Sex-Chromosome Homomorphy in Palearctic Tree Frogs Results from Both Turnovers and X-Y Recombination.

Contrasting with birds and mammals, poikilothermic vertebrates often have homomorphic sex chromosomes, possibly resulting from high rates of sex-chromosome turnovers and/or occasional X-Y recombination. Strong support for the latter mechanism was provided by four species of European tree frogs, which inherited from a common ancestor (∼5 Ma) the same pair of homomorphic sex chromosomes (linkage group 1, LG1), harboring the candidate sex-determining gene Dmrt1. Here, we test sex linkage of LG1 across six additional species of the Eurasian Hyla radiation with divergence times ranging from 6 to 40 Ma. LG1 turns out to be sex linked in six of nine resolved cases. Mapping the patterns of sex linkage to the Hyla phylogeny reveals several transitions in sex-determination systems within the last 10 My, including one switch in heterogamety. Phylogenetic trees of DNA sequences along LG1 are consistent with occasional X-Y recombination in all species where LG1 is sex linked. These patterns argue against one of the main potential causes for turnovers, namely the accumulation of deleterious mutations on nonrecombining chromosomes. Sibship analyses show that LG1 recombination is strongly reduced in males from most species investigated, including some in which it is autosomal. Intrinsically low male recombination might facilitate the evolution of male heterogamety, and the presence of important genes from the sex-determination cascade might predispose LG1 to become a sex chromosome.

Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening.

This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non-laboratory aspects such as information and counseling), education of professionals, systematic evaluation of all aspects of prenatal screening, development of better evaluation tools in the light of the aim of the practice, accountability to all stakeholders including children born from screened pregnancies and persons living with the conditions targeted in prenatal screening and promotion of equity of access.

Tracing the associations between sex, the atypical and the combined atypical-melancholic depression subtypes: A path analysis.

BACKGROUND: Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. METHODS: The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. RESULTS: Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. LIMITATIONS: The use of cross-sectional data does not allow causal conclusions. CONCLUSIONS: This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care.

Hepatitis C Virus Awareness Among Men Who Have Sex With Men in Southwest Switzerland.

BACKGROUND: In Switzerland, the incidence of hepatitis C virus (HCV) infection in HIV-positive men who have sex with men (MSM) rose 18-fold between 1998 and 2011. We aimed to evaluate transmission risk factors, awareness, and seroprevalence of HCV among MSM in southwest Switzerland. METHODS: From 1st June 2011 to 31st August 2012, trained health care professionals invited individuals attending (1) MSM screening clinics and (2) indoor and outdoor meeting areas to complete an anonymous questionnaire. Consenting participants were rapid tested for HCV (OraQuick HCV Rapid Antibody Test). RESULTS: Of 918 MSM approached, 654 agreed to participate, most of whom (536, 82%) were enrolled via MSM screening clinics. Of 654 participants, 21 (3.2%) disclosed being HIV positive; 140 (21%) had unknown HIV status. In the preceding 12 months, 357 (55%) of 654 participants reported unprotected anal intercourse (UAI) and 321 (49%) of 654 participants reported UAI with partners of different/unknown HIV status. Not HIV serosorting was reported more frequently among HIV-positive individuals (76%, P < 0.001). Three hundred two participants (46%) were aware of HCV, awareness being higher among clinic than meeting area participants (49% vs. 33%, P = 0.04). One individual (of 654; 0.2%), with a negative HIV test result 18 months previously was newly diagnosed as being HCV positive on rapid testing. CONCLUSIONS: In this sample of predominantly HIV-negative MSM, half the participants were aware of HCV and HCV seroprevalence was low. However, high rates of UAI and of UAI without HIV serosorting were reported. Given the increasing incidence of HCV among HIV-positive men, we propose that HCV counseling should be offered to MSM regardless of HIV status, with testing offered to those at high risk.

Personality effects and sex differences on the international affective picture system (IAPS) : a Spanish and Swiss study

The present study analyses the relationship between Anxiety and Impulsivity personality factors and emotions, by controlling for country and sex effects in a sample of Spanish and Swiss university students. Emotions were assessed through the International Affective Picture System (IAPS) of pictures (valence/arousal) using the Self-Assessment Manikin (SAM) procedure. The mixed valence/arousal groups' pictures were formed according to Tok, Koyuncu, Dural and Catikkas procedure (2010). Results showed that females scored significantly higher in Anxiety factor and men in Impulsivity factor in both countries. The effect of sex was highly significant for Anxiety (ŋ2: 0.12), but there was no significant effect of the country. Also, females obtained higher scores in the four valence/arousal pictures groups. The sex effect was particularly robust for negative valence-high arousal (ŋ2: 0.13). Impulsivity correlated with high ratings of positive valence-high arousal while Anxiety correlated with high ratings of negative valence-high arousal and with high ratings of negative valence-low arousal in both sexes, although scores were higher for females. Structural Equation Modelling confirmed these relationships. Nevertheless, Anxiety and Impulsivity explained only a small amount of the accounted variance of the self-reported valence and arousal of the pictures.

