77 research outputs found

    A Combination of Nutriments Improves Mitochondrial Biogenesis and Function in Skeletal Muscle of Type 2 Diabetic Goto–Kakizaki Rats

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    BACKGROUND: Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA), and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-alpha (Ppar alpha), peroxisome proliferator-activated receptor-delta (Ppar delta), and carnitine palmitoyl transferase-1 (Mcpt-1) and activity of mitochondrial complex I and II in skeletal muscle. All of these effects of mitochondrial nutrients are comparable to that of the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain. CONCLUSIONS/SIGNIFICANCE: These data suggest that a combination of mitochondrial targeting nutrients may improve skeletal mitochondrial dysfunction and exert hypoglycemic effects, without causing weight gain

    Uncoupling Protein-4 (UCP4) Increases ATP Supply by Interacting with Mitochondrial Complex II in Neuroblastoma Cells

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    Mitochondrial uncoupling protein-4 (UCP4) protects against Complex I deficiency as induced by 1-methyl-4-phenylpyridinium (MPP+), but how UCP4 affects mitochondrial function is unclear. Here we investigated how UCP4 affects mitochondrial bioenergetics in SH-SY5Y cells. Cells stably overexpressing UCP4 exhibited higher oxygen consumption (10.1%, p<0.01), with 20% greater proton leak than vector controls (p<0.01). Increased ATP supply was observed in UCP4-overexpressing cells compared to controls (p<0.05). Although state 4 and state 3 respiration rates of UCP4-overexpressing and control cells were similar, Complex II activity in UCP4-overexpressing cells was 30% higher (p<0.05), associated with protein binding between UCP4 and Complex II, but not that of either Complex I or IV. Mitochondrial ADP consumption by succinate-induced respiration was 26% higher in UCP4-overexpressing cells, with 20% higher ADP:O ratio (p<0.05). ADP/ATP exchange rate was not altered by UCP4 overexpression, as shown by unchanged mitochondrial ADP uptake activity. UCP4 overexpression retained normal mitochondrial morphology in situ, with similar mitochondrial membrane potential compared to controls. Our findings elucidate how UCP4 overexpression increases ATP synthesis by specifically interacting with Complex II. This highlights a unique role of UCP4 as a potential regulatory target to modulate mitochondrial Complex II and ATP output in preserving existing neurons against energy crisis

    The PLATO 2.0 mission

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    PLATO 2.0 has recently been selected for ESA's M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s candence) providing a wide field-of-view (2232 deg 2) and a large photometric magnitude range (4-16 mag). It focusses on bright (4-11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4-10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2-3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e.g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmosphere. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA's Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science

    Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

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    This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

    Multi-messenger observations of a binary neutron star merger

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    On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

    First observation of a doubly charged tetraquark and its neutral partner

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    A combined amplitude analysis is performed for the decays B0→D‟0Ds+π−B^0 \rightarrow \overline{D}^0 D^+_s\pi^- and B+→D−Ds+π+B^+\rightarrow D^- D^+_s\pi^+, which are related by isospin symmetry. The analysis is based on data collected by the LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8 and 13 TeV\,\rm{TeV}. The full data sample corresponds to an integrated luminosity of 9 fb−1\,\rm{fb^{-1}}. Two new resonant states with masses of 2.908±0.011±0.020 GeV2.908\pm0.011\pm0.020\,\rm{GeV} and widths of 0.136±0.023±0.011 GeV0.136\pm0.023\pm0.011\,\rm{GeV} are observed, which decay to Ds+π+D^+_s\pi^+ and Ds+π−D^+_s\pi^- respectively. The former state indicates the first observation of a doubly charged open-charm tetraquark state with minimal quark content [csˉudˉ][c\bar{s}u\bar{d}], and the latter state is a neutral tetraquark composed of [csˉuˉd][c\bar{s}\bar{u}d] quarks. Both states are found to have spin-parity 0+0^+, and their resonant parameters are consistent with each other, which suggests that they belong to an isospin triplet.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-026.html (LHCb public pages

    Search for the doubly heavy baryon Ξbc+\it{\Xi}_{bc}^{+} decaying to J/ψΞc+J/\it{\psi} \it{\Xi}_{c}^{+}

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    A first search for the Ξbc+→J/ψΞc+\it{\Xi}_{bc}^{+}\to J/\it{\psi}\it{\Xi}_{c}^{+} decay is performed by the LHCb experiment with a data sample of proton-proton collisions, corresponding to an integrated luminosity of 9 fb−19\,\mathrm{fb}^{-1} recorded at centre-of-mass energies of 7, 8, and 13 TeV13\mathrm{\,Te\kern -0.1em V}. Two peaking structures are seen with a local (global) significance of 4.3 (2.8)4.3\,(2.8) and 4.1 (2.4)4.1\,(2.4) standard deviations at masses of 6571 MeV ⁣/c26571\,\mathrm{Me\kern -0.1em V\!/}c^2 and 6694 MeV ⁣/c26694\,\mathrm{Me\kern -0.1em V\!/}c^2, respectively. Upper limits are set on the Ξbc+\it{\Xi}_{bc}^{+} baryon production cross-section times the branching fraction relative to that of the Bc+→J/ψDs+B_{c}^{+}\to J/\it{\psi} D_{s}^{+} decay at centre-of-mass energies of 8 and 13 TeV13\mathrm{\,Te\kern -0.1em V}, in the Ξbc+\it{\Xi}_{bc}^{+} and in the Bc+B_{c}^{+} rapidity and transverse-momentum ranges from 2.0 to 4.5 and 0 to 20 GeV ⁣/c20\,\mathrm{Ge\kern -0.1em V\!/}c, respectively. Upper limits are presented as a function of the Ξbc+\it{\Xi}_{bc}^{+} mass and lifetime.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-005.html (LHCb public pages

    Amplitude analysis of B0→D‟0Ds+π−B^0 \rightarrow \overline{D}^0 D_s^+ \pi^- and B+→D−Ds+π+B^+ \rightarrow D^- D_s^+ \pi^+ decays

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    Resonant contributions in B0→D‟0Ds+π−B^0 \rightarrow \overline{D}^0 D^+_s\pi^- and B+→D−Ds+π+B^+\rightarrow D^- D^+_s\pi^+ decays are determined with an amplitude analysis, which is performed both separately and simultaneously, where in the latter case isospin symmetry between the decays is assumed. The analysis is based on data collected by the LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8 and 13 TeV\rm{TeV}. The full data sample corresponds to an integrated luminosity of 9 fb−1\rm fb^{-1}. A doubly charged spin-0 open-charm tetraquark candidate together with a neutral partner, both with masses near 2.9 GeV2.9\,\rm{GeV}, are observed in the DsπD_s\pi decay channel.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-027.html (LHCb public pages
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