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Fitness components at the octanol dehydrogenase locus in Drosophila melanogaster.

Experiments were performed to study the fitness at the Odh locus in Drosophila melanogaster. Populations previously treated with alcohol (5% in the medium) were transferred to media containing more (10%) or no alcohol. Odh genotype frequencies of second instar larvae and mature adults were determined in each generation. Selection appeared at a significant level in both experimental populations. Net fitness and larva-to-adult survival were investigated. To interpret our results the constant and frequency-dependent models of selection were tested. Both larva-to-adult survival and net fitness were found to be significantly correlated with genotype frequencies. Thus the frequency-dependence of net fitness was due to the larva-to-adult survival.

Alcohol Oxidoreductases↗

Intragenic suppression of the temperature-sensitivity caused by a mutation in a gene controlling transcription (fit) in Escherichia coli.

Starting from a transcription-defective strain harbouring a temperature-sensitive mutation in the fit gene, a rifampicin-resistant, temperature-insensitive derivative has been isolated. Genetic analysis of this derivative demonstrated the presence of a second temperature-sensitive mutation in the same gene. The two mutations mutually suppress each other's phenotype. From cotransduction experiments, the fit gene has been mapped 0.32 min and 0.16 min clockwise from the aroD and pps loci, respectively, at 37.5 min on the linkage map. The mutants harbouring either or both of the fit mutations are defective in RNA synthesis at the non-permissive temperature. The fit gene product is suggested to function as an accessory transcription factor.

Escherichia coli↗

Feasibility of the transparent cap-fitted colonoscope for screening and mucosal resection.

PURPOSE: A transparent plastic cap of 17 mm in outer diameter, 15 mm in inner diameter, and 10 mm in length can be easily attached to the tip of a colonoscope. By using the cap, a better view of the lesions hiding at the opposite side of the fold can be obtained. When a flat colonic lesion is found, a submucosal injection of saline solution is performed, the target mucosa is sucked inside the cap, snared under a full endoscopic suction, and resected by an electrical current. This procedure is called endoscopic mucosal resection using transparent cap-fitted endoscope (EMRC). Feasibility of the cap-fitted colonoscope for screening colonoscopic examination and mucosal resection was evaluated. MATERIALS AND METHODS: One hundred forty patients were randomly allocated for screening with a normal colonoscope (NCF) or that with the cap-fitted colonoscope (CCF). Average time for insertion up to the cecum, patients' discomfort during insertion expressed in 4 degrees, and average number of lesions found in one patient were compared. Thirty lesions randomly allocated for mucosal resection with conventional strip biopsy or EMRC were also evaluated. RESULTS: Time consumed for insertion up to the cecum with the CCF (12.4 +/- 6.6 minutes) was the same as that with the NCF (12.3 +/- 5.2 minutes), and there was no significant difference in patients' discomfort; however, the average number of lesions found in one patient was larger when using the CCF (0.86 +/- 0.96) than when using the NCF (0.58 +/- 0.81). For mucosal resection, 40 flat or wide-based lesions including 6 mucosal carcinomas were resected with EMRC. We experienced only one pinhole perforation of the ascending colon by heat damage, which was treated successfully by surgery. There was no other major complication or recurrence. CONCLUSION: The cap-fitted endoscope was equal in maneuverability, was excellent in sensitivity in comparison with the regular colonoscope, and was thought to be feasible both in screening and mucosal resection.

Aged↗

Validation of curve-fitting method for blood retention of 99mTc-GSA: comparison with blood sampling method.

We investigated a curve-fitting method for the rate of blood retention of 99mTc-galactosyl serum albumin (GSA) as a substitute for the blood sampling method. Seven healthy volunteers and 27 patients with liver disease underwent 99mTc-GSA scanning. After normalization of the y-intercept as 100 percent, a biexponential regression curve for the precordial time-activity curve provided the percent injected dose (%ID) of 99mTc-GSA in the blood without blood sampling. The discrepancy between %ID obtained by the curve-fitting method and that by the multiple blood samples was minimal in normal volunteers 3.1 +/- 2.1% (mean+/-standard deviation, n = 77 sampling). Slightly greater discrepancy was observed in patients with liver disease (7.5 +/- 6.1%, n = 135 sampling). The %ID at 15 min after injection obtained from the fitted curve was significantly greater in patients with liver cirrhosis than in the controls (53.2 +/- 11.6%, n = 13; vs. 31.9 +/- 2.8%, n = 7, p < 0.0001). There was a highly linear correlation between the %IDs of 99mTc-GSA and the plasma retention rate for indocyanine green (r = -0.869, p < 0.0001, n = 27). These results indicate that the curve-fitting method provides an accurate %ID of 99mTc-GSA and could be a substitute for the blood sampling method.

Adult↗

Disability after clinical fracture in postmenopausal women with low bone density: the fracture intervention trial (FIT).

Relatively little is known about outcomes following clinical osteoporotic fractures at nonhip, nonvertebral skeletal sites. To address this issue, we prospectively assessed post-fracture disability at multiple skeletal sites in a population of 909 older (aged 55-81 years), community-dwelling women with low femoral neck bone mineral density who had experienced a fracture while enrolled in the Fracture Intervention Trial (FIT). FIT is a randomized, double-masked, placebo-controlled trial that was designed to determine the effect of alendronate on fracture incidence, and the current study was conducted as a secondary analysis of FIT data. Following incident clinical fractures, FIT participants were followed prospectively for assessment of site-specific, fracture-related disability. Measures of disability were self-reported days hospitalized or confined to bed because of the fracture ('bed days') and days of reduced usual activities because of the fracture ('limited activity days'). Of fracture types evaluated, those of the hip resulted in the highest percentage of subjects with any bed days or limited activity days after fracture (94% with any bed days and 100% with any limited activity days), though the mean number of bed days and limited activity days appeared highest after lumbar vertebral fractures (25.8 mean bed days and 158.5 mean limited activity days). Substantial disability also was reported after fractures of thoracic vertebrae, humerus, distal forearm, ankle and foot. Within fracture types, post-fracture disability was highly variable, ranging from none to more than 6 months.

Activities of Daily Living↗

The impact of message mutation on the fitness of a genetic code.

The Standard Genetic Code is organized such that similar codons encode similar amino acids. One explanation suggested that the Standard Code is the result of natural selection to reduce the fitness "load" that derives from the mutation and mistranslation of protein-coding genes. We review the arguments against the mutational load-minimizing hypothesis and argue that they need to be reassessed. We review recent analyses of the organization of the Standard Code and conclude that under cautious interpretation they support the mutational load-minimizing hypothesis. We then present a deterministic asexual model with which we study the mode of selection for load minimization. In this model, individual fitness is determined by a protein phenotype resulting from the translation of a mutable set of protein-coding genes. We show that an equilibrium fitness may be associated with a population with the same genetic code and that genetic codes that assign similar codons to similar amino acids have a higher fitness. We also show that the number of mutant codons in each individual at equilibrium, which determines the strength of selection for load minimization, reflects a long-term evolutionary balance between mutations in messages and selection on proteins, rather than the number of mutations that occur in a single generation, as has been assumed by previous authors. We thereby establish that selection for mutational load minimization acts at the level of an individual in a single generation. We conclude with comments on the shortcomings and advantages of load minimization over other hypotheses for the origin of the Standard Code.

Amino Acids↗

The effects of cementless femoral stem shape and proximal surface texture on 'fit-and-fill' characteristics and on bone remodeling.

We measured the post-operative radiological "fit and fill" of two different femoral stem designs, one with a straight proximally porous-coated (Bi-Metric, n=50) and the other with a proximally anatomic, hydroxyapatite-coated and distally over-reamed stem (ABG, n=26). A comparison was then made between the clinical and radiological 5-year follow-up data of these two series and also of the bone remodeling changes around the stems. The observed differences in "fit and fill" parameters in the metaphyseal region were minute. However, in the diaphyseal bone the straight stem had substantially more cortical contact. The clinical results were excellent for both groups. Subsidence (>2 mm) was more frequent with the anatomical ABG stems, although the ABG stems had better bone ingrowth in the lower metaphyseal area. The present results indicate that the anatomical design may improve the fit and fill of a femoral stem in the metaphysis. On the other hand, a looser fill of the diaphyseal bone made the stems of this type more susceptible to subsidence. The straight stem with tight diaphyseal fit showed excellent stability, but the good bone ingrowth and remodeling around the distal part of the stem indicates stress transfer through this region and increased stress shielding of the proximal metaphyseal femur.

Adult↗

Protected polymorphism in the two-locus haploid model with unpredictable fitnesses.

In an unpredictable environment, the distributions of alleles from which polymorphism can be maintained forever belong to a certain set, the C-viability kernel. Such a set is calculated in the two-locus haploid model, as well as the corresponding fitnesses at any time which make this maintenance possible. The dependence of the C-viability kernel on the set U of admissible fitnesses and on the recombination rate r is studied. Notably, the C-viability kernel varies rapidly in the neighborhood of equal fitness of AB and ab; it becomes empty when ab has a fitness below a certain function, which is delineated, of the recombination rate. The properties of the two-locus model under constraints, out of equilibrium and with unpredictable selection are thus presented.

Alleles↗

Feasibility of fitness tests in subjects with chronic pain (fibromyalgia): discordance between cycling and 2-km walking tests.

Altogether, 69 out of 98 fibromyalgia (FMS) patients who attended a 2-week multidisciplinary inpatient course and a 1-week control period 3 months later completed 2-km walking tests and stepwise-increased cycling tests at entry and after 3 months. The purpose was to compare the feasibility of the two fitness tests for assessment of FMS patients. The results showed a substantially lower fitness level in the results of the 2-km walking test than in the cycling test in the same patients: mean maximum VO2 was 28.5 ml/kg per min vs 34.6 ml/kg per min, respectively. At entry and after the 3-month training period, the correlations between the two tests were very poor, i.e., with Spearman's r coefficients of 0.37 and 0.34, respectively (P < 0.01), intraclass correlation coefficients (ICC) 0.20 (95% CI -0.29 to 0.50) and 0.47 (95% CI 0.15 to 0.67), reliability coefficients (alpha) 0.54 and 0.47, and Kendal-T coefficients 0.32 and 0.41 for ordinal correlation of the test results. The results did not correlate with pain, which remained at initial levels for the 3 months of follow-up. Principally, these tests should both measure the same property, i.e., the fitness of fibromyalgia syndrome (FMS) patients, but the results differed substantially. The 2-km walking test showed a markedly lower fitness level than the cycling test in the same patients. The primary explanation for this difference might be difficulties in controlling test performance. especially in walking. The 2-km walking test would not appear recommendable for subjects with chronic pain syndrome, e.g., fibromyalgia.

Adult↗

Biomechanical testing of quadriceps tendon-patellar bone grafts: an alternative graft source for press-fit anterior cruciate ligament reconstruction?

INTRODUCTION: Press-fit fixation of bone-patellar tendon-bone (BPTB) grafts in anterior cruciate ligament (ACL) reconstruction has been analyzed biomechanically in previous studies; however, the use of quadriceps tendon-patellar bone (QTPB) grafts has not been studied so far. It is hypothesized that QTPB grafts provide primary fixation strength comparable to BPTB grafts in press-fit ACL reconstruction with respect to bone plug length and loading angle. MATERIALS AND METHODS: Fifty-two QTPB grafts were harvested from fresh human cadaver knees (mean age 73.3 years) with the length of the patellar bone plug being either 15 mm (Group I) or 25 mm (Group II). The grafts were anchored within fresh porcine femora (mean age 12 months) using a press-fit fixation technique. Forty-eight specimens were loaded to failure at 10 mm/s with varying loading angles of 0 degrees , 30 degrees , and 60 degrees until failure. A microradiographic pre-post-implantation analysis was conducted on four grafts. RESULTS: The biomechanical testing showed a significant difference in the ultimate failure loads comparing Group I (mean 224+/-79.3 N) to Group II (mean 339+/-61.4 N), both showing mean ultimate failure loads to increase with rising loading angle. The predominant mode of failure was graft pullout at axial loading and tendon rupture at 60 degrees loading angle. The microradiographic analysis revealed an iatrogenic damage of the bone-tendon junction on the cancellous aspect of the bone plug in all trials, corresponding with the site of impactor placement during implantation. CONCLUSION: QTPB grafts provide a loading capability comparable to BPTB grafts in press-fit ACL reconstruction. The broad and profound area of quadriceps tendon attachment to the patellar bone plug makes graft implantation demanding.

Aged↗

Nine months aerobic fitness induced changes on blood lipids and lipoproteins in untrained subjects versus controls.

Regular endurance exercise has favorable effects on cardiovascular risk factors. However, the impact of an exercise-induced change in aerobic fitness on blood lipids is often inconsistent. The purpose of this study was to investigate the effect of nine consecutive months of training on aerobic fitness and blood lipids in untrained adults. Thirty subjects 35-55 years of age (wt: 73.1 +/- 13.6 kg, height 171.1 +/- 9.0 cm, %body fat 24.6 +/- 6.3%, 14 males and 16 females) were randomly assigned to an exercise (EG) (N = 20) and control (CG) (N = 10) group. All subjects completed an incremental treadmill test, anthropometric measurements, and venous blood sample collection before and after the 9 months of exercise. Participants in the exercise group were supervised and adjusted for improvements in running performance, whereas no change was administered for the control group. One-way and multivariate ANOVA was conducted to determine significant differences in means for time and group in selected variables [body mass, % body fat, BMI; VO(2peak), km/h at 2.0 (v-LA2) and 4.0 (v-LA4) mmol l(-1) blood lactate (LA) concentration, km/h of the last load (v-max); TC, LDL-C, HDL-C, TG, Apo B, Apo A-1, and Lp (a)]. Correlation coefficients and multivariate regression analysis was used to determine the association between aerobic fitness and blood lipids. The exercise group improved significantly (P < 0.0001) in VO(2peak), v-LA2, v-LA4, v-max and exhibited a significant decrease in Apo B (P < 0.04) compared to the control group (NS). In 9 months, E achieved 24% increase in VO(2peak) and 18% reduction in Apo B, denoting the impact of cardiovascular fitness on cardiovascular risk.

Adult↗

Fitness optimization of Daphnia in a trade-off between food and temperature.

In thermally stratified lakes with a deep chlorophyll maximum (DCM), Daphnia face a trade-off between food availability and optimum development temperatures. We hypothesize that Daphnia optimize their fitness by allocating the time spent in the different vertical habitats depending on the distribution of algal resources and the temperature gradient. We used the plankton towers (large indoor mesocosms) to study the vertical distribution of a population of Daphnia hyalina x galeata in three different temperature gradients with a DCM. Additionally, we determined the fitness of Daphnia in the epilimnion and hypolimnion by transferring water from these layers into flow-through systems where we raised Daphnia and assessed their juvenile growth rate as a measure of fitness. The fitness distribution was correlated with the vertical distribution. The vertical distribution most likely reflected the proportions of time Daphnia allocated to dwelling in the two vertical habitats.

Adaptation, Physiological↗

Effects of self-fertilization, environmental stress and exposure to xenobiotics on fitness-related traits of the freshwater snail Lymnaea stagnalis.

Genetic and ecological factors may interact in their effects on fitness. Such interactions are thus to be expected between inbreeding and exposure of a population to a toxicant. The magnitude of inbreeding depression is thought to increase in stressful environments. To test this hypothesis, we investigated the combined effects of environmental conditions and inbreeding on fitness in the self-fertile snail Lymnaea stagnalis, using a stress gradient (0-2) applied to a 100 isolated and paired lineages: laboratory control (0), outdoor microcosm control (1) and pesticide exposure under outdoor microcosm conditions (2). Outdoor stress conditions were maintained for 28 days prior to measurements of fitness traits (fecundity, hatching success, and size at hatching) under laboratory conditions, so that delayed environmental effects could be estimated. Under laboratory control conditions, we found significant initial family level heterogeneity for most measured traits, including physiological performances as assessed through energetic biomarkers. Whatever the environmental conditions, inbreeding depression was very low for progeny performances. Negative values of self-fertilization depression (SFD) were obtained. Unexpectedly, SFD showed a negative relationship with the assumed stress intensity, reflecting a higher sensitivity under pairing than under selfing, mostly due to parental fecundity. This suggests that stressful conditions may favour selfing. Stress intensity increased the distribution limits of both depression indices, suggesting that changes in fitness are less predictable in a population under stress. Implications of such findings for environmental risk assessment of pesticides are discussed.

Animals↗

Genetic architecture of two fitness-related traits in Drosophila melanogaster: ovariole number and thorax length.

In Drosophila melanogaster, ovariole number and thorax length are morphological characters thought to be associated with fitness. Maximum daily egg production in females is positively correlated with ovariole number, while thorax length is correlated with male reproductive success and female fecundity. Though both traits are related to fitness, ovariole number is likely to be under stabilizing selection, while thorax length appears to be under directional selection. Current research has focused on examining the sources of variation for ovariole number in relation to fitness, with a view towards elucidating how segregating variation is maintained in natural populations. Here, we utilize a diallel design to explore the genetic architecture of ovariole number and thorax length in nine isogenic lines derived from a natural population. The full diallel design allows the estimation of general combining ability (GCA), specific combining ability (SCA), and also describes variation due to reciprocal effects (RGCA and RSCA). Ovariole number and thorax length differed with respect to their genetic architecture, reflective of the independent selective forces acting on the traits. For ovariole number, GCA accounted for the majority (67.3%) of variation segregating between the lines, with no evidence of reciprocal effects or inbreeding depression; SCA accounted for a small percentage (3.9%) of the variance, suggesting dominance variation; no reciprocal effects were observed. In contrast, for thorax length, the majority of the non-error variance was accounted for by SCA (17.9%), with only one third as much variance (6.2%) due to GCA. Interestingly, RSCA (nuclear-extranuclear interactions) accounted for slightly more variation (7.5%) than GCA in these data. Thus, genetic variation for thorax length is largely in accord with predictions for a fitness trait under directional selection: little additive genetic variation and substantial dominance variation (including a suggestion of inbreeding depression); while the mechanisms underlying the maintenance of variation for ovariole number are more complex.

