Long Non-Coding RNA ZFAS1 Is a Major Regulator of Epithelial-Mesenchymal Transition through miR-200/ZEB1/E-Cadherin, Vimentin Signaling in Colon Adenocarcinoma

Colon adenocarcinoma is a common cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition is a major regulator of cancer metastasis, and increased understanding of this process is essential to improve patient outcomes. Long non-coding RNA (lncRNA) are important regulators of carcinogenesis. To identify lncRNAs associated with colon carcinogenesis, we performed an exploratory differential gene expression analysis comparing paired colon adenocarcinoma and normal colon epithelium using an RNA-sequencing data set. This analysis identified lncRNA ZFAS1 as significantly increased in colon cancer compared to normal colon epithelium. This finding was validated in an institutional cohort using laser capture microdissection. ZFAS1 was also found to be principally located in the cellular cytoplasm. ZFAS1 knockdown was associated with decreased cellular proliferation, migration, and invasion in two colon cancer cell lines (HT29 and SW480). MicroRNA-200b and microRNA-200c (miR-200b and miR-200c) are experimentally validated targets of ZFAS1, and this interaction was confirmed using reciprocal gene knockdown. ZFAS1 knockdown regulated ZEB1 gene expression and downstream targets E-cadherin and vimentin. Knockdown of miR-200b or miR-200c reversed the effect of ZFAS1 knockdown in the ZEB1/E-cadherin, vimentin signaling cascade, and the effects of cellular migration and invasion, but not cellular proliferation. ZFAS1 knockdown was also associated with decreased tumor growth in an in vivo mouse model. These results demonstrate the critical importance of ZFAS1 as a regulator of the miR-200/ZEB1/E-cadherin, vimentin signaling cascade

Contrasting Responses to Harvesting and Environmental Drivers of Fast and Slow Life History Species

According to their main life history traits, organisms can be arranged in a continuum from fast (species with small body size, short lifespan and high fecundity) to slow (species with opposite characteristics). Life history determines the responses of organisms to natural and anthropogenic factors, as slow species are expected to be more sensitive than fast species to perturbations. Owing to their contrasting traits, cephalopods and elasmobranchs are typical examples of fast and slow strategies, respectively. We investigated the responses of these two contrasting strategies to fishing exploitation and environmental conditions (temperature, productivity and depth) using generalized additive models. Our results confirmed the foreseen contrasting responses of cephalopods and elasmobranchs to natural (environment) and anthropogenic (harvesting) influences. Even though a priori foreseen, we did expect neither the clear-cut differential responses between groups nor the homogeneous sensitivity to the same factors within the two taxonomic groups. Apart from depth, which affected both groups equally, cephalopods and elasmobranchs were exclusively affected by environmental conditions and fishing exploitation, respectively. Owing to its short, annual cycle, cephalopods do not have overlapping generations and consequently lack the buffering effects conferred by different age classes observed in multi-aged species such as elasmobranchs. We suggest that cephalopods are sensitive to short-term perturbations, such as seasonal environmental changes, because they lack this buffering effect but they are in turn not influenced by continuous, long-term moderate disturbances such as fishing because of its high population growth and turnover. The contrary would apply to elasmobranchs, whose multi-aged population structure would buffer the seasonal environmental effects, but they would display strong responses to uninterrupted harvesting due to its low population resilience. Besides providing empirical evidence to the theoretically predicted contrasting responses of cephalopods and elasmobranchs to disturbances, our results are useful for the sustainable exploitation of these resourcesVersión del editor4,411

Not Available

Not AvailableNot AvailableNot Availabl

Do changes in environmental and fishing pressures impact marine communities? An empirical assessment. Journal of Applied Ecology

The development of ecosystem approaches to environmental management implies the need to account for multiple pressures on ecosystems. Trends in multiple metrics that respond differently to changes in major environmental pressures need to be combined to evaluate the impacts of fishing and environmental changes on fish communities. 2. An exploited fish community is viewed as a three-level food chain in which the two upper levels, or functional groups, are targeted by fishing fleets, while the lowest level is subject to environmental variation. Qualitative modelling is used to predict changes at the two upper levels, that is, top-down vs. bottom-up perturbations. Abundance and length metrics are calculated from survey data for 14 Mediterranean and East-Atlantic groundfish shelf communities at both population and functional group levels. The joint likelihood of time trends in metrics is used to evaluate the evidence for different causes of changes. 3. A wide diversity of impacts is found to have equal evidence at the population level within each community. Consistency between the impacts identified and changes in pressures known from independent information is found at the functional group and community level. The results suggest that there is some compensation between species within functional groups. 4. Synthesis and applications. The method can be used to conduct an integrated assessment of community dynamics subject to multiple pressures. Joint trends in metrics provide evidence of which known pressures are having an impact on the community, and thus, which management actions should be taken to mitigate these changes

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software