The epigenetic regulator Histone Deacetylase 1 promotes transcription of a core neurogenic programme in zebrafish embryos

<p>Abstract</p> <p>Background</p> <p>The epigenetic regulator Histone Deacetylase 1 (Hdac1) is required for specification and patterning of neurones and myelinating glia during development of the vertebrate central nervous system (CNS). This co-ordinating function for Hdac1 is evolutionarily conserved in zebrafish and mouse, but the mechanism of action of Hdac1 in the developing CNS is not well-understood.</p> <p>Results</p> <p>A genome-wide comparative analysis of the transcriptomes of Hdac1-deficient and wild-type zebrafish embryos was performed, which identified an extensive programme of gene expression that is regulated by Hdac1 in the developing embryo. Using time-resolved expression profiling of embryos, we then identified a small subset of 54 genes within the Hdac1-regulated transcriptome that specifically exhibit robust and sustained Hdac1-dependent expression from early neurogenesis onwards. 18 of these 54 stringently Hdac1-regulated genes encode DNA-binding transcription factors that are implicated in promoting neuronal specification and CNS patterning, including the proneural bHLH proteins Ascl1a and Ascl1b, as well as Neurod4 and Neurod. Relatively few genes are strongly repressed by Hdac1 but expression of the Notch target gene <it>her6 </it>is attenuated by Hdac1 in specific sub-regions of the developing CNS, from early stages of neurogenesis onwards. Selected members of the stringently Hdac1-regulated group of genes were tested for Hdac1 binding to their promoter-proximal <it>cis</it>-regulatory elements. Surprisingly, we found that Hdac1 is specifically and stably associated with DNA sequences within the promoter region of <it>ascl1b </it>during neurogenesis, and that this Hdac1-<it>ascl1b </it>interaction is abolished in <it>hdac1 </it>mutant embryos.</p> <p>Conclusions</p> <p>We conclude that Hdac1 regulates histone acetylation and methylation in the developing zebrafish embryo and promotes the sustained, co-ordinate transcription of a small set of transcription factor genes that control expansion and diversification of cell fates within the developing CNS. Our <it>in vivo </it>chromatin immunoprecipitation results also suggest a specific function for Hdac1 in directly regulating transcription of a key member of this group of genes, <it>ascl1b</it>, from the beginning of neurogenesis onwards. Taken together, our observations indicate a novel role for Hdac1 as a positive regulator of gene transcription during development of the vertebrate CNS, in addition to its more well-established function in transcriptional repression.</p

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-

Responsible management: Engaging moral reflexive practice through threshold concepts

YesIn this conceptual paper we argue that, to date, principles of responsible management have not impacted practice as anticipated because of a disconnect between knowledge and practice. This disconnect means that an awareness of ethical concerns, by itself, does not help students take personal responsibility for their actions. We suggest that an abstract knowledge of principles has to be supplemented by an engaged understanding of the responsibility of managers and leaders to actively challenge irresponsible practices. We argue that a form of moral reflexive practice drawing on an understanding of threshold concepts is central to responsible management, and provides a gateway to transformative learning. Our conceptual argument leads to implications for management and professional education

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

Measurement of the Branching Fraction of the Decay B+→π+π−ℓ+νℓ\boldsymbol{B^{+}\to\pi^{+}\pi^{-}\ell^{+}\nu_\ell} in Fully Reconstructed Events at Belle

We present an analysis of the exclusive $B^{+}\to\pi^{+}\pi^{-}\ell^{+}\nu_{\ell}$ decay, where $\ell$ represents an electron or a muon, with the assumption of charge-conjugation symmetry and lepton universality. The analysis uses the full $\Upsilon(4S)$ data sample collected by the Belle detector, corresponding to 711 fb$^{-1}$ of integrated luminosity. We select the events by fully reconstructing one $B$ meson in hadronic decay modes, subsequently determining the properties of the other $B$ meson. We extract the signal yields using a binned maximum-likelihood fit to the missing-mass squared distribution in bins of the invariant mass of the two pions or the momentum transfer squared. We measure a total branching fraction of ${{\cal B}(B^{+}\to \pi^{+}\pi^{-}\ell^{+}\nu_{\ell})= [22.7 ^{+1.9}_{-1.6} (\mathrm{stat}) \pm 3.5(\mathrm{syst}) ]\times 10^{-5}}$, where the uncertainties are statistical and systematic, respectively. This result is the first reported measurement of this decay.Comment: 23 pages, 19 figure

