Tamoxifen mechanically deactivates hepatic stellate cells via the G protein-coupled estrogen receptor

Tamoxifen has been used for many years to target estrogen receptor signalling in breast cancer cells. Tamoxifen is also an agonist of the G protein-coupled estrogen receptor (GPER), a GPCR ubiquitously expressed in tissues that mediates the acute response to estrogens. Here we report that tamoxifen promotes mechanical quiescence in hepatic stellate cells (HSCs), stromal fibroblast-like cells whose activation triggers and perpetuates liver fibrosis in hepatocellular carcinomas. This mechanical deactivation is mediated by the GPER/RhoA/myosin axis and induces YAP deactivation. We report that tamoxifen decreases the levels of hypoxia-inducible factor-1 alpha (HIF-1α) and the synthesis of extracellular matrix proteins through a mechanical mechanism that involves actomyosin-dependent contractility and mechanosensing of tissue stiffness. Our results implicate GPER-mediated estrogen signalling in the mechanosensory-driven activation of HSCs and put forward estrogenic signalling as an option for mechanical reprogramming of myofibroblast-like cells in the tumour microenvironment. Tamoxifen, with half a century of safe clinical use, might lead this strategy of drug repositioning.Peer reviewe

Effects of vessel traffic on relative abundance and behaviour of cetaceans : the case of the bottlenose dolphins in the Archipelago de La Maddalena, north-western Mediterranean sea

Acknowledgements This study was part of the Tursiops Project of the Dolphin Research Centre of Caprera, La Maddalena. Financial and logistical support was provided by the Centro Turistico Studentesco (CTS) and by the National Park of the Archipelago de La Maddalena. We thank the Natural Reserve of Bocche di Bonifacio for the support provided during data collection. The authors thank the numerous volunteers of the Caprera Dolphin Research Centre and especially Marco Ferraro, Mirko Ugo, Angela Pira and Maurizio Piras whose assistance during field observation and skills as a boat driver were invaluable.Peer reviewedPostprin

Use of Complex Lie Symmetries for Linearization of Systems of Differential Equations - II: Partial Differential Equations

The linearization of complex ordinary differential equations is studied by extending Lie's criteria for linearizability to complex functions of complex variables. It is shown that the linearization of complex ordinary differential equations implies the linearizability of systems of partial differential equations corresponding to those complex ordinary differential equations. The invertible complex transformations can be used to obtain invertible real transformations that map a system of nonlinear partial differential equations into a system of linear partial differential equation. Explicit invariant criteria are given that provide procedures for writing down the solutions of the linearized equations. A few non-trivial examples are mentioned.Comment: This paper along with its first part ODE-I were combined in a single research paper "Linearizability criteria for systems of two second-order differential equations by complex methods" which has been published in Nonlinear Dynamics. Due to citations of both parts I and II these are not replaced with the above published articl

Realizations of Real Low-Dimensional Lie Algebras

Using a new powerful technique based on the notion of megaideal, we construct a complete set of inequivalent realizations of real Lie algebras of dimension no greater than four in vector fields on a space of an arbitrary (finite) number of variables. Our classification amends and essentially generalizes earlier works on the subject. Known results on classification of low-dimensional real Lie algebras, their automorphisms, differentiations, ideals, subalgebras and realizations are reviewed.Comment: LaTeX2e, 39 pages. Essentially exetended version. Misprints in Appendix are correcte

Which contamination of the seagrass Posidonia oceanica along the Provence coast (France, nw mediterranean sea) ?

International audienc

Does trophic level drive organic and metallic contamination in coral reef organisms?

International audienceMetallic and organic pollutants constitute a serious threat for coral reef ecosystems, potentially affecting a great number of species interacting within complex trophodynamic processes. Pesticides, PCBs and trace elements were measured on coral reef communities of three Pacific islands (Moorea, Wallis and New Caledonia) in relation with d15N values, a proxy of trophic level. Several potential sources of organic matter, benthic invertebrates and fish belonging to various trophic strategies were sampled at each island. Wallis and New Caledonia displayed, respectively, the highest concentrations of pesticides and trace elements. In the three islands, most trace element concentrations (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and V) decreased when d15N was rising (i.e. bioreduction), whereas Hg and Se biomagnified with increasing d15N values. Only few trace elements in some islands did not show any significant trend in relation with d15N (i.e., Ag in New Caledonia, Zn in Wallis and As plus Zn in Moorea). PCBs concentrations showed a significant bioreduction in New Caledonia and in Moorea, but a significant biomagnification in Wallis. Aldrin and heptachlor were the only pesticides to show a similar significant bioreduction in the three islands. Other pesticides, such as chlordecone, diazinon, endosulfan I and II, heptachlor-epoxide A and B, lindane and pp’-DDE displayed contrasted patterns (e.g. chlordecone significantly biomagnified in New Caledonia, significantly bioreduced in Wallis and did not displayed any significant trend in Moorea). Finally, for unclear reasons, Moorea displayed only negative significant correlations between d15N and all pesticides (except pp’-DDT). Our results highlight that trophic level, here assessed through d15N values, is a good predictor of metallic trace elements biomagnification or bioreduction in coral reef organisms. However, at large spatial scale, trophic level relevance to predict pesticides and PCBs biomagnification or bioreduction should be considered with caution and studied in close relation with local characteristics

