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PubMed2003

Natural selection and inheritance of breeding time and clutch size in the collared flycatcher.

Many characteristics of organisms in free-living populations appear to be under directional selection, possess additive genetic variance, and yet show no evolutionary response to selection. Avian breeding time and clutch size are often-cited examples of such characters. We report analyses of inheritance of, and selection on, these traits in a long-term study of a wild population of the collared flycatcher Ficedula albicollis. We used mixed model analysis with REML estimation ("animal models") to make full use of the information in complex multigenerational pedigrees. Heritability of laying date, but not clutch size, was lower than that estimated previously using parent-offspring regressions, although for both traits there was evidence of substantial additive genetic variance (h2 = 0.19 and 0.29, respectively). Laying date and clutch size were negatively genetically correlated (rA = -0.41 +/- 0.09), implying that selection on one of the traits would cause a correlated response in the other, but there was little evidence to suggest that evolution of either trait would be constrained by correlations with other phenotypic characters. Analysis of selection on these traits in females revealed consistent strong directional fecundity selection for earlier breeding at the level of the phenotype (beta = -0.28 +/- 0.03), but little evidence for stabilising selection on breeding time. We found no evidence that clutch size was independently under selection. Analysis of fecundity selection on breeding values for laying date, estimated from an animal model, indicated that selection acts directly on additive genetic variance underlying breeding time (beta = -0.20 +/- 0.04), but not on clutch size (beta = 0.03 +/- 0.05). In contrast, selection on laying date via adult female survival fluctuated in sign between years, and was opposite in sign for selection on phenotypes (negative) and breeding values (positive). Our data thus suggest that any evolutionary response to selection on laying date is partially constrained by underlying life-history trade-offs, and illustrate the difficulties in using purely phenotypic measures and incomplete fitness estimates to assess evolution of life-history trade-offs. We discuss some of the difficulties associated with understanding the evolution of laying date and clutch size in natural populations.

Animals↗
PubMed1999

Entacapone, a catechol-O-methyltransferase inhibitor for treating Parkinson's disease: review and current status.

Levodopa, a dopamine precursor administered with a decarboxylase inhibitor, is the principal therapy for treating the symptoms of Parkinson's disease. Unfortunately, after approximately 2-5 years, it frequently loses its beneficial effects as evidenced by motor fluctuations. Entacapone (Comtan) is a selective, reversible catechol-O-methyltransferase inhibitor that dose-dependently increases the peripheral bioavailability of levodopa and prolongs its duration of action. Early studies confirmed that treatment with entacapone resulted in increased striatal uptake of levodopa after iv. administration of [18F] levodopa. Preclinical studies confirmed decreased formation of COMT-dependent metabolites, including 3-O methyldopa and homovanillic acid. Clinical studies performed in patients with motor fluctuations have shown that entacapone prolonged the duration of motor response by an average of 1-1.3 h. Parkinsonian patients receiving therapeutic doses of dopamine agonists and selegiline also experienced an incremental improvement in 'on' time when entacapone was added to their drug regimen. At present, there are no published safety studies beyond six to twelve months in duration, or studies in nonfluctuating patients. Based on the clinical trial data available, entacapone is well-tolerated in the majority of patients. Dopaminergic-related adverse effects include dyskinesias, nausea and dizziness. Non-dopaminergic adverse effects include diarrhoea, abdominal discomfort and discoloration of urine. Diarrhoea is occasionally severe and may require discontinuation of therapy. Of 406 entacapone-treated subjects, there was one incidence of elevated liver transaminases, although this was attributed to an underlying disorder. In the US, Phase III trials have been completed and a New Drug Application (NDA) has been filed. In Europe, the drug received a favourable review and is currently available.

Journal Article↗
PubMed2005

The case for urgent carotid endarterectomy.

The high mortality rate previously reported and the absence of proven advantage of urgent carotid endarterectomy over natural history, has discouraged consideration of this operation. We want to report on two patients with stroke in evolution and fluctuating stroke, who underwent immediate surgery with excellent results. With these cases we aim to demonstrate that selected patients with stroke in evolution or fluctuating stroke due to recent carotid thrombosis have a good prognosis after emergency surgery. We think that in these selected cases endovascular therapy is at this moment a waste of time.

Aged↗
PubMedDate not supplied

[Daily observations (1970-1992) of fluctuations in frequency of occurrence of a sector structure in bacterial colonies selected from open air and from S. aureus cultures].

