A Network-Scale Modeling Framework for Stream Metabolism, Ecosystem Efficiency, and Their Response to Climate Change

Climate change and the predicted warmer temperatures and more extreme hydrological regimes could affect freshwater ecosystems and their energy pathways. To appreciate the complex spatial and temporal interactions of carbon cycling in flowing waters, ecosystem metabolism (gross primary production [GPP] and ecosystem respiration [ER]) must be resolved at the scale of an entire river network. Here, we propose a meta-ecosystem framework that couples light and temperature regimes with a reach-scale ecosystem model and integrates network structure, catchment land cover, and the hydrologic regime. The model simulates the distributed functioning of dissolved and particulate organic carbon, autotrophic biomass, and thus ecosystem metabolism, and reproduces fairly well the metabolic regimes observed in 12 reaches of the Ybbs River network, Austria. Results show that the annual network-scale metabolism was heterotrophic, yet with a clear peak of autotrophy in spring. Autochthonous energy sources contributed 43% of the total ER. We further investigated the effect of altered thermal and hydrologic regimes on metabolism and ecosystem efficiency. We predicted that an increase of 2.5? in average stream water temperature could boost ER and GPP by 31% (24%-57%) and 28% (5%-57%), respectively. The effect of flashier hydrologic regimes is more complex and depends on autotrophic biomass density. The analysis shows the complex interactions between environmental conditions and biota in shaping stream metabolism and highlights the existing knowledge gaps for reliable predictions of the effects of climate change in these ecosystems

Radiotherapy-induced miR-223 prevents relapse of breast cancer by targeting the EGF pathway

In breast cancer (BC) patients, local recurrences often arise in proximity of the surgical scar, suggesting that response to surgery may have a causative role. Radiotherapy (RT) after lumpectomy significantly reduces the risk of recurrence. We investigated the direct effects of surgery and of RT delivered intraoperatively (IORT), by collecting irradiated and non-irradiated breast tissues from BC patients, after tumor removal. These breast tissue specimens have been profiled for their microRNA (miR) expression, in search of differentially expressed miR among patients treated or not with IORT. Our results demonstrate that IORT elicits effects that go beyond the direct killing of residual tumor cells. IORT altered the wound response, inducing the expression of miR-223 in the peri-tumoral breast tissue. miR-223 downregulated the local expression of epidermal growth factor (EGF), leading to decreased activation of EGF receptor (EGFR) on target cells and, eventually, dampening a positive EGF-EGFR autocrine/paracrine stimulation loop induced by the post-surgical wound-healing response. Accordingly, both RT-induced miR-223 and peri-operative inhibition of EGFR efficiently prevented BC cell growth and reduced recurrence formation in mouse models of BC. Our study uncovers unknown effects of RT delivered on a wounded tissue and prompts to the use of anti-EGFR treatments, in a peri-operative treatment schedule, aimed to timely treat BC patients and restrain recurrence formation.Oncogene advance online publication, 15 February 2016; doi:10.1038/onc.2016.23

A global view of the proteome perturbations by Hsp90 inhibitors

Heat shock protein 90 (Hsp90) is a highly efficient molecular chaperone and a major hub in the protein network that maintains cellular homeostasis and function. The qualitative and quantitative changes and rewiring of this protein network in tumor cells make them vastly dependent on Hsp90, which therefore becomes a key target to fight cancer. The inhibition of Hsp90 creates a profound transformation in the cell proteome. In this chapter, we review and analyze the most recent efforts that take advantage of the druggability of Hsp90 in order to understand the global changes at the proteome level that this inhibition produces. The considerable impact that the targeting of Hsp90 has on the structure of these protein networks is also discussed