Background At a molecular level, insects utilize members of several highly divergent and unrelated families of cell-surface chemosensory receptors for detection of volatile odorants. Most odors are detected via a family of odorant receptors (ORs), which form heteromeric complexes consisting of a well-conserved OR co-receptor (Orco) ion channel and a non-conserved tuning OR that provides coding specificity to each complex. Orco functions as a non-selective cation channel and is expressed in the majority of olfactory receptor neurons (ORNs). As the destructive behaviors of many insects are principally driven by olfaction, Orco represents a novel target for behavior-based control strategies. While many natural and synthetic odorants have been shown to agonize Orco/Or complexes, only a single direct Orco modulator, VUAA1, has been described. In an effort to identify additional Orco modulators, we have investigated the structure/activity relationships around VUAA1. Results A search of our compound library identified several VUAA1 analogs that were selected for evaluation against HEK cells expressing Orco from the malaria vector Anopheles gambiae (AgOrco). While the majority of compounds displayed no activity, many of these analogs possess no intrinsic efficacy, but instead, act as competitive VUAA1 antagonists. Using calcium mobilization assays, patch clamp electrophysiology, and single sensillum in vivo recording, we demonstrate that one such candidate, VU0183254, is a specific allosteric modulator of OR signaling, capable of broadly inhibiting odor-mediated OR complex activation. Conclusions We have described and characterized the first Orco antagonist, that is capable of non-competitively inhibiting odorant-evoked activation of OR complexes, thereby providing additional insight into the structure/function of this unique family of ligand-gated ion channels. While Orco antagonists are likely to have limited utility in insect control programs, they represent important pharmacological tools that will facilitate the investigation of the molecular mechanisms underlying insect olfactory signal transduction.
This work was supported in part by the National Science Foundation through Grants PHY76-04761 and CHE75-01565, and in part by the Army Research Office through Grant DAAG29-76-G-0236.
Ion beams with energies in the range 1–2 keV are used to sputter neutral Zr atoms from a polycrystalline surface. Laser induced fluorescence detection is used to obtain angular distributions of sputtered neutrals as a function of ion impact direction, ion mass, ion energy, and spin–orbit state of the exiting atoms. About 40% of the sputtered atoms are excited. Angular distributions depend weakly on ion mass and energy. The angular distributions are fitted well by a modified form of the Roosendaal and Saunders model of sputtering.
The kinetics of chemisorption of nitrogen on a polycrystalline tungsten ribbon were studied under ultra-high vacuum conditions by a flow method using a flash-filament technique similar to that described by Becker & Hartman (1953). The change of contact potential of the tungsten ribbon during the chemisorption reaction was simultaneously measured by continuous monitoring of the characteristics of a space-charge limited diode with the ribbon used as anode. Both the ‘sticking probability’ and the apparent dipole moment of the adsorbed layer change markedly at a coverage of 2⋅5 x 10 14 atoms/cm 2 at room temperature. At higher temperatures the changes in both sticking probabilities and apparent dipole moments occur at lower coverages. The requirements of a simple two-site adsorption model to explain these results are discussed, and are compared with kinetic theories recently given by Ehrlich (1955, 1956 a ), Kisliuk (1957, 1958) and Gundry & Tompkins (1956).
The resolution of the supernumerary rotational rainbow structure in state-to-state differential cross sections for ${\mathrm{Na}}_{2}$-Ne collisions which had been predicted by infinite-order sudden-approximation theory is reported. These data, by proving the existence of such a structure in quantitative agreement with the infinite-order sudden-approximation theory, answer one of the major remaining questions in the physics of rotationally inelastic scattering.
The work described is relative to the problem of state densities in semi-conductors near a gap edge. The local density approximation (LDA) is explained and modifications to its original form described. In the linear chain, choice of the appropriate sub-chain length as the 'beat length', already shown to determine the range of a localized state, results in an unambiguous expression for the density of states N(E). An excellent fit is obtained to Monte Carlo results. The phenomenon of the 'locking' of psi to the well distribution is shown to exist in three dimensions, and the consequent applicability of the LDA to amorphous materials is argued for.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Abstract Background Chemosensory signal transduction guides the behavior of many insects, including Anopheles gambiae , the major vector for human malaria in sub-Saharan Africa. To better understand the molecular basis of mosquito chemosensation we have used whole transcriptome RNA sequencing (RNA-seq) to compare transcript expression profiles between the two major chemosensory tissues, the antennae and maxillary palps, of adult female and male An. gambiae . Results We compared chemosensory tissue transcriptomes to whole body transcriptomes of each sex to identify chemosensory enhanced genes. In the six data sets analyzed, we detected expression of nearly all known chemosensory genes and found them to be highly enriched in both olfactory tissues of males and females. While the maxillary palps of both sexes demonstrated strict chemosensory gene expression overlap, we observed acute differences in sensory specialization between male and female antennae. The relatively high expression levels of chemosensory genes in the female antennae reveal its role as an organ predominately assigned to chemosensation. Remarkably, the expression of these genes was highly conserved in the male antennae, but at much lower relative levels. Alternatively, consistent with a role in mating, the male antennae displayed significant enhancement of genes involved in audition, while the female enhancement of these genes was observed, but to a lesser degree. Conclusions These findings suggest that the chemoreceptive spectrum, as defined by gene expression profiles, is largely similar in female and male An. gambiae . However, assuming sensory receptor expression levels are correlated with sensitivity in each case, we posit that male and female antennae are perceptive to the same stimuli, but possess inverse receptive prioritizations and sensitivities. Here we have demonstrated the use of RNA-seq to characterize the sensory specializations of an important disease vector and grounded future studies investigating chemosensory processes.