Evaluation of pollutant exposure by chemical and biological markers in a Mediterranean French urban stream: A step for in situ calibration of multixenobiotic resistance transporter expression as biomarker in Chironomidae larvae

International audienceThis study was aimed at semi-quantifying the membrane density of multixenobiotic resistance (MXR) transporters in Chironomidae Orthocladiinae larvae from an urban stream by ELISA assay. The relationships between the MXR transporter membrane density and limnological parameters and pollutant concentrations, 16 priority polycyclic aromatic hydrocarbons (PAHs), as per the US Environmental Protection Agency (EPA) and seven polychlorobiphenyl congeners (PCBs), were assessed. Midge larvae were collected, and limnological parameters and pollutant concentrations were measured in three sites of a French Mediterranean urban stream, two located after sewage treatment plants, and one closed to the river mouth, and in two additional sites, one on the stream tributary, and one in a non-urbanized stream located in the same region. Results show that the PAH and PCB contamination levels are different between sites and that some congener concentrations are above their threshold toxic effect level (TEL). The MXR transporter membrane density was significantly higher in larvae from the tributary, the most polluted site, as compared with larvae from the non-urbanized stream. The MXR transporter density was positively correlated with 10 of the 16 US-EPA PAH concentrations and the increase in the MXR transporter density seems to be due to the US-EPA PAH concentrations that were above their TEL. No relations with PCB concentrations or limnological parameters were found. The results suggest that the MXR transporter membrane density in Chironomidae larvae could be an interesting biological marker of PAH exposure in freshwater ecosystems

Pempom (volet 1) : polluants émergents, polluants organiques et métaux lours ; sources et devenir dans les écosystèmes récifo-lagonaires

Workshop "Au fil de l'eau", Nouméa, NCL, 17-/09/2019 - 18/09/201

Prevalence and intensity of Loa loa infection over twenty-three years in three communities of the Mbalmayo health district (Central Cameroon)

Abstract Background Loiasis is a vector-borne parasitic disease due to Loa loa and transmitted to humans by tabanids of the genus Chrysops. Loiasis has been historically considered as the second or third most common reason for medical consultation after malaria, and a recent study has reported an excess mortality associated with the infection. However, the clinical impact of this filarial disease is yet to be elucidated, and it is still considered a benign disease eliciting very little attention. As a consequence of post-treatment severe adverse events occurring in individuals harboring very high Loa microfilarial loads, ivermectin is not recommended in onchocerciasis hypo-endemic areas that are co-endemic for loiasis. Without treatment, it is likely that the transmission of the disease and the morbidity associated with the infection will increase over time. This study aimed at investigating the long-term trends in prevalence and intensity of Loa loa infection in an area where no mass anti-filarial treatment has ever been distributed. Methods A cross-sectional survey was conducted in three communities of the Mbalmayo health district (Central Cameroon). All volunteers, males and females aged five years and above, underwent daytime calibrated thick blood smears (CTBS) to search for L. loa microfilariae (mf). A structured questionnaire was administered to assess the history of both loiasis related clinical signs and migration of enrollees. Results The prevalence of loiasis was 27.3% (95% CI: 22.3–32.9) in the three surveyed communities, with a mean mf density of 1922.7 (sd: 6623.2) mf/mL. Loa loa infection rate was higher amongst females than in males (p = 0.0001) and was positively associated with age of (OR = 1.018; p = 0.007). The intensity of infection was higher among males than in females (p < 0.0001), and displayed a convex in form trends with age groups. The follow up over 23 years revealed that both the rate and intensity of infection were similar to baseline. Conclusions The prevalence and intensity of Loa loa infection 23 years on is stable over time, indicating that this filarial disease might be noncumulative as regarded till now