The ancient phosphatidylinositol 3-kinase signaling system is a master regulator of energy and carbon metabolism in algae

Algae undergo a complete metabolic transformation under stress by arresting cell growth, inducing autophagy and hyperaccumulating biofuel precursors such as triacylglycerols and starch. However, the regulatory mechanisms behind this stress-induced transformation are still unclear. Here, we use biochemical, mutational, and “omics” approaches to demonstrate that PI3K signaling mediates the homeostasis of energy molecules and influences carbon metabolism in algae. In Chlamydomonas reinhardtii, the inhibition and knockdown (KD) of algal class III PI3K led to significantly decreased cell growth, altered cell morphology, and higher lipid and starch contents. Lipid profiling of wild-type and PI3K KD lines showed significantly reduced membrane lipid breakdown under nitrogen starvation (-N) in the KD. RNA-seq and network analyses showed that under -N conditions, the KD line carried out lipogenesis rather than lipid hydrolysis by initiating de novo fatty acid biosynthesis, which was supported by tricarboxylic acid cycle down-regulation and via acetyl-CoA synthesis from glycolysis. Remarkably, autophagic responses did not have primacy over inositide signaling in algae, unlike in mammals and vascular plants. The mutant displayed a fundamental shift in intracellular energy flux, analogous to that in tumor cells. The high free fatty acid levels and reduced mitochondrial ATP generation led to decreased cell viability. These results indicate that the PI3K signal transduction pathway is the metabolic gatekeeper restraining biofuel yields, thus maintaining fitness and viability under stress in algae. This study demonstrates the existence of homeostasis between starch and lipid synthesis controlled by lipid signaling in algae and expands our understanding of such processes, with biotechnological and evolutionary implications.Ministry of Science, ICT and Future Planning 2015M3A6A2065697Ministry of Oceans and Fisheries 2015018

Observation of an alternative χc0(2P)\chi_{c0}(2P) candidate in e+e−→J/ψDDˉe^+ e^- \rightarrow J/\psi D \bar{D}

We perform a full amplitude analysis of the process $e^+ e^- \rightarrow J/\psi D \bar{D}$, where $D$ refers to either $D^0$ or $D^+$. A new charmoniumlike state $X^*(3860)$ that decays to $D \bar{D}$ is observed with a significance of $6.5\sigma$. Its mass is ($3862^{+26}_{-32}{}^{+40}_{-13}$) MeV/$c^2$ and width is ($201^{+154}_{-67}{}^{+88}_{-82}$) MeV. The $J^{PC}=0^{++}$ hypothesis is favored over the $2^{++}$ hypothesis at the level of $2.5\sigma$. The analysis is based on the 980 $\mathrm{fb}^{-1}$ data sample collected by the Belle detector at the asymmetric-energy $e^+ e^-$ collider KEKB.Comment: 17 pages, 11 figure

Measurement of the τ\tau lepton polarization and R(D∗)R(D^*) in the decay Bˉ→D∗τ−νˉτ\bar{B} \to D^* \tau^- \bar{\nu}_\tau

We report the first measurement of the $\tau$ lepton polarization $P_\tau(D^*)$ in the decay $\bar{B} \rightarrow D^* \tau^- \bar{\nu}_\tau$ as well as a new measurement of the ratio of the branching fractions $R(D^{*}) = \mathcal{B}(\bar {B} \rightarrow D^* \tau^- \bar{\nu}_\tau) / \mathcal{B}(\bar{B} \rightarrow D^* \ell^- \bar{\nu}_\ell)$, where $\ell^-$ denotes an electron or a muon, and the $\tau$ is reconstructed in the modes $\tau^- \rightarrow \pi^- \nu_\tau$ and $\tau^- \rightarrow \rho^- \nu_\tau$. We use the full data sample of $772 \times 10^6$ $B{\bar B}$ pairs recorded with the Belle detector at the KEKB electron-positron collider. Our results, $P_\tau(D^*) = -0.38 \pm 0.51 {\rm (stat.)} ^{+0.21}_{-0.16} {\rm (syst.)}$ and $R(D^*) = 0.270 \pm 0.035{\rm (stat.)} ^{+0.028}_{-0.025}{\rm (syst.)}$, are consistent with the theoretical predictions of the Standard Model.Comment: 7 pages, 2 figures, submitted to Physical Review Letters; one figure was removed from the first versio

