Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery

Isospin dependence of the eta prime meson production in nucleon-nucleon collisions

A comparison of the close-to-threshold total cross section for the eta prime production in pp --> pp eta prime and pn --> pn eta prime reactions constitutes a tool to investigate the eta prime meson structure and the reaction mechanism in the channels of isospin I=0 and I=1 and may provide insight into the flavour-singlet (perhaps also into gluonium) content of the eta prime meson. In this contribution we present preliminary results of measurement of the quasi-free production of the eta prime meson in the proton-neutron collisions conducted using the COSY-11 facility.Comment: Presented at 10th International Workshop on Meson Production, Properties and Interaction (MESON 2008), Cracow, Poland, 6 - 10 June 200

Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates

In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF1) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a−/− zebrafish mutant, pinotage (pnttq209), which lacks one of the two IF1 paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1−/− mice thus confirming a regulatory axis, which interlinks IF1 and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF1 and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development

Precision measurement of σ(e+e−→π+π−γ)/σ(e+e−→μ+μ−γ)\sigma(e^+e^-\rightarrow\pi^+\pi^-\gamma)/\sigma(e^+e^-\rightarrow \mu^+\mu^-\gamma) and determination of the π+π−\pi^+\pi^- contribution to the muon anomaly with the KLOE detector

We have measured the ratio $\sigma(e^+e^-\rightarrow\pi^+\pi^-\gamma)/\sigma(e^+e^-\rightarrow \mu^+\mu^-\gamma)$, with the KLOE detector at DA$\Phi$NE for a total integrated luminosity of $\sim$ 240 pb$^{-1}$. From this ratio we obtain the cross section $\sigma(e^+e^-\rightarrow\pi^+\pi^-)$. From the cross section we determine the pion form factor $|F_\pi|^2$ and the two-pion contribution to the muon anomaly $a_\mu$ for $0.592<M_{\pi\pi}<0.975$ GeV, $\Delta^{\pi\pi} a_\mu$= $({\rm 385.1\pm1.1_{stat}\pm2.7_{sys+theo}})\times10^{-10}$. This result confirms the current discrepancy between the Standard Model calculation and the experimental measurement of the muon anomaly.Comment: 18 pages, 8 figures, minor text corrections, one table added, version to appear on Physics Letters

A new limit on the CP violating decay KS -> 3pi0 with the KLOE experiment

We have carried out a new direct search for the CP violating decay KS -> 3pi0 with 1.7 fb^-1 of e+e- collisions collected by the KLOE detector at the phi-factory DAFNE. We have searched for this decay in a sample of about 5.9 x 10^8 KS KL events tagging the KS by means of the KL interaction in the calorimeter and requiring six prompt photons. With respect to our previous search, the analysis has been improved by increasing of a factor four the tagged sample and by a more effective background rejection of fake KS tags and spurious clusters. We find no candidates in data and simulated background samples, while we expect 0.12 standard model events. Normalizing to the number of KS -> 2pi0 events in the same sample, we set the upper limit on BR(KS -> 3pi0 < 2.6 x 10^-8 at 90% C.L., five times lower than the previous limit. We also set the upper limit on the eta_000 parameter, |eta_000 | < 0.0088 at 90% C.L., improving by a factor two the latest direct measurement.Comment: Accepted for publication in Physics Letters B (15 pages, 13 figures

Measurement of {\eta} meson production in {\gamma}{\gamma} interactions and {\Gamma}({\eta}-->{\gamma}{\gamma}) with the KLOE detector

We present a measurement of {\eta} meson production in photon-photon interactions produced by electron-positron beams colliding with \sqrt{s}=1 GeV. The measurement is done with the KLOE detector at the \phi-factory DA{\Phi}NE with an integrated luminosity of 0.24 fb^{-1}. The e^+e^- --> e^+e^-{\eta} cross section is measured without detecting the outgoing electron and positron, selecting the decays {\eta}-->{\pi}^+{\pi}^-{\pi}^0 and {\eta}-->{\pi}^0{\pi}^0{\pi}^0. The most relevant background is due to e^+e^- --> {\eta}{\gamma} when the monochromatic photon escapes detection. The cross section for this process is measured as {\sigma}(e^+e^- -->{\eta}{\gamma}) = (856 \pm 8_{stat} \pm 16_{syst}) pb. The combined result for the e^+e^- -->e^+e^-{\eta} cross section is {\sigma}(e^+e^- -->e^+e^-{\eta}) = (32.72 \pm 1.27_{stat} \pm 0.70_{syst}) pb. From this we derive the partial width {\Gamma}({\eta}-->{\gamma}{\gamma}) = (520 \pm 20_{stat} \pm 13_{syst}) eV. This is in agreement with the world average and is the most precise measurement to date.Comment: Version accepted by JHE

Proposal for taking data with the KLOE-2 detector at the DAΦ\PhiNE collider upgraded in energy

This document reviews the physics program of the KLOE-2 detector at DA$\Phi$NE upgraded in energy and provides a simple solution to run the collider above the $\phi$-peak (up to 2, possibly 2.5 GeV). It is shown how a precise measurement of the multihadronic cross section in the energy region up to 2 (possibly 2.5) GeV would have a major impact on the tests of the Standard Model through a precise determination of the anomalous magnetic moment of the muon and the effective fine-structure constant at the $M_Z$ scale. With a luminosity of about $10^{32}$cm$^{-2}$s$^{-1}$, DA$\Phi$NE upgraded in energy can perform a scan in the region from 1 to 2.5 GeV in one year by collecting an integrated luminosity of 20 pb$^{-1}$ (corresponding to a few days of data taking) for single point, assuming an energy step of 25 MeV. A few years of data taking in this region would provide important tests of QCD and effective theories by $\gamma\gamma$ physics with open thresholds for pseudo-scalar (like the $\eta'$), scalar ($f_0,f'_0$, etc...) and axial-vector ($a_1$, etc...) mesons; vector-mesons spectroscopy and baryon form factors; tests of CVC and searches for exotics. In the final part of the document a technical solution for the energy upgrade of DA$\Phi$NE is proposed.Comment: 19 pages, 8 figure

KLOE results in kaon physics and prospects for KLOE-2

The phi-factory DAPHNE offers a possibility to select pure kaon beams, charged and neutral ones. In particular, neutral kaons from phi->KS KL are produced in pairs and the detection of a KS (KL) tags the presence of a KL (KS). This allows to perform precise measurements of kaon properties by means of KLOE detector. Another advantage of a phi-factory consists in fact that the neutral kaon pairs are produced in a pure quantum state (J^(PC) = 1^(--)), which allowsto investigate CP and CPT symmetries via quantum interference effects, as well as the basic principles of quantum mechanics.A review of the most recent results of the KLOE experiment at DAPHNE using pure kaon beams or via quantum interferometry is presented together with prospects for kaon physics at KLOE-2.Comment: 5 pages, 4 figures, From Phi To Psi 2011 conference, to be published in Nuclear Physics B (Proceedings Supplements