Animals↗

Accuracy of optimized chemical-exchange parameters derived by fitting CPMG R2 dispersion profiles when R2(0a) not = R2(0b).

The transverse relaxation rate, R2, measured as a function of the effective field (R2 dispersion) using a Carr-Purcell-Meiboom-Gill (CPMG) pulse train, is well suited to detect conformational exchange in proteins. The dispersion data are commonly fitted by a two-site (sites a and b) exchange model with four parameters: the relative population, pa, the difference in chemical shifts of the two sites, deltaomega, the correlation time for exchange, tau(ex), and the intrinsic relaxation rate (i.e., transverse relaxation rate in the absence of chemical exchange), R2(0). Although the intrinsic relaxation rates of the two sites, R2(0a) and R2(0b), can differ, they are normally assumed to be the same (i.e., R2(0a) = R2(0b) = R2(0)) when fitting dispersion data. The purpose of this investigation is to determine the magnitudes of the errors in the optimized exchange parameters that are introduced by the assumption that R2(0a) = R2(0b). In order to accomplish this goal, we first generated synthetic constant-time CPMG R2 dispersion data assuming two-site exchange with R2(0a) not equal R2(0b), and then fitted the synthetic data assuming two-site exchange with R2(0) = R2(0a) = R2(0b). Although all the synthetic data generated assuming R2(0a) not equal R2(0b) were well fitted (assuming R2(0a) = R2(0b)), the optimized values of pa and tau(ex) differed from their true values, whereas the optimized values of deltaomega values did not. A theoretical analysis using the Carver-Richards equation explains these results, and yields simple, general equations for estimating the magnitudes of the errors in the optimized parameters, as a function of (R2(0a) - R2(0b)).

Bias↗

A stable linear algorithm for fitting the lognormal model to survival data.

The lognormal model can be fitted to survival data using a stable linear algorithm. When tested on 800 sets of mathematically generated data, this method proved more stable and efficient than the iterative method of maximum likelihood, which requires initial estimates of model parameters and failed to fit a substantial fraction of data sets. Though maximum likelihood yielded more consistent estimates of proportion cured, mean, and standard deviation of log(survival time), the linear normal algorithm may nevertheless prove useful for these purposes: (i) computing initial estimates of model parameters for the maximum likelihood method; (ii) fitting data sets that cannot be fit by this method; and (iii) deriving the lognormal model directly from cumulative mortality.

Algorithms↗

Tooth surface fitting and three-dimensional display using hidden surface removal technique.

Bi-cubic parametric spline surface is applied for surface-fitting of the external surface and canal of tooth based on its crown-to-root, cross-sectional data obtained by X-ray scanning. For three-dimensional display of the fitted surfaces, a technique for fast removal of the hidden surfaces is also reported. The selection of the accumulated chord length or coordinate component as parameter make it possible to fit any kind of surface smoothly. For displaying or plotting a well-fitted surface, a method capable of discriminating the grades for sequential removal of the hidden surfaces is developed for substantial reduction of computing time.

Algorithms↗

Fitting smooth curves to noisy indicator-dilution and other unimodal data.

A linear least squares method for fitting noisy unimodal functions such as indicator-dilution curves with piecewise stretched exponential functions is described. Stretched exponential functions have the form z(t) = alpha t beta e gamma t, where alpha, beta, and gamma are constants. These functions are particularly useful for fitting experimental data that spans several orders of magnitude is non-Gaussian, high skewed, and long tailed. In addition, the method allows for specifying external restrictions on the smooth curve that might be required by physical constraints on the data. These constraints can take the form of restrictions on the value of the fitting function at certain points or the value of the derivatives in certain regions. To determine the necessary constants in the fitting functions, a linear least squares problem with linear equality and inequality constraints is solved.

Algorithms↗