Perturbation of the Developmental Potential of Preimplantation Mouse Embryos by Hydroxyurea

Women are advised not to attempt pregnancy while on hydroxyurea (HU) due to the teratogenic effects of this agent, based on results obtained from animal studies. Several case reports suggest that HU may have minimal or no teratogenic effects on the developing human fetus. Fourteen cases of HU therapy in pregnant patients diagnosed with acute or chronic myelogenous leukemia, primary thrombocythemia, or sickle cell disease (SCD) have been reported. Three pregnancies were terminated by elective abortion; 1 woman developed eclampsia and delivered a phenotypically normal stillborn infant. All other patients delivered live, healthy infants without congenital anomalies. We contend that case studies such as these have too few patients and cannot effectively address the adverse effect of HU on preimplantation embryo or fetuses. The objective of this study was to assess the risks associated with a clinically relevant dose of HU used for the treatment of SCD, on ovulation rate and embryo development, using adult C57BL/6J female mice as a model. In Experiment 1, adult female mice were randomly assigned to a treatment or a control group (N = 20/group). Treatment consisted of oral HU (30 mg/kg) for 28 days; while control mice received saline (HU vehicle). Five days to the cessation of HU dosing, all mice were subjected to folliculogenesis induction with pregnant mare serum gonadotropin (PMSG). Five mice/group were anesthetized at 48 hours post PMSG to facilitate blood collection via cardiac puncture for estradiol-17β (E2) measurement by RIA. Ovulation was induced in the remaining mice at 48 hours post PMSG with human chorionic gonadotropin (hCG) and immediately caged with adult males for mating. Five plugged female mice/group were sacrificed for the determination of ovulation rate. The remaining mated mice were sacrificed about 26 hours post hCG, ovaries excised and weighed and embryos harvested and cultured in Whitten’s medium (WM) supplemented with CZBt. In Experiments 2 and 3, (N = 10/Experiment) folliculogenesis and ovulation were induced in untreated mice followed by mating. Recovered embryos were either exposed continuously (Experiment 2) or intermittently (Experiment 3) to bioavailable HU (18 μg HU/mL of WM + CZBt) or WM + CZBt only (control). Treated mice sustained decreased ovarian wt, ovulation rate and circulating E2 compared with controls (P < 0.05). Fewer embryos retrieved from HU-treated mice developed to blastocyst stage (32%) compared with those from controls (60%; P < 0.05). Furthermore, continuous or intermittent in vitro exposures of embryos to HU also resulted in reduced development to blastocyst stage (continuous HU, 9 vs. control, 63%; P < 0.05; intermittent HU, 20 vs. control, 62%; P < 0.05) with embryos exposed continuously to HU in vitro fairing worse. Even though HU is well tolerated, our data suggest that it compromises folliculogenesis and the ability of generated embryos to develop. Therefore, designed studies with larger numbers of patients receiving HU during pregnancy, with longer follow-up of exposed children and more careful assessment of embryo/fetotoxic effects, are required before this agent can be promoted as safe in pregnancy

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Strengthening accountability for improved maternal and newborn health : a mapping of studies in Sub-Saharan Africa

To describe the types of maternal and newborn health program accountability mechanisms implemented and evaluated in recent years in Sub-Saharan Africa, how these have been implemented, their effectiveness, and future prospects to improve governance and MNH outcomes.; A structured review selected 38 peer-reviewed papers between 2006 and 2016 in Sub-Saharan Africa to include in the analysis.; Performance accountability in MNH through maternal and perinatal death surveillance was the most common accountability mechanism used. Political and democratic accountability through advocacy, human rights, and global tracking of progress on indicators achieved greatest results when multiple stakeholders were involved. Financial accountability can be effective but depend on external support. Overall, this review shows that accountability is more effective when clear expectations are backed by social and political advocacy and multistakeholder engagement, and supported by incentives for positive action.; There are few accountability mechanisms in MNH in Sub-Saharan Africa between decision-makers and those affected by those decisions with both the power and the will to enforce answerability. Increasing accountability depends not only on how mechanisms are enforced but also, on how providers and managers understand accountability

Large hydraulic safety margins protect Neotropical canopy rainforest tree species against hydraulic failure during drought

AbstractKey messageAbundant Neotropical canopy-tree species are more resistant to drought-induced branch embolism than what is currently admitted. Large hydraulic safety margins protect them from hydraulic failure under actual drought conditions.ContextXylem vulnerability to embolism, which is associated to survival under extreme drought conditions, is being increasingly studied in the tropics, but data on the risk of hydraulic failure for lowland Neotropical rainforest canopy-tree species, thought to be highly vulnerable, are lacking.AimsThe purpose of this study was to gain more knowledge on species drought-resistance characteristics in branches and leaves and the risk of hydraulic failure of abundant rainforest canopy-tree species during the dry season.MethodsWe first assessed the range of branch xylem vulnerability to embolism using the flow-centrifuge technique on 1-m-long sun-exposed branches and evaluated hydraulic safety margins with leaf turgor loss point and midday water potential during normal- and severe-intensity dry seasons for a large set of Amazonian rainforest canopy-tree species.ResultsTree species exhibited a broad range of embolism resistance, with the pressure threshold inducing 50% loss of branch hydraulic conductivity varying from − 1.86 to − 7.63 MPa. Conversely, we found low variability in leaf turgor loss point and dry season midday leaf water potential, and mostly large, positive hydraulic safety margins.ConclusionsRainforest canopy-tree species growing under elevated mean annual precipitation can have high resistance to embolism and are more resistant than what was previously thought. Thanks to early leaf turgor loss and high embolism resistance, most species have a low risk of hydraulic failure and are well able to withstand normal and even severe dry seasons