External Validation of the Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) Score for Predicting Stroke-Associated Pneumonia in the Athens Stroke Registry.

BACKGROUND AND PURPOSE: The Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) score was developed recently for predicting stroke-associated pneumonia (SAP), one of the most common complications after stroke. The aim of the present study was to externally validate the ISAN score. METHODS: Data included in the Athens Stroke Registry between June 1992 and December 2011 were used for this analysis. Inclusion criteria were the availability of all ISAN score variables (prestroke independence, sex, age, National Institutes of Health Stroke Scale score). Receiver operating characteristic curves and linear regression analyses were used to determine the discriminatory power of the score and to assess the correlation between actual and predicted pneumonia in the study population. Separate analyses were performed for patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). RESULTS: The analysis included 3204 patients (AIS: 2732, ICH: 472). The ISAN score demonstrated excellent discrimination in patients with AIS (area under the curve [AUC]: .83 [95% confidence interval {CI}: .81-.85]). In the ICH group, the score was less effective (AUC: .69 [95% CI: .63-.74]). Higher-risk groups of ISAN score were associated with an increased relative risk of SAP; risk increase was more prominent in the AIS population. Predicted pneumonia correlated very well with actual pneumonia (AIS group: R(2) = .885; β-coefficient = .941, P < .001; ICH group: R(2) = .880, β-coefficient = .938, P < .001). CONCLUSIONS: In our external validation in the Athens Stroke Registry cohort, the ISAN score predicted SAP very accurately in AIS patients and demonstrated good discriminatory power in the ICH group. Further validation and assessment of clinical usefulness would strengthen the score's utility further.

Retinal damage induced by commercial light emitting diodes (LEDs).

Spectra of "white LEDs" are characterized by an intense emission in the blue region of the visible spectrum, absent in daylight spectra. This blue component and the high intensity of emission are the main sources of concern about the health risks of LEDs with respect to their toxicity to the eye and the retina. The aim of our study was to elucidate the role of blue light from LEDs in retinal damage. Commercially available white LEDs and four different blue LEDs (507, 473, 467, and 449nm) were used for exposure experiments on Wistar rats. Immunohistochemical stain, transmission electron microscopy, and Western blot were used to exam the retinas. We evaluated LED-induced retinal cell damage by studying oxidative stress, stress response pathways, and the identification of cell death pathways. LED light caused a state of suffering of the retina with oxidative damage and retinal injury. We observed a loss of photoreceptors and the activation of caspase-independent apoptosis, necroptosis, and necrosis. A wavelength dependence of the effects was observed. Phototoxicity of LEDs on the retina is characterized by a strong damage of photoreceptors and by the induction of necrosis.

Sex ratio bias, male aggression, and population collapse in lizards.

The adult sex ratio (ASR) is a key parameter of the demography of human and other animal populations, yet the causes of variation in ASR, how individuals respond to this variation, and how their response feeds back into population dynamics remain poorly understood. A prevalent hypothesis is that ASR is regulated by intrasexual competition, which would cause more mortality or emigration in the sex of increasing frequency. Our experimental manipulation of populations of the common lizard (Lacerta vivipara) shows the opposite effect. Male mortality and emigration are not higher under male-biased ASR. Rather, an excess of adult males begets aggression toward adult females, whose survival and fecundity drop, along with their emigration rate. The ensuing prediction that adult male skew should be amplified and total population size should decline is supported by long-term data. Numerical projections show that this amplifying effect causes a major risk of population extinction. In general, such an "evolutionary trap" toward extinction threatens populations in which there is a substantial mating cost for females, and environmental changes or management practices skew the ASR toward males.

Operational sex ratio, sexual conflict and the intensity of sexual selection.

Modern sexual selection theory indicates that reproductive costs rather than the operational sex ratio predict the intensity of sexual selection. We investigated sexual selection in the polygynandrous common lizard Lacerta vivipara. This species shows male aggression, causing high mating costs for females when adult sex ratios (ASR) are male-biased. We manipulated ASR in 12 experimental populations and quantified the intensity of sexual selection based on the relationship between reproductive success and body size. In sharp contrast to classical sexual selection theory predictions, positive directional sexual selection on male size was stronger and positive directional selection on female size weaker in female-biased populations than in male-biased populations. Thus, consistent with modern theory, directional sexual selection on male size was weaker in populations with higher female mating costs. This suggests that the costs of breeding, but not the operational sex ratio, correctly predicted the strength of sexual selection.

Sex- and melanism-specific variations in the oxidative status of adult tawny owls in response to manipulated reproductive effort.

Oxidative stress, determined by the balance between the production of damaging reactive oxygen species (ROS) and antioxidant defences, is hypothesized to play an important role in shaping the cost of reproduction and life history trade-offs. To test this hypothesis, we manipulated reproductive effort in 94 breeding pairs of tawny owls (Strix aluco) to investigate the sex- and melanism-specific effects on markers of oxidative stress in red blood cells (RBCs). This colour polymorphic bird species shows sex-specific division of labour and melanism-specific history strategies. Brood sizes at hatching were experimentally enlarged or reduced to increase or decrease reproductive effort, respectively. We obtained an integrative measure of the oxidative balance by measuring ROS production by RBCs, intracellular antioxidant glutathione levels and membrane resistance to ROS. We found that light melanic males (the sex undertaking offspring food provisioning) produced more ROS than darker conspecifics, but only when rearing an enlarged brood. In both sexes, light melanic individuals had also a larger pool of intracellular antioxidant glutathione than darker owls under relaxed reproductive conditions (i.e. reduced brood), but not when investing substantial effort in current reproduction (enlarged brood). Finally, resistance to oxidative stress was differently affected by the brood size manipulation experiment in males and females independently of their plumage coloration. Altogether, our results support the hypothesis that reproductive effort can alter the oxidative balance in a sex- and colour-specific way. This further emphasizes the close link between melanin-based coloration and life history strategies.

High-density linkage maps fail to detect any genetic component to sex determination in a Rana temporaria family.

Sex chromosome differentiation in Rana temporaria varies strikingly among populations or families: whereas some males display well-differentiated Y haplotypes at microsatellite markers on linkage group 2 (LG2 ), others are genetically undistinguishable from females. We analysed with RADseq markers one family from a Swiss lowland population with no differentiated sex chromosomes, and where sibship analyses had failed to detect any association between the phenotypic sex of progeny and parental haplotypes. Offspring were reared in a common tank in outdoor conditions and sexed at the froglet stage. We could map a total of 2177 SNPs (1123 in the mother, 1054 in the father), recovering in both adults 13 linkage groups (= chromosome pairs) that were strongly syntenic to Xenopus tropicalis despite > 200 My divergence. Sexes differed strikingly in the localization of crossovers, which were uniformly distributed in the female but limited to chromosome ends in the male. None of the 2177 markers showed significant association with offspring sex. Considering the very high power of our analysis, we conclude that sex determination was not genetic in this family; which factors determined sex remain to be investigated.

Female common lizards (Lacerta vivipara) do not adjust their sex-biased investment in relation to the adult sex ratio.

Sex allocation theory predicts that facultative maternal investment in the rare sex should be favoured by natural selection when breeders experience predictable variation in adult sex ratios (ASRs). We found significant spatial and predictable interannual changes in local ASRs within a natural population of the common lizard where the mean ASR is female-biased, thus validating the key assumptions of adaptive sex ratio models. We tested for facultative maternal investment in the rare sex during and after an experimental perturbation of the ASR by creating populations with female-biased or male-biased ASR. Mothers did not adjust their clutch sex ratio during or after the ASR perturbation, but produced sons with a higher body condition in male-biased populations. However, this differential sex allocation did not result in growth or survival differences in offspring. Our results thus contradict the predictions of adaptive models and challenge the idea that facultative investment in the rare sex might be a mechanism regulating the population sex ratio.

What young people with spina bifida want to know about sex and are not being told.

OBJECTIVE: The aim of this paper was to examine sexual knowledge, concerns and needs of youth with spina bifida (SB) to inform the medical community on ways to better support their sexual health. METHODS: As part of the Video Intervention/Prevention Assessment (VIA) - transitions, a prospective cohort study, 309 h of video data were collected from 14 participants (13-28 years old) with SB. Participants were loaned a video camcorder for 8-12 weeks to shoot visual narratives about any aspects of their lives. V/A visual narratives were analysed with grounded theory using NVivo. RESULTS: Out of 14 participants, 11 (six women) addressed issues surrounding romantic relationships and sexuality in their video clips. Analysis revealed shared concerns, questions and challenges regarding sexuality gathered under four main themes: romantic relationships, sexuality, fertility and parenthood, and need for more talk on sexuality. CONCLUSIONS: Youth with SB reported difficulties in finding answers to questions regarding their sexuality, romantic relationships and fertility. This study revealed a need for help from the medical community to inform and empower youth with SB in the area of sexual health. Through sexual and reproductive health education with patients and parents starting at an early age, medical providers can further encourage healthy emotional and physical development in adolescents transitioning into adulthood.

High-density sex-specific linkage maps of a European tree frog (Hyla arborea) identify the sex chromosome without information on offspring sex.

Identifying homology between sex chromosomes of different species is essential to understanding the evolution of sex determination. Here, we show that the identity of a homomorphic sex chromosome pair can be established using a linkage map, without information on offspring sex. By comparing sex-specific maps of the European tree frog Hyla arborea, we find that the sex chromosome (linkage group 1) shows a threefold difference in marker number between the male and female maps. In contrast, the number of markers on each autosome is similar between the two maps. We also find strongly conserved synteny between H. arborea and Xenopus tropicalis across 200 million years of evolution, suggesting that the rate of chromosomal rearrangement in anurans is low. Finally, we show that recombination in males is greatly reduced at the centers of large chromosomes, consistent with previous cytogenetic findings. Our research shows the importance of high-density linkage maps for studies of recombination, chromosomal rearrangement and the genetic architecture of ecologically or economically important traits.