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PubMed2003

Measuring mast seeding behavior: relationships among population variation, individual variation and synchrony.

Mast seeding, or masting, is the variable production of flowers, seeds, or fruit across years more or less synchronously by individuals within a population. A critical issue is the extent to which temporal variation in seed production over a collection of individuals can be viewed as arising from a combination of individual variation and synchrony among individuals. Studies of masting typically quantify such variation in terms of the coefficient of variation (CV). In this paper we examine mathematically how the population CV relates to the mean individual CV and synchrony, concluding that the relationship is a complex one which cannot isolate an overall measure of synchrony, and involves additional factors, principally the number of plants sampled and the mean productivity per plant. Our development suggests some simple approximate relationships of population CV to individual variability, synchrony and the number of individuals. These were found to fit quite well when applied to data from 59 studies which included seed production at the individual level.

Chronobiology Phenomena↗

PubMed2000

The "supply hypothesis" and medical practice variation in primary care: testing economic and clinical models of inter-practitioner variation.

Medical practice variation (MPV) is marked, apparently ubiquitous across the health sector, well documented, and continues to be a focus of professional and policy interest. MPV have stimulated two paths of investigation, one economic in emphasis and the other more-clinical in orientation; while health economists have stressed the potential role of income incentives in medical decision-making, health services research has tended to emphasise clinical ambiguity as a factor in practitioner decisions. Both sets of explanations converge in an implicit "supply hypothesis" that posits contextual practitioner and practice attributes as influential in clinical decisions. Data on inter-practitioner variation are taken from a large and representative regional survey of general practitioners in New Zealand, a country in which unsubsidised fee-for-service is the predominant mode of remuneration in primary care. The paper assesses the impact on three important areas of clinical decision-making prescribing, test ordering, request for follow-up -- of three key conceptual dimensions -- income incentives, physician agency, and clinical ambiguity (operationalised as local doctor density, practitioner encounter initiation, and diagnostic uncertainty respectively). Predictions are made about inter-practitioner variations in the rate of clinical activity in the three areas. The results of the analysis using multi-level statistical techniques are: 1. the extent of competition -- local doctor density -- seems to have no effect on the pattern of clinical decision-making; 2. doctor-initiated visits are, if anything, associated with lower rates of intervention; 3. diagnostic uncertainty is associated with higher rates of investigations and follow-up, both of which have clinical plausibility; 4. there is no significant interaction effect between density and uncertainty. It is concluded that, for the clinical activities studied and for the practitioner attributes as operationalised in this investigation, a clinical, rather than an economic, model of practitioner decision-making provides a more plausible interpretation of inter-practitioner variation in rates of clinical activity in general practice. The "supply hypothesis" requires further analytical refinement and empirical assessment before it can be applied as a generic explanatory framework for MPV.

Family Practice↗

PubMed1997

Intestinal fatty acid-binding protein variation associated with variation in the response of plasma lipoproteins to dietary fibre.

Increased dietary fibre intake is a component of prudent dietary advice, although the mechanism of its beneficial effect is unclear. Furthermore, plasma lipoprotein response to dietary fibre seems to vary both between individuals and according to the type of fibre consumed. Two common genetic variants, A54 and T54, of the intestinal fatty acid-binding protein gene (FABP2) have different in vitro binding affinities for long-chain fatty acids. We have hypothesized that variation in FABP2 would be associated with interindividual variation in the response of plasma lipoproteins to either dietary soluble or insoluble fibre. We studied 43 subjects who participated in a year-long cross-over study of the effect of insoluble and soluble fibre on plasma lipoproteins. We tested for associations between FABP2 genotypes and the response of plasma lipoproteins to dietary fibre. When compared with subjects homozygous for FABP2 A54, we found that subjects with FABP2 T54 had significantly greater decreases in plasma total and low-density lipoprotein (LDL)-cholesterol and apoB during the period when the diet was high in soluble fibre than during the period when the diet was high in insoluble fibre. Furthermore, compared with subjects with the FABP2 A54 allele, subjects with the FABP2 T54 allele had significantly lower secretion of total fecal bile acids, but this did not increase with dietary soluble fibre. Genetic variation in FABP2 may thus contribute to interindividual variation in the response of plasma lipoproteins to different dietary fibres, but the mechanism does not appear to be related to increases in fecal bile acid secretion.

Bile Acids and Salts↗

PubMed2004

Neisseria meningitidis undergoes PilC phase variation and PilE sequence variation during invasive disease.

Neisseria meningitidis colonizes the upper respiratory tract (URT), enters the blood stream, and reaches the cerebrospinal fluid (CSF). In the present study, we show that bacteria isolated from the URT adhere better to human epithelial cells, compared with bacteria from blood or CSF, which suggests that important changes of virulence-associated proteins take place during bacterial dissemination. Phase variation in the pilus adhesin PilC and sequence variation in the pilus subunit PilE occurred among strains from 1 patient. Changes were not found in the invasion-associated opacity proteins or in lipooligosaccharides. PilC was frequently expressed in serogroup B strains and in URT strains but was often switched off in other serogroups and in CSF strains. Strains lacking PilC showed impaired adhesion to epithelial cells. These data argue that N. meningitidis undergoes PilC phase variation and PilE sequence variation during invasive disease.

Amino Acid Sequence↗

PubMed1992

Patterns of naturally occurring restriction map variation, dopa decarboxylase activity variation and linkage disequilibrium in the Ddc gene region of Drosophila melanogaster.

Forty-six second-chromosome lines of Drosophila melanogaster isolated from five natural populations were surveyed for restriction map variation in a 65-kb region surrounding the gene (Ddc) encoding dopa decarboxylase (DDC). Sixty-nine restriction sites were scored, 13 of which were polymorphic. Average heterozygosity per nucleotide was estimated to be 0.005. Eight large (0.7-5.0 kb) inserts, two small inserts (100 and 200 bp) and three small deletions (100-300 bp) were also observed across the 65-kb region. We see no evidence for a reduction in either nucleotide heterozygosity or insertion/deletion variation in the central 26-kb segment containing Ddc and a dense cluster of lethal complementation groups and transcripts (greater than or equal to 9 genes) compared to that seen in the adjacent regions (totaling 39 kb) in which only a single gene and transcript has been detected, or to that observed for other gene regions in D. melanogaster. The distribution of restriction site variation shows no significant departure from that expected under an equilibrium neutral model. However insertions and deletions show a significant departure from neutrality in that they are too rare in frequency, consistent with them being deleterious on average. Significant linkage disequilibrium among variants exists across much of the 65-kb region. Lower regional rates of recombination combined with the influence of polymorphic chromosomal inversions, rather than epistatic selection among genes in the dense cluster, probably are sufficient explanations for the creation and/or maintenance of the linkage disequilibrium observed in the Ddc region. We have also assayed adult DDC enzyme activity in these same lines. Twofold variation in activity among lines is observed within our sample. Significant associations are observed between level of DDC enzyme activity and restriction map variants. Surprisingly, one line with a 5.0-kb insert within an intron and one line with a 1.5-kb insert near the 5' end of Ddc each show normal adult DDC activities.

Animals↗

PubMed2001

Genetic variation in the human urea transporter-2 is associated with variation in blood pressure.

The kidney, by regulating the volume of fluid in the body, plays a key role in regulating blood pressure (BP). The kidney uses primarily sodium and, to a lesser extent, urea to maintain the appropriate volume of fluid. Genetic variation in proteins that determine sodium reabsorption and excretion is known to significantly influence BP. However, the influence of genetic variation in urea transporters on BP has not been examined. We determined therefore whether nucleotide variation in the kidney-specific human urea transporter, HUT2, is associated with variation in BP. After determining the genomic structure of the coding sequence, seven single nucleotide polymorphisms (SNPs) were identified. Two of the SNPs result in Val/Ile and Ala/Thr amino acid substitutions at positions 227 and 357 in the HUT2 open reading frame, respectively. Another SNP is silent and four others are in introns or the 3' untranslated region. Over 1000 hypertensive and low-normotensive individuals of Chinese origin were typed for five of these SNPs using a high-throughput genotyping method. The Ile227 and Ala357 alleles were associated with low diastolic BP in men but not women, with odds ratios 2.1 [95% confidence interval (CI) 1.5-2.7, P < 0.001] and 1.5 (95% CI 1.2-1.8, P < 0.001), respectively. There was a similar trend for systolic BP, and odds ratios for the Ile227 and Ala357 alleles were 1.7 (95% CI 1.2-2.3, P = 0.002) and 1.3 (95% CI 1.1-1.6, P = 0.007), respectively, in men.

