p38 alpha MAP Kinase Controls IL-17 Synthesis in Vogt-Koyanagi-Harada Syndrome and Experimental Autoimmune Uveitis

PURPOSE. Interleukin (IL)-17, which is responsible for the initial influx of leukocytes into the target tissue, was recently described as the main cytokine involved in autoimmune diseases. Vogt-Koyanagi-Harada (VKH) syndrome is a significant cause of noninfectious blindness in the world. Herein the authors aimed at unraveling the involvement of IL-17 in VKH and in experimental autoimmune uveitis, focusing on the signaling pathways involved in IL-17 synthesis. METHODS. Mice were immunized with 161-180 peptide and pertussis toxin. Draining lymph node cells, harvested 21 days after immunization, were cultured in the presence or absence of p38 alpha mitogen-activated protein kinase (MAPK) inhibitor (SB203580) and assayed for cytokine production and quantification of CD4(+)IL-17(+) cells. Mice received intraocular injections of SB203580, and disease severity was evaluated by histologic examination of the enucleated eyes at day 21. CD4(+) lymphocytes from MSK-1/2-deficient mice, human CD4(+) cells silenced with MSK1 siRNA, or peripheral blood mononuclear cells (PBMCs) from VKH patients were cultured in the presence or absence of p38 alpha MAPK inhibitor and then assayed for IL-17, IFN-gamma, and IL-4 production. RESULTS. The inhibition of p38 alpha MAPK fully blocked the synthesis of IL-17 by PBMCs from VKH patients and lymphocytes from EAU mice. The absence of the msk1/2 gene resulted in failure to produce IL-17 by murine and human lymphocytes. Interestingly, intraocular injections of SB203580 in EAU mice did not suppress development of the disease. CONCLUSIONS. These data show that p38 alpha MAPK-MSK1/2 is involved in the control of IL-17 synthesis by CD4(+) T cells and that inhibition of p38 alpha MAPK in vitro suppresses IL-17 synthesis but that inhibition of this kinase in vivo did not protect from EAU. (Invest Ophthalmol Vis Sci. 2010;51:3567-3574) DOI: 10.1167/iovs.09-4393

In Vitro and In Vivo Antiplasmodial Activities of Risedronate and Its Interference with Protein Prenylation in Plasmodium falciparum

The increasing resistance of malarial parasites to almost all available drugs calls for the identification of new compounds and the detection of novel targets. Here, we establish the antimalarial activities of risedronate, one of the most potent bisphosphonates clinically used to treat bone resorption diseases, against blood stages of Plasmodium falciparum (50% inhibitory concentration [IC(50)] of 20.3 +/- 1.0 mu M). We also suggest a mechanism of action for risedronate against the intraerythrocytic stage of P. falciparum and show that protein prenylation seems to be modulated directly by this drug. Risedronate inhibits the transfer of the farnesyl pyrophosphate group to parasite proteins, an effect not observed for the transfer of geranylgeranyl pyrophosphate. Our in vivo experiments further demonstrate that risedronate leads to an 88.9% inhibition of the rodent parasite Plasmodium berghei in mice on the seventh day of treatment; however, risedronate treatment did not result in a general increase of survival rates.

Photoproduction of J/psi and of high mass e(+)e(-) in ultra-peripheral Au plus Au collisions at root s(NN)=200 GeV

We present the first measurement of photoproduction of J/psi and of two-photon production of high-mass e(+)e(-) pairs in electromagnetic (or ultra-peripheral) nucleus-nucleus interactions, using Au + Au data at root s(NN) = 200 GeV. The events are tagged with forward neutrons emitted following Coulomb excitation of one or both Au* nuclei. The event sample consists of 28 events with m(e+e-) > 2 GeV/c(2) with zero like-sign background. The measured cross sections at midrapidity of d sigma/dy (J/psi + Xn, y = 0) = 76 +/- 33 (stat) +/- 11 (syst) pb and d(2)sigma /dm dy (e(+) e(-) + Xn, y = 0) = 86 +/- 23(stat) +/- 16(syst) mu b/ (GeV/c(2)) for m(e+e-) epsilon vertical bar 2.0, 2.8 vertical bar GeV/c(2) have been compared and found to be consistent with models for photoproduction of J/psi and QED based calculations of two-photon production of e(+)e(-) pairs. (C) 2009 Elsevier B.V. All rights reserved.

