A Missense Mutation in Canine CLN6 in an Australian Shepherd with Neuronal Ceroid Lipofuscinosis

The childhood neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases that are progressive and ultimately fatal. An Australian Shepherd that exhibited a progressive neurological disorder with signs similar to human NCL was evaluated. The cerebral cortex, cerebellum, and retina were found to contain massive accumulations of autofluorescent inclusions characteristic of the NCLs. Nucleotide sequence analysis of DNA from the affected dog identified a T to C variant (c.829T>C) in exon 7 of CLN6. Mutations in the human ortholog underlie a late-infantile form of NCL in humans. The T-to-C transition results in a tryptophan to arginine amino acid change in the predicted protein sequence. Tryptophans occur at homologous positions in the CLN6 proteins from all 13 other vertebrates evaluated. The c.829T>C transition is a strong candidate for the causative mutation in this NCL-affected dog. Dogs with this mutation could serve as a model for the analogous human disorder

Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function

Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor γ chain (γc), which is mutated in humans with X-linked severe combined immunodeficiency. We now report that IL-21 synergistically acts with IL-15 to potently promote the proliferation of both memory (CD44high) and naive (CD44low) phenotype CD8+ T cells and augment interferon-γ production in vitro. IL-21 also cooperated, albeit more weakly, with IL-7, but not with IL-2. Correspondingly, the expansion and cytotoxicity of CD8+ T cells were impaired in IL-21R−/− mice. Moreover, in vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas. Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15

Systems signatures reveal unique remission-path of Type 2 diabetes following Roux-en-Y gastric bypass surgery

Roux-en-Y Gastric bypass surgery (RYGB) is emerging as a powerful tool for treatment of obesity and may also cause remission of type 2 diabetes. However, the molecular mechanism of RYGB leading to diabetes remission independent of weight loss remains elusive. In this study, we profiled plasma metabolites and proteins of 10 normal glucose-tolerant obese (NO) and 9 diabetic obese (DO) patients before and 1-week, 3-months, 1-year after RYGB. 146 proteins and 128 metabolites from both NO and DO groups at all four stages were selected for further analysis. By analyzing a set of bi-molecular associations among the corresponding network of the subjects with our newly developed computational method, we defined the represented physiological states (called the edge-states that reflect the interactions among the bio-molecules), and the related molecular networks of NO and DO patients, respectively. The principal component analyses (PCA) revealed that the edge states of the post-RYGB NO subjects were significantly different from those of the post-RYGB DO patients. Particularly, the time-dependent changes of the molecular hub-networks differed between DO and NO groups after RYGB. In conclusion, by developing molecular network-based systems signatures, we for the first time reveal that RYGB generates a unique path for diabetes remission independent of weight loss

Measurements of the observed cross sections for exclusive light hadron production in e^+e^- annihilation at \sqrt{s}= 3.773 and 3.650 GeV

By analyzing the data sets of 17.3 pb$^{-1}$ taken at $\sqrt{s}=3.773$ GeV and 6.5 pb$^{-1}$ taken at $\sqrt{s}=3.650$ GeV with the BESII detector at the BEPC collider, we have measured the observed cross sections for 12 exclusive light hadron final states produced in $e^+e^-$ annihilation at the two energy points. We have also set the upper limits on the observed cross sections and the branching fractions for $\psi(3770)$ decay to these final states at 90% C.L.Comment: 8 pages, 5 figur

Observation of a near-threshold enhancement in the \omega\phi mass spectrum from the doubly OZI suppressed decay J/\psi \to \gamma \omega \phi

An enhancement near threshold is observed in the \omega \phi invariant mass spectrum from the doubly OZI suppressed decays of J/\psi \to \gamma \omega \phi, based on a sample of 5.8 X 10^7 J/\psi events collected with the BESII detector. A partial wave analysis shows that this enhancement favors J^P = 0^+, and its mass and width are M = 1812^{+19}_{-26} (stat) +- 18 (syst) MeV/c^2 and \Gamma = 105+-20 (stat) +- 28$(syst) MeV/c^2. The product branching fraction is determined to be B(J/\psi\to \gamma X) B(X\to\omega\phi) = (2.61 +- 0.27 (stat) +- 0.65$ (syst)) X 10^{-4}.Comment: Accepted by PRL, the version to be appeared in PR

Experimental study of ψ(2S)\psi(2S) decays to \K^+ K^- \pi^+ \pi^- \pi^0 final states

$K^+K^-\pi^+\pi^-\pi^0$ final states are studied using a sample of $14\times10^6$ $\psi(2S)$ decays collected with the Beijing Spectrometer (BESII) at the Beijing Electron-Position Collider. The branching fractions of $\psi(2S)$ decays to $K^+K^-\pi^+\pi^-\pi^0$, $\omega K^+ K^-$, $\omega f_0(1710)$, $K^{\ast}(892)^0 K^- \pi^+\pi^0+c.c.$, $K^{\ast}(892)^{+} K^- \pi^+\pi^- +c.c.$, $K^{\ast}(892)^{+} K^- \rho^0+c.c.$ and $K^{\ast}(892)^0 K^-\rho^+ + c.c.$ are determined. The first two agree with previous measurements, and the last five are first measurements.Comment: 19 pages, 9 figure

First observation of ψ(2S)→pnˉπ−+c.c.\psi(2S) \to p \bar{n} \pi^- +c.c.

