Personal receptor repertoires: olfaction as a model

ABSTRACT: BACKGROUND: Information on nucleotide diversity along completely sequenced human genomes has increased tremendously over the last few years. This makes it possible to reassess the diversity status of distinct receptor proteins in different human individuals. To this end, we focused on the complete inventory of human olfactory receptor coding regions as a model for personal receptor repertoires. RESULTS: By performing data-mining from public and private sources we scored genetic variations in 413 intact OR loci, for which one or more individuals had an intact open reading frame. Using 1000 Genomes Project haplotypes, we identified a total of 4069 full-length polypeptide variants encoded by these OR loci, average of ~10 per locus, constituting a lower limit for the effective human OR repertoire. Each individual is found to harbor as many as 600 OR allelic variants, ~50% higher than the locus count. Because OR neuronal expression is allelically excluded, this has direct effect on smell perception diversity of the species. We further identified 244 OR segregating pseudogenes (SPGs), loci showing both intact and pseudogene forms in the population, twenty-six of which are annotatively "resurrected" from a pseudogene status in the reference genome. Using a custom SNP microarray we validated 150 SPGs in a cohort of 468 individuals, with every individual genome averaging 36 disrupted sequence variations, 15 in homozygote form. Finally, we generated a multi-source compendium of 63 OR loci harboring deletion Copy Number Variations (CNVs). Our combined data suggest that 271 of the 413 intact OR loci (66%) are affected by nonfunctional SNPs/indels and/or CNVs. CONCLUSIONS: These results portray a case of unusually high genetic diversity, and suggest that individual humans have a highly personalized inventory of functional olfactory receptors, a conclusion that might apply to other receptor multigene families.     

Genetics of canine olfaction and receptor diversity

Olfaction is a particularly important sense in the dog. Humans selected for this capacity during the domestication process, and selection has continued to be employed to enhance this ability. In this review we first describe the different olfactory systems that exist and the different odorant receptors that are expressed in those systems. We then focus on the dog olfactory receptors by describing the olfactory receptor gene repertoire and its polymorphisms. Finally, we discuss the different uses of dog olfaction and the questions that still need to be studied.     

Bark beetle olfaction: Pheromone receptor system in Dendroctonus frontalis

Differential adaptation of antennal olfactory acceptors and electroantennogram (EAG) techniques were used to describe the acceptor population for pheromones and host compounds. All acceptors appeared to have some degree of specificity for the pheromone, frontalin. This conclusion was verified by both EAG and single unit recordings. The oxygen containing pheromones occupied a larger percentage of the acceptors than the hydrocarbon host tree terpenes. Pheromones produced by one sex occupied a larger percentage of the pheromone acceptors in the opposite sex. Single unit recordings indicated a chiral acceptor. (-)-Exo-brevicomin stimulation elicited a greater number of impulses in the cells recorded than equal quantities of the (+)-enantiomer. Electrophysiological data correlated well with behavioral rôles attributed the compounds tested.     

When predator odour makes groups stronger: effects on behavioural and chemical adaptations in two termite species

1. Being able to detect a predator before any physical contact is crucial for individual survival. Predator presence can be detected thanks to several types of signal, such as chemical cues. Chemical signals are produced by predators for their protection against desiccation, for their communication, or possibly as a side‐effect of their activity. In insects, chemical communication plays a key role in diverse biological processes, including prey‐predator or plant‐insect interactions, courtship behaviour, and kin or species recognition. 2. Cuticular hydrocarbons (CHCs) are specifically involved in recognition processes and social organisation (division of labour, caste ratios) in social insects. Here, the questions raised are whether termites can detect a predator with their cuticular compounds and whether the predator‐produced compounds can influence their prey. 3. The responses of termites Reticulitermes grassei (Clément, 1978) and Reticulitermes flavipes (Kollar, 1837) to the presence of the cuticular compounds produced by a predator, the ant species Lasius niger (Linnaeus, 1758), were investigated. More specifically, the study quantified termite traits such as caste ratios, mortality rates, CHC profile homogeneity and aggressiveness of workers after 2 months' exposure to predator‐produced compounds. 4. The results show that the predator odour did affect the aggressiveness of the native species R. grassei but not of the invasive R. flavipes. The caste ratios and the mortality rates were not affected for both species. 5. Differences between species are discussed around the native or invasive status of each species, along with the role played by chemical cues on behavioural and chemical adaptations.     

A piezoelectric biosensor as an olfactory receptor for odour detection: electronic nose

Humans can detect and differentiate the presence of different odours even at trace levels of these odorous compounds. The odour quantification of any particular samples is normally based on conventional panel decisions. Other analytical instruments could be used to detect trace levels of odorous molecules. This study presents the results of a biological sensor system subject to different odorants. The system consists of a sensor in which the isolated olfactory receptor proteins (ORPs) from bullfrogs (Rana spp.) were coated onto the surface of a piezoelectric (PZ) electrode, similar to the mechanism of human olfaction. The PZ crystal served as a signal transducer. The results indicate rapid (about 400 s), reversible, and longterm (up to 3 months) stable responses to different volatile compounds such as n-caproic acid, isoamyl acetate, n-decyl alcohol, beta-ionone, linalool, and ethyl caporate. The sensitivity of the sensor ranges from 10(-6)-10(-7) g, fully correlated with the olfactory threshold values of human noses. An array of six sensors consisting of five fractionated ORPs and one referenced phospholipid probe is able to respond to different odorants and form a typical fingerprint for each odorant.     

Chimerical categories: caste, race, and genetics

Is discrimination based on caste equivalent to racism? This paper explores the complex relationship between genetic, race and caste. It also discusses the debate over the exclusion of a discussion of caste‐based discrimination at the 2001 World Conference against Racism, Racial Discrimination, Xenophobia and Related Intolerance held in Durban, South Africa.     

Perireceptor and receptor events in olfaction. Comparison of concentration and flux detectors: a modeling study

Transduction in chemosensory cells begins with the association of ligand molecules to receptor proteins borne by the cell membrane. The receptor-ligand complexes formed act as signaling compounds that trigger a G-protein cascade. This receptor-ligand interaction, described here by a single-step or double-step reaction, depends on factors controlling the access of the ligand molecules to the cell membrane. Two basic mechanisms can be distinguished: concentration detectors (CD), in which the ligand can freely diffuse to the membrane, and flux detectors (FD), in which it accumulates irreversibly in a distinct perireceptor space where it is chemically deactivated. These two systems, plus their generalization, are investigated and compared. The transient and steady-state numbers of complexes are studied as a function of the external ligand concentration. The biological significance of the results is shown in a well-studied example of FD, the insect sex-pheromone olfactory receptor neuron. How the number of complexes can code for the intensity of stimulation is analyzed using the size, dynamic range and sensitivity of the steady-state responses, and the time needed to reach a predefined level of the transient responses. It is shown that the FD design affords a large increase in sensitivity (a shift of the threshold response towards low concentration) with respect to the CD design, which is paid for by a lesser ability to follow fast changes in stimulus intensity.     

Teleost isotocin receptor: structure, functional expression, mRNA distribution and phylogeny

A cDNA encoding a receptor for the oxytocin-related peptide isotocin has been identified by screening a lambda gt11 library constructed from poly(A)⁺ RNA of the hypothalamic region of the teleost Catostomus commersoni. The probe used was obtained by PCR amplification of white sucker genomic DNA using degenerate primers based on conserved sequences in the mammalian receptor counterparts. The full-length cDNA specifies a polypeptide of 390 amino acid residues that displays the typical hydrophobicity profile of a seven transmembrane domain receptor and which exhibits greatest similarity to mammalian oxytocin receptors. Oocytes that express the cloned receptor respond to the application of isotocin by an induction of membrane chloride currents indicating that it is coupled to the inositol phosphate/calcium pathway. The isotocin receptor (ITR) can also be activated by vasotocin, mesotocin, oxytocin and Arg-vasopressin, although these have lower potencies than isotocin. ITR-encoding mRNA has been detected in brain, intestine, bladder, skeletal muscle, lateral line, gills and kidney indicating that this receptor may mediate a variety of physiological functions.     

The fish odour syndrome: biochemical,familial, and clinical aspects.

OBJECTIVES--To study the biochemical, familial, and clinical features of the fish odour syndrome among subjects with suspected body malodour. DESIGN--Subjects who responded to a newspaper article were screened for the fish odour syndrome by interview and biochemical tests. Families of subjects with the syndrome were tested if possible. SETTING--St Mary''s Hospital, London, and some interviews at subjects'' homes. SUBJECTS--187 subjects (28 males) with suspected body malodour, of whom 156 (19 males) underwent biochemical tests. Five families of six of the subjects with the fish odour syndrome agreed to further tests. MAIN OUTCOME MEASURES--Amounts of trimethylamine and trimethylamine N-oxide in urine collected over 24 hours under normal dietary conditions and for eight hours after oral challenge with 600 mg trimethylamine. RESULTS--The fish odour syndrome was diagnosed in 11 subjects: the percentage of total trimethylamine excreted in their urine samples that was oxidised to trimethylamine N-oxide was < 55% under normal dietary conditions and < 25% after oral challenge with trimethylamine (in normal subjects > 80% of trimethylamine was N-oxidised). Parents of six of the subjects with the syndrome were tested: all showed impaired N-oxidation of excreted trimethylamine (< 80%) after oral challenge, indicating that they were heterozygous carriers of the allele for the syndrome. The syndrome was associated with various psychosocial reactions including clinical depression. CONCLUSIONS--The fish odour syndrome can be inherited in an autosomal recessive fashion. It should be considered as a possible causative factor in patients complaining of body malodour.     

The prefrontal cortex: categories,concepts and cognition

The ability to generalize behaviour-guiding principles and concepts from experience is key to intelligent, goal-directed behaviour. It allows us to deal efficiently with a complex world and to adapt readily to novel situations. We review evidence that the prefrontal cortex-the cortical area that reaches its greatest elaboration in primates-plays a central part in acquiring and representing this information. The prefrontal cortex receives highly processed information from all major forebrain systems, and neurophysiological studies suggest that it synthesizes this into representations of learned task contingencies, concepts and task rules. In short, the prefrontal cortex seems to underlie our internal representations of the 'rules of the game'. This may provide the necessary foundation for the complex behaviour of primates, in whom this structure is most elaborate.     

Controlling light absorption and photoelectric properties of coumarin-triphenylaminedye by different acceptor functional groups

The ground state and excited state properties of three coumarin dyes, ZCJ1, ZCJ2 and ZCJ3, including ground state structures, energy levels, absorption spectra and driving forces of electron injection, were investigated via density functional theory (DFT) and time-dependent density functional theory (TD-DFT). In addition, five new molecules ZCJ3-1, ZCJ3-2, ZCJ3-3, ZCJ3-4 and ZCJ3-5 were designed through the introduction of a –CN group into molecule ZCJ3. The ground state and excited state properties of the five designed molecules were also calculated and compared with that of the original molecule, aiming to investigate the effect of different position of –CN groups on the optical and electrical properties of dye molecules. Moreover, the external electric field was taken into account. The results indicated that all three original molecules have better absorption within the visible-light range, and the molecule with a thiophene–thiophene conjugated bridge enables a red shift of the absorption spectrum. The molecule with a thiophene–benzene ring conjugated bridge enables the increase of driving force of electron injection. The energy levels, spectra and driving force of electron injection for the designed molecules are discussed in terms of studying their potential utility in dye-sensitized solar cells.     

Cortical contributions to olfaction: plasticity and perception

In most sensory systems, the sensory cortex is the place where sensation approaches perception. As described in this review, olfaction is no different. The olfactory system includes both primary and higher order cortical regions. These cortical structures perform computations that take highly analytical afferent input and synthesize it into configural odor objects. Cortical plasticity plays an important role in this synthesis and may underlie olfactory perceptual learning. Olfactory cortex is also involved in odor memory and association of odors with multimodal input and contexts. Finally, the olfactory cortex serves as an important sensory gate, modulating information throughput based on recent experience and behavioral state.     

Human body odour, symmetry and attractiveness.

Several studies have found body and facial symmetry as well as attractiveness to be human mate choice criteria. These characteristics are presumed to signal developmental stability. Human body odour has been shown to influence female mate choice depending on the immune system, but the question of whether smell could signal general mate quality, as do other cues, was not addressed in previous studies. We compared ratings of body odour, attractiveness, and measurements of facial and body asymmetry of 16 male and 19 female subjects. Subjects wore a T-shirt for three consecutive nights under controlled conditions. Opposite-sex raters judged the odour of the T-shirts and another group evaluated portraits of the subjects for attractiveness. We measured seven bilateral traits of the subject's body to assess body asymmetry. Facial asymmetry was examined by distance measurements of portrait photographs. The results showed a significant positive correlation between facial attractiveness and sexiness of body odour for female subjects. We found positive relationships between body odour and attractiveness and negative ones between smell and body asymmetry for males only if female odour raters were in the most fertile phase of their menstrual cycle. The outcomes are discussed in the light of different male and female reproductive strategies.     

Adaptive pattern classification and universal recoding: II. Feedback,expectation, olfaction,illusions

Part I of this paper describes a model for the parallel development and adult coding of neural feature detectors. It shows how any set of arbitrary spatial patterns can be recoded, or transformed, into any other spatial patterns (universal recoding), if there are sufficiently many cells in the network's cortex. This code is, however, unstable through time if arbitrarily many patterns can perturb a fixed number of cortical cells. This paper shows how to stabilize the code in the general case using feedback between cellular sites. A biochemically defined critical period is not necessary to stabilize the code, nor is it sufficient to ensure useful coding properties.We ask how short term memory can be reset in response to temporal sequences of spatial patterns. This leads to a context-dependent code in which no feature detector need uniquely characterize an input pattern; yet unique classification by the pattern of activity across feature detectors is possible. This property uses learned expectation mechanisms whereby unexpected patterns are temporarily suppressed and/or activate nonspecific arousal. The simplest case describes reciprocal interactions via trainable synaptic pathways (long term memory traces) between two recurrent on-center off-surround networks undergoing mass action (shunting) interactions. This unit can establish an adaptive resonance, or reverberation, between two regions if their coded patterns match, and can suppress the reverberation if their patterns do not match. This concept yields a model of olfactory coding within the olfactory bulb and prepyriform cortex. The resonance idea also includes the establishment of reverberation between conditioned reinforcers and generators of contingent negative variation if presently avialable sensory cues are compatible with the network's drive requirements at that time; and a search and lock mechanism whereby the disparity between two patterns can be minimized and the minimal disparity images locked into position. Stabilizing the code uses attentional mechanisms, in particular nonspecific arousal as a tuning and search device. We suggest that arousal is gated by a chemical transmitter system—for example, norepinephrine—whose relative states of accumulation at antagonistic pairs of on-cells and off-cells through time can shift the spatial pattern of STM activity across a field of feature detectors. For example, a sudden arousal increment in response to an un-expected pattern can reverse, or rebound, these relative activities, thereby suppressing incorrectly classified populations. The rebound mechanism has formal properties analogous to negative afterimages and spatial frequency adaptation.Supported in part by the Advanced Research Projects Agency under ONR Contract No. N00014-76-C-0185     

Psychophysical methodology in odour pollution research: the measurement of poultry house odour detectability and intensity

The main purpose of the present experiment was to develop amethodology for the measurement of the detectability and intensityof agricultural odorants using established psychological procedures. Twelve odorants from three poultry houses differing amongstothers in their manure treatment systems were bag sampled andinvestigated in a controlled laboratory setting. Using a simpleone port dilution olfactometer, six subjects judged the airdiluted concentrations presented. The detectability of the odorants was studied using a procedurerelated to signal detection theory; the perceived odour intensitywas measured by the method of direct magnitude estimation. Thedetectability and psychophysical functions were constructed,and a rationale was developed for anchoring the psychophysicalfunctions from the twelve odorants investigated. Over the period of investigation the exponents of the psychophysicalfunctions obtained for odorants sampled from the same poultryhouse were very similar. Differences in this respect betweenodorants of different poultry houses appeared to be large. However,it was observed that the estimated intensities of undilutedodorants obtained from the same poultry house varied to someextent. These findings were discussed from a methodologicalpoint of view. ^*Present address to which all correspondence should be sent:Department of Human Nutrition, Agricultural University, De Dreijen11, 6703 BC Wageningen, The Netherlands