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PubMed2006

Fetal heart rate variability in growth restricted fetuses.

Intrauterine growth restriction (IUGR) remains a major problem in perinatal medicine because of the variety of its underlying causes and the prediction of its outcome. Characteristics of heartbeat interval patterns are associated with neuro-vegetative and humoral regulatory processes. Fetal magnetocardiography allows non-invasive assessment of these processes with high precision throughout the second half of gestation. The aim of our study was the analysis of linear and non-linear parameters of fetal heart rate fluctuations to distinguish between IUGR fetuses and a cohort of normal subjects, both pre-selected from heart-rate traces representing a quiet state of activity in the third trimester of gestation.

Algorithms↗
PubMed1999

[Physiopathology of sleep obstructive respiratory disorders. Experimental methods and practical applications].

Recent progress in the physiology of the upper airways has led to significant advances in evaluating the dynamics of upper airway occlusion during sleep. Measuring the collapsibility of the upper airways and localizing the site of obstruction should theoretically lead to efficacious non-mechanical treatment and enable selection of patients susceptible of benefiting from surgical procedures. From a diagnostic point of view, fluctuations in the nasal pressure curve appear to give more precise information on ventilatory changes and their association with disrupted sleep pattern than conventional parameters such as thermistance signals or induction plethysmography. Again, from a pathophysiological point of view, little is known about the role or tissue inflammation and repeated upper airway trauma in the transition from simple snoring to sleep apnea syndrome. Current studies lead to the conclusion that the dilatroy muscles of the upper airways in the apneic subject are the target for adaptive trophic, immunohistochemical and metabolic phenomena in response to stimulation comparable to training against resistance. Although there is no evidence that sleep affects neuromuscular activity in apneic subjects, the disappearance of compensatory hyperactivity on awakening and the reduction of muscle contraction efficacy (transmission of the dilatory force to soft tissues) observed in patients may explain the greater instability of the upper airways characteristic of sleep apnea syndrome.

Humans↗
PubMed1975

Formation of auto-rosettes by peripheral blood lymphocytes.

A mean of 3-4% (0-5-19-5%) of the peripheral blood lymphocytes of normal adults were shown to bind three or more autologous erythrocytes in vitro to form auto-rosettes. Marked individual fluctuations were observed. Increased percentages were observed in patients with cancer, but not in other selected groups, including a group who had undergone thymectomy for myasthenia gravis. Auto-rosette formation was shown to be a property of T cells by the demonstration of (a) simultaneous binding of autologous and sheep erythrocytes, (b) non-inhibition of auto-rosette formation by anti-immunoglobulin, and (c) formation of auto-rosettes by mitogen-stimulated T blasts. Auto rosette formation is a property of high percentages of human thymocytes, and of lymphocytes treated with neuraminidase or stimulated to blast-cell trans-formation by phytomitogens. It is suggested that auto-rosette formation by these cells is related to their relatively low content of cell-coat sialic acid, as compared with untreated T lymphocytes. The possible influence of the cell coat on lymphocyte function is discussed briefly.

Animals↗
PubMed2003

Catechol-O-methyl transferase (COMT) inhibitors in patients with Parkinson's disease: is COMT genotype a useful indicator of clinical efficacy?

In clinical practice, two potent and selective catechol-O-methyl transferase (COMT) inhibitors are available for the control of motor fluctuation in patients with Parkinson's disease. However, because of the complexity of fluctuating motor symptoms, it is difficult to evaluate the clinical efficacy of COMT inhibitors in each individual. Therefore, an objective factor predicting the clinical efficacy of COMT inhibitors is needed. Individual variation in COMT activity is regulated by a single nucleotide of the COMT gene on the long arm of chromosome 22. Therefore, there could be a correlation between COMT genotype and the clinical efficacy of COMT inhibitors. Three double-blind studies evaluating the efficacy of a single or repeated doses of a COMT inhibitor failed to find significant difference in the improvement in the duration of daily 'on' time and degree of motor abilities between patients with different COMT genotypes. Furthermore, there were no significant differences in the severity and frequency of dopaminergic adverse effects between patients with different COMT genotypes. These data suggest that the COMT genotype is not a major factor in deciding the clinical efficacy of COMT inhibitors.

Animals↗
PubMed1991

[Evaluating parachute-drop stress by measuring blood lipids].

An attempt to evaluate parachute-drop related stress by determining the blood lipid profile (cholesterol, LDL, HDL, apo-A, apo-B, and triglycerides) is reported. Measurements were made on starting the parachute course, just before the first jump, and just after the third jump. On these 3 occasions 38 combat troops answered psychological questionnaires and 30 of them gave blood samples. While there were significant fluctuations in level of all blood lipids and their apoproteins, they could not be correlated selectively with presumed levels of stress. The well-known difficulties in field studies in controlling crucial factors such as the exact timing of the measurements and food intake (specific diet or fasting) make questionable the use of biochemical markers in measuring stress under the conditions of our study. It is possible that the high rate of refusal to give blood samples biased the findings.

Apolipoproteins A↗
PubMed1998

Biorhythmic influences on functional capacity of human muscle and physiological responses.

UNLABELLED: Previously, this laboratory has demonstrated that exhaustive aerobic exercise performance is not subject to significant chronobiological variation between 0800 and 2000 h, but certain physiological responses to maximal aerobic effort do fluctuate significantly within that time frame. PURPOSE: The purpose of the present investigation was to determine whether muscle performance, and selected physiological responses to resistance exercise, was significantly influenced by time of day effects. METHODS: Ten healthy, but untrained, men (21.1+/-0.6 yr, mean +/- SE) volunteered to participate in the study. In a balanced and randomized study design, each subject performed resistance exercise protocols on an isokinetic dynamometer with maximal effort at 0800 h, 1200 h, 1600 h, and 2000 h. Selected physiological and hormonal data were recorded before and immediately following the exercise stimulus. RESULTS: The data demonstrated significant chronobiological oscillation in peak torque, average power, maximal work in a single repetition, and total work per set. Interestingly, this oscillation was manifested only at the fastest velocities of limb movement utilized. Pre- and postexercise rectal temperature exhibited significant time of day fluctuation, as did postexercise blood pressure. Plasma levels of testosterone and cortisol also displayed significant biorhythmicity under both pre- and postexercise conditions. However, exercise-induced responses (pre- to postexercise differences) of those steroid hormones did not exhibit significant biorythmic variation. Although plasma concentrations of both testosterone and cortisol were highest at 0800 h, testosterone to cortisol ratios were greatest at 2000 h. CONCLUSIONS: In summary, these data suggest that maximal muscle performance does vary within the segment of the day when exercise typically occurs (0800-2000 h) but that this variation is specific to speed of movement.

Adult↗
PubMed1985

Cytosolic free calcium-ion concentration in cleaving embryonic cells of Oryzias latipes measured with calcium-selective microelectrodes.

Calcium-selective microelectrodes were used to measure the free calcium-ion concentration ([Ca2+]i) in early-cleaving embryonic cells of the golden medaka, Oryzias latipes, a fresh water teleost fish. Embryos could be dechorionated as early as the four-cell stage using a three-step technique consisting of removal of some yolk to enlarge the perivitelline space, partial digestion of the chorion with pancreatin, and removal of the weakened chorion with forceps. Dechorionated embryos underwent cleavage at a normal rate. Intracellular cytosolic [Ca2+]i was monitored by impaling blastomeres first with a microelectrode filled with 5 M potassium acetate to measure membrane potential, and a few minutes later with a calcium-selective microelectrode. During nine rounds of cytokinesis from a total of six different embryos, cytosolic [Ca2+]i remained constant (with apparently random fluctuations of less than +/- 0.1 microM). During two successive cleavages in one embryo, however, [Ca2+]i rose transiently fourfold above the original resting level to 1.32 and 1.20 microM in synchrony with each period of cytokinesis and returned after each rise to submicromolar levels. Because a calcium-selective microelectrode can detect [Ca2+]i changes only in the immediate vicinity of its 2-microns tip, we interpreted these data to suggest that, although [Ca2+]i in most areas of the cytosol remains between 0.01 and 0.40 microM (mean of 0.14 microM), there may be small regions of the cell in which [Ca2+]i undergoes a substantial increase at the time of cleavage. Evidence also is presented to suggest that the membrane potential in these blastomeres undergoes a slow net hyperpolarization during early cleavage stages.

Animals↗
PubMed2006

Natural selection for kinetic stability is a likely origin of correlations between mutational effects on protein energetics and frequencies of amino acid occurrences in sequence alignments.

It appears plausible that natural selection constrains, to some extent at least, the stability in many natural proteins. If, during protein evolution, stability fluctuates within a comparatively narrow range, then mutations are expected to be fixed with frequencies that reflect mutational effects on stability. Indeed, we recently reported a robust correlation between the effect of 27 conservative mutations on the thermodynamic stability (unfolding free energy) of Escherichia coli thioredoxin and the frequencies of residues occurrences in sequence alignments. We show here that this correlation likely implies a lower limit to thermodynamic stability of only a few kJ/mol below the unfolding free energy of the wild-type (WT) protein. We suggest, therefore, that the correlation does not reflect natural selection of thermodynamic stability by itself, but of some other factor which is linked to thermodynamic stability for the mutations under study. We propose that this other factor is the kinetic stability of thioredoxin in vivo, since( i) kinetic stability relates to irreversible denaturation, (ii) the rate of irreversible denaturation in a crowded cellular environment (or in a harsh extracellular environment) is probably determined by the rate of unfolding, and (iii) the half-life for unfolding changes in an exponential manner with activation free energy and, consequently, comparatively small free energy effects can have deleterious consequences for kinetic stability. This proposal is supported by the results of a kinetic study of the WT form and the 27 single-mutant variants of E. coli thioredoxin based on the global analyses of chevron plots and equilibrium unfolding profiles determined from double-jump unfolding assays. This kinetic study suggests, furthermore, one of the factors that may contribute to the high activation free energy for unfolding in thioredoxin (required for kinetic stability), namely the energetic optimization of native-state residue environments in regions, which become disrupted in the transition state for unfolding.

Amino Acid Sequence↗
PubMed2001

Multiplicity of infection and the evolution of hybrid incompatibility in segmented viruses.

Some viral genomes are divided into segments. When multiple viruses infect a single cell, progeny form by reassorted mixtures of genomic segments. Hybrid incompatibilities arise when a progeny virus has incompatible segments from different parental viruses. Hybrid incompatibility has been observed in influenza and in the multiparticle plant virus Dianthovirus. Hybrid incompatibility provides an opportunity to study rates of viral evolution, divergence and speciation, and the extent of epistatic interactions among components of the viral genome. This paper presents mathematical and computer simulation models to study hybrid incompatibility between diverging strains. The models identify multiplicity of infection as a key factor. When many viral particles infect each host cell, the effective ploidy of the genetic system is high. High ploidy dilutes the contribution of each locus to the phenotype, weakening the selective intensity on each locus. Weaker selection on variant alleles allows the population to maintain greater genetic diversity and to be more easily perturbed by stochastic fluctuations. Greater diversity and stochastic fluctuations explore more widely the space of epistatic interactions, causing more frequent shifts among favoured combinations of alleles. Variable ploidy of viral genetics differs from standard Mendelian genetics.

Computer Simulation↗
PubMedDate not supplied

Fetal origins of developmental plasticity: are fetal cues reliable predictors of future nutritional environments?

Evidence that fetal nutrition triggers permanent adjustments in a wide range of systems and health outcomes is stimulating interest in the evolutionary significance of these responses. This review evaluates the postnatal adaptive significance of fetal developmental plasticity from the perspective of life history theory and evolutionary models of energy partitioning. Birthweight is positively related to multiple metabolically costly postnatal functions, suggesting that the fetus has the capacity to distribute the burden of energy insufficiency when faced with a nutritionally challenging environment. Lowering total requirements may reduce the risk of negative energy balance, which disproportionately impacts functions that are not essential for survival but that are crucial for reproductive success. The long-term benefit of these metabolic adjustments is contingent upon the fetus having access to a cue that is predictive of its future nutritional environment, a problem complicated in a long-lived species by short-term ecologic fluctuations like seasonality. Evidence is reviewed suggesting that the flow of nutrients reaching the fetus provides an integrated signal of nutrition as experienced by recent matrilineal ancestors, which effectively limits the responsiveness to short-term ecologic fluctuations during any given pregnancy. This capacity for fetal nutrition to minimize the growth response to transient ecologic fluctuations is defined here as intergenerational "phenotypic inertia," and is hypothesized to allow the fetus to cut through the "noise" of seasonal or other stochastic influences to read the "signal" of longer-term ecologic trends. As a mode of adaptation, phenotypic inertia may help the organism cope with ecologic trends too gradual to be tracked by conventional developmental plasticity, but too rapid to be tracked by natural selection. From an applied perspective, if a trait like fetal growth is designed to minimize the effects of short-term fluctuations by integrating information across generations, public health interventions may be most effective if focused not on the individual but on the matriline.

Adaptation, Physiological↗
PubMed1998

Sexual selection related to developmental stability in Drosophila buzzatii.

Relationships among developmental stability, sexual selection, and body size were examined in the cactophilic fly Drosophila buzzatii. Developmental stability, as measured in terms of fluctuating asymmetry (FA) of wing length, was positively associated to male's copulatory success in a mass-mating experiment with wild-reared flies. Previous studies showed that body size is positively correlated with mating success and other fitness components in this species, but no phenotypic correlation between wing asymmetry and size was found in the present study. Thus, wing asymmetry does not indicate male quality in terms of phenotypic variation in body size. This study suggests that sexual selection against wing asymmetry may be mediated through unknown factors related to developmental stability rather than body size.

Analysis of Variance↗
PubMed2007

Environmental variation and experience-related differences in the demography of the long-lived black-browed albatross.

1. It has been largely demonstrated that demographic performances of animals increase with age or experience as a result of an improvement of foraging skills, an increasing reproductive effort or a selection process. However, little is known about the age or experience-related response of populations to environmental variations. Theoretical studies consider that age-related variations of the performances are greater under more restricting conditions, but this has rarely been tested. 2. We tested this hypothesis on a long-lived species, black browed albatross Thalassarche melanophrys Temminck, using a long-term capture-mark-recapture data set. We investigated the responses of a population to climate, by studying the effects of climatic factors and breeding experience on survival and breeding success. 3. First-time breeders appear to be poorer performers compared with experienced adults, with lower reproductive success and lower survival. In addition, interannual variations of demographic traits were partly explained by climatic indices, reflecting environmental variations. The survival probability of black-browed albatrosses varied with experience and climate, and differences being greater under harsh conditions. By contrast, the reproductive success of inexperienced individuals was affected by climatic fluctuations in the same way as the experienced ones. 4. First breeding event acts as a strong selective process on the highly heterogeneous class of inexperienced individuals, suggesting the increase in survival and breeding success with experience may mainly reflect a reduction in the heterogeneity among individual qualities.

Animals↗
PubMed1985

Solvent structure and enzyme activity.

Enzymes are fluctuating particles in thermal equilibrium with their solvent environment. A variety of models of enzyme action have postulated selective excitation of enzyme vibrational modes or triggering of correlated motion of catalytic groups through collisions with solvent particles as the basis of catalytic activity. Solvent composition and structure are expected to influence such interactions. Solutes such as p-dioxane, t-butanol, and tetraalkylammonium chlorides are known to be strong perturbants of the structure of water. However, when the kinetic parameters of two enzymes, carboxypeptidase A and alpha-chymotrypsin, were examined carefully in aqueous mixtures containing these solutes, no significant influence of solvent structure or mass composition on the catalytic rate constant was found. The results indicate, furthermore, that, within the low viscosity limit, fluctuations in enzyme structure that are responsible for activated processes in the catalytically rate limiting step appear not to be significantly influenced by dynamic processes in the bulk solvent.

Binding Sites↗
PubMed2002

The fireside hypothesis: was there differential selection to tolerate air pollution during human evolution?

It is believed that sometime around 1.9 million years ago early hominid ancestors began to migrate out of Africa. Migration north and away from the equator would have forced early humans to encounter seasonal fluctuations in temperature. As a means of adapting to cold climates, the use of fire undoubtedly played an important role. We hypothesize that progressive exposure to toxic airborne particles produced from combustion created selective pressure to develop an adaptation to the inhalation of smoke. In this paper we test this hypothesis using archival data on the incidence of different cancers among geographically distinct human populations. As predicted from evolutionary theory, the incidence of lung cancer is inversely proportional to the ostensible reliance on fire of geographically different groups during human evolutionary history.

Adaptation, Physiological↗
PubMed2005

Single chromophore spectroscopy of MEH-PPV: homing-in on the elementary emissive species in conjugated polymers.

