New results from the AMANDA Neutrino Telescope Bernardini, Elisa; Ackermann, M.; Ahrens, J. ...
Nuclear physics. Section B, Proceedings supplement,
08/2005, Letnik:
145
Journal Article
The Antarctic Muon and Neutrino Detector Array (AMANDA) is a Čerenkov telescope which uses the south polar ice cap to search for neutrinos from extraterrestrial sources. We present a preliminary ...reconstruction of the energy spectrum of atmospheric neutrinos above a few TeV and several recent results on searches for high-energy astrophysical neutrinos, both non-localized and emitted by point-like sources.
We present the results of a search for point sources of high energy neutrinos in the northern hemisphere using AMANDA-II data collected in the year 2000. Included are flux limits on several AGN ...blazars, microquasars, magnetars and other candidate neutrino sources. A search for excesses above a random background of cosmic-ray-induced atmospheric neutrinos and misreconstructed downgoing cosmic-ray muons reveals no statistically significant neutrino point sources. We show that AMANDA-II has achieved the sensitivity required to probe known TeV gamma-ray sources such as the blazar Markarian 501 in its 1997 flaring state at a level where neutrino and gamma-ray fluxes are equal.
Background: Arginine being a common substrate for arginase and nitric oxide synthase (NOS) an imbalance between enzymes could lead to a shift in airway responses. Reports suggest that increased ...arginase reduces the substrate availability to NOS and attributes to the airway hyperresponsiveness. Hence, inhibition of arginase might enhance the bioavailability of arginine to NOS and generates nitric oxide (NO) a bronchodilator. Molecules from Ephedra and Eugenia caryophyllus are documented for bronchodilator properties. However, the mechanism of action of these molecules for enhancing bronchodilation is not well characterized. The objective of the present study is to assess whether these molecules could inhibit the arginase by binding at its active site and helps in bronchodilation using in silco approach.
Methods: The crystal structures of the arginase and NOS enzymes were selected from the protein database. The molecules from Ephedra and Eugenia caryophyllus were obtained from Pubchem. Drug likeliness and bioactivity of the molecules were assessed by Molinspiration. The successful molecules were docked with active sites of enzymes using docking software, and the docked complexes were analyzed using Accelrys Discovery Studio.
Results: Molecules from Ephedra and Eugenia caryophyllus were able to interact to arginase at the active site whereas away from the active site in case of NOS. The molecules showed differential binding affinities, and some of them had higher binding affinity than substrate arginine.
Conclusion: In silico study suggests that molecules of Ephedra and Eugenia were capable of blocking the active site of arginase. We speculate that if these molecules are used as therapeutics, they could inhibit the arginase activity and this might increase arginine availability to NOS to produce NO which acts as bronchodilator. Our study suggests that molecules which bind to active site of arginine and do not affect the active site of NOS might be the potential molecules for arginase associated asthma.
Peptides of Rv0679c a membrane protein of the cell envelope (16.6 KDa) of Mycobacterium tuberculosis (M. tb), inhibited entry of live bacilli into epithelial (A549) and macrophage (U937) cell lines ...in vitro, suggesting a possible role in invasion. Receptors associated with Rv0679c antigen entry into cell lines were not characterized. We are reporting that Rv0679c peptides could bind to Toll like receptors (TLRs), the principal class of pathogen recognition receptors on host cells (PRR) by docking studies. Peptide structures were predicted using PEP FOLD and docking of truncated peptides with TLR's was performed using Cluspro 2.0. Docked complexes were analyzed using Swiss-PDB Viewer. Nine peptides of Rv0679c protein assessed were able to bind to TLR2-1 and TLR 4-MD2; however the binding energy was better with TLR 4-MD2. Peptide 30985 (-866.4 kcal/mol) has better binding energy with TLR2-1, in contrast peptide 30982 showed a better binding energy to TLR 4-MD2 dimer with a score of -1291.7 kcal/mol. Interactive residue analysis revealed that GLU 173 and SER 454 of TLR 1; ARG 447 and ARG 486 of TLR2; ARG 264 of TLR 4 and SER 120, LYS 122 and GLU 92 of MD2 region are predominant residues interacting with peptides of Rv0679c protein. Our study suggests that predominant residues and receptors of TLR2 and TLR4 are important for Rv0679c protein binding, which could further lead to invasion of M. tb into the host cell.
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