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PubMed2005

Ion selectivity of scorpion toxin-induced pores in cardiac myocytes.

The lytic activity of parabutoporin (PP) and opistoporin 1 (OP1) on mammalian and bacterial membranes have been described. We investigated pore-formation and ion selectivity in cardiac myocytes by measuring the whole cell leak current by means of the patch clamp technique. Pore formation was observed as the induction of leak currents. Ion selectivity of the pores was indicated by the shift of the reversal potential (E(rev)) upon substitution of intra- and extra-cellular ions. Results were compared with the effect of gramicidin A (gramA). PP and OP1 induced a fluctuating leak current and indicate non-selectivity of PP-induced pores. PP- and OP1-induced pores are between 1.38 and 1.78 nm in diameter.

Animals↗
PubMed2004

Fitness consequences of avian personalities in a fluctuating environment.

Individual animals differ in the way they cope with challenges in their environment, comparable with variation in human personalities. The proximate basis of variation in personality traits has received considerable attention, and one general finding is that personality traits have a substantial genetic basis. This poses the question of how variation in personality is maintained in natural populations. We show that selection on a personality trait with high heritability fluctuates across years within a natural bird population. Annual adult survival was related to this personality trait (behaviour in novel environments) but the effects were always opposite for males and females, and reversed between years. The number of offspring surviving to breeding was also related to their parents' personalities, and again selection changed between years. The observed annual changes in selection pressures coincided with changes in environmental conditions (masting of beeches) that affect the competitive regimes of the birds. We expect that the observed fluctuations in environmental factors lead to fluctuations in competition for space and food, and these, in association with variations in population density, lead to a variation in selection pressure, which maintains genetic variation in personalities.

Animals↗
PubMed1989

Antagonistic co-evolution and the evolution of genotypic randomization.

Antagonistic co-evolution, such as the pursuit and flight of host-parasite co-evolution, easily generates cyclical co-evolutionary dynamics. It is well known that a fluctuating, contrary environment may favour the evolution of recombination, but previous analyses have shown that the optimal rate of recombination declines as the period of the environmental fluctuations gets longer. It is here shown that the direction of selection for recombination (for higher or lower rates) may only be sensitive to fluctuation period if the fluctuations are generated by non-co-evolving features of the environment, such as changes in climate. In the simple model of this paper, co-evolutionary cycling provides an advantage for recombination that is independent of period length. This independence of period length necessitates a new framework for understanding the advantage of recombination in the context of co-evolution. In the model studied in this paper it is the phase difference of the host and parasite trajectories that is the relevant feature, and phase relationships are independent of the co-evolutionary cycle time. That is, the phase difference of the oscillations is independent of their frequency.

Biological Evolution↗
PubMed1993

[Heterogeneous selection in a subdivided population with unstable deme sizes].

The influence of small deme sizes oscillations in a one-locus two-allele model is considered. The dependence of frequency deviations from the fluctuation numbers is obtained. The new method of selection coefficients and migration matrix estimation from the deme numbers and the allele frequencies observations is found.

Alleles↗
PubMed1995

Contamination of the genome by very slightly deleterious mutations: why have we not died 100 times over?

It is well known that when s, the selection coefficient against a deleterious mutation, is below approximately 1/4Ne, where Ne is the effective population size, the expected frequency of this mutation is approximately 0.5, if forward and backward mutation rates are similar. Thus, if the genome size, G, in nucleotides substantially exceeds the Ne of the whole species, there is a dangerous range of selection coefficients, 1/G < s < 1/4Ne. Mutations with s within this range are neutral enough to accumulate almost freely, but are still deleterious enough to make an impact at the level of the whole genome. In many vertebrates Ne approximately 10(4), while G approximately 10(9), so that the dangerous range includes more than four orders of magnitude. If substitutions at 10% of all nucleotide sites have selection coefficients within this range with the mean 10(-6), an average individual carries approximately 100 lethal equivalents. Some data suggest that a substantial fraction of nucleotides typical to a species may, indeed, be suboptimal. When selection acts on different mutations independently, this implies too high a mutation load. This paradox cannot be resolved by invoking beneficial mutations or environmental fluctuations. Several possible resolutions are considered, including soft selection and synergistic epistasis among very slightly deleterious mutations.

Animals↗
PubMed1992

Frequent and rapid emergence of mutated pre-C sequences in HBV from e-antigen positive carriers who seroconvert to anti-HBe during interferon treatment.

Hepatitis B virus (HBV) variants which cannot express e-antigen (HBeAg) are characteristic for many viremic anti-HBe positive chronic carriers who often have particularly severe and fluctuating hepatitis. Whether such variants are selected for and are less amenable to interferon treatment is under dispute. Therefore, by DNA amplification and direct sequencing we have investigated the emergence of HBV pre-C sequence variants in nine e-antigen positive chronic carriers, all of whom seroconverted to anti-HBe or lost HBeAg during interferon treatment, and in three of whom no viral DNA was detectable after interferon treatment. In most, but not all of the patients we found newly emerging pre-C sequences in a subpopulation of the viral genomes that included silent point mutations, amino acid changes, start and stop codon and frameshift mutations. The emergence of these mutations was paralleled by a drastic decrease of viremia during treatment. The observed mutations appeared most frequently during interferon treatment. Some of the mutations appeared or disappeared late after interferon treatment concomitant with anti-HBe antibody development. The appearance or lack of mutations in the pre-C region of a subpopulation of HBV of these patients was independent of successful virus elimination. These data indicate that interferon treatment is frequently associated with the simultaneous fall in titer of viral DNA by several orders of magnitude and the emergence of novel pre-C sequences, some of them preventing HBeAg expression. However, the presumably immune-mediated selection for pre-C mutant viruses and decrease in viremia under interferon treatment appears not to be prognostic for successful or unsuccessful virus elimination.

Adult↗
PubMed1978

Interactions between intrinsic membrane protein and electric field. An approach to studying nerve excitability.

We have approached the problem of nerve excitability through three questions: (a) What is the diagram for a channel? That is, what conformational states can the protein assume, and what transitions between these conformations are permitted? (b) What is the channel conductance associated with each conformation the channel can assume? (c) How do the rates for conformational transition depend upon membrane potential? These three questions arise from a standard statistical mechanical treatment of a nerve membrane containing several classes of identical, independent channels. Gating of channels, in this view, is associated with conformational changes of the channel protein, and it is assumed these conformations are distinct. The precise formulation of these questions is presented in terms of the theoretical treatment, and the approaches we have taken to answer the questions are indicated. Our present results indicate: Transition rates should depend exponentially on membrane potential over a limited voltage range, but probably will show a more complex dependence for extremes of the range; channels probably can take on only two conductances, open and shut, but more complicated situations are not entirely excluded; the diagram for a channel cannot be determined from standard voltage clamp data alone, but by studying gating currents and conductance fluctuations, it should be possible to select between alternative plausible physical mechanisms.

Biological Transport↗
PubMed1980

Stimulation of adrenal cell proliferation in normal rats by carcinogen-induced serum factors.

The mitotic activity of the adrenal cortex shows diurnal variations. Irrespective of these fluctuations, single doses of 2-acetylaminofluorene selectively stimulate cell division in the zona fasciculata. The serum from 2-acetylaminofluorene-treated rats also acts mitogenically after transfer to intact recipients. After simultaneous administration of 3-methylcholanthrene and 2-acetylaminofluorene the mitotic action of the serum is lost. The proliferative response of the adrenal cortex is supposed to be systemically mediated by growth factors which are induced by the carcinogen.

2-Acetylaminofluorene↗
PubMed2000

Vegetation stability in the Southeastern Brazilian coastal area from 5500 to 1400 14C yr BP deduced from charcoal analysis.

