The generation of complex morphological features requires the precisely orchestrated expression of numerous genes during development. While several traits have been resolved to evolutionary changes ...within a single gene, the evolutionary path by which genes derive co-localized or mutually excluded expression patterns is currently a mystery. Here we investigate how the Drosophila pigmentation gene network was altered in Drosophila prostipennis, a species in the Drosophila melanogaster subgroup, that evolved expanded abdominal pigmentation. We show that this expansion involved broadened expression of the melanin-promoting enzyme genes tan and yellow, and a reciprocal withdrawn pattern of the melanin-suppressing enzyme gene ebony. To examine whether these coordinated changes to the network were generated through mutations in the cis-regulatory elements (CREs) of these genes, we cloned and tested CREs of D. prostipennis tan, ebony, and yellow in transgenic reporter assays. Regulatory regions of both tan and ebony failed to recapitulate the derived D. prostipennis expression phenotype, implicating the modification of a factor or factors upstream of both genes. However, the D. prostipennis yellow cis-regulatory region recapitulated the expanded expression pattern observed in this species, implicating causative mutations in cis to yellow. Our results provide an example in which a coordinated expression program evolved through independent changes at multiple loci, rather than through changes to a single “master regulator” directing a suite of downstream target genes. This implies a complex network structure in which each gene may be subject to a unique set of inputs, and resultantly may require individualized evolutionary paths to yield correlated gene expression patterns.
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•Coordinated patterning of three genes underlies an expanded pigmentation phenotype.•Complimentary changes to tan and ebony are caused by altered trans-acting factors.•Direct changes in cis to yellow contributed to its expanded expression pattern.•The evolution of coordinated expression patterns can be uncoupled from one another.
For HIV-1 serodiscordant couples, HIV-1 exposure and risk of transmission is heightened during pregnancy attempts, but safer conception strategies can reduce risk. As safer conception programs are ...scaled up, understanding couples' preferences and experiences can be useful for programmatic recommendations. We followed 1013 high-risk, heterosexual HIV-1 serodiscordant couples from Kenya and Uganda for two years in an open-label delivery study of integrated pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), the Partners Demonstration Project. We used descriptive statistics to describe the cohort and multivariate logistic regression to characterize women who reported use of a safer conception strategy by their first annual visit. 66% (569/859) of women in the study were HIV-infected and 73% (627/859) desired children in the future. At the first annual visit, 59% of women recognized PrEP, 58% ART, 50% timed condomless sex, 23% self-insemination, and fewer than 10% recognized male circumcision, STI treatment, artificial insemination, and sperm washing as safer conception strategies. Among those recognizing these strategies and desiring pregnancy, 37% reported using PrEP, 14% ART, and 30% timed condomless sex. Women who reported discussing their fertility desires with their male partners were more likely to report having used at least one strategy for safer conception (adjusted odds ratio = 1.91, 95% confidence interval:1.26-2.89). Recognition of use of safer conception strategies among women who expressed fertility desires was low, with ARV-based strategies and self-insemination the more commonly recognized and used strategies. Programs supporting HIV-1 serodiscordant couples can provide opportunities for couples to talk about their fertility desires and foster communication around safer conception practices.
Understanding fertility desires and preferences for HIV prevention among individuals living with HIV, including the potential use of pre-exposure prophylaxis (PrEP) by HIV uninfected partners, can ...inform the delivery of safer conception counseling to reduce the risk of HIV transmission during pregnancy attempts. Men and women, predominantly heterosexual, engaged in HIV care in Seattle, WA, self-administered a questionnaire and we abstracted antiretroviral therapy (ART) status and HIV viral levels from medical records. We summarized participants' sexual behavior, fertility desires, and preferences for safer conception strategies and used log-binomial regression to identify demographic, sexual, and behavioral factors associated with perceived acceptability of PrEP for HIV uninfected partners during pregnancy attempts. 52% of the 150 participants were female and the mean age was 48 years (range 23-74). 94.7% of participants were using ART and 79.3% had HIV viral load < 40 copies/mL. 22.2% of men and 34.6% of women reported that a healthcare provider had initiated discussion about fertility desires. 28.7% of participants were reproductive-age and desired children. Among sexually active reproductive-age participants with fertility desires, 56.3% reported inconsistent condom use and 62.5% did not report using effective birth control. 74.4% of reproductive age participants with fertility desires perceived that PrEP would be acceptable to an HIV uninfected partner and there were no significant predictors of PrEP acceptability. Nearly one third of reproductive-aged individuals living with HIV expressed fertility desires, highlighting a need for safer conception counseling in this setting. PrEP and ART were favored safer conception strategies.
There is a variability regarding timing of consent and personnel used in patient recruitment for neonatal research. We explored the associations between the study personnel and timing of consent with ...parents' decisional conflict and ultimately their decision to enroll.
This was a multi-site, cross-sectional survey conducted between August 2015 and October 2017. Participants were parents approached to enroll their 24-28-week infant in a clinical trial. Parents completed an interviewer-administered 61-item questionnaire.
Overall, 163 surveys were completed; 105 by parents of enrolled infants and 58 by parents of non-enrolled infants (54.5% participation rate). Neither the individual requesting nor timing of consent was associated with parents' knowledge score, decisional conflict, or decision to enroll. Parents preferred to be approached prenatally and by their infant's doctor.
Study designers and IRBs may allow flexibility in personnel and timing of consent as it is respectful of parents and may enhance trial enrollment.
Context: Supporting people affected by HIV-1 in achieving their reproductive goals while minimizing the risk of HIV-1 transmission is a public health imperative. Background: For HIV-1 serodiscordant ...couples, HIV-1 exposure and risk of transmission to the uninfected partner and unborn children is heightened during pregnancy attempts but safer conception strategies can mitigate risk. Understanding couples’ choices and experiences with safer conception can be useful for programmatic recommendations as safer conception programs are scaled up. Methods: 1013 high-risk, heterosexual HIV-1 serodiscordant couples from Kenya and Uganda were followed for two years in an open-label delivery study of integrated pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), the Partners Demonstration Project. Annually, we assessed participant experience with safer conception strategies. Multivariate logistic regression was used to characterize women who reported ever having used a safer conception strategy during their first annual visit. Results: 859 couples were included in analysis. 66% of couples had HIV-infected women and 86% desired future children. The median age for women was 27 (interquartile range: 23-32). At the first annual visit, 32% of women reported use of a safer conception strategy ever in their life: 14% reported using ART, 16% PrEP, 3% self-insemination, and 2% STI treatment. Women who reported discussing their fertility desires with their male partners (adjusted odds ratio (aOR) = 1.91, 95% confidence interval (CI) 1.26-2.589), had no living children at the time of study enrollment (aOR = 1.71, 95% CI 1.14-2.57), and were HIV-uninfected (aOR = 1.56, 95% CI 1.11-2.20) were more likely to report having used at least one safer conception strategy. Conclusions: HIV-1 prevention counseling for serodiscordant couples should integrate opportunities for couples to share their fertility desires and discuss preferences for safer conception strategies.
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