Skeletal muscle AMPK is not activated during 2 h of moderate intensity exercise at ~65% VO2peak in endurance trained men

Key points: AMP-activated protein kinase (AMPK) is considered a major regulator of skeletal muscle metabolism during exercise. However, we previously showed that, although AMPK activity increases by 8–10-fold during ∼120 min of exercise at ∼65% (Formula presented.) in untrained individuals, there is no increase in these individuals after only 10 days of exercise training (longitudinal study). In a cross-sectional study, we show that there is also a lack of activation of skeletal muscle AMPK during 120 min of cycling exercise at 65% (Formula presented.) in endurance-trained individuals. These findings indicate that AMPK is not an important regulator of exercise metabolism during 120 min of exercise at 65% (Formula presented.) in endurance trained men. It is important that more energy is directed towards examining other potential regulators of exercise metabolism. Abstract: AMP-activated protein kinase (AMPK) is considered a major regulator of skeletal muscle metabolism during exercise. Indeed, AMPK is activated during exercise and activation of AMPK by 5-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) increases skeletal muscle glucose uptake and fat oxidation. However, we have previously shown that, although AMPK activity increases by 8–10-fold during ∼120 min of exercise at ∼65% (Formula presented.) in untrained individuals, there is no increase in these individuals after only 10 days of exercise training (longitudinal study). In a cross-sectional study, we examined whether there is also a lack of activation of skeletal muscle AMPK during 120 min of cycling exercise at 65% (Formula presented.) in endurance-trained individuals. Eleven untrained (UT; (Formula presented.) = 37.9 ± 5.6 ml.kg−1 min−1) and seven endurance trained (ET; (Formula presented.) = 61.8 ± 2.2 ml.kg−1 min−1) males completed 120 min of cycling exercise at 66 ± 4% (Formula presented.) (UT: 100 ± 21 W; ET: 190 ± 15 W). Muscle biopsies were obtained at rest and following 30 and 120 min of exercise. Muscle glycogen was significantly (P < 0.05) higher before exercise in ET and decreased similarly during exercise in the ET and UT individuals. Exercise significantly increased calculated skeletal muscle free AMP content and more so in the UT individuals. Exercise significantly (P < 0.05) increased skeletal muscle AMPK α2 activity (4-fold), AMPK αThr172 phosphorylation (2-fold) and ACCβ Ser222 phosphorylation (2-fold) in the UT individuals but not in the ET individuals. These findings indicate that AMPK is not an important regulator of exercise metabolism during 120 min of exercise at 65% (Formula presented.) in endurance trained men

Skeletal muscle AMPK is not activated during 2 h of moderate intensity exercise at ∼65% VO2 peak in endurance trained men

KEY POINTS: AMP-activated protein kinase (AMPK) is considered a major regulator of skeletal muscle metabolism during exercise. However, we previously showed that, although AMPK activity increases by 8-10-fold during ∼120 min of exercise at ∼65% V ̇ O 2 peak in untrained individuals, there is no increase in these individuals after only 10 days of exercise training (longitudinal study). In a cross-sectional study, we show that there is also a lack of activation of skeletal muscle AMPK during 120 min of cycling exercise at 65% V ̇ O 2 peak in endurance-trained individuals. These findings indicate that AMPK is not an important regulator of exercise metabolism during 120 min of exercise at 65% V ̇ O 2 peak in endurance trained men. It is important that more energy is directed towards examining other potential regulators of exercise metabolism. ABSTRACT: AMP-activated protein kinase (AMPK) is considered a major regulator of skeletal muscle metabolism during exercise. Indeed, AMPK is activated during exercise and activation of AMPK by 5-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) increases skeletal muscle glucose uptake and fat oxidation. However, we have previously shown that, although AMPK activity increases by 8-10-fold during ∼120 min of exercise at ∼65% V ̇ O 2 peak in untrained individuals, there is no increase in these individuals after only 10 days of exercise training (longitudinal study). In a cross-sectional study, we examined whether there is also a lack of activation of skeletal muscle AMPK during 120 min of cycling exercise at 65% V ̇ O 2 peak in endurance-trained individuals. Eleven untrained (UT; V ̇ O 2 peak = 37.9 ± 5.6 ml.kg-1  min-1 ) and seven endurance trained (ET; V ̇ O 2 peak = 61.8 ± 2.2 ml.kg-1  min-1 ) males completed 120 min of cycling exercise at 66 ± 4% V ̇ O 2 peak (UT: 100 ± 21 W; ET: 190 ± 15 W). Muscle biopsies were obtained at rest and following 30 and 120 min of exercise. Muscle glycogen was significantly (P < 0.05) higher before exercise in ET and decreased similarly during exercise in the ET and UT individuals. Exercise significantly increased calculated skeletal muscle free AMP content and more so in the UT individuals. Exercise significantly (P < 0.05) increased skeletal muscle AMPK α2 activity (4-fold), AMPK αThr172 phosphorylation (2-fold) and ACCβ Ser222 phosphorylation (2-fold) in the UT individuals but not in the ET individuals. These findings indicate that AMPK is not an important regulator of exercise metabolism during 120 min of exercise at 65% V ̇ O 2 peak in endurance trained men

Methods of sputum processing for cell counts, immunocytochemistry and in situ hybridisation.

