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PubMed1976

The unit of selection in Drosophila mercatorum. I. The interation of selection and meiosis in parthenogenetic strains.

An important problem in population genetics is the determination of the level of genetic organization to which fitness measures can be ascribed that yield an adequate description or prediction of the outcome of selection in populations. To study this problem, we used two strains of Drosophila merca torum (S-1-Im and O-3-Im) that are capable of both sexual and parthenogenetic reproduction, a feature that allows us to experimentally control many factors which affect genetic variability. Both S and O reproduce parthenogenetically by "pronuclear duplication," a mechanism that retains normal meiosis (and hence crossing over and assortment) but results in homozygosity for all loci in a single generation. Since an isozyme survey indicated that S and O differ at a third of their loci, we hypothesized that S and O have adapted in genetically distinct fashions to the genetic environment of total homozygosity. This is tested by breeding females that are S-O hybrids for 100%, 60% and 40% of their genetic backgrounds, and scoring their respective pathenogenetic progenies for four isozyme and two visible markers. The data collected gave evidence for a coadaptation to total homozygosity involving non-additive and non-multiplicative interactions between non-alleles. As the perturbation of the parental coadapted genotypes by meiosis increases (i.e., the greater the degree of S-O hybridity), the level of genetic material which behaves as an additive/multiplicative fitness unit becomes larger. Selective neutrality of genetic variation may be an artifact of our failure to measure the proper genetic unit of selection.

Animals↗
PubMed2004

Selection bias in semen studies due to self-selection of volunteers.

BACKGROUND: Reports of a secular decrease in semen quality remain controversial, particularly due to the possibility of selection bias. We aimed to describe the potential bias due to self-selection of volunteers in semen studies involving fecund men. METHODS: Using data from the French multicentre study REPRHOM, we compared the characteristics of the partners of pregnant women for three levels of participation: completion of a refusal questionnaire (n = 698), agreement to complete the study questionnaires only (n = 676) and agreement to complete the study questionnaires and give a semen sample (n = 331, 13% of the subjects approached). RESULTS: Poorly educated men refused more often to participate than highly educated men. Semen providers were more likely to have experienced unfavourable pregnancy outcomes (odds ratio 1.68, 95% confidence interval 1.14-2.49) compared with participants completing the questionnaires only. Time to pregnancy was similar for all participants. CONCLUSIONS: This study demonstrates the existence of selection bias in semen studies associated with fertility and socio-demographic characteristics of men. The results of semen analysis for this population sample cannot be extrapolated to the whole population from which the volunteers originate. More information is required on who participates, and participation rates should be reported in semen studies to make it possible to interpret the results correctly.

Adult↗
PubMedDate not supplied

Comparison of crossbred and purebred selection for a heterotic trait in highly selected populations of Tribolium.

Selection on the basis of crossbred performance (RRS) was compared for 11 generations to within-line selection based on purebred performance (WLS) for a heterotic trait, 13-day larval weight in Tribolium populations previously subjected to 30 generations of purebred selection. RRS crossbreds gained slightly less than crossbreds of WLS populations. RRS purebreds showed a much smaller composite populations were greater than those observed for the continued populations. A model for the genetic control of larval weight is suggested in which there are both dominant and overdominant loci and homozygotes are less fit than heterozygotes.

Animals↗
PubMed2003

Effect of selection for growth on onset of sexual maturity in randombred and growth-selected lines of Japanese quail.

An experiment was conducted to determine the effect of selection for growth (BW) on the onset of reproduction (first egg) in Japanese quail hens from growth-selected (HW) and randombred (R1) lines. The HW line had undergone over 40 generations of selection for increased 4-wk BW and was originally developed from the R1 line. Data were collected over two consecutive hatches and summarized by hatch and within lines. Body weight at 35 d of age was positively correlated with BW at sexual maturity (first egg) in both the R1 and HW lines, but these correlations were not significant in both hatches for either line (Hatch 1-R1; Hatch 2-HW; P < or = 0.05). There was a negative correlation between age at sexual maturity (days to first egg) and 35 d BW in both lines with the exception of the HW hens in Hatch 2. Age at sexual maturity and BW at sexual maturity was positively correlated (P < or = 0.001) in the R1 line but did not show the same relationship in the HW line. Age at sexual maturity and weight of the abdominal fat pad were positively correlated in the R1 line (Hatch 1, P < or = 0.01; Hatch 2, P < or = 0.001), but this relationship was not significant in the HW line. Age at sexual maturity and follicle number was negatively correlated in both lines but was not significant in Hatch 2 of the HW line. Follicle size, however, was positively correlated with days to first egg in only Hatch 2 (P < or = 0.001) of the HW line. The data suggest that the relationships between the onset of sexual maturity and both reproductive parameters and carcass traits in hens from consecutive hatches of HW quail are less clear than in the R1 line.

