Sex-dependent age modulation of frontostriatal and temporo-parietal activation during cognitive control

Developmental functional imaging studies of cognitive control show progressive age-related increase in task-relevant fronto-striatal activation in male development from childhood to adulthood. Little is known, however, about how gender affects this functional development. In this study, we used event related functional magnetic resonance imaging to examine effects of sex, age, and their interaction on brain activation during attentional switching and interference inhibition, in 63 male and female adolescents and adults, aged 13 to 38. Linear age correlations were observed across all subjects in task-specific frontal, striatal and temporo-parietal activation. Gender analysis revealed increased activation in females relative to males in fronto-striatal areas during the Switch task, and laterality effects in the Simon task, with females showing increased left inferior prefrontal and temporal activation, and males showing increased right inferior prefrontal and parietal activation. Increased prefrontal activation clusters in females and increased parietal activation clusters in males furthermore overlapped with clusters that were age-correlated across the whole group, potentially reflecting more mature prefrontal brain activation patterns for females, and more mature parietal activation patterns for males. Gender by age interactions further supported this dissociation, revealing exclusive female-specific age correlations in inferior and medial prefrontal brain regions during both tasks, and exclusive male-specific age correlations in superior parietal (Switch task) and temporal regions (Simon task). These findings show increased recruitment of age-correlated prefrontal activation in females, and of age-correlated parietal activation in males, during tasks of cognitive control. Gender differences in frontal and parietal recruitment may thus be related to gender differences in the neurofunctional maturation of these brain regions.

Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome

Genetic studies of autism spectrum conditions (ASC) have mostly focused on the "low functioning" severe clinical subgroup, treating it as a rare disorder. However, ASC is now thought to be relatively common ( approximately 1%), and representing one end of a quasi-normal distribution of autistic traits in the general population. Here we report a study of common genetic variation in candidate genes associated with autistic traits and Asperger syndrome (AS). We tested single nucleotide polymorphisms in 68 candidate genes in three functional groups (sex steroid synthesis/transport, neural connectivity, and social-emotional responsivity) in two experiments. These were (a) an association study of relevant behavioral traits (the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ)) in a population sample (n=349); and (b) a case-control association study on a sample of people with AS, a "high-functioning" subgroup of ASC (n=174). 27 genes showed a nominally significant association with autistic traits and/or ASC diagnosis. Of these, 19 genes showed nominally significant association with AQ/EQ. In the sex steroid group, this included ESR2 and CYP11B1. In the neural connectivity group, this included HOXA1, NTRK1, and NLGN4X. In the socio-responsivity behavior group, this included MAOB, AVPR1B, and WFS1. Fourteen genes showed nominally significant association with AS. In the sex steroid group, this included CYP17A1 and CYP19A1. In the socio-emotional behavior group, this included OXT. Six genes were nominally associated in both experiments, providing a partial replication. Eleven genes survived family wise error rate (FWER) correction using permutations across both experiments, which is greater than would be expected by chance. CYP11B1 and NTRK1 emerged as significantly associated genes in both experiments, after FWER correction (P<0.05). This is the first candidate-gene association study of AS and of autistic traits. The most promising candidate genes require independent replication and fine mapping.

The effect of ram replacement and sex ratio on the sexual response of anoestrous ewes

It is accepted that an important source of variation in the response of anoestrous ewes, to the introduction of rams, is the intensity of male stimulation. The aim of this study was to investigate strategies capable of increasing the impact and transmission of the ram stimuli. In Experiment 1, two groups of seven ewes (Bluefaced Leicester male x Swaledale female) were individually penned with one ram and for the next 6 h the rams either remained in the pen or were replaced hourly. Blood samples revealed no difference in the pattern of plasma LH secretion. In Experiment 2, three groups of 16 ewes were either introduced to one ram, individually (H) or in groups of 8 (L), or remained isolated. Ram introduction increased the plasma LH pulsatility (P < 0.001). H ewes displayed more (nine versus six) male-induced LH pulses (pulses occurring within the first 45 min) and more pulses per 8 h intervals than the L group of ewes (1.9 +/- 0.3 versus 1.3 +/- 0.3), but these differences were not significant. It was concluded that (i) frequent replacement of rams within a few hours following ram introduction to ewes does not further improve the response of ewes, especially if the ram:ewe ratio is high; (ii) the characterization of the plasma LH secretion parameters during a period of 6-8 h does not seem to be an effective method to detect small differences in the intensity of stimulation received by the ewes when exposed to rams; (iii) North Country Mule ewes (Bluefaced Leicester male x Swaledale female) in the UK respond to the presence of rams in spring (late oestrous/early anoestrous season) with an elevation in plasma LH secretion. (c) 2005 Elsevier B.V. All rights reserved.

