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Automatic assessment of electromyogram quality.

Power spectrum analysis of the diaphragm electromyogram (EMGdi) is time consuming, and no criteria have been developed to objectively quantify contamination of the signal. The present work describes a set of computer algorithms that automatically select EMGdi free of the electrocardiogram and numerically quantify the common artifacts that affect the EMGdi. The algorithms were tested 1) on human EMGdi (n = 5) obtained with esophageal electrodes positioned at the level of the gastroesophageal junction, 2) on EMGdi obtained in mongrel dogs (n = 5) with intramuscular electrodes in the costal diaphragm, and 3) on computer-simulated power spectra. For authentic and simulated power spectra, indexes were obtained by the algorithms and were able to quantify signal disturbances induced by noise, electrode motion, esophageal peristalsis (in humans), and non-QRS complex-related electrocardiogram activity. With the index inclusion thresholds set to levels that allowed for a high signal acceptance rate with relatively small artifact-induced fluctuations (10-15%) of the EMGdi center frequency, the computer algorithms were found to be as reliable as or more reliable than other methods, including careful visual selection of the time domain signals by experienced analysts. In conclusion, the frequency domain application of computer algorithms offers a reliable and reproducible means to objectively quantify the sources that contaminate the interference pattern EMG.

Algorithms↗

Fluctuating asymmetry in the Mus musculus hybrid zone: a heterotic effect in disrupted co-adapted genomes.

Developmental stability reflects the organism's ability to buffer minor developmental accidents and is often estimated by measuring the fluctuating asymmetry. Either implicitly or explicitly, numerous authors have assumed that developmental stability is correlated with overall fitness. If this is the case, changes in morphological asymmetry across a hybrid zone could be used as a measure of the selection on hybrid genomes. Developmental stability in hybrid populations is theoretically related to the genetic distance between hybridizing taxa, and results from a balance between the stabilizing effect due to increased heterozygosity and the disruptive effect caused by breakdown of genomic co-adaptation. Here we have compared the amount of fluctuating asymmetry across a transect of the hybrid zone between the two European subspecies of the house mouse (Mus musculus domesticus and M. m. musculus) in Denmark. For the first time in any natural hybrid zone we found an increased developmental stability in the populations with mixed genomes. Moreover, the apparently beneficial effect of hybridization on the developmental stability of the hybrid mice contrasts with the results of both genetic and parasitological studies which show that hybrid dysgenesis occurs in this zone. Our results suggest that the barrier to gene flow in the Mus musculus hybrid zone may result from the disruption of relatively few gene systems. They also lead us to reassess the relation between developmental stability expressed as fluctuating asymmetry, co-adaptation and overall fitness.

Adaptation, Physiological↗

Quantification of group 5 grass pollen allergens in house dust.

BACKGROUND: It is widely known and accepted that grass pollen is a major outdoor cause of hay fever. However, it is of virtual importance for grass pollen allergic patients with symptoms all the year round to know the concentration of grass pollen allergens in their homes. OBJECTIVE: The main objective of this study was to quantify the amount of grass pollen allergen in mass units (microg Phl p 5) in dust settled indoors and to detect the distribution of allergenic activity in different sampling locations of homes. Furthermore, we studied the seasonal fluctuation of allergen content in dust samples. METHODS: We adapted the two site binding assay for detection of group 5 grass pollen allergens in samples from randomly selected homes in Hamburg (n = 371), Erfurt (n = 396), Hettstedt (n = 353), Zerbst (n = 289) and Bitterfeld (n = 226), Germany. Dust samples were collected from floor of living room (LR), bedroom (BR) or children's room (CR) and mattress (MA) during period of June 1995 to August 1998. The amount of the major grass group 5 allergens was detected in microg/g dust. RESULTS: Phl p 5 was detected in 67% of the samples analysed (n = 4760). The range was between undetectable (< 0.03 microg/g dust) and 81 microg/g dust. Phl p 5 levels were significantly higher in the dust from LR (geometric mean 0.117 microg/g dust) or BR/CR floors (geometric mean 0.098 microg/g dust) than in mattresses (geometric mean 0.043 microg/g dust). We observed seasonal fluctuation of indoor Phl p 5 levels with peak in June but also annual differences. Thus Phl p 5 content indoors reflects also the different quantities of pollen counts of annual courses. During pollination period we found two times higher Phl p 5 levels (0.172 microg/g dust, P < 0.001) than outside of grass pollination season (0.095 microg/g dust). The indoor Phl p 5 levels outside of season seem to be independent of pollination before. We suppose that settled pollen grains or allergenic material from outdoor particles carried indoors via footwear and clothes accumulates in house dust. CONCLUSION: Although we not known how the allergens in settled dust are equilibrated with those in the air, the considerable high level of Phl p 5 in indoor dust even during periods when no grass pollen is present in the atmosphere may be an important cause of pollen-allergy symptoms outside of season.

