as asthma and chronic obstructive pulmonary disease (COPD)

Topological defects: A problem for cyclic universes?

We study the behaviour of cosmic string networks in contracting universes, and discuss some of their possible consequences. We note that there is a fundamental time asymmetry between defect network evolution for an expanding universe and a contracting universe. A string network with negligible loop production and small-scale structure will asymptotically behave during the collapse phase as a radiation fluid. In realistic networks these two effects are important, making this solution only approximate. We derive new scaling solutions describing this effect, and test them against high-resolution numerical simulations. A string network in a contracting universe, together with the gravitational radiation background it has generated, can significantly affect the dynamics of the universe both locally and globally. The network can be an important source of radiation, entropy and inhomogeneity. We discuss the possible implications of these findings for bouncing and cyclic cosmological models.Comment: 11 RevTeX 4 pages, 6 figures; version to appear in Phys. Rev.

Universal Correlations of Coulomb Blockade Conductance Peaks and the Rotation Scaling in Quantum Dots

We show that the parametric correlations of the conductance peak amplitudes of a chaotic or weakly disordered quantum dot in the Coulomb blockade regime become universal upon an appropriate scaling of the parameter. We compute the universal forms of this correlator for both cases of conserved and broken time reversal symmetry. For a symmetric dot the correlator is independent of the details in each lead such as the number of channels and their correlation. We derive a new scaling, which we call the rotation scaling, that can be computed directly from the dot's eigenfunction rotation rate or alternatively from the conductance peak heights, and therefore does not require knowledge of the spectrum of the dot. The relation of the rotation scaling to the level velocity scaling is discussed. The exact analytic form of the conductance peak correlator is derived at short distances. We also calculate the universal distributions of the average level width velocity for various values of the scaled parameter. The universality is illustrated in an Anderson model of a disordered dot.Comment: 35 pages, RevTex, 6 Postscript figure

Evidence-Based Recommendations for Local Antimicrobial Strategies and Dead Space Management in Fracture-Related Infection

Summary:Fracture-related infection (FRI) remains a challenging complication that imposes a heavy burden on orthopaedic trauma patients. The surgical management eradicates the local infectious focus and if necessary facilitates bone healing. Treatment success is associated with debridement of all dead and poorly vascularized tissue. However, debridement is often associated with the formation of a dead space, which provides an ideal environment for bacteria and is a potential site for recurrent infection. Dead space management is therefore of critical importance. For this reason, the use of locally delivered antimicrobials has gained attention not only for local antimicrobial activity but also for dead space management. Local antimicrobial therapy has been widely studied in periprosthetic joint infection, without addressing the specific problems of FRI. Furthermore, the literature presents a wide array of methods and guidelines with respect to the use of local antimicrobials. The present review describes the scientific evidence related to dead space management with a focus on the currently available local antimicrobial strategies in the management of FRI.Level of Evidence:Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence

Avoiding lodging in irrigated spring wheat. I. Stem and root structural requirements

A model of the lodging process has been successfully adapted for use on spring wheat grown in North-West Mexico (NWM). The lodging model was used to estimate the lodging-associated traits required to enable spring wheat grown in NWM with a typical yield of 6 t ha−1 and plant height of 0.7 m to achieve a lodging return period of 25 years. Target traits included a root plate spread of 51 mm and stem strength of the bottom internode of 268 N mm. These target traits increased to 54.5 mm and 325 N mm, respectively, for a crop yielding 10 t ha−1. Analysis of multiple genotypes across three growing seasons enabled relationships between both stem strength and root plate spread with structural dry matter to be quantified. A NWM lodging resistant ideotype yielding 6 t ha−1 would require 3.93 t ha−1 of structural stem biomass and 1.10 t ha−1 of root biomass in the top 10 cm of soil, which would result in a harvest index (HI) of 0.46 after accounting for chaff and leaf biomass. A crop yielding 10 t ha−1 would achieve a HI of 0.54 for 0.7 m tall plants or 0.41 for more typical 1.0 m tall plants. This study indicates that for plant breeders to achieve both high yields and lodging-proofness they must either breed for greater total biomass or develop high yielding germplasm from shorter crops

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters