Periodic oscillations in the mortality of mice infected by a protozoan parasite (Plasmodium Berghei) (a five year study)

Abstract

The application of statistical periodic analysis confirms the existence of significant periodic fluctuations in the mortality of mice infected with a rodent malaria (Plasmodium berghei). The mice were obtained from a single commercial breeder and were kept under strict controlled environmental conditions. The duration of the study was five years. The infection was induced by weekly mouse‐to‐mouse passages of infected blood. The cumulative mortality at day 7 after the infection of each weekly passage was used for the study variable.

Analysis of the data shows that there are two periodic fluctuations in the mortality; a major one with a period of 48 weeks and a second, half of that — 24 weeks. The peaks of the 24‐week period appear to coincide with the peaks of the 48 week cycle. These periodic fluctuations are unlikely to be caused by random coincidence.     

Functional development of chemosensory systems in the fish ontogeny

Regularities of the functional development of chemosensory systems in the ontogeny of fish has been studied, i.e., the olfactory system, the taste system, and the common chemical sense. The olfactory system begins to function and provides response of juveniles to chemical signals before the taste system. Embryos that have hatched from eggs but that do not yet take food exhibit nonspecialized motor responses to olfactory stimuli already. Immediately after the transition to exogenous feeding, olfactory sensitivity to signals which elicit defensive and feeding behavioral responses begins to form and the ability to differentiate between similar odors develops. The reception of a limited number of taste stimuli occurs in the larvae during the transition to exogenous feeding. With age, the spectrum of effective taste substances expands and the time spent on the definition of palatability by juvenile fishes reduces. Functional development of individual components of the taste system arises heterochronously, i.e., the external (extraoral) form of taste reception arises earlier and more rapidly, and the oral (intraoral) form of taste reception arises slower. No information is available about the functional development of the common chemical sense in the ontogeny of fish. It is assumed that the function of the chemosensory system arises in fish in early larval stages.     

Functional development of chemosensory systems in the ontogeny of fish

Regularities of the functional development of chemosensory systems in the ontogeny of fish has been studied, i.e., the olfactory system, the taste system, and the common chemical sense. The olfactory system begins to function and provides response of juveniles to chemical signals before the taste system. Embryos that have hatched from coating but that do not yet feed exhibit nonspecialized motor responses to olfactory stimuli already. Immediately after the transition to exogenous nutrition, olfactory sensitivity to signals which elicit defensive and feeding behavioral responses begins to form and the ability to differentiate between similar odors develops. The reception of a limited number of taste stimuli occurs in the larvae during the transition to exogenous nutrition. With age, the spectrum of effective taste substances expands and the time spent on the definition of palatability by juvenile fishes reduces. Functional development of individual components of the taste system arises heterochronously, i.e., the outer (extraoral) form of taste reception arises earlier and more rapidly, and the buccal (intraoral) form of taste reception arises slower. No information is available about the functional development of the common chemical sense in the ontogeny of fish. It is assumed that the function of the chemosensory system arises in fish in early larval instar.     

Rhythmical Variations Accompanying Gustatory Stimulation Observed by Means of Localization Phenomena

When two taste stimuli are presented, one to each side of the tongue, with a time delay of up to 1 msec., the taste sensation seems to move across the tongue. This phenomenon which is similar to directional hearing, can be used to show periodic fluctuations in sensation magnitude as well as other aspects of sensation. When the apparatus was refined to present taste stimuli, it was possible to observe rhythmic changes in the perception of taste. An analogy is demonstrated between hearing and taste sensation, even to some quantitative values.     

A physico-chemical theory of sweet and bitter taste excitation based on the properties of the plasma membrane