Using 14 million $\psi(2S)$ events collected with the Beijing Spectrometer (BESII) at the Beijing Electron-Positron Collider, the branching fractions of $\psi(2S)$ decays to $p \bar{n} \pi^-$ and $\bar{p} n \pi^+$ and the branching fractions of the main background channels $\psi(2S) \to p \bar{n} \pi^-\pi^0$, $\psi(2S) \to \gamma\chi_{c0} \to \gamma p \bar{n} \pi^-$, $\psi(2S) \to \gamma\chi_{c2} \to \gamma p \bar{n} \pi^-$, and $\psi(2S) \to \gamma \chi_{cJ} \to \gamma p \bar{n} \pi^- \pi^0$ are determined. The contributions of the $N^{\ast}$ resonances in $\psi(2S) \to p \bar{n} \pi^- +c.c.$ are also discussed.Comment: 19 pages, 8 figures, add vertex requirement systematic erro

Search for psi(3770)\ra\rho\pi at the BESII detector at the Beijing Electron-Positron Collider

Non-$D\bar{D}$ decay \psppto \rhopi is searched for using a data sample of $(17.3\pm 0.5) pb^{-1}$ taken at the center-of-mass energy of 3.773 GeV by the BESII detector at the BEPC. No \rhopi signal is observed, and the upper limit of the cross section is measured to be \sigma(\EETO \rhopi)<6.0 pb at 90% C. L. Considering the interference between the continuum amplitude and the \pspp resonance amplitude, the branching fraction of \pspp decays to $\rho\pi$ is determined to be \BR(\pspp\ra\rho\pi)\in(6.0\times10^{-6}, 2.4\times10^{-3}) at 90% C. L. This is in agreement with the prediction of the $S$- and $D$-wave mixing scheme of the charmonium states for solving the ``\rhopi puzzle'' between \jpsi and \psp decays.Comment: 15 pages, 5 figure

Measurements of the observed cross sections for e+e−→e^+e^-\to exclusive light hadrons containing π0π0\pi^0\pi^0 at s=3.773\sqrt s= 3.773, 3.650 and 3.6648 GeV

By analyzing the data sets of 17.3, 6.5 and 1.0 pb$^{-1}$ taken, respectively, at $\sqrt s= 3.773$, 3.650 and 3.6648 GeV with the BES-II detector at the BEPC collider, we measure the observed cross sections for $e^+e^-\to \pi^+\pi^-\pi^0\pi^0$, $K^+K^-\pi^0\pi^0$, $2(\pi^+\pi^-\pi^0)$, $K^+K^-\pi^+\pi^-\pi^0\pi^0$ and $3(\pi^+\pi^-)\pi^0\pi^0$ at the three energy points. Based on these cross sections we set the upper limits on the observed cross sections and the branching fractions for $\psi(3770)$ decay into these final states at 90% C.L..Comment: 7 pages, 2 figure

Partial Wave Analysis of χc0→π+π−K+K−\chi_{c0}\to\pi^+\pi^-K^+K^-

A partial wave analysis of $\chi_{c0}\to\pi^+\pi^-K^+K^-$ in $\psi(2S)\to\gamma\chi_{c0}$ decay is presented using a sample of 14 million $\psi(2S)$ events accumulated by the BES II detector. The data are fitted to the sum of relativistic covariant tensor amplitudes for intermediate resonant decay modes. From the fit, significant contributions to $\chi_{c0}$ decays from the channels $f_0(980)f_0(980)$, $f_0(980)f_0(2200)$, $f_0(1370)f_0(1710)$, $K^*(892)^0\bar K^*(892)^0$, $K^*_0(1430)\bar K^*_0(1430)$, $K^*_0(1430)\bar K^*_2(1430) + c.c.$, and $K_1(1270)K$ are found. Flavor-SU(3)-violating $K_1(1270)-K_1(1400)$ asymmetry is observed. Values obtained for the masses and widths of the resonances $f_0(1710)$, $f_0(2200)$, $f_0(1370)$, and $K^*_0(1430)$ are presented.Comment: 16 pages, 9 figures, and 4 table