Molecular survey of trichothecene genotypes of Fusarium graminearum species complex from barley in southern Brazil.

Fusarium head blight is a disease of primary concern to small-grain cereals of Brazil, including barley. Its main causal agent, Fusarium graminearum species complex (Fg complex)¸ is able to produce mycotoxins, especially deoxynivalenol (DON) and nivalenol (NIV), that usually contaminate grain. Strains that produce DON may also produce its acetylated derivatives: 3-acetyl-DON (3-ADON) and 15-acetyl-DON (15-ADON). Ninety two isolates were obtained from samplings of barley grain during three years (2007, 2008 and 2009) from several fields in both southern and northern production regions of Rio Grande do Sul state, Brazil. These isolates were examined for polymerase chain-reaction-based (PCR) trichothecene genotype based on the amplification of portions of Tri3 and Tri12. There was no effect of year or region on the proportion of trichothecene genotypes. Overall, 66% of the strains (61/92) were 15-ADON, 4.4% (4/92) were 3-ADON and 29.3% (27/92) were NIV. The overall NIV/DON ratio estimated (0.41) was five times higher than that found in previous studies with strains from wheat grown in the same region. Species identification of nine strains representing the trichothecene genotypes, based on comparisons of DNA sequences of portions of the PHO, RED and URA genes with sequences from curated reference isolates of Fusarium from GenBank, revealed that they belong to F. graminearum sensu stricto (four 15-ADON and one 3-ADON strain), F. meridionale (three NIV strains) and F. austroamericanum (one 3-ADON strain). These results add to the current regional knowledge of trichothecene genotypes and species within the Fg complex affecting barley in the region.

Are we Genomic Mosaics? Variations of the Genome of Somatic Cells can Contribute to Diversify our Phenotypes.

Theoretical and experimental evidences support the hypothesis that the genomes and the epigenomes may be different in the somatic cells of complex organisms. In the genome, the differences range from single base substitutions to chromosome number; in the epigenome, they entail multiple postsynthetic modifications of the chromatin. Somatic genome variations (SGV) may accumulate during development in response both to genetic programs, which may differ from tissue to tissue, and to environmental stimuli, which are often undetected and generally irreproducible. SGV may jeopardize physiological cellular functions, but also create novel coding and regulatory sequences, to be exposed to intraorganismal Darwinian selection. Genomes acknowledged as comparatively poor in genes, such as humans', could thus increase their pristine informational endowment. A better understanding of SGV will contribute to basic issues such as the "nature vs nurture" dualism and the inheritance of acquired characters. On the applied side, they may explain the low yield of cloning via somatic cell nuclear transfer, provide clues to some of the problems associated with transdifferentiation, and interfere with individual DNA analysis. SGV may be unique in the different cells types and in the different developmental stages, and thus explain the several hundred gaps persisting in the human genomes "completed" so far. They may compound the variations associated to our epigenomes and make of each of us an "(epi)genomic" mosaic. An ensuing paradigm is the possibility that a single genome (the ephemeral one assembled at fertilization) has the capacity to generate several different brains in response to different environments.

In vitro photostability and photoprotection studies of a novel 'multi-active' UV-absorber.

This paper reports on the synthesis and properties of a new UV-absorber (OC-NO) based on the most popular UV filter worldwide, ethylhexyl methoxycinnamate (OMC) in which the methoxy group has been replaced with a pyrrolidine nitroxide bearing antioxidant activity. This sunscreen active has therefore both UV-absorbing and antioxidant properties which could ideally address both the UV-B and UV-A skin photo-damage. For broad-spectrum coverage, the combinations of OC-NO with two commonly used UV-A absorbers (BMDBM and DHHB) were also studied. The results obtained reveal that OC-NO: (a) is as photostable as OMC after UV-A exposure; (b) acts as free radical scavenger as demonstrated by EPR and chemical studies; (c) reduces UV-A and UV-A+BMDBM induced lipid peroxidation in liposomes and cells, measured as reduced TBARS levels and increased C11-BODIPY red fluorescence, respectively; (d) has comparable antioxidant activity to that of vitamin E and BHT commonly used in skin care formulations; (e) is non-cytotoxic to human skin fibroblasts as assessed with the MTT assay when exposed to increasing doses of UV-A; and (f) OC-NO+DHHB is a promising, photostable broad spectrum UV-filter combination that concomitantly reduces UV-induced free radical damage. These results suggest that nitroxide/antioxidant-based UV-absorbers may pave the way for the utilization of 'multi-active' ingredients in sunscreens thereby reducing the number of ingredients in these formulations.