Air Pollution, Indoor↗

Computerized electroencephalographic mapping in hypomagnesian spasmophilic syndromes.

Out of 397 patients presenting hypomagnesaemia there were selected for this study only 107 cases with neurotic and neuromuscular clinical picture (sometimes with short and simple loss of consciousness) without any sign of organic cerebral lesion. The dosing of the seric and erythrocytic magnesium was performed by means of a colorimetric method of Mann and Yoe, modified by the authors. In all the cases, the EEG and EMG changes were studied by simultaneous recording of the EEG and EMG before, during and after hyperpnoea. In these 107 selected cases (divided into three groups: children, adolescents and adults) the computerized electroencephalographic maps (CEM) were carried out by an original method, transcribing the primary data of Hjorth's NSD parameters (Amplitudes and Frequencies) into a Romanian M-118 microcomputer, by a technique with analog-digital conversion. The CEM (in white-black and in colour cartography) were performed for various epochs, including the sequential ones (second by second, all along the EEG discharges during and after hyperpnoea). By these methods, we analyzed the dynamic fluctuation and temporo-spatial cortical distribution of the sinusoidal slow waves generated by the reticulate neuronal hypersynchrony. The CEM showed some differences in the three groups of hypomagnesemic syndromes selected.

Diagnosis, Computer-Assisted↗

Soil moisture redistribution as a mechanism of facilitation in savanna tree-shrub clusters.

Plant-soil water relations were examined in the context of a selective removal study conducted in tree-shrub communities occupying different but contiguous soil types (small discrete clusters on shallow, duplex soils versus larger, extensive groves on deep, sandy soils) in a subtropical savanna parkland. We (1) tested for the occurrence of soil moisture redistribution by hydraulic lift (HL), (2) determined the influence of edaphic factors on HL, and (3) evaluated the significance of HL for overstory tree-understory shrub interactions. Diel cycling and nocturnal increases in soil water potential (Psisoil), characteristic signatures of HL, occurred intermittently throughout an annual growth cycle in both communities over a range of moisture levels (Psisoil=-0.5 to -6.0 MPa) but only when soils were distinctly stratified with depth (dry surface/wet deep soil layers). The magnitude of mean (+/-SE) diel fluctuations in Psisoil (0.19+/-0.01 MPa) did not differ on the two community types, though HL occurred more frequently in groves (deep soils) than clusters (shallow soils). Selective removal of either Prosopis glandulosa overstory or mixed-species shrub understory reduced the frequency of HL, indicating that Prosopis and at least one other woody species was conducting HL. For Zanthoxylum fagara, a shallow-rooted understory shrub, Prosopis removal from clusters decreased leaf water potential (Psileaf) and net CO2 exchange (A) during periods of HL. In contrast, overstory removal had neutral to positive effects on more deeply-rooted shrub species (Berberis trifoliolata and Condalia hookeri). Removal of the shrub understory in groves increased A in the overstory Prosopis. Results indicate the following: (a) HL is common but temporally dynamic in these savanna tree-shrub communities; (b) edaphic factors influencing the degree of overstory/understory development, rooting patterns and soil moisture distribution influence HL; (c) net interactions between overstory and understory elements in these woody patches can be positive, negative and neutral over an annual cycle, and (d) Prosopis-mediated HL is an important mechanism of faciliation for some, but not all, understory shrubs.

