Distinguishing mechanisms underlying EMT tristability

Abstract Background The Epithelial-Mesenchymal Transition (EMT) endows epithelial-looking cells with enhanced migratory ability during embryonic development and tissue repair. EMT can also be co-opted by cancer cells to acquire metastatic potential and drug-resistance. Recent research has argued that epithelial (E) cells can undergo either a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype that typically displays collective migration, or a complete EMT to adopt a mesenchymal (M) phenotype that shows individual migration. The core EMT regulatory network - miR-34/SNAIL/miR-200/ZEB1 - has been identified by various studies, but how this network regulates the transitions among the E, E/M, and M phenotypes remains controversial. Two major mathematical models – ternary chimera switch (TCS) and cascading bistable switches (CBS) - that both focus on the miR-34/SNAIL/miR-200/ZEB1 network, have been proposed to elucidate the EMT dynamics, but a detailed analysis of how well either or both of these two models can capture recent experimental observations about EMT dynamics remains to be done. Results Here, via an integrated experimental and theoretical approach, we first show that both these two models can be used to understand the two-step transition of EMT - E→E/M→M, the different responses of SNAIL and ZEB1 to exogenous TGF-β and the irreversibility of complete EMT. Next, we present new experimental results that tend to discriminate between these two models. We show that ZEB1 is present at intermediate levels in the hybrid E/M H1975 cells, and that in HMLE cells, overexpression of SNAIL is not sufficient to initiate EMT in the absence of ZEB1 and FOXC2. Conclusions These experimental results argue in favor of the TCS model proposing that miR-200/ZEB1 behaves as a three-way decision-making switch enabling transitions among the E, hybrid E/M and M phenotypes

Mathematical modeling and mass transfer considerations in supercritical fluid extraction of Posidonia oceanica residues

WOS: 000325830700031Posidonia oceanica residues were extracted with supercritical CO2 in order to isolate phenolic compounds. The process was optimized by developing a mathematical model based on mass transfer mechanism consisting of adsorption of supercritical fluid on the solid particles, desorption of solute and convective transfer of solute phase along the column. Henry relation between solute concentrations on the surface of the solid (Cs) and in the solid (q) was approximated in order to describe the adsorption/desorption equilibrium. The model parameters such as solid-liquid film mass transfer coefficient (kf), molecular diffusivity coefficient (D-AB) and axial dispersion (D-ax) were estimated using empirical methods. The linear driving force model was applied to improve the yield of total phenolic acid recovery. The optimum parameters were elicited as 25 MPa, 323.15 K and a co-solvent mass ratio of 20% yielding 34.97 mu g per gram of dry feed and the model satisfactorily described the extraction yield which can be used for scale-up purposes. (C) 2013 Elsevier B.V. All rights reserved.Scientific and Technical Research Council of Turkey, TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [110M790]The research fund provided by the Scientific and Technical Research Council of Turkey, TUBITAK (110M790) is highly appreciated

Transformation of Posidonia oceanica residues to bioethanol

WOS: 000330820800047Posidonia oceanica is important species of the marine ecosystems. However, large quantities of residues reaching the coastlines create pollution and high costs are required for their disposal. The objective was to investigate the bioconversion efficiency of P. oceanica residues as a source of feedstock in order to propose alternative solutions to the landfill. The residues were collected from the west coast of Turkey and hydrolyzed by both dilute sulfuric acid and cellulase. The maximum yield of reducing sugars was 21.6 g/L under the optimal conditions of enzyme pretreatment (7.5g substrate, 20 FPU, 90h), whereas 39.2 g/L was reached by consecutive enzymatic and acid hydrolysis. Bioethanol yield based on the sugar consumed was 62.3% corresponding to a productivity of 0.46 kg/m(3) h in flasks, whereas 0.76 kg/m(3) h was achieved in 2 L bioreactor. The results showed that P. oceanica residues can be utilized as a potential feedstock for the production of bioethanol. (C) 2013 Elsevier B.V. All rights reserved.Scientific and Technical Research Council of Turkey, TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [110M790]The research fund provided by the Scientific and Technical Research Council of Turkey, TUBITAK (110M790) is highly appreciated. We also acknowledge Novozyme, Istanbul for donation of Celtic CTec2

An integrated process for conversion of Zostera marina residues to bioethanol

Zostera marina is an aquatic plant forming wide grasslands and considered as the lungs of the marine ecosystems. However, the residues reaching the coastlines create nuisance and high costs are required for their disposal. The objective was to investigate the potential of Z. marina residues as a source of secondary metabolites and feedstock in order to propose alternative solutions to the landfill. The supercritical CO2 extract had a total phenol value of 55.4 mg GAE/g extract and a radical scavenging capacity of 71.4%. Considering the raffinate phase, 3% higher hemicellulose content was reached after supercritical CO2 treatment. Enzymatic hydrolysis revealed 31.45% and the yield of simultaneous saccharification and fermentation was 8.72% corresponding to a productivity of 0.273 kg/(m3 h). An integrated process is proposed, where supercritical fluid extraction can act both as the main process to obtain solvent-free pharmaceutical compounds and a pretreatment method in order to loosen the lignin structure, thereby liberating some of the hemicellulose in the matrix

Review on Catalytic Biomass Gasification for Hydrogen Production as a Sustainable Energy Form and Social, Technological, Economic, Environmental, and Political Analysis of Catalysts

Sustainable energy production is a worldwide concern due to the adverse effects and limited availability of fossil fuels, requiring the development of suitable environmentally friendly alternatives. Hydrogen is considered a sustainable future energy source owing to its unique properties as a clean and nontoxic fuel with high energy yield and abundance. Hydrogen can be produced through renewable and nonrenewable sources where the production method and feedstock used are indicators of whether they are carbon-neutral or not. Biomass is one of the renewable hydrogen sources that is also available in large quantities and can be used in different conversion methods to produce fuel, heat, chemicals, etc. Biomass gasification is a promising technology to generate carbon-neutral hydrogen. However, tar production during this process is the biggest obstacle limiting hydrogen production and commercialization of biomass gasification technology. This review focuses on hydrogen production through catalytic biomass gasification. The effect of different catalysts to enhance hydrogen production is reviewed, and social, technological, economic, environmental, and political (STEEP) analysis of catalysts is carried out to demonstrate challenges in the field and the development of catalysts.Ege University Scientific Research Projects Coordination Unit [FDK-2020- 22276]; Scientific and Technological Research Council of Turkey (TUBITAK) [2211C]; council of higher education (YOK)This study is supported by Ege University Scientific Research Projects Coordination Unit. Project number: FDK-2020-22276. We are gratef u l to Ege University Planning and Monitoring Coordination of Organizational Development and Directorate of Library and Documentation for their support with editing and proofreading services for this study. Many thanks to BioRender who helped us create the graphical abstract. The authors express their thanks to the Scientific and Technological Research Council of Turkey (TUBITAK) for the fellowship 2211C and also their thank s to the council of higher education (YOK) for 100/2000 scholarships. The authors would like to thank Dilvin Cebi for her contributions to the study

Bioconversion of hazelnut shell using near critical water pretreatment for second generation biofuel production

