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PubMed2005

[Effect of sour TCM compound recipe on insulin resistance in experimental rats with diabetes mellitus type 2].

OBJECTIVE: To study the effect of sour TCM compound Recipe (SCCR) on insulin resistance in experimental rats with diabetes mellitus type 2 (DM2), under the guidance of TCM doctrine of "sour restrains sweet". METHODS: Model rats of DM2 were established by 8 weeks' feeding with high calorie forage combined with intraperitoneal injection of small dose of streptozotocin, and treated with SCCR (15 g/kg of crude drug/day). Levels of fasting blood glucose (FBG), serum insulin, free fatty acids (FFA), tumor necrosis factor a (TNF-alpha), combining capacity and constant of insulin receptor in liver were determined before treatment and 4, 8 and 12 weeks after treatment, and the insulin sensitive index was calculated. The data were compared with those in the model group (untreated), sweet TCM compound recipe group and bitter TCM compound group (treated with sweet and bitter Chinese drugs respectively) and the control group (treated with dimethyldiguanide). RESULTS: SCCR could markedly reduce the FBG, serum FFA and TNF-alpha levels in rat model of DM2, stimulate the secretion of insulin, raise the combining capacity and constant of insulin receptor in liver and improve the insulin sensitivity, as compared with the effect of sweet or bitter Chinese compound recipe, the difference was significant (P < 0.05). CONCLUSION: SCCR could improve the glucose metabolic disorder and ameliorate the degree of insulin resistance in DM2 model rats, with the effect superior to those with sweet or bitter taste, which illustrates primarily that the therapeutic principle of "sour restrains sweet" of TCM is true of science in a certain degree and having its guiding significance in clinical practice.

Animals↗
PubMed1991

Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships.

The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.

Amino Acid Sequence↗
PubMed2004

The importance of the lateral line in nocturnal predation of piscivorous catfish.

In a previous study we showed that nocturnal piscivorous catfish track the wake left by a swimming prey fish to locate it, following past locations to detect the present location of the prey. In a wake there are hydrodynamic as well as chemical signatures that both contain information on location and suitability of the prey. In order to determine how these two wake stimuli are utilised in prey tracking, we conducted experiments in catfish in which either the lateral line or the external gustation was ablated. We found that a functional lateral line is indispensable for following the wake of swimming prey. The frequency of attack and capture was greatly diminished and the attacks that did occur were considerably delayed when the lateral line was ablated. In contrast, catfish with ablated external taste still followed the wakes of their prey prior to attacking, albeit their attacks were delayed. The external taste sense, which was reported earlier to be necessary for finding stationary (dead) food, seems to play a minor role in the localisation of moving prey. Our finding suggests that an important function of the lateral line is to mediate wake-tracking in predatory fish.

Animals↗
PubMed1994

Conformation and sweet tastes of L-aspartyl dipeptide methyl esters.

In order to investigate the conformational preferences to elicit tastes, conformational free energy calculations using an empirical potential (ECEPP/2) and the hydration shell model were carried out on the L-aspartyl dipeptide methyl esters, L-(+)HAsp(-)-L-Xaa-OMe, in the hydrated state, where Xaa includes sweet (Phe, Tyr, Met, and Gly), bitter (Ala, Trp, Val, Leu, and Ile), and tasteless (Ser, Thr, and Abu) residues. The refined preferred conformation of the Phe dipeptide (aspartame) with side chain chi 1/2 conformation g- is g-Fg- in the hydrated state, which is consistent with the structure deduced from 1H-nmr experiments. Irrespective of the Xaa and taste, all the dipeptides have the same conformation for the Asp residue, which is attributable to the hydrogen bond between protonated amino hydrogen and carboxylate oxygen and the favored hydration of the carboxylate group. This implies that the L-aspartyl residue is a necessary factor for the dipeptides to be sweet not a sufficient factor. The computed conformational preferences for sweet, bitter, and tasteless dipeptides in the hydrated state indicate to us that the conformation about the N--C alpha bond of the Xaa residue, i.e., the orientation of the hydrophobic moiety with respect to the AH/B functionalities in the aspartyl moiety, seems to be crucial to elicit the tastes. In addition, the hydrophobicity and the size of the Xaa residue are found to play a major role in determining the tastes. These well accord with the related works reported previously.

Aspartic Acid↗
PubMed1985

Ultrastructure of mouse vallate taste buds. I. Taste cells and their associated synapses.

The ultrastructural features of murine vallate taste bud cells and their associated synapses have been examined in thin and thick sections with conventional transmission electron microscopy and high-voltage electron microscopy. Computer-assisted reconstructions from serial sections were utilized to aid in visualization of taste bud cell-nerve fiber synapses. We have classified taste bud cells on the basis of previously established criteria-namely, size of the nucleus, shape and density of chromatin, density of cytoplasm, and presence or absence of dense-cored or clear vesicles, other cytoplasmic organelles, and synaptic foci. Both dark cells and light cells are present, as well as cells with intermediate morphological characteristics. Synapses were observed from taste bud cells onto nerve fiber processes. In virtually all instances, synapses are associated with the nuclear region of the taste cell. These synapses are characterized by the presence of 40-70 nm clear vesicles embedded in a thickened presynaptic membrane separated from the postsynaptic membrane by a 16-30 nm cleft. Synapses are not unique to any particular cell type. Dark, intermediate, and light cells all synapse onto nerve fibers. Two general types of synapses exist: spot (or macular) and fingerlike. In the latter, the postsynaptic region of the neuronal process protrudes into an invagination of the taste cell membrane. Differences in synaptic morphology are not correlated with taste cell type. In some cases a single taste cell was observed to possess both macular and fingerlike synapses adjacent to one another, forming a synaptic complex onto a single neuronal process. On the basis of the presence of synaptic contacts, we conclude that both "dark" and "light" cells are gustatory receptors.

Animals↗
PubMed2004

Genetic relationships between sex-specific traits in beef cattle: mature weight, weight adjusted for body condition score, height and body condition score of cows, and carcass traits of their steer relatives.

Data from the first four cycles of the Germplasm Evaluation Program at the U.S. Meat Animal Research Center (USMARC) were used to investigate genetic relationships between mature weight (MW, n = 37,710), mature weight adjusted for body condition score (AMW, n = 37,676), mature height (HT, n = 37,123), and BCS (n = 37,676) from 4- to 8-yr old cows (n = 1,800) and carcass traits (n = 4,027) measured on their crossbred paternal half-sib steers. Covariance components among traits were estimated using REML. Carcass traits were adjusted for age at slaughter. Estimates of heritability for hot carcass weight (HCWT); percentage of retail product; percentage of fat; percentage of bone; longissimus muscle area; fat thickness adjusted visually; estimated kidney, pelvic, and heart fat percentage; marbling score; Warner-Bratzler shear force; and taste panel tenderness measured on steers were moderate to high (0.26 to 0.65), suggesting that selection for carcass and meat traits could be effective. Estimates of heritability for taste panel flavor and taste panel juiciness were low and negligible (0.05 and 0.01, respectively). Estimates of heritability from cow data over all ages and seasons were high for MW, AMW, and HT (0.52, 0.57, 0.71; respectively) and relatively low for BCS (0.16). Pairwise analyses for each female mature trait with each carcass trait were done with bivariate animal models. Estimates of genetic correlations between cow mature size and carcass composition or meat quality traits, with the exception of HCWT, were relatively low. Selection for cow mature size (weight and/or height) could be effective and would not be expected to result in much, if any, correlated changes in carcass and meat composition traits. However, genetic correlations of cow traits, with the possible exception of BCS, with HCWT may be too large to ignore. Selection for steers with greater HCWT would lead to larger cows.

Adipose Tissue↗
PubMed1996

Measurement of membrane potential and [Ca2+]i in cell ensembles: application to the study of glutamate taste in mice.

We have studied the spectral properties of the voltage-sensitive dye, 1-(3-sulfonatopropyl)-4-[beta [2-(di-n-octylamino)-6-naphtyl]vinyl] pyridinium betaine (di-8-ANEPPS), and the Ca(2+)-sensitive dye, fura-2, in azolectin liposomes and in isolated taste buds from mouse. We find that the fluorescence excitation spectra of di-8-ANEPPS and fura-2 are largely nonoverlapping, allowing alternate ratio measurements of membrane potential and intracellular calcium ([Ca2+]i). There is a small spillover of di-8-ANEPPS fluorescence at the excitation wavelengths used for fura-2 (340 and 360 nm). However, voltage-induced changes in the fluorescence of di-8-ANEPPS, excited at the fura-2 wavelengths, are small. In addition, di-8-ANEPPS fluorescence is localized to the membrane, whereas fura-2 fluorescence is distributed throughout the cytoplasm. Because of this, the effect of spillover of di-8-ANEPPS fluorescence in the [Ca2+]i estimate is < 1%, under the appropriate conditions. We have applied this method to study of the responses of multiple taste cells within isolated taste buds. We show that membrane potential and [Ca2+]i can be measured alternately in isolated taste buds from mouse. Stimulation with glutamate and glutamate analogs indicates that taste cells express both metabotropic and ionotropic receptors. The data suggest that the receptors responding to 2-amino-4-phosphonobutyrate (L-AP4), presumably metabotropic L-glutamate receptors, do not mediate excitatory glutamate taste responses.

