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At least 469 records · Page 26Linked to original sources
PubMed1996

Circadian rhythm in the Ca(2+)-inhibitable adenylyl activity of the rat striatum.

In the present study, we demonstrate that the Ca(2+)-inhibitable adenylyl cyclase (AC) activity in the striatum exhibits a daily oscillation with a peak occurring around 10:00 h. A circadian fluctuation of the AC activity evoked by an A2a adenosine-selective agonist was also observed. Intrastriatal injection of an A2a-selective adenosine agonist or antagonist during the interval in which the Ca(2+)-inhibitable AC activity was at its peak resulted in a more significant alteration of locomotor activity than those observed at a later interval. The marked circadian variation in the Ca(2+)-inhibitable AC activity in the striatum appears to cause a circadian fluctuation in the action of at least one neuromodulator.

Adenosine↗
PubMed2003

Interaction between genetic and inductive factors controlling the expression of dispersal and dormancy morphs in dimorphic astigmatic mites.

Some astigmatic mites display dimorphic deutonymphs (hypopus) which are facultatively intercalated in their development cycle between protonymph and tritonymph. Such species, among them Glycyphagus privatus and Glycyphagus ornatus show three potential developmental pathways: (1) to bypass the hypopus stage and develop directly from the protonymph to the tritonymph and the subsequent reproductive stage when conditions are favorable; (2) to leave the original site and disperse by means of a phoretic hypopus morph; or (3) to survive inimical life conditions in the natal environment by means of a sedentary hypopus morph. By producing both dispersing (and afterwards at the arrival site reproducing) and sedentary (drought-hardy and dormancy-prone) progeny each single parent attains a selective advantage through a risk-reducing insurance against irregularly fluctuating and often fatal life conditions of their temporary patch habitats. Both genetic heterogeneity and ecological plasticity for hypopus production adapt the Glycyphagus species to cope with variation in the environment. Both traits (for dispersal and survival) are extremely polymorphic with genotypes ranging from low to high propensities for production of each hypopus type. There is a substantial environmental effect on genetic expression such that expression of both morphs depends on the quality of food. This ecological response allows a fast reaction of the mite to the current trophic environment. Phoretic morphs are predominantly expressed at favorable trophic conditions and sedentary morphs at poor trophic conditions. Ecological influences may override genetic propensities and vice versa. Although selection imposed by changing environmental patterns adjusts the frequencies of genotypes over generations and provides for long-term adaptation, the short-term process of environmental induction adapts the population within a generation to transient-habitat disturbances. The interaction of genetic and ecological determinants explains the varying proportions of directly developing mites, phoretic hypopodes, and sedentary hypopodes, in a population at any moment.

Animals↗
PubMed1996

Selection of hepatitis C virus quasispecies during interferon treatment.

Preliminary studies have shown that hepatitis C virus (HCV) quasispecies populations after interferon therapy are different from those before interferon, suggesting that selection of HCV quasispecies occurs during IFN treatment. To confirm this, fluctuations of HCV quasispecies populations were investigated by single strand conformation polymorphism analysis in eight patients who remained viremic during interferon treatment. In all patients, HCV quasispecies populations changed in 1 to 4 months after the start of interferon therapy. In seven patients, a minor population of HCV quasispecies that was present before the interferon therapy was selected and became predominant during the therapy, whereas the abundance of the other quasispecies was reduced. In the other patients, new HCV quasispecies that had not been detected before interferon therapy appeared and replaced the pretreatment HCV. In contrast, no significant changes were observed during the pretreatment period in these patients. In two patients, deduced amino acid sequences of the hypervariable region were identical despite the difference in nucleotide sequences between interferon-sensitive and interferon-resistant HCV. Thus, selection of HCV quasispecies occurs during interferon treatment and immune responses to the hypervariable region may not be the determining factor of the selection.

