Tissue-specific deregulation of selected HDACs characterizes ALS progression in mouse models: pharmacological characterization of SIRT1 and SIRT2 pathways

Acetylation homeostasis is thought to play a role in amyotrophic lateral sclerosis, and treatment with inhibitors of histone deacetylases has been considered a potential and attractive therapeutic approach, despite the lack of a thorough study of this class of proteins. In this study, we have considerably extended previous knowledge on the expression of 13 histone deacetylases in tissues (spinal cord and muscle) from mice carrying two different ALS-linked SOD1 mutations (G93A-SOD1 and G86R-SOD1). We have then focused on class III histone deacetylases SIRT1 and SIRT2 that are considered relevant in neurodegenerative diseases. SIRT1 decreases in the spinal cord, but increases in muscle during the progression of the disease, and a similar expression pattern is observed in the corresponding cell models (neuroblastoma and myoblasts). SIRT2 mRNA expression increases in the spinal cord in both G93A-SOD1 and G86R-SOD1 mice but protein expression is substantially unchanged in all the models examined. At variance with other sirtuin modulators (sirtinol, AGK2 and SRT1720), the well-known SIRT1 inhibitor Ex527 has positive effects on survival of neuronal cells expressing mutant SOD1, but this effect is neither mediated by SIRT1 inhibition nor by SIRT2 inhibition. These data call for caution in proposing sirtuin modulation as a target for treatment

LSQ14efd: observations of the cooling of a shock break-out event in a type Ic Supernova

We present the photometric and spectroscopic evolution of the type Ic supernova LSQ14efd, discovered by the La Silla QUEST survey and followed by PESSTO. LSQ14efd was discovered few days after explosion and the observations cover up to ~100 days. The early photometric points show the signature of the cooling of the shock break-out event experienced by the progenitor at the time of the supernova explosion, one of the first for a type Ic supernova. A comparison with type Ic supernova spectra shows that LSQ14efd is quite similar to the type Ic SN 2004aw. These two supernovae have kinetic energies that are intermediate between standard Ic explosions and those which are the most energetic explosions known (e.g. SN 1998bw). We computed an analytical model for the light-curve peak and estimated the mass of the ejecta 6.3 +/- 0.5 Msun, a synthesized nickel mass of 0.25 Msun and a kinetic energy of Ekin = 5.6 +/- 0.5 x 10^51 erg. No connection between LSQ14efd and a GRB event could be established. However we point out that the supernova shows some spectroscopic similarities with the peculiar SN-Ia 1999ac and the SN-Iax SN 2008A. A core-collapse origin is most probable considering the spectroscopic, photometric evolution and the detection of the cooling of the shock break-out

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Fortnightly changes in water transport direction across the mouth of a narrow estuary

This research investigates the dynamics of the axial tidal flow and residual circulation at the lower Guadiana Estuary, south Portugal, a narrow mesotidal estuary with low freshwater inputs. Current data were collected near the deepest part of the channel for 21 months and across the channel during two (spring and neap) tidal cycles. Results indicate that at the deep channel, depth-averaged currents are stronger and longer during the ebb at spring and during the flood at neap, resulting in opposite water transport directions at a fortnightly time scale. The net water transport across the entire channel is up-estuary at spring and down-estuary at neap, i.e., opposite to the one at the deep channel. At spring tide, when the estuary is considered to be well mixed, the observed pattern of circulation (outflow in the deep channel, inflow over the shoals) results from the combination of the Stokes transport and compensating return flow, which varies laterally with the bathymetry. At neap tide (in particular for those of lowest amplitude each month), inflows at the deep channel are consistently associated with the development of gravitational circulation. Comparisons with previous studies suggest that the baroclinic pressure gradient (rather than internal tidal asymmetries) is the main driver of the residual water transport. Our observations also indicate that the flushing out of the water accumulated up-estuary (at spring) may also produce strong unidirectional barotropic outflow across the entire channel around neap tide.info:eu-repo/semantics/publishedVersio

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Beam Energy and Centrality Dependence of Direct-Photon Emission from Ultrarelativistic Heavy-Ion Collisions.

The PHENIX collaboration presents first measurements of low-momentum (0.41  GeV/c) direct-photon yield dN_{γ}^{dir}/dη is a smooth function of dN_{ch}/dη and can be well described as proportional to (dN_{ch}/dη)^{α} with α≈1.25. This scaling behavior holds for a wide range of beam energies at the Relativistic Heavy Ion Collider and the Large Hadron Collider, for centrality selected samples, as well as for different A+A collision systems. At a given beam energy, the scaling also holds for high p_{T} (&gt;5  GeV/c), but when results from different collision energies are compared, an additional sqrt[s_{NN}]-dependent multiplicative factor is needed to describe the integrated-direct-photon yield

