Prion infection impairs cholesterol metabolism in neuronal cells

Conversion of prion protein (PrPC) into a pathological isoform (PrPSc) during prion infection occurs in lipid rafts and is dependent on cholesterol. Here, we show that prion infection increases the abundance of cholesterol transporter, ATP-binding cassette transporter type A1 (ATP-binding cassette transporter type A1), but reduces cholesterol efflux from neuronal cells leading to the accumulation of cellular cholesterol. Increased abundance of ABCA1 in prion disease was confirmed in prion-infected mice. Mechanistically, conversion of PrPC to the pathological isoform led to PrPSc accumulation in rafts, displacement of ABCA1 from rafts and the cell surface, and enhanced internalization of ABCA1. These effects were abolished with reversal of prion infection or by loading cells with cholesterol. Stimulation of ABCA1 expression with liver X receptor agonist or overexpression of heterologous ABCA1 reduced the conversion of prion protein into the pathological form upon infection. These findings demonstrate a reciprocal connection between prion infection and cellular cholesterol metabolism, which plays an important role in the pathogenesis of prion infection in neuronal cells

MicroRNA-223 coordinates cholesterol homeostasis

Results from this study represent a breakthrough in our understanding of posttranscriptional control of cholesterol metabolism and how microRNAs (miRNAs) are at the heart of cholesterol regulatory circuitry and homeostasis. Although cells are adept at maintaining proper cholesterol levels, it was unknown how cells posttranscriptionally coordinate cholesterol uptake, efflux, and synthesis. MicroRNA-223 (miR-223) transcription and expression are maintained by cholesterol, and, as a feedback network, miR-223 inhibits cholesterol biosynthesis and uptake and increases cholesterol efflux. This study clearly demonstrates the extensive role that miRNAs play in coordinating metabolic adaptation to disease and general homeostasis. This work highlights a unique regulatory control point for cholesterol homeostasis and illustrates how important the study of miRNAs is to the greater understanding of dyslipidemia and cardiovascular disease

First observations of hc→h_c \to hadrons

Based on $(4.48 \pm 0.03) \times 10^{8}$ $\psi(3686)$ events collected with the BESIII detector, five $h_c$ hadronic decays are searched for via process $\psi(3686) \to \pi^0 h_c$. Three of them, $h_c \to p \bar{p} \pi^+ \pi^-$, $\pi^+ \pi^- \pi^0$, and $2(\pi^+ \pi^-) \pi^0$ are observed for the first time, with statistical significances of 7.4$\sigma$, $4.9\sigma$, and 9.1$\sigma$, and branching fractions of $(2.89\pm0.32\pm0.55)\times10^{-3}$, $(1.60\pm0.40\pm0.32)\times10^{-3}$, and $(7.44\pm0.94\pm1.56)\times10^{-3}$, respectively, where the first uncertainties are statistical and the second systematic. No significant signal is observed for the other two decay modes, and the corresponding upper limits of the branching fractions are determined to be $B(h_c \to 3(\pi^+ \pi^-) \pi^0)<8.7\times10^{-3}$ and $B(h_c \to K^+ K^- \pi^+ \pi^-)<5.8\times10^{-4}$ at 90% confidence level.Comment: 17 pages, 16 figure

Search for the decay J/ψ→γ+invisibleJ/\psi\to\gamma + \rm {invisible}

We search for $J/\psi$ radiative decays into a weakly interacting neutral particle, namely an invisible particle, using the $J/\psi$ produced through the process $\psi(3686)\to\pi^+\pi^-J/\psi$ in a data sample of $(448.1\pm2.9)\times 10^6$ $\psi(3686)$ decays collected by the BESIII detector at BEPCII. No significant signal is observed. Using a modified frequentist method, upper limits on the branching fractions are set under different assumptions of invisible particle masses up to 1.2 $\mathrm{\ Ge\kern -0.1em V}/c^2$. The upper limit corresponding to an invisible particle with zero mass is 7.0$\times 10^{-7}$ at the 90\% confidence level

Measurements of Weak Decay Asymmetries of Λc+→pKS0\Lambda_c^+\to pK_S^0, Λπ+\Lambda\pi^+, Σ+π0\Sigma^+\pi^0, and Σ0π+\Sigma^0\pi^+

Using $e^+e^-\to\Lambda_c^+\bar\Lambda_c^-$ production from a 567 pb$^{-1}$ data sample collected by BESIII at 4.6 GeV, a full angular analysis is carried out simultaneously on the four decay modes of $\Lambda_c^+\to pK_S^0$, $\Lambda \pi^+$, $\Sigma^+\pi^0$, and $\Sigma^0\pi^+$. For the first time, the $\Lambda_c^+$ transverse polarization is studied in unpolarized $e^+e^-$ collisions, where a non-zero effect is observed with a statistical significance of 2.1$\sigma$. The decay asymmetry parameters of the $\Lambda_c^+$ weak hadronic decays into $pK_S^0$, $\Lambda\pi^+$, $\Sigma^+\pi^0$ and $\Sigma^0\pi^+$ are measured to be $0.18\pm0.43(\rm{stat})\pm0.14(\rm{syst})$, $-0.80\pm0.11(\rm{stat})\pm0.02(\rm{syst})$, $-0.57\pm0.10(\rm{stat})\pm0.07(\rm{syst})$, and $-0.73\pm0.17(\rm{stat})\pm0.07(\rm{syst})$, respectively. In comparison with previous results, the measurements for the $\Lambda\pi^+$ and $\Sigma^+\pi^0$ modes are consistent but with improved precision, while the parameters for the $pK_S^0$ and $\Sigma^0\pi^+$ modes are measured for the first time