Late childbearing and its impact on adverse pregnancy outcome: stillbirth, preterm delivery and low birth weight.

BACKGROUND: The role of parental ageing on the incidence of adverse pregnancy outcome is based on increased morbidity and obstetric problems during pregnancy and delivery in old mothers, and on the accumulation of spontaneous harmful mutations for continuous cell divisions during spermatogenesis in old fathers. The aim of this study is to estimate the impact of paternal and maternal ageing on the risk of adverse pregnancy outcome. DATA AND METHODS: From the group of 3,616,622 Italian singletons born in 1990-1996 we estimated the risks of stillbirth, preterm birth (<37 weeks of gestation) in live births, and low birth-weight (< 2.3 Kg) in live full-term births. The risks were estimated as a function of maternal and paternal ageing through logistic regression models, which included, as covariates, parity (1st, 2nd, > or =3rd) and family education (low, < or =8 years of schooling for both parents; high, >8 years for at least one parent). Parental ages were examined as quantitative (in one year classes) or categorical factors (in three classes: fathers 20-29, 30-39, > or =40; mothers 20-29, 30-34, > or =35). RESULTS AND CONCLUSIONS: We found that, compared with 20-29-year old parents, mothers > or =30 years and fathers > or =40 years are at risk of adverse pregnancy outcome. The effects are more relevant for preterm births and greater in the least than in the most favourable birth conditions, i.e., in first-born children of less educated families than in second-born children of highly educated families. For the risk of a preterm delivery, the odds ratio is OR = 1.32 [1.28-1.36] in mothers aged 30-34 years, and OR=1.97 [1.88-2.07] in mothers 235 years in the least favourable conditions, and OR = 1.14 [1.10-1.18] and OR = 1.56 [1.22-1.27] respectively, in the most favourable conditions. The impact of paternal ageing is smaller but significant in fathers > or =40 years: for the risk of a preterm birth, the odds ratio is OR = 1.40 [1.33-1.47] in the least favourable conditions, and OR = 1.14 [1.08-1.21] in the most favourable conditions. This last, baseline risk might be indicative of a paternal genetic component associated with childbearing in advanced age.

Late paternity and stillbirth risk.

BACKGROUND: The role of paternal ageing on the incidence of some genetic diseases in offspring depends on the hypothesis that spontaneous mutations accumulate due to continuous cell divisions during spermatogenesis. We examined the effect of paternal age on the complex multifactorial character, stillbirth. METHODS: In 3,619,647 Italian singletons born in 1990-1996 we evaluated stillbirth risk as a function of paternal ageing by means of multiple logistic regression models, which included maternal age and family education, as categorical covariates and interactions. The categorical risk was estimated for mothers and fathers beyond threshold ages of 35 and 40 years, respectively. RESULTS: Stillbirth risk increases with paternal ageing in mothers > or =30 years old, and maternal age and family education modify the impact. In families with low education, the risk accounts for odds ratio (OR) 1.015 [95% confidence interval (CI) 1.01-1.02] in mothers aged 30-34 years, and for OR 1.032 (95% CI 1.02-1.04) in mothers aged > or =35 years; in families with higher education the risk accounts for OR 1.008 (95% CI 1.00-1.02) and OR 1.025 (95% CI 1.01-1.04), respectively, in mothers aged 30-34 and > or =35 years. In these latter families, for mothers aged <35 and fathers > or =40 years the risk accounts for OR 1.12 (95% CI 1.00-1.25). CONCLUSIONS: The effect of paternal ageing on stillbirth risk is revealed in mothers aged > or =30 years and is modified by family education. In mothers aged 30-34 years from families with high education, the increase imputable to paternal ageing might be indicative of a genetic component.

Changes in twinning rate: Italy 1950-1996.

BACKGROUND: In the wide-ranging debate about the potential monitors of population fertility, twinning rate has been considered a candidate. In the developed countries, a decline in spontaneous twinning rate began around 1950 and continued until the late 1970s. The decrease in mean maternal age at delivery and the number of children per family have been considered as possible reasons for the decrease. The rise in twinning rates, which began in the 1980s, is probably due to the spread of assisted reproduction, at least for older mothers. METHODS: The temporal trend in twinning rate and the relationship with maternal age at delivery and birth order in the Italian population were analysed. RESULTS: The recent increase in twinning rate can be mainly attributed to the recourse to assisted reproduction techniques, as demonstrated by the twinning frequency among older primiparae. The twinning rate recently observed in young mothers approximates to the value of the 1950s, which is assumed to represent a 'natural' fertility condition. CONCLUSIONS: On the assumption that twinning is an indicator of fertility, and hence of population fitness, the present data seem to suggest that natural fertility has been slightly increasing in the Italian population.

