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PubMed2000

Evaluation of sequence variation and selection in the bindin locus of the red sea urchin, Strongylocentrotus franciscanus.

Recent evidence suggests that gamete recognition proteins may be subjected to directed evolutionary pressure that enhances sequence variability. We evaluated whether diversity enhancing selection is operating on a marine invertebrate fertilization protein by examining the intraspecific DNA sequence variation of a 273-base pair region located at the 5' end of the sperm bindin locus in 134 adult red sea urchins (Strongylocentrotus franciscanus). Bindin is a sperm recognition protein that mediates species-specific gamete interactions in sea urchins. The region of the bindin locus examined was found to be polymorphic with 14 alleles. Mean pairwise comparison of the 14 alleles indicates moderate sequence diversity (p-distance = 1.06). No evidence of diversity enhancing selection was found. It was not possible to reject the null hypothesis that the sequence variation observed in S. franciscanus bindin is a result of neutral evolution. Statistical evaluation of expected proportions of replacement and silent nucleotide substitutions, observed versus expected proportions of radical replacement substitutions, and conformance to the McDonald and Kreitman test of neutral evolution all indicate that random mutation followed by genetic drift created the polymorphisms observed in bindin. Observed frequencies were also highly similar to results expected for a neutrally evolving locus, suggesting that the polymorphism observed in the 5' region of S. franciscanus bindin is a result of neutral evolution.

Alleles↗

PubMed1982

Neuropeptide effects on memory in aged monkeys.

The effects of several neuropeptides were evaluated using a non-human primate model of age-related memory impairments. Several doses of ACTH4-10, lysine vasopressin, arginine vasopressin, oxytocin and somatostatin were each tested in several aged monkeys. Because data from a large number of non-drug control sessions was collected before, during and after this study, it was possible to define the normal range of control performance for each monkey and statistically determine whether a change in performance under any single dose of drug reflected a significant change from the particular monkey's normal baseline performance. Although none of the neuropeptides produced consistent group effects, evaluations of individual subjects against their own baseline performance revealed reliable changes at certain doses. Arginine vasopressin appeared to produce the best overall effects with three of the five monkeys exhibiting reliable changes in performance from baseline. These same three monkeys also responded positively to the lysine form. Oxytocin impaired memory in three of the six aged monkeys tested over a wide range of doses. Three of six aged monkeys performed better under ACTH4-10 compared to baseline; however, in two of these cases only a single dose was effective. The performance of only one subject was improved under somatostatin, and this was at a single dose only. The data reported here provide evidence for neuropeptides producing behavioral improvement in non-human primates using an appetitive task, eliminating a popular criticism that the data in this literature has depended too heavily on the testing of rodents in shock-motivated tasks. Additionally, the improvements observed in this study involve a behavior that it naturally impaired by age and one which has many operational similarities and some empirical relevance to measures of recent memory in humans. However, these positive findings must be tempered by the lack of robust effects and high individual variation observed.

Adrenocorticotropic Hormone↗

PubMed1995

Pharmacokinetics and pharmacodynamics of oxycodone when given intravenously and rectally to adult patients with cancer pain.

The single-dose pharmacokinetics and pharmacodynamics of oxycodone administered by the intravenous and rectal routes were determined in 12 adult cancer patients with moderate to severe cancer pain (visual analog scale [VAS] score, approximately 5). Oxycodone was administered by the intravenous and rectal routes with open drug administration and a cross-over design. After single-dose intravenous administration (7.9 +/- 1.5 mg, mean +/- SD), the mean (+/- SD) terminal half-life was 3.4 h (+/- 1.1), the mean (+/- SD) plasma clearance was 45.4 L/h (+/- 10.1), and the mean (+/- SD) volume of distribution in the terminal phase was 3.0 L/kg (+/- 1.1). After rectal oxycodone (30 mg), the mean (+/- SD) absorption lag time was 0.52 h (+/- 0.29) and the mean (+/- SD) absolute bioavailability was 61.6% (+/- 30.2%). Intravenous oxycodone was associated with a rapid onset of pain relief (5-8 min) in contrast to the 0.5- to 1.0-h delay observed after rectal administration. However, rectal oxycodone provided analgesia of much longer duration (approximately 8-12 h) than did intravenous oxycodone (approximately 4 h). There were no significant differences (P > 0.05) in the incidence and severity of side effects between intravenous and rectal oxycodone. The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study emphasizes the need for individualized dosing regimens.

