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Partitioning non-linearities in the response of honey bee olfactory receptor neurons to binary odors.

In many organisms, of which honey bees are one example, a general (i.e., non-pheromonal) olfactory receptor neuron may respond to some odorants by increasing its firing rate and to others by decreasing its firing rate. In the latter case, this decrease will be with respect to a background firing rate determined by intrinsic (internal noise) and extrinsic (background odors) factors. To analyse receptor neurons of this complexity, we extend Beidler's model of receptor protein activation dynamics to account for the competition between depolarizing and hyperpolarizing pathways and couple the model to a phenomenological description of the non-linear relationship between the proportion of activate membrane receptors and the receptor cell spike generation rates. We then examine the implications of this theory for predicting the response of receptor neurons to odor mixtures based on their response to pure odorants at concentrations matched to the mixture. We derive inequalities that must be satisfied under our normative model, and propose that deviations from the model be designated as synergisms and inhibitions, depending on the direction in which various equalities and inequalities are violated. We then apply our inequalities to identifying synergisms and inhibitions in data analysed in a different way elsewhere (Akers, R.P. and Getz, W.M. Response of olfactory receptor neurons in honey bees to odorants and their binary mixtures. J. Comp. Physiol. (in press)). In these data regarding the response of honey bee placode sensilla to a number of odorants and their binary combinations, we demonstrate the presence of synergisms and inhibitions--that is, elevated or repressed responses that are not due to competitive interactions of mixture component odorants for receptor sites or Beidler (Beidler, L.M., 1962. Taste receptor stimulation. Prog. Biophys. Biophys. Chem. 12, 107-151) saturation mechanisms.

Animals↗

The molecular signature of selection underlying human adaptations.

In the last decade, advances in human population genetics and comparative genomics have resulted in important contributions to our understanding of human genetic diversity and genetic adaptation. For the first time, we are able to reliably detect the signature of natural selection from patterns of DNA polymorphism. Identifying the effects of natural selection in this way provides a crucial piece of evidence needed to support hypotheses of human adaptation. This review provides a detailed description of the theory and analytical approaches used to detect signatures of natural selection in the human genome. We discuss these methods in relation to four classic human traits--skin color, the Duffy blood group, bitter-taste sensation, and lactase persistence. By highlighting these four traits we are able to discuss the ways in which analyses of DNA polymorphism can lead to inferences regarding past histories of selection. Specifically, we can infer the importance of specific regimes of selection (i.e. directional selection, balancing selection, and purifying selection) in the evolution of a trait because these different types of selection leave different patterns of DNA polymorphism. In addition, we demonstrate how these types of data can be used to estimate the time frame in which selection operated on a trait. As the field has advanced, a general issue that has come to the forefront is how specific demographic events in human history, such as population expansions, bottlenecks, and subdivision of populations, have also left a signature across the genome that can interfere with our detection of the footprint of selection at particular genes. Therefore, we discuss this general problem with respect to the four traits reviewed here, and describe the ways in which the signature of selection can be teased from a background signature of demographic history. Finally, we move from a discussion of analyses of selection motivated by a "candidate-gene" approach, in which a priori information led to the analysis of specific gene, to discussion of "genome-scanning" approaches that are directed at discovering new genes that have been under positive selection. Such scans can be designed to detect those genes that have been positively selected in our divergence from chimpanzees, as well as those genes that have been under selection as human populations have migrated, differentiated, and adapted to specific geographic environments. We predict that both approaches will be applied in the future, enabling a greater insight into human species-wide adaptations, as well as the specific adaptations of human populations.

Animals↗

Chemical and sensory characterization of DOC red wines from Marche (Italy) related to vintage and grape cultivars.

Monomeric phenols, color and copigmentation parameters, pigments with different chemical structure, tannin, glucose, fructose, glycerol, ethanol, and organic acids were determined in DOC red wines from Marche (Italy), obtained during three different vintages ranging from 1996 to 2000. The intensity of the bitter and astringent tastes of the wines was determined with panel tastings. Lacrima di Morro and Vernaccia di Serrapetrona (obtained from local cultivars) were different from Rosso Piceno, Rosso Piceno Superiore, and Rosso Conero (produced from different percentages of Sangiovese and Montepulciano). Vernaccia, a red, sweet, "spumante" wine, was an outlier. Lacrima showed a low tannin content, a high content of small pigments and phenols, and a high ratio of copigmented color, which persisted after 3 years of aging. The chemical determinations accounted for a high percentage of variability of measured panel astringency, copigmented color, and measured wine absorbance at 520 nm. It was not possible to create a predictive model for bitterness.