Aging↗
PubMed2003

Patterns and mechanisms of selection on a family-diagnostic trait: evidence from experimental manipulation and lifetime fitness selection gradients.

Plant traits that show little variation across higher taxa are often used as diagnostic traits, but the reason for the stasis of such traits remains unclear. Wild radish, Raphanus raphanistrum, exhibits tetradynamous stamens (four long and two short, producing a dimorphism in anther height within each flower), as do the vast majority of the more than 3,000 species in the Brassicaceae. Here we examine the hypothesis that selection maintains the stasis of dimorphic anther height by investigating the effects of this trait on pollen removal, seed siring success, and seed set in R. raphanistrum using both experimental and observational methods. Observational selection gradient analysis based on lifetime seed siring success provided evidence for an optimum dimorphism that was greater than zero in one of three years. In both experimentally manipulated and unmanipulated flowers, more pollen was removed in single visits from flowers with less dimorphism. There was no significant effect of anther dimorphism on female fitness (seed set). Therefore, there is some evidence to suggest that selection is maintaining anther dimorphism in wild radish, and that higher male fitness might result from restriction of single-visit pollen removal. We discuss these results in light of pollen presentation theory.

Flowers↗
PubMed1992

The evolution of eutherian spermatozoa and underlying selective forces: female selection and sperm competition.

We have examined sperm morphology and dimensions in Eutherian mammals. In most Eutherians, sperm heads are round or oval and spermatozoa have short tails (average sperm length about 65 microns; range = 33-121 microns). Rodents, however, clearly depart from the typical Eutherian pattern in that they show a broad array of head morphs and an extreme range of sperm dimensions (35-250 microns). In order to trace the evolutionary changes that rodent sperm have undergone, we have used phylogenetic relationships based on biogeographical, morphological, chromosomal and genic data, and we have superimposed onto them the information available on sperm traits. Analyses were carried out for five rodent groups on which enough information was available. The evolutionary trends which emerged from these studies have two main points in common: throughout evolution spermatozoa have become enlarged and morphologically more complex, and this process seems to have taken place independently in different lineages. A general model was developed which outlines the different evolutionary pathways that rodent sperm have undergone. The adaptive significance of the increase in head complexity and the elongation of the sperm tail remains obscure. We have integrated information from evolutionary, physiological and behavioural studies to address this issue. We argue that two main selective forces may have favoured these changes: female selection within the reproductive tract and sperm competition. The female tract represents a formidable barrier for spermatozoa and its provides an environment where numerous interactions take place. The extent of these barriers and the complexity of these poorly understood interactions suggest that females may be exercising a strong selection, which may enable them to favour particular types of spermatozoa or ejaculates from particular males. Throughout their evolution males must have evolved adaptations to overcome these barriers, and the conflicting interests of choosy females. Sperm competition is a potent evolutionary force among mammals, which has influenced not only the evolution of sperm numbers but also changes in sperm dimensions. Thus, sperm competition has favoured the elongation of the sperm tail, which has led to the attainment of faster swimming speed, an important factor when sperm from rival males compete to reach the ova first.

Animals↗
PubMedDate not supplied

Prediction error variance and expected response to selection, when selection is based on the best predictor - for Gaussian and threshold characters, traits following a Poisson mixed model and survival traits.

In this paper, we consider selection based on the best predictor of animal additive genetic values in Gaussian linear mixed models, threshold models, Poisson mixed models, and log normal frailty models for survival data (including models with time-dependent covariates with associated fixed or random effects). In the different models, expressions are given (when these can be found - otherwise unbiased estimates are given) for prediction error variance, accuracy of selection and expected response to selection on the additive genetic scale and on the observed scale. The expressions given for non Gaussian traits are generalisations of the well-known formulas for Gaussian traits - and reflect, for Poisson mixed models and frailty models for survival data, the hierarchal structure of the models. In general the ratio of the additive genetic variance to the total variance in the Gaussian part of the model (heritability on the normally distributed level of the model) or a generalised version of heritability plays a central role in these formulas.

Analysis of Variance↗
PubMed2004

Estrogen and selective estrogen receptor modulators exert neuroprotective effects and stimulate the expression of selective Alzheimer's disease indicator-1, a recently discovered antiapoptotic gene, in human neuroblast long-term cell cultures.

According to the fact that Alzheimer's disease (AD) is more common in postmenopausal women, estrogen treatment has been proposed. Experimental studies, still mostly performed using animal models, demonstrated that estrogen exerts neuroprotective effects. We previously established neuroblast long-term cell cultures from human fetal olfactory epithelium. In the present study, we addressed the role of estrogen in these unique human cells, which express both the estrogen receptor (ER)-alpha and ERbeta. We found that 17beta-estradiol (17betaE(2)) and the selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen exerted neuroprotective effects, which were independent of cell proliferation, by increasing resistance against beta-amyloid-induced toxicity, with the exception of the highest concentrations of raloxifene (10 and 100 nm). In addition, 17betaE(2) exposure protected from oxidative stress, reduced apoptosis, and increased the expression of the catalytic subunit of telomerase. Furthermore, we evaluated by quantitative real-time RT-PCR whether estrogen/SERMs modulate the expression of the recently discovered seladin-1 (selective AD indicator-1) gene, which exerts neuroprotective effects and is down-regulated in AD-vulnerable brain regions. 17betaE(2) (100 pm to 100 nm) and SERMs (1 nm) significantly increased the amount of seladin-1 mRNA. Conversely, 10 and 100 nm raloxifene reduced the expression of seladin-1. The effect of estrogen appears mainly mediated by ERalpha because the selective ERalpha agonist propylpyrazole-triol determined a much greater increase of seladin-1 expression than the ERbeta agonist diarylpropionitrile. Our results add new evidence, using human neuronal cells, for a beneficial effect of estrogen in preventing neurodegenerative diseases and suggest for the first time that seladin-1 may mediate this effect.

Amyloid beta-Peptides↗
PubMed2002

Definition of the molecular and cellular mechanisms underlying the tissue-selective agonist/antagonist activities of selective estrogen receptor modulators.

The term selective estrogen receptor modulators describes a group of pharmaceuticals that function as estrogen receptor (ER) agonists in some tissues but that oppose estrogen action in others. Although the name for this class of drugs has been adopted only recently, the concept is not new, as compounds exhibiting tissue-selective ER agonist/antagonist properties have been around for nearly 40 years. What is new is the idea that it may be possible to capitalize on the paradoxical activities of these drugs and develop them as target organ-selective ER agonists for the treatment of osteoporosis and other estrogenopathies. This realization has provided the impetus for research in this area, the progress of which is discussed in this review.

Animals↗
PubMed2005

Divergent selection for uterine capacity in rabbits. I. Genetic parameters and response to selection.

A 10-generation divergent selection experiment for uterine capacity (UC) measured as litter size in unilaterally ovariectomized females was carried out in rabbits. A total of 2,996 observations on uterine capacity of does (up to four parities) was recorded. Laparoscopy was performed at d 12 of their second gestation, and ovulation rate (OR) and number of implanted embryos (IE) were recorded in 735 does. Prenatal survival (PS) was assessed as UC/OR, embryo survival (ES) as IE/OR, and fetal survival (FS) as UC/IE. Genetic parameters and genetic trends were inferred using Bayesian methods. Marginal posterior distributions of all unknowns were estimated by Gibbs sampling. Heritabilities of UC, OR, IE, ES, FS, and PS were 0.11, 0.32, 0.22, 0.04, 0.14, and 0.09, respectively. Genetic and phenotypic correlations between FS and ES were low, suggesting different biological mechanisms for the two periods of survival. After 10 generations of selection, the divergence was approximately 1.5 rabbits, or approximately 1% per generation. Approximately one-half of this response was obtained in the first two generations of selection, which may suggest the presence of a major gene segregating in the base population.