Administration, Rectal↗

PubMedDate not supplied

Intra- and inter-observer variability in the assessment of testicular descent.

Measurements of the distance between the testis and the pubic tubercle have been used to differentiate retractile testes from "real" cryptorchidism and to measure the effect of therapy. The intra- and inter-observer variation of these measurements was determined in 21 boys with incompletely descended testes treated with placebo. Patients were investigated in supine and squatting position, before and during moderate caudal traction. In squatting position the average distance is 20 mm greater than in supine position. The intra-observer SD is approximately 10 mm. It is doubtful if quantitative measurements can be used to define retractile testes. The wide prediction intervals should be taken into account in interpreting results of therapy.

Administration, Intranasal↗

PubMed2004

Higher intake of DK265 corn silage by dairy cattle.

In this experiment, intake of DK265 3-way corn hybrid by dairy cattle was compared specifically with intake 1) of its bm3 isogenic form, 2) of its 2 related single-way hybrids, and 3) of 2 controls that were registered hybrids of similar earliness. Both dry matter (DM) and lignin contents were similar in all hybrids except for the bm3 hybrid, which was less lignified. There was a tendency for lower starch content and, correlatively, higher neutral detergent fiber content in DK265 and in the 2 related single-way hybrids. Significant intake differences were observed between hybrids; the highest intake was recorded for the bm3 hybrid. Among normal hybrids, DK265 and one of its related single-way hybrids registered significantly higher intakes than other hybrids. Among normal hybrids, cell wall digestibility and/or lignin content did not explain all of the variations observed for intake, whereas the higher intake of DK265 bm3 could be related to its lower lignin content as compared with isogenic DK265. It was hypothesized that the higher intake observed for the DK265 hybrid was probably related to specific friability traits that are not relevantly measured through the usual tests used in corn breeding.

Animals↗

PubMed2002

Through a genome, darkly: comparative analysis of plant chromosomal DNA.

Plant nuclear genomes encompass a wide range of variation in size and nucleotide composition with diverse arrangements of chromosomal segments, repetitive sequences and distribution of genes. Comparative genomic analysis may be undertaken at different levels of organisation, which are reflected in this review, together with a focus on the genetic and functional significance of the observed variation. Patterns of genome organisation have been revealed which reflect the different underlying mechanisms and constraints driving change. Thus comparative issues of genome size, nucleotide sequence composition and genome heterogeneity are provided as a background to understanding the different levels of segmental and repetitive sequence duplication and distribution of genes. The extent of synteny and collinearity revealed by recent genetic and sequence comparisons is discussed, together with a consideration of problems associated with such analyses. The possible origins and mechanisms of variation in genome size and organisation are covered, including the prevalence of duplication at different levels of organisation. The likely genetic, functional and adaptive consequences of replicated loci are discussed with evidence from comparative studies. The scope for comparative analysis of epigenetic plant genome variation is considered. Finally, opportunities for applying comparative genomics to isolating genes and understanding complex crop genomes are addressed.

DNA, Plant↗

PubMed2004

Mantle segmentation along the Oman ophiolite fossil mid-ocean ridge.

It has been difficult to relate the segmentation of mid-ocean ridges to processes occurring in the Earth's underlying mantle, as the mantle is rarely sampled directly and chemical variations observed in lavas at the surface are heavily influenced by details of their production as melt extracted from the mantle. Our understanding of such mantle processes has therefore relied on the analysis of pieces of fossil oceanic lithosphere now exposed at the Earth's surface, known as ophiolites. Here we present the phase chemistry and whole-rock major- and trace-element contents of 174 samples of the mantle collected along over 400 km of the Oman Sultanate ophiolite. We show that, when analysed along the fossil ridge, variations of elemental ratios sensitive to the melting process define a three-dimensional geometry of mantle upwellings, which can be related to the segmentation observed in modern mid-ocean ridge environments.