Observation of a structure in e+e−→ϕη′e^+e^- \to \phi \eta^{\prime} at s\sqrt{s} from 2.05 to 3.08 GeV

The process $e^{+}e^{-} \to \phi \eta^{\prime}$ has been studied for the first time in detail using data sample collected with the BESIII detector at the BEPCII collider at center of mass energies from 2.05 to 3.08 GeV. A resonance with quantum numbers $J^{PC}=1^{--}$ is observed with mass $M$ = (2177.5 $\pm$ 4.8 (stat) $\pm$ 19.5 (syst)) MeV/${ \it{c}^{\mathrm{2}}}$ and width $\Gamma$ = (149.0 $\pm$ 15.6 (stat) $\pm$ 8.9 (syst)) MeV with a statistical significance larger than 10$\sigma$. The observed structure could be identified with the $\phi(2170)$, then the ratio of partial width between the $\phi \eta^{\prime}$ by BESIII and $\phi \eta$ by BABAR is ($\mathcal{B}^{R}_{\phi \eta}\Gamma^{R}_{ee})/{(\mathcal{B}^{R}_{\phi \eta^{\prime}}\Gamma^{R}_{ee})}$ = 0.23 $\pm$ 0.10 (stat) $\pm$ 0.18 (syst), which is smaller than the prediction of the $s\bar{s}g$ hybrid models by several orders of magnitude

Search for the reaction channel e+e−→ηcηπ+π− at center-of-mass energies from 4.23 to 4.60 GeV

Using data collected with the BESIII detector operating at the Beijing Electron Positron Collider, we search for the process e+e-→ηcηπ+π-. The search is performed using five large datasets recorded at center-of-mass energies of 4.23, 4.26, 4.36, 4.42, and 4.60 GeV. The ηc meson is reconstructed in 16 exclusive decay modes. No signal is observed in the ηc mass region at any center-of-mass energy. The upper limits on the reaction cross sections are determined to be 6.2, 10.8, 27.6, 22.6 and 23.7 pb at the 90% confidence level at the center-of-mass energies listed above

Model-independent determination of the relative strong-phase difference between D0D^0 and Dˉ0→KS,L0π+π−\bar{D}^0\rightarrow K^0_{S,L}\pi^+\pi^- and its impact on the measurement of the CKM angle γ/ϕ3\gamma/\phi_3

Crucial inputs for a variety of $CP$-violation studies can be determined through the analysis of pairs of quantum-entangled neutral $D$ mesons, which are produced in the decay of the $\psi(3770)$ resonance. The relative strong-phase parameters between $D^0$ and $\bar{D}^0$ in the decays $D^0\rightarrow K^0_{S,L}\pi^+\pi^-$ are studied using 2.93~${\rm fb}^{-1}$ of $e^+e^-$ annihilation data delivered by the BEPCII collider and collected by the BESIII detector at a center-of-mass energy of 3.773 GeV. Results are presented in regions of the phase space of the decay. These are the most precise measurements to date of the strong-phase parameters in $D \to K_{S,L}^0\pi^+\pi^-$ decays. Using these parameters, the associated uncertainty on the Cabibbo-Kobayashi-Maskawa angle $\gamma/\phi_3$ is expected to be between $0.7^\circ$ and $1.2^\circ$, for an analysis using the decay $B^{\pm}\rightarrow DK^{\pm}$, $D\rightarrow K^0_S\pi^+\pi^-$, where $D$ represents a superposition of $D^0$ and $\bar{D^0}$ states. This is a factor of three smaller than that achievable with previous measurements. Furthermore, these results provide valuable input for charm-mixing studies, other measurements of $CP$ violation, and the measurement of strong-phase parameters for other $D$-decay modes.Comment: 34 pages, 10 figure

Search for the decay Ds+→γe+νeD_s^+\rightarrow \gamma e^+\nu_e

A search for the rare radiative leptonic decay $D_s^+\to\gamma e^+\nu_e$ is performed for the first time using electron-positron collision data corresponding to an integrated luminosity of 3.19 fb$^{-1}$, collected with the BESIII detector at a center-of-mass energy of 4.178 GeV. No evidence for the $D_s^+\to\gamma e^+\nu_e$ decay is seen and an upper limit of $\mathcal B(D_s^+\to\gamma e^+\nu_e)<1.3\times 10^{-4}$ is set on the partial branching fraction at a 90\% confidence level for radiative photon energies $E_{\gamma}^*>0.01$~GeV.Comment: 9 pages, 7 figure