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Effects of genetic background on prostate and taste bud carcinogenesis due to SV40 T antigen expression under probasin gene promoter control.

The incidence of prostate carcinomas in African-American men is greater than in white men, indicating genetic factors are involved in risk of this neoplasia. Recently, we have developed a transgenic rat model of prostate cancer, featuring development of malignancies within 15 weeks of age at very high incidence. Male transgenic rats with a Sprague-Dawley genetic background were mated with wild-type females of F344, Wistar and ACI strains. F1 male transgenic hybrids with female Wistar and ACI rats had significantly lowered incidences of prostate carcinomas. However, the serum level of testosterone, and expression of the transgene, probasin, and the androgen receptor did not correlate with the strain variation in tumor development. Furthermore, immunohistochemical analysis of the SV40 Tag and the androgen receptor also did not reveal any differences between the strains. The transgenic rats additionally developed taste bud neuroblastomas at 100% incidence and this was suppressed in F1 male transgenic offspring with the ACI, but not the other strains. These results clearly show that genetic background influences prostate carcinogenesis and taste bud tumorigenesis in rats and that the present transgenic rats could provide a good model to identify specific factors.

Androgen-Binding Protein↗

The frog taste disc: a prototype of the vertebrate gustatory organ.

The frog taste disc (TD) is apparently the largest gustatory organ found in vertebrates and seems to differentiate into a specialized variety of the prototypic scheme of the taste bud. An explanation for this unusual organization is lacking although it is possible to speculate the existence of environmental and nutritional requirements. Up to the present time, the most common model of the TD was based on two main cell types (sensory and sustentacular). This model may oversimplify the morphology of this structure since more numerous cell types have been described. We now propose a new model of the TD, based on comprehensive data on the ultrastructure of the organ obtained in the last 20 years. The main conclusions are the following: (1) the TD is a pluristratified epithelium with a general organization similar to that of the olfactory and vomeronasal epithelium; (2) it has skeleton composed of three different types of epithelial cells; (3) the chemoreceptorial surface is covered by different microenvironments; (4) three different types of neuro-epithelial systems are present; the type II is an 'open' sensory cell with axonal contacts devoid of vesicles; the type III is an 'open' sensory cell with synaptic-like junctions; the type i.v. is a 'closed' sensory cell with a 'Merkel-neurite complex'; (5) the nerve fibers in the basal plexus are mostly cholinergic while the peridiscal nerve fibers are mostly peptidergic. The presence of several cell types in the TD must be considered using these large receptors in electrophysiological studies or as a source of isolated cells, and their complexity must induce caution in the interpretation of the data. Text books of histology usually describe the peripheral structures associated with taste as very simple: an idea that probably must be revised. A taste organ is a highly complex structure composed of several sensory systems and a comparative approach can aid comprehension of its general organization. The study of the 'large taste organs' present in some species of amphibians can provide useful data for knowledge of the gustatory system of vertebrates.

Animals↗

Physical entropy and the senses.

With reference to two specific modalities of sensation, the taste of saltiness of chloride salts, and the loudness of steady tones, it is shown that the laws of sensation (logarithmic and power laws) are expressions of the entropy per mole of the stimulus. That is, the laws of sensation are linear functions of molar entropy. In partial verification of this hypothesis, we are able to derive an approximate value for the gas constant, a fundamental physical constant, directly from psychophysical measurements. The significance of our observation lies in the linking of the phenomenon of "sensation" directly to a physical measure. It suggests that if the laws of physics are universal, the laws of sensation and perception are similarly universal. It also connects the sensation of a simple, steady physical signal with the molecular structure of the signal: the greater the number of microstates or complexions of the stimulus signal, the greater the magnitude of the sensation (saltiness or loudness). The hypothesis is currently tested on two sensory modalities.

Entropy↗

The 5-HT1A agonist 8-OH-DPAT dose-dependently interferes with the establishment and the expression of lithium-induced conditioned rejection reactions in rats.