Fruit↗

Dental status and satisfaction with oral function in a sample of community-dwelling elderly people in Japan.

The purpose of this study was to determine the influence of dental status on oral function and satisfaction among a group of independently living elderly persons in an urban area of Japan. The study sample consisted of participants of the Senior Citizens' College from 1995 to 1999. Their dental status and oral satisfaction were measured by a questionnaire. The number of usable questionnaires was 3967, or 80.8% of the total sample. The mean age of the subjects was 66.5+/-4.3 years, and 52.2% were male. Twenty-nine percent of them had a natural dentition, and 7.0% were edentulous in both jaws. The prevalence of edentulism in the study sample was significantly lower (p < 0.01) than that for the national survey. Overall, 66.4% of the subjects were satisfied with their ability to chew, 56.2% with the appearance of their teeth, 63.1% with their ability to speak clearly, and 76.5% with their ability to taste food. For complete-denture wearers, the greatest dissatisfaction was with speech (28.5%); however, for the RPD wearers, it was with chewing ability (21.7%). Sixty-one percent of complete-denture wearers reported that they were satisfied with their chewing ability, but only 11% of them could eat all three of the evaluated foods without difficulty. The multiple stepwise logistic regression analyses showed that both dental status and self-assessed general health had a significant association with dissatisfaction with all four oral functions and self-assessed impairment of chewing ability. There were significant associations between the elderly subjects' dental status and oral function.

Aged↗

Structure-taste relationships for disubstituted phenylsulfamate tastants using classification and regression tree (CART) analysis.

Forty-two new disubstituted phenylsulfamates have been synthesized, and 30 of these have been combined with 40 already available from earlier work to create a training database of 70 compounds. On the basis of panel taste data these were divided into three categories, N (nonsweet), N/S (nonsweet/sweet), and (S) sweet, and a "sweetness value" or weighting was also calculated for each compound. Using these 70 compounds as a training set and a series of nine predictors derived from Corey-Pauling-Koltun (CPK) models, calculated from the PC SPARTAN PRO program and Hammett sigma values taken from the literature, a classification and regression tree analysis (CART) was carried out leading to a regression tree that correctly classified 62 of the 70 compounds (89% overall correct classification). The tree's predictive ability varies for the different taste categories, and for nonsweet compounds it is virtually 100%; for nonsweet/sweet compounds it is 66%, and for sweet compounds it is approximately 75%. This tree correctly predicted taste categories for 10 compounds from a test set of 12 randomly selected from among the 42 new compounds (83% correct classification). Therefore, it can be used with a good degree of confidence to predict the tastes of disubstituted phenylsulfamates. For the design of new sweeteners, appropriate values or ranges of the descriptors are derived.

Cyclamates↗

The importance of electrostatic potential in the interaction of sweet proteins with the sweet taste receptor.

In addition to many small molecular mass sweeteners there are in nature a few sweet proteins. The molecular volume of sweet proteins is so different from that of common sweeteners that it was difficult to understand how molecules as large as proteins can activate a receptor designed to host small molecules. We have recently shown that sweet proteins can activate the sweet receptor by a mechanism of interaction, called ''wedge model", in which proteins fit a large cavity of the receptor with wedge-shaped surfaces of their structures. In order to substantiate this model we have designed, expressed and characterized seven mutants of MNEI, a single chain monellin. Three uncharged residues of the interaction surface, Met42, Tyr63 and Tyr65, were changed either into acidic or basic residues whereas Asp68, a key acidic residue, was changed into a basic one. As a general trend, we observe that an increase of the negative charge is much more detrimental for sweetness than an increase of positive charge. In addition we show that by a careful choice of a residue at the center of the interface between MNEI and receptor, it is possible even to increase the sweetness of MNEI. These results are fully consistent with the wedge model.

Binding Sites↗

Characterizing bitterness: identification of key structural features and development of a classification model.

