In Vitro Effects of the Endocrine Disruptor p,p’-DDT on Human Follitropin Receptor

BACKGROUND: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p\u27-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p\u27-DDT exposure and reproductive abnormalities. OBJECTIVES: To investigate the putative effects of p,p\u27-DDT on the human follitropin receptor (FSHR) function. METHODS AND RESULTS: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p\u27-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p\u27-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p\u27-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p\u27-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p\u27-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p\u27-DDT was dependent on the FSHR. In addition, p,p\u27-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p\u27-DDT and potentiation of the FSHR response to FSH by p,p\u27-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p\u27-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p\u27-DDT and 16a into the FSHR transmembrane bundle. CONCLUSION:p,p\u27-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein-coupled receptors are additional targets of endocrine disruptor

Black holes and Hawking radiation in spacetime and its analogues

These notes introduce the fundamentals of black hole geometry, the thermality of the vacuum, and the Hawking effect, in spacetime and its analogues. Stimulated emission of Hawking radiation, the trans-Planckian question, short wavelength dispersion, and white hole radiation in the setting of analogue models are also discussed. No prior knowledge of differential geometry, general relativity, or quantum field theory in curved spacetime is assumed.Comment: 31 pages, 9 figures; to appear in the proceedings of the IX SIGRAV School on 'Analogue Gravity', Como (Italy), May 2011, eds. D. Faccio et. al. (Springer

Toward Forecasting Volcanic Eruptions using Seismic Noise

During inter-eruption periods, magma pressurization yields subtle changes of the elastic properties of volcanic edifices. We use the reproducibility properties of the ambient seismic noise recorded on the Piton de la Fournaise volcano to measure relative seismic velocity variations of less than 0.1 % with a temporal resolution of one day. Our results show that five studied volcanic eruptions were preceded by clearly detectable seismic velocity decreases within the zone of magma injection. These precursors reflect the edifice dilatation induced by magma pressurization and can be useful indicators to improve the forecasting of volcanic eruptions.Comment: Supplementary information: http://www-lgit.obs.ujf-grenoble.fr/~fbrengui/brenguier_SI.pdf Supplementary video: http://www-lgit.obs.ujf-grenoble.fr/~fbrengui/brenguierMovieVolcano.av