Journal Article↗

PubMed1992

Electrophoretic analysis of low and high activity forms of catechol-O-methyltransferase in human erythrocytes.

Analysis of the catechol-O-methyltransferase (COMT) enzyme in human RBC lysates from 15 samples exhibiting inherited variations in level of activity and thermal stability was performed. Electrophoretic blotting and immune fixation was carried out following sodium dodecyl sulfate polyacrylamide gel electrophoresis or isoelectric focusing of lysate protein. These techniques did not reveal a major structural alteration of the protein that could account for the observed variation in enzyme activity or thermal stability. Future studies utilizing molecular genetic techniques should make it possible to determine the basis for inherited variations in human RBC COMT activity and thermal stability.

Catechol O-Methyltransferase↗

PubMed1996

An investigation of the mechanics of tactile sense using two-dimensional models of the primate fingertip.

Tactile information about an object in contact with the skin surface is contained in the spatio-temporal load distribution on the skin, the corresponding stresses and strains at mechanosensitive receptor locations within the skin, and the associated pattern of electrical impulses produced by the receptor population. At present, although the responses of the receptors to known stimuli can be recorded, no experimental techniques exist to observe either the load distribution on the skin or the corresponding stress-state at the receptor locations. In this paper, the role of mechanics in the neural coding of tactile information is investigated using simple models of the primate fingertip. Four models that range in geometry from a semi-infinite medium to a cylindrical finger with a rigid bone, and composed of linear elastic media, are analyzed under plane strain conditions using the finite element method. The results show that the model geometry has a significant influence on the surface load distribution as well as the subsurface stress and strain fields for a given mechanical stimulus. The elastic medium acts like a spatial low pass filter with the property that deeper the receptor location, the more blurred the tactile information. None of the models predicted the experimentally observed surface deflection profiles under line loads as closely as a simple heterogeneous waterbed model that treated the fingerpad as a membrane enclosing an incompressible fluid (Srinivasan, 1989). This waterbed model, however, predicted a uniform state of stress inside the fingertip and thus failed to explain the spatial variations observed in the neural response. For the cylindrical model indented by rectangular gratings, the maximum compressive strain and strain energy density at typical receptor locations emerged as the two strain measures that were directly related to the electrophysiologically recorded response rate of slowly adapting type I (SAI) mechanoreceptors. Strain energy density is a better candidate to be the relevant stimulus for SAIs, since it is a scalar that is invariant with respect to receptor orientations and is a direct measure of the distortion of the receptor caused by the loads imposed on the skin.

Algorithms↗

PubMed1991

Commercial rodent diets and nephrocalcinosis in weanling female rats.

This study addresses the questions to what extent commercial rodent diets would induce nephrocalcinosis, and which dietary components would be responsible for inducing this condition. For this purpose, 10 commercial diets were analysed for selected components and fed to weanling female rats. On the basis of histological inspection of kidney sections, two diets were found to produce significant nephrocalcinosis. The condition could be considered relatively mild because concentrations of Ca in kidney tissue were not increased. There was considerable variation between the commercial diets in the (analysed) concentrations of Ca, P, Mg and protein as well as in the diet-induced urinary pH, urinary volume and caecal weight. Of these parameters, only the dietary Ca:P ratio and group mean urinary pH correlated significantly with the observed variation in group mean calcification scores, the relationships being negative. It is suggested that the Ca:P ratio of commercial rodent diets is an important determinant of nephrocalcinosis.

Animal Feed↗

PubMed2004

SNP discovery and typing technologies for pharmacogenomics.

Genetic variation in the human genome occurs predominantly as single nucleotide polymorphisms (SNPs). Our DNA may contain as many as ten million SNPs, of which three million or more are likely to differ between any two unrelated individuals. These three million genetic differences make a significant contribution to the observed variation in complex human phenotypes, such as disease susceptibility and our responses to drugs or environmental chemicals. Large-scale association studies taking place throughout the drug development process can help to identify such differences and tailor drugs and dose regimens to particular genotype classes. The need for such large-scale studies has driven the development of high-throughout SNP discovery and typing technologies, which are the subject of this review.

