This proteotyping approach complements conventional PCR approaches and should aid in the monitoring of the evolution of the influenza virus in both humans and animals. (C) 2010 Elsevier B.V. All rights reserved.”
“Voltage-gated sodium channels (Nay channels) play a pivotal click here role in neuronal excitability; they are specifically targeted by mu-conotoxins from the venom of marine cone snails. These peptide toxins bind to the outer vestibule of the channel pore thereby blocking ion conduction through Nay channels. mu-Conotoxin

SIIIA from Conus striatus was shown to be a potent inhibitor of neuronal sodium channels and to display analgesic effects in mice, albeit the molecular targets are not unambiguously known. We therefore studied recombinant Nay channels expressed in mammalian cells using the whole-cell patch-clamp method. Synthetic mu SIIIA slowly and partially

blocked rat Na(V)1.4 channels with an apparent IC(50) of 0.56 +/- 0.29 mu M; the block was not complete, leaving at high concentration a residual current component of about 10% with a correspondingly reduced single-channel conductance. At 10 mu M, mu SIIIA potently blocked rat Na(V)1.2, rat and human Na(V)1.4, and mouse Na(V)1.6 channels; human Na(V)1.7 channels were only inhibited by 58.1 +/- 4.9%, whereas human Na(V)1.5 as well as rat and human Na(V)1.8 were insensitive. Employing domain chimeras between rNa(V)1.4 and hNa(V)1.5, we located the determinants for mu SIIIA Adenosine specificity in the first half of the channel GSK461364 purchase protein with a major contribution of domain-2 and a minor contribution of domain-1. The latter was largely accounted for by the alteration in the TTX-binding site (Tyr401 in rNa(V)1.4, Cys for Na(V)1.5, and Ser for Na(V)1.8). Introduction of domain-2 pore loops of all tested channel isoforms into rNa(V)1.4 conferred the mu SIIIA phenotype of the respective donor channels highlighting the importance of the domain-2 pore loop as the major determinant for mu SIIIA’s subtype specificity. Single-site substitutions identified residue Ala728 in rNa(V)1.4

as crucial for its high sensitivity toward mu SIIIA. Likewise, Asn889 at the homologous position in hNa(V)1.7 is responsible for the channel’s reduced mu SIIIA sensitivity. These results will pave the way for the rational design of selective Nay-channel antagonists for research and medical applications. (C) 2011 Elsevier Ltd. All rights reserved.”
“Antibodies to non-structural protein 1 (NS1) of West Nile virus (WNV) have been used to differentiate WNV infection from infection by serologically cross-reactive flaviviruses, including Japanese encephalitis virus (JEV), in horses. However, since the inactivated West Nile (WN) vaccine has been reported to induce NS1 antibodies, there is concern about the reliability of using NS1-based assays for testing vaccinated horses.