The frequencies of sector structure occurrence in different bacteria colonies (SSC) denuded from open air every day in period from 1970 to 1982 years and also in laboratory cultures Staphylococcus Aureus from 1984 to 1992 were investigated. The value SSC was expressed in percents to general number of colonies. Variations of average SSC is found out distinctly expressed opposition to 11-years cycle of Solar activity for the same period of time. The year cycle SSC was registered also with local maxima in June, August and November and global minimum in March. SSC also were observed on level of sea, on height about 1000 m over the level of sea and in gallery under the rock of thickness 1400 m (Gran Cacco, National laboratory, Assergi). The value of SSC has its maximum on height 1000 M and its minimum in gallery under the rock; it is possible, SSC depends on the intensity of space galactic rays. The results of experience, executed in April-July 1992 on cultures S.aureus have compared with average (on ten-day time periods) values for the same months of 1984-1991. Good correlation of these two curves of SSC was received. Array of measurements received from 1970 to 1992 and made conclusions can be used for long-term forecasts of cosmophysical fluctuating phenomena at least on latitude between Rome and Milano.

Air Microbiology↗
PubMed1999

The Red Queen and Fluctuating Epistasis: A Population Genetic Analysis of Antagonistic Coevolution.

Host-parasite coevolution has been shown to provide an advantage to recombination, but the selective mechanism underlying this advantage is unclear. One possibility is that recombination increases the frequency of advantageous genotypes that are disproportionately rare because of fluctuating epistasis. However, for this mechanism to work, epistasis for fitness must fluctuate over a very narrow timescale: two to five generations. Alternatively, recombination may speed up the response to directional selection by breaking up linkage disequilibria that decrease additive genetic variance. Here we analyze the results of a numerical simulation of host-parasite coevolution to assess the importance of these two mechanisms. We find that linkage disequilibria may tend to increase, rather than decrease, additive genetic variance. In addition, the sign of epistasis changes every two to five generations under several of the parameter values investigated, and epistasis and linkage disequilibrium are frequently of opposite signs. These results are consistent with the idea that selection for recombination is mediated by fluctuating epistasis. Finally, we explore the conditions under which an allele causing free recombination can spread in a nonrecombining host population and find general agreement between the predictions of a population genetic model of fluctuating epistasis and our simulation model.

Red Queen↗
PubMed2004

Ecotypic differentiation and phenotypic plasticity in reproductive traits of Armadillidium vulgare (Isopoda: Oniscidea).

Armadillidium vulgare differed in growth and survivorship on two field sites. Growth rates were higher at a site with consistently higher quality food than at the other site where less high-quality food was produced and which was less predictably accessible. Survivorship was higher at the second site where temperature fluctuations were consistently smaller. Individuals from the two populations were kept for 6 months under the same food and temperature conditions and patterns of resource allocation to reproductive traits analysed. Members of the population from the site with good growth conditions had significantly higher reproductive allocation, by 13.5%, and larger broods, by 9.1%, than those from the site with poor growth conditions. Contrary to theoretical predictions, they also had significantly larger offspring, by 7.5% dry mass. Larger offspring survived better than small ones. This differential survivorship, by 20% for a 3.4% difference in live mass, was much more pronounced under conditions of moisture stress and under fluctuating temperature regimes. Larger offspring would therefore be at a selective advantage on the site with more severe temperature fluctuations. Phenotypic plasticity in reproductive traits in response to experimental changes in food quality, temperature and crowding were monitored. Reproductive allocation was increased by 20.8% under conditions of higher food quality, by 14.7% at higher temperatures, and by 12.5% under less crowded conditions. Brood size, but not offspring dry mass, increased when food quality increased. When crowding increased by 25.0%, the size of broods remained the same but the dry mass of individual offspring decreased by 11.2%. Members of the population from the site with more variable access to high-quality food showed more plasticity in reproductive traits in response to changes in food supply than members of the population from the site with the more predictable food supply. Members of the population from the site with more stable temperatures showed less plasticity to temperature changes than members of the population from the site with greater temperature fluctuations. It is concluded that the observed microevolutionary processes and phenotypic plasticity have adaptative value as responses to spatial and temporal heterogeneity in environmental conditions.

Adaptation, Physiological↗
PubMed1978

Genetic characterization of hydroxyurea-resistance in Chinese hamster ovary cells.

