400 research outputs found

    The Huntington's disease mutation impairs Huntingtin's role in the transport of NF-κB from the synapse to the nucleus

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    Expansion of a polyglutamine (polyQ) tract in the Huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Loss of the normal function of Htt is thought to be an important pathogenetic component of HD. However, the function of wild-type Htt is not well defined. Htt is thought to be a multifunctional protein that plays distinct roles in several biological processes, including synaptic transmission, intracellular transport and neuronal transcription. Here, we show with biochemical and live cell imaging studies that wild-type Htt stimulates the transport of nuclear factor κ light-chain-enhancer of activated B cells (NF-κB) out of dendritic spines (where NF-κB is activated by excitatory synaptic input) and supports a high level of active NF-κB in neuronal nuclei (where NF-κB stimulates the transcription of target genes). We show that this novel function of Htt is impaired by the polyQ expansion and thus may contribute to the etiology of HD

    Compton Scattering from the Deuteron and Extracted Neutron Polarizabilities

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    Differential cross sections for Compton scattering from the deuteron were measured at MAX-lab for incident photon energies of 55 MeV and 66 MeV at nominal laboratory angles of 4545^\circ, 125125^\circ, and 135135^\circ. Tagged photons were scattered from liquid deuterium and detected in three NaI spectrometers. By comparing the data with theoretical calculations in the framework of a one-boson-exchange potential model, the sum and difference of the isospin-averaged nucleon polarizabilities, αN+βN=17.4±3.7\alpha_N + \beta_N = 17.4 \pm 3.7 and αNβN=6.4±2.4\alpha_N - \beta_N = 6.4 \pm 2.4 (in units of 10410^{-4} fm3^3), have been determined. By combining the latter with the global-averaged value for αpβp\alpha_p - \beta_p and using the predictions of the Baldin sum rule for the sum of the nucleon polarizabilities, we have obtained values for the neutron electric and magnetic polarizabilities of αn=8.8±2.4\alpha_n= 8.8 \pm 2.4(total) ±3.0\pm 3.0(model) and βn=6.52.4\beta_n = 6.5 \mp 2.4(total) 3.0\mp 3.0(model), respectively.Comment: 4 pages, 2 figures, revtex. The text is substantially revised. The cross sections are slightly different due to improvements in the analysi

    Electromagnetic Polarizabilities of Nucleons bound in 40^{40}Ca, 16^{16}O and 4^4He

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    Differential cross sections for elastic scattering of photons have been measured for 40^{40}Ca at energies of 58 and 74 MeV and for 16^{16}O and 4^4He at 61 MeV, in the angular range from 45o^o to 150o^o. Evidence is obtained that there are no significant in-medium modifications of the electromagnetic polarizabilities except for those originating from meson exchange currents.Comment: 20 pages including 5 Figure

    Antimalarial drug artemether inhibits neuroinflammation in BV2 microglia through Nrf2-dependent mechanisms

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    Artemether, a lipid-soluble derivative of artemisinin has been reported to possess anti-inflammatory properties. In this study, we have investigated the molecular mechanisms involved in the inhibition of neuroinflammation by the drug. The effects of artemether on neuroinflammation-mediated HT22 neuronal toxicity were also investigated in a BV2 microglia/HT22 neuron co-culture. To investigate effects on neuroinflammation, we used LPS-stimulated BV2 microglia treated with artemether (5-40µM) for 24 hours. ELISAs and western blotting were used to detect pro inflammatory cytokines, nitric oxide, PGE2, iNOS, COX-2 and mPGES-1. BACE-1 activity and Aβ levels were measured with ELISA kits. Protein levels of targets in NF-kappaB and p38 MAPK signalling, as well as HO-1, NQO1 and Nrf2 were also measured with western blot. NF-kappaB binding to the DNA was investigated using EMSA. MTT, DNA fragmentation and ROS assays in BV2-HT22 neuronal co-culture were used to evaluate the effects of artemether on neuroinflammation-induced neuronal death. The role of Nrf2 in the anti-inflammatory activity of artemether was investigated in BV2 cells transfected with Nrf2 siRNA. Artemether significantly suppressed pro-inflammatory mediators (NO/iNOS, PGE2/COX-2/mPGES-1, TNFα, and IL-6), Aβ and BACE-1 in BV2 cells following LPS stimulation. These effects of artemether were shown to be mediated through inhibition of NF-kappaB and p38MAPK signalling. Artemether produced increased levels of HO-1, NQO1 and GSH in BV2 microglia. The drug activated Nrf2 activity by increasing nuclear translocation of Nrf2 and its binding to antioxidant response elements in BV2 cells. Transfection of BV2 microglia with Nrf2 siRNA resulted in the loss of both anti-inflammatory and neuroprotective activities of artemether. We conclude that artemether induces Nrf2 expression and suggest that Nrf2 mediates the anti-inflammatory effect of artemether in BV2 microglia. Our results suggest that this drug has a therapeutic potential in neurodegenerative disorders

    Toxoplasma-Infection in swine and their serological determination in meat-juice samples using an IgM and IgG-Antibody Assay

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    Toxoplasma gondii is found too rarely in macrophages and neural, ocular, or muscle tissue to serve as a useful diagnostic test. Active Toxoplasma infection is best diagnosed by serology. Small occidial oocysts ofToxoplasma are briefly shed in feces. Toxoplasma gondii-specific IgM is detectable in serum within 2 or 4 weeks after induction of toxoplasmosis; these titers generally are negative within 16 weeks after infection. After induction of infection, Toxoplasma -specific IgG can be detected in serum within 4 weeks after infection. In this study we introduce the combined determination of T.gondii- IgM and IgG Antibodies m Meat Juice samples

    Detection of Campylobacter antibodies in swine meat juice - a first case study

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    The genus Campylobacter is a gram-negtaive, non-spore forming rod with several species. Campylobacter infections are present in the intestine of many animal species and has been isolated, for instance, from cattle, sheep and pigs, respectively. In the majority of cases the isolation of Campylobacter merely indicates an a-symptomatic presence in the gut, although it also can be associated with enteritis. The aim of this study is to check the possibility using serological antibody detection for the estimation of the herd prevalence of Campylobacter infections

    The combination of two Salmonella-antigen test systems for reliable diagnostic of Salmonellosis in stockbreeding pigs

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    Salmonella enterica is a facultative intracellular pathogen that is capable of causing disease in a range of hosts. The genus Salmonella covers more than 2,400 different serotypes, whereof some specific clones have become very dominant in one or more host species and have been able to spread worldwide. Nevertheless, all serotypes must be considered potential human pathogens
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