Coupled spin models for magnetic variation of planets and stars

Geomagnetism is characterized by intermittent polarity reversals and rapid fluctuations. We have recently proposed a coupled macro-spin model to describe these dynamics based on the idea that the whole dynamo mechanism is described by the coherent interactions of many small dynamo elements. In this paper, we further develop this idea and construct a minimal model for magnetic variations. This simple model naturally yields many of the observed features of geomagnetism: its time evolution, the power spectrum, the frequency distribution of stable polarity periods, etc. This model has coexistent two phases; i.e. the cluster phase which determines the global dipole magnetic moment and the expanded phase which gives random perpetual perturbations that yield intermittent polarity flip of the dipole moment. This model can also describe the synchronization of the spin oscillation. This corresponds to the case of sun and the model well describes the quasi-regular cycles of the solar magnetism. Furthermore, by analyzing the relevant terms of MHD equation based on our model, we have obtained a scaling relation for the magnetism for planets, satellites, sun, and stars. Comparing it with various observations, we can estimate the scale of the macro-spins.Comment: 16 pages, 9 figure

Six Decades of Research on Human Fetal Gonadal Steroids

Acknowledgments: All authors wish to dedicate this review to Bernard Jégou who enabled their meeting, and who was a perpetual source of inspiration for their research on human fetal gonads and in particular on their steroidogenic capacities with testes as ovaries. Funding: This work was funded by the European Union’s Horizon 2020 FREIA (grant agreement No. 825100) and the Marie Skłodowska‐Curie PROTECTED projects (grant agreement No. 722634 to P.A.F.). P.A.F., S.C.P., P.L., and L.L. are FREIA project recipients. T.L. was a recipient of funding from the French agency for food and safety (Anses).Peer reviewedPublisher PD

Dynamics of the transcriptional landscape during human fetal testis and ovary development

Acknowledgements We thank all members of the SEQanswers forums for helpful advice; Steven Salzberg and Cole Trapnell for continuous support with the ‘Tuxedo’ suite; and the UCSC Genome team members. Sequencing was performed by the GenomEast platform, a member of the ‘France Génomique’ consortium (ANR-10-INBS-0009). We thank Ms Linda Robertson, Ms Margaret Fraser, Ms Samantha Flannigan (University of Aberdeen) and the staff at Grampian NHS Pregnancy Counselling Service and all the staff of the Department of Obstetrics and Gynecology of the Rennes Sud Hospital for their expert assistance and help, and the participating women, without whom this study would not have been possible. The authors are grateful for Ms Gersende Lacombe and Mr Laurent Deleurme from the Biosit CytomeTri cytometry core facility of Rennes 1 University. Funding French National Institute of Health and Medical Research (Inserm); University of Rennes 1; French School of Public Health (EHESP); Swiss National Science Foundation [SNF n° CRS115_171007 to B.J.]; the French National Research Agency [ANR n° 16-CE14-0017-02 and n°18-CE14-0038-02 to F.C]; Medical Research Council [MR/L010011/1 to PAF]; European Community’s Seventh Framework Programme (FP7/2007–2013) [under grant agreement no 212885 to PAF]; European Union’s Horizon 2020 Research and Innovation Programme [under grant agreement no 825100 to P.A.F. and S.M.G.].Peer reviewedPostprin

Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants

Reproduced with permission from Environmental Health PerspectivesNumerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life.Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals.We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10-12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures.We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose-response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight.Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life.We thank all the staff of the Department of Obstetrics and Gynecology and the Department of Pediatric Surgery of the Rennes Sud Hospital (Rennes, France) and the participating women, without whom this study would not have been possible. We acknowledge the financial supports from the Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES) ; CHEMIX-EST-12-171, ChemPSy- EST-13-081, Institut National de la Santé et de la Recherche Médicale (Inserm). P.Gaudriault is a recipient of a stipend of the Fondation pour la Recherche Médicale

Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals

Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause-effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difficult to assess the risks chemical exposures pose to a woman's reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can affect female reproductive health. We have a special focus on effects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause-effect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This effort is an important step towards better safeguarding the reproductive health of all girls and women.Peer reviewe

Safeguarding Female Reproductive Health against Endocrine Disrupting Chemicals : The FREIA Project

Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 825100.Peer reviewedPublisher PD

A roadmap for the Human Developmental Cell Atlas

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development