Genetic Testing↗

PubMed2006

Taxonomic position and geographical distribution of the common sheep G1 and camel G6 strains of Echinococcus granulosus in three African countries.

The taxonomic and phylogenetic status of Echinococcus granulosus strains are still controversial and under discussion. In the present study, we investigated the genetic polymorphism of E. granulosus isolates originating from three countries of Africa, including a region of Algeria, where the common G1 sheep and the camel G6 strains coexist sympatrically. Seventy-one hydatid cysts were collected from sheep, cattle, camels, and humans. Two mitochondrial markers (cox1 and nad1) were used for strain identification. Two nuclear markers (actII and hbx2) were used to study the possible occurrence of cross-fertilization. Despite the heterogeneity observed among the G1 isolates, they were all localized within one robust cluster. A second strong cluster was also observed containing all of the G6 isolates. Both strains appeared as two distinct groups, and no cases of interbreeding were found. Thus, the attribution of a species rank can be suggested. We also found the Tasmanian sheep G2 strain for the first time in Africa. Because of the slight variations observed between the common sheep and the Tasmanian sheep strains, further studies should be carried out to elucidate the epidemiological relevance of this genetic discrimination.

Algeria↗

PubMed1990

Radiosensitivity throughout the cell cycle and repair of potentially lethal damage and DNA double-strand breaks in an X-ray-sensitive CHO mutant.

The response to ionizing radiation of synchronized and plateau-phase populations of xrs-5 cells was studied at the DNA and cellular level. Induction and repair of DNA double-strand breaks (dsb) were measured by the non-unwinding filter elution technique. Biphasic survival curves were obtained throughout the cell cycle as well as in the plateau phase, suggesting the presence in the cultures of a radiation-sensitive and a radiation-resistant subpopulation. Delayed plating of plateau-phase xrs-5 cells did not significantly modify cell survival indicating a deficiency in the repair of potentially lethal damage (PLD). Post-irradiation treatment with araA further indicated a deficiency in the repair of a form of PLD sensitive to this drug in the radiation-sensitive subpopulation. The radiosensitivity of synchronized populations decreased as cells progressed through S. Cells in late S were found to be most resistant to radiation, whereas cells irradiated in G2 + M had a sensitivity similar to that of cells irradiated in G1. The decrease in radiosensitivity in S was tentatively attributed to an increase in the proportion of radioresistant cells in the cell population. Preliminary analysis of the results obtained, assuming the presence of two subpopulations showing an exponential response as a function of dose, indicated no change in the D0 values of the radiation-sensitive and the radiation-resistant component throughout the cell cycle. The D0 value of the radiation-resistant component was similar to the D0 of repair-proficient CHO cells. At no stage in the cell cycle were shoulder-type survival curves observed. Transient expression of the xrs-5 repair gene may underlie the observed variation of radiosensitivity throughout the cell cycle. This gene expression could occur either at random, in a subpopulation of cells independent of cell cycle phase, or in a specific manner related to gene replication and the hemimethylated state transiently found immediately thereafter. It is proposed that the resistant tail observed in the survival curves throughout the cell cycle is due to the former phenomenon, and the decreased radiosensitivity in late S to the latter. xrs-5 cells were found to be deficient in dsb repair in the plateau phase of growth, as well as in G1 and mid-S phase. The latter observation indicates that the reduction in radiation sensitivity in S is not associated with a modulation in the ability of cells to repair dsb.

Animals↗

PubMed1995

Time series forecasts of poison center call volume.