Adult↗
PubMed1998

Stochastic kinetic analysis of developmental pathway bifurcation in phage lambda-infected Escherichia coli cells.

Fluctuations in rates of gene expression can produce highly erratic time patterns of protein production in individual cells and wide diversity in instantaneous protein concentrations across cell populations. When two independently produced regulatory proteins acting at low cellular concentrations competitively control a switch point in a pathway, stochastic variations in their concentrations can produce probabilistic pathway selection, so that an initially homogeneous cell population partitions into distinct phenotypic subpopulations. Many pathogenic organisms, for example, use this mechanism to randomly switch surface features to evade host responses. This coupling between molecular-level fluctuations and macroscopic phenotype selection is analyzed using the phage lambda lysis-lysogeny decision circuit as a model system. The fraction of infected cells selecting the lysogenic pathway at different phage:cell ratios, predicted using a molecular-level stochastic kinetic model of the genetic regulatory circuit, is consistent with experimental observations. The kinetic model of the decision circuit uses the stochastic formulation of chemical kinetics, stochastic mechanisms of gene expression, and a statistical-thermodynamic model of promoter regulation. Conventional deterministic kinetics cannot be used to predict statistics of regulatory systems that produce probabilistic outcomes. Rather, a stochastic kinetic analysis must be used to predict statistics of regulatory outcomes for such stochastically regulated systems.

Bacteriophage lambda↗
PubMed1990

Spontaneous [Ca2+]i fluctuations in rat chromaffin cells do not require inositol 1,4,5-trisphosphate elevations but are generated by a caffeine- and ryanodine-sensitive intracellular Ca2+ store.

A considerable fraction (65%) of single rat chromaffin cells loaded with the fluorescent [Ca2+]i indicator fura-2 exhibited spontaneous rhythmic fluctuations with an average period of approximately 100 s. Parallel patch clamp experiments as well as fura-2 experiments carried out in Ca2(+)-free and other modified media in the presence of Ca2+ and Na+ channel blockers indicated an origin from intracellular stores. Appropriate concentrations of agonists (bradykinin and histamine) for receptors (B2 and H1) that trigger generation of inositol 1,4,5-trisphosphate induced increased fluctuation frequency, recruitment of silent cells, and large [Ca2+]i changes at high doses. These effects were blocked by cell pretreatment with neomycin, a drug that inhibits inositol 1,4,5-trisphosphate generation. In contrast, spontaneous fluctuations and the effects of another drug, caffeine, which also induced increased frequency and recruitment, were unaffected by neomycin. Ryanodine caused first a prolongation and then (approximately 10 min) a block of both spontaneous fluctuations and caffeine effects, where the single transients after bradykinin and histamine were maintained. Caffeine and ryanodine are known to affect selectively the process of calcium-induced Ca2+ release; this is the first demonstration of [Ca2+]i fluctuation activity arising from Ca2(+)-induced Ca2+ release in nonmuscle cells with no strict requirement for inositol 1,4,5-trisphosphate involvement.

Adrenal Medulla↗
PubMed2001

Comments on biological asymmetry.

