AXL as a modulator of sunitinib response in glioblastoma cell lines

Receptor tyrosine kinase (RTK) targeted therapy has been explored for glioblastoma treatment. However, it is unclear which RTK inhibitors are the most effective and there are no predictive biomarkers available. We recently identified the RTK AXL as a putative target for the pan-RTK inhibitors cediranib and sunitinib, which are under clinical trials for glioblastoma patients. Here, we provide evidence that AXL activity can modulate sunitinib response in glioblastoma cell lines. We found that AXL knockdown conferred lower sensitivity to sunitinib by rescuing migratory defects and inhibiting apoptosis in cells expressing high AXL basal levels. Accordingly, overactivation of AXL by its ligand GAS6 rendered AXL positive glioblastoma cells more sensitive to sunitinib. AXL knockdown induced a cellular rewiring of several growth signaling pathways through activation of RTKs, such as EGFR, as well as intracellular pathways such as MAPK and AKT. The combination of sunitinib with a specific AKT inhibitor reverted the resistance of AXL-silenced cells to sunitinib. Together, our results suggest that sunitinib inhibits AXL and AXL activation status modulates therapy response of glioblastoma cells to sunitinib. Moreover, it indicates that combining sunitinib therapy with AKT pathway inhibitors could overcome sunitinib resistance.This work was funded by Fundacao para a Ciencia e Tecnologia (FCT), Portugal (project: PTDC/SAU-TOX/114549/2009). Olga Martinho is a recipient of a Post-Doc fellowship (UMINHO/BPD/32/2013) from QREN. We would like to acknowledge Dr. Shuang-En Chuang from the National Health Research Institute, Taiwan, for providing AXL vectors, and Dr. Raquel Andrade for critical review of the manuscript

Subsidence Hazard in Limestone Cavities: The Case of “Grutas da Moeda” (Fátima, Central Portugal)

“Grutas da Moeda” are natural touristic caves, located in the plateau of São Mamede, near Sanctuary of Fátima, in Portugal. They have been opened to the public since 1974, and receives about 75,000 visitors per year, from 76 nationalities. They are located in the “Maciço Calcário Estremenho”, composed by limestone deposits of the Middle Jurassic (Bathonian), corresponding to the Serra de Aire formation. The geological risk assessment is fundamental to guarantee the safety of its visitors and staff; therefore, it is intended to develop geotechnical monitoring methodologies in order to collect data to understand the risks that may be associated with this natural cavity and to identify critical areas of collapse. There are four main alignments (faults/joints), which assume parallelism with the development of the caves. The trend of the layers in the cave is approximately N30ºE; 17ºSE. In the year 2015, a geophysical study was carried out, using the 3D electrical resistivity method and, for one of the areas in particular, the georadar method. The georadar method allowed to map the anomalies corresponding to empty spaces that have been identified with the 3D electrical resistivity technique. This paper presents the results obtained, as well as proposals for geotechnical measures to mitigate the risk of collapse subsidence.GeoBioTe

Reducing scrap and improving an air conditioning pipe production line

30th International Conference on Flexible Automation and Intelligent Manufacturing (FAIM2021) -15-18 June 2021, Athens, GreeceThe automotive industry is considered one of the most demanding and competitive sectors in the global market. This increasingly implies having a stable and optimized production process, always with a view to continuous improvement. Therefore, it is very important to be aware of all the waste that is generated in all production and logistics operations and take action to reduce them. In this regard and considering the process of producing air conditioning pipes for the automotive industry, a high scrap value was detected mainly due to soldering process. Therefore, the entire production process is analyzed in order to identify the main causes behind the high scrap value. Several Lean and quality tools are used to reduce not only the amount of scrap but also to increase the line productivity. In order to face this challenge, after elaborating the action plan and corresponding implementation, the scrap value is reduced by 12% in general, and productivity increased by 29%, 55% and 22.5% in three different references produced by the same machine. Although this solution is a bit expensive, the corresponding payback is reduced, so it can easily be applied transversally to other similar machines allowing extremely interesting gains in the short term.Andresa Baptista acknowledges the financial support of CIDEM- Research Center of Mechanical Engineering, FCT –Portuguese Foundation for the Development of Science and Technology, Ministry of Science, Technology and Higher ducation, under the Project UID/EMS/0615/2019.info:eu-repo/semantics/publishedVersio

Smart monitoring of constructed wetlands to improve efficiency and water quality

The Smart monitoring of constructed wetlands to improve efficiency and water quality (SmarterCW) project aims to monitor biological wastewater treatment processes by gathering continuous data from remote water and environmental sensors. The acquired data can be processed and analysed through data science tools to better understand the complex and coupled phenomena underneath wastewater treatment, as well as, to monitor and optimize the system performance. The results will improve the efficiency and control of nature-based wastewater treatment technologies. The methodology comprises the following tasks and activities: Implementation of a set of electrochemical sensors in the input and output flow streams of pilot-scale constructed wetlands; Acquisition of water quality parameters such as pH, electrical conductivity, temperature, and ionic compounds; Acquisition of environmental parameters, such as temperature and humidity; Application of data analysis tools to design and optimize conceptual models to correlate pollutants removal with operative parameters in green technologies for wastewater treatment. This methodology was applied to a patent-protected pilot-scale modular constructed wetland in which filling media consists of a mixture of solid waste. The system is complemented by a high-level IoT communication layer structure to support remote real-time water and environmental monitoring, system performance, and data dissemination. The project contributes to: Water and Environment through the efficient management and use of water resources and waste reduction, management, treatment, and valorisation; Materials and raw-materials through efficient, secure, and sustainable use of resources; and Environmental Education promoting environmental awareness and best environmental practices through the dissemination of scientific data and results using Information and Communication Technologies (ICT) tools and IoT platforms. The project also contributes to giving response to Societal Challenges, such as Environment protection, sustainable management of natural resources, water, biodiversity, and ecosystems; Enabling the transition to a green society and economy through eco-innovation.info:eu-repo/semantics/submittedVersio