Carbon Dioxide↗

Population dynamics of mutant alleles under maternal effect in plant populations.

Fitness interactions via maternal effects were analyzed by constructing a mathematical model. Here, the fitness of an individual is determined by its own phenotype and the maternal phenotype. It is assumed that two alternative phenotypic states are determined by two alleles at a single locus. Under this assumption, the model developed here reduces to a social selection model of human populations that considers that the fitness of an individual is determined by the individual as well as the parental phenotypes. The effect on genetic variability of random fluctuations in the magnitude of maternal effects was studied by considering the fixation probability and the equilibrium frequency of mutant genes. It is shown that genetic variability decreases as the magnitude of variation in maternal effect intensity increases.

Alleles↗

A method for assessing alertness fluctuations from EEG spectra.

The object of the study was to develop a method for automatic evaluation of the vigilance level using the EEG frequency pattern. Forty-one EEG records were selected as training material, being considered representative of either a fully alert EEG, or sleep stage I. In the same epochs, 22 different variables based on EEG spectral analysis were calculated. Multiple regression analysis was applied to determine the correlation between the spectral values and the assigned levels of vigilance. The coefficients obtained were applied to the spectral values of 265 epochs belonging to another set of tracings, for estimation of the vigilance level. The correlation between the automatic and visual finding was 0.89 in the training material and 0.86 in the test material. The method can be used to evaluate the mean vigilance level and its variance, rhythmicity and trend during the examination. The preliminary results suggest that objective measurement of alertness can be of value in many applications, such as in pharmacological research, in evaluation of certain psychic symptoms and in working environment studies.

Arousal↗

The evolution of population stability as a by-product of life-history evolution.

Proposed mechanisms for the evolution of population stability include group selection through longterm persistence, individual selection acting directly on stability determining the demographic parameters, and the evolution of stability as a by-product of life-history evolution. None of these hypotheses currently has clear empirical support. Using two sets of Drosophila melanogaster populations, we provide experimental evidence of stability evolving as a correlated response to selection on traits not directly related to demography. Four populations (FEJs) were selected for faster development and early reproduction for 125 generations, and the other four (JBs) were ancestral controls. All FEJ and JB populations have been maintained on discrete generations at moderate density, thus eliminating differential selection on stability determining demographic parameters. We derived eight small populations from each FEJ and JB population, and subjected four small populations each to either stabilizing or destabilizing food regimes. Census data on these 64 small populations over 20 generations clearly showed that the FEJ populations have significantly less temporal fluctuations in their numbers in both food regimes compared to their controls. This greater stability of the FEJ populations is probably a by-product of the evolution of reduced fecundity and pre-adult survivorship, as a correlated response to selection for rapid development.

Animals↗

Differential effects of partial hepatectomy and carbon tetrachloride administration on induction of liver cell foci in a model for detection of initiation activity.

Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CCl(4)) administration on induction of glutathione S-transferase placental form (GST-P)-positive foci were investigated in a model for detection of initiation activity. Firstly, we surveyed cell proliferation kinetics and fluctuation in cytochrome P450 (CYP) mRNA levels by means of relative-quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and CYP 2E1 apoprotein amount by immunoblotting (experiment I) after PH or CCl(4) administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CCl(4) administration and induction of liver cell foci, the non-hepatocarcinogen, 1,2-dimethylhydrazine (DMH) was administered to 7-week-old male F344 rats and initiated populations were selected using the resistant hepatocyte model (experiment II). In experiment I, the values of all CYP isozyme mRNAs after PH or CCl(4) administration were drastically decreased at the 12-h time point. From 72 h, mRNAs for all CYP isozymes began increasing, with complete recovery after 7 days. The CYP 2E1 apoprotein content in the PH group fluctuated weakly, whereas in the CCl(4) group it had decreased rapidly after 12 h and was still low at the 48 h point. In experiment II, induction of GST-P-positive foci was related to cell kinetics in the PH group, with about a 6-h time lag between time for carcinogen administration giving greatest induction of GST-P-positive foci and peaks in bromodeoxyuridine (BrdU) labeling, presumably due to the necessity for bioactivation of DMH. With CCl(4) administration, induction of foci appeared dependent on the recovery of CYP 2E1. In conclusion, PH was able to induce cell proliferation with maintenance of CYP 2E1, therefore being advantageous for induction of liver cell foci in models to detect initiation activity.