Gross forms of asymmetry of biological structure, hence of development, are generally considered abnormalities of conformation with "perfect" symmetry, whether bilateral or radial, being regarded as the "ideal" form. This notion, primarily a cultural deceit of neo-Platonic origin, can easily be shown to be wrong or at best only skin-deep by any student of anatomy or surgery who finds the heart not in the midline but, most of the time on the left, liver on the right, gut coiled and disposed in a certain direction with appendix in the right lower quadrant, and so forth. Indeed, since the beginning of Amphioxus, a major effect of evolutionary developmental modification has been the abolition of the visceral symmetry which characterized this cephalochordate with introduction of a specific pattern of asymmetry called laterality determination. This embryonic process, which is beginning to yield its universal molecular basis, is probably not responsible for another type of biological phenomenon designated fluctuating asymmetry well known to anthropologists (on the basis of quantitative studies of morphometric traits of teeth, appendicular skeleton, dermatoglyphics) and well-known to the ancients who in their most beautiful Hellenistic sculptures introduced deliberate asymmetries into facial structure and expression. Photographic images constructed of 2 right or 2 left facial halves may differ to a starling degree from the authentic face (Fig. 1). The relatively random nature of fluctuating asymmetry makes it less likely to be under strong natural selection. 1 Middle panel: Frontal view of face of a normal man. Left panel: "Artificial" face constructed out of two right halves of the same face. Right panel: Face constructed out of two left halves. A careful study of the right and left panels makes it easier to appreciate the actual degree of asymmetry present in the unaltered middle image/face. However, in addition to laterality determination and fluctuating asymmetry, there are additional forms of biological asymmetry which have other biological bases such as Lyonization, somatic/clonal mosaicism, mosaic aneuploidy/polyploidy, chimaerism, and developmental "resistance" seen with especial clarity in virtually every hereditary limb malformation. In this paper we will attempt to enumerate the causal forms and bases of biological asymmetry.

Aneuploidy↗
PubMed1991

Statistical models of the overdispersed molecular clock.

The most commonly used statistical model to describe the rate constancy of molecular evolution (molecular clock) is a simple Poisson process in which the variance of the number of amino acid or nucleotide substitutions in a particular gene should be equal to the mean and henceforth the dispersion index, the ratio of the variance to the mean, should be equal to one. Recent sequence data, however, have shown that the substitutional process in molecular evolution is often considerably overdispersed and have called into question the generality of using a simple Poisson process. Several efforts have been made to develop more realistic models of molecular evolution. In this paper, I will show that the spatial (site-specific) variation in the rate of molecular evolution is an improbable cause of the overdispersion and then review various statistical models which take the temporal variation into account. Although these models do not immediately specify what the mechanisms of molecular evolution might be, they do make qualitatively different predictions and give some insight into their inference. One way to distinguish them is suggested. In addition, effects of selected substitutions that presumably occur after a major change in a molecule are quasi-quantitatively examined. It is most likely that the overdispersion of molecular clock is due either to a major molecular reconfiguration (fluctuating neutral space) led by a series of subliminal neutral changes or to selected substitutions fine-tuning a molecule after a major molecular change. Although the latter possibility, of course, violates the simplest neutrality assumption, it would not impair the neutral theory as a whole.

Biological Evolution↗
PubMed1992

Late direct angioplasty in patients with myocardial infarction and fluctuating chest pain.

Myocardial infarctions may be associated with reduced but persistent blood flow to the infarct zone. We developed clinical criteria to select patients likely to have persistent perfusion to the infarct zone in the setting of acute myocardial infarction. Twenty-four consecutive patients with fluctuating pain and/or ST segment elevation who presented within 24 hours of the onset of infarction were studied with coronary angiography followed by direct percutaneous transluminal coronary angioplasty. Sixty-seven percent of patients had residual flow to the infarct territory. Eighteen patients had repeat angiography on day 9.4 +/- 4.1, and all arteries were patent (21% +/- 12% stenosis). Ejection fraction had risen from 50.0% +/- 15% to 54.0% +/- 14% (p less than 0.05). At follow-up (9.1 +/- 4.6 months), one patient died of noncardiac causes, and five redeveloped angina and underwent repeat procedures. Patients with fluctuating symptoms and/or ST segments are likely to have residual flow to the infarct zone, and late angioplasty may improve ventricular function in this group.

Angina Pectoris↗
PubMed1992

The origin of His+ revertants of Salmonella typhimurium obtained on selective medium.