This work describes the first approach in the development of a comprehensive classification method for bitterness of small molecules. The data set comprises 649 bitter and 13 530 randomly selected molecules from the MDL Drug Data Repository (MDDR) which are analyzed by circular fingerprints (MOLPRINT 2D) and information-gain feature selection. The feature selection proposes substructural features which are statistically correlated to bitterness. Classification is performed on the selected features via a naïve Bayes classifier. The substructural features upon which the classification is based are able to discriminate between bitter and random compounds, and thus we propose they are also functionally responsible for causing the bitter taste. Such substructures include various sugar moieties as well as highly branched carbon scaffolds. Cynaropicrine contains a number of the substructural features found to be statistically associated with bitterness and thus was correctly predicted to be bitter by our model. Alternatively, both promethazine and saccharin contain fewer of these substructural features, and thus the bitterness in these compounds was not identified. Two different classes of bitter compounds were identified, namely those which are larger and contain mainly oxygen and carbon and often sugar moieties, and those which are rather smaller and contain additional nitrogen and/or sulfur fragments. The classifier is able to predict 72.1% of the bitter compounds. Feature selection reduces the number of false-positives while also increasing the number of false negatives to 69.5% of bitter compounds correctly predicted. Overall, the method presented here presents both one of the largest databases of bitter compounds presently available as well as a relatively reliable classification method.

Algorithms↗

Anxiety-like state associates with taste to produce conditioned taste aversion.

BACKGROUND: The interactions among experience, emotion, and memory are considered to be instrumental in the ontogeny and maintenance of acquired emotional and behavioral disorders (e.g., phobias). Here we address the question whether an anxiety-like state can associate with taste to produce conditioned taste aversion (CTA). METHODS: We have used an anxiogenic agent, the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP), to induce an anxiety-like emotional state in rats after consumption of an unfamiliar tastant. RESULTS: The anxiogenic agent induced CTA. The mCPP-induced CTA could be prevented by concomitant administration of ethanol, which is known to reverse mCPP-induced anxiety-like behavior, at a concentration that had no effect on CTA memory. In contrast, ethanol did not prevent LiCl-induced CTA. Administration of mCPP before the consumption of the tastant had no effect on the preference for that tastant. CONCLUSIONS: Taken together, these results indicate that anxiety-like state can serve as the unconditioned stimulus in CTA training. This finding may be relevant to the ontogeny of pathologies involving food aversion.

Animals↗

Recovery of memory in chicks after disruption during learning: the reversibility of amnesia induced by protein synthesis inhibitors.

Protein synthesis inhibitors given during learning are known to disrupt memory in various animal species in several models of learning. However, there are suggestions that amnesia induced by protein synthesis inhibitors is not permanent--memory can be recovered by a reminder procedure, i.e., by presenting the animal with one of the components of the external environment which was part of the learning situation. The aim of the present work was to determine the existence of the reminder phenomenon in a well-studied model of single-session training to passive avoidance in chicks. Cycloheximide and anisomycin were used to induce amnesia. Reminder was performed using the aversive taste of methylanthranilate 24 h after training, and testing was conducted 48 h after training. The results obtained provide evidence that memory disrupted by protein synthesis inhibitors in chicks can be recovered by the reminder procedure.

Amnesia↗

Planning a spit tobacco cessation intervention: identification of beliefs associated with addiction.

We examine the relationship between beliefs regarding spit tobacco (ST) use and addiction among 473 male college athletes who currently use ST. Beliefs were assessed using methods prescribed by the Theory of Reasoned Action. Independent associations between beliefs and addiction, defined by self-reported amount of ST used per week, were found via multivariate polychotomous regression modeling. We found that with increasing addiction level, athletes were significantly more likely to believe that "ST helps me relax," "ST keeps me alert," "ST tastes good," and "ST is addicting." All athletes believed that clinicians, parents, and girlfriends do not approve of their ST use, but that male peers, coaches, and professional athletes are fairly indifferent about it. To increase quit rates, highly addicted ST users may require an intensive cessation program including nicotine replacement to overcome symptoms of withdrawal, oral substitutes for the enjoyable taste of ST, and the support of male peers and athletes who influence their social norms.

Adolescent↗

The neurocognitive bases of human multimodal food perception: sensory integration.