Hydroxyurea is an excellent selective agent for obtaining drug-resistant mutants. At a frequency of approximately 1 X 10(-5) it was possible to select, in a single step, colonies that exhibited significant resistance to the cytotoxic effects of the drug. These hydroxyurea-resistant cell lines maintained their resistant phenotype after extensive cultivation in the absence of the drug. Reconstruction experiments indicated that the expression of hydroxyurea-resistance and the frequency of drug-resistant colonies was independent of cell densities up to 5 X 10(5) cells per 100-mm selection plate. Luria-Delbrück fluctuation analyses indicated that the appearance of hydroxyurea-resistant cells in wild type populations occurred spontaneously and at a rate of 4.8 X 10(-6) per cell per generation in the presence of 0.33 mM drug. Studies with the mutagen, ethyl methane sulfonate indicated that it was capable of increasing the frequency of hydroxyurea-resistant cells by a factor of approximately 10. Also, cell-cell hybridization experiments showed that hydroxyurea-resistance behaves as a dominant or codominant trait and that hydroxyurea-resistance was a useful new genetic marker for selection of somatic cell hybrids. Furthermore, similar to many other drug-resistant cell lines hydroxyurea-resistant cells were found to exhibit an altered sensitivity to a number of non-selective agents (guanazole, N-carbamoyloxyurea, formamidoxime, and hydroxyurethane). Except for guanazole these compounds are structurally very similar to hydroxyurea and may be expected to have similar modes of action. The results presented in this paper support the view that hydroxyurea-resistance is expressed as a normal genetic trait and is a useful genetic marker for somatic cell genetic studies.

Animals↗
PubMed2003

[Ecological implication and behavior mechanism of food selection of mammalian herbivores].

This paper is aimed to review the research progress in the behavior mechanism of food selection of mammalian herbivore. The study of food preference of mammalian herbivores is a prominent field of research in foraging ecology. It was put forth that nutritious hypotheses, plant secondary compounds hypotheses, nutrient balance hypotheses, optimal foraging theory, and conditioned flavor aversion hypotheses could explain the food preference of mammalian herbivores. Animals learn about foods through affective system and cognitive system. Social learning is a form of phenotype plasticity, and enable individuals to acquire adaptive behavior patterns suitable for local habitats. Early experience by the offspring mediated by social learning through the mother may play an important role in determination of food preference in the life. Where the environment is relatively stable, offspring may copy the food choices of older individuals, whereas in highly fluctuating environments, those individuals that select food on a trial and error basis are likely to obtain a more nutritious diet that those imitating the older adults.

Animals↗
PubMed2006

Strong regional heterogeneity in base composition evolution on the Drosophila X chromosome.

Fluctuations in base composition appear to be prevalent in Drosophila and mammal genome evolution, but their timescale, genomic breadth, and causes remain obscure. Here, we study base composition evolution within the X chromosomes of Drosophila melanogaster and five of its close relatives. Substitutions were inferred on six extant and two ancestral lineages for 14 near-telomeric and 9 nontelomeric genes. GC content evolution is highly variable both within the genome and within the phylogenetic tree. In the lineages leading to D. yakuba and D. orena, GC content at silent sites has increased rapidly near telomeres, but has decreased in more proximal (nontelomeric) regions. D. orena shows a 17-fold excess of GC-increasing vs. AT-increasing synonymous changes within a small (approximately 130-kb) region close to the telomeric end. Base composition changes within introns are consistent with changes in mutation patterns, but stronger GC elevation at synonymous sites suggests contributions of natural selection or biased gene conversion. The Drosophila yakuba lineage shows a less extreme elevation of GC content distributed over a wider genetic region (approximately 1.2 Mb). A lack of change in GC content for most introns within this region suggests a role of natural selection in localized base composition fluctuations.

Animals↗
PubMed2005

Seasonal fluctuations in birth weight and neonatal limb length; does prenatal vitamin D influence neonatal size and shape?

BACKGROUND: Birth weight is known to fluctuate with season of birth, however, there is little information about seasonal variation in neonatal anthropometric measures. AIMS: The aim of this study was to examine seasonal fluctuations in birth weight and selected anthropometric measures. STUDY DESIGN AND SUBJECTS: The birth weight of singletons born after at least 37 weeks gestation was extracted from a perinatal register in south-east Queensland (n=350,171). Mean monthly birth weights for this period were examined. Based on a separate birth cohort, principal component analysis was undertaken on neonatal anthropometric measures (n=1233). Seasonality was assessed by (a) spectral analysis of time series data, (b) monthly and seasonal comparison of outcomes. RESULTS: Based on register data, birth weight displayed clear annual periodicity. Birth weight differed significantly when compared by month and season. Infants born in October were the heaviest (3484 g), while May-born infants were the lightest (3459 g; P=0.001). Based on the cohort anthropometric data, three components were identified related to (a) overall size, (b) limb length, and (c) head size and skin-fold thickness. Each of these components displayed significant seasonal variation. In particular, prominent seasonal fluctuations in limb length were identified, with peak limb length associated with winter/spring birth. CONCLUSION: Environmental factors that have regular seasonal fluctuation influence both the size and shape of neonates. Animal experiments suggest that prenatal hypovitaminosis D may underlie greater limb length. Because birth weight and limb length are associated with a broad range of important health outcomes, the seasonal exposures underlying these effects warrant further scrutiny from a public health perspective.

Birth Weight↗
PubMed2000

Directionality theory and the evolution of body size.

Directionality theory, a dynamic theory of evolution that integrates population genetics with demography, is based on the concept of evolutionary entropy, a measure of the variability in the age of reproducing individuals in a population. The main tenets of the theory are three principles relating the response to the ecological constraints a population experiences, with trends in entropy as the population evolves under mutation and natural selection. (i) Stationary size or fluctuations around a stationary size (bounded growth): a unidirectional increase in entropy; (ii) prolonged episodes of exponential growth (unbounded growth), large population size: a unidirectional decrease in entropy; and (iii) prolonged episodes of exponential growth (unbounded growth), small population size: random, non-directional change in entropy. We invoke these principles, together with an allometric relationship between entropy, and the morphometric variable body size, to provide evolutionary explanations of three empirical patterns pertaining to trends in body size, namely (i) Cope's rule, the tendency towards size increase within phyletic lineages; (ii) the island rule, which pertains to changes in body size that occur as species migrate from mainland populations to colonize island habitats; and (iii) Bergmann's rule, the tendency towards size increase with increasing latitude. The observation that these ecotypic patterns can be explained in terms of the directionality principles for entropy underscores the significance of evolutionary entropy as a unifying concept in forging a link between micro-evolution, the dynamics of gene frequency change, and macro-evolution, dynamic changes in morphometric variables.

Animals↗
PubMed2005

Coupled dynamics of DNA breathing and of proteins that selectively bind to single-stranded DNA.

We study the size fluctuations of a local denaturation zone in a DNA molecule in the presence of proteins that selectively bind to single-stranded DNA, based on a (2+1)-dimensional master equation. By tuning the physical parameters we can drive the system from undisturbed bubble fluctuations to full, binding-protein-induced denaturation. We determine the effective free-energy landscape of the DNA bubble and explore its relaxation modes.

Binding Sites↗
PubMed2005

Quantum dissociation of an edge of a Luttinger liquid.

In a Luttinger liquid phase of one-dimensional molecular matter the strength of zero-point motion can be characterized by dimensionless De Boer's number quantifying the interplay of quantum fluctuations and two-body interactions. Selecting the latter in the Morse form we show that dissociation of the Luttinger liquid is a process initiated at the system edge. The latter becomes unstable against quantum fluctuations at a value of De Boer's number which is smaller than that of the bulk instability which parallels the classical phenomenon of surface melting.

Journal Article↗
PubMed2002

The hidden thermodynamics of a zinc finger.

The Zn finger provides a model for studies of protein structure and stability. Its core contains a conserved phenylalanine residue adjoining three architectural elements: a beta-hairpin, an alpha-helix and a tetrahedral Zn(2+)-binding site. Here, we demonstrate that the consensus Phe is not required for high-affinity Zn(2+) binding but contributes to the specification of a precise DNA-binding surface. Substitution of Phe by leucine in a ZFY peptide permits Zn(2+)-dependent folding. Although a native-like structure is retained, structural fluctuations lead to attenuation of selected nuclear Overhauser enhancements and accelerated amide proton exchange. Surprisingly, wild-type Zn affinity is maintained by entropy-enthalpy compensation (EEC): a hidden entropy penalty (TDeltaDeltaS 7kcal/mol) is balanced by enhanced enthalpy of association (DeltaDeltaH -7kcal/mol) at 25 degrees C. Because the variant is less well ordered than the Phe-anchored domain, the net change in entropy is opposite to the apparent change in configurational entropy. By analogy to the thermodynamics of organometallic complexation, we propose that EEC arises from differences in solvent reorganization. Exclusion of Leu among biological sequences suggests an evolutionary constraint on the dynamics of a Zn finger.

Amides↗
PubMed1986

Characterization of a calcium-activated potassium channel from rabbit intestinal smooth muscle incorporated into planar bilayers.