Charcoal analysis of six shell mounds showed that no major changes of the mainland vegetation ecosystem have taken place along the southeastern Brazilian coast (22 degrees 53'-22 degrees 57'S, 42 degrees 03'-42 degrees 33'W) from 5500 to 1400 14C yr BP. These shell mounds have been occupied by sedentary fisher-gatherer-hunters. Charcoal fragments retrieved from vertical profiles in the archaeological sites were examined; taxonomic determinations were based on a reference collection of charred woods and a program for computer-aided identification. Charcoal assemblages of all the studied sites present taxa from various restinga vegetation types, mangroves, xeromorphic coastal forest, and inland Atlantic Forest. The restinga ecosystem, characteristic of the Brazilian coast, is associated with sandy beach ridges; the restinga forest was much more abundant during the studied period than nowadays. The charcoal assemblages represent mainly the local vegetation; a regional reconstruction depends on the study of numerous sites. In the Cabo Frio region, open restinga taxa are more abundant in the Sambaqui do Forte, while forest elements are more important in the Sambaquis Salinas Peroano and Boca da Barra. The sites studied in the Arraial do Cabo (Sambaqui da Ponta da Cabeça) and in the Saquarema regions (Sambaquis da Pontinha and da Beirada) show that open restinga formations were locally predominant. A comparison of multivariate analysis applied to both charcoal assemblages and to phytosociological data of the extant vegetation showed a good correspondence between the charcoal spectra and the present vegetation. The high taxonomic diversity of archaeological charcoal samples and numerous fragments showing traces of decay before charring suggests that aleatory gathering of dead wood constituted the main source of firewood for fisher-gatherer-hunters populations. Condalia sp. was probably selected for cultural reasons.The only significant fluctuations on the charcoal spectra relate to the mangrove vegetation. Two relatively humid episodes (recorded from ca. 5500 to 4900/4500 and from ca. 2300 to 2000 14C yr BP), intercalated by two episodes of increased dryness with increased lagoon salinity (from ca. 4900/4500 to 2300 and from ca. 2000 to 1400 14C yr BP) were recorded in the Cabo Frio region. The changes in mangrove vegetation cannot be attributed to sea-level variations, for the three regressive and the two transgressive episodes identified for the Brazilian coast during this period are not in phase with the development of mangroves. The stability of the mainland vegetation ecosystem is probably due to the edaphic character of the coastal environments, which makes coastal formations much more resistant to climatic variations and less sensitive to climatic change. We propose that this environmental stability was a decisive factor in the maintenance of the fisher-gatherer-hunter sociocultural system.

Journal Article↗
PubMed1998

Rapid attainment of steady state plasma drug concentrations within precise limits.

We describe a method of rapidly obtaining a specified steady state plasma concentration of an intravenous drug within precise limits. The technique requires an initial bolus to raise the plasma concentration to the upper limit followed by a series of constant-rate infusions each of which is associated with a minimum plasma concentration equal to the lower limit. The infusion rate is stepped down when the plasma concentration returns to the upper limit. Computer simulation, based on the method, is used to generate plasma concentration-time curves with fluctuations of up to 10% about selected steady state concentrations of amrinone, esmolol, lidocaine, midazolam, propofol, and theophylline. The utility of this general approach to intravenous dosing and potential limitations of the method are discussed.

Computer Simulation↗
PubMedDate not supplied

Effects of food shortage and oversupply on energy utilization, histology, and function of the gut in nestling song thrushes (Turdus philomelos).

We measured food intake, digestive efficiency, body mass increments, resting metabolic rate (RMR), carcass fat content, size and histological structure of the gut, and the rate of intestinal brush border uptake of l-proline in song thrush (Turdus philomelos) nestlings subjected to food shortage or food surplus under laboratory conditions. We assigned nestlings between 3 and 7 d of age to one of the following treatments: (1) food restriction, which resulted in a slowed growth at the rate found in undernourished, wild nestlings; (2) overfeeding, which totally suppressed begging; and (3) intermediate feeding. Threefold differences in energy consumption caused fivefold differences in body mass increments of the nestlings. Despite this, body mass-corrected RMR and intestinal mass were not affected by the feeding regime. The energy content of fecal output was highest in food-restricted birds, while their carcass fat content was lowest among treatment groups. Intestinal uptake rates of l-proline were low in the overfed and intermediate-fed young but significantly increased in the food-restricted birds, who attempted to maximize their rates of growth and development within the restrictive limits set by feeding regime. We noted a marked decrease of intestinal villi height in overfed birds as compared to intermediate-fed and food-restricted nestlings. We conclude that song thrush nestlings are characterized by a limited plasticity of their developmental program, which prohibits overfed nestlings from significantly up-regulating their gut function to accommodate increased food intake. This suggests that they already grew at a rate close to their physiological maximum. We suggest two interpretations: (1) under natural conditions, song thrush nestlings do not face frequent, unpredictable fluctuations in food abundance that could select for developmental plasticity, or (2) strong selection for uniform adult phenotypes prevents flexible developmental trajectories, which would result in a diversity of adult phenotypes.