Since the first attempts to use standardised methods for sampling induced airways sputum, two methods for processing the expectorate have evolved. The first involves selecting all viscid or denser portions from the expectorated sample with the aid of an inverted microscope. This method has been extensively evaluated and reported in detail. The second approach involves processing the entire expectorate, comprising sputum plus variable amounts of saliva. Recent modifications to this method include collecting saliva and sputum separately in order to reduce salivary contamination. Both methods have advantages and disadvantages. The advantages of using selected sputum are: squamous cell contamination is v5%, making cell counting easier and quicker to perform, the total cell count (TCC) can be expressed per gram of lower airway secretions, and concentrations of chemicals in the fluid phase are unaffected by the confounding influence of saliva, and can be accurately corrected for dilution. The disadvantage is that selection takes a few minutes longer to perform and requires an inverted microscope. The advantage of using the entire expectorate is that the technique is quicker to perform, but there are some disadvantages that require consideration. The expectorate contains a variable mixture of sputum plus saliva which maydilute the sputum and confound its analysis. The reproducibility of cell counts has been reported to be lower if squamous cell contamination represents w20% of all recovered cells. There is conflicting data as to whether or not differential cell counts (DCCs) differ between the two methods. One study reported a higher percentage of eosinophils in sputum processed by the selection method compared to the entire expectorate but this has not been confirmed in other studies. Although, both the selected sputum and the entire expectorate methods have the same ability to distinguish asthmatics or bronchitics from healthy subjects, they are not interchangeable, and, once a technique has been adopted for a given study, it should always be applied

Through the looking GLASS: HST spectroscopy of faint galaxies lensed by the Frontier Fields cluster MACS0717.5+3745

The Grism Lens-Amplified Survey from Space (GLASS) is a Hubble Space Telescope (HST) Large Program, which will obtain 140 orbits of grism spectroscopy of the core and infall regions of 10 galaxy clusters, selected to be among the very best cosmic telescopes. Extensive HST imaging is available from many sources including the CLASH and Frontier Fields programs. We introduce the survey by analyzing spectra of faint multiply-imaged galaxies and $z\gtrsim6$ galaxy candidates obtained from the first seven orbits out of fourteen targeting the core of the Frontier Fields cluster MACS0717.5+3745. Using the G102 and G141 grisms to cover the wavelength range 0.8-1.7$\mu$m, we confirm 4 strongly lensed systems by detecting emission lines in each of the images. For the 9 $z\gtrsim6$ galaxy candidates clear from contamination, we do not detect any emission lines down to a seven-orbit 1$\sigma$ noise level of $\sim$5$\times$10$^{-18}$erg s$^{-1}$cm$^{-2}$. Taking lensing magnification into account, our flux sensitivity reaches $\sim$0.2-5$\times$10$^{-18}$erg s$^{-1}$cm$^{-2}$. These limits over an uninterrupted wavelength range rule out the possibility that the high-$z$ galaxy candidates are instead strong line emitters at lower redshift. These results show that by means of careful modeling of the background - and with the assistance of lensing magnification - interesting flux limits can be reached for large numbers of objects, avoiding pre-selection and the wavelength restrictions inherent to ground-based multi-slit spectroscopy. These observations confirm the power of slitless HST spectroscopy even in fields as crowded as a cluster core.Comment: Accepted by ApJ letters, 8 pages, 4 figures, GLASS website at http://glass.physics.ucsb.ed

The Grism Lens-Amplified Survey from Space (GLASS). I. Survey overview and first data release

We give an overview of the Grism Lens Amplified Survey from Space (GLASS), a large Hubble Space Telescope program aimed at obtaining grism spectroscopy of the fields of ten massive clusters of galaxies at redshift z=0.308-0.686, including the Hubble Frontier Fields (HFF). The Wide Field Camera 3 yields near infrared spectra of the cluster cores, covering the wavelength range 0.81-1.69mum through grisms G102 and G141, while the Advanced Camera for Surveys in parallel mode provides G800L spectra of the infall regions of the clusters. The WFC3 spectra are taken at two almost orthogonal position angles in order to minimize the effects of confusion. After summarizing the scientific drivers of GLASS, we describe the sample selection as well as the observing strategy and data processing pipeline. We then utilize MACSJ0717.5+3745, a HFF cluster and the first one observed by GLASS, to illustrate the data quality and the high-level data products. Each spectrum brighter than H_AB=23 is visually inspected by at least two co-authors and a redshift is measured when sufficient information is present in the spectra. Furthermore, we conducted a thorough search for emission lines through all the GLASS WFC3 spectra with the aim of measuring redshifts for sources with continuum fainter than H_AB=23. We provide a catalog of 139 emission-line based spectroscopic redshifts for extragalactic sources, including three new redshifts of multiple image systems (one probable, two tentative). In addition to the data itself we also release software tools that are helpful to navigate the data.Comment: ApJ in press. GLASS data available at https://archive.stsci.edu/prepds/glass/ . More info on GLASS available at http://glass.physics.ucsb.edu