Interaction of vesicles from a microsomal fraction of rabbit intestinal smooth muscle with planar bilayers promotes the incorporation of a large conductance potassium-selective channel. The channel conductance fluctuates between two states: closed and open and the fraction of time the channel dwells in the open state is a function of the electric potential difference and the calcium concentrations. This channel seems to correspond to a Ca-activated K channel described by other authors in smooth muscle cells with the patch-clamp technique. Single-channel conductance is a saturating function of the potassium concentration. The relationship between conductance and concentration cannot be described by a hyperbolic function, suggesting multiple occupancy of the channel. The single-channel conductance is 230 pS in symmetrical 0.1 M KCl. Current is a linear function of the applied voltage in the range between -100 and +100 mV, at concentrations of 0.1 M KCl or higher. At lower concentrations, current-to-voltage curves bend symmetrically to the voltage axis. Sodium, lithium and cesium ions do not pass through the channel and the permeability for Rb is 66% that of potassium. All these alkali cations and Ca2+ block the channel in a voltage-dependent manner. A two-site three-barrier model on Eyring absolute reaction rate theory can account for the conduction and blocking characteristics.

Animals↗
PubMed2002

Two-photon fluorescence coincidence analysis: rapid measurements of enzyme kinetics.

Dual-color fluorescence cross-correlation analysis is a powerful tool for probing interactions of different fluorescently labeled molecules in aqueous solution. The concept is the selective observation of coordinated spontaneous fluctuations in two separate detection channels that unambiguously reflect the existence of physical or chemical linkages among the different fluorescent species. It has previously been shown that the evaluation of cross-correlation amplitudes, i.e., coincidence factors, is sufficient to extract essential information about the kinetics of formation or cleavage of chemical or physical bonds. Confocal fluorescence coincidence analysis (CFCA) (Winkler et al., Proc. Natl. Acad. Sci. U.S.A. 96:1375-1378, 1999) emphasizes short analysis times and simplified data evaluation and is thus particularly useful for screening applications or measurements on live cells where small illumination doses need to be applied. The recent use of two-photon fluorescence excitation has simplified dual- or multicolor measurements by enabling the simultaneous excitation of largely different dye molecules by a single infra-red laser line (Heinze et al., Proc. Natl. Acad. Sci. U.S.A. 97:10377-10382, 2000). It is demonstrated here that a combination of CFCA with two-photon excitation allows for minimization of analysis times for multicomponent systems down to some hundreds of milliseconds, while preserving all known advantages of two-photon excitation. By introducing crucial measurement parameters, experimental limits for the reduction of sampling times are discussed for the special case of distinguishing positive from negative samples in an endonucleolytic cleavage assay.

Algorithms↗
PubMed1986

Diurnal change in refraction, corneal curvature, visual acuity, and intraocular pressure after radial keratotomy in the PERK Study.

Selected patients who complained of fluctuating visual acuity in the Prospective Evaluation of Radial Keratotomy (PERK) Study were examined before 8:00 a.m. and after 7:00 p.m. on the same day to determine diurnal change in uncorrected visual acuity, best corrected visual acuity, manifest refractive error, average central keratometric power, and intraocular pressure. Sixty-three operated eyes were examined at three months, while 46 operated and 40 unoperated contralateral eyes were examined at one year after radial keratotomy. One year after surgery, 42% of the operated eyes had an increase in minus power of the manifest refraction of 0.50 to 1.25 diopters, 26% of the eyes changed their uncorrected visual acuity by 2 to 4 Snellen lines, and 35% of the operated eyes showed central steepening of the cornea by 0.50 to 1.25 diopters. These changes in the operated eyes at one year were similar to the changes at three months. Minimal diurnal changes occurred in the unoperated eyes at one year. Only 11% of the unoperated eyes changed their manifest refraction by 0.50 to 1.00 diopters, none changed their uncorrected visual acuity by 2 to 4 Snellen lines, and only one of the unoperated eyes changed its central keratometric power by 0.50 diopters. This study documents that many patients who experience diurnal fluctuation of vision have steepening of the cornea and an increase in the minus power of their refraction during the day.

Biomechanical Phenomena↗
PubMed2000

Immobilized liposome chromatography for refolding and purification of protein.

Small unilamellar liposomes were utilized as a kind of aqueous two-phase system and artificial chaperone which specifically recognize protein conformation with fluctuated structure. Liposomes showed highly selective binding ability to conformationally changed proteins treated with various concentrations of guanidinium hydrochloride, as evaluated by immobilized liposome chromatography (ILC). In refolding of proteins, liposomes bound to refolding intermediate of proteins and prevented them from forming intermolecular aggregates. Refolding of bovine carbonic anhydrase, lysozyme and ribonuclease A was significantly improved in the presence of liposomes. Furthermore, by utilizing ILC, refolding of proteins was also successfully and simply carried out with considerable high reactivation yield.

Animals↗