Dilepton mass spectra in p plus p collisions at root s=200 GeV

PHENIX has measured the electron-positron pair mass spectrum from 0 to 8 GeV/c(2) in p + p collisions at root s = 200 GeV. The contributions from light meson decays to e(+)e(-) pairs have been determined based on measurements of hadron production cross sections by PHENIX. Within the systematic uncertainty of similar to 20% they account for all e(+)e(-) pairs in the mass region below similar to 1 GeV/c(2). The e(+)e(-) pair yield remaining after subtracting these contributions is dominated by semileptonic decays of charmed hadrons correlated through flavor conservation. Using the spectral shape predicted by PYTHIA, we estimate the charm production cross section to be 544 +/- 39(stat) +/- 142(syst) +/- 200(model) pb. which is consistent with QCD calculations and measurements of single leptons by PHENIX. (C) 2008 Elsevier BV. All rights reserved.

Performance Improvement of Tomographic Image Reconstruction Based on DSP Processors

This paper presents the use of a multiprocessor architecture for the performance improvement of tomographic image reconstruction. Image reconstruction in computed tomography (CT) is an intensive task for single-processor systems. We investigate the filtered image reconstruction suitability based on DSPs organized for parallel processing and its comparison with the Message Passing Interface (MPI) library. The experimental results show that the speedups observed for both platforms were increased in the same direction of the image resolution. In addition, the execution time to communication time ratios (Rt/Rc) as a function of the sample size have shown a narrow variation for the DSP platform in comparison with the MPI platform, which indicates its better performance for parallel image reconstruction.

Direct detection of underivatized chitooligosaccharides produced through chitinase action using capillary zone electrophoresis

Capillary electrophoresis with capacitively coupled contactless conductivity detection was successfully used to quantify N-acetylglucosamine and five N-acetyl-chitooligosaccharides (C2-C6) produced after reaction with a purified chitinase (TmChi) from Tenebrio molitor (Coleoptera). No derivatization process was necessary. The separation was developed using 10 mM NaOH with 10% (v/v) acetonitrile as background electrolyte and homemade equipment with a system that avoids the harmful effect of electrolysis. The limit of detection for all oligosaccharides was ca. 3 mu M, and the results indicated that the larger the oligosaccharide, the higher the sensitivity. Analysis of the chitooligosaccharides produced revealed that TmChi has an endolytic cleavage pattern with C5 as the best substrate (higher catalytic efficiency k(cat)/K-M) releasing C2 and C3. (c) 2007 Elsevier Inc. All rights reserved.

Investigating the formation and the properties of monoalkyl carbonates in aqueous medium using capillary electrophoresis with capacitively coupled contactless conductivity detection

Although alkyl carbonic acids (ACAs) and their salts are referred to as instable species in aqueous medium, we demonstrate that a monoalkyl carbonate (MAC) can in fact be easily formed from bicarbonate and an alcohol even in the presence of a high amount of water. A CE system with two capacitively coupled contactless conductivity detectors (C(4)Ds) was used to obtain different parameters about these species and their reactions. Based on the mobilities obtained for a series of alcohols ranging from 1 to 5 carbons, the coefficients of diffusion and the hydrodynamic radii were calculated. When compared with the equivalent carboxylates, MACs have radii systematically smaller. Although the precise pK(a) values of the ACAs could not be obtained, because of the fast decomposition in acid medium, it was possible, for the first time, to show that they are below 4.0. This result suggests that the acidity of an ACA is quite similar to the first hydrogen of H(2)CO(3). Using a new approach to indirectly calibrate the C(4)D, the kinetic constants and the equilibrium constants of formation were also obtained. The results suggest that the increase in the chain length makes the MACs less stable and more inert.