Animals↗
PubMed1978

Correlation of chemical structure and taste in the cyclamate series and the steric nature of the chemoreceptor site.

The requirements of compounds in the cyclamate series for sweet taste stimulation are: synclinal conformation between NH and SO in the aminosulphonate group, length less than 0.7 nm of the group on the nitrogen, and hydrophobic character of the latter group. A hypothetical receptor site for these compounds should have a spatial barrier at a distance of about 0.7 nm from the nitrogen interaction point with the receptor site, and a hydrophobic interaction area between the nitrogen interaction point and the barrier.

Chemical Phenomena↗
PubMed1981

A genetic analysis of taste threshold for phenylthiocarbamide.

Taste threshold for phenylthiocarbamide (PTC) was measured in 393 offspring from the families of 85 monozygotic (MZ) twin pairs. PTC scores were bimodally distributed with modes at one and eight and the antimode at five. Because of the non-normality of the distribution, a jackknife procedure was used to obtain 95% confidence intervals for the estimates of genetic, maternal, and environmental parameters. Analyses which assumed no epistasis and which included additive genetic effects revealed that 37.9% of the observed variation in PTC threshold was due to additive genetic effects, 16.6% was due to dominance effects, 14.2% was due to maternal effects, 13.7% was due to a common sibship environment, and 17.6% was due to random environmental effects, yielding a broad sense heritability of 0.55 for the threshold ability to taste PTC. Analyses which did not include additive genetic effects revealed 26.6% of the observed variance was due to dominance effects, 23.6% to maternal effects, and 49.8% to environmental effects at the 0.67 confidence levels, but that environmental factors accounted for 72.4% and dominance effects for 23.6% of the observed variation at the 95% level.

Adolescent↗
PubMed2002

A model for the functioning of family 3 GPCRs.

Family 3 G-protein-coupled receptors (GPCRs) comprise the metabotropic glutamate (mglu) receptors, GABA(B) receptors, Ca(2+)-sensing receptors and some taste and putative pheromone receptors. All are composed of two domains, an extracellular ligand-binding domain and a transmembrane heptahelical domain that activates G proteins. Here we propose a model for the function of family 3 GPCRs that takes into account their structure. This model fits with specific pharmacological features of some family 3 GPCRs, such as modulation by positive and negative allosteric regulators. The model also reveals differences between GABA(B) receptors and Group I mglu receptors: in the former there is "tight" functional coupling between the two domains of the receptor whereas the "loose" coupling in the latter gives these receptors specific features not shared by many other GPCRs.

Binding, Competitive↗
PubMed1983

Structure-activity studies on sulfamate sweetners III: structure-taste relationships for heterosulfamates.

Eleven heterosulfamates have been synthesized, characterized, and evaluated for sweetness. Measurements of the molecular dimensions (x, y, z, and V) of these sulfamates and 22 others that had been reported previously and evaluated for sweetness have been made using Corey-Pauling-Koltun space-filling models. The first-order molecular connectivities (1Xv) of all the heterosulfamates have been calculated. The statistical technique of linear discriminant analysis was applied to the complete set of 33 compounds and to a reduced set of 27 compounds. The analysis was performed using the above five variables (x, y, z, V, and 1Xv) and various subsets thereof. For the complete set of compounds, seven variable subsets were identified which yielded correct classifications of 27 and 28 compounds. A similar analysis of the reduced set did not improve the misclassification rate.

Chemical Phenomena↗
PubMed1999

Interspecific and intraspecific competition as causes of direct and delayed density dependence in a fluctuating vole population.

