BRCA1 protein dose-dependent risk for embryonic oxidative DNA damage, embryopathies and neurodevelopmental disorders with and without ethanol exposure.

Although widely known as a tumor suppressor, the breast cancer 1 susceptibility protein (BRCA1) is also important in development, where it regulates fetal DNA repair pathways that protect against DNA damage caused by physiological and drug-enhanced levels of reactive oxygen species (ROS). We previously showed that conditional heterozygous (+/-) knockout (cKO) mouse embryos with a minor 28% BRCA1 deficiency developed normally in culture, but when exposed to the ROS-initiating drug, alcohol (ethanol, EtOH), exhibited embryopathies not evident in wild-type (+/+) littermates. Herein, we characterized a directBrca1 +/- knockout (KO) model with a 2-fold greater (58%) reduction in BRCA1 protein vs. the cKO model. We also characterized and compared learning & memory deficits in both the cKO and KO models. Even saline-exposed Brca1 +/- vs. +/+ KO progeny exhibited enhanced oxidative DNA damage and embryopathies in embryo culture and learning & memory deficits in females in vivo, which were not observed in the cKO model, revealing the potential pathogenicity of physiological ROS levels. The embryopathic EtOH concentration for cultured direct KO embryos was half that for cKO embryos, and EtOH affected Brca1 +/+ embryos only in the direct KO model. The spectrum and severity of EtOH embryopathies in culture were greater in both Brca1 +/- vs. +/+ embryos, and direct KO vs. cKO +/- embryos. Motor coordination deficits were evident in both male and female Brca1 +/- KO progeny exposed in utero to EtOH. The results in our direct KO model with a greater BRCA1 deficiency vs. cKO mice provide the first evidence for BRCA1 protein dose-dependent susceptibility to developmental disorders caused by physiological and drug-enhanced oxidative stress.

The UN Joint Group of Experts on the Scientific Aspects of Marine Environmental Protection (GESAMP) - An ocean science-policy interface standing the test of time.

Addressing the wide range of marine pollution problems facing the global ocean requires a continual transfer of credible, relevant and timely scientific information to policy and decision makers in coastal and ocean management. The United Nations GESAMP (Joint Group of Experts on the Scientific Aspects of Marine Environmental Protection) is a long-standing scientific advisory group providing such information on a wide range of marine topics and emerging issues of concern to ten UN Sponsoring Organizations. This paper presents an overview of GESAMPs operation and examples of its current work. The group's scientific output is often cited by national governments, inter-governmental groups, and a range of non-governmental groups. Given the growing concerns about ocean health and the impacts of many stressors in an era of climate change, the development of timely and effective ocean policy and decision making would benefit from wider recognition and application of GESAMPs work.