A novel antibody-dependent cellular cytotoxicity epitope in gp120 is identified by two monoclonal antibodies isolated from a long-term survivor of human immunodeficiency virus type 1 infection

Two monoclonal antibodies (MAbs), 42F and 43F, were isolated some 14 months apart from a single long-term survivor of human immunodeficiency virus type 1 (HIV-1) infection. These MAbs were found to be indistinguishable in terms of their isotypes, specificities, affinities, and biological activities. Both 42F and 43F directed substantial antibody-dependent cellular cytotoxicity (ADCC) against cells infected with four divergent lab-adapted strains of HIV-1, but no neutralizing activity against these strains was detectable. The ability of MAbs 42F and 43F, as well as that of MAbs against two other gp120 epitopes, to direct ADCC against uninfected CD4+ cells to which recombinant gp120SF2 had been adsorbed (i.e., "innocent bystanders") was demonstrated to be less efficient by at least an order of magnitude than their ability to direct ADCC against HIV-1-infected cells. Flow cytometry analyses showed that 42F and 43F also bind to native primary isolate Envs from clades B and E expressed on cell surfaces. By direct binding and competition assays, it was demonstrated that the 42F/43F epitope lies in a domain of gp120 outside the previously described CD4-binding site and V3 loop ADCC epitope clusters. Immunoblot analysis revealed that the 42F/43F epitope is not dependent on disulfide bonds or N-linked glycans in gp120. Epitope mapping of 42F and 43F by binding to linear peptides demonstrated specificity of these MAbs for a sequence of 10 amino acids in the C5 domain comprising residues 491 to 500 (Los Alamos National Laboratory numbering for the HXB2 strain). Thus, 42F and 43F define a new ADCC epitope in gp120. Because of the relative conservation of this epitope and the fact that it appears to have been significantly immunogenic in the individual from which these MAbs were derived, it may prove to be a useful component of HIV vaccines. Furthermore, these MAbs may be used as tools to probe the potential importance of ADCC as an antiviral activity in HIV-1 infection.     

The Effect of Verbal Context on Olfactory Perception.

Three experiments were conducted to examine how verbal context and sensory stimulation interact to influence odor hedonic perception. Eight common odors were presented in their natural and synthetic forms, and verbal labels designating name and source (natural, synthetic) information were either explicitly given, self-generated, falsely provided, or not provided. Results revealed that verbal information about source influenced hedonic ratings whether or not the odorant itself was also present. When odorants were presented without verbal labels, olfactory evaluations were based in sensation. Name and source information contributed different levels of meaning and influence to perceptual evaluations. The findings are discussed with reference to an experiential-collocation model for odor-label interactions and a dual-coding hypothesis for olfactory perception. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Energy-efficient coding with discrete stochastic events

We investigate the energy efficiency of signaling mechanisms that transfer information by means of discrete stochastic events, such as the opening or closing of an ion channel. Using a simple model for the generation of graded electrical signals by sodium and potassium channels, we find optimum numbers of channels that maximize energy efficiency. The optima depend on several factors: the relative magnitudes of the signaling cost (current flow through channels), the fixed cost of maintaining the system, the reliability of the input, additional sources of noise, and the relative costs of upstream and downstream mechanisms. We also analyze how the statistics of input signals influence energy efficiency. We find that energy-efficient signal ensembles favor a bimodal distribution of channel activations and contain only a very small fraction of large inputs when energy is scarce. We conclude that when energy use is a significant constraint, trade-offs between information transfer and energy can strongly influence the number of signaling molecules and synapses used by neurons and the manner in which these mechanisms represent information.     

On-line data bases for chemical patent searches

The most important of the data bases available for chemical on-line searches are presented and their suitability for various types of patent searches are shown with the aid of examples.     

Identification of opiate/receptor binding in vivo

The displacement of small amounts of tritiumlabbelled antagonists or agonists by increasing amounts of unlabelled antagonists in mouse brain in vivo offered the possibility of characterizing properties of opiate receptors in the intact animal. The displacement effect was stereospecific, saturable and dependent upon the affinity of the substance investigated. At brain concentrations of 0.3 nM, 75% of 3H-diprenorphine, 60% of 3H-naltrexone and 50% of 3H-naloxone were displaced by high amounts of the respective unlabelled drug. Comparison of the in vivo data with receptor binding in vitro revealed similar results in respect to binding sites and receptor affinity. The displacement was different in various brain areas. The time course of the displacement was also different for the various substances used and seems to reflect differences in the speed of association and dissociation to and from the receptors. The displacement of 3H-etorphine by naltrexone could be correlated with the reversal of analgesia.     

Volumetric analysis of mice lungs in a clinical magnetic resonance imaging scanner

Small animal models are widely used to study various pathologies. Magnetic resonance imaging (MRI) allows investigation of these animals in a non-invasive way. Therefore, the aim of our study was to develop and evaluate a low-cost approach to measure lung volumes in small animal MRI using a clinical scanner and a specially designed RF coil. Five mice (three of an established emphysema model and two controls) were investigated in a 1.0-T clinical scanner using a specially built small animal saddle coil and three different three-dimensional sequences; overall imaging time was approximately 16 min. Lung volumes were calculated from these images using an interactive watershed transform algorithm for semi-automatic image segmentation. The gold standard for the volume measurement was water displacement after surgical explantation. MRI measured volumes correlated significantly with ex vivo measurements on the explanted lungs (r = 0.99 to 0.89; p < 0.05). Mean lung volume in emphysema model mice was larger than in controls. High-resolution, small animal MRI using a clinical scanner is feasible for volumetric analysis and provides an alternative to a dedicated small animal scanner.     

High efficiency CIGS based solar cells with electrodeposited ZnO:Cl as transparent conducting oxide front contact

In this paper high efficiency (up to 15.8%) Mo/Cu(In,Ga)Se₂/CdS/i‐ZnO solar cells terminated with an electrodeposited ZnO:Cl window layer are reported. The optoelectronic properties of these cells are comparable to reference cells terminated with standard sputtered ZnO:Al. The use of an electrochemical step, a low cost and easily up‐scalable method, in the fabrication process of this type of solar cell, opens the possibility to lower their production price and make them more competitive. The optimization involves a soft annealing treatment (T ≤ 150°C) under atmospheric conditions after the electrodeposition which improves the transparency of the ZnO:Cl layers in the infrared region, the short circuit current and the fill factor of the I–V curve. These changes are related to the increase of one order of magnitude (up to 5 × 10² Ω⁻¹·cm⁻¹) of the lateral conductivity of the electrochemical layer due to an improvement of the free carrier mobility. Copyright © 2010 John Wiley & Sons, Ltd.     

Protein Microarray Copying: Easy on-Demand Protein Microarray Generation Compatible with Fluorescence and Label-Free Real-Time Analysis

Protein microarrays are essential to understand complex protein interaction networks. Their production, however, is a challenge and renders this technology unattractive for many laboratories. Recent developments in cell-free protein microarray generation offer new opportunities, but are still expensive and cumbersome in practice. Herein, we describe a cost-effective and user-friendly method for the cell-free production of protein microarrays. From a polydimethylsiloxane (PDMS) flow cell containing an expressible DNA microarray, proteins of interest are synthesised by cell-free expression and then immobilised on a capture surface. The resulting protein microarray can be regarded as a “copy” of the DNA microarray. 2 His₆- and Halo-tagged fluorescent reference proteins were used to demonstrate the functionality of nickel nitrilotriacetic acid (Ni-NTA) and Halo-bind surfaces in this copy system. The described process can be repeated several times on the same DNA microarray. The identity and functionality of the proteins were proven during the copy process by their fluorescence and on the surface through a fluorescent immune assay. Also, single-colour reflectometry (SCORE) was applied to show that, on such copied arrays, real-time binding kinetic measurements were possible.