Animals↗

[Antibiotic residues and digestive microflora].

Can antibiotic residues modify the human gut flora, and select drug resistant bacteria? In volunteers given ampicillin (1.5 mg/d) or oxytetracyclin (2 mg/d), the fecal excretion of resistant enterobacteria was not changed significantly. However a possible effect would be hidden in human beings by the huge day to day fluctuations in the resistant bacterial populations. Heteroxenic mice (i.e. germfree mice associated with the flora of a human donor) and dixenic mice (i.e. mice harboring 2 isogenic strains, one of which carries an R-plasmid) are possible models to study the gut flora in vivo without contaminations and interfering factors. Minimum selecting doses in these models are between 0.5 and 10 mg antibiotic per liter of drinking water. These doses are smaller than what a consumer could ingest in food. Last, fecal resistant enterobacteria directly come from contamined food, as shown by their clearance from stools of volunteers eating a sterile diet. Hence antibiotic residues do not modify meaningfully the gut flora.

Animals↗

[Antibiotic residues and digestive microflora].

Can antibiotic residues modify the human gut flora, and select drug resistant bacteria? In volunteers given ampicillin (1.5 mg/d) or oxytetracycline (2 mg/d), the fecal excretion of resistant enterobacteria was not changed significantly. However a possible effect would be hidden in human beings by the huge day to day fluctuations in the resistant bacterial populations. Heteroxenic mice (i.e. germfree mice associated with the flora of a human donor) and dixenic mice (i.e. mice harboring 2 isogenic strains, one of which carries an R-plasmid) are possible models to study the gut flora in vivo without contaminations and interfering factors. Minimum selecting doses in these models are between 0.5 and 10 mg antibiotic per liter of drinking water. These doses are smaller than what a consumer could ingest in food. Last, fecal resistant enterobacteria directly come from contaminated food, as shown by their clearance from stools of volunteers eating a sterile diet. Hence antibiotic residues do not modify significantly the gut flora.

Animals↗

Emerging role of lipids of Candida albicans, a pathogenic dimorphic yeast.

It is clear that C. albicans lipids have gained tremendous importance in recent years. In addition to being a barrier for entrance of various metabolites, it also provides the site of action for the synthesis of enzyme(s) involved in cell wall morphogenesis and antifungal action. While alterations in lipid composition during a yeast to mycelia transition have been observed, in most of the studies, lipid fluctuations reported could have been due to various environmental factors involved in the induction of morphogenesis [4,5]. A clear understanding of lipid biosynthesis and metabolic blocks due to antifungal action is likely to shed further light on selective interactions of antifungals. Despite the multifacet role of lipids in various functions of this pathogenic yeast, their exact involvement is poorly understood. The situation is little better with regard to ergosterol and its metabolism. Ergosterol is, indeed, important for anti-candidal activity and appears to be involved in the morphogenesis of C. albicans. The fluctuation in phospholipid composition have led to altered properties of plasma membrane namely, membrane fluidity, transport activities and drug sensitivity, which suggest that-a critical level of individual phospholipid is important for proper functioning of the plasma membrane. What the exact role is of individual phospholipid is far from clear. Many unanswered questions relating to the role of PI and sphingomyelin in signal transduction, involvement of phospholipases in the maintenance of phospholipid composition, and role of lipid transfer proteins in assembly and asymmetry of lipids are some aspects which merit further work.

Candida albicans↗

Three-year follow-up of a community-based cohort of men with untreated benign prostatic hyperplasia.