Summary This paper is concerned with physical and chemical changes occurring in the taste buds due to the presence of sapid substances, and not with the nervous mechanism transmitting impulses to the brain. From this standpoint taste phenomena are closely allied with general cell physiology or pharmacology. It has been shown that the great majority of anesthetic or toxic substances have a bitter taste and it is considered that the same structural changes occur in the cell membranes in taste buds as in other cells of the body when such substances are present. From consideration of a large amount of experimental data on the taste of organic compounds it is shown that thesweet and bitter substances are chemically very closely related and there is no line of demarcation between them. In many homologous series there is a continuous (rather than discontinuous) transition from sweet to bitter. Sweet substances having a bitter after-taste are also common.It has been pointed out that it is a general property of anesthetics to be stimulants (i. e. to accelerate cell activities)when in low concentrations. The continuous transition from stimulant to narcotic action is correlated with the sweet-bitter transition. FollowingClowes, Lillie and others the cell membrane is looked upon as a balanced emulsion partly of the water in oil type and partly of the reverse type.The phenomena cited above have been explained in terms of adsorption and surface tension action of substances on this emulsion system and the consequent changes in cell membrane permeability due to changes in the phase ratio of the emulsion types.     

Neuromodulation of Transduction and Signal Processing in the End Organs of Taste

Chemical synapses transmit gustatory signals from taste receptorcells to sensory afferent axons. Chemical (and electrical) synapsesalso provide a lateral pathway for cells within the taste budto communicate. Lateral synaptic pathways may represent someform of signal processing in the peripheral end organs of taste.Efferent synaptic input may also regulate sensory transductionin taste buds. To date, the synaptic neurotransmitter(s) orneuromodulator(s) released at chemical synapses in taste budshave not been identified unambiguously. This paper summarizesthe attempts that have been made over the past 40 years to identifythe neuroactive substances acting at taste bud synapses. Wereview the four traditional criteria for identifying chemicaltransmitters elsewhere in the nervous system—localization,uptake/degradation, release and physiological actions—andapply these criteria to neuroactive substances in taste buds.The most complete evidence to date implicates serotonin as aneuromodulator of taste transduction in the end organs. However,studies also suggest that adrenergic, cholinergic and peptidergicneurotransmission may be involved in taste buds. Chem. Senses21: 353–365, 1996.     

Channels as taste receptors in vertebrates

Taste reception is fundamental for proper selection of food and beverages. Chemicals detected as taste stimuli by vertebrates include a large variety of substances, ranging from inorganic ions (e.g., Na⁺, H⁺) to more complex molecules (e.g., sucrose, amino acids, alkaloids). Specialized epithelial cells, called taste receptor cells (TRCs), express specific membrane proteins that function as receptors for taste stimuli. Classical view of the early events in chemical detection was based on the assumption that taste substances bind to membrane receptors in TRCs without permeating the tissue. Although this model is still valid for some chemicals, such as sucrose, it does not hold for small ions, such as Na⁺, that actually diffuse inside the taste tissue through ion channels. Electrophysiological, pharmacological, biochemical, and molecular biological studies have provided evidence that indeed TRCs use ion channels to reveal the presence of certain substances in foodstuff. In this review, we focus on the functional and molecular properties of ion channels that serve as receptors in taste transduction.     

Asymptotics applied to a neural network

A mathematical model of neural processing is proposed which incorporates a theory for the storage of information. The model consists of a network of neurons that linearly processes incoming neural activity. The network stores the input by modifying the synaptic properties of all of its neurons. The model lends support to a distributive theory of memory using synaptic modification. The dynamics of the processing and storage are represented by a discrete system. Asymptotic analysis is applied to the system to show the learning capabilities of the network under constant input. Results are also given to predict the network's ability to learn periodic input, and input subjected to small random fluctuations.     

Spectral resolution of cardio-circulatory variations in men measured by autorhythmometry over 2 years

An analogue of the periodogram method for unequally spaced data is presented with a view to resolving the frequency structure of the observations. The algorithm is explicitly based on the sequential least squares procedure. In particular, the key concept is that the with-in-plot spectral analysis can be augmented by the between-plot information to make inferences about common characteristics. It is also shown how the between-plot random variations can be incorporated into the multiple harmonic regression model. A detailed spectral analysis investigates the periodic fluctuations in four cardio-circulatory variables, measured by autorhythmometric observation by eight men at rest and extending over a time span of 2 years. The spectral curves show the existence of circadian and circaseptan rhythmicities. The amplitude modulation of the dian rhythm by circaseptan variation is assimilated with the rhythmicity of work during the week. The blood-pressure variables situate their maximum annual peak in the winter period. These quasi-periodic fluctuations appear to be related to the amount of physical activity performed in time by the subjects.     

Taste sensitivity in the embryo of the domestic fowl

Two experiments were carried out to investigate the sense of taste in embryos of the domestic fowl. In the first, four taste substances; NaCl, HCl, glucose and SOA were diluted with distilled water and the response was compared with that to distilled water alone. No significant effects of taste were found. In the second experiment five taste substances: HCl, fructose, NaCl, KCl and quinine were diluted with fluids normally imbibed by the embryo: amniotic and/or allantoic fluid taken from other eggs. These solutions and also distilled water were compared with egg-fluid alone. A highly significant effect of the five solutions was found showing that the taste system becomes functional before the time of hatching. Distilled water produced on an unexpectedly large response in the embryo; possible reasons for this are discussed.     

A theoretical and experimental study of ionic shifts induced by K depletion and replacement.

The mutual synchronization or entrainment of inter-connected self-oscillatory systems is relevant in a number of biological models. It forms the basis of a currently-accepted model for the electrical “slow-wave” activity in the mammalian gastro-intestinal tract, and is of interest in oscillator population studies for circadian rhythm research. In this paper, conditions of almost-entrainment when periodic fluctuations in amplitude and/or frequency occur are analysed using the method of harmonic balance. The effects of oscillator non-linearity and different types of coupling component are demonstrated, and results are compared with spectral analysis of simulated oscillators.     

Responses of lipid membranes of taste sensor to astringent and pungent substances

Astringent substances and pungent substances were studied usinga multichannel taste sensor with lipid membranes. The electric-potentialpattern constructed of eight outputs from the membranes hasinformation of taste quality and intensity. Pungent substances,such as capsaicin, pipeline and allyl isothiocyanate, had noeffect on the membrane potentials of the lipid membranes. Onthe other hand, astringent substances such as tannic acid, catechin,gallic acid and chlorogenic acid changed the potentials remarkably.A principal component analysis of the patterns in electric potentialchanges caused by tbe taste substances revealed the astringencyis located between bitterness and sourness.     

Gene clustering based on clusterwide mutual information.

Cluster analysis of gene-wide expression data from DNA microarray hybridization studies has proved to be a useful tool for identifying biologically relevant groupings of genes and constructing gene regulatory networks. The motivation for considering mutual information is its capacity to measure a general dependence among gene random variables. We propose a novel clustering strategy based on minimizing mutual information among gene clusters. Simulated annealing is employed to solve the optimization problem. Bootstrap techniques are employed to get more accurate estimates of mutual information when the data sample size is small. Moreover, we propose to combine the mutual information criterion and traditional distance criteria such as the Euclidean distance and the fuzzy membership metric in designing the clustering algorithm. The performances of the new clustering methods are compared with those of some existing methods, using both synthesized data and experimental data. It is seen that the clustering algorithm based on a combined metric of mutual information and fuzzy membership achieves the best performance. The supplemental material is available at www.gspsnap.tamu.edu/gspweb/zxb/glioma_zxb.     

Oral chemical irritation: does it reduce perceived taste intensity?

In an experiment in which capsaicin was presented in physicalmixture with taste stimuli, no reduction in perceived tasteintensity, relative to the control condition, was observed.This result is inconsistent with previous reports of taste intensityreductions when oral chemical irritants were only periodicallyinterspersed among taste stimuli (Lawless et al., 1985; Lawlessand Stevens, 1984). A second experiment directly compared thetwo presentation formats and their respective control conditionsin a repeated-measures design. The results of that test confirmthat greater apparent reductions in taste intensity are observedwhen the oral irritant is presented as a periodic rinse eventhough perceived irritation under rinse conditions regularlyfalls to levels significantly below those maintained with mixturepresentations. This observation indicates that much of the apparentmasking of taste intensity in the presence of oral irritationis not directly related to irritation level but is sensitiveto procedural variation.     

灵长类苦味受体基因研究进展

在鲜味、甜味、苦味、咸味和酸味5种味觉形式中,苦味能避免动物摄入有毒有害物质,在动物的生存中发挥着特别重要的作用。苦味味觉的产生依赖于苦味物质与苦味受体的相互作用。苦味受体由苦味受体基因Tas2rs编码,此类基因在不同物种中数量变化较大以适应不同的需求。目前的研究在灵长类中鉴别出了若干苦味受体的配体,并发现有的苦味受体基因所经受的选择压在类群之间、基因之间甚至同一基因不同功能区之间都存在着变化。本文从苦味受体作用的多样性特点,受体与配体的对应关系、受体基因进化模式与食性之间的关系、苦味受体基因的适应性进化方面对灵长类苦味受体基因进行了综述,以期为苦味受体基因在灵长类中的深入研究提供参考。     

A receptor model for binary mixtures applied to the sweetness of fructose and glucose: De Graaf and Frijters revisited

Assuming that two substances (e.g. tastants or odorants) sharea common type of receptor, a binary mixture model is derivedfrom the equations for the equilibrium constants for the separateand combined reactions of the substances and the hypothesizedreceptor(s). It is assumed that a multimolecular interactionbetween stimulant molecules and a receptor or between a stimulantmolecule and several receptors may occur forming a stimulant–receptorcomplex. This model provides a significantly superior fit tothe sweetness data of De Graaf and Frijters (1986) on mixturesof fructose and glucose than an alternative model based on Beidler's(1962) theory of taste stimulation applied to mixtures. (InBeidler's model a unimolecular interaction is assumed betweena stimulant molecule and a receptor.) Estimates of the parametersof the model provide information on the relative stoichiometriccoefficients of the reactants and the relative equilibrium constantsfor the reactions between the receptor and the substances alone.The derived model should have a broad domain of applicationin studying the interaction between ligands and receptors, andis not limited to applications in the chemical senses or topsychophysical experiments in particular.     

Distinctive communication networks in inactive states of β2-adrenergic receptor: Mutual information and entropy transfer analysis

Mutual information and entropy transfer analysis employed on two inactive states of human beta-2 adrenergic receptor (β₂-AR) unraveled distinct communication pathways. Previously, a so-called “highly” inactive state of the receptor was observed during 1.5 microsecond long molecular dynamics simulation where the largest intracellular loop (ICL3) was swiftly packed onto the G-protein binding cavity, becoming entirely inaccessible. Mutual information quantifying the degree of correspondence between backbone-C_α fluctuations was mostly shared between intra- and extra-cellular loop regions in the original inactive state, but shifted to entirely different regions in this latest inactive state. Interestingly, the largest amount of mutual information was always shared among the mobile regions. Irrespective of the conformational state, polar residues always contributed more to mutual information than hydrophobic residues, and also the number of polar-polar residue pairs shared the highest degree of mutual information compared to those incorporating hydrophobic residues. Entropy transfer, quantifying the correspondence between backbone-C_α fluctuations at different timesteps, revealed a distinctive pathway directed from the extracellular site toward intracellular portions in this recently exposed inactive state for which the direction of information flow was the reverse of that observed in the original inactive state where the mobile ICL3 and its intracellular surroundings drove the future fluctuations of extracellular regions.     

Synergistic responses of the chorda tympani to mixtures of umami and sweet substances in rats

It has been known that umami substances such as monosodium L-glutamate (MSG) and 5'-inosine monophosphate (IMP) elicit a unique taste called 'umami' in humans. One of the characteristics of the umami taste is synergism: the synergistic enhancement of the magnitude of response produced by the addition of 5'-ribonucleotides to MSG. In addition to this well-documented synergism, we report here for the first time on another type of synergism between a glutamate receptor agonist, L-AP4, and sweet substances, by analyzing the chorda tympani responses in rats. The results are as follows: (i) when L-AP4 was mixed with one of the sweet substances, such as sucrose, glucose, fructose and maltose, large synergistic responses were observed. (ii) These synergistic responses, except to L-AP4 + sucrose, were not suppressed by sweet taste suppressants, gurmarin and pronase E. (iii) These synergistic responses were not suppressed by either metabotropic or ionotropic glutamate receptor antagonists. (iv) Fibers that responded well to the binary mixtures of L-AP4 and sweet substances also responded well to NaCl and HCl, but very weakly to sucrose. These findings are different from the characteristics of synergism between glutamate and IMP. The multiple transduction mechanisms for the umami taste in rat taste cells are discussed.