A 3- to 5-year cycle of vole abundances is a characteristic phenomenon in the ecology of northern regions, and their explanation stands as a central theoretical challenge in population ecology. Although many species of voles usually coexist and are in severe competition for food and breeding space, the role of interspecific competition in vole cycles has never been evaluated statistically. After studying community effects on the population dynamics of the gray-sided vole (Clethrionomys rufocanus) in the subarctic birch forest at Kilpisjärvi, Finland, we report statistical results showing that both interspecific and intraspecific effects are important in the direct year-to-year density dependence. However, interspecific effects are not detectable in the 2-year delayed density dependence that is crucial for generating the characteristic cycles. Furthermore, we show that most of the competition takes place during the winter. The results are evaluated against two models of community dynamics. One assumes that the delayed effects are caused by an interaction with a specialist predator, and the other assumes that they are caused by overgrazing food plants. These statistical results show that vole cycles may be generated by a species-specific trophic interaction. The results also suggest that the gray-sided vole may be the focal species in the birch-forest community, as field voles may be in the taiga and as lemmings may be on the tundra.

Animals↗
PubMed2000

Linking gustatory neurobiology to behavior in vertebrates.

Technological advances in neuroscience in general, and molecular biology in particular, offer tremendous experimental opportunities for researchers studying the vertebrate gustatory system. Ultimately, however, the neurobiological events must be linked to the taste-related behavior of the animal. Although there has been some promising work in this regard, progress has been hampered by an absence of a unified theoretical framework regarding function, unconfirmed assumptions inherent in many experimental designs, and a misguided predilection for researchers to interpret results from a variety of vertebrate models in the context of human psychophysics. This review article offers a heuristic for the organization of taste function and encourages greater coordination between behavioral and neurobiological approaches to the problem of understanding gustatory processes in the nervous system. The potential power of such coordinated efforts is discussed as well as the possible interpretive pitfalls associated with the neural analysis of gustation.

Animals↗
PubMed2005

Development of structure-taste relationships for monosubstituted phenylsulfamate sweeteners using classification and regression tree (CART) analysis.

Twenty monosubstituted phenylsulfamates (cyclamates) have been synthesized and have had their taste portfolios determined. These have been combined with 63 compounds already in the literature to give a database of 83 ortho, meta, and para compounds. A training set of 75 compounds was randomly selected leaving eight compounds as a test set. A series of nine predictors determined with Corey-Pauling-Koltun models, calculated from the PC SPARTAN PRO program and Hammett sigma values taken mainly from the literature, have been used to establish structure-taste relationships for these types of sweeteners. The taste panel data for all compounds were categorized into three classes, namely, sweet (S), nonsweet (N), and sweet/nonsweet (N/S), and a novel "sweetness value" or weighting was also calculated for each compound. Linear and quadratic discriminant analysis were first used with the S, N, and N/S data, but the results were somewhat disappointing. Classification and regression tree analysis using the sweetness values for all 75 compounds was more successful, and only 14 were misclassified and six of the eight test set compounds were correctly classified. For the 29 meta compounds, one subset using just two parameters classified 83% of these compounds. Finally, using various methods, predictions were made on the likely tastes of a number of meta compounds and a striking agreement was found between the tree prediction and those given by earlier models. This appears to offer a strong vindication of the tree approach.

Cyclamates↗
PubMed1984

Salivary clearance of sugar and its effects on pH changes by Streptococcus mitior in an artificial mouth.

We recently developed a computer model of oral sugar clearance (Dawes, 1983), and an artificial mouth has now been constructed which will allow variation in the salivary parameters identified in the model and the study of their effects on bacterial acid production. Using a thin layer of S. mitior, strain 572, over a miniature Sb electrode to measure bacterial pH changes during sugar clearance from the "mouth", we found that three consecutive sets of "Stephan curves" could be obtained with the same bacteria during one day. In each of several experimental series, one salivary parameter was varied, while other parameters were held constant. The maximum pH decrease and the surface area of the registered Stephan curve (delta pH.min) were used as measures of acid production. The results indicate that the volume of "saliva" in the mouth before and after swallowing, the unstimulated salivary flow rate, and the buffer capacity had significant influences on the extent of the pH changes. Other factors, such as the maximum flow rate, the delay between start of stimulation and maximum flow, the volume of saliva in the mouth at time zero, and the taste threshold for sugar, were of lesser importance, confirming some predictions from the computer model.

Buffers↗