OBJECTIVE: To describe changes over 3 years in urinary symptom severity and bothersomeness and in interference caused by symptoms in selected everyday activities in a cohort of men with untreated benign prostatic hyperplasia (BPH). METHODS: A prospective study of a community-based cohort of 217 men from Forth Valley, Scotland, which satisfied a working clinical definition of symptomatic BPH and had not received treatment, were followed up at 1 and 3 years. RESULTS: Significant increases occurred in both mean symptom and bothersome levels for nocturia, urgency, dribbling, intermittency and incomplete emptying. Considerable proportions of men recorded changes in symptom levels, with the most fluctuation occurring for dribbling, weak stream and frequency-changes in bothersome levels showed a similar pattern. An increased number of men experienced some degree of interference in two or more selected everyday activities, but mean interference levels showed little change. CONCLUSIONS: Increasing trends in symptom prevalence, bother-someness and in the proportions of men experiencing interference in everyday activities were established over the 3 years, despite considerable within-subject variation.

Adult↗

Dynamics of different functional parts of bacteriorhodopsin: H-2H labeling and neutron scattering.

We show that dynamics of specific amino acids within a protein can be characterized by neutron spectroscopy and hydrogen-deuterium labeling, and we present data on the motions of a selected set of groups within bacteriorhodopsin (BR), the retinal-based proton pump in the purple membrane of halophilic Archaea. Elastic incoherent neutron scattering experiments allow the definition of motions in the nano- to picosecond time scale and have revealed a dynamical transition from a harmonic to a softer, anharmonic atomic fluctuation regime in the global behavior of proteins. Biological activity in proteins is correlated with this transition, suggesting that flexibility is required for function. Elastic incoherent neutron scattering is dominated by H atom scattering, and to study the dynamics of a selected part of BR, fully deuterated purple membrane with BR containing H-retinal, H-tryptophan, and H-methionine was prepared biosynthetically in Halobacterium salinarum. These amino acids cluster in the functional center of the protein. In contrast to the protein globally, the thermal motions of the labeled atoms were found to be shielded from solvent melting effects at 260 K. Above this temperature, the labeled groups appear as more rigid than the rest of the protein, with a significantly smaller mean square amplitude of motion. These experimental results quantify the dynamical heterogeneity of BR (which meets the functional requirements of global flexibility), on the one hand, to allow large conformational changes in the molecule and of a more rigid region in the protein, on the other, to control stereo-specific selection of retinal conformations.

Amino Acids↗

Asymmetrical, agonist-induced fluctuations in local extracellular [Ca(2+)] in intact polarized epithelia.

We recently proposed that extracellular Ca(2+) ions participate in a novel form of intercellular communication involving the extracellular Ca(2+)-sensing receptor (CaR). Here, using Ca(2+)-selective microelectrodes, we directly measured the profile of agonist-induced [Ca(2+)]ext changes in restricted domains near the basolateral or luminal membranes of polarized gastric acid-secreting cells. The Ca(2+)-mobilizing agonist carbachol elicited a transient, La(3+)-sensitive decrease in basolateral [Ca(2+)] (average approximately 250 microM, but as large as 530 microM). Conversely, carbachol evoked an HgCl2-sensitive increase in [Ca(2+)] (average approximately 400 microM, but as large as 520 microM) in the lumen of single gastric glands. Both responses were significantly reduced by pre-treatment with sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) pump inhibitors or with the intracellular Ca(2+) chelator BAPTA-AM. Immunofluorescence experiments demonstrated an asymmetric localization of plasma membrane Ca(2+) ATPase (PMCA), which appeared to be partially co-localized with CaR and the gastric H(+)/K(+)-ATPase in the apical membrane of the acid-secreting cells. Our data indicate that agonist stimulation results in local fluctuations in [Ca(2+)]ext that would be sufficient to modulate the activity of the CaR on neighboring cells.

Adenosine Triphosphatases↗

On modeling the irregular fluctuations in microbial counts.