Triplet repeats, over-expanded in neuromuscular diseases, are under-represented in mammalian DNA: a survey of models.

Simple tandem repeats represent more than 1% of the human genome: occasionally they exhibit intergenerational expansibility and are associated with neuromuscular diseases. In transgenic mice the same sequences elicit similar symptoms, but do not expand. We have searched for di-, tri-, and tetra-repeats in the published DNA sequences of chromosomes 21 and 22 of Homo sapiens, as well as in more than five megabases of Mus musculus DNA. Human and murine DNA sequences show a shortage in frequency and base coverage of tri-repeats as compared to di- and tetra-repeats. In murine sequences the cumulative frequency of di-, tri-, and tetra-repeats and their overall base coverage are about threefold higher than in human. Models for both the shortage of tri-repeats found in man and mouse and for their dynamic expansions are discussed. We propose that some of the 10 possible tri-repeats may be more prone than others to assume unusual structures capable of interfering with DNA synthesis: hence the shortage of tri-repeats. If such repeats are located at the 3'end of a chain growing and thus approaching another chain annealed to the same template, as Okazaki fragments do during discontinuous and encumbered replication, a combination of strand displacement, template switch, and branch migration may produce structures resistant to removal, hence the expansion of tri-repeats.

Paternal HLA genotype and offspring sex ratio.

For twenty years, W.H. James has been proposing that the sex hormone level of both parents could control at least a quota of the secondary sex ratio variation at the time of conception. Observations supporting this hypothesis have come from investigations on some diseases related to the human leukocyte antigen (HLA). In the present study on 1102 healthy Italian families, we investigated the potential effect on the offspring sex ratio of HLA-B alleles on the basis of a genetic model. We defined three subsets of HLA-B alleles and hypothesized a locus (L) with three alleles, L(H), L(N), L(B15), on the basis of the positive, neutral, or negative effect on the testosterone level. According to the genetic model and the dominance relation L(H) > L(B15) > L(N), six genotypic and three phenotypic classes (H, N, B15) can be expected. We found a significantly high number of daughters (66%) born to fathers carrying the B15 phenotype. This result suggests an effect of the HLA-B15 allele on the secondary sex ratio, mediated by a low testosterone level.

Sex ratio at reproductive age: changes over the last century in the Italian population.

The radical improvement in living conditions experienced in Italy during the last century caused a reduction in male extra-mortality during the prereproductive years. As a consequence, a progressive increase in the sex ratio at the beginning of the reproductive age (15-19 years) occurred, so that in recent times the sex ratio in the young adult population has approached the almost constant value of 1.06 observed at birth. We calculated that the sex composition would be the same in newborns and in young adults in about one generation: obviously, we have to assume that the sex differentials in mortality and migration are constant over time. The 1:1 equilibrium between sexes, which maximizes reproductive success, occurred in the 15-19 age group at the beginning of the century and shifted to the 30-35 age group in the 1990s. We compared the 1993-1995 sex ratios in different age groups in European Union countries and observed that in Italy as well as in other Mediterranean countries the numerical equality between sexes is reached at 30-35 years of age, while in north-central Europe it is reached later, approximately at the end of reproductive life.

Natural selection and reproductive behavior in Italy, 1930-1993.

We studied the relaxation of natural selection affecting the newborn population in Italy between 1930 and 1993 due to the decrease in the stillbirth (mortality) rate and the simultaneous changes in women's reproductive behavior (strategies). Results show that, apart from a drastic overall reduction, the stillbirth rate has varied among different groups of neonates. The present stillbirth rate of less than 5 per thousand, observed in 8 of the 20 phenotypic classes defined on the basis of maternal age at delivery and neonate birth order, most likely represents an unavoidable biological or genetic cost. A 9 per thousand stillbirth rate, about twice the potential minimum, exists among neonates born to women delivering at advanced age (> or = 35): the risk they face at the first or, in adverse living conditions, the fourth pregnancy could, however, be decreased by a policy aimed at countering the tendency to delay maternity and improving antenatal care in economically disadvantaged areas of the country.

Reduced male births in major Italian cities.

The downward trend in the sex ratio at birth that has occurred in several countries over the last 30 years was postulated to signal a deterioration in environmental conditions, particularly unfavourable for male conception and fetus survival. In Italy, in contrast, an upward trend has been observed. Assuming that exposure to reproductive hazards occurs mainly in the major cities, we contrasted the 1970-1995 sex ratio trend for the metropolitan area (defined as the four provinces containing the largest Italian cities) with that for the non-metropolitan area (defined as the rest of the country). In the metropolitan area, the proportion of live-born males showed a negative trend significantly different from the positive trend observed in the rest of the country. Moreover, the stillbirth rate among males was constantly and significantly higher in the metropolitan area. Our results suggest that the decrease in the sex ratio at birth observed in the metropolitan area might be interpreted as a signal of increasing exposure to hazardous environmental conditions for male conceptions and neonates.

Risks of preterm delivery and association with maternal age, birth order, and fetal gender.

The risk of preterm delivery in a recent sample (1990-1994) of Italian liveborns was examined, taking into account child birth order, and maternal age and education in addition to the fetal gender. Univariate analyses showed that a higher risk was associated with male than female babies, with first- than second-born children, with older mothers, and with less educated mothers. The relative weights of the factors examined were evaluated through logistic regression analyses and the highest and the lowest risks were found to be associated with advanced maternal age and male fetal gender respectively. Our findings therefore suggest that biological factors associated more with advanced maternal age than with the male gender of the fetus may influence premature onset of labour.

Past malaria, thalassemia and woman fertility in southern Italy.

The role of natural selection in maintaining the thalassemia polymorphism is examined in a southern Italy district, in the past affected by malaria endemia. The Haldane's hypothesis that the thalassemia heterozygotes enjoy more protection than the normal homozygotes against the risk of malaria infection, seems to be confirmed by this indirect study at population level. The higher number of children born of the women who lived in the highly endemic villages, where the highest proportion of heterozygotes occurs, supports the hypothesis that the woman fertility contributes to the thalassemia maintenance. The joint effects of the acquired and inherited immunities and of the reproductive compensation are assumed as the mechanisms through which malaria and thalassemia influence fertility.

Sex ratio and parental age gap.

We tested the hypothesis that a large age difference between parents can shift the sex ratio at birth in favor of males, as Manning et al. (1997) suggested in their analysis of English and Welsh data. Among children born in Lombardy (northern Italy) in 1990 and 1991, we observed an anomalous excess of males born to a particular subsample of parents with a wide age gap (> 15 yr) between them; in the overall sample the father-mother age gap does not significantly contribute to the determination of the child's sex.

Natural selection in industrialized countries: a study of three generations of Italian newborns.

We have studied the impact of natural selection on the Italian population, analysing the relationship between stillbirth and three related variables: birth weight, birth order and maternal age. A progressive relaxation of selection with time has been demonstrated by the reduction of the Haldane index calculated with respect to the three variables.

Heterogeneous effects of natural selection on the Italian newborns.

We have studied the impact of natural selection through stillbirth on the Italian population, taking into account the socio-economic heterogeneity of the country. The results suggest that older age at delivery and lower cultural level of the mothers, indicators of critical biological and socio-economic conditions, even at present increase stillbirth risk. Moreover, in the less favourable environment of the southern regions, selection is still sex-specific.

Early selection and sex composition in Italy: a study at the regional level.

We have chosen four Italian regions with different degrees of industrialization and socioeconomic levels to study environmental differences in the sex ratio. The improvement in living and sanitary conditions during the last century has led to a progressive reduction in early male extramortality, and the sex ratio at birth has been almost unchanged at least to the first year of life and probably up to reproductive age. To investigate whether socioeconomic, cultural, or biological factors still influence the sex ratio at birth, we studied the stillbirth rate and the relations between newborn viability and sex composition as a function of maternal age and educational level. Our results suggest that in less favorable environments early selection against male newborns is almost twice that against female newborns when the mothers are the least favored for socioeconomic status, cultural level, and biological conditions (older than 39 years).

Sharing at the major histocompatibility complex affects the secondary sex ratio in differing ways.

We analysed the effect of HLA loci on the secondary sex ratio, and investigated whether allele sharing between parents and between mother and child, or child homozygosity, affected the viability of male embryos, which are generally less resistant to unfavourable conditions during pregnancy. The sharing conditions at the B and DR loci showed significantly differing effects: HLA-B seemed to favour female births, while, in pregnancies subsequent to the first, HLA-DR seemed to favour male births. Both HLA-B and DR loci seemed to work through immunological mechanisms.