Blood Pressure↗

PubMed2006

Sequence variation in the coding region of the melanocortin-1 receptor gene (MC1R) is not associated with plumage variation in the blue-crowned manakin (Lepidothrix coronata).

Avian plumage traits are the targets of both natural and sexual selection. Consequently, genetic changes resulting in plumage variation among closely related taxa might represent important evolutionary events. The molecular basis of such differences, however, is unknown in most cases. Sequence variation in the melanocortin-1 receptor gene (MC1R) is associated with melanistic phenotypes in many vertebrate taxa, including several avian species. The blue-crowned manakin (Lepidothrix coronata), a widespread, sexually dichromatic passerine, exhibits striking geographic variation in male plumage colour across its range in southern Central America and western Amazonia. Northern males are black with brilliant blue crowns whereas southern males are green with lighter blue crowns. We sequenced 810 bp of the MC1R coding region in 23 individuals spanning the range of male plumage variation. The only variable sites we detected among L. coronata sequences were four synonymous substitutions, none of which were strictly associated with either plumage type. Similarly, comparative analyses showed that L. coronata sequences were monomorphic at the three amino acid sites hypothesized to be functionally important in other birds. These results demonstrate that genes other than MC1R underlie melanic plumage polymorphism in blue-crowned manakins.

Animals↗

PubMed2005

Variation for neutral markers is correlated with variation for quantitative traits in the plant pathogenic fungus Mycosphaerella graminicola.

We compared genetic variation and population differentiation at RFLP marker loci with seven quantitative characters including fungicide resistance, temperature sensitivity, pycnidial size, pycnidial density, colony size, percentage of leaves covered by pycnidia (PLACP) and percentage of leaves covered by lesions (PLACL) in Mycosphaerella graminicola populations sampled from four regions. Wide variation in population differentiation was found across the quantitative traits assayed. Fungicide resistance, temperature sensitivity, and PLACP displayed a significantly higher Q(ST) than G(ST), consistent with selection for local adaptation, while pycnidial size, pycnidial density and colony size displayed a lower or significantly lower Q(ST) than G(ST), consistent with constraining selection. There was not a statistical difference between Q(ST) and G(ST) in PLACL. We also found a positive and significant correlation between genetic variation in molecular marker loci and quantitative traits at the multitrait scale, suggesting that estimates of overall genetic variation for quantitative traits in M. graminicola could be derived from analysis of the molecular genetic markers.

Ascomycota↗

PubMed2004

Population genetic variation in gene expression is associated with phenotypic variation in Saccharomyces cerevisiae.

BACKGROUND: The relationship between genetic variation in gene expression and phenotypic variation observable in nature is not well understood. Identifying how many phenotypes are associated with differences in gene expression and how many gene-expression differences are associated with a phenotype is important to understanding the molecular basis and evolution of complex traits. RESULTS: We compared levels of gene expression among nine natural isolates of Saccharomyces cerevisiae grown either in the presence or absence of copper sulfate. Of the nine strains, two show a reduced growth rate and two others are rust colored in the presence of copper sulfate. We identified 633 genes that show significant differences in expression among strains. Of these genes, 20 were correlated with resistance to copper sulfate and 24 were correlated with rust coloration. The function of these genes in combination with their expression pattern suggests the presence of both correlative and causative expression differences. But the majority of differentially expressed genes were not correlated with either phenotype and showed the same expression pattern both in the presence and absence of copper sulfate. To determine whether these expression differences may contribute to phenotypic variation under other environmental conditions, we examined one phenotype, freeze tolerance, predicted by the differential expression of the aquaporin gene AQY2. We found freeze tolerance is associated with the expression of AQY2. CONCLUSIONS: Gene expression differences provide substantial insight into the molecular basis of naturally occurring traits and can be used to predict environment dependent phenotypic variation.

Color↗

PubMed1988

The diurnal variation in plasma homovanillic acid level persists but the variation in 3-methoxy-4-hydroxyphenylglycol level is abolished under constant conditions.

Plasma concentrations of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined every two hours for two consecutive days in seven depressed patients and seven matched normal controls. On the first day subjects followed their regular ward routine. On the second day they were placed on a regimen in which activity, posture, diet, and wakefulness were held constant. There were significant diurnal variations in both MHPG and HVA concentrations on the baseline day, whereas on the constant routine, a diurnal variation was present only in HVA. We conclude that diurnal variations in plasma MHPG are evoked by changes in physical activity, posture, or other factors controlled on the constant routine, and that a major component of the diurnal variation in plasma HVA concentrations is regulated by a circadian oscillator that is independent of sleep or activity.

Adult↗

PubMed2004

In humans, the seasonal variation in poly-unsaturated fatty acids is related to the seasonal variation in violent suicide and serotonergic markers of violent suicide.

BACKGROUND: Depression is accompanied by a depletion of n-3 poly-unsaturated fatty acids (PUFAs). There is also a negative correlation between suicide and fish-oil intake (rich in n-3 PUFAs) across different countries. Both depression and suicide show a seasonal variation and are related to disorders in the serotonergic system. AIMS: The present study was carried out to determine if there is a seasonal variation in the PUFA fractions in serum phospholipids and whether there are significant relationships between lowered n-3 PUFA status and the seasonal variation in the number of suicide deaths and serotonergic markers of suicide. METHODS: We took monthly blood samples during 1 calendar year from 23 healthy volunteers and analyzed the PUFA composition in serum phospholipids and related those data to the annual variation in the mean weekly number of suicides for Belgium and the Bmax [3H]-paroxetine binding to platelets in the same 23 subjects. RESULTS: Significant annual rhythms were detected in the long-chain PUFAs only, i.e. arachidonic acid (C20: 4n-6; AA), eicosapentaenoic acid (C20: 5n-3; EPA), and docosahexaenoic acid (C22: 6n-3; DHA). There was a significant correlation between the changes over the last 2 weeks in AA and EPA and the mean weekly number of violent, but not nonviolent, suicide deaths in Belgium. There was a significant correlation between the PUFAs, AA and DHA, and the Bmax [3H]-paroxetine binding to platelets. CONCLUSIONS: Our results show that there is a true seasonality in long-chain PUFAs, such as AA, EPA and DHA. The results suggest that the seasonality in PUFAs may be related to the incidence of violent suicide and the expression of the serotonin transporter complex.

Arachidonic Acid↗

PubMed2001

Variation in clinical decision making is a partial explanation for geographical variation in lower extremity amputation rates.

BACKGROUND: Rates of lower extremity amputation vary significantly both between and within countries. The variation does not appear to support differences in need as an explanation. This study set out to see if variations in clinical decision making might contribute to the explanation. METHODS: Based on an extensive audit database of lower extremity amputations and revascularization operations, a decision model was produced. Drawing on items in this model allowed the selection of six clinical cases that differed in their probability of having amputation as the outcome. Two cases had 80 per cent or more, two cases had 45--55 per cent and two cases had 20 per cent or less probability of amputation. Each of ten consultant vascular surgeons looked at these cases without knowledge of their probability of outcome and decided on amputation or revascularization. RESULTS: Overall the chance-adjusted level of agreement (kappa coefficient) between the decisions made by ten surgeons on the six clinical cases and the actual outcome was 0.46, indicating a moderate level of agreement. The kappa coefficient for individual surgeons showed complete agreement (kappa = 1) for four, substantial agreement (kappa = 0.66) for four, fair agreement (kappa = 0.32) for one and no agreement other than at a chance level (kappa = 0) for one surgeon. CONCLUSION: Variations in the clinical decisions made by vascular surgeons given the same patient are likely to explain at least a part of the observed geographical variation in rates of lower extremity amputation. Consensus guidelines may enable more consistent decision making for this problem.

Aged↗

PubMed2001

Frequency variations of discrete cranial traits in major human populations. II. Hypostotic variations.