RATIONALE: The present experiments evaluated the potential of the 5-HT(1A )agonist, 8-OH-DPAT (DPAT), which reduces serotonin availability, to interfere with both the establishment and with the expression of lithium-induced conditioned rejection reactions (experiment 1) and lithium-induced taste avoidance (experiment 2). OBJECTIVES. To determine the effect of reduced serotonin availability on conditioned rejection reactions, a rat model of nausea. METHODS: Rats were injected with 8-OH-DPAT [at doses of 0.0 (saline), 0.01 or 0.1 mg/kg, SC] 30 min prior to exposure to 0.1% saccharin solution by intra-oral infusion (experiment 1) or by bottle presentation (experiment 2). Immediately following saccharin exposure, rats were injected with 20 ml/kg lithium chloride (0.15 M) or 20 ml/kg saline solution. On each of three test trials, rats were injected with DPAT [0.0 (saline), 0.01 and 0.1 mg/kg, SC; counterbalanced order], 30 min prior to exposure to saccharin solution by intra-oral infusion (experiment 1) or by a two-bottle test (experiment 2: saccharin and water). RESULTS: DPAT interfered with both the establishment (at a dose of 0.1 mg/kg, SC) and with the expression (at doses of 0.01 and 0.1 mg/kg, SC) of lithium-induced conditioned rejection reactions; however, DPAT did not modulate taste avoidance in a consumption test. CONCLUSIONS: These results indicate that conditioned rejection reactions, but not taste avoidance, can be attenuated by the anti-emetic agent, 8-OH-DPAT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Development of rat chorda tympani sodium responses: evidence for age-dependent changes in global amiloride-sensitive Na(+) channel kinetics.

In rat, chorda tympani nerve taste responses to Na(+) salts increase between roughly 10 and 45 days of age to reach stable, mature magnitudes. Previous evidence from in vitro preparations and from taste nerve responses using Na(+) channel blockers suggests that the physiological basis for this developmental increase in gustatory Na(+) sensitivity is the progressive addition of functional, Na(+) transduction elements (i.e., amiloride-sensitive Na(+) channels) to the apical membranes of fungiform papilla taste receptor cells. To avoid potential confounding effects of pharmacological interventions and to permit quantification of aggregate Na(+) channel behavior using a kinetic model, we obtained chorda tympani nerve responses to NaCl and sodium gluconate (NaGlu) during receptive field voltage clamp in rats aged from 12-14 to 60 days and older (60+ days). Significant, age-dependent increases in chorda tympani responses to these stimuli occurred as expected. Importantly, apical Na(+) channel density, estimated from an apical Na(+) channel kinetic model, increased monotonically with age. The maximum rate of Na(+) response increase occurred between postnatal days 12-14 and 29-31. In addition, estimated Na(+) channel affinity increased between 12-14 and 19-23 days of age, i.e., on a time course distinct from that of the maximum rate of Na(+) response increase. Finally, estimates of the fraction of clamp voltage dropped across taste receptor apical membranes decreased between 19-23 and 29-31 days of age for NaCl but remained stable for NaGlu. The stimulus dependence of this change is consistent with a developmental increase in taste bud tight junctional Cl(-) ion permeability that lags behind the developmental increase in apical Na(+) channel density. A significant, indirect anion influence on apical Na(+) channel properties was present at all ages tested. This influence was evident in the higher apparent apical Na(+) channel affinities obtained for NaCl relative to NaGlu. This stimulus-dependent modulation of apical Na(+) channel apparent affinity relies on differences in the transepithelial potentials between NaCl and NaGlu. These originate from differences in paracellular anion permeability but act also on the driving force for Na(+) through apical Na(+) channels. Detection of such an influence on taste depends fundamentally on the preservation of taste bud polarity and on a direct measure of sensory function, such as the response of primary afferents.

Aging↗

Crystal structure of a sweet tasting protein thaumatin I, at 1.65 A resolution.

