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The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.
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OBJECTIVE: During infection, metabolism and immunity react dynamically to promote survival through mechanisms that remain unclear. Pro-opiomelanocortin (POMC) cleavage products are produced and released in the brain and in the pituitary gland. One POMC cleavage product, alpha-melanocyte-stimulating hormone (α-MSH), is known to regulate food intake and energy expenditure and has anti-inflammatory effects. However, it is not known whether α-MSH is required to regulate physiological anti-inflammatory responses. We recently developed a novel mouse model with a targeted mutation in Pomc (Pomctm1/tm1 mice) to block production of all α-MSH forms which are required to regulate metabolism. To test whether endogenous α-MSH is required to regulate immune responses, we compared acute bacterial lipopolysaccharide (LPS)-induced inflammation between Pomctm1/tm1 and wild-type Pomcwt/wt mice. METHODS: We challenged 10- to 14-week-old male Pomctm1/tm1 and Pomcwt/wt mice with single i.p. injections of either saline or low-dose LPS (100 µg/kg) and monitored immune and metabolic responses. We used telemetry to measure core body temperature (Tb), ELISA to measure circulating cytokines, corticosterone and α-MSH, and metabolic chambers to measure body weight, food intake, activity, and respiration. We also developed a mass spectrometry method to measure three forms of α-MSH produced in the mouse hypothalamus and pituitary gland. RESULTS: LPS induced an exaggerated immune response in Pomctm1/tm1 compared to Pomcwt/wt mice. Both groups of mice were hypoactive and hypothermic following LPS administration, but Pomctm1/tm1 mice were significantly more hypothermic compared to control mice injected with LPS. Pomctm1/tm1 mice also had reduced oxygen consumption and impaired metabolic responses to LPS compared to controls. Pomctm1/tm1 mice had increased levels of key proinflammatory cytokines at 2 h and 4 h post LPS injection compared to Pomcwt/wt mice. Lastly, Pomcwt/wt mice injected with LPS compared to saline had increased total α-MSH in circulation 2 h post injection. CONCLUSIONS: Our data indicate endogenous α-MSH contributes to the inflammatory immune responses triggered by low-dose LPS administration and suggest that targeting the melanocortin system could be a potential therapeutic for the treatment of sepsis or inflammatory disease.
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Inflamação , Lipopolissacarídeos , Pró-Opiomelanocortina , alfa-MSH , Animais , alfa-MSH/metabolismo , alfa-MSH/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Masculino , Pró-Opiomelanocortina/metabolismo , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Corticosterona/metabolismo , Corticosterona/sangueRESUMO
AIMS/HYPOTHESIS: Type 2 diabetes mellitus is associated with reduced incretin effects. Although previous studies have shown that hyperglycaemia contributes to impaired incretin responses in beta cells, it is largely unknown how hyperlipidaemia, another feature of type 2 diabetes, contributes to impaired glucagon-like peptide 1 (GLP-1) response. Here, we investigated the effects of NEFA on incretin receptor signalling and examined the glucose-lowering efficacy of incretin-based drugs in combination with the lipid-lowering agent bezafibrate. METHODS: We used db/db mice to examine the in vivo efficacy of the treatment. Beta cell lines and mouse islets were used to examine GLP-1 and glucose-dependent insulinotropic peptide receptor signalling. RESULTS: Palmitate treatment decreased Glp1r expression in rodent insulinoma cell lines and isolated islets. This was associated with impairment of the following: GLP-1-stimulated cAMP production, phosphorylation of cAMP-responsive elements binding protein (CREB) and insulin secretion. In insulinoma cell lines, the expression of exogenous Glp1r restored cAMP production and the phosphorylation of CREB. Treatment with bezafibrate in combination with des-fluoro-sitagliptin or exendin-4 led to more robust glycaemic control, associated with improved islet morphology and beta cell mass in db/db mice. CONCLUSIONS/INTERPRETATION: Elevated NEFA contributes to impaired responsiveness to GLP-1, partially through downregulation of GLP-1 receptor signalling. Improvements in lipid control in mouse models of obesity and diabetes increase the efficacy of incretin-based therapy.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Incretinas/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Receptores de Glucagon/metabolismo , Animais , Receptor do Peptídeo Semelhante ao Glucagon 1 , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
With a sample of (225.2±2.8)×10(6) J/ψ events registered in the BESIII detector, J/ψâγπ(+)π(-)η(') is studied using two η(') decay modes: η(')âπ(+)π(-)η and η(')âγρ(0). The X(1835), which was previously observed by BESII, is confirmed with a statistical significance that is larger than 20σ. In addition, in the π(+)π(-)η(') invariant-mass spectrum, the X(2120) and the X(2370), are observed with statistical significances larger than 7.2σ and 6.4σ, respectively. For the X(1835), the angular distribution of the radiative photon is consistent with expectations for a pseudoscalar.
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Using (106±4)×10â»6 ψ(3686) events accumulated with the BESIII detector at the BEPCII eâºeâ» collider, we present the first measurement of decays of χ(c1) to vector meson pairs φφ, ωω, and ωφ. The branching fractions are measured to be (4.4±0.3±0.5)×10â»4, (6.0±0.3±0.7)×10â»4, and (2.2±0.6±0.2)×10â»5, for χ(c1)âφφ, ωω, and ωφ, respectively, which indicates that the hadron helicity selection rule is significantly violated in χ(cJ) decays. In addition, the measurement of χ(cJ)âωφ provides the first indication of the rate of doubly OZI-suppressed χ(cJ) decay. Finally, we present improved measurements for the branching fractions of χ(c0) and χ(c2) to vector meson pairs.
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We present results of a study of the decay J/ψ â ωηπ+ π- using a sample of (225.2 ± 2.8) × 10(6) J/ψ events collected by the BESIII detector, and report the observation of a new process J/ψ â ωX(1870) with a statistical significance of 7.2σ, in which X(1870) decays to a(0)(±)(980)π±. Fitting to ηπ+ π- mass spectrum yields a mass M = 1877.3 ± 6.3(stat)(-7.4)(+3.4)(syst) MeV/c(2), a width Γ = 57 ± 12(stat)(-4)(+19)(syst) MeV/c(2), and a product branching fraction B(J/ψ â ωX) × B(Xâa(0)(±)(980)π±) × B(a(0) (±)(980) â ηπ±) = [1.50 ± 0.26(stat)(-0.36)(+0.72) (syst)] × 10(-4). Signals for J/ψ â ωf(1)(1285) and J/ψ â ω η(1405) are also clearly observed and measured.
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The decays ψ'âγπ(0), γη and γη' are studied using data collected with the BESIII detector at the BEPCII e(+)e(-) collider. The processes ψ'âγπ(0) and ψ'âγη are observed for the first time with signal significances of 4.6σ and 4.3σ, respectively. The branching fractions are determined to be B(ψ'âγπ(0))=(1.58±0.40±0.13)×10(-6), B(ψ'âγη)=(1.38±0.48±0.09)×10(-6), and B(ψ'âγη')=(126±3±8)×10(-6), where the first errors are statistical and the second ones systematic.
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The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.