Cyclodextrin modulation of gallic acid in vitro antibacterial activity

The substitution of large spectrum antibiotics for natural bioactive molecules (especially polyphenolics) for the treatment of wound infections has come into prominence in the pharmaceutical industry. However, the use of such molecules depends on their stability during environmental stress and on their ability to reach the action site without losing biological properties. The application of cyclodextrins as a vehicle for polyphenolics protection has been documented and appears to enhance the properties of bioactive molecules. Therefore, the encapsulation of gallic acid, an antibacterial agent with low stability, by -cyclodextrin, (2-hydroxy) propyl--cyclodextrin and methyl--cyclodextrin, was investigated. Encapsulation by -cyclodextrin was confirmed for pH 3 and 5, with similar stability parameters. The (2-hydroxy) propyl--cyclodextrin and methyl--cyclodextrin interactions with gallic acid were only confirmed at pH 3. Among the three cyclodextrins, better gallic acid encapsulation were observed for (2-hydroxy) propyl--cyclodextrin, followed by -cyclodextrin and methyl--cyclodextrin. The effect of cyclodextrin encapsulation on the gallic acid antibacterial activity was also analysed. The antibacterial activity of the inclusion complexes was investigated here for the first time. According to the results, encapsulation of gallic acid by (2-hydroxy) propyl--cyclodextrin seems to be a viable option for the treatment of skin and soft tissue infections, since this inclusion complex has good stability and antibacterial activity.The authors are grateful for the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the Project "BioHealth-Biotechnology and Bioengineering approaches to improve health quality", Ref. NORTE-07-0124-FEDER-000027, co-funded by the "Programa Operacional Regional do Norte" (ON.2-O Novo Norte), QREN, FEDER. The authors also acknowledge the project "Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB", Ref. FCOMP-01-0124-FEDER-027462. This work is, also, funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through FCT-Foundation for Science and Technology under the project PEst-C/CTM/UI0264/2011. Additionally, the authors would like to thank the FCT for the grant for E. Pinho (SFRH/BD/62665/2009)

Effect of femoral head size, subject weight and activity level on acetabular cement mantle stress following total hip arthroplasty

In cases where cemented components are used in total hip arthroplasty, damage or disruption of the cement mantle can lead to aseptic loosening and joint failure. Currently, the relationship between subject activity level, obesity and prosthetic femoral head size and the risk of aseptic loosening of the acetabular component in cemented THA is not well understood. This study aims to provide an insight into this. Finite element models, validated with experimental data, were developed to investigate stresses in the acetabular cement mantle and pelvic bone resulting from the use of three prosthetic femoral head sizes, during a variety of daily activities and one high impact activity (stumbling) for a range of subject body weights. We found that stresses in the superior quadrants of the cortical bone‐cement interface increased with prosthetic head size, patient weight and activity level. In stumbling, average von Mises stresses (22.4 MPa) exceeded the bone cement yield strength for an obese subject (143 kg) indicating that the cement mantle would fail. Our results support the view that obesity and activity level are potential risk factors for aseptic loosening of the acetabular component and provide insight into the increased risk of joint failure associated with larger prosthetic femoral heads

Pan-STARRS and PESSTO search for an optical counterpart to the LIGO gravitational-wave source GW150914

This is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw1893We searched for an optical counterpart to the first gravitational wave source discovered by LIGO (GW150914), using a combination of the Pan-STARRS1 wide-field telescope and the PESSTO spectroscopic follow-up programme. As the final LIGO sky maps changed during analysis, the total probability of the source being spatially coincident with our fields was finally only 4.2 per cent. Therefore we discuss our results primarily as a demonstration of the survey capability of Pan-STARRS and spectroscopic capability of PESSTO. We mapped out 442 square degrees of the northern sky region of the initial map. We discovered 56 astrophysical transients over a period of 41 days from the discovery of the source. Of these, 19 were spectroscopically classified and a further 13 have host galaxy redshifts. All transients appear to be fairly normal supernovae and AGN variability and none is obviously linked with GW150914. We illustrate the sensitivity of our survey by defining parameterised lightcurves with timescales of 4, 20 and 40 days and use the sensitivity of the Pan-STARRS1 images to set limits on the luminosities of possible sources. The Pan-STARRS1 images reach limiting magnitudes of $\textit{i}$$_{P\rceil}$ = 19.2, 20.0 and 20.8 respectively for the three timescales. For long timescale parameterised lightcurves (with FWHM≃40d) we set upper limits of $\textit{M}$$_{i}$ ≤ −17.2$^{−0.9}_{+1.4}$ if the distance to GW150914 is $\textit{D}_{\lfloor}$ = 400 ± 200 Mpc. The number of type Ia SN we find in the survey is similar to that expected from the cosmic SN rate, indicating a reasonably complete efficiency in recovering supernova like transients out to $\textit{D}_{\lfloor}$ = 400 ± 200 Mpc.Pan-STARRS is supported by the University of Hawaii and the National Aeronautics and Space Administration's Planetary Defense Office under Grant No. NNX14AM74G. The Pan-STARRS-LIGO effort is in collaboration with the LIGO Consortium and supported by Queen's University Belfast. The Pan-STARRS1 Sky Surveys have been made possible through contributions by the Institute for Astronomy, the University of Hawaii, the Pan-STARRS Project Office, the Max Planck Society and its participating institutes, the Max Planck Institute for Astronomy, Heidelberg and the Max Planck Institute for Extraterrestrial Physics, Garching, The Johns Hopkins University, Durham University, the University of Edinburgh, the Queen's University Belfast, the Harvard-Smithsonian Center for Astrophysics, the Las Cumbres Observatory Global Telescope Network Incorporated, the National Central University of Taiwan, the Space Telescope Science Institute, and the National Aeronautics and Space Administration under Grant No. NNX08AR22G issued through the Planetary Science Division of the NASA Science Mission Directorate, the National Science Foundation Grant No. AST-1238877, the University of Maryland, Eotvos Lorand University (ELTE), and the Los Alamos National Laboratory. This work is based (in part) on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile as part of PESSTO, (the Public ESO Spectroscopic Survey for Transient Objects Survey) ESO programs 188.D-3003, 191.D-0935. Some of the data presented herein were obtained at the Palomar Observatory, California Institute of Technology. SJS acknowledges funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no [291222] and STFC grants ST/I001123/1 and ST/L000709/1. MF is supported by the European Union FP7 programme through ERC grant number 320360. KM acknowledges support from the STFC through an Ernest Rutherford Fellowship FOE acknowledges support from FONDECYT through postdoctoral grant 3140326. This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration and data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation