Effect of Nasal Dilators on Perceived Odor Intensity

Subjects wearing nasal dilators rated olfactory stimuli as beingmore intense compared with ratings done without nasal expansion.The results support a perceptual constancy model in olfaction.Chem. Senses 22: 177–180, 1997. ¹Present address: Biology Department, St Lawrence UniversityCanton, NY 13617, USA ²Present address: PO Box 802, Drew University, Madison, NJ 07940,USA     

Bimodal (Taste/Tactile) Fibers Innervate the Maxillary Barbel in the Channel Catfish

Analysis of single fibers isolated from a branch of the facial/trigeminalcomplex innervating the maxillary barbel of the channel catfish,Ictalurus punctatus, indicated the existence of bimodal (taste/tactile)fibers. Of the 60 single fibers recorded, 14 (23%) respondedto both taste (amino acid) and tactile stimulation, 43 (72%)were responsive to only tactile stimulation and three (5%) respondedonly to taste stimulation. Quinine hydrochloride at a concentrationof 1.0 mM suppressed the mechanosensory activity of the bimodalfibers, but had no effect on the tactile-only fibers. Chem.Senses 22: 477–482, 1997. ¹Current address: Department of Otolaryngology, Kagoshima UniversityMedical School, 8-35-1 Sakuragaoka, Kagoshima 890, Japan ²Current address: Department of Oral Physiology, Ohu UniversitySchool of Detistry, 31-1 Misumido, Tomita, Koriyama, Fukushima963, Japan     

INHIBITION OF CONTRACTION RESPONSES OF HYDRA

The contraction reponse ot hydra to intermittent light stimulationmay be inhibited by exposing the animal to reduced glutathione(GSH). Such inhibitory acthity is dependent on: (1) the concentrationof GSH; (2) the pH of the medium; (3) previous exposure to GSH;and (4) the nutritional state of the animal. Hydra adapt tolO^–5 M GSH so that after approximately an hour the frequenciesof lightinduced contractions are restored to control levels.Such adaptation to GSH is due to changes occurring within theanimal rather than to the degradation of the glutathione molecule.S-methyl glutathione blocks contractions in response to light,showing that the sulfhydryl group is not essential for inhibition.Analogs with sterically large groups substituted for the sulfhydrylgroup, such as oxidized glutathione and S-acetyl glutathione,have no inhibitory activity. These compounds, however, reducethe inhibitory effect of GSH, indicating competition for theGSH receptor. Contractions of hydra in response to intermittent mechanicalagitation are also inhibited by GSH. The duration of inhibitionis dependent on the GSH concentration. Both oxidized glutathioneand S-acetyl glutathione reduce the inhibitory effect of GSH. Hydra adapted to the dark for 24 hours show a marked suppressionof contractions in response to mechanical agitation when exposedto light. On exposure to light, such animals elongate to approximatelyone and a half times their dark adapted length, and are relativelyinsensitive to agitation. The mechanisms by which such stimuliinhibit the contraction responses of hydra remain to be determined.     

Induction of a Calcium-dependent Long-term Enhancement of Excitability in the Rat Olfactory Bulb

We have investigated whether a transient increase in extracellularcalcium concentration is able to induce long-term modificationof neuronal excitability in the olfactory bulb. High-calciumartificial cerebrospinal fluid containing picrotoxin (Ca-PTXsolution) was applied locally near the mitral cell layer througha push-pull device for 10 min in anaesthetized rats. Changesin the neuronal excitability were monitored through electrically-evokedfield potentials. Application of the Ca-PTX solution induceda rapid increase in the granule cell response amplitude, whereasmitral/tufted cells response amplitude increased more progressivelyand reached its maximum within a few hours. The increase inmitral/tufted cells response and granule cells response reachedbetween 30 and 100% in experiments which lasted for 4–8h. Pre-application of amino-phosphonovalerate (NMDA receptorblocker) potently reduced both short- and long-term enhancementproduced by the Ca-PTX solution. Neither application of thehigh calcium solution alone nor the picrotoxin solution aloneinduced long-term changes. The results point out the possibleimportance of Ca²⁺ and NMDA receptors in persistent forms ofolfactory bulb plasticity. Relevance of this phenomenon in normalolfactory bulb physiology remains to be examined. Chem. Senses21: 159–168, 1996. ¹Present address: California Institute of Technology, Divisionof Biology 216-76, Pasadena, CA 91125, USA     

Thermodynamic Roles of Solubility in Taste Responses of Amino Acids

Bitter, sour and sweet responses of amino acids were relatedto their solubilities S_w, which are virtually equal to the reciprocalsof activity coefficients at infinite dilution in water _w, andalso related to their excess partial molar entropies of transferTS_t^E. Chem. Senses 21: 405–409, 1996. Present address: 5-32-12 Tamanawa, Kamakura-shi, 247 Japan     

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     

Electrophysiological Evidence for the Broad Distribution of Specific Odorant Receptor Molecules across the Olfactory Organ of the Channel Catfish

To determine if there is a spatial segregation of responsivenessto odorants within the olfactory epithelium, microelectroderecordings were obtained from small populations of olfactoryreceptor neurons located across different lamellar sensory regionsof the olfactory organ of the channel catfish, lctalurus punctatus.Stimuli included L-alanine, L-methionine, L-arginine hydrochloride,L-glutamic acid, ATP and a mixture of bile salts—odorantspreviously reported to stimulate independent receptor sitesin aquatic species. The peak integrated olfactory receptor responsesat each recording site were standardized to the response toL-alanine. The relative stimulatory effectiveness of the stimuliwas preserved across the 10 olfactory lamellae recording sites.These data support previous molecular biological results ofa broad distribution of receptor neurons that express specificreceptor genes across the olfactory organ of the channel catfish.Chem. Senses 21: 519-527, 1996. ¹Present address: Institute of Cognitive and Computational SciencesGeorgetown University Medical Center, Washington, DC 20007,USA     

Recalling Taste Intensities in Sweetened and Salted Liquids

The effect of training on recalling taste intensities over 6weeks was studied using an ad libitum mixing procedure. Subjectstasted sweet and salty standards labeled as ‘weak’and ‘strong’ (3 and 8% sucrose in redcurrant juice;0.4 and 1.2% NaCl in beef broth). They subsequently mixed unsweetenedand sweetened juice, and unsalted and salted broth, to producetaste intensities that corresponded to the standards. A minimumtraining (MT) group (n = 13) produced comparison stimuli bytasting and directly comparing with standards in one sessiononly; an extensive training (ET) group (n = 13) did this insix sessions before producing comparison stimuli based on memoryonly at 1 h, 1 day, 1 week and 6 weeks. An upward bias (chemicallydetermined concentrations of comparison stimuli exceeding thoseof standards) occurred at 1 day or 1 week in MT subjects for‘weak’ and ‘strong’ sweetness, and for‘strong’ saltiness, and sustained thereafter. Theupward tendency was also observed in ET subjects but was significantonly for ‘strong’ sweetness. It is important torecognize memory effects such as the one described, as theyaffect food perceptions and can be a major source of bias insensory food research. Chem. Senses 21: 29–34, 1996. ³Current address: Psychonomics Department, Utrecht University,Heidelberglaan 2, 3584 CS Utrecht, The Netherlands     

BicOverlapper: a tool for bicluster visualization

Summary: BicOverlapper is a tool to visualize biclusters fromgene-expression matrices in a way that helps to compare biclusteringmethods, to unravel trends and to highlight relevant genes andconditions. A visual approach can complement biological andstatistical analysis and reduce the time spent by specialistsinterpreting the results of biclustering algorithms. The techniqueis based on a force-directed graph where biclusters are representedas flexible overlapped groups of genes and conditions. Availability: The BicOverlapper software and supplementary materialare available at http://vis.usal.es/bicoverlapper Contact: rodri{at}usal.es Associate Editor: John Quackenbush The first two authors should be reported as joint first authors.     

GlycoBase and autoGU: tools for HPLC-based glycan analysis

Summary: The development of robust high-performance liquid chromatography(HPLC) technologies continues to improve the detailed analysisand sequencing of glycan structures released from glycoproteins.Here, we present a database (GlycoBase) and analytical tool(autoGU) to assist the interpretation and assignment of HPLC-glycanprofiles. GlycoBase is a relational database which containsthe HPLC elution positions for over 350 2-AB labelled N-glycanstructures together with predicted products of exoglycosidasedigestions. AutoGU assigns provisional structures to each integratedHPLC peak and, when used in combination with exoglycosidasedigestions, progressively assigns each structure automaticallybased on the footprint data. These tools are potentially verypromising and facilitate basic research as well as the quantitativehigh-throughput analysis of low concentrations of glycans releasedfrom glycoproteins. Availability: http://glycobase.ucd.ie Contact: matthew.campbell{at}nibrt.ie Associate Editor: Limsoon Wong Present address: Dublin-Oxford Glycobiology Laboratory, NationalInstitute for Bioprocessing Research and Training, Conway Institute,University College Dublin, Dublin, Ireland. Present address: Ludger Ltd, Culham Science Centre, Abingdon,Oxfordshire OX14 3EB., UK.     

The occurrence and properties of dihydrofolate reductase in pea seedlings

Dihydrofolate reductase (E.C. 1.5.1.3 [EC] ) was found in pea seedlingsand was partially purified by treatments with ammonium sulfate,protamine sulfate and by DEAE-cellulose column chromatography.Some properties of the enzyme were investigated. Optimum pHfor the reaction was 6.5. In the enzyme reaction, FAH₂ and NADPH₂were specifically required. MICHAELIS constants for FAH₂ andNADPH₂ were 4.3x10^–6 M and 4.0x10^–5 M, respectively.Folate antagonists such as aminopterin, methotrexate and pyrimethaminewere potent inhibitors of this enzyme. Enzyme activity was almostcompletely inhibited at a concentration of 10^–7 M of aminopterinand methotrexate and 10^–6 M of pyrimethamine. Growth of germinating pea seeds was inhibited by aminopterin,methotrexate and pyrimethamine, and it recovered significantlywith a tetrahydro-derivative of folate, CF, but not with dihydrofolicor folic acid. These results suggest that growth inhibitionof pea seedlings by these antagonists is due to inhibition ofdihydrofolate reductase in seedlings. ¹Studies on the enzymatic synthesis and metabolism of folatecoenzymes in plants IV. (For the previous paper, Part III, seeReference (21)) . Part of this paper was presented at the AnnualMeeting of the Agricultural Chemical Society of Japan held atTokyo on April 4, 1967 (Received October 8, 1969; )     

Celestial3D: a novel method for 3D visualization of familial data

Summary: Traditional two-dimensional (2D) software programsfor drawing pedigrees are limited when dealing with extendedpedigrees. In successive generations, the number of individualsgrows exponentially, leading to an unworkable amount of spacerequired in the horizontal direction for 2D displays. In addition,it is not always possible to place closely related individualsnear each other due to the lack of space in 2Ds. To addressthese issues we have developed three-dimensional (3D) pedigreedrawing techniques to enable clearer visualization of extendedpedigrees. Currently no other methods are available for displayingextended pedigrees in 3Ds. We have made freely available a softwaretool—‘Celestial3D’—that implements thesenovel techniques. Availability: Freely available to non-commercial users Contact: celestial3d{at}genepi.org.au Supplementary information: www.genepi.org.au/celestial3d Associate Editor: Martin Bishop ¹A more extensive list of software tools appears in the SupplementaryMaterial.     

Capsaicin Modifies Responses of Rat Chorda Tympani Nerve Fibers to NaCl

Single-fiber preparations of the rat chorda tympani (CT) nervewere used to study the mechanism of action of capsaicin on salt-tastetransduction. Capsaicin selectively suppressed the responsesto NaCl of the CT nerve fibers (N-fibers) that are sodium-specific(insensitive or poorly sensitive to potassium). Among the morebroadly responsive, cation-sensitive fibers (E-fibers) thereare two subtypes, both of which responded to capsaicin but indifferent ways (‘enhanced’ type and ‘suppressed’type). In both N- and E-fibers, 5% ethanol (the vehicle forcapsaicin) slightly reduced the response to 100 mM NaCl. Thesuppressive effect of capsaicin on the response of the N-typefibers to 100 mM NaCl was significantly stronger than the effectof 5% ethanol. The suppression lasted for at least 20 s afterthe simultaneous application of 100 p.p.m. capsaicin-100 mMNaCl. These results indicate that 100 p.p.m. capsaicin can modifythe response of CT fibers to NaCl. The observed effect of capsaicinon gustatory fibers could be the net result of opposite suppressiveand enhancing processes in the taste buds cells and excitedintra- or extragemmal trigeminal nerve endings. Chem. Senses22: 249–255, 1997. ^*These authors contributed equally to this study     

LibSBML: an API library for SBML

Summary: LibSBML is an application programming interface libraryfor reading, writing, manipulating and validating content expressedin the Systems Biology Markup Language (SBML) format. It iswritten in ISO C and C++, provides language bindings for CommonLisp, Java, Python, Perl, MATLAB and Octave, and includes manyfeatures that facilitate adoption and use of both SBML and thelibrary. Developers can embed libSBML in their applications,saving themselves the work of implementing their own SBML parsing,manipulation and validation software. Availability: LibSBML 3 was released in August 2007. Sourcecode, binaries and documentation are freely available underLGPL open-source terms from http://sbml.org/software/libsbml. Contact: sbml-team{at}caltech.edu Associate Editor: Olga Troyanskaya The first two authors should be regarded as First Author.     

Vasopressin Modulates Membrane Properties of Taste Cells Isolated from Bullfrogs

The effect of arginine vasopressin (AVP) on the membrane propertieswas analyzed in isolated bullfrog taste cells using a perforatedwhole-cell patch-clamp technique. AVP (100 nM) induced threekinds of responses in rod-type taste cells: appearance of inwardcurrent, inhibition of voltage ramp-induced outward currentand enhancement of the outward current. The Ca²⁺-ionophore ionomycin(3 µM) also induced inward current in taste cells. A membrane-permeablecAMP analog, 8-CPT-cAMP (0.3 mM) inhibited voltage ramp-inducedoutward current in some rod cells, but enhanced the currentin other rod cells. The results suggest that AVP may increaseeither intracellular Ca²⁺ level or cAMP level in taste cells,modulating the membrane excitability. Chem. Senses 21: 739–745,1996.     

Model-based analysis of non-specific binding for background correction of high-density oligonucleotide microarrays

Motivation: High-density DNA microarrays provide us with usefultools for analyzing DNA and RNA comprehensively. However, thebackground signal caused by the non-specific binding (NSB) betweenprobe and target makes it difficult to obtain accurate measurements.To remove the background signal, there is a set of backgroundprobes on Affymetrix Exon arrays to represent the amount ofnon-specific signals, and an accurate estimation of non-specificsignals using these background probes is desirable for improvementof microarray analyses. Results: We developed a thermodynamic model of NSB on shortnucleotide microarrays in which the NSBs are modeled by duplexformation of probes and multiple hypothetical targets. We fittedthe observed signal intensities of the background probes withthose expected by the model to obtain the model parameters.As a result, we found that the presented model can improve theaccuracy of prediction of non-specific signals in comparisonwith previously proposed methods. This result will provide auseful method to correct for the background signal in oligonucleotidemicroarray analysis. Availability: The software is implemented in the R languageand can be downloaded from our website (http://www-shimizu.ist.osaka-u.ac.jp/shimizu_lab/MSNS/). Contact: furusawa{at}ist.osaka-u.ac.jp Supplementary information: Supplementary data are availableat Bioinformatics online. The authors wish it to be known that, in their opinion, thefirst two authors should be regarded as joint First Authors. Associate Editor: Trey Ideker     

From pull-down data to protein interaction networks and complexes with biological relevance

Motivation: Recent improvements in high-throughput Mass Spectrometry(MS) technology have expedited genome-wide discovery of protein–proteininteractions by providing a capability of detecting proteincomplexes in a physiological setting. Computational inferenceof protein interaction networks and protein complexes from MSdata are challenging. Advances are required in developing robustand seamlessly integrated procedures for assessment of protein–proteininteraction affinities, mathematical representation of proteininteraction networks, discovery of protein complexes and evaluationof their biological relevance. Results: A multi-step but easy-to-follow framework for identifyingprotein complexes from MS pull-down data is introduced. It assessesinteraction affinity between two proteins based on similarityof their co-purification patterns derived from MS data. It constructsa protein interaction network by adopting a knowledge-guidedthreshold selection method. Based on the network, it identifiesprotein complexes and infers their core components using a graph-theoreticalapproach. It deploys a statistical evaluation procedure to assessbiological relevance of each found complex. On Saccharomycescerevisiae pull-down data, the framework outperformed othermore complicated schemes by at least 10% in F₁-measure and identified610 protein complexes with high-functional homogeneity basedon the enrichment in Gene Ontology (GO) annotation. Manual examinationof the complexes brought forward the hypotheses on cause offalse identifications. Namely, co-purification of differentprotein complexes as mediated by a common non-protein molecule,such as DNA, might be a source of false positives. Protein identificationbias in pull-down technology, such as the hydrophilic bias couldresult in false negatives. Contact: samatovan{at}ornl.gov Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Jonathan Wren Present address: Department of Biomedical Informatics, VanderbiltUniversity, Nashville, TN 37232. The authors wish it to be known that, in their opinion, thefirst two authors should be regarded as joint First Authors.     

Planktivory by larval Odontesthes bonariensis (Atherinidae: Pisces) and its effects on zooplankton community structure

This paper describes the effect of predation by larvae of theatherinid Odontesthes bonariensis upon the zooplankton communityduring a 3-month experiment Three-day-old larvae were stockedin 45 m² concrete tanks at rates of 100 and 200 fish m^–2Gut content analyses showed that the larvae consumed relativelysmall prey all along the experiment Morphological (mouth width)and physiological (gastric inefficiency) constraints seems tohave precluded the capture of the largest prey. The prey community,however, showed all the symptoms generally ascribed to size-selectivepredation upon the largest individuals: decrease in maximumzooplankton size and mean cladoceran size, decrease in cladoceranand copepod biomass, extinction of the largest zooplankton species(Daphnia stmilis), increase in rotifer biomass, etc It is concludedthat size-selective predation is not a necessary condition forthe commonly observed decrease in zooplankton size after theincrease in density of a vertebrate predator. The ecologicalimplications of this result are discussed. Present address: Department of Biology, Lehigh University, WilliamsHall 31, Bethlehem, PA 18015-3189, USA     

Disease association tests by inferring ancestral haplotypes using a hidden markov model

Motivation: Most genome-wide association studies rely on singlenucleotide polymorphism (SNP) analyses to identify causal loci.The increased stringency required for genome-wide analyses (withper-SNP significance threshold typically 10^–7) meansthat many real signals will be missed. Thus it is still highlyrelevant to develop methods with improved power at low typeI error. Haplotype-based methods provide a promising approach;however, they suffer from statistical problems such as abundanceof rare haplotypes and ambiguity in defining haplotype blockboundaries. Results: We have developed an ancestral haplotype clustering(AncesHC) association method which addresses many of these problems.It can be applied to biallelic or multiallelic markers typedin haploid, diploid or multiploid organisms, and also handlesmissing genotypes. Our model is free from the assumption ofa rigid block structure but recognizes a block-like structureif it exists in the data. We employ a Hidden Markov Model (HMM)to cluster the haplotypes into groups of predicted common ancestralorigin. We then test each cluster for association with diseaseby comparing the numbers of cases and controls with 0, 1 and2 chromosomes in the cluster. We demonstrate the power of thisapproach by simulation of case-control status under a rangeof disease models for 1500 outcrossed mice originating fromeight inbred lines. Our results suggest that AncesHC has substantiallymore power than single-SNP analyses to detect disease association,and is also more powerful than the cladistic haplotype clusteringmethod CLADHC. Availability: The software can be downloaded from http://www.imperial.ac.uk/medicine/people/l.coin Contact: I.coin{at}imperial.ac.uk Supplementary Information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop