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PubMed2003

Change in frequency of a rare mutant allele: a general formula and applications to partial inbreeding models.

We deduce and prove a general formula to approximate the change in frequency of a mutant allele under weak selection, when this allele is introduced in small frequency into a population which was previously at a fixation state. We apply the formula to autosomal genes in partial selfing models and to autosomal as well as sex-linked genes in partial sib mating models. It is shown that the fate of a rare mutant allele depends not only on the selection parameters, the inbreeding coefficient and the reproductive values of the sexes in sex-differentiated populations, but also on coefficients of relatedness between mates. This is interpreted as a kin selection effect caused by inbreeding per se.

Alleles↗

PubMed2006

Biological control of Rhipicephalus (Boophilus) annulatus by different strains of Metarhizium anisopliae, Beauveria bassiana and Lecanicillium psalliotae fungi.

Virulence of 11 native strains of entomopathogenic fungi; Metarhizium anisopliae (three strains), Beauveria bassiana (six strains) and Lecanicillium psalliotae (two strains) collected from different parts of Iran, were studied against different developmental stages of Rhipicephalus (Boophilus) annulatus. After the exposure of ticks to the fungal strains in different concentrations (i.e. 10(3), 10(5), 10(7) conidia/ml), various parameters such as mortality rate and reproductive efficiency of engorged females, mortality of unfed tick larvae and eclosion percentage of infected eggs were evaluated to determine the fungal virulence. Based on the obtained results, five strains including M. anisopliae (IRAN 437 C and DEMI 001), B. bassiana (IRAN 403 C) and L. psalliotae (IRAN 468 C and IRAN 518 C) were found to be virulent to various stages of tick developmental cycle. Mortality rate of engorged females was found to be dose-dependent with regard to the conidial concentration used. Total mortality rates of 90-100%, 70% and 56.6% were observed for M. anisopliae (IRAN 437 C and DEMI 001), B. bassiana (IRAN 403 C) and L. psalliotae (IRAN 468 C), 6-11 days post inoculation (PI) with 10(7) conidia/ml, respectively. Most strains were able to inhibit egg laying by females in the range of 0-26% in different conidial concentrations. The results indicated that the mean egg laying of treated engorged tick females exposed to M. anisopliae (IRAN 437 C) was less than the mean values of those treated with other fungal strains. Results revealed 89.1%, 35.5% and 56.3% decrease in egg hatchability and 88.69%, 78.15% and 59.74% reduction in reproductive efficiency of the ticks using 10(7) conidia/ml of M. anisopliae (IRAN 437 C), B. bassiana (IRAN 403 C) and L. psalliotae (IRAN 468 C), respectively. In general, the entomopathogenic effects of native M. anisopliae and B. bassiana against various developmental stages of R. (B.) annulatus were confirmed in the present work. Likewise, although L. psalliotae, which was introduced for the first time as an entomopathogenic fungus against tick had not more than 13.3% mortality effect against adult females, but its effect on egg hatchability and reproductive efficiency was remarkable.

Animals↗

PubMed1995

Short-term endocrine response to gonadotropin-releasing hormone agonist initiated in the early follicular, midluteal, or late luteal phase in normally cycling women.

OBJECTIVE: To determine short-term pituitary and ovarian hormonal responses to GnRH agonist (GnRH-a) administered during various phases of the menstrual cycle, in the absence of controlled ovarian hyperstimulation (COH), to determine its independent effect on hormonal parameters previously demonstrated to influence assisted reproductive technology cycle outcome. DESIGN: Prospective, randomized, controlled crossover study of five regularly cycling women. The GnRH-a, leuprolide acetate (LA), was administered 1 mg SC daily for 5 days beginning on cycle day 3 (early follicular); 8 days post-LH surge (midluteal); or 13 days post-LH surge (late-luteal). SETTING: Clinical research unit at a tertiary care medical center. MAIN OUTCOME MEASURES: Serum gonadotropins (LH and FSH) and gonadal steroids (E2, estrone [E1], P, A, and T) measured daily during GnRH-a administration begun in the early follicular, midluteal, or late luteal phase of the menstrual cycle. Gonadotropin pulse amplitude and frequency were determined after frequent serum sampling on the 2nd day of GnRH-a administration in each treatment cycle. RESULTS: Serum LH elevations, 4- to 10-fold greater than observed for FSH, did not differ by cycle day of GnRH-a initiation. Initial increases in FSH did not differ by cycle day, however, early follicular initiation resulted in a more pronounced suppression of FSH. Mean LH pulse amplitude and frequency increased to a similar extent in all three groups, however, FSH pulse amplitude and frequency varied significantly by cycle day of GnRH-a initiation. Gonadotropin-releasing hormone agonist initiated in the early follicular phase resulted in significant increases in E2, E1, and P levels compared with both midluteal or late luteal. Increases in serum androgens were significantly greater after early follicular and late luteal initiation as compared with midluteal GnRH-a initiation. CONCLUSIONS: Relative FSH suppression and marked androgen elevations in both late luteal and early follicular groups, which may have potential detrimental effects on oocytes of the developing cohort, suggest little advantage of late luteal or early follicular over midluteal initiation of GnRH-a for COH.

Adult↗

PubMed2000

An explicit approach to evolutionarily stable dispersal strategies: no cost of dispersal.

The evolution of dispersal is examined by looking at evolutionarily stable strategies (ESS) for dispersal parameters in discrete time multisite models without any cost of dispersal. ESS are investigated analytically, based on explicit results on sensitivity analysis of matrix models. The basic model considers an arbitrary number of sites and a single age class. An ESS for dispersal parameters is obtained when the spatial reproductive values, calculated at the density-dependent population equilibrium, are equal across sites. From this basic formulation, one derives equivalently that all local populations should be at equilibrium in the absence of migration, and that dispersal between sites should be balanced, i.e., the numbers of individuals arriving to and leaving a site are equal. These results are then generalized to a model with several age classes. Equal age-specific reproductive values do not however imply balanced dispersal in this case. Our results generalize to any number of sites and age classes those available ¿M. Doebeli, Dispersal and dynamics, Theoret. Popul. 47 (1995) 82 for two sites and one age class.

Age Distribution↗

PubMed2003

Contaminant exposure and effects in Baltic ringed and grey seals as assessed by biomarkers.

The Baltic Sea ecosystem has suffered from a heavy pollutant load for more than three decades. Persistent organic pollutants (POPs) and heavy metals have been of most concern due to their persistence and toxic properties. Ringed seals (Phoca hispida baltica) and grey seals (Halichoerus grypus) living in the Baltic Sea have been suffering from pathological impairments, including reproductive disturbances, which have resulted in a depressed reproductive capacity. We investigated several biochemical parameters as potential biomarkers for exposure to and effects of the contaminant load in the Baltic seals. Seals from less polluted areas were used as reference material in terms of the pollution load. In both Baltic seal populations, the levels of some biochemical parameters diverged from those in the reference seals, and some of these showed a clear correlation with the individual contaminant load. Of the potential bioindicators, we propose cytochrome P4501A activity and vitamin E levels, in blubber or plasma, as exposure biomarkers for polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) in both species. The arylhydrocarbon receptor-mediated chemical-activated luciferase gene expression (CALUX) response reflects the whole PCB and DDT burden in ringed seals. Retinyl palmitate (vitamin A) levels showed a negative correlation with the individual POP load, and is proposed as potential effect biomarkers for the depletion of the vitamin A stores. As the nutritional levels of both vitamin A and E have an impact on the vitamin levels in the seals, more information on the dietary vitamin levels is needed before any conclusions can be drawn. As the relationship between biochemical parameters and contaminants varied between the two species, species-specific characteristics has to be considered when monitoring the health status and possible toxic effects of the contaminant load in ringed and grey seals.

Animals↗

PubMed2003

Steady-state distribution of metals among metallothionein and other cytosolic ligands and links to cytotoxicity in bivalves living along a polymetallic gradient.

The present study was designed to assess the environmental effects of metals in a field setting. We explored exposure-->bioaccumulation-->effects relationships in freshwater molluscs exposed to metals in their natural habitat. Indigenous floater mussels (Pyganodon grandis) were collected from ten limnologically similar lakes located along a Cd, Cu and Zn gradient. Ambient free-metal ion concentrations were estimated as a measure of metal exposure. Metallothionein (MT) was measured in mussel gills and metal partitioning among the various cytosolic protein pools was determined by size exclusion chromatography. Various biomarkers were also measured, including malondialdehyde (MDA) concentrations in the gills and in the digestive gland, glutathione-peroxidase and glutathione-reductase activities in the digestive gland, and lipid concentrations in the gonad. Cadmium and MT concentrations in the gill cytosol increased along the contamination gradient, but Cu and Zn levels were independent of the ambient free-metal ion concentrations. The distribution of Cd among the various cytosolic complexes remained quite constant: 80% in the MT-like pool, 7% in the low molecular weight pool (LMW<1.8 kDa) and 13% in the high molecular weight pool (HMW>18 kDa). For these chronically exposed molluscs there was thus no threshold exposure concentration above which spillover of Cd occurred from the MT pool to other cytosolic ligands. However, the presence of Cd in the LMW and HMW fractions suggests that metal detoxification was imperfect, i.e. that P. grandis was subject to some Cd-related stress at low chronic exposure concentrations. Consistent with this suggestion, MDA concentrations, an indicator of oxidative stress, increased with gill cytosolic Cd. In the digestive gland, MDA concentrations were unrelated to any of the measured metals, but glutathione-peroxidase and glutathione-reductase activities increased with gill cytosolic copper. We speculate that cytosolic Cu catalyses the production of reactive oxygen species, to which the organism reacts by increasing activities of the two enzymes, thus preventing the accumulation of reactive oxygen species. Lipid concentrations in the gonad did not decrease with any of the measured toxicological parameters, suggesting that energy reserves for reproduction were not compromised in the metal-contaminated mussels. The results of the present study, where chronically exposed bivalves were collected from their natural habitat along a metal contamination gradient, contrast markedly with what would have been predicted on the basis of experimental metal exposures, and clearly demonstrate the need to study metal exposure-->bioaccumulation-->effects relationships in natural populations.

Animals↗

PubMed2003

Calibrating the telomere clock in common terns, Sterna hirundo.

Field biologists often work with animals for which there are no prior history. A marker of an animal's age would offer insight into how age and experience affect reproductive success and other life history parameters. We previously reported that length of telomere restriction fragments shorten predictably with age in the captive zebra finch (Taeniopygia guttata). This paper reports that telomeres can also be used to gain knowledge on the age structure of wild, long-lived common terns (Sterna hirundo). Although ages cannot be determined precisely from telomere lengths alone, birds can be classified into broad age-classes. This technique can provide useful information about the age of individuals in cases where their previous histories are unknown.

Aging↗

PubMed1999

Seasonal variation of peroxisomal enzyme activities and peroxisomal structure in mussels Mytilus galloprovincialis and its relationship with the lipid content.

Variations in structure and function of peroxisomes in digestive tissues of marine mussels have been proposed to be valid biomarkers of environmental contamination by organic xenobiotics. The aim of the present work was to study the seasonal variations in peroxisomal enzyme activities, catalase, palmitoyl-CoA oxidase (AOX) and D-amino acid oxidase (DAOX) and peroxisomal structure in mussels. Peroxisomal changes were related to the seasonal variation in the contents of neutral lipids in the digestive gland as the lipid metabolism in mussels is subjected to seasonal variations linked to the reproductive cycle and food intake. Significant higher catalase activities were recorded from April to June when compared to the rest of the year and AOX activity was also markedly induced during the late winter and spring (February to May) with maximal activities in April. DAOX activity did not vary seasonally, the highest activities being measured in November, February and May. Stereological studies of peroxisomes in digestive tubule cells revealed significantly higher volume, surface and numerical densities in animals collected in spring and summer. Changes in peroxisomal volume density were found to be significantly and positively correlated with changes in AOX and catalase activities. The peroxisomal structure and enzyme activities were negatively correlated with the lipid contents of digestive tubules. In April, the volume density occupied by neutral lipids was higher in duct epithelia while previously it was higher in digestive tubule epithelia. This trend was maintained during the period in which peroxisomes were more abundant until July. In the following September, digestive tubules recovered their lipid load. It is concluded that seasonal changes related to food intake and reproductive cycle induce changes in peroxisomal parameters that can be compared to typical peroxisome proliferation, with a 25-fold increase in AOX activity and an 8-fold increase in the peroxisomal numerical density in early spring.

Animals↗

PubMed2005

The influence of ligand field effects on the magnetic exchange of high-spin Co(II)-semiquinonate complexes.

[Co(Me(4)cyclam)(tropolonate)](PF(6)) was synthesised and structurally characterised. Its electronic and W-band EPR spectra have been analysed by means of the angular overlap calculation of the Spin Hamiltonian parameters that provided also a satisfactory reproduction of the temperature dependence of the magnetic susceptibility. The present results can be interpreted assuming a pseudo-octahedral character for the Co(II) center. This prompted us to reconsider the model formerly used for the analysis of the magnetic coupling between hs-Co(II) and the paramagnetic o-semiquinonate ligand in the corresponding derivatives [Co(Me(4)cyclam)(PhenSQ)](PF(6)) and [Co(Me(4)cyclam)(DTBSQ)](PF(6)). These results indicate that the effect of the magnetic coupling is active only below 50 K and that a more refined model of exchange coupling between Co(II) and semiquinonato ligands is needed to quantitatively analyze the magnetic behaviour of this class of systems.

Journal Article↗

PubMedDate not supplied

Does inbreeding lead to decreased human fertility?

In most Western countries there is a widespread belief, fostered in part by historical prejudice and religious proscription, that inbreeding in human populations causes a reduction in fertility. Support for this belief has been claimed in HLA-based studies, with increased rates of fetal losses suggested in HLA-compatible unions. To critically assess the overall status of fertility in consanguineous unions, data on 30 populations resident in six countries were collated from a systematic review of the literature. The mean numbers of live births were then compared in four consanguinity test categories, ranging from second cousin to uncle-niece/double first cousin, and corresponding non-consanguineous reference groups. Linear regressions indicated a positive association between consanguinity and fertility at all levels of inbreeding, attaining statistical significance at first cousin level (p < 0.0001). The results were, however, subject to a number of potential limitations, in particular lack of control for important socio-demographic variables. To overcome this problem, data on first cousin marriages were abstracted from the National Family and Health Survey conducted in India during 1992-1993. Multivariate analysis showed that fertility in first cousin unions was positively influenced by a number of variables, including illiteracy, earlier age at marriage and lower contraceptive uptake, but the most important of these parameters were duration of marriage and reproductive compensation. In net terms, consanguinity was not found to be associated either with a significant positive or negative effect on fertility.

Adolescent↗

PubMed1999

Effects of hypercholesterolaemia on Leydig and Sertoli cell secretory function and the overall sperm fertilizing capacity in the rabbit.

The effects of hypercholesterolaemia on testicular endocrine and exocrine function were evaluated. The influence of hypercholesterolaemia on sperm quality, quantity, and fertilizing potential was also determined. Ten mature rabbits (group A) were fed chow containing 3% cholesterol for 12 weeks. Ten control rabbits (group B) were fed normal chow for the same period. At the end of the experimental period testosterone profiles and sperm parameters were evaluated and the sperm reproductive potential was assessed by in vitro fertilization (IVF) techniques. Peripheral serum testosterone responses to testicular stimulation with human chorionic gonadotrophin, androgen-binding protein activity in testicular cytosols, sperm concentration, sperm motility, length of sperm midpiece, and IVF outcome were all significantly lower in group A than in group B. In contrast, serum cholesterol concentrations were significantly higher in group A. There were no significant differences in either testicular versus intra-abdominal temperature differences or cholesterol concentrations in seminal plasma or testicular tissue between groups A and B. The results suggest that hypercholesterolaemia has a detrimental effect on Leydig and Sertoli cell secretory function, spermatogenesis, epididymal sperm maturation process, and the overall sperm fertilizing capacity.

Animals↗

PubMed1999

Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigative tool.

Studies have shown that ovarian failure is a common side-effect of chemotherapy treatment; however, continuation of regular menses post-treatment does not necessarily imply that the ovaries have escaped damage. This animal study measures directly the primordial follicle (PMF) loss following exposure to chemotherapy and evaluates reproductive outcome following significant destruction of the PMF population. Inbred Balb/c mice aged 5-6 weeks were administered different doses of an alkylating agent, cyclophosphamide, and the total number of PMF remaining in both ovaries was counted. Results show that cyclophosphamide causes PMF destruction in proportion to increasing dose (P = 0.0001). Reproductive performance was assessed after exposure to 75 mg/kg cyclophosphamide, a dose which destroys approximately 50% of PMF reserve, by evaluation of ovulation, mating and pregnancy rates. Reproductive potential of treated mice was not affected compared with controls despite the significant loss of PMF. Our results indicate that reproductive performance is not an accurate parameter for assessing ovarian injury. Rather, histological counting of PMF number more directly reflects the damage caused by chemotherapy to the ovary. This method can be used as a sensitive, inexpensive tool to gauge the damage to fertility caused by new chemotherapy agents or protocols.

Animals↗

PubMed2006

Intra-individual variation in sperm chromatin structure assay parameters in men from infertile couples: clinical implications.

BACKGROUND: Sperm DNA integrity is an important factor in the prognosis of male fertility. In this study, we investigated intra-individual variation of sperm chromatin structure assay (SCSA) parameters in infertility patients undergoing assisted reproductive techniques (ARTs). METHODS: Retrospective study of 282 consecutive patients referred for ART [intrauterine insemination (IUI), IVF or ICSI] with repeated (between 2 and 5) SCSA measurements. RESULTS: Mean coefficient of variation (CV) of DNA Fragmentation Index (DFI) for repeated SCSA measurements was 29%. A high proportion [37%; 95% confidence interval (CI): 27%, 49%] of patients with DFI >30% in the first test had DFI <30% in the second test. Also, a considerable proportion (27%; 95% CI : 16%, 40%) of patients with 21-30% DFI values in the first test had DFI >30% in the second test. CONCLUSIONS: Intra-individual variability in DFI is significant, therefore repeated SCSA measurements are recommended. The biological mechanisms behind these variations remain to be elucidated.

Chromatin↗

PubMed1992

Combined effects of body size, parity, and menstrual events on breast cancer incidence in seven countries.

A biologically motivated breast cancer incidence rate function was fit to data from a published case-control study conducted in countries whose incidence is high (Wales and the United States), moderate (Brazil, Greece, and Yugoslavia), and low (Japan and Taiwan). The data include personal characteristics of 3,925 breast cancer cases and 11,327 controls interviewed in selected hospitals in 1964-1968. Parameters in the function specify the dependence of age-specific breast cancer incidence rates on age at menarche, age at menopause, occurrence and timing of full-term pregnancies, and body mass. Parameters were estimated separately for high-, moderate-, and low-risk countries. Examination of residuals provided little evidence of inadequacy of the fitted function in describing combined effects of the characteristics studied. The following patterns were seen in all three risk groups: 1) Incidence rates jump to a higher level after first childbirth, but then increase with age more slowly thereafter. 2) Rates increase with age more slowly after menopause than before. 3) Rates change quadratically with body mass index among all women, although the main trend varies: Rates decrease with body mass among premenopausal women in high-risk countries, but increase with body mass in all other groups of women. Similarities of parameter estimates across countries suggest that reproductive events and body fat exert similar effects on all women, regardless of breast cancer rates in their country of residence.

Adult↗

PubMed2004

Recombination and loss of complementation: a more than two-fold cost for parthenogenesis.

Certain types of asexual reproduction lead to loss of complementation, that is unmasking of recessive deleterious alleles. A theoretical measure of this loss is calculated for apomixis, automixis and endomitosis in the cases of diploidy and polyploidy. The effect of the consequent unmasking of deleterious recessive mutations on fitness is also calculated. Results show that, depending on the number of lethal equivalents and on the frequency of recombination, the cost produced by loss of complementation after few generations of asexual reproduction may be greater than the two-fold cost of meiosis. Maintaining complementation may, therefore, provide a general short-term advantage for sexual reproduction. Apomixis can replace sexual reproduction under a wide range of parameters only if it is associated with triploidy or tetraploidy, which is consistent with our knowledge of the distribution of apomixis.

Alleles↗

PubMed1985

Comparative aspects of circulating erythrocytes in the trophic and reproductive phases of European eel. Ultrastructure and cytochemistry.

Different cytochemical and morphological parameters were used to compare the functional patterns of the erythrocytes in the transition from the trophic (yellow eel) to the reproductive (silver eel) phases of European eel (Anguilla anguilla L.). Data on the nucleus were obtained by microdensitometric (Feulgen reaction) and cytofluoremetric (propidium iodide and Hoechst 33342 fluorochromization) evaluations of DNA staining intensity. In the silver eel, chromatin condensation was more heterogeneous and chromatin also appeared to be looser. The fluorochromes provided information on the different degrees of organization of the chromatin filament, with regard to both primary and higher order DNA structure. In the silver eel, the fine structure showed a higher number of erythrocytes with large euchromatinic areas and the heterochromatinic component was occasionally present in scattered clumps. As for the cytoplasm, in the silver eel a positive correlation could be established between the presence of intact cytoplasmic organelles (mitochondria, Golgi complexes, ribosomes, etc.) and the high fluorescence intensity. This aspect is revealed through the detection of definite membrane components such as glycoconjugates and primary amino groups (PAS reaction and fluorescamine staining, respectively). All these findings allowed us to establish that the transition from the trophic to the premigratory reproductive phase is marked by a higher heterogeneity of the erythrocytes, due to different cell maturation levels. This fact can be ascribed to different metabolic requirements as well as to a more intense erythropoiesis, typical of the most active phase of the eel's life.

Aging↗

PubMed1978

Breaks induced in the deoxyribonucleic acid of aerosolized Escherichia coli by ozonized cyclohexene.

The inactivation of aerosolized Escherichia coli by ozone, cyclohexene, and ozonized cyclohexene was studied. The parameters for damage were loss of reproduction and introduction of breaks in the deoxyribonucleic acid (DNA). Aerosolization of E. coli in clean air at 80 percent relative humidity or in air containing either ozone or cyclohexene hardly affected survival; however, some breaks per DNA molecule were induced, as shown by sucrose gradient sedimentation of the DNA. Aerosolization of E. coli in air containing ozonized cyclohexene at 80 percent relative humidity decreased the survival by a factor of 10(3) or more after 1 h of exposure and induced many breaks in the DNA.

Aerosols↗

PubMed2005

The pre-vaccination regional epidemiological landscape of measles in Italy: contact patterns, effort needed for eradication, and comparison with other regions of Europe.

BACKGROUND: Strong regional heterogeneity and generally sub-optimal rates of measles vaccination in Italy have, to date, hampered attainment of WHO targets for measles elimination, and have generated the need for the new Italian National Measles Elimination Plan. Crucial to success of the plan is the identification of intervention priorities based upon a clear picture of the regional epidemiology of measles derived from the use of data to estimate basic parameters. Previous estimates of measles force of infection for Italy have appeared anomalously low. It has been argued elsewhere that this results from Italian selective under-reporting by age of cases and that the true measles force of infection in Italy is probably similar to that of other European countries. A deeper examination of the evidence for this conjecture is undertaken in the present paper. METHODS: Using monthly regional case notifications data from 1949 to the start of vaccination in 1976 and notifications by age from 1971-76, summary equilibrium parameters (force of infection (FOI), basic reproductive ratio (R0) and critical vaccination coverage (pc)) are calculated for each region and for each of 5 plausible contact patterns. An analysis of the spectra of incidence profiles is also carried out. Finally a transmission dynamics model is employed to explore the correspondence between projections using different estimates of force of infection and data on seroprevalence in Italy. RESULTS: FOI estimates are lower than comparable European FOIs and there is substantial regional heterogeneity in basic reproductive ratios; certain patterns of contact matrices are demonstrated to be unfeasible. Most regions show evidence of 3-year epidemic cycles or longer, and compared with England & Wales there appears to be little synchronisation between regions. Modelling results suggest that the lower FOI estimated from corrected aggregate national data matches serological data more closely than that estimated from typical European data. CONCLUSION: Results suggest forces of infection in Italy, though everywhere remaining below the typical European level, are historically higher in the South where currently vaccination coverage is lowest. There appears to be little evidence to support the suggestion that a higher true force of infection is masked by age bias in reporting.

Journal Article↗