The spontaneous reversion to His+ of the Salmonella typhimurium alleles hisD3052 and hisG46 was investigated. In fluctuation tests, the expected "jackpot" distribution of His+ revertants was not observed. The experimental distributions were close to Poisson distribution. The redistribution test showed no significant differences in the His+ colony counts between spread and unspread plates. An attempt at indirect selection of His+ revertants in fluid medium failed. It was also shown that the mean number of His+ reversion events and the mean number of revertants per plate were similar. At the same time, kanamycin-resistant mutants had jackpot distribution. Selection for His+ revertants (histidine starvation) did not increase mutation to Kanr.

Alleles↗
PubMed2004

Selection on insect immunity in the wild.

The strength of selection on immune function in wild populations has only been examined in a few vertebrate species. We report the results from a study measuring selection on a key insect immune enzyme, phenoloxidase (PO), in a wild population of the damselfly Calopteryx xanthostoma. We followed individually marked males from the pre-reproductive adult phase and recorded their lifetime mating success. We found positive selection on PO activity in response to an immune insult, but no selection on wing-spot quality, a trait actively displayed to females during courtship. We suggest that positive selection on PO activity in the year of study may be explained by annual fluctuations in parasite loads.

Animals↗
PubMed1996

Absence of relationships between selected human factors and natural infectivity of Plasmodium falciparum to mosquitoes in an area of high transmission.

The effects of sex, age of the human host, patency of asexual and sexual stages and seasonality on infectiousness of Plasmodium falciparum to mosquitoes were investigated in a rural village in southern Tanzania between 1992 and 1994. Villagers from randomized subgroups of households were surveyed for malaria parasites. Gametocyte and trophozoite prevalences were age dependent and fluctuated without any clear pattern of seasonality. A sample of 107 participants, selected to include an excess of gametocyte carriers, slept under bednets with holes cut into the sides for 3 weeks. A total of 3837 Anopheles gambiae s.l. and 5403 A. funestus recovered from these bednets, was examined for all oocysts 5-7 days after feeding or for oocysts less than 17.5 microns in diameter 2-3 days after feeding. Additional blood slides from participants were taken twice weekly. The 5-7 day oocyst rates were 12.1% in A. gambiae s.l. and 10.9% in A. funestus and 2-3 day rates were 3.6 and 4.9%, respectively. The higher rates using the former method were attributed to previous infection. There were strong correlations in the levels of infection in both vectors when they fed on the same hosts. However, patent gametocytaemia was only weakly associated with the development of oocysts in the mosquito. Infectiousness was not related to host age, sex, or the season.

Adolescent↗
PubMed1986

What can be learnt about selection from gene frequency distribution?

Polymorphism has been studied at the Esterase 6 locus in the Yellow Fever mosquito Aedes aegypti (L.) in laboratory stocks. At least 12 alleles are present, with up to four coexisting in a stock. The allele frequency distribution is quite sharply peaked at a mode of about 0.25. The experimental data are compared with the results of simulation based on two models, one in which the initial global distribution is taken to be the stationary distribution obtained from the neutral model assuming M = 4 mu Ne = 1 and the other in which the initial global distribution is generated from the experimental populations studied. The results suggest that the patterns observed are not likely to arise through random fluctuation of frequencies in neutral alleles, but that some kind of selection maintains polymorphism, either in the wild or in the laboratory, or both.

Aedes↗
PubMed2000

Circular YAC vectors containing short mammalian origin sequences are maintained under selection as HeLa episomes.

pYACneo, a 15.8-kb plasmid, contains a bacterial origin, G418-resistance gene, and yeast ARS, CEN, and TEL elements. Three mammalian origins have been cloned into this circular vector: 343, a 448-bp chromosomal origin from a transcribed region of human chromosome 6q; X24, a 4.3-kb element containing the hamster DHFR origin of bidirectional replication (oribeta), and S3, a 1.1-kb human anti-cruciform purified autonomously replicating sequence. The resulting constructs have been transfected into HeLa cells, and G418-resistant subcultures were isolated. The frequency of G418-resistant transformation was 1.7-8.7 times higher with origin-containing YACneo than with vector alone. After >45 generations under G418 selection, the presence of episomal versus integrated constructs was assessed by fluctuation assay and by PCR of supercoiled, circular, and linear genomic cellular DNAs separated on ethidium bromide-cesium chloride gradients. In stable G418-resistant subcultures transfected with vector alone or with linearized constructs, as well as in some subcultures transfected with circular origin-containing constructs, resistance was conferred by integration into the host genome. However, several examples were found of G418-resistant transfectants maintaining the Y.343 and the YAC.S3 circular constructs in a strictly episomal state after long-term culture in selective medium, with 80-90% stability per cell division. The episomes were found to replicate semiconservatively in a bromodeoxyuridine pulse-labeling assay for </=130 cell generations after transfection. Furthermore, after </=172 cell generations rescued episomal DNA could be isolated intact and unrearranged, and could be used to retransform bacteria. These versatile constructs, containing mammalian origins, have the capacity for further modification with human telomere or large putative centromere elements, in an effort to move towards construction of a human artificial chromosome.

Bromodeoxyuridine↗
PubMed2001

Induced fit DNA recognition by a minor groove binding analogue of Hoechst 33258: fluctuations in DNA A tract structure investigated by NMR and molecular dynamics simulations.

NMR analysis and molecular dynamics simulations of d(GGTAATTACC)(2) and its complex with a tetrahydropyrimidinium analogue of Hoechst 33258 suggest that DNA minor groove recognition in solution involves a combination of conformational selection and induced fit, rather than binding to a preorganised site. Analysis of structural fluctuations in the bound and unbound states suggests that the degree of induced fit observed is primarily a consequence of optimising van der Waals contacts with the walls of the minor groove resulting in groove narrowing through: (i) changes in base step parameters, including increased helical twist and propeller twist; (ii) changes to the sugar-phosphate backbone conformation to engulf the bound ligand; (iii) suppression of bending modes at the TpA steps. In contrast, the geometrical arrangement of hydrogen bond acceptors on the groove floor appears to be relatively insensitive to DNA conformation (helical twist and propeller twist). We suggest that effective recognition of DNA sequences (in this case an A tract structure) appears to depend to a significant extent on the sequence being flexible enough to be able to adopt the geometrically optimal conformation compatible with the various binding interactions, rather than involving 'lock and key' recognition.

Base Sequence↗
PubMed2002

[Effects of simulated weightlessness on EEG frequency fluctuation characteristics].

Objective. To develop a method of EEG monitoring under special environment, which is of value for astronauts selection and training. Method. Weightlessness was simulated by means of -6 degrees head down bed rest (HDBR). Rest EEG was recorded in 12 male subjects (aged 18-22) with eyes-closed and then analyzed by means of EEG frequency-fluctuation analysis system. Result. Before HDBR, the dominant order at parietal and occiput was 10, 9, 11 Hz; At frontal and temporal regions 9 Hz competed with 10 Hz for the main dominant component, while the third was 7 Hz. During HDBR, reversible changes of position and interrelation between 7, 8, 9, 10, 11 and 12 Hz appeared, and the frequency components and their regions involved spread gradually. The probability of 7 Hz and 8 Hz dominance increased, while 10 Hz and 11 Hz dominance decreased. At parietal, occiput and post-temporal regions, 9 Hz competed with 10 Hz for the main dominant component, the third was 7 Hz. At frontal and pre-temporal regions, 9 Hz occupied the main dominant position, while the second was 7 Hz (at right-frontal regions, it even occupied the main dominant position), the third was 10 Hz. Conclusion. Simulated weightlessness cause change of EEG dominant-frequency fluctuation competitive structure significantly. Brain adaptation function decrease, and headache can be easily induced. There exists a potential influence on brain function.

Adolescent↗
PubMed1988

Fluctuations in spontaneous discharge of hippocampal theta cells during sleep-waking states and PCPA-induced insomnia.

1. The spontaneous activity of hippocampal theta cells in head-restrained cats was recorded during slow-wave sleep (SWS), paradoxical sleep (PS), and the attentive state of bird watching (BW). We also recorded theta cell activity during a state of insomnia with pontogeniculoocipital (PGO) waves, which was induced by the administration of p-chlorophenylalanine (PCPA), a selective inhibitor of serotonin synthesis. 2. The time-dependent structure of fluctuations in theta cell activity was evaluated by power spectral analysis and Markovian analysis. The coefficient of variation for these time series was used as a measure of the variability of theta cell activity, which indicates the relative amplitude of fluctuations. 3. During SWS, theta cell activity showed a larger variability and a flat spectrum, i.e., low Markovian properties. During PS, this activity exhibited smaller variability and high spectral density in a low-frequency band (0.01-1.0 Hz), i.e., high Markovian properties. During BW, variability, spectral and Markovian properties were intermediate. 4. The firing pattern of theta cells during PCPA-induced insomnia was similar to that during PS. However, after the administration of either a serotonin agonist, 5-Methoxy-N,N-dimethyltryptamine, or a choline antagonist, atropine sulfate, theta cell activity no longer exhibited PS-like fluctuations, revealing instead a firing pattern similar to that during SWS. 5. During PS and PCPA-induced insomnia, not only the unit activity of theta cells, but PGO activity and theta wave frequency exhibited slow fluctuations, i.e., the high spectral density in the low-frequency band (0.01-1.0 Hz). 6. Cross-correlation analyses were performed between the fluctuations in theta cell activity, theta wave frequency, and PGO activity. These fluctuations correlated with each other during both PS and PCPA-induced insomnia. Bursts of PGO waves especially contributed to these cross-correlations. 7. These results suggest, first, that the slow fluctuations of the theta cell activity during PS and PCPA-induced insomnia is the physiological expression of the removal of aminergic influences and, secondly, that they are dependent on cholinergic mechanisms, including PGO generators.

Action Potentials↗
PubMed1999

A quantitative model of the Simpson-Baldwin Effect.

G. G. Simpson was the first to explain the Baldwin Effect completely in terms of the theory of natural selection. A genetic version of a seemingly non-hereditary adaptation may arise when natural selection acts on the likelihood of having an adaptive trait not just on the trait itself. We present a quantitative model of the Simpson-Baldwin Effect. Organisms in the model have mutable ranges of phenotypic plasticity. The distribution of phenotypes in a population depends largely on the extent of environmental stochasticity. When the environment undergoes intermediate rates of fluctuation, the Simpson-Baldwin effect arises through the interaction of natural selection and mutation on norms of reaction. In a highly volatile environment, organisms benefit from plasticity, and consequently do not experience a Simpson-Baldwin channeling of phenotypic possibility.

Animals↗
PubMed1989

Gap detection as a function of stimulus bandwidth with fixed high-frequency cutoff in normal-hearing and hearing-impaired listeners.

Gap detection was measured as a function of noise bandwidth with constant high-frequency cutoff in both normal-hearing and cochlear-impaired listeners. Band-widening functions were measured in a low-frequency region (0.6-kHz upper cutoff) and a high-frequency region (2.2-kHz upper cutoff). Measures of frequency selectivity were also obtained in the two frequency regions. The results for the normal-hearing listeners indicated that, on a double logarithmic scale, gap thresholds improved more steeply with increasing bandwidth in the higher frequency region than in the lower. However, performance at the narrow bandwidths was independent of frequency region. For the cochlear-impaired listeners, gap thresholds were generally longer than normal in both frequency regions. However, in the higher frequency region, progressively more listeners approached normal values as bandwidth was increased. The elevated gap thresholds were due in part to the higher absolute thresholds and in part to poor ability to process stimulus fluctuation. No correspondence was found between gap detection performance and frequency selectivity.

Acoustic Stimulation↗