Effects of dietary curcumin in growth performance, oxidative status and gut morphometry and function of gilthead seabream postlarvae

An imbalance in the production and detoxification of reactive oxygen species and other oxidants can disrupt a l l types of cellular compounds, and lead to a state of oxidative stress. Preventing this state is essential to improve growth and health in animal production. Therefore, the aim of this work was to assess i f the dieta r y supple-mentation of curcumin cou l d improve the antioxidant status and intestine structu r e and functionalit y of gilthead seabream postlarvae, with the global objective of improving fish growth performance and robustness. Two experimental diets supplemented with different doses of curcumin (LOW and HIGH diets), and a commercial diet were fed to quadruplicate groups of postlarvae, for 20 days. At the end of the feeding trial fish fed the supple-mented diets significantly improved their antioxidant status compared to CTRL fed fish. LOW and HIGH fed fish presented lower protein oxidative damage (P 0.05). In conclusion, dieta r y curcumin supplementation was able to enhance gilthead seabream postlarvae robustness through a modulation of the oxidative status, increasing total antioxidant capacity and decreasing protein oxidative damage. This data pro-vide evidence that curcumin can be a suitable feed additive to promote heath status and robustness of fish at early stages of development, therefore contributing for the development and sustainabilit y of marine fish hatchery production.info:eu-repo/semantics/publishedVersio

Dietary curcumin promotes gilthead seabream larvae digestive capacity and modulates oxidative status

The larval stage is highly prone to stress due to the ontogenetic and metabolic alterations occurring in fish. Curcumin inclusion in diets has been shown to improve growth by modulating oxidative status, immune response, and/or feed digestibility in several fish species. The aim of the present work was to assess if dietary curcumin could promote marine fish larvae digestive maturation and improve robustness. Gilthead seabream larvae were fed a diet supplemented with curcumin at dose of 0 (CTRL), 1.5 (LOW), or 3.0 g/Kg feed for 27 days. From 4 to 24 days after hatching (DAH), no differences were observed in growth performance. At the end of the experiment (31 DAH) LOW larvae had a better condition factor than CTRL fish. Moreover, HIGH larvae showed higher trypsin and chymotrypsin activity when compared to CTRL fish. LOW and HIGH larvae were able to maintain the mitochondrial reactive oxygen species production during development, in contrast to CTRL larvae. In conclusion, curcumin supplementation seems to promote larvae digestive capacity and modulate the oxidative status during ontogeny. Furthermore, the present results provide new insights on the impacts of dietary antioxidants on marine larvae development and a possible improvement of robustness in the short and long term.ALG-01-0145-FEDER-029151info:eu-repo/semantics/publishedVersio

Electrospun nanosized cellulose fibers using ionic liquids at room temperature

Aiming at replacing the noxious solvents commonly employed, ionic-liquid-based solvents have been recently explored as novel non-volatile and non-flammable media for the electrospinning of polymers. In this work, nanosized and biodegradable cellulose fibers were obtained by electrospinning at room temperature using a pure ionic liquid or a binary mixture of two selected ionic liquids. The electrospinning of 8 wt% cellulose in 1-ethyl-3-methylimidazolium acetate medium (a low viscosity and room temperature ionic liquid capable of efficiently dissolving cellulose) showed to produce electrospun fibers with average diameters within (470 ± 110) nm. With the goal of tailoring the surface tension of the spinning dope, a surface active ionic liquid was further added in a 0.10 : 0.90 mole fraction ratio. Electrospun cellulose fibers from the binary mixture composed of 1-ethyl-3-methylimidazolium acetate and 1-decyl-3-methylimidazolium chloride ionic liquids presented average diameters within (120 ± 55) nm. Scanning electron microscopy, X-ray diffraction analysis, nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric assays were used as core methods to evaluate the structural integrity, morphology and crystallinity of the raw, electrospun, and regenerated samples of cellulose. Moreover, the photoluminescence spectra of both raw and electrospun fibers were acquired, and compared, indicating that the cellulose emitting centers are not affected by the dissolution of cellulose in ionic liquids. Finally, the use of non-volatile solvents in electrospinning coupled to a water coagulation bath allows the recovery of the ionic fluid, and represents a step forward into the search of environmentally friendly alternatives to the conventional approaches

Nanosafety: an evolving concept to bring the safest possible nanomaterials to society and environment

The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drugs, food, water treatment, and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity, and (epi)genotoxicity. In addition, new technologies, such as organs-on-chips and sophisticated sensors, are under development and/or adaptation. All the information generated is used to develop new in silico approaches trying to predict the potential effects of newly developed materials. The overall evaluation of nanomaterials from their production to their final disposal chain is completed using the life cycle assessment (LCA), which is becoming an important element of nanosafety considering sustainability and environmental impact. In this review, we give an overview of all these elements of nanosafety.European Union’s H2020 project Sinfonia (N.857253). SbDToolBox, with reference NORTE-01-0145-FEDER-000047, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fun