This review addresses a fundamental neuroscientific question in food perception: how multimodal features of food are integrated. Much research and conceptualization has emerged related to multisensory integration in vision, audition and somatosensation, while it remains poorly understood and researched within the chemical and mouth feel senses. This review aims to bridge this gap. We discuss the main concepts in the fields of auditory, visual and somatosensory multisensory integration and relate them to oral-sensory (gustatory and somatosensory) and olfactory (orolfactory) interactions. We systematically review the psychophysical literature pertaining to intra- and intermodal interactions related to food perception, while making explicit distinctions between peripheral and central interactions. As the neural bases of crossmodal orolfaction currently are poorly understood, we introduce several plausible neuroscientific models, which provide a framework for further neuroscientific exploration in this area. We are guided by a new meta-analysis of the odor-taste neuroimaging literature, as well as by single-unit, anatomical and psychophysical studies. Finally, we propose strong involvement of recurrent neural networks in multisensory integration and make suggestions for future research.

Animals↗

The prolongation of the in vitro dissolution of a soluble drug (phenethicillin potassium) by microencapsulation with ethyl cellulose.

Microcapsules of phenethicillin potassium as a model water-soluble drug, coated with ethyl cellulose, have been prepared (core: wall ratios 1:1, 1:2 and 1:3) in which the taste has been masked, the odour almost eliminated and the release retarded. Sieve analysis showed that with decreasing core: wall ratios there was a trend towards increasing amounts of larger sized microcapsules. At constant core:wall ratios in vitro release of drug was generally greatest from the larger microcapsules. This result correlated with the surface areas of the microcapsules which became less as the asymmetry of the microcapsules diminished with decrease in microcapsule size. There was a linear relation between the amount of ethyl cellulose and the time for 60% release of drug, and the release pattern was analogous to that from insoluble porous matrices. Scanning electron micrographs showed the microcapsules to be irregularly shaped with circular surface pores, and they did not alter in shape or size during dissolution. Tableting of 1:1 core: wall ratio microcapsules significantly further retarded the dissolution.

Capsules↗

Dark, bitter-tasting nectar functions as a filter of flower visitors in a bird-pollinated plant.

Floral nectar is offered by plants to animals as a reward for pollination. While nectar is typically a clear liquid containing sugar and trace amounts of amino acids, colored nectar has evolved in several plant families. Here we explore the functional significance of the phenolic compounds that impart a dark brown color to the nectar of the South African succulent shrub Aloe vryheidensis. Flowers of this aloe are visited for their nectar by a suite of short-billed birds that are occasional nectarivores, including bulbuls, white-eyes, rock thrushes, and chats. Dark-capped Bulbuls were more likely to probe model flowers containing dark nectar than those containing clear nectar, suggesting a potential signaling function for dark nectar. However, the main effect of the phenolics appears to be to repel "unwanted" nectarivores that find their bitter taste unpalatable. Nectar-feeding honey bees and sunbirds are morphologically mismatched for pollinating A. vryheidensis flowers and strongly reject its nectar. However, the frugivorous and insectivorous birds that effectively pollinate this aloe are seemingly unaffected by the nectar's bitter taste. Thus the dark phenolic component of the nectar appears to function as a floral filter by attracting some animals visually and deterring others by its taste.

Aloe↗

Suckling and sucrose ingestion suppress persistent hyperalgesia and spinal Fos expression after forepaw inflammation in infant rats.

Sweet taste and nonnutritive suckling produce analgesia to transient noxious stimuli in infant rats and humans. The present study evaluated the pain-modulating effects of sucrose and suckling in a rat model of persistent pain and hyperalgesia that mimics the response to tissue injury in humans. Fore- and hindpaw withdrawal latencies from a 30 degrees or 48 degrees C brass stylus were determined in 10-day-old rats following paw inflammation induced by complete Freund's adjuvant (CFA; 1:1 injected s.c. in a 0.01 ml volume). CFA markedly decreased escape latencies to both 48 degrees and 30 degrees C stimulation, thereby demonstrating thermal hyperalgesia and mechanical allodynia. The combination of nonnutritive suckling and sucrose (7.5%, 0.01-0.06 ml/min) infusion markedly increased escape latencies to forepaw stimulation in both CFA-treated and control rats. In contrast, intraoral sucrose and suckling did not increase hindpaw withdrawal latencies in either control or CFA-inflamed rats. The effect was specific to sweet taste because neither water nor isotonic saline infusion affected forepaw escape latencies. Parallel findings were obtained for CFA-induced Fos-like immunoreactivity (Fos-LI), a marker of neuronal activation. Fos-LI was selectively induced in cervical and lumbar regions ipsilateral to forepaw and hindpaw inflammation, respectively. Suckling-sucrose treatment significantly reduced Fos-LI at the cervical but not at the lumbar regions. These findings demonstrate: (i) the development of persistent pain and hyperalgesia in 10-day-old rats that can be attenuated by endogenous pain-modulating systems activated by taste and nonnutritive suckling; (ii) the mediation of the sucrose-suckling analgesia and antihyperalgesia at the spinal level; and (iii) a differential rostrocaudal maturation of descending pain-modulating systems to the spinal cord of 10-day-old rats. These findings may provide new clinical approaches for engaging endogenous analgesic mechanisms in infants following tissue injury and inflammation.