WOS: 000528188600007The global energy deficiency and depletion of fossil fuels have raised concerns leading to a wide scale examination of alternative and renewable energy sources. Lignocellulosic biomass that is one of the renewable energy sources has major potential in the world and it has a wide variety of sources including agricultural residues such as cotton stalk, corn stover, wheat straw, etc. Including over 65% cellulose and hemicelluloses content, these materials can be hydrolyzed into monomeric sugars and then can be converted into biofuels and other industrial products. the main objective of this study is bioethanol production with bioconversion of lignocellulosic biomass, namely hazelnut shell. in order to efficiently utilize this raw material for ethanol production by degrading the lignocellulosic structure, an effective pretreatment is required. LHW, a near critical water pretreatment method, is chosen for this particular research due to its unique environmental and economic properties. the experiment design was prepared with Response Surface Estimation Method (RSM) by Design Expert software. the experiment parameters were selected as temperature (100-200 degrees C), pressure (80-200 bar) and flow rate (2-8 ml/min). the optimum condition (OC) for the process was determined as 138 degrees C, 2 ml/min and 200 bar according to the Dinitrosaliclic acid (DNS) method. Additionally, in order to achieve maximum ethanol concentration, the condition producing maximum reducing sugar content is determined. Separated hydrolysis and fermentation (SHF) process was used for bioethanol production. Enzymatic hydrolysis was conducted with a part of solid residue obtained from the maximum ethanol condition (MEC) for bioethanol production. MEC is 200 degrees C, 2 ml/min and 200 bar. Under MEC, at the end of the fermentation process maximum ethanol yield was 44.89% with 0.5 g of solid loading. the main purpose of the study is to determine the effects of different solid loading rates in the enzymatic hydrolysis stage of SHF process to ethanol production as a result of fermentation. There are several pretreatment methods for this process. It is concluded that the superior qualifies of LHW pretreatment in means of environmental friendliness, non-toxic and non-corrosive byproducts, water usage instead of other chemical additives, degradation of lignocellulosic structure and low cost were suitable for the intended purpose of bioethanol production using hazelnut shell.Ege UniversityEge University [FGA-2018-20029]This study was supported by the scientific research coordinator of the Ege University with the FGA-2018-20029 project number

Cytotoxic responses of carnosic acid and doxorubicin on breast cancer cells in butterfly-shaped microchips in comparison to 2D and 3D culture

WOS: 000398104900012PubMed ID: 28191587Two dimensional (2D) cell culture systems lack the ability to mimic in vivo conditions resulting in limitations for preclinical cell-based drug and toxicity screening assays and modelling tumor biology. Alternatively, 3D cell culture systems mimic the specificity of native tissue with better physiological integrity. In this regard, microfluidic chips have gained wide applicability for in vitro 3D cancer cell studies. The aim of this research was to develop a 3D biomimetic model comprising culture of breast cancer cells in butterfly-shaped microchip to determine the cytotoxicity of carnosic acid and doxorubicin on both estrogen dependent (MCF-7) and independent (MDAMB231) breast cancer cells along with healthy mammary epithelial cells (MCF-10A) in 2D, 3D Matrigel (TM) and butterfly-shaped microchip environment. According to the developed mimetic model, carnosic acid exhibited a higher cytotoxicity towards MDAMB 231, while doxorubicin was more effective against MCF-7. Although the cell viabilities were higher in comparison to 2D and 3D cell culture systems, the responses of the investigated molecules were different in the microchips based on the molecular weight and structural complexity indicating the importance of biomimicry in a physiologically relevant matrix

Optimization and mathematical modeling of mass transfer between Zostera marina residues and supercritical CO2 modified with ethanol

Supercritical CO2 extraction of phenolic compounds from Zostera marina residues was optimized by developing a mathematical model based on mass transfer balances. A linear driving force model was applied considering model parameters such as solute concentration on the surface of the solid (Cs) and in the supercritical fluid phase (Cf), film mass transfer coefficient (kf) and molecular diffusivity (DAB) and axial dispersion (Dax) coefficients. Henry's law was used to describe the equilibrium state of solid and fluid phases. The results of the proposed model were compared to that of the experimental data in terms of transport properties and extraction yield at various temperatures (303.15, 323.15, 353.15 K), pressures (15, 25, 35 MPa) and co-solvent mass ratios (0, 10, 20%). The optimum parameters were elicited as 25 MPa, 353.15 K and a co-solvent ratio of 20% yielding 77.22 μg g−1 dry feed. The model satisfactorily described the extraction yield which can be used for scale-up purposes