Low-temperature, single-molecule spectroscopy can provide unparalleled access to the primary emissive species of conjugated polymers. We demonstrate this with the example of one of the most commonly studied polymers, poly(2-methoxy-5-(2'-ethylhexoxy)-1,4-phenylenevinylene), MEH-PPV, which is shown to exhibit sharp fluorescence signatures over one hundred times narrower than the ensemble. These unprecedented narrow emission features can be assigned to single chromophores on the polymer chain, which are selectively addressed by the narrow band excitation. As with organic dye systems, the emission from single chromophores is not static with time, but shows a substantial spectral fluctuation. We find that, for single chromophores, this spectral fluctuation always follows a universal Gaussian statistical distribution. High-resolution spectroscopy provides unique insight into low-energy vibrational modes in the polymer emission, which are generally inaccessible with conventional spectroscopic methods such as site-selective fluorescence or Raman spectroscopy. Interchromophoric coupling can also occur owing to the flexible nature of the polymer backbone. This leads to substantial spectral broadening and a loss of resolution in the vibronic progression. We observe reversible switching within one single molecule between narrow and broad emission, which directly correlates with a discrete switching in emission intensity. We conclude that one and the same single molecule can support aggregated and nonaggregated emission, that is, emission from isolated and aggregated chromophores in one single molecule, rather than the tendency for aggregate emission being intrinsic to the molecule.

Journal Article↗
PubMed1989

Fisherian and Wrightian theories of speciation.

Fisher's theory of sexual selection, Wright's shifting-balance theory, and recent models based on them are reviewed as mechanisms of animal speciation. The joint evolution of mating preferences and secondary sexual characters can cause rapid nonadaptive phenotypic divergence and premating isolation between geographically separated populations, or along a cline. Extensive comparative data on Drosophila species support the suggestion of R. A. Fisher and T. Dobzhansky that the evolution of mating preferences can reinforce partial postmating isolation between sympatric populations. The interaction of natural selection and random genetic drift in local populations with a small effective size can produce a rapid transition between relatively stable phenotypes separated by an adaptive valley, or between chromosomal rearrangements with a heterozygote disadvantage. Large demographic fluctuations, such as frequent random local extinction and colonization, are required for the rapid spread of new adaptations (or karyotypes) when intermediate phenotypes (or rearrangement heterozygotes) are selected against.

Animals↗
PubMed2005

Breath-group intelligibility in dysarthria: characteristics and underlying correlates.

PURPOSE: This study was designed to determine whether within-speaker fluctuations in speech intelligibility occurred among speakers with dysarthria who produced a reading passage, and, if they did, whether selected linguistic and acoustic variables predicted the variations in speech intelligibility. METHOD: Participants with dysarthria included a total of 10 persons with Parkinson's disease and amyotrophic lateral sclerosis; a control group of 10 neurologically normal speakers was also studied. Each participant read a passage that was subsequently separated into consecutive breath groups for estimates of individual breath group intelligibility. Sixty listeners participated in 2 perceptual experiments, generating intelligibility scores across speakers and for each breath group produced by speakers with dysarthria. RESULTS: Individual participants with dysarthria had fluctuations in intelligibility across breath groups. Breath groups of participants with dysarthria had fewer average words and reduced interquartile ranges for the 2nd formant, the latter a global measure of articulatory mobility. Regression analyses with intelligibility measures as the criterion variable and linguistic and acoustic measures as predictor variables produced significant functions both within and across speakers, but the solutions were not the same. CONCLUSIONS: Linguistic or acoustic variables that predict across-speaker variations in speech intelligibility may not function in the same way when within-speaker variations in intelligibility are considered.

Adult↗
PubMed1974

Population structure in relation to cost of selection.

The opposing requirements in an evolving population for a rapid rate of multiple gene substitution and for the maintenance of normal population size can be reconciled in a variety of ways. The ways out of the impasse suggested here invoke deviations from the usual assumption of a large continuous population with constant numbers. In a colonial population system there may be significant random fluctuations in the accidental mortality rate between different colonies; and those colonies with reduced numbers of accidental deaths could tolerate the larger number of selective deaths that go hand in hand with rapid evolution. In new daughter colonies founded by one or a few colonizing individuals from a large polymorphic ancestral population, some genes may reach complete fixation in one or a few generations, without the usual concomitant selective cost. Or, in the same setup, the favored alleles may change by chance from rare to moderately common, but not to complete fixation, during the founding of some daughter colonies; and this raises the allele frequencies above the low range, where the cost of selection is greatest, so that the cost of further selective changes is bearable.

Alleles↗