Daily or other periodic microbial counts in many foods, particularly ground meats, poultry, and raw milk, show an irregular fluctuating pattern. The cause of the fluctuations is the interplay of many random factors that tend to promote or inhibit microbial growth. Therefore, the actual size of a microbial population can vary randomly around a typical level or around a trend determined, for example, by seasonal variations or changing sanitary conditions. Fluctuations around a fixed level can often be modeled as a sequence of independent counts having a lognormal or other parametric distribution. The independence of the counts and the type of distribution can be established by standard statistical tests. Once selected, the distribution function can be used to estimate the probability of encountering a population in any given size range. The model can be modified to describe sequences that include zero counts, which are the result of the organisms' absence, or of the failure of the method to detect them. In the case of fluctuations around a trend, a modified version of the model can be used to estimate the probability of deviations from the trend. A more thorough modification is required in order to account for fluctuating patterns that include outbursts of appreciable duration, like those caused by massive contamination of a water reservoir.

Animals↗

Further studies on circadian hormone rhythms after local pharmacological destruction of the serotoninergic innervation of the rat suprachiasmatic region before the onset of the corticosterone rhythm.

In previous studies we observed that local pharmacological destruction of the serotoninergic innervation of the hypothalamic suprachiasmatic nucleus before the onset of the circadian plasma corticosterone rhythm interferes with the appearance of the corticosterone rhythm up to the age of two months. In the present investigations we studied other hormone rhythms in such rats and tested animals for corticosterone rhythm when they were older than two months. We found normal circadian fluctuations in plasma testosterone and prolactin levels, variations in growth hormone concentrations, but no changes in plasma corticosterone levels of 63-day-old rats receiving 5,7-dihydroxytryptamine, a neurotoxin selectively destroying the serotoninergic structures, into the suprachiasmatic nucleus at the age of 16 days. Rats did show circadian variations in plasma corticosterone concentrations when tested 3 months after treatment with the neurotoxin. In these latter animals, a significant amount of serotonin-immunoreactive fibers and terminals were evident in the suprachiasmatic nucleus. Only a very few of such elements were seen in rats with a shorter postoperative survival. Our data support the view that serotoninergic innervation of the suprachiasmatic nucleus is essential for the onset of the circadian fluctuations of plasma corticosterone concentrations.

5,7-Dihydroxytryptamine↗

On the holistic approach in cellular and cancer biology: nonlinearity, complexity, and quasi-determinism of the dynamic cellular network.

A keystone of the molecular reductionist approach to cellular biology is a specific deductive strategy relating genotype to phenotype-two distinct categories. This relationship is based on the assumption that the intermediary cellular network of actively transcribed genes and their regulatory elements is deterministic (i.e., a link between expression of a gene and a phenotypic trait can always be identified, and evolution of the network in time is predetermined). However, experimental data suggest that the relationship between genotype and phenotype is nonbijective (i.e., a gene can contribute to the emergence of more than just one phenotypic trait or a phenotypic trait can be determined by expression of several genes). This implies nonlinearity (i.e., lack of the proportional relationship between input and the outcome), complexity (i.e. emergence of the hierarchical network of multiple cross-interacting elements that is sensitive to initial conditions, possesses multiple equilibria, organizes spontaneously into different morphological patterns, and is controlled in dispersed rather than centralized manner), and quasi-determinism (i.e., coexistence of deterministic and nondeterministic events) of the network. Nonlinearity within the space of the cellular molecular events underlies the existence of a fractal structure within a number of metabolic processes, and patterns of tissue growth, which is measured experimentally as a fractal dimension. Because of its complexity, the same phenotype can be associated with a number of alternative sequences of cellular events. Moreover, the primary cause initiating phenotypic evolution of cells such as malignant transformation can be favored probabilistically, but not identified unequivocally. Thermodynamic fluctuations of energy rather than gene mutations, the material traits of the fluctuations alter both the molecular and informational structure of the network. Then, the interplay between deterministic chaos, complexity, self-organization, and natural selection drives formation of malignant phenotype. This concept offers a novel perspective for investigation of tumorigenesis without invalidating current molecular findings. The essay integrates the ideas of the sciences of complexity in a biological context.

Genotype↗