Animals↗

The representation of taste quality in the mammalian nervous system.

The process by which the mammalian nervous system represents the features of a sapid stimulus that lead to a perception of taste quality has long been controversial. The labeled-line (sparse coding) view differs from the across-neuron pattern (ensemble) counterpoint in proposing that activity in a given class of neurons is necessary and sufficient to generate a specific taste perception. This article critically reviews molecular, electro-physiological, and behavioral findings that bear on the issue. In the peripheral gustatory system, the authors conclude that most qualities appear to be signaled by labeled lines; however, elements of both types of coding characterize signaling of sodium salts. Given the heterogeneity of neuronal tuning functions in the brain, the central coding mechanism is less clear. Both sparse coding and neuronal ensemble models remain viable possibilities. Furthermore, temporal patterns of discharge could contribute additional information. Ultimately, until specific classes of neurons can be selectively manipulated and perceptual consequences assessed, it will be difficult to go beyond mere correlation and conclusively discern the validity of these coding models.

Afferent Pathways↗

Redundant basal forebrain modulation in taste aversion memory formation.

Mnemonic deficits resulting from excitotoxic lesion of the basal forebrain have been classically attributed to the resulting depletion of cortical acetylcholine activity. It has been demonstrated that in spite of the strong cholinergic depletion after injections into the basal forebrain of the immunotoxin 192IgG-saporin, no detectable deficit can be found in the acquisition of several learning tasks, including conditioned taste aversion. Conversely, NMDA-induced lesions of the basal forebrain strongly impair taste aversion learning. In this study we show that 192IgG-saporin produces an efficient and selective cholinergic deafferentation of the rat neocortex but not the amygdala. Furthermore, a stronger relationship between severity of memory impairment after NMDA lesions and basoamygdaloid cholinergic deafferentation was found. Therefore, in a second experiment, we show that combining NMDA-induced lesions into the basolateral amygdala with 192IgG-saporin injections into the basal forebrain results in a strong disruption of taste aversion learning, whereas none of these treatments were by themselves capable of producing any detectable impairment in this learning task. The double lesion effect was only paralleled by simple NMDA lesions into the basal forebrain, suggesting that the learning deficits associated to excitotoxic lesions of the basal forebrain are the result of the simultaneous destruction of the corticopetal and basoamygdaloid interaction. A model is proposed, according to which the modulation of learning processes exerted by the basal forebrain can be redundantly performed by both the basocortical and basoamygdaloid pathway.

Acetylcholinesterase↗

The High-Ethanol Preferring rat as a model to study the shift between alcohol abuse and dependence.

The High-Ethanol Preferring line of rats (HEP), recently selected by R.D. Myers, is characterised by a high voluntary consumption of alcohol (3-4 g/kg/day for males and 6-8 g/kg/day for females, when a 10% ethanol solution is available as a choice vs. water) and a high sensitivity to taste reinforcement (saccharin, quinine). Our previous data obtained with HEP rats showed no evidence of development of dependence after long-term sustained alcohol intake. In this study, we subjected these rats to several long-term administration protocols suggested to favour the development of alcohol dependence, including multiple alcohol concentrations or sweetened alcohol solutions (ethanol 10% or 20%+saccharin), and deprivation periods. The results showed no increase in alcohol consumption, no shift of preference for alcohol solutions when offered as a free choice vs. a preferred saccharin solution, and a very limited alcohol-deprivation effect when alcohol is made available after a period of deprivation, the three criteria used to demonstrate the development of dependence. Regardless of the method used, HEP rats failed to show dependence after long-term, heavy ethanol consumption. Resistance to ethanol dependence may in fact be genetically influenced and the HEP rat appears as a valuable model to search for factors involved in the transition from alcohol abuse to dependence.

Alcohol Drinking↗