ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer

We have previously shown that during pregnancy the E-twenty-six (ETS) transcription factor ELF5 directs the differentiation of mammary progenitor cells toward the estrogen receptor (ER)-negative and milk producing cell lineage, raising the possibility that ELF5 may suppress the estrogen sensitivity of breast cancers. To test this we constructed inducible models of ELF5 expression in ER positive luminal breast cancer cells and interrogated them using transcript profiling and chromatin immunoprecipitation of DNA followed by DNA sequencing (ChIP-Seq). ELF5 suppressed ER and FOXA1 expression and broadly suppressed ER-driven patterns of gene expression including sets of genes distinguishing the luminal molecular subtype. Direct transcriptional targets of ELF5, which included FOXA1, EGFR, and MYC, accurately classified a large cohort of breast cancers into their intrinsic molecular subtypes, predicted ER status with high precision, and defined groups with differential prognosis. Knockdown of ELF5 in basal breast cancer cell lines suppressed basal patterns of gene expression and produced a shift in molecular subtype toward the claudin-low and normal-like groups. Luminal breast cancer cells that acquired resistance to the antiestrogen Tamoxifen showed greatly elevated levels of ELF5 and its transcriptional signature, and became dependent on ELF5 for proliferation, compared to the parental cells. Thus ELF5 provides a key transcriptional determinant of breast cancer molecular subtype by suppression of estrogen sensitivity in luminal breast cancer cells and promotion of basal characteristics in basal breast cancer cells, an action that may be utilised to acquire antiestrogen resistance

The current state of the use of large wood in river restoration and management

Trees fall naturally into rivers generating flow heterogeneity, inducing geomorphological features, and creating habitats for biota. Wood is increasingly used in restoration projects and the potential of wood acting as leaky barriers to deliver natural flood management by “slowing the flow” is recognised. However, wood in rivers can pose a risk to infrastructure and locally increase flood hazards. The aim of this paper is to provide an up-to-date summary of the benefits and risks associated with using wood to promote geomorphological processes to restore and manage rivers. This summary was developed through a workshop that brought together academics, river managers, restoration practitioners and consultants in the UK to share science and best-practice on wood in rivers. A consensus was developed on four key issues: (i) hydro-geomorphological effects, (ii) current use in restoration and management, (iii) uncertainties and risks, and (iv) tools and guidance required to inform process-based restoration and management

Tropical Rains Controlling Deposition of Saharan Dust Across the North Atlantic Ocean

Mineral dust plays an important role in the atmospheric radiation budget as well as in the ocean carbon cycle through fertilization and by ballasting of settling organic matter. However, observational records of open-ocean dust deposition are sparse. Here, we present the spatial and temporal evolution of Saharan dust deposition over 2 years from marine sediment traps across the North Atlantic, directly below the core of the Saharan dust plume, with highest dust fluxes observed in summer. We combined the observed deposition fluxes with model simulations and satellite observations and argue that dust deposition in the Atlantic is predominantly controlled by summer rains. The dominant depositional pathway changes from wet deposition in summer to dry deposition in winter. Wet deposition has previously been suggested to increase the release of dust-derived nutrients and their bioavailability, which may be a key contributor to surface-ocean productivity in remote and oligotrophic parts of the oceans

hCEACAM1-4L downregulates hDAF-associated signalling after being recognized by the Dr adhesin of diffusely adhering Escherichia coli.

International audienceHuman decay accelerating factor (hDAF, CD55) and members of the carcinoembryonic-antigen-related cell-adhesion molecules (hCEACAMs) family are recognized as receptors by Gram-negative, diffusely adhering Escherichia coli (DAEC) strains expressing Afa/Dr adhesins. We report here that hCEACAM1-4L has a key function in downregulating the protein tyrosine Src kinase associated with hDAF signalling. After infecting HeLa epithelial cells stably transfected with hCEACAM1-4L cDNA with Dr adhesin-positive E. coli, the amount of the pTyr(416)-active form of the Src protein decreased, whereas that of the pTyr(527)-inactive form of Src protein did not increase. This downregulation of the Src protein implies that part of the hCEACAM1-4L protein had been translocated into lipid rafts, the protein was phosphorylated at Tyr residues in the cytoplasmic domain, and it was physically associated with the protein tyrosine phosphatase, SHP-2. Finally, we found that the hCEACAM1-4L-associated SHP-2 was not phosphorylated and lacked phosphatase activity, suggesting that the downregulation of Src protein associated with hDAF signalling results from the absence of dephosphorylation of the pTyr(527)-inactive form necessary for Src kinase activation