The crystal structure of thaumatin I, a potently sweet protein isolated from the fruits of the West African shrub, Thaumatococcus danielli Benth, has been refined at a resolution better than 1.65 A using a combination of energy minimization and stereochemically restrained least-squares methods. The final model consists of all 207 amino acids, 28 alternate amino acid conformers and 236 waters, with a crystallographic R-factor of 0.145 for 19,877 reflections having F > 4 sigma F between 10.0 A and 1.65 A (R = 0.167 for all 24,022 reflections). The model has good stereochemistry, with root-mean-square deviations from ideal values for bond and angle distances of 0.014 A and 0.029 A, respectively. The estimated root-mean-square co-ordinate error is 0.15 A. The current model confirms the previously reported 3.1 A C alpha trace in both main chain connectivity and disulfide topology, including two disulfide bonds, that differed from the earlier reported biochemical determination. The structure contains three domains. The core of the molecule consists of an eleven-stranded, flattened beta-sandwich folded into two Greek key motifs. All beta-strands in this sandwich are antiparallel except the parallel N-terminal and the C-terminal strands. The average hydrogen bond length in this sandwich is 2.89 A, with an angle of 155.1 degrees. Two beta-bulges are found in one of the sheets. The second domain consists of two beta-strands forming a beta-ribbon and connected by an omega-loop, and contains a proline residue in cis conformation. This structural motif folds back against the main sandwich to form a smaller sandwich-like structure. The third domain is a disulfide-rich region stretching away from the sandwich portion of the molecule. It contains one alpha-helix and three short helical fragments. Two of the helical segments are connected by an unusually sharp turn, stabilized by a disulfide bridge. One of the three disulfide bonds in this domain takes on two conformations.

Amino Acid Sequence↗

Modulation of taste reactivity by intestinal distension in rats.

Discomfort created by intestinal distension may play a role in controlling intake behavior. We analyzed these effects in details by the taste reactivity test in Long-Evans rats. A balloon inserted into a separated Thiry-Vella intestinal loop was distended with different volumes of water (0.05, 0.09, 0.12, and 0.28 mL, respectively). Saccharin solution (0.001 M) was infused into the mouth via an implanted oral cannula nine times for 30 s, with 5-min intertrial intervals. The balloon was distended after the second and released following the seventh trial. Taste reactivity (TR) elements were videotaped and later analyzed for appetitive and aversive responses. The number of appetitive responses decreased after gut distension, whereas aversive elements were infrequent and stable. It is suggested that pleasantness of the taste stimulus decreased independently of the discomfort, which remained mild but steady; that is, sweet taste gradually lost its hedonic value but was not accompanied by an acquired aversion of the same taste. This finding may point to the difference of the motivational and discriminative effects of the internal stimuli.

Animals↗

Influence of response variability on the coding performance of central gustatory neurons.

We explored how variability in responding to taste stimuli could impact the signaling of taste quality information by neuron types and individual cells in the nucleus of the solitary tract. One hundred sixty-two neurons recorded from anesthetized rats were grouped using multivariate analysis of taste responses to the following (in m): 0.5 sucrose, 0.1 NaCl, 0.01 HCl, and 0.01 quinine-HCl. Neurons fell into one of three groups corresponding to cell types that responded optimally to sucrose, NaCl, or HCl. A statistical model was used to examine whether responses observed among neurons within each group could be correctly attributed to the optimal stimulus or another tastant on the basis of spike count. Results revealed poor classification performance in some cases attributable to wide variations in the sensitivities of neurons that compose a cell type. This outcome leads us to question whether neuron types could faithfully encode a single taste quality. We then theoretically explored whether a hypothetical observer of individual neurons could discriminate between spiking rates to different tastants during the first second of stimulus processing. Spike rate was found to be an unreliable predictor of stimulus quality for each neuron tested. However, additional analyses suggested that taste stimuli could be identified by a reader that attends to the relative spiking activities of different kinds of neurons in parallel. Rather than assigning meaning to individual neurons or categories of them, central gustatory circuits may signal quality information using a strategy that involves the relative activities of neurons with different sensitivities to tastants.

Action Potentials↗

A trivariate model of participation, fertility and wages: the Italian case.

Italy has unusually low fertility by Organization of Economic Cooperation and Development standards, accompanied by unusually low female participation in paid work. This paper addresses the issue of the empirical relationship between fertility, female participation in the labor market and wages with these Italian "peculiarities" as a backcloth. A trivariate model of participation, fertility and wages has been constructed and estimated using three pooled cross-sections of Italian micro data, allowing for the identification of cohort effects. This model follows a "purist" approach: the participation and fertility decisions, as well as the wage equation, are modeled as completely joint. The cohort effects turn out to be significant: the point estimates do not appear to confirm actual trends, which are negative for fertility and positive for participation. The female wage is the most important variable influencing the propensity to have children and the propensity to participate in the labor market, casting doubt on suggestions that observed trends are the products of shifts in women's "tastes".

Demography↗

Behavioral and pharmacological unravelling of memory formation.

A brief description of how a passive avoidance task, using one day-old chicks, has been used to test for memory formation is given. Chicks will peck at bright shiny beads but if a bead is painted with a bitter tasting chemical, after tasting it once, the chicks will refuse to peck on subsequent presentation of that bead. The chick associates the bitter taste with the particular characteristics of the bead. These experiments have led to the development of a model of memory. The basic model is made of short-term memory, which lasts 10 minutes, intermediate memory that has two phases A and B and lasts for 30 minutes and finally long-term memory. The use of certain classes of drugs to prolong, delay or abolish the various phases is described and then it is shown that many hormones and certain behavioral manipulations can modulate memory. Experiments are described which examine not only the temporal storage but delineate spatial storage within the brain. A brief discussion of current methodologies for looking at the exact spatial location of memory traces is given. The article concludes by emphasizing how even minor differences in protocols across laboratories can have large effects on the memory traces and stresses the significance of the narrow temporal windows, around the training trial, when memory can be modulated.

Animals↗

Enhanced responses of the chorda tympani nerve to sugars in the ventromedial hypothalamic obese rat.

Sweet taste sensitivity in obese rats with lesions of the ventromedial hypothalamus (VMH) was studied by examining chorda tympani nerve responses to various taste stimuli including sugars. In the early progressive phase of obesity (2 wk after creating VMH lesions), there was no significant difference in the nerve responses to any taste stimulus between sham-operated and VMH-lesioned rats. In contrast, in the late phase of obesity (15-18 wk after VMH lesions), the magnitude of responses to sugars (except for fructose) was prominently greater than that in age-matched controls. High-fat diet-induced obese rats and streptozotocin-diabetic rats also showed greater chorda tympani nerve responses to sugars as was observed in VMH-lesioned obese rats, indicating that VMH lesions might not be specifically related to the enhanced gustatory neural responses to sugars. Although it has been demonstrated that the enhanced responses of the chorda tympani nerve to sugars in genetically diabetic db/db mice is largely attributable to the lack of the direct suppressive effect of leptin on the taste receptor cells, plasma leptin levels were not correlated with the changes in chorda tympani responsiveness to sugars in these models of obesity and diabetes. Accordingly, our results suggest that some chronic factors, including high blood glucose, inefficiency of insulin action, or leptin resistance may be related to the enhancement of chorda tympani nerve responses to sugars.

Animals↗

Design of virtual libraries of umami-tasting molecules.

The introduction of molecular tools in food research offers the possibility to the food industry to benefit from the experience gained in the field by pharmaceutical companies. In this work we are showing how in silico virtual screening techniques based on molecular similarity were applied for identifying novel umami-tasting compounds. The results obtained suggest that 5'-ribonucleotides and monosodium glutamate might elicit the fifth basic taste via the same molecular mechanism. New algorithms were developed and used in this work, such as the dimension reduction of data sets by singular value decomposition and the introduction of the correlation dimension as a natural dimension of a chemical space. It is shown that the representations of molecular data sets in chemical spaces possess self-similar properties, characteristic of fractal objects.

Algorithms↗

Tongue replantation in an animal model.

Although the tongue is not a vital organ in sustaining life, it may be a vital organ in sustaining the will to live in many people. As carcinoma of the tongue represents the majority of the 30,000 oral cavity cancers diagnosed per year in the United States, many patients face the potential consequences of resection of part or all of the tongue for cure. To date, reconstructive options do not restore optimal tongue function including articulation, swallowing, taste, or sensation. With the ultimate goal of improving tongue reconstruction, we report on a successfully performed autograft transplantation of the tongue in an animal model. Before undertaking allograft transplantation of the tongue, an autograft tongue transplant would be attempted to identify the feasibility of such a procedure and to determine the similarity of an animal model with human techniques. The dog's neck, tongue, and oral anatomy represent an excellent animal model for tongue reconstruction. This procedure can be performed successfully in an animal model. The only previously published replantation of the tongue involved the reattachment of the anterior portion of a human tongue after physical trauma. To our knowledge, the enclosed report represents the first successful total excision and replantation of the tongue in either a human or animal model.

