Subjects With Early-Onset Type 2 Diabetes Show Defective Activation of the Skeletal Muscle PGC-1α/Mitofusin-2 Regulatory Pathway in Response to Physical Activity

Objective: Type 2 diabetes is associated with insulin resistance and skeletal muscle mitochondrial dysfunction. We have found that subjects with early-onset type 2 diabetes show incapacity to increase Vo2max in response to chronic exercise. This suggests a defect in muscle mitochondrial response to exercise. Here, we have explored the nature of the mechanisms involved. Research design and methods: Muscle biopsies were collected from young type 2 diabetic subjects and obese control subjects before and after acute or chronic exercise protocols, and the expression of genes and/or proteins relevant to mitochondrial function was measured. In particular, the regulatory pathway peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha/mitofusin-2 (Mfn2) was analyzed. Results: At baseline, subjects with diabetes showed reduced expression (by 26%) of the mitochondrial fusion protein Mfn2 and a 39% reduction of the alpha-subunit of ATP synthase. Porin expression was unchanged, consistent with normal mitochondrial mass. Chronic exercise led to a 2.8-fold increase in Mfn2, as well as increases in porin, and the alpha-subunit of ATP synthase in muscle from control subjects. However, Mfn2 was unchanged after chronic exercise in individuals with diabetes, whereas porin and alpha-subunit of ATP synthase were increased. Acute exercise caused a fourfold increase in PGC-1alpha expression in muscle from control subjects but not in subjects with diabetes. Conclusions: Our results demonstrate alterations in the regulatory pathway that controls PGC-1alpha expression and induction of Mfn2 in muscle from patients with early-onset type 2 diabetes. Patients with early-onset type 2 diabetes display abnormalities in the exercise-dependent pathway that regulates the expression of PGC-1alpha and Mfn2.</p

The Standard Model from a New Phase Transition on the Lattice

Several years ago it was conjectured in the so-called Roma Approach, that gauge fixing is an essential ingredient in the lattice formulation of chiral gauge theories. In this paper we discuss in detail how the gauge-fixing approach may be realized. As in the usual (gauge invariant) lattice formulation, the continuum limit corresponds to a gaussian fixed point, that now controls both the transversal and the longitudinal modes of the gauge field. A key role is played by a new phase transition separating a conventional Higgs or Higgs-confinement phase, from a phase with broken rotational invariance. In the continuum limit we expect to find a scaling region, where the lattice correlators reproduce the euclidean correlation functions of the target (chiral) gauge theory, in the corresponding continuum gauge.Comment: 16 pages, revtex, one figure. Clarifications made, mainly in sections 3 and 6 that deal with the fermion action, to appear in Phys Rev

Rhodococcus opacus B4: a promising bacterium for production of biofuels and biobased chemicals

Bacterial lipids have relevant applications in the production of renewable fuels and biobased oleochemicals. The genus Rhodococcus is one of the most relevant lipid producers due to its capability to accumulate those compounds, mainly triacylglycerols (TAG), when cultivated on different defined substrates, namely sugars, organic acids and hydrocarbons but also on complex carbon sources present in industrial wastes. In this work, the production of storage lipids by Rhodococcus opacus B4 using glucose, acetate and hexadecane is reported for the first time and its productivity compared with Rhodococcus opacus PD630, the best TAG producer bacterium reported. Both strains accumulated mainly TAG from all carbon sources, being influenced by the carbon source itself and by the duration of the accumulation period. R. opacus B4 produced 0.09 and 0.14 g L1 at 24 and 72 h, with hexadecane as carbon source, which was 2 and 3.3 fold higher than the volumetric production obtained by R. opacus PD630. Both strains presented similar fatty acids (FA) profiles in intact cells while in TAG produced fraction, R. opacus B4 revealed a higher variability in fatty acid composition than R. opacus PD630, when both strains were cultivated on hexadecane. The obtained results open new perspectives for the use of R. opacus B4 to produce TAG, in particular using oily (alkane-contaminated) waste and wastewater as cheap raw-materials. Combining TAG production with hydrocarbons degradation is a promising strategy to achieve environmental remediation while producing added value compounds.This work was financially supported by the Portuguese Science Foundation (FCT) and European Social Fund (ESF, POPH-QREN) through the Grant given to A.R. Castro (SFRH/BD/64500/2009), the FCT Strategic Project of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462)

The influence of statins on the free intracellular calcium concentration in human umbilical vein endothelial cells

BACKGROUND: Statins are cholesterol-lowering drugs that are widely used to reduce the risk of cardiac infarction. Their beneficial clinical effects, however, are not restricted to their influence on cholesterol production. As several studies have shown that they have a potency of relaxing blood vessels. METHODS: We measured the effects of statins on the intracellular free calcium concentration ([Ca(2+)](i)) in human umbilical vein endothelial cells (HUVEC) after acute application and 24-h-preincubation of statins. RESULTS: Incubation of the cells for 24 h with cerivastatin or fluvastatin significantly increased the resting [Ca(2+)](i). For cerivastatin this effect manifested at a concentration of 1 μM. Increase of resting [Ca(2+)](i )in the presence of cerivastatin also occurred when the nitric oxide synthase was inhibited. Transient Ca(2+ )release induced by histamine was not affected. CONCLUSIONS: The increase of resting [Ca(2+)](i )after incubation with cerivastatin or fluvastatin may provide an explanation for the direct effects of statins on the endothelial-dependent vasodilatation and restoration of endothelial activity in vivo

The 2HWC HAWC Observatory Gamma Ray Catalog

We present the first catalog of TeV gamma-ray sources realized with the recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the most sensitive wide field-of-view TeV telescope currently in operation, with a 1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an instantaneous field of view >1.5 sr and >90% duty cycle, it continuously surveys and monitors the sky for gamma ray energies between hundreds GeV and tens of TeV. HAWC is located in Mexico at a latitude of 19 degree North and was completed in March 2015. Here, we present the 2HWC catalog, which is the result of the first source search realized with the complete HAWC detector. Realized with 507 days of data and represents the most sensitive TeV survey to date for such a large fraction of the sky. A total of 39 sources were detected, with an expected contamination of 0.5 due to background fluctuation. Out of these sources, 16 are more than one degree away from any previously reported TeV source. The source list, including the position measurement, spectrum measurement, and uncertainties, is reported. Seven of the detected sources may be associated with pulsar wind nebulae, two with supernova remnants, two with blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa

Multiple thermochronometers applied to the quantitative analysis of compressive systems: The southern sub-Andean fold and thrust belt of Bolivia: From source rock to trap

The evolution of fold and thrust belts requires time data restrictions to determine the rates related to the interaction of surface and subsurface processes and to quantify the time relationship between the components of the petroleum system: reservoir, seal, source rock and trap. The sub-Andean fold-and-thrust belt in the Bolivian territory in general, and the regional transect that links the structures of Curuyuqui-Carohuaicho-Tatarenda-Borebigua-Charagua and Mandeyapecua in particular, constitutes a complex multi-variable system in which the definition of time-Temperature (t-T) trajectories has led to new suitable structural and stratigraphic conclusions. The integration of multiple thermochronological-geochronological systems (Apatite Fission Track, Apatite (U-Th-Sm)/He and UPb SHRIMP on zircon) and the existing surface and subsurface geological constraints made it possible to develop a chrono-kinematic characterization of fault-related anticlines, defining their formation chronology, structural growth rate and link between them in the study area. Furthermore, it was also possible to perform a quantitative analysis of the subsidence-burial and exhumation-erosion phenomena that occurred from the deposition of Silurian-Devonian source rocks to the present time, providing relevant determinations to the modeling of the Oil & Gas system.Fil: Hernandez, Juan I.. Geomap S.a.; ArgentinaFil: Hernández, Roberto M.. Geomap S.a.; ArgentinaFil: Dalenz Farjat, Alejandra. Geomap S.a.; ArgentinaFil: Cristallini, Ernesto Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Geología. Laboratorio de Modelado Geológico; ArgentinaFil: Alvarez, Luis A.. Geomap S.a.; ArgentinaFil: Dellmans, Luis M.. Geomap S.a.; ArgentinaFil: Costilla, Marcos Roberto. Geomap S.a.; ArgentinaFil: Alvarez, Andres F.. Geomap S.a.; ArgentinaFil: Becchio, Raul Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Bordese, Sofia. lA - Te Andes S.A. Laboratorio de Termocronología de Los Andes; ArgentinaFil: Arzadún, Guadalupe. lA - Te Andes S.A. Laboratorio de Termocronología de Los Andes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guibaldo, Cristina. lA - Te Andes S.A. Laboratorio de Termocronología de Los Andes; ArgentinaFil: Glasmacher, Ulrich A.. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Tomezzoli, Renata Nela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Stockli, Daniel F.. University of Texas; Estados UnidosFil: Fuentes, Facundo. YPF - Tecnología; ArgentinaFil: Soria Galvarro, Jaime. YPF - Tecnología; ArgentinaFil: Rosales, Adolfo. YPF - Tecnología; ArgentinaFil: Dzelalija, Francisco. YPF - Tecnología; ArgentinaFil: Haring, Claudio. YPF - Tecnología; Argentin

Daily monitoring of TeV gamma-ray emission from Mrk 421, Mrk 501, and the Crab Nebula with HAWC

We present results from daily monitoring of gamma rays in the energy range $\sim0.5$ to $\sim100$ TeV with the first 17 months of data from the High Altitude Water Cherenkov (HAWC) Observatory. Its wide field of view of 2 steradians and duty cycle of $>95$% are unique features compared to other TeV observatories that allow us to observe every source that transits over HAWC for up to $\sim6$ hours each sidereal day. This regular sampling yields unprecedented light curves from unbiased measurements that are independent of seasons or weather conditions. For the Crab Nebula as a reference source we find no variability in the TeV band. Our main focus is the study of the TeV blazars Markarian (Mrk) 421 and Mrk 501. A spectral fit for Mrk 421 yields a power law index $\Gamma=2.21 \pm0.14_{\mathrm{stat}}\pm0.20_{\mathrm{sys}}$ and an exponential cut-off $E_0=5.4 \pm 1.1_{\mathrm{stat}}\pm 1.0_{\mathrm{sys}}$ TeV. For Mrk 501, we find an index $\Gamma=1.60\pm 0.30_{\mathrm{stat}} \pm 0.20_{\mathrm{sys}}$ and exponential cut-off $E_0=5.7\pm 1.6_{\mathrm{stat}} \pm 1.0_{\mathrm{sys}}$ TeV. The light curves for both sources show clear variability and a Bayesian analysis is applied to identify changes between flux states. The highest per-transit fluxes observed from Mrk 421 exceed the Crab Nebula flux by a factor of approximately five. For Mrk 501, several transits show fluxes in excess of three times the Crab Nebula flux. In a comparison to lower energy gamma-ray and X-ray monitoring data with comparable sampling we cannot identify clear counterparts for the most significant flaring features observed by HAWC.Comment: 18 pages, 10 figures, accepted for publication in The Astrophysical Journa

The Sloan Digital Sky Survey Reverberation Mapping Project : the MBH–host relations at 0.2 ∼< z ∼< 0.6 from reverberation mapping and Hubble Space Telescope imaging

Funding: Y.S. acknowledges support from an Alfred P. Sloan Research Fellowship and NSF grants AST-1715579, AST-2009947. Support for Program number HST-GO-14109 was provided through a grant from the STScI under NASA contract NAS5-26555. L.C.H. was supported by the National Key R&D Program of China (2016YFA0400702) and the National Science Foundation of China (11721303, 11991052). E.D.B. is supported by Padua University grants DOR1715817/17, DOR1885254/18, and DOR1935272/19 and by MIUR grant PRIN 201720173ML3WW_001. J.V.H.S.and K.H. acknowledge funds from a Science and Technology Facilities Council grant ST/R000824/1.We present the results of a pilot Hubble Space Telescope (HST) imaging study of the host galaxies of ten quasars from the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project. Probing more than an order of magnitude in BH and stellar masses, our sample is the first statistical sample to study the BH-host correlations beyond z>0.3 with reliable BH masses from reverberation mapping rather than from single-epoch spectroscopy. We perform image decomposition in two HST bands (UVIS-F606W and IR-F110W) to measure host colors and estimate stellar masses using empirical relations between broad-band colors and the mass-to-light ratio. The stellar masses of our targets are mostly dominated by a bulge component. The BH masses and stellar masses of our sample broadly follow the same correlations found for local RM AGN and quiescent bulge-dominant galaxies, with no strong evidence of evolution in the MBH-M*bulge relation to z~0.6. We further compare the host light fraction from HST imaging decomposition to that estimated from spectral decomposition. We found a good correlation between the host fractions derived with both methods. However, the host fraction derived from spectral decomposition is systematically smaller than that from imaging decomposition by ~30%, indicating different systematics in both approaches. This study paves the way for upcoming more ambitious host galaxy studies of quasars with direct RM-based BH masses at high redshift.PostprintPeer reviewe

Constraining the pˉ/p\bar{p}/p Ratio in TeV Cosmic Rays with Observations of the Moon Shadow by HAWC

An indirect measurement of the antiproton flux in cosmic rays is possible as the particles undergo deflection by the geomagnetic field. This effect can be measured by studying the deficit in the flux, or shadow, created by the Moon as it absorbs cosmic rays that are headed towards the Earth. The shadow is displaced from the actual position of the Moon due to geomagnetic deflection, which is a function of the energy and charge of the cosmic rays. The displacement provides a natural tool for momentum/charge discrimination that can be used to study the composition of cosmic rays. Using 33 months of data comprising more than 80 billion cosmic rays measured by the High Altitude Water Cherenkov (HAWC) observatory, we have analyzed the Moon shadow to search for TeV antiprotons in cosmic rays. We present our first upper limits on the $\bar{p}/p$ fraction, which in the absence of any direct measurements, provide the tightest available constraints of $\sim1\%$ on the antiproton fraction for energies between 1 and 10 TeV.Comment: 10 pages, 5 figures. Accepted by Physical Review