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

CsI(Tl) Pulse Shape Discrimination with the Belle II Electromagnetic Calorimeter as a Novel Method to Improve Particle Identification at Electron-Positron Colliders

This paper describes the implementation and performance of CsI(Tl) pulse shape discrimination for the Belle II electromagnetic calorimeter, representing the first application of CsI(Tl) pulse shape discrimination for particle identification at an electron-positron collider. The pulse shape characterization algorithms applied by the Belle II calorimeter are described. Control samples of $\gamma$, $\mu^+$, $\pi^\pm$, $K^\pm$ and $p/\bar{p}$ are used to demonstrate the significant insight into the secondary particle composition of calorimeter clusters that is provided by CsI(Tl) pulse shape discrimination. Comparisons with simulation are presented and provide further validation for newly developed CsI(Tl) scintillation response simulation techniques, which when incorporated with GEANT4 simulations allow the particle dependent scintillation response of CsI(Tl) to be modelled. Comparisons between data and simulation also demonstrate that pulse shape discrimination can be a new tool to identify sources of improvement in the simulation of hadronic interactions in materials. The $K_L^0$ efficiency and photon-as-hadron fake-rate of a multivariate classifier that is trained to use pulse shape discrimination is presented and comparisons are made to a shower-shape based approach. CsI(Tl) pulse shape discrimination is shown to reduce the photon-as-hadron fake-rate by over a factor of 3 at photon energies of 0.2 GeV and over a factor 10 at photon energies of 1 GeV

Search for B0 decays to invisible final states (+γ) at Belle

© 2020 authors. We report searches for B0→invisible and B0→invisible+γ decays, where the energy of the photon is required to be larger than 0.5 GeV. These results are obtained from a 711 fb-1 data sample that contains 772×106BB¯ pairs and was collected near the ϒ(4S) resonance with the Belle detector at the KEKB e+e- collider. We observe no significant signal for either decay and set upper limits on their branching fractions at 90% confidence level of B(B0→invisible)\u3c7.8×10-5 and B(B0→invisible+γ)\u3c1.6×10-5

Emergence of unusual human rotavirus strains in Salento, Italy, during 2006–2007

<p>Abstract</p> <p>Background</p> <p>In recent years, rotavirus genotyping by RT-PCR has provided valuable information about the diversity of rotaviruses (RV) circulating throughout the world.</p> <p>The purpose of the present study was to monitor the prevalence of the different G and P genotypes of rotaviruses circulating in Salento and detect any uncommon or novel types.</p> <p>Methods</p> <p>During the period from January 2006 to December 2007, a total of 243 rotavirus positive stool samples were collected from children with diarrhoea admitted to four Hospitals in the province of Lecce (Copertino, Galatina, Gallipoli and Tricase).</p> <p>All the specimens were tested for RV by real time PCR and genotyped for VP7 (G-type) and VP4 (P-type) gene by reverse transcription (RT) and multiplex PCR using different type specific primers.</p> <p>Results</p> <p>In course of this study we identified 4 common G&P combinations viz. G2P[8], G1P[8], G2P[4] and G9P[8] amongst 59.8% of the typeable rotavirus positives.</p> <p>Rotavirus G2P[8] was recognized as the most widespread genotype during the sentinel-based survey in Salento.</p> <p>The detection of other novel and unusual strains, such as G2P[10], G4P[10], G8P[4], G9P[11] and G10P[8] is noteworthy.</p> <p>Furthermore, a significant number of mixed infections were observed during the survey period but G3P[8] rotaviruses were not detected.</p> <p>Conclusion</p> <p>This study highlights the genetic diversity among rotaviruses isolated from children in Salento and the emergence of some novel strains. Therefore, it is highly essential to continuously monitor for these strains so as to assess the impact of vaccines on RV strains circulating in Salento and understand the effect of strain variation on efficacy of presently available vaccines.</p