Animals↗
PubMed2001

Selected cell and selective microenvironment in neoplastic development.

Recent analysis of genetic alterations in human cancer points to a major role for selection in neoplastic development but provides few details about the dynamics of the process. Many such details, however, have emerged from quantitative studies of spontaneous transformation among mammalian cells in culture. The chief insight of these studies is that there is a continuous generation of variants in proliferative potential among growing cells that provides the substratum for progressive development to a frankly neoplastic state when selective growth conditions are persistently applied. Much of the selection occurs before the cells are capable of producing discrete neoplastic foci. The varied observations in cell culture draw attention to analogous features of carcinogenesis in experimental animals and the development of human cancer.

Animals↗
PubMed1979

[Survival of the mutant clone. III. Catastrophic selection. The inadequacy of the selection coefficient for assessing clone fate].

Majorant estimations of the probabilities pr for the surviving of the clone of the dividing cells have been obtained in the catastrophic situation (monotonous diminishing of the clone almost to zero during the period of time from t=0 to t=T, T approximately 100 generation). At t=0 the clone consisted of 10(6) individuals. Average selection coefficient (s) was found to determine pr only roughly, that is the clone with s greater than --0.09 survives almost in all cases, whereas the clone with s greater than --0.13 becomes extinct practically always. Within this interval ps-inversion can be observed, i.e. preferential surviving of the clone with a worse s value. Results of three communications lead to the conclusion that the mutants with small selective advantage practically cannot be selected.

Cell Survival↗
PubMed1994

[Effects of maximal possible potential selection in the world population. New data on selection structure in the CIS nations].

New information on maximal possible potential selection and its component values in some ethno-territorial groups in CIS was presented. The heterogeneity observed in the Crow's index and its components can be explained as a result of the differences in the social economic status of the groups studied and the influence of climate geographical factors. The data gathered during the biodemographical study of 67 populations allowed to detect regularities of the effects of selective factors in world population: non-random and discrete nature of considered populations distribution in the coordinate space of selection components associated with differential mortality (I) and differential fertility (I) was shown. Differentiation of three big aggregations of populations was shown: urbanized contemporary communities with low I values; small endogamous populations, mostly of hunters and gatherers; small towns' populations and rural populations with balanced reproductive indices. Microevolutionary changes take place in the latter conglomerate even now, statistically subdividing it into two clusters. A proposition was made about the existence of "ecological optimum" for populations intermediate between advanced industrial communities and communities of hunters and gatherers, corresponding to the population size and the nature and rate of population reproduction.

Commonwealth of Independent States↗
PubMed1979

Urinary MHPG levels and tricyclic antidepressant drug selection. A preliminary communication on improved drug selection in clinical practice.

The 24-hour urinary 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) output was used as the basis for selection of tricyclic antidepressant drug therapy for the depressed patient population treated by one psychiatrist over a period of ten months in a psychiatric clinic. Use of MHPG output level as the criterion for drug selection resulted in significantly better clinical results than had been obtained previously by the same psychiatrist using more traditional selection methods on a similar depressed patient population. A correlation was noted between patients' pretreatment MHPG output levels and three symptoms of depression (guilt, agitation, and diurnal variation) as measured on the Hamilton Rating Scale for Depression.

Adult↗
PubMedDate not supplied

Fluorescence-based selection of retrovirally transduced cells in congenital erythropoietic porphyria: direct selection based on the expression of the therapeutic gene.

BACKGROUND: Congenital erythropoietic porphyria (CEP) is an inherited disease caused by a deficiency of uroporphyrinogen III synthase, the fourth enzyme of the haem biosynthesis pathway. It is characterized by accumulation of uroporphyrin I in the bone marrow, peripheral blood and other organs. The prognosis of CEP is poor with death occurring in early adult life and available treatments are only symptomatic and unsatisfactory. In vitro gene transfer experiments have documented the feasibility of gene therapy via haematopoietic stem cells to treat this disease. To facilitate future ex vivo gene therapy in humans, the design of efficient selection procedures to increase the frequency of genetically corrected cells prior to autologous transplantation is a critical step. METHODS: An alternative selection procedure based upon expression of a transferred gene was performed on a lymphoblastoid (LB) cell line from a patient with congenital erythropoietic porphyria to obtain high frequencies of genetically modified cells. The presence of exogeneous delta-aminolevulinic acid (ALA), a haem precursor, induces an increase in porphyrin accumulation in LB deficient cells. Porphyrins exhibit a specific fluorescent emission and can be detected by cytofluorimetry under ultraviolet excitation. RESULTS: In genetically modified cells, the restored metabolic flow from ALA to haem led to a lesser accumulation of porphyrins in the cells, which were easily separated from the deficient cells by flow cytometry cell sorting. CONCLUSION: This selection process represents a rapid and efficient procedure and an excellent alternative to the use of potentially harmful gene markers in retroviral vectors.

Adult↗
PubMed1978

A selective and sensitive assay for urinary metanephrine and normetanephrine using gas chromatography mass spectrometry with selected ion monitoring.

Vapor phase methodology for quantitative analysis of urine for metanephrine and normetanephrine as the pentafluoropropionyl derivative is described. The use of selected ion monitoring provided sufficient sensitivity and selectivity that milliliter aliquots of urine required only a simple scheme of sample processing; preliminary purification consisted of percolation through a column of XAD-2 followed by solvent extraction. The sample extracts were converted to the pentafluoropropionyl derivatives and analyzed by gas chromatography mass spectrometry with selected ion monitoring. Quantitative analysis was based on alpha[2H2]-beta-[2H1]metanephrine and alpha-[2H2]-beta-[2H1]normetanephrine which were added to the urine sample at the outset. The calibration plots for metanephrine and normetanephrine were linear from 10 ng ml-1 to 2000 ng ml-1 of urine permitting the detection of metanephrine and normetanephrine levels throughout the normal range and well into the subnormal range. Examples of application of the methodology to clinical investigation are described. The overall reproducibility of the sample processing methodology and instrumentation was assessed by replicate analyses of the same urine sample over a period of several weeks; the coefficient of variation was +/- 2.5% (n = 8).

Chromatography, Gas↗
PubMed2005

As fast and selective as enzymatic ligations: unpaired nucleobases increase the selectivity of DNA-controlled native chemical PNA ligation.

DNA-controlled reactions offer interesting opportunities in biological, chemical, and nanosciences. In practical applications, such as in DNA sequence analysis, the sequence fidelity of the chemical-ligation reaction is of central importance. We present a ligation reaction that is as fast as and much more selective than enzymatic T4 ligase-mediated oligonucleotide ligations. The selectivity was higher than 3000-fold in discriminating matched from singly mismatched DNA templates. It is demonstrated that this enormous selectivity is the hallmark of the particular ligation architecture, which is distinct from previous ligation architectures designed as "nick ligations". Interestingly, the fidelity of the native chemical ligation of peptide nucleic acids was increased by more than one order of magnitude when performing the ligation in such a way that an abasic-site mimic was formed opposite an unpaired template base. It is shown that the high sequence fidelity of the abasic ligation could facilitate the MALDI-TOF mass-spectrometric analysis of early cancer onset by allowing the detection of as little as 0.2 % of single-base mutant DNA in the presence of 99.8 % wild-type DNA.

Catalysis↗
PubMed1995

Paraquat resistance and starvation conditions in the selection of longevity extremes in Drosophila melanogaster populations previously selected for long and short developmental period.

This paper analyzes the interaction between resistance to free radicals, development under starvation conditions, sex, and its consequences to the lifespan of Drosophila melanogaster populations selected for developmental time and longevity. Our data suggest that the interaction between these physiological and environmental parameters is modulated largely by the pre-imaginal developmental time, since the response to selection for longevity extremes depends strongly on the previous selection for developmental time extremes.

Animals↗