Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

Clinical study in epidural injection with lappaconitine compound for post-operative analgesia

In this study, the effect and side-effect of epidural injection with lappaconitine compound for post-operative analgesia was observed. One hundred and twenty patients were randomly divided into 4 groups. Lappaconitine compound (LB) consisted of 12 mg of lappaconitine and 22.5 mg of bupivacaine, was given to group A (the group of observation), and lappaconitine 12 mg, bupivacaine 22.5 mg and morphine 2 mg to group B, C and D respectively for control. All were given by epidural injection with single blind method during post-operative pain of incision operation. Result showed that the initiating of analgesia was quicker in group A and C than that in group B and D, and the efficacy was group D > A > C > B. There was significant difference between group A and B in the above two parameters, P < 0.01 and P < 0.05. The analgisia maintenence time of single injection was D > A > B > C, that of group D was significantly longer than that of group A (P < 0.01). It indicated that the epidural injection with LB was more rapid and potent than that with lappaconitine alone in post-operative analgesia, and the former had no side-effect, it was safer than morphine.     

Screening mixtures for biological activity by NMR

Development of the new drugs often involves the screening of compound libraries for biological activity. Currently, the biologically active component can only be identified if either a pure compound is being tested or if the components of a mixture are spatially separated, for example, on beads. Here, we present an NMR technique based on the transferred nuclear Overhauser effect (transfer NOE) that allows identification and structural characterization of biologically active molecules from a mixture. As an example we demonstrate that from mixtures of oligosaccharides only alpha-L-Fuc-(1-->6)-beta-D-GlcNAc-OMe binds to Aleuria aurantia agglutinin. The sign of transferred NOEs is opposite to NOEs of small molecules that do not bind to the protein and, thus, an unequivocal identification of molecules with binding activity is possible. Normally, the selection of bound ligands is further facilitated in that the absolute intensity of transfer NOEs is much greater than that of NOEs of non-binding molecules. In addition, transfer NOEs provide information on the three-dimensional structure of the ligands in the bound state. Therefore, measuring transfer NOEs of mixtures of small molecules in the presence of large molecules, like proteins, should significantly enhance the options for screening mixtures of compounds for biological activity.     

A linkage map of human chromosome 21:43 PCR markers at average intervals of 2.5 cM

A genetic linkage map of human chromosome 21q (HC21q) containing 43 markers genotyped by the polymerase chain reaction in the CEPH pedigrees is presented. The markers placed on this map are highly polymorphic with an average heterozygosity of 61%. The average interval size of the markers localized at 1000:1 odds is 2.5 cM. The map has a total length of 65.5 cM, with male and female lengths of 47.7 and 83.3 cM, respectively. The genotypes used in the construction of this map were subjected to rigorous error checking, which is reflected in the shorter map length compared to previous maps; the estimated error rate in genotyping is less than 0.04%. As noted in previous linkage maps there is increased recombination in females on proximal HC 21q and in the male in a region near the telomere. This map of HC 21 represents a highly informative and dense meiotic linkage map and will be useful in linking disease phenotypes to loci on this chromosome.     

Electromagnetic scattering by a straight thin wire

The traveling-wave energy, which multiply diffracts on a straight thin wire, is represented as a sum of terms, each with a distinct physical meaning, that can be individually examined in the time domain. Expressions for each scattering mechanism on a straight thin wire are cast in the form of four basic electromagnetic wave concepts: diffraction, attachment, launch, and reflection. Using the basic mechanisms from P.Ya. Ufimtsev (1962), each of the scattering mechanisms is included into the total scattered field for the straight thin wire. Scattering as a function of angle and frequency is then compared to the moment-method solution. These analytic expressions are then extended to a lossy wire with a simple approximate modification using the propagation velocity on the wire as derived from the Sommerfeld wave on a straight lossy wire. Both the perfectly conducting and lossy wire solutions are compared to moment-method results, and excellent agreement is found. As is common with asymptotic solutions, when the electrical length of wire is smaller than 0.2 λ the results lose accuracy. The expressions modified to approximate the scattering for the lossy thin wire yield excellent agreement even for lossy wires where the wire radius is on the order of skin depth     

Choice With Initial and Terminal Link Reinforcement: An Alternative Self-Control Paradigm.

Self-control is demonstrated when a less desirable immediate outcome is chosen to ensure a substantially better future. In a novel animal analogue of this situation, primary reinforcement was delivered in both the initial and terminal links of a concurrent chain schedule. Rats made initial link choices between equal amounts of ethanol-free or ethanol-containing milk. Choosing the ethanol-free reinforcer resulted in delivery of the larger terminal link reinforcer and was thus analogous to self-control. Self-control decreased as the delay between initial and terminal links increased. The results have implications for human choice situations where decisions are made between two immediately available reinforcement alternatives each associated with a different delayed outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)