75 research outputs found

    HNF1α inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines

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    <p>Abstract</p> <p>Background</p> <p>Hepatocyte Nuclear Factor 1α (HNF1α) is an atypical homeodomain-containing transcription factor that transactivates liver-specific genes including albumin, α-1-antitrypsin and α- and ÎČ-fibrinogen. Biallelic inactivating mutations of <it>HNF1A </it>have been frequently identified in hepatocellular adenomas (HCA), rare benign liver tumors usually developed in women under oral contraceptives, and in rare cases of hepatocellular carcinomas developed in non-cirrhotic liver. HNF1α-mutated HCA (H-HCA) are characterized by a marked steatosis and show activation of glycolysis, lipogenesis, translational machinery and mTOR pathway. We studied the consequences of HNF1α silencing in hepatic cell lines, HepG2 and Hep3B and we reproduced most of the deregulations identified in H-HCA.</p> <p>Methods</p> <p>We transfected hepatoma cell lines HepG2 and Hep3B with siRNA targeting HNF1α and obtained a strong inhibition of HNF1α expression. We then looked at the phenotypic changes by microscopy and studied changes in gene expression using qRT-PCR and Western Blot.</p> <p>Results</p> <p>Hepatocytes transfected with HNF1α siRNA underwent severe phenotypic changes with loss of cell-cell contacts and development of migration structures. In HNF1α-inhibited cells, hepatocyte and epithelial markers were diminished and mesenchymal markers were over-expressed. This epithelial-mesenchymal transition (EMT) was related to the up regulation of several EMT transcription factors, in particular <it>SNAIL </it>and <it>SLUG</it>. We also found an overexpression of TGFÎČ1, an EMT initiator, in both cells transfected with HNF1α siRNA and H-HCA. Moreover, TGFÎČ1 expression is strongly correlated to HNF1α expression in cell models, suggesting regulation of TGFÎČ1 expression by HNF1α.</p> <p>Conclusion</p> <p>Our results suggest that HNF1α is not only important for hepatocyte differentiation, but has also a role in the maintenance of epithelial phenotype in hepatocytes.</p

    Inflation and Dark Energy from spectroscopy at z &gt; 2

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    Constructing Social Problems in an Age of Globalization: A French-American Comparison

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    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≀ 18 years: 69, 48, 23; 85%), older adults (≄ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

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    Formulating a Low-Alkalinity, High-Resistance and Low-Heat Concrete for Radioactive Waste Repositories

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    International audienceInvestigations were carried out in order to formulate and characterize low-alkalinity and low-heat cements which would be compatible with an underground waste repository environment. Several systems comprising Ordinary Portland Cement (OPC), a fast-reacting pozzolan (silica fume (SF) or metakaolin (MK)) and, in some cases, a slow-reacting product (fly ash (FA) or blastfurnace slag (BFS)) were compared. Promising results were obtained with some binary mixtures of OPC and SF, and with some ternary blends of OPC, SF and FA or BFS pH of water in equilibrium with the fully hydrated cements dropped below 11. Dependence of the properties of standard mortars on the high contents of FA and SF in the low-pH blends was examined. Combining SF and FA seemed attractive since SF compensated for the low reactivity of FA, while FA allowed to reduce the water demand, and dimensional variations of the mortars. Finally, low-heat (ΔT\Delta T<20°C under semi-adiabatic conditions) and high strength (≈70−80\approx 70-80 MPa) concretes were prepared from two low-pH cements a binary blend made from 60% of OPC and 40% of SF, and a ternary blend including 37.5% OPC, 32.5% SF and 30% FA

    A generic drying model for cassava products

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    International audienceDrying is a a critical step in many food processes, e.g. in the production of cassava flour. No specific Computer Aided Engineering (CAE) tool is available to assist in the design of cassava drying equipment. In this study, a convective-diffusive model was selected in the literature for its genericity and suitability for engineering purposes. Three drying kinetics were sufficient to identify the required temperature-dependent effective diffusivity. They were measured under 40–80∘C air, flowing perpendicular to the cassava cylinders. For validation, a total of 36 kinetics were measured on four cassava products of different origins, levels of transformation, geometries, dried in air flows at 40–80∘C, parallel or perpendicular to the product layer. Using 3 properties taken from the literature and few straightforward lab measurements, the model was able to accurately predict (RMSE: 0.04 d.b.) all drying kinetics for cassava products from flour to root cuts
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