Induction of Osmolyte Pathways in Skeletal Muscle Inflammation: Novel Biomarkers for Myositis

We recently identified osmolyte accumulators as novel biomarkers for chronic skeletal muscle inflammation and weakness, but their precise involvement in inflammatory myopathies remains elusive. In the current study, we demonstrate in vitro that, in myoblasts and myotubes exposed to pro-inflammatory cytokines or increased salt concentration, mRNA levels of the osmolyte carriers SLC5A3, SLC6A6, SLC6A12, and AKR1B1 enzyme can be upregulated. Induction of SLC6A12 and AKR1B1 was confirmed at the protein level using immunofluorescence and Western blotting. Gene silencing by specific siRNAs revealed that these factors were vital for muscle cells under hyperosmotic conditions. Pro-inflammatory cytokines activated mitogen-activated protein kinases, nuclear factor κB as well as nuclear factor of activated T-cells 5 mRNA expression. In muscle biopsies from patients with polymyositis or sporadic inclusion body myositis, osmolyte pathway activation was observed in regenerating muscle fibers. In addition, the osmolyte carriers SLC5A3 and SLC6A12 localized to subsets of immune cells, most notably to the endomysial macrophages and T-cells. Collectively, this study unveiled that muscle cells respond to osmotic and inflammatory stress by osmolyte pathway activation, likely orchestrating general protection of the tissue. Moreover, pro-inflammatory properties are attributed to SLC5A3 and SLC6A12 in auto-aggressive macrophages and T-cells in inflamed skeletal muscle

Psychologische Merkmale jugendlicher Patienten vor einer Gewichtsreduktionsbehandlung

Übergewicht und Adipositas zeigen bei Kindern und Jugendlichen eine hohe Prävalenz und Persistenz. Entsprechende Therapien sind kaum individualisiert und zeigen nur moderate Erfolge. Die Psychopathologie bleibt zumeist unberücksichtigt. Die vorliegende Studie hat die Psychopathologie von Jugendlichen mit Übergewicht und Adipositas (N = 201, Alter 12 – 17 Jahre) vor einer Gewichtsreduktionsbehandlung erhoben und Alters- sowie Geschlechtseffekte untersucht. Mittels Fragebögen wurden selbstberichtet die allgemeine Symptombelastung, Essstörungs- und allgemeine Psychopathologie, gewichtsbezogene Selbststigmatisierung und die körperliche und psychische Lebensqualität erhoben. Mädchen zeigten hypothesenkonform ein höheres Maß an gewichtsbezogener Selbststigmatisierung und eine stärkere Essstörungspsychopathologie als Jungen. Ältere Jugendliche berichteten eine geringere Lebensqualität als jüngere. Vergleiche zu Referenzgruppen aus Bevölkerungs- und Normierungsstichproben zeigten auffälligere Werte bei Jugendlichen mit Übergewicht und Adipositas für alle untersuchten Parameter. Eine auffällige Psychopathologie ist demzufolge ein wichtiges Korrelat bei Jugendlichen mit hohem Gewichtsstatus und ein potenzieller Einflussfaktor auf den Erfolg einer Gewichtsreduktionsbehandlung. Zukünftige Studien sollten die Psychopathologie bei Übergewicht und Adipositas weiter differenzieren und therapeutische Ressourcen evaluieren.Overweight and obesity in children and adolescents are highly prevalent and persistent. Current weight loss treatments are rarely individualized and show only small to moderate efficacy. Only rarely, psychopathological parameters are considered. The present study evaluated the psychopathology of adolescents with overweight and obesity (N = 201, ages 12 – 17 years) prior to obesity treatment. The data were analyzed for age and sex effects. Self-report questionnaires assessed general symptom burden, eating disorder and general psychopathology, weight-related self-stigmatization, and physical and mental quality of life. Girls showed higher rates of weight-related self-stigmatization and higher disordered eating behavior compared to boys. Older adolescents reported a lower quality of life compared to younger adolescents. In normative comparisons with population-based samples and norms, adolescents with overweight and obesity showed significantly adverse outcomes in all parameters. Thus, this study identified psychopathology as an important factor in adolescents with high weight status that may affect obesity treatment. Future studies should examine psychopathology more differentially and determine therapeutic resources in adolescent overweight and obesity

Quantifying feedback from narrow line region outflows in nearby active galaxies II. Spatially resolved mass outflow rates for the QSO2 Markarian 34

We present spatially resolved mass outflow rate measurements (M˙ out) for the narrow line region of Markarian 34, the nearest Compton-thick type 2 quasar (QSO2). Spectra obtained with the Hubble Space Telescope and at Apache Point Observatory reveal complex kinematics, with distinct signatures of outflow and rotation within 2 kpc of the nucleus. Using multi-component photoionization models, we find that the outflow contains a total ionized gas mass of M≈1.6×106Me. Combining this with the kinematics yields a peak outflow rate of M˙ out » 2.0 0.4 Me yr−1 at a distance of 470 pc from the nucleus, with a spatially integrated kinetic energy of E≈1.4×1055 erg. These outflows are more energetic than those observed in Mrk 573 and NGC 4151, supporting a correlation between luminosity and outflow strength even though they have similar peak outflow rates. The mix of rotational and outflowing components suggests that spatially resolved observations are required to determine accurate outflow parameters in systems with complex kinematics

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

Measurement of the top pair production cross section in 8 TeV proton-proton collisions using kinematic information in the lepton plus jets final state with ATLAS

A measurement is presented of the $t\bar{t}$ inclusive production cross-section in $pp$ collisions at a center-of-mass energy of $\sqrt{s}=8$ TeV using data collected by the ATLAS detector at the CERN Large Hadron Collider. The measurement was performed in the lepton+jets final state using a data set corresponding to an integrated luminosity of 20.3 fb$^{-1}$. The cross-section was obtained using a likelihood discriminant fit and $b$-jet identification was used to improve the signal-to-background ratio. The inclusive $t\bar{t}$ production cross-section was measured to be $260\pm 1{\textrm{(stat.)}} ^{+22}_{-23} {\textrm{(syst.)}}\pm 8{\textrm{(lumi.)}}\pm 4{\mathrm{(beam)}}$ pb assuming a top-quark mass of 172.5 GeV, in good agreement with the theoretical prediction of $253^{+13}_{-15}$ pb. The $t\bar{t}\to (e,\mu)+{\mathrm{jets}}$ production cross-section in the fiducial region determined by the detector acceptance is also reported.Comment: Published version, 19 pages plus author list (35 pages total), 3 figures, 2 tables, all figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/TOPQ-2013-06

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured