Olfactory Discrimination Ability for Aliphatic Esters in Squirrel Monkeys and Humans

Using a behavioral paradigm designed to simulate olfactory-guidedforaging, the ability of five squirrel monkeys to distinguishiso-amyl acetate from n-and iso-forms of other acetic esters(ethyl acetate to decyl acetate) and from other esters carryingthe iso-amyl group (iso-amyl propionate to iso-amyl capronate)was investigated. We found (i) that all five animals were clearlyable to discriminate between all odor pairs tested; (ii) a significantnegative correlation between discrimination performance andstructural similarity of odorants in terms of differences incarbon chain length of both the aliphatic alcohol group andthe aliphatic acid group of the esters; and (iii) that iso-and n-amyl acetate were perceived as qualitatively similar despitedifferent steric conformation. Using a triple-forced choiceprocedure, 20 human subjects were tested on the same tasks inparallel and showed a very similar pattern of discriminationperformance compared with the squirrel monkeys. Thus, the resultsof this study provide evidence of well-developed olfactory discriminationability in squirrel monkeys for aliphatic esters and supportthe assumption that human and non-human primates may share commonprinciples of odor quality perception. Chem. Senses 22: 457–465,1997.     

Individual differences in thresholds and quality reports of human subjects to various odors

Sixty-three subjects were selected on the basis of their relativeability (n = 30) or inability (n = 33) to detect the intenseurine–sweaty odor of the diastereoisomeric ketone, cis-4-(4'-t-butylcyclohexyl)-4-methyl-2-pentanone (pemenone). Absolute thresholds were determined,and quality reports and hedonic ratings were obtained for near-thresholdconcentrations of pemenone and five other odorous compounds.Several of these compounds were selected because large individualdifferences in sensitivity (specific anosmias) were known toexist. A principal compound analysis of threshold concentrationsindicated that three orthogonal factors well described the relationshipsbetween sensitivities to the compounds. Threshold concentrationsof pemenone and androstenone were highly correlated and thefirst factor was defined by relationships between those odorantsand isovaleric acid, all modally putrid-smelling compounds.Subjects relatively osmic for pemenone generally reported aputrid odor for pemenone, but anosmics reported mostly otherqualities. These relationships between relative sensitivityand the quality reports elicited by the different compoundsare consistent with a multiple-profile model of odor qualityperception. That model postulates that most odor molecules interactwith more than one perceptual channel (receptor process) andthat any individual alteration in the relative specificity ordeletion in the number of such receptor processes could alterthe pattern of interaction and thus should give rise to alterationsin the quality or intensity of the resulting odor perception.     

Odor Perception and Beliefs about Risk

Although the perceptual response to environmental odors canbe quite variable, such variation has often been attributedto differences in individual sensitivity. An information-processinganalysis of odor perception, however, treats both the receptionand the subsequent evaluation of odor information as determinantsof the perceptual response. Two experiments investigated whethera factor that influenced the evaluation stage affected the judgementof odor quality and the degree of adaptation to the odor. Peoplewere surveyed in order to measure their tacit perceptions ofthe healthfulness or hazardousness of nine common olfactorystimuli, and the instructional context influenced quality perception.In a second experiment subjects were exposed to an ambient odorunder one of three different conditions, and odorant characterizationinfluenced the degree of adaptation to the odor. Subjects whowere led to believe the odor was a natural, healthy extractshowed adaptation; those told that the odor was potentiallyhazardous showed apparent sensitization; while those told thatthe odor was a common olfactory test odorant showed a mixedpattern: some exhibited adaptation, whereas others showed sensitization.However, detection thresholds obtained before and after exposureshowed adaptation effects that are characteristic of continuousexposure. These findings raise the possibility that cognitivefactors may be modulating the overall sensory perception ofodor exposure (i) for some individuals who exhibit extreme sensitivityto odors and (ii) in situations where adaptation to environmentalodors is expected but does not occur. Chem. Senses 21: 447–458,1996.     

Odor Perception Phenotypes: Multiple, Specific Hyperosmias to Musks

Olfactory detection thresholds for 11 structurally diverse muskodorants and one non-musk odorant were obtained from 32 subjects.Hierarchical cluster analysis produced four groups of subjects.One group (n = 12) was uniformly sensitive to all musks; another(n = 16) was uniformly insensitive. Two groups of subjects containedotherwise insensitive individuals who were exceptionally sensitiveto cyclopentadecanone and musk xylol (n = 2) and to delta9-hexadecenolactoneand tonalid (n = 2) respectively. We propose that the lattertwo groups are odor perception phenotypes (MSHM1 and MSHM2)that consist of multiple, specific hyperosmias to musk odorants.Chem. Senses 21: 411– 416, 1996. ¹Present address: Synesthetics, Inc., Montclair, NJ 07043, USA     

Semantic, typicality and odor representation: a cross-cultural study

This study investigated odor-category organization in threecultures by evaluating (i) the relationship between linguisticand perceptual categorization and (ii) the existence of an internalstructure of odor categories. In the first experiment, threegroups of 30 participants from American, French and Vietnamesecultures performed a sorting task. The first group sorted 40odorants on the basis of odor similarity, the second group sorted40 odor names on the basis of name similarity and the last groupsorted 40 odor names on the basis of imagined odor similarity.Results showed that odor categorization was based on perceptualor conceptual similarity and was in part independent of wordand imagined categorizations. In the second experiment, anothergroup of 30 participants from each culture rated the typicalityof the odorants for 11 odor categories. Results showed thatsome odorants were rated as more typical than others. Moreover,the typicality gradient predicted the odor space obtained inthe odor sorting task in a consensual way among the three cultures.These results suggest that, as for other categories, odor categoriesare based on perceptual similarities rather than on semanticcues. Moreover odor-category structure might have a core representationwhich might be common to different cultures with boundarieswhich might be more culturally dependent.     

Amiloride Effects on Taste Quality: Comparison of Single and Multiple Response Category Procedures

Although there is compelling evidence that amiloride reducesthe intensity of Na⁺ and Li⁺ salts in humans, its effects onsaltiness are conflicting. Many salts elicit not only a saltytaste but also one or more side tastes (sweetness, sournessor bitterness). Some studies have shown a suppression of saltinessby amiloride; others show no effect on saltiness but a significantreduction in sourness. In the experiments demonstrating a reductionof saltiness, subjects estimated only saltiness; in those showingan amiloride effect on sourness and not saltiness, subjectsestimated all qualities on each trial. The present study examinesthe role of the psychophysical method in these conflicting results.We have investigated the effects of amiloride on taste qualityby modifying only the instructions to the subjects, keepingall other variables constant. One group of subjects (intensity-only)gave magnitude estimates of the overall intensity of a LiCIconcentration series. A second group (salty-only) was instructedto estimate the saltiness of the stimuli, and a third group(sour-only) estimated their sourness. Finally, a fourth group(profile) rated all of the taste qualities on each stimuluspresentation, using a modified taste profile method. The ratingsof all groups were made comparable by the use of 0.1 mM quinine-HCIas a modulus. When subjects used only one response category,amiloride reduced their estimates (of intensity, saltiness orsourness), but if subjects attended to all four qualities, amiloridespecifically reduced the sourness of LJCI and had no significanteffect on its saltiness. Comparison of the saltiness estimatesof the salty-only group to the sum of the salty and sour estimatesof the profile group demonstrated that subjects combined thesesensations when presented with only one response alternative.To reveal the effect of amiloride on a specific quality of asalt, the psychophysical method must allow subjects to attendto all qualities on each trial. These data and previous resultssuggest that apical Na⁺ channels on the taste receptor cellmembrane mediate the sourness but not the saltiness of Na⁺ andLi⁺ salts. Chem. Senses 22: 267–275, 1997.     

Evaluating the 'Labeled Magnitude Scale' for Measuring Sensations of Taste and Smell

The Labeled Magnitude Scale (LMS) is a semantic scale of perceptualintensity characterized by a quasi-logarithmic spacing of itsverbal labels. The LMS had previously been shown to yield psychophysicalfunctions equivalent to magnitude estimation (ME) when gustatory,thermal and nociceptive stimuli were presented and rated together,and the upper bound of the LMS was defined as the ‘strongestimaginable oral sensation’. The present study comparedthe LMS to ME within the more limited contexts of taste andsmell. In Experiment 1, subjects used both methods to rate eithertaste intensity produced by sucrose and NaCl or odor intensityproduced by acetic acid and phenyl ethyl alcohol, with the upperbound of the LMS defined as either the ‘strongest imaginabletaste’ or the ‘strongest imaginable odor’.The LMS produced psychophysical functions equivalent to thoseproduced by ME. In Experiment 2 a new group of subjects usedboth methods to rate the intensity of three different tastequalities, with the upper bound of the LMS defined as the ‘strongestimaginable [sweetness, saltiness, or bitterness]’. Inall three cases the LMS produced steeper functions than didME. Experiment 3 tested the hypothesis that the LMS yields datacomparable to ME only when the perceptual domain under studyincludes painful sensations. This hypothesis was supported whenthe LMS again produced steeper functions than ME after subjectshad been explicitly instructed to omit painful sensations (e.g.the ‘burn’ of hot peppers) from the concept of ‘strongestimaginable taste’. We conclude that the LMS can be usedto scale sensations of taste and smell when they are broadlydefined, but that it should be modified for use in scaling specifictaste (and probably odor) qualities. The implications of theseresults for theoretical issues related to ME, category-ratioscales and the size of the perceptual range in different sensorymodalities are discussed. Chem. Senses 21: 323–334, 1996.     

Divergence of mate recognition in the African striped mouse (Rhabdomys)

Mate recognition systems (MRSs) are complex signal-receivertraits. The present study addressed the roles of phylogeny,ecology, and geography in shaping the MRS of the African stripedmouse (Rhabdomys), which has a wide distribution in southernAfrica. Two putative species are recognized, which have differentecologies: Rhabdomys pumilio (arid) and Rhabdomys dilectus (mesic).The latter may be further subdivided into 2 subspecies (R. dilectusdilectus and R. dilectus chakae). Using 2 discrete populationsper taxon, we investigated within- and between-taxon variationsin male odor quality and female perception using habituation-discriminationand habituation-generalization tests, and female preferencein 2-way choice tests. Our results indicate: 1) no within-taxonvariation in odor quality, perception, or preference; 2) the2 subspecies of R. dilectus carry signals of different qualitiesbut share a common odor characteristic distinct from that ofR. pumilio; 3) female R. pumilio did not show a preference whentheir own species and R. d. chakae odors were presented simultaneouslybut displayed assortative preference when the alternative wasR. d. dilectus; 4) females of the 2 subspecies showed dissimilarpreferences: R. d. chakae for the genetically more similar taxonand R. d. dilectus for the most different one. Although we couldnot rule out the influence of ecology, we concluded that phylogenyappeared a more parsimonious explanation for the pattern ofdivergence in Rhabdomys. Further, we discuss our results inlight of current models on signal-receiver coevolution.     

CellLine, a stochastic cell lineage simulator

Summary: We present CellLine, a simulator of the dynamics ofgene regulatory networks (GRN) in the cells of a lineage. Fromuser-defined reactions and initial substance quantities, itgenerates cell lineages, i.e. genealogic pedigrees of cellsrelated through mitotic division. Each cell's dynamics is drivenby a delayed stochastic simulation algorithm (delayed SSA),allowing multiple time delayed reactions. The cells of the lineage can be individually subject to ‘perturbations’,such as gene deletion, duplication and mutation. External interventions,such as adding or removing a substance at a given moment, canbe specified. Cell differentiation lineages, where differentiationis stochastically driven or externally induced, can be modeledas well. Finally, CellLine can generate and simulate the dynamicsof multiple copies of any given cell of the lineage. As examples of CellLine use, we simulate the following systems:cell lineages containing a model of the P53-Mdm2 feedback loop,a differentiation lineage where each cell contains a 4 generepressilator (a bistable circuit), a model of the differentiationof the cells of the retinal mosaic required for color visionin Drosophila melanogaster, where the differentiation pathwaydepends on one substance's concentration that is controlledby a stochastic process, and a 9 gene GRN to illustrate theadvantage of using CellLine rather than simulating multipleindependent cells, in cases where the cells of the lineage aredynamically correlated. Availability: The CellLine program, instructions and examplesare available at http://www.cs.tut.fi/~sanchesr/CellLine/CellLine.html Contact: andre.sanchesribeiro{at}tut.fi Associate Editor: Limsoon Wong     

A new algorithm for cluster analysis of genomic methylation: the Helicobacter pylori case

Motivation: The genomic methylation analysis is useful to typebacteria that have a high number of expressed type II methyltransferases.Methyltransferases are usually committed to Restriction andModification (R-M) systems, in which the restriction endonucleaseimposes high pressure on the expression of the cognate methyltransferasethat hinder R-M system loss. Conventional cluster methods donot reflect this tendency. An algorithm was developed for dendrogramconstruction reflecting the propensity for conservation of R-MType II systems. Results: The new algorithm was applied to 52 Helicobacter pyloristrains from different geographical regions and compared withconventional clustering methods. The algorithm works by firstgrouping strains that share a common minimum set of R-M systemsand gradually adds strains according to the number of the R-Msystems acquired. Dendrograms revealed a cluster of Africanstrains, which suggest that R-M systems are present in H.pylorigenome since its human host migrates from Africa. Availability: The software files are available at http://www.ff.ul.pt/paginas/jvitor/Bioinformatics/MCRM_algorithm.zip Contact: filipavale{at}fe.ucp.pt Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop     

Psychophysical and Psychohedonic Functions of Four Common Food Flavours in Elderly Subjects

This study was designed to determine the cause of potentialdifferences in optimal preferred flavour concentrations in fourcommon food items between young and elderly subjects. The mainobjective was to investigate whether the differences in concentration-pleasantnessfunctions could be attributed to differences in concentration-intensity(psychophysical) functions, or to differences in intensity-pleasantness(psychohedonic) functions. Groups of elderly subjects (n = 31)and young subjects (n = 25) judged four series of food items(bouillon, tomato soup, chocolate custard and orange lemonade),each with five geometrically spaced flavour concentration levels.In addition, all participants judged a series of grey surfacesas a reference series. Stimuli were judged on a 10-point scalewith respect to perceived intensity and pleasantness. The resultsshowed that the responses to the various stimuli in the seriesof grey surfaces were almost equivalent for young and elderlysubjects. The older subjects had higher optimal flavour concentrationsthan young subjects for each of the four food items. The differencescould be attributed to differences in both psychophysical andpsychohedonic functions for all four flavours. However, changesin psychohedonic functions were less pronounced for the savouryflavours than for the sweet flavours. The higher optimal preferredflavour concentration level for the elderly could be partlyexplained by the phenomenon that the elderly need higher concentrationlevels than young subjects in order to obtain a similar perceivedintensity level. Chem. Senses, 21: 293ndash;302, 1996.     

Sidestream smoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs

Bonham, A. C., K. S. Kott, and J. P. Joad. Sidestreamsmoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs. J. Appl.Physiol. 81(4): 1715-1722, 1996.We determinedthe effect of sidestream tobacco smoke (SS) exposure on responses oflung rapidly adapting receptors (RARs), peak tracheal pressure (Ptr),and arterial blood pressure (ABP) to substance P in young guinea pigs.Guinea pigs were exposed to SS or filtered air fromday 8 to days41-45 of life. They were then anesthetized andgiven three doses of intravenous substance P (1.56-4.94 nmol/kg).SS exposure augmented substance P-evoked increases in RAR activity(P = 0.029 by analysis of variance) but not substance P-evoked increases in peak Ptr or decreases in ABP.Neurokinin 1-receptor blockade (CP-96345, 400 nmol/kg) attenuatedsubstance P-evoked increases in RAR activity(P = 0.001) and ABP(P = 0.009) but not in peak Ptr(P = 0.06). Thus chronic exposure toSS in young guinea pigs exaggerates RAR responsiveness to substance P. The findings may help explain the increased incidence of airwayhyperresponsiveness and cough in children chronically exposed toenvironmental tobacco smoke.

     

Magnitude-matching: the measurement of taste and smell

In the method of magnitude-matching, subjects try to judge intensitiesof sensations from two or more modalities on a single, commonscale. Using responses to one modality as a standard makes itpossible to compare subjects' suprathreshold perceptions onthe other, test modality. A series of ten experiments revealedthe following: (i) magnitude-matching ‘works’: withboth loudness of tones and lightness of grays as standards,tasters versus nontasters of 6-n-prophylthiouracil (PROP) (asdefined by a threshold criterion) show much greater responceto suprathreshold PROP and slightly greater response to surcose;(ii) though superior to rating-scale judgements of sensory intensitymade without reference to a second modality, magnitude-matchingis not, however, flawless: the cross-modality matching relationproduced by a set of magnitude-matches depends systematicallyon the contextual sets of stimulus levels presented for judgement;(iii) with taste as the standard, old versus young subjectsshowed only a 25% decrement in responce to the odor intensityof butanol when both groups recieved the same physical (concentration)levels, but a >50% decrement in responce when both groupsrecieved about the same perceptual levels; (iv) magnitude-matchesare much the same whether subjets make their judgements on abounded rating-scale or an open-ended magnitude-estimation scale:and (v) loudness, lightness and odor intensity serve about equallyin magnitude-matching with taste intensity.     

Central Processing of Odor Concentration is a Temporal Phenomenon as Revealed by Chemosensory Event-Related Potentials (CSERP)

Chemosensory event-related potentials (CSERP) can be used toexamine central nervous odor processing. An important questionfor understanding odor perception is how different concentrationsare processed. In the present study two odors were chosen whichactivate either the olfactory (linalool) or the trigeminal (menthol)system. Both odors were presented to 11 subjects in four differentconcentrations. Four subjects had to attend actively to theodors while the others perceived the odors under passive attention.The results showed that increased concentrations of the olfactorystimulus resulted in shorter latencies of the N1 component butdid not affect the amplitudes of the CSERP. However, the amplitudesof the stimulus dependent, exogenous components (N1, P2) increasedwith higher concentrations of the trigeminal stimulus. The amplitudeof the late positive complex, which reflects endogenous processes,was usually larger when the odorous stimuli had to be attendedto actively. It is concluded that olfactory intensity codingresults in a qualitatively different but not in a stronger neuronalresponse of the human brain. Chem. Senses 22: 9–26, 1997.     

Ultrastructure and Secretion of the Secretory Cells of Two Species ofFagoniaL. (Zygophyllaceae)

The ultrastructure and secretion of the secretory cells of theglandular trichomes ofFagonia mollisandF. glutinosawere studied.The most important finding of this study is that two speciesof the same genus produce the lipophilic component of the secretorymaterial in completely different ways and at different siteswithin the cell. In the early stages of development of secretorycells ofF. mollis,numerous mitochondria, containing myelin-likestructures, occur in the basal part of the cell. Above them,highly-elongate elements, which are suspected to develop frommitochondria with myelin-like structures, are present. Thesehave been termed ‘modified mitochondria’. It issuggested that the myelin-like structures are precursors ofthe lipophilic material ofF. mollis.InF. glutinosa,the lipophilicmaterial appears first in the plastids as plastoglobuli. Polysaccharidesappear to be produced by dictyosomes in both species. Secretionof the secretory substance to the outside of the protoplastappears to be granulocrine.Copyright 1998 Annals of Botany Company Fagonia mollis,Fagonia glutinosa,glandular trichomes, secretory cell, mitochondria, modified mitochondria, plastids, dictyosomes, lipophilic material, myelin-like structures, polysaccharides     

MMG: a probabilistic tool to identify submodules of metabolic pathways

Motivation: A fundamental task in systems biology is the identificationof groups of genes that are involved in the cellular responseto particular signals. At its simplest level, this often reducesto identifying biological quantities (mRNA abundance, enzymeconcentrations, etc.) which are differentially expressed intwo different conditions. Popular approaches involve using t-teststatistics, based on modelling the data as arising from a mixturedistribution. A common assumption of these approaches is thatthe data are independent and identically distributed; however,biological quantities are usually related through a complex(weighted) network of interactions, and often the more pertinentquestion is which subnetworks are differentially expressed,rather than which genes. Furthermore, in many interesting cases(such as high-throughput proteomics and metabolomics), onlyvery partial observations are available, resulting in the needfor efficient imputation techniques. Results: We introduce Mixture Model on Graphs (MMG), a novelprobabilistic model to identify differentially expressed submodulesof biological networks and pathways. The method can easily incorporateinformation about weights in the network, is robust againstmissing data and can be easily generalized to directed networks.We propose an efficient sampling strategy to infer posteriorprobabilities of differential expression, as well as posteriorprobabilities over the model parameters. We assess our methodon artificial data demonstrating significant improvements overstandard mixture model clustering. Analysis of our model resultson quantitative high-throughput proteomic data leads to theidentification of biologically significant subnetworks, as wellas the prediction of the expression level of a number of enzymes,some of which are then verified experimentally. Availability: MATLAB code is available from http://www.dcs.shef.ac.uk/~guido/software.html Contact: guido{at}dcs.shef.ac.uk Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Jonathan Wren     

An analytical pipeline for genomic representations used for cytosine methylation studies

Motivation: Representations of the genome can be generated bythe selection of a subpopulation of restriction fragments usingligation-mediated PCR. Such representations form the basis fora number of high-throughput assays, including the HELP assayto study cytosine methylation. We find that HELP data analysisis complicated not only by PCR amplification heterogeneity butalso by a complex and variable distribution of cytosine methylation.To address this, we created an analytical pipeline and novelnormalization approach that improves concordance between microarray-deriveddata and single locus validation results, demonstrating thevalue of the analytical approach. A major influence on the PCRamplification is the size of the restriction fragment, requiringa quantile normalization approach that reduces the influenceof fragment length on signal intensity. Here we describe allof the components of the pipeline, which can also be appliedto data derived from other assays based on genomic representations. Contact: jgreally{at}aecom.yu.edu Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Joaquin Dopazo