Five discrete hypostotic cranial traits, tympanic dehiscence, ovale-spinosum confluence, metopism, transverse zygomatic suture vestige, and biasterionic suture, were investigated in 81 human population samples. Except for ovale-spinosum confluence, marked asymmetric occurrences of the bilateral traits were not detected in the majority of the samples. Significant intertrait association was observed mainly between the biasterionic suture and other sutural variations including accessory ossicles. The traits showing relatively consistent sex differences across diverse populations were tympanic dehiscence, which is predominant in females, and biasterionic suture in males. On a world scale, the 5 hypostotic cranial traits showed distinctive patterns of geographical variation. Different clinal variations within and between macrogeographical areas such as western and eastern parts of the Old World were found for the frequencies of the traits. The Ainu may be the most distinct outlier in the eastern Asian region on the basis of the incidence of the traits, especially the transverse zygomatic suture vestige. The interregional variation without reasonable adaptive value and nonadaptive shift of the possible outliers presented in this study suggest that the genetic background for the occurrence of these traits cannot be excluded completely.

Cranial Sutures↗

PubMed1992

Can small-area analysis detect variation in surgery rates? The power of small-area variation analysis.

A variety of statistical methods can be used in small-area analysis to test whether there is more variation than would be expected by chance alone. However, the power of these methods to detect existing variation has never been studied. The authors used data regarding back surgery in Washington State to suggest several types of variation that might exist (alternative hypotheses), and then used computer simulation to determine the power, or the probability of detecting this variation. The chi-square test had the highest power of all methods considered against most alternative hypotheses. Power is higher if there are no multiple admissions, rates are higher, and counties have larger or similar population size. Problems of accounting for multiple admissions, adjustment for age and sex, choosing the optimum size of small areas, and detection of outliers also are discussed.

Age Factors↗

PubMed2001

Small variations in multiple parameters account for wide variations in HIV-1 set-points: a novel modelling approach.

Steady-state levels of HIV-1 viraemia in the plasma vary more than a 1,000-fold between HIV-positive patients and are thought to be influenced by several different host and viral factors such as host target cell availability, host anti-HIV immune response and the virulence of the virus. Previous mathematical models have taken the form of classical ecological food-chain models and are unable to account for this multifactorial nature of the disease. These models suggest that the steady-state viral load (i.e. the set-point) is determined by immune response parameters only. We have devised a generalized consensus model in which the conventional parameters are replaced by so-called 'process functions'. This very general approach yields results that are insensitive to the precise form of the mathematical model. Here we applied the approach to HIV-1 infections by estimating the steady-state values of several process functions from published patient data. Importantly, these estimates are generic because they are independent of the precise form of the underlying processes. We recorded the variation in the estimated steady-state values of the process functions in a group of HIV-1 patients. We developed a novel model by providing explicit expressions for the process functions having the highest patient-to-patient variation in their estimated values. Small variations from patient to patient for several parameters of the new model collectively accounted for the large variations observed in the steady-state viral burden. The novel model remains in full agreement with previous models and data.

HIV Infections↗

PubMed1993

Circadian variation in serum cortisol and circulating neutrophils are markers for circadian variation of bone marrow proliferation in cancer patients.

Serum cortisol, circulating white blood cells and DNA cell cycle distribution in bone marrow cells were measured during daytime (11.00) and at midnight (24.00) over single 24-hour periods in 15 cancer patients. The neutrophils and fraction of bone marrow cells in S-phase showed the same circadian variation as cortisol with higher values in daytime as compared to midnight in 11 patients with a normal cortisol rhythm (p < 0.05). The lymphocytes, eosinophils and basophils all had significantly higher values at midnight as compared to daytime. There were significant correlations between cortisol and neutrophils, lymphocytes, eosinophils and basophils. The correlation between neutrophils and fractions of bone marrow cells in S-phase and S + G2/M-phase were highly significant (r = 0.74, p = 0.0001 and r = 0.72, p = 0.0001, respectively). In 8 of 13 patients (61.5%) without bone marrow infiltration both cortisol and neutrophils showed identical circadian variation as bone marrow cells in S-phase and S + G2/M-phase. Furthermore, for the total series a significant correlation between S-phase, cortisol and neutrophils was found by multiple regression analysis (p < 0.0001). These findings strengthen the possibility of using the circadian variation in cortisol and neutrophils as marker rhythms for circadian variation in bone marrow proliferation, thus allowing optimization of cytotoxic therapy and individualization of chronotherapy.