Measurement of eta_c(1S), eta_c(2S) and non-resonant eta' pi+ pi- production via two-photon collisions

We report the measurement of gamma gamma to eta_c(1S), eta_c(2S) to eta' pi+ pi- with eta' decays to gamma rho and eta pi+ pi- using 941 fb^{-1} of data collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. The eta_c(1S) mass and width are measured to be M = [2984.6\pm0.7 (stat.)\pm2.2 (syst.)] MeV/c^{2} and \Gamma = [30.8^{+2.3}_{-2.2}~(stat.) \pm 2.5~(syst.)] MeV, respectively. First observation of eta_c(2S) to eta' pi+ pi- with a significance of 5.5sigma including systematic error is obtained, and the eta_c(2S) mass is measured to be M = [3635.1\pm3.7~(stat.)\pm2.9~(syst.)] MeV/c^{2}. The products of the two-photon decay width and branching fraction (B) of decays to eta'pi+ pi- are determined to be \Gamma_{gamma gamma}B = [65.4\pm2.6~(stat.)\pm6.9~(syst.)] eV for eta_c(1S) and [5.6^{+1.2}_{-1.1}~(stat.)\pm1.1~(syst.)] eV for eta_c(2S). A new decay mode for the eta_c(1S) to eta'f_0(2080) with f_0(2080) to pi+ pi- is observed with a statistical significance of 20sigma. The f_0(2080) mass and width are determined to be M = [2083^{+63}_{-66}~(stat.)\pm 32~(syst.)] MeV/c^{2} and \Gamma = [178^{+60}_{-178}~(stat.) \pm 55~(syst.)] MeV. The cross sections for gamma gamma to eta' pi+ pi- and eta'f_{2}(1270) are measured for the first time.Comment: 19 pages, 14 figure

Inclusive study of bottomonium production in association with an η\eta meson in e+e−e^+e^- annihilations near Υ(5S)\Upsilon(5S)

We study bottomonium production in association with an $\eta$ meson in $e^+e^-$ annihilations near the $\Upsilon(5S)$, at a center of mass energy of $\sqrt{s}=10.866\,$GeV. The results are based on the $121.4\,$fb$^{-1}$ data sample collected by the Belle experiment at the asymmetric energy KEKB collider. Only the $\eta$ meson is reconstructed and the missing-mass spectrum of $\eta$ candidates is investigated. We observe the $e^+e^-\to\eta\Upsilon_J(1D)$ process and find evidence for the $e^+e^-\to\eta\Upsilon(2S)$ process, while no significant signals of $\Upsilon(1S)$, $h_b(1P)$, nor $h_b(2P)$ are found. Cross sections for the studied processes are reported.Comment: Submitted to EPJ-

KAI1 suppresses HIF-1α and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer

<p>Abstract</p> <p>Background</p> <p>KAI1 was initially identified as a metastasis-suppressor gene in prostate cancer. It is a member of the tetraspan transmembrane superfamily (TM4SF) of membrane glycoproteins. As part of a tetraspanin-enriched microdomain (TEM), KAI1 inhibits tumor metastasis by negative regulation of Src. However, the underlying regulatory mechanism has not yet been fully elucidated. CUB-domain-containing protein 1 (CDCP1), which was previously known as tetraspanin-interacting protein in TEM, promoted metastasis via enhancement of Src activity. To better understand how KAI1 is involved in the negative regulation of Src, we here examined the function of KAI1 in CDCP1-mediated Src kinase activation and the consequences of this process, focusing on HIF-1 α and VEGF expression.</p> <p>Methods</p> <p>We used the human prostate cancer cell line PC3 which was devoid of KAI1 expression. Vector-transfected cells (PC3-GFP clone #8) and KAI1-expressing PC3 clones (PC3-KAI1 clone #5 and #6) were picked after stable transfection with KAI1 cDNA and selection in 800 <it>μ</it>g/ml G418. Protein levels were assessed by immunoblotting and VEGF reporter gene activity was measured by assaying luciferase activitiy. We followed tumor growth <it>in vivo </it>and immunohistochemistry was performed for detection of HIF-1, CDCP1, and VHL protein level.</p> <p>Results</p> <p>We demonstrated that Hypoxia-inducible factor 1α (HIF-1α) and VEGF expression were significantly inhibited by restoration of KAI1 in PC3 cells. In response to KAI1 expression, CDCP1-enhanced Src activation was down-regulated and the level of von Hippel-Lindau (VHL) protein was significantly increased. In an <it>in vivo </it>xenograft model, KAI1 inhibited the expression of CDCP1 and HIF-1α.</p> <p>Conclusions</p> <p>These novel observations may indicate that KAI1 exerts profound metastasis-suppressor activity in the tumor malignancy process via inhibition of CDCP1-mediated Src activation, followed by VHL-induced HIF-1α degradation and, ultimately, decreased VEGF expression.</p

Measurement of the CKM Matrix Element ∣Vcb∣|V_{cb}| from B0→D∗−ℓ+νℓB^{0} \to D^{*-} \ell^+ \nu_\ell at Belle

We present a new measurement of the CKM matrix element $|V_{cb}|$ from $B^{0} \to D^{*-} \ell^+ \nu_\ell$ decays, reconstructed with the full Belle data set of $711 \, \rm fb^{-1}$ integrated luminosity. Two form factor parameterizations, originally conceived by the Caprini-Lellouch-Neubert (CLN) and the Boyd, Grinstein and Lebed (BGL) groups, are used to extract the product $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}|$ and the decay form factors, where $\mathcal{F}(1)$ is the normalization factor and $\eta_{\rm EW}$ is a small electroweak correction. In the CLN parameterization we find $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}| = (35.06 \pm 0.15 \pm 0.56) \times 10^{-3}$, $\rho^{2}=1.106 \pm 0.031 \pm 0.007$, $R_{1}(1)=1.229 \pm 0.028 \pm 0.009$, $R_{2}(1)=0.852 \pm 0.021 \pm 0.006$. For the BGL parameterization we obtain $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}|= (34.93 \pm 0.23 \pm 0.59)\times 10^{-3}$, which is consistent with the World Average when correcting for $\mathcal{F}(1)\eta_{\rm EW}$. The branching fraction of $B^{0} \to D^{*-} \ell^+ \nu_\ell$ is measured to be $\mathcal{B}(B^{0}\rightarrow D^{*-}\ell^{+}\nu_{\ell}) = (4.90 \pm 0.02 \pm 0.16)\%$. We also present a new test of lepton flavor universality violation in semileptonic $B$ decays, $\frac{{\cal B }(B^0 \to D^{*-} e^+ \nu)}{{\cal B }(B^0 \to D^{*-} \mu^+ \nu)} = 1.01 \pm 0.01 \pm 0.03~$. The errors correspond to the statistical and systematic uncertainties respectively. This is the most precise measurement of $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}|$ and form factors to date and the first experimental study of the BGL form factor parameterization in an experimental measurement

Search for CPCP violation in the D+→π+π0D^{+}\to\pi^{+}\pi^{0} decay at Belle

We search for $CP$ violation in the charged charm meson decay $D^{+}\to\pi^{+}\pi^{0}$, based on a data sample corresponding to an integrated luminosity of $\rm 921~fb^{-1}$ collected by the Belle experiment at the KEKB $e^{+}e^{-}$ asymmetric-energy collider. The measured $CP$ violating asymmetry is $[+2.31\pm1.24({\rm stat})\pm0.23({\rm syst})]\%$, which is consistent with the standard model prediction and has a significantly improved precision compared to previous results.Comment: 8 pages, 3 figure

p-Glycoprotein ABCB5 and YB-1 expression plays a role in increased heterogeneity of breast cancer cells: correlations with cell fusion and doxorubicin resistance

<p>Abstract</p> <p>Background</p> <p>Cancer cells recurrently develop into acquired resistance to the administered drugs. The iatrogenic mechanisms of induced chemotherapy-resistance remain elusive and the degree of drug resistance did not exclusively correlate with reductions of drug accumulation, suggesting that drug resistance may involve additional mechanisms. Our aim is to define the potential targets, that makes drug-sensitive MCF-7 breast cancer cells turn to drug-resistant, for the anti-cancer drug development against drug resistant breast cancer cells.</p> <p>Methods</p> <p>Doxorubicin resistant human breast MCF-7 clones were generated. The doxorubicin-induced cell fusion events were examined. Heterokaryons were identified and sorted by FACS. In the development of doxorubicin resistance, cell-fusion associated genes, from the previous results of microarray, were verified using dot blot array and quantitative RT-PCR. The doxorubicin-induced expression patterns of pro-survival and pro-apoptotic genes were validated.</p> <p>Results</p> <p>YB-1 and ABCB5 were up regulated in the doxorubicin treated MCF-7 cells that resulted in certain degree of genomic instability that accompanied by the drug resistance phenotype. Cell fusion increased diversity within the cell population and doxorubicin resistant MCF-7 cells emerged probably through clonal selection. Most of the drug resistant hybrid cells were anchorage independent. But some of the anchorage dependent MCF-7 cells exhibited several unique morphological appearances suggesting minor population of the fused cells maybe de-differentiated and have progenitor cell like characteristics.</p> <p>Conclusion</p> <p>Our work provides valuable insight into the drug induced cell fusion event and outcome, and suggests YB-1, GST, ABCB5 and ERK3 could be potential targets for the anti-cancer drug development against drug resistant breast cancer cells. Especially, the ERK-3 serine/threonine kinase is specifically up-regulated in the resistant cells and known to be susceptible to synthetic antagonists.</p

Measurement of the Decays B→ηℓνℓ\boldsymbol{B\to\eta\ell\nu_\ell} and B→η′ℓνℓ\boldsymbol{B\to\eta^\prime\ell\nu_\ell} in Fully Reconstructed Events at Belle

We report branching fraction measurements of the decays $B^+\to\eta\ell^+\nu_\ell$ and $B^+\to\eta^\prime\ell^+\nu_\ell$ based on 711~fb$^{-1}$ of data collected near the $\Upsilon(4S)$ resonance with the Belle experiment at the KEKB asymmetric-energy $e^+e^-$ collider. This data sample contains 772 million $B\bar B$~events. One of the two $B$~mesons is fully reconstructed in a hadronic decay mode. Among the remaining ("signal-$B$") daughters, we search for the $\eta$~meson in two decay channels, $\eta\to\gamma\gamma$ and $\eta\to\pi^+\pi^-\pi^0$, and reconstruct the $\eta^{\prime}$~meson in $\eta^\prime\to\eta\pi^+\pi^-$ with subsequent decay of the $\eta$ into $\gamma\gamma$. Combining the two $\eta$ modes and using an extended maximum likelihood, the $B^+\to\eta\ell^+\nu_\ell$ branching fraction is measured to be $(4.2\pm 1.1 (\rm stat.)\pm 0.3 (\rm syst.))\times 10^{-5}$. For $B^+\to\eta^\prime\ell^+\nu_\ell$, we observe no significant signal and set an upper limit of $0.72\times 10^{-4}$ at 90\% confidence level.Comment: 8 pages, 4 figure