We tested the hypothesis that time series analysis can provide accurate predictions of future poison center telephone call volume by a prospective stochastic time series modeling of calls to a university-based regional poison center. All callers evaluated and managed during two sequential years had the time and date of the call recorded in a computer database. Time series variables were formed for poison center calls per hour. Prediction models were developed from the 1992 data and included four types: raw observations, moving average, means with moving average smoothing, and autoregressive integrated moving average. Forecasts from each model were tested against observations from the first 26 weeks of 1993. Each model's adequacy was tested on residuals by autocorrelation functions, integrated periodograms, linear regression, and differences among the variances. A total of 44,584 calls were received in 1992 and 24,781 in the first half of 1993. Large periodic variations in call volume with time of day were found (p < 0.001). The model based on arithmetic means of each hour of the week with three-point moving average smoothing yielded the most accurate forecasts and explained 58.5% of the variation observed in the 1993 test series (p < 0.001). Time series analysis can provide powerful, accurate short range forecasts of future poison center telephone call volume. Simpler, less expensive models performed best in this study.

Computers↗

PubMed1979

Intercomparison study on the determination of single administration toxicity in rats.

In 1977, the Commission of the European Communities initiated an intercomparison study to determine the single administration oral LD50 value in rats of each of 5 chemicals with the aims of comparing experimentation technologies, determining the degree of variation in the results and the various parameters used to establish the LD50 value, and establishing a common protocol for the determination of the LD50 value. Sixty-five laboratories in 8 countries took part in the first study. The significant variation in protocol may have led to the large interlaboratory variation observed in the results. Therefore, participating laboratories carried out a second study using a common protocol, preceded by a pilot study. A total of 100 laboratories in 13 countries participated. A majority of results of the second study are currently being analyzed, and the indications are that the interlaboratory variation has been significantly reduced.

Animals↗

PubMedDate not supplied

Seasonality of births in human populations.

Seasonal fluctuations in births have been observed in virtually all human populations. In this paper we re-examine the seasonality of births with two main objectives in mind. The first is to provide an overview of the basic facts about the seasonality of births, presenting new estimates of the seasonal patterns. Seasonality is an important if not dominant source of nontrend variation in births in virtually all populations, but there are dramatic and puzzling differences across countries and time periods in the pattern of seasonal variation observed in particular populations. The second purpose of the paper is to survey the leading hypotheses about birth seasonality that have appeared in the literature and to discuss the consistency of these hypotheses with observed seasonal patterns. Using our estimates of seasonal patterns along with other evidence in the literature, we conclude that no single explanation receives strong, consistent support from the data.

Delivery, Obstetric↗

PubMed1991

Evolution in molecular structure and adaptive variance in metabolism.

1. A hypothesis is advanced to the effect that all metabolites, even minor ones, are expressed as a result of stimuli and are directed against or support actions on receptor systems. 2. In particular the hypothesis emphasizes the dynamic character of the secondary metabolite pattern as a function of physiological or environmental conditions and that the variations observed reflect the evolution of receptors. 3. Predictions based on this principle are experimentally verifiable. 4. The hypothesis has major implications in the entire area of life sciences.

Biological Evolution↗

PubMed2004

Comparative study of genetic variation at 15 STR loci in three isolated populations of the Bosnian mountain area.

Fifteen autosomal STR loci (D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, VWA, D8S1179, TPOX, and FGA) were studied in three geographically close but isolated populations from the Bosnian mountain area. The three villages are Bobovica, Dejcici, and Lukomir. DNA was obtained from 83 individuals, and the allele frequencies and genetic diversity among the three sample groups were compared. In addition, seven of the STR loci (CSF1PO, D13S317, D3S1358, D5S818, D7S820, FGA, TH01) were used in a comparative population analysis of the Bjelasnica-Treskavica region and the Adriatic islands of Brac, Hvar, and Korcula. Although the sample sizes are relatively small, the observed variation within any of the small isolated populations is high and comparable to less isolated groups. In addition, even though the populations are geographically isolated, the STR data are similar among the populations. The most significant frequency differences were observed at the TH01 locus. Although the specific allele distributions in any untyped population cannot be determined a priori, we find support for a high degree of diversity for the STR loci in most populations. In addition, the multiple locus profile is highly informative not only for various population studies but also for forensic studies, even when specific population data are not available.

Bosnia and Herzegovina↗