The aberrant expression in epithelial cells of the mesenchymal isoform of FGFR2 controls the negative crosstalk between EMT and autophagy

Signalling of the epithelial splicing variant of fibroblast growth factor receptor 2 (FGFR2b) triggers both differentiation and autophagy, while the aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells induces impaired differentiation, inhibition of autophagy as well as the induction of the epithelial-mesenchymal transition (EMT). In light of the widely proposed negative loop linking autophagy and EMT in the early steps of carcinogenesis, here we investigated the possible involvement of FGFR2c aberrant expression and signalling in orchestrating this crosstalk in human keratinocytes. Biochemical, molecular, quantitative immunofluorescence analysis and in vitro invasion assays, coupled to the use of specific substrate inhibitors and transient or stable silencing approaches, showed that AKT/MTOR and PKCε are the two hub signalling pathways, downstream FGFR2c, intersecting with each other in the control of both the inhibition of autophagy and the induction of EMT and invasive behaviour. These results indicate that the expression of FGFR2c, possibly resulting from FGFR2 isoform switch, could represent a key upstream event responsible for the establishment of a negative interplay between autophagy and EMT, which contributes to the assessment of a pathological oncogenic profile in epithelial cells

A symmetry classification for a class of (2+1)-nonlinear wave equation

In this paper, a symmetry classification of a $(2+1)$-nonlinear wave equation $u_{tt}-f(u)(u_{xx}+u_{yy})=0$ where $f(u)$ is a smooth function on $u$, using Lie group method, is given. The basic infinitesimal method for calculating symmetry groups is presented, and used to determine the general symmetry group of this $(2+1)$-nonlinear wave equation

A protective role for autophagy in vitiligo

A growing number of studies supports the existence of a dynamic interplay between energetic metabolism and autophagy, whose induction represents an adaptive response against several stress conditions. Autophagy is an evolutionarily conserved and a highly orchestrated catabolic recycling process that guarantees cellular homeostasis. To date, the exact role of autophagy in vitiligo pathogenesis is still not clear. Here, we provide the first evidence that autophagy occurs in melanocytes and fibroblasts from non-lesional skin of vitiligo patients, as a result of metabolic surveillance response. More precisely, this study is the first to reveal that induction of autophagy exerts a protective role against the intrinsic metabolic stress and attempts to antagonize degenerative processes in normal appearing vitiligo skin, where melanocytes and fibroblasts are already prone to premature senescence

A phase II study of primary dose-dense sequential doxorubicin plus cyclophosphamide and docetaxel in cT4 breast cancer

Background: Dose-dense chemotherapy with anthracyclines and taxanes has improved either disease free survival or overall survival in high risk patients with early breast cancer. Patients and Methods: The activity and safety of a dose-dense schedule (q14 days) of adriamycin 60 mg/sqm and cyclophosphamide 600 mg/sqm (AC) x 4 cycles followed by docetaxel 75 mg/sqm for 4 cycles with hematopoietic support in patients with stage IIIB breast cancer was explored. Patients with ER >= 10% tumors received concomitant endocrine therapy with 3-month triptorelin and letrozole. Results: Fifteen patients with histologically proven cT4b (three patients) and cT4d (twelve patients) MO breast cancer were enrolled. Median age was 48 years (range 25-66). Eight clinical responses including one pathological complete remission (pCR), three stable disease (including minor responses) and four progression of disease, one during AC and three during taxotere, were observed. Four patients had grade 3-4 non hematological toxicities and all except one discontinued treatment. Conclusion: Due to the high rate of progressive disease, this schedule should not represent a standard option in cT4 breast cancer

Investigating a Science Gateway for an Agent-Based Simulation Application Using REPAST

The benefits of using e-Infrastructure environments, such as cloud, grid, and high performance computing, for performing scientific experiments could be quite significant. In particular, modeling and simulation, which can serve as a key decision making and system analysis tool, could benefit immensely from such environments ranging from issues of how a community of practice could access a simulation to how it could be run quickly. However, the access and use of these e-Infrastructure environments may present a completely different set of challenges, most especially for non-ICT users. Science Gateways (SG), which are digital interfaces to advanced technologies, can be used to overcome the challenges of running many simulations on e- Infrastructures in a reasonable amount of time. In this work, we developed a SG, based on the Liferay portal framework and the Catania grid and cloud engine. We show how an Agent- Based infection simulation, which has been implemented using the Recursive Porous Agent Simulation Toolkit (REPAST) Simphony, can be ported to a Science Gateway and deployed on distributed computing infrastructures. This demonstration illustrates how this technology can be used easily to allow multiple users across the world to access a simulation and to execute their applications in an e-Infrastructures environment.Special thanks go to the team at the University of Catania for their support and the provision of the infrastructures that enable the execution of our ABMS application jobs. This work was part-funded by the H2020 project Energising Scientific Endeavour through Science Gateways and e-Infrastructures in Africa (Sci-GaIA) (project number 654237)

Biomimetic Carbon-Fiber Systems Engineering: A Modular Design Strategy to Generate Biofunctional Composites from Graphene and Carbon Nanofibers

electrical conductivity. It is additionally advantageous if such materials resembled the structural and biochemical features of the natural extracellular environment. Here we show a novel modular design strategy to engineer biomimetic carbon-fiber based scaffolds. Highly porous ceramic zinc oxide (ZnO) microstructures serve as 3D sacrificial templates and are infiltrated with carbon nanotube (CNT) or graphene dispersions. Once the CNTs and graphene uniformly coat the ZnO template, the ZnO is either removed by hydrolysis or converted into carbon by chemical vapor deposition (CVD). The resulting 3D carbon scaffolds are both hierarchically ordered and free-standing. The properties of the micro-fibrous scaffolds were tailored with a high porosity (up to 93 %), high Young’s modulus (~0.027 to ~22 MPa), and an electrical conductivity of (~0.1 to ~330 S/m), as well as different surface compositions. Cell viability and fibroblast proliferation rate and protein adsorption rate assays have shown that the generated scaffolds are biocompatible and have a high protein adsorption capacity (up to 77.32 ±6.95 mg/cm3), so that they not only are able to resemble the ECM structurally, but also biochemically. The scaffolds also allow for the successful growth and adhesion of fibroblast cells showing that we provide a novel, highly scalable modular design strategy to generate biocompatible carbon-fiber systems that mimic the extracellular matrix with the additional feature of conductivity.RA gratefully acknowledges partial project funding by the Deutsche Forschungsgemeinschaft under contract FOR1616. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. GrapheneCore2 785219. CS is supported by the European Research Council (ERC StG 336104 CELLINSPIRED, ERC PoC 768740 CHANNELMAT), by the German Research Foundation (RTG 2154, SFB 1261 project B7). MT acknowledges support from the German Academic Exchange Service (DAAD) through a research grant for doctoral candidates (91526555-57048249). We acknowledge funding from EPSRC grants EP/P02534X/1, ERC grant 319277 (Hetero2D) the Royal Academy of Engineering Enterprise Scheme, the Trinity College, Cambridge, and the Isaac Newton Trust