Adult↗

PubMed1992

Circadian variation in ischemic threshold. A mechanism underlying the circadian variation in ischemic events.

BACKGROUND: There is a circadian pattern in the occurrence of cardiac events in patients with coronary artery disease. Whether changes in coronary vascular tone contribute to these phenomena is unknown. We measured the ischemic threshold, defined as either the heart rate or rate-pressure product at 1-mm ST segment depression during treadmill exercise and used it as an index of the lowest coronary vascular resistance; the premise was that when ischemic threshold became lower, coronary vascular resistance was higher, and vice versa. METHODS AND RESULTS: Fifteen patients (group A) with stable coronary artery disease underwent four identical treadmill exercise tests in 24 hours, and ischemic threshold was measured as the heart rate at the onset of 1-mm ST depression. Before each treadmill test, postischemic forearm vascular resistance was measured after 5 minutes of forearm occlusion, using strain-gauge plethysmography. Sixteen additional patients (group B) underwent two treadmill tests at 8 AM and 1 PM, and ischemic threshold was measured as the heart rate-blood pressure product at 1-mm ST depression. A circadian variation was noted: In group A, the heart rate-derived ischemic threshold was lower at 8 AM and 9 PM compared with noon and 5 PM (p less than 0.03). Also, in group B, the rate-pressure product-derived ischemic threshold was 8 +/- 2% lower at 8 AM compared with 1 PM (p = 0.008). A circadian variation parallel to the observed variation in ischemic threshold was also noted in the postischemic forearm blood flow, which was lower in the morning and at night (p less than 0.004). There was a strong correlation between postischemic forearm blood flow and ischemic threshold (p less than 0.0001), such that ischemic threshold was lower at the time of day when postischemic forearm blood flow was lower, and vice versa. CONCLUSIONS: A lower ischemic threshold in the morning suggests that the ischemia-induced coronary vascular resistance is increased at this time, a finding supported by a similar variation in postischemic forearm vascular resistance. Parallel changes in forearm and coronary resistance suggest that generalized (neural or humoral factors) rather than local factors are responsible for the observed circadian changes. Increased coronary tone in the mornings may not only contribute to the higher incidence of transient ischemia but may help trigger acute cardiac events at this time.

Aged↗

PubMed2003

Diurnal variation in rat liver thyroid hormone receptor (TR)-alpha messenger ribonucleic acid (mRNA) is dependent on the biological clock in the suprachiasmatic nucleus, whereas diurnal variation of TR beta 1 mRNA is modified by food intake.

Previous studies have shown a diurnal variation of certain isoforms of thyroid hormone receptors (TR) in rat liver. The genesis of these diurnal changes is still unknown. To clarify whether the biological clock, located in the hypothalamic suprachiasmatic nucleus (SCN), is involved, we made selective SCN lesions. Rats with an SCN lesion lost their circadian rhythm of plasma corticosterone and TSH when compared with intact animals. TR alpha 1 and TR alpha 2 mRNA expression of control rats was higher in the light period than in the dark period; changes that were abolished in the rats with SCN lesions. In contrast, liver TR beta 1 mRNA of intact rats showed a diurnal variation that failed to reach statistical significance. To evaluate whether these effects could be explained indirectly by the disappearance of rhythmic feeding behavior in rats with SCN lesions, we performed a second experiment in which otherwise intact animals were subjected to a regular feeding (RF) schedule, with one meal every 4 h. When compared with rats with free access to food, RF only affected TR beta 1 mRNA expression and had no effect on the diurnal changes in TR alpha 1 and TR alpha 2. We conclude that liver TR beta 1 expression is most clearly affected by food intake. Diurnal changes in liver TR alpha 1 and TR alpha 2 are controlled by the biological clock in the SCN but not via changes in the daily rhythm of food intake. The findings may have physiological relevance for diurnal variation of T(3)-dependent gene expression, which is supported by a diurnal variation in the expression of the 5'-deiodinase gene.

Animals↗