Effects of a sex-ratio distorting endosymbiont on mtDNA variation in a global insect pest

Background: Patterns of mtDNA variation within a species reflect long-term population structure, but may also be influenced by maternally inherited endosymbionts, such as Wolbachia. These bacteria often alter host reproductive biology and can drive particular mtDNA haplotypes through populations. We investigated the impacts of Wolbachia infection and geography on mtDNA variation in the diamondback moth, a major global pest whose geographic distribution reflects both natural processes and transport via human agricultural activities. Results: The mtDNA phylogeny of 95 individuals sampled from 10 countries on four continents revealed two major clades. One contained only Wolbachia-infected individuals from Malaysia and Kenya, while the other contained only uninfected individuals, from all countries including Malaysia and Kenya. Within the uninfected group was a further clade containing all individuals from Australasia and displaying very limited sequence variation. In contrast, a biparental nuclear gene phylogeny did not have infected and uninfected clades, supporting the notion that maternally-inherited Wolbachia are responsible for the mtDNA pattern. Only about 5% (15/306) of our global sample of individuals was infected with the plutWBI isolate and even within infected local populations, many insects were uninfected. Comparisons of infected and uninfected isofemale lines revealed that plutWBI is associated with sex ratio distortion. Uninfected lines have a 1:1 sex ratio, while infected ones show a 2:1 female bias. Conclusion: The main correlate of mtDNA variation in P. xylostella is presence or absence of the plutWBI infection. This is associated with substantial sex ratio distortion and the underlying mechanisms deserve further study. In contrast, geographic origin is a poor predictor of moth mtDNA sequences, reflecting human activity in moving the insects around the globe. The exception is a clade of Australasian individuals, which may reflect a bottleneck during their recent introduction to this region.

Genotypic sex determination enabled adaptive radiations of extinct marine reptiles

Adaptive radiations often follow the evolution of key traits, such as the origin of the amniotic egg and the subsequent radiation of terrestrial vertebrates. The mechanism by which a species determines the sex of its offspring has been linked to critical ecological and life-history traits(1-3) but not to major adaptive radiations, in part because sex-determining mechanisms do not fossilize. Here we establish a previously unknown coevolutionary relationship in 94 amniote species between sex-determining mechanism and whether a species bears live young or lays eggs. We use that relationship to predict the sex-determining mechanism in three independent lineages of extinct Mesozoic marine reptiles (mosasaurs, sauropterygians and ichthyosaurs), each of which is known from fossils to have evolved live birth(4-7). Our results indicate that each lineage evolved genotypic sex determination before acquiring live birth. This enabled their pelagic radiations, where the relatively stable temperatures of the open ocean constrain temperature-dependent sex determination in amniote species. Freed from the need to move and nest on land(4,5,8), extreme physical adaptations to a pelagic lifestyle evolved in each group, such as the fluked tails, dorsal fins and wing-shaped limbs of ichthyosaurs. With the inclusion of ichthyosaurs, mosasaurs and sauropterygians, genotypic sex determination is present in all known fully pelagic amniote groups (sea snakes, sirenians and cetaceans), suggesting that this mode of sex determination and the subsequent evolution of live birth are key traits required for marine adaptive radiations in amniote lineages.

Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study

Background: The lipid-modulatory effects of high intakes of the fish-oil fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well established and likely to contribute to cardioprotective benefits. Objectives: We aimed to determine the effect of moderate EPA and DHA intakes (< 2 g EPA + DHA/d) on the plasma fatty acid profile, lipid and apolipoprotein concentrations, lipoprotein subclass distribution, and markers of oxidative status. We also aimed to examine the effect of age, sex, and apolipoprotein E (APOE) genotype on the observed responses. Design: Three hundred twelve adults aged 20-70 y, who were prospectively recruited according to age, sex, and APOE genotype, completed a double-blind placebo-controlled crossover study. Participants consumed control oil, 0.7 g EPA + DHA/d (0.7FO), and 1.8 g EPA + DHA/d (1.8FO) capsules in random order, each for an 8-wk intervention period, separated by 12-wk washout periods. Results: In the group as a whole, 8% and 11% lower plasma triacylglycerol concentrations were evident after 0.7FO and 1.8FO, respectively (P < 0.001): significant sex x treatment (P = 0.038) and sex x genotype x treatment (P = 0.032) interactions were observed, and the greatest triacylglycerol-lowering responses (reductions of 15% and 23% after 0.7FO and 1.8FO, respectively) were evident in APOE4 men. Furthermore, lower VLDL-cholesterol (P = 0.026) and higher LDL-cholesterol (P = 0.010), HDL-cholesterol (P < 0.001), and HDL2 (P < 0.001) concentrations were evident after fish-oil intervention. Conclusions: Supplements providing EPA + DHA at doses as low as 0.7 g/d have a significant effect on the plasma lipid profile. The results of the current trial, which used a prospective recruitment approach to examine the responses in population subgroups, are indicative of a greater triacylglycerol-lowering action of long-chain n-3 polyunsaturated fatty acids in males than in females.

Sex and outcrossing in a sessile freshwater invertebrate

1. The freshwater bryozoan Cristatella mucedo, in common with other sessile, benthic freshwater taxa, has an unusual life history: sex occurs during a relatively brief period near the start of the growing season, and overwintering occurs in the form of asexually produced dormant propagules (statoblasts). Consistent observed heterozygosity (Ho) deficits in C. mucedo populations have previously suggested that inbreeding is common, although a possible contribution of a Wahlund effect to low Ho could not be discounted. 2. We have used microsatellite data in the first study based on codominant markers to genetically characterise maternal colonies and larval offspring of C. mucedo . The 'population' represented by the larvae was in Hardy-Weinberg equilibrium, which has previously been found in only one of 39 populations of C. mucedo . At least 64% of larvae were the products of outcrossing. We suggest that the unusual early timing of sex may be a strategy to maximise rates of outcrossing within populations of sessile freshwater invertebrates.

Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study

Background: The lipid-modulatory effects of high intakes of the fish-oil fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well established and likely to contribute to cardioprotective benefits. Objectives: We aimed to determine the effect of moderate EPA and DHA intakes (< 2 g EPA + DHA/d) on the plasma fatty acid profile, lipid and apolipoprotein concentrations, lipoprotein subclass distribution, and markers of oxidative status. We also aimed to examine the effect of age, sex, and apolipoprotein E (APOE) genotype on the observed responses. Design: Three hundred twelve adults aged 20-70 y, who were prospectively recruited according to age, sex, and APOE genotype, completed a double-blind placebo-controlled crossover study. Participants consumed control oil, 0.7 g EPA + DHA/d (0.7FO), and 1.8 g EPA + DHA/d (1.8FO) capsules in random order, each for an 8-wk intervention period, separated by 12-wk washout periods. Results: In the group as a whole, 8% and 11% lower plasma triacylglycerol concentrations were evident after 0.7FO and 1.8FO, respectively (P < 0.001): significant sex x treatment (P = 0.038) and sex x genotype x treatment (P = 0.032) interactions were observed, and the greatest triacylglycerol-lowering responses (reductions of 15% and 23% after 0.7FO and 1.8FO, respectively) were evident in APOE4 men. Furthermore, lower VLDL-cholesterol (P = 0.026) and higher LDL-cholesterol (P = 0.010), HDL-cholesterol (P < 0.001), and HDL2 (P < 0.001) concentrations were evident after fish-oil intervention. Conclusions: Supplements providing EPA + DHA at doses as low as 0.7 g/d have a significant effect on the plasma lipid profile. The results of the current trial, which used a prospective recruitment approach to examine the responses in population subgroups, are indicative of a greater triacylglycerol-lowering action of long-chain n-3 polyunsaturated fatty acids in males than in females.

Sex differences in common marmosets (Callithrix jacchus) in response to an unfamiliar food task

There is a growing body of information on sex differences In callitrichid behaviour that includes the animals' performance in food tasks. For example, both reproductive and non-reproductive adult females have been found to be more successful than adult males in solving food tasks. In this study ten adult male and ten adult female common marmosets (Callithrix jacchus), housed individually, were tested with an unfamiliar task that involved the extraction of an embedded food. The task was to open a plastic canister that contained a raisin; the open end was covered with parchment paper. Each marmoset was given 15 trials in three blocks of 5 consecutive days. We measured the latency for each animal to open the lid and get the raisin-by one of five strategies that spontaneously emerged. The females learned the task faster and more efficiently than males; all the females opened the canister on day 1, for instance, in contrast to seven of the males on the same day. Females also progressively decreased the time that they took to open the tube. The final latency on day 15, for instance, was significantly shorter for the females. These results are consistent with relevant literature for callitrichids and cannot be accounted for in terms of differences in mental abilities, strength, hand morphology, or energy requirements. Further investigation is necessary to clarify the reasons for these differences.

'They did not have a word': the parental quest to locate a 'true sex' for their intersex children

Given the paucity of research in this area, the primary aim of this study was to explore how parents of infants with unclear sex at birth made sense of 'intersex'. Qualitative methods were, used (semi-structured interviews, interpretative phenomenological analysis) with 10 parents to generate pertinent themes and provide ideas for further research. Our analysis highlights the fundamental shock engendered by the uncertain sex status of children, and documents parental struggles to negotiate a coherent sex identity for their children. Findings are discussed in light of the rigid two-sex system which pervades medicine and everyday life, and we argue that greater understanding of the complexity of sex and gender is required in order to facilitate better service provision and, ultimately, greater informed consent and parental participation regarding decisions about their children's status.

Sex allocation and local mate competition in Old World non-pollinating fig wasps

The populations of many species are structured such that mating is not random and occurs between members of local patches. When patches are founded by a single female and all matings occur between siblings, brothers may compete with each other for matings with their sisters. This local mate competition (LMC) selects for a female-biased sex ratio, especially in species where females have control over offspring sex, as in the parasitic Hymenoptera. Two factors are predicted to decrease the degree of female bias: (1) an increase in the number of foundress females in the patch and (2) an increase in the fraction of individuals mating after dispersal from the natal patch. Pollinating fig wasps are well known as classic examples of species where all matings occur in the local patch. We studied non-pollinating fig wasps, which are more diverse than the pollinating fig wasps and also provide natural experimental groups of species with different male morphologies that are linked to different mating structures. In this group of wasps, species with wingless males mate in the local patch (i.e. the fig fruit) while winged male species mate after dispersal. Species with both kinds of male have a mixture of local and non-local mating. Data from 44 species show that sex ratios (defined as the proportion of males) are in accordance with theoretical predictions: wingless male species < wing-dimorphic male species < winged male species. These results are also supported by a formal comparative analysis that controls for phylogeny. The foundress number is difficult to estimate directly for non-pollinating fig wasps but a robust indirect method leads to the prediction that foundress number, and hence sex ratio, should increase with the proportion of patches occupied in a crop. This result is supported strongly across 19 species with wingless males, but not across 8 species with winged males. The mean sex ratios for species with winged males are not significantly different from 0.5, and the absence of the correlation observed across species with wingless males may reflect weak selection to adjust the sex ratio in species whose population mating structure tends not to be subdivided. The same relationship is also predicted to occur within species if individual females adjust their sex ratios facultatively. This final prediction was not supported by data from a wingless male species, a male wing-dimorphic species or a winged male species.