Discovery of the First-in-Class GSK-3β/HDAC Dual Inhibitor as Disease-Modifying Agent to Combat Alzheimer's Disease

Several evidence pointed out the role of epigenetics in Alzheimer's disease (AD) revealing strictly relationships between epigenetic and "classical" AD targets. Based on the reported connection among histone deacetylases (HDACs) and glycogen synthase kinase 3β (GSK-3β), herein we present the discovery and the biochemical characterization of the first-in-class hit compound able to exert promising anti-AD effects by modulating the targeted proteins in the low micromolar range of concentration. Compound 11 induces an increase in histone acetylation and a reduction of tau phosphorylation. It is nontoxic and protective against H 2 O 2 and 6-OHDA stimuli in SH-SY5Y and in CGN cell lines, respectively. Moreover, it promotes neurogenesis and displays immunomodulatory effects. Compound 11 shows no lethality in a wt-zebrafish model (<100 μM) and high water solubility

Il sistema agro-alimentare dell’Emilia-Romagna, Rapporto 2014

Il Rapporto 2014 sul Sistema Agroalimentare dell'Emilia-Romagna rappresenta un importante contributo alla conoscenza di un settore fondamentale dell'economia regionale, un utile strumento per gli operatori e una guida per le politiche degli enti locali. Il Rapporto si apre con due capitoli che descrivono da un lato, lo scenario internazionale e, dall'altro le politiche comunitarie e nazionali, per il settore agroalimentare, che modificano lo scenario nel quale gli operatori saranno chiamati a muoversi dal 2014 al 2020. I principali cambiamenti congiunturali del sistema agroalimentare regionale occupano la parte central del Rapporto, con Quattro capitol dedicati all'agricoltura. Successivamente vengono affrontati gli altri aspetti rilevanti del sistema agro-alimentare regionale partendo dall'industria alimentare, con le dinamiche congiunturali e alcuni approfondimenti strutturali dell'occupazione

Measurement of the polarization of the Xi0 (anti-Xi0) hyperon beam by the NA48/1 experiment

A total of 368415 Xi(0) --> Lambda Xi(0) and 31 171 (Xi(0)) over bar --> (Lambda) over bar pi(0) were selected from data recorded in the NA48/1 experiment during 2002 data taking. From this sample, the polarization of Xi(0) and (Xi(0)) over bar hyperons was measured to be P(Xi 0) = -0.102 +/- 0.012(stat) +/- 0.008(syst) and P((Xi 0) over bar) = -0.01 +/- 0.04(stat) 0.008(syst). The dependence of P(Xi 0) on the Xi(0) transverse momentum with respect to the primary proton beam is also presented. With the same data sample. the ratio of (Xi(0)) over bar and Xi(0) fluxes in proton collisions at 400 GeV/c oil a beryllium target was measure

Search for heavy neutrinos in K+→μ+νμK^+ \rightarrow \mu^+ \nu_{\mu} decays

International audienceThe NA62 experiment recorded a large sample of K+→μ+νμ decays in 2007. A peak search has been performed in the reconstructed missing mass spectrum. In the absence of a signal, limits in the range 2×10−6 to 10−5 have been set on the squared mixing matrix element |Uμ4|2 between muon and heavy neutrino states, for heavy neutrino masses in the range 300–375 MeV/ c2 . The result extends the range of masses for which upper limits have been set on the value of |Uμ4|2 in previous production search experiments

Determination of the relative decay rate KS -> πeν / KL -> πeν

The decay rate of K-S -> pi ev relative to the rate of K-L -> pi rev has been measured by the NA48 Collaboration in a neutral kaon beam originating from 400 GeV proton-Be interactions at the CERN SPS. The result is 0.993 +/- 0.026(stat) +/- 0.022(syst), compatible with I in agreement with the Standard Model prediction at tree level. It implies B R (K-S -> pi ev) = (7.05 +/- 0.18(stat) +/- 0.16(syst)) X 10(-4)

New high statistics measurement of K-e4 decay form factors and pi pi scattering phase shifts

We report results from a new measurement of the K-e4 decay K-+/- -> pi(+)pi(-)e(+/-)nu by the NA48/2 collaboration at the CERN SPS, based on a partial sample of more than 670 000 K-e4 decays in both charged modes collected in 2003. The form factors of the hadronic current (F,G,H) and pi pi phase difference (delta=delta(s)-delta(p)) have been measured in ten independent bins of the pi pi mass spectrum to investigate their variation. A sizeable acceptance at large pi pi mass, a low background and a very good resolution contribute to an improved experimental accuracy, a factor two better than in the previous measurement, when extracting the pi pi scattering lengths a(0) (0) and a(0) (2). Under the assumption of isospin symmetry and using numerical solutions of the Roy equations, the following values are obtained in the plane (a(0) (0),a(0) (2)): a(0) (0)=0.233 +/- 0.016(stat)+/- 0.007(syst),a(0) (2)=-0.0471 +/- 0.011(stat)+/- 0.004syst. The presence of potentially large isospin effects is also considered and will allow comparison with precise predictions from Chiral Perturbation Theory

First observation and study of the K±→π0π0μ±νK^{\pm} \rightarrow \pi^{0} \pi^{0} \mu^{\pm} \nu decay

The NA48/2 experiment at CERN reports the first observation of the $K^{\pm} \rightarrow \pi^{0} \pi^{0} \mu^{\pm} \nu$ decay based on a sample of 2437 candidates with 15% background contamination collected in 2003-2004. The decay branching ratio in the kinematic region of the squared dilepton mass above $0.03$~GeV$^2/c^4$ is measured to be $(0.65 \pm 0.03) \times 10^{-6}$. The extrapolation to the full kinematic space, using a specific model, is found to be $(3.45 \pm 0.17) \times 10^{-6}$, in agreement with chiral perturbation theory predictions

Measurement of the form factors of charged kaon semileptonic decays

International audienceA measurement of the form factors of charged kaon semileptonic decays is presented, based on 4.4 × 10$^{6}$K$^{±}$ → π$^{0}$e$^{±}$ν$_{e}$ (K$_{e3}^{±}$ ) and 2.3 × 10$^{6}$K$^{±}$ → π$^{0}$μ±ν$_{μ}$ (K$_{μ3}^{±}$ ) decays collected in 2004 by the NA48/2 experiment. The results are obtained with improved precision as compared to earlier measurements. The combination of measurements in the K$_{e3}^{±}$ and K$_{μ3}^{±}$ modes is also presented

First observation and study of the K±→π0π0μ±νK^{\pm} \rightarrow \pi^{0} \pi^{0} \mu^{\pm} \nu decay

International audienceThe NA48/2 experiment at CERN reports the first observation of the K$^{±}$ → π$^{0}$π$^{0}$μ$^{±}$ν decay based on a sample of 2437 candidates with 15% background contamination collected in 2003–2004. The decay branching ratio in the kinematic region of the squared dilepton mass above 0.03 GeV$^{2}$/c$^{4}$ is measured to be (0.65 ± 0.03) × 10$^{−6}$. The extrapolation to the full kinematic space, using a specific model, is found to be (3.45 ± 0.16) × 10$^{−6}$, in agreement with chiral perturbation theory predictions