omega --> pi0 gamma* and phi --> pi0 gamma* Transition form factors in dispersion theory

We calculate the omega --> pi0 gamma* and phi --> pi0 gamma* electromagnetic transition form factors based on dispersion theory, relying solely on a previous dispersive analysis of the corresponding three-pion decays and the pion vector form factor. We compare our findings to recent measurements of the omega --> pi0 mu+ mu- decay spectrum by the NA60 collaboration, and strongly encourage experimental investigation of the Okubo-Zweig-Iizuka-forbidden phi --> pi0 l+ l- decays in order to understand the strong deviations from vector-meson dominance found in these transition form factors.Comment: 11 pages, 8 figures; references updated, version published in Phys. Rev.

EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies

In 2009, two groups independently linked human mutations in the inwardly rectifying K+ channel Kir4.1 (gene name KCNJ10) to a syndrome affecting the central nervous system (CNS), hearing, and renal tubular salt reabsorption. The autosomal recessive syndrome has been named EAST (epilepsy, ataxia, sensorineural deafness, and renal tubulopathy) or SeSAME syndrome (seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance), accordingly. Renal dysfunction in EAST/SeSAME patients results in loss of Na+, K+, and Mg2+ with urine, activation of the renin–angiotensin–aldosterone system, and hypokalemic metabolic alkalosis. Kir4.1 is highly expressed in affected organs: the CNS, inner ear, and kidney. In the kidney, it mostly forms heteromeric channels with Kir5.1 (KCNJ16). Biallelic loss-of-function mutations of Kir5.1 can also have disease significance, but the clinical symptoms differ substantially from those of EAST/SeSAME syndrome: although sensorineural hearing loss and hypokalemia are replicated, there is no alkalosis, but rather acidosis of variable severity; in contrast to EAST/SeSAME syndrome, the CNS is unaffected. This review provides a framework for understanding some of these differences and will guide the reader through the growing literature on Kir4.1 and Kir5.1, discussing the complex disease mechanisms and the variable expression of disease symptoms from a molecular and systems physiology perspective. Knowledge of the pathophysiology of these diseases and their multifaceted clinical spectrum is an important prerequisite for making the correct diagnosis and forms the basis for personalized therapies

Determinants of anion-proton coupling in mammalian endosomal CLC proteins.

Many proteins of the CLC gene family are Cl(-) channels, whereas others, like the bacterial ecClC-1 or mammalian ClC-4 and -5, mediate Cl(-)/H(+) exchange. Mutating a "gating glutamate" (Glu-224 in ClC-4 and Glu-211 in ClC-5) converted these exchangers into anion conductances, as did the neutralization of another, intracellular "proton glutamate" in ecClC-1. We show here that neutralizing the proton glutamate of ClC-4 (Glu-281) and ClC-5 (Glu-268), but not replacing it with aspartate, histidine, or tyrosine, rather abolished Cl(-) and H(+) transport. Surface expression was unchanged by these mutations. Uncoupled Cl(-) transport could be restored in the ClC-4(E281A) and ClC-5(E268A) proton glutamate mutations by additionally neutralizing the gating glutamates, suggesting that wild type proteins transport anions only when protons are supplied through a cytoplasmic H(+) donor. Each monomeric unit of the dimeric protein was found to be able to carry out Cl(-)/H(+) exchange independently from the transport activity of the neighboring subunit. NO(3)(-) or SCN(-) transport was partially uncoupled from H(+) countertransport but still depended on the proton glutamate. Inserting proton glutamates into CLC channels altered their gating but failed to convert them into Cl(-)/H(+) exchangers. Noise analysis indicated that ClC-5 switches between silent and transporting states with an apparent unitary conductance of 0.5 picosiemens. Our results are consistent with the idea that Cl(-)/H(+) exchange of the endosomal ClC-4 and -5 proteins relies on proton delivery from an intracellular titratable residue at position 268 (numbering of ClC-5) and that the strong rectification of currents arises from the voltage-dependent proton transfer from Glu-268 to Glu-211

Search for the 3He-eta bound state at COSY-11

We have measured excitation function for dp -> ppp_pi- reaction near the eta production threshold. We observe an enhancement of the counting rate above the threshold which can originate from the production of the eta meson in the reaction dp -> 3He eta and its subsequent absorption on neutron in the 3He nucleus leading to creation of the p_pi- pair.Comment: Presented at 10th International Workshop on Meson Production, Properties and Interaction (MESON 2008), Cracow, Poland, 6 - 10 June 2008, 4 pages, 4 figures,references adde

Determination of the total width of the eta' meson

Taking advantage of both the low-emittance proton-beam of the Cooler Synchrotron COSY and the high momentum precision of the COSY-11 detector system, the mass distribution of the eta' meson was measured with a resolution of 0.33 MeV/c^2 (FWHM), improving the experimental mass resolution by almost an order of magnitude with respect to previous results. Based on the sample of more than 2300 reconstructed pp --> pp eta' events the total width of the eta' meson was determined to be 0.226 +- 0.017(stat.) +- 0.014(syst.) MeV/c^2.Comment: 4 pages, 4 figure

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

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