The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state

Mutations in the extracellular M2-M3 loop of the glycine receptor (GlyR) alpha1 subunit have been shown previously to affect channel gating. In this study, the substituted cysteine accessibility method was used to investigate whether a structural rearrangement of the M2-M3 loop accompanies GlyR activation. All residues from R271C to V277C were covalently modified by both positively charged methanethiosulfonate ethyltrimethylammonium (MTSET) and negatively charged methanethiosulfonate ethylsulfonate (MTSES), implying that these residues form an irregular surface loop. The MTSET modification rate of all residues from R271C to K276C was faster in the glycine-bound state than in the unliganded state. MTSES modification of A272C, L274C, and V277C was also faster in the glycine-bound state. These results demonstrate that the surface accessibility of the M2-M3 loop is increased as the channel transitions from the closed to the open state, implying that either the loop itself or an overlying domain moves during channel activation.

Ivermectin, an unconventional agonist of the glycine receptor chloride channel

The effects of the antihelmintic, ivermectin, were investigated in recombinantly expressed human alpha (1) homomeric and alpha (1)beta heteromeric glycine receptors (GlyRs), At low (0.03 muM) concentrations ivermectin potentiated the response to sub-saturating glycine concentrations, and at higher (greater than or equal to0.03 muM) concentrations it irreversibly activated both alpha (1) homomeric and alpha (1)beta heteromeric GlyRs. Relative to glycine-gated currents, ivermectin-gated currents exhibited a dramatically reduced sensitivity to inhibition by strychnine, picrotoxin, and zinc. The insensitivity to strychnine could not be explained by ivermectin preventing the access of strychnine to its binding site. Furthermore, the elimination of a known glycine- and strychnine-binding site by site-directed mutagenesis had little effect on ivermectin sensitivity, demonstrating that the ivermectin- and glycine-binding sites were not identical. Ivermectin strongly and irreversibly activated a fast-desensitizing mutant GlyR after it had been completely desensitized by a saturating concentration of glycine. Finally, a mutation known to impair dramatically the glycine signal transduction mechanism had little effect on the apparent affinity or efficacy of ivermectin, Together, these findings indicate that ivermectin activates the GlyR by a novel mechanism.

A novel target-field method for finite-length magnetic resonance shim coils: I. Zonal shims

This paper presents a new approach for the design of genuinely finite-length shim and gradient coils, intended for use in magnetic resonance imaging equipment. A cylindrical target region is located asymmetrically, at an arbitrary position within a coil of finite length. A desired target field is specified on the surface of that region, and a method is given that enables winding patterns on the surface of the coil to be designed, to produce the desired field at the inner target region. The method uses a minimization technique combined with regularization, to find the current density on the surface of the coil. The method is illustrated for linear, quadratic and cubic magnetic target fields located asymmetrically within a finite-length coil.

Functional annotation of a full-length mouse cDNA collection

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Exact solution at integrable coupling of a model for the Josephson effect between small metallic grains

A model is introduced for two reduced BCS systems which are coupled through the transfer of Cooper pairs between the systems. The model may thus be used in the analysis of the Josephson effect arising from pair tunneling between two strongly coupled small metallic grains. At a particular coupling strength the model is integrable and explicit results are derived for the energy spectrum, conserved operators, integrals of motion, and wave function scalar products. It is also shown that form factors can be obtained for the calculation of correlation functions. Furthermore, a connection with perturbed conformal field theory is made.

Investigations into a power-combining structure using a reflect array of dual-feed aperture-coupled microstrip patch antennas

This paper details an investigation of a power combiner that uses a reflect array of dual-feed aperture-coupled microstrip patch antennas and a corporate-fed dual-polarized array as a signal distributing/combining device. In this configuration, elements of the reflect array receive a linearly polarized wave and retransmit it with an orthogonal polarization using variable-length sections of microstrip lines connecting receive and transmit ports. By applying appropriate lengths of these delay lines, the array focuses the transmitted wave onto the feed array. The operation of the combiner is investigated for a small-size circular reflect array for the cases of -3 dB, -6 dB and -10 dB edge illumination by the 2 x 2-element dual-polarized array.

The effect of the cleaner fish Labroides dimidiatus on the capsalid monogenean Benedenia lolo parasite of the labrid fish Hemigymnus melapterus

The cleaner fish Labroides dimidiatus affected the pigmented monogenean parasite Benedenia lolo on the fish Hemigymnus melapterus (Labridae) held in aquaria. The effect of cleaner fish varied with the size class of fish; only small fish [a posteriori size class < 11-5 cm standard length (L-S)] exposed to cleaner fish had fewer monogeneans compared with fish not exposed to cleaner fish. The abundance of monogeneans on large fish (a posteriori size class > 11-5 cut L-S) was not affected by cleaner fish. The size-frequency distributions of monogeneans on both size-classes of H. melapterus were affected by cleaner fish. Fish exposed to cleaner fish had fewer large (> 3 mm) and more small (< 1 mm) monogeneans than fish not exposed to cleaner fish, suggesting cleaner fish selectively removed larger monogeneans. This difference was more pronounced on large fish. In the absence of cleaner fish, small fish had almost as many monogeneans as large fish; they also had more small monogeneans than the large fish, suggesting small fish were more vulnerable to infection by monogeneans than larger fish. This suggests that the cleaner fish L. dimidiatus has the potential to control benedeniine monogeneans on captive fish and highlights the importance of taking into account fish size in studies of the effect of cleaner fish on ectoparasites. (C) 2002 The Fisheries Society of the British Isles. Published by Elsevier Science Ltd. All rights reserved.

A conjecture on small embeddings of partial Steiner triple systems

A well-known, and unresolved, conjecture states that every partial Steiner triple system of order u can be embedded in a Steiner triple system of order v for all v equivalent to 1 or 3 (mod 6), v greater than or equal to 2u + 1. However, some partial Steiner triple systems of order u can be embedded in Steiner triple systems of order v < 2u + 1. A more general conjecture that considers these small embeddings is presented and verified for some cases. (C) 2002 Wiley Periodicals, Inc.