Extreme AGN Feedback and Cool Core Destruction in the X-ray Luminous Galaxy Cluster MACS J1931.8-2634

We report on a deep, multiwavelength study of the galaxy cluster MACS J1931.8-2634 using Chandra X-ray, Subaru optical, and VLA 1.4 GHz radio data. This cluster (z=0.352) harbors one of the most X-ray luminous cool cores yet discovered, with an equivalent mass cooling rate within the central 50 kpc is approximately 700 solar masses/yr. Unique features observed in the central core of MACSJ1931.8-2634 hint to a wealth of past activity that has greatly disrupted the original cool core. We observe a spiral of relatively cool, dense, X-ray emitting gas connected to the cool core, as well as highly elongated intracluster light (ICL) surrounding the cD galaxy. Extended radio emission is observed surrounding the central AGN, elongated in the east-west direction, spatially coincident with X-ray cavities. The power input required to inflate these `bubbles' is estimated from both the X-ray and radio emission to reside between 4 and 14e45 erg/s, putting it among the most powerful jets ever observed. This combination of a powerful AGN outburst and bulk motion of the cool core have resulted in two X-ray bright ridges to form to the north and south of the central AGN at a distance of approximately 25 kpc. The northern ridge has spectral characteristics typical of cool cores and is consistent with being a remnant of the cool core after it was disrupted by the AGN and bulk motions. It is also the site of H-alpha filaments and young stars. The X-ray spectroscopic cooling rate associated with this ridge is approximately 165 solar masses/yr, which agrees with the estimate of the star formation rate from broad-band optical imaging (170 solar masses/yr). MACS J1931.8-2634 appears to harbor one of most profoundly disrupted low entropy cores observed in a cluster, and offers new insights into the survivability of cool cores in the context of hierarchical structure formation.Comment: 19 pages, 15 figures, 5 tables. Accepted by MNRAS for publication September 30 201

Deja Vu All Over Again: The Reappearance of Supernova Refsdal

In Hubble Space Telescope (HST) imaging taken on 2014 November 10, four images of supernova (SN) "Refsdal" (redshift z = 1.49) appeared in an Einstein-cross-like configuration (images S1–S4) around an early-type galaxy in the cluster MACS J1149.5+2223 (z = 0.54). Almost all lens models of the cluster have predicted that the SN should reappear within a year in a second host-galaxy image created by the cluster's potential. In HST observations taken on 2015 December 11, we find a new source at the predicted position of the new image of SN Refsdal approximately $8^{\prime\prime}$ from the previous images S1–S4. This marks the first time the appearance of a SN at a particular time and location in the sky was successfully predicted in advance! We use these data and the light curve from the first four observed images of SN Refsdal to place constraints on the relative time delay and magnification of the new image (SX) compared to images S1–S4. This enables us, for the first time, to test "blind" lens model predictions of both magnifications and time delays for a lensed SN. We find that the timing and brightness of the new image are consistent with the blind predictions of a fraction of the models. The reappearance illustrates the discriminatory power of this blind test and its utility to uncover sources of systematic uncertainty. From planned HST photometry, we expect to reach a precision of 1%–2% on the time delay between S1–S4 and SX

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Multiple images of a highly magnified supernova formed by an early-type cluster galaxy lens

In 1964, Refsdal hypothesized that a supernova whose light traversed multiple paths around a strong gravitational lens could be used to measure the rate of cosmic expansion. We report the discovery of such a system. In Hubble Space Telescope imaging, we have found four images of a single supernova forming an Einstein cross configuration around a redshift z = 0.54 elliptical galaxy in the MACS J1149.6+2223 cluster. The cluster's gravitational potential also creates multiple images of the z = 1.49 spiral supernova host galaxy, and a future appearance of the supernova elsewhere in the cluster field is expected. The magnifications and staggered arrivals of the supernova images probe the cosmic expansion rate, as well as the distribution of matter in the galaxy and cluster lenses

Measurement of the t(t)over-bar production cross section in the dilepton channel in pp collisions at √s=8 TeV

The top-antitop quark (t (t) over bar) production cross section is measured in proton-proton collisions at root s = 8 TeV with the CMS experiment at the LHC, using a data sample corresponding to an integrated luminosity of 5.3 fb(-1). The measurement is performed by analysing events with a pair of electrons or muons, or one electron and one muon, and at least two jets, one of which is identified as originating from hadronisation of a bottom quark. The measured cross section is 239 +/- 2 (stat.) +/- 11 (syst.) +/- 6 (lum.) pb, for an assumed top-quark mass of 172.5 GeV, in agreement with the prediction of the standard model