Anastomosis, Surgical↗

Cognitive, motivational, social, and environmental influences on children's food choices.

This study tested the applicability of a cognitive-motivational model of health behavior to children's food choices. A sample of 107 elementary schoolchildren provided ratings of 15 foods in terms of possible choice criteria (e.g., how tasty or healthful specific foods were) and social or environmental influences (e.g., whether foods were eaten by friends or were easy to get). Several measures of food consumption were taken, and cognitive-developmental level was assessed. Within-person correlations were calculated between food choices and each choice criterion and social/environmental factor. These "correlational indices" of influences on food choice subsequently were used to identify five distinct subgroups in the sample. Children at the operational level of cognitive development tended to be in one of three groups characterized by health orientation in food choice, taste orientation, or multiple-motive orientation. Dietary quality was poorest in the taste-oriented group. Children at the preoperational level tended to have one of two undifferentiated patterns of values across the correlational indices. Results provide evidence of: the viability of cognitive-motivational models to explain children's food choices, the promise of within-person research methodology, and the potential for enhanced health behavior-change programs by use of population segmentation and tailored interventions.

Adolescent↗

Thermal gating of TRP ion channels: food for thought?

Members of the family of transient receptor potential (TRP) ion channels mediate a wide range of sensory modalities, including thermosensation and taste. Among the "thermo-TRPs," some, such as TRPV1, are activated by warm temperatures, whereas others, such as TRPM8, are activated by cold. How is temperature able to have such strong and opposing effects on these related channels? Although at a structural level the answer to this question is not known, an elegant biophysical model has been proposed that accounts for the different thermosensitivities of TRP channels. This model posits that temperature acts by shifting the inherent weak voltage sensitivity of TRPV1 and TRPM8 in opposite directions, thus promoting opening of TRPV1 at warm temperatures and TRPM8 at cold temperatures. TRPM5, which is distantly related to TRPM8, is a Ca2+-activated cation channel expressed in taste cells that is essential for sweet, bitter, and umami tastes. Like TRPV1 and TRPM8, TRPM5 is weakly sensitive to voltage and thus may also be temperature sensitive. A recent report shows that activity of TRPM5 is increased at warm temperatures, suggesting that heat may enhance the perception of taste through direct modulation of the putative taste transduction channel.

Animals↗

Taste cell responses in the frog are modulated by parasympathetic efferent nerve fibers.

We studied the anatomical properties of parasympathetic postganglionic neurons in the frog tongue and their modulatory effects on taste cell responses. Most of the parasympathetic ganglion cell bodies in the tongue were found in extremely small nerve bundles running near the fungiform papillae, which originate from the lingual branches of the glossopharyngeal (GP) nerve. The density of parasympathetic postganglionic neurons in the tongue was 8000-11,000/mm(3) of the extremely small nerve bundle. The mean major axis of parasympathetic ganglion cell bodies was 21 microm, and the mean length of parasympathetic postganglionic neurons was 1.45 mm. Electrical stimulation at 30 Hz of either the GP nerve or the papillary nerve produced slow hyperpolarizing potentials (HPs) in taste cells. After nicotinic acetyl choline receptors on the parasympathetic ganglion cells in the tongue had been blocked by intravenous (i.v.) injection of D-tubocurarine (1 mg/kg), stimulation of the GP nerve did not induce any slow HPs in taste cells but that of the papillary nerve did. A further i.v. injection of a substance P NK-1 antagonist, L-703,606, blocked the slow HPs induced by the papillary nerve stimulation. This suggests that the parasympathetic postganglionic efferent fibers innervate taste cells and are related to a generation of the slow HPs and that substance P is released from the parasympathetic postganglionic axon terminals. When the resting membrane potential of a taste cell was hyperpolarized by a prolonged slow HP, the gustatory receptor potentials for NaCl and sugar stimuli were enhanced in amplitude, but those for quinine-HCl and acetic acid stimuli remained unchanged. It is concluded that frog taste cell responses are modulated by activities of parasympathetic postganglionic efferent fibers innervating these cells.

Acetic Acid↗