Adipose Tissue↗
PubMed1982

Isolation and characterization of Vibrio vulnificus from two Florida estuaries.

Vibrio vulnificus was enumerated in seawater and shellfish from two Florida estuaries at selected seasonal intervals. There were significant fluctuations in the presence and numbers of V. vulnificus. Relatively high seawater temperature and salinity favored the presence of V. vulnificus in both seawater and shellfish samples.

Animals↗
PubMed1994

Serum thyroglobulin in hospitalized chronic geriatric patients: its relationship to age, non-thyroidal illness, goitre and thyroid dysfunction in a follow-up study.

The objectives were to determine whether the serum thyroglobulin (TG) level is influenced by age or by non-thyroidal illness (NTI) of the aged, to investigate the constancy of the TG level after 1- and 2-month intervals and to investigate if the TG level could help to differentiate whether a subnormal thyrotrophin (TSH) level in a geriatric patient is caused by autonomous thyroid function, by age or by NTI. Two-hundred and twenty-six non-selected, chronic hospitalized patients over 60 years old and 82 healthy adults (20-40 years) participated in the study, and TSH, thyroxine, free thyroxine, triiodothyronine and TG were estimated. In 122 euthyroid geriatric patients with normal TSH the mean TG was normal (12.18 micrograms/l), but elevated (> 45 micrograms/l) TG values occurred more often than in healthy control persons (15/122 vs 3/82; chi 2(1) = 4.54, p = 0.03). The severity of the clinical state of the euthyroid patients had no influence on the TG values. If TG was measured after 1 and/or 2 months, in only 3/123 non-selected geriatric patients was there a fluctuation between the normal and abnormal range (versus fluctuation of the corresponding TSH values in 19/123 cases; chi 2(1) = 12.78, p = 0.0012). In 28 patients with subnormal TSH, a normal TG value had a predictive value of 0.6 to exclude autonomous thyroid function. Age and NTI of the geriatric patients have no significant influence on their mean TG level but high TG levels occur more often, even in euthyroid patients. The predictive value of TG is not sufficiently high to allow a clear differentiation of whether a subnormal TSH is caused by autonomous thyroid function or by the age process or by NTI. Nevertheless, the advantage of TG estimation to be more constant than TSH could be of benefit in screening studies.

Aged↗
PubMed2005

Low-dose vitamin K to augment anticoagulation control.

STUDY OBJECTIVES: To determine the effect of daily low-dose oral vitamin K supplementation on reducing variations in the international normalized ratios (INRs) in patients taking warfarin. DESIGN: Retrospective analysis. SETTING: Anticoagulation clinic in a large, private-practice hematology group. PATIENTS: Eight motivated patients (three men, five women), aged 45-79 years, receiving anticoagulant therapy with warfarin, whose INRs had been fluctuating for reasons not associated with identifiable changes in diet, warfarin dosage, activity level, illness, or changes in drug therapy. INTERVENTION: Daily supplementation with oral vitamin K, starting with 100 microg/day MEASUREMENTS AND MAIN RESULTS: Anticoagulation providers monitored INR responses; all documented INR values were included in the analysis, even those intentionally allowed outside the therapeutic range when dosages were adjusted for procedures. After dietary vitamin K supplementation, INR fluctuations diminished in nearly all patients. Overall, a significant decrease was noted in the INR standard deviation (p<0.05), and more INRs were in the therapeutic range after the start of supplementation. Allowing for small fluctuations on either side of the target range, the number of INRs within 0.2 units of the target range increased from 32% to 57% (relative increase 76%). Time in range also increased by a similar degree. CONCLUSION: Supplementation with daily low-dose oral vitamin K significantly increased the number of INRs in range as well as the time in range, and decreased INR fluctuation in this small series of selected patients.

Aged↗
PubMed2002

Myofibrillar creatine kinase activity inferred from a 3D model.

Myofibrillar creatine kinase (CK) that buffers ATP during fluctuating muscle energy metabolism has been selected for studies of conformational changes underlying the cellular control of enzyme activity. The force field was computed for three energetic states, namely for the substrate-free CK molecule, for the molecule conjugated with the MgATP complex, and for the molecule conjugated with the pair of reactants MgATP-creatine. Without its substrates, the enzyme molecule assumes an inactive "open" form. Upon binding of the MgATP complex, the CK molecule takes up a reactive "closed" conformation. Subsequent binding of creatine yields a nonreactive "intermediary" conformation. Acid-base catalysis is considered to be the basic principle for the reversible transfer of the phosphoryl group between the substrates. The results indicate that the substrate-induced energy minimizing conformational changes do not represent a sufficient condition for CK activity and that some other essential component of physiological control at the cellular level is involved in the transition from the intermediary to the closed structure of the molecule.

Acid-Base Equilibrium↗
PubMedDate not supplied

Independent expression of autoantibodies in systemic lupus erythematosus.

Antibodies to components of the cell nucleus have been viewed as specific serological markers of systemic lupus erythematosus (SLE). To determine whether these autoantibodies exhibit common regulation of their expression, antibody levels have been quantitatively assessed in serial samples from patients producing at least 2 different antibody specificities. In a comparison of the peak antibody levels as a measure of immune responsiveness, the magnitude of the antiDNA response varied independently of either the antiSm or the antiRNP responses. Serial analysis with selected patients demonstrated that antiDNA levels fluctuated according to a pattern related to disease activity. In the same patients, however, antiSm and antiRNP antibodies showed little variation in level, with no consistent relationship to disease activity. Furthermore, following therapy, antiDNA levels fell while neither antiSm nor antiRNP levels showed significant alteration. These results suggest that in SLE, autoantibodies may arise from distinct immunoregulatory disturbances, each characterized by a unique relationship to disease activity and response to therapy.

Antibodies, Antinuclear↗
PubMedDate not supplied

Circadian rhythmic hepatic biliary flow, constituents, concentrations and excretory rates in patients after cholecystectomy.

Twelve adult patients with indwelling common bile duct T-tube were selected for the study of circadian fluctuation of biliary excretion. From the 10th postoperative day on when the enterohepatic circulation was well reestablished a 5 ml bile sample was collected at the end of each 4-h interval for 3 to 4 days for determination of the concentrations of various biliary constituents. This was followed by measurement of bile flow rate by collecting the bile continuously through the T-tube at 4-h intervals for another 3 to 4 days. One quarter of the twelve patients showed no persistent daily fluctuation of all the variables studied. A circadian rhythm was demonstrated by single cosinor rhythmometry in the biliary concentrations of bile acid, cholesterol, phospholipid, bilirubin, alkaline phosphatase, and lactate dehydrogenase in the remaining nine patients. Among them six also showed a circadian fluctuation of hepatic bile flow. The lack of synchronization of the rhythm of the concentrations of various biliary constituents with the bile flow rate resulted in undetectability of a circadian rhythm for their excretory rate in the great majority of patients. Those few patients in whom a rhythm remained to be detectable had a much reduced amplitude but the same acrophase. We concluded that bile flow rate played a major role in the circadian rhythm of biliary excretion and might coordinate the fluctuation of the concentrations of various biliary constituents. However, a true circadian rhythm for their concentrations also existed at least in certain subjects.

Adolescent↗
PubMed2005

Habitat dependent associations between parasitism and fluctuating asymmetry among endemic stickleback populations.

Inconsistencies in the relationship between fluctuating asymmetry (FA) and fitness may be due to selection acting on the degree of trait asymmetry that differs among populations or among traits. We assessed relationships between parasite susceptibility and fluctuating asymmetry in the number of bony lateral plates among 83 populations of freshwater Gasterosteus aculeatus (three spined stickleback) and among lateral plate positions that vary in the selection they experience for symmetry. The correlation between FA and parasite infection was highly variable among samples. Excess of infected asymmetric G. aculeatus increased significantly as the robustness of structural predator defences decreased. This effect was found for one parasite species only (Eustrongylides sp.) and was slightly stronger in females. In addition, there was a trend for there to be an excess of infected females asymmetric in those lateral plates positions that did not experience selection for their symmetry, although the trend only approached significance. These results suggest that selection for trait symmetry can obscure relationships between fitness and individual-wide developmental stability, providing one possible explanation for some of the heterogeneity in FA/fitness relationships seen in the literature. These results are also consistent with previous reports showing that ecological segregation between symmetric and asymmetric G. aculeatus and between